Routine Monthly High-Dose Vitamin D Supplementation Does Not Reduce Mortality in the Elderly, Trial Shows

Vitamin D is an essential nutrient whose role in bone growth and health, including preventing bone softening in children (rickets) and adults (osteomalacia), is well-documented.[1]

However, the benefits of this vitamin for improving longevity are uncertain. Although evidence from observational studies suggests an association between low vitamin D levels in the blood and acute or chronic adverse health outcomes,[2] no previous large, randomized clinical trial of high-dose vitamin D supplementation has studied death as a primary outcome.

To address this evidence gap, a well-designed, Australian government-funded, placebo-controlled clinical trial called the D-Health Trial assessed the effect of monthly high-dose oral vitamin D supplementation for five years on mortality as a primary outcome in the elderly.[3] The trial, which is the largest that has examined this issue to date, showed that long-term supplementation with monthly high-dose vitamin D was not useful for decreasing all-cause (overall) mortality in elderly adults who were not screened for vitamin D deficiency.

The results of the D-Health trial were published in the February 2022 issue of The Lancet Diabetes and Endocrinology.

Vitamin D sources and daily requirements

Vitamin D is available in several foods. It is found naturally in some fatty fishes, fish-liver oils, egg yolks and chicken livers. Food producers in the U.S. also fortify many foods with vitamin D, including milk, orange juice and breakfast cereals. In addition, vitamin D is produced naturally in the skin during direct exposure to sunlight. Some experts suggest that up to 30 minutes of sun exposure, particularly between 10 a.m. and 4 p.m., at least twice weekly to the face, arms, hands and legs without sunscreen leads to sufficient vitamin D synthesis.[4] People with dark skin and the elderly are less able to produce vitamin D from sunlight.[5],[6]

Several forms of vitamin D supplements are available for people who clearly have inadequate vitamin D dietary intake and skin production from sun exposure. The most commonly used forms are cholecalciferol, also known as vitamin D₃, and ergocalciferol, or vitamin D₂.[7]

Overall, U.S. nutritional guidelines recommend that healthy adults up to age 70 consume 600 international units (IU) of vitamin D daily.[8] After age 70, the recommended daily allowance increases to 800 IU.

There is no consensus about the threshold for vitamin D sufficiency; however, vitamin D₃ blood levels of 50 nanomoles per liter (nmol/L) or more are generally considered adequate for most people.[9]

The D-Health Trial[10]

A total of 21,310 Australian subjects whose ages ranged from 60 to 84 years enrolled in the trial until its completion and were randomized to one of the two trial groups: 10,661 received a monthly gel capsule with 60,000 IU of vitamin D and the remaining 10,649 received monthly placebo gel capsules.

Subjects in both groups took their assigned capsules for five years and the researchers evaluated the trial outcomes one year later to capture any prolonged effects of vitamin D supplementation.

Of the total sample, 54% were men and the mean age was 69 years. The trial excluded subjects with self-reported history of certain conditions including kidney stones, hypercalcemia (high blood calcium levels), hyperparathyroidism (overactivity of the parathyroid gland) and osteomalacia. Retention in the trial and compliance with assigned capsules among subjects of both groups were high.

Because the researchers were interested in routine administration of vitamin D in the elderly, they did not screen the subjects for vitamin D deficiency before enrolling them in the trial. However, subjects in both groups were vitamin D-replete; average D₃ blood levels in randomly sampled vitamin D and placebo subjects during the trial follow-up were 115 and 77 nmol/L, respectively.

Using six-year follow-up data, the researchers found that all-cause mortality and mortality from cancer and cardiovascular disease were similar among subjects in the two groups. In fact, an exploratory analysis that excluded data from the first two years of follow-up found a mild increase in cancer mortality among subjects in the vitamin D group.

Therefore, the researchers concluded that routine supplementation of older adults with vitamin D in populations that are largely vitamin D-replete is unlikely to reduce overall or cardiovascular mortality. They also cautioned against long-term use of the trial’s high vitamin D dosing regimen in the real world.

An important shortcoming of the trial is that it was not focused on subjects with low vitamin D blood levels, who may be more likely to benefit from vitamin D supplementation.[11]

What You Can Do

You should not take high-dose vitamin D supplements to reduce your risk of death. You generally do not need to take any vitamin D supplements unless you do not consume enough vitamin D from dietary sources, do not get enough direct exposure to sunlight or have a medical condition that predisposes you to vitamin D deficiency.[12] Talk to your doctor before taking vitamin D or any other supplement to avoid overdosing and related adverse effects.
 

References

[1] Office of Dietary Supplements. National Institutes of Health. Vitamin D: Fact sheet for health professionals. April 22, 2022. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/. Accessed May 31, 2022.

[2] Schoenmakers I. Vitamin D supplementation and mortality. Lancet Diabetes Endocrinol. 2022;10(2):88-90.

[3] Neale RE, Baxter C, Romero BD, et al. The D-Health trial: a randomised controlled trial of the effect of vitamin D on mortality. Lancet Diabetes Endocrinol. 2022;10(2):120-128.

[4] Office of Dietary Supplements. National Institutes of Health. Vitamin D: Fact sheet for health professionals. April 22, 2022. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/. Accessed May 31, 2022.

[5] Ibid.

[6] MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest. 1985;76(4):1536-1538.

[7] Ibid.

[8] Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press.

[9] Office of Dietary Supplements. National Institutes of Health. Vitamin D: Fact sheet for health professionals. April 22, 2022. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/. Accessed May 31, 2022.

[10] Neale RE, Baxter C, Romero BD, et al. The D-Health trial: a randomised controlled trial of the effect of vitamin D on mortality. Lancet Diabetes Endocrinol. 2022;10(2):120-128.

[11] Schoenmakers I. Vitamin D supplementation and mortality. Lancet Diabetes Endocrinol. 2022;10(2):88-90.

[12] Office of Dietary Supplements. National Institutes of Health. Vitamin D: Fact sheet for health professionals. April 22, 2022. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/. Accessed May 31, 2022.