The Inconsistent Data on the Effect of Vitamin D on Muscle Function

J Spine, ISSN: 2165-7939 JSP an open access journal, Volume 1 • Issue 5 • 1000e107
Giulio Pioli1 and Andrea Giusti2
1Geriatrics Unit, Department of Neuromotor Physiology, ASMN-IRCCS, Reggio Emilia, Italy
2Bone Clinic, Department of Gerontology and Musculoskeletal Sciences, Galliera Hospital, Genoa, Italy
•Corresponding author: Giulio Pioli, Geriatrics Unit, Department of Neuromotor Physiology, ASMN-IRCCS, Viale Risorgimento, 80, 42100 Reggio Emilia, Italy, Tel: +39-0522206188; Fax: +39-0522206122; E-mail: giulio.pioli at asmn.re.it
Received October 10, 2012; Accepted October 11, 2012; Published October 13, 2012
Citation: Pioli G, Giusti A (2012) The Inconsistent Data on the Effect of Vitamin D on Muscle Function. J Spine 1:e107.

Proximal myopathy and muscular weakness are one of the hallmarks of severe osteomalacia, together with the defective mineralization of newly formed bone matrix and bone pain [1]. Muscles biopsy studies have demonstrated that prolonged Vitamin D deficiency may produce a selective atrophy of type 2 muscular fibers, which are characterized by short, fast bursts of power and rapid fatigue [1].

The muscular tissue has a high specific nuclear receptor for 1,25-dihydroxyVitamin D [1,25(OH)2D], the active form of Vitamin D. In animal models, the presence of a non-functioning Vitamin D receptor (VDR) has been associated with subnormal muscle fibers, which presented with a diameter about 20% smaller [2].

Observational studies investigating differences in physical performances between patients with different levels of serum 25-hydroxy-Vitamin D [25(OH)D], the precursor of 1,25(OH)2D and the most suitable indicator of Vitamin D status, found very inconsistent results. Marantes et al. [3] evaluated muscle mass and strength (e.g. hand grip) according to the 25(OH)D level in a large cohort of community-dwelling adults. They did not find any difference in the parameters assessed between quartiles of 25(OH)D, even when they compared subjects with more severe Vitamin D deficiency [25(OH) D<10 ng/ml and controls [[3].

Consistently with observational studies, randomized-controlled trials (RCTs) specifically designed to improve muscle performances trough Vitamin D supplementation/therapy led to contradictory results. In a systematic review published about 10 years ago, Latham [4] considered 13 trials undertaken to evaluate the effects of plain Vitamin D or its metabolites on physical function [4]. Ten studies did not demonstrate any positive result, while three showed a beneficial effect of Vitamin D combined with calcium on physical function [4]. In a more recent meta-analysis, Muir et al. [5] found that Vitamin D supplementation is capable of improving balance tests, producing, for example, a reduction of postural sway, but they failed to prove a valuable effect on lower extremity strength [5].

These inconsistencies arising from published observational and intervention studies may suggest that when administered to the general population Vitamin D has a poor and limited effect on muscle performances.

Bischoff-Ferrari et al. [6] has recently demonstrated that Vitamin D supplementation significantly reduces the risk of fracture only in those subjects receiving at least 800 IU per day [6]. A threshold level of efficacy for cholecalciferol daily dose and, consequently, for the serum 25(OH)D value achieved is likely for any action of Vitamin D, including muscle strength and function. Thus, the studies using low doses of Vitamin D (at least lower than 800 IU per day) could not be able to detect any beneficial effect of cholecalciferol supplementation just because of an inadequate intake, and due to failure in achieving the threshold for serum 25(OH)D in the majority of studied patients [7-9].

Notably, the relationship between serum 25(OH)D and muscle performances seems to be represented by a plateau shape rather than a linear one. In the Longitudinal Aging Study Amsterdam, the strength of this relationship leveled off for values of serum 25(OH)D above 30 ng/ml [10], indicating that it is unlikely any further improvement of muscle strength for serum 25(OH)D levels above this limit of 30 ng/ml.

These observations could, therefore, explain the reason why Vitamin D supplementation produced no significant effect in RCTs that enrolled patients with a mean basal serum 25(OH)D value close to the reference range [11-13]. On the other hand, it seems that improvements in muscle strength and function may be easily induced by plain Vitamin D supplementation in those subjects with Vitamin D deficiency, simply by contrasting the detrimental effects of deficiency on the muscles. Overall, these observations suggest that Vitamin D has just a physiologic role for muscle cells function rather than pharmacological effects.

Another relevant factor that may contribute to explain the huge variability in the results of RCTs is the choice of the test used to evaluate muscle performances. As Vitamin D seems to affect selectively the type 2 muscular fibers, the tools more sensitive and appropriate to define its beneficial effects should be those tests evaluating quick and short movements. For this reason, balance sway resulted, in general, positively influenced by Vitamin D supplementation, while handgrip or leg strength that needs more prolonged contraction gave more variable and inconsistent results.

Finally some recent reports described a relationship between muscle strength and some VDR polymorphisms [14]. Even if these data warrant further confirmation, an increase of serum 25(OH)D level could have different effects according to the VDR genotype (e.g. associated to higher or lower muscle power).

Summarizing, the effects of Vitamin D supplementation on muscle function and strength still need to be investigated in high quality RCTs taking into account all the variables above described potentially affecting the results. In particular, these studies should enroll only patients with very low serum 25 OHD values, should provide an adequate intake of cholecalciferol capable to normalize serum 25(OH)D (>30 ng/ml), and should assess muscle function using tests investigating quick movements rather than endurance. Finally, an analysis on VDR genotype should be provided to better interpret the final results.

Acknowledgment

Giulio Pioli declares no financial relationships with any organizations that might have an interest in the submitted work. Andrea Giusti is a member of the Advisory Board of the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases (SIOMMMS) and he has received consulting fees from Novartis, Procter and Gamble, Eli Lilly and InFoMed (ECM provider, Milano, Italy).

References

1. Yoshikawa S, Nakamura T, Tanabe H, Imamura T (1979) Osteomalacic myopathy. Endocrinol Jpn 26: 65-72.
2. Endo I, Inoue D, Mitsui T, Umaki Y, Akaike M, et al. (2003) Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. Endocrinology 144: 5138-5144.
3. Marantes I, Achenbach SJ, Atkinson EJ, Khosla S, Melton LJ 3rd, et al. (2011) Is vitamin D a determinant of muscle mass and strength? J Bone Miner Res 26: 2860-2871.
4. Latham NK, Anderson CS, Reid IR (2003) Effects of vitamin D supplementation on strength, physical performance, and falls in older persons: a systematic review. J Am Geriatr Soc 51: 1219-1226.
5. Muir SW, Montero-Odasso M (2011) Effect of vitamin D supplementation on muscle strength, gait and balance in older adults: a systematic review and meta-analysis. J Am Geriatr Soc 59: 2291-2300.
6. Bischoff-Ferrari HA, Willett WC, Orav EJ, Lips P, Meunier PJ, et al. (2012) A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med 367: 40-49.
7. Bunout D, Barrera G, Leiva L, Gattas V, de la Maza MP, et al. (2006) Effects of vitamin D supplementation and exercise training on physical performance in Chilean vitamin D deficient elderly subjects. Exp Gerontol 41: 746-752.
8. Janssen HC, Samson MM, Verhaar HJ (2010) Muscle strength and mobility in vitamin D-insufficient female geriatric patients: a randomized controlled trial on vitamin D and calcium supplementation. Aging Clin Exp Res 22: 78-84.
9. Latham NK, Anderson CS, Lee A, Bennett DA, Moseley A, et al. (2003) A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS). J Am Geriatr Soc 51: 291-299.
10. Wicherts IS, van Schoor NM, Boeke AJ, Visser M, Deeg DJ, et al. (2007) Vitamin D status predicts physical performance and its decline in older persons. J Clin Endocrinol Metab 92: 2058-2065.
11. Grady D, Halloran B, Cummings S, Leveille S, Wells L, et al. (1991) 1,25-Dihydroxyvitamin D3 and muscle strength in the elderly: a randomized controlled trial. J Clin Endocrinol Metab 73: 1111-1117.
12. Kenny AM, Biskup B, Robbins B, Marcella G, Burleson JA (2003) Effects of vitamin D supplementation on strength, physical function, and health perception in older, community-dwelling men. J Am Geriatr Soc 51: 1762-1767.
13. Glendenning P, Zhu K, Inderjeeth C, Howat P, Lewis JR, et al. (2011) Effects of three monthly oral 150,000 IU cholecalciferol supplementation on falls, mobility and muscle strength in older postmenopausal women: a randomised controlled trial. J Bone Miner Res.
14. Barr R, Macdonald H, Stewart A, McGuigan F, Rogers A, et al. (2010) Association between vitamin D receptor gene polymorphisms, falls, balance and muscle power: results from two independent studies (APOSS and OPUS). Osteoporos Int 21: 457-466.
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

See also VitaminDWiki

• Athletes need at least 40 ng of vitamin D – literature review Oct 2012
• More than 40 ng/ml vitamin D for Athletes – July 2010 nice tables
• Athletes need 50 ng/ml of Vitamin D – Cannell and Hollis – 2009
• Overview Sports and vitamin D which has the following summary
  Athletes are helped by vitamin D by:

1. Faster reaction time
2. Far fewer colds/flus during the winter
3. Less sore/tired after a workout
4. Fewer micro-cracks and broken bones
5. Bones which do break heal much more quickly
6. Increased VO2 and exercise endurance Feb 2011
7. Indoor athletes especially need vitamin D
8. Professional indoor athletes are starting to take vitamin D and/or use UV beds
9. Olympic athletes have used UV/vitamin D since the 1930's
10. The biggest gain from the use of vitamin D is by those who exercise less than 2 hours per day.
11. Reduced muscle fatigue with 10,000 IU vitamin D daily
12. Muscle strength improved when vitamin D added: 3 Meta-analysis
13. Reduced Concussions
    See also: Sports and Vitamin D category 279 items

• NASA thinks spacestation personnel only need 800 IU of vitamin D – Sept 2012 Loss of muscle strength while in space
• Google Search VitaminDWiki for sarcopenia muscle loss - 61 items Aug 2012
• Extraskeletal effects of vitamin D – May 2011 includes muscle loss
• Vitamin D improves muscle strength if deficient – meta-analysis - Oct 2010
• Overview Seniors and Vitamin D
• Vitamin D is one of the treatments for sarcopenia – Nov 2012
• Loss of muscle strength –sarcopenia – one of the suspects is vitamin D – Aug 2012 which has the following graphic

Wikipedia Nov 2012

• Type I fibers appear red due to the presence of the oxygen binding protein myoglobin.
  These fibers are suited for endurance and are slow to fatigue because they use oxidative metabolism to generate ATP.
• Type II fibers are white due to the absence of myoglobin and a reliance on glycolytic enzymes.
  These fibers are efficient for short bursts of speed and power and use both oxidative metabolism and anaerobic metabolism depending on the particular sub-type.
  These fibers are quicker to fatigue.