Active vitamin D counteracts age-related muscle loss

Age-related muscle loss, also known as sarcopenia, is characterized by a progressive decline in muscle mass, which increases the risk of various diseases and premature death. Evidence suggests that active vitamin D regulates muscle protein synthesis and thereby helps prevent sarcopenia, particularly in people with prediabetes. This is reported in a Japanese placebo-controlled study published in Metabolism.

From the age of 50, the body naturally loses 1-2 percent of its muscle mass per year, and after 60, the process accelerates. Excessive loss of muscle mass and strength may result in sarcopenia, which can reduce quality of life. Type 2 diabetes, prediabetes, and overweight also increase the risk of sarcopenia. In severe cases, sarcopenia is associated with higher risks of falls, other diseases, nursing home admission, hospitalization, and premature death.
With a growing elderly population worldwide and the global spread of type 2 diabetes, sarcopenia has become an increasing human and socio-economic challenge. Overall, sarcopenia may be linked to hormonal changes, physical inactivity, and an unhealthy diet - including insufficient intake of proteins (amino acids) and other nutrients needed for muscle building.
While animal studies have shown that vitamin D supplementation has a positive effect on sarcopenia, randomized controlled trials in humans have produced mixed results regarding muscle mass, strength, and physical performance. To some extent, this may be because the doses used were too low to optimize blood levels of the nutrient. It may also be due to the fact that overweight individuals and those with prediabetes or diabetes have difficulty converting vitamin D from sunlight or standard supplements into the active steroid form (calcitriol/1,25-dihydroxyvitamin D3).
The new Japanese study therefore aimed to investigate the effects of supplementation with eldecalcitol, a form of vitamin D equivalent to the active form, calcitriol.
The study included 32 prediabetic men and women over 30 years of age who did not have sarcopenia. Participants were divided into two groups: one received daily supplements of the active vitamin D form, while the other received a placebo. The study lasted one year.
Before the study began and at its conclusion, researchers examined changes in molecules involved in muscle tissue synthesis and breakdown. They also measured participants’ total muscle and fat mass using various analytical methods.
The study revealed that one year of treatment with the active vitamin D form, compared with placebo, resulted in:

• Higher phosphorylation of specific signaling pathways (mTOR and FOXO1), associated with increased muscle mass and strength
• Greater muscle mass
• Lower fat mass

The researchers concluded that the active form of vitamin D both regulates protein synthesis for muscle building and counteracts muscle breakdown, thereby helping prevent sarcopenia.

Vitamin D activation and why it’s challenging in diabetes and overweight

Vitamin D regulates approximately 10 percent of our genes and many other functions that are critical not only for muscle building but also for bone health, immune function, the nervous system, blood sugar regulation, cancer prevention, and more.
The form of vitamin D (cholecalciferol) that we normally produce in our skin from UVB sunlight or obtain from supplements is inactive. First, the liver converts cholecalciferol into calcidiol, which is measured in the blood as 25-hydroxyvitamin D3. In order to be used for various functions, calcidiol must further be converted in the kidneys and other tissues into the active steroid form, calcitriol (1,25-dihydroxyvitamin D3).
Magnesium is also required for these conversions in the liver, kidneys, and other tissues. Magnesium deficiency, which is widespread, can therefore reduce the effectiveness of vitamin D obtained from sunlight or standard supplements. Studies show that overweight individuals, prediabetics, and diabetics often have low magnesium levels and have greater difficulty converting vitamin D due to metabolic disturbances.
In any case, it is important to maintain optimal blood levels of vitamin D (above 75 nmol/L), often requiring higher doses than official recommendations - especially for those who are overweight or have prediabetes/diabetes.
You can read more about this in the following article:

»The link between magnesium deficiency, overweight, diabetes, and metabolic disorders«

References:

Tetsuya Kawahara et al. Anti-sarcopenic effects of active vitamin D through modulation of anabolic and catabolic signaling pathways in human skeletal muscle: A randomized controlled trial. Metabolism 2025

Ligia J Dominguez et al. The Role of Magnesium in the Pathogenesis of Metabolic Disorders. Nutrients 2022 May