These findings come from the Vitamins and Lifestyle (VITAL) cohort study and were published online August 22 in the Journal of Clinical Oncology.
“Our data shows that taking high doses of B6 and B12 over a very long period of time could contribute to lung cancer incidence rates in male smokers. This is certainly a concern worthy of further evaluation,” commented lead author, Theodore Brasky, PhD, from The Ohio State University Comprehensive Cancer Center, Columbus, in a statement.
He emphasized, however, that the doses involved were well above those found in a daily multivitamin tablet.
“These are doses that can only be obtained from taking high-dose B vitamin supplements, and these supplements are many times the U.S. Recommended Dietary Allowance,” he said
This point was also emphasized by several experts not involved in the study.
The National Institutes of Health Office of Dietary Supplements suggests that men who are age 51 years and older need B6 at a dose of 1.7 mg daily (women, 1.5 mg daily), while for B12 the recommended dose for adults is 2.4 µg daily.
In this study, men who were taking the highest dose of vitamin B supplements (and who were found to have a two-fold increased risk in lung cancer compared with men not taking supplements) had been taking B6 at 20 mg daily and B12 at 55 µg daily for 10 years.
The VITAL study had 77,118 participants, aged 50 to 76 years, who were recruited between October 2000 and December 2002.
For this study, Dr Brasky and colleagues focused on the 808 participants who developed incident, primary invasive lung cancers, as ascertained by prospectively linking the participants to a population-based cancer registry.
Just over half (55%) of these patients with lung cancer were men (n = 449).
The team then studied the vitamin supplement use among these patients with lung cancer. This was based on recall — participants answered questionnaires about the supplement use, as well as food intake and smoking habits.
The team found an association between vitamin B supplements and lung cancer among men, but not among women.
Men who had taken the highest doses were nearly twice as likely to develop lung cancer as men who had not taken supplements.
Men who were smokers and who were taking B6 at this high dose were three times as likely — and male smokers taking B12 at this high dose were four times as likely — to develop lung cancer as men not taking these supplements.
The analysis controlled for numerous factors, including personal smoking history, age, race, education, body size, alcohol consumption, personal history of cancer or chronic lung disease, family history of lung cancer, and use of anti-inflammatory drugs.
“This sets all of these other influencing factors as equal, so we are left with a less confounded effect of long-term B6 and B12 super-supplementation,” Dr Brasky commented.
The researchers address the intriguing finding of why the association was seen only in men and not women, who actually formed a sizeable proportion of the study population (44% of total).