Fw: [MSersLife] some of my research on supplements LONG

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[Norton AntiSpam] [MSersLife] some of my research on supplements LONG

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CAN SUPPLEMENTS TAKE THE PLACE OF A BAD DIET?

by W. Saul

(Reprinted with permission from the Journal of Orthomolecular Medicine, 2003; Vol. 18, Numbers 3 and 4, p. 213-216.)

Can supplements take the place of a bad diet?

They'd better.

In spite of decades of intense and well-funded mass education, "70 percent of all adults and children in the U.S. do not eat the recommended five to nine servings of fruits and vegetables a day for good health," according to an April 25, 2002 press release by the National Cancer Institute. (1) And when a "serving" of fruit may be a 6-ounce glass of juice and a "serving" of a vegetable is a mere half-cup of beans, it really makes you think.

Since at least half of all Americans take vitamin supplements every day, one might be tempted to say that, to a considerable degree, the people have already answered this article's title's question. The public now, finally, has the support of orthodox medicine. After years of disparaging supplements, the Journal of the American Medical Association has recently published the recommendation that every person take a multivitamin daily (2,3), saying that "(S)uboptimal intake of some vitamins, above levels causing classic vitamin deficiency, is a risk factor for chronic diseases and common in the general population, especially the elderly." Therefore, JAMA's intent goes beyond routine nutritional insurance for widespread bad-to-borderline diets. The goal is stated in the article's title: Vitamins for chronic disease prevention in adults. It is a sensible idea whose time should have come generations ago.

Supplementation's harshest critics have traditionally railed against vitamins (especially in large doses) as being outright "dangerous" and at the very least "a waste of money." Even as late as this year, the New York Times (4) expanded the attack to question folic acid supplementation and even the practice of taking a daily multivitamin, saying, "vitamin supplements cannot correct for a poor diet (and that) multivitamins have not been shown to prevent any disease."

The NY Times may have neglected to emphasize the real story: people eat terribly.

Though eating less fat, more Westerners are more obese than ever before, and in the United States, an astounding 80% of persons over the age of 25 are overweight. Nearly two-thirds of all Americans (more than 120 million people) are overweight or obese, according to the 1999-2000 National Health and Nutrition Examination. (5) Protein and sugar intake is still astronomically high and fruit and vegetable consumption is still ridiculously low.

While vitamin supplements do not produce weight loss, persons trying to lose weight face a nutritional adequacy problem of their own. Approximately 50 million Americans admit to being "on a diet" at any given time. Virtually all popular unsupplemented weight loss plans are nutrient deficient. For many, eating less food means eating fewer food-source vitamins. Taking supplements can be seen as especially important for all people that are dieting.

Dieticians have set themselves the heroic but probably unattainable goal of getting every person to eat well every day. Even if obtained, such vitamin intake as good diet provides is inadequate to maintain optimum health for everyday people in real-life situations. Tens of millions of women have a special concern. Oral contraceptives lower serum levels of B-vitamins, especially B-6, plus niacin (B-3), thiamin (B-1), riboflavin (B-2), folic acid, vitamin C and B-12. (6). Ladies, when is the last time your physician instructed you to be sure to take supplemental vitamin C and B-complex vitamins as long as you are on the Pill?

Furthermore, government vitamin recommendations are so low as to resemble a test so easy, a standard so minimal, that you would think no one can possibly fail. For example, the US Reference Daily Intake (RDI) for vitamin E is 30 International Units. It is widely appreciated that at least 100 IU of vitamin E (and probably 400 IU or more) daily is required to prevent a great deal of cardiovascular and other disease. Yet it is literally impossible to obtain 100 IU of vitamin E from even the most perfectly planned diet.

To demonstrate this, I've challenged my nutrition students to create a few days of "balanced" meals, using the food composition tables in any nutrition textbook, to achieve 100 IU of vitamin E per day. They could attempt their objective with any combination of foods and any plausible number of portions of each food. The only limitation was that they had to design meals that a person would actually be willing to eat. As this ruled out prescribing whole grains by the pound and vegetable oils by the cup, they could not do it. Nor can the general public. Most people do not even get 30 IU of vitamin E a day. In fact, most get only 17 IU. (7)

"Supplements" by definition are designed to fill nutritional gaps in a bad diet. They fill in what may be surprisingly large gaps in a good diet as well. In the case of vitamin E, doing so is likely to save millions of lives. The New England Journal of Medicine had two articles in the May 20, 1993 issue (8,9) showing that persons taking vitamin E supplements had an approximately 40% reduction in cardiovascular disease. Nearly 40,000 men and 87,000 women took part in the studies. The more vitamin E they took, and the longer they took it, the less cardiovascular disease they experienced.

A 1996 double-blind, placebo-controlled study of 2,002 patients with clogged arteries demonstrated a 77% decreased risk of heart attack in those taking 400 to 800 IU of vitamin E. (10) Again, such effective quantities of vitamin E positively cannot be obtained from diet alone. 800 IU is 2,667% of the US RDI for vitamin E. Is that a lot, or is the government recommendation too low?

Even a modest quantity of vitamin C prevents disease and saves lives. Just 500 mg daily results in a 42 percent lower risk of death from heart disease and a 35 percent lower risk of death from any cause. (11) Since two-thirds of the population is not eating sufficient fruits and vegetables, the only way to close the gap is with vitamin supplements.

To illustrate how extraordinarily important supplements are to persons with a questionable diet, consider this: Children who eat hot dogs once a week double their risk of a brain tumor. Kids eating more than twelve hot dogs a month (that's barely three hot dogs a week) have nearly ten times the risk of leukemia as children who ate none. (12) However, hot-dog eating children taking supplemental vitamins were shown to have a reduced risk of cancer. (13) It is curious that, while theorizing many "potential" dangers of vitamins, the media often choose to ignore the very real cancer-prevention benefits of supplementation.

Critics also fail to point out how economical supplements are. For low-income households, taking a two-cent vitamin C tablet and a three-cent multivitamin, readily obtainable from any Wal-Mart or discount store, is vastly cheaper than getting those vitamins by eating right. The uncomfortable truth is that it is often less expensive to supplement than to buy nutritious food, especially out-of-season fresh produce. And those who wish to follow Linus ing's perennially wise recommendation to take daily multi-gram doses of vitamin C can do so easily and cheaply. Few people can afford to eat several dozen oranges a day.

Since the ancient Egyptians, through the time of Hippocrates, and right up to the present, poor diet has been described and decried by physicians. Little has changed for the better, and much has changed for the worse. Though nutritionists place a nearly Puritanical emphasis on food selection as our vitamin source, everyone else eats because they are hungry, because it makes them feel better, and because it gives such hedonistic pleasure. No one likes the "food police." Telling people what they should do is rarely an unqualified success, and with something as intensely personal as food, well, good luck. We could, of course, legislate Good Food Laws and make it against the law to make, sell, or eat junk. That is as likely to work as Prohibition. It presents me with novel images of seven-year-olds bootlegging Kool-Aid and their parents running Twinkies across state lines.

Our somewhat less draconian choice of "noble experiment" has been to educate, to implore, and to exhort the citizenry to be "choosy chewers," to "eat a balanced diet" and follow the food groups charts. The result? Obesity is more prevalent and cancer is no less prevalent. Cardiovascular disease is still the number one killer of men and women. "Health is the fastest growing failing business in western civilization," writes Emanuel Cheraskin, M.D., in Human Health and Homeostasis. (14) "We can say with reasonable certainty that only about six percent of the adult population can qualify as 'clinically' healthy." (p 9) We can try to sort out each of the many negative behavior variables (such as smoking) which certainly must be factored in. When we have done so, we are left with the completely unavoidable conclusion that our dinner tables are killing us.

The good diet vs. supplement controversy may be reduced to four logical choices:

a) Shall we eat right and take supplements and be healthy?

Or, shall we eat right and take no supplements, be vitamin E and C deficient for our entire lifespan, and greatly increase our risk of sickness and death at any age?

c) Or, shall we eat wrong and take no supplements, and be even worse off?

d) Or, shall we eat wrong, but take daily vitamin supplements, and be a lot less sickly than if we did not take supplements?

While each of these four options constitutes a popular choice, there is one best health-promoting conclusion: Supplements make any dietary lifestyle, whether good or bad, significantly better. Supplements are an easy, practical entry-level better-nutrition solution for the public. A television-educated populace is more likely to take some tablets than to eat organ meats, wheat germ, bean sprouts and ample vegetables. Media supplement-scare-stories notwithstanding, taking supplements is not the problem; it is a solution. Malnutrition is the problem.

In 1998, the American Association of Poison Control Centers' Toxic Exposure Surveillance System reported the following fatalities from vitamin supplements:

Adult multiple vitamins: 0

Pediatric multiple vitamins: 0

(And, incidentally, there were no deaths from vitamin C, vitamin E, folic acid, nor from any other vitamin whatsoever.) (15)

On the other hand, according to DeRose, M.D., M.P.H., "300,000 Americans die annually from poor nutrition choices." (16)

As it has been for thousands of years of human history, so the malnutrition problem remains with us today. Only in the last century have supplements even been available. Their continued use represents a true public health breakthrough on a par with clean drinking water and sanitary sewers, and can be expected to save as many lives. But as long as USDA Food Stamps may be used to buy a box of doughnuts, but are not allowed by law to be used to buy multivitamins, there is a task in front of us. Vitamin supplements, like air bags, can save lives. We should advocate them without ceasing.

References:

1. http://www.hhs.gov/news/press/2002pres/20020425.html

2. Fletcher RH and Fairfield KM. Vitamins for Chronic Disease Prevention in Adults: Clinical Applications JAMA. 2002; 287:3127-3129.

3. Fairfield KM and Fletcher RH. Vitamins for Chronic Disease Prevention in Adults: Scientific Review JAMA. 2002; 287:3116-3126.

4. Kolata G. Vitamins: More may be too many. The New York Times. April 29, 2003.

5. Flegal KM, Carroll MD, Ogden CL, CL. Prevalence and trends in obesity among US adults, 1999-2000. JAMA. 2002 Oct 9; 288(14):1723-7.

6. Wynn V. Vitamins and oral contraceptive use. Lancet. 1975 Mar 8;1(7906):561-4.

7. Antioxidants: What they are and what they do. Harvard Health Letter. Feb 1999; 24(5).

8. Stampfer MJ, Hennekens CH, Manson, J., Colditz GA, Rosner B. and Willett, WC. (1993) Vitamin E consumption and the risk of coronary disease in women. New England Journal of Medicine. 328:1444-1449.

9. Rimm EB, Stampfer, MJ, Ascherio A, Giovannucci E, Colditz, GA and Willett WC. (1993) Vitamin E consumption and the risk of coronary heart disease in men. New England Journal of Medicine 328:1450-1456.

10. s, NG et al. Randomized controlled trial of vitamin E in patients with coronary artery disease: Cambridge Heart Antioxidant Study (CHAOS)," The Lancet, March 23, 1996; 347:781-786.

11. Enstrom JE, Kanim LE, and Klein MA. Vitamin C intake and mortality among a sample of the United States population. Epidemiology 3 (1992):194–202.

12. s JM, Preston- S, London SJ, Bowman JD, Buckley JD, DC. Processed meats and risk of childhood leukemia (California, USA). Cancer Causes Control. 1994 Mar; 5(2):195-202.

13. Sarasua S, Savitz DA. Cured and broiled meat consumption in relation to childhood cancer: Denver, Colorado (United States). Cancer Causes Control. 1994 Mar; 5(2):141-8.

14. Cheraskin E. Human Health and Homeostasis. 1999. Birmingham, AL: Natural Reader Press.

15. Rosenbloom M. Vitamin toxicity. http://www.eMedicine.com . October 23, 2001.

16. DeRose DJ. The WellnessWise Electronic Journal. Vol 1, No. 8; September 3, 1995. http://www.lifetalk.net/anewstart/wellnesswise/ww_95sep03.html

Antioxidants in Health and Disease: The Big Picture E. Cheraskin, MD, DMD (Reprinted with permission of the author and the Journal of Orthomolecular Medicine 10: #2, 89-96, Second Quarter, 1995.)

Abstract In December 1993, four reports appeared describing the ecology of macular degeneration (MD). (1-4) It was generally agreed that the environmental contribution includes sunlight. It was suggested that the antioxidants serve to counter the oxidative damage. In any case, the articles prompted a letter to the editor entitled, "Now That We Have All The Pieces... Why Is There Still A Puzzle?” (5) This was intended to indicate that we still have very little opportunity to slow and/or stop the degenerative process. We have even less knowledge about how to reverse and/or prevent MD.

This report is intended to cast additional light on the subject It is suggested that, viewed in the bigger picture, the total body concept, significant changes in macular degeneration and other diseases may occur when larger-than-recommended amounts of the antioxidants are supplied. Additionally, it is proposed that the therapy be instituted for longer periods of time and begun earlier in life. It is hoped that this report will continue more action in the pursuit of this approach to macular degeneration.

Introduction The literature is replete with information which suggests that a common denominator in the aging process and in the major diseases associated with aging is oxidative damage. This has led to an interest in the use of antioxidants in the prevention and treatment of such problems. There are hundreds, if not thousands, of articles on this subject. Some are retrospective; other prospective. They deal with large and small samples of short and long duration. They range from the womb to the tomb. Most of them are of an epidemiologic (correlational) nature. However, many are concerned with intervention and possibly provide causal data.

This report will outline evidence to show that the antioxidants are necessary, singly, in combinations, in larger amounts than generally held, and must be started much earlier in life. Hence, we will attempt to emphasize the relationship of antioxidants to common disorders such as heart disease, cancer, diabetes, arthritis, cataracts, and macular degeneration as well as other syndromes through an examination of 40 representative studies in the English language literature.

Vitamin A Studies Included (Table 1) are five representative studies of vitamin A consumption in health and disease. (6-10) According to the Subcommittee on Foods and Nutrition of the National Research Council, the daily recommended requirements (RDA) for vitamin A are 5,000 and 4,000 IU respectively for men and women. (11) It is clear from Table 1 that much larger amounts than proposed for healthy people in the RDA are needed. Additionally, the evidence from these studies suggest that there were no side effects.

It is generally recognized that vitamin A blood levels below 10 mcg% are considered evidence of obvious deficiency. (12) Olson contends that the normal range is 20 to 50 mcg% and therefore anything above 50 is high.

Table 2 summarizes the studies on vitamin A in the blood in health and sickness. You will note that the reports shown suggest that what Olson call high levels are probably the desired amounts.

Vitamin C Studies According to the Recommended Dietary Allowances, 60 mg of vitamin C is the suggested normal requirement. (11)Table 3 features studies which underscore the desirability of larger-than-recommended amounts. (18-22) It will be noted that amounts as large as three grams per dose provide remarkable consequences.

Back in the '40s, the Interdepartmental Committee on Nutrition for National Defense (ICNND) began to set the standards for optimal plasma vitamin C. Originally, acceptability was anything above 0.1 mg%. Through the '40s, the figures were changed to 0.2 and then 0.4 mg%. Most of the literature today considers 0.4 mg% as being a satisfactory blood vitamin C level. In this connection, Block points out that 15% of white men, 65-74 years of age, in the U.S. today have blood ascorbate levels below 0.4 mg%.(23) Chandra views 0.5 to 2.0 mg% as the acceptable range. (24) It is clear from Table 4 that the best clinical results parallel plasma levels above 1.0 mg%. (17, 25-28)

Vitamin E Studies According to the RDA, 30 mg of vitamin E or 10 mg of alpha tocopherol is considered the recommendation for healthy man.(11) It will be noted (Table 5) that amounts ranging from 400 to 3200 mgs contribute to the solution of many classical problems. (29-33)

There is not much in the literature regarding the optimal blood vitamin E levels. MachIm, in his book (34) indicates that anything less than 0.7 mg% is deficient, levels between 0.7 and 0.9 are low, and values above 0.9 mg% are acceptable. Simonoff adds the fact that the blood levels of vitamin E are different in the sexes and at different ages. (35) For example, in the young adult, the values should be 1.6 to 1.9 mg% and decrease with age to 0.9 to 1.1 mg% in the elderly. In the light of these so-called norms, it is interesting (Table 6) that salutary effects seem to parallel higher blood vitamin E levels. (14, 36-39)

Other Antioxidants While vitamins A, C, and E have been recognized for a long time for their antioxidant properties, there are others such as zinc, selenium, and bioflavinoids which directly or indirectly serve as free radical scavengers. Perhaps the one receiving the most attention at the moment is the carotenoids and particularly beta carotene. Since beta carotene serves as a provitamin A, there are suggestions as to its daily requirement. (11) However, beta carotene also serves an independent function as an antioxidant. The requirement in this regard is not very clear.

Table 7 outlines the relationship of dietary beta carotene to some of our major problems. (40-44) There seems to be no question but that beta carotene in larger-than-generally recommended amounts exert salutary effects.

In line with our earlier format, Table 8 outlines the blood carotene levels. (14, 45-48) In general, the levels in health are considerably larger than those with illness.

The Antioxidant Index Perhaps more importantly is the observation that the relationship between various antioxidants in health and disease are sharpened when they are viewed as an antioxidant index. For example, macular degeneration, (26) colorectal adenomas, (49) rheumatoid arthritis, (50) cancer, (51) and cardiovascular disease, (52) become even more meaningful when viewed in terms of conditions of antioxidants rather than single ones.

Comments We have been trying to answer the question of the role of antioxidants in the aging process and in age-related diseases. We think that we have some of the answers. It would seem, from what has transpired, that the antioxidants are important in the prevention and treatment of these problems. However, there are still unanswered questions. We still do not know all of the antioxidants. We are still not sure of the dosages except that they are larger than usually recommended. We have little information about the amounts for different diseases. For example, are the dosages larger for macular degeneration than heart disease? Or, are the amounts more a function of the oxidative damage? And, perhaps more importantly, we do not have the time frame period.

Since the disturbances associated with aging and these age-related diseases are characterized by a long incubation period and an insidious clinical course, the question of when one should institute an antioxidant program is still unresolved. The one thing we know for sure is starting when the disease appears is too late.

Summary and Conclusions In the final analysis, how we fare is a function of two sets of interdependent factors. On the one hand, we are at the mercy of numerous environmental threats, such as physical, chemical, microbial, thermic, actinic, and psychologic. For macular degeneration, the dominant one is solar radiation; for lung cancer, it is tobacco consumption. However, how we fare is also a function of how well we tolerate these environmental challenges. These protective systems are collectively referred to as resistance/susceptibility, constitution, predisposition, immunocompetence, homeostasis and/or harmony. The antioxidants serve as an important ingredient in building resistance and reducing susceptibility and largely because of its free radical scavenging action. However, how much, when and for how long are still the burning questions. At the moment, in the light of these 40 representative studies, macular degeneration and cataracts enjoy positions like heart disease and cancer.

(Table 1 in the original paper contains Dietary Vitamin A Levels)

Reference # 6/ Precancer In a study of oral leukoplakia, patients were given 200,000 IU of vitamin A per week for six months versus placebo capsules. Fifty-seven per cent of vitamin A supplemented patients had complete remission and, during that time, no new lesions appeared.

#7/HIV A study was done with 25 HIV patients with CD4+ T cell counts less than 800. Thirty-two per cent of the subjects had retinol levels less than 30 mcg%. Subjects taking a daily multivitamin containing modest amounts of vitamin A (1500-2100 mcg) had higher serum retinol levels than those taking no supplements (72 versus 42 mcg%). These observations suggest that even modest doses of vitamin A can have significant impact on serum retinol levels in advanced HIV patients.

#8/ Cancer A case control study conducted among a cohort of chemical manufacturing employees provided an opportunity to test the hypothesis that lung cancer risk is inversely related to dietary intake of vitamin A. Subjects in the lowest tercile of vitamin A intake (less than 62,000 lU/week) had approximately twice the risk of lung cancer as those in the highest (greater than 100,000 IUI week).

#9/Respiratory Tract Infections Preschool-age children (157) with a history of frequent respiratory illness were randomized into vitamin A supplemented (450 mcg/day) and placebo groups. Respiratory symptoms were recorded on a daily basis over a period of 11 months. The children who received the supplement experienced 19% fewer episodes of respiratory symptomatology than their placebo counterparts.

#10/Mortality Mortality of Sumatran children randomized to receive a 200,000 IU vitamin A capsule (n=9776) was compared with those who did not (n=2447). During the four months after completion of the first distribution, mortality among the recipients was 75 per cent less than the nonrecipients. One capsule every six months may provide adequate protection for the vast majority of children.

(Table 2 in the original paper contains Blood Vitamin A Levels)

Reference # 13/Measles In a study of children in Long Beach, California, the blood levels in youngsters with measles was 24 mcg%; in those with nonmeasles 26 mcg%; and in the well kids 40 mcg%.

#14/ Alzheimer's Disease Elderly people with Alzheimer's Disease post-infarct-dementia and controls were examined. The average vitamin A levels were 45 mcg% in Alzheimer's Disease compared to an average 61 mcg% in the control group.

#15/ Cancer The vitamin A blood levels of patients with pulmonary cancer, non-cancer pulmonary disease, and controls were compared. The levels were 45.6 mcg% (range 20.2 to 79.5) for the pulmonary cancer subjects; 64.3 mcg% (range 43.6 to 80.8) for the patients with noncancer pulmonary disease; and 68.4 mcg% (range 52.6 to 101.2) in the controls.

#16/ Bronchopulmonary Disease This study showed that low vitamin A levels (less than 10 mcg%) observed in infants with bronchopulmonary dysplasia (BPD), and implies that therapeutic administration of vitamin A may help prevent and treat BPD.

#17/ Cardiovascular Disease There is data from the cross-cultural European comparisons of the Edinburgh Aging Control Study and of the Basel Prospective Study. They show, for the first time with fair probability, that vitamin A concentrations needed to decrease ischemic heart disease risk are 63 to 80 mcg%.

(Table 3 in the original paper contains Dietary Vitamin C Levels)

Reference #18/Infertility One gram of ascorbic acid per day for 60 days was provided to 20 clearly-diagnosed infertile, but otherwise healthy, men. A separate control group of 20 men were placebo-supplemented. At the end of these two months, conception occurred unanimously only in the vitamin C supplemented couples!

#19/Diabetes A study of the small blood vessels of the skin and retina was carried out in 24 normal subjects and 12 diabetics. The experiment revealed very clearly that the capillary strength of both the eye and skin of all diabetics improved during the vitamin C treatment (one gram/day) and worsened when it was discontinued.

#20/Mental Illness The manic/depressive state was assessed in 24 subjects who completed two generally accepted psychometric tests. Each patient was provided with either a three gram ascorbic acid effervescent tablet or a placebo. In the vitamin C treated group, the severity of the bipolar state was reduced within the first hour and then declined even more rapidly between the second and fourth hours. No change occurred in the placebo subset.

#21/Life Expectancy In a reexamination of a large federal government study, it was discovered that those men who consumed 300 to 400 mgs of vitamin C daily compared with those who consumed less than 50 mgs showed art overall mortality reduction of 42% principally due to a decline in heart disease and cancer. This translates into living approximately six years longer!

#22/ Cardiovascular Disease A 1000 mg ascorbic acid tablet or a placebo was supplemented daily to 20 adults for two six-week periods in a randomized, crossover design. Under these conditions, vitamin C supplementation reduced the systolic pressure.

(Table 4 in the original paper contains Blood Vitamin C Levels)

Reference #25/Periodontal Disease In a study of 24 adult volunteers with initially low and partially even deficient plasma vitamin C values, the hydroxyproline and proline content was measured before and after supplementation. There was a statistically significant rise but not before the plasma ascorbate level was above 0.9 mg%. The optimal plasma vitamin C level which was associated with the highest hydroxyproline and proline content in periodontal tissue ranged between 1.0 and 1.3 mg%.

#17/Heart Disease The most recent work on risk factors in ischemic heart disease (IHD) is available from several cross-cultural epidemiologic studies. They all suggest, for the first time with fair probability, that protection against IHD is paralleled by vitamin C levels in the range of 0.7 to 0.9 mg%.

#26/ Macular Degeneration From the Eye Disease Case Control Study Group, there is evidence that blood levels of vitamin C in the 0.7 to 1.6 mg% range have a risk of one third to one half that in blood levels below 0.7 mg% for macular degeneration.

#27/ Hypertension In a study of 685 patients without known hypertension, it was discovered that the higher the plasma vitamin C level, the lower the systolic and diastolic pressure. Specifically, with plasma ascorbic acid (PAA) of 0.7 mg%, the blood pressure was 147/83 mm Hg; with PAA of 1.4 mg%, the pressure was 139/78 mm Hg.

#28/ Cataracts A classification was designed of three blood ascorbate levels; less than 0.7 mg%, greater than 1.6 mg%, and a group with plasma levels at intermediate range. Persons with the lowest ascorbate intake status had 11-fold the risk of developing cataracts in the posterior region of the lens as individuals with the highest ascorbate levels.

(Table 5 in the original paper contains Dietary Vitamin E Levels)

Reference #29/ Cardiovascular Disease One of the major signs of peripheral arterial disease (PAD) is intermittent claudication. In a double-blind study, 1600 mgs of alpha tocopherol a day significantly reduced (66%) this important sign of cardiovascular disease.

#30/Parkinson's Disease A comparison was made of the clinical picture of Parkinson's Disease as measured by a Unified Parkinson's Disease Scale, in patients taking vitamin E in dosages from 400 to 3200 IU per day versus those not taking vitamin E. The overall and individual performance, mentation, activities of daily living, motor examination, and complications of daily living improved only in the supplemented group.

#31/Rheumatoid Arthritis The use of 1200 mg per day of vitamin E was studied in rheumatoid arthritis patients in Austria. The evidence suggests an inverse relationship between the consumption of vitamin E and a reduction in pain and stiffness.

#32/ Cataracts A case control group of 175 cataract patients, 55 years of age or older, were matched with a like number of cataract-free subjects. The incidence of cataracts was shown to be half in those consuming more than 400 IU of vitamin E per day.

#33/Immune Response The effect of daily vitamin E supplementation (800 IU alpha tocopherol for 30 days) on immune responses of 32 healthy subjects (60+ years old) was examined in a placebo-controlled, double-blind trial in a metabolic research unit. The data suggest that vitamin E supplementation improves immune responsiveness in healthy elderly.

(Table 6 in the original paper contains Blood Vitamin E Levels)

Reference #36/ Immune Response In a metabolic unit, using a double blind protocol, immune response was studied in a group receiving vitamin E (8OOmg per day) versus placebo. The increased immunocompetence was matched by blood vitamin E levels which jumped from 1.1 to 3.1 mg%. No such change in blood vitamin E occurred in the control group (1.1 to 1.0 mg%).

#14/Alzheimer's Disease A comparison of vitamin E blood levels in Alzheimer's Disease (0.8 mg%), infarct-dementia (0.7 mg%) and in a group of controls (1.3 mg%) indicates that the vitamin F levels in the healthy subjects are approximately double that in the sick people.

#37/ Cataracts In the Baltimore Longitudinal Study on Aging; using a case control design, the prediction of cataracts correlated with serum vitamin E. Specifically, those with the lowest blood levels (0.8 mg%) had an odds ratio of almost double those in the upper terciles (1.3 mg%).

#38/ Macular Degeneration In the Baltimore Longitudinal Study, it was shown that those with macular degeneration (MD) have alpha tocopherol levels of 0.8 versus 1.3 mg% in the quartile free of MD. Hence, macular degeneration occurs twice as often in patients with low levels.

#39/Diabetes Blood levels following supplementation of 2000 IU of vitamin F daily for two weeks was studied. The average serum tocopherol increased from 1.48 to 5.06 mg/g. This is the first time levels over 5 mg/g in the blood have been reported.

(Table 7 in the original paper contains Dietary Beta Carotene Levels)

Reference #40/ Cardiovascular Disease In the Nurses' Health Study in which a cohort of 121,000 US female nurses ages 30-55 were followed, those who consumed more than 15-20 mg/day of beta carotene had 40% lower risk of stroke and 22% lower risk of heart attack, compared to women who reported eating less than 6 mg/day.

#41/ Cancer At the moment, this is the largest study of dietary factors and lung cancer in nonsmokers. The evidence suggests that dietary beta carotene and raw fruits and vegetables reduce the risk of lung cancer in nonsmoking men and women.

#42/ Immune Response Immune system response to short-term, high-dose beta carotene supplementation was examined. Supplements of 180 mg of beta carotene per day for two weeks increased the number of T4 lymphocytes (helper cells) and did not effect the T8 lymphocytes (suppressor cells).

#43/ Precancer In a study of 24 people with oral leukoplakia, given 30 mg/day of beta carotene for 3 to 6 months, there was a 71% response rate. Of particular importance was the fact that no clinically significant toxicity was observed during this trial that could be attributable to beta carotene.

#44/Mortality A study was conducted regarding the association between consumption of vegetables high in beta carotene and cardiovascular mortality in a prospective cohort of 1299 elderly Massachusetts residents. Those consuming the greatest amount (in the upper quartile) of beta carotene rich foods had one half the risk of cardiovascular mortality as those in the lowest quartile.

(Table 8 in the original paper contains Blood Carotenoid Levels)

Reference #14/ Alzheimer's Disease The blood carotene levels were 7 to 23 mcg% in Alzheimer's Disease; 7 to 16 mcg% in multi-infarct dementia patients versus 7 to 82 mcg% in controls.

#45/ Precancer In oral and pharyngeal cancer, the blood carotene levels were 39.5 in cases versus 61.5 mcg% in control patients.

#46/Measles Beta carotene levels were 35.0 mcg% in children with measles and kerotomalacia versus 39.0 mcg% in kids with measles without kerotomalacia as compared with 64.0 mcg % in health controls.

#47/ Macular Degeneration The Eye Disease Case Control Study Group discovered that the chances of having macular degeneration is reduced about half in those demonstrating the larger amounts of carotenoids in the blood (greater than 69 mcg%).

#48/ Cardiovascular Disease A 12-year follow-up of cardiovascular mortality in the Basel Prospective Study revealed a significantly increased relative risk of ischemic heart disease and stroke of a magnitude of two-fold at initially low plasma levels of carotene (less than 12 mcg%) independent of the classical cardiovascular risk factors.

References 1. , L.J. Age-Related Macular Degeneration: The Current Understanding of the Status of Clinicopathology, Diagnosis and Management. Journal of the American Optometric Association 64:# 12, 822-837,-December 1993.

2. Richer, S.P. Is There a Prevention and Treatment Strategy for Macular Degeneration? Journal of the American Optometric Association 62:#12, 838-850, December 1993.

3. Kaminski, M.S., Yolton, D.P., Jordan, W.T., Yolton, R.L. Evaluation of Dietary Antioxidant Levels and Supplementation with ICAPS-Plus and Ocuvite. Journal of the American Optometric Association 64:12,862-870, December 1993.

4. Van der Hagen, A.M., Yolton, D.P., Kaminski, M.S., Yolton, R.L. Free Radicals and Antioxidant Supplementation: A Review of Their Roles in Age-Related Macular Degeneration. Journal of the American Optometric Association 64:#1 2, 871-878, December 1993

5. Cheraskin, E. Macular Degeneration: Now That We Have All The Pieces.. .Why is There Still a Puzzle? Journal of the American Optometric Association (to be published)

6. Stitch, H.F., Hornsby, A.P., Mathew, B., Sankaranarayana, R., Krishnannair, M. Response to Oral Leukoplakias to the Administration of Vitamin A. Cancer Letters 40:#1, 93-101, May 1988.

7. Ward, B.J., Humphrey, J.H., Clement, L., Chaisson, R.E. Vitamin A Status in HIV Infection. Nutrition Research 13: 157-166, 1993.

8. Bond, G.G., , F.E, Cook, R.R. Dietary Vitamin A and Lung Cancer: Results of a Case-Control Study Among Chemical Workers. Nutrition and Cancer 9:2 & 3, 109-121, 1987.

9. Pinnock, C.B., , R.M., Badcock, N.R. Vitamin A Status in Children Who are Prone to Respiratory Tract Infections. Australian Pediatric Journal 22:#2, 95-99, May 1986.

10. Tarwotjo, I., Sommer, A., West, K.P., Jr., Djunaedi, E., Mele, L., Hawkins, B., Aceh Study Group. Influence of Participation on Mortality in a Randomized Trial of Vitamin A Prophylaxis. American Journal of clinical Nutrition 45:#6, 1466-1471, June 1987.

11. Food and Nutrition Board/Commission of Life Sciences/National Research Council. Recommended Dietary Allowances. Tenth Edition. 1989. Washington D.C., National Academy Press

12. Olson, J.A. Vitamin A. IN: MachIm, L.J. Handbook of Vitamins: Nutritional, Biochemical and Clinical Aspects. 1984. New York, Marcel Dekker, Inc.

13. Arrieta, A.C., Zaleska, M., Stutman, H.R., Marks, M.I. Vitamin A Levels in Children with Measles in Long Beach, California. Journal of Pediatrics 12:#l, 75-78, July 1992.

14. Zaman, Z., Roche, S., Fieldman, P., Frost, P.G., Niriella, D.C., Cayley, A.C.D. Plasma Concentrations of Vitamins A and E and Cartotenoids in Alzheimer's Disease. Age and Aging 21:2, 91-94, March 1992

15. Basu, T.K., son, D., Jenner, M., , D.C., Sakula, A. Plasma Vitamin A in Patients with Bronchial Carcinoma. British Journal of Cancer 33:#l, 119-121 January 1976.

16. Editors. Low Plasma Vitamin A Levels in Preterm Neonates with Bronchopulmonary Dysplasia. Nutrition Reviews 44:#6, 202-204, June 1986.

17. Gey, K.F., Moser, U.K., Jordan, P., Stahelin, H.B., Eichholzer, M., Ludin, E. Increased Risk of Cardiovascular Disease at Suboptimal Plasma Concentrations of Essential Antioxidants: An Epidemiological Update with Special Attention on Carotene and Vitamin C. American Journal of Clinical Nutrition 57: 787S-808S, 1993.

18. , W.A., Harden, T.E., Dawson, E.B. Apparent Effect of Ascorbic Acid Medication on Semen Metal Levels. Fertility and Sterility 32:#4, 455-459, 1979.

19. , B.D., Butterfield, W.J.H. Vitamin C Supplements and Diabetic Cutaneous Capillary Fragility. British Medical Journal 3:#5977, 205-207, July 25, 1975.

20. Naylor, G.J., , A.H.W. Vanadium: A Possible Aetiological Factor in Manic Depressive Illness. Psychological Medicine 11:249-256, 1981.

21. Enstrom, JE., Kanim, L.D., Klein, M.A. Vitamin C Intake Among a Sample of the United States Population. Epidemiology 3 :3, 194-202, 1992.

22. Osilesi, 0., Trout, D.L., Ogunwole, J.O., Glover, E.E. Blood Pressure and Plasma Lipids During Ascorbic Acid Supplementation in Borderline Hypertensive and Normotensive Adults. Nutrition Research 11: 405-412,1991.

23.Block, G. Vitamin C, Cancer and Aging. Age 16:#2, 55-58, April 1993.

24. Chandra, R.K. Effect of Vitamin and Trace Element Supplementation on Immune Responses and Infection in Elderly Subjects. The Lancet340: 8828, 1124-1 127, November 7, 1992.

25. Buzina, R., Aurer-Kozelu, J., Srkak-Jorgic, D., Buhler, E., Gey, K.F. Increase of Gingival Hydroxyproline and Pro line by Improvement of Ascorbic Acid Status in Man. International Journal for Vitamin and Nutrition Research 56:#4, 367-372, 1986.

26. Eye Disease Case-Control Study Group. Antioxidant Status and Neovascular Age-Related Macular Degeneration. Archives of Opthamology 11 1:#l, 104-109, January1993.

27. Jacques, P.F., Relationship of Vitamin C Status to Cholesterol and Blood Pressure. ls of the New York Academy of Sciences 669: 205-214, 1992.

28.Jacques, P.F., Chylack, L.T., Jr. Epidemiologic Evidence of a Role for the Antioxidant Vitamins and Carotenoids in Cataract Prevention. American Journal of Clinical Nutrition 53: 3520S-3525S, 1991.

29. . H.T.G., Fenna, D., MacBeth, R.A. Alpha Tocopherol in the Treatment of Intermittent Claudication. Surgery, Gynecology and Obstetrics 132:#4, 662-666, April 1971.

30. Factor, S.A., Weiner, W.J. Retrospective Evaluation of Vitamin E Therapy in Parkinson's Disease. ls of the New York Academy of Sciences 570: 441-442, 1989.

31. Scherak, 0., Kolarz, G. Vitamin E and Rheumatoid Arthritis. Arthritis and Rheumatism 34:#9,1205-1206, September 1991.

32. on, J.M., Donner, A.P., Trevithick, J.R. Vitamin E Intake and Risk of Cataracts in Humans. ls of the New York Academy of Sciences 570: 372-382, 1989.

33. Meydani, S.N., Barklund, M.P., Liu, S., Meydani, M., , R.A., Cannon, J.G., Morrow, F.D., Rocklin, R., Blumberg, J.B. Effect of Vitamin E Supplementation on Immune Responsiveness of Healthy Elderly Subjects. FASEB Journal 3: A1057, 1989.

34. Machlin, L.J. Handbook of Vitamins: National, Biochemical and Clinical Aspects. 1984. New York, Marcel Dekker, Inc.

35. Simonff, M., Sergeang, C., Gamier, N., Moretto, P., Vlabador, Y., Simonoff, G., Conri, C. Antioxidant Status (Selenium), Vitamins A and E and Aging. EXS 62: 368-397, 1992.

36. Meydani, S.N., Barkiund, M.P., Liu, S., Meydani, M., , R.A., Cannon, J.G., Morrow, F.D., Rocklin, R., Blumberg, J.B. Vitamin E Supplementation Enhances Cell-Mediated Immunity in Healthy Elderly Subjects. American Journal of Clinical Nutrition 52:#3, 557-563, September 1990.

37. Vitale, S., West, S., Hallfrisch, J., Alston, C., Wang, F., Moorman, C., Muller, D., Singh, V., , H.R. Plasma Antioxidants and Risk of Cortical and Nuclear Cataract. Epidemiology 4:#3, 195-203, May 1993.

38. West, S., Vitale, S., Hallfrisch, J., Munoz, B., Muller, D., Bressler, S., Bressler, N.M. Are Antioxidants or Supplements Protective for Age-Related Macular Degeneration? Archives of Opthamology 1 12:#2, 222-227, February 1994.

39. Bierenbaum, M.L., Noonan, F.J., Machlin, L.J., Machim, S., Stier, A., , P.B., Naso, A.M., Fleischman, A.I. The Effect of Supplemental Vitamin Eon Serum Parameters in Diabetics, Post Coronary and Normal Subjects. Nutrition Reports International 31:#6, 1171-1180, June 1985.

40. Manson, J.E., Stampfer, M.J., Willett, W.C., et al. A Prospective Study of Antioxidant Vitamins and Incidence of Coronary Heart Disease in Women. Circulation 84:#4, 11-546, 1991. Abstract

41 Mayne, S.T., Janerish, D.T., Greenwald, P., Shorost, S., Tucci, C., Zaman, M.B., Melamed, M.R., Kiely, M., McKneally, M.F. Dietary Beta Carotene and Lung Cancer Risk in U.S. Nonsmokers. Journal of the National Cancer Institute 86:#1, 33-38, January 1984.

42. , M., Newmark, H., , R.G. Oral Beta Carotene Can Increase the Number of OKT4+ Cells in Human Blood. Immunology Letters 9:221-224, 1985.

43. Garewal, H.S., Meyskens, F.L., Killen, D., Reeves, D., Kiersch, T.A., Ellerson, H., Strosberg, A., King, D., Steinbronn, K. Response of Oral Leukoplakia to Beta Carotene. Journal of Clinical Oncology 8:1715-1720, 1990.

44. Gaziano, M., Manson, J.E., Branch, L.G., LaMotte, F., Colditz, G.A., Buring, J.E., Hennekens, C.H. Dietary Beta Carotene and Decreased Cardiovascular Mortality in an Elderly Cohort. Journal of the American College of Cardiology 1 9:#3, (supplement A) 377A, March 1, 1992.

45. Ibrahim, K., Jafarey, N.A., Zuberi, S.J. Plasma Vitamin A and Carotene Levels in Squamous Cell Carcinoma of Oral Cavity and Oropharnyx. Clinical Oncology 3:203-207, 1977.

46. Laditan, A.A.O., Fafunso, M. Serum Levels of Vitamin A, Beta Carotene and Albumin in Children with Measles. East African Medical Journal 58:#l, 51-55, January 1981.

47. Eye Disease Case Control Study Group. Risk Factors for Neovascular Age-Related Macular Degeneration. Archives of Opthamology; I 10:#12, 1701-1708, December 1992.

48. Gey, K.F., Stahelin, H.B., Eichholzer, M. Poor Plasma Status of Carotene and Vitamin C is Associated with Higher Mortality from Ischemic Heart Disease and Stroke: Basel Prospective Study. Clinical Investigator 71:#1, 3-6, January 1993.

49. Roncucci, L., DiDonato, P., Carati, L., Ferreri, A., Perini, M., Bertoni, G., Bedogni, G., Paris, B., Syanoni, F., Girola, M., Ponz de Leon, M. Antioxidant Vitamins or Lactulose for the Prevention of the Recurrence of Colorectal Adenomas. Diseases of the Colon and Rectum 36:#3, 227-234, March 1993.

50. Heliovaara, M., Knekt, P., Aho, K., Aaran, R.K., Aromaa, A. Serum Antioxidants and Risk of Rheumatoid Arthritis. ls of the Rheumatic Diseases 53:#1, 51-53, January 1994.

51. Eichholzer, M., Stahelin, H.B., Gey, K.F. Inverse Correlation Between Essential Antioxidants in Plasma and Subsequent Risk to Develop Cancer, Ischemic Heart Disease and Stroke Respectively: 12-Year Follow-up of the Prospective Basel Study. EXS 62:398-410, 1992.

52. Manson, J.E., Stampfer, M.J, Willett, W.C., Colditz, G.A., Speizer, F.E., Hennekens, C.H. Antioxidant Vitamins and Secondary Prevention of Cardiovascular Disease in High Risk Women. Circulation 88:#4, (Part 2), 1-70, October 1993.

B-INFORMED ABOUT B-VITAMINS

The safety record of the B-complex vitamins is extraordinarily good. Since their discovery, beginning with thiamin (B-1) in 1911, many thousands of studies have verified an unequaled therapeutic value of these essential substances. Side effects have been rare, and toxicity is nearly nonexistent, even at the highest doses. Some cautions are in order, of course, and here are some of the most important.

Vitamin B-6 (pyridoxine) has been reported to cause temporary neurological symptoms such as heaviness, tingling or numbness of the limbs in persons taking very large doses. It is very important to realize that such cases are not common, and when they do occur usually result from huge doses of pyridoxine TAKEN ALONE. The B-vitamins are a team, and work best as a team. Upsetting the balance by taking a lot of just one is like devoting all your baseball practice time to your pitcher. You might get a lot of strikeouts, but if anybody hits one, you are in trouble. No one player has ever won a World Series by himself, and no single B-vitamin can do the job that the whole "team" can do.

B-6 by itself in doses of 2,000 to 6,000 milligrams daily (that's one thousand to three thousand times the US RDA!) can produce side effects and is therefore way too much to take. Very, very few persons report symptoms on 1,000 mg daily, and only the rarest reports go any lower. When taken with, or as part of, a complete B-complex supplement, B-6 side effects other than a harmless deeper-colored urine are virtually unknown.

Premenstrual tension symptoms often improve dramatically with only a few hundred mg/day of extra B-6. There is no need to "push the envelope" and take thousands of milligrams when hundreds will do. At least 50 to 100 mg of supplemental B-6 daily is a virtual necessity for women taking oral contraceptives. The "pill" causes some abnormal physiological changes that create a deficiency of B-6, as well as lower serum levels of thiamine (B-1), and riboflavin (B-2), and niacin (B-3), and folic acid, and B-12, and vitamin C! (Wynn, V. Lancet, March 8, 1975)

Laboratory animals receiving the human B-6 dose equivalent of just 75 mg daily do not get strokes, even when fed a lousy diet (Atherosclerosis, vol. 22, 1975, pp 125-127) Since women on oral contraceptives are three times more likely at any age to have a stroke, there is an important lesson here. B-6 deficiency produces hardening of the arteries (Rinehart and Greenberg, American Journal of Pathology, vol. 25, 1949, pp 481-496.) Furthermore, B-6 is necessary in order for your body to produce lecithin. Lecithin, a lipid- transporting substance from soy, has been used clinically to clear out fatty livers... and even clogged arteries. Another connection.

Niacin (vitamin B-3) has been used in doses up to tens of thousands of milligrams per day for over 40 years by psychiatrists. It is an effective alternative treatment for severe depression, psychotic behavior, and schizophrenia. Most physicians have ignored niacin's usefulness until rather recently. Niacin has finally gained popularity as one of the cheapest ways to lower serum cholesterol. Changes in liver function tests have been reported in persons taking one to five thousand milligrams daily of niacin BY ITSELF. Three important points have generally gone unnoticed:

1. Niacin is much better tolerated when given with Vitamin C. Abram Hoffer, M.D. pioneered high dose niacin therapy back in the 1950's. He repeatedly published his observations that gram-sized doses of vitamin C greatly improve a patient's niacin tolerance. Dr. Hoffer recommended at least as much vitamin C per dose as niacin. With three thousand milligrams of niacin per day, then, one would need a MINIMUM of three thousand milligrams of vitamin C. The medical profession's unfounded resistance to large doses of vitamin C is embarrassingly well known. It is useless to blame niacin for side effects caused by ignoring expert medical advice on how to use it correctly along with vitamin C.

Zannoni at the University of Michigan Medical School has shown that vitamin C protects the liver itself. Even doses as low as 500 milligrams daily helped prevent fatty buildup and cirrhosis. 5,000 mg of vitamin C per day appears to actually flush fats from the liver. (Ritter, M. "Study Says Vitamin C Could Cut Liver Damage," Associated Press, October 11, 1986) F. R. Klenner, M.D. showed that very large doses of vitamin C (between 500 to 900 mg per kilogram body weight per day) can cure hepatitis in two to four days (, L. H., ed. Clinical Guide To The Use Of VitaminC, Life Science Press, Tacoma Washington, 1988, pp 22-23).

2. Niacin is also one of the team of B-vitamins and needs any massive intake to be at least partly balanced with the rest of the B-complex, just like B-6 mentioned above. Would you pay for a tune up for your car and change only one spark plug? If you have several kids, would you feed only one? Would you pay for cable TV if there were only one channel? Taking only one B-vitamin is neither logical nor efficient. So avoid doing it unless there is a good reason.

3. Many, perhaps most, persons showing changes in their liver function tests upon ingestion of large amounts of niacin have been using alcohol. Accurate information about sizable alcohol consumption is very difficult to get from a patient: the more they use, the less they'll tell. Two thirds of all American adults drink alcohol, averaging out to be about three drinks per day, seven days a week, 52 weeks a year. If you do not drink that much, then somebody out there is drinking MORE.

Alcohol does nothing if it doesn't hurt the liver. The French have the highest per capita consumption of alcohol in the world. They also have the world's highest percentage of deaths from cirrhosis of the liver. Working hard, the human liver can detoxify about one drink every two hours. Know anyone who drinks at a faster rate than that? Then marvel that they have a liver that functions at all. Alcohol is a drug, and consumption and abuse is more widespread and more serious than most persons imagine. Over two thirds of all hospital admissions of the elderly are alcohol related. (New York State Office of Alcoholism and Substance Abuse Services, Oasas Today, 1:1, Sept-Oct. 1992)

The liver undergoes profound changes in both its endoplasmic reticula and its microsomal enzymes in order to detoxify alcohol. The unbalanced introduction of very large doses of niacin to an overloaded liver may well overtax an alcohol-strained system. This is likely where some changes in liver function tests come from (American Journal of Medicine, vol 86, April, 1989, page 431 and vol. 87, August 1989, page 248; American Journal of Cardiology, vol. 64, October 1, 1989 page 728).

4. Any hepatotoxic effects of niacin are almost invariably associated with the sustained release form (Journal of the American Medical Association, March 2, 1994). Sustained release niacin generally enables higher doses with less "flushing." However, that warm sensation called flushing indicates niacin saturation. Sustained release delivery may therefore be hiding this sign that the body has had enough niacin at a given time.

5. Simply reducing the dosage reduces side effects. (Naito, H. "Reducing Cardiac Deaths with Hypolipidemic Drugs," Postgraduate Medicine, vol 82, no. 6, November 1987; Figge, H. L. et al: "Nicotinic Acid: A Review of its Clinical Use in the Treatment of Lipid Disorders," Pharmacotherapy, Vol. 8, no. 5, 1988) Since the regular "immediate release" form of niacin also is effective in lowering total cholesterol and actually improves beneficial HDL levels, why not just use the plain tablets? Take less, but more often, and you approximate the idea of a sustained release tablet, but with a lower dose. If there is a flush, reduce the dose. The idea is to be comfortable. It is better to be able to use less of the vitamin for a long time than to use a lot, have trouble, and quit. American physicians often over prescribe anyway, and niacin is no exception.

Niacin is not a magic cholesterol bullet, nor is cholesterol the only factor in heart disease. Niacin is PART of the picture, part of the B-vitamin team, and part of a total health program. Granted, niacin is indeed important. This is shown by even our inadequate US RDA, which recommends many times more niacin than any other B-vitamin. However, persons truly seeking to lower their cholesterol need to eat more fiber, more vegetables (especially carrots), more vitamins E and C, and to exercise more. They also need to eat less sugar, less fat, less meat, and reduce stress. There are ZERO harmful effects (and countless side BENEFITS) in taking these steps.

People who do not want to change their diet and do not want to change their lifestyle ask doctors for a pill instead. There is no such thing as monotherapy for cardiovascular disease. If there was, we'd all use it and be saving literally a million lives each year. Is it really that big a surprise that niacin alone isn't enough to do the job right?

REFERENCES:

Alcohol:

Ray, O. and Ksir, C. Drugs, Society and Human Behavior, chapter 9. Mosby, 1990 (I'm sure most of the great book titles are already taken, so don't be fooled by this one. This is an excellent book: clear, fact-filled and well written. Highly recommended.)

, R. J. Nutrition and Alcoholism (1951) and Alcoholism: The Nutritional Approach (1959) may be out of print but are worth the search.

Therapeutic Uses of the B-Vitamins:

Bicknell and Prescott, The Vitamins in Medicine, 3rd ed., 1953 (This out-of-print work stands as the definitive summary of most all vitamin research up to the date of its publication. There are many thousands of references here.)

Cheraskin, et al: Psychodietetics, Bantam Books, 1974 (A deservedly popular book, loaded with references.)

Hoffer, A. and , M. Orthomolecular Nutrition, Keats, 1978 ("Orthomolecular" essentially means "megavitamin." Good introductory work.)

ing, L. How To Live Longer and Feel Better, Freeman, 1986. (Still the best single health book ever written. Here is a good place to begin you investigation of vitamin therapeutics.)

Psychiatric Utility of Niacin:

Hawkins, D. and ing, L. Orthomolecular Psychiatry, Freeman, 1973 (Here, in one big volume, is more information than most doctors ever want to admit exists on using niacin, especially in treating depression and psychoses.)

Hoffer, Abram Niacin Therapy in Psychiatry, , 1962 (This is what started it all; note the publishing date. Nobody knows niacin like Dr. Hoffer.)

Hoffer, A. and Osmond, H. The Chemical Basis of Clinical Psychiatry, ,Springfield, Ill. (Even more in depth study of the biochemistry and uses of niacin.)

Remember to try your library's Interlibrary Loan service to obtain out-of-print works.

Copyright C 1999 and prior years W. Saul. From the book PAPERBACK CLINIC, available from Saul, PhD, Number 8 Van Buren Street, Holley, New York 14470 USA.

VITAMIN E: A CURE IN SEARCH OF RECOGNITION

by W. Saul

(Reprinted with permission from the Journal of Orthomolecular Medicine, 2003; Vol. 18, Numbers 3 and 4, p. 205-212.)

"Some doctors claim that vitamin E helps many heart cases, but the official view is that the substance has not been proved of value in treating heart disease."

This statement could have been taken verbatim from any of a number of recent news media reports. But in fact, this particular quote is from a 1953 article in Maclean's Magazine entitled "The Fight Over Vitamin E." (1)

Half a century later, it would seem that little has changed.

"(W)e do not support the continued use of vitamin E treatment and discourage the inclusion of vitamin E in future primary and secondary prevention trials in patients at high risk of coronary artery disease." (2)

This statement is from a 2003 analysis that looked at studies employing daily treatment dosages between 50 and 800 IU. Yet since the 1940's, clinicians have been reporting that vitamin E dosages between 450 and 1,600 IU or more are required to effectively treat cardiovascular disease. I would enjoy seeing a meta-analysis of the work of Drs. Wilfrid and Evan Shute, who treated coronary thrombosis with 450 to 1,600 IU; angina with 450 to 1,600 IU; and thrombophlebitis with 600 to 1,600 IU of vitamin E daily. (3) The recent Lancet meta-analysis did not include them. There is nothing capricious about either study selection or dosage choice. Researchers and analysts know full well that high dosage will obtain different results than low dosage. Statistical analysis of meaningless studies will rarely enable a meaningful conclusion.

DOUBLE STANDARD

Countless comedians have made fun of the incompetent physician who, when called late at night during a life-threatening disease crisis, says, "take two aspirin and call me in the morning." Now it’s no longer funny. Recently, one of the largest pharmaceutical conglomerates in the world ran prime-time national television commercials that declared: "Bayer aspirin may actually help stop you from dying if you take it during a heart attack." The company also promotes such use of its product on the Internet. (4) This statement comes forth after a century of widespread aspirin consumption. Cardiovascular disease remains the number one killer of men and women and there are over a million heart attacks annually in the US alone.

If you produced a TV ad that said that megadoses of wheat germ oil, or the vitamin E in it, could save your life by preventing a heart attack, not only would people disbelieve you, you’d also be subject to arrest for breaking federal law. Foods and vitamins may not be advertised as treatments for specific diseases. "All statements of nutritional support for dietary supplements must be accompanied by a two-part disclaimer on the product label: that the statement has not been evaluated by FDA and that the product is not intended to "diagnose, treat, cure or prevent any disease."" (5)

Yet even traditional nutrition textbooks acknowledge the extensive scientific proof of successful treatment of intermittent claudication with vitamin E. "This therapy helps reduce the arterial blockage," says Nutrition and Diet Therapy, Seventh Edition, a standard dietetics work. (6) Unless there be something absolutely unique about arterial real estate between the knee and the ankle, would not vitamin E also help "reduce the blockage" in other arteries? This is rationale the Shutes used when, 65 years ago, they employed vitamin E to successfully treat circulatory diseases in thousands of patients, using daily dosages as high as 3,200 IU. For that achievement, they were praised by their patients and ostracized from the ranks of orthodox physicians.

By 1971, it was increasingly clear that the Shutes had gotten it right. Intermittent claudication, now regarded as a reliable sign of peripheral arterial disease, was shown by double-blind study to be diminished 66% with the use of vitamin E. The dosage administered was 1600 mg/day. (7)

A TORRID HISTORY

1922 was the year the USSR was formed and "Little Orphan Annie" began. Trumpeter Al Hirt and future heart transplant pioneer Christiaan Barnard were born. Graham Bell died. And vitamin E was discovered by H. M. and K. S. Bishop. (8)

In 1936, ' team had isolated alpha tocopherol from wheat germ oil and vitamin E was beginning to be widely appreciated, and the consequences of deficiency better known. Health Culture Magazine for January, 1936 said, "The fertility food factor (is) now called vitamin E. Excepting for the abundance of that vitamin in whole grains, there could not have been any perpetuation of the human race. Its absence from the diet makes for irreparable sterility occasioned by a complete degeneration of the germinal cells of the male generative glands. (T)he expectant mother requires vitamin E to insure the carriage of her charge to a complete and natural term. If her diet is deficient in vitamin E . . . the woman is very apt to abort. . . It is more difficult to insure a liberal vitamin E supply in the daily average diet than to insure an adequate supply of any other known vitamin." (9)

And that very same year, 1936, the Shutes were already at work employing tocopherol from wheat germ oil to relieve angina symptoms. (10)

Since the word "tocopherol" is taken from the Greek words for "to carry offspring" or "to bring forth childbirth," it is easy enough to see how Evan Shute and other obstetricians were drawn into the work. As early as 1931, Vogt-Moller of Denmark successfully treated habitual abortion in human females with wheat germ oil vitamin E. By 1939 he had treated several hundred women with a success rate of about 80%. In 1937, both Young in England and the Shutes in Canada reported success in combating threatened abortion and pregnancy toxemias as well. A. L. Bacharach's 1940 statistical analysis of published clinical results "show quite definitely that vitamin E is of value in recurrent abortions." (11) And also in 1940, the Shutes were curing atherosclerosis with vitamin E. By 1946, thrombosis, phlebitis, and claudication.

Yet when the MDR's (Minimum Daily Requirements) first came out in 1941, there was no mention of vitamin E. It was not until 1959 that vitamin E was recognized by the U.S. Food and Drug Administration as necessary for human existence, and not until 1968 that any government recommendation for vitamin E would be issued. That year, the Food and Nutrition Board of the US National Research Council offered its first Recommended Daily Allowance: 30 IU. It has been as low as 15 IU in 1974 . In 2000, it was set at 22 IU (15 mg) for all persons, including pregnant women. This is somewhat odd in view a 70-year established research history showing how vital vitamin E is during gestation. It is another curious fact that today, when the public has been urged to increase its consumption of unsaturated fats, the official dietary recommendation for vitamin E is substantially lower than it was 35 years ago. "The requirement for vitamin E is related to the amount of polyunsaturated fatty acids (PUFAs) consumed in the diet. The higher the amount of PUFAs, the more vitamin E is required." (12)

One reason the RDA was lowered is that "dieticians were having difficulty devising diets of natural foods which had the recommended amount (30 IU) of vitamin E." (13) There are about 39 IU of vitamin E in an 8-ounce cup of olive oil. A full pound of peanuts yields 34 IU. Professor Max K. Horwitt, Ph.D., who spent 15 years serving on The Food and Nutrition Board's RDA committees, said in an interview that "The average intake by adults, without supplements, seems to be about 8 milligrams of alpha-tocopherol per day, or 8 tocopherol equivalents. This is equivalent to 12 International Units (IU)." (14) So it might be said that, in the end, the accommodation was not to raise the bridge but rather to lower the river.

Vitamin E is the body's chief fat-soluble antioxidant. It is a powerful one indeed, when you consider that 22 IU is presumed adequate to protect each one of the tens of trillions of body cells in a human being. Even though there has been a veritable explosion in antioxidant research since 1968, the RDA for vitamin E has been decreased.

POSTAL FRAUD

"Any claim in the labeling of drugs or of foods offered for special dietary use, by reason of Vitamin E, that there is need for dietary supplementation with Vitamin E, will be considered false." (United States Post Office Department Docket No. 1/187 (March 15, 1961)

On October 26, 1959, the US government charged an organization known as the Cardiac Society with postal fraud for selling 30 IU vitamin E capsules through the mail. Specifically, the charge was "the operation of a scheme or device for obtaining money through the mails by means of false and fraudulent pretenses, representations or promises . . . that Respondent's product 'E-FEROL 30 I.U.' (containing vitamin E) is therapeutically effective and beneficial in the treatment of heart and cardiovascular diseases for any person so afflicted; that Respondent's said product will prevent heart disease; that "It (vitamin E) is the key both to the prevention and treatment of all those conditions in which a lack of blood supply due to thickened or blocked blood vessels or a lack of oxygen is a part or the whole story of the disease"; that "Vitamin E seems to be a natural anti-thrombin in the human blood stream. . . It is the only substance preventing the clotting of blood which is not dangerous"; that the book "Your Heart and Vitamin E" tells you "What Vitamin E is and Does, How It Treats Heart Disease, Its Success In Circulatory Diseases, Your Foods' Deficiency in Vitamin E" . . . That "It (the book) explains medical facts in every-day language concerning the help that is available for sufferers from diseases of the heart and blood vessels such as Coronary Heart Disease, Angina Pectoris, Phlebitis, Buerger's Disease, Diabetes, Strokes, etc." (15)

A four-day hearing in Washington, D.C. generated sufficient testimony to fill "four volumes totaling 856 pages. Seventy-six exhibits were received in evidence. . . for the consideration of the Hearing Examiner. His Initial Decision covers forty-two pages."

It is an oddity of history that, at the height of the Cuban Missile Crisis, the United States of America found both the reason and the resources to prosecute such a case as this.

"The record here shows that the consensus of medical opinion is that Respondent's claims are false and that this is the universality of medical opinion on the subject. Numerous tests and experiments have been conducted to attempt to substantiate the claims made by Respondent that Vitamin E is efficacious for treatment of a number of conditions but these have failed to substantiate the claims. It appears perfectly clear from the testimony of the expert witnesses that Respondent's claims and representations are devoid of scientific support. . . The Hearing Examiner correctly found that the Respondent intends to deceive by its false representation and that actual fraud under established law is proven. . . A fraud order shall issue forthwith forbidding the delivery of mail and the payment of money orders incident to such scheme, to the Respondent, its agents and representatives, all in accordance with 39 U.S.C. 259 and 732." (15)

After this, all mail addressed to the Cardiac Society was returned to the sender, with "Fraudulent" stamped on the envelope.

DOSAGE AND UTILITY

Vitamin E has many clinically important and seemingly unrelated properties. In their books (16, 17, 18, 19, 20, 21) the Shutes discuss a number of them.

1) Vitamin E strengthens and regulates heartbeat, like digitalis and similar drugs, at a dose adjusted between 800 to 3,000 IU daily.

2) Vitamin E reduces inflammation and scarring when frequently applied topically to burns or to sites of lacerations or surgical incisions. Internally, vitamin E helps to very gradually break down thrombi at a maintained oral dose of between 800 IU and 3,000 IU.

3) Vitamin E has an oxygen-sparing effect on the heart, enabling the heart can do more work on less oxygen. The benefit for recovering heart attack patients is considerable. 1,200 to 2,000 IU daily relieves angina very well. My father, duly diagnosed with angina, gradually worked up to 1,600 IU over a period of a few weeks. He never had an angina symptom again. In this, he had the identical success that thousands of Shute patients had.

4) Vitamin E moderately prolongs prothrombin clotting time, decreases platelet adhesion, and has a limited "blood thinning" effect. This is the reason behind the Shutes' using vitamin E (1,000 - 2,000 IU/day) for thrombophlebitis and related conditions. The pharmaceutical industry and the medical profession are well aware of vitamin E's anticoagulant property and that "very high doses of this vitamin may act synergistically with anticoagulant drugs." (21) However, this also means that vitamin E can, entirely or in part, substitute for such drugs but do so more safely. Perhaps this is best summed up by surgeon Alton Ochsner, M.D. (1896-1981) who said, "Vitamin E is a potent inhibitor of thrombin that does not produce a hemorrhagic tendency and therefore is a safe prophylactic against venous thrombosis." (23)

5) Vitamin E is a modest vasodilator, promotes collateral circulation, and consequently offers great benefits to diabetes patients. (24) The Shutes used a dose of about 800 IU or more, tailored to the patient. For this, among other reasons, Evan Shute, author of over 100 scientific papers, was literally judged to be a fraud by the United States Post Office Department. The 1961 court decision said, "Vascular degenerations in a diabetic are not effectively treated in the use of vitamin E in any dosage. . . vitamin E has been thoroughly studied and that there is no doubt whatsoever as to its lack of utility." (15)

This statement was premature to say the least. The "thorough study" of vitamin E was not quite completed by 1961. Thirty-eight years later, a crossover study of 36 patients who had Type I diabetes, and retinal blood flows that were significantly lower than non-diabetics, showed that those taking 1,800 IU of vitamin E daily obtained normal retinal blood flow. The patients with the worst initial readings improved the most. "(V)itamin E may potentially provide additional risk reduction for the development of retinopathy or nephropathy in addition to those achievable through intensive insulin therapy alone. Vitamin E is a low-cost, readily available compound associated with few known side effects; thus, its use could have a dramatic socioeconomic impact if found to be efficacious in delaying the onset of diabetic retinopathy and/or nephropathy." (25) Vitamin E also works synergistically with insulin to lower high blood pressure in diabetics. (26)

QUANTITY AND QUALITY

The most common reason for irreproducibility of successful vitamin E cures is either a failure to use enough of it, or a failure to use the natural form (D-alpha, plus mixed natural tocopherols), or both. For example, in an oft-quoted negative study (27), researchers who gave 300 milligrams of synthetic vitamin E to patients who had recently had a heart attack saw no beneficial effect. Such failure is to be expected. You can set up any experiment to fail. The Shutes would have used only the natural form, and four times as much.

Natural vitamin E is always the dextro- (right-handed) form. On the other hand, "synthetic vitamin E is a mixture of eight isomers in equal proportions containing only 12.5% of d-alpha tocopherol. One mg of dl-alpha tocopherol has the lowest Vitamin E equivalence of any of the common vitamin E preparations." (28)

There may be other differences. "Vitamin E derived from natural sources is obtained by molecular distillation and, in most cases, subsequent methylation and esterification of edible vegetable oil products. Synthetic vitamin E is produced from fossil plant material (coal tar) by condensation of trimethylhydroquinone with isophytol." (12)

While personal philosophy is the only possible basis for a decision to conduct a study using only the synthetic form of a vitamin, the use of low dosage is generally explained away by alleging doubts about safety.

SAFETY

The most elementary of forensic arguments is, where are the bodies? Poison control statistics report no deaths from vitamin E. (29) There is a reason for this. Vitamin E is a safe and remarkably non-toxic substance. Even the 2000 report by the Institute of Medicine of the National Academy of Sciences, which actually recommends against taking supplemental vitamin E, specifically acknowledges that 1,000 mg (1,500 IU) is a "tolerable upper intake level . . . that is likely to pose no risk of adverse health effects for almost all individuals in the general population." (30) The Shutes observed no evidence of harm with doses as high as 8,000 IU/day. In fact, "toxicity symptoms have not been reported even at intakes of 800 IU per kilogram of body weight daily for 5 months" according to the Food and Nutrition Board. (31) This demonstrated safe level would work out to be around 60,000 IU daily for an average adult, some 2,700 times the RDA!

In addition to an awareness of anticoagulation medications, "Dr. Shute advises starting with small doses for patients who have rheumatic heart disease. He starts with 90 IU. and very slowly works up the dose. The reason for this is that if too much is given at the beginning the increased strength of the heartbeat may create some difficulty. The same applies to heart failure. The initial dose should be small and gradually increased. If this is done the final dose can safely reach 800 to 1200 IU." (31)

SAFETY IN THE ELDERLY

A Columbia University study reported progression of Alzheimer's disease was significantly slowed in patients taking high daily doses (2,000 IU) of vitamin E for two years. (32) The vitamin worked better than the drug selegiline did. The patients in the Alzheimer's study tolerated their vitamin E doses well. Perhaps the real story is that 2,000 IU per day for two years is safe for the elderly.

SAFETY IN CHILDREN

Children using anti-epileptic medication have reduced plasma levels of vitamin E, a sign of vitamin E deficiency. So doctors at the University of Toronto gave epileptic children 400 IU of vitamin E per day for several months, along with their medication. This combined treatment reduced the frequency of seizures in most of the children by over 60 percent. Half of them "had a 90 to 100 percent reduction in seizures." (33) This extraordinary result is also proof of the safety of 400 IU of vitamin E per day in children (equivalent to at least 800 to 1,200 IU/day for an adult). "There were no adverse side effects," said the researchers. It also provides a clear example of pharmaceutical use creating a vitamin deficiency, and an unassailable justification for supplementation.

SAFETY IN INFANTS

Overexposure to oxygen has been a major cause of retrolental fibroplasia (retinopathy of prematurity) and subsequent blindness in premature infants. Incubator oxygen retina damage is now prevented by giving preemies 100 mg E per kilogram body weight. That dose is equivalent to an adult dose of about 7,000 IU for an average-weight adult. "There have been no detrimental side effects" from such treatment, said the New England Journal of Medicine, Dec. 3, 1981. (34) Nevertheless, the 1989 (sixth) edition of the textbook Nutrition and Diet Therapy (6) advised that "healthy persons stand the chance of developing signs of toxicity with the megadoses that are recommended in these studies." (p. 225) That incorrect statement was dropped in the book's next edition. Instead, the 7th edition (1993) said under "Toxicity Effects" that "Vitamin E is the only one of the fat-soluble vitamins for which no toxic effect in humans is known. Its use as a supplement has not shown harmful effects." (p 186)

IMMUNE FUNCTION

"Worst Pills, Best Pills" is a monthly newsletter published by Public Citizen, Ralph Nader’s "Health Research Group." http://www.citizen.org/hrg/ The October, 2002 issue (Vol 8, No 10) contained this statement by editor Sidney M. Wolfe, M.D.: "You should not take dietary supplements. These products have not been tested or shown to be effective for any use, and their safety is unknown. The only exception to this advice is an inexpensive vitamin or mineral preparation." (p 80) On page 77, the doctor presents a JAMA study (35) alleging that a mere 200 mg of vitamin E is somehow detrimental to patients over the age of 60 with respiratory tract infections.

But there are other studies that Public Citizen might do well to present to its readership. Emanuel Cheraskin, M.D., writes: "The effect of daily vitamin E supplementation (800 IU alpha tocopherol for 30 days) on immune responses of 32 healthy subjects (60+ years old) was examined in a placebo-controlled, double-blind trial in a metabolic research unit. The data suggest that vitamin E supplementation improves immune responsiveness in healthy elderly." (36) In a second study, "using a double blind protocol, immune response was studied in a group receiving vitamin E (800 mg per day) versus placebo. The increased immunocompetence was matched by blood vitamin E levels which jumped from 1.1 to 3.1 mg%. No such change in blood vitamin E occurred in the control group (1.1 to 1.0 mg%)." (37)

A recent and perhaps even more important study looked at patients with colon cancer "who received a daily dose of 750 mg of vitamin E during a period of 2 weeks. Short-term supplementation with high doses of dietary vitamin E leads to increased CD4:CD8 ratios and to enhanced capacity by their T cells to produce the T helper 1 cytokines interleukin 2 and IFN-gamma. In 10 of 12 patients, an increase of 10% or more (average, 22%) in the number of T cells producing interleukin 2 was seen after 2 weeks of vitamin E supplementation." The authors concluded that "dietary vitamin E may be used to improve the immune functions in patients with advanced cancer." That improvement was achieved in only two weeks merits special attention. (38)

Note that the doses in these positive studies were nearly four times the dose used in the negative JAMA study cited by Dr. Wolfe.

HYPERTENSION

Recent research has indicated that Vitamin E normalizes high blood pressure. (39, 40, 41) In some hypertensive persons, commencement of very large vitamin E doses may cause a slight temporary increase in blood pressure, although maintained supplementation can then be expected to lower it. The solution is to increase the vitamin gradually, along with the proper monitoring that hypertensive patients should have anyway. High blood pressure has been called the "silent killer," and nearly one-third of adults have it. It is all too frequently unrecognized and untreated.

Nearly half of all deaths are due to cardiovascular diseases, and often the first symptom is death. Advocating daily supplementation with several hundred IU's of vitamin E would be good public health policy. Yet vitamin E, for decades lampooned as a "cure in search of a disease," remains virtually the "silent healer" for as much as the public has been advised of its benefits.

Back in 1985, Linus ing wrote: "The failure of the medical establishment during the last forty years to recognize the value of Vitamin E in controlling heart disease is responsible for a tremendous amount of unnecessary suffering and for many early deaths. The interesting story of the efforts to suppress the Shute discoveries about Vitamin E illustrates the shocking bias of organized medicine against nutritional measures for achieving improved health." (10, vii)

Dr. ing would most likely have appreciated this comment from a recent Harvard Health Letter: "A consistent body of research indicates that vitamin E may protect people against heart disease. . . The data generally indicate that taking doses ranging from 100 to 800 IU (International Units) per day may lower the risk of heart disease by 30%-40%." (42) Over half a century ago, the Shute brothers and colleagues showed that, with even higher doses than those, and with an insistence on the use of natural vitamin E, the results are better still.

References:

1. Hutton, (1953) The fight over vitamin E. Maclean's Magazine, June 15.

2. Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol, EJ. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 2003; 361: 2017-23.

3. Natural alpha tocopherol (vitamin E) in the treatment of cardiovascular and renal diseases. http://www.doctoryourself.com/shute_protocol.html

4. http://www.bayeraspirin.com/news/heart_attack.htm

5. Dietary Supplements: An Advertising Guide for Industry, Part 3. Federal Trade Commission. http://www.ftc.gov/bcp/conline/pubs/buspubs/dietsupp.htm#Application

6. SR. Nutrition and Diet Therapy, Seventh Edition. St. Louis: Mosby, 1993. (p 186). Sixth edition, 1989. (p 225).

7. HTG, Fenna D, MacBeth RA. Alpha Tocopherol in the Treatment of Intermittent Claudication. Surgery, Gynecology and Obstetrics 132:#4, 662-666, April 1971.

8. HM and Bishop KS. On the existence of a hitherto unrecognized dietary factor essential for reproduction. Science 56: 650, 1922.

9. Pacini AJ. Why we need vitamin E. Health Culture Magazine, January, 1936.

10. Shute E, and Shute JCM (ed). The vitamin E story. Burlington, Ontario: Welch Publishing, 1985.

11. British Medical Journal, i, 890, 1940 (cited in Bicknell & Prescott. The vitamins in medicine. Milwaukee: Lee Foundation, 1953, p 632)

12. Roche Vitamins: vitamin E in human nutrition. http://www.roche-vitamins.com/home/what/what-hnh/what-hnh-vitamins/what-hnh-vitamin-e

13. Horwitt MK. Vitamin E: a reexamination. American Journal of Clinical Nutrition, 29(5):569-78. 1976.

14. HealthWorld Online Interviews with Nutritional Experts: ''Vitamin E and the RDA'' http://www.healthy.net

15. United States Post Office Department Docket No. 1/187. March 15, 1961. http://www.usps.gov/judicial/1961deci/1-187.htm

16. Shute EV et al. The heart and vitamin E. London, Canada: Shute Foundation for Medical Research, 1963.

17. Shute WE. (Dr. Wilfred Shute's) Complete updated vitamin E book. New Canaan, CT: Keats, 1975.

18. Shute WE and Taub HJ. Vitamin E for ailing and healthy hearts. New York: Pyramid House, 1975.

19. Shute WE. Health Preserver. Emmaus, PA: Rodale Press, 1977.

20. Shute WE. The Vitamin E Book. New Canaan, CT: Keats Publishing, 1978.

21. Shute WE. Your Child and Vitamin E. New Canaan, CT: Keats Publishing, 1979

22. Butterworth, Jr. CE. Vitamin Safety: A current appraisal. Backgrounder, Vol 5, No 1. Vitamin Nutrition Information Service, 1994.

23. Letter. New England Journal of Medicine 271, 4; July 23, 1964.

24. Shute, Vogelsang, Skelton and Shute. Surg., Gyn. and Obst. 86:1. 1948.

25. Bursell SE, Clermont AC, Aiello LP, Aiello LM, Schlossman DK, Feener EP, Laffel L, King GL. High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes. Diabetes Care. 1999 Aug; 22(8):1245-51.

26. Koo JR, Ni Z, Oviesi F, Vaziri ND. Antioxidant therapy potentiates antihypertensive action of insulin in diabetic rats. Clin Exp Hypertens. 2002 Jul;24(5):333-44.

27. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet. 1999 Aug 7;354(9177):447-55.

28. Hoffer A. Personal communication, June 2003.

29. Rosenbloom M. Vitamin toxicity. http://www.eMedicine.com . October 23, 2001.

30. Vita-Mania: RDA for C, E Raised; Limits Set

http://abcnews.go.com/sections/living/DailyNews/vitamin000411.html

The Associated Press, Washington, April 11, 2000.

31. Rosenberg H and Feldzamen AN. The book of vitamin therapy. New York: Berkley Publishing Corp, 1974.

32. Sano M, Ernesto C, RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, Schneider LS, Thal LJ. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease ative Study. N Engl J Med. Apr 24; 336(17):1216-22. 1997.

33. Ogunmekan AO, Hwang PA. A randomized, double-blind, placebo-controlled, clinical trial of D-alpha-tocopheryl acetate (vitamin E), as add-on therapy, for epilepsy in children. Epilepsia. 1989 Jan-Feb; 30(1):84-9.

34. Hittner HM, Godio LB, Rudolph AJ, JM, -Prats JA, Friedman Z, Kautz JA, Monaco WA. Retrolental fibroplasia: efficacy of vitamin E in a double-blind clinical study of preterm infants. N Engl J Med. 1981 Dec 3; 305(23):1365-71.

35. Graat JM, Schouten EG, Kok FJ. Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. JAMA. 2002 Aug 14;288(6): 715-21.

36. Cheraskin E. Antioxidants in health and disease: the big picture. Journal of Orthomolecular Medicine 10: #2, 89-96, Second Quarter, 1995, citing Meydani, S.N., Barklund, M.P., Liu, S., Meydani, M., , R.A., Cannon, J.G., Morrow, F.D., Rocklin, R., Blumberg, J.B. Effect of Vitamin E Supplementation on Immune Responsiveness of Healthy Elderly Subjects. FASEB Journal 3: A1057, 1989.

37. Meydani, S.N., Barkiund, M.P., Liu, S., Meydani, M., , R.A., Cannon, J.G., Morrow, F.D., Rocklin, R., Blumberg, J.B. Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects. American Journal of Clinical Nutrition 52:#3, 557-563, September 1990.

38. Malmberg KJ, Lenkei R, sson M, Ohlum T, Ichihara F, Glimelius B, Frodin JE, Masucci G, Kiessling R. A short-term dietary supplementation of high doses of vitamin E increases T helper 1 cytokine production in patients with advanced colorectal cancer. Clin Cancer Res. 2002 Jun; 8(6):1772-8.

39. Vasdev S, Gill V, Parai S, Longerich L, Gadag V. Dietary vitamin E supplementation lowers blood pressure in spontaneously hypertensive rats. Mol Cell Biochem. 2002 Sep; 238(1-2):111-7.

40. Vaziri ND, Ni Z, Oveisi F, Liang K, Pandian R. Enhanced nitric oxide inactivation and protein nitration by reactive oxygen species in renal insufficiency. Hypertension. 2002 Jan; 39(1):135-41.

41. Galley HF, Thornton J, Howdle PD, BE, Webster NR. Combination oral antioxidant supplementation reduces blood pressure. Clin Sci (Lond). 1997 Apr;92(4):361-5.

42. President and Fellows of Harvard College. Antioxidants: what they are and what they do. Harvard Health Letter. Feb 1999; 24(5)

A bibliography of selected books and papers by Wilfrid and Evan Shute is posted at http://www.doctoryourself.com/biblio_shute.html .

Dr. Evan Shute's autiobiography, The Vitamin E Story, was reviewed by Saul in the Journal of Orthomolecular Medicine, Volume 17, Number 3, Third Quarter, 2002 (p 179-181) and is also posted online at http://www.doctoryourself.com/estory.htm .

VITAMIN D: Deficiency, Diversity and Dosage

by W. Saul

(Reprinted with permission from the Journal of Orthomolecular Medicine, 2003; Vol. 18, Numbers 3 and 4, p. 194-204.)

"Vitamin D deficiency is a major unrecognized health problem." ( F. Holick, M.D., Boston University Medical Center)

There have been many papers published on vitamin D. A Medline search for "vitamin D" will yield over 32,000 matches. It is well established that insufficient quantities of the vitamin contribute to osteopenia, osteomalacia, and osteoporosis. However, there is so much new interest in "boneless" applications of vitamin D that the topic was featured in the June, 2003 Reader's Digest. (1)

Vitamin D was first isolated from tuna fish oil in 1936, and synthesized in 1952. It is a prohormone sterol which the body manufactures, given sunlight, from 7-dehydrocholesterol. Vitamin D 3 (C27H44O, cholecalciferol) is the form we and other animals make, and what is found in fish liver oil. Oddly enough, fish cannot synthesize vitamin D. They get theirs early in the food chain from planktonic algae, and big fish eat little fish, and we eat them.

Vitamin D 2 (C28H44O) is made from ergosterol, not cholesterol, and consequently is called ergocalciferol. This is the form that is found in plants, and that is also man-made by ultraviolet irradiation of ergosterol, and that is usually added to milk and found in most American supplements. Vitamin D3 is more commonly used as a supplement in Europe. (2) As a curiosity, reindeer lichen contains both vitamin D2 and D3. (3)

Although D2 and D3 differ by a single carbon atom, there is evidence that D3 is more efficiently utilized in chicks (4) and, more to the point, in humans. "The assumption that vitamins D2 and D3 have equal nutritional value is probably wrong and should be reconsidered." (5)

There are two commercial sources of natural vitamin D3: fish liver oil and an oil extracted from wool. "If a label lists 'vitamin D3 (cholecalciferol)' then it is from wool oil. This is considered a vegetarian source (the animal is not harmed, just sheared), but not vegan. Fish liver oil will be in parentheses if it is the source." (6) Animals can obtain vitamin D from licking their fur, and in humans, rickets can be successfully treated by rubbing cod liver oil into the skin.

LONG-TERM SAFETY

As with all vitamins, there is ongoing and ever-protracted debate about vitamin D's safety and effectiveness. In the end, the issue really boils down to dosage. Because vitamin D can be made in the body, given sufficient sunlight, it has been considered more of a hormone than a vitamin. This terminology is likely to prejudice any consideration of megadoses, and that is unfortunate. Government-sponsored "tolerable" or "safe upper limits" (UL) for vitamin D have been established, perhaps based as much on speculation as on available facts. For babies under one year, that "upper limit" is 1,000 IU (25 mcg) per day. For everyone else, including pregnant and nursing women, it is 2,000 IU (50 mcg) per day. (7) These "safe upper limits" may be excessively conservative. Vieth et al write, "The 100-microg/d (4,000 IU/day) dosage of vitamin D3 effectively increased 25(OH)D to high-normal concentrations in practically all adults and serum 25(OH)D remained within the physiologic range; therefore, we consider 100 microg vitamin D3/d (4,000 IU/day) to be a safe intake." (8)

Vitamin D has sometimes been regarded as the most potentially dangerous vitamin. In his 2001 article "Vitamin Toxicity," Mark Rosenbloom, MD, writes that, for vitamin D, "Acute toxic dose is not established, and chronic toxic dose is more than 50,000 IU/day in adults. In children, 400 IU/day is potentially toxic. A wide variance in potential toxicity exists." There were no fatalities cited. (9)

The Merck Manual's assessment is somewhat different: "Vitamin D 1000 µg (40,000 IU)/day produces toxicity within 1 to 4 months in infants, and as little as 75 µg (3,000 IU)/day can produce toxicity over years. Toxic effects have occurred in adults receiving 2,500 µg (100,000 IU)/day for several months." (10)

The Merck Manual's lowest "toxicity" figure for "infants" of 3,000 IU is substantially higher than Dr. Rosenbloom's "potentially toxic" figure of 400 IU for presumably older and larger "children." "Potentially toxic" is very different than "toxic." Moreover, "toxic" is very different than "death." The choice to use the word "toxic" may serve to convey a false impression of immediate and mortal danger. There are numerous symptomatic warnings before serious toxic effects occur. Merck says, "The first symptoms are anorexia, nausea, and vomiting, followed by polyuria, polydipsia, weakness, nervousness, and pruritus. (Eventually) renal function is impaired. . . Metastatic calcifications may occur, particularly in the kidneys. In Great Britain, so-called hypercalcemia in infancy with failure to thrive has occurred with a daily vitamin D intake of 50 to 75 µg (2000 to 3000 IU)." (10) Though the details and duration of intake are not stated, a body-weight comparison suggests that if an infant weighed 10 pounds, that would be the dose equivalent of approximately 32,000 to 48,000 IU per day for an average adult.

A widely-used nutrition textbook that I taught from (11) said that 2,000 IU daily for an adult is toxic (p 220-221). In this same textbook, on the same page, there was an error that, by the author's own standard, could likely be fatal to the reader's baby. A "Caution" statement on page 221 indicated the daily vitamin D requirement for an infant as 10 MILLIGRAMS. This is 1,000 times the correct figure, which is 10 micrograms. 10 milligrams is 400,000 IU; 10 micrograms is 400 IU. That textbook typo is a far greater mistake than any health nut would ever make. By the next edition, the mistake had been corrected.

This is not an isolated instance. As recently as July, 2003, the website of a major university medical school (12) made the same mistake of stating milligrams (mg) instead of micrograms (mcg). This abbreviation error, amounting to a difference of three orders of magnitude, was present no fewer than six times in a single article. One of the medical school's statements read, "The upper limit of safety for vitamin D established by the Food and Nutrition Board of the Institute of Medicine is 25 mg (1000 IU) daily for infants and 50 mg (2000 IU) for children and adults." Actually, 25 mg would be one million IU/day, and 50 mg is two million IU/day. Mark Twain's advice comes to mind: "Be careful in reading health books. You may die of a misprint." Perhaps it is a testament to the safety of vitamin D that there has never been a report of any reader deaths from medical school-induced hypervitaminosis. Additionally, if nutrition textbook and medical school proofreaders can confuse milligrams with micrograms, then certainly the public can. This may serve as a practical example of the advantage of using International Units in discussing and labeling the fat-soluble vitamins.

It is instructive to note that as far back as 1939, some truly enormous doses of vitamin D were in fact found to be far less deadly than one might expect. In several countries, most infants, including preemies, survived 200,000 to as many as 600,000 units of vitamin D given in a single injected or oral dose. These are incredibly high quantities, especially when they are considered in relation to a premature infant's body weight. (13) Pregnant women have likewise been given two huge oral doses of vitamin D (600,000 IU) during the 7th and 8th months. (14)

In 2003, vitamin D's safety margins appear pretty much unchanged. This year, the British Medical Journal published a double-blind controlled trial of 100,000 IU vitamin D3 given orally to over 2,000 elderly patients once every four months, for five years. The authors reported, in addition to greatly reduced fracture rates, that the high-dose therapy was "without adverse effects in men and women." (15)

It may be readily be conceded that huge but occasional doses are insufficient to produce toxicity because vitamin D is fat-soluble, stored by the body, and it takes many months of very high doses to produce calcification of soft tissues, such as the lung and kidneys. "Overdose," "toxic," and "fatal" are very strong, yet very different terms that are often used interchangeably by critics of vitamin supplementation. Most overdoses are not toxic, and most toxicities are not fatal.

Current US Daily Reference Intakes (DRI) for vitamin D are:

Infants 0-12 months, 200 IU (5 micrograms)

Males and females 1-50 years, 200 IU (5 mcg)

51-70 years, 400 IU (10 mcg)

71 years and older, 600 IU (15 mcg)

Pregnant or nursing women, 200 IU (5 mcg) (7)

Formerly, the US RDA for vitamin D was only 5 mcg (200 IU) for older adults. The present recommendations are an improvement. However, there is evidence that even three times the DRI for an adult is inadequate if a person is not receiving adequate sunlight. (16) DRI or RDA levels are certainly not therapeutic levels, as the treatment of rickets generally requires a dose of 1,600 IU/day, and may require a daily dosage of 50,000 to as much as 300,000 IU in resistant cases. (17)

Current widely-publicized government recommendations are probably inadequate for disease prevention. Reinhold Vieth, Ph.D., writes, "For adults, the 5-microgram (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension. Total-body sun exposure easily provides the equivalent of 250 microg (10,000 IU) vitamin D/day, suggesting that this is a physiologic limit. . . .Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 microg (10,000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of greater than or equal to 1,000 microg (40,000 IU)/d. Because vitamin D is potentially toxic, intake of >25 microg (1,000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 microg (2,000 IU)/d is too low by at least 5-fold." (18)

These figures, high though they may seem, may actually be fairly conservative. The Nutrition Desk Reference, Second Edition (19) states that, for vitamin D, "The threshold for toxicity is 500 to 600 micrograms per kilogram body weight per day." (p 40) "Toxic" in this particular instance must mean "death," as this figure is presumably based on the US Environmental Protection Agency's published oral LD50 for female rats of 619 mg/kg (20). 500 to 600 mcg is the equivalent of 20,000 to 24,000 IU, per kilogram body weight per day. By comparison, this would mean that for an average (70 kg) adult human, toxicity would occur at an astounding 1,400,000 to 1,680,000 IU/day. In ducks, it is even higher: EPA's LD 50 for mallards is greater than 2000 mg/kg, more than three times that for female rats.

Even if such figures were not directly applicable to human beings, vitamin D must remain one of the most non-toxic substances imaginable. It might be speculated that at least some of the recent increase of interest in vitamin D analogs is due, in part, to patent- and profit-driven attempts to chemically sidestep the presumed dangers of high doses of inexpensive, natural vitamin D. If the vitamin is non-toxic, incentive to develop pharmaceutical analogs largely disappears.

There are, of course, some reasonable cautions with its use. Persons with hyperparathyroidism, lymphoma, lupus erythematosus, tuberculosis, sarcoidosis, kidney disease, or those taking digitalis, calcium channel-blockers, or thiazide diuretics, should have physician supervision before and while taking extra vitamin D. Hyperparathyroidism has been successfully managed with 50,000 to 200,000 IU of vitamin D daily (21). When employing large doses of vitamin D, periodic testing is highly advisable.

DEFICIENCY

Vitamin D deficiency is, of course, to found in people who do not take supplements, who receive little sun exposure, and who do not drink vitamin D fortified milk. A recent study (22) indicates that about a quarter of supposedly bone-growing American adolescents are likely vitamin D deficient. "Additionally, phenytoin (Dilantin), primidone (Mysoline), and phenobarbital for seizures; corticosteroids; cimetidine (Tagamet) for ulcers; the blood-thinning drug heparin; and the antituberculosis drugs isoniazid (INH) and rifampin may interfere with vitamin D absorption or activity." (23) Cyclosporine and carbamazepene also negatively interfere with vitamin D. Vitamin D deficiency is prevalent in the elderly, who all too commonly eat the worst diet, take the most medication, and get the least sunlight. Furthermore, the normal aging process itself decreases the body's ability to make vitamin D from what sunlight may be received. In any age group, even a relatively wholesome-appearing diet heavy in cereal grains reduces the availability of vitamin D in the body. (24)

OSTEOPOROSIS

For decades, a milk-fed (and dairy industry-educated) public has had its attention focused on calcium and largely diverted from the "other" important osteoporosis-preventing factor: vitamin D. Not only is vitamin D necessary for calcium deposition in the body, it is necessary for getting calcium into the body in the first place. "(P)assive diffusion (dictated by calcium intake) is not the major mechanism by which dietary calcium is absorbed by normal adult humans. The vitamin D-dependent processes are more important quantitatively and thus constitute a major determinant of calcium status. Individuals who are not exposed to sunlight may be especially at risk." (25)

Most persons with osteoporosis have low vitamin D levels. Along with calcium, 800 IU of vitamin D daily has been shown in a double-blind placebo-controlled study to increase bone density, and to reduce hip fractures by an astounding 43%. (26) Fractures and their complications are a major cause of death in the elderly. Up to "27% of all hip fracture victims die within six months of their fall, usually of complications following surgery or from infections." (27) There are over 250,000 hip fractures annually among persons over age 65, and probably "90% of all fractures past age 60 are due to osteoporosis." (28) Vitamin D therapy can save lives as well as bones. The fact that the DRI of vitamin D is tripled for the elderly is an indication that this fact is not unknown. But 600 IU of vitamin D for a 71 year old is probably too little, and for some, too late.

Such was nearly the case for my mother, a grand mal epileptic who took phenytoin (Dilantin) for nearly 50 years. As she aged, she began to fracture easily. This problem continued even after she was put on calcium supplements accompanied by an RDA-level vitamin D supplement. But after her vitamin D intake was raised to 2,000 IU/day, she never broke a bone again. This is true even though she still fell from time to time, sometimes so severely that she required inpatient care. But there were no more fractures. Epileptics may need as much as 4000 IU daily. (29) "Interestingly, vitamin D may offer another benefit for osteoporosis: studies have found that when older individuals take vitamin D supplements, they have less of a tendency to sway while standing or walking, and may therefore be less likely to fall." (23)

RICKETS

Childhood rickets remains a larger public health problem than might be expected. "Until recently, rickets secondary to vitamin D deficiency was considered a medical oddity rather than a clinical reality in Catalonia (Spain). However, recent data show a reemergence of the disease in the infancy. Nutritional rickets . . . mainly affects immigrant infants and children from Sub-Saharan Africa and Morocco, black or dark-skinned, fed with maternal milk alone, without vitamin D supplementation and with little sun exposure. Systematic, preventive supplementation with vitamin D is essential in these populations." (30)

Such is the case elsewhere as well, such as on the sunny island of Crete, where "A full-term male infant presented with clinical and biochemical findings consistent with the diagnosis of congenital rickets: weak muscle tone, craniotabes, episodes of tremor, hypocalcaemia, elevated serum alkaline phosphatase, secondary hyperparathyroidism, decreased 25-hydroxyvitamin D and normal 1,25-dihydroxyvitamin D serum levels. The mother's history and biochemical findings suggested nutritional vitamin D deficiency. . . It is surprising that this case occurred in an affluent setting, in the Mediterranean island of Crete, with an abundance of sunlight throughout the year." The authors assert that "a high index of suspicion is required for prompt diagnosis and treatment, thus preventing complications." (31) Seizures may be a symptom of rickets. (32, 33, 34)

"A high index of suspicion" of vitamin D deficiency would be a good policy for clinicians in the United States as well. Rickets has been observed in Texas (35) and in North Carolina, where "Thirty patients with nutritional rickets were first seen between 1990 and June of 1999. Over half of the cases occurred in 1998 and the first half of 1999. All patients were African American children who were breast fed without receiving supplemental vitamin D. . . Factors that may have contributed to the increase in referrals of children with nutritional rickets include more African American women breast-feeding, fewer infants receiving vitamin D supplements, and mothers and children exposed to less sunlight. We recommend that all dark-skinned breast-fed infants and children receive vitamin D supplementation." (36)

Heavily pigmented skin blocks up to 95% of UV radiation to the deepest skin layers. Additionally, now-widespread air pollution interferes with vitamin D synthesis in two almost paradoxical ways. Particulate pollution reduces the amount of sunlight people may receive, and ozone depletion causes people to minimize exposure to what sunlight there is. As people are cover their skin to avoid skin cancer, they reduce their vitamin D.

On 4 August 2002, Reuters News Service reported that "the number of cases of rickets in the United States has crept up in recent years. Breast milk contains many valuable nutrients but not enough Vitamin D to meet the daily requirement of 200 International Units. Exposure to the sun's rays normally generates Vitamin D in the skin, but applying sun block stops that process."

FOOD FORTIFICATION

With the exception of oily fish, foods do not contain a significant amount of vitamin D. Because of concern over mercury levels, eating the flesh of fish may not be practical advice, and, while it contains no mercury, there is widespread dislike for cod liver oil. Since the 1930's, vitamin D has been added to fluid milk but not to other milk products. More recently, it has also been added to flour to reduce rickets among immigrants to Britain. (10)

It is cheap and reliable for people to get their vitamin D from enriched foods. Iodine, iron and some of the B-vitamins are other examples of nutrients that have been added to foods for decades. That action should be seen for what it is: a national policy effectively acknowledging that the masses eat so inadequately that they are otherwise unable to avoid the most obvious clinical ramifications of the most classic of nutrient deficiencies, including iodine-deficiency goiter, iron-deficiency anemia, and pellagra. In the case of vitamin D, it is a tacit statement about safety as well. With 400 IU added per quart, it is easy for many a milk-drinking teenager to easily quadruple the DRI of 200 IU/day. Few dieticians appear worried that many people are routinely and substantially exceeding government DRI's for vitamin D.

Adding fluoride to public water supplies is a similar, if less well reasoned, application of government intervention. There has been nearly as much interest in trying to strengthen bones with fluoride as there has been in using vitamin D. But not only does fluoridation fail to protect bones from fracture, it actually contributes to increased fractures. (37, 38)

Additionally, both the National Toxicology Program and the National Cancer Institute found a fluoride-related increase in osteosarcoma in young males. (39) Water fluoridation isn't particularly effective in preventing dental caries, resulting in an average of one half of one filling less per user per lifetime. (40)

OBESITY

Supplements, not sunlight, may be necessary for overweight persons because they are less than half as able to utilize cutaneously-synthesized vitamin D3 compared to lean persons. Since approximately two-thirds of all Americans are overweight or obese, this is a very significant public health problem. "In the obese subjects oral vitamin D was more bioavailable than vitamin D from sunlight exposure . . . The authors propose that vitamin D is being sequestered in body fat in obese persons, giving rise to a relative deficiency which could be corrected with oral administration of extra vitamin D." (41)

DIVERSITY OF USES

Controversy over vitamin D therapy increases with the distance research moves away from the skeleton. There is growing evidence that the "sunshine vitamin" may be vastly more important to human health than previously thought and commonly taught. Vitamin D metabolite (1,25-dihydroxyvitamin D) receptors (VDR), writes F. Holick, M.D., "are present not only in the intestine and bone, but in a wide variety of other tissues, including the brain, heart, stomach, pancreas, activated T and B lymphocytes, skin, gonads, etc. 1,25(OH)(2)D is one of the most potent substances to inhibit proliferation of both normal and hyperproliferative cells and induce them to mature. . . Chronic vitamin D deficiency may have serious adverse consequences, including increased risk of hypertension, multiple sclerosis, cancers of the colon, prostate, breast, and ovary, and type 1 diabetes." (42)

It is noteworthy that skin cancer may actually be prevented by what many feel causes it: sunshine. (43, 44) Krispin Sullivan, author of Naked at Noon: Understanding Sunlight and Vitamin D, writes: "One of the known protectors of skin cells from pre-cancerous changes is vitamin D. For most Americans the primary source of vitamin D is sunlight. UV-B, the only band of light producing vitamin D, is significantly present only midday during summer months in most of the U.S., the exact time we are advised to avoid sunlight. UV-B is blocked by sunscreen." (45) Over-exposure to sunlight does not cause vitamin D toxicity. Persisting concerns over sun exposure are arguments in favor of its nutritional equivalent: oral vitamin D supplementation.

MULTIPLE SCLEROSIS

Persons with multiple sclerosis typically are vitamin D deficient and demonstrate dramatically reduced bone mass. Unsurprisingly, such bone loss appears to be directly caused by insufficient vitamin D (46) and can "be safely and inexpensively corrected by the routine use of vitamin D supplements." (47)

More importantly, vitamin D may have a key role in the progression of multiple sclerosis itself. et al write, "(E)xogenous 1,25-dihydroxyvitamin D3, the hormonal form of vitamin D3, can completely prevent experimental autoimmune encephalomyelitis (EAE), a widely accepted mouse model of human multiple sclerosis (MS) . . . (T)he hormonal form of vitamin D3 is a selective immune system regulator inhibiting this autoimmune disease. Thus, under low-sunlight conditions, insufficient vitamin D3 is produced, limiting production of 1,25-dihydroxyvitamin D3, providing a risk for MS. . . This theory can explain the striking geographic distribution of MS, which is nearly zero in equatorial regions and increases dramatically with latitude in both hemispheres. . . MS may be preventable in genetically susceptible individuals with early intervention strategies that provide adequate levels of hormonally active 1,25-dihydroxyvitamin D3 or its analogs." (48) Dr. adds that "Inheriting genetic risk factors for multiple sclerosis (MS) is not sufficient to cause this demyelinating disease of the central nervous system; exposure to environmental risk factors is also required." (49)

In a review article, "Vitamin D Supplementation in the Fight Against Multiple Sclerosis (50), Ashton F. Embry credits P. Goldberg (51, 52) with being the first to propose that vitamin D is an important factor in the development of MS. Goldberg "postulated that such a close correspondence between low sunlight and MS was due to low vitamin D production in the population. Goldberg also showed that within areas of low sunlight (e.g. Norway) differences in MS prevalence could be explained by dietary factors which affect vitamin D production. Such factors include the amount of fish eaten (increases vitamin D) and the amount of grains consumed (reduces vitamin D levels due to the action of phytates). To explain how vitamin D levels were related to MS, Goldberg proposed that genetically susceptible individuals may need larger than normal amounts of vitamin D during myelin formation and that insufficient vitamin D during childhood might result in defective myelin which would be susceptible to breakdown in later life. Goldberg's ideas were completely ignored by medical researchers."

At least at the time they were. Eventually it was demonstrated that vitamin D hormone could prevent or halt not only an animal form of MS (53, 54) but there had been a clinical study (55) showing that vitamin D, along with calcium and magnesium, reduced the relapse rate in humans with multiple sclerosis. Frederick R. Klenner, M.D., reported success using vitamin and mineral therapy for multiple sclerosis over thirty years ago. (56, 57, 58)

HEART DISEASE AND OTHER CLINICAL USES

Vitamin D has an important role in cardiovascular health. (59, 60) For example, not only can it prevent hypertension, it can help treat it. (61, 62) "Hypertension appears to improve with vitamin D supplementation whether or not the vitamin is deficient." (63) This is an important point.

Congestive heart failure (CHF) may be caused by vitamin D deficiency. "Low vitamin D status can explain alterations in mineral metabolism as well as myocardial dysfunction in the CHF patients, and it may therefore be a contributing factor in the pathogenesis of CHF." (64) Not surprisingly, bone loss is associated with congestive heart failure. (65) Dilated cardiomyopathy has been linked with rickets, both of which "responded well to supplemental calcium and vitamin D." (66)

Scleroderma has responded favorably to long-term oral vitamin D3 (1,25-dihydroxycholecalciferol) therapy (67) and psoriasis has been successfully treated, not only with vitamin D analogues, but with topical vitamin D3. (68) Vitamin D deficiency may be a contributing cause of inflammatory bowel disease, and might be an effective treatment. (69) Over 50 years ago, lupus vulgaris (tuberculosis of the skin) was reported successfully treated with 150,000 IU of vitamin D daily for six to eight months. (70)

Colon cancer is clearly related to poor vitamin D nutrition (71, 72, 73). Inadequate vitamin D levels are also associated with ovarian cancer (74), polycystic ovary syndrome, (75) rheumatoid arthritis (76), and lupus (77). Infants receiving vitamin D supplements show as much as an 80% reduction in type I diabetes. (78, 79, 80, 81). A Medline search will reveal nearly 300 papers on fighting prostate cancer with vitamin D and its derivatives, and nearly 400 in relation to D and breast cancer.

DEFICIENCY AND DIVERSITY: A SUMMARY

Vitamin D deficiency is cause or contributor to a wide variety of diseases, many of which appear unrelated to bone problems. So important is this vitamin for the entire population that it is necessary for milk to be enriched with it. Most persons do not get adequate vitamin D from sunlight, and the problem compounded for the obese and for the elderly. For those individuals, and for any person on any of a number of commonly prescribed medications, vitamin D supplementation is mandatory.

Government recommended dietary intakes of 200 to 600 IU/day are too low, according to the weight of clinical evidence. Government "tolerable" or "safe upper intake levels" (UL) of 1,000 to 2,000 IU/day are likewise too low, and largely unsupported by toxicological evidence. An optimum health recommendation of 1,000 to 4,000 IU/day, in total from all sources, is not unreasonable for the vast majority of healthy adults. Effective therapeutic levels for illness may be far higher. When high doses are used, appropriate testing and monitoring is recommended. It would be unreasonable to deny a therapeutic trial of vitamin D in cases of multiple sclerosis, scleroderma, psoriasis, congestive heart failure, hypertension, and various forms of cancer.

Excessive avoidance of sunlight, and sensational but unscientific dread of relatively high-dose vitamin D side effects does more than merely set the stage for a population of rickety children and fracture-ridden elderly. Overestimates and outright misstatements of vitamin D's "potential toxicity" open new marketing avenues for the development of vitamin D-like drugs, a commercial opportunity that the pharmaceutical industry has not overlooked.

ON DANGERS AND DOSAGE: A CONCLUDING COMMENT

Hypervitaminosis articles are popular with the media, sometimes even making it into the pages of the Wall Street Journal. On April 30, 1992, Stipp reported that between 1990 and 1992, "a series of patients with vitamin D overdoses began turning up at Boston hospitals." One of these patients subsequently died from drug complications, and the case went to court. (82) "Essentially, this was a product liability action against the producer of dairy products, specifically milk which contained excessive amounts of Vitamin D. The plaintiff's decedent purportedly suffered from elevated levels of Vitamin D in her bloodstream which required medication which in turn allegedly compromised her immune system, leading to her death." (83) This is the one and only vitamin D-related death I could find confirmation of anywhere, and even this one was not directly due to the vitamin, but rather to side effects of medication.

A physiology textbook later stated that "At least 19 cases of vitamin D toxicity were reported in the Boston area during 1992. Symptoms included fatigue, weight loss, and potentially severe damage to the kidneys and cardiovascular system. The problems resulted from drinking milk fortified with vitamin D. Due to problems at one dairy, some of the milk sold had over 230,000 units of vitamin D per quart instead of the usual 400 units per quart. The incident highlighted the need for quality control in the production, and care in the consumption, of vitamin supplements." (84)

Such a conclusion is inaccurate. The incident might just as well be taken to be an unintentional proof of vitamin safety, even in ridiculously high overdosage situations. It is certainly noteworthy that 580 times the normal amount of vitamin D produced, at most, one alleged fatality over a two-year period. Furthermore, there was a total of fewer than two dozen toxicity reports, for the entire Boston metropolitan area, after large numbers of people had been ingesting close to a quarter of a million units of vitamin D per liter of milk day after day, month after month, for up to two years. This borders on the extraordinary. Events such as this demonstrate that the margin for error with vitamin D is very large indeed. Though the news reported about the vitamin's toxicity, the real story was the vitamin's safety. The scientific literature confirms the vitamin's value.

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83. http://www.dwpm.com/content/main/litigation00_news.php3

84. i FH. Hypervitaminosis. Anatomy and Physiology, Chapter 25: Metabolism and Energetics. NY: Prentice Hall, 2000. http://media.pearsoncmg.com/ph/esm/esm_martini_fundanaphy_5/bb/obj/25/CH25/html/ch25_8_4.html

Topics like this one sound quacky, so let's set the matter straight from the start:

If you do not like getting shots of B-12, you should be aware that intranasal absorption is the next best thing. Oral administration of B-12 is largely ineffective. This goes for so-called sublingual B-12 supplements as well.

VITAMIN B-12, unlike other B vitamins, is stored in muscle and other organs of the body. A little B-12 goes a long way, what is stored lasts a long time, and it may take YEARS to deplete your body’s reserves. But sooner or later, usually later (after age 40), not only do poor eating habits catch up with us, but we also lose the ability to efficiently absorb what B-12 we do get from food.

COBALAMIN is the proper name for vitamin B-12. It is a really huge molecule (C 63, H 90, O 14, P, Co). The "Co" is for the one cobalt atom at its core. B-12 is obtained mostly, but not exclusively, by eating animal products such as dairy and meat. If you therefore think that you have to eat meat to get your B-12, consider this: Where do grass-and-grain-eating cattle get THEIR vitamin B-12? From synthesis by microorganisms in their gastrointestinal tract, that's where. And such synthesis in vegetarian animals is so tremendous that their milk and flesh is OUR source of B-12. But it all actually came from their bacteria.

Yes, B-12 is also synthesized in the human GI tract, but not reliably enough for most people. Such synthesis as occurs may be enhanced by a good vegetarian diet that favors an internal population of beneficial, B-12 making bacteria.

But with our diets, we will need more than they can provide. Nutritional yeast, fermented soy foods such as tempeh, and sprouts (according to some sources) are vegetarian sources of dietary B-12.

But there still is a physiological hurdle to cross.

Absorption of dietary B-12 takes place in the very last part of the small intestine, right before the colon. Absorption requires a biochemical helper molecule called “intrinsic factor,” which is a glycoprotein normally secreted by cells lining your stomach. Strong stomach hydrochloric acid is also required to split up this huge molecule. (That's why a weak acid like vitamin C (ascorbic acid) is harmless to B-12, persistent myths to the contrary).

Incidentally, even sublingual (under-the-tongue) B-12 supplements are probably ineffective because the cobalamin molecule is too large to diffuse through the mucosa of the mouth.

And if your body no longer makes intrinsic factor like it should, you cannot absorb oral B-12 supplements very well, either.

The end result can be pernicious anemia, which is more than the classical inability to make enough hemoglobin for your red blood cells. Pernicious anemia also results in a sore mouth and tongue, assorted burning and tingling sensations (paresthesia), and eventually neurologic damage. I think Meniere’s, and dementia symptoms mistaken for Alzheimer’s disease, might be a manifestation of this.

While there is a urine test for B-12 deficiency (the "isotope-dilution assay for urinary methylmalonic acid"), to get it right it is necessary to measure the cerebrospinal fluid, not the blood, to get accurate B-12 readings. If you are not a Spinal Tap fan, consider a simple, non-invasive therapeutic trial of B-12. This is so inexpensive and safe that it would be difficult to deny it to anyone. I would suggest your doctor try a 1,000 microgram (mcg) injection at least once a week. Compared to the US RDA of only about 3 mcg, that dose may appear rather hefty. But given the miserable nature of Meniere’s, erring on the high side may be preferable to unnecessarily delaying recovery. And l know of no side effects whatsoever to B-12 overdose.

If you do not like the idea of getting shots of B-12, you should be aware that intra-nasal (that is, by way of the nose) absorption is the next best thing. It sounds pretty weird, as duly promised at the beginning of this section, but it is an efficient delivery method for large-sized molecules whether you like the sound of it or not.

Your nose has two choices:

1) Buy ready-to-use, over-the-counter B-12 gel, which you will occasionally find for sale in a pharmacy or health food store. Some products come in individual disposable packets. These are pricey.

2) Make your own B-12 intra-nasal supplement. It is cheap, easy and best done behind closed doors. Obtain your doctor’s OK before trying this procedure. Take any B-12 tablet (between 100 to 1,000 mcg) and grind it into a powder between two tablespoons. Add water, just a few drops at a time, to make a soft paste. With a “Q-Tip,” it’s generic equivalent, or your clean pinkie finger, gently swab the paste inside your nose up to a comfortable level. Do not push; use no force whatsoever. The excipients (tableting ingredients) are more likely to bother your schnoz than the B-12 is. If it irritates you, try using less, or a different brand of tablet. I’d try this two times a week for a month or two.

Feel free to quit at any time, and get B-12 shots instead. Once in a great while, doctors (such as “Children’s Doctor” Lendon H. , M.D.) will even teach you how to give yourself your B-12 shots, but that remains a singularly rare event.

Hence this nose news.

Copyright 2002 and prior years by Saul, Number 8 Van Buren Street, Holley, New York 14470 USA Telephone (716) 638-5357. Reprinting requires the advance written permission of the author

SOME NOTES ON NIACINAMIDE THERAPY FOR ARTHRITIS by Kaufman, M.D., Ph.D. (Reprinted with the kind permission of Charlotte Kaufman)

The (more frequent) 250 mg dose of niacinamide is 40 to 50 % more effective in the treatment of arthritis than the (less frequent) 500 mg. dose. As an illustration, see the reprint of my Tom Spies Memorial Lecture: Niacinamide, a Most Neglected Vitamin. This illustrative case history begins on page 17 column 2 and continues on page 18 column 2.

Do not use hard gelatin capsules containing 250 mg niacinamide because they do not deliver niacinamide as efficiently as 250mg niacinamide in thin gelatin capsules in the treatment of joint dysfunction (arthritis).

In my paper in J. Amer Geriat. Society, 1955 3:927-936 I noted that niacinamide (alone or combined with other vitamins) in a thousand patient-years of use has caused no adverse side effects.

Some brands of niacinamide on the market today contains excipients that act as preservatives, probably meant to prolong shelf life. Some patients have severe adverse reactions to these preparations while most do not experience any ill effects.

Niacinamide has un-gated entrance to the central nervous system. It has a strong affinity for the central nervous system's benzodiazepine receptors and causes a pleasant calmative effect. In addition, it improves central nervous system function in the kinds of central nervous symptom impairments noted in my 1943 book, starting on page 3.

Please keep in mind niacinamide is a systemic therapeutic agent. It measurably improves joint mobility, muscle strength, decreases fatigability. It increases maximal muscle working capacity, reduces or completely eliminates arthritic joint pain. Niacinamide heals broken strands of DNA and improves many kinds of CNS functioning.

Some joints are so injured by the arthritic process that no amount of niacinamide therapy will cause improvement in joint mobility, but it takes three months of niacinamide therapy before you can conclude this, since some joints are slow to heal.

WILLIAM KAUFMAN, PhD, MD January 13,1998

SO EXACTLY WHAT IS A ROSE HIP, ANYWAY? Any biologist knows that roses don't have hips because they are not vertebrates. Ha! Okay, back on task:

Rose hips are the fruit of a rose bush. All flowers give rise to fruits, and the rose is no exception. When I hike (just got back from another one), I look for wild or feral rosebushes and munch out on the "hips" as soon as they are ready (usually early autumn). They are often found on the bushes throughout the entire winter, just waiting for you to come along. Eaten fresh or dried, they are high in vitamin C.

Rose hips are a rich source of bioflavinoids. Bioflavinoids improve uptake and utilization of vitamin C. Albert Szent-Gyorgyi won the Nobel prize for his research with vitamin C and related factors back in the 30's. He actually proposed the term "Vitamin P" for the ("protective"?) phytochemicals in bioflavinoids. In a rather adorable, unplanned bit of research, Szent-Gyorgyi was feeding pure vitamin C to his lab animals. One evening, some of them snuck out of their cage and ate his dinner when he wasn't looking: the meal consisted of stuffed green peppers. Szent-Gyorgyi observed that the animals that ate the peppers seemed to require considerably less pure ascorbic acid than did the less lucky critters. Peppers, along with many fruits and vegetables, are high in bioflavinoids.

Many folks would do well to note this next section: there is so very little rose hips powder in most "rose-hips C" tablets that it is a waste of money to pay extra for what amounts to nearly zilch. I (in agreement with Linus ing) recommend that people buy the cheapest vitamin C they can find, and take a lot of it. This means moderate amounts very frequently. The only reason to pay more for "C" is if you have a sensitive tummy and need a buffered form, and rose hips have essentially nothing to do with that.

I recommend that people take cheap C, AND eat right. Foods are a lousy source of vitamin C but an excellent source of bioflavinoids. Vitamin C tablets are a lousy source of bioflavinoids, but a good source of C. Good match.

And by the way, a green or red pepper IS a fruit. So are pumpkins, green beans and squash. They all come from flowers. A rose by any other name?

References: R.E. and P.R. (1971) Natural and synthetic sources of vitamin C. J. Sci. Food. Agric. 22 551 552.

E. and R.E. (1984) The influence of bioflavonoids on the absorption of vitamin C. IRCS Med. Sci. 12 320

Vinson J A, Bose P. (1983) Comparative bioavailability of synthetic and natural vitamin C in Guinea pigs. Nutr Rep Intl 27(4):875.

Vinson J A, Bose P. (1988) Comparative bioavailability to humans of ascorbic acid alone or in a citrus extract. Am J Clin Nutr 48:6014.

Copyright 2001 and prior years by Saul, Number 8 Van Buren Street, Holley, New York 14470 USA Telephone (585) 638-5357

Vitamin B-3: Niacin and It's Amide by A. Hoffer, M.D., Ph.D.

The first water soluble vitamins were numbered in sequence according to priority of discovery. But after their chemical structure was determined they were given scientific names. The third one to be discovered was the anti-pellagra vitamin before it was shown to be niacin. But the use of the number B-3 did not stay in the literature very long. It was replaced by nicotinic acid and its amide (also known medically as niacin and its amide). The name was changed to remove the similarity to nicotine, a poison.

The term vitamin B-3 was reintroduced by my friend Bill W., co-founder of Alcoholics Anonymous, (Bill ). We met in New York in 1960. Humphry Osmond and I introduced him to the concept of mega vitamin therapy. We described the results we had seen with our schizophrenic patients, some of whom were also alcoholic. We also told him about its many other properties. It was therapeutic for arthritis, for some cases of senility and it lowered cholesterol levels.

Bill was very curious about it and began to take niacin, 3 g daily. Within a few weeks fatigue and depression which had plagued him for years were gone. He gave it to 30 of his close friends in AA and persuaded them to try it. Within 6 months he was convinced that it would be very helpful to alcoholics. Of the thirty, 10 were free of anxiety, tension and depression in one month. Another 10 were well in two months. He decided that the chemical or medical terms for this vitamin were not appropriate. He wanted to persuade members of AA, especially the doctors in AA, that this would be a useful addition to treatment and he needed a term that could be more readily popularized. He asked me the names that had been used. I told him it was originally known as vitamin B-3. This was the term Bill wanted. In his first report to physicians in AA he called it "The Vitamin B-3 Therapy." Thousands of copies of this extraordinary pamphlet were distributed. Eventually the name came back and today even the most conservative medical journals are using the term vitamin B-3.

Bill became unpopular with the members of the board of AA International. The medical members who had been appointed by Bill, felt that he had no business messing about with treatment using vitamins. They also "knew" vitamin B-3 could not be therapeutic as Bill had found it to be. For this reason Bill provided information to the medical members of AA outside of the National Board, distributing three of his amazing pamphlets. They are now not readily available.

Vitamin B-3 exists as the amide in nature, in nicotinamide adenine dinucleotide (NAD). Pure nicotinamide and niacin are synthetics. Niacin was known as a chemical for about 100 years before it was recognized to be vitamin B-3. It is made from nicotine, a poison produced in the tobacco plant to protect itself against its predators, but in the wonderful economy of nature which does not waste any structures, when the nicotine is simplified by cracking open one of the rings, it becomes the immensely valuable vitamin B-3.

Vitamin B-3 is made in the body from the amino acid tryptophan. On the average 1 mg of vitamin B-3 is made from 60 mg of tryptophan, about 1.5% Since it is made in the body it does not meet the definition of a vitamin; these are defined as substances that can not be made. It should have been classified with the amino acids, but long usage of the term vitamin has given it permanent status as a vitamin. The 1.5% conversion rate is a compromise based upon the conversion of tryptophan to N-methyl nicotinamide and its metabolites in human subjects. I suspect that one day in the far distant future none of the tryptophan will be converted into vitamin B-3 and it then will truly be a vitamin. According to Horwitt [1], the amount converted is not inflexible but varies with patients and conditions. For example, women pregnant in their last three months convert tryptophan to niacin metabolites three times as efficiently as in non-pregnant females. Also there is evidence that contraceptive steroids, estrogens, stimulate tryptophan oxygenase, the enzyme that converts the tryptophan into niacin.

This observation raises some interesting speculations. Women, on average, live longer then men. It has been shown for men that giving them niacin increases their longevity. [2] Is the increased longevity in women the result of greater conversion of tryptophan into niacin under the stimulus of their increase in estrogen production? Does the same phenomenon explain the decrease in the incidence of coronary disease in women?

The best-known vitamin deficiency disease is pellagra. More accurately it is a tryptophan deficiency disease since tryptophan alone can cure the early stages. Pellagra was endemic in the southern U.S.A. until the beginning of the last world war. It can be described by the four D's: dermatitis, diarrhea, dementia and death. The dementia is a late stage phenomenon. In the early stages it resembles much more the schizophrenias, and can only with difficulty be distinguished from it. The only certain method used by early pellagrologists was to give their patients in the mental hospitals small amounts of nicotinic acid. If they recovered they diagnosed them pellagra, if they did not they diagnosed them schizophrenia. This was good for some of their patients but was not good for psychiatry since it prevented any continuing interest in working with the vitamin for their patients who did not recover fast, but who might have done so had they given them a lot more for a much longer period of time, the way we started doing this in Saskatchewan. I consider it one of the schizophrenic syndromes.

Indications I have been involved in establishing two of the major uses for vitamin B-3, apart from its role in preventing and treating pellagra. These are its action in lowering high cholesterol levels [3] and in elevating high density lipoprotein cholesterol levels (HDL), and its therapeutic role in the schizophrenias and other psychiatric conditions. It has been found helpful for many other diseases or conditions. These are psychiatric disorders including children with learning and behavioral disorders, the addictions including alcoholism and drug addiction, the schizophrenias, some of the senile states. Its efficacy for a large number of both mental and physical conditions is an advantage to patients and to their doctors who use the vitamin, but is difficult to accept by the medical profession raised on the belief that there must be one drug for each disease, and that when any substance appears to be too effective for many conditions, it must be due entirely to its placebo effect, something like the old snake oils.

I have thought about this for a long time and have within the past year become convinced that this vitamin is so versatile because it moderates or relieves the body of the pernicious effect of chronic stress. It therefore frees the body to carry on its routine function of repairing itself more efficiently. The current excitement in medicine is the recognition that hyperoxidation, the formation of free radicals, is one of the basic damaging processes in the body. These hyperexcited molecules destroy molecules and damage tissues at the cellular level and at the tissue level.

All living tissue which depends on oxygen for respiration has to protect itself against these free radicals. Plants use one type of antioxidants and animals use another type. Fortunately there is a wide overlap and the same antioxidants such as vitamin C are used by both plants and animals. There is growing recognition that the system adrenaline -> adrenochrome plays a major role in the reactions to stress. I have elaborated this in a further report for this journal. [4]

The catecholamines, of which adrenalin is the best known example, and the aminochromes, of which adrenochrome is the best known example, are intimately involved in stress reactions. Therefore to moderate the influence of stress or to negate it, one must use compounds which prevent these substances from damaging the body. Vitamin B-3 is a specific antidote to adrenalin, and the antioxidants such as vitamin C, Vitamin E, beta carotene, selenium and others protect the body against the effect of the free radicals by removing them more rapidly from the body. Any disease or condition which is stress related ought therefore to respond to the combined use of vitamin B-3 and these antioxidants provided they are all given in optimum doses, whether small or large as in orthomolecular therapy. I will therefore list briefly the many indications for the use of vitamin B-3.

For each condition I will describe one case to illustrate the therapeutic response. For each condition I can refer to hundreds and thousands of case histories and have already in the literature described many of them in detail. [5]

Psychiatric 1) The Schizophrenias. I have reviewed this for this journal. [6]

2) Children with Learning and/or Behavioral Disorders.

In 1960 seven year-old Bruce came to see me with his father. Bruce had been diagnosed as mentally retarded. He could not read, could not concentrate, and was developing serious behavioral problems such as cutting school without his parents' knowledge. He was being prepared for special classes for the retarded. He excreted large amounts of kryptopyrrole, the first child to be tested. I started him on nicotinamide, one gram tid. Within four months he was well. He graduated from high school, is now married, has been fully employed and has been paying income tax. He is one case out of about 1500 I have seen since 1960.

Current treatment is more complicated as described in this Journal. [7]

3) Organic Confusional States, non-Alzheimers forms of dementia, electroconvulsive therapy-induced memory disturbances.

In 1954 I observed how nicotinic acid relieved a severe case of post ECT amnesia in one month. Since then I have routinely given it in conjunction with ECT to markedly decrease the memory disturbance that may occur during and after this treatment. I would never give any patient ECT without the concomitant use of nicotinic acid. It is very helpful, especially in cardiovascular-induced forms of dementia as it reverses sludging of the red blood cell and permits proper oxygenation of the cells of the body. For further information see Niacin Therapy in Psychiatry. [8]

In September 1992, Mr. C., 76 years-old, requested help with his memory. He was terribly absentminded. If he decided to do something, by the time he arrived where he wanted to do it he had forgotten what it was he wanted to do. His short-term memory was very poor and his long-term memory was beginning to be affected. I started him on a comprehensive vitamin program including niacinamide 1.5 G daily. Within a month he began to improve. I added niacin to his program. By February 1993 he was normal. April 26, 1993, he told me he had been so well he had concluded he no longer needed any niacin and decreased the dose from 3.0 G to 1.5 G daily. He remained on the rest of the program. Soon he noted that his short term memory was failing him again. I advised him to stay on the full dose the rest of his life.

4) An antidote against d-LSD,9,10 and against adrenochrome. [5]

5) Alcoholism.

Bill W. conducted the first clinical trial of the use of nicotinic for treating members of Alcoholics Anonymous. [11] He found that 20 out of thirty subjects were relieved of their anxiety, tension and fatigue in two months of taking this vitamin, 1 G tid. I found it very useful in treating patients who were both alcoholic and schizophrenic. The first large trial was conducted by Hawkins who reported a better than 90% recovery rate on about 90 patients. Since then it has been used by many physicians who treat alcoholics. Dr. in Detroit has reported the largest series of patients. [12]

Physical 1. Cardiovascular Of the two major findings made by my research group in Saskatchewan, the nicotinic acid-cholesterol connection is well known and nicotinic acid is used worldwide as an economical, effective and safe compound for lowering cholesterol and elevating high density cholesterol. As a result of my interest in nicotinic acid, Altschul, Hoffer and [3] discovered that this vitamin, given in gram doses per day, lowered cholesterol levels. Since then it was found it also elevates high density lipoprotein cholesterol thus bringing the ratio of total over HDL to below 5.

In the National Coronary Study, Canner [2] showed that nicotinic acid decreased mortality and prolonged life. Between 1966 and 1975, five drugs used to lower cholesterol levels were compared to placebo in 8341 men, ages 30 to 64, who had suffered a myocardial infarction at least three months before entering the study. About 6000 were alive at the end of the study. Nine years later, only niacin had decreased the death rate significantly from all causes. Mortality decreased 11% and longevity increased by two years. The death rate from cancer was also decreased.

This was a very fortunate finding because it led to the approval by the FDA of this vitamin in mega doses for cholesterol problems and opened up the use of this vitamin in large doses for other conditions as well. This occurred at a time when the FDA was doing its best not to recognize the value of megavitamin therapy. Its position has not altered over the past four decades.

Our finding opened up the second major wave of interest in vitamins. The first wave started around 1900 when it was shown that these compounds were very effective in small doses in curing vitamin deficiency diseases and in preventing their occurrence. This was the preventive phase of vitamin use. The second wave recognized that they have therapeutic properties not directly related to vitamin deficiency diseases but may have to be used in large doses. This was the second or present wave wherein vitamins are used in therapy for more than deficiency diseases. Our discovery that nicotinic acid was an hypocholesterolemic compound is credited as the first paper to initiate the second wave and paved the way for orthomolecular medicine which came along several years later.

2. Arthritis I first observed the beneficial effects of vitamin B-3 in 1953 and 1954. I was then exploring the potential benefits and side effects from this vitamin. Several of the patients who were given this vitamin would report after several months that their arthritis was better. At first this was a surprise since in the psychiatric history I had taken I had not asked about joint pain. This report of improvement happened so often I could not ignore it. A few years later I discovered that Prof. W. Kaufman had studied the use of this vitamin for the arthritides before 1950 and had published two books describing his remarkable results. [13] Since that time this vitamin has been a very important component of the orthomolecular regimen for treating arthritis.

The following case illustrates both the response which can occur and the complexity of the orthomolecular regimen. Patients who are early into their arthritis respond much more effectively and are not left with residual disability.

K.V. came to my office April 15, 1982. She was in a wheelchair pushed by her husband. He was exhausted, depressed, and she was one of the sickest patients I have ever seen. She weighed under 90 pounds. She sat in the chair on her ankles which were crossed beneath her body because she was not able to straighten them out. Her arms were held in front of her, close to her body, and her fingers were permanently deformed and claw-like. She told me she had been deeply depressed for many years because of the severe pain and her major impairment. As she was being wheeled into my office I saw how ill she was and immediately concluded there was nothing I could do for her, and had to decide how I could let her know without sending her even deeper into despair. However I changed my mind when she suddenly said, "Dr. Hoffer, I know no one can ever cure me but if you could only help me with my pain. The pain in my back is unbearable. I just want to get rid of the pain in my back." I realized then she had a lot of determination and inner strength and that it was worthwhile to try and help her.

She began to suffer from severe pain in her joints in 1952. In 1957 it was diagnosed as arthritis. Until 1962 her condition fluctuated and then she had to go into a wheelchair some part of the day. She was still able to walk although not for long until 1967. In 1969 she depended on the wheelchair most of the time, and by 1973 she was there permanently. For awhile she was able to propel herself with her feet. After that she was permanently dependent on help. For the three years before she saw me she had gotten some home care but most of the care was provided by her husband. He had retired from his job when I first saw them. He provided the nursing care equivalent to four nurses on 8 hour shifts including holiday time. He had to carry her to the bathroom, bathe her, cook and feed her. He was as exhausted as she was but he was able to carry on.

She was severely deformed, especially her hands, suffered continuous pain, worse in her arms, and hips and her back. Her ankles were badly swollen and she had to wear pressure bandages. Her muscles also were very painful most of the day. She was able to feed herself and to crochet with her few useful fingers, but it must have been extremely difficult. She was not able to write nor type which she used to do with a pencil. A few months earlier she had been suicidal. On top of this severe pain and discomfort she had no appetite, was not hungry and a full meal would nauseate her. Her skin was dry, she had patches of eczema, and she had white areas in her nails.

I advised her to eliminate sugar, potatoes, tomatoes and peppers, (about 10% of arthritics have allergic reactions to the solanine family of plants). She was to add niacinamide 500 mg four times daily (following the work of W. Kaufman), ascorbic acid 500 mg four times daily (as an anti-stress nutrient and for subclinical scurvy), pyridoxine 250 mg per day (found to have anti-arthritic properties by Dr. J. Ellis), zinc sulfate 220 mg per day (the white areas in her nails indicated she was deficient in zinc), flaxseed oil 2 tablespoons and cod liver oil 1 tablespoon per day (her skin condition indicated she had a deficiency of omega 3 essential fatty acids). The detailed treatment of arthritis and the references are described in my book. [14]

One month later a new couple came into my room. Her husband was smiling, relaxed and cheerful as he pushed his wife in in her chair. She was sitting with her legs dangling down, smiling as well. I immediately knew that she was a lot better. I began to ask her about her various symptoms she had had previously. After a few minutes she impatiently broke in to say, "Dr. Hoffer, the pain in my back is all gone." She no longer bled from her bowel, she no longer bruised all over her body, she was more comfortable, the pain in her back was easily controlled with aspirin and was gone from her hips, (it had not helped before). She was cheerful and laughed in my office. Her heart was regular at last. I added inositol niacinate 500 mg four times daily to her program.

She came back June 17, 1982, and had improved even more. She was able to pull herself up from the prone position on her bed for the first time in 15 years, and she was free of depression. I increased her ascorbic acid to 1 gram four times daily and added vitamin E 800 IU. Because she had shown such dramatic improvement I advised her she need no longer come to see me.

September 1, 1982, she called me on the telephone. I asked her how she was getting along. She said she was making even more progress. I then asked her how had she been able to get to the phone. She replied she was able to get around alone in her chair. Then she added she had not called for herself but for her husband. He had been suffering from a cold for a few days, she was nursing him, and she wanted some advice for him.

After another visit October 28, 1983, I wrote to her doctor "Today Mrs. K.V. reported she had stayed on the whole vitamin program very rigorously for 18 months, but since that time had slacked off somewhat. She is regaining a lot of her muscle strength, can now sit in her wheelchair without difficulty, can also wheel herself around in her wheelchair but, of course, can not do anything useful with her hands because her fingers are so awful. She would like to become more independent and perhaps could do so if something could be done about her fingers and also about her hip. I am delighted she has arranged to see a plastic surgeon to see if something can be done to get her hand mobilized once more. I have asked her to continue with the vitamins but because she had difficulty taking so many pills she will take a preparation called Multijet which is available from Portland and contains all the vitamins and minerals and can be dissolved in juice. She will also take inositol niacinate 3 grams daily."

I saw her again March 24, 1988. About 4 of her vertebra had collapsed and she was suffering more pain which was alleviated by Darvon. It had not been possible to treat her hands surgically. She had been able to eat by herself until six months before this last visit. She had been taking small amounts of vitamins. She was able to use a motorized chair. She had been depressed. I wrote to her doctor, "She had gone off the total vitamin program about two or three years ago. It is very difficult for her to swallow and I can understand her reluctance to carry on with this. I have therefore suggested that she take a minimal program which would include inositol niacinate 3 grams daily, ascorbic acid 1 gram three times, linseed oil 2 capsules and cod liver oil 2 capsules. Her spirits are good and I think she is coming along considering the severe deterioration of her body as a result of the arthritis over the past few decades." She was last seen by her doctor in the fall of 1989.

Her husband was referred. I saw him May 18, 1982. He complained of headaches and a sense of pressure about his head present for three years. This followed a series of light strokes. I advised him to take niacin 3 grams daily plus other vitamins including vitamin C. By September 1983 he was well and when seen last March 24, 1988 was still normal.

3. Juvenile Diabetes Dr. Elliot, Professor of Child Health Research at University of Auckland Medical School is testing 40,000 five-year old children for the presence of specific antibodies that indicate diabetes will develop. Those who have the antibodies will be given nicotinamide. This will prevent the development of diabetes in most the children who are vulnerable. According to the Rotarian for March 1993 this project began 8 years ago and has 3200 relatives in the study. Of these, 182 had antibodies and 76 were given nicotinamide. Only 5 have become diabetic compared to 37 that would have been expected. Since 1988 over 20,100 school children have been tested. None have become diabetic compared to 47 from the untested comparable group. A similar study is underway in London, Ontario.

4. Cancer Recent findings have shown that vitamin B-3 does have anti-cancer properties. This was discussed at a meeting in Texas in 1987, son and son. [15] The topic of this international conference was "Niacin, Nutrition, ADP-Ribosylation and Cancer," and was the 8th conference of this series.

Niacin, niacinamide and nicotinamide adenine dinucleotide (NAD) are interconvertable via a pyridine nucleotide cycle. NAD, the coenzyme, is hydrolyzed or split into niacinamide and adenosine dinucleotide phosphate (ADP-ribose). Niacinamide is converted into niacin, which in turn is once more built into NAD. The enzyme which splits ADP is known as poly (ADP-ribose) polymerase, or poly (ADP) synthetase, or poly (ADP-ribose) transferase. Poly (ADP-ribose) polymerase is activated when strands of deoxyribonucleic acid (DNA) are broken. The enzyme transfers NAD to the ADP-ribose polymer, binding it onto a number of proteins. The poly (ADP-ribose) activated by DNA breaks helps repair the breaks by unwinding the nucleosomal structure of damaged chromatids. It also may increase the activity of DNA ligase. This enzyme cuts damaged ends off strands of DNA and increases the cell's capacity to repair itself. Damage caused by any carcinogenic factor, radiation, chemicals, is thus to a degree neutralized or counteracted.

son and son, conference organizers, hypothesized that niacin prevents cancer. They treated two groups of human cells with carcinogens. The group given adequate niacin developed tumors at a rate only 10% of the rate in the group deficient in niacin. Dr. M. son is quoted as saying, "We know that diet is a major risk factor, that diet has both beneficial and detrimental components. What we cannot assess at this point is the optimal amount of niacin in the diet... The fact that we don't have pellagra does not mean we are getting enough niacin to confer resistance to cancer." About 20 mg per day of niacin will prevent pellagra in people who are not chronic pellagrins. The latter may require 25 times as much niacin to remain free of pellagra.

Vitamin B-3 may increase the therapeutic efficacy of anti-cancer treatment. In mice, niacinamide increased the toxicity of irradiation against tumors. The combination of normobaric carbogen with nicotinamide could be an effective method of enhancing tumor radiosensitivity in clinical radiotherapy where hypoxia limits the outcome of treatment. Chaplin, Horsman and Aoki16 found that nicotinamide was the best drug for increasing radiosensitivity compared to a series of analogues. The vitamin worked because it enhanced blood flow to the tumor. Nicotinamide also enhanced the effect of chemotherapy. They suggested that niacin may offer some cardioprotection during long-term adriamycin chemotherapy.

Further evidence that vitamin B-3 is involved in cancer is the report by Nakagawa, Miyazaki, Okui, Kato, Moriyama and Fujimura [17] that in animals there is a direct relationship between the activity of nicotinamide methyl transferase and the presence of cancer. Measuring the amount of N-methyl nicotinamide was used to measure the activity of the enzyme. In other words, in animals with cancer there is increased destruction of nicotinamide, thus making less available for the pyridine nucleotide cycle. This finding applied to all tumors except the solid tumors, lung carcinoma and melanoma B-16.

Gerson [18] treated a series of cancer patients with special diets and with some nutrients including niacin 50 mg 8 to 10 times per day, dicalcium phosphate with vitamin D, vitamins A and D, and liver injections. He found that all the cancer cases were benefited in that they became healthier and in many cases the tumors regressed. In a subsequent report Gerson elaborated on his diet. He now emphasized a high potassium over sodium diet, ascorbic acid, niacin, brewers yeast and lugols iodine. Right after the war there was no ready supply of vitamins as there is today. I would consider the use of these nutrients in combination very original and enterprising. Dr. Gerson was the first physician to emphasize the use of multivitamins and some multiminerals. More details are in Hoffer. [19]

Additional evidence that vitamin B-3 is therapeutic for cancer arises from the National Coronary Study, Canner. [2]

5. Concentration Camp Survivors In 1960 I planned to study the effect of nicotinic acid on a large number of aging people living in a sheltered home. A new one had been built. I approached the director of this home, Mr. Porteous. I arranged to meet him and told him what I would like to do and why. I gave him an outline of its properties, its side effects and why I thought it might be helpful. Mr. Porteous agreed and we started this investigation. A short while after my first contact Mr. Porteous came to my office at University Hospital. He wanted to take nicotinic acid himself, he told me, so that he could discuss the reaction more intelligently with people living in his institution. He wanted to know if it would be safe to do so.

That fall he came again to talk to me and this time he said he wanted to tell me what had happened to him. Then I discovered he had been with the Canadian troops who had sailed to Hong Kong in 1940, had been promptly captured by the Japanese and had survived 44 months in one of their notorious prisoner of war camps.

Twenty-five percent of the Canadian soldiers died in these camps. They suffered from severe malnutrition from starvation and nutrient deficiency. They suffered from beri beri, pellagra, scurvy, infectious diseases, and brutality from the guards.

Porteous, a physical education instructor, had been fit weighing about 190 pounds when he got there. When he returned home he weighed only 2/3rds of that. On the way home in a hospital ship the soldiers were fed and given extra vitamins in the form of rice polishings. There were few vitamins available then in tablets or capsules. He seemingly recovered but had remained very ill. He suffered from both psychological and physical symptoms. He was anxious, fearful and slightly paranoid. Thus, he could never be comfortable sitting in a room unless he sat facing the door. This must have arisen from the fear of the guards. Physically he had severe arthritis. He could not raise his arms above his shoulders. He suffered from heat and cold sensitivity. In the morning he needed his wife's help in getting out of bed and to get started for the day. He had severe insomina. For this he was given barbiturates in the evening and to help awaken him in the morning, he was given amphetamines.

Later I read the growing literature on the Hong Kong veterans and there is no doubt they were severely and permanently damaged. They suffered from a high death rate due to heart disease, crippling arthritis, blindness and a host of other conditions.

Having outlined his background he then told me that two weeks after he started to take nicotinic acid, 1 gram after each meal, he was normal. He was able to raise his arms to their full extension, and he was free of all the symptoms which had plagued him for so long. When I began to prepare my report [20] I obtained his Veterans Administration Chart. It came to me in two cardboard boxes and weighed over ten pounds, but over 95% of it was accumulated before he started on the vitamin. For the ten years after he started on the vitamin there was very little additional material. One could judge the efficacy of the vitamin by weighing the chart paper before and after he started on it. Porteous remained well as long as he stayed on the vitamin until his death when he was Lieutenant Governor of Saskatchewan. In 1962, after having been well for two years, he went on a holiday to the mountains with his son and he forgot to take his nicotinic acid with him. By the time he returned home almost the entire symptomatology had returned.

Porteous was enthusiastic about nicotinic acid and began to tell all his friends about it. He told his doctor. His doctor cautioned him that he might damage his liver. Porteous replied that if it meant he could stay as well as he was until he died from a liver ailment he would still not go off it. His doctor became an enthusiast as well and within a few years had started over 300 of his patients on the vitamin. He never saw any examples of liver disease from nicotinic acid.

I have treated over 20 prisoners from Japanese camps and from European concentration camps since then with equally good results. I estimated that one year in these camps was equivalent to 4 years of aging, i.e. four years in camp would age a prisoner the equivalent of 16 years of normal living.

Porteous wanted every prisoner of war from the eastern camps treated as he had been. He was not successful in persuading the Government of Canada that nicotinic acid would be very helpful so he turned to fellow prisoners, both in Canada (Hong Kong Veterans) and to American Ex-Prisoners of War. These American veterans suffered just as much as had the Canadian soldiers since they were treated in exactly the same abysmal way. The ones who started on the vitamin showed the same response. Recently one of these soldiers, a retired officer, wrote to me after being on nicotinic acid 20 years that he felt great, owed it to the vitamin and that when his arteries were examined during a simple operation they were completely normal. He wrote, "About two years ago, I was hit, was bleeding down the neck. The MDs took the opportunity to repair me. They said the arteries under the ears look like they had never been used."

There is an important lesson from the experiences of these veterans and their response to megadoses of nicotinic acid. This is that every human exposed to severe stress and malnutrition for a long enough period of time will develop a permanent need for large amounts of this vitamin and perhaps for several others.

This is happening on a large scale in Africa where the combination of starvation, malnutrition and brutality is reproducing the conditions suffered by the veterans. Those who survive will be permanently damaged biochemically, and will remain a burden to themselves and to the community where they live. Will society have the good sense to help them recover by making this vitamin available to them in optimum doses?

Doses The optimum dose range is not as wide as it is for ascorbic acid, but it is wide enough to require different recommendations for different classes of diseases. As is always the case with nutrients, each individual must determine their own optimum level. With nicotinic acid this is done by increasing the dose until the flush (vasodilation) is gone, or is so slight it is not a problem.

One can start with as low a dose as 100 mg taken three times each day after meals and gradually increase it. I usually start with 500 mg each dose and often will start with 1 gram per dose especially for cases of arthritis, for schizophrenics, for alcoholics and for a few elderly patients. However, with elderly patients it is better to start small and work it up slowly.

No person should be given nicotinic acid without explaining to them that they will have a flush which will vary in intensity from none to very severe. If this is explained carefully, and if they are told that in time the flush will not be a problem, they will not mind. The flush may remain too intense for a few patients and the nicotinic acid may have to be replaced by a slow release preparation or by some of the esters, for example, inositol niacinate. The latter is a very good preparation with very little flush and most find it very acceptable even when they were not able to accept the nicotinic acid itself. It is rather expensive but with quantity production the price might come down.

The flush starts in the forehead with a warning tingle. Then it intensifies. The rate of the development of the flush depends upon so many factors it is impossible to predict what course it will follow.

The following factors decrease the intensity of the flush: a cold meal, taking it after a meal, taking aspirin before, using an antihistamine in advance.

The following factors make the flush more intense: a hot meal, a hot drink, an empty stomach, chewing the tablets and the rate at which the tablets break down in liquid.

From the forehead and face the flush travels down the rest of the body, usually stopping somewhere in the chest but may extend to the toes. With continued use the flush gradually recedes and eventually may be only a tingling sensation in the forehead. If the person stops taking the vitamin for a day or more the sequence of flushing will be re-experienced. Some people never do flush and a few only begin to flush after several years of taking the vitamin. With nicotinamide there should be no flushing but I have found that about 2% will flush. This may be due to rapid conversion of the nicotinamide to nicotinic acid in the body.

When the dose is too high for both forms of the vitamin the patients will suffer from nausea at first, and then if the dose is not reduced it will lead to vomiting. These side effects may be used to determine what is the optimum dose. When they do occur the dose is reduced until it is just below the nausea level. With children the first indication may be loss of appetite. If this does occur the vitamin must be stopped for a few days and then may be resumed at a lower level. Very few can take more than 6 grams per day of the nicotinamide. With nicotinic acid it is possible to go much higher. Many schizophrenics have taken up to 30 grams per day with no difficulty. The dose will alter over time and if on a dose where there were no problems, they may develop in time. Usually this indicates that the patient is getting better and does not need as much. I have divided all patients who might benefit from vitamin B-3 into the following categories.

Category 1. These are people who are well or nearly well, and have no obvious disease. They are interested in maintaining their good health or in improving it. They may be under increased stress. The optimum dose range varies between 0.5 to 3 grams daily. The same doses apply to nicotinamide.

Category 2. Everyone under physiological stress, such as pregnancy and lactation, suffering from acute illness such as the common cold or flu, or other diseases that do not threaten death. All the psychiatric syndromes are included in this group including the schizophrenias and the senile states. It also includes the very large group of people with high blood cholesterol levels or low HDL when it is desired to restore these blood values to normal. The dose range is 1 gram to 10 grams daily. For nicotinamide the range is 1 1/2 g to 6 g.

Nicotinamide does not affect cholesterol levels.

Side Effects Here are Dr. Marks' conclusions. [21]

"A tingling or flushing sensation in the skin after relatively large doses (in excess of 75 mg) of nicotinic acid is a rather common phenomenon. It is the result of dilation of the blood vessels that is one of the natural actions of nicotinic acid and one for which it is used therapeutically. Whether this should therefore be regarded as a true adverse reaction is a moot point. The reaction clears regularly after about 20 minutes and is not harmful to the individual. It is very rare for this reaction to occur at less than three times the RDA, even in very sensitive individuals. In most people much larger quantities are required. The related substance nicotinamide only very rarely produces this reaction and in consequence this is the form generally used for vitamin supplementation.

"Doses of 200 mg to 10 g daily of the acid have been used therapeutically to lower blood cholesterol levels under medical control for periods of up to 10 years or more and though some reactions have occurred at these very high dosages, they have rapidly responded to cessation of therapy, and have often cleared even when therapy has been continued.

"In isolated cases, transient liver disorders, rashes, dry skin and excessive pigmentation have been seen. The tolerance to glucose has been reduced in diabetics and patients with peptic ulcers have experienced increased pain. No serious reaction have been reported however even in these high doses. The available evidence suggests that 10 times the RDA is safe (about 100 mg)."

Dr. Marks is cautious about recommending that doses of 100 mg are safe. In my opinion, based upon 40 years of experience with this vitamin the dose ranges I have recommended above are safe. However with the higher doses medical supervision is necessary.

Jaundice is very rare. Fewer that ten cases have been reported in the medical literature. I have seen none in ten years. When jaundice dose occur it is usually an obstructive type and clears when the vitamin is discontinued. I have been able to get schizophrenic patients back on nicotinic acid after the jaundice cleared and it did not recur.

Four serious cases have been reported, all involving a sustained release preparation. Mullin, Greenson & (1989) [22] reported that a 44 year-old man was treated with crystalline nicotinic acid, 6 grams daily, and after 16 months was normal. He then began to take a sustained-release preparation, same dose. Within three days he developed nausea, vomiting, abdominal pain, dark urine. He had severe hepatic failure and required a liver transplant. Henkin, & Segrest found three patients who developed hepatitis with sustained release nicotinic acid. When this was replaced with crystalline nicotinic acid there was no recurrent liver damage. [23]

Since jaundice in people who have not been taking nicotinic acid is fairly common it is possible there is a random association. The liver function tests may indicate there is a problem when in fact there is not. Nicotinic acid should be stopped for five days before the liver function tests are given. One patient who had no problem with nicotinic acid for lowering cholesterol switched to the slow release preparations and became ill. When he resumed the original nicotinic acid he was well again with no further evidence of liver dysfunction. I have not seen any cases reported anywhere else. I have described much more fully the side effects of this vitamin elsewhere. [24]

Inositol hexaniacinate is an ester of inositol and nicotinic acid. Each inositol molecule contains six nicotinic acid molecules. This ester is broken down slowly in the body. It is as effective as nicotinic acid and is almost free of side effects. There is very little flushing, gastrointestinal distress and other uncommon side effects. Inositol, considered one of the lesser important B vitamins, does have a function in the body as a messenger molecule and may add something to the therapeutic properties of the nicotinic acid.

Conclusion Vitamin B-3 is a very effective nutrient in treating a large number of psychiatric and medical diseases but its beneficial effect is enhanced when the rest of the orthomolecular program is included. The combination of vitamin B-3 and the antioxidant nutrients is a great anti-stress program.

Reprinted with the permission of the author: Abram Hoffer, M.D., Ph.D. Suite 3 - 2727 Quadra St , British Columbia V8T 4E5 Canada

References 1. Horwitt MK: Modern Nutrition in Health and Disease. Fifth Ed. RS Goodhart and ME Shils. Lea & Febiger, Phil. 1974.

2. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ & Freidewald W: Fifteen year mortality Coronary Drug Project; patients long term benefit with niacin. American Coll Cardiology 8:1245-1255, 1986.

3. Altschul R, Hoffer A & JD: Influence of Nicotinic Acid on Serum Cholesterol in Man. Arch Biochem Biophys 54:558-559, 1955.

4. Hoffer A: The Schizophrenia, Stress and Adrenochrome Hypothesis. In Press, 1995.

5. Hoffer A: Orthomolecular Medicine for Physicians. Keats Pub, New Canaan, CT, 1989.

6. Hoffer A: The treatment of schizophrenia. In Press 1995.

7. Hoffer A: The Development of Orthomolecular Medicine. In Press, 1995.

8. Hoffer A: Niacin Therapy in Psychiatry. C. C. , Springfield, IL, 1962.

Hoffer A & Osmond H: New Hope For Alcoholics, University Books, New York, 1966. Written by Fannie Kahan.

Hoffer A & M: Nutrients to Age Without Senility. Keats Pub Inc, New Canaan, CT, 1980.

Hoffer A & M: Smart Nutrients. A Guide to Nutrients That Can Prevent and Reverse Senility. Avery Publishing Group, Garden City Park, New York, 1994.

9. Agnew N & Hoffer A: Nicotinic Acid Modified Lysergic Acid Diethylamide Psychosis. J Ment Science 101:12-27, 1955.

10. Ivanova RA, Milstein GT, Smirnova LS & Fantchenko ND: The Influence of Nicotinic Acid on an Experimental Psychosis Produced by LSD 25. Journal of Neuropathology and Psychiatry of CC Korsakoff 64:1172-1176, 1964. In Russian. Translated by Dr. T.E. Weckowicz.

11. B: The Vitamin B-3 Therapy: The First Communication to A.A.'s Physicians and A Second Communication to A.A.'s Physicians, 1967 and 1968.

12. RF: A five year field trial of massive nicotinic acid therapy of alcoholics in Michigan. Journal of Orthomolecular Psychiatry 3:327-331, 1974.

RF: Status report concerning the use of megadose nicotinic acid in alcoholics. Journal of Orthomolecular Psychiatry 7:52-55, 1978.

13. Kaufman W: Common Forms of Niacinamide Deficiency Disease: Aniacin Amidosis. Yale University Press, New Haven, CT, 1943.

Kaufman W: The Common Form of Joint Dysfunction: Its Incidence and Treatment. E.L. Hildreth and Co., Brattelboro, VT, 1949.

14. Hoffer A: Orthomolecular Medicine For Physicians, Keats Pub, New Canaan, CT, 1989.

15. son M & son E: Niacin, nutrition, ADP-ribosylation and cancer. The 8th International Symposium on ADP- Ribosylation, Texas College of Osteopathic Medicine, Fort Worth, TX, 1987.

Titus K: Scientists link niacin and cancer prevention. The D.O. 28:93-97, 1987.

Hostetler D: sons put broad strokes in the niacin/cancer picture. The D.O. 28:103-104, 1987.

16. Chaplin DJ, Horsman MP & Aoki DS: Nicotinamide, Fluosol DA and Carbogen: a strategy to reoxygenate acutely and chronically hypoxic cells in vivo. British Journal of Cancer 63:109-113, 1990.

17. Nakagawa K, Miyazaka M, Okui K, Kato N, Moriyama Y & Fujimura S: N1-methylnicotinamide level in the blood after nicotinamide loading as further evidence for malignant tumor burden. Jap. J. Cancer Research 82:277-1283, 1991.

18. Gerson M: Dietary considerations in malignant neoplastic disease. A prelimary report. The Review of Gastroenterology 12:419-425, 1945.

Gerson M: Effects of a combined dietary regime on patients with malignant tumors. Experimental Medicine and Surgery 7:299-317, 1949.

19. Hoffer A: Orthomolecular Oncology. In, Adjuvant Nutrition in Cancer Treatment, Ed. P. Quillin & R. M. . 1992 Symposium Proceedings, Sponsored by Cancer Treatment Research Foundation and American College of Nutrition. Cancer Treatment Research Foundation, 3455 Salt Creek Lane, Suite 200, Arlington Heights, IL 60005-1090, 331-362, 1994.

20. Hoffer A: Hong Kong Veterans Study. J Orthomolecular Psychiatry 3:34-36, 1974.

21. Marks J: Vitamin Safety. Vitamin Information Status Paper, F. Hoffman La Roche & Co., Basle, 1989.

22. Mullin GE, Greenson JK & MC: Fulminant hepatic failure after ingestion of sustained-release nicotinic acid. Ann Internal Medicine 111:253-255, 1989.

23. Henkin Y, KC & Segrest JP: Rechallenge with crystalline niacin after drug-induced hepatitis from sustained-release niacin. J. American Medical Assn. 264:241-243, 1990.

24. Hoffer A: Niacin Therapy in Psychiatry. C. C. , Springfield, IL, 1962.

Hoffer A: Safety, Side Effects and Relative Lack of Toxicity of Nicotinic acid and Nicotinamide. Schizophrenia 1:78-87, 1969.

Hoffer A: Vitamin B-3 (Niacin) Update. New Roles For a Key Nutrient in Diabetes, Cancer, Heart Disease and Other Major Health Problems. Keats Pub, Inc., New Canaan, CT, 1990.

Food supplements don't do much good in the bottle. Here are ways to make vitamin taking easier:

* Take vitamin and mineral supplements with meals when possible. If between meals, have more liquid (juice, milk or water) than just enough to get the tablet down. Both these methods dilute the supplement so a person is less likely to notice a tablet in the tummy.

* Many vitamins (notably vitamin C) are available in powdered form. Some multiple vitamins are, too.

* Persons sensitive to regular vitamin C (ascorbic acid) may take buffered C. It is available as calcium ascorbate or sometimes as magnesium ascorbate. AscorBATE is non-acidic vitamin C. Some buffered vitamin C is just ascorbic acid mixed with some ground up dolomite (a natural calcium-rich rock). This is usually cheaper, but one teaspoon may provide only 2,000 milligrams (mg) of vitamin C. One teaspoon of calcium ascorbate may provide 4,000 mg of C. Because you tend to get what you pay for, always read the label.

* For children, there are very tasty chewable vitamins and liquid preparations for infants. For more information, you might want to read another short paper of mine called "How to get little kids to take their vitamins with a minimum of fuss."

* The elderly may not fully assimilate the contents of a vitamin tablet because of a weaker digestive system. Powdered supplements are especially useful here. You can cover the taste best with tasty fruit juice.

* If you cannot find powdered supplements, you can make your own. Gelatin capsules may easily be pulled apart. Tablets can be crushed between two spoons. The result is utterly unflavored, so mix with juice or applesauce. That, or just take the tablet and be done with it!

* The shelf life of liquid and powdered vitamins is much shorter than vitamins in capsules or tightly-pressed tablets. We often put our vitamin C powder in small, easily-closed bottles and work from them. Read expiration dates whenever you buy vitamins. If there is NOT an expiration date, that might tell you something.

* Any time you introduce something new in your diet you are more likely to notice it (and maybe grumble about it!) I suspect it is much like everything else: it takes time to get used to new routines. Most people easily take vitamin tablets. Surveys show that the MAJORITY of Americans do take vitamin supplements regularly. Something good must be happening.

* If a certain vitamin supplement does not agree with you, you might want to simply try a different brand. Like ice cream, some products are artificially colored or artificially flavored. Natural brands tend to be better in this regard. Always read the label, looking for what is NOT in the tablet as well as what is. It is worth remembering that many times a person is having a problem only with the tableting ingredients (called excipients, or fillers).

* For brand suggestions, you might ask friends what ones they like and why. Health food stores are very willing to try to help you select an appropriate supplement. Health professionals may have an opinion as well.

* Remember to consider the source of your nutritional information. A store might just want to make a buck. Many doctors have NEVER had even one good course in nutrition. There are some dietitians who are actually opposed to citizens taking food supplements. Few pharmacists take the time to investigate the therapeutic value of vitamins, and even fewer store clerks and cashiers know about what they sell.

The solution? Let the buyer beware and, to alter Shakespeare a bit, "Get thee to a library, go!" You need to know what you are doing, and WHY. May I suggest you begin by borrowing (or buying) HOW TO LIVE LONGER AND FEEL BETTER, by Linus ing. My Dad always said that when you want to know something, go to the organ-grinder, not his monkey. Dr. ing is an expert on vitamin supplementation and his book is outstanding.

* Remember to always read the label. There is much information there. Some supplements are higher potency than others. Sometimes you need to take two or even six tablets to get the full label claim.

* Incidently, I have NO financial connection whatsoever with any manufacturer, distributor, or seller of any nutritional product. Believe me, there have been plenty of offers. I think it is important to avoid brand bias or special interests.

* The most truthful answer I know to "What is the best brand of vitamins to take?" is that there are at least a dozen good brands. It is a bit like asking, "What is the best car for me to buy?" The decision depends on what suits you, and there may be several good choices.

* The above answer doesn't satisfy everyone. Here is the ultimate way to find out which supplement brands are the best: write directly to each manufacturer. I suggest you politely ask for a FULL DISCLOSURE OF ALL INGREDIENTS AND EXCIPIENTS IN EVERY NUTRITIONAL PRODUCT THE COMPANY SELLS. There is additional information and hints on how to form your letter in another paper of mine called "What's in the bottle? ...and how to find out." On this website, it is indexed as “VITAMIN LABELS.”

Copyright C 1999 and prior years W. Saul. From the books QUACK DOCTOR and PAPERBACK CLINIC, available from Dr. Saul, Number 8 Van Buren Street, Holley, New York 14470.

The Health of the Naturopath: Vitamin Supplementation and Psychologic State by E. Cheraskin, M.D., D.M.D.

Introduction It is generally agreed that aging is associated with impaired immune responses and increased infection-related morbidity. In 1992, an eminent immunologist from Newfoundland, Canada and s Hopkins assessed the effect of physiologic amounts of vitamins and trace elements on immunocompetence and occurrence of infection-related illness. (1) He assigned 96 independently living ambulatory, healthy elderly individuals to receive either routine daily maintenance vitamin supplementation or a placebo. Nutrient status and immunologic variables were assessed at baseline and at 12 months, and the frequency of illness due to infection was ascertained.

Subjects in the supplemented group had higher numbers of certain T-cell sub-sets and natural killer cells, enhanced proliferation response to mitogen, increased interleukin-2 production, and higher antibody response and natural killer cell activity. These subjects were less likely than those in the placebo group to have illness due to infections (23 versus 48 days per year).

He concluded that supplementation with a modest physiologic amount of micro-nutrients improved immunity and decreased the risk of infection in old age. In a subsequent double-blind, placebo-controlled study, 35 additional healthy, noninstitutionalized elderly subjects were once again supplied with multivitamin versus placebo supplementation. (2) Pike and Chandra note that giving micro-nutrients can play a crucial role in the maintenance of normal immune function in the elderly. This piece of work received very little attention because of its lack of drama. After all, these were just ordinary healthy elderly people given a simple multivitamin trace mineral tablet!

It is interesting, in light of these Newfoundland studies, that a recent USDA survey of food intake, reported only 1% of Americans meet the minimum standards for dietary adequacy. (3) A Naturopathic Study In a continuing study of male naturopaths (n=70) who are graduates of the Clayton College of Natural Health, we supplied them with the Cornell Medical Index Health Questionnaire (CMI). The CMI has been time tested by allopaths for approximately 50 years. It contains over 200 questions in informal language. The answers are expressed as A-L (organic findings) and M-R (psychologic symptoms and signs). One of the queries (#169 for males) asks the question, "Do you use vitamins regularly?" Our survey revealed that 87% of these men took a vitamin/mineral supplement on a daily basis.

Results Our study disclosed three additional findings. The total number of CMI complaints was not significantly different in those who did or did not take vitamins (21.0 versus 21.3). Secondly, the most statistically significant point was the total number of psychologic complaints in those who took vitamins daily (3.1) compared to those who did not (5.6). Specifically, those taking vitamins showed a reduction in inadequacy (.6 as against 1.4), depression (.2 in contrast to .4), sensitivity (.7 versus .9), anger (.5 balanced against 1.2) and tension (.5 compared to 1.0).

Discussion It is obvious that multivitamin/trace mineral supplementation alters psychologic state significantly. It is also apparent that there are other positive and negative lifestyles. For example, in answer to the question, "Do you get regular (daily) exercise?" 50 individuals, or 74%, responded affirmatively. These will be discussed in a later paper. (4) There are still other factors which enter into this picture. Some of the samples are too small to measure since very few of the naturopaths smoke, consume alcohol or drink coffee/tea.

Summary and Conclusions There are many positive and negative lifestyle factors to be considered. The Newfoundland group has shown the reduction in annual number of doctor visits (for infection) from 48 to 23 days by routine vitamin supplementation. For the first time, the Clayton group emphasizes the role of vitamins on psychologic state. Specifically, there is a reduction in inadequacy, depression, sensitivity, anger and tension. Other lifestyle characteristics will be pursued in papers to follow.

References Chandra RK: Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. The Lancet 1992; 340/8828:1124-1127.

Pike J, Chandra, RK: Effect of vitamin and trace element supplementation on immune indices in healthy elderly international J Vitamin Nutr Res, 1995;65/2 117-120.

(Editor) Do We Really Need to Eat Like a Horse to be as Healthy as One? National Nutritional Foods Association Newsletter 1998; 12/4:13.

Cheraskin, E. The Health of the Naturopath: Physical Activity. Manuscript in preparation. Natural Medicine Journal 1: #10, 12-15, December 1998

(Reprinted with permission of the author)

Vitamin Deficiency, Megadoses, and Some Supplemental History A letter by Kaufman, M.D., Ph.D. April 7,1992 (Reprinted with the kind permission of Charlotte Kaufman)

My attention has been called to the cover story on vitamins which appeared in the April 6,1992 Time magazine. Another major article on nutrition appeared in the March 10,1992 New York Times with the heading on page B5 "Vitamins Win Support as Potent Agents of Health" and on page B9 "New Support for Vitamins as Agents of Health." Both articles were probaby inspired by a New York Academy of Sciences meeting held in Arlington ,Virginia some weeks ago on the theme of Vitamins, Nutrition and Health.

I will comment on the Time magazine's feature article on Vitamins a little later. Now, I'll list the vitamins that were first available commercially from 1934 through 1940 from Merck & Co.. More than a half century ago I started to use these vitamins in the successful treatment of my patients who had a variety of health problems.

1934 Ascorbic Acid (vitamin C) 1937 Thiamine Hydrochloride (vitamin B 1) 1938 Nicotinic acid (niacin) 1938 Nicotinic acid amide (niacinamide) 1938 Riboflavin (vitamin B 2) 1940 Pyridoxine Hydijphlonde (vitamin B 6) 1940 Alpha-tocopherol (Vitamin E) 1940 Vitamin K I 1940 Menadione (Has strong vitamin K activity) 1940 Calcium pantothenate (vitamin B 5)

Vitamin A and D were available before 1934, Biotin in 1943, and Beta carotene, vitamin B 12, and folic acid soon thereafter.

Thus, none of these vitamins are "ny-come-lately's. In over a half century, a huge medical literature is available on the diagnosis of vitamin deficiencies and the safe therapeutic use of vitamins even when some were used in megadoses. Food as food and additional vitamins, macro- and micro-minerals supplements are often important factors in improving the health and well being of many millions of people in this country.

DIET First of all, food and water must serve as the basis for diets, nutrition and the support of life provided the food can be eaten by the person, then be digested, metabolized properly and used to run the machinery of life, supply needed energy and provide materials for cellular repair. However, it has never been proven scientifically with double blind controls that food and water alone can provide all the nutrients in amounts that will ensure optimal long term health to all individuals.

Humans display considerable biochemical individuality, and therefore there are also differences in nutritional needs for different people. A diet that is healthful for a non-allergic person, may make another person allergic to some of the components of such a diet quite ill. Individuals foods can vary greatly in their nutritional content at the time of purchase. Food tables will not dependably tell you the vitamin and mineral content of the food you are purchasing. Simply putting vinegar on a freshly cut cole slaw salad will cause a 53% loss of vitamin C content in an hour. Potatoes are a good source of vitamin C. But reconstituting dehydrated potato flakes to make mashed potatoes and keeping this on the steam table for an hour will eliminate all the vitamin C. Oranges and potatoes held in storage for many months before being sold to grocery stores will have a decreased nutritional value. Cooking foods in a conventional manner can cause considerable loss of both heat labile and heat stable vitamins as well as of minerals. A nutritionally important oil has been genetically engineered out of soybeans to decrease spoilage which simultaneously decreased this type of soybean's nutritional value.

Now that preservation of some foods by exposure to heavy doses of radiation is being allowed, it would not be surprising if these foods have their nutritional value diminished plus the possibility that some of the molecular changes in the foods caused by the radiation may engender toxic substances which over time might cause ill-health. Milling wheat to make white flour causes a 70 to 80% loss of vitamins and minerals which, despite the so-called current “enrichment,” leaves white bread inferior to whole wheat bread nutritionally because the loss of vitamin B6, vitamin E, chromium, manganese and fiber, all of which have not been corrected by additional supplementation.

DOCTORS WHO BELIEVE FOOD ALONE SUPPLIES ALL NUTRITIONAL NEEDS Doctors who believe that you can get all the nourishment including vitamins and minerals you need to sustain optimal health throughout life from food alone can be very smug. They have the equivalent of an orthodox religious belief: "food is everything." They don't have to concern themselves with the fact that the nutritional value of foods their patient eats may be greatly inferior to the listed nutritional values given in food tables. They don't have to concern themselves looking for evidences of malnutrition as long as the patient eats food that sustains his weight. The patient's diet may not include whole grains or organ meats, a diet that will cause the patient to have a chromium deficiency which deepens over time leading to important and potentially lethal forms of degenerative diseases which the "food is everything" doctor will mistakenly ascribe to aging alone These "food is everything" doctors don't have to trouble themselves with thinking about how a patient's health can be improved over the long term by providing him with the additional beneficial vitamins, macro- and micro- mineral supplements tailored to his actual nutritional needs.

During the early part of World War II, GI's whose severe wound infections were treated with penicillin had to save all their urine so that the penicillin which had been excreted in their urine could be recovered and then used to treat other GI's with life threatening wound infections. If one only considered the penicillin that was excreted in the urine and not the benefits that the GI had in having his infection cured by penicillin, one could sneer that penicillin's only function was to give the GI an expensive urine. If one considered only the function of penicillin in the GI's body, one would have to marvel at the miracle of its curing a potentially lethal infection,

The two-liner attributed to Dr. Victor Herbert in the Time magazine's vitamin article "We get all the vitamins we need in our diets. Taking supplements only gives you an expensive urine" completely overlooks the benefits vitamin supplements can produce in our bodies before being excreted in our urine.

MOST DOCTORS ARE NUTRITIONALLY ILLITERATE The subject of nutrition is not taught well in most medical schools. Thus, medical students, residents, doctors, and medical faculty may not even be able to recognize classic vitamin deficiencies. The University of Alabama's Dr. Butterworth referred to in the Time magazine article on vitamins, was a guest lecturer at Yale University School of Medicine some twenty years ago when I attended his lecture. During his talk on the nutrition of surgical patients, Dr. Butterworth showed a large number of color slides of a patient who had classic pellagra and of another patient who had classic scurvy. Not a single medical student, resident, dietician or faculty member attending the lecture was able to make the correct diagnosis. If doctors fail to recognize classic vitamin these afflicted patients cannot receive prompt life-saving vitamin treatment. But even worse, medical students are not taught to recognize the enormously prevalent non-classic vitamin deficiency (and micro- and macro-mineral deficiency) disorders which impair the health and well being of many millions of Americans. Unless such conditions are recognized, they cannot receive "curative" treatment. Furthermore, such undiagnosed non-classic vitamin (and mineral) deficiency patients instead of being given the "curative" vitamins (and minerals) they need, they often are given drugs which they do not need Thus, in addition to unneeded pharmacologic effects, they are also exposed to the drugs' health reducing side-effects.

In 1992, what do United States medical schools teach medical students about nutrition? n Burros in her column entitled "EATING WELL" which appeared in the April 1,1992 New York Times gives a stunning answer to this question.

"Only about one third of the 125 or so medical schools require students to take courses in nutrition. And, most of the courses are short. The one at Cornell is eight hours...." "The University of Alabama at Birmingham in one of the exceptions requiring 52 hours of nutrition education for its medical students."... "The remaining two thirds of this country's medical schools only offer elective courses. (Editor's note: Professor Emanuel Cheraskin, M.D., D.M.D., is another one of the persons we can thank for the superior nutrition program at the U. of Alabama at Birmingham.)

"Nutrition, of course is laced through the many departments in medical school--physiology, gastroenterology, cardiology, biochemistry. But students do not necessarily recognize that it can be applied to preventive medicine. ... Dr. Young said "All studies show that if information is not taught as nutrition but is incorporated into other courses, students come away not knowing that it is nutrition. They think of it as physiology or whatever and so they do not use it in terms of practical applications of preventive medical care.”... In a recent survey conducted in the southeastern region of the United States in 1986, eighty-five percent of the medical students were dissatisfied with the amount of medical nutrition education and sixty percent were dissatisfied with the quality

"Without question," Dr. Weinsier said, "A greater awareness and knowledge (of nutrition) among physicians could well impact on the prevalence of disease...”

Is it any wonder that most doctors are nutritional illiterates? Is it any wonder why doctors who are nutritional illiterates, often hide their lack of nutritional knowledge under the aegis "food provides all the nutrition a person will ever need"?

For the last half century, there have been recommendations that nutrition should be taught in medical schools as a required course. Currently, experts suggest that all medical schools should devote at least 40 hours to teaching medical students nutrition.

LINUS PAULING I have had an "off and on" correspondence with Dr. Linus ing for several decades. He has referred to my use of niacinamide in the treatment of arthritis in some of his publications on nutrition. Some years ago, ing's foundation invited me to come to California to work with Dr. ing on cancer research. Unfortunately, at that time I could not make such a move.

I think the three reporters who made the denigrating statement in the Time Magazine's Vitamin article "Certainly Linus ing lost much of his Nobel-Laureate luster when he began championing Vitamin C back in the 1970's as a panacea for everything from the common cold to cancer" were very remiss in not first reading and then calling attention in their article to the important government sponsored meeting which resulted in the following report:

SPECIAL COMMUNICATION: VITAMIN C: BIOLOGIC FUNCTIONS AND RELATION TO CANCER. SPONSORED BY NATIONAL CANCER INSTITUTE AND NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES. SEPTEMBER 10-12,1990, BETHESDA, MARYLAND

"(T)here has been considerable public interest in the possibility of a role of this vitamin (vitamin C) in cancer. In order that this debate might take place in a rigorous and informed manner, we attempted to bring together not only the latest research on basic actions, such as free-radical scavenging or enzyme functions, but also some of the basic laboratory and animal studies relating to cancer

"The well known anti-oxidant and free-radical scavenging activities (of vitamin C) are discussed in the first series of papers. Because free-radical damage and formation of lipid peroxides are suspected in carcinogenesis as well as cardiovascular disease, this (vitamin C) may be important for disease prevention

"Approximately half of the symposium addressed the role of ascorbate in cancer prevention or as adjuvant in cancer therapy, primarily in animal models. In vitro studies included research on oncogenic transformations and effects on the HIV virus. Moreover, several researchers presented data that suggest a role for ascorbate in reducing the toxicity or improving the effectiveness of conventional (anti-cancer) therapies. Finally, a review is presented of all human epidemiologic studies between vitamin C and cancer prevention."

Here are a few statement's taken from Gladys Block's abstract, EPIDEMIOLOGIC DATA ON THE ROLE OF ASCORBIC ACID IN CANCER PREVENTION".

"Approximately three-fourths of the epidemiological studies (33 of 46) of the role of vitamin C in cancer incidence or mortality have found statistically significant protection effects…The evidence for a protective effect of vitamin C or some component of fruits is strong and consistent for cancers of the esophagus, larynx, oral cavity and pancreas and there is strong evidence for cancers of the stomach and cervix….A major meta-analysis of breast cancer studies suggests a significant protective role for vitamin C in that cancer as well. While it is likely that ascorbic acid, carotenoids, folate, and other factors in fruits and vegetables act jointly, an increasingly important role for ascorbic acid (Vitamin C) in cancer prevention would appear to be emerging."

I cannot take the time to note all the titles of abstracts that indicate vitamin C inhibits the growth of cancer. However, to give you the flavor, I will cite just three:

(1) INHIBITING EFFECT OF ASCORBIC ACID. ON THE GROWTH OF HUMAN MAMMARY TUMOR XENOGRAFTS IN MICE,

(2) INHIBITION BY VITAMIN C OF INCIDENCE AND SEVERITY OF RENAL TUMORS INDUCED BY ESTRADIOL OR DI ETHYLSTI LBESTEROL

(3) REDUCED INCIDENCE AND TUMOR BURDEN IN SPONTANEOUS MOUSE MAMMARY TUMORS AND UV--INDUCED TUMORS WITH INCREASING ASCORBIC ACID.

Thus, Linus ing's view that Vitamin C has important anti-cancer properties is gaining substantial support in current laboratory and animal experiments. Where are the people who formerly ridiculed his ideas that vitamin C has anti-cancer actions?

A word about Vitamin C for colds: In the early 1940's, the health service of one of a mid-west University prescribed vitamin C to relieve students' nasal congestion associated with colds. Although Charlotte and I go decades without having colds, we have used 250 milligram doses of vitamin C to decongested our nasal membranes when these get congested from a variety of allergies. However, this effect of vitamin C has a short half-life. Thus, it needs to be given at one and a half to two hour intervals during the day and upon awakening during the night. This keeps the nasal membranes decongested, reduces pain and discomfort and prevents sinusitis. Usually, in 24 hours there is no further need to take vitamin C in this manner.

THE FDA The Time magazine article points out that the FDA are planning to destroy the RDA (Recommend Daily Allowance) system as a practical guide to the amounts of various nutrients that would be required to provide decent nutrition to infants, children and adolescents, adult males of different ages, women of different ages, pregnant and lactating women. According to the article in Time magazine, the FDA plans replacing the RDA system with the so-called Reference Daily Intake.

The RDI system proposes to ignore the RDA's for different age groups and sexes. ,,"Instead of endorsing an allotment appropriate to ravenousm fast growing teenage males, it would simply average the RDA's for different age groups. The new figures are considerably lower, and are a better barometer nutritional needs. Essentially the reflect the requirements of adult women.", This new system the FDA have created slashes the RDA's of Vitamin A, B's, C E and other nutrients from 10 to 80%. This will allow food manufacturers to put food products on the market legally that are much less nutritious than the ones that now have to conform to the RDA system.

There is already an enormous amount of malnutrition in this country because the large population of the poor cannot afford decent nutrition and much of their ill-health and lack of initiative is based on such malnutrition. The FDA will worsen this situation with its reduction of the RDA's.

One of the very important documents in the field of nutrition, is the Bulletin of the National Research Council Number 109 November 1943 "INADEQUTE DIETS AND NUTRITIONAL DEFICIENCIES IN THE UNITED STATES, THEIR PREVALENCE AND SIGNIFICANCE," published by the National Research Council, National Academy of sciences, Washington, D.C. This was the "REPORT OF THE COMMITTEE ON DIAGNOSIS AND PATHOLOGY OF NUTRITIONAL DEFICIENCIES. FOOD AND NUTRITION BOARD.

Its conclusions and recommendations are just as applicable to today's widespread malnutrition as they were when this report was issued

Items taken from the Summary and Conclusions of this Report:

"All the evidence from numerous surveys over the past ten years to the present among persons of all ages in many localities is without exception in complete agreement that inadequate diets are widespread in the nation. Although an appreciable percentage of diets failing to meet the Council's recommended dietary allowances were more than 50 percent deficient in amounts of several essential nutriments, most of the diets were less than 50 percent deficient. Accordingly, there is widespread prevalence of moderately deficient diets.

"All the data from numerous surveys with new methods among persons of all ages in many regions are entirely in accord in showing that deficiency states are rife throughout the nation. Relatively few are the traditional severe acute types, Most are milder in intensity and gradual in their course. Predominantly they are subacute or chronic states: some marked, but very many mild or moderate..."

"From this evidence it is clear that there is both a preventive and corrective problem. On the preventive side, it is evident that production of sufficient food should be maintained and that effective distribution of proper food is needed. For the latter, it would seem advisable to give further consideration to the program of judicious enrichment of appropriate foods since this would add much to the guarantee of successful nutrition. It is also evident that diet education must be intensified and extended to the utmost and raised to new heights of effectiveness."...

"On the corrective side, there is need for detection and therapeutic treatment of deficiency states among the population. For this project it is necessary to disseminate the new diagnostic methods among the medical and public health professions. Foremost among the steps in this direction would be (1) preparation of a handbook on methods of detecting deficiency states (2) establishment of training centers for instruction in the medical aspects of nutrition, especially the diagnosis of deficiency states; and, (3) introduction of adequate courses in nutrition, particularly its clinical aspects, into medical schools."

The conditions that existed nutritionally in the 1930's and early 1940's are just about the same as exist now in the working poor, in those on public assistance and even in those better off economically. The suggestions made about the need for prevention and curative measures are just as needed today as they were in the 1930's and 1940's.. So is the need for adequate instruction in nutrition for every medical student in every medical school. So is proper nutritional enrichment of foods.

What the FDA is planning to destroy the RDA system of nutritional standards and substituting an illogical system, RDI (Reference Daily Intake) that promotes a severe reduction of nutritional standards in a manner which if followed would ensure a great increase in nutritional deficiencies in the population of the United States.

What is astonishing in the Time magazine article is that leaders in nutrition make such statements "The long term effects of high-dose supplements are still unknown and doctors warn of dangers even in the short term….Advises Dr. Walter Willett of the Harvard School of Pubic Health: "At this time I don't take megadoses, I'm not ruling out that in two or three years we might change our mind."

What has been known for more than a half century is that vitamins even in properly chosen megadoses (and macro- and micro-mineral supplements can greatly improve the long term health and well-being of many persons eating their ordinary diets. Some of these older observations that vitamins can improve health are just being rediscovered as if they were brand new scientific findings The rediscovery of old and proven observations can't believe their own findings, They call their conclusions tentative, and seem afraid of recommending vitamin megadoses that should be widely be used in nutritional treatment.

If doctors want to know the long term effects of various vitamin megadoses, they have to go back and study the literature. Since most articles and books on this subject cannot be found by electronic means, it requires that they make such a literature search manually,

The FDA's rejection of the three nutritional applications (which proposed to use vitamins to treat disease) as being premature also is part of the anti-nutritional bias. Just think: if a nutritional approach would delay myocardial infarctions by ten or fifteen years. Would not this be crippling blow to the profits of pharmaceutical companies that produce cardiac medications and cholesterol reducing agents?

(My wife) Charlotte and I have taken megadoses of vitamins (and appropriate amounts of macro-and micro-minerals). The fact that we are alive today is attributable to the beneficial effects of this nutritional supplementation. Dr. Linus ing has taken megadoses of vitamin C for decades.

One fascinating thing is that from 2 to 5% of all hospital admissions result from severe adverse effects from prescription drugs. Yet, doctors have no compunction in prescribing these.

VITAMIN D SUPPLEMENTATION IN THE FIGHT AGAINST MULTIPLE SCLEROSIS

Ashton F. Embry

INTRODUCTION

Many different supplements are recommended for people with MS and it is worthwhile to examine the science and logic behind any given supplement recommendation. Vitamin D, the sunshine vitamin, is not often strongly advocated for MS, although small dosages (~200-400 IU) are usually part of a total vitamin recommendation. I have recently read a number of papers on the relationship between vitamin D and MS and the best summary of this topic is by et al (1997). This information has convinced me that persons with MS could possibly significantly benefit from a substantially higher supplementation of vitamin D than is currently proposed in various self help books (e.g. Graham, 1989) or suggested by clinicians.

In this essay I will present a brief discussion of vitamin D and follow that with the scientific evidence which supports the concept that vitamin D likely plays an important role in controlling autoimmunity and MS. Such evidence consists of epidemiological data, animal experiments, immunological analyses, genetics and the results of small clinical trials which used vitamin D or a metabolite as the therapeutic agent. When all the data are considered as a whole, it becomes apparent that adequate supplementation of vitamin D may well be beneficial and, given the very low cost and safety of such a therapy, persons with MS might want to make sure they are receiving sufficient amounts each day.

The key questions of, how much vitamin D is needed, is this amount safe and how can one best obtain this amount, are also addressed. Vitamin D is a fat- soluble vitamin and can be toxic in large dosages. Thus it is very important to examine current data in regards to vitamin D safety and reasonable sources of the vitamin. In the final part of the essay, vitamin D intake is examined in an evolutionary perspective and a summary on how vitamin D fits in the overall "Paleolithic Prescription" for MS concludes the essay.

VITAMIN D

A detailed discussion of the chemistry of vitamin D is far beyond my capabilities and the scope of this essay. For those wanting such information, DeLuca and Zierold (1998) provide a very good overview of the chemistry of vitamin D and its receptor. A few points are worth mentioning to help one gain an appreciation of what vitamin D is, how it is activated in the body, and the role it plays in health and illness. The primary source of this nutrient is not from diet but rather from a chemical photolysis reaction in the skin. When UV light from the sun penetrates the epidermis, it is absorbed by a metabolite of cholesterol (7-dehyrocholestrol) which is then converted into vitamin D (calciferol). Notably Vitamin D is biologically inert and is metabolized in the liver to produce 25(OH)D (calcidiol) which is the main form of circulating vitamin D. Although this substance is also inactive, its concentration in the blood provides a good assessment of a person's vitamin D level and the relationship of various levels of 25(OH)D to health will be discussed later. The final step in the vitamin D story is that 25(OH)D is converted to an active hormone, 1,25(OH)2D (calcitriol), in the kidneys.

The main role of vitamin D, through the actions of its metabolized hormone, calcitriol, is to regulate the amount of calcium and phosphorous in circulation. In this way it has a major impact on bone growth or lack thereof (rickets, osteoporosis) and, when most people think of vitamin D, they think of it in this context. When calcium levels are low (usually due to insufficient vitamin D and calcium intake), the body activates the parathyroid gland, which produces PTH (parathyroid hormone). This hormone kicks starts vitamin D hormone production and helps to remove calcium from the bones to be used in more important functions. Thus a measurement of PTH also provides a good proxy for vitamin D levels in circulation. When adequate vitamin D is available there is generally no need for the body to produce PTH and serum levels of this hormone are negligible.

As will be discussed below, recent research has uncovered more roles for vitamin D besides calcium regulation. The most relevant of these functions is as an immune regulator which has obvious implications for its putative role in MS and other autoimmune diseases.

SCIENTIFIC DATA RELATING VITAMIN D TO MS

Goldberg (1974a, 1974b) first proposed the concept that vitamin D was an important factor in MS. He marshalled a variety of epidemiological data to make a case for vitamin D being a factor in the onset and progression of MS. Goldberg emphasized the conspicuous high prevalence of MS in areas which receive a relatively low amount of sunlight. Acheson et al (1960) had earlier documented this relationship between MS prevalence and sunlight with a very impressive negative correlation between MS prevalence and hours of sunshine. Goldberg (1974a) took the next step and postulated that such a close correspondence between low sunlight and MS was due to low vitamin D production in the population. Goldberg (1974a) also showed that within areas of low sunlight (e.g. Norway) differences in MS prevalence could be explained by dietary factors which affect vitamin D production. Such factors include the amount of fish eaten (increases vitamin D) and the amount of grains consumed (reduces vitamin D levels due to the action of phytates). To explain how vitamin D levels were related to MS, Goldberg (1974b) proposed that genetically susceptible individuals may need larger than normal amounts of vitamin D during myelin formation and that insufficient vitamin D during childhood might result in defective myelin which would be susceptible to breakdown in later life. Goldberg's ideas were completely ignored by medical researchers, although, as will be discussed later, he was able to organize a small clinical trial to test his concept.

Goldberg's innovative hypothesis that vitamin D is a key factor in the development of MS and for explaining the distinctive geographic variations in MS prevalence is just as attractive today as it was 26 years ago. Science started to catch up with Goldberg in the early 80s with the recognition that immune cells carry a receptor for the active hormone of vitamin D (1,25-(OH)2D) and that this hormone likely regulates immune functions (Bhalla et al, 1983).

This discovery led to ongoing research efforts which continue to uncover a number of important ways in which vitamin D hormone affects the immune system. One area of research in this regard was a number of experimental studies with mice and rats which are genetically susceptible to animal forms of autoimmune disease such as EAE (closely resembles MS). These studies showed that injections of vitamin D hormone could protect against or arrest the animal forms of MS (Lemire and Archer, 1991; Cantorna et al, 1996), type 1 diabetes (Mathieu et al, 1994), rheumatoid arthritis (Cantorna et al, 1998a) and lupus (Lemire et al, 1992). Furthermore, immunological analyses done in conjunction with these experiments revealed the following immune-regulating actions for vitamin D hormone:

Suppresses antibody production by B cells and the proliferation of T cells in the thymus (Yang et al, 1993).

Upregulates cytokines TGF-beta and IL-4. These proteins, which are produced by immune cells, act as suppressants of inflammatory T cells (Cantorna et al, 1998b).

Inhibits production of pro-inflammatory cytokines such as IL-1, IL-2, TNF and IFN gamma (Muller and Bendtzen, 1996) which also reduces inflamammatory reactions.

Interferes with T helper function and inhibits the passive transfer of cellular immunity by Th in vivo (set, 1994)

Inhibits the production of NO (nitric oxide) by immune cells (Garrion et al, 1997). NO has been identified as one of the most destructive products of the immune system and is an important factor in demyelination.

Inhibits the proliferation of activated and memory T cells (Muller and Bendtzen, 1992). Such cells are the main mediators of the inflammatory autoimmune reactions of MS.

Exerts immunomodulating effects in the CNS by inducing a profound downregulation of antigen _expression by both infiltrating and resident antigen presenting cells (e.g. macrophages) (Nataf et al, 1996).

In summary, vitamin D hormone has numerous effects on the immune system and acts within the CNS. All of these effects have the combined result of significantly reducing inflammatory autoimmune reactions from occurring and they readily explain why vitamin D hormone is so effective in suppressing a variety of animal autoimmune diseases including EAE (animal MS) ( et al, 1997).

On the basis of the impressive immunomodulating effects of vitamin D, Schwartz (1993) hypothesized that the well established reduction of MS attacks during pregnancy and their increased occurrence following pregnancy was due in part or whole to the natural large increases in production of vitamin D hormone during pregnancy and its rapid decline afterwards. Such a hypothesis seems very plausible and hopefully will be followed up.

Genetic data also implicate vitamin D in MS and Fukazawa et al (1999) demonstrated an association between vitamin D receptor genes and MS.

Vitamin D has been used as a therapeutic agent in only a few small clinical trials. Notably Goldberg helped to organize a small trial in the early 80s (Goldberg et al, 1986). Ten subjects took 5000 IU/day of vitamin D along with about 1000mg of Ca and 600mg of Mg for two years. The subjects acted as their own controls with the exacerbation rates during the trial compared with the subjects' historical rates of exacerbation. A notable decline in exacerbation rate was noted, although the small size of the trial makes the results equivocal. Despite these results and all the scientific data showing that vitamin D would be a good therapeutic agent, no follow-up, better controlled trials have ever been done for vitamin D and MS.

A small clinical trial for RA and a vitamin D metabolite was recently done by Andjelkovic et al (1999) over a three-month time period. The results were positive: "Therapy showed a positive effect on disease activity in 89% of the patients (45% with complete remission and 45% with a satisfactory effect). Only two patients (11%) showed no improvement, but no new symptoms occurred". Another relevant study was a large-scale investigation of the effects of vitamin D supplementation in infants and the associated risk of type 1 diabetes (Eurodiab Study Group, 1999). This study clearly demonstrated that supplementation with vitamin D was associated with a decreased risk of type 1 diabetes.

In summary, a variety of data, from epidemiology, animal experiments, immunological investigations, genetics and small clinical trials indicates that vitamin D can have a suppressant effect on autoimmune reactions and help to slow autoimmune disease. Thus its use as a supplement by persons with MS or other similar autoimmune diseases, such as rheumatoid arthritis and Crohn's, seems warranted.

SUPPLEMENTATION AND SAFETY

The above scientific data suggest that it is important for persons with cell-mediated autoimmune diseases, including MS, to have sufficient intake of vitamin D. In this section the questions of, how much, where to get it and is it safe, are addressed. The best reference for the answers to these questions is a recent, comprehensive review by Vieth (1999) entitled "Vitamin D Supplementation, 25-hydroxyvitamin D concentrations and Safety". The answers to the above questions are provided in this excellent paper and readers wanting more information than provided below are referred to it.

On the question of how much, Vieth (1999) first notes that humans evolved having a relatively large intake of vitamin D, with a naked human in Africa likely getting at least 10000 IU a day. He then reviews all the literature on intake of vitamin D and resultant levels of 25(OH)D and PTH. The key here is that when adequate levels of 25(OH)D (an intermediate metabolite of vitamin D) are circulating there is no need for the body to produce PTH (parathyroid hormone). On the basis of all the available data, Vieth (1999) concludes that it is desirable to have 100-125 nmol/litre of 25(OH)D in circulation. Furthermore, he notes, that to achieve this amount, an intake of about 4000 IU of vitamin D a day is required. As described earlier, the main source of vitamin D is the sun and in hot climates (south of 40 N) such an intake is readily possible if an individual spends a reasonable time in the sun. However, in colder climates, like those of Canada, northern USA and northwest Europe, it is almost impossible to average 4000 IU a day because for at least six months of the year intake from the sun is negligible at best. Even during the few hot summer months an individual would have to spend considerable time in the sun to achieve the required intake.

Thus in areas of low sunlight, supplements provide a reasonable alternative for vitamin D intake. As Vieth (1999) notes "From what is known now, there is no practical difference whether vitamin D is acquired from ultraviolet exposed skin of through diet". Cod liver oil, fish and vitamin D fortified foods are the usual dietary sources used to get vitamin D. However these sources usually supply much less than 1000 IU/day and the fortified foods provide a synthetic form of vitamin D (D2) which is substantially inferior to the natural vitamin D3 (Trang et al,1998). Furthermore, because cod liver oil also contains large amounts of vitamin A, it would not be feasible to get 4000 IU of vitamin D from it because of potential problems with too much vitamin A. Fortunately there are specific vitamin D3 supplements which are usually small 1000 IU pills and a bottle of 100 costs less than $10 ($5 CDN in Calgary). This would seem to be the most reasonable source of 4000 IU a day.

Vieth (1999) also addresses the safety issue of vitamin D at length. He shows that the "no observed adverse effect level (NOAEL)" is at least 10,000 IU/day. The lowest observed adverse effect level (LAOEL) is 40,000 IU/day. Thus 10,000 IU/day is definitely safe (assuming no hypersensitivity) and 40,000 IU/day is definitely a problem. It would be next to impossible for anyone living in a northern area to get too much vitamin D from sunlight and a 4000 IU supplement. Thus such a supplementation level is safe for anyone who is not hypersensitive to vitamin D.

It must be stressed that adequate calcium and magnesium intake must accompany vitamin D supplementation as discussed by Goldberg et al (1986). Cantorna et al (1999) recently demonstrated that calcium levels strongly affect the action of vitamin D for suppressing EAE in mice. Calcium intake should be in the range of 600-900 mg/day with magnesium intake being about the same as this.

In summary, a daily intake of vitamin D of 4000 IU along with 800 mg of both calcium and magnesium are required for adequate levels of metabolized vitamin D products to be maintained in circulation. For those in low sunlight climates, such a vitamin D intake is most easily achieved with a daily supplement of 4000 IU of a vitamin D3 product.

VITAMIN D IN A PALEOLITHIC PERSPECTIVE

Eaton and Konner (1985) hypothesized that, with the advent of agriculture and the subsequent industrial and technological revolutions, consequent changes in dietary habits and major shifts in the intake of various nutrients have adversely affected human health. They suggest that these major changes are in part responsible for a myriad of "genetic-environmental" diseases including heart disease, stroke, type 2 diabetes and various forms of cancer. As discussed in Cordain (1999) and Cordain et al (in press), this concept can be readily applied to autoimmune diseases. In this context it is useful to examine changes in vitamin D intake during the two million year evolution of human beings and how such changes are related to the rise of MS.

Humans lived in hot climates throughout most of their development and thus they experienced a relatively large intake of vitamin D from sunlight. Natural selection would have ensured that the human genome became very compatible with such an intake, estimated to be in the range of 10000 IU a day. This would have resulted in circulating concentrations of 25(OH)D of between 100 and 140 nmol/litre which can regarded as the optimal level of vitamin D. Such a concentration supplied all the vitamin D hormone required for a variety of functions including the maintenance of a strong skeletal structure and the control of autoimmune reactions induced by foreign antigens derived mainly from infectious agents. The importance of adequate vitamin D for human health is underscored by the fact that evolution produced a very simple and seemingly fail-safe method for its attainment.

As humans migrated out of Africa into temperate areas, less sun-derived vitamin D became available and daily intakes likely fell somewhat. However, because long periods were spent outside hunting and gathering, most Paleolithic people still obtained sufficient vitamin D (>4000 IU/day) and readily maintained an adequate serum concentration of 25(OH)D throughout the year.

With the advent of agriculture about 8000 years ago and the ensuing population explosion, maintaining adequate levels of vitamin D and its metabolites started to become a problem for the first time in human history. Population pressures forced humans to migrate into even more hostile areas in terms of cold climates and low sunlight. They also tended to eat less fish and spend much more time out of the sun. Significantly, two of the main foods of agriculture have an adverse effect on the action of vitamin D. Grains, which are the number one food of agriculture, contain phytate or phytic acid which counters the action of vitamin D (Willis and Fairney, 1972). Cordain (1999) also discusses the role of grain consumption in vitamin D deficiency. Goldberg (1974a) raised this point and showed that areas where grains were grown in Norway tended to have the highest rates of MS. Notably, the only common grain with a very low phytate content is rice.

Another food introduced into the human diet by agriculture is milk. Milk may also have an adverse effect on vitamin D by affecting the vitamin D receptor on cells. -Maceda et al (1991) demonstrated that part of the bovine albumin protein of milk is a molecular mimic of the vitamin D receptor. Thus an immune reaction against that milk protein can potentially result in an autoimmune reaction against the vitamin D receptor. This would significantly lower the effectiveness of vitamin D hormone to bind with a variety of cells (including immune cells) and carry out its important functions.

Our modern lifestyle has only exacerbated the problem of vitamin D deficiency and large populations now inhabit low annual sunlight areas. The consumption of fish is very low in many agricultural areas where diets are completely dominated by high phytate, gluten grains and dairy products. A dominance of indoor jobs, fears of skin cancer and the use of sunscreens have reduced exposure times to sunlight further such that, even in summer, many people do not get anywhere near the required vitamin D intake from sunlight. Thus it would appear that chronic vitamin D deficiency (<100nmol/litre of 25(OH)D) in large populations which live in low sunlight climates is a Neolithic problem and is caused by a variety of lifestyles factors which greatly differ from those of the Paleolithic when adequate vitamin D was readily obtained.

Notably persons with MS tend to be at the problematic end of the deficiency spectrum (<50 nmol/litre 25(OH)D). The reasons for this higher than normal deficiency is likely multifold and includes the tendency for persons with MS to spend less time outside doing various laborious or sporting activities, the use of steroidal drugs in treatment, diets with an abundance of grains and milk and no encouragement from their doctors or MS societies to take sufficient vitamin D supplements. A study of 80 persons with MS by Nieves et al (1994) revealed a mean level of 25(OH)D of only 43 nmol/litre with a quarter of the subjects " having frank vitamin D deficiency (<25nmol/l). Not surprisingly the bone mineral density of most of the subjects was very low. Sadly, this study indicates that many people with MS likely do not have enough vitamin D intake to maintain their bones let alone to counter autoimmune reactions. A more recent study by Cosman et al (1998) supported the findings of Nieves et al (1994).

With both the general Paleolithic perspective and the documented low levels of vitamin D in persons with MS in mind, it is worth discussing the role vitamin D plays in the overall development of MS. First of all it is important to differentiate between autoimmunity and autoimmune disease. Autoimmunity is the production of immune cells which are autoaggressive and such a phenonomen has most probably been present throughout human development. It is well established that autoaggressive immune cells are produced during infections (Matzinger, 1998) and the reason for this is that the body must maintain a vast repertoire of immune cells to ensure protection against a huge number of pathogens. Thus the common occurrence of cross-reactive immune cells which react against both foreign and self-antigens represents an evolved compromise between maximum protection against foreign invaders and maximum protection against autoimmunity. Through the actions of the suppressor side of the immune system, evolution has also ensured that the sporadic production of autoaggressive immune cells due to random infections would not go unchecked and result in uncontrolled autoimmunity. Such runaway autoimmunity is called autoimmune disease. Thus, although autoimmunity has always been with us, autoimmune disease is likely a relatively new phenonomen in human development and is due to a relatively recent loss of control (suppression) of sporadically produced autoaggresive immune cells by a portion of the population.

The best explanation for the recent rise in autoimmune disease is that new environmental agents have upset the delicate balance between the production and suppression of autoaggressive immune cells either by increasing autoimmune reactions or by hindering the control of such reactions. When the balance tips towards increased autoimmune reactions and/or decreased suppression, autoimmunity can progress to autoimmune disease. The profoundly different dietary regimen, which began with the adoption of agriculture, is one obvious source of such new, immune-disruptive agents. The Paleolithic diet was dominated by fruits, vegetables and lean wild meats which had a low saturated fat content. The main foods "recently" introduced by agriculture are grains (i.e. grass seed), dairy products and meat from domesticated animals which has a very high saturated fat content. As discussed in detail by Cordain (1999) and Cordain et al (in press), it would appear that proteins from various foods introduced by the Neolithic agricultural revolution (e.g. gluten, dairy, legumes) result in autoimmune reactions mainly by increasing intestinal permeability and by mimicking infectious and self-antigens. The great increase in the consumption of saturated fat also contributes to an increase in inflammatory reactions (Fraser et al, 1999).

Such food-driven autoimmune reactions, although of relatively low magnitude in comparison with infection-driven autoimmune reactions, occur almost on a daily basis. They have a significant cumulative effect and thus recently introduced foods are clearly suitable candidates for the agents which result in harmless autoimmunity becoming problematic autoimmune disease in genetically susceptible persons.

This increase in Neolithic dietary elements that contribute to autoimmune reactions is matched by a notable decrease during the Neolithic of nutrients that play a significant role in the suppression of autoimmune reactions. These suppression-inducing nutrients include both omega 3 fats (fish oil) (Calder, 1998 ) and vitamin D (references herein). Thus the newly adopted dietary habits of agriculture promote autoimmune disease both by increasing autoimmune reactions and by lessening anti-inflammatory responses. Not surprisingly, MS and other autoimmune diseases are most common in areas where the dietary regimen contains a dominance of pro-inflammatory food types and a paucity of anti-inflammatory nutrients. The common deficiency of vitamin D is just one of numerous Neolithic nutritional factors which, in combination with the ever present infectious agents, result in a variety of autoimmune diseases in these areas. Consequently, it is just one of a number of factors which must be reversed if one hopes to successfully combat an autoimmune disease.

As discussed above, it appears the best method of reversing vitamin D deficiency is to use a supplement of 4000 IU which will result in optimal levels of vitamin D metabolites. This in turn should result in increased suppression of autoimmune reactions precipitated by food and infectious agents and help to turn the tide against uncontrolled autoimmunity. It seems only reasonable that a person's best hope of controlling an autoimmune disease is to reverse as many of the adverse Neolithic influences, including vitamin D deficiency, as possible.

SUMMARY

An abundance of scientific evidence indicates that vitamin D deficiency is associated with MS onset and progression. Such evidence includes epidemiology which demonstrates that high prevalence rates of MS closely track areas of low intake of vitamin D. Animal experiments reveal that vitamin D hormone can suppress a variety of animal autoimmune diseases including EAE, the animal equivalent of MS. Furthermore, associated immunological studies have shown that vitamin D hormone has a number of immunomodulating functions, all of which contribute to the suppression of inflammatory autoimmune reactions. Small clinical trials have suggested that vitamin D has some efficacy in slowing autoimmune disease progression although no properly controlled trials have been conducted.

Vitamin D can be readily attained from exposure to sunlight and studies have shown that the optimal intake of vitamin D is about 4000- 6000 IU a day. This results in a circulation concentration of 25(OH)D ( a vitamin D metabolite) of 100-125 nmol/litre and this level seems to be required for the proper functioning of all vitamin D-dependent systems. In colder, low sunlight areas such an intake from the sun is impossible for most of the year and it is important to use supplements to makeup the shortfall in vitamin D supply. Currently suggested supplement levels of 200-400 IU are much too low. A daily supplement of 4000 IU of vitamin D3 seems warranted for people who do not get a lot of exposure to sunlight throughout the year. This amount is well below the no observed adverse effect level which is conservatively placed at 10000 IU/day and thus such supplementation is safe for anyone who is not hypersensitive to vitamin D.

Throughout most of the two million years of human development, humans had a relatively high intake of vitamin D (~5000-10,000 IU/day) from the sun. Major environmental changes brought on by the agricultural, industrial and technological revolutions have resulted in large populations in northern climates experiencing a subclinical and chronic vitamin D deficiency and this deficiency is more pronounced in persons with MS. Vitamin D deficiency is just one of a number of nutrient-related factors which play a role in MS. Notably the dietary regimens which contain the most pro-inflammatory food types (e.g. gluten, dairy, saturated fat) and the least anti-inflammatory nutrients ( vitamin D, omega 3 fats) occur in areas in which MS and other autoimmune diseases are most common. To combat MS, a person must change their lifestyle with diet revision being perhaps the most useful modification. As part of this change, it is important to ensure that sufficient vitamin D (4000 IU/day) is acquired through sun exposure and supplements.

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MONDAY, Jan. 12 (HealthDayNews) -- Vitamin D supplements may greatly lower a woman's risk of multiple sclerosis (MS), contends a study in the Jan. 13 issue of Neurology.

The study found women who take vitamin D supplements through multivitamins are 40 percent less likely to develop MS than women who don't take supplements.

"These results need to be confirmed with additional research, but it's exciting to think that something as simple as taking a multivitamin could reduce your risk of developing MS," study author Kassandra Munger, of the Harvard School of Public Health, says in a prepared statement.

She and her colleagues examined data from two large studies that examined women's diets and their use of multivitamin supplements. Women with the highest intake of vitamin D from supplements (400 International Units or more per day) were 40 percent less likely to develop MS than those who took no supplements.

Women who had a high intake of vitamin D from food and supplements also had a lower risk of developing MS. But women who relied solely on food for their intake of vitamin D did not have a lower risk of developing the disease.

Vitamin D May Prevent MS

Dosage Found in Multivitamins Reduces Risk by 40%

By Sid KirchheimerWebMD Medical News

Reviewed By Brunilda Nazario, MDon Monday, January 12, 2004

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Jan. 12, 2004 -- Evidence continues to mount showing that a little vitamin D can do a lot of good. The latest: A new study indicating that women who get doses typically found in daily multivitamin supplements -- of at least 400 international units -- are 40% less likely to develop multiple sclerosis compared with those not taking over-the-counter supplements.

This finding, by a team of Harvard researchers and published in this week's issue of Neurology, comes just a few days after another study links vitamin D deficiency with an increased risk of rheumatoid arthritis. Like MS, rheumatoid arthritis is an autoimmune disorder, a classification for some 80 different ailments in which the immune system mistakenly attacks healthy tissue and organs in the body.

"We've known for some time that vitamin D can affect function of the immune system, which could explain why it seems beneficial to both of these autoimmune conditions," says Kassandra Munger, MSc, of Harvard School of Public Health, a researcher for this study. "In animal studies, vitamin D been shown to suppress the autoimmune response in rats with a disorder very similar to MS."

Other recent studies link vitamin D deficiency to a greater risk of other ailments, including heart disease, diabetes, unexplained muscle and joint pain, and various forms of cancer. As with MS and other autoimmune diseases, the secret may be in how this nutrient affects cell activity.

"We need adequate amounts of vitamin D to keep cell growth and activity in check," says Holick, MD, PhD, director of the Vitamin D Research Lab at Boston University Medical Center and considered by many to be the nation's leading authority on this vitamin. When the body is deficient in this crucial nutrient -- best known for coming from sunlight -- cells can go haywire, become overly active or multiplying too quickly.

That's why the new finding doesn't surprise Holick, who wasn't involved in it. "It's been well-known that if you live at a higher altitude, where there's less sun exposure, you're at a higher risk of developing MS," he tells WebMD. Conversely, if you live in a sunny climate where vitamin D can easily be absorbed year-round from sunlight for your first 10 years, "it imprints on you a decreased MS risk that can last a lifetime," Holick explains.

Munger's results are encouraging because 20% to 80% of Americans may already be vitamin D deficient -- at least during winter months. While as little as 10 minutes of sun exposure on bare, unprotected skin can prevent deficiencies in warm and sunny months, it's virtually impossible for most Americans to get that kind of exposure this time of year.

Good food sources of vitamin D include:

Fortified milk, 8 ounces contain approximately 100 IU of vitamin D

Cod liver oil, 1 tablespoon contains approximately 1300 IU of vitamin D

Cold-water fish such as salmon and herring, 3 ounces contain approximately 400 to 750 IU of vitamin D respectively.

However, Munger says that no matter where they lived (which could help determine their vitamin D exposure from sunlight), her study's participants who got the highest intake of vitamin D from supplements had the lowest risk of developing MS. Interestingly, those whose vitamin D came only from food, but not pills, had no such decreased risk -- no matter their intake.

Her study is part of the ongoing Nurses' Health Study that has been tracking, for nearly 20 years, how various nutritional and lifestyle habits impact health in some 190,000 women. It's the latest evidence to show that something as simple as taking a multivitamin can offer significant protection against a disease that afflicts some 400,000 Americans. Although the cause of MS is unknown, experts believe it is partly an autoimmune disease that causes lesions within the brain and spinal cord, slowing or blocking nerve signals that control muscle coordination, visual sensation, and other vital functions.

"Very few of the women in our study were taking 'straight' vitamin D supplements," Munger tells WebMD. "Mostly, they got these benefits from a regular multivitamin pill with the standard dosage of vitamin D. While it's too early to conclusively recommend taking multivitamins to prevent MS, certainly many people have advocated taking them for other reasons."

Holick has long recommended that most Americans -- especially those living in cold or gray winter climates -- take a multivitamin and an additional vitamin D supplement of between 400 and 1,000 IU to prevent possible deficiencies. "My guess is that these study participants probably consumed closer to 600 IUs in their multivitamins," he tells WebMD.

"We found that taking vitamin supplements of 1,000 IUs caused changes in blood chemistry that indicated positive effects for multiple sclerosis patients -- basically, it reduced their symptoms," says Margherita Cantorna, PhD, assistant professor of nutrition at Penn State University who headed that study. A longtime researcher on how vitamin D impacts multiple sclerosis, she was not involved in Munger's study, but like Holick, says she isn't surprised by the findings.

"It's pretty clear that when levels of vitamin D are too low, there's a greater tendency for cells that cause autoimmune problems to come out in those genetically susceptible people," Cantorna tells WebMD. "And it's pretty clear that taking supplemental vitamin D is a good idea. You're hard-pressed to get enough vitamin D solely from food or from sunlight in the winter."

SOURCES: Munger, K, Neurology; Jan. 13, 2004; vol 62; pp 60-65. Kassandra Munger, MSc, nutrition researcher, Harvard School of Public Health, Boston. Holick, MD, PhD, director, The Vitamin D Research Lab; director, The General Clinical Research Center; professor of medicine, dermatology, physiology and biophysics, Boston University Medical Center, Boston. Margherita Cantorna, PhD, assistant professor of nutrition, Penn State University, State College, Pa. Saag, K. Arthritis and Rheumatism, January 2004; vol. 50; pp. 72-77.