The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 6 No.
3 • June 2003
Preventing Falls with Vitamin D and Calcium—A Possible Mechanism
A recent paper reports a double-blind, randomized trial of 122 elderly women (mean age 85.3 years) in long-stay geriatric care who received either 1200 mg calcium plus 800 IU cholecalciferol (Cal+D) or 1200 mg calcium (Cal) per day over a 12-week treatment period. The numbers of falls per person were compared between these two groups. The researchers also measured musculoskeletal function (summed score of knee flexor and extensor strength, grip strength, and the timed “up & go” test). Before treatment, the mean observed number of falls per person per week in the Cal+D group was 0.059, and in the Cal group it was 0.056. In the 12-week treatment period, the mean number of falls per person per week was 0.034 in the Cal+D group, and 0.076 in the Cal group. After adjustment, Cal+D treatment accounted for a 49% reduction in falls (95% CI, 14-71%; P<0.01). Musculoskeletal function improved significantly in the Cal+D group (P = 0.0094). In fact, a single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone.
Vitamin D may have direct effect on muscle
There has been evidence for a possible direct effect of vitamin D on muscle for quite some time. For example, a 1979 paper reported improved muscle function in 11 patients treated with the vitamin D analogue 1-alpha-hydroxycholecalciferol and calcium for 3–6 months. In addition, they found that the treatment induced an increase in the relative number of oxidative fast-twitch a (or type IIA) muscle fibers accompanied by a reduction of the oxidative fast-twitch b (type IIB) fibers, with an increase in the cross-sectional area of the fast-twitch b fibers. There were no changes in the slow-twitch fibers. (The authors note that the vitamin D analogue they used is rapidly converted in vivo into the natural form of vitamin D, 1,25-dihydroxycholecalciferol.)
The cytokine IL-4 required for muscle growth
The process of muscle growth requires the fusion of myoblasts with myotubes. This process requires multiple steps involving cell migration, alignment, recognition, adhesion, and membrane fusion. A recent paper reports that the second phase of myoblast fusion that occurs with myotubes is dependent on the cytokine IL-4 and the IL-4Ralpha subunit of the IL-4 receptor. IL-4 had, before the publication of this new paper, already been known to be involved in the regulation of cell fusion in macrophages and, after the paper, in the fusion of muscle cells. The authors propose that IL-4 may mediate the fusion of myoblasts by increasing the expression of cell-adhesion molecules [for example, IL-4 can induce the expression of intracellular adhesion molecule-1 (ICAM-1) on myoblasts].
Vitamin D stimulates IL-4 production
As reported in reference 4, vitamin D (1,25-dihydroxyvitamin D3) can either prevent or markedly suppress autoimmune diseases such as autoimmune encephalomyelitis, rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, and inflammatory bowel disease. The autoimmune effects of vitamin D almost always require that animals be maintained on a normal or elevated calcium diet. Possible mechanisms for these effects have been studied, including vitamin D-stimulated transforming growth factor (TGFbeta-1) and interleukin 4 (IL-4) production. The increased IL-4 might, on the basis of the findings on IL-4 and muscle growth, help explain the muscle-function improvements found in the two clinical studies above.
Vitamin A antagonizes the calcium response to vitamin D5
This paper notes that the highest incidence of osteoporosis is found in northern Europe, where sunlight exposure is limited and vitamin A intake is high. These researchers studied the acute effects of vitamins A and D on calcium homeostasis in nine healthy humans. The effects on the subjects of 15 mg of retinyl palmitate (27,255 IU of vitamin A), 2 µg of 1,25-dihydroxyvitamin D3, 15 mg of retinyl palmitate plus 2 µg of 1,25-dihydroxyvitamin D3, and placebo were examined in a double-blind crossover study. Intake of retinyl palmitate resulted in a significant decrease of serum calcium when taken alone and diminished the response to vitamin D3 when A and D were taken in combination. They conclude that the amount of vitamin A found in about one serving of liver antagonizes the rapid intestinal calcium response to physiological levels of vitamin D in man.
Our current daily recommended intake of our basic daily multinutrient supplement contains 1000 IU of vitamin D and 5000 IU of vitamin A. Most people can take up to 2000 IU of vitamin D per day safely. We have reduced the vitamin A intake from 8000 to 5000 in recognition of, among other things, its interference with vitamin D.
- 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).
- Sorensen et al. Myopathy in bone loss of ageing: improvement by treatment with 1-alpha-hydroxycholecalciferol and calcium. Clin Sci 56:157-61 (1979).
- Horsley et al. IL-4 acts as a myoblast recruitment factor during mammalian muscle growth. Cell 113:483-94 (2003).
- Deluca and Cantorna. Vitamin D: its role and uses in immunology. FASEB J 15:2579-85 (2001).
- Johansson and Melhus. Vitamin A antagonizes calcium response to vitamin D in man. J Bone Min Res 16(10):1899-1905 (2001).