Re: fructose for improved ATP? - Rich

[Guest guest]

,

My impression is that this was written quite a long time ago. The

most recent reference cited is dated 1993, and Dr. Cheney is said

there to be in Charlotte. He hasn't practiced there in a long

time. I doubt that he would still subscribe today to what he wrote

then, though I can't speak for him.

From my point of view, increasing the intake of carbohydrates,

including fructose, would not be beneficial for most PWCs. The

problem with it is that in my opinion the Krebs cycle has partial

blockades, and can't handle processing the pyruvate that comes from

glycolysis of carbohydrates at a high enough rate to keep up. As a

result, the pyruvate either gets converted to lactate or not, but

both of them have to be either burned by tissues that can burn them

(such as heart muscle) or they have to be processed by the liver,

via gluconeogenesis, to make glucose, which is returned to the

blood. There's no way to get rid of the excess glucose other than

to convert it to stored fat, which causes weight gain. So eating

more carbohydrates is not such a good idea, in my opinion, for most

PWCs, and I suspect that Dr. Cheney would agree with that today.

Rich

> Hi Rich,

> In a paper found at

http://dspace.dial.pipex.com/comcare/docs/me0048.txt Cheney says the

following:

> " Mitochondrial dysfunction and loss of dominant ATP or energy

generator would obviously result in an up-regulation of anaerobic

metabolism or glycolysis to compensate.....It is noted that this

system runs on carbohydrates and especially fructose. It should be

no surprise then that CFS patients crave carbohydrates. If they eat

fat, they cannot consume it in the mitochondria, due at least in

part to acylcarnitine deficiency, and therefore fat storage

increases as does body weight. Serum cholesterol and triglycerides

increase in some individuals...An obvious approach would be to

increase carbohydrates and reduce fat intake. The use of fructose

combined with chromium to improve its entry into the cell might also

improve ATP generation. "

>

> You have said that it is difficult for PWCs to burn carbohydrates

and fats as fuels and have hypothesized that a process called

anaplerosis allows amino acids to get by the blockages in the Krebs

cycle to provide fuel that is missing with the loss of the carbs and

fats. So protein becomes the fuel of choice. Because so many PWC do

well on high protein diets, this sounds good to my struggling-to-

understand, non-scientific mind but it doesn't seem to square with

what Cheney says. Or does it? I couldn't find a date for the Cheney

info and wonder if it might be a dated piece of information with

more research done since. Could you fill me in on this?

>

> Thanks a lot.

>

>

>

>

[Guest guest]

Hi, Jim.

Thanks for your comments. I'll make some in response below:

>

> Hi ,

>

> I know that you had directed your question to Rich but I thought

> I'd assist.

>

> Your question is a good one.

>

> If pyruvate cannot be processed quickly enough due to blockages in

> the mitochondrial processes, the excess pyruvate is converted to

> lactic acid. (If this conversion is not done the cell could run

low

> on NAD+ and then glycolysis could become blocked. Pyruvate + NADH -

->

> lactic acid + NAD+)

Whether or not this conversion happens depends on how well the

mitochondrial shuttles can keep up with the production of NADH in

the glycolysis, which takes place in the cytosol, outside the

mitochondria. If the shuttles can't keep up, the cells perform

anaerobic glycolysis, producing lactate. If the shuttles can keep

up, then the cells operate on aerobic glycolysis and produce

pyruvate.

>

> (Note: This is where I see CFS and FMS differentiate. In FMS the

> enzyme that converts pyruvate to lactic acid is in low quantity so

> there is an increase of pyruvate in the cell. In CFS this enzyme

is

> able to carry out this function and hence there is an increase in

> lactic acid. This is described in the presentation on my website

at

> http://www.xmission.com/~total/temple/index.html)

I don't think it is as clearcut as that. I realize that Eisenger et

al. reported elevated pyruvate in PWFs. Some PWCs seem to have a

higher degree of lactic acid production than others, which I think

is evidenced by a burning sensation in the muscles with little or

even no exercise. Others don't seem to experience this.

There's also a range of response to alcohol, which I think has its

effect in CFS by shutting down the Cori cycle. Some PWCs are

devastated by this, indicating that they are very dependent on the

Cori cycle. Others can tolerate alcohol pretty well. This either

means that they are not relying on glycolysis and the Cori cycle as

much as the others, or that their livers have larger capacity to

process alcohol and still keep up gluconeogenesis to complete the

Cori cycle. I'm not sure which. Some of the cases I've studied who

can handle alcohol alright were pretty hefty drinkers before they

got ill, and maybe they " trained " their livers to have a higher

capacity. I'm not sure about this yet.

>

> The lactic acid from the cell is transported via the bloodstream

> back to the liver, where the lactic acid is converted to

glycogen.

> The glycogen is essentially taken out of circulation until there

is a

> need for more glucose. When there is a need for more glucose then

> the hormone glycogon, produced in the pancreas, signals that

glycogen

> should be changed back into glucose and put back into the

bloodstream

> for delivery to the cells.

Under normal conditions, you're right, this is the way it works.

However, in PWCs who continue to consume carbohydrates above their

cells' capacity to completely burn it up, I think they will soon

exceed the liver's capacity to store glycogen. It can hold about 8

to 10 % of its wet weight as glycogen, according to my biochemistry

textbooks. The buildup of glycogen acts as a regulatory mechanism

to limit its further buildup. Once the glycogen storage is at

capacity, the liver has no choice but to dump the glucose back into

the blood, where the elevated insulin will eventually push it into

fat cells to make stored fat out of it.

There are diseases called glycogen storage diseases in which the

amount of glycogen stored in the liver can rise higher than this.

This produces hepatomegaly (enlarged liver), which can be seen by

ultrasound exam of the abdomen. While some PWCs do have

hepatomegaly, I don't think that most of them do, so I don't think

the normal glycogen storage limits are usually exceeded in PWCs.

>

> There is not an increase in blood glucose levels from this

> recycling of pyruvate.

Well, I guess we differ on this point. The glucose does rise, and

if the pancreas is working properly, it puts out insulin and pushes

the excess glucose into the fat cells, so that it doesn't rise to

dangerous levels.

>

> However, due to the blockages in the mitochondria it is possible

> that blood glucose levels remain elevated for a longer time.

Glucose

> is removed from the blood only as fast as it can be processed

inside

> the cells. If the burning of glucose inside the cells is slowed,

> then the glucose will be removed from the blood at a slower rate,

> effectively keeping the blood glucose levels elevated longer.

>

> Glucose moves into the cell by facilitated diffusion. Insulin,

> signals the cell to open the channels to allow glucose to enter

the

> cell but diffusion pushes the glucose into the cell. The glucose

> moves from areas of higher concentration (the blood) to areas of

> lower concentration (the cell, assuming that the glucose inside

the

> cell has been burned).

>

> See the animation at

>

http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/pancreas/in

s

> ulin_phys.html

>

> If there is still glucose inside the cell then insulin can signal

for

> the gates to open, the gates can open but glucose cannot move into

> the cell because there is already glucose inside the cell, a

> concentration gradient does not exist to move the glucose into the

> cell.

>

> The Insulin receptor on the cell is an ATPase, an enzyme that

> requires ATP to function. It may be possible that a reduction in

ATP

> could also impede the flow of glucose into the cell.

>

> This scenario kind of sounds similar to type II diabetes, which

> affects an estimated 16 million people in the US.

>

> So what can be done to help? Increasing metabolism will cause

> glucose to be burned more quickly and ATP to be generated. Under

> normal circumstances, in a healthy individual, exercise would

> increase metabolism. But in the case of CFS/FMS where there are

> blocks to energy production in the mitochondria, exercise will

cause

> in increase in pyruvate (or lactic acid) and create more

problems.

> Another way to increase metabolism is to increase the temperature.

> ( reference http://www.people.virginia.edu/~rjh9u/actenz.html )

Personally, I favor efforts to remove the partial blockades in the

Krebs cycles, so the carbohydrates can be completely burned. I

think that building glutathione will help this. In the meantime, a

diet low in sugars and starches as well as nonessential fats, but

high in protein, with some vegetables that grow above the ground is

a beneficial diet for many PWCs.

>

> I hope that this has helped you better understand what is going on.

>

> All the best,

> Jim

Rich

[Guest guest]

Hi Rich,

Thanks for filling in the gaps in my explanation.

I agree with you that the blocks to mitochondria processes must be

removed. And, glutathione may do this in time. However, per

Cheney's presentation in Dallas a couple years ago, he diagrammed how

glutathione production follows the production of ATP. The conclusion

I drew from that was that until ATP production increases, glutathione

production will remain low.

Enzyme levels are likely low inside the cells, add to that the

lower body temperature associated with CFS/FMS (due to low ATP) and

metabolism is severely impaired. I think that raising the body

temperature helps restore a little metabolism for a short while, so

that some of the cellular processes may take place and produce more

ATP. This will help with production of glutathione (that is if

production is limited by insufficient ATP).

I agree with your dietary suggestions. However, with the high

protein diet if HCl production is reduced in the stomach then

complete protein breakdown may be impaired. If a leaky gut situation

exists this may create an allergic response to the food.

Your thoughts and corrections are appreciated.

All the best,

Jim

> >

> > So what can be done to help? Increasing metabolism will cause

> > glucose to be burned more quickly and ATP to be generated. Under

> > normal circumstances, in a healthy individual, exercise would

> > increase metabolism. But in the case of CFS/FMS where there are

> > blocks to energy production in the mitochondria, exercise will

> cause

> > in increase in pyruvate (or lactic acid) and create more

> problems.

> > Another way to increase metabolism is to increase the temperature.

> > ( reference http://www.people.virginia.edu/~rjh9u/actenz.html )

>

> Personally, I favor efforts to remove the partial blockades in the

> Krebs cycles, so the carbohydrates can be completely burned. I

> think that building glutathione will help this. In the meantime, a

> diet low in sugars and starches as well as nonessential fats, but

> high in protein, with some vegetables that grow above the ground is

> a beneficial diet for many PWCs.

[Guest guest]

Hi, Jim.

Thanks again for the comments.

I don't recall Dr. Cheney saying that. I think it's the other way

around, i.e. you have to raise the glutathione to remove the partial

blockades in the Krebs cycles, due to elevated peroxynitrite, in

order to raise the production of ATP. I'll have to go back and look

at the tape. Do you mean the one from 1999 or the more recent one?

Concerning the stomach acid deficiency and the leaky gut issue, I

agree that they have to be dealt with before good digestion and

absorption can take place, and to knock down the food intolerances.

Those are some of the reasons I agree with Dr. Corsello on treating

the G.I. issues up front, as I said in my " Strawman Treatment

Protocol, " which put in the Links section of this list.

Concerning the heating, that does seem to help people, particularly

the PWFs. I'm not sure what the mechanism is, though. Improved

blood perfusion may be part of it. At the Orthomolecular Health-

Medicine Society meeting a while back I tried out an FIR tunnel for

10 minutes myself. It really seemed to help a sore muscle in my

back! I got the sensation of the deep heating you have talked about.

Rich

>

> Hi Rich,

>

> Thanks for filling in the gaps in my explanation.

>

> I agree with you that the blocks to mitochondria processes must

be

> removed. And, glutathione may do this in time. However, per

> Cheney's presentation in Dallas a couple years ago, he diagrammed

how

> glutathione production follows the production of ATP. The

conclusion

> I drew from that was that until ATP production increases,

glutathione

> production will remain low.

>

> Enzyme levels are likely low inside the cells, add to that the

> lower body temperature associated with CFS/FMS (due to low ATP)

and

> metabolism is severely impaired. I think that raising the body

> temperature helps restore a little metabolism for a short while,

so

> that some of the cellular processes may take place and produce

more

> ATP. This will help with production of glutathione (that is if

> production is limited by insufficient ATP).

>

> I agree with your dietary suggestions. However, with the high

> protein diet if HCl production is reduced in the stomach then

> complete protein breakdown may be impaired. If a leaky gut

situation

> exists this may create an allergic response to the food.

>

> Your thoughts and corrections are appreciated.

>

> All the best,

> Jim

>

> > >

> > > So what can be done to help? Increasing metabolism will cause

> > > glucose to be burned more quickly and ATP to be generated.

Under

> > > normal circumstances, in a healthy individual, exercise would

> > > increase metabolism. But in the case of CFS/FMS where there

are

> > > blocks to energy production in the mitochondria, exercise will

> > cause

> > > in increase in pyruvate (or lactic acid) and create more

> > problems.

> > > Another way to increase metabolism is to increase the

temperature.

> > > ( reference http://www.people.virginia.edu/~rjh9u/actenz.html )

> >

> > Personally, I favor efforts to remove the partial blockades in

the

> > Krebs cycles, so the carbohydrates can be completely burned. I

> > think that building glutathione will help this. In the

meantime, a

> > diet low in sugars and starches as well as nonessential fats,

but

> > high in protein, with some vegetables that grow above the ground

is

> > a beneficial diet for many PWCs.

[Guest guest]

Hi Rich,

The Cheney tape that I have is the one that was distributed by the

Dallas CFIDS group. I think it was either 1999, or 2000. I'll watch

it again to make sure I heard it correctly, it was about 3/4 into the

presentation.

I'll take a look at the strawman treatment protocol, I had been

meaning to ask for more info on that.

All the best,

Jim

[Guest guest]

Roxy,

I'm wondering whether you might have a leaky gut, that has produced

some food sensitivities. Have you been tested for food

sensitivities, such as with an ELISA-ACT test or by an elimination

diet? How about leaky gut? Have you had an intestinal permeability

test?

Rich

> I have been following this thread with interest, hoping

> it might shed some light on my bad experiences with

> low-carb eating.

>

> I have repeatedly tried eating a diet of just

> vegetables and protein, partly because my doctor says I

> have reactive hypoglycemia. When I am on this low-carb

> regimen, my fatigue, pain and muscle weakness are

> severely worsened, and I always end up with a sinus

> infection after a couple of weeks of eating this way.

> And, strangely, even though I am overweight, I do not

> lose any weight on this diet (my husband does lose

> weight on this diet). Before I got CFS, I went on the

> Atkins diet many times with good results. I have

> hypochloridia, according to the capsule test, but take

> betaine HCl for this.

>

> Any thoughts on what this might reveal about my

> situation? I am at my wits' end...

>

> Roxy

[Guest guest]

Annette,

I think it would certainly be worthwhile trying to build up your

folic acid level. A dosage in the range of 400 to 1,000 micrograms

per day would probably be beneficial. Absorption of folic acid

supplements is best if taken on an empty stomach. Folate in food is

only absorbed at about 50%.

Here's some information about folic acid in CFS:

Folic acid participates in the synthesis of DNA, RNA, and proteins.

It is involved in DNA replication and repair, maintenance of the

integrity of the genome, and regulation of gene expression. Folate

deficiency produces megaloblastic anemia. Other symptoms and signs

of folate deficiency are weakness, fatigue, irritability, headache,

difficulty concentrating, cramps, palpitations, shortness of breath,

and atrophic glossitis. The similarity of this list with the list of

symptoms found in CFS prompted a search for folate deficiency in

this disorder.

son et al. (1993) and son (1994) measured serum folate in

60 patients who met a set of criteria based on the criteria for CFS

of Holmes et al. (1988) and Sharpe et al. (1991). These measurements

were initiated on the basis that earlier work by son et al. in

viral and mycoplasmal infections had shown low serum folate. They

reported that 50% of the patients were found to be deficient in

serum folate, and an additional 13% had low borderline values. A

review of their diets did not reveal low folic acid intakes. On the

other hand, Regland et al. (1997) found normal levels of serum

folate in 24 women who satisfied both the Holmes et al. (1988)

criteria for CFS and the ACR criteria (Wolfe et al., 1990) for FM.

It is not clear why the results of these two studies differed.

Bengtsson et al. (1986) tested the serum folate levels in 36 primary

FM patients who met the Yunus, Masi, Calabro, , and enbaum

(1981) FM criteria, and found normal levels in all of them.

Kaslow, Rucker, and Onishi (1989) evaluated the effect on patients

who met the Holmes et al. (1988) criteria for CFS of intramuscular

self-injections of an extract of bovine liver together with added

folic acid and cyanocobalamin. The daily dosage was 800 micrograms

of folic acid and 220 micrograms of cyanocobalamin equivalent.

Fourteen patients participated in a crossover study in which all

received one week of the treatment and one week of placebo. In

addition, eleven 11 patients completed a follow-on open-label

treatment that lasted two more weeks. Although significant

improvements in functional status and symptoms were found with both

the treatment and the placebo, the former was not found to be more

effective than the latter.

As Werbach (2000) has pointed out, the dosage and duration in this

trial were much smaller than those successfully used to treat

depression and fatigue in cases of folate deficiency (Botez, Botez,

Leveille, Bielmann, & Cadotte, 1979; Godfrey et al., 1990). In the

first of these, the dosage and duration were 10,000 micrograms per

day (orally) and two to three months to relieve fatigue and

depression. In the second, 15,000 micrograms per day were given

orally for six months.

Rich

> Hi list,

>

> I've been following this discussion with great

> interest. Does anyone know where FOLIC Acid fits into

> this.

>

> I just had a test result and my Folic Acid level was

> very low.

>

> Kindest regards,

> Annette

[Guest guest]

Roxy,

Great Smokies lab (http://www.gsdl.com) has a test called Intestinal

Permeability Assessment. You drink a solution of lactulose and

mannitol, and then collect urine for six hours. By looking at the

ratio of lactulose to mannitol in the urine, they can get a measure

of how leaky your gut is.

Most food sensitivities are not Type 1 IgE mediated allergies.

Rather, they are delayed types 2,3 or 4 sensitivities. These

require a different type of test, such as the -ACT test (the

website is

http://www.parentsofallergicchildren.org/elisa_act_test.htm

and the e-mail address is clientservices@...) This test is

not cheap, but some people are able to get it covered by insurance.

I don't see how hypercoagulation would cause the response to the

diet that you described. It seems more likely to me that you have a

leaky gut and are responding to one or more foods in the diet by

developing food sensitivities as the immune system responds to large

protein fragments that leak into the blood stream.

Another thing you could try would be to rotate your menu so that you

don't eat the same food for a week in between. If delayed

sensitivities are being developed, this should prevent it from

happening.

In the long run, though, if you have leaky gut, the thing to do is

to fix your gut. If that turns out to be the case, I think that Dr.

Corsello's bowel treatment protocol is a good one. It's described

in her book, " The Ageless Woman, " available from

http://www.corsello.com

Rich

> Rich,

>

> Thanks so much for your response. I don't recall any tests for

leaky gut -- which labs do you think are best for these tests? I

tested positive on several foods on an ELISA IgG test for food

> sensitivities, as well as elevated anti-gliadin SIgA on Diagnos-

Techs adrenal panel, but wasn't eating any of the suspect foods

while on the low-carb diet. I wondered also if my diet reaction

> could be related to hypercoagulation. I'm waiting for the Hemex

kit to do the ISAC panel.

>

> Roxy