Dietary Determinants of Plasma Homocysteine Concentrations

Division of Human Nutrition, Wageningen University, Nutrition and Health Programme, Wageningen, The Netherlands.
Seminars in Vascular Medicine 06/2005; 5(2):110-23. DOI: 10.1055/s-2005-872397
Source: PubMed


Severe hyperhomocysteinemia is typically caused by rare enzymatic defects or by renal failure. In contrast, mild to moderate hyperhomocysteinemia chiefly results from suboptimal status of nutritional factors involved in homocysteine metabolism. Low dietary intake of folate is the most important nutritional cause of elevated homocysteine (tHcy) concentrations. Folic acid is more effective than dietary folate in lowering tHcy concentrations, and a daily dose of 400 mug of folic acid is the minimum daily dose associated with the maximum tHcy-lowering effect ( approximately 20-25% reduction). Mean fasting tHcy concentrations have dropped substantially in populations with mandatory folic acid fortification, and other B-vitamins, such as vitamin B (12), are important determinants of tHcy levels in this setting. Vitamins B (2) and B (6) have little influence on fasting tHcy concentrations, although the former may be relevant in individuals with the MTHFR 677 TT-genotype, and the latter may improve tHcy catabolism in elderly individuals. Betaine and choline can lower fasting tHcy concentrations to a similar extent as folic acid, particularly in the setting of a high intake of methionine. Consumption of tea and coffee increase tHcy concentrations by up to 20%. A high-protein meal also increases tHcy, but these changes are transient, and levels return to normal after an overnight fast. Serine and cystine also influence the methionine-induced postprandial rise in tHcy concentrations. In conclusion, alteration in dietary intake or use of folic acid supplements can substantially lower tHcy concentrations. However, it is not known whether lowering tHcy levels can reduce the risk of cardiovascular disease or cognitive decline or prevent pregnancy complications or osteoporosis.

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    • "Nevertheless, recent randomised clinical trials designed to lower tHcy concentrations have proven ineffective in preventing cardiovascular events (Bonaa et al. 2006; Lonn et al. 2006), so that controversy still exists. In addition to its role on cardiovascular morbidity, recent research has suggested that tHcy might also be implicated in several other age-related pathologies, such as Alzheimer's disease, dementia (Clarke et al. 1998; Morris, 2003) and osteoporosis (Verhoef & de Groot, 2005), although the mechanisms underlying these associations have not yet been elucidated. "
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    ABSTRACT: Although total plasma homocysteine (tHcy) has been extensively studied as a risk factor of CVD, longitudinal evidence on its association with mortality is scarce, especially among the elderly. The study cohort consisted of 215 subjects (eighty-eight male and 127 female), aged 60 years or older, recruited in fourteen elderly care institutions from Asturias (Spain). All participants were free of major chronic pathology and took no vitamin and/or mineral supplements. Baseline determinations included tHcy in plasma and folate, vitamin B12 and Se in serum. Survival analyses were performed by quintiles of these factors after 6 years (mean follow-up time 4.3 years) by means of Cox regression models. During follow-up time sixty participants died. tHcy above 16.7 micromol/l was associated with an increased risk of mortality in the sample (relative risk 2.30 (95 % CI 1.02, 5.17)). Among the nutritional determinants of tHcy evaluated, folate and Se were not predictive of death risk of the cohort, while vitamin B12 showed inconsistent results. Nevertheless, mortality was significantly lower at higher serum Se levels (upper quintile), but this effect was restricted to women. Higher tHcy in both sexes and lower serum Se in women were found to be independently associated with an increased risk of death in elderly subjects.
    British Journal Of Nutrition 07/2007; 97(6):1138-43. DOI:10.1017/S0007114507691958 · 3.45 Impact Factor
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    • "After additional adjustment for dietary B-vitamins and for plasma folate and vitamin B 12 , whole-grain bread, eggs, sweets, citrus fruits, carrots, onions and non-processed meat remained significantly associated with plasma tHcy concentration . This could be due to residual confounding, or that these food groups or items contain choline, betaine or methionine (Jacques et al. 2001; Verhoef & de Groot, 2005; Cho et al. 2006). A high content of these compounds has been reported in eggs, whole-wheat bread, meat and liver, and a lower content in fruits and vegetables (Zeisel et al. 2003; US Department of Agriculture, 2005). "
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    ABSTRACT: Established dietary predictors of plasma total homocysteine (tHcy) include folate, riboflavin, and vitamins B6 and B12, while information is scarce regarding other dietary components. The aim of this study was to examine the relation between a variety of food groups, food items and nutrients, and plasma tHcy in a large population-based study. The study population included 5812 men and women aged 47-49 and 71-74 years who completed a 169-item FFQ. tHcy was examined across quartiles of dietary components by multiple linear regression analyses adjusting for age, sex, energy intake, various risk factors for elevated tHcy, as well as for dietary and plasma B-vitamins. Among 4578 non-users of vitamin supplements, intake of vegetables, fruits, cereals, eggs, fish and milk, as well as chicken and non-processed meats were inversely associated with tHcy level. The estimated mean difference in tHcy per increasing quartile of intake ranged from - 0.11 (95 % CI - 0.21, - 0.01) micromol/l for milk to - 0.32 (95 % CI - 0.42, - 0.22) micromol/l for vegetables. Positive associations were found for sweets and cakes. Whole-grain bread was significantly inversely related to tHcy only after additional adjustment for dietary and plasma B-vitamins. The nutrients folate, vitamin B6, B12, and riboflavin were inversely related to tHcy. Complex carbohydrates were inversely, and fat positively associated with tHcy, also after adjustment for dietary and plasma B-vitamins. In conclusion, food items rich in B-vitamins and with a low content of fat and sugar were related to lower tHcy levels. Eggs, chicken, non-processed meat, fish and milk were inversely associated with tHcy.
    British Journal Of Nutrition 07/2007; 98(1):201-10. DOI:10.1017/S0007114507691788 · 3.45 Impact Factor
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    • "The mechanism for the effect of caffeine is not known, but it has been suggested that caffeine may act as a vitamin B 6 antagonist (Verhoef et al. 2002). A range of other dietary factors can also influence tHcy metabolism (Verhoef & de Groot, 2005). Thus, the overall effects of a polyphenol-and caffeine-containing beverage may be influenced by food. "
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    ABSTRACT: Plasma total homocysteine concentrations (tHcy) are a putative risk factor for CVD. Tea is a rich dietary source of polyphenols and caffeine, both of which may raise tHcy. However, it is possible that much of any effect is transitory and may be influenced by the consumption of food. Our objective was to investigate the acute effect of tea, at a dose representative of ordinary population intakes, on tHcy and to determine whether consumption of a meal influences the magnitude of any effect. Measurements of tHcy were performed in twenty participants at baseline and 3.5 h after drinking three cups of black tea or hot water (consumed at time 0, 1.5 and 3 h) with and without a meal: a total of four treatments administered in random order. Drinking tea resulted in an acute increase in tHcy (0-30 (95 % CI 0.04, 0.56) micromol/l, P=0.022). The meal resulted in an acute decrease in tHcy (-0.42 (95 % CI -0.68, -0.16) micromol/l, P=0.002). There was no interaction between tea and meal on tHcy (P=0.40); that is, the effect of tea on tHcy was not different in the fasting and non-fasting state. Our results suggest that drinking black tea can cause a small acute increase in tHcy and that this effect is not enhanced in the non-fasting state. Given that results of population studies have generally shown a negative association between tea intake and tHcy, the significance of these findings to CVD risk remains uncertain.
    British Journal Of Nutrition 06/2007; 97(5):842-6. DOI:10.1017/S0007114507669190 · 3.45 Impact Factor
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Lisette C P G M de Groot