Study under review: The Effects of Four Doses of Vitamin D Supplements on Falls in Older Adults : A Response-Adaptive, Randomized Clinical Trial
An estimated one in four (28.7%) U.S. adults older than 65 had a fall in 2014. One in four (25%) of those falls resulted in an injury. Falls among older adults ultimately resulted in nearly $32 billion in related medical expenses in 2015. Alleviating this burden represents an opportunity to foster the health and safety of older people and decrease medical expenses. This is, however, a complex problem.
Vitamin D has been suggested as a primary target for intervention for two main reasons. First, it plays a critical role in bone formation, healthy bone structure, and bone mineral density. These effects on bone integrity could mitigate the damage done by falls when they occur. (Read more about fractures and vitamin D in this March 2018 Study Deep Dives article.) Vitamin D is also essential for muscle function, suggesting it could play a role in preventing falls in the first place by maintaining strength, balance, and coordination. However results from a 2018 clinical trial in post-menopausal women suggests that higher dose (2,800 IU) supplementation might actually decrease muscle strength (read the Mini here).
Second, vitamin D deficiency and insufficiency is widespread, with 28.9% of U.S. adults meeting the Endocrine Society’s criteria for deficiency (25(OH)D of less than 50 nmol/L) and 41.4% of adults considered to have insufficient levels (25(OH)D levels (50–75 nmol/L). Furthermore, adults older than 60 years old are around 63% more likely to have vitamin D deficiency and 46% more likely to have vitamin D insufficiency than young adults. This age-related decrease in vitamin D status may be the result of decreased synthesis from ultraviolet light, decreased mobility and thus decreased exposure to ultraviolet light, decreased vitamin D receptor expression, and inadequate dietary vitamin D intake. Overall, the high prevalence of vitamin D insufficiency and deficiency in high-risk older populations means that plenty of people could potentially benefit from supplementation.
It’s reasonable to say, based on previous research, that vitamin D supplementation in the context of severe vitamin D deficiency (less than 20–25 nmol/L) is important for modifying the risk of falls, muscle function, and improving bone mineral density. But what about the efficacy of supplementing in a population with marginal deficiency or insufficiency, i.e. people who probably don’t need high doses of vitamin D to achieve adequacy? Unfortunately, the results of numerous individual studies are mixed, with some studies suggesting mild benefit, others no benefit, and still others implying potential harm.
For example, one nine-month RCT testing the effects of 150,000 IU of vitamin D3 supplementation every three months in older, community-dwelling, postmenopausal women showed no differences between vitamin D and placebo on adverse effects, falls, mobility, or muscle strength. A three-year RCT testing 800 IU of D3 daily with 500 mg of calcium vs. placebo in community dwelling older men and women showed that supplementation reduced fall risk in women, especially those with low baseline physical activity, but did not show a significant effect on men. Another study of note showed that among older community-dwelling women, annual oral administration of 500,000 IU of D3 resulted in an increased risk of falls and fractures, confirming the lackluster or sometimes detrimental effects of vitamin D supplements on fall risk.
One comparative review has attempted to clarify why different meta-analyses of vitamin D and fall risk come to different conclusions. The authors conclude that it comes down to issues that could be found in any meta-analysis: differences in study inclusion/exclusion, differences in data extraction, and differences in statistical analysis.
When it comes to falls and frailty, all the evidence points to a U-shaped relationship between vitamin D levels and fall risk, similar to what researchers have noted for cancer, cardiovascular disease, and fractures. Supplementing with vitamin D to adequacy appears to significantly improve fall risk, but supplementing beyond adequacy may do more harm than good.
Prior to the initiation of the present study in 2015, there had been a number of recommendations for vitamin D supplementation for fall prevention in older adults, each based on extensive reviews. Even though each set of guidelines aims to summarize the totality of clinical evidence, each one arrived at a different, sometimes substantially different, conclusion. The main takeaways of these guidelines are laid out in Figure 1.
|Organization||Blood level targets||Dose of supplemental vitamin D||Applicable population|
American Geriatrics Society Workgroup on Vitamin D Supplementation for Older Adults
25(OH)D concentration of 75 nmol/L (30 ng/mL) as a minimum goal.
At least 1,000 IU daily alongside calcium.
Everyone over 65 years old, whether or not they live independently or in an institutionalized setting.
States that an exact target is somewhat controversial, but defers to the standard definitions of 25(OH)D) levels of 50 nmol/L (20 ng/mL) indicating deficiency, and 75 nmol/L (30 ng/mL) indicating insufficiency.
At least 600–800 IU daily, but up to 2,000 IU daily may be needed to raise 20(OH)D to sufficient levels.
600 IU is the lowest dose for people ages 50–70, an 800 IU for people 70 and above.
International Osteoporosis Foundation
25(OH)D concentration of 75 nmol/L (30 ng/mL) as a minimum goal.
800–1,000 IU daily would make many, but not all, people vitamin D sufficient. But since higher doses haven’t been established to prevent falls, they don’t necessarily recommend higher doses for all older adults.
People ages 60–65 years and up.
US Preventive Services Task Force
Only to prevent deficiency (25(OH)D concentration below 50 nmol/L or 20 ng/mL).
Not applicable: This group recommends against the routine use of vitamin D supplementation to prevent falls or fractures.
Community-dwelling people over 65 years without osteoporosis and without vitamin D deficiency.
Institute of Medicine
Not applicable for fall prevention.
Insufficient evidence for fall prevention. This group recommends sticking with the RDA of 800 IU daily intake for this age group, supplementing as needed to achieve that intake level.
Adults 70 years and older.
As a result of the suggestive, but ultimately inconclusive, research around vitamin D supplementation and fall risk, the National Institute on Aging (NIA) funded a clinical trial to assess the dose-response relationship between vitamin D ranging from the minimum dose necessary for adequacy to the upper limit of official recommendations and falls in a high-risk population.
Vitamin D deficiency is associated with poor bone health, poor muscle health, general frailty, and increased risk for falls, yet it is not entirely clear whether this relationship is causal. Vitamin D supplementation has been recommended for preventing falls in older adults by a number of organizations, and recommended against by others, reflecting the inconsistent results seen in clinical trials. This study, funded by the National Institute of Aging, aimed to clarify the effect of different doses of vitamin D on risk of falls in community-dwelling older adults with baseline deficient/insufficient vitamin D status.
Other Articles in Issue #77 (March 2021)
NERD Mini: Takeaways from the ISSN's position on caffeine and exercise performance
We break down some key takeaways from the International Society for Sports Nutrition's newly-updated position stance on caffeine's use in exercise performance.
D-creasing asthma symptoms with supplementation
Calcifediol is the form of vitamin D that's often checked in the blood to monitor vitamin D levels. This trial found that supplementing this form of vitamin D can improve asthma symptoms in people with vitamin D insufficiency.
Deep Dive: Micronutrients with micro-effects for preventing and treating acute respiratory infections
This meta-analysis found evidence that supplementing vitamins C and D may prevent the risk of acute respiratory infections, but only by a tiny amount. Zinc has a more sizable effect, but only once symptoms have set in.
The effects of full fasting vs. modified fasting on cognitive performance
How does full fasting impact mental functioning compared to very low-calorie intake over the course of a day? This study aimed to find out.
Nulls: November–December 2020
Highlights include omega-3's lack of impact on bipolar disorder, whether adding vitamin C to iron helps iron deficiency anemia outcomes, and more!
Battling exercise-induced muscle damage with omega-3s
This small study provides preliminary evidence that a high-dose mix of EPA and DHA may combat early post-exercise muscle soreness.
Deeper Dive: Do I have to choose between osteoporosis and heart disease?
A recent meta-analysis suggests that calcium supplementation leads to a small but significant increased risk of heart disease. In this review, we put this risk in context.