A small study in mice suggests that a dosage of vitamin D five times the current recommended amount for older adults could slow the development of frailty. However, the researchers now need to confirm this finding in humans.
Doctors currently define a person as “frail” if they display three or more of the following five characteristics:
- unexpected weight loss
- weak grip strength
- self-reported exhaustion
- low levels of physical activity
- slow walking speed
Frailty tends to increase with age, affecting around half of individuals aged over 85 years. It is associated with disability, loss of independence, and increased rates of mortality.
Research suggests that people who have low levels of vitamin D in their blood are more likely to become frail. This is a particularly pressing concern, as up to 1 billion people globally may have insufficient levels.
The body can synthesize its own vitamin D when the skin has exposure to the UV light in sunlight. However, during winter months in higher latitudes, and for people who spend most of their time indoors, the principal sources of vitamin D are diet and supplements.
There is some uncertainty about the amounts of vitamin D a person should consume.
The National Academy of Medicine recommend a daily intake of 600 international units (IU) for adults aged 19–70 years and 800 IU per day for individuals aged 70+ years.
According to a research group at the Veterans Affairs Western New York Healthcare System and the University at Buffalo — both in Buffalo, NY — these recommendations are largely based on optimizing bone health.
They believe that much higher levels are necessary to maintain muscle strength and prevent frailty.
Their previous research in “middle-aged” mice suggests that a long-term insufficient intake of vitamin D in middle age may result in an impaired capacity for anaerobic exercise, decreased muscle mass, and increased amounts of adipose, or fat, tissue.
Their latest work in mice, which appears in the journal Nutrients, indicates that not getting enough of the vitamin in older age may accelerate the development of frailty.
“We found that in aged mice, low levels of vitamin D [resulted] in physical declines, such as reduced grip strength and grip endurance — the ability to sustain a grip — and that they started developing as soon as 1 month after reduction of vitamin D intake,” says first study author Kenneth L. Seldeen, Ph.D.
Crucially, vitamin D only protected the mice from these effects when intake was several times higher than the equivalent recommended intake for older adults.
“To slow the progression of frailty, it actually took greater amounts of vitamin D than what is currently considered sufficient for a human,” says Seldeen.
The scientists monitored mice aged 24–28 months, which equates to 65–80-year-old humans. At the start of the study, they divided the animals into three groups:
- insufficient intake of vitamin D (defined as 125 IU per kilogram [kg] of feed)
- sufficient intake (1,000 IU per kg of feed)
- “hypersufficient” intake (8,000 IU per kg of feed)
Over the next 4 months, they assessed the animals’ physical performance and scored them on five tests of frailty equivalent to those that doctors use to assess humans.
By the end of the study period, the mice that had an insufficient or sufficient intake of vitamin D were significantly more frail than they had been at the start of the experiment.
By contrast, the mice with a hypersufficient intake were slightly more frail by the end of the study, but the increase was not statistically significant.
It is also worth noting that although there was an increase in frailty scores, by the 4-month endpoint, none of the groups of mice met the researchers’ definition of frail.
The researchers already recommend that older human adults take a minimum of 2,000 IU of vitamin D per day.
“This is particularly important for our frail geriatric patients,” says senior study author Dr. Bruce R. Troen, a professor of medicine. “But based upon our research, we believe that a lifetime of ample vitamin D supplementation will optimize long-term functional capacity and health.”
The new study suggests that a maximum daily dosage of 4,000 IU, which the National Academy of Medicine consider the safe upper limit, would be necessary to slow the progression of frailty in old age.
A dose of 1 IU is equivalent to 0.025 micrograms (mcg) of vitamin D in a supplement, so 4,000 IU is equivalent to 100 mcg.
Lack of research in humans
A single, brief, and very small study in male mice is limited evidence to address the question of the optimum dosage of vitamin D for older human adults.
Also, the complicated nature of the findings is highlighted by a lack of impact on measures such as muscle mass or treadmill performance.
However, a clinical investigation would need to run for at least 5 years to validate the results in humans, say the study authors. They add that it may not be safe to test persistently high or low levels of vitamin D over such a long period.
As Seldeen explains, “Using an animal model, we are able to examine these potentially riskier levels of vitamin D and the biological impacts during aging.”
“Also, doing so in genetically identical mice all living the same lifestyle, compared to the complexity of human diversity, allows greater focus on the specific effects caused by the different vitamin D levels.” – Kenneth L. Seldeen, Ph.D.
Nonetheless, human studies are accepted to be important in ensuring safe dietary guidelines for people, and the researchers do plan to pursue such studies in the future.