Hu Jing, Juan WenYen, Sahyoun Nadine R
University of Maryland, Department of Nutrition and Food Science, College Park, Maryland, United States of America.
Office of Nutrition, Labeling and Dietary Supplements, Center for Food Safety and Applied Nutrition, United States Food and Drug Administration, College Park, Maryland, United States of America.
PLoS One. 2016 Feb 10;11(2):e0148697. doi: 10.1371/journal.pone.0148697. eCollection 2016.
After the 1998 mandatory folic acid fortification of enriched cereal-grain products in the U.S., safety concerns were raised that excess consumption of folic acid and high blood folate biomarkers detected in adults may increase the risk of certain types of cancer.
Baseline data from about 1400 participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2002, aged ≥ 57 years were linked to Medicare and mortality files through December 31, 2007. Using cox proportional hazards regression models, we assessed associations between dietary folate equivalents, folate biomarkers, the presence of unmetabolized folic acid and, overall cancer incidence.
With 8,114 person-years of follow-up (median follow-up, 6.3 years), about 125 cancer cases were identified. After adjusting for confounders, the hazard ratios of the highest quartile versus the second quartile of RBC folate and dietary folate equivalents were 0.54 (95% CI: 0.31-0.93) and 0.54 (95% CI: 0.30-0.95), respectively. Additionally, serum and RBC folate as continuous variables were inversely and significantly associated with cancer incidence (p<0.01). No significant associations were observed between the presence of unmetabolized folic acid, intake of naturally-occurring food folate or folic acid separately, and cancer incidence.
High total folate intake and biomarkers in older adults appear to be protective against cancer in post-folic acid fortification years. This study does not show a negative impact of current level of folic acid fortification on cancer risk. As this is one of the few studies to examine the association between unmetabolized folic acid and cancer outcome, a study including a larger nationwide representative sample of the U.S. population is needed.
1998年美国对强化谷物制品强制添加叶酸后，有人担心成人过量摄入叶酸以及检测到的高血液叶酸生物标志物可能会增加某些类型癌症的风险。
1999 - 2002年美国国家健康与营养检查调查（NHANES）中约1400名年龄≥57岁参与者的基线数据与医疗保险和死亡率档案相链接，随访至2007年12月31日。使用Cox比例风险回归模型，我们评估了膳食叶酸当量、叶酸生物标志物、未代谢叶酸的存在与总体癌症发病率之间的关联。
随访8114人年（中位随访时间为6.3年），共识别出约125例癌症病例。在调整混杂因素后，红细胞叶酸和膳食叶酸当量最高四分位数与第二四分位数的风险比分别为0.54（95%置信区间：0.31 - 0.93）和0.54（95%置信区间：0.30 - 0.95）。此外，血清和红细胞叶酸作为连续变量与癌症发病率呈显著负相关（p<0.01）。未代谢叶酸的存在、天然食物叶酸或叶酸单独摄入量与癌症发病率之间未观察到显著关联。
在叶酸强化后的年份里，老年人高叶酸总摄入量和生物标志物似乎对癌症具有保护作用。本研究未显示当前叶酸强化水平对癌症风险有负面影响。由于这是少数研究未代谢叶酸与癌症结局之间关联的研究之一，因此需要开展一项纳入更大规模全国代表性美国人群样本的研究。
