Homocysteine, iron and cardiovascular disease: a hypothesis

Area of Science:

• Biochemistry
• Cardiovascular Science
• Nutritional Science

Background:

• Elevated total homocysteine (tHcy) is a known cardiovascular disease (CVD) risk factor.
• B-vitamin supplementation trials have largely failed to reduce CVD risk despite correcting hyperhomocysteinemia.

Purpose of the Study:

• To investigate the role of iron in homocysteine metabolism and its potential link to cardiovascular disease.
• To propose a new hypothesis where free iron, not just tHcy, is a key CVD risk factor.

Main Methods:

• Review of existing research on iron's catalytic role in homocysteine formation.
• Analysis of findings on iron-catalyzed thioether metabolism and oxygen free radical generation.

Main Results:

• Iron (Fe) catalyzes the formation of homocysteine (Hcy) from precursors like methionine.
• Elevated non-protein-bound iron (free Fe) is proposed to increase circulating tHcy.
• Free Fe also catalyzes oxygen free radical formation, contributing to vascular damage.

Conclusions:

• Circulating tHcy may serve as a surrogate marker for free iron levels.
• Free iron is identified as a significant, independent risk factor for cardiovascular disease.
• This finding offers a new perspective on CVD pathogenesis and potential therapeutic targets beyond B-vitamins.