Vitamin D

Vitamin D deficiency is widespread and may result in a vast array of health consequences including osteoporosis, falls, increased cancer risk and altered glucose and lipid metabolism – the pathogenesis of diabetes and CVD. It plays an essential role in muscle and bone health, immunity and muscle signaling and has been linked with autoimmune disorders such as multiple sclerosis (Cantorna et al. 2006; Cherniak et al. 2008; Ford et al. 2005; Mathieu et al. 2005). Obesity has been associated with decreased bioavailability of vitamin D, and percentage body fat is inversely related to vitamin D levels and directly correlated with parathyroid hormone (PTH) levels (Snijder et al. 2005; Wortsman et al. 2000).

The skeletal effects of hypovitaminosis D are evidenced in progressive stages such as calcium malabsorption with secondary elevation of PTH, increased bone remodeling and osteoporosis and further histologic changes related to continued lack of calcium and poor mineralization (Heaney 1999).

Individuals with SCI have an increased occurrence of vitamin D deficiency, resulting from a number of factors including decreased exposure to sunlight, inadequate dietary intake and the effect of medications (Hummel et al. 2012). In turn, vitamin D deficiency promotes calcium deficiency and secondary hyperparathyroidism, resulting in further bone loss and exacerbating osteoporosis. Myopathy and nonspecific musculoskeletal pain may also develop as a consequence of vitamin D deficiency (Bauman et al. 2005; Holick 2005).

Bauman et al. (1995) reported that 32 of 100 SCI subjects had 25(OH)D levels below normal range and 11 of 32 had elevated serum PTH levels. Zhou et al. (1993) measured the 25(OH)D, serum calcium, magnesium and albumin concentrations of 92 men with SCI, 38 of whom had single or multiple pressure ulcers, and compared these values with those of non-SCI controls. The SCI group had lower serum 25(OH)D, total calcium, and albumin concentrations. Individuals with tetraplegia had lower 25(OH)D levels than those with paraplegia. Additionally, the SCI subgroup with pressure ulcers demonstrated significantly lower serum 25(OH)D, calcium and magnesium levels than the SCI subjects without ulcers.

Serum 25-hydroxyvitamin D is the best test for assessing vitamin D levels in the following clinical scenarios where patient vitamin D levels may be abnormal including (Thatcher & Clark 2011):

• Significant renal or liver disease
• Osteomalacia, osteopenia or osteoporosis
• Malabsorption syndromes
• Hypo or hypercalcemia/hyperphosphatemia
• Hypo or hyperparathyroidism
• Prescribed medications that affect vitamin D metabolism such as phenobarbital, carbamazepine, phenytoin and valproate
• Prescribed medications that might interfere with vitamin D absorption such as cholestyramine, colestpiol and orlistat
• Unexplained increased levels of serum alkaline phosphatase
  Intake of high dose vitamin D combined with symptoms suggesting vitamin D toxicosis, i.e., hypervitaminosis D

There is increasing support for vitamin D supplementation beyond present recommendations. Additional studies are needed to establish the best diagnostic and supplementation guidelines for different populations (Cherniak et al. 2008).

Discussion

A high-level RCT by Amorim et al. (2018) determined the effects that creatine (3g daily) versus vitamin D (25000 IU each two weeks) supplementation had on muscle strength in 13 chronic SCI individuals undergoing resistance training. The mean value of 25(OH)D from all participants prior to the intervention was 13.3ng/ml . 71.4% were deficient in vitamin D (<20ng/ml), 28.6% had insufficient values of vitamin D (20–30ng/ml) with no participant being reported with sufficiency status. The corrected arm muscle area improved significantly (p<0.05) in creatine group relatively to the control group. There was a significant correlation (p<0.05) between the one repetition maximum Pec deck and levels of vitamin D. It was concluded that supplementation with creatine may improve muscle strength parameters in individuals with SCI. Vitamin D deficiency is highly prevalent in this population. An initial screening of vitamin D levels at the beginning of the physical rehabilitation process is recommended.

A case-control study by Beal et al. (2018) determined that persons with SCI consume much less than the recommended guidelines for daily vitamin D consumption. 20 male chronic SCI patients were assigned to either a high vitamin D intake group, or a low vitamin D intake group. The high vitamin D group had an average intake of 5.33 ± 4.14 mcg compared to low vitamin D group, 0.74±0.24 mcg. None of the participants met the recommended guidelines for daily vitamin D intake. The higher vitamin D group had a significantly lower (p=0.035) total cholesterol (148.00±14.12 mg/dl) than the lower vitamin D group (171.80±36.22 mg/dl). Vitamin D adjusted to total dietary intake was positively correlated to improvement in Si and Sg (p<0.05). These results suggest that the high vitamin D intake group consumed greater total caloric intake with similar macronutrients compared to the low vitamin D intake. Serum vitamin D levels were not evaluated in this study; however, study authors expect that their population to have 25(OH)D levels within a similar range to Bauman et al. (2005) [10.2–19.6 ng/mL.52]. The calcium intake for the higher vitamin D intake group was within the daily calcium recommendation (700–1300 mg/d),1 while the calcium intake for the lower vitamin D intake group was significantly lower than that daily recommendation

Bauman et al. (2005) determined that healthy individuals with chronic SCI living in the community had vitamin D deficiency. Ten subjects with chronic SCI and a diagnosis of absolute vitamin D (25(OH)D) deficiency received 50 ug (2000 IU) of vitamin D3 twice per week for two weeks in addition to 1.5 grams (1500 mg) of elemental calcium daily. Serum 25(OH)D levels significantly increased by day 14; however, levels remained below normal range in eight out of ten subjects. Serum calcium level was not significantly different, urinary calcium significantly increased, and serum PTH levels significantly decreased. In their second study Bauman et al. (2005) gave forty subjects 10 ug (400 IU) of vitamin D3 daily in addition to a multivitamin that contained 10 ug (400 IU) vitamin D3 daily for 12 months. All subjects received this treatment regardless of their initial serum vitamin D status. Subjects were encouraged to have at least 0.8 grams (800 mg) of calcium in their daily diet and were supplemented daily with 0.5 grams (500 mg) elemental calcium. Vitamin D levels significantly increased between baseline and follow-up at 6 and 12 months. There was no significant association between level of injury and baseline 25(OH)D levels. Serum and ionized calcium were not significantly different after 12 months of treatment although serum PTH was significantly reduced at 6 and 12 months. It is important to note that at baseline, 33 of the 40 subjects had 25(OH)D levels that were below the lower limit of normal, and that after 12 months of supplementation at 800 IU, only eight of the 40 subjects had serum 25(OH)D values greater than 30 ng/mL. These levels are not adequate in reversing elevated parathyroid levels and reducing bone turnover, despite significant decreases in PTH at 12 months. In conclusion, vitamin D3 supplementation resulted in significant increases in 25(OH)D levels and reductions in PTH; however, suboptimal 25(OH)D levels persisted, suggesting the need for higher doses of vitamin D3 supplementation and/or longer periods of administration.

Conclusion

There is level 1b evidence (from one RCT: Amorim et al. 2018) that supplementation with creatine, as well as vitamin D may improve muscle strength parameters in individuals with spinal cord injury.

There is level 3 evidence (from one case-control study: Beal et al. 2018) that chronic SCI patients suffer from hypovitaminosis of vitamin D. Increasing the daily intake of vitamin D improves glucose homeostasis, and may also improve total cholesterol.

There is level 4 evidence (from one pre-post study: Bauman et al. 2005) that vitamin D supplementation raises serum 25(OH)D levels in persons with chronic SCI. However, the dose and duration required to ensure vitamin D sufficiency remains unclear.