Ebbing Marta, Bønaa Kaare Harald, Nygård Ottar, Arnesen Egil, Ueland Per Magne, Nordrehaug Jan Erik, Rasmussen Knut, Njølstad Inger, Refsum Helga, Nilsen Dennis W, Tverdal Aage, Meyer Klaus, Vollset Stein Emil
Department of Heart Disease, Haukeland University Hospital, Jonas Liesvei 65, Bergen, Norway 5021.
JAMA. 2009 Nov 18;302(19):2119-26. doi: 10.1001/jama.2009.1622.
Recently, concern has been raised about the safety of folic acid, particularly in relation to cancer risk.
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.
Oral treatment with folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) and vitamin B(6) (40 mg/d) (n = 1708); folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) (n = 1703); vitamin B(6) alone (40 mg/d) (n = 1705); or placebo (n = 1721).
Cancer incidence, cancer mortality, and all-cause mortality.
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 B(12) 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 B(12) 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 B(12) 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 B(12). Vitamin B(6) treatment was not associated with any significant effects.
Treatment with folic acid plus vitamin B(12) 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.
clinicaltrials.gov Identifier: NCT00671346.
最近，人们对叶酸的安全性提出了担忧，尤其是与癌症风险相关的问题。
在两项随机对照试验中评估B族维生素治疗对癌症结局和全因死亡率的影响。
设计、背景和参与者：对两项随机、双盲、安慰剂对照临床试验（挪威维生素试验和挪威西部B族维生素干预试验）的参与者进行联合分析和延长随访。1998年至2005年期间，共有6837例缺血性心脏病患者接受了B族维生素或安慰剂治疗，并随访至2007年12月31日。
口服叶酸（0.8毫克/天）加维生素B12（0.4毫克/天）和维生素B6（40毫克/天）（n = 1708）；叶酸（0.8毫克/天）加维生素B12（0.4毫克/天）（n = 1703）；单独使用维生素B6（40毫克/天）（n = 1705）；或安慰剂（n = 1721）。
癌症发病率、癌症死亡率和全因死亡率。
在研究治疗期间，服用叶酸的参与者血清叶酸浓度中位数增加了6倍多。经过中位数39个月的治疗和额外38个月的试验后观察随访，接受叶酸加维生素B12治疗的341名参与者（10.0%）被诊断患有癌症，而未接受此类治疗的288名参与者（8.4%）被诊断患有癌症（风险比[HR]，1.21；95%置信区间[CI]，1.03 - 1.41；P = 0.02）。接受叶酸加维生素B12治疗的136人（4.0%）死于癌症，而未接受此类治疗的100人（2.9%）死于癌症（HR，1.38；95%CI，1.07 - 1.79；P = 0.01）。接受叶酸加维生素B12治疗的548名患者（16.1%）死于任何原因，而未接受此类治疗的473名患者（13.8%）死于任何原因（HR，1.18；95%CI，1.04 - 1.33；P = 0.01）。结果主要由接受叶酸加维生素B12治疗的参与者肺癌发病率增加所致。维生素B6治疗未产生任何显著影响。
在挪威，食物未强化叶酸，缺血性心脏病患者接受叶酸加维生素B12治疗与癌症结局增加和全因死亡率增加相关。
clinicaltrials.gov标识符：NCT00671346。
