VITAMIN D AFTER 50: WHAT THE BIG TRIALS ACTUALLY FOUND

Vitamin D has a reputation as the easy supplement: cheap, widely taken, and linked in the popular imagination to bones, muscle, and falls. The large randomized trials have tested those ideas directly, and what they measured is more specific than that reputation.

Fractures: the VITAL ancillary study

The largest test of vitamin D for bone health is an ancillary study of the VITAL trial, published in the New England Journal of Medicine in 2022 (LeBoff et al.). It followed 25,871 adults, men 50 and older and women 55 and older, randomized to 2,000 IU of vitamin D3 daily or placebo, with a median follow-up of 5.3 years.

Supplemental vitamin D3 did not have a significant effect on total fractures, which occurred in 769 of 12,927 participants on vitamin D and 782 of 12,944 on placebo (hazard ratio 0.98, 95% CI 0.89 to 1.08). There was no significant effect on nonvertebral fractures (HR 0.97) or hip fractures (HR 1.01). The treatment effect did not differ by age, sex, race or ethnic group, body-mass index, or baseline blood vitamin D level.

The scope matters. VITAL enrolled generally healthy adults who were not selected for vitamin D deficiency, low bone mass, or osteoporosis. It tells you about supplementation in that population. It does not test treatment of a diagnosed deficiency or osteoporosis under a physician's care.

Falls: the STURDY trial

STURDY, published in Annals of Internal Medicine in 2021 (Appel et al.), enrolled 688 adults aged 70 and older who were at elevated fall risk and had blood 25(OH)D levels between 25 and 72.5 nmol/L. It compared four daily doses: 200 IU as the control, and 1,000, 2,000, or 4,000 IU.

In the dose-finding stage, the rate of first falls or death was higher in the 2,000 and 4,000 IU groups than in the 1,000 IU group. The hazard ratios versus 1,000 IU were 1.54 (95% CI 1.01 to 2.34) for 2,000 IU and 1.41 (95% CI 0.92 to 2.16) for 4,000 IU. The 4,000 IU interval crosses 1.

The 1,000 IU dose was then carried forward and compared with 200 IU. It did not prevent falls (HR 0.94, 95% CI 0.76 to 1.15). Analyses of falls with adverse outcomes suggested greater risk in the 1,000 IU group than in the 200 IU group: serious falls HR 1.87 (95% CI 1.03 to 3.41) and falls with hospitalization HR 2.48 (95% CI 1.13 to 5.46).

The authors noted two limitations: the control group received 200 IU rather than a placebo, and dose finding ended before its prespecified thresholds were reached. Their conclusion was that doses of 1,000 IU or higher did not prevent falls compared with 200 IU, and that several analyses raised safety concerns about doses of 1,000 IU or higher.

Strength and performance in athletes

Low vitamin D is common in athletes. A 2015 systematic review and meta-analysis in Sports Medicine (Farrokhyar et al.) pooled 23 studies and 2,313 athletes, mean age 22.5, and found 56 percent (95% CI 44 to 67) had inadequate levels. Risk was higher in winter and spring (RR 1.85) and for indoor sports (RR 1.19). That population was young and mostly male.

Whether supplementation changes strength is a separate question. A 2024 systematic review and meta-analysis in Frontiers in Nutrition (Han et al.) pooled 10 randomized controlled trials with 318 athletes:

• Overall strength: SMD 0.18 (95% CI −0.02 to 0.37), p = 0.08, not significant
• 1-RM bench press: SMD −0.15, p = 0.47
• Handgrip: SMD 0.21, p = 0.35
• Vertical jump: SMD 0.21, p = 0.17
• Quadriceps contraction: SMD 0.57 (95% CI 0.04 to 1.11), p = 0.04, the one significant finding

Supplementation raised blood levels. The authors concluded that, with limited available studies, it "cannot warrant significant overall enhancements in muscle strength" when athletes reach adequate blood levels through supplementation.

What the trials do and don't cover

These trials tested supplementation in adults who were mostly not selected for deficiency. Treating a measured deficiency is a different clinical question, and a 25(OH)D blood test is how that question gets answered. It often isn't on a standard panel unless requested.

For falls specifically, exercise has its own evidence base. A 2019 Cochrane review (Sherrington et al., 108 trials, 23,407 participants) rated balance and functional exercise as reducing the rate of falls with high-certainty evidence (rate ratio 0.76).

The Protocol

• Ask for a 25(OH)D level at your next blood draw.
• If you are deficient, treat it with your doctor, and retest rather than assuming a dose worked.
• If you are taking a high daily dose without a documented deficiency, raise it with your physician. STURDY's safety signals appeared at 1,000 IU and above, and dose decisions depend on your own levels, kidney function, and calcium intake.
• For fall risk, the Cochrane evidence above is for balance and functional exercise.