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Re: B12, homocysteine, & heart disease
(Also posted in the B12 overdose / megadose thread):
Quote:
Korn
From
http://www.cancerresearchuk.org/abou...gyourrisk/diet
Eating lots of red or processed meat is a risk factor for bowel cancer. There is also some evidence that breast, lung, prostate and pancreatic cancers are linked to a diet high in red or processed meat.
(I know there is some controversy about breast cancer/meat link. Korn).
Commenting this post from 2005, there are now new, related findings about B12 and (mainly lung) cancer:
Here's the abstract:
http://jama.ama-assn.org/cgi/content/short/302/19/2119
Quote:
Results During study treatment, median serum folate concentration increased more than 6-fold among participants given folic acid. After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B12 vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B12 vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07-1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B12 vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04-1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B12. Vitamin B6 treatment was not associated with any significant effects.
Conclusion: Treatment with folic acid plus vitamin B12 was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods.
The study is discussed here: Treatment With Folic Acid, Vitamin B12 Associated With Increased Risk of Cancer, Death
High Doses of B Vitamins Associated With Increased Decline in Kidney Function for Patients With Kidney Disease from Diabetes
Quote:
According to background information in the article, several observational studies have shown a significant association between high concentrations of plasma total homocysteine and the risk of developing diabetic nephropathy, retinopathy, and vascular diseases, including myocardial infarction (MI; heart attack) and stroke. B-vitamin therapy (folic acid, vitamin B6, and vitamin B12) has been shown to lower the plasma concentration of homocysteine.
Andrew A. House, M.D., of the University of Western Ontario, and J. David Spence, M.D., of the Robarts Research Institute, London, Ontario, and colleagues conducted a study to examine whether B-vitamin therapy would slow the progression of diabetic nephropathy and prevent vascular events in 238 patients with type 1 or 2 diabetes. The randomized, placebo-controlled trial was conducted at five university medical centers in Canada between May 2001 and July 2007. Patients received single tablet of B vitamins containing folic acid (2.5 mg/d), vitamin B6 (25 mg/d), and vitamin B12 (1 mg/d), or matching placebo. The primary outcome was change in radionuclide glomerular filtration rate (GFR; a measure of kidney function) between baseline and 36 months. Other outcomes included dialysis and a composite of heart attack, stroke, revascularization and all-cause death. Plasma total homocysteine was measured. Participants were followed-up for an average of 31.9 months.
Among the results, the researchers found that participants assigned to the B-vitamin group had a greater decrease in radionuclide GFR (and subsequently poorer kidney function) compared with the placebo group. Also, participants randomized to receive B vitamins had a significantly greater number of cardiovascular and cerebrovascular events, with the 36-month risk of a composite outcome, including heart attack, stroke, revascularization, and all-cause mortality that was double in the B-vitamin group, compared to the placebo group. There was no difference in requirement of dialysis.
Regarding plasma total homocysteine levels, at 36 months, participants in the B-vitamin group had an average decrease while participants in the placebo group had an average increase.
"Given the recent large-scale clinical trials showing no treatment benefit, and our trial demonstrating harm, it would be prudent to discourage the use of high-dose B vitamins as a homocysteine-lowering strategy outside the framework of properly conducted clinical research," the authors conclude.
Heart disease: B-Vitamin Pills Have No Effect, Review Finds
Quote:
Certain B-vitamins, specifically B12, B9 (folic acid) and B6, influence levels of an amino acid in the blood called homocysteine. High levels of this molecule are associated with an increased risk of heart disease. It has been suggested that giving B-vitamin supplements could help regulate levels of homocysteine, thereby reducing the risk of cardiovascular disease and death. But according to the researchers, there is no scientific basis for this claim.
The review included eight trials involving a total of 24,210 people. None of the eight trials individually supported the idea that giving B-vitamin supplements could prevent cardiovascular disease. Together the data show that B-vitamin supplements, whether compared with placebos or standard care, have no effect on the incidence of heart attack, stroke or death associated with heart disease.
"Prescription of these supplements cannot be justified, unless new evidence from large high quality trials alters our conclusions. There are currently three ongoing trials that will help to consolidate or challenge these findings," says Martí-Carvajal.
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Re: B12, homocysteine, & heart disease
First a short summary of the main topic that's being discussed in this thread:
There has been an ongoing disagreement for many years, regarding the link between homocysteine levels, B vitamins and heart disease.
To simplify: "Group A" have insisted that since high homocysteine levels often are associated with reduced risk of heart disease, the reason for the reduced heart disease risk is the lower homocysteine level itself.
"Group B" has emphasized that even if there's a link between low homocysteine levels and heart health, lowering people's homocysteine levels as such doesn't necessarily mean reduced heart disease risk, because maybe the changes seen is homocysteine levels and heart disease risk aren't 'cause and result', but that both the reduced risk and the homocysteine levels are symptoms of something else. In short, changing homocysteine levels as such may not be the reason that the heart disease risk will be altered.
Vegans often have higher levels of vitamin B6 than non-vegans, but lower levels of B12 than non-vegans. Both B6 and B12 affects homocysteine levels.
A lot of research have found links between intake of various B12-rich animal products and health problems. Some of these reports can be found in our Are animal products healthy? section, inside the Human Evolution subforum. These reports usually never claim that the reason for the reported health problems are high B12 levels, and we know that having too low B12 levels is a bad idea, and potentially dangerous. But if these studies would have included detail information about the B12 levels of the participants, we can almost be 100% certain that the link between eg. cancer and animal products in many cases isn't only a link between cancer and animal products, but between cancer and increased B12 levels. Why? Because the one nutrient that sticks out when comparing people who consume animal products with people who don't, is B12: vegans have lower B12 levels, non-vegans have higher B12 levels.
Here are some of the cancer risks associated with intake of various animal products: Prostate cancer, breast cancer, esophageal cancers, vision loss, pancreatic cancer, type 1 diabetes, high blood pressure, arthritis, lung disease, colorectal cancer, bladder cancer, ovarian cancer, testicular cancer, uterine cancer, leukemia/stomach cancer, bone marrow cancer.
But when consuming meat, eggs or dairy products, chunks of meat or pieces of eggs aren't floating around in our lungs, ovaries or bladders. The animal products are broken down, and in terms of cancer risk, we need to look at what it is that animal products contain, in large amounts, that plants don't have (in such large amounts, or at all). Animal fats, animal proteins and B12 is essential here.
The solution is not to ignore B12, because too low B12 levels are also associated with lots of health problems. Is the solution to increase our B12 levels to the levels (5-15 mcg) meat eaters consume? Tricky question. But read on...
In my previous post, I quoted some new-ish findings from various sources:
• "Treatment with folic acid plus vitamin B12 was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway"
• "The researchers found that participants assigned to the B-vitamin group had a greater decrease in radionuclide GFR (and subsequently poorer kidney function) compared with the placebo group"
• "Participants randomized to receive B vitamins had a significantly greater number of cardiovascular and cerebrovascular events"
• "All-cause mortality was double in the B-vitamin group, compared to the placebo group"
• "Given the recent large-scale clinical trials showing no treatment benefit, and our trial demonstrating harm, it would be prudent to discourage the use of high-dose B vitamins as a homocysteine-lowering strategy outside the framework of properly conducted clinical research."
• "Together the data show that B-vitamin supplements, whether compared with placebos or standard care, have no effect on the incidence of heart attack, stroke or death associated with heart disease"
• "Prescription of these supplements cannot be justified, unless new evidence from large high quality trials alters our conclusions"
These studies were not made on vegans, and in spite of these conclusions, people with a minimal or no B12 intake could still benefit from B12 intake, and see real health improvements from taking supplements. Lots of environmental and life style issues causes B12 levels in water, humans, plants and soil to become artificially low, and we all need to deal with that.
Still: what is it that causes the link between high homocysteine and increased heart disease risk, if it's not the homocysteine itself?
Here's an interesting study:
Vitamin B6 and Heart Health
Quote:
High blood levels of homocysteine have been associated with cardiovascular disease. A new study in humans, published in the American Journal of Clinical Nutrition, found that higher blood levels of the active form of vitamin B6 (pyridoxal-5’-phosphate or PLP), may reduce cardiovascular disease risk other than by just reducing blood homocysteine. As levels of PLP increase, an inflammatory protein (CRP) and a marker for oxidative stress decline, both of which may indicate a reduced risk for cardiovascular disease.
More here: http://www.ajcn.org/cgi/content/abstract/91/2/337
More later, about three related topics:
1) If low homocysteine levels are good for heart health, and vegans have higher homocysteine levels than non-vegans, why do vegans have so healthy hearts?
2) In which cases have links between disease (as opposed to 'allergic reactions') and high B12 levels been documented?
3) If B6 and B12 is good for the heart, but high amounts of B12 area associated with various potential side effects (eg. certain types of cancer), isn't the ongoing B12/vegan discussion actually focusing on the benefits of eating vegan, since vegan food is rich in B6, and low in B12?
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Re: B12, homocysteine, & heart disease
Here are two new studies, when seen together, may explain why vegans have so healthy hearts in spite of having a lower B12 intake:
Serum concentrations of vitamin B12 and folate in British male omnivores, vegetarians and vegans: results from a cross-sectional analysis of the EPIC-Oxford cohort study.
Quote:
Background/Objectives:Vegans, and to a lesser extent vegetarians, have low average circulating concentrations of vitamin B12; however, the relation between factors such as age or time on these diets and vitamin B12 concentrations is not clear. The objectives of this study were to investigate differences in serum vitamin B12 and folate concentrations between omnivores, vegetarians and vegans and to ascertain whether vitamin B12 concentrations differed by age and time on the diet.Subjects/Methods:A cross-sectional analysis involving 689 men (226 omnivores, 231 vegetarians and 232 vegans) from the European Prospective Investigation into Cancer and Nutrition Oxford cohort.Results:Mean serum vitamin B12 was highest among omnivores (281, 95% CI: 270-292 pmol/l), intermediate among vegetarians (182, 95% CI: 175-189 pmol/l) and lowest among vegans (122, 95% CI: 117-127 pmol/l). In all, 52% of vegans, 7% of vegetarians and one omnivore were classified as vitamin B12 deficient (defined as serum vitamin B12 <118 pmol/l). There was no significant association between age or duration of adherence to a vegetarian or a vegan diet and serum vitamin B12. In contrast, folate concentrations were highest among vegans, intermediate among vegetarians and lowest among omnivores, but only two men (both omnivores) were categorized as folate deficient (defined as serum folate <6.3 nmol/l).Conclusion:Vegans have lower vitamin B12 concentrations, but higher folate concentrations, than vegetarians and omnivores. Half of the vegans were categorized as vitamin B12 deficient and would be expected to have a higher risk of developing clinical symptoms related to vitamin B12 deficiency.European Journal of Clinical Nutrition advance online publication, 21 July 2010; doi:10.1038/ejcn.2010.142.
Oral supplementation of folic acid for two months reduces total serum homocysteine levels in hyperhomocysteinemic Greek children.
Quote:
Background & Aim: Hyperhomocysteimemia is a cardiovascular risk factor even among children. Supplementation of oral folic acid may reduce homocysteine levels to normal. However, data is limited at this point for healthy children and adolescents.Methods: Five hundre and twenty four children participated in the study; Twenty six of them were found to be hyperho mocysteinemic(>95(th) percentile for age). Twenty of them received 5 mg of folic acid twice per week for two consecutive months while the other six received a diet rich in dietary folate.Results: Serum homocysteine levels were statistically significantly decreased from 13.1 (10-24.2 micromol/L ) to 7.7 (4.9- 15.2 micromol/L), p<0.001. Serum folate levels were significantly rose from 4.3 (3-20 ng/mL) to 16.8 (7-20 ng/mL), p<0.001. On the contrary, no important changes were observed in the above parameters in children to whom a diet rich in folic acid was recommended. Homocysteine levels were found to be positively associated with age (r=0.314, p<0.001), BMI (r=0.192, p<0.001), WC (r = 0.215, p<0.001), simple sugars (r= 0.182, p<0.001 ) and negatively associated with folic acid (r = -0.331, p<0.001), vitamin B12 (r = -0.214, p<0.001) and dietary folic acid (r= -0.228, p=0.003).Conclusions: Oral folic acid 5 mg twice per week may efficiently reduce serum homocysteine levels and increase serum folic acid levels in healthy children with increased homocysteine levels (>95(th) percentile for age). Hyperhomocysteinemia in childhood may be a predictive factor of cardiovascular disease. In addition, these results may offer more help to health practioners in order to establish more prospective studies to elucidate the relationship between homocysteine, folic acid and heart disease in children.
PMID: 20596265 [PubMed - in process]PMCID: PMC2895291Free PMC Article
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Re: B12, homocysteine, & heart disease
Another study:
Vitamin B-12 status is not associated with plasma homocysteine in parents and their preschool children: lacto-ovo, lacto, and ovo vegetarians and omnivores.
Quote:
OBJECTIVE: Vegetarians may be at risk of certain nutrient deficiencies, particularly vitamin B-12. Vitamin B-12 deficiency may increase plasma homocysteine concentration and thus may potentially increase the risk of cardiovascular disease in vegetarians. The purpose of this study was to assess and compare plasma homocysteine and vitamin B-12 status in vegetarian and omnivorous preschool children and their parents. In addition, the association between parents' and children's homocysteine and vitamin B-12 concentration was also examined. METHODS: Fifty-six omnivores (28 preschool children and one of their parents), 34 lacto-ovo vegetarians (16 parents and 18 children), 5 ovo vegetarians (2 parents and 3 children), 1 lacto vegetarian parent, and 2 vegan parents were enrolled in this study. The mean age of preschool children was 5.1 +/- 1.3 years and that of their parent was 35.4 +/- 4.2 years. Nutrient intakes were recorded using 3-day dietary records. Fasting venous blood samples were obtained to measure serum creatinine, high-sensitivity C-reactive protein, hematological parameters, plasma homocysteine, serum folate, and vitamin B-12 concentrations. RESULTS: There was no significant difference in dietary folate intake between vegetarian and omnivores within parent and child groups. The mean plasma homocysteine level of vegetarian parents and their children was in the physiological range, and they had slightly but not significantly higher plasma homocysteine levels than omnivores. Omnivorous parents and their children had significantly higher vitamin B-12 intake than vegetarian participants but similar serum vitamin B-12 concentrations. Plasma homocysteine concentration was significantly and negatively associated with only serum folate levels (beta = -0.15) and dietary vitamin B-12 intake (beta = -0.05) in the omnivorous parents after adjusting for age, gender, body mass index, and serum creatinine. CONCLUSION: Vegetarian parents and their preschool children had a lower vitamin B-12 intake than omnivorous parents and their preschool children but similar plasma vitamin B-12 and homocysteine concentrations. Plasma homocysteine was not associated with serum vitamin B-12 levels in the parent, child, or pooled group.
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Re: B12, homocysteine, & heart disease
Is a low blood level of vitamin B12 a cardiovascular and diabetes risk factor? A systematic review of cohort studies.
Quote:
PURPOSE: To assess the prior hypothesis that low blood vitamin B12, partly through hyperhomocysteinemia and partly through direct effects, increases the risk of cardiovascular diseases and diabetes. As background, we also extracted all-cause mortality from the studies that met our criteria. METHODS: A systematic review of prospective cohort studies identified through searching six electronic databases, screening of reference lists, and citation search. Included studies reported data on the association between vitamin B12 blood levels, or other appropriate surrogate biological markers e.g. holotranscobalamin or serum/urine methylmalonic acid, and fatal or non-fatal incident diabetes and cardiovascular events. RESULTS: Seven studies were included. Studies differed regarding the population studied, length of follow-up, study outcomes, and data analysis-a narrative synthesis approach was performed to examine the results. Most studies met few of the quality assessment criteria which were adapted from the Scottish Intercollegiate Guidelines Network (SIGN). Only one high-quality study reported that low B12 increased the risk of incident cerebral ischaemia (RR = 1.76; 95% CI = 1.16-2.68). After controlling for homocysteine, the association persisted although weakened (RR = 1.57; 95% CI = 1.02-2.43), suggesting that the effects of low B12 were only partly mediated by homocysteine. In two studies, higher B12 levels were associated with a greater risk of total mortality (RR = 1.00; 95% CI = 1.00-1.00 and HR = 1.15; 95% CI = 1.08-1.22, respectively) and combined fatal and non-fatal coronary events (RR = 1.00; 95% CI = 1.00-1.00). No association between study outcomes and vitamin B12 levels was found in four other studies. CONCLUSIONS: Surprisingly, there is only very limited evidence that vitamin B12 deficiency predisposes to the risk of mortality and morbidity from either cardiovascular diseases or diabetes in adults. Current data do not support vitamin B12 supplementation to reduce the risk of cardiovascular diseases or diabetes.
PMID: 20585951 [PubMed - as supplied by publisher]
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Re: B12, homocysteine, & heart disease
Serum homocysteine and folate concentrations are associated with prevalent age-related hearing loss.
Quote:
Abstract
Elevated total serum homocysteine (tHcy) concentrations associated with vitamin B-12 or folate deficiencies may adversely affect blood flow to the cochlea, leading to age-related hearing loss (presbycusis). However, only 2 small cross-sectional studies have assessed the link between folate, vitamin B-12, or tHcy and presbycusis. We aimed to determine both the cross-sectional and longitudinal association between serum concentrations of folate, vitamin B-12, or tHcy and risk of age-related hearing loss. The Blue Mountains Hearing Study is a population-based survey of age-related hearing loss (1997-1999 to 2002-2004). Presbycusis was measured in 2956 participants (aged >or=50 y) and was defined as the pure-tone average of frequencies 0.5, 1.0, 2.0, and 4.0 kHz >25 dB hearing level (HL). Serum concentrations of folate, vitamin B-12, and tHcy were determined from blood samples. Participants with elevated tHcy (>20 micromol/L) concentrations had a 64% increased likelihood of prevalent hearing loss (>25 dB HL) [multivariate-adjusted odds ratio (OR) 1.64; 95% CI, 1.06-2.53]. Low serum folate levels (<11 nmol/L) increased the odds of prevalent mild hearing loss (>25-40 dB HL), multivariate-adjusted [OR 1.37 (CI 1.04-1.81)]. Serum vitamin B-12, however, was not significantly associated with prevalent hearing loss. Serum folate, vitamin B-12, and tHcy concentrations were also not significantly associated with an increased risk of incident hearing loss. Serum concentrations of tHcy and folate were associated with age-related hearing loss cross-sectionally, but no temporal links were observed, which could be due to insufficient study power. Further, large prospective studies will be required in the future to assess these associations.
PMID: 20573942 [PubMed - indexed for MEDLINE]
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Re: B12, homocysteine, & heart disease
Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial.
Quote:
Abstract
CONTEXT: Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal. OBJECTIVE: To assess the effects of reducing homocysteine levels with folic acid and vitamin B(12) on vascular and nonvascular outcomes. DESIGN, SETTING, AND PATIENTS: Double-blind randomized controlled trial of 12,064 survivors of myocardial infarction in secondary care hospitals in the United Kingdom between 1998 and 2008. INTERVENTIONS: 2 mg folic acid plus 1 mg vitamin B(12) daily vs matching placebo. MAIN OUTCOME MEASURES: First major vascular event, defined as major coronary event (coronary death, myocardial infarction, or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization. RESULTS: Allocation to the study vitamins reduced homocysteine by a mean of 3.8 micromol/L (28%). During 6.7 years of follow-up, major vascular events occurred in 1537 of 6033 participants (25.5%) allocated folic acid plus vitamin B(12) vs 1493 of 6031 participants (24.8%) allocated placebo (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.97-1.12; P = .28). There were no apparent effects on major coronary events (vitamins, 1229 [20.4%], vs placebo, 1185 [19.6%]; RR, 1.05; 95% CI, 0.97-1.13), stroke (vitamins, 269 [4.5%], vs placebo, 265 [4.4%]; RR, 1.02; 95% CI, 0.86-1.21), or noncoronary revascularizations (vitamins, 178 [3.0%], vs placebo, 152 [2.5%]; RR, 1.18; 95% CI, 0.95-1.46). Nor were there significant differences in the numbers of deaths attributed to vascular causes (vitamins, 578 [9.6%], vs placebo, 559 [9.3%]) or nonvascular causes (vitamins, 405 [6.7%], vs placebo, 392 [6.5%]) or in the incidence of any cancer (vitamins, 678 [11.2%], vs placebo, 639 [10.6%]). CONCLUSION: Substantial long-term reductions in blood homocysteine levels with folic acid and vitamin B(12) supplementation did not have beneficial effects on vascular outcomes but were also not associated with adverse effects on cancer incidence. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN74348595.
PMID: 20571015 [PubMed - indexed for MEDLINE]
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Re: B12, homocysteine, & heart disease
Dietary folate and vitamin b6 and B12 intake in relation to mortality from cardiovascular diseases: Japan collaborative cohort study.
Quote:
Stroke. 2010 Jun;41(6):1285-9. Epub 2010 Apr 15.
Dietary folate and vitamin b6 and B12 intake in relation to mortality from cardiovascular diseases: Japan collaborative cohort study.
Cui R, Iso H, Date C, Kikuchi S, Tamakoshi A; Japan Collaborative Cohort Study Group.
Department of Social and Environmental Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita-shi, Osaka 565-0871 Japan.
Abstract
BACKGROUND AND PURPOSE: The association of dietary folate and B vitamin intakes with risk of cardiovascular disease is controversial, and the evidence in Asian populations is limited. METHODS: A total of 23 119 men and 35 611 women, age 40 to 79 years, completed a food frequency questionnaire in the Japan Collaborative Cohort Study. During the median 14-year follow-up, there were 986 deaths from stroke, 424 from coronary heart disease, and 2087 from cardiovascular disease. RESULTS: Dietary folate and vitamin B(6) intakes were inversely associated with mortality from heart failure for men and with mortality from stroke, coronary heart disease, and total cardiovascular disease for women. These inverse associations did not change materially after adjustment for cardiovascular risk factors. No association was found between vitamin B(12) intake and mortality risk. CONCLUSIONS: High dietary intakes of folate and vitamin B(6) were associated with reduced risk of mortality from stroke, coronary heart disease, and heart failure among Japanese.
PMID: 20395608 [PubMed - indexed for MEDLINE]
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Re: B12, homocysteine, & heart disease
Determinants of homocysteine levels in Ivorian rural population.
Quote:
Tiahou G, Dupuy AM, Jaussent I, Sees D, Cristol JP, Badiou S.
Laboratoire de Biochimie Médicale, Université Bouake, Bouake, Cote d'Ivoire.
Abstract
In the present study, homocysteine (Hcy) and vitamin B status were determined in healthy subjects living in two opposite regions of the Ivory Coast. Fifty-six subjects from a coastal region (Bodou) having a fish-based diet and 56 subjects from a mountainous area (Glanle) having a vegetarian diet were tested to sample Hcy, folate, vitamin B12, creatinine, and lipid levels, as well as inflammation and nutritional parameters. An increased prevalence of Hcy > or = 15 micromol/L was observed, reaching 60 % of all subjects. The Bodou group exhibited significantly higher Hcy levels than the Glanle group [20.1 (9.7 - 41.4) vs. 13.6 (5.5 - 48.7) micromol/L, p<0.0001], despite higher vitamin B12 levels [593 (163 - 1860) vs. 234 (83 - 585) pg/mL, p<0.0001]. Although folate levels were lower in subjects from Bodou compared to Glanle [3.2 (2.0 - 7.3) vs. 6.0 (1.9 - 18.2) ng/mL, p<0.0001], there was no significant relationship with Hcy levels in any groups. Interestingly, there were significantly higher creatinine levels in subjects from Bodou compared to Glanle and a significant positive relationship with Hcy levels was evident in each group. In conclusion, Hcy levels in an Ivorian population having a fish-based diet appeared significantly higher compared to subjects having a vegetarian diet. However, folate and vitamin B12 status did not emerge as the major determinants of this difference; a stronger relationship was observed with creatinine levels.
PMID: 20533218 [PubMed - indexed for MEDLINE]
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B12 Deficient Vegan Male With Higher Risk Of Heart Attack
A friend of mine, who is a 50 year old male vegan just got his B12 and homocsyeine test results. They show he is at an increased risk of heart attack. Luckily, this is easily resolved with B12 supplementation. This is the 3rd male friend who has tested low for B12. The others didn't test their homocysteine though.
I think maybe too many vegans neglect making sure they have adequate B12 and don't realise how serious the risks can be. While a vegan diet is generally healthy, we have to make sure we take care of the B12 issue. I know this is mentioned a lot, but better safe than sorry.
See full details at Vegan B12 Test Results.
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Re: B12 Deficient Vegan Male With Higher Risk Of Heart Attack
Some comments....
Quote:
The B12 test was conducted in order to measure B12 serum levels. This test can produce false negatives and false positives, so an MMA urine test was also ordered. The MMA urine test is a more accurate test for B12 levels, because MMA levels rise as B12 levels fall. So a high MMA reading would mean a B12 deficiency, even if the B12 serum levels tested as normal.
I'm sure MMA tests for now also is a good idea, but MMA tests are also said to be inaccurate.
One test showed that more than 50% of all (non-vegan, I assume) seniors had MMA levels outside the normal range. It's also been stated that even if the B12 levels are low, and the MMA levels are normal, the actual B12 levels are acceptable.
Quote:
High homocyseine levels can lead to blood clotting, heart attack and stroke, so it was considered essential that this was tested.
Have you seen any of the articles referred to in our homocysteine thread? There has been an increasing amount of articles over the years suggesting that high homocysteine levels are a symptom, and not a cause for high B12 levels. Not that high hCy levels are something to strive for at all, but treating the symptoms won't always help, or help at all. Please have a look at the thread and let me know what you think...
Quote:
Vitamin B12 level was 193 pg/ml, compared to a normal range of 240-1000. In Japan, the normal range starts at 400.
I think Japan have the highest low threshold for 'normal' of all countries - after they raised it from 200 pg/ml (145 pM) to 550 pg/ml (400 pM). If I'm not mistaken, a few countries (Australia??) even consider 100 pmol (circa 135 pg/ml) as the minimum level to be considered normal.
More discussion about normal ranges here: http://www.pernicious-anaemia-societ...topic.php?t=21
Quote:
So this result shows quite a deficiency,which isn't surprising given the fact that the person is vegan and hasn't supplemented with B12 for 3-5 years.
That would of course depend on a lot of factors, eg. lifestyle/how many B12 antagonistic elements he is exposed to, which country which has the most correct and useful reference for 'normal', if vegans need as much B12 as others etc.
Quote:
Homocysteine level was 14.9 umol/l. This is an extremely high reading and means that there is an increased risk of heart attack.
According to three of the four first result I got when I just googled normal range for homocysteine, it's in the normal range (under 15). But of course we don't want too high hCy levels.
Quote:
Without being tested for B12 deficiency, this person could possibly have died of a heart attack, due to high homocysteine levels.
Again, please have a look at our thread about homocysteine, B12 and heart disease. It's long, but the newest studies are found at the end of the thread. We don't want to take any risks, or to have too little B12, which is easy to get due to a lot of reasons, but we have to differentiate between facts and assumptions.
When a link between homocysteine and B12 levels were discovered, suggestions about reducing the max. accepted, 'normal' range were suggested, but at the moment, the trend seems to be to think that the link between B12 and Hcy isn't exactly what it appeared to be. I don't have any personal opinions about what the upper, accepted level for hCy should be.
There's some interesting info here as well, re. the use of the term B12 deficiency/deficient:
http://www.b12.com/uMMA.htm
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Re: B12, homocysteine, & heart disease
ETA; I just merged this threads with the homocysteine/heart disease, since they are about the same topic.
And for those who are interested, here 's the conversion table needed for converting pmol to pg/mL and vice versa:
pmol/l x 1.3553 = pg/mL
pg/mL x 0.7378 = pmol/L
Quote:
Vitamin B12 level was 193 pg/ml, compared to a normal range of 240-1000
I just looked at minimum B12 levels from lots of countries like US, UK etc, and converted all the values to pg/ml. I did not include Japan and Canada, because it's currently unclear to me what the actual minimum numbers are. More about that later.
Anyway, the average minimum I got, after the conversion, was 187 pg/mL. Only one country had a normal range starting as high as 240 - Finland, which has 180 pmol/L. I wonder which country is it that has a normal range of 240-1000 pg/ml?
Most of our members come from UK and US. UK has a value equal to the average for these 19 places: 187 pg/mL. Northern Ireland has 158 pg/mL. US has 180 pg/mL. With all due respect, I don't think it's really relevant, in a B12 context, to talk about that this guy's B12 levels as a deficiency case, where he could have died of a heart attack when his levels are within what lots of countries consider normal.
Maybe these values will be updated, and I'll make a table soon, in a separate thread, showing what's considered normal range for as many countries as possible.
This vegan's MMA results could of course change the outcome of this test - but since he, in spite of not having taken any supplements for 3-5 years, still has a B12 level within the range of what eg. UK considers normal, this sounds more like great news than bad news. :-)
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Re: B12, homocysteine, & heart disease
Sorry, if this is the wrong place to ask this question but what causes heart disease in non-vegans then? Does B12 deficiency contribute to non vegans disease or is it just in vegans?
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Re: B12, homocysteine, & heart disease
Quote:
Sorry, if this is the wrong place to ask this question but what causes heart disease in non-vegans then?
There are conflicting theories about that, but in general vegans should pay more attention to B12 than non-vegans (and non-vegans need to pay more attention to certain other nutrients more than vegans).
One thing to take into consideration is that while some reports say that increased B12 levels have no effect on heart disease for the average population, it could still have an effect for people with marginal B12 levels - but there's an increasing agreement, it seems, that the factors that cause heart disease also cause high homocysteine levels, which is why it may not help only to reduce the hcy levels.
Among things that can contribute to increased risk of various heart problems are high blood pressure, high cholesterol, high triglycerides, obesity/overweight, diabetes, smoking, lack of physical activity, age, (emotional) stress, heredity, birth control pills, alcohol, some medications, drug abuse, excessive alcohol or caffeine use, bacteria, viruses, parasites, unhealthy fat and other dietary reasons, too much salt and much more. And even if it would be confirmed once and for all that high homocysteine is a result of the many conditions that cause unhealthy hearts, the high homocysteine levels could possibly also influence the situation in a negative direction. When studies come to conflicting conclusions, there may be still something useful in all of them... Also, remember that even if a vegan is a vegan today, s/he may have been eating meat and unhealthy fats for the past 30 years, and these 30 years most likely have an affect on him/her health even if he quits all his bad habits.
I'm sorry if I have posted some of these links earlier, but here's some more interesting reading:
Vitamin and mineral supplements for cancer prevention: issues and evidence
Vitamins and minerals: ineffective in preventing cancer and cardiovascular disease
Plants, not Pills, for Vitamins and Minerals
I have to emphasize, again, that I'm not trying to convince anyone that they shall ignore their levels of B12, MMA or other significant factors, or that some of the studies I have quoted are correct while others are totally wrong. I think the only way to get a good overview of the available facts is too look at the big picture, and not to stare only one some of the facts that have been presented.
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Re: B12, homocysteine, & heart disease
I suppose the bottom line is it isn't good for anyone to be deficient in any vitamin I suppose. Severe iron deficiency can produce left ventricular dysfunction and overt heart failure for example. Then again too much iron can cause heart problems too. I like to keep an open mind with regard to all the medical evidence as one year they tell us one thing and the next they say the exact opposite.
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Re: B12, homocysteine, & heart disease
Here's a raw vegan doctor, Fred Bisci, which I've heard about before. He's now 80-81 years old, and is talking about exercise, LDL, HDL, homocysteine and more.
http://www.youtube.com/watch?v=k2tYXUyFAxs
More here.
Among many things, he mentions a topic that isn't discussed so often when homocysteine is discussed - urea, also mentioned here: http://forum.lowcarber.org/archive/index.php/t-54420
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Re: B12, homocysteine, & heart disease
Food sources of betaine
Quote:
Betaine is used to treat a condition called homocystinuria, in which the body's inability to break down certain proteins causes a buildup of those proteins in the blood. This buildup leads to problems such as fatigue, seizures, vision problems and blood clots. While betaine is available as a powder supplement, it can also be found in food. A doctor should be consulted before using betaine; other medications may be prescribed to take along with the betaine.
Quinoa
Uncooked Quinoa contains 630 mg of betaine in every 100 grams. Quinoa is a versatile grain that is easy to digest. It can be substituted for other grains in many recipes and is often included in soups and salads.
Spinach
Raw spinach contains 550 mg of betaine in every 100 grams. Spinach is used in a variety of recipes and can be used as a substitute for lettuce in salads. It can also be used in sandwiches, cooked in stir-fries or eaten alone.
Bran Cereals
Ready-to-eat bran cereals contain between 291 and 360 mg of betaine in every 100 grams. This is a very convenient source of betaine and also provides a good source of fiber.
Beets
Beets, whether canned or fresh, contain between 220 to 250 mg of betaine per 100 grams. Beets are a sweet root vegetable that can be cooked as a side dish or even pickled. They are often shredded and added to salads.
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Re: B12, homocysteine, & heart disease
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Re: B12, homocysteine, & heart disease
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Re: B12, homocysteine, & heart disease
Is hyperhomocysteinemia due to the oxidative depletion of folate rather than to insufficient dietary intake? (2001) PMID: 11592434
---
A critical evaluation of the relationship between serum vitamin B, folate and total homocysteine with cognitive impairment in the elderly. (2004) PMID: 15250847
Quote:
Serum total homocysteine is negatively correlated with neuropsychological tests scores. But the evidence does not support a correlation between serum vitamin B(12) or folate and cognitive impairment in people aged over 60 years. Hence, there is little evidence to justify treating cognitive impairment with vitamin B(12) or folate supplementation. This is consistent with the findings from recent systematic reviews of randomized double-blind trials, which have not found any evidence of potential benefit of vitamin supplementation. Further research is required in order to establish whether raised serum total homocysteine is a cause or consequence of disease.
Comment: As mentioned earlier, if this information is correct, it may not necessarily apply to all; eg. to people with very low B12 levels. Also - humans don't need B12 only for homocysteine reasons, meaning that even if increasing our B12 levels shouldn't cause any homocysteine related improvements, we may still need to improve B12 status for other reasons.
Homocysteine, folic acid and vitamin B12 levels in maternal and umbilical cord plasma and homocysteine levels in placenta in pregnant women with pre-eclampsia.
(PMID: 21040211, 2011)
Quote:
Maternal and fetal serum homocysteine levels were found to be significantly higher in severe pre-eclampsia group compared to mild pre-eclampsia and control groups suggesting that elevated serum levels of homocysteine might be associated with severity of pre-eclampsia. On the other hand it seems like elevated serum homocysteine levels were not associated with deficiency of folic acid and vitamin B12.
Vitamin B12 deficiency in African American and white octogenarians and centenarians in Georgia(2010) PMID: 20424799
Quote:
CONCLUSIONS: Centenarians and octogenarians are at high risk for vitamin B12 deficiency for many of the same reasons identified in other older adult populations. Given the numerous potential adverse consequences of poor vitamin B12 status, efforts are needed to ensure vitamin B12 adequacy in these older adults.
In logistic regression analysis, the probability of being vitamin B12-deficient was significantly increased by being a centenarian vs. octogenarian, by being white vs. African American, by increasing severity of atrophic gastritis, and by not taking oral B-vitamin supplements, but was not related to gender, living arrangements, or animal food intake.
Although higher intake of animal products usually is associated with higher B12 levels, this particular study suggests something else. I guess we'll see more studies in the future finding that higher intake of B12 (eg. in animal products) doesn't always represent a linear increase in serum B12 levels - for a couple of reasons. One is that B12 absorption rates don't follow B12 intake linearly, as discussed here: At what levels is B12 absorption best? This means that if someone consumes eg. 5 mcg B12, only circa 1.4 mcg may be absorbed, but if she consumes, say, 0.3 mcg B12, all of it may be absorbed.
The other thing is that studies like this usually ignore all the B12 antagonistic factors. At some point, these studies will hopefully be more valid than they are today, by including info about sugar consumption, alcohol and coffee intake etc.. Currently, most if these studies aren't necessarily valid not for humans as a species, but for humans living in a very B12 unfriendly environment. These factors could, at least to some degree, explain the outcome of the Georgia study.
Folate and cobalamin deficiencies and hyperhomocysteinemia in Bangladesh
(2005) (PMCID: PMC2204145, NIHMSID: NIHMS32637)
The prevalence of hyperhomocysteinemia was markedly greater among men than among women. Folate was lower, whereas cobalamin was higher among men than among women. Folate explained 15% and cobalamin explained 5% of the variation in homocysteine concentrations. For men, folate and cobalamin were positively correlated with urinary creatinine. Smoking and betelnut use were independent negative predictors of folate.
Quote:
Conclusions: Bangladeshi men have a high prevalence of hyperhomocysteinemia, which is more closely associated with folate than with cobalamin, although other factors, eg, smoking and betelnut use, may also contribute to its cause. The positive correlations between urinary creatinine and plasma folate and cobalamin were unanticipated and could suggest that, in marginal nutrition, these vitamins may be limiting for creatine biosynthesis.
This is one of the few studies which contain specific suggestions re. how important folate is (for homocysteine) compared with how important cobalamin (B12) is. 15% vs. 5% somehow suggests that folate is three times as important as cobalamin. But presence of B12 is also important for folate to do it's 'job'.
Vegans usually have healthy folate levels. Many non-vegans don't, which is why folate fortification of food is normal in some countries, meaning that they're all eating fortified food due to the low folate levels in a typical omnivorous diet. (I wonder if omnivores discussing B12 levels with vegans are aware that they may already be taking supplements through their food, without even asking for it?). Omnivores usually have higher B12 levels than vegans, which is why there's all this focus on B12 fortification/supplementation for vegans.
I wonder why eg. the governments who have decided to fortify eg. flour with folate don't work harder to make people eat more plant based food, since folate is easy to get enough of on a vegan diet. Having said that, I wouldn't be surprised if the minimum levels of folate will be increased in the future.
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Re: B12, homocysteine, & creatine
Our creatine levels influence our homocysteine levels. Creatine supplementation has caused increased homocysteine levels, so we don't want too high creatine levels. Too low creatine levels aren't good either, because dietary creatine intake also reduces the levels of homocysteine in the blood stream. Maybe high dietary intake of creatine (from meat and fish) to some degree can explain cases of hyperhomocysteina among non-vegans.
People who don't eat 'skeletal muscle sources' (meat and fish) rely on their body’s capacity to synthesize creatine from the amino acids arginine, glycine and methionine.
L-arginine is found in peanuts, walnuts, brazilnuts, coconuts, oat, wheat, legumes such as soybean and chickpea - and even chocolate. Glycine is found eg. in beans and some nuts/seeds (peanuts, sesame, safflower, cotton) - look here for more info: http://top200foodsources.com/Nutrients/Glycine/516/g.
Methionine can be found in fruits, vegetables, whole grains and fermented foods. Since excessive methionine intake, together with inadequate intake of B9/B6/B12 can increase the conversion of methionine to homocysteine, we don't want too much of it of course, and since methionine is found in animal products, and animal products also sometimes contain high B12 levels, the negative effect of the Hcy-increasing amino acids in these products may, at least to some extent, regulate by the higher B12 levels. This both suggests that people on a diet high in animal products also may need more B12 than vegans, but also that vegans need to make sure they eat proper food, including protein rich food containing arginine, glycine and methionine, since these amino acids contribute to better homocysteine levels by helping the body to synthesize creatine.
Some related studies:
The effect of L-arginine and creatine on vascular function and homocysteine metabolism
Quote:
The unexpected increase in homocysteine levels following creatine supplementation could have adverse effects and merits further study, since creatine is a commonly used dietary supplement.
Effects of creatine supplementation on homocysteine levels and lipid peroxidation in rats.
Quote:
Hyperhomocysteinaemia is an independent risk factor for CVD. Recent data show a relationship between homocysteine (Hcy) and free radical formation. Since creatine synthesis is responsible for most of the methyl group transfers that result in Hcy formation, creatine supplementation might inhibit Hcy production and reduce free radical formation. The present study investigated the effects of creatine supplementation on Hcy levels and lipid peroxidation biomarkers.
[...]
We conclude that creatine supplementation reduces plasma Hcy levels and lipid peroxidation biomarkers, suggesting a protective role against oxidative damage.
Oral Creatine Supplements Lower Plasma Homocysteine Concentrations in Humans
http://pilladvised.com/2010/07/creat...e-supplement/:
Quote:
Another study, from Boston University School of Medicine, found that 3 weeks of creatine supplementation raised blood levels of homocysteine by 10-20%. Homocysteine is an amino acid that is toxic to blood vessels. The authors of this study believed that the increase in homocysteine with creatine was due to impairment of kidney function.
Here's some info from a commercial site: http://www.creatinemonohydrate.net/homocysteinemia.html
More later.
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Re: B12, homocysteine, & heart disease
Choline is often grouped with the B-vitamins, and can be found in eg. cauliflower, spinach, wheat germ, quinoa, amaranth, soy lecithin, navy/kidney beans, tofu, almonds and peanuts (peanut butter) grapefruit, rice and more. As with everything else, we don't want too much or too little of it.
Vegans who eat too much junk food will eat less real food, and may therefore have reduced choline levels. This will affect their homocysteine levels in a negative direction, as discussed in eg. this study:
Choline, homocysteine, and pregnancy (2005)
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Re: B12, homocysteine, & heart disease
Physiologic changes in homocysteine metabolism in pregnancy: A longitudinal study in Spain (March 2011):
Quote:
CONCLUSION: Although tHcy seems to be physiologically low in this Spanish population and unrelated to folate and B12 nutritional status, C677T MTHFR genotype, and some pregnancy complications, we support the statement that appropriate folate concentration may be important throughout pregnancy to prevent abnormalities associated with altered status (e.g., neural tube defects). According to our study, supplementation with folic acid seems to achieve this purpose because diet alone may be insufficient. In addition, a poor vitamin B12 status, as measured by plasma levels, may indicate that supplementation of both vitamins is needed.
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Re: B12, homocysteine, & heart disease
Homocysteine levels ["HH"] and the metabolic syndrome ["MS") in a Mediterranean population: A case-control study
Quote:
Our results do not indicate a link between MS or its individual components with HH, and diabetes was the only relevant contribution. Cardiovascular disease risk due to MS and HH seems to share no common mechanisms.
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Re: B12, homocysteine, & heart disease
Intake of folate, vitamin B6 and vitamin B12 and the risk of CHD: the Japan Public Health Center-Based Prospective Study Cohort (Feb 2008)
Quote:
RESULTS: After 468,472 person-years of follow-up, 251 coronary heart disease incidents were documented. Coronary heart disease and definite myocardial infarction were inversely associated with dietary intake of folate, VB(6) and VB(12) after adjustment for age and sex, but the associations were attenuated after further adjustment for smoking, dietary and other cardiovascular risk factors. However, among non-multivitamin supplement users, multivariable hazard ratios (95% confidence intervals) in the highest vs. lowest quintiles of VB(6) intake were 0.60 (0.37-0.97) for total coronary heart disease and 0.52 (0.29-0.91) for definite myocardial infarction, and the inverse associations with VB(12) were marginally significant. The combination of below-median intake of three vitamins or of only B(6) conferred a twice excess risk of total coronary heart disease.
CONCLUSIONS: Dietary intake of VB(6) was associated with a reduced risk of coronary heart disease among middle-aged non-multivitamin supplement users. Dietary folate and VB(12) were also suggested to be protective factors for coronary heart disease.
PMID: 18460491
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Re: B12, homocysteine, & heart disease
This study from January this year, suggests that hyperhomocysteinemia decreases bone blood flow, and contains an interesting element. The homocysteine levels were altered by adding Hcy (0.67 g/L) in the test objects' drinking water for 8 weeks - in other words, not by giving them B12. And yes - for some silly reason this was not performed on humans....
Body weight, Hcy, vitamin B12, and folate were measured. And this is the part that could be more significant that it may seem at first: "The results indicated that Hcy levels were significantly higher in the Hcy-treated group than in control rats, whereas vitamin B12 levels were lower in the Hcy-treated group compared with control rats."
Doesn't this somehow suggest that increased homocysteine lowers the B12 levels? If this is correct, this would affect how many of these researchers would interpret findings about B12 and homocysteine in the future. It could suggest that the link that some people still seem to insist as the most valid 'fact' about this, namely that studies finding that people with high Hcy levels often have low B12 levels also could be a result of something in their bodies/lifestyle/diet that would increase the Hcy levels, which again would lower the B12 levels.
This, of course, wouldn't alter the fact that B12 levels also may increase Hcy levels.
PMID: 21339911
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Re: B12, homocysteine, & heart disease
Here's another new study, again questioning the theory that "normal B12 levels = normal homocysteine levels" or "low B12 levels = elevated Hcy levels:
Serum vitamin B12 concentrations within reference values do not exclude functional vitamin B12 deficiency in PKU patients of various ages (Jan 2011)
Quote:
RESULTS: Eight patients had vitamin B(12) concentrations below normal. Out of these eight patients, two had elevated MMA and/or Hcy concentrations. Ten other patients with normal vitamin B(12) concentrations had elevated concentrations of MMA and/or Hcy.
CONCLUSIONS: A vitamin B(12) concentration within the reference range does not automatically imply a sufficient vitamin B(12) status. We recommend measuring serum MMA, or alternatively plasma Hcy, yearly in all PKU patients to diagnose functional vitamin B(12) deficiency.
PMID: 21030277
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Re: B12, homocysteine, & heart disease
Effect of Folic Acid and B-Vitamins on Risk of Cardiovascular Events and Total Mortality among Women at High Risk for Cardiovascular Disease: A Randomized Trial (May 2009)
Quote:
CONCLUSION
Over the longest follow-up recorded thus far, a combination of folic acid/vitamin B6/vitamin B12 did not reduce a combined endpoint of total cardiovascular events among high-risk women despite significant homocysteine lowering.
(PMCID: PMC2684623)
So - this study suggests that even heavy supplementation didn't help these people much in terms of "a combined endpoint of total cardiovascular events"- but the supplementation did lower the homocysteine levels significantly. The result may of course not be transferable to people with very low B12 levels.
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Re: B12, homocysteine, & heart disease
The homocysteine hypothesis: Still relevant to the prevention and treatment of cardiovascular disease? (2010)
Quote:
Although evidence suggests that the homocysteine hypothesis is still relevant as a predictor of cardiovascular risk, we cannot conclude that measuring the homocysteine level is useful in guiding treatment. Furthermore, studies of primary and secondary prevention show no evidence that taking folic acid or other B vitamins lowers the risk of cardiovascular events.
Key points
Factors that can cause the plasma homocysteine concentration to be high include deficiencies of vitamin B6, vitamin B12, and folic acid; renal insufficiency; and genetic variants in enzymes responsible for homocysteine metabolism.
Higher plasma homocysteine levels are associated with a higher risk of cardiovascular, cerebrovascular, and peripheral arterial disease.
Supplementation of B vitamins and folic acid can lower plasma homocysteine levels.
Randomized controlled trials of supplementation to prevent cardiovascular events and other adverse outcomes have had mostly negative results. However, most patients in these trials had normal baseline plasma homocysteine levels.
Needed are randomized trials to see if supplementation improves outcomes in patients with high homocysteine levels.
doi: 10.3949/ccjm.77a.10036
Cleveland Clinic Journal of Medicine December 2010 vol. 77 12 911-918
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Re: B12, homocysteine, & heart disease
Hi there Korn, just a question. A few days ago I was reading a post of yours with a study showing that people taking B12 supplements actually had increased risks of heart deasease. I can't find it anymore. Do you remember where it could have been posted? thank you
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Re: B12, homocysteine, & heart disease
Hi,
maybe you are thinking of some of these findings:
Treatment with folic acid plus vitamin B12 was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods.
Among the results, the researchers found that participants assigned to the B-vitamin group had a greater decrease in radionuclide GFR (and subsequently poorer kidney function) compared with the placebo group.
Also, participants randomized to receive B vitamins had a significantly greater number of cardiovascular and cerebrovascular events, with the 36-month risk of a composite outcome, including heart attack, stroke, revascularization, and all-cause mortality that was double in the B-vitamin group, compared to the placebo group.
Higher vitamin B12 levels were associated with greater mortality, but it is unclear whether vitamin B12 is a marker or a surrogate marker or even a substance that directly causes death. Further investigation is needed to clarify.
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Re: B12, homocysteine, & heart disease
Homocysteine has been discussed for many decades. The first known case involving disease associated with high homocysteine levels is from 1933. For those who are interested, here's the article which gave the discussion about the link between B vitamins, homocysteine and heart disease a major boost back in 1969:
Vascular Pathology of Homocysteinemia: Implications for the Pathogenesis of Arteriosclerosis
Here's an article from Time, 1997, which comments how the focus on homocysteine has increased:
Beyond Cholesterol
A few years later (2003), this article, also based around the same, Norwegian group of researchers, shows that when looking at the link between homocysteine/heart disease factors like smoking, exercise, BMI, coffee consumption, certain types of medication, diet, some members of the vitamin B family etc had to be taken into consideration. The article stated that further studies will show if the treatments that reduce homocysteine will improve the situation for patients with heart disease. (Some of these studies have been quoted earlier in this thread.)
The Kilmer McCully Heart Protection Diet, (McCully launched the homocysteine/heart disease theory) is discussed here:
"Another area McCully would modify is the FDA recommendation to consume two or three servings of meat, poultry, fish, dry beans, eggs or nuts a day. Putting beans and nuts in this group is problematic, he says, because it suggests that plant and animal proteins are interchangeable: "The truth is that plant protein, lacking in the essential amino acids, is quite different from animal protein, which contains plentiful essential amino acids. Therefore, depending only on plants for protein is not a good idea because the protein is inferior." McCully is now around 80, and I don't know when this interview was made, but it seems that it must have been quite a while ago. Or - it may may be quite a while ago since "the father" of the homocysteine theory was updating his info about proteins from plants...
From the same article/interview:
"He suggests a daily intake of two or three servings of protein from fish, meats, poultry, eggs or cheese. Yes we have said eggs, which along with whole milk and fresh butter represent a major departure from the failed low cholesterol / low fat diet of the past. Fallon and Enig's "The Oiling of America" should be required reading for every primary care physician in this country. A return to the farm diet of rural American youth with lard, butter and whole milk is now very much back in vogue."
In this interview, McCully states that "As we understand it now, perhaps the single most important factor is a dietary imbalance between too much methionine from dietary protein and too little of the three B vitamins which are needed to break down or get rid of excess levels of homocysteine; namely vitamin B-6, vitamin B-12 and folic acid." This could possibly suggest (as mentioned in another post) that people on a diet very high in protein/methionine have an increased heart disease/homocysteine risk compared with others.
McCully says in the same interview: "The clearest evidence in humans is that homocysteine is involved in the increased risk of neural tube defects in children that are born to mothers who are deficient in folic acid. These folate-deficient mothers tend to have a higher level of homocysteine in their blood, and the amniotic fluid itself has a higher level of homocysteine than in those in mothers who have a normal folate intake."
He also says "In these synthetic studies I have discovered a compound that is formed between homocysteine thiolactone and vitamin A acid (retinoic acid), a substance called thioretinamide. This substance is anticarcinogenic and antineoplastic in animal models. Furthermore, thioretinamide forms an additional complex with vitamin B-12, a substance known as thioretinaco. This compound is also anticarcinogenic and antineoplastic in animal models. We believe, as I published in my 1994 monograph, that the activation of this thioretinaco occurs through ozone oxidation of the sulfur atoms of homocysteine. This oxidation reaction may cause it to be a highly effective anti-cancer compound." Since high B12 levels are associated both associated with increased mortality in elders and certain cancer types in general, and since increased intake of animal products in general is associated with increased risk of the most common cancer types and other severe health problems, it seems that it would be better to achieve good levels of the thioretinaco substance by combining vitamin A acid with B12 from non-animal sources.
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Re: B12, homocysteine, & heart disease
Low vitamin B6 but not homocyst(e)ine is associated with increased risk of stroke and transient ischemic attack in the era of folic acid grain fortification. PMID: 12738890
Many other studies have found links between homocysteine and heart disease, but getting enough B6 (and B9/B12) is a good idea anyway!
Here are some B6 sources:
Ready-to-eat cereal, 100% fortified, ¾ c 2.00 mg 100 % of RDA
Potato, Baked, flesh and skin, 1 medium 0.70 mg 35 % of RDA
Banana, raw, 1 medium 0.68 mg 34 % of RDA
Garbanzo beans, canned, ½ c 0.57 mg 30 % of RDA
Ready-to-eat cereal, 25% fortified, ¾ c 0.50 mg 25 % of RDA
Oatmeal, instant, fortified, 1 packet 0.42 mg 20 % of RDA
Sunflower seeds, kernels, dry roasted, 1 oz 0.23 mg 10 % of RDA
Spinach, frozen, cooked, ½ c 0.14 mg 8 % of RDA
Tomato juice, canned, 6 oz 0.20 mcg 10 % of RDA
Avocado, raw, sliced, ½ cup 0.20 mg 10 % of RDA
Wheat bran, crude or unprocessed, ¼ c 0.18 mg 10 % of RDA
Peanut butter, smooth, 2 Tbs. 0.15 mg 8 % of RDA
Walnuts, English/Persian, 1 oz 0.15mg 8 % of RDA
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Re: B12, homocysteine, & heart disease
The status of plasma homocysteine and related B-vitamins in healthy young vegetarians and nonvegetarians. PMID: 12638029
Quote:
RESULTS: There was no significant difference in vitamin B-6 intake between the two groups, although the vegetarian group had a significantly lower vitamin B-12 intake than the nonvegetarian group. Vegetarian subjects had significantly lower mean plasma PLP and vitamin B-12 concentrations than did nonvegetarian subjects (p < 0.05); however, a significantly higher mean plasma folate concentration was found in the vegetarian group. Vegetarian subjects had a significantly higher mean plasma homocysteine concentration than nonvegetarian subjects (13.2 +/- 7.9 vs. 9.8 +/- 2.2 micromol/L). Negative correlations were seen between plasma homocysteine and vitamin B-12 concentrations in the vegetarian (p = 0.004), nonvegetarian (p = 0.026), and pooled (p < 0.001) groups. From best subsets regression analyses, the plasma homocysteine concentration could be significantly predicted by total protein intake (p = 0.027) and plasma vitamin B-12 concentration (p = 0.005) in the pooled group. When the intake of protein is not considered, vitamin B-12 concentration is still a strong predictor of plasma homocysteine concentration (p = 0.012).
CONCLUSIONS: Vitamin B-12 intake and mean plasma vitamin B-12 concentration were lower for vegetarian subjects than for nonvegetarian subjects, leading to an increase in plasma homocysteine concentration. Vitamin B-6 and folate had little effect on plasma homocysteine concentration when individuals had adequate vitamin B-6 and folate status.
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Re: B12, homocysteine, & heart disease
Homocysteine, Folic Acid and the Heart: an Association Unravels
by Alice Park, Feb. 22, 2012
Quote:
We may have the final word on homocysteine: higher blood levels of the amino acid don’t raise people’s risk of heart disease after all.Several decades ago, studies of children born with an unusual genetic defect, which led them to make excessive amounts of homocysteine, found that they also suffered from higher rates of heart disease. That led researchers to wonder whether the amino acid, which is critical to many proteins, was an independent risk factor for heart problems.Because people with high levels of homocysteine also tend to have low levels of B vitamins, doctors speculated that giving them supplements of the B vitamin folic acid, which helps break down homocysteine, would protect them from heart attacks. But research failed to bear out the theory: in a seven-year study of 12,064 heart-attack survivors, published in 2010, participants who took daily supplements of folic acid and vitamin B12 had 28% lower levels of homocysteine in the blood, but no reduction in heart events or stroke, compared with people taking placebo.Other studies investigating the connection between homocysteine and heart disease were inconclusive; some showed that higher levels of the amino acid were linked to an increased risk of problems, while others failed to show a strong connection.
MORE: Folic Acid, B12 Don’t Lower Heart Disease Risks
In the latest study, led by Robert Clarke, of the University of Oxford Clinical Trials Service Unit, researchers took advantage of genetic studies to clarify the relationship. Clarke and his team studied 116,000 patients, some of whom had heart problems and all of whom had genetic analysis done for mutations in a gene involved in homocysteine production.The genetic aberration led to a 20% increase in the participants’ blood homocysteine levels, compared with those without the genetic change, but they were not at any increased risk of having heart disease. “These results settle the homocysteine question fairly reliably,” says Clarke, whose study was published in PLoS Medicine. “These people have a lifelong increase of 20% in their homocysteine levels, but we convincingly showed there is no association between this genetic variant and cardiovascular disease risk. We think this closes the door on that chapter.”Due to the lack of strong evidence favoring a connection, the American Heart Association (AHA) does not consider homocysteine a risk factor for heart disease, nor does it discuss folate as way to protect the heart. “There is no evidence to recommend [folic] acid supplementation for heart disease,” says Dr. Donna Arnett, president-elect of the AHA and chair of the department of epidemiology at University of Alabama Birmingham. “This study closes the door on that.”Subgroups of patients, however, may still benefit from folate for heart. (And, of course, pregnant moms should take it to lower the risk of neural tube defects.) Arnett says that the elderly tend to lose folate as they age, and supplementing their deficiencies may lower their risk of heart disease as well, but there are no studies confirming this theory yet.
MORE: Low Vitamin B12 Linked to Smaller Brains and Cognitive Decline
In the meantime, the results serve as a reminder that supplements aren’t always effective at preventing disease, and as appealing as they might seem, their effect isn’t often supported by solid scientific evidence.
Read more: http://healthland.time.com/2012/02/2...#ixzz1nC0HbNwZ
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Re: B12, homocysteine, & heart disease
Quote:
Korn
Quote:
"Elevated homocysteine levels are easily reduced with the intake of certain nutrients involved in methylation. Such nutrients include folic acid with its cofactors, vitamins B6 and B12, plus what is proving to be the most efficient and cost-effective methyl donor of all, Trimethylglycine (TMG).
**TMG (also known as anhydrous betaine) is a naturally occurring phytonutrient found in a variety of plants and animals, with highest concentrations in beets, leafy green vegetables, and legumes. Since it can be difficult to eat enough of these foods to provide the body with sufficient methyl groups, supplementation may be necessary. Studies have demonstrated that TMG, folic acid, and B12 can reduce elevated levels of homocysteine to normal. The best methyl donor is TMG, because it has 3 methyl groups.
I eat a lot of beets, broccoli, and spinach, all known to contain homocystine lowering betaine (TMG). But I don't eat the green leaves of the broccoli, just the broccoli itself – what about you guys? Do you use the leaves?
We humans have the enzymes for the biosynthesis of Trimethylglycine (TMG) from Choline. Choline is found in fruits, vegetables, etc..
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Re: B12, homocysteine, & heart disease
Treatment With B Vitamins and Incidence of Cancer in Patients With Previous Stroke or Transient Ischemic Attack: Results of a Randomized Placebo-Controlled Trial. [PMID: 22474057] [April 2012]
An excerpt:
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Daily administration of folic acid, vitamin B(6), and vitamin B(12) to 8164 patients with recent stroke or transient ischemic attack for a median of 3.4 years had no significant effect, compared with placebo, on cancer incidence or mortality. However, a post hoc subgroup analysis raises the hypothesis that folic acid treatment may increase the incidence of cancer among diabetics and reduce the incidence of cancer among nondiabetics with a history of stroke or transient ischemic attack.
That's yet another reason to get B9 from food and not from supplements, isn't it?
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Re: B12, homocysteine, & heart disease
This article somehow questions the valiue of looking at homocysteine levels as the only marker for B12 status - at least among patients of vascular disease:
Lowering homocysteine and modifying nutritional status with folic acid and vitamin B(12) in Indian patients of vascular disease.
Quote:
Hyperhomocysteinemia is more commonly associated with vascular disease in Indians than in the western populations. It is caused by genetic polymorphisms or dietary deficiencies of the B vitamins. We attempted to identify the association of hyperhomocysteinemia with vitamin B(12) and folate in Indian patients of vascular disease. Homocysteine, vitamin B(12) and folate levels were estimated in 100 controls and 100 patients of vascular disease. Homocysteine estimation was repeated in 73 patients on different vitamin supplements for 6 months. Homocysteine exhibited a significant negative correlation with B(12) only in cerebrovascular disease and peripheral vascular diseasepatients, and with folate in coronary artery disease and cerebrovascular disease patients as well as controls. Single daily dose of folate was as effective as a combination of folate and cobalamin in reducing plasma homocysteine concentrations. Low levels of B(12) contribute to the higher incidence of cerebrovascular disease and peripheral vascular disease, and low folate levels account for higher prevalence of hyperhomocysteinemia in coronary artery disease and cerebrovascular disease. Moreover, irrespective of the cause of hyperhomocysteinemia, folate is known to ameliorate it. Hence, large-scale corrective measures like food fortification or dietary supplementation with folate might benefit the Indian population and reduce the incidence and morbidity of vascular disease.
"Single daily dose of folate was as effective as a combination of folate and cobalamin in reducing plasma homocysteine concentrations", could, if seen isolated from the other information in tha text, suggest that taking B12 in order to improve homocysteine levels and ther by reduce the risk of heart disease doesn't make sense... but here's the important part: "Low levels of B(12) contribute to the higher incidence of cerebrovascular disease and peripheral vascular disease [...]".
In other words: even if B12 according to this particular study doesn't help in order to reduce homocysteine levels, B12 is still important to reduce cerebrovascular disease and peripheral vascular disease.
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Re: B12, homocysteine, & heart disease
New research finds that vegetarians are 32 percent less likely to die or need hospital treatment as a result of heart disease.
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New research from University of Oxford may provide some clues. A study of 44,500 people in England and Scotland revealed that vegetarians were 32 percent less likely to die or to need hospital treatment as a result of heart disease.
The scientists looked at data from 15,100 vegetarians and 29,400 people who ate meat and fish. During the course of the 11-year study, 169 participants died from heart disease and 1,066 required hospital treatment —and those individuals were more likely to have been meat and fish eaters than vegetarians.
Differences in cholesterol levels, blood pressure and body weight are thought to be behind the numbers.
“Most of the difference in risk is probably caused by effects on cholesterol and blood pressure,” said Dr. Francesca Crowe, lead author of the study at the Cancer Epidemiology Unit, University of Oxford. “Vegetarians probably have a lower intake of saturated fat, so it makes senses there is a lower risk of heart disease."
The Oxford team calculated the risk reduction at 32 percent after accounting for other factors such as age, smoking, alcohol intake, physical activity, educational level and socioeconomic background. Crowe said, "The main message is that diet is an important determinant of heart health.”
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Re: B12, homocysteine, & heart disease
Link: Cardiovascular disease mortality and cancer incidence in vegetarians: a meta-analysis and systematic review. [PMID 22677895]
Quote:
Conclusions: Our results suggest that vegetarians have a significantly lower ischemic heart disease mortality (29%) and overall cancerincidence (18%) than nonvegetarians.