Only Selected Folate-Deficient Elderly Should Take Supplements: Study

[Guest guest]

*My NOTE: Looking at the 2 studies below - good reason NOT to recommend

folic acid with the " old " caveat " It won't hurt you " . Glad to see they are

NOT recommending, unless there is a need.*

*Study 1*: In elderly patients with folate deficiency, supplementation

boosts blood levels but doesn't usually cut homocysteine concentrations,

researchers report in a September 16th online paper in the American Journal

of Epidemiology.

In general, " older adults should not take folic acid supplements for the

purpose of homocysteine lowering, " lead author Dr. Cheryl A. M.

told Reuters Health by e-mail.

That's because folic acid supplements don't lower homocysteine

concentrations in healthy older adults unless they have low serum folate

concentrations, she said.

But, she added, " While our data suggest that folic acid may lower

homocysteine levels in those with low serum folate concentrations, this

warrants further study because our study was not designed to assess effects

in those with low serum folate -- these analyses were secondary. "

Dr. of s Hopkins University, Baltimore, and colleagues say

folate deficiency affects as many as 40% of older Americans and can

contribute to increased homocysteine concentration. Adequate levels may help

prevent cardiovascular and other diseases.

In a randomized trial, 133 healthy participants aged 60 to 90 years took

either placebo or folic acid 100, 400, 1,000, or 2,000 mcg per day.

At baseline, there were no significant differences among the groups in serum

concentrations of folate (overall mean, 5.7 ng/mL) or homocysteine (8.3

micromoles/L).

At six weeks, the placebo and 100 mcg groups had similar folate levels, but

in the others, serum folate rose in parallel with the folic acid dose.

However, for homocysteine there was no dose-response relationship or

difference between placebo and active treatment groups.

Nevertheless, when analysis was restricted to participants with the lowest

baseline folate concentrations (less than 4.5 ng/mL), there was a trend

toward decreased homocysteine levels with increasing folic acid dose.

*Am J Epidemiol. *Posted online September 16, 2010.

Abstract<http://aje.oxfordjournals.org/content/early/2010/09/16/aje.kwq197.abstr\

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*Study 2*: Data from Chile show that there has been an increase in the rate

of colorectal cancer since 2000, when the government introduced a mandatory

program of fortification of wheat flour. A similar increase was reported in

the United States and Canada in the late 1990s, after the introduction of

folic-acid fortification there.

The aim of folic-acid fortification is to reduce neural tube defects, a

result of folate deficiency during pregnancy and, in this, the programs have

been successful. In Chile, these complications were reduced by 40% in 1

year.

But could the downside be an increase in the risk for colorectal cancer?

The latest data, published online February 2 in the *European Journal of

Gastroenterology & Hepatology*, suggest that it might be. Hirsch, MD,

MSc, and colleagues from the University of Chile, in Santiago, analyzed

hospital-discharge data for two 4-year periods -- before folic-acid

fortification (1992-1996) and after (2001-2004) -- and found a significant

increase in reported cases of colon cancer. The increase was 162% in people

45 to 64 years and 190% in people 65 to 79 years.

Most other diseases showed no consistent patterns of change, they note.

There was a small increase in breast cancer, smaller than that seen for

colon cancer, but the authors note that this could probably be attributed to

2 programs for breast cancer introduced in 2000, one for early detection and

the other guaranteeing universal access to treatment.

The researchers acknowledge that there could be other explanations for the

finding, such as the rise in obesity (which increased from 19.7% in 1997 to

22% in 2003). However, Dr. Hirsch pointed out to *Medscape Oncology* that

there were no changes in the hospital-discharge data for cardiovascular

disease during that time.

" Our data provide new evidence that a folate-fortification program could be

associated with an additional risk of colon cancer, " Dr. Hirsch and

colleagues conclude.

One problem with this study is that it uses indirect data for the incidence

of colon cancer, say critics. There are no cancer registries in Chile, so

the researchers used the diagnosis indicated on hospital-discharge forms as

a proxy for disease incidence.

This is an important limitation of the study, said Reinhold Stockbrugger,

MD, one of the editors of the *European Journal of Gastroenterology &

Hepatology. * " Discharge rates are influenced by healthcare politics,

increasing access to healthcare for new strata of the population with

increased cancer risk, and so forth, " he comments in a press release issued

by the Journal.

" This study provides only a weak indirect indication of a causal

relationship between folate enrichment and colorectal cancer, " Dr. Reinhold

said. However, he added that the finding is " similar to that reported in the

United States and Canada. "

Those data appeared nearly 2 years ago (*Cancer Epidemiol Biomarkers Prev*.

2007; 16:1325-1329), in a study by Mason, MD, and colleagues from the

Mayor US Department of Agriculture Human Nutrition Research Center on

Aging at Tufts University, in Boston, Massachusetts. That study used

incidence data from nationwide cancer registries and showed significant

increases in colorectal cancer rates in both the United States and Canada.

Folic-acid fortification began in the United States in 1996 and in Canada in

1997, and became mandatory in both countries in 1998, Dr. Mason and

colleagues note. Concurrently, both countries experienced " abrupt reversals "

of the downward trend in colorectal cancer incidence that they had enjoyed.

In the United States, rates started to increase in 1996 and peaked in 1998;

in Canada, rates began to rise in 1998 and peaked in 2000. Both rates have

continued to exceed pre-1996/97 levels.

At the time, Dr. Mason and colleagues stressed that the observations did not

prove a causal link, and they emphasized the " very compelling body of

scientific evidence that has accrued over the past 15 years that indicates

that supplemental folic acid protects against neural tube defects. "

Walter Willet, MD, DrPH, an expert on diet, nutrition, and cancer from

Harvard School of Public Health, in Boston, Massachusetts, told *Medscape

Oncology*: " I am quite certain that we are not causing an epidemic of

colorectal cancer with folic acid fortification of flour. " He pointed out

that mortality rates from this cancer are continuing to decline steadily,

and that, at the time the increase in incidence was noted in the United

States, there had been an increase in colonoscopy. In addition, Dr. Willet

pointed out, folic acid reduces the incidence of neural tube defects, and

there is evidence that it is protective against stroke.

*Total Amount of Folic Acid Important?*

Dr. Mason and colleagues also note that there is evidence that " habitually

high intakes of dietary folate are protective against colorectal cancer. "

They suggest, however, that the pharmaceutical form of folate (i.e., folic

acid, which is used in fortification of foods and in vitamin tablets) might

act differently than dietary folate, and they note that there is literature

to suggest that a high intake of folic acid can accelerate the growth of

established neoplasma. Adding substantial quantities of folic acid to the

food supply in the mid-1990s might have facilitated the transformation of

colorectal adenomas (which are found in 35% to 50% of Americans) into larger

cancers, they suggest.

In the United States, folic acid was added to flour at a concentration of

140 ìg/100 g (compared with 150 ìg/100 g in Canada and 220 ìg/100 g in

Chile). But Dr. Mason and colleagues note that many breakfast cereals are

fortified and that many Americans take vitamin supplements that include

folic acid at a dose of 400 ìg per pill.

In an interview with *Medscape Oncology*, Dr. Mason said that the new data

from Chile " contribute to this concern that the total amount of folic acid

present in the food stream can potentially contribute to an increase in

certain types of cancer. " However, he also said that the Chilean data are

" weak in some regard, " in that they rely on a surrogate end point of

hospital-discharge data rather than cancer-incidence data.

Another recent publication has added to the concern about folic acid and

cancer, he noted. New data from the Aspirin/Folate Polyp Prevention Study,

published last month (*J Natl Cancer Inst*. 2009;101:432-435), show a 3-fold

increase in prostate cancer among men who took the folate supplement,

compared with men who took placebo.

This is cancer in a different organ, and the folic acid was in a supplement

rather than in fortified foodstuff, but this observation " contributes to the

concern, " Dr. Mason commented. " There is a real concern that there are

certain types of cancers common in the older population that are in an

indolent phase of slow development, but their development may be accelerated

by too much folic acid, " Dr. Mason said. One example is the colorectal

adenoma, " which sits in the colon for a decade before it evolves into a

cancer, as far as anyone can tell. " A second example is dysplastic prostatic

nodules, which are seen in most men when they reach 70 to 90 years of age;

the majority of these do not become clinically significant, and these men

die of other causes, he added.

" In both situations, these are indolent precancerous lesions, which, with a

bit of tweaking, might be pushed over the edge to evolve into clinically

significant cancer, " Dr. Mason said.

Is folic acid one of the factors that could push an indolent lesion into

cancer?

" We cannot prove causality, " Dr. Mason said, " but this is highly

biologically plausible. " This is a " smoldering concern, " but at the moment

there are not enough data to lead to any changes in the current policy of

folic-acid fortification in those countries that have already implemented

it, Dr. Mason said. But the matter is being debated, particularly by

countries around the world (and the European Union) that are considering

whether or not to implement such a policy. Dr. Mason recently took part in a

meeting of experts in Sweden to discuss these matters, and has written a

comprehensive review of the issue (*Nutr Rev*. 2009,67;206-212).

It is not just a question of folic-acid fortification of food, however;

there is also the issue of folic-acid supplementation, such as in

multivitamin pills. Dr. Mason noted that recent data from the US Centers for

Disease Control suggest that 70% to 80% of the general adult population has

detectable levels of folic acid in the blood, but " under more natural

conditions, folic acid would not even be present in the blood. "

Dr. Mason said he is attracted to the proposal that has been suggested in

the United Kingdom, namely that, if folic-acid fortification goes ahead,

there should be a reduction in the folic-acid component of vitamin and other

supplement products. The dose of folic acid would need to be cut quite

dramatically, he suggested, from the current 400 ìg in a daily tablet to

around 50 to 100 ìg.

*The researchers have disclosed no relevant financial relationships.*

*Eur J Gastroenterol Hepatol*. Published online before print February 2,

2009.

Abstract<http://www.ncbi.nlm.nih.gov/sites/entrez?orig_db=PubMed & db=pubmed & cmd=S\

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--

Ortiz, MS, RD

*The FRUGAL Dietitian* <http://www.thefrugaldietitian.com>

Check out my blog: mixture of deals and nutrition

* " Older Dietitians " - seasoned to PERFECTION**

*