B12, homocysteine, & heart disease

[Korn]

From http://ods.od.nih.gov/factsheets/vitaminb6/

"A deficiency of vitamin B12, folate, or vitamin B6 may increase your blood level of homocysteine, an amino acid normally found in your blood. There is evidence that an elevated blood level of homocysteine is an independent risk factor for heart disease and stroke. The evidence suggests that high levels of homocysteine may damage coronary arteries (34) or make it easier for blood clotting cells called platelets to clump together and form a clot. However, there is currently no evidence available to suggest that lowering homocysteine level with vitamins will actually reduce your risk of heart disease. Clinical intervention trials are needed to determine whether supplementation with vitamin B12, folic acid, or vitamin B6 can help protect you against developing coronary heart disease."
Source: National Institutes of Health (USA).

[Korn]

From http://www.wddty.co.uk/archive/e-news%20No%20078%20-%2015%20Apr%202004.html :

What causes heart disease? We've asked the question a few times in recent bulletins, and we've had several responses back. Answers have ranged from 'loads of things' to 'dunno', to 'trans fatty acids'.

Homocysteine has been mentioned in these articles, and as new research has thrown further light on the subject, it seems a good time to get a better understanding of its role in heart disease.

Homocysteine is an amino acid that accumulates in the blood. When levels become abnormally high it is known as homocystinuria, and it was first linked to heart disease in Irish research published in 1962.

But it was Kilmer McCully, then a resident pathologist at Massachusetts General Hospital, who recognized that homocysteine could cause cardio-vascular diseases such as athersclerosis at far lower levels than the Irish researchers thought. He published his findings in 1969, and he was rewarded for his efforts by being banished from Harvard University and he lost his job at the Massachusetts hospital.

His views certainly seemed heretical. Cholesterol and clogged arteries were not the cause of heart disease, but were merely the symptoms of an under-lying cause - raised homocysteine levels. A diet rich in vitamin B6, B12 and folic acid could reduce homocysteine to levels that were not life threatening, he postulated.

Although medicine has finally accepted the theory, it has done so begrudgingly and has never fully taken on board the full implication of McCully's discovery. To this day many specialists still work with the old paradigm that cholesterol is the problem.

Their view seems to be supported by a new piece of research among 3,680 adult Americans who had suffered a heart attack. Half were given high-dose vitamin B, made up of 25 mg pyridoxine, 0.4 mg cobalamin (B12) and 2.5 mg folic acid, while the rest were given the same in low doses.

Although homocysteine levels were reduced more in the high-dose group, not surprisingly, there wasn't a significant difference between the two groups in terms of stroke and further heart attacks.

So is there a flaw in McCully's theory? Not necessarily, as the research team from Wake Forest University School of Medicine in North Carolina, admits. In the first place, the study period, at two years, could have been too short It's equally as possible that the participants' homocysteine levels weren't critical in the first place, thanks in part to the US government initiative to fortify grain with folate.

It could also be that raised homocysteine levels are yet another marker for heart disease, a theory that is supported by some research. Perhaps, after all, 'dunno' is the correct response when people want to know the cause of heart disease, but, if so, it's a 'dunno' of a far richer quality.

(Source: Journal of the American Medical Association, 2004; 291: 565-75).

[eve]

Yesterday's Times of India had something to say about widespread deficiency of B12 among vegetarians, leading to stroke and heart attacks among young people. It refers to the deficiency leading to concentration of homocysteine. This is the url:
http://www1.timesofindia.indiatimes.com/cms.dll/articleshow?msid=780050

[Korn]

We discussed that article here. (http://www.veganforum.com/forums/showthread.php?t=664) ;)

[Korn]

Here's a quote from another article (http://www.bodyandfitness.com/Information/Health/Research/b12.htm) about B12 and homocysteine (one of several that reminds us that even if B12 is known to reduce homocysteine levels, there is still discussion regarding whether high homocysteine levels are a result or cause of heart disease).

"As the redevelopment authority inside your body, B12 can make trouble for your heart if it goes on strike. Along with folic acid and B6, it is needed to break down an amino acid by-product called homocysteine. When you don’t have enough, blood levels of homocysteine rise, "and high levels of homocysteine seem to increase your risk for heart disease and stroke even more than high cholesterol," Dr. Pinto says.


Homocysteine damages the cells lining the blood vessels, creating rough spots that attract cholesterol deposits and issue invitations for blood to start clotting. Exactly how much of the three B vitamins you need to prevent this problem isn’t known. In one study where people received daily doses of 400 micrograms of B12, 1 milligram of folic acid, and 10 milligrams of B6, homocysteine levels dropped significantly.


So far, researchers have found that high levels of homocysteine are associated with heart disease and that B vitamins can help lower homocysteine levels. They are trying to complete the circle by showing that lowering homocysteine levels with B vitamins can also lower heart disease risk, says Dr. Allen."

[Korn]

...and from http://www.solgar.co.uk/healthnotes/healthnotes.asp?ContentID=1029002 :

"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."

[...]

"Lifestyle changes that may be helpful


According to a recent study, both cigarette smoking and coffee consumption were associated with increased homocysteine levels.30 These findings are consistent with studies that have found both smoking and caffeine consumption to be associated with an increased risk of both cardiovascular disease and osteoporosis. The link between coffee and increased homocysteine has been confirmed by some researchers,31 but not others.32


In one study, a diverse group of people participated in a week-long programme that included a strict vegan diet, stress management and spirituality enhancement sessions, group support, and exclusion of tobacco, alcohol, and caffeine.33 B vitamin supplements known to reduce blood homocysteine levels were not provided. After only one week in the programme, the average homocysteine level fell 13%."

[Korn]

There's also an article here (http://www.ffnmag.com/ASP/subscriberLogin.asp?from=artdisp&strArticleId=382&strIssueId=2) (subscription needed) about the same topic, called "Homocysteine: Cause Or Effect Of CVD (cardiovascular disease)?", confirm the above mentioned disagreement:

"Despite the extensive evidence implicating homocysteine as a clear risk factor, the conclusion that homocysteine may be a cause of CVD, rather than an effect, is less clear, and the subject of much current debate."

[Korn]

And, just like there are many factors that can increase homocysteine levels (tobacco, alcohol, coffeine), there are several ways to reduce homocysteine levels. B12 is important, folic acid might be even more important, and according to several sites, for example this one, (http://216.239.59.104/search?q=cache:AKkulIHV7SwJ:www2.vitaminconnection .com/101_txt/2000_33_TMG.html+Reducing+Homocysteine+Levels+with +Trienethyiglydne&hl=en)....:

"Elevated homocysteine levels are easily reduced with the intake of certain nutrients involved in methylation. Such nutrients include folic acid with its cofactors, vitamins B6 and B12, plus what is proving to be the most efficient and cost-effective methyl donor of all, Trimethylglycine (TMG).
**TMG (also known as anhydrous betaine) is a naturally occurring phytonutrient found in a variety of plants and animals, with highest concentrations in beets, leafy green vegetables, and legumes. Since it can be difficult to eat enough of these foods to provide the body with sufficient methyl groups, supplementation may be necessary. Studies have demonstrated that TMG, folic acid, and B12 can reduce elevated levels of homocysteine to normal. The best methyl donor is TMG, because it has 3 methyl groups. Furthermore, after losing its methyl group, TMG becomes DMG (dimethyiglycine), a well-recognized energy-boosting nutrient."

[eve]

Anger and hostility correlate with the risk of heart disease. A preliminary study found a link between high homocysteine levels and hostility and repressed anger. 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.

Something tells me that this makes a lot of sense, and it is something I'm concerned about even here on this forum. A lot of anger is revealed, and I worry about the harm this does to the angry person.

Of course we read or see things that are horrid, and many people think it is perfectly natural to be angry about whatever it is. But it is not natural, especially if one has developed a sense of detachment. This doesn't mean we don't care about the cruelty. For example yesterday in the paper there was a case - not some huge case, but a case nonetheless - of a group of teenagers who tortured to death two little kittens. How can anyone not feel for those helpless, suffering kittens? However, we need to avoid making ourselves sick within, and possibly harming our hearts. One way is simply to write a letter to the authorities concerned, another way is to put in an extra day at the animal sanctuary, or, if at an educational establishment, give out leaflets, etc, etc. For each of us there is a way that is better than swearing and yelling. In fact, a person can't meditate if their mind is shaking with anger.

[Korn]

From http://www.health-diets.net/research/heartdisease.htm:

'In a study on 100 men with hyperhomocysteinaemia, treated with folic acid, vitamin B6, vitamin B12 or a combination of the vitamins, it was found that folic acid was the most effective in reducing homocysteine levels and that the combination treatment was not more effective than folic acid alone. Ubbink JB et al: Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr Oct 124(10):1927-33, 1994.

But also: "Supplementation with folic acid reduces both high and normal plasma homocysteine levels, especially if combined with vitamin B12". Brattstrom L: Vitamins as homocysteine-lowering agents. J Nutr 126(4 Suppl):1276S-80S, 1996'.

More here. (http://www.health-diets.net/research/heartdisease.htm) And here. (http://jama.ama-assn.org/content/274/13/1049.abstract)

[Korn]

Sugar is also one of many causes of elevated homocysteine levels, according to several sources. Elevated homocysteine levels are associated with high blood pressure, and according toHarry G. Preuss, M.D., of Georgetown University Medical School (http://www2.rpa.net/~rcfisher/heart.htm), 'sugar may be as big a villain in raising blood pressures as salt'. In her list of '146 reasons why sugar is ruining your health', Nancy Appleton, Ph. D (http://www.nancyappleton.com/) is also mentioning that sugar can raise homocysteine levels in the blood stream.

[Korn]

Below is some excerpts from http://www.lef.org/magazine/mag2001/aug2001_report_folic_01.html . (The article, Battling Heart Disease with B Vitamins by Angela Pirisi, is not specifically related to the vegan diet). I have personally marked some of the text in bold.


Scientists long ago warned us about the cardiovascular dangers of a high-fat diet, sedentary lifestyle, smoking, high cholesterol-triglycerides and diabetes. In recent years, research has uncovered yet another important culprit in the development of heart disease, namely homocysteine. Study after study over the past decade has shown that, regardless of being clear of other risk factors, even mildly elevated levels of homocysteine in one’s bloodstream can single out victims by making them susceptible to heart disease. Homocysteine is a naturally occurring amino acid in the body which, in excessive amounts, tends to build up in the blood and is believed to be at the root of arterial inflammation and damage. What recent research has also turned up is the discovery that folic acid, vitamin B12 and vitamin B6 supplementation can be used successfully to lower homocysteine levels.


Besides reducing homocysteine concentrations, increasing folic acid, vitamin B6 and B12 intake also works against heart disease by improving vascular endothelial function and related flow-mediated vasodilation.(1-2) A Polish study showed that an eight-week treatment with folic acid (5 milligrams daily), vitamin B6 (300 milligrams daily) and B12 (1000 micrograms weekly) not only cut in half homocysteine levels (from 20 to 10 micromoles/liter). It also diminished the production of a blood-clotting enzyme, thrombin, which plays a proliferative role in heart disease and stroke.(3)
Low circulating levels of folate were linked to a 50% greater risk of vascular disease in men. The same study also found that low levels of vitamin B6 increased the risk two to threefold in both sexes.

Nutrient status
As scientists attempted to measure homocysteine levels, they began to look for other markers of high homocysteine levels and their associated cardiovascular (and cerebrovascular) risks. One large focus has been the vital role that certain nutritional deficiencies might play in affecting homocysteine levels and precipitating the arterial damage that leads to cardiovascular disease. So, as much as scientists have devoted time to studying the merits of folic acid and vitamin B12 in reducing the risk of heart disease and stroke, demonstrating the harmful impact of nutritional deficiencies has taught researchers even more about certain vitamins as a preventative means.

For instance, recent studies have noted that suboptimal serum levels of folic acid, vitamin B12and vitamin B6 may underlie the development of atherosclerosis and coronary heart disease. Why? It’s believed that such deficiencies lead to inadequate production of S-adenosyl-methionine, creating a state of turmoil called hypomethylation. And this, in turn, may damage the DNA in arterial cells, leading to the mutation and proliferation of smooth-muscle cells, thus paving the way for atherosclerosis. Many experts believe, however, that vitamin supplementation can not only correct the nutritional deficiencies but also help to reverse the atherosclerotic process in people with existing heart disease.(4)

More specifically, low folate status has been seen as one culprit that precipitates the development of cardiovascular disease. The most recent findings suggest that people with the lowest folate status had more than twice the risk of dying from cardiovascular disease as those with the highest levels of the nutrient. The National Heart, Lung and Blood Institute, Bethseda, MD reported such findings after examining the serum folate concentrations of 689 adults, ages 30 to 75, without cardiovascular disease or diabetes.(5)


Similarly, a 15-year Canadian study involving over 5000 men and women with no history of heart disease, aged 35 to 79, showed that the lower the folate levels, the higher was the risk of heart disease-related death. It reported that people with low blood folate levels (below 6.8 nanomoles per liter) have a 69% increase in the risk of fatal coronary heart disease than individuals with higher levels (above 13.6 nanomoles per liter).(6) These study findings are very significant, for one, because the sample included both young and old, male and female. As well, the results point to a correlation between lower blood folate values and mortality, as opposed to just a risk of heart disease, or arterial blockage and damage. What’s even more interesting is that the researchers found an inflated risk of death even in people with so-called normal folate status, which calls into question whether we should be boosting our recommended daily allowance. Meanwhile, one multicenter European study, which compared 750 male and female patients with vascular disease to 800 healthy controls, found that low circulating levels of folate were linked to a 50% greater risk of vascular disease in men. The same study also found that low levels of vitamin B6 increased the risk two to threefold in both sexes.(7)

One study by researchers at the University of Chile even found that, in contrast to other findings, folate levels—and not vitamin B12—were notably low in people with atherosclerosis. The team of scientists had compared serum homocysteine, folate and vitamin B12 measurements among 32 patients with peripheral vascular disease versus 24 healthy controls, and 52 patients with coronary artery disease versus 42 matched controls. Results showed that homocysteine and vitamin B12 levels didn’t vary greatly among patients and controls, but that folate levels were 37% lower in vascular patients and 22% lower in coronary patients compared to controls.(8)

A vitamin B12 deficiency has also been noted as contributing to cardiovascular disease. Consider, for instance, evidence from one study conducted in the Slovak Republic that showed that the frequency of high homocysteine levels is higher in vegans (53%) and vegetarians (28%) compared to omnivores (5%).(9) It’s believed that the reasons for the huge discrepancies lies in vitamin intake, particularly vitamin B12, as vegans consume none from dietary sources, and vegetarians only consume about one third the amount that omnivores do (124% versus 383% of the RDA). In fact, this study, which examined 62 vegetarians, 32 vegans and 59 omnivores, found that 78% of the vegans studied were vitamin B12-deficient, as were 24% of vegetarians, but 0% of the omnivores showed a deficiency. Folate levels, however, were comparable among the three groups. The authors concluded that vitamin B12 deficiency was chiefly responsible for mildly elevated homocysteine levels in vegans and vegetarians.

Similarly, in many developing countries, studies have found diets low in folate and vitamin B12 are what may account for the increased risk of both cardiovascular disease and neural tube defects. In fact, when US researchers measured the folate and vitamin B12 status of adolescent girls in northern Nigeria of marrying and childbearing age (12 to 16 years), 9% of the subjects had serum vitamin B12 concentrations that fell below the lower limit of the reference range for their age group. This was consistent, said the authors, with the fact that their diet lacks vitamin B12.(10)

Meanwhile, according to a 1998 report by the American Heart Association,(11) about one fifth of the US population may stand a heightened risk of heart attack and stroke because their diet lacks a sufficient amount of vitamin B6 and folic acid. While previous research has suggested that elevated homocysteine levels were the result of too little vitamin B6 or folic acid, the authors of this report were surprised to find that vitamin B6 deficiency was linked to heart disease and stroke risk independently of where homocysteine levels stood. A B6 deficiency was found among 20% of subjects, and levels of these nutrients were generally lower in individuals with heart disease or stroke than in healthy controls. More importantly, those demonstrating a deficiency had twice the risk of heart disease and stroke. Some research suggests that dietary deficiencies of folic acid, vitamin B12 and vitamin B6 seem common among elderly people in North America, which might represent “one pathogenic factor related to the incidence of hyperhomocys-teinaemia.”(12) Such deficiencies might also offer a reason why high homocysteine levels seem to prevail among 30% to 40% of the elderly population compared to only 5% to 10% of the general population.(13)

Support for supplementation
Such findings build a strong case for encouraging people to meet their daily requirements of B vitamins. As it stands, though, the average intake among the US adult population is 200 micrograms of folic acid. And food sources, particularly with regards to folic acid, fall short of supplying what the body needs, since only about 50% of it may be bioavailable.(14) As a recent study established, synthetic folic acid from fortified foods or supplements is 1.7 times more bioavailable than food-source folate, which means 100 micrograms of folic acid being equivalent to 170 micrograms of food folate.(15) Moreover, individuals with malabsorption problems, be it from a genetic glitch, gastrointestinal diseases, age or existing cardiovascular disease, may need to step up their daily intake through supplementation just to meet the recommended daily allowance. A researcher at Emory University, Atlanta, GA, Godfrey P. Oakley, Jr., MD, MSPM, even argues that “approximately 70% of the adult population in the United States is exposed to a risk factor for cardiovascular disease—an elevated plasma homocysteine concentration—that can be easily avoided simply by consuming a B vitamin supplement.”(16)


For the full article, follow the link above...

[Korn]

From http://www.yourhealthbase.com/vitamin_B12.html :



BONN, GERMANY. There is increasing evidence that high blood levels of the amino acid homocysteine increases the risk of vascular disease, coronary heart disease, neural tube defects, and Alzheimer's disease. Folic acid supplementation is known to lower homocysteine levels and laws have recently been passed in the United States mandating folic acid fortification of bread and cereal. Now researchers at the University of Bonn report that folic acid's homocysteine lowering capacity can be markedly increased by also supplementing with vitamin B-12 (cobalamin).

Their study involved 150 young, healthy women (average age of 24 years) who after a four-week washout period were randomized into three groups.

• Group 1 received a daily supplement of 400 micrograms of folic acid.
• Group 2 received 400 micrograms/day of folic acid and 6 micrograms/day of vitamin B-12.
• Group 3 received 400 micrograms/day of folic acid and 400 micrograms/day of vitamin B-12.

After four weeks the average concentration of plasma homocysteine had dropped by 11 per cent in group 1, 15 per cent in group 2, and 18 per cent in group 3.

The researchers noted that study participants with high initial homocysteine concentrations benefited more from supplementation than did women with lower initial homocysteine levels. It was also noted that vitamin B-12 levels increased significantly over the four-week period in the women whose supplements included vitamin B-12. This provides further proof that oral vitamin B-12 is indeed adequately absorbed. The researchers conclude that the benefits of folate supplementation can be markedly enhanced by the addition of vitamin B-12. They point out that vitamin B-12 deficiency is widespread especially among the elderly. The addition of vitamin B-12 to folic acid supplements also prevents the possibility that supplementation with just folic acid could mask pernicious anaemia resulting from a vitamin B-12 deficiency which in turn may lead to irreversible nerve damage.
Bronstrup, Anja, et al. Effects of folic acid and combinations of folic acid and vitamin B-12 on plasma homocysteine concentrations in healthy, young women. American Journal of Clinical Nutrition, Vol. 68, November 1998, pp. 1104-10

In other words, adding a lot of B12 to group three improved the homocysteine levels by only 7% more than the control group that got only folic acid.

[Korn]

From http://www.yourhealthbase.com/vitamin_B12.html :



*Major new risk factor for heart disease discovered
VANCOUVER, CANADA. It is becoming increasingly evident that an elevated blood level of homocysteine is a potent risk factor for cardiovascular disease. Recent studies also suggest that high homocysteine levels may be associated with kidney disease, psoriasis, breast cancer, and acute lymphoblastic leukemia. Extensive past research has shown a close link between the development of neural-tube defects in babies and the mother's homocysteine level prior to and during pregnancy. Researchers at the University of British Columbia have just released a major report that summarizes the current knowledge about homocysteine and its effect on health. Homocysteine is formed in human tissues during the metabolism of methionine, a sulfur-containing essential amino acid. A normal, desirable level is 10 micromol/L or less. A level of 12 micromol/L is considered borderline and levels of 15 micromol/L or above are considered to be indicative of increased risk for cardiovascular disease. Several factors (age, smoking, vitamin deficiencies, and genetic abnormalities) have been linked to increased homocysteine levels. Medications that interact with folate such as methotrexate, carbamazepine, phenytoin, and colestipol/niacin combinations have also been linked to increased homocysteine levels. The researchers reviewed 23 studies dealing with the association between atherosclerosis and homocysteine levels and found that patients with vascular diseases had an average level of homocysteine that was 26 per cent higher than the level in healthy subjects. One study found that a homocysteine level of 4 micromol/L above normal corresponds to a 41 per cent increase in the risk of developing vascular disease. Another study estimates that the lives of 56,000 Americans could be saved every year if average homocysteine levels were lowered by 5 micromol/L. The researchers conclude that abnormally high homocysteine levels are a potent risk factor for cardiovascular and several other diseases. They point out that elevated homocysteine levels can, in most cases, be safely and effectively lowered by supplementation with as little as 400 micrograms per day of folic acid. Other researchers have found that a combination of folic acid (0.4-10 mg/day), vitamin B-12 (50-1000 micrograms/day), and vitamin B-6 (10-300 mg/day) is highly effective in lowering homocysteine levels. (153 references). Medical doctors at the University of Wisconsin echo the findings of the Canadian researchers in a separate report and describe a case of a 57-year-old man who lowered his homocysteine level from 29 micromol/L to 2 micromol/L by supplementing with 800 micrograms/day of folic acid for two months.
Moghadasian, Mohammed H., et al. Homocysteine and coronary artery disease. Archives of Internal Medicine, Vol. 157, November 10, 1997, pp. 2299-2308
Fallest-Strobl, Patricia C., et al. Homocysteine: A new risk factor for atherosclerosis. American Family Physician, Vol. 56, October 15, 1997, pp. 1607-12

Most of the literature I have seen on homocysteine seem to focus more on B6 and folic acid (B9) than on B12.

[Korn]

"Elevated homocysteine levels are easily reduced with the intake of certain nutrients involved in methylation. Such nutrients include folic acid with its cofactors, vitamins B6 and B12, plus what is proving to be the most efficient and cost-effective methyl donor of all, Trimethylglycine (TMG).
**TMG (also known as anhydrous betaine) is a naturally occurring phytonutrient found in a variety of plants and animals, with highest concentrations in beets, leafy green vegetables, and legumes. Since it can be difficult to eat enough of these foods to provide the body with sufficient methyl groups, supplementation may be necessary. Studies have demonstrated that TMG, folic acid, and B12 can reduce elevated levels of homocysteine to normal. The best methyl donor is TMG, because it has 3 methyl groups.

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?

[Korn]

From http://www.vrp.com/art/666.asp :



Vitamin E and Homocysteine

Researchers have long suspected that folic acid and vitamins B6 and B12 can protect against high levels of homocysteine--an amino acid associated with heart disease. Recently, however, scientists have begun to realize that another nutrient may play an equally important role in guarding against homocysteine-related damage.

In the August 1 issue of the American Journal of Cardiology, researchers reported that vitamin E can prevent homocysteine-related damage to blood vessels. In a double-blind, crossover study, researchers gave ten healthy subjects L-methionine (an amino acid found in red meats that increases homocysteine levels) either with or without 1,200 iu of vitamin E. The high homocysteine levels that resulted from methionine administration without vitamin E treatment clearly damaged the vessels, but administration of vitamin E completely reversed the homocysteine-related damage.

Reference:
Raghuveer G, Sinkey CA, Chenard C, Stumbo P, Haynes WG.

Effect of vitamin E on resistance vessel endothelial dysfunction induced by methionine. Am J Cardiol. 2001; Aug 1;88(3):285-90

[Korn]

From http://www.vrp.com/art/1016.asp :


Vitamins C and E: Italian scientists studied the effects of 800 IU of Vitamin E and 1 gram of vitamin E on 20 healthy men and women after experimentally induced hyperhomocystenemia (elevated blood homocysteine) in the subjects. The researchers reported that “Pretreatment with antioxidant vitamin supplements normalized both the level of cardiovascular risk and the impairment of endothelial functions following acute hyperhomocystenemia.” It appears from this study that consumption of high amounts of antioxidant vitamins may be protective against elevated homocysteine levels. (30)

[Korn]

Homocysteine Risks Extend Beyond Stroke and Heart Disease
by Ward Dean, MD (2003)

http://www.vrp.com/pdf/JuneNews2003.pdf

[Korn]

More about the Italian study:



The good news is that when researchers added the 1,000 mg of vitamin C and 800 IU of vitamin E along with the methionine load, homocysteine's pro-blood-clot effects were almost completely prevented. That is, the blood clotting parameters remained normal despite a drastic increase in blood homocysteine levels.


It appears that the combination of vitamins C and E may be an antidote to homocysteine, and one that works more quickly than traditional treatments such as vitamins B6, B12 and folic acid. These vitamins can lower homocysteine levels over the course of a few weeks. In contrast, vitamins C and E can act within hours. While they don't actually reduce homocysteine, these vitamins appear to protect the blood from clotting.


This study has a few important practical implications for people at risk for heart disease or stroke, although additional studies must be done to further support these findings.


First, increasing homocysteine by overloading on protein foods or methionine-containing high-protein supplements can be dangerous.


Second, adding the antioxidant vitamins C and E as well as homocysteine-lowering B6, B12 and folate should help keep blood thin. By thinning the blood, it appears as though vitamins C and E might reduce the threat of other acute proclotting triggers such as smoking, exertion, a high-fat meal or emotional distress. However, while these two nutrients may protect against high homocysteine levels for a few hours, the duration of their protective effect is unknown. Considering vitamin E is stored in fat, a single dose should be available in the body for days, depending on how fast the vitamin is metabolized. However, vitamin C dissolves in water and is excreted in the urine. Thus, for those at risk, I'd urge a 1 to 2 g twice daily vitamin C dose. ( http://www.newhope.com/nutritionsciencenews/NSN_backs/Dec_00/homocysteine.cfm)

[Korn]

*Homocysteine: is it a clinically important cardiovascular risk factor?
Cleve Clin J Med. 2004 Sep;71(9):729-34.
Elevated plasma homocysteine is associated with an increased risk of myocardial infarction, stroke, and venous thromboembolism. Folic acid and other B vitamins lower high homocysteine levels, but whether this therapy confers a clinical benefit has yet to be determined. Until we know the results of ongoing clinical trials of homocysteine -lowering therapy, testing for and treating elevated homocysteine is probably justified only in patients with known cardiovascular disease or who are at high risk. http://www.raysahelian.com/homocysteine.html

[Korn]

Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women.
Olthof MR. J Nutr. 2003 Dec;133(12):4135-8.
High plasma homocysteine is a risk for cardiovascular disease and can be lowered through supplementation with 6 g/d of betaine. However, dietary intake of betaine is approximately 0.5-2 g/d. Therefore, we investigated whether betaine supplementation in the range of dietary intake lowers plasma homocysteine concentrations in healthy adults. Four groups of 19 healthy subjects ingested three doses of betaine or placebo daily for 6 wk. A methionine loading test was performed during run in, on d 1 of betaine supplementation, and after 2 and 6 wk of betaine supplementation. Fasting plasma homocysteine after 6-wk daily intakes of 1.5, 3 and 6 g of betaine was 12% less than in the placebo group, respectively. Furthermore, the increase in plasma homocysteine after methionine loading on the 1st d of betaine supplementation was 16% less than in the placebo group, respectively, and after 6 wk of supplementation was 23% less, respectively. Thus, doses of betaine in the range of dietary intake reduce fasting and postmethionine loading plasma homocysteine concentrations. A betaine-rich diet might therefore lower cardiovascular disease risk.

More about betaine and homocysteine here. (http://www.ajcn.org/content/80/3/539.full)



*Studies in healthy volunteers with plasma homocysteine concentrations in the normal range show that betaine supplementation lowers plasma fasting homocysteine dose-dependently to up to 20% for a dose of 6 g/d of betaine. Moreover, betaine acutely reduces the increase in homocysteine after methionine loading by up to 50%, whereas folic acid has no effect. Betaine doses in the range of dietary intake also lower homocysteine. This implies that betaine can be an important food component that attenuates homocysteine rises after meals. If homocysteine plays a causal role in the development of cardiovascular disease, a diet rich in betaine or choline might benefit cardiovascular health through its homocysteine-lowering effects. However betaine and choline may adversely affect serum lipid concentrations, which can of course increase risk of cardiovascular disease. However, whether the potential beneficial health effects of betaine and choline outweigh the possible adverse effects on serum lipids is as yet unclear.
http://www.raysahelian.com/homocysteine.html


ETA: Food Sources of Betaine (beets and spinach) (http://www.livestrong.com/article/291527-food-sources-of-betaine/):

Beets
The USDA recognizes beets as a source of betaine, stating that it has been shown to provide anti-inflammatory, antioxidant and detox support in the body. The betaine is concentration in the peel and the flesh of the beets making this food a good addition to the diet. Beets can be boiled and added to salads along with fresh vegetables and walnuts for a healthy and nutrient-rich meal.
Spinach
Spinach is a healthy vegetable that can be lightly steamed or eaten raw. The USDA states that spinach is one of the primary food sources of betaine. Due to its betaine content, spinach may be a good food in protecting against high homocysteine levels, fatigue and osteoporosis. Adding spinach to a sandwich prepared on whole grain bread can combine two good sources of betaine for a nutrient-rich meal.

[Korn]

From http://www.merck.com/mrkshared/mmg/sec8/ch60/ch60b.jsp :


Although vitamin B12 plays a role in homocysteine metabolism and arteriosclerosis, folic acid appears to play a much more significant role.

Early (and reversible) vitamin B12 deficiency may elevate the methylmalonic acid level before the serum vitamin level falls. The Schilling test is not as useful in the elderly because decreased vitamin B12 absorption is usually not due to lack of intrinsic factor, and treatment of all vitamin B12 deficiency is similar. Because it is not known which cases will progress to anemia or neurologic injury if untreated, treatment is recommended.

[Korn]

Excerpt from The Helena Cardiology Clinic (
http://www.helenacardiology.com/Papers/vitamins_and_heart_disease.htm )



Folic acid is the treatment of choice to reduce high homocysteine levels. A diet rich in fruits and vegetables and low in fat increases folate levels and lowers the level of homocysteine. A meta-analysis of 12 randomized trials involving 1,114 patients showed that a daily supplement of 0.5-5.0 mg of folic acid and 0.5 mg of vitamin B12 decreases homocysteine levels by 25% to 30%. Most of these trials show a significant reduction with folic acid and vitamin B12 when compared with placebo, although normal levels of homocysteine were not reached. There appeared to be no benefit with larger doses. These lowering effects should translate into favorable clinical outcomes, although it will need to be proven in large randomized trials.

The link between elevated homocysteine levels and cardiovascular disease has not been established. Therefore, although trials have established that folic acid reduces homocysteine levels, whether these lower levels benefit cardiovascular patients is not yet known. Ongoing trials that are using folic acid either alone or in combination with vitamin B6 or vitamin B12 should determine what, if any, effect homocysteine reduction has on the prevention and progression of cardiovascular disease.

[Korn]

From http://www.heall.com/body/healthupdates/vitamins/vitaminssave20billiondollars.html :


It has been confirmed in a number of studies that elevated homocysteine concentrations are associated with increased risk of CHD. Folic acid, vitamin B6, and B12 are cofactors in the metabolism of homocysteine and are all effective in reducing homocysteine levels.


Following methionine loading (a precursor of homocysteine), B6 supplementation resulted in a 22.1% reduction of homocysteine levels and folic acid/B12 resulted in a 26.2% decrease.


Rimm et al found a significant inverse relationship between dietary intakes of folate and B6 with morbidity and mortality from CHD.


Mildly elevated homocysteine concentrations were reduced by 30% in subjects who received folate/B6/B12 supplementation, by 32% in those who received B vitamins plus antioxidants (C, alpha-tocopherol, and beta-carotene), and a non-significant increase of 5.1% was noted in patients receiving only antioxidants.

[Korn]

Unfortunately, some sources give the false impression that diets low in B12 always cause an increase in homocysteine (hcy) levels, and that the only way to deal with too much homocysteine is to get more B12 (meaning, that if you should achieve this by changing your diet you'd have to start to eat more food that had high B12 levels. )

The following is from one of many articles that suggest that B12 is less important than folic acid when it comes to improve too high hcy levels. The article contains several examples of people who lowered their homocysteine levels by taking a low B12 diet.

Plant foods are often rich in folic acid.



Since homocysteine is produced from methionine, intake of large amounts of methionine would presumably increase homocysteine levels. Indeed, ingestion of supplemental methionine is used experimentally as a way to increase homocysteine levels.27 Foods high in methionine that have also been linked with an increased risk of heart disease include meat and eggs. The extent to which consumption of these foods affects the risk of heart disease as a result of their methionine content remains unknown.


A controlled trial showed that eating a diet high in fruits and vegetables containing folic acid, beta-carotene and vitamin C effectively lowered homocysteine levels.28 Healthy people were assigned to either a diet containing a pound of fruits and vegetables per day, or to a diet containing three and a half ounces of fruits and vegetables per day. After four weeks, those eating the higher amount of fruits and vegetables had an 11% lower homocysteine level compared with those eating the lower amount of fruits and vegetables.


Another study of men with heart disease demonstrated that consumption of whole-grain and legume powder at breakfast, instead of their usual breakfast of refined rice, resulted in a significant reduction in homocysteine levels.29

Lifestyle changes that may be helpful

According to a recent study, both cigarette smoking and coffee consumption were associated with increased homocysteine levels.30 These findings are consistent with studies that have found both smoking and caffeine consumption to be associated with an increased risk of both cardiovascular disease and osteoporosis. The link between coffee and increased homocysteine has been confirmed by some researchers,31 but not others.32


In one study, a diverse group of people participated in a week-long program that included a strict vegan diet, stress management and spirituality enhancement sessions, group support, and exclusion of tobacco, alcohol, and caffeine.33 B vitamin supplements known to reduce blood homocysteine levels were not provided. After only one week in the program, the average homocysteine level fell 13%.


Nutritional supplements that may be helpful

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

More (http://www.vitacost.com/science/hn/Concern/High_Homocysteine.htm)