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/03HealthPromotion/homocysteine.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/query.fcgi?cmd=retrieve&db=pubmed&list_uids=10475890&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 (http://www.physsportsmed.com/issues/1999/07_99/news.htm) 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 (http://www.ajph.org/cgi/content/abstract/90/10/1636?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=vitamin+B12&searchid=1135781294004_1520&FIRSTINDEX=0&sortspec=relevance&journalcode=ajph)


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 (http://www.ajph.org/cgi/content/abstract/90/10/1636?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=vitamin+B12&searchid=1135781294004_1520&FIRSTINDEX=0&sortspec=relevance&journalcode=ajph)

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 (http://www.nytimes.com/2006/03/12/health/12cnd-heart.html) 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 (http://sciencelinks.jp/j-east/display.php?id=000020030703A0066633) 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 (http://sciencelinks.jp/j-east/display.php?id=000020051405A0371130) 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 (http://www.diseaseproof.com/archives/cardiovascular-disease-research-vitamin-b-ineffective-against-heart-disease.html) 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 (http://www.uib.no/ueland/Pages/LOCUS.html).

[Korn]

From http://www.drmcdougall.com/misc/2005nl/oct/051000folic.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 (http://www.all-creatures.org/health/plants.html):



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 (http://www.drmcdougall.com/misc/2007nl/nov/b12.htm):




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.