The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 9 No.
2 • April 2006
Glucocorticoids Induce Muscle Wasting: Could Vitamin D Provide Protection?
Part of the process of sarcopenia (loss of muscle mass with aging) may involve the action of glucocorticoids, which not only enhance muscle protein degradation but also reduce protein synthesis. A study of young (4–5 weeks), adult (10–11 months), and old (21–22 months) rats receiving the synthetic glucocorticoid dexamethasone (Dex) in their drinking water showed that Dex did not alter muscle-protein synthesis stimulation by leucine in young rats, but muscles from adult and old rats became totally resistant to the anabolic effects of leucine. Moreover, the recovery of leucine responsiveness after Dex treatment discontinuation in the old rats was slower than that in younger rats. One of the mechanisms by which glucocorticoids affect muscle protein synthesis is by inducing insulin resistance, the inhibition of muscle response to insulin, an anabolic hormone.
The published data support an association between vitamin D deficiency and reduced insulin sensitivity and pancreatic beta-cell dysfunction (an impairment in insulin secretion). One paper studied the relationship between blood levels of vitamin D on plasma glucose concentration and insulin sensitivity in 126 healthy glucose-tolerant (fasting glucose levels below 110 mg/dL) human subjects. The authors found that there was a significant positive correlation of vitamin D concentration with insulin sensitivity and a negative effect of vitamin D deficiency on pancreatic beta-cell function. An oral glucose tolerance test showed that there was “a significant and negative interaction of 25(OH)D [vitamin D metabolite] concentration with 60-, 90-, and 120-minute post-challenge [i.e., following a standard glucose bolus] plasma glucose concentrations.” Subjects with vitamin D deficiency were at increased risk of the metabolic syndrome (as determined by analysis of risk factors) as compared to those with normal vitamin D levels. Here, the authors report that “… serum 25-hydroxyvitamin D explained only 6% of the variation in insulin sensitivity in our study.”
The researchers also cite studies in which vitamin D supplementation improved insulin secretion in vitamin D-deficient and nondiabetic subjects, as well as in patients with type 2 diabetes. Hence, we suggest that adequate vitamin D levels may help to attenuate the negative effects of glucocorticoids on insulin sensitivity.
While we have no specific information linking vitamin D to muscle-protein synthesis in response to glucocorticoids or leucine stimulation, it is interesting to note that higher vitamin D levels in a population of 4100 ambulatory U.S. adults greater than or equal to 60 were associated with better lower-extremity function. Vitamin D receptors have been identified in muscle. Cross-sectional studies have shown that elderly persons with higher vitamin D serum levels have increased muscle strength and fewer falls. A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone in a study of 122 elderly women (mean age 85.3 years). The 62 individuals on the vitamin D plus calcium regimen received 1200 mg calcium plus 800 IU cholecalciferol (vitamin D), while the 60 subjects not receiving vitamin D received 1200 mg calcium; treatment lasted 12 weeks.
- Rieu et al. Glucocorticoid excess induces a prolonged leucine resistance on muscle protein synthesis in old rats. Exp Gerontol 39:1315-21 (2004).
- Chiu et al. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 79:820-5 (2004).
- Chiu. Reply to M Manco et al. and to MF McCarty [their letters to the editor commenting on the paper cited in Ref 2 above]. Am J Clin Nutr 80(5):1452-3 (2004).
- Bischoff-Ferrari et al. Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged greater than or equal to 60 y. Am J Clin Nutr 80:752-8 (2004).
- Bischoff et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Min Res 18(2):343-51 (2003).