Koehler K M, Romero L J, Stauber P M, Pareo-Tubbeh S L, Liang H C, Baumgartner R N, Garry P J, Allen R H, Stabler S P
Clinical Nutrition Program, University of New Mexico School of Medicine, Albuquerque 87131-5666, USA.
J Am Coll Nutr. 1996 Aug;15(4):364-76. doi: 10.1080/07315724.1996.10718611.
An elevated serum concentration of the metabolite, homocysteine (Hcys): 1) can indicate folate or vitamin B12 deficiency, 2) is an independent risk factor for vascular disease. The metabolite, methylmalonic acid (MMA), is elevated in deficiency of vitamin B12, but not folate. The purpose of this study was to determine the effect of self-selected vitamin supplementation and other variables on serum Hcys and MMA concentrations in elderly men and women.
Serum concentrations of Hcys, MMA, folate and vitamin B12 were measured for elderly volunteers, age 68-96 years, and compared for those consuming (26 men, 25 women) and not consuming (24 men, 25 women) self-selected vitamin supplements.
Compared with the nonsupplemented group, the supplemented group had lower mean serum MMA (208 +/- 162 vs. 241 +/- 98 nmol/L [+/- SD]) and Hcys (9.5 +/- 2.6 vs. 11.2 +/- 2.7 mumol/L); and higher serum vitamin B12 (391 +/- 174 vs 292 +/- 107 pmol/L), and serum folate (46 +/- 15 vs. 24 +/- 10 nmol/L) p < 0.05. Among all 100 subjects, the prevalence of serum vitamin B12 < 221 pmol/L (300 pg/mL) was 18; MMA > 271 nmol/L, 16; Hcys > 16.2 mumol/L, 3; folate < 5.0 nmol/L, none. Based on serum vitamin B12 < 221 nmol/L with elevated serum MMA, vitamin B12 deficiency was probable in seven subjects, of whom two were supplemented. All three subjects with elevated serum Hcys had elevated serum MMA as well, suggesting vitamin B12 deficiency or renal insufficiency. A stepwise linear regression model for serum Hcys explained 61.7% of the variance, and included (in order) serum creatinine, folate, vitamin B12, albumin, age and body mass index (BMI). A model with serum MMA replacing serum vitamin B12 explained 64.1% of the variance in serum Hcys. Folate did not enter the model for supplemented subjects, supporting a "threshold effect": serum Hcys was inversely related to serum folate at lower serum folate (nonsupplemented subjects), but at higher serum folate (supplemented subjects), the relationship was flat. In supplemented subjects, serum Hcys was still related to vitamin B12 status, confirming that tissue deficiency of the vitamin was present.
Results showed potential usefulness of serum MMA and Hcys in identifying subclinical or tissue deficiency of vitamin B12. Clinicians should be aware of the risk of vitamin B12 deficiency in older people and of current screening algorithms using serum metabolites. These elderly volunteers had generally good folate status; nevertheless, some subjects seemed likely to benefit from an improvement in folate status that would reduce their serum Hcys within the normal range. The role of serum creatinine in the normal range in predicting serum Hcys, a vascular disease risk factor, remains unexplained.
代谢物同型半胱氨酸（Hcys）血清浓度升高：1）可提示叶酸或维生素B12缺乏；2）是血管疾病的独立危险因素。代谢物甲基丙二酸（MMA）在维生素B12缺乏而非叶酸缺乏时升高。本研究的目的是确定自行选择的维生素补充剂及其他变量对老年男性和女性血清Hcys和MMA浓度的影响。
检测了68 - 96岁老年志愿者的血清Hcys、MMA、叶酸和维生素B12浓度，并对服用（26名男性，25名女性）和未服用（24名男性，25名女性）自行选择的维生素补充剂的志愿者进行了比较。
与未补充组相比，补充组的血清MMA平均水平较低（208±162 vs. 241±98 nmol/L[±标准差]），Hcys水平也较低（9.5±2.6 vs. 11.2±2.7 μmol/L）；血清维生素B12水平较高（391±174 vs 292±107 pmol/L），血清叶酸水平较高（46±15 vs. 24±10 nmol/L），p<0.05。在所有100名受试者中，血清维生素B12<221 pmol/L（300 pg/mL）的患病率为18%；MMA>271 nmol/L的患病率为16%；Hcys>16.2 μmol/L的患病率为3%；叶酸<5.0 nmol/L的患病率为0。基于血清维生素B12<221 nmol/L且血清MMA升高，7名受试者可能存在维生素B12缺乏，其中2名受试者服用了补充剂。血清Hcys升高的所有3名受试者血清MMA也升高，提示维生素B12缺乏或肾功能不全。血清Hcys的逐步线性回归模型解释了61.7%的方差，依次包括血清肌酐、叶酸、维生素B12、白蛋白、年龄和体重指数（BMI）。用血清MMA替代血清维生素B12的模型解释了血清Hcys方差的64.1%。叶酸未进入补充组受试者的模型，支持“阈值效应”：在血清叶酸水平较低时（未补充组受试者），血清Hcys与血清叶酸呈负相关，但在血清叶酸水平较高时（补充组受试者），这种关系不明显。在补充组受试者中，血清Hcys仍与维生素B12状态相关，证实存在该维生素的组织缺乏。
结果表明血清MMA和Hcys在识别维生素B12亚临床或组织缺乏方面具有潜在用途。临床医生应意识到老年人维生素B12缺乏的风险以及目前使用血清代谢物的筛查算法。这些老年志愿者的叶酸状态总体良好；然而，一些受试者似乎可能从改善叶酸状态中获益，这将使他们的血清Hcys降至正常范围内。血清肌酐在正常范围内预测血管疾病危险因素血清Hcys的作用仍无法解释。
