Homocysteine, vitamins, and vascular disease prevention

Abstract

In mid-20th century United States, deaths from vascular disease reached a peak incidence in 1955, but little was known about the underlying causes of this epidemic of disease. The significance of homocysteine in human disease was unknown until 1962, when cases of homocystinuria were first associated with vascular disease. Analysis of an archival case of homocystinuria from 1933 and a case of cobalamin C disease from 1968 led to the conclusion that homocysteine causes vascular disease by a direct effect of the amino acid on arterial cells and tissues. The homocysteine theory of arteriosclerosis attributes one of the underlying causes of vascular disease to elevation of blood homocysteine concentrations as the result of dietary, genetic, metabolic, hormonal, or toxic factors. Dietary deficiency of vitamin B-6 and folic acid and absorptive deficiency of vitamin B-12, which result from traditional food processing or abnormal absorption of B vitamins, are important factors in causing elevations in blood homocysteine. Numerous clinical and epidemiologic studies have established elevated blood homocysteine as a potent independent risk factor for vascular disease in the general population. Dietary improvement, providing abundant vitamin B-6, folic acid, and cobalamin, may prevent vascular disease by lowering blood homocysteine. The dramatic decline in cardiovascular mortality in the United States since 1950 may possibly be attributable in part to voluntary fortification of the food supply with vitamin B-6 and folic acid. Fortification of the US food supply with folic acid in 1998, as mandated by the US Food and Drug Administration, was associated with a further decline in mortality from vascular disease, presumably because of increased blood folate and decreased blood homocysteine in the population.

Persistent Sex Disparity in Midlife Stroke Prevalence in the United States

“…An elevated homocysteine level was defined as a homocysteine level >8.5 µmol/l. This cutoff was selected because: the introduction of mandatory folic acid fortification in 1998 reduced the mean plasma homocysteine levels to approximately 8–10 µmol/l [16,17] and homocysteine is directly correlated with vascular risk across a wide range of values [18,19]. Smoking was defined by self-reported history of smoking >100 cigarettes.…”

Pronounced association of elevated serum homocysteine with stroke in subgroups of individuals: A nationwide study

“…This cutoff was selected because the introduction of mandatory folic acid fortification in 1998 reduced the mean plasma tHcy levels to 8 to 10 μmol/L [15,16] and some experts suggest starting treatment at a level ≥10 μmol/L [17].…”

Homocysteine-lowering therapy for preventing atherothrombotic events: Its role in high risk population

“…Homocysteine is metabolized through folic acid, vitamin B 6, and vitamin B 12 dependent pathways [2]. Folic acid, vitamin B 6, and vitamin B 12 deficiency inhibit the breakdown of homocysteine, thus increasing the intracellular homocysteine concentration exerts a detrimental effect on vascular wall and especially on endothelial cells by triggering pro-atherogenic and prothrombotic mechanisms [3]. Epidemiological evidence, as well as data from retrospective and prospective clinical studies has established elevated homocysteine levels as a potent independent risk factor for atherothrombotic vascular disease [4][5][6].…”

“…Lyme borreliosis (Lyme disease, LB) is the most prevalent arthropod-borne zoonosis in the Northern hemisphere [1][2][3]. This multisystem infectious disease with a wide spectrum of clinical symptoms is caused by a phylogenetically-distinct group of spirochetes, known as Borrelia burgdorferi sensu lato (Borrelia afzelii, B. garinii, and B. burgdorferi sensu stricto), and classified in the family Spirochaetaceae [1][2][3].…”

“…This multisystem infectious disease with a wide spectrum of clinical symptoms is caused by a phylogenetically-distinct group of spirochetes, known as Borrelia burgdorferi sensu lato (Borrelia afzelii, B. garinii, and B. burgdorferi sensu stricto), and classified in the family Spirochaetaceae [1][2][3]. All three genospecies are endemic in Europe, whereas only B. burgdorferi sensu stricto occurs in North America [1][2][3].…”