In this article, we present four research insights highlighting the diverse and emerging roles of vitamin D in metabolic regulation, pediatric type 1 diabetes, and neuroinflammatory conditions such as clinically isolated syndrome and multiple sclerosis.
The following summaries are based on expert research briefings originally shared in the Vitamin Professor Newsletter by Dr. Gene Bruno.
High-dose vitamin D increased allocation of calories to muscle instead of fat
Obesity occurs because the body stores surplus calories as fat rather than as muscle. Fat secretes a hormone, leptin, that modulates energy balance (food intake). Changes in fat mass are mirrored by changes in serum leptin. Elevated leptin prompts the brain to decrease appetite and increase energy expenditure. In obesity, however, impaired leptin sensitivity mutes these leptin-mediated changes. We have limited understanding of what controls leptin production by fat or leptin sensitivity in the brain. Muscle produces a hormone, myostatin, that plays a role in muscle analogous to the one that leptin plays in fat. Absent myostatin leads to increased muscle mass and strength. As with leptin, we also do not know what controls myostatin production or sensitivity. Although fat mass and muscle mass are closely linked, the interplay between leptin and myostatin remains obscure. This mouse study[2] described an interplay linked via vitamin D. Conventionally, it is thought that vitamin D improves strength via trophic effects at the muscle. However, this study found that high dose dietary vitamin D allocated excess calories to muscle and linear growth instead of storage as fat. Vitamin D mediated this allocation by decreasing myostatin production and increasing leptin production and sensitivity. That is, high dose vitamin D improved integration of organismal energy balance. Obesity, aging and other chronic inflammatory diseases are associated with increased fat mass and decreased muscle mass and function (e.g. sarcopenia). This work provided a physiologic framework for how high-dose vitamin D would increase allocation of calories to muscle instead of fat in these pathologies. Additionally, this work revealed a novel link between the myostatin and leptin signaling whereby myostatin conveys energy needs to modulate leptin effects on calorie allocation. This result provided evidence to update the conventional model of energy stores sensing to a new model of energy balance sensing. In this proposed model, integration of leptin and myostatin signaling allows control of body composition independent of weight. Furthermore, this work revealed how physiologic seasonal variation in vitamin D may be important in controlling season-specific metabolism and calorie allocation to fat in winter and muscle and growth in summer.
Note: This was an animal study, so until such time as a human study is conducted on this topic we won’t know if results will be the same in humans. Also, the information presented is a preprint and has not yet been peer reviewed by a journal.
Vitamin D supplementation in type 1 juvenile diabetes mellitus
To evaluate the effect of vitamin D supplementation on vitamin D deficiency (VDD) and glycemic control in children and adolescents with type 1 diabetes mellitus (T1DM), a clinical trial[iii] was conducted. Participants with VDD (25(OH)D < 30 ng/mL) were allocated to the intervention group and oral supplementation with cholecalciferol was prescribed at a dose of 2000 IU/day for 12 weeks. Sociodemographic, clinical, laboratory, lifestyle, anthropometric data and the Fok-I polymorphism (rs2228570) vitamin D receptor were collected. Of the 133 participants, 77.4 % were assigned to the intervention group (n = 103). Results were that serum 25(OH)D concentration increased from 19.2 ± 6.2 to 30.9 ± 10.1 ng/mL. A minimal effect was shown on glycemic control. A higher dose of insulin and a high BMI (p = 0.059) were associated with lower serum 25(OH)D concentration, and sedentary (p = 0.004) associated with higher HbA1C after 12 weeks of supplementation. In conclusion, oral cholecalciferol supplementation was effective in correcting VDD, and this intervention had a minimal effect on glycemic control.
Vitamin D3 for clinically isolated syndrome typical for multiple sclerosis
A two-year, parallel, double-blind, randomized placebo-controlled clinical trial[2] was conducted to evaluate the efficacy of high-dose cholecalciferol as monotherapy in reducing disease activity in patients with clinically isolated syndrome (CIS) typical for multiple sclerosis (MS). This trial including 303 patients (median age, 34 [28-42] years; 70% women) who were randomized 1:1 to receive oral cholecalciferol 100,000 IU (n = 163) or placebo (n = 153) every 2 weeks for 24 months. The primary outcome measure was disease activity, defined as occurrence of a relapse and/or MRI activity (new and/or contrast-enhancing lesions) over 24 months of follow-up, also analyzed as separate secondary outcomes. Results were that disease activity was observed in 94 patients (60.3%) in the vitamin D group and 109 patients (74.1%) in the placebo group (P=0.004), and median time to disease activity was longer in the vitamin D group (432 vs 224 days; P=0.003). All 3 secondary MRI outcomes reported significant differences favoring the vitamin D group vs the placebo group: MRI activity (89 patients [57.1%] vs 96 patients [65.3%]; P=0.02), new lesions (72 patients [46.2%] vs 87 patients [59.2%]; P=0.003), and contrast-enhancing lesions (29 patients [18.6%] vs 50 patients [34.0%]; P=0.001). Severe adverse events occurred in 17 patients in the vitamin D group and 13 in the placebo group, none of which were related to cholecalciferol. In conclusion, oral cholecalciferol 100,000 IU every 2 weeks significantly reduced disease activity in CIS and early relapsing-remitting MS. These results warrant further investigation, including the potential role of pulse high-dose vitamin D as add-on therapy.
Vitamin D supplementation for multiple sclerosis
Multiple sclerosis (MS) is characterized by chronic neuroinflammation and oxidative stress. Vitamin D is believed to exert immunomodulatory and antioxidant effects, yet its impact on specific inflammatory proteins such as CHI3L1 (YKL-40) in MS remains unclear. This study[1] evaluated whether 8-week vitamin D3 supplementation affects serum CHI3L1 levels, oxidative stress markers, and antioxidant enzyme activities in patients with MS. In this single-arm pre-post clinical trial, 35 patients with MS (aged 30-56 years) received oral vitamin D3 supplementation (50 000 IU/week) for 8 weeks. Results were that vitamin D3 supplementation significantly increased serum 25(OH)D levels (20.80 ± 8.6 to 39.11 ± 12.26 ng/mL; p < 0.001). CHI3L1 concentration decreased by 21.7% (33.28 ± 8.9 to 26.05 ± 9.1 ng/mL; p < 0.001). oxidative stress was reduced, evidenced by lower TOS (1.55 ± 0.50 to 0.59 ± 0.23 mmol H2O2 equiv./L; p < 0.001) and MDA (0.08 ± 0.03 to 0.05 ± 0.026 nmol/mL; p < 0.001). Antioxidant capacity improved, as demonstrated by elevated TAC (0.622 ± 0.138 to 0.797 ± 0.15 mmol Fe2+/L; p < 0.001) and increased activities of SOD (10.5%; p < 0.001), CAT (19.5%; p < 0.001), and GPx (35.6%; p < 0.05). Significant inverse correlations were observed between serum 25(OH)D and CHI3L1 (r = -0.999, p < 0.001), TOS (r = -0.456, p = 0.0058), and MDA (r = -0.577, p < 0.001). In conclusion, vitamin D3 supplementation was associated with reductions in CHI3L1 and oxidative stress markers, while suggesting enhancement of antioxidant capacity. This observed biomarker changes support vitamin D3 as a potential adjunct therapy targeting interconnected pathological pathways in MS.
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The four short research highlights presented in this article are adapted from recent editions of the Vitamin Professor Newsletter by Dr. Gene Bruno. His curated updates translate current scientific findings into practical, formulation-relevant knowledge for the nutraceutical and health-ingredient community.
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Dr. Gene Bruno, DBM, MS, RH(AHG) is a 47-year veteran of the dietary supplement industry, and for 20 of those years he served as Professor of Nutraceutical Science at Huntington University of Health Sciences. He now serves as Chief Scientific Officer for Nutraland USA. As “The Vitamin Professor™”, Gene will share the most recent research on nutraceuticals in this free bimonthly newsletter. Make sure to subscribe.
