Hyperhomocysteinemia and Low Pyridoxal Phosphate

Robinson, Killian; Mayer, E; Miller, Dave P.; Green, Ralph; Lente, Frederick Van; Gupta, Anjan; Kottke‐Marchant, Kandice; Savon, Susan R.; Selhub, Jacob; Nissen, Steven E.; Kutner, Michael; Topol, Eric J.; Jacobsen, Donald W.

doi:10.1161/01.cir.92.10.2825

Cited by 328 publications

(93 citation statements)

References 29 publications

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“…Increased dietary methionine or deficiencies of folic acid and vitamin B6 and/or vitamin B12 can lead to hyperhomocysteinemia in humans (43)(44)(45) and animals (32,35,46,47). However, the mechanisms by which elevated levels of homocysteine promote the pathological changes associated with hyperhomocysteinemia are poorly understood.…”

Section: Figurementioning

confidence: 99%

Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways

et al. 2001

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Section: Figurementioning

confidence: 99%

Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways

et al. 2001

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“…Although the effect of vitamin B 6 supplementation on homocysteine is unclear at present, low vitamin B 6 status has been demonstrated to be an independent risk factor for cardiovascular disease (Serfontein et al, 1985;Robinson et al, 1995;Chan et al, 2002). The present study was undertaken to ascertain whether various doses of vitamin B 6 supplementation would have beneficial effects on lowering fasting plasma homocysteine concentrations in CAD patients.…”

Section: Introductionmentioning

confidence: 96%

Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease

et al. 2004

Eur J Clin Nutr

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Objective: To investigate whether vitamin B 6 supplementation had a beneficial effect on lowering fasting plasma homocysteine concentrations in coronary artery disease (CAD) patients. Design: A single-blind intervention study. Setting: The study was performed at the Taichung Veterans General Hospital, the central part of Taiwan. Subjects: A total of 50 subjects were identified by cardiac catheterization to have at least 70% stenosis of one major coronary artery. In all, 42 patients successfully completed this study. Interventions: Patients were randomly assigned to one of five groups and treated with a daily dose of placebo (n ¼ 8), 5 mg vitamin B 6 (n ¼ 8), 10 mg vitamin B 6 (n ¼ 8), 50 mg vitamin B 6 (n ¼ 9), or 5 mg folic acid combined with 0.25 mg vitamin B 12 (n ¼ 9) for 12 weeks. Main outcome measures: Nutrient intakes were recorded by using 24-h diet recalls when patients returned to the cardiology clinic before the intervention (week 0) and at week 12. Vitamin B 6 status was assessed by direct measures (plasma pyridoxal 5 0 -phosphate) and indirect measures (erythrocyte alanine and aspartate aminotransaminase activity coefficient). Fasting plasma homocysteine, serum folic acid, and vitamin B 12 were measured. Results: Fasting plasma homocysteine concentration did not respond to high or low doses of vitamin B 6 when compared with a placebo treatment after 12 weeks of supplementation. The mean fasting plasma homocysteine concentration, however, decreased significantly after 12 weeks of folic acid combined with vitamin B 12 supplementation (P ¼ 0.047). Further, within group, mean fasting plasma homocysteine concentration was nonsignificantly increased by 25.5, 16.2, and 18.3% in placebo, 10 mg/day and 50 mg/day vitamin B 6 supplemented groups, respectively; whereas folic acid combined with vitamin B 12 supplementation significantly reduced fasting plasma homocysteine concentration by 32% (Po0.001). Conclusions: Our results indicate that vitamin B 6 supplementation alone is less effective than folic acid combined with vitamin B 12 in lowering plasma homocysteine concentrations in CAD patients.

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“…It is a key branch point intermediate in the ubiquitous methionine cycle, the function of which is to generate one-carbon methyl groups for transmethylation reactions that are essential to all life forms. During the past decade, homocysteine has received increasing attention, as elevated levels of homocysteine have been implicated as an independent risk factor for cardiovascular disease (Robinson et al 1995) and have also been associated with various other diseases and/or clinical conditions, including Alzheimer's disease (McCaddon et al 1998), neural tube defects (Mills et al 1995;de la Calle et al 2003), schizophrenia (Applebaum et al 2004), endstage renal disease (van Guldener and Stehouwer 2003), osteoporosis (Villadsen et al 2005), non-insulindependent diabetes (de Luis et al 2005;Buysschaert et al 2004), etc. Although elevated levels of homocysteine have been associated with several diseases, the mechanism underlying the deleterious effects of homocysteine has not yet been completely elucidated.…”

Section: Introductionmentioning

confidence: 99%

Homocysteine levels are associated with MTHFR A1298C polymorphism in Indian population

et al. 2005

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An elevated level of homocysteine is an independent risk factor for cardiovascular diseases and is associated with other complex disorders. Homocysteine levels can be elevated due to dietary and/or genetic factors. A majority of Indian population have a low level of vitamin B12 (presumably due to vegetarian diet)-a critical nutritional factor, deficiency of which results in hyperhomocysteinemia. Hence, polymorphisms in the genes responsible for homocysteine metabolism can be perceived to have a greater impact in relation to hyperhomocysteinemia in Indian population. For this reason, the effects of diet and/or methylenetetrahydrofolate reductase (MTHFR) polymorphism were assessed in 200 individuals having varying homocysteine levels. Homocysteine levels were significantly elevated in individuals adhering to a vegetarian diet (P=0.019) or having MTHFR A1298C polymorphism (P=0.006). The minor allele frequency (MAF) of MTHFR C677T and A1298C was 0.15 and 0.44 respectively in this cohort. Since the MAF of these polymorphisms differed considerably from Caucasian and other Asian populations, frequencies of these polymorphisms were also determined in more than 400 individuals from different ethnic populations, selected from the entire country based on their geographical location and linguistic lineage, and was found to be similar to that of our cohort. The fact that MTHFR A1298C polymorphism is significantly associated with homocysteine levels, and that the CC genotype is present at a higher frequency in the Indian population, makes it extremely relevant in terms of its potential impact on hyperhomocysteinemia.

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Hyperhomocysteinemia and Low Pyridoxal Phosphate

Cited by 328 publications

References 29 publications

Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways

Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways

Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease

Homocysteine levels are associated with MTHFR A1298C polymorphism in Indian population

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