Elsevier

The Journal of Nutrition

Volume 136, Issue 6, June 2006, Pages 1726S-1730S
The Journal of Nutrition

The Many Facets of Hyperhomocysteinemia: Studies from the Framingham Cohorts12

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ABSTRACT

Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of 2 pathways: remethylation, which requires folic acid and B-12 coenzymes, and transsulfuration, which requires pyridoxal-5′-phosphate, the B-6 coenzyme. Data from several studies suggest that mild elevations of homocysteine in plasma are a risk factor for occlusive vascular disease. In the Framingham studies we have shown that plasma total homocysteine concentration is inversely related to the intake and plasma levels of folate and vitamin B-6 as well as vitamin B-12 plasma levels. Almost two-thirds of the prevalence of high homocysteine is attributable to low vitamin status or intake. Elevated homocysteine concentrations in plasma are a risk factor for prevalence of extracranial carotid artery stenosis of at least 25% in both men and women. Prospectively elevated plasma homocysteine is associated with increased total and CVD mortality, increased incidence of stroke, increased incidence of dementia and Alzheimer’s disease, increased incidence of bone fracture, and higher prevalence of chronic heart failure. This multitude of relationships between elevated plasma total homocysteine and diseases that afflict the elderly point to the existence of a common denominator that may be responsible for these diseases. Whether this denominator is homocysteine itself or whether homocysteine is merely a marker remains to be determined.

KEY WORDS

total homocysteine
folate
vitamin B-12
vitamin B-6
cardiovascular disease
stenosis
stroke
dementia
bone fractures
chronic heart failure

Abbreviations

CHD
coronary heart disease
CHF
congestive heart failure
LV
left ventricular
PLP
pyridoxal-5′-phosphate
tHcy
total homocysteine.

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1

Published in a supplement to The Journal of Nutrition. Presented at the conference “The Fifth Workshop on the Assessment of Adequate Intake of Dietary Amino Acids” held October 24–25, 2005 in Los Angeles. The conference was sponsored by the International Council on Amino Acid Science (ICAAS). The organizing committee for the workshop and guest editors for the supplement were David H. Baker, Dennis M. Bier, Luc Cynober, Yuzo Hayashi, Motoni Kadowaki, and Andrew G. Renwick. Guest editors disclosure: all editors received travel support from ICAAS to attend the workshop.

2

This material is based on work supported by the U.S. Department of Agriculture, under agreement No. 1950-51520-008. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author and do not necessarily reflect the view of the U.S. Dept of Agriculture.