B12, homocysteine, & heart disease

[Korn]

From http://www.kroger.com/hn/Concern/High_Homocysteine.htm

Homocysteine, a normal breakdown product of the essential amino acid methionine, is believed to exert several toxic effects.


A growing body of evidence suggests that an elevated homocysteine level is a risk factor for heart disease, independent of other known risk factors, such as elevated serum cholesterol and hypertension.1 2 The evidence is not all one-sided, however. In some research the link has appeared only in women,3 and a few scientists still have doubts about the importance of elevations in homocysteine for anyone.4 The clear association between elevated homocysteine levels and heart disease reported in most studies5 does not conclusively prove that homocysteine causes heart disease. It might only be a marker for something else that is the real culprit.6 Nonetheless, many cardiologists take seriously the association between elevations in homocysteine and increased risk of heart disease.


Anger and hostility correlate with the risk of heart disease.7 8 A preliminary study found a link between high homocysteine levels and hostility and repressed anger.9 While anger, hostility, high homocysteine, and heart disease all appear to be tied together, which of these is cause and which is effect remains somewhat unclear.


Increased homocysteine levels may also be a risk factor for the development of many other conditions, including stroke,10 thromboembolism11 (blood clots that can dislodge and cause stroke, heart attack, and other complications), osteoporosis,12 inflammatory bowel disease (Crohn’s disease and ulcerative colitis),13 Alzheimer’s disease,14 death from diabetes,15 miscarriage,16 17 18 19 20 other complications of pregnancy,21 22 23 24 25 and hypothyroidism.26


Scientists have yet to prove that elevated homocysteine levels cause any of these diseases. However, most doctors believe that high homocysteine increases the risk of at least heart disease. Fortunately, homocysteine levels can easily be reduced with safe and inexpensive B vitamin supplementation.

[...]Vitamin B6, folic acid, and vitamin B12 all play a role in converting homocysteine to other substances within the body. By so doing, they consistently lower homocysteine levels in research trials,34 35 36 a finding that is now well accepted. Several studies have used (and some doctors recommend) 400–1,000 mcg of folic acid per day, 10–50 mg of vitamin B6 per day, and 50–300 mcg of vitamin B12 per day.


Of these three vitamins, folic acid supplementation lowers homocysteine levels the most for the average person.37 38 It also effectively lowers homocysteine in people on kidney dialysis.39 In 1996, the FDA required that all enriched flour, rice, pasta, cornmeal, and other grain products contain 140 mcg of folic acid per 3½ ounces.40 This level of fortification has led to a measurable decrease in homocysteine levels.41 However, even higher levels of food fortification with folic acid have been reported to be more effective in lowering homocysteine,42 suggesting that the FDA-mandated supplementation is inadequate to optimally protect people against high homocysteine levels. Therefore, people wishing to lower their homocysteine levels should continue to take folic acid supplements despite the FDA-mandated fortification program.


Betaine (trimethylglycine) (6 grams per day) and choline (2 grams per day) have each been shown to lower homocysteine levels.43 44 More recently, 1.5 grams of betaine per day, an amount similar to that in a typical diet, also has been found to lower homocysteine levels.45 Doctors usually consider supplementation with these nutrients only when supplementation with folic acid, vitamin B6, and vitamin B12 do not reduce homocysteine levels sufficiently. The results of this study, however, point to the potential benefit of increasing one’s intake of foods rich in betaine (such as whole wheat, spinach, beets, and other plant foods).


Niacin, a form of vitamin B3, is sometimes given in large amounts to people with elevated cholesterol levels. A controlled study found that 1,000 mg or more per day of niacin raised homocysteine levels.46 Since other actions of niacin lower heart disease risk,47 48 the importance of this finding is unclear. Nonetheless, large amounts of niacin should never be taken without consulting a doctor.

[Korn]

From http://www.quackwatch.org/03HealthPr...ocysteine.html

Dietary supplementation with folic acid can reduce elevated homocysteine levels in most patients. The usual therapeutic dose is 1 mg/day. When this is not effective, vitamins B6 and/or B12 can be added to the regimen, which should be continued permanently. Some doctors routinely recommend that patients known to have atherosclerosis take B-vitamin supplements without being tested to determine whether their homocysteine level is elevated. They reason that since supplementation is harmless and since elevated homocysteine levels might be a factor, testing is not worth bothering with. Even though some patients may be helped with this "shotgun" strategy, I believe it is far better to (a) find out whether a problem exists and (b) to be certain that if homocysteine levels are elevated, the vitamin regimen is adjusted to be sure that lowering is achieved.
[...]
Lowering the serum concentration of homocysteine has been proven to reduce the risk of adverse cardiovascular events among people with homocystinuria. Studies have not yet determined whether lowering homocysteine levels reduces the incidence of heart attacks or strokes among people with mildly elevated homocysteine levels [7,8], but many experts believe that scientific studies will prove that it does. This belief has been strongly supported by a four-year study in which 101 men with vascular disease were given supplementary doses of folic acid, B6 , and B12. Ultrasound examinations of their carotid arteries found a decrease in the amount of carortid plaque in their arteries, with the greatest effect in those whose homocyteine levels had been highest before the treatment began [9].

[Korn]

From http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract (1999)

Eikelboom JW, Lonn E, Genest J Jr, Hankey G, Yusuf S.

Preventive Cardiology and Therapeutics Program, McMaster University, Hamilton, Ontario, Canada.

PURPOSE: To review epidemiologic studies on the association between homocyst(e)ine level and risk for cardiovascular disease and the potential benefits of homocysteine-decreasing therapies. DATA SOURCES: Computerized and manual searches of the literature on total homocysteine levels and cardiovascular disease. STUDY SELECTION: Prospective studies and major retrospective epidemiologic studies evaluating the association between homocyst(e)ine levels and cardiovascular disease and the association between blood levels or dietary intake of folate, vitamin B6, and vitamin B12 and cardiovascular disease. DATA EXTRACTION: Relevant data on patient population, plasma homocyst(e)ine levels, duration of follow-up, and main results were extracted from studies that met the inclusion criteria. DATA SYNTHESIS: The designs and results of studies included in this review are summarized. A formal meta-analysis was not performed because the studies were heterogeneous in method and design. CONCLUSIONS: Results of epidemiologic studies suggest that moderately elevated plasma or serum homocyst(e)ine levels are prevalent in the general population and are associated with an increased risk for cardiovascular disease, independent of classic cardiovascular risk factors. Simple, inexpensive, nontoxic therapy with folic acid, vitamin B6, and vitamin B12 reduces plasma homocyst(e)ine levels. Although the association between homocyst(e)ine levels and cardiovascular disease is generally strong and biologically plausible, the data from the prospective studies are less consistent. In addition, epidemiologic observations of an association between hyperhomocyst(e)inemia and cardiovascular risk do not prove the existence of a causal relation. Therefore, the effectiveness of folate, vitamin B6, and vitamin B12 in reducing cardiovascular morbidity and mortality requires rigorous testing in randomized clinical trials. Several such trials are under way; their results may greatly affect cardiovascular morbidity and mortality, given the simplicity and low cost of vitamin therapy.

Publication Types:
Review

Review, Tutorial


PMID: 10475890 [PubMed - indexed for MEDLINE]

[StevieP]

New research is indicating popping vit. B tablets may not be the answer:

http://news.bbc.co.uk/1/hi/health/4218186.stm

[Roxy]

Either way......I think the moral of the story is that we should make sure we are receiving enough B vitamins and folate. I do take a B-multi from time to time, when I think I need it. What about folate though? I don't take anything for that. What kinds of foods can it be found in?

[DianeVegan]

Roxy, you should get 400 mcg of folic acid (folate) every day if you have even a chance of becoming pregnant. This has been very well studied and shown to greatly reduce the occurrence of spina bifida and other central nervous system disorders in newborns. The good news is that most vegans have no problem getting enough folate because the sources are:

Leafy green vegetables, asparagus, avocado, broccoli, brussels sprouts, cauliflower, corn, beets, parsnips, squash, sweet potatoes, tomatos, oranges, grapefruit, bananas, cantaloupe, strawberries, legumes, peanuts, sunflower seeds, sesame tahini, nutritional yeast, whole and folate-enriched grains and grain products.

Getting adequate iron and vitamin C helps with absorption.

(Taken from my favorite vegan resource - "Becoming Vegan" by those vegan dieticians)

[StevieP]

This recent research is very interesting.

The combiened studies on mortality show that the vegetarians are out living vegans, and the vegans are living as long as the healthiest meat eaters. These results were a bit of a surpise - we expected the vegans to do better, as they have lower blood pressure, lower colesteral, lower weight, few cancers etc. It appearts the weakness in the vegan diet were low omega-3 intake and high homocysteine levels, caused by lower B12 intake and hence they are dying from strokes.

Omega-3 is address by havoing flax seed on your breakfast in the morning.

Concerning B12, we have been adviced to take B12 supplements or make sure we have enough B12 fortified food.

More and more research is indicating that taking supplements does not have the same positive effect as consumimg food with those vitimins in.

This research is showing, that even if taking B vits to lower homocysteine levels does work, it does not translate into a lower stroke risk, maybe the opposite. This could be bad news for vegans using B12 supplements.

Of course, this research has not been done on vegans and we don't know if the same effect is seen with the fortication of food.

[Roxy]

Thanks Diane - by looking at that list of foods - it seems that I would get a good intake of folate in my diet

[DianeVegan]

StevieP,

Please keep in mind that unless those vegans in the study were vegan for years and eating a healthy diet then they may have been poor subjects to study. If they used vegans for instance who: became vegan due to heart disease, became vegan to lose weight, became vegan but never gave up processed foods, became vegan due to a diagnoses of cancer - well, you get the picture. Also, since there are such fewer vegans than vegetarians and omnivores, I would want a study with a very large number of vegans before I would believe the data.

I read a LOT of medical studies and the authors almost always suggest that a larger study needs to be done to confirm their findings. Odd that this never makes it into magazines or the nightly news.

[StevieP]

StevieP,

Please keep in mind that unless those vegans in the study were vegan for years and eating a healthy diet then they may have been poor subjects to study. If they used vegans for instance who: became vegan due to heart disease, became vegan to lose weight, became vegan but never gave up processed foods, became vegan due to a diagnoses of cancer - well, you get the picture.

The quoted recent study was not using vegans. It was merely a study on whether consuming B vits decreased the chance of a stroke based on the theory that raised high homocysteine increases the likelyhoold of a stroke.

And since there has been an assumed connected between high homocysteine and stroke and vegan mortality, this study should be of concern to those recommeding B12 intake via supplements.

In know Dr Stephen Walsh of the Vegan Society is aware of the study. I look forward to his views on it and one what bearing it has on the Society's advice.

I read a LOT of medical studies and the authors almost always suggest that a larger study needs to be done to confirm their findings.

Yes, one study is not proof, but this is a fairly large one.

Odd that this never makes it into magazines or the nightly news.

I guess homocysteine is not a sexy subject!

[DianeVegan]

The quoted recent study was not using vegans. It was merely a study on whether consuming B vits decreased the chance of a stroke based on the theory that raised high homocysteine increases the likelyhoold of a stroke


I guess homocysteine is not a sexy subject!

I must have read your post wrong - it was a combined study, not a controlled study. I thought they were just comparing vegans vs. vegetarians vs. omnivores. All these studies make my vision go blurry sometimes!

Oh, but I think homocysteine is a very sexy subject, don't you? However, I was referring to the fact that the news doesn't seem to mention when a study is too small to generalize or that the results aren't all that earth shattering. (In smooth announcer's voice - Homocysteine - Is yours too low? Should you be concerned? Up next, how to protect your family. )

[eve]

StevieP said that more and more research is indicating that taking supplements does not have the same positive effect as consuming food with those vitamins in them. I'm sure that this is perfectly true for all supplements, which have been shown to be a waste of time, with the sole exception of B12 - for that we either take a tablet or food that has B12 added.

[Korn]

This research is showing, that even if taking B vits to lower homocysteine levels does work, it does not translate into a lower stroke risk, maybe the opposite. This could be bad news for vegans using B12 supplements.

Whether decreasing homocysteine levels actually causes less cases of heart disease has been discussed for a number of years (not only in our forum/this thread)... Here are some excerpts from an article published in 1999:

Homocysteine and Heart Disease: A Culprit, or Just a Suspect?

A growing body of evidence links high levels of the circulating amino acid homocysteine with an increased risk of cardiovascular (CV) disease. But whether homocysteine will join the list of major risk factors or turn out to be a marker for some as-yet-unknown process remains in doubt.

[...]

Homocysteine is formed during the metabolism of methionine, an essential amino acid (2). The substance has been under suspicion as a possible player in CV disease for decades, and many studies have tied hyperhomocysteinemia to an increased risk (1). One meta-analysis (3) indicated that in 15 studies, hyperhomocysteinemia imparted a 70% increase in the risk of coronary artery disease. The same analysis found greater increments in risks for stroke and peripheral vascular disease.

However, five recent prospective studies failed to show a link between homocysteine and CV disease, the AHA report states. Perhaps more important, no randomized prospective trials have yet shown that lowering homocysteine will reduce the risk of CV disease (though such trials are underway).

[...]

But Hennekens remains cautious. He says the relative risks linking homocysteine with CV disease are generally higher in retrospective studies than in prospective studies—about 1.7 vs 1.2 to 1.3. "I think we shouldn't make the same mistake with homocysteine that we made with beta-carotene and we may be making with vitamin E," he adds. "We declare victory on an inadequate totality of evidence."

Even if we know that there is a link between high homocysteine levels and heart disease, this doesn't necessarily mean that increasing the homocysteine levels by eating pills means a reduced risk for heart failure.

There will always be people who say ie. that it doesn't matter if you don't get enough sunlight as long as you take vitamin D supplements. There seem to be more and more evidence suggesting that we both need realsunlight and need to stop a development/lifestyle that makes B12 less available and disturbs B12 even after consumption.

[Korn]

Here are some excerpts from the article quoted in the BBC-article:

Taking B vitamins to ward off heart attacks and stroke does no good and may even be harmful, say experts.
Scientists had thought that these drugs might be useful by lowering levels of a blood substance called homocysteine which has been linked heart risk.

However, a large study looking at this has found no benefit even though homocysteine went down with these supplement pills.

The work was revealed in Stockholm at a European Society of Cardiology meeting.

Professor Peter Weissberg, medical director of the British Heart Foundation

The Norwegian Vitamin Trial (NORVIT) researchers from the University of Tromsø looked at 4,749 heart attack survivors who had been divided into four groups.

In addition to their standard heart medicines, the groups received either daily folic acid (itself a B vitamin), daily vitamin B6, both folic acid and vitamin B6 or a dummy drug for three years.

After three and a half years, those who had been taking either folic acid or vitamin B6 alone had only a small increase in the risk of cardiovascular disease (heart attack or stroke), compared with those who had received the placebo.

However, those who had taken both folic acid and vitamin B6 each day had a 20% increased risk of heart attack and stroke, despite their homocysteine levels going down by up to 30%.

No protection

The results also showed there was a 40% increase in the risk of new cancers in the group taking folic acid, which the researchers said warranted further investigation.

Author Professor Kaare Harald Bønaa said: "The results of the NORVIT trial are important because they tell doctors that prescribing high doses of B vitamins will not prevent heart disease or stroke.

"B vitamins should be prescribed only to patients who have B vitamin deficiency."

Professor Peter Weissberg, medical director of the British Heart Foundation, said: "People should not be taking folic acid and vitamin B6 to stop them having a heart attack because it won't.

"The study shows a significant increase in heart attacks and strokes."

However, he said there was no reason for pregnant women and those hoping to conceive to stop taking folic acid by itself. Folic acid is recommended for such women to reduce the risk of birth defects.

Patrick Holford, founder of the Institute for Optimum Nutrition, questioned the validity of the study findings.

"Given the extensive cocktail of drugs these patients were on, and the late stage they were in the disease process, it's unlikely there was much room for improvement.

"We are still awaiting the definitive trial that takes people with high blood homocysteine levels, which is the indicator of B vitamin need, gives them B16, B12 and folic acid, and measures the reduction in heart attacks or strokes

If you have read earlier posts in this thread, it should be pretty clear that there has been disagreement for quite a while about this issue. There has also been lack of research. Some of the most reliable people have been saying 'we don't have enough info yet' for a number of years.

Some vegan sites (luckily, not all) recommend people to eat B12, B6 and folic acid (and other supplements) whether they are deficient or not. There's talk about supplements for vegans (containing B12, B6 and folic acid) that are 'suitable for everyone'. I find this very questionable.

It may strengthen the misconception that vegans, you need to add a lot of nutrients (unlike non-vegans). But most of all, I find it surprising that some of these sites do not inform about the discussion that has been going on for many years, focusing on whether high homocysteine levels are the cause or effect of heart disease - and/or an effect of other elements that can cause heart disease.

[Korn]

From ajph.org

OBJECTIVES: This study assessed the association of dietary folate, vitamin B6, and vitamin B12 with cardiovascular mortality. METHODS: Poisson regression analyses assessed coronary/cerebrovascular mortality rates via nutrient data obtained from the National Nutrition Survey, which recorded 7-day food intakes from a national sample of 21,155 households. RESULTS: In regard to coronary mortality, male and female rate ratios (highest vs lowest quintile) were 0.83 (95% confidence interval [CI] = 0.77, 0.91) and 0.95 (95% CI = 0.86, 1.05), respectively, for folate and 0.74 (95% CI = 0.65, 0.84) and 0.86 (95% CI = 0.73, 0.99), respectively, for B12. Intake of folate and B6 (but not B12) was significantly associated with cerebrovascular mortality. CONCLUSIONS: B vitamins are associated with cardiovascular mortality in the general population.

[herbwormwood]

I eat a lot of beets, broccoli, and spinach, all known to contain homocystine lowering betaine (TMG). But I don't eat the green leaves of the broccoli, just the broccoli itself – what about you guys? Do you use the leaves?

It depends what state they are in. If they are young, fresh and not woody I eat them. Why wouldn't I eat them? Also if the stalk isn't too woody I eat that too, cut up small.
As for B Vitamins in general, I use Engevita most days. Also Alpro soya milk with added B12. And the margarine substitute I use has B12 in it. I have fortified breakfast cereal a few times a week too.
Because of this so far I have not seen the need to take a supplement.

[herbwormwood]

From ajph.org

This abstract does not say what the B12 source was. Were they meat eaters? Did they have a bad diet?
If they had a high meat diet maybe that was why their B vitamin levels were high?

[Korn]

Sure. I posted the link only because it is one of several sources that emphasize the the link between folate/B6 levels and cerebrovascular mortality: "Intake of folate and B6 (but not B12) was significantly associated with cerebrovascular mortality". Some writers give the opposite impression of what these studies concluded with, namely that B12 levels are 'significantly associated with cerebrovascular mortality', but that folate and B6 are not...

[Korn]

From http://www.mary-anns.com/Homocysteine%20article.htm

How is the homocysteine level measured, and what do the results mean?
Homocysteine is measured using a simple blood test. It can be measured at any time of day. It is not necessary to prepare in any special way for the blood test (such as fasting). Most hospital labs can measure homocysteine, or a blood sample can be sent out to a special lab.

A healthy homocysteine level is less than 12 µmol per Litre. A level greater than 12 µmol per L is considered high. If your homocysteine level is 12 to 15 µmol per L and you have blockages in any blood vessel, you need to lower your homocysteine to less than 12 µmol per L. If you have no other major risk factors for cardiovascular disease and you do not have atherosclerosis, it may be okay for you to have a modestly high level of homocysteine (12 to 15 µmol per L). Many other writers now consider anything over 6 to be too high.

How can I lower a high homocysteine level?
Eating more fruits and vegetables (especially leafy green vegetables) can help lower your homocysteine level by increasing how much folate you get in your diet. Good sources of folate include all fresh fruit and vegetables especially dark green leafy veg, lentils, chickpeas, asparagus, oranges, avocado, beetroot, spinach, lettuce, fresh herbs, papaya and most beans. Folate is sometimes called "folic acid." Generally folic acid is the supplement form and folate is what is found naturally in plants. Cooking destroys folate so it is best eaten raw. Make sure that your intestines are healthy by avoiding antibiotic foods such as onion or garlic or medication, or take a regular bacteria replacement if you do eat these food such as acidophilus and bifida. The best types contain fructo-oliogosaccarides or FOS, which is the food the bacteria need to multiply. These bacteria encourage the manufacture of B12 in the intestines.

Avoid garlic or onion? I'm in trouble!

[herbwormwood]

That website is a puff for a product called BarleyLife. I'm always suspicious when someone is trying to sell something.

[Korn]

I'm always suspicious when someone is trying to sell something.

So am I...


Here are some excerpts from an article discussing the link homocysteine levels and B12 from the US Office of Dietary Supplements / National Institutes of Health (the article was last updated 4/26/2006):

http://ods.od.nih.gov/factsheets/vitaminb12.asp

Researchers have long been interested in the potential connection between vitamin B12 deficiency and dementia [28]. A recent review examined correlations between cognitive skills, homocysteine levels, and blood levels of folate, vitamin B12 and vitamin B6. The authors suggested that vitamin B12 deficiency may decrease levels of substances needed for the metabolism of neurotransmitters [29]. Neurotransmitters are chemicals that transmit nerve signals. Reduced levels of neurotransmitters may result in cognitive impairment. In 142 individuals considered at risk for dementia, researchers found that a daily supplement providing 2 milligrams (mg) folic acid and 1 mg vitamin B12, taken for 12 weeks, lowered homocysteine levels by 30%. They also demonstrated that cognitive impairment was significantly associated with elevated plasma total homocysteine. However, the decrease in homocysteine levels seen with the use of vitamin supplements did not improve cognition [30]. It is too soon to make any recommendations, but is an intriguing area of research.

Vitamin B12, folate, and vitamin B6 are involved in homocysteine metabolism. In fact, a deficiency of vitamin B12, folate, or vitamin B6 may increase blood levels of homocysteine. Recent studies found that vitamin B12 and folic acid supplements decreased homocysteine levels in subjects with vascular disease and in young adult women. The most significant drop in homocysteine level was seen when folic acid was taken alone [48-49].

That's quite different from other studies, who suggest that folic acid (B9) should not be taken alone, but with B12 (and B6).

A significant decrease in homocysteine levels also occurred in older men and women who took a multivitamin/ multimineral supplement for 8 weeks [50]. The supplement taken provided 100% of Daily Values (DVs) for nutrients in the supplement.

Evidence supports a role for folic acid and vitamin B12 supplements for lowering homocysteine levels, however this does not mean that these supplements will decrease the risk of cardiovascular disease. Clinical intervention trials are underway to determine whether folic acid, vitamin B12, and vitamin B6 supplements can lower risk of coronary heart disease. It is premature to recommend vitamin B12 supplements for the prevention of heart disease until results of ongoing randomized clinical trials positively link increased vitamin B12 intake from supplements with decreased homocysteine levels AND decreased risk of cardiovascular disease.

It's interesting to see that the National Institutes of Health (in 2006) suggests that it is premature to recommend vitamin B12 supplements for the prevention of heart disease, while some vegans (and vegan organizations) seem to be 100% convinced (and have been convinced since long before 2006) that one by taking B12 supplements will avoid or minimize heart disease risks. This may or may not be correct, but unfortunately, the nuances are often missing in information from people who are 100% pro or against taking supplements, and the result is often that outsiders to the vegan movement get the false impression that vegans need to worry about more nutrients than non-vegans.

It's also interesting to see that while the National Institute of Health in a neutral/scientific manner states that fortified cereals are one of the few sources of vitamin B12 from plants, some vegan sites claim that the only reliable vegan sources of B12 are foods fortified with B12 and B12 supplements. What is it that makes these vegans write as if they have information that nobody else has found, and which isn't documented?

[Korn]

Re. homocysteine and heart disease, I don't know who is right and who is wrong here. Elevated homocysteine levels are assoicated with various health problems, and doesn't seem to be anything to strive for.

Anyway, an article called Studies Find B Vitamins Don't Prevent Heart Attacks in NYT refers to several studies that arrived at the same conclusion. The fact that they arrive at the same conclusion of course doesn't mean that they are right - or that their conclusions necessarily are valid for people with very low B12 levels, but here are some excerpts from the New York Times-article:

All three studies had the same result — the vitamins drove patients' homocysteine levels down so much, nearly a third, that if the hypothesis were correct, patients taking them should have been better off. Instead, they had about the same number of heart attacks and strokes as the patients taking placebos.

"The evidence is clear that this type of vitamin therapy is really not effective in reversing or benefiting advanced vascular disease," said the hypothesis's father, Dr. Kilmer McCully of the V.A. Boston Health Care System in West Roxbury. Dr. McCully first proposed that homocysteine caused heart disease in 1969 and literally sacrificed his career to the hypothesis.

But he and others say that more research is needed, adding that there might be a more complex biochemical picture than researchers had imagined.

Others say that as far as they are concerned, the hypothesis, once so promising, is dead.

One of the New England Journal of Medicine papers, sponsored by the Canadian Institutes of Health Research, involved 5,522 patients aged 55 or older who had diabetes, or who had had a heart attack or who had documented heart disease. They were randomly assigned to take 2.5 milligrams a day of folic acid, 50 milligrams of vitamin B6 and 1 milligram of vitamin B12 or to take a placebo and were followed for five years.

The other study, the Norwegian Vitamin Trial, involved 3,749 men and women aged 30 to 85 who had recently had a heart attack. They were randomly assigned to take one of four regimens: vitamin B12 and B6; folic acid and vitamin B6; vitamin B6; or placebo. The study lasted for three years and four months.

The third study, published last year in the Journal of the American Medical Association, involved 3,680 stroke patients randomized to take the vitamins or not.

Dr. Joseph Loscalzo of Brigham and Women's Hospital in Boston, commented on the three studies in an editorial accompanying the papers in The New England Journal of Medicine: "The consistency among the results leads to the unequivocal conclusion that there is no clinical benefit of the use of folic acid and vitamin B12 (with or without vitamin B6) in patients with established vascular disease."

"One could say this dismisses the homocysteine hypothesis," Dr. Loscalzo said in a telephone interview. But he is not so ready to let it go, citing, "abundant evidence that argues that homocysteine has an adverse effect on blood vessels and should contribute to atherosclerosis."

And so, Dr. Loscalzo says, "if you believe those observations, you have to think of an alternative explanation." He suggests it may involve chemical reactions in the blood vessels whereby B vitamins themselves cause cells to divide and plaque to grow. Homocysteine may be a culprit, but doses of B vitamins that exceed the recommended daily amounts that can be obtained from foods may have deleterious effects that cancel out their good effect of homocysteine lowering.

He also thought it was possible that B vitamins might be helpful if people took them earlier, before heart disease had a chance to develop.

Others are ready to move on.

"We were surprised but as scientists we accept the finding," Dr. Kaare Bonaa said in a telephone interview. Dr. Bonaa, the lead author of the Norwegian study and a professor of medicine at the University of Tromso in Tromso, Norway.

"The whole homocysteine story should be rethought," says Dr. Yusuf.

The most likely explanation for the studies' results, he says, is that homocysteine levels never were causing disease. Instead, he says, they are a sign of heart disease, just like fever is a sign of an infection. Treating a fever with aspirin does not cure the disease and lowering homocysteine levels with B vitamins does not cure disease either, he says.

"We had a significant drop in homocysteine levels but practically no result," Dr. Yusuf said. "Pretty compelling, isn't it?"

[Korn]

Here's another study concluding that folic acid treatment alone may be sufficient for "decreasing negative effects of homocysteine" (but see one of the posts on the previous page regarding how this relates to vegans).

This study, OTOH, concludes that the deleterious effects of this compound (homocysteine)can be annulled by the supplementation of vitamins - Vit B12, folic acid, Vit B6."

[Korn]

In this article, Joel Fuhrman comments upon the studies that claim that vitamin B is ineffective against heart disease. It's interesting reading, and is focusing on high homocysteine as an indicator of a poor diet as very important even treating the homocysteine deficiency with pills as such may not reduce heart disease risk.

He quotes Gina Kolata (a writer in NYT) quoting a doctor at McMaster University in Hamilton, Ontario:

The most likely explanation for the studies' results, Dr. Yusuf said, was that homocysteine levels were not the cause of disease. Instead, he said, they are probably a sign of heart disease, much like fever is a sign of infection. Treating a fever with aspirin does not cure the infection, and lowering homocysteine levels with B vitamins does not cure disease either.

He also writes "Consider an abnormal homocysteine that may require treatment above 15, not above 10. Levels between 10 and 15 have not been consistently associated with worse outcomes" (Source: Sacco RL, Anand K, Lee HS, et al. Homocysteine and the risk of ischemic stroke in a triethnic cohort: the Northern Manhattan Study. Stroke 2004;35(10):2263-2269.)

Not only is homocysteine a controversial topic, the amount of homocysteine which should be considered abnormally is also a controversial topic.


Some claim that most vegans consume enough B12 to avoid anaemia and nervous system damage, but that many do not get enough to minimise potential risk of heart disease (or pregnancy complications). Heart disease and pregnancy complications never should be taken lightly. However, a statement that could interpreted as the if only reason (for men - we don't get pregnant) to pay attention to B12 is the heart disease risk combined with several studies claiming that lowering homocysteine levels with supplements may not have an effect possibly could lead people to thing that if the main reason to take B12 is heart disease (which is linked with homocysteine levels), and this after all may not have much of an effect, I don't need to pay attention to B12.

I think everybody should pay attention to B12, because B12 seem to be a useful marker for health in general. There are hundreds of reasons that we all (vegans and non-vegans) could have low B12 levels, and even if the association between homocysteine, B12 and heart disease may not document what some people claim that though it would, too low B12 levels are still bad for humans and other animals.

It is said that the circa 5000 mcg (=5 mg) B12 that can be stored stored in the liver may be enough to last for up to 30 years or more (even if no extra B12 is consumed during these years), which could suggests that healthy people with a well functioning B12 recycle process actually may use less than 0.5 mcg B12 pr. day - if these numbers are correct. There's no reason to avoid B12 for 30 years - and probably impossible too, but those of you who pay attention to the difference between mg (milligram) and mcg (microgram) know how microscopic our B12 needs are (I'll post a chart showing this later).

If we actually need to absorb (as opposed to consume) 0.5 mcg B12 daily, and if we eat 1kg food pr day (some claim that the average is circa 50% higher, others will eat a lot less), and we need to eat food with an average absorbed level of 0.5 mcg B12 pr. day, whatever we eat needs an average absorption level of 0.05 mcg B12 pr. 100g (based on a lifestyle and a diet without B12 inhibitors like coffee, tea or chlorinated water.) IMO it's important to bear this in mind we see studies about B12 in plants: it is often said that plants contain practically no B12... we need practically no B12. 0.05 mcg is what you get if you take a gram and divide it into 20 million small pieces!

Enough maths for now - homocysteine will most likely be a controversial topic for years to come. If you want to read more about some of the many homocysteine studies that has been going in for some time now in Norway (some of them are mentioned earlier in this thread), have a look here.

[Korn]

From http://www.drmcdougall.com/misc/2005...51000folic.htm

An excerpt:

Folic Acid Supplements are a Health Hazard

Stop Folic Acid Pills Now
Limit Your Intake of Fortified Flour Products (in the USA)
Don’t Lower Your Homocysteine Levels with Supplements

Taking supplements with as little as 0.8 mg/day of folic acid has been shown to increase your risk of dying of heart disease and cancer, according to the results of the first large randomized treatment trial to carefully examine this issue.1 The Norwegian Vitamin Trial (NORVIT) of 3,749 patients, who were followed for 3.5 years was designed to show the benefits of taking supplements—but the results were contrary to expectations. Folic acid supplementation was found to lower homocysteine levels by 28%., but to increase relative risks of heart attack, stroke, and death by 20%, along with a more than a 30% increase in cancer. Those with the highest baseline homocysteine levels (13 umol/L or greater) suffered the most harm from taking supplements of folic acid.



Homocysteine Is Only a Risk Factor

Elevated levels of the amino acid homocysteine, found with a blood test have been associated with many common diseases, including heart disease, strokes, venous thrombosis, dementia, and Alzheimer’s disease. The commonly made, but incorrect, assumption is that these diseases are caused by elevated homocysteine in the body and the solution is to give medications (vitamin pills) to fix the problem.

However, homocysteine is not the problem. Elevated homocysteine is only a sign that the body is becoming diseased and at risk of a tragedy. We call this type of sign a “risk factor”—it predicts future risk, but it is not a disease in itself—no one dies of an elevated homocysteine level—most commonly, clogged heart arteries are the actual cause of death for those people showing this sign. So what is the real meaning of this risk factor?

Homocysteine levels increase when people eat more meat and fewer vegetables. These same dietary habits cause other signs (risk factors)—indicating a higher chance of death and disability—to rise; like cholesterol, triglycerides, uric acid, blood sugar, lipoprotein a, C-reactive protein, blood pressure, and body weight. Fortunately, correcting the poor diet heals the underlying disease, and at the same time the risk factors show improvement.

Folic Acid Supplements Overload the Body

Consuming more than 0.2 mg of folic acid daily floods the bloodstream with this vitamin, overloading the metabolic capacities of the body, causing imbalances that increase the risk of heart disease and cancer.2 Folic acid is a synthetic version of the natural vitamin, folate, found in plant foods. Folate from food is essential for good health. Folic acid sold in capsules is a medication at best and a toxin at worst. When given in doses of 0.8 mg it will lower homocysteine by about 30% (3 to 4 umol/L).3 Higher doses than 0.8 mg have no greater benefit for lowering blood levels of homocysteine.

Folic Acid Mandated for U.S. Cereal Products



January 1998 was the mandatory deadline for the fortification of grain products with folic acid in the United States. Folic acid was added to flours used to make bread, rolls, and crackers. Another hefty source of this supplement comes from enriched (vitamin-added) “ready-to-eat cereals.”

Since 1998, folic acid intake has increased significantly in every segment of the U.S. population with the average additional intake of 0.22 mg/day.3,4 Remember, as little is .2 mg causes overloads and imbalances with an increased risk of illness . A significant segment of the USA population is now consuming over 1 mg/day of folic acid daily—an amount found by the NORVIT study to increase the risk of heart disease and cancer.

Doctors Harm Patients with Supplements

Cardiologists are fond of recommending vitamin pills to treat elevated homocysteine in hopes of preventing further heart disease in their patients. One of the most commonly prescribed preparations is called Foltx – a combination of 2.5 mg of folic Acid, 25 mg of vitamin B6, and 2 mg of vitamin B12. A recent study showed a similar preparation reduced the homocysteine levels of patients with a history of stroke by 2 units (umol/L), but found no difference in risk of future strokes, heart attacks, or death compared to a control group.5


Another recent study showing folic acid actually causes the heart arteries to close should cause doctors to mend their prescribing practices. After six months of supplementation in 636 heart patients with stents (stents are wire-mesh supports placed in the coronary arteries during angioplasty), the Folate After Coronary Intervention Trial found those patients taking folic acid had significantly more narrowing of the arteries, more artery closure (restenosis), and more major adverse cardiac events compared to those taking placebo—the exact opposite of what investigators had expected to find.6,7 As expected, the homocysteine blood levels were reduced by the above treatment. The authors recommended that the routine administration of folate treatment not be advocated at the present time.

To balance this out, here's what the same doctor says about supplements in another article:

When Supplements Benefit

Vitamins and minerals can be used as medications to cause effects – this is different than supplementation to promote natural health. Realize that all medications have adverse effects accompanying their intended, positive effects.

Vitamin C will not prevent common colds but may provide a modest benefit in reducing the duration of symptoms of colds.[21]

Vitamin D may delay loss of bone in elderly, but sunlight is the right source of this vitamin.[22]

Folic acid lowers homocysteine, but there is no evidence yet from controlled studies that this translates into reduced cardiovascular disease or cancer.[23]

Folic acid will prevent birth (neural tube) defects.[23]

Vitamin B12 should be taken when following a strict vegan diet – like the McDougall diet – if followed for more than three years or if pregnant or nursing.

Iodine supplementation prevents thyroid disease in areas of the world where iodine deficiency is endemic.[24]

Iron supplementation is used for treating iron deficiency diseases, like anemia (most of the time iron deficiency is due to other correctable causes, like bleeding, dairy products, etc.)

McDougall recommends that pregnant, nursing and long time (3 years or more) vegans take a B12 supplement, and comments the need for B12 supplementation here:

Why would a plant-food-based diet, heralded as a preventative and cure for our most common chronic diseases be deficient in any way? Such a diet appears to be the proper, intended, diet for humans, except for this one blemish. The reason for this apparent inconsistency is we now live in unnatural conditions—our surroundings have been sanitized by fanatical washing, powerful cleansers, antiseptics, and antibiotics. Since the germ theory of disease was developed by Louis Pasteur in 1877 our society has waged an all-out war on these tiny creatures—most of them extremely beneficial with only a very few acting as pathogens. The rare case of B12 deficiency may be one important consequence of too much cleanliness.

Since people can be B12 deficient already before they go vegan, writing anything that gives an impression that vegans don't need B12 supplements during their first three years is a good idea - but other than that, I think most of Dr. McDougall's writings make a lot of sense.

[Korn]

The link between homocysteine, B6 / B12 / B9 and heart disease is still being discussed.

From yesterday's news:

Vitamin B, Folate Supplements Won't Help Heart
In fact, new study hints they might be hazardous

TUESDAY, Aug. 19 (HealthDay News) -- A study to determine whether folic acid and vitamin B supplements help the heart has been cut short, because the pills weren't doing any good and might have even caused participants harm.


"This confirms what a lot of recent studies have found -- no benefit of taking vitamin B supplements to reduce the risk of heart disease, and it raises a few red flags," said Alice H. Lichtenstein, Gershoff professor of nutrition at Tufts University, Boston.

In the new study, reported in the Aug. 20 issue of the Journal of the American Medical Association, physicians at Haukeland University Hospital in Bergen, Norway, enrolled almost 3,100 volunteers. Three-quarters of them took various doses of vitamin B and folic acid (which is chemically a B vitamin), while the others got a placebo, an inactive substance.

The study was ended early, after an average follow-up of 38 months, because "we could not detect any preventive effect of intervention with folic acid plus vitamin B12 or with vitamin B6 on mortality or major cardiovascular events," the researchers reported.

They did find a slight reduction of stroke, but also a slight increase of cancer in those taking folic acid, but neither of these results reached statistical significance. The study was ended, because another Norwegian study of folic acid and vitamin B supplementation has also hinted at an increased incidence of cancer among users.

But the real bottom line here, according to Lichtenstein, is that "there is no evidence that individuals should take B vitamins to decrease the risk of heart disease, and there may be some evidence that they shouldn't."

[...]

The trials were initiated, because observational studies did link high blood levels of a protein called homocysteine with an increased risk of cardiovascular disease. In the new study, homocysteine levels did go down by 30 percent over the course of three years in people taking folic acid and vitamin B. However, there was no related effect on the risk of cardiovascular events.

[Korn]

They also demonstrated that cognitive impairment was significantly associated with elevated plasma total homocysteine. However, the decrease in homocysteine levels seen with the use of vitamin supplements did not improve cognition [30]. It is too soon to make any recommendations, but is an intriguing area of research.

Here's a link to an article about that very topic:
B12, Folate May Reduce Homocysteine Levels Without Affecting Cognition

Dec. 19, 2005 — Although supplementation for up to a year with oral B12 and folate substantially reduces total homocysteine levels in elderly patients with vascular disease, there is no effect on cognition, according to the results of the largest randomized trial to date, reported in the December issue of the American Journal of Clinical Nutrition.

"Homocysteine is an independent risk factor for vascular disease and is associated with dementia in older people," write David J. Stott, MD, from the University of Glasgow, Scotland, United Kingdom, and colleagues. "Potential mechanisms include altered endothelial and hemostatic function."

In this factorial 2 x 2 x 2, double-blind, placebo-controlled study, 185 patients 65 years or older with ischemic vascular disease were randomized to 3 active treatments: folic acid (2.5 mg) plus vitamin B12 (500 μg), vitamin B6 (25 mg), and riboflavin (25 mg). Endpoints included plasma homocysteine, fibrinogen, and von Willebrand factor at 3 months, and cognitive change measured with the Letter Digit Coding Test and the Telephone Interview of Cognitive Status after 1 year.

Mean plasma homocysteine concentration was 16.5 ± 6.4 μmol/L at baseline. It was 5.0 μmol/L (95% confidence interval [CI], 3.8 - 6.2) lower in patients given folic acid plus vitamin B12 than in patients not given folic acid plus vitamin B12, but it did not change significantly with vitamin B6 or riboflavin treatment.

[Korn]

Homocysteine: A Cardiovascular Risk
Factor Worth Considering


An excerpt:

Dietary supplementation with folic acid can reduce elevated homocysteine levels in most patients. The usual therapeutic dose is 1 mg/day. When this is not effective, vitamins B6 and/or B12 can be added to the regimen, which should be continued permanently. Some doctors routinely recommend that patients known to have atherosclerosis take B-vitamin supplements without being tested to determine whether their homocysteine level is elevated. They reason that since supplementation is harmless and since elevated homocysteine levels might be a factor, testing is not worth bothering with. Even though some patients may be helped with this "shotgun" strategy, I believe it is far better to (a) find out whether a problem exists and (b) to be certain that if homocysteine levels are elevated, the vitamin regimen is adjusted to be sure that lowering is achieved.

A recent study that followed 80,000 women for 14 years found that the incidence of heart attacks was lowest among those who used multivitamins or had the highest intake of folic acid and B6 from dietary sources [6]. This data parallels the finding that elevated homocysteine levels are associated with a higher incidence of heart disease. However, the researchers measured folic acid blood levels but did not measure homocysteine or B12 levels. Rather, they assumed that low folic acid levels were caused by inadequate dietary intake. Victor Herbert, M.D., a leading expert on B12 metabolism, has pointed out that the low folic acid levels among the experimental subjects could have been caused by decreased B12 absorption related to getting older.

Lowering the serum concentration of homocysteine has been proven to reduce the risk of adverse cardiovascular events among people with homocystinuria. Studies have not yet determined whether lowering homocysteine levels reduces the incidence of heart attacks or strokes among people with mildly elevated homocysteine levels [7,8], but many experts believe that scientific studies will prove that it does. This belief has been strongly supported by a four-year study in which 101 men with vascular disease were given supplementary doses of folic acid, B6 , and B12. Ultrasound examinations of their carotid arteries found a decrease in the amount of carortid plaque in their arteries, with the greatest effect in those whose homocyteine levels had been highest before the treatment began [9].

Screening for elevated homocysteine levels is advisable for individuals who manifest coronary artery disease that is out of proportion to their traditional risk factors or who have a family history of premature atherosclerotic disease. Levels above 9 or 10 µmol/l warrant treatment. The effect of supplementation is usually apparent within a month. The laboratory test can be obtained for about $40. Some physicians recommend that all patients with atherosclerotic disease be screened. A recent study of the effect on homocysteine of either folic acid or B12 alone found that the body adjusts its reliance on one or the other and that supplementing with both provides a more certain way to improve homocysteine levels [10].

At least a dozen large-scale studies following a total of more than 60,000 people are underway in the United States, Canada, and Europe to examine the effects of lowering blood homocysteine levels on the incidence of heart attacks and/or strokes [9,11]. The longest one so far involved 553 patients who had had successful angioplasty has found that lowering homocysteine levels significantly decreased the incidence of major cardiac events after angioplasty. The participants were randomly assigned to receive a combination of folic acid, vitamin B12, and vitamin B6 or a placebo for 6 months and were followed for about six more months. The study found that the incidence of heart attacks, death and need for repeat revascularization were about one third less in the vitamin group than in the control group [12].


[...]

This article was revised on March 29, 2003.

[Korn]

http://www.streetdirectory.com/trave..._vitamins.html

The trouble was that in 2005 researchers at John Hopkins University published a whole series of reports that found rather disappointing results by and largely to do with the intake of Vitamin E. Indeed their findings went as far as to say that in certain cases, large daily doses (400 IU and over) actually went as far as increasing the risk of Mortality. This was followed in 2006 with the results published in the New England Journal of Medicine of a study by and largely to do with the intake of Vitamin B. The study showed that despite the various properties that the Vitamin B types displayed, they were no more likely to reduce the incidence of Heart Attacks or other cardiovascular problems than the placebos given as part of the same study.

[Korn]

From http://www.sciencedirect.com/science...36f5401c2fa9b6


Vegan Diet-Based Lifestyle Program Rapidly Lowers Homocysteine Levels
by David J. DeRose M.D., M.P.H.a, 1, Zeno L. Charles-Marcel M.D.b, a, Judith M. Jamison Ph.D., R.D.a, Joshua E. Muscat M.P.H.c, Marc A. Braman M.D.a, Gerard D. McLane Dr.P.H.a and J. Keith Mullen M.T. (A.S.C.P.)d

Background. Plasma homocysteine levels have been directly associated with cardiac disease risk. Current research raises concerns as to whether comprehensive lifestyle approaches including a plant-based diet may interact with other known modulators of homocysteine levels.
Methods. We report our observations of homocysteine levels in 40 self-selected subjects who participated in a vegan diet-based lifestyle program. Each subject attended a residential lifestyle change program at the Lifestyle Center of America in Sulphur, Oklahoma and had fasting plasma total homocysteine measured on enrollment and then after 1 week of lifestyle intervention. The intervention included a vegan diet, moderate physical exercise, stress management and spirituality enhancement sessions, group support, and exclusion of tobacco, alcohol, and caffeine. B vitamin supplements known to reduce blood homocysteine levels were not provided.
Results. Subjects' mean homocysteine levels fell 13%: from 8.66 μmol/L (SD 2.7 μmol/L) to 7.53 μmol/L (SD 2.12 μmol/L; P < 0.0001). Subgroup analysis showed that homocysteine decreased across a range of demographic and diagnostic categories.
Conclusions. Our results suggest that broad-based lifestyle interventions favorably impact homocysteine levels. Furthermore, analysis of Lifestyle Center of America program components suggests that other factors in addition to B vitamin intake may be involved in the observed homocysteine lowering.

[Korn]

(Also posted in the B12 overdose / megadose thread):

From http://www.cancerresearchuk.org/abou...gyourrisk/diet
Eating lots of red or processed meat is a risk factor for bowel cancer. There is also some evidence that breast, lung, prostate and pancreatic cancers are linked to a diet high in red or processed meat.
(I know there is some controversy about breast cancer/meat link. Korn).

Commenting this post from 2005, there are now new, related findings about B12 and (mainly lung) cancer:

Here's the abstract:
http://jama.ama-assn.org/cgi/content/short/302/19/2119

Results During study treatment, median serum folate concentration increased more than 6-fold among participants given folic acid. After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B12 vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B12 vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07-1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B12 vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04-1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B12. Vitamin B6 treatment was not associated with any significant effects.

Conclusion: Treatment with folic acid plus vitamin B12 was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods.

The study is discussed here: Treatment With Folic Acid, Vitamin B12 Associated With Increased Risk of Cancer, Death

High Doses of B Vitamins Associated With Increased Decline in Kidney Function for Patients With Kidney Disease from Diabetes

According to background information in the article, several observational studies have shown a significant association between high concentrations of plasma total homocysteine and the risk of developing diabetic nephropathy, retinopathy, and vascular diseases, including myocardial infarction (MI; heart attack) and stroke. B-vitamin therapy (folic acid, vitamin B6, and vitamin B12) has been shown to lower the plasma concentration of homocysteine.
Andrew A. House, M.D., of the University of Western Ontario, and J. David Spence, M.D., of the Robarts Research Institute, London, Ontario, and colleagues conducted a study to examine whether B-vitamin therapy would slow the progression of diabetic nephropathy and prevent vascular events in 238 patients with type 1 or 2 diabetes. The randomized, placebo-controlled trial was conducted at five university medical centers in Canada between May 2001 and July 2007. Patients received single tablet of B vitamins containing folic acid (2.5 mg/d), vitamin B6 (25 mg/d), and vitamin B12 (1 mg/d), or matching placebo. The primary outcome was change in radionuclide glomerular filtration rate (GFR; a measure of kidney function) between baseline and 36 months. Other outcomes included dialysis and a composite of heart attack, stroke, revascularization and all-cause death. Plasma total homocysteine was measured. Participants were followed-up for an average of 31.9 months.
Among the results, the researchers found that participants assigned to the B-vitamin group had a greater decrease in radionuclide GFR (and subsequently poorer kidney function) compared with the placebo group. Also, participants randomized to receive B vitamins had a significantly greater number of cardiovascular and cerebrovascular events, with the 36-month risk of a composite outcome, including heart attack, stroke, revascularization, and all-cause mortality that was double in the B-vitamin group, compared to the placebo group. There was no difference in requirement of dialysis.
Regarding plasma total homocysteine levels, at 36 months, participants in the B-vitamin group had an average decrease while participants in the placebo group had an average increase.
"Given the recent large-scale clinical trials showing no treatment benefit, and our trial demonstrating harm, it would be prudent to discourage the use of high-dose B vitamins as a homocysteine-lowering strategy outside the framework of properly conducted clinical research," the authors conclude.

Heart disease: B-Vitamin Pills Have No Effect, Review Finds

Certain B-vitamins, specifically B12, B9 (folic acid) and B6, influence levels of an amino acid in the blood called homocysteine. High levels of this molecule are associated with an increased risk of heart disease. It has been suggested that giving B-vitamin supplements could help regulate levels of homocysteine, thereby reducing the risk of cardiovascular disease and death. But according to the researchers, there is no scientific basis for this claim.
The review included eight trials involving a total of 24,210 people. None of the eight trials individually supported the idea that giving B-vitamin supplements could prevent cardiovascular disease. Together the data show that B-vitamin supplements, whether compared with placebos or standard care, have no effect on the incidence of heart attack, stroke or death associated with heart disease.
"Prescription of these supplements cannot be justified, unless new evidence from large high quality trials alters our conclusions. There are currently three ongoing trials that will help to consolidate or challenge these findings," says Martí-Carvajal.

[Korn]

First a short summary of the main topic that's being discussed in this thread:

There has been an ongoing disagreement for many years, regarding the link between homocysteine levels, B vitamins and heart disease.

To simplify: "Group A" have insisted that since high homocysteine levels often are associated with reduced risk of heart disease, the reason for the reduced heart disease risk is the lower homocysteine level itself.

"Group B" has emphasized that even if there's a link between low homocysteine levels and heart health, lowering people's homocysteine levels as such doesn't necessarily mean reduced heart disease risk, because maybe the changes seen is homocysteine levels and heart disease risk aren't 'cause and result', but that both the reduced risk and the homocysteine levels are symptoms of something else. In short, changing homocysteine levels as such may not be the reason that the heart disease risk will be altered.

Vegans often have higher levels of vitamin B6 than non-vegans, but lower levels of B12 than non-vegans. Both B6 and B12 affects homocysteine levels.

A lot of research have found links between intake of various B12-rich animal products and health problems. Some of these reports can be found in our Are animal products healthy? section, inside the Human Evolution subforum. These reports usually never claim that the reason for the reported health problems are high B12 levels, and we know that having too low B12 levels is a bad idea, and potentially dangerous. But if these studies would have included detail information about the B12 levels of the participants, we can almost be 100% certain that the link between eg. cancer and animal products in many cases isn't only a link between cancer and animal products, but between cancer and increased B12 levels. Why? Because the one nutrient that sticks out when comparing people who consume animal products with people who don't, is B12: vegans have lower B12 levels, non-vegans have higher B12 levels.

Here are some of the cancer risks associated with intake of various animal products: Prostate cancer, breast cancer, esophageal cancers, vision loss, pancreatic cancer, type 1 diabetes, high blood pressure, arthritis, lung disease, colorectal cancer, bladder cancer, ovarian cancer, testicular cancer, uterine cancer, leukemia/stomach cancer, bone marrow cancer.

But when consuming meat, eggs or dairy products, chunks of meat or pieces of eggs aren't floating around in our lungs, ovaries or bladders. The animal products are broken down, and in terms of cancer risk, we need to look at what it is that animal products contain, in large amounts, that plants don't have (in such large amounts, or at all). Animal fats, animal proteins and B12 is essential here.

The solution is not to ignore B12, because too low B12 levels are also associated with lots of health problems. Is the solution to increase our B12 levels to the levels (5-15 mcg) meat eaters consume? Tricky question. But read on...

In my previous post, I quoted some new-ish findings from various sources:
• "Treatment with folic acid plus vitamin B12 was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway"
• "The researchers found that participants assigned to the B-vitamin group had a greater decrease in radionuclide GFR (and subsequently poorer kidney function) compared with the placebo group"
• "Participants randomized to receive B vitamins had a significantly greater number of cardiovascular and cerebrovascular events"
• "All-cause mortality was double in the B-vitamin group, compared to the placebo group"
• "Given the recent large-scale clinical trials showing no treatment benefit, and our trial demonstrating harm, it would be prudent to discourage the use of high-dose B vitamins as a homocysteine-lowering strategy outside the framework of properly conducted clinical research."
• "Together the data show that B-vitamin supplements, whether compared with placebos or standard care, have no effect on the incidence of heart attack, stroke or death associated with heart disease"
• "Prescription of these supplements cannot be justified, unless new evidence from large high quality trials alters our conclusions"

These studies were not made on vegans, and in spite of these conclusions, people with a minimal or no B12 intake could still benefit from B12 intake, and see real health improvements from taking supplements. Lots of environmental and life style issues causes B12 levels in water, humans, plants and soil to become artificially low, and we all need to deal with that.


Still: what is it that causes the link between high homocysteine and increased heart disease risk, if it's not the homocysteine itself?


Here's an interesting study:
Vitamin B6 and Heart Health

High blood levels of homocysteine have been associated with cardiovascular disease. A new study in humans, published in the American Journal of Clinical Nutrition, found that higher blood levels of the active form of vitamin B6 (pyridoxal-5’-phosphate or PLP), may reduce cardiovascular disease risk other than by just reducing blood homocysteine. As levels of PLP increase, an inflammatory protein (CRP) and a marker for oxidative stress decline, both of which may indicate a reduced risk for cardiovascular disease.

More here: http://www.ajcn.org/cgi/content/abstract/91/2/337


More later, about three related topics:
1) If low homocysteine levels are good for heart health, and vegans have higher homocysteine levels than non-vegans, why do vegans have so healthy hearts?
2) In which cases have links between disease (as opposed to 'allergic reactions') and high B12 levels been documented?
3) If B6 and B12 is good for the heart, but high amounts of B12 area associated with various potential side effects (eg. certain types of cancer), isn't the ongoing B12/vegan discussion actually focusing on the benefits of eating vegan, since vegan food is rich in B6, and low in B12?

[Korn]

Here are two new studies, when seen together, may explain why vegans have so healthy hearts in spite of having a lower B12 intake:

Serum concentrations of vitamin B12 and folate in British male omnivores, vegetarians and vegans: results from a cross-sectional analysis of the EPIC-Oxford cohort study.

Background/Objectives:Vegans, and to a lesser extent vegetarians, have low average circulating concentrations of vitamin B12; however, the relation between factors such as age or time on these diets and vitamin B12 concentrations is not clear. The objectives of this study were to investigate differences in serum vitamin B12 and folate concentrations between omnivores, vegetarians and vegans and to ascertain whether vitamin B12 concentrations differed by age and time on the diet.Subjects/Methods:A cross-sectional analysis involving 689 men (226 omnivores, 231 vegetarians and 232 vegans) from the European Prospective Investigation into Cancer and Nutrition Oxford cohort.Results:Mean serum vitamin B12 was highest among omnivores (281, 95% CI: 270-292 pmol/l), intermediate among vegetarians (182, 95% CI: 175-189 pmol/l) and lowest among vegans (122, 95% CI: 117-127 pmol/l). In all, 52% of vegans, 7% of vegetarians and one omnivore were classified as vitamin B12 deficient (defined as serum vitamin B12 <118 pmol/l). There was no significant association between age or duration of adherence to a vegetarian or a vegan diet and serum vitamin B12. In contrast, folate concentrations were highest among vegans, intermediate among vegetarians and lowest among omnivores, but only two men (both omnivores) were categorized as folate deficient (defined as serum folate <6.3 nmol/l).Conclusion:Vegans have lower vitamin B12 concentrations, but higher folate concentrations, than vegetarians and omnivores. Half of the vegans were categorized as vitamin B12 deficient and would be expected to have a higher risk of developing clinical symptoms related to vitamin B12 deficiency.European Journal of Clinical Nutrition advance online publication, 21 July 2010; doi:10.1038/ejcn.2010.142.

Oral supplementation of folic acid for two months reduces total serum homocysteine levels in hyperhomocysteinemic Greek children.

Background & Aim: Hyperhomocysteimemia is a cardiovascular risk factor even among children. Supplementation of oral folic acid may reduce homocysteine levels to normal. However, data is limited at this point for healthy children and adolescents.Methods: Five hundre and twenty four children participated in the study; Twenty six of them were found to be hyperho mocysteinemic(>95(th) percentile for age). Twenty of them received 5 mg of folic acid twice per week for two consecutive months while the other six received a diet rich in dietary folate.Results: Serum homocysteine levels were statistically significantly decreased from 13.1 (10-24.2 micromol/L ) to 7.7 (4.9- 15.2 micromol/L), p<0.001. Serum folate levels were significantly rose from 4.3 (3-20 ng/mL) to 16.8 (7-20 ng/mL), p<0.001. On the contrary, no important changes were observed in the above parameters in children to whom a diet rich in folic acid was recommended. Homocysteine levels were found to be positively associated with age (r=0.314, p<0.001), BMI (r=0.192, p<0.001), WC (r = 0.215, p<0.001), simple sugars (r= 0.182, p<0.001 ) and negatively associated with folic acid (r = -0.331, p<0.001), vitamin B12 (r = -0.214, p<0.001) and dietary folic acid (r= -0.228, p=0.003).Conclusions: Oral folic acid 5 mg twice per week may efficiently reduce serum homocysteine levels and increase serum folic acid levels in healthy children with increased homocysteine levels (>95(th) percentile for age). Hyperhomocysteinemia in childhood may be a predictive factor of cardiovascular disease. In addition, these results may offer more help to health practioners in order to establish more prospective studies to elucidate the relationship between homocysteine, folic acid and heart disease in children.

PMID: 20596265 [PubMed - in process]PMCID: PMC2895291Free PMC Article

[Korn]

Another study:

Vitamin B-12 status is not associated with plasma homocysteine in parents and their preschool children: lacto-ovo, lacto, and ovo vegetarians and omnivores.

OBJECTIVE: Vegetarians may be at risk of certain nutrient deficiencies, particularly vitamin B-12. Vitamin B-12 deficiency may increase plasma homocysteine concentration and thus may potentially increase the risk of cardiovascular disease in vegetarians. The purpose of this study was to assess and compare plasma homocysteine and vitamin B-12 status in vegetarian and omnivorous preschool children and their parents. In addition, the association between parents' and children's homocysteine and vitamin B-12 concentration was also examined. METHODS: Fifty-six omnivores (28 preschool children and one of their parents), 34 lacto-ovo vegetarians (16 parents and 18 children), 5 ovo vegetarians (2 parents and 3 children), 1 lacto vegetarian parent, and 2 vegan parents were enrolled in this study. The mean age of preschool children was 5.1 +/- 1.3 years and that of their parent was 35.4 +/- 4.2 years. Nutrient intakes were recorded using 3-day dietary records. Fasting venous blood samples were obtained to measure serum creatinine, high-sensitivity C-reactive protein, hematological parameters, plasma homocysteine, serum folate, and vitamin B-12 concentrations. RESULTS: There was no significant difference in dietary folate intake between vegetarian and omnivores within parent and child groups. The mean plasma homocysteine level of vegetarian parents and their children was in the physiological range, and they had slightly but not significantly higher plasma homocysteine levels than omnivores. Omnivorous parents and their children had significantly higher vitamin B-12 intake than vegetarian participants but similar serum vitamin B-12 concentrations. Plasma homocysteine concentration was significantly and negatively associated with only serum folate levels (beta = -0.15) and dietary vitamin B-12 intake (beta = -0.05) in the omnivorous parents after adjusting for age, gender, body mass index, and serum creatinine. CONCLUSION: Vegetarian parents and their preschool children had a lower vitamin B-12 intake than omnivorous parents and their preschool children but similar plasma vitamin B-12 and homocysteine concentrations. Plasma homocysteine was not associated with serum vitamin B-12 levels in the parent, child, or pooled group.

[Korn]

Is a low blood level of vitamin B12 a cardiovascular and diabetes risk factor? A systematic review of cohort studies.

PURPOSE: To assess the prior hypothesis that low blood vitamin B12, partly through hyperhomocysteinemia and partly through direct effects, increases the risk of cardiovascular diseases and diabetes. As background, we also extracted all-cause mortality from the studies that met our criteria. METHODS: A systematic review of prospective cohort studies identified through searching six electronic databases, screening of reference lists, and citation search. Included studies reported data on the association between vitamin B12 blood levels, or other appropriate surrogate biological markers e.g. holotranscobalamin or serum/urine methylmalonic acid, and fatal or non-fatal incident diabetes and cardiovascular events. RESULTS: Seven studies were included. Studies differed regarding the population studied, length of follow-up, study outcomes, and data analysis-a narrative synthesis approach was performed to examine the results. Most studies met few of the quality assessment criteria which were adapted from the Scottish Intercollegiate Guidelines Network (SIGN). Only one high-quality study reported that low B12 increased the risk of incident cerebral ischaemia (RR = 1.76; 95% CI = 1.16-2.68). After controlling for homocysteine, the association persisted although weakened (RR = 1.57; 95% CI = 1.02-2.43), suggesting that the effects of low B12 were only partly mediated by homocysteine. In two studies, higher B12 levels were associated with a greater risk of total mortality (RR = 1.00; 95% CI = 1.00-1.00 and HR = 1.15; 95% CI = 1.08-1.22, respectively) and combined fatal and non-fatal coronary events (RR = 1.00; 95% CI = 1.00-1.00). No association between study outcomes and vitamin B12 levels was found in four other studies. CONCLUSIONS: Surprisingly, there is only very limited evidence that vitamin B12 deficiency predisposes to the risk of mortality and morbidity from either cardiovascular diseases or diabetes in adults. Current data do not support vitamin B12 supplementation to reduce the risk of cardiovascular diseases or diabetes.

PMID: 20585951 [PubMed - as supplied by publisher]

[Korn]

Serum homocysteine and folate concentrations are associated with prevalent age-related hearing loss.

Abstract
Elevated total serum homocysteine (tHcy) concentrations associated with vitamin B-12 or folate deficiencies may adversely affect blood flow to the cochlea, leading to age-related hearing loss (presbycusis). However, only 2 small cross-sectional studies have assessed the link between folate, vitamin B-12, or tHcy and presbycusis. We aimed to determine both the cross-sectional and longitudinal association between serum concentrations of folate, vitamin B-12, or tHcy and risk of age-related hearing loss. The Blue Mountains Hearing Study is a population-based survey of age-related hearing loss (1997-1999 to 2002-2004). Presbycusis was measured in 2956 participants (aged >or=50 y) and was defined as the pure-tone average of frequencies 0.5, 1.0, 2.0, and 4.0 kHz >25 dB hearing level (HL). Serum concentrations of folate, vitamin B-12, and tHcy were determined from blood samples. Participants with elevated tHcy (>20 micromol/L) concentrations had a 64% increased likelihood of prevalent hearing loss (>25 dB HL) [multivariate-adjusted odds ratio (OR) 1.64; 95% CI, 1.06-2.53]. Low serum folate levels (<11 nmol/L) increased the odds of prevalent mild hearing loss (>25-40 dB HL), multivariate-adjusted [OR 1.37 (CI 1.04-1.81)]. Serum vitamin B-12, however, was not significantly associated with prevalent hearing loss. Serum folate, vitamin B-12, and tHcy concentrations were also not significantly associated with an increased risk of incident hearing loss. Serum concentrations of tHcy and folate were associated with age-related hearing loss cross-sectionally, but no temporal links were observed, which could be due to insufficient study power. Further, large prospective studies will be required in the future to assess these associations.

PMID: 20573942 [PubMed - indexed for MEDLINE]

[Korn]

Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial.

Abstract
CONTEXT: Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal. OBJECTIVE: To assess the effects of reducing homocysteine levels with folic acid and vitamin B(12) on vascular and nonvascular outcomes. DESIGN, SETTING, AND PATIENTS: Double-blind randomized controlled trial of 12,064 survivors of myocardial infarction in secondary care hospitals in the United Kingdom between 1998 and 2008. INTERVENTIONS: 2 mg folic acid plus 1 mg vitamin B(12) daily vs matching placebo. MAIN OUTCOME MEASURES: First major vascular event, defined as major coronary event (coronary death, myocardial infarction, or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization. RESULTS: Allocation to the study vitamins reduced homocysteine by a mean of 3.8 micromol/L (28%). During 6.7 years of follow-up, major vascular events occurred in 1537 of 6033 participants (25.5%) allocated folic acid plus vitamin B(12) vs 1493 of 6031 participants (24.8%) allocated placebo (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.97-1.12; P = .28). There were no apparent effects on major coronary events (vitamins, 1229 [20.4%], vs placebo, 1185 [19.6%]; RR, 1.05; 95% CI, 0.97-1.13), stroke (vitamins, 269 [4.5%], vs placebo, 265 [4.4%]; RR, 1.02; 95% CI, 0.86-1.21), or noncoronary revascularizations (vitamins, 178 [3.0%], vs placebo, 152 [2.5%]; RR, 1.18; 95% CI, 0.95-1.46). Nor were there significant differences in the numbers of deaths attributed to vascular causes (vitamins, 578 [9.6%], vs placebo, 559 [9.3%]) or nonvascular causes (vitamins, 405 [6.7%], vs placebo, 392 [6.5%]) or in the incidence of any cancer (vitamins, 678 [11.2%], vs placebo, 639 [10.6%]). CONCLUSION: Substantial long-term reductions in blood homocysteine levels with folic acid and vitamin B(12) supplementation did not have beneficial effects on vascular outcomes but were also not associated with adverse effects on cancer incidence. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN74348595.

PMID: 20571015 [PubMed - indexed for MEDLINE]

[Korn]

Dietary folate and vitamin b6 and B12 intake in relation to mortality from cardiovascular diseases: Japan collaborative cohort study.

Stroke. 2010 Jun;41(6):1285-9. Epub 2010 Apr 15.
Dietary folate and vitamin b6 and B12 intake in relation to mortality from cardiovascular diseases: Japan collaborative cohort study.
Cui R, Iso H, Date C, Kikuchi S, Tamakoshi A; Japan Collaborative Cohort Study Group.

Department of Social and Environmental Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita-shi, Osaka 565-0871 Japan.
Abstract
BACKGROUND AND PURPOSE: The association of dietary folate and B vitamin intakes with risk of cardiovascular disease is controversial, and the evidence in Asian populations is limited. METHODS: A total of 23 119 men and 35 611 women, age 40 to 79 years, completed a food frequency questionnaire in the Japan Collaborative Cohort Study. During the median 14-year follow-up, there were 986 deaths from stroke, 424 from coronary heart disease, and 2087 from cardiovascular disease. RESULTS: Dietary folate and vitamin B(6) intakes were inversely associated with mortality from heart failure for men and with mortality from stroke, coronary heart disease, and total cardiovascular disease for women. These inverse associations did not change materially after adjustment for cardiovascular risk factors. No association was found between vitamin B(12) intake and mortality risk. CONCLUSIONS: High dietary intakes of folate and vitamin B(6) were associated with reduced risk of mortality from stroke, coronary heart disease, and heart failure among Japanese.

PMID: 20395608 [PubMed - indexed for MEDLINE]

[Korn]

Determinants of homocysteine levels in Ivorian rural population.

Tiahou G, Dupuy AM, Jaussent I, Sees D, Cristol JP, Badiou S.

Laboratoire de Biochimie Médicale, Université Bouake, Bouake, Cote d'Ivoire.
Abstract
In the present study, homocysteine (Hcy) and vitamin B status were determined in healthy subjects living in two opposite regions of the Ivory Coast. Fifty-six subjects from a coastal region (Bodou) having a fish-based diet and 56 subjects from a mountainous area (Glanle) having a vegetarian diet were tested to sample Hcy, folate, vitamin B12, creatinine, and lipid levels, as well as inflammation and nutritional parameters. An increased prevalence of Hcy > or = 15 micromol/L was observed, reaching 60 % of all subjects. The Bodou group exhibited significantly higher Hcy levels than the Glanle group [20.1 (9.7 - 41.4) vs. 13.6 (5.5 - 48.7) micromol/L, p<0.0001], despite higher vitamin B12 levels [593 (163 - 1860) vs. 234 (83 - 585) pg/mL, p<0.0001]. Although folate levels were lower in subjects from Bodou compared to Glanle [3.2 (2.0 - 7.3) vs. 6.0 (1.9 - 18.2) ng/mL, p<0.0001], there was no significant relationship with Hcy levels in any groups. Interestingly, there were significantly higher creatinine levels in subjects from Bodou compared to Glanle and a significant positive relationship with Hcy levels was evident in each group. In conclusion, Hcy levels in an Ivorian population having a fish-based diet appeared significantly higher compared to subjects having a vegetarian diet. However, folate and vitamin B12 status did not emerge as the major determinants of this difference; a stronger relationship was observed with creatinine levels.

PMID: 20533218 [PubMed - indexed for MEDLINE]

[katieli]

A friend of mine, who is a 50 year old male vegan just got his B12 and homocsyeine test results. They show he is at an increased risk of heart attack. Luckily, this is easily resolved with B12 supplementation. This is the 3rd male friend who has tested low for B12. The others didn't test their homocysteine though.

I think maybe too many vegans neglect making sure they have adequate B12 and don't realise how serious the risks can be. While a vegan diet is generally healthy, we have to make sure we take care of the B12 issue. I know this is mentioned a lot, but better safe than sorry.

See full details at Vegan B12 Test Results.

[Korn]

Some comments....

The B12 test was conducted in order to measure B12 serum levels. This test can produce false negatives and false positives, so an MMA urine test was also ordered. The MMA urine test is a more accurate test for B12 levels, because MMA levels rise as B12 levels fall. So a high MMA reading would mean a B12 deficiency, even if the B12 serum levels tested as normal.

I'm sure MMA tests for now also is a good idea, but MMA tests are also said to be inaccurate.
One test showed that more than 50% of all (non-vegan, I assume) seniors had MMA levels outside the normal range. It's also been stated that even if the B12 levels are low, and the MMA levels are normal, the actual B12 levels are acceptable.

High homocyseine levels can lead to blood clotting, heart attack and stroke, so it was considered essential that this was tested.

Have you seen any of the articles referred to in our homocysteine thread? There has been an increasing amount of articles over the years suggesting that high homocysteine levels are a symptom, and not a cause for high B12 levels. Not that high hCy levels are something to strive for at all, but treating the symptoms won't always help, or help at all. Please have a look at the thread and let me know what you think...

Vitamin B12 level was 193 pg/ml, compared to a normal range of 240-1000. In Japan, the normal range starts at 400.

I think Japan have the highest low threshold for 'normal' of all countries - after they raised it from 200 pg/ml (145 pM) to 550 pg/ml (400 pM). If I'm not mistaken, a few countries (Australia??) even consider 100 pmol (circa 135 pg/ml) as the minimum level to be considered normal.


More discussion about normal ranges here: http://www.pernicious-anaemia-societ...topic.php?t=21

So this result shows quite a deficiency,which isn't surprising given the fact that the person is vegan and hasn't supplemented with B12 for 3-5 years.

That would of course depend on a lot of factors, eg. lifestyle/how many B12 antagonistic elements he is exposed to, which country which has the most correct and useful reference for 'normal', if vegans need as much B12 as others etc.

Homocysteine level was 14.9 umol/l. This is an extremely high reading and means that there is an increased risk of heart attack.

According to three of the four first result I got when I just googled normal range for homocysteine, it's in the normal range (under 15). But of course we don't want too high hCy levels.

Without being tested for B12 deficiency, this person could possibly have died of a heart attack, due to high homocysteine levels.

Again, please have a look at our thread about homocysteine, B12 and heart disease. It's long, but the newest studies are found at the end of the thread. We don't want to take any risks, or to have too little B12, which is easy to get due to a lot of reasons, but we have to differentiate between facts and assumptions.

When a link between homocysteine and B12 levels were discovered, suggestions about reducing the max. accepted, 'normal' range were suggested, but at the moment, the trend seems to be to think that the link between B12 and Hcy isn't exactly what it appeared to be. I don't have any personal opinions about what the upper, accepted level for hCy should be.


There's some interesting info here as well, re. the use of the term B12 deficiency/deficient:
http://www.b12.com/uMMA.htm

[Korn]

ETA; I just merged this threads with the homocysteine/heart disease, since they are about the same topic.

And for those who are interested, here 's the conversion table needed for converting pmol to pg/mL and vice versa:


pmol/l x 1.3553 = pg/mL
pg/mL x 0.7378 = pmol/L

Vitamin B12 level was 193 pg/ml, compared to a normal range of 240-1000

I just looked at minimum B12 levels from lots of countries like US, UK etc, and converted all the values to pg/ml. I did not include Japan and Canada, because it's currently unclear to me what the actual minimum numbers are. More about that later.

Anyway, the average minimum I got, after the conversion, was 187 pg/mL. Only one country had a normal range starting as high as 240 - Finland, which has 180 pmol/L. I wonder which country is it that has a normal range of 240-1000 pg/ml?

Most of our members come from UK and US. UK has a value equal to the average for these 19 places: 187 pg/mL. Northern Ireland has 158 pg/mL. US has 180 pg/mL. With all due respect, I don't think it's really relevant, in a B12 context, to talk about that this guy's B12 levels as a deficiency case, where he could have died of a heart attack when his levels are within what lots of countries consider normal.

Maybe these values will be updated, and I'll make a table soon, in a separate thread, showing what's considered normal range for as many countries as possible.

This vegan's MMA results could of course change the outcome of this test - but since he, in spite of not having taken any supplements for 3-5 years, still has a B12 level within the range of what eg. UK considers normal, this sounds more like great news than bad news.

[sandra]

Sorry, if this is the wrong place to ask this question but what causes heart disease in non-vegans then? Does B12 deficiency contribute to non vegans disease or is it just in vegans?

[Korn]

Sorry, if this is the wrong place to ask this question but what causes heart disease in non-vegans then?

There are conflicting theories about that, but in general vegans should pay more attention to B12 than non-vegans (and non-vegans need to pay more attention to certain other nutrients more than vegans).

One thing to take into consideration is that while some reports say that increased B12 levels have no effect on heart disease for the average population, it could still have an effect for people with marginal B12 levels - but there's an increasing agreement, it seems, that the factors that cause heart disease also cause high homocysteine levels, which is why it may not help only to reduce the hcy levels.

Among things that can contribute to increased risk of various heart problems are high blood pressure, high cholesterol, high triglycerides, obesity/overweight, diabetes, smoking, lack of physical activity, age, (emotional) stress, heredity, birth control pills, alcohol, some medications, drug abuse, excessive alcohol or caffeine use, bacteria, viruses, parasites, unhealthy fat and other dietary reasons, too much salt and much more. And even if it would be confirmed once and for all that high homocysteine is a result of the many conditions that cause unhealthy hearts, the high homocysteine levels could possibly also influence the situation in a negative direction. When studies come to conflicting conclusions, there may be still something useful in all of them... Also, remember that even if a vegan is a vegan today, s/he may have been eating meat and unhealthy fats for the past 30 years, and these 30 years most likely have an affect on him/her health even if he quits all his bad habits.

I'm sorry if I have posted some of these links earlier, but here's some more interesting reading:

Vitamin and mineral supplements for cancer prevention: issues and evidence
Vitamins and minerals: ineffective in preventing cancer and cardiovascular disease
Plants, not Pills, for Vitamins and Minerals

I have to emphasize, again, that I'm not trying to convince anyone that they shall ignore their levels of B12, MMA or other significant factors, or that some of the studies I have quoted are correct while others are totally wrong. I think the only way to get a good overview of the available facts is too look at the big picture, and not to stare only one some of the facts that have been presented.

[sandra]

I suppose the bottom line is it isn't good for anyone to be deficient in any vitamin I suppose. Severe iron deficiency can produce left ventricular dysfunction and overt heart failure for example. Then again too much iron can cause heart problems too. I like to keep an open mind with regard to all the medical evidence as one year they tell us one thing and the next they say the exact opposite.

[Korn]

Here's a raw vegan doctor, Fred Bisci, which I've heard about before. He's now 80-81 years old, and is talking about exercise, LDL, HDL, homocysteine and more.


More here.

Among many things, he mentions a topic that isn't discussed so often when homocysteine is discussed - urea, also mentioned here: http://forum.lowcarber.org/archive/index.php/t-54420

[Korn]

Food sources of betaine

Betaine is used to treat a condition called homocystinuria, in which the body's inability to break down certain proteins causes a buildup of those proteins in the blood. This buildup leads to problems such as fatigue, seizures, vision problems and blood clots. While betaine is available as a powder supplement, it can also be found in food. A doctor should be consulted before using betaine; other medications may be prescribed to take along with the betaine.
Quinoa
Uncooked Quinoa contains 630 mg of betaine in every 100 grams. Quinoa is a versatile grain that is easy to digest. It can be substituted for other grains in many recipes and is often included in soups and salads.
Spinach
Raw spinach contains 550 mg of betaine in every 100 grams. Spinach is used in a variety of recipes and can be used as a substitute for lettuce in salads. It can also be used in sandwiches, cooked in stir-fries or eaten alone.
Bran Cereals
Ready-to-eat bran cereals contain between 291 and 360 mg of betaine in every 100 grams. This is a very convenient source of betaine and also provides a good source of fiber.
Beets
Beets, whether canned or fresh, contain between 220 to 250 mg of betaine per 100 grams. Beets are a sweet root vegetable that can be cooked as a side dish or even pickled. They are often shredded and added to salads.

[Korn]

I don't think I've posted this one (from 1998) before:
Vitamin Supplementation Reduces Blood Homocysteine Levels

[Korn]

About exercise and homocysteine levels:
Influence of Training Volume and Acute Physical Exercise on the Homocysteine Levels in Endurance-Trained Men: Interactions with Plasma Folate and Vitamin B12
Regular Exercise Appears to Lower Homocysteine Levels in Stroke Patients: Presented at ISC
Exercise Decreases Plasma Total Homocysteine in Overweight Young Women with Polycystic Ovary Syndrome
Levels of homocysteine are inversely associated with cardiovascular fitness in women, but not in men
Exercise lowers homocysteine
...but also this one:
Homocysteine Increases during Endurance Exercise



ETA: Acute variations in homocysteine levels are related to creatine changes induced by physical activity

After exercise rHcy decreased, tHcy was unchanged while Cn increased. Gly, Arg and Met at the end of exercise remained unaffected whereas, interestingly, GAA decreased in both sub-groups while Orn was significant diminished in athletes and, although not significantly, the same trend was observable in the sedentaries group.

Conclusion

These findings support an interesting hypothesis on the key role of the creatine haemoconcentration as an important modality by which physical exercise would affect plasma Hcy levels.

[Korn]

Is hyperhomocysteinemia due to the oxidative depletion of folate rather than to insufficient dietary intake? (2001) PMID: 11592434

---

A critical evaluation of the relationship between serum vitamin B, folate and total homocysteine with cognitive impairment in the elderly. (2004) PMID: 15250847

Serum total homocysteine is negatively correlated with neuropsychological tests scores. But the evidence does not support a correlation between serum vitamin B(12) or folate and cognitive impairment in people aged over 60 years. Hence, there is little evidence to justify treating cognitive impairment with vitamin B(12) or folate supplementation. This is consistent with the findings from recent systematic reviews of randomized double-blind trials, which have not found any evidence of potential benefit of vitamin supplementation. Further research is required in order to establish whether raised serum total homocysteine is a cause or consequence of disease.

Comment: As mentioned earlier, if this information is correct, it may not necessarily apply to all; eg. to people with very low B12 levels. Also - humans don't need B12 only for homocysteine reasons, meaning that even if increasing our B12 levels shouldn't cause any homocysteine related improvements, we may still need to improve B12 status for other reasons.

Homocysteine, folic acid and vitamin B12 levels in maternal and umbilical cord plasma and homocysteine levels in placenta in pregnant women with pre-eclampsia.
(PMID: 21040211, 2011)

Maternal and fetal serum homocysteine levels were found to be significantly higher in severe pre-eclampsia group compared to mild pre-eclampsia and control groups suggesting that elevated serum levels of homocysteine might be associated with severity of pre-eclampsia. On the other hand it seems like elevated serum homocysteine levels were not associated with deficiency of folic acid and vitamin B12.

Vitamin B12 deficiency in African American and white octogenarians and centenarians in Georgia(2010) PMID: 20424799

CONCLUSIONS: Centenarians and octogenarians are at high risk for vitamin B12 deficiency for many of the same reasons identified in other older adult populations. Given the numerous potential adverse consequences of poor vitamin B12 status, efforts are needed to ensure vitamin B12 adequacy in these older adults.

In logistic regression analysis, the probability of being vitamin B12-deficient was significantly increased by being a centenarian vs. octogenarian, by being white vs. African American, by increasing severity of atrophic gastritis, and by not taking oral B-vitamin supplements, but was not related to gender, living arrangements, or animal food intake.

Although higher intake of animal products usually is associated with higher B12 levels, this particular study suggests something else. I guess we'll see more studies in the future finding that higher intake of B12 (eg. in animal products) doesn't always represent a linear increase in serum B12 levels - for a couple of reasons. One is that B12 absorption rates don't follow B12 intake linearly, as discussed here: At what levels is B12 absorption best? This means that if someone consumes eg. 5 mcg B12, only circa 1.4 mcg may be absorbed, but if she consumes, say, 0.3 mcg B12, all of it may be absorbed.
The other thing is that studies like this usually ignore all the B12 antagonistic factors. At some point, these studies will hopefully be more valid than they are today, by including info about sugar consumption, alcohol and coffee intake etc.. Currently, most if these studies aren't necessarily valid not for humans as a species, but for humans living in a very B12 unfriendly environment. These factors could, at least to some degree, explain the outcome of the Georgia study.

Folate and cobalamin deficiencies and hyperhomocysteinemia in Bangladesh
(2005) (PMCID: PMC2204145, NIHMSID: NIHMS32637)
The prevalence of hyperhomocysteinemia was markedly greater among men than among women. Folate was lower, whereas cobalamin was higher among men than among women. Folate explained 15% and cobalamin explained 5% of the variation in homocysteine concentrations. For men, folate and cobalamin were positively correlated with urinary creatinine. Smoking and betelnut use were independent negative predictors of folate.

Conclusions: Bangladeshi men have a high prevalence of hyperhomocysteinemia, which is more closely associated with folate than with cobalamin, although other factors, eg, smoking and betelnut use, may also contribute to its cause. The positive correlations between urinary creatinine and plasma folate and cobalamin were unanticipated and could suggest that, in marginal nutrition, these vitamins may be limiting for creatine biosynthesis.

This is one of the few studies which contain specific suggestions re. how important folate is (for homocysteine) compared with how important cobalamin (B12) is. 15% vs. 5% somehow suggests that folate is three times as important as cobalamin. But presence of B12 is also important for folate to do it's 'job'.

Vegans usually have healthy folate levels. Many non-vegans don't, which is why folate fortification of food is normal in some countries, meaning that they're all eating fortified food due to the low folate levels in a typical omnivorous diet. (I wonder if omnivores discussing B12 levels with vegans are aware that they may already be taking supplements through their food, without even asking for it?). Omnivores usually have higher B12 levels than vegans, which is why there's all this focus on B12 fortification/supplementation for vegans.

I wonder why eg. the governments who have decided to fortify eg. flour with folate don't work harder to make people eat more plant based food, since folate is easy to get enough of on a vegan diet. Having said that, I wouldn't be surprised if the minimum levels of folate will be increased in the future.