Vitamin supplementation in healthy patients: What does the evidence support?

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doi:doi: 10.12788/jfp.0288

Applied Evidence

Vitamin supplementation in healthy patients: What does the evidence support?

J Fam Pract. 2021 October;70(8):386-398d | doi: 10.12788/jfp.0288

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References

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119. Hemilä H, Louhiala P. Vitamin C for preventing and treating pneumonia. Cochrane Database Syst Rev. 2013;(8):CD005532. doi:10.1002/14651858.CD005532.pub3

120. Padhani ZA, Moazzam Z, Ashraf A, et al. Vitamin C supplementation for prevention and treatment of pneumonia. Cochrane Database Syst Rev. 2020;4:CD013134. doi:10.1002/14651858.CD013134.pub2

121. Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of cancer in adults. Cochrane Database Syst Rev. 2014;(6):CD007469. doi:10.1002/14651858.CD007469.pub2

122. Autier P, Mullie P, Macacu A, et al. Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol. 2017;5:986-1004. doi:10.1016/S2213-8587(17)30357-1

123. Wagner CL, Greer FR; American Academy of Pediatrics Section on Breastfeeding, American Academy of Pediatrics Committee on Nutrition. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008;122:1142-1152. doi:10.1542/peds.2008-1862

124. Hollis BW, Wagner CL, Howard CR, et al. Maternal versus infant vitamin D supplementation during lactation: a randomized controlled trial. Pediatrics. 2015;136:625-634. doi:10.1542/peds.2015-1669

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Vitamin B12

Vitamers: Cyanocobalamin; hydroxocobalamin; methylcobalamin; adenosylcobalamin

Physiologic role: Required for red blood cell formation, neurologic function, and DNA synthesis

Dietary sources: Only in animal products: fish, poultry, meat, eggs, and milk/dairy products. Not present in plant foods. Fortified cereals, nutritional yeast are sources for vegans/vegetarians.

Given their linked physiologic roles, vitamins B9 and B12 are frequently studied together. Folate and cobalamins play key roles in nucleic acid synthesis and amino acid metabolism, with their most clinically significant role in hematopoiesis. Vitamin B12 is also essential to normal neurologic function.²

The US Preventive Services Task Force (USPSTF) recommends preconceptual folate supplementation of 0.4-0.8 mg/d in women of childbearing age to decrease the risk of fetal neural tube defects (grade A).²¹ This is supported by high-quality RCT evidence demonstrating a protective effect of daily folate supplementation in preventing neural tube defects.²² Folate supplementation’s effect on other fetal birth defects has been investigated, but no benefit has been demonstrated. While observational studies have suggested an inverse relationship with folate status and fetal autism spectrum disorder,^23-25 the RCT data is mixed.²⁶

A potential role for folate in cancer prevention has been extensively investigated. An expert panel of the National Toxicology Program (NTP) concluded that folate supplementation does not reduce cancer risk in people with adequate baseline folate status based on high-quality meta-analysis data.^27,104 Conversely, long-term follow-up from RCTs demonstrated an increased risk of colorectal adenomas and cancers,^28,29 leading the NTP panel to conclude there is sufficient concern for adverse effects of folate on cancer growth to justify further research.¹⁰⁴

While observational studies have found a correlation of increased risk for disease with lower antioxidant serum levels, RCTs have not demonstrated a reduction in disease risk with supplementation.

Given folate and vitamin B12’s homocysteine-reducing effects, it has been theorized that supplementation may protect from cardiovascular disease. However, despite extensive research, there remains no consistent patient-oriented outcomes data to support such a benefit.^31,32,105

The evidence is mixed but generally has found no benefit of folate or vitamin B12 supplementation on cognitive function.^18,33-35 Finally, RCT data has failed to demonstrate a reduction in fracture risk with supplementation.^36,106

The takeaway: High-quality RCT evidence demonstrates a protective effect of preconceptual daily folate supplementation in preventing neural tube defects.²² The USPSTF recommends preconceptual folate supplementation of 0.4-0.8 mg/d in women of childbearing age to decrease the risk of fetal neural tube defects.

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