据11月18日刊JAMA上的一则研究披露，挪威是一个食物中没有增补叶酸的国家。该国的心脏病患者如果接受了叶酸和维生素B12的治疗，其罹患癌症及死于任何原因的风险都会有相关的增加。
根据文章的背景资料，大多数的流行病学调查发现，在叶酸（是一种B族维生素）的摄取与结肠直肠癌风险之间存在着逆相关，尽管这种相关性在其它的癌症中是不一致的或是阙如的。文章的作者写道：“实验室的证据表明，叶酸缺乏可促进初始阶段的癌症发生，而高剂量的叶酸可能会促进癌细胞的生长。自1998年以来，许多国家，其中包括美国，开始在面粉和谷类产品中进行叶酸增补以降低出生时发生神经管缺陷的风险。” “最近，人们对叶酸的安全性，尤其是有关其致癌风险的担心开始出现。”
Haukeland University Hospital, Bergen, Norway的Marta Ebbing, M.D.及其同僚对挪威的2个在缺血性心脏病患者中进行的降低同型半胱氨酸的试验结果进行了分析。在该试验中，那些被分配接受叶酸治疗的小组的癌症发生率发生了统计学上没有显著意义的增加。
这2则随机化的、有安慰剂作对照的临床试验中包括了6837名有缺血性心脏病的患者，他们在1998年和2005年之间接受了B族维生素或是安慰剂的治疗。对这些患者的随访一直持续到2007年的12月31日。这些患者被随机分配接受口服叶酸（0.8 mg/天）加叶维生素B12 （0.4 mg/天）加维生素B6（40 mg/天）[n = 1708] ； 叶酸（0.8 mg/天）加维生素B12（0.4 mg/天）[n = 1703] ；仅仅服用维生素B6（40 mg/天）[n = 1705]；或服用安慰剂 [n = 1721] 。在研究治疗期间，中位（中点）血清叶酸浓度在服用叶酸的参与者中增加了6倍以上。
研究人员发现，在经过中位数为39个月的治疗及另外38个月的试验后观察随访之后，在没有接受叶酸加维生素B12的人中有288人（占8.4%）被诊断患有癌症，而在接受了叶酸和维生素B12治疗的人中，被诊断罹患癌症者有341人（10.0%），癌症风险的增加幅度为21%。在没有接受叶酸加维生素B12治疗者中，共有100位患者死于癌症（占2.9%），而在接受了叶酸加维生素B12的治疗者中，共有136名患者死于癌症（占4.0%），其死于癌症的风险增幅为38%。在没有接受叶酸加维生素B12的治疗者中，共有16.1%的患者死于任何的原因，而在接受了叶酸加维生素B12的治疗者中，共有13.8%的患者死于任何的原因。
文章的作者写道：“这些结果主要是受到这些接受了叶酸加维生素B12的参与者中肺癌发生率增加的影响。维生素B6的治疗与任何其它的明显的功效都没有相关性。”
“我们的结果需要在其它的人群中得到确认。但它强调了在人们从食品补充剂及强化食品中广泛摄取叶酸之后对其安全性监控的诉求。”（生物谷Bioon.com）
生物谷推荐原始出处：
JAMA. 2009;302(19):2119-2126.
Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B12
Marta Ebbing, MD; Kaare Harald B?naa, MD, PhD; Ottar Nyg?rd, MD, PhD; Egil Arnesen, MD; Per Magne Ueland, MD, PhD; Jan Erik Nordrehaug, MD, PhD; Knut Rasmussen, MD, PhD; Inger Nj?lstad, MD, PhD; Helga Refsum, MD, PhD; Dennis W. Nilsen, MD, PhD; Aage Tverdal, PhD; Klaus Meyer, PhD; Stein Emil Vollset, MD, DrPH
Context Recently, concern has been raised about the safety of folic acid, particularly in relation to cancer risk.
Objective To evaluate effects of treatment with B vitamins on cancer outcomes and all-cause mortality in 2 randomized controlled trials.
Design, Setting, and Participants Combined analysis and extended follow-up of participants from 2 randomized, double-blind, placebo-controlled clinical trials (Norwegian Vitamin Trial and Western Norway B Vitamin Intervention Trial). A total of 6837 patients with ischemic heart disease were treated with B vitamins or placebo between 1998 and 2005, and were followed up through December 31, 2007.
Interventions Oral treatment with folic acid (0.8 mg/d) plus vitamin B12 (0.4 mg/d) and vitamin B6 (40 mg/d) (n = 1708); folic acid (0.8 mg/d) plus vitamin B12 (0.4 mg/d) (n = 1703); vitamin B6 alone (40 mg/d) (n = 1705); or placebo (n = 1721).
Main Outcome Measures Cancer incidence, cancer mortality, and all-cause mortality.
Results During study treatment, median serum folate concentration increased more than 6-fold among participants given folic acid. After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B12 vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B12 vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07-1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B12 vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04-1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B12. Vitamin B6 treatment was not associated with any significant effects.
Conclusion Treatment with folic acid plus vitamin B12 was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods.
