Vitamin D supplementation increases strength of lower muscles – Meta-analysis April 2019

Effect of vitamin D supplementation on upper and lower limb muscle strength and muscle power in athletes: A meta-analysis
PLoS One. 2019 Apr 30;14(4):e0215826. doi: 10.1371/journal.pone.0215826. eCollection 2019.
Zhang L1, Quan M1, Cao ZB1.

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BACKGROUND:
Vitamin D may play a role in skeletal muscle because of the discovery of VDR in skeletal muscle. However, vitamin D deficiency is a global problem, including athletes. Studies examining the effect of vitamin D supplementation on muscle function in athletes have inconsistent results. Therefore, we aimed to quantitatively summarize the evidence for the effect of vitamin D supplementation on skeletal muscle strength and explosive power of athletes using a meta-analysis.

METHODS:
PubMed, EMBASE, Cochrane Library, and Web of Science were searched for studies to identify randomized controlled trials or controlled trials meeting the inclusion criteria. By a meta-analysis, effect sizes (standardized mean differences, SMD) with 95% confidence intervals (CI) was calculated to compare reported outcomes across studies, I2 index was used to assessing heterogeneity, and heterogeneity factors were identified by regression analysis. The potential publication and sensitivity analyses were also assessed.

RESULTS:
Eight RCTs involving 284 athletes were included. The protocols used to evaluate the muscle strength of athletes were inconsistent across the included studies, and muscle explosive power was assessed via vertical jump tests. The results indicated that vitamin D supplementation had no impact on overall muscle strength outcomes (SMD 0.05, 95% CI: -0.39 to 0.48, p = 0.84).
In subgroup analysis, vitamin D supplementation had an effect on

• lower-limb muscle strength (SMD 0.55, 95% CI:0.12 to 0.98, p = 0.01)
• but not upper-limb muscle strength (SMD -0.19, 95% CI:-0.73 to 0.36, p = 0.50)
• or muscle explosive power (SMD 0.05, 95% CI:-0.24 to 0.34, p = 0.73).
• Vitamin D supplementation was more effective for athletes trained indoors (SMD 0.48, 95% CI:0.06 to 0.90, p = 0.02).

CONCLUSIONS:
Vitamin D supplementation positively affected lower limb muscle strength in athletes, but not upper limb muscle strength or muscle power. Different muscle groups and functions may respond differently to vitamin D supplementation. Additional studies should focus on determining the appropriate vitamin D supplementation methods and optimal serum 25(OH)D levels for athletes.

REGISTRATION:
The protocol for our study is registered in the international prospective register of systematic reviews (PROSPERO registration number CRD42016045872).

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Discussion

The purpose of the present meta-analysis was to evaluate the effect of vitamin D supplementation on upper and lower limb muscle strength and muscle explosive power in professional athletes and college athletes. The results of the included studies demonstrated a significant effect of vitamin D supplementation on lower limb muscle strength in athletes, but not on upper limb muscle strength or muscle power.
There are few meta-analyses of controlled or randomized controlled trials that have discussed the effects of vitamin D supplementation on skeletal muscle fitness using different inclusion criteria, and they report inconsistent conclusions. Farrokhyar et al. [21] found hand grip strength increased significantly after 12 weeks of vitamin D supplementation. Tomlinson et al. [34] observed that vitamin D supplementation improved both upper and lower limb muscle strength. The previous review of Tomlinson et al. contained highly heterogeneous populations, including athletic and non-athletic populations, while our participants were healthy, active athletes with an average age of 19 years, supplemented by vitamin D alone. Our study performed the quantitative meta-analysis using a more consistent study population, and included a larger number of studies (8 RCTs in athletes), and thus, provided a larger sample and more representative results.
Increasing evidence showed that vitamin D exerted important roles in skeletal muscle fitness, and affected muscle function through regulating both calcium-phosphorous homeostasis and related protein transcription [3, 4, 35]. Vitamin D receptor (VDR) and 1,25(OH)2D (the active metabolite of vitamin D) have been shown to have a key function in this relationship as proven by several human or animal studies. A significant association between the VDR genotypes and muscle strength was observed in elderly [36], young [37, 38], and mixed populations [3, 39]. However, it cannot be ignored that evidence is limited and some studies failed to observe an association between different polymorphisms and various muscle function measurements [3,
40,41]. The animal studies also provided insights into this relationship. Girgis et al. found that vitamin D receptor knockout (VDRKO) resulted in a significant decrease in muscle strength and muscle fibers size [42]. Furthermore, the active metabolite of vitamin D, 1,25(OH)2D, could regulate mitochondrial function, dynamics, and enzyme function in human skeletal muscle cells [5], which may partly explain the underlying mechanism of the effect of vitamin D on skeletal muscle function from a metabolic point of view. A longitudinal study showed that cho- lecalciferol therapy for 10-12 weeks augmented muscle mitochondrial maximal oxidative phosphorylation in vitamin D-deficient individuals [7]. This issue should be explored in more depth.

The response of muscle strength to vitamin D supplementation

The effect of vitamin D supplementation on muscle function was firstly reported in the previous studies of myopathy patients, whose muscle strength improved remarkably after vitamin D treatment [43-45]. Ceglia and Pojednic, et al. found that vitamin D supplementation in older women not only increased muscle fiber size [46], but also the intramyonuclear VDR concentration [46,4Z], and a significant increase in VDR percent in type II fibers was further observed [46]. The interaction between VDR and muscle fiber type needs to be explored. It seemed that elderly or low baseline vitamin D population may get more beneficial effect of vitamin D supplementation on muscle function [48-50].
Our observation of a significant effect of vitamin D supplementation on the muscle strength of lower but not upper limbs is consistent with the findings of Cangussu et al.[4Z]. The mechanisms for the suggested differential effect of vitamin D on upper and lower limb muscle strength remains unclear but may be associated with several factors.
First, VDR expression of different muscle groups may contribute to the differential effects between the upper and lower limb musculature. Previous studies in cell culture and animals have indicated that the content of VDR in target tissues was positively associated with the functional response level of tissues to vitamin D [51-53]. Future studies are needed to explore the observation.
Second, it is possible that upper limb strength measures (e.g. isometric handgrip dynamometry) are less sensitive to modest changes in muscle strength and thus lack sufficient power to detect small but significant strength gains in the upper extremities [54]. Thus, sensitive and standardized measurement techniques for athletes are urgently needed. Moreover, the lower limbs are more frequently utilized for load bearing during daily life and exercise compared with the upper limbs, which may enhance neuromuscular modulation of leg strength by stimuli [55] and increase the capillary density in leg muscle [56]. Therefore, compared to upper limb muscle, lower limb muscle strength may react to vitamin D supplementation more quickly and obviously.
We also found that vitamin D supplementation duration of less than 3 months demonstrated a statistically significant improvement of muscle strength, whereas supplementation for 3 months did not. However, this result should be interpreted with caution. All studies lasting 3 months, included seven upper limb muscle strength tests and one lower limb muscle strength; thus, the merged results may be influenced by the higher number of upper limb muscle strength tests.

Optimal vitamin D level for muscle function

The optimal vitamin D level for muscle strength is a focus of ongoing research, but currently remains unresolved. The Institute of Medicine (IOM) recommends that vitamin D deficiency is defined as serum 25(OH)D concentration below 50 nmol/L, and vitamin D sufficiency as at least 50 nmol/L and preferably more than 75 nmol/L. However, the IOM report stressed that its recommendations for vitamin D were based primarily on the intake (and serum 25(OH)D concentration) needed to ensure skeletal health [57], while the recommendations serum 25 (OH)D concentrations for preserving neuromuscular performance have yet to be established. The optimal levels of 25(OH)D for athletes have not been defined either.
The studies included in our meta-analysis had a wide range of baseline vitamin D concentrations (29-93 nmol/L). Despite a significant increase in vitamin D status being reported in all the included studies, the change in magnitude of muscle strength and muscle power outcomes did not entirely correspond to the increase in concentration. Close et al. [16] reported a significant increase in muscle strength and vertical jump height after vitamin D supplementation. Wyon et al. [32] and Fairbairn et al. [33] also found a significant increase in some of the muscle strength measurements. Other included studies did not observe a significant change in muscle function after vitamin D intervention, although vitamin D concentration was up to 114 nmol/L, and the average change of vitamin D concentration was 32 nmol/L. Some randomized trial in elderly found that although high doses of vitamin D were effective in reaching the threshold of 75 nmol/L of 25(OH)D concentration, it may have deleterious effects on muscle function and the risk of falls [58-60]. It’s also worth noting that supplementation with high doses of vitamin D to subjects without vitamin D deficiency may have no effects [17, 30] or negative effects [61]. Thus, the biochemical safety of vitamin D supplementation for the athletes also need to be considered. And it raised a question as to whether an optimal vitamin D concentration for muscle function existed, especially for athletes. Furthermore, even if it exists, what should it be based on?
The lowest 25(OH)D levels of athletes are typically observed in the winter and early spring [62]. To ensure vitamin D sufficiency in mid-winter, Galan et al. [63] suggested that a serum 25-hydroxyvitamin D concentration of 122.7 nmol/L was required in early autumn to avoid levels falling below 75 nmol/L among professional football players.
The choice of an indoor or outdoor training environment also influences sun exposure and thus ultimately affects vitamin D synthesis. Emerging evidence has indicated that athletes who train outdoors have higher vitamin D levels compared to those who train indoor or avoid peak daylight hours, regardless of latitude or season [64,65]. Our meta-analysis suggests that vitamin D supplementation may be more effective for athletes who perform indoor training. Moreover, as athletes in weightrestricting sports may be more prone to vitamin D deficiency than others [16], we suggested that their vitamin D status be tested regularly. Altogether, vitamin D deficiency in athletes, especially in athletes training indoors, should be treated with vitamin D supplementation appropriately, in order to achieve an adequate vitamin D concentration. However, it is not recommended that athletes take large amounts of vitamin D for the purpose of improving sports performance or training effect, due to insufficient evidence in this regard.

Change in muscle power

No significant effect of vitamin D supplementation on muscle power was found, which may indicate that muscle strength and power have different responses to vitamin D supplementation in athletes. Muscle power, for example vertical jump, mainly utilizes fast-twitch fibers (type II), while muscle strength may utilize both type I and type II or type II muscle [66]. Muscle power has been shown to decrease more rapidly than strength in elderly individuals with sarcopenia [67]. Another study on elderly subjects [68] suggested a type II fiber-focused response to vitamin D3 supplementation. Some studies have shown that vitamin D deficiency results in proximal muscle weakness with a reduction in type II muscle fiber [35,66]. While the data on younger athletes with better muscle function are still limited, it is not possible to determine whether the different responses of muscle strength and power in athletes is related to muscle fiber type.
Furthermore, since many athletic events are either defined by or heavily dependent on muscle power, muscle power impacts athletic performance (e.g. sprinting, jumping). Some of the included studies also measured athletic performance. Close et al. [16] found significant improvement in 10 m sprint and vertical jump in the vitamin D supplementation group, whereas the placebo group showed no change. By contrast, other studies showed that increasing serum 25(OH)D had no significant effect on sprint performance [17, 30,33]. Thus, while vitamin D supplementation may improve muscle strength, the lack of improvement in power suggests that there may not be any direct benefit to athletic performance.

Strengths and limitations

This report is the first meta-analysis to quantitatively assess the effects of vitamin D supplementation on muscle strength and power in highly trained athletes in RCTs. Sensitivity analysis revealed that our results were stable. However, this study also has some limitations. First, the variety of training programs and sports of included athletes may be a limitation. However, all studies reported the subjects performing specified training plans. Second, the possibility that potentially relevant studies may have been missed due to the limitation of our search to English-language publications in our study cannot be excluded.

Conclusions

This meta-analysis demonstrated that, while it showed no improvement in muscle power, vitamin D supplementation had a significant effect on lower limb muscle strength, especially in athletes who train indoors. These findings suggest that achieving vitamin D-sufficient status through supplementation of vitamin D is necessary for maintaining greater muscle strength, and there may be a discrepancy between upper and lower limb muscle strength in response to vitamin D supplementation among athletes, especially those who train indoors.