Is there a window of opportunity for the therapeutic use of vitamin D in multiple sclerosis?

Zorzella-Pezavento, Sofia Fernanda Gonçalves; Mimura, Luiza Ayumi Nishiyama; Denadai, Marina Bonifácio; Souza, William Danilo Fernandes de; Fraga-Silva, Thais Fernanda de Campos; Sartori, Alexandrina

doi:10.4103/1673-5374.335139

Cited by 8 publications

(3 citation statements)

References 181 publications

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“…Furthermore, 25(OH)D3 is metabolized into 1,25(OH) 2 D3 (Supplementary Fig. 7 ), which exerts immunomodulatory effects and regulates neurogenesis and neuroprotection, potentially contributing to the potential protective effects of D3 in multiple sclerosis 48 . The 25(OH)D3 is also metabolized into 24,25(OH) 2 D3 (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

An ultra-sensitive and high-throughput trapping-micro-LC-MS method for quantification of circulating vitamin D metabolites and application in multiple sclerosis patients

Qu,

Zhang,

Weinstock-Guttman

et al. 2024

Sci Rep

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Quantitative analysis of the biologically-active metabolites of vitamin D (VitD), which are crucial in regulating various physiological and pathological processes, is important for clinical investigations. Liquid chromatography-tandem mass spectrometry (LC-MS) has been widely used for this purpose but existing LC-MS methods face challenges in achieving highly sensitive and accurate quantification of low-abundance VitD metabolites while maintaining high throughput and robustness. Here we developed a novel pipeline that combines a trapping-micro-LC-(T-µLC) with narrow-window-isolation selected-reaction monitoring MS(NWI-SRM) for ultra-sensitive, robust and high-throughput quantification of VitD metabolites in serum samples after derivatization. The selective-trapping and delivery approach efficiently removes matrix components, enabling high-capacity sample loading and enhancing sensitivity, throughput, and robustness. The NWI-SRM further improves the sensitivity by providing high selectivity. The lower limits of quantification (LOQs) achieved were markedly lower than any existing LC-MS methods: 1.0 pg/mL for 1,25(OH)2D3, 5.0 pg/mL for 24,25(OH)2D3, 30 pg/mL for both 25(OH)D2 and 25(OH)D3, all within a 9-min cycle. The method is applied to quantify VitD metabolites from 218 patients with multiple sclerosis. This study revealed negative correlations(r=− 0.44 to − 0.51) between the levels of 25(OH)D2 and all the three D3 metabolites in multiple sclerosis patients.

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Section: Resultsmentioning

confidence: 99%

An ultra-sensitive and high-throughput trapping-micro-LC-MS method for quantification of circulating vitamin D metabolites and application in multiple sclerosis patients

Qu,

Zhang,

Weinstock-Guttman

et al. 2024

Sci Rep

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show abstract

“…VitD stimulates the expression of the glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), BDNF, NT3 [98,99], and the p75 NT receptor (p75 NTR ) in neurons, glial cells, and Schwann cells [97]. Reduction in vitD promoted neurotrophic factor expression due to vitD deficiency may result in neurons becoming more susceptible to damage [97,98,100,101].…”

Section: Primary Prevention Of Depressive States By Influencing Activ...mentioning

confidence: 99%

Multiple sclerosis with comorbidity depression and its association with vitamin D deficiency in a narrative review of the current literature

Goischke

2023

Explor Neurosci

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Over the past decade, knowledge of the pathophysiology and immunology of multiple sclerosis (MS) and depression, and the complex links to vitamin D (VitD) balance, has increased rapidly. Both diseases are characterized by an imbalance of proinflammatory and antiinflammatory cytokines, increased serum neurofilament light chains (sNfLs), disruption of the blood-brain barrier (BBB), abolition of the physiological function of the various types of microglia (MG), decreased calcidiol-serum levels, and disorders of the gut microbiome in combination with hyperactivity of the hypothalamic-pituitary-adrenal (HPA)-axis/microbiome-gut-brain-axis characterized. In depression, stress initiates cellular and molecular changes in the brain via increased cortisol release in the HPA-axis. Microglial activation and neuronal damage as well as dysregulation of neuroplastic and neurotrophic factors complete the spectrum of pathological damage. It is shown that gut dysbiosis leads to increased gut permeability, which favors endotoxemia and ultimately paves the way to systemic inflammation. A VitD supplementation could restore the balance of microorganisms in the intestine and reduce the inflammatory processes at various levels. VitD promotes regulatory T cell (Treg) proliferation, inhibits the expression of T helper 1 (Th1) cells and Th17 immune cells, and inhibits proinflammatory interleukin-17 (IL-17). 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] reduces also the secretion of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Increased calcitriol levels lead to a reduction in MG activation, oxidative stress, and lower BBB permeability. An early, permanent, daily sufficient VitD supplementation as an add-on therapy under control of the serum 25-hydroxyvitamin D [s25(OH)D] levels is an essential therapeutic tool to slow down the disability caused by MS and thereby primarily prevent or reduce the stress and subsequently the manifestation of depression. Through the future continuous measurement of the biomarkers serum neurofilament ligth chains and glial fibrillary acidic proteins as well as the s25(OH)D level in MS and comorbidity depression, future therapy successes or failures can be avoided.

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“…Multi vitaminic supplementation (e.g., A and D): quite convincing data show that higher vitamin intake/serum levels correlate with lower risk of MS development but not convincing on the contrary [85]. Possible detrimental effects of overdosing require vitamin-level monitoring [86,87].…”

Section: Multi Vitaminicmentioning

confidence: 99%

Multiple Sclerosis—Related Dietary and Nutritional Issues: An Updated Scoping Review with a Focus on Pediatrics

Mandato,

Colucci,

Lanzillo

et al. 2023

Children

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Purpose. Lifestyle/dietetic habits play an important role in the development and progression of multiple sclerosis (MS) disease. Here, we examine the basic pathomechanisms underlying intestinal and brain barrier modifications in MS and consider diets and dietary supplementations proposed over time to complement pharmacological therapies for improving disease outcome both in adults and in children. Methods. Scoping literature search about evidence-based findings in MS-related gut-brain axis (GBA) pathophysiology and nutritional issues at all ages. Findings. Data show that (1) no universal best diet exists, (2) healthy/balanced diets are, however, necessary to safeguard the adequate intake of all essential nutrients, (3) diets with high intakes of fruits, vegetables, whole grains, and lean proteins that limit processed foods, sugar, and saturated fat appear beneficial for their antioxidant and anti-inflammatory properties and their ability to shape a gut microbiota that respects the gut and brain barriers, (4) obesity may trigger MS onset and/or its less favorable course, especially in pediatric-onset MS. Vitamin D and polyunsaturated fatty acids are the most studied supplements for reducing MS-associated inflammation. Conclusions. Pending results from other and/or newer approaches targeting the GBA (e.g., pre- and probiotics, engineered probiotics, fecal-microbiota transplantation), accurate counseling in choosing adequate diet and maintaining physical activity remains recommended for MS prevention and management both in adults and children.

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Is there a window of opportunity for the therapeutic use of vitamin D in multiple sclerosis?

Cited by 8 publications

References 181 publications

An ultra-sensitive and high-throughput trapping-micro-LC-MS method for quantification of circulating vitamin D metabolites and application in multiple sclerosis patients

An ultra-sensitive and high-throughput trapping-micro-LC-MS method for quantification of circulating vitamin D metabolites and application in multiple sclerosis patients

Multiple sclerosis with comorbidity depression and its association with vitamin D deficiency in a narrative review of the current literature

Multiple Sclerosis—Related Dietary and Nutritional Issues: An Updated Scoping Review with a Focus on Pediatrics

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