scholarly journals Homocysteine-lowering vitamins do not lower plasmaS-adenosylhomocysteine in older people with elevated homocysteine concentrations

2010 ◽  
Vol 103 (11) ◽  
pp. 1629-1634 ◽  
Author(s):  
Timothy J. Green ◽  
C. Murray Skeaff ◽  
Jennifer A. McMahon ◽  
Bernard J. Venn ◽  
Sheila M. Williams ◽  
...  

Elevated plasma total homocysteine (tHcy) is a risk factor for vascular disease but lowering tHcy with B-vitamins, including folate, has generally not reduced vascular events in secondary prevention trials. Elevated plasmaS-adenosylhomocysteine (AdoHcy) concentration may be a more sensitive indicator of vascular disease than plasma tHcy. However, unlike tHcy, plasma AdoHcy did not correlate with folate concentration in one study indicating that folate supplementation may not lower AdoHcy. Our aim was to determine whether providing B-vitamin supplements to healthy older people with elevated tHcy (>13 μmol/l) affects plasma AdoHcy andS-adenosylmethionine (AdoMet) concentrations. Healthy older participants (n276; ≥ 65 years) were randomised to receive a daily supplement containing folate (1 mg), vitamin B12(500 μg) and vitamin B6(10 mg), or placebo, for 2 years. Of these participants, we selected the first fifty participants in each treatment group and measured plasma AdoHcy and AdoMet. Plasma tHcy was 4·4 (95 % CI 3·2, 5·6;P < 0·001) μmol/l lower at 2 years in the vitamins group compared with the placebo group. At 2 years, there were no significant differences in plasma AdoMet (+4 % (95 % CI − 2, 11);P = 0·19), AdoHcy ( − 1 % (95 % CI − 10, 8);P = 0·61) or the AdoMet:AdoHcy ratio (0·22 (95 % CI − 0·04, 0·49);P = 0·10) between the two groups. In conclusion, B-vitamin supplementation of older people lowered plasma tHcy but had no effect on plasma AdoMet or AdoHcy concentration. If elevated plasma AdoHcy is detrimental, this may explain why B-vitamins have generally failed to reduce vascular events in clinical trials.

2008 ◽  
Vol 67 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Robert Clarke

Elevated plasma homocysteine (Hcy) concentrations have been implicated with risk of cognitive impairment and dementia, but it is unclear whether low vitamin B12 or folate status is responsible for cognitive decline. Most studies reporting associations between cognitive function and Hcy or B-vitamins have used a cross-sectional or case–control design and have been unable to exclude the possibility that such associations are a result of the disease rather than being causal. The Hcy hypothesis of dementia has attracted considerable interest, as Hcy can be easily lowered by folic acid and vitamin B12, raising the prospect that B-vitamin supplementation could lower the risk of dementia. While some trials assessing effects on cognitive function have used folic acid alone, vitamin B12 alone or a combination, few trials have included a sufficient number of participants to provide reliable evidence. An individual-patient-data meta-analysis of all randomised trials of the effects on cognitive function and vascular risk of lowering Hcy with B-vitamins will maximise the power to assess the epidemiologically-predicted differences in risk. Among the twelve large randomised Hcy-lowering trials for prevention of vascular disease, data should be available on about 30 000 participants with cognitive function. The principal investigators of such trials have agreed to combine individual-participant data from their trials after their separate publication.


2000 ◽  
Vol 59 (2) ◽  
pp. 221-237 ◽  
Author(s):  
Michelle C. McKinley

Numerous case–control and prospective studies have identified elevated plasma homocysteine as a strong independent risk factor for cerebovascular, cardiovascular and peripheral vascular disease. Homocysteine is formed as a result of the breakdown of the dietary amino acid methionine. Once formed, homocysteine is either remethylated to methionine, or undergoes a trans-sulfuration reaction to form cysteine. The re-methylation of homocysteine to methionine is dependent on three B-vitamins, i.e. riboflavin, vitamin B12and folate. The second pathway of homocysteine metabolism is the trans-sulfuration pathway which requires both vitamin B6and riboflavin for its activity. Thus, up to four B-vitamins are required for intracellular homocysteine metabolism. Many studies have noted strong inverse relationships between homocysteine levels and the status of both vitamin B12and folate. However, the relationship between vitamin B6status and homocysteine is still uncertain. Similarly, numerous intervention studies have demonstrated effective lowering of homocysteine levels as a result of folate and vitamin B12supplementation, while the homocysteine-lowering ability of vitamin B6is unclear. Even though riboflavin plays a crucial role in both the trans-sulfuration and remethylation pathways of homocysteine metabolism, the relationship between riboflavin status and homocysteine levels has not been investigated. The exact mechanism that explains the vascular toxicity of elevated homocysteine levels is unknown at present, studies indicate that it is both atherogenic and thrombogenic. To date, no randomized clinical trial has demonstrated that lowering of homocysteine levels is beneficial in terms of reducing the prevalence of vascular disease. It is probable, however, that optimal B-vitamin status is important in the prevention of vascular disease.


1962 ◽  
Vol 42 (2) ◽  
pp. 183-190 ◽  
Author(s):  
B. D. Owen ◽  
A. Reddon ◽  
F. Whiting

Ninety-two sows and two hundred and sixteen pigs were employed in four gestation-lactation and three growing-finishing experiments to determine the adequacy of barley grown on the Grey Wooded soils of the Peace River region in northwestern Canada, as a source of riboflavin, pantothenic and nicotinic acid in swine rations. Vitamin B12 was assessed as a dietary essential in the all-plant rations. In the gestation-lactation experiments sow gains during gestation were greater in the B-vitamin supplemented lot and a trend toward heavier weaning weights of pigs was evident. Vitamin supplementation increased the level of vitamin B12 in sow’s milk collected 1 week post-partum and of both riboflavin and pantothenic acid collected 1 week and 6 weeks post-partum. Nicotinic acid content of sows’ milk was unaffected by supplementation. There was a highly significant decrease in riboflavin level in both control and supplemented lots between 1 and 6 weeks following parturition. The decrease was greatest in the unsupplemented lot.B-vitamin supplementation did not affect growing period gains or pig carcass quality in the growing-finishing experiments. However, certain significant growth responses were noted in the finishing period.The data indicate that the basal rations employed contained adequate riboflavin, pantothenic and nicotinic acid to support normal gestation, lactation and growth in Yorkshire swine.


2005 ◽  
Vol 85 (3) ◽  
pp. 389-399 ◽  
Author(s):  
D. E. Santschi ◽  
J. Chiquette ◽  
R. Berthiaume ◽  
R. Martineau ◽  
J. J. Matte ◽  
...  

Two studies were undertaken to verify the effect of the forage to concentrate ratio of the diet on B-vitamin concentrations in ruminal contents. In Study 1, eight primiparous and eight multiparous cows were used in a cross-over design, and concentrations of biotin, folates and vitamin B12 were determined in ruminal fluid and plasma of cows fed a high-forage (HF; 58:42 forage to concentrate ratio; DM basis) or a low-forage (LF; 37:63 forage to concentrate ratio; DM basis) diet. In Study 2, six ruminally cannulated lactating cows were used in a cross-over design to evaluate the effects of forage to concentrate ratio (HF = 60:40; LF = 40:60; DM basis) on concentrations of seven B-vitamins in the particle-free fluid and in both liquid- and solid-associated bacteria. Results showed that B-vitamins were present mainly in the bacterial fractions of the ruminal content, while only limited amounts were found in the surrounding fluid. A change in the forage to concentrate ratio had a greater effect on vitamin concentration in the bacteria associated with the solid fraction than in those present in the liquid portion of the rumen. The most noticeable effects of a low forage diet were an increase in riboflavin, but a decrease in true vitamin B12 concentrations in solid-associated bacteria as well as a decrease in biotin concentration in particle-free fluid. In conclusion, it appears that ruminal B-vitamin concentration is altered by changes in the forage to concentrate ratio, which suggests that the supply of vitamins to dairy cows is influenced by diet composition. Key words: B-vitamins, dairy cow, ruminal fractions, forage to concentrate ratio


2017 ◽  
Vol 117 (1) ◽  
pp. 124-133 ◽  
Author(s):  
I. Iglesia ◽  
I. Huybrechts ◽  
M. González-Gross ◽  
T. Mouratidou ◽  
J. Santabárbara ◽  
...  

AbstractThis study aimed to examine the association between vitamin B6, folate and vitamin B12biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43 % males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) andn-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found withn-6:n-3 ratio,trans-fatty acids and oleic:stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15·85 µmol/l of EPA (Pvalue <0·01), whereas an increase of 10 nmol/l of tHcy in males produces a decrease of 2·06 µmol/l of DHA (Pvalue <0·05). Positive associations between B-vitamins and specific fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.


2020 ◽  
Vol 150 (5) ◽  
pp. 1223-1229 ◽  
Author(s):  
Gauri Desai ◽  
Marie Vahter ◽  
Elena I Queirolo ◽  
Fabiana Peregalli ◽  
Nelly Mañay ◽  
...  

ABSTRACT Background Detoxification of inorganic arsenic (iAs) occurs when it methylates to form monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Lower proportions of urinary iAs and MMA, and higher proportions of DMA indicate efficient methylation. The role of B-vitamins in iAs methylation in children with low-level arsenic exposure is understudied. Objectives Our study objective was to assess the association between B-vitamin intake and iAs methylation in children with low-level arsenic exposure (&lt;50 µg/L in water; urinary arsenic 5–50 µg/L). Methods We conducted a cross-sectional study in 290 ∼7-y-old children in Montevideo. Intake of thiamin, riboflavin, niacin, vitamin B-6, and vitamin B-12 was calculated by averaging 2 nonconsecutive 24-h recalls. Total urinary arsenic concentration was measured as the sum of urinary iAs, MMA, and DMA, and adjusted for urinary specific gravity; iAs methylation was measured as urinary percentage As, percentage MMA, and percentage DMA. Arsenic concentrations from household water sources were assessed. Linear regressions tested the relationships between individual energy-adjusted B-vitamins and iAs methylation. Results Median (range) arsenic concentrations in urine and water were 9.9 (2.2–48.7) and 0.45 (0.1–18.9) µg/L, respectively. The median (range) of urinary percentage iAs, percentage MMA, and percentage DMA was 10.6% (0.0–33.8), 9.7% (2.6–24.8), and 79.1% (58.5–95.4), respectively. The median (range) intake levels of thiamin, riboflavin, niacin, and vitamin B-6 were 0.81 (0.19–2.56), 1.0 (0.30–2.24), 8.6 (3.5–23.3), and 0.67 (0.25–1.73) mg/1000 kcal, respectively, whereas those of folate and vitamin B-12 were 216 (75–466) and 1.7 (0.34–8.3) µg/1000 kcal, respectively. Vitamin B-6 intake was inversely associated with urinary percentage MMA (β = −1.60; 95% CI: −3.07, −0.15). No other statistically significant associations were observed. Conclusions Although vitamin B-6 intake was inversely associated with urinary percentage MMA, our findings suggest limited support for a relation between B-vitamin intake and iAs methylation in children exposed to low-level arsenic.


2017 ◽  
Vol 114 (13) ◽  
pp. 3503-3508 ◽  
Author(s):  
Jia Zhong ◽  
Oskar Karlsson ◽  
Guan Wang ◽  
Jun Li ◽  
Yichen Guo ◽  
...  

Acute exposure to fine particle (PM2.5) induces DNA methylation changes implicated in inflammation and oxidative stress. We conducted a crossover trial to determine whether B-vitamin supplementation averts such changes. Ten healthy adults blindly received a 2-h, controlled-exposure experiment to sham under placebo, PM2.5 (250 μg/m3) under placebo, and PM2.5 (250 μg/m3) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. We profiled epigenome-wide methylation before and after each experiment using the Infinium HumanMethylation450 BeadChip in peripheral CD4+ T-helper cells. PM2.5 induced methylation changes in genes involved in mitochondrial oxidative energy metabolism. B-vitamin supplementation prevented these changes. Likewise, PM2.5 depleted 11.1% [95% confidence interval (CI), 0.4%, 21.7%; P = 0.04] of mitochondrial DNA content compared with sham, and B-vitamin supplementation attenuated the PM2.5 effect by 102% (Pinteraction = 0.01). Our study indicates that individual-level prevention may be used to complement regulations and control potential mechanistic pathways underlying the adverse PM2.5 effects, with possible significant public health benefit in areas with frequent PM2.5 peaks.


2018 ◽  
Vol 3 (2) ◽  
pp. 51-58 ◽  
Author(s):  
Graeme J Hankey

Supplementation with B vitamins (vitamin B9(folic acid), vitamin B12 and vitamin B6) lowers blood total homocysteine (tHcy) concentrations by about 25% and reduces the relative risk of stroke overall by about 10% (risk ratio (RR) 0.90, 95% CI 0.82 to 0.99) compared with placebo. Homocysteine-lowering interventions have no significant effect on myocardial infarction, death from any cause or adverse outcomes. Factors that appear to modify the effect of B vitamins on stroke risk include low folic acid status, high tHcy, high cyanocobalamin dose in patients with impaired renal function and concurrent antiplatelet therapy. In regions with increasing levels or established policies of population folate supplementation, evidence from observational genetic epidemiological studies and randomised controlled clinical trials is concordant in suggesting an absence of benefit from lowering of homocysteine with folic acid for prevention of stroke. Clinical trials indicate that in countries which mandate folic acid fortification of food, folic acid supplementation has no significant effect on reducing stroke risk (RR 1.05, 95% CI 0.90 to 1.23). However, in countries without mandatory folic acid food fortification, folic acid supplementation reduces the risk of stroke by about 15% (RR 0.85, 95% CI 0.77 to 0.94). Folic acid alone or in combination with minimal cyanocobalamin (≤0.05 mg/day) is associated with an even greater reduction in risk of future stroke by 25% (RR 0.75, 95% CI 0.66 to 0.86), whereas the combination of folic acid and a higher dose of cyanocobalamin (≥0.4 mg/day) is not associated with a reduced risk of future stroke (RR 0.95, 95% CI 0.86 to 1.05). The lack of benefit of folic acid plus higher doses of cyanocobalamin (≥0.4 mg/day) was observed in trials which all included participants with chronic kidney disease. Because metabolic B12 deficiency is very common and usually not diagnosed, future randomised trials of homocysteine-lowering interventions for stroke prevention should probably test a combination of folic acid and methylcobalamin or hydroxocobalamin instead of cyanocobalamin, and perhaps vitamin B6.


2013 ◽  
Vol 109 (5) ◽  
pp. 785-794 ◽  
Author(s):  
Derek Obersby ◽  
David C. Chappell ◽  
Andrew Dunnett ◽  
Amalia A. Tsiami

There is strong evidence indicating that elevated plasma total homocysteine (tHcy) levels are a major independent biomarker and/or a contributor to chronic conditions, such as CVD. A deficiency of vitamin B12can elevate homocysteine. Vegetarians are a group of the population who are potentially at greater risk of vitamin B12deficiency than omnivores. This is the first systematic review and meta-analysis to appraise a range of studies that compared the homocysteine and vitamin B12levels of vegetarians and omnivores. The search methods employed identified 443 entries, from which, by screening using set inclusion and exclusion criteria, six eligible cohort case studies and eleven cross-sectional studies from 1999 to 2010 were revealed, which compared concentrations of plasma tHcy and serum vitamin B12of omnivores, lactovegetarians or lacto-ovovegetarians and vegans. Of the identified seventeen studies (3230 participants), only two studies reported that vegan concentrations of plasma tHcy and serum vitamin B12did not differ from omnivores. The present study confirmed that an inverse relationship exists between plasma tHcy and serum vitamin B12, from which it can be concluded that the usual dietary source of vitamin B12is animal products and those who choose to omit or restrict these products are destined to become vitamin B12deficient. At present, the available supplement, which is usually used for fortification of food, is the unreliable cyanocobalamin. A well-designed study is needed to investigate a reliable and suitable supplement to normalise the elevated plasma tHcy of a high majority of vegetarians. This would fill the gaps in the present nutritional scientific knowledge.


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