Vitamin D and/or calcium deficient diets may differentially affect muscle fiber neuromuscular junction innervation

Gifondorwa, David J.; Thompson, Tyran D.; Wiley, June; Culver, Alexander; Shetler, Pamela; Rocha, Guilherme; Li, Yanfei; Krishnan, Venkatesh; Bryant, Henry U.

doi:10.1002/mus.25146

Cited by 22 publications

(14 citation statements)

References 85 publications

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“…Myocytes express VDRs which, when bound to active Vitamin D, exert genomic and non-genomic effects that can modulate cellular physiology and maintain normal muscle function [32]. Genomic effects include upregulation of gene programs promoting myoblast differentiation, muscle regeneration, neuromuscular junction maintenance and calcium/ phosphate homeostasis [33,34]. These programs may be in play in denervating disease as the muscle attempts to compensate for atrophy, myofiber death, and loss of muscle power.…”

Section: Discussionmentioning

confidence: 99%

The vitamin D activator CYP27B1 is upregulated in muscle fibers in denervating disease and can track progression in amyotrophic lateral sclerosis

Kazamel

Kwon

et al. 2020

The Journal of Steroid Biochemistry and Molecular Biology

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Extra-renal expression of Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1) has been well recognized and reflects the importance of intracrine/paracrine vitamin D signaling in different tissues under physiological and pathological conditions. In a prior RNA sequencing project, we identified CYP27B1 mRNA as upregulated in muscle samples from patients with amyotrophic lateral sclerosis (ALS) compared to normal controls. Our aims here were: (1) to validate this finding in a larger sample set including disease controls, (2) to determine which cell type is expressing CYP27B1 protein in muscle tissue, (3) to correlate CYP27B1 mRNA expression with disease progression in the SOD1 G93A ALS mouse and in ALS patients. We assessed CYP27B1 expression by qPCR, western blot, and immunohistochemistry in a repository of muscle samples from ALS, disease controls (myopathy and non-ALS neuropathic disease), normal subjects, and muscle samples from the SOD1 G93A mouse. Eight ALS patients were studied prospectively over 6-12 months with serial muscle biopsies. We found that CYP27B1 mRNA and protein levels were significantly increased in ALS versus normal and myopathy muscle samples. Neuropathy samples had increased CYP27B1 mRNA and protein expression but at a lower level than the ALS group. Immunohistochemistry showed that CYP27B1 localized to myofibers, especially those with features of denervation. In the SOD1 G93A mouse, CYP27B1 mRNA and protein were detected in skeletal muscle in early pre-symptomatic stages and increased through end-stage. In the human study, increases in CYP27B1 mRNA in muscle biopsies correlated with disease progression rates over the same time period. In summary, we show for the first time that CYP27B1 mRNA and protein expression are elevated in muscle fibers in denervating disease, especially ALS, where mRNA levels can potentially serve as a surrogate marker for tracking

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Section: Discussionmentioning

confidence: 99%

The vitamin D activator CYP27B1 is upregulated in muscle fibers in denervating disease and can track progression in amyotrophic lateral sclerosis

Kazamel

Kwon

et al. 2020

The Journal of Steroid Biochemistry and Molecular Biology

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“…The physiological mechanism linking vitamin D to pain is not yet fully elucidated. Evidence from both clinical and animal studies suggest that insufficient levels of vitamin D affect both peripheral [ 30 , 31 ] and parasympathetic nerve function [ 32 ]. Presence of vitamin D receptors (VDR) and vitamin D activating enzymes in the central nervous system (CNS) as well as effects of vitamin D on neurotransmitters have been suggested to explain the link between pain and vitamin D in patients with fibromyalgia [ 33 ].…”

Section: Vitamin D—synthesis Physiological Effects and Pathophysimentioning

confidence: 99%

Vitamin D in Pain Management

Frankling

Björkhem‐Bergman

2017

IJMS

110

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Vitamin D is a hormone synthesized in the skin in the presence of sunlight. Like other hormones, vitamin D plays a role in a wide range of processes in the body. Here we review the possible role of vitamin D in nociceptive and inflammatory pain. In observational studies, low vitamin D levels have been associated with increased pain and higher opioid doses. Recent interventional studies have shown promising effects of vitamin D supplementation on cancer pain and muscular pain—but only in patients with insufficient levels of vitamin D when starting intervention. Possible mechanisms for vitamin D in pain management are the anti-inflammatory effects mediated by reduced cytokine and prostaglandin release and effects on T-cell responses. The recent finding of vitamin D-mediated inhibition of Prostaglandin E2 (PGE2) is especially interesting and exhibits a credible mechanistic explanation. Having reviewed current literature, we suggest that patients with deficient levels defined as 25-hydroxyvitamin D (25-OHD) levels <30 nmol/L are most likely to benefit from supplementation, while individuals with 25-OHD >50 nmol/L probably have little benefit from supplementation. Our conclusion is that vitamin D may constitute a safe, simple and potentially beneficial way to reduce pain among patients with vitamin D deficiency, but that more randomized and placebo-controlled studies are needed before any firm conclusions can be drawn.

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“…The physiological mechanism linking vitamin D to pain is not yet elucidated. Evidence from both clinical and animal studies suggest that insufficient levels of vitamin D affect both peripheral [ 26 , 27 ] and parasympathetic nerve function [ 28 ]. Vitamin D also has anti-inflammatory effects, especially on the T-cell response [ 29 ], and this might decrease inflammatory-mediated pain.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D supplementation to palliative cancer patients shows positive effects on pain and infections—Results from a matched case-control study

et al. 2017

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BackgroundWe previously showed an association between low vitamin D levels and high opioid doses to alleviate pain in palliative cancer patients. The aim of this case-controlled study was to investigate if vitamin D supplementation could improve pain management, quality of life (QoL) and decrease infections in palliative cancer patients.MethodsThirty-nine palliative cancer patients with levels of 25-hydroxyvitamin D < 75 nmol/L were supplemented with vitamin D 4000 IE/day, and were compared to 39 untreated, matched “control”-patients from a previous study at the same ward. Opioid doses, antibiotic consumption and QoL-scores measured with the Edmonton Symptom Assessment Scale (ESAS) were monitored. The primary endpoint was the change from baseline after 1 and 3 months compared between the groups using linear regression with adjustment for a potential cofounding factor.ResultsAfter 1 month the vitamin D treated group had a significantly decreased fentanyl dose compared to the untreated group with a difference of 46 μg/h; 95% CI 24–78, which increased further at 3 months to 91 μg/h; 95% CI 56–140 μg/h. The ESAS QoL-score improved in the Vitamin D group the first month; -1.4; 95% CI -2.6 - (-0.21). The vitamin D-treated group had significantly lower consumption of antibiotics after 3 months compared to the untreated group, the difference was -26%; 95%CI -0.41%–(-0.12%). Vitamin D was well tolerated by all patients and no adverse events were reported.ConclusionVitamin D supplementation to palliative cancer patients is safe and improvement in pain management is noted as early as 1 month after treatment. Decreased infections are noted 3 months after vitamin D treatment. The results from this pilot-study have been used for the power-calculation of a future randomized, placebo-controlled, double-blind study called “Palliative-D” that will start in Nov 2017 and will include 254 palliative cancer patients.

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Vitamin D and/or calcium deficient diets may differentially affect muscle fiber neuromuscular junction innervation

Abstract: These data suggest that detrimental effects of a Vit. D deficient or a Vit. D and Ca deficient diet may be a result of differential alterations in the structure and function of the NMJ and a lack of a sustained stress response in muscles. Muscle Nerve 54: 1120-1132, 2016.

Cited by 22 publications

References 85 publications

The vitamin D activator CYP27B1 is upregulated in muscle fibers in denervating disease and can track progression in amyotrophic lateral sclerosis

The vitamin D activator CYP27B1 is upregulated in muscle fibers in denervating disease and can track progression in amyotrophic lateral sclerosis

Vitamin D in Pain Management

Vitamin D supplementation to palliative cancer patients shows positive effects on pain and infections—Results from a matched case-control study

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