McCully Kilmer S
Pathology and Laboratory Medicine Service, Department of Veterans Affairs Medical Center, West Roxbury, MA, USA.
Am J Clin Nutr. 2007 Nov;86(5):1563S-8S. doi: 10.1093/ajcn/86.5.1563S.
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.
在20世纪中叶的美国，血管疾病导致的死亡人数在1955年达到峰值发病率，但对于这场疾病流行的潜在原因却知之甚少。直到1962年，同型胱氨酸尿症病例首次与血管疾病相关联时，同型半胱氨酸在人类疾病中的重要性才为人所知。对1933年的一例同型胱氨酸尿症存档病例和1968年的一例钴胺素C病病例进行分析后得出结论：同型半胱氨酸通过该氨基酸对动脉细胞和组织的直接作用导致血管疾病。动脉粥样硬化的同型半胱氨酸理论将血管疾病的潜在原因之一归结为饮食、遗传、代谢、激素或毒性因素导致血液中同型半胱氨酸浓度升高。传统食品加工或维生素B异常吸收导致的维生素B-6和叶酸饮食缺乏以及维生素B-12吸收缺乏，是导致血液中同型半胱氨酸升高的重要因素。众多临床和流行病学研究已证实，血液中同型半胱氨酸升高是普通人群血管疾病的一个强大独立危险因素。通过提供丰富的维生素B-6、叶酸和钴胺素改善饮食，可能通过降低血液中同型半胱氨酸来预防血管疾病。自1950年以来美国心血管疾病死亡率的显著下降可能部分归因于食品供应中自愿添加了维生素B-6和叶酸。根据美国食品药品监督管理局的规定，1998年美国食品供应中添加了叶酸，这与血管疾病死亡率的进一步下降相关，推测是因为人群中血液叶酸增加且血液同型半胱氨酸减少。
