Vitamin supplementation is popular among US adults; however, both insufficient and excess intakes of a nutrient may be harmful and lead to unexpected adverse effects. Results from a study of female registered nurses demonstrated that excessive intake of vitamins B6 and B12 was associated with an increased risk for hip fracture, according to JAMA Network Open.

Postmenopausal women from the Nurses’ Health Study (n=75,864) were followed up for vitamin B use from June 1984 to May 2014; the study was conducted from July 2016 to June 2018. Women were administered questionnaires every 2 years assessing medical history, lifestyle, and disease risk factors and identifying incident diagnoses. On every follow-up questionnaire, information about hip fracture was requested, including the date of occurrence and description of circumstances. A total of 2304 fractures were recorded in all women respondents.

Diet was assessed with a semi-quantitative food frequency questionnaire (FFQ) in 1984, 1986, and every 4 years thereafter until 2010. Respondents reported their habitual frequency of consumption of specified serving sizes of more than 130 foods. The FFQ also assessed the current use of supplements such as vitamin B6, folic acid, vitamin B complex, and vitamin B12, including daily dosage. Additional non-dietary measures such as weight and exercise were reported on all biennial follow-up questionnaires. Questions on balance and walking were initiated on questionnaires in 1992 and questions on falls and anemia were included from 1998 onward.

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Median age at hip fracture was 75.8; these respondents had a median body mass index (BMI) of 24.3 and cumulative average intakes of total vitamins B6 and B12 of 3.6 and 12.1, respectively. Compared with the reference range of total vitamin B6 intake of <2 mg/d, an intake of at least 35 mg/d was associated with an increased risk for hip fracture. For total vitamin B12, intakes of at least 30 µg/d were associated with a nonsignificant increased risk for hip fracture compared with intakes <5 µg/d, and risk increased with increasing intake.

Women with a high intake of both vitamins had a significantly increased risk for hip fracture compared with a low intake of both vitamins. Risk was not significantly elevated for medium-intake of both vitamins. Women with a BMI of <25 were at increased risk for hip fracture with vitamins B6 and B12.

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“In this large prospective cohort study of postmenopausal women in the Nurses’ Health Study, we found that a combined high intake of vitamins B6 and B12 was associated with an increased risk of hip fracture,” the investigators concluded. “These findings add to previous studies suggesting that vitamin supplements should be used cautiously because adverse effects can occur.”


Meyer HE, Willett WC, Fung TT, Holvik K, Feskanich D. Association of high intakes of vitamins B6 and B12 from food and supplements with risk of hip fracture among postmenopausal women in the Nurses’ Health Study. JAMA Netw Open. 2091;2(5):e193591.