A combined high intake of vitamins B6 and B12, much higher than recommended dietary allowances (RDAs), is linked to an increased hip fracture risk, new data show.
"The RDAs are established to meet the nutritional requirements of almost the entire population. Despite that, use of high-dose vitamin supplementation far exceeding the RDAs is common, often without any definite indication and in the absence of clear evidence of benefit," write Haakon E. Meyer, MD, PhD, Department of Community Medicine and Global Health, University of Oslo, Norway, and colleagues.
"These findings add to previous studies suggesting that vitamin supplements should be used cautiously because adverse effects can occur," they continue.
Meyer, also from the Department of Nutrition at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts, and colleagues published their findings online May 10 in JAMA Network Open.
The researchers analyzed data from the Nurses' Health Study (NHS). The prospective cohort study included 75,864 postmenopausal women who were followed from June 1984 through May 2014. Participants in the NHS completed a baseline questionnaire about medical history, lifestyle, and disease risk factors, and biennial follow-up questionnaires thereafter. Approximately every 4 years, extensive dietary information was also collected.
During follow-up, 2304 participants (3%) had a hip fracture. The median age at time of fracture was 75.8 years (range, 46.7 – 93.0) years. The mean body mass index among those who experienced hip fractures was 24.3 kg/m2.
Among those with a hip fracture, the median cumulative average intakes of total vitamins B6 and B12 were 3.6 mg/day (interquartile range, 4.8) of total vitamin B6 and 12.1 μg/day (interquartile range, 11.7) of total vitamin B12.
Compared with those who consumed less than 2 mg/day of total vitamin B6, those whose intake was 35 mg/day or higher had an increased risk for hip fracture after adjusting for potential dietary and nondietary confounders (relative risk [RR], 1.29; 95% confidence interval [CI], 1.04 - 1.59; P = .06 for linear trend).
Total vitamin B12 intake of 30 μg/day or higher was linked to a trend toward higher risk for hip fracture compared with intakes lower than 5 μg/day (RR, 1.25; 95% CI, 0.98 - 1.58), but the difference did not reach statistical significance. However, this risk rose linearly as intake increased (RR, 1.01; 95% CI, 1.00 - 1.03 per 10-μg/day increase in total intake; P for linear trend = .02).
The highest risk was seen in women whose combined intake of both vitamins was high (B6, ≥35mg/day and B12, ≥20 μg/day); hip fracture risk for these women was increased by almost 50% (RR, 1.47; 95% CI, 1.15 - 1.89) compared with women whose intake of both vitamins was low (B6, <2mg/day and B12, <10 μg/day).
The risk was not significantly higher among women whose intake of both vitamins was in the medium range (RR, 1.18; 95% CI, 0.98 - 1.42).
"Few women had low intakes of one vitamin and high intakes of the other" the researchers note.
The researchers say possible biological explanations for the study findings are unclear, but they emphasize that the women's intake of both vitamins far exceeded recommended dietary allowances.
Strengths of the study include its large cohort and the biennial in-depth assessments of diet, supplement intake, and other possible confounders.
Still, the researchers say they could not exclude the possibility that some women began taking supplements as a result of poor health, and the use of questionnaires may have influenced the quality of data collected. The authors caution that the findings may only apply to women of white race/ethnicity.
The study authors have disclosed no relevant financial relationships.
JAMA Network Open. Published online May 10, 2019. Full text
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