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Re: B12, homocysteine, & heart disease
From http://lib1.store.vip.sc5.yahoo.com/...vviews02b2.htm :
Quote:
Homocysteine - Recent medical studies from the Framingham Heart Study in Massachusetts have concluded that high Homocysteine levels are an independent risk factor for heart disease. Without getting into the specific biochemistry let me state that homocysteine is an intermediate product in the normal metabolism of methionine. Methionine is an essential amino acid found in many of our food sources. We must receive methionine in our food (meat, eggs, fish, legumes, etc.) for proper functioning of many of our metabolic pathways. We convert the methionine in our diet first to homocysteine, then cysteine, then taurine. As long as this process occurs successfully there is no problem.
The rate limiting step in this process is the availability of certain B vitamins. The three B vitamins involved are Folic Acid(B9), B6 & B12. Recent studies have shown that the cause of B6 & B12 deficiency is usually a genetic factor while the missing folic acid is primarily from diet.
A high homocysteine level in the blood is a risk factor for heart disease, specifically heart attack. This risk is an independent risk similar in severity to smoking, high cholesterol and too much weight. Smokers increase their risk even more.
The way that homocysteine increases heart attack risk is by allowing LDL Cholesterol to oxidate. This causes the epithelial cells which line the arteries to become less stable. Researchers believe that this causes cholesterol plaques to break loose and cause an occlusion leading to a heart attack. The simple solution for removing this risk is to take a vitamin B supplement. Usually strong B-Complex such as B-100 will provide enough of B6, B12 and folic acid to reduce homocysteine levels to a normal level. During the study of homocysteine metabolism and heart disease it was noted that the group which took folic acid alone did not have a statistically significant higher risk then the group taking all three B vitamins. For this reason we recommend supplementing your diet with a single 400mcg folic acid tablet a day. If you are already taking any combination of vitamin tablets which deliver this 400mcg then you do not need any additional amount.
The study he/she refers to re. the lack of effect of taking three B vitamins instead of folic acid alone, could possibly be misunderstood (by vegans) as 'B12 is not important'.... remember, this study was not performed on long term vegans, but on meat eaters, who normally have higher levels of B12 than most vegans.
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Re: B12, homocysteine, & heart disease
Here's an article about current analytical methods for measuring total homocysteine in plasma, from homocysteine.net, last updated in April 2005.
From the introduction:
Quote:
Elevated concentration of plasma homocysteine has been a focus of research interest since it was established that it plays a major role in the cause and effect chain linking lifestyle, nutrition and cardiovascular disease (1). During the seven years following the publication of the first meta-analysis of the relationship between plasma total homocysteine and cardiovascular disease (2), the study has been cited 1255 times, reflecting the enormous research activity involved in the further clarification of the many questions that remain unanswered. While we wait for the results of the crucial intervention studies on the effect of vitamin supplementation in the prevention of cardiovascular disease (3), measurement of total homocysteine in plasma has found its way into risk assessment of individuals in many clinical settings.
This is the background for the steadily increasing demand for the analysis of total homocysteine in plasma meeting the research and clinical laboratories today. In this short review, the different laboratory methods in past, present and potential future use will be discussed critically.
The full article: http://www.homocysteine.net/pages/me...1/jmoller.html
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Re: B12, homocysteine, & heart disease
From a discussion about homocysteine and Alzheimer, from Health On The Net Foundation (2002):
Quote:
Blood Molecule Boosts Risk of Stroke, Alzheimer's
Study finds even moderate homocysteine levels raise odds
By Ed Edelson
HealthScoutNews Reporter
THURSDAY, Oct. 3 (HealthScoutNews) -- Moderately high blood levels of the amino acid homocysteine -- levels seen in a quarter of the adult population -- are linked to a substantial increase in the risk of Alzheimer's disease, other dementias and stroke.
"People deemed to have normal levels of homocysteine are in fact at elevated risk for stroke and dementia," says Stephen P. McIlroy, a lecturer in geriatric medicine at Queens University in Belfast, Northern Ireland. He reports the finding in the October issue of Stroke .
The research shows the need for a large-scale study to see whether taking supplements containing folic acid and B vitamins, which reduce blood levels of homocysteine, can lower the incidence of Alzheimer's disease and stroke, McIlroy says.
Other studies have linked elevated homocysteine levels to Alzheimer's disease, heart disease and stroke, but McIlroy's study finds a risk at lower levels than have been reported. He and his colleagues looked at homocysteine levels in 83 Alzheimer's patients, 78 patients with dementia caused by poor blood flow to the brain, 64 stroke patients and 71 healthy volunteers. All were in their 70s.
The study used a cutoff line of homocysteine levels found in the upper 25 percent of the healthy volunteers. After correcting for known risk factors such as smoking, blood cholesterol and blood pressure, the researchers say that readings above that level are associated with a 2.9 times greater risk of Alzheimer's disease, a 5.5 times greater risk of stroke, and a 4.9 times greater risk of dementia due to poor blood flow to the brain.
Laboratory studies have shown that homocysteine and molecules produced when it is metabolized can attack blood vessels and nerves. However, there has been a running debate about whether elevated homocysteine levels cause blood vessel and nerve damage or are just associated with processes that cause the damage. The case for cause-and-effect is compelling, McIlroy says.
"There are too many studies saying that high homocysteine levels are linked to dementia and stroke," he says. "I certainly think it is a cause, a very easily modifiable risk factor for dementia and stroke."
However, Bill Thies, vice president for medical and scientific affairs for the Alzheimer's Association, says it's too early to be recommending supplements for prevention.
"These kinds of studies don't give you cause-and-effect information," he says. "They just point you in a direction."
As for a prevention trial, Thies says it would be more difficult to do in the United States than in Northern Ireland. Many foods here are fortified with folic acid to prevent birth defects, something that's not done there, he says, and that might muddy the results of any American trial.
A study of Alzheimer's patients to see whether folic acid and vitamins B12 and B6 can slow progression of the disease is being started in the United States, Thies says. Positive results from that trial could lead to a bigger preventive study, he says.
The Alzheimer's Association has no official position on self-medication with folic acid and vitamin B, Thies says. A basic rule is that "anyone should not be taking anything without consulting their physician, and if you take anything, you should tell your physician," he says.
Folic acid and vitamin B supplements are generally agreed to be innocuous, Thies says, but "there is no such thing as a completely safe drug." Since various studies have suggested that taking aspirin, other anti-clotting drugs, estrogen or other medications might reduce the risk of Alzheimer's, "you could end up taking a fair collection of pills without evidence that they might be effective or what the risk is," he says.
http://www.hon.ch/News/HSN/509450.html
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Re: B12, homocysteine, & heart disease
http://www.abbottdiagnostics.com/You...ts/chdrisk.cfm
Quote:
The authors found that 10% of the population's risk for CHD appears attributable to homocysteine and that a 5 µmol/L homocysteine increment elevates CHD risk by an amount equivalent to a 20 mg/dL increase in serum cholesterol. Hyperhomocysteinemia has also been shown to have a high prevalence in patients with both cerebrovascular and large artery disease.
In studies performed after Boushey's meta-analysis, similar findings have been described. Malinow and associates measured plasma homocysteine concentrations in survivors of myocardial infarction (MI) and in control subjects from Northern Ireland and France. They reported that plasma homocysteine levels were higher in the Irish than in the French and that subjects with MI had higher levels than controls. They concluded that a "global excess of risk for MI was graded across the distribution of plasma homocysteine concentration" and that the elevated homocysteine levels in the Irish may explain that population's increased incidence of CHD.
As explained by Dr. Genest, one of the problems in interpreting the data on homocysteine and CHD is that many of the studies are of the case-controlled type, a valuable methodology that has inherent limitations. Among prospective, nested, case-control studies, the association has not been as consistent.
Top of page
For example, while the British Regional Heart Study and the British United Provident Association (BUPA) trial showed an increased relative risk of CHD in patients with hyperhomocysteinemia (RR = 2.8 and 2.9, respectively), other studies have not. In fact, the Atherosclerosis Risk in Communities (ARIC) study questioned the role of homocysteine as a causative risk factor for HD in men (but not women). Confounders that may limit the role of homocysteine as an independent risk factor variable include vitamin B6 intake, renal function, smoking, fibrinogen, D-dimer, and C-reactive protein. Although univariate analysis shows a strong and consistent association between homocysteine and cardiovascular disease in case-control studies, this does not prove a causal relationship. According to Dr. Genest, the exact role of homocysteine in CHD awaits the results of prospective trials currently in progress.
Jacques Genest, Jr, MD
Associate Professor, University of Montreal
Director, Cardiovascular, Genetics Laboratory
Clinical Research Institute of Montreal
Montreal, Quebec, Canada
[...]Page last modified: June 16, 2005
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Re: B12, homocysteine, & heart disease
This site refers to 'Diabetes Care 2000;23:1348-1352', and writes:
Quote:
Insulin May Raise Homocysteine
Overweight children with high levels of the hormone insulin in their blood are also likely to have high levels of homocysteine, a substance that appears to raise the risk of heart disease, stroke, and birth defects, as well as possibly other adverse effects as well.
In addition, these children and adolescents appear to have lower levels of folate, a vitamin that can lower homocysteine levels.
The combination of elevated homocysteine and reduced folate could put these children at increased risk for developing heart disease, explain researchers from the University of Graz in Austria, who studied the link in 84 children and adolescents.
"The implication of our finding might be that reduction of cardiovascular risk factors (such as) body fat and insulin -- by dieting and/or physical activity -- might improve homocysteine metabolism," Dr. Siegfried Gallistl, the study's lead author, explained in an interview with Reuters Health. He also noted that that insulin appears to inhibit enzymes that play a role in homocysteine metabolism.
Insulin is the hormone responsible for getting glucose (sugar) in the blood into cells throughout the body to use as fuel. The cells of people with type 2 diabetes do not respond adequately to insulin. As a result, levels of both glucose and insulin in the blood remain high.
"Our study demonstrates for the first time that insulin is a main correlate of homocysteine in obese children and adolescents and suggests that (high insulin) may contribute to impairment of homocysteine metabolism in childhood obesity," the researchers conclude.
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Re: B12, homocysteine, & heart disease
An excerpt from The American Journal of Clinical Nutrition
Quote:
Homocysteine and cardiovascular disease: cause or effect?
Lars Brattström and David EL Wilcken
Abstract
Both markedly and mildly elevated circulating homocysteine concentrations are associated with increased risk of vascular occlusion. Here we review possible mechanisms that mediate these effects. Inborn errors of homocysteine metabolism result in markedly elevated plasma homocysteine (200–300 µmol/L) and thromboembolic (mainly venous) disease: treatment to lower but not to normalize these concentrations prevents vascular events. Mild homocysteine elevation (>15 µmol/L) occurs in 20–30% of patients with atherosclerotic disease. Usually, this is easily normalized with oral folate and ongoing trials are assessing the effect of folate treatment on outcomes. Although there is evidence of endothelial dysfunction with both markedly and mildly elevated homocysteine concentrations, the elevated homocysteine concentration in atherosclerotic patients is also associated with most standard vascular risk factors, and importantly, with early decline in renal function, which is common in atherosclerosis. Decline in renal function alone causes elevated plasma homocysteine (and cysteine). These observations suggest that mild hyperhomocysteinemia could often be an effect rather than a cause of atherosclerotic disease. Data on the common C677T methylenetetrahydrofolate reductase polymorphism supports this, in that, although homozygosity is a frequent cause of mild hyperhomocysteinemia when plasma folate is below median population concentrations, it appears not to increase cardiovascular risk. Indeed, there is recent evidence suggesting an acute antioxidant effect of folic acid independent of its effect on homocysteine concentrations. This antioxidant mechanism may oppose an oxidant effect of homocysteine and be relevant to treatment of patients with vascular disease, especially those with chronic renal insufficiency. Such patients have moderately elevated plasma homocysteine and greatly increased cardiovascular risk that is largely unexplained.
INTRODUCTION
Despite the impressive epidemiologic evidence that mild hyperhomocysteinemia is an independent risk factor for atherosclerotic and atherothrombotic vascular disease, we have become increasingly doubtful as to whether modest elevations of plasma homocysteine may be causally involved in the pathogenesis of atherosclerosis. As will be outlined in this review, there are now substantial indications that a modest elevation of plasma homocysteine is usually benign and is a consequence rather than a cause of atherosclerosis.
[...]
CONCLUSIONS
It has been established that lowering the markedly elevated circulating homocysteine concentrations found in patients with the inborn error of homocystinuria due to CBS deficiency, even to suboptimal concentrations, greatly reduces cardiovascular risk (20, 139). This finding defines a key role for grossly elevated homocysteine concentrations in the pathogenesis of vascular disease. The relevance to vascular risk of mild hyperhomocysteinemia is, however, still undetermined. The results of the many ongoing homocysteine-lowering trials with folic acid in vascular patients may certainly clarify whether folate therapy is relevant to cardiovascular risk in the general population and will provide much important information (38). However, if the trials show a positive effect of supplementation they will not of course separate the effects of oral folate supplementation from those of lowering homocysteine concentration. This might be done by comparing folic acid and betaine therapy in such patients because both lower circulating homocysteine but by different mechanisms. This would be an extremely interesting study but one that is unlikely to be done.
American Journal of Clinical Nutrition, Vol. 72, No. 2, 315-323, August 2000
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Re: B12, homocysteine, & heart disease
From the University of Kuopio:
Quote:
Homocysteine and other CVD risk factors
High circulating Hcy concentrations may increase the risk of CVD when present with other CVD risk factors. For example, there is some evidence that in hypercholesterolemic patients the risk of an atherosclerotic event was about three times higher in patients with high plasma tHcy concentrations compared to those with low tHcy concentrations. Another study done in subjects with elevated LDL cholesterol concentrations suggests that even mildly increased plasma tHcy levels are of crucial importance for deterioration of endothelial function. Increased risk of mortality in the subjects with both elevated cholesterol and tHcy concentrations may at least partly be explained by deterioration of endothelial function.
Similar findings to those found in hypercholesterolemic patients have also been reported in case of increased plasma fibrinogen levels or in smokers. The increased risk with increased fibrinogen and tHcy concentrations could be explained by their complementary roles in the platelet activation-aggregation cascade. Fibrinogen represents a major step in platelet aggregation while homocysteine impairs nitric oxide production and also contributes to the generation of oxidized species. In some studies smoking has been shown to increase plasma tHcy concentrations, but in the KIHD study population this is not seen. Smokers have an increased risk of vascular disease in general and according to some recent research the risk is greatly increased in the presence of a raised plasma tHcy concentration when compared with non-smokers.
Currently Jyrki Virtanen is studying the effects of high plasma tHcy concentration on CVD risk in men of the KIHD study, who also have other CVD risk factors. These include smoking, high serum total and LDL cholesterol and apo-B apolipoprotein concentrations and high plasma fibrinogen concentration. Preliminary results would seem to indicate that although tHcy alone is not a risk factor for CVD in this study population, it may increase the risk when present with above mentioned risk factors.
Homocysteine and methionine
Since Hcy is formed from an essential dietary amino acid methionine, high intakes of methionine increase the plasma tHcy concentrations. This happens because the capacity of the transsulfuration pathway is exceeded and Hcy is excreted from cells. Elevation of plasma tHcy occurs, for example, in the oral methionine loading test, in which a large dose of methionine (0.1 g/kg body weight of L-methionine) is ingested to diagnose hyperhomocysteinemia. It could be speculated that a long-term high methionine intake from diet could lead to modest but chronic plasma tHcy concentrations, which in turn could increase the risk of CVD.
Homocysteine and stroke
Although high plasma tHcy has been suggested to be a risk factor for CVD, its role as a risk factor for stroke is more controversial. Although most case-control studies suggest it to be a risk factor for stroke, the results from prospective studies are conflicting. Two recent meta-analyses, however, have concluded that Hcy might increase the risk of stroke. The mechanisms through which Hcy could cause stroke are its hypercoagulative effects in ischemic stroke and promotion of plaque rupture in hemorrhagic stroke. Jyrki Virtanen's next paper will concern the role of high plasma tHcy concentration in the risk of overall and ischaemic stroke in the KIHD study population.
Conclusion
Although folate or folic acid intake could lower the risk of CVD through reducing plasma tHcy concentrations, elevated homocysteine may also be only a marker for low folate and/or vitamin B6 status or an indicator of an unhealthy lifestyle rather than a causal risk factor per se. Ongoing intervention trials will indicate whether homocysteine-lowering through vitamin supplementation prevents heart diseases, or are the measured circulating high homocysteine and low folate levels just markers of unhealthy lifestyle.
More information about our studies:
sari.voutilainen@uku.fi,
jyrki.virtanen@uku.fi
More: http://www.uku.fi/nutritionepidemiologists/folate.htm
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Re: B12, homocysteine, & heart disease
From http://www.quackwatch.org/03HealthPr...ocysteine.html :
Quote:
Homocysteine: A Cardiovascular Risk
Factor Worth Considering
Stephen Barrett, M.D.
At least nine well-known risk factors can help predict the likelihood of heart attacks and strokes: heredity, being male, advancing age, cigarette smoking, high blood pressure, diabetes, obesity (especially excess abdominal fat), lack of physical activity, and abnormal blood cholesterol levels. The more of these risk factors a person has, the greater the likelihood of becoming ill. Heredity, gender, and age cannot be modified, but the others can be influenced by the individual's behavior. Modifying these factors can lower the risk of having a heart attack.
During the past few years, elevated blood levels of homocysteine (a sulfur-containing amino acid) have been linked to increased risk of premature coronary artery disease, stroke, and thromboembolism (venous blood clots), even among people who have normal cholesterol levels. Abnormal homocysteine levels appear to contribute to atherosclerosis in at least three ways: (1) a direct toxic effect that damages the cells lining the inside of the arteries, (2) interference with clotting factors, and (3) oxidation of low-density lipoproteins (LDL).
A recent study compared 131 patients with severe blockages in two coronary arteries, 88 patients with moderate blockage of one coronary artery, and another group of healthy individuals without heart disease. The researchers found a linear relationship between blood homocysteine levels and severity of the coronary blockages: For every 10% elevation of homocysteine, there was nearly the same rise in the risk of developing severe coronary heart disease [1]. Another study has found that postmenopausal women with elevated homocysteine levels had a higher incidence of coronary heart disease [2]. Another study found that homocysteine levels were much higher in people who developed vein clots than in similar people who did not [3]. Yet another study found that elevated homocysteine levels may ne associated with an increased risk of stroke in people who already have coronary heart disease [4]
Blood for measuring serum homocysteine levels is drawn after a 12-hour fast. Levels between 5 and 15 micromoles per liter (µmol/L) are considered normal. Abnormal concentrations are classified as moderate (16-30), intermediate (31-100), and severe (greater than 100 µmol/L). [5]
The connection between homocysteine and cardiovascular disease was suspected about 25 years ago when it was observed that people with a rare condition called homocystinuria are prone to develop severe cardiovascular disease in their teens and twenties. In this condition, an enzyme deficiency causes homocysteine to accumulate in the blood and to be excreted in the urine. Recent studies suggest that elevated blood homocysteine levels are as important as high blood cholesterol levels and can operate independently. Some 10% to 20% of cases of coronary heart disease have been linked to elevated homocysteine levels. Both hereditary and dietary factors may be involved.
Homocystinuria is transmitted by a recessive gene. If both parents transmit the gene, the resultant offspring have very high plasma homocysteine levels. People who receive the defective gene from only one parent do not develop the disease but often have a mildly elevated plasma level of homocysteine. About one person in 100 carries one such gene. Abnormal elevation also occurs among people whose diet contains inadequate amounts of folic acid, vitamin B6, or vitamin B12. Regardless of the cause of the elevation, supplementation with one or more of these vitamins can lower plasma levels of homocysteine.
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].
Since folic acid is nontoxic, it seems prudent to treat elevated homocysteine levels based on current knowledge. The process should be supervised by a well-informed physician.
Caution: Elevated homocysteine levels can be caused by vitamin B12 deficiency due to impaired absorption of B12 caused by gastric atrophy (damage to the lining of the stomach). B12 deficiency leads to anemia and, if not corrected in time, will permanently damage the nervous system. Folic acid supplements will correct the anemia (which can serve as a warning sign before nerve damage develops), but they do not prevent the damage. For this reason, people over 50 who take folic acid supplements should also take at least 25 micrograms of vitamin B12 per day, a dose large enough to enable adequate amounts to be absorbed. Dr. Herbert believes that everyone over age 50 should take B12 supplements anyway, because gastric atrophy is common as people age. Products containing 100 mcg per pill are readily available.
References
Verhoef P and others. Plasma total homocysteine, B vitamins, and risk of coronary atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology 17:989-995, 1997.
Ridker PM and others. Homocysteine and risk of cardiovascular disease among postmenopausal women. JAMA 281:1817-1821, 1999.
Loralie J and others. Hyperhomocyst(e)inemia and the Increased Risk of Venous Thromboembolism. Archives of Internal Medicine 160:961-964, 2000.
Tanne D and others. Prospective study of serum homocysteine and risk of ischemic stroke among patients with preexisting coronary heart disease. Stroke 34:632-636, 2003.
Kang SS and others. Hyperhomocyst(e)inemia as a risk factor for occlusive vascular disease. Annual Review of Nutrition 12:279-298, 1992.Rimm EB and others. Folate and Vitamin B6 from Diet and Supplements in Relation to Risk of Coronary Heart Disease among Women. JAMA 279:359-364, 1998.
Malinow MR and others. Homocyst(e)ine, diet, and cardiovascular diseases: A statement for healthcare professionals from the nutrition committee, American Heart Association. Circulation 99:178-182, 1999.
Eikelboom JW and others. Homocyst(e)ine and cardiovascular disease: A critical review of the epidemiologic evidence. Annals of Internal Medicine 131:363-375, 1999.
Hackam DG and others. What level of plasma homocyst(e)ine should be treated? Effects of vitamin therapy on progression of carotid atherosclerosis in patients with homocyst(e)ine levels above and below 14 micromol/L. American Journal of Hypertension 13:105-100, 2000.
Genest J Jr and others. Homocysteine: To screen and treat or wait and see? Canadian Medical Association Journal 163:37-38, 2000. [PDF}
Quinlivan EP and others. Importance of both folic acid and vitamin B12 in reduction of risk of vascular disease. Lancet 359:227-228, 2002. [PDF]
Booth GL, Wang EL, with the Canadian Task Force on Preventive Health Care. Preventive health care, 2000 update: screening and management of hypohomocysteinemia for the prevention of coronary artery disease events. Canadian Medical Association Journal 163:21-29, 2000. [PDF]
Schnyder G and others. Homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention. The Swiss Heart Study: A randomized controlled trial. JAMA 288:973-979, 2002
This article was revised on March 29, 2003.
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Re: B12, homocysteine, & heart disease
From http://www.homocysteine.com/bkchap2.html
Quote:
Carotid artery intimal-medial wall thickening and plasma homocyst(e)ine in asymptomatic adults. The Atherosclerosis Risk in Communities Study.
Malinow MR; Nieto FJ; Szklo M; Chambless LE; Bond G: Circulation* (United States), Apr 1993, 87(4) p1107-13
Editor's Comment:
I remember meeting Dr. Malinow in New York City in Dr. Victor Herbert's apartment. This was followed by a great Thai dinner on 59th street. I took the opportunity to discuss Dr. Malinow's homocysteine studies and found him to be a credible, brilliant researcher who was ahead of his time. The following work is a landmark study of great importance.
Dr. Malinow constructed a rather simple, noninvasive study using ultrasound to measure the thickness of the wall of the carotid arteries, the vessels that pipe all of the blood to the head. It is these vessels that when thickened and narrowed lead to strokes and the so-called TIA (transient ischemic attack). The study as presented below shows that if your homocysteine level is high, in the upper twenty percent, the chances for a thickened artery wall are more than three times greater than for someone having a level in the lowest 20%.
Plasma levels of homocysteine are elevated in certain patients with occlusive arterial diseases. We extended these findings to asymptomatic adults. METHODS AND RESULTS. We determined plasma homocysteine levels in 287 pairs of asymptomatic adults. Cases and controls were defined on the basis of intimal-medial thickness of the carotid wall as measured by B-mode ultrasound. Study subjects had no history of atherosclerotic disease and were selected from a probability sample of 15,800 men and women between 45 and 64 years old. Subjects with thickened intimal-medial carotid walls (cases) had higher plasma homocysteine levels than controls (p 0.001). The odds ratio for having a thickened carotid artery wall was 3.15 (p 0.001) for subjects in the top quintile of plasma homocysteine levels ( 10.5 mumol/L) compared with those in the bottom quintile ( 5.88 mumol/L). CONCLUSIONS: The present study as well as observations on the common occurrence of elevated plasma homocysteine levels in patients with occlusive arterial diseases suggest that clinical trials should be conducted to determine whether normalization of hyperhomocysteinemia may prevent progression of atherosclerosis.
Quote:
romotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis.*
Tsai JC; Perrella MA; Yoshizumi M; Hsieh CM; Haber E; Schlegel R; Lee ME: JProc Natl Acad Sci U S A* (United States), Jul 5 1994, 91(14) p6369-73 Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, MA.
Editor's Comment:
This study by Tsai and associates from a prominent laboratory is very provocative. Modern theories of the mechanisms of atherosclerosis propose that an initial toxic event leads to damage of the innermost blood vessel lining cells, the intimal or endothelial cells. After this comes the monocyte scavenger cells and sticky granulocytes (both white blood cells) in an attempt to repair the damage. This is to no avail for the repair mechanism itself becomes a confounding damaging force.
Monocytes change shape as they bore their way into the blood vessel wall and secrete materials that help turn on other cells to grow. They, in concert with other cells, start to imbibe oxidized lipoprotein-cholesterol forming what have been called "foam cells". The following study points to homocysteine's ability to not only damage endothelial cells (the initial event of atherosclerosis) but also to stimulate the overgrowth of blood vessel smooth muscle cells, a hallmark of atherosclerosis.
Plasma homocysteine levels are elevated in 20-30% of all patients with premature atherosclerosis. Although elevated homocysteine levels have been recognized as an independent risk factor for myocardial infarction and stroke, the mechanism by which these elevated levels cause atherosclerosis is unknown. To understand the role of homocysteine in the pathogenesis of atherosclerosis, we examined the effect of homocysteine on the growth of both vascular smooth muscle cells and endothelial cells at concentrations similar to those observed in clinical studies. As little as 0.1 mM homocysteine caused a 25% increase in DNA synthesis, and homocysteine at 1 mM increased DNA synthesis by 4.5-fold in rat aortic smooth muscle cells (RASMC). In contrast, homocysteine caused a dose-dependent decrease in DNA synthesis in human umbilical vein endothelial cells. Homocysteine increased mRNA levels of cyclin D1 and cyclin A in RASMC by 3- and 15-fold, respectively, indicating that homocysteine induced the mRNA of cyclins important for the reentry of quiescent RASMC into the cell cycle. Furthermore, homocysteine promoted proliferation of quiescent RASMC, an effect markedly amplified by 2% serum. The growth-promoting effect of homocysteine on vascular smooth muscle cells, together with its inhibitory effect on endothelial cell growth, represents an important mechanism to explain homocysteine-induced atherosclerosis.
Quote:
Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis.* Selhub J; Jacques PF; Bostom AG. D'Agostino RB; Wilson PW; Belanger AJ; O'Leary DH; Wolf PA; Schaefer EJ; Rosenberg IH: Comment in: N Engl J Med 1995 Feb 2; 332(5):328-9* Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111.
Editor's Comment:
Dr. Selhub has written extensively on homocysteine and atherosclerosis. Here is a study that not only confirms the results of Malinow's work cited above but also correlates high blood levels of homocysteine with decreased ingestion of vitamins B6 and folic acid. The authors were also able to correlate lower serum levels of these vitamins in patients with thickened carotid arteries and high homocysteine.
Later, in another chapter, I will present evidence revealing that it is next to impossible to ingest enough folic acid from a healthy diet to suppress homocysteine to its lowest and safest level. The roles played by* vitamin B6 and folic acid are critical and will be explained in detail in the chapter on homocysteine metabolism.
Epidemiological studies have identified hyperhomocysteinemia as a possible risk factor for atherosclerosis. We determined the risk of carotid-artery atherosclerosis in relation to both plasma homocysteine concentrations and nutritional determinants of hyperhomocysteinemia. METHODS. We performed a cross-sectional study of 1041 elderly subjects (418 men and 623 women; age range, 67 to 96 years) from the Framingham Heart Study. We examined the relation between the maximal degree of stenosis of the extracranial carotid arteries (as assessed by ultrasonography) and plasma homocysteine concentrations, as well as plasma concentrations and intakes of vitamins involved in homocysteine metabolism, including folate, vitamin B12, and vitamin B6. The subjects were classified into two categories according to the findings in the more diseased of the two carotid vessels: stenosis of 0 to 24 percent and stenosis of 25 to 100 percent. RESULTS. The prevalence of carotid stenosis of or = 25 percent was 43 percent in the men and 34 percent in the women. The odds ratio for stenosis of or = 25 percent was 2.0 (95 percent confidence interval, 1.4 to 2.9) for subjects with the highest plasma homocysteine concentrations ( or = 14.4 mumol per liter) as compared with those with the lowest concentrations ( or = 9.1 mumol per liter), after adjustment for sex, age, plasma high-density lipoprotein cholesterol concentration, systolic blood pressure, and smoking status (P 0.001 for trend). Plasma concentrations of folate and pyridoxal-5'-phosphate (the coenzyme form of vitamin B6) and the level of folate intake were inversely associated with carotid-artery stenosis after adjustment for age, sex, and other risk factors. CONCLUSIONS. High plasma homocysteine concentrations and low concentrations of folate and vitamin B6, through their role in homocysteine metabolism, are associated with an increased risk of extracranial carotid-artery stenosis in the elderly.
Quote:
Serum total homocysteine and coronary heart disease.* Arnesen E, Refsum H, Bonaa KH, Ueland PM, Forde OH, Nordrehaug JE Int J Epidemiol 1995 Aug;24(4):704-9* Institute of Community Medicine, University of Tromso, Norway.
Editor's Comment:
This study evaluated 21,826 subjects and confirmed the association of high homocysteine levels with heart attack. It also found the absence of a threshold value for homocysteine above which heart attacks occur. This means that those with lower homocysteine levels will have a lower chance of having a heart attack. As we shall discuss in another chapter, therapy with appropriate doses of vitamins will lower serum homocysteine levels by up to 50%.
Several studies have observed high plasma levels of homocysteine among patients with coronary heart disease (CHD). The only prospective study was based on US physicians, and concluded that homocysteine was associated with subsequent myocardial infarction (MI). However, the association was limited to those above a threshold level of homocysteine. METHODS. We conducted a nested case-control study among the 21,826 subjects, aged 12-61 years, who were surveyed in the municipality of Tromso, Norway. Among those free from MI at the screening, 123 later developed CHD. Four controls were selected for each case. RESULTS. Level of homocysteine was higher in cases than in controls (12.7 +/- 4.7 versus 11.3 +/- 3.7 mumol/l (mean +/- SD); P = 0.002). The relative risk for a 4 mumol/l increase in serum homocysteine was 1.41 (95% confidence interval (CI): 1.16-1.71). Adjusting for possible cofounders reduced the relative risk to 1.32 (95% CI: 1.05-1.65). There was no threshold level above which serum homocysteine is associated with CHD events. CONCLUSIONS. In the general population serum total homocysteine is an independent risk factor for CHD with no threshold level.
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Re: B12, homocysteine, & heart disease
Excerpts from http://www.medic8.com/healthguide/ar...ocysteine.html
Quote:
HOMOCYSTEINE AND VASCULAR DISEASE - a patient's guide
Dr Michael Crooke - Biochemistry Pathologist
What is Homocysteine?
Homocysteine is an amino acid found in blood and other body fluids. It is a breakdown product of another amino acid (methionine). Once homocysteine is formed it can be further broken down and excreted or it can be reconverted to methionine. This reconversion is important, as methionine is an essential amino acid.
If the excretory or recycling processes are not functioning efficiently then levels of homocysteine in the blood will increase. Both the breakdown and recycling processes are controlled by enzymes and these enzymes require adequate levels of vitamins for proper activity. In the case of the breakdown process vitamin B6 is important, and for recycling of homocysteine to methionine, vitamin B12 and folate are necessary. The overall evidence is that folate may be most important in keeping homocysteine at lower levels.
What is the significance of homocysteine?
The importance of homocysteine is that higher levels in blood have been linked to a higher chance of developing vascular disease (heart attacks, strokes and blockage of the arteries to the legs). High homocysteine is also associated with a higher frequency of venous thrombosis (clots).
These associations of homocysteine with vascular disease do not prove that homocysteine is a cause of the disease. They are in the category of circumstantial evidence, qualifying homocysteine as a strong risk factor and allowing the reasonable hypothesis that it is a cause of cardiovascular disease. The final link in proving a cause is to show that reducing levels of a risk factor leads to reduction in disease and these studies have not yet been completed for homocysteine.
[...]
The current situation for homocysteine is much the same as existed for cholesterol 10-15 years ago, i.e. it is only a risk factor although there are plausible reasons that it may be a cause of vascular disease. The strength of the association of high homocysteine with vascular disease, especially coronary artery disease, is just as high as that for cholesterol, so it is important that the final research studies are completed. These will show whether or not lowering homocysteine does decrease the risks of vascular disease and should also help to define safe methods of lowering homocysteine. Despite the high risk association of homocysteine, there is no guarantee that the trials will be successful. Associations can easily be questionable.
[...]
Further studies have confirmed that the risk associated with homocysteine is also seen in the general population, at much lower levels of homocysteine than found in homocystinuria. In fact, the risk is graded over the whole range of homocysteine levels found in what would be regarded as normal populations. The usual range of homocysteine found in the plasma (blood) of 95% of people is 5- 15 umol/L. The evidence suggests that any increase of 5 umol/L, even within this so called normal range, inreases the risk of a clinical event related to heart disease by about 1.5 fold.
The evidence is even stronger when those with the top 20% of homocysteine levels within the range of 5-15 umol/L are compared with those with the bottom 80% of homocysteine levels. The increased risk is then up to two fold. The magnitude of this increased risk is similar to that seen for the top 20% of cholesterol levels and for smokers versus non-smokers. Levels of homocysteine over 15 umol/L confer even higher risk.
These risk associations are sustained, and may be even stronger, in these people who are already known to have arterial disease. For example, in one study of people known to have coronary artery disease, 25% of those with homocysteine over 15 umol/L died over a five year period, compared with only 4% of those with homocysteine under 9 umol/L.
These studies of populations (epidemiology) have all been consistent in showing the risk association of vascular disease with homocysteine, across over 20 studies. The overall conclusion is that homocysteine is confirmed as a risk factor for vascular disease, completely independent of any other risk factors. While consistent, these studies do not prove cause and effect. However, there is a strong possibility that homocysteine is likely to be a contributing cause of arteriosclerotic vascular disease (hardening of the arteries).
[...]
The final biological evidence is that homocysteine causes damage to the cells which line blood vessels when these cells are grown in cell cultures to which homocysteine is added. This damage, if it occurs in the body, would be expected to promote the formation of atheroma and thrombosis.
What causes homocysteine to be higher than may be desirable?
The chemical reactions determining homocysteine levels in the blood are complex. The key point to understand is that a deficiency of folate may result in higher levels.
A number of factors affect these reactions but there is a wealth of evidence to suggest that levels of blood (serum)folate are most important. Normally about 50% of homocysteine is reconverted to methionine by the enzyme methionine synthase in steps which also require folate, vitamin B12 and the enzyme methylenetetrahydrofolate reductase (MTHFR). Folate acts as a methyl donor for the overall reaction and thus deficiency of folate would be expected to impair the conversion of homocysteine to methionine, thus causing increased levels of homocysteine.
There is consistent evidence that plasma homocysteine is inversely related to serum folate, i.e. higher folate gives lower homocysteine and vice versa. This relationship holds at levels of folate which have previously been considered to be normal.
Furthermore, the risk of coronary heart disease has been clearly linked to lower levels of serum folate and long term studies have shown an inverse association between a high folate diet and both coronary and carotid artery disease. Most notable is the Nurses Study in which 80,000 women were followed up for 14 years. The risk of heart attack was reduced by 30-50% in those who consumed the most folate/folic acid, compared with those who consumed the least. This reduced risk was considered to be most likely due to the effects of high folate consumption to reduce homocysteine, although the study was not set up to prove this point.
A number of other clinical trials have shown that supplementation of the diet with folic acid does lower homocysteine and a summary of all studies indicates that, on average, 0.5mg of folic acid reduces homocysteine by about 25% (e.g. from 12 to 9). Greater reductions were seen if the subjects had initially high pre-treatment levels of homocysteine or lower initial levels of serum folate. Small additional effects to lower homocysteine were seen when the diets were also supplemented with vitamin B12. These were all short term dietary studies and there was no attempt to study any changes in vascular disease.
[n]The conclusion from all these dietary studies is that up to 40-50% of the population have insufficient intake of natural food folate to lower homocysteine to the levels associated with lower vascular risk (homocysteine under 9 umol/L).
Furthermore, it is probable that the currently stated reference (normal) ranges for serum folate are set too low. The usual lower limit stated is around 7 umol/L, but to minimise homocysteine levels the lower level should be around 15 umol/L and some people will need much higher levels than this to minimise homocysteine.[/b]
[...]
Higher homocysteine levels are also found, on average, in men compared with woman, in smokers, and there is a tendency for levels to increase with age. This latter effect may be related to poorer diet in older people i.e. less folate and vitamin B12. Excessive coffee drinking also tends to increase homocysteine.
[...]
It is of interest that in the United States it has been mandatory, since 1st January 1998, that all cereal based foods be supplemented by the manufacturers with folic acid, at 140mg/100g. This will add about 100 mg of folic acid (equivalent to 200 mg of food folate) to the average diet. (Note 100 mg equals 0.1mg). The reason for this legislation was not related to possible prevention of heart disease but rather to the fact that this level of supplementation will help prevent neural tube defects (spina bifida and anencephaly). It has been clearly shown that when pregnant woman consume folic acid supplements, in addition to natural food folate, a large proportion of cases of spina bifida are prevented. [b]It is difficult, even with the best diet, to reach the daily amount of folate/folic acid required so supplementation is necessary. In New Zealand it is recommended that all pregnant women take folic acid supplements.
The legislation caused controversy in the United States with some health authorities arguing that the supplementation should have been greater, not only to prevent spina bifida, but also to reduce the risk of vascular disease in the whole population by lowering average levels of homocysteine in response to adequate folic acid.
The critics, the prestigious Centre for Disease Control among them, argue that since there is clear evidence that a substantial proportion of the population consume insufficient folate in food, the cereal based foods should have been supplemented with a minimum of 0.35mg/100g of folic acid and that 0.7mg/100g would be safe [...].
It can certainly do no harm to increase folate containing foods in the diet. Examples of these are green/leafy vegetables such as broccoli, or spinach, starch beans such as kidney beans, butter beans, peas, corn, cauliflower, nuts, avocado, wheat bran, wholegrain cereals and most fruits, especially citrus fruits. Most nutritional authorities would recommend at least five daily servings of foods from this group as part of a healthy diet, also likely to benefit cholesterol levels. If this level of intake can be achieved it is arguable that most people would not benefit further from supplementation with folic acid.
[...]
The only known risk of folic acid is in people who might have vitamin B12 deficiency. Folic acid supplements can mask the symptoms of vitamin B12 deficiency. The elderly are especially at risk, as vitamin B12 deficiency is relatively common in this group. Even so, only doses of folic acid of over 0.8mg are likely to cause a problem. The obvious solution is to measure both serum folate and vitamin B12 before folic acid supplements are taken and, if appropriate, to also take vitamin B12.
You've probably read - a lot of times - that it's almost impossible to get enough B12 to keep the homocysteine levels down on a vegan diet. Non-vegans who read about folate and homocysteine have probably have seen, equally many times, that it's almost impossible to get enough folate (to keep the homocysteine levels 'safe') on a non-vegan diet.
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Re: B12, homocysteine, & heart disease
From http://www.kroger.com/hn/Concern/High_Homocysteine.htm
Quote:
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 3˝ 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.
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Re: B12, homocysteine, & heart disease
From http://www.quackwatch.org/03HealthPr...ocysteine.html
Quote:
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].
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Re: B12, homocysteine, & heart disease
From http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract (1999)
Quote:
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]
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Re: Battling Heart Disease with B Vitamins
New research is indicating popping vit. B tablets may not be the answer:
http://news.bbc.co.uk/1/hi/health/4218186.stm
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Re: Battling Heart Disease with B Vitamins
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?
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Re: Battling Heart Disease with B Vitamins
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)
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Re: Battling Heart Disease with B Vitamins
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.
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Re: Battling Heart Disease with B Vitamins
Thanks Diane - by looking at that list of foods - it seems that I would get a good intake of folate in my diet :)
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Re: Battling Heart Disease with B Vitamins
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.
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Re: Battling Heart Disease with B Vitamins
Quote:
Dianecrna
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.
Quote:
Dianecrna
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.
Quote:
Dianecrna
Odd that this never makes it into magazines or the nightly news.
I guess homocysteine is not a sexy subject!
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Re: Battling Heart Disease with B Vitamins
Quote:
StevieP
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. ) ;)
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Re: Battling Heart Disease with B Vitamins
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.
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Re: Battling Heart Disease with B Vitamins
Quote:
StevieP
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:
Quote:
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.
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Re: B12, homocysteine, & heart disease
Here are some excerpts from the article quoted in the BBC-article:
Quote:
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 Tromsř 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 Břnaa 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.
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Re: B12, homocysteine, & heart disease
From ajph.org
Quote:
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.
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Re: B12, homocysteine, & heart disease
Quote:
Korn
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.
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Re: B12, homocysteine, & heart disease
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?
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Re: B12, homocysteine, & heart disease
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...
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Re: B12, homocysteine, & heart disease
From http://www.mary-anns.com/Homocysteine%20article.htm
Quote:
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! :)
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Re: B12, homocysteine, & heart disease
That website is a puff for a product called BarleyLife. I'm always suspicious when someone is trying to sell something.
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Re: B12, homocysteine, & heart disease
Quote:
herbwormwood
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
Quote:
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.
Quote:
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).
Quote:
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?
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Re: B12, homocysteine, & heart disease
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:
Quote:
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.
Quote:
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.
Quote:
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?"
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Re: B12, homocysteine, & heart disease
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."
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Re: B12, homocysteine, & heart disease
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:
Quote:
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.
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Re: B12, homocysteine, & heart disease
From http://www.drmcdougall.com/misc/2005...51000folic.htm
An excerpt:
Quote:
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:
Quote:
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:
Quote:
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.
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Re: B12, homocysteine, & heart disease
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
Quote:
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.
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Re: B12, homocysteine, & heart disease
Quote:
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
Quote:
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.
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Re: B12, homocysteine, & heart disease
Homocysteine: A Cardiovascular Risk
Factor Worth Considering
An excerpt:
Quote:
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.
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Re: B12, homocysteine, & heart disease
http://www.streetdirectory.com/trave..._vitamins.html
Quote:
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.
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Re: B12, homocysteine, & heart disease
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
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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.