Homocysteine: Its Possible Emerging Role in At-Risk Population Groups

Abstract

Increased plasma homocysteine is a risk factor for several pathological disorders. The present review focused on the role of homocysteine (Hcy) in different population groups, especially in risk conditions (pregnancy, infancy, old age), and on its relevance as a marker or etiological factor of the diseases in these age groups, focusing on the nutritional treatment of elevated Hcy levels. In pregnancy, Hcy levels were investigated in relation to the increased risk of adverse pregnancy outcomes such as small size for gestational age at birth, preeclampsia, recurrent abortions, low birth weight, or intrauterine growth restriction. In pediatric populations, Hcy levels are important not only for cardiovascular disease, obesity, and renal disease, but the most interesting evidence concerns study of elevated levels of Hcy in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Finally, a focus on the principal pathologies of the elderly (cardiovascular and neurodegenerative disease, osteoporosis and physical function) is presented. The metabolism of Hcy is influenced by B vitamins, and Hcy-lowering vitamin treatments have been proposed. However, clinical trials have not reached a consensus about the effectiveness of vitamin supplementation on the reduction of Hcy levels and improvement of pathological condition, especially in elderly patients with overt pathologies, suggesting that other dietary and non-dietary factors are involved in high Hcy levels. The importance of novel experimental designs focusing on intra-individual variability as a complement to the typical case-control experimental designs and the study of interactions between different factors it should be emphasized.

Keywords: adolescents; children; elderly; homocysteine; pregnancy.

Figure 1

Schematic representation of pathways of Hcy metabolism (DHFR = dihydrofolate reductase; THF = tetrahydrofolate; SHMT = serinehydroxymethyltransferase; MTHF = methylenetetrahydrofolate; MTHFR = 5,10-methylene-THF reductase; ATP = adenosine triphosphate; MAT = methionine adenosyltransferase; ADP = adenosine diphosphate; SAM = S-adenosylmethionine; SAH = S-adenosylHcy; BHMT = betaine-Hcy S-methyltransferase; CBS = cystathionine β-synthase; CSE = cystathionase; GSH = glutathione; H₂S = hydrogen sulphide).

Figure 2

Forms of Hcy present in human plasma.