Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy

Gomaa, Adel A.; Abdel-Wadood, Yasmin A.; Thabet, Romany H.; Gomaa, Ghada A.

doi:10.1007/s10787-023-01383-x

Cited by 3 publications

(2 citation statements)

References 132 publications

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“…In doing this, they have shown the promise of clinical value as both preventatives and therapeutics in various disease scenarios. Using COVID-19 as an example, it is instructive to consider the now-demonstrated utility of the micronutrient vitamin D3 in this disease’s severity [ 46 , 47 , 48 ]. The clinical picture here is well-supported by vitamin D’s reported ability to improve airway barrier function, as well as reduce the airway barrier compromise caused by proinflammatory TNF-α in in vitro studies [ 29 , 45 ].…”

Section: Micronutrient Reduction Of Barrier Leakmentioning

confidence: 99%

Micronutrients at Supplemental Levels, Tight Junctions and Epithelial Barrier Function: A Narrative Review

DiGuilio,

Del Rio,

Harty

et al. 2024

IJMS

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Disease modifiers, whether from cancer, sepsis, systemic inflammation, or microbial pathogens, all appear to induce epithelial barrier leak, with induced changes of the Tight Junctional (TJ) complex being pivotal to the process. This leak—and the ensuant breakdown of compartmentation—plays a central role in disease morbidity on many levels. Accumulation of lung water in the luminal compartment of airways was a major driver of morbidity and mortality in COVID-19 and is an excellent example of the phenomenon. Increasing awareness of the ability of micronutrients to improve basal barrier function and reduce barrier compromise in pathophysiology may prove to be a low-cost, safe, and easily administered prophylactic and/or therapeutic option amenable to large populations. The growing appreciation of the clinical utility of supplemental doses of Vitamin D in COVID-19 is but one example. This narrative review is intended to propose a general theory on how and why micronutrients—at levels above normal dietary intake—successfully remodel TJs and improve barrier function. It discusses the key difference between dietary/Recommended Daily Allowance (RDA) levels of micronutrients versus supplemental levels, and why the latter are needed in disease situations. It advances a hypothesis for why signal transduction regulation of barrier function may require these higher supplemental doses to achieve the TJ remodeling and other barrier element changes that are clinically beneficial.

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Section: Micronutrient Reduction Of Barrier Leakmentioning

confidence: 99%

Micronutrients at Supplemental Levels, Tight Junctions and Epithelial Barrier Function: A Narrative Review

DiGuilio,

Del Rio,

Harty

et al. 2024

IJMS

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“…Metformin may enhance vitamin D receptor sensitivity by improving AMPK signaling, thereby augmenting its lung-protective effects. 132 Sorafenib, commonly used in chemotherapy for non-small cell lung cancer (NSCLC), showed in a phase II clinical trial involving KRAS-mutant advanced NSCLC that combining sorafenib with metformin enhanced AMPK activity, which improved the inhibition of cancer cell proliferation and had a beneficial impact on tumor regression. 133 …”

Section: Ampk/nrf2 Signaling Pathwaymentioning

confidence: 99%

Targeting the AMPK/Nrf2 Pathway: A Novel Therapeutic Approach for Acute Lung Injury

Huang,

Ren,

Yuan

et al. 2024

JIR

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ALI(acute lung injury) is a severe respiratory dysfunction caused by various intrapulmonary and extrapulmonary factors. It is primarily characterized by oxidative stress and affects the integrity of the pulmonary barrier. In severe cases, ALI can progress to ARDS(acute respiratory distress syndrome), a condition that poses a serious threat to the lives of affected patients. To date, the etiological mechanisms underlying ALI remain elusive, and available therapeutic options are quite limited. AMPK(AMP-activated protein kinase), an essential serine/threonine protein kinase, performs a pivotal function in the regulation of cellular energy levels and cellular regulatory mechanisms, including the detection of redox signals and mitigating oxidative stress. Meanwhile, Nrf2(nuclear factor erythroid 2-related factor 2), a critical transcription factor, alleviates inflammation and oxidative responses by interacting with multiple signaling pathways and contributing to the modulation of oxidative enzymes associated with inflammation and programmed cell death. Indeed, AMPK induces the dissociation of Nrf2 from Keap1(kelch-like ECH-associated protein-1) and facilitates its translocation into the nucleus to trigger the transcription of downstream antioxidant genes, ultimately suppressing the expression of inflammatory cells in the lungs. Given their roles, AMPK and Nrf2 hold promise as novel treatment targets for ALI. This study aimed to summarise the current status of research on the AMPK/Nrf2 signaling pathway in ALI, encompassing recently reported natural compounds and drugs that can activate the AMPK/Nrf2 signaling pathway to alleviate lung injury, and provide a theoretical reference for early intervention in lung injury and future research on lung protection.

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Effects of an 8‐week high‐dose vitamin D supplementation on fatigue and neuropsychiatric manifestations in post‐COVID syndrome: A randomized controlled trial

Charoenporn,

Tungsukruthai,

Teacharushatakit

et al. 2024

Psychiatry Clin Neurosci

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AimThis study evaluated the effectiveness of high‐dose vitamin D supplementation in alleviating fatigue and neuropsychiatric symptoms in post‐COVID syndrome.MethodsIn an 8‐week, double‐blind, randomized, placebo‐controlled trial, 80 patients with post‐COVID fatigue or neuropsychiatric symptoms were enrolled. Participants were randomly assigned to receive either 60,000 IU of vitamin D weekly (n = 40) or a placebo (n = 40) for 8 weeks. Clinical outcomes were assessed using the 11‐item Chalder Fatigue Scale (CFQ‐11); 21‐item Depression, Anxiety, and Stress Scale (DASS‐21); Pittsburgh Sleep Quality Index (PSQI); Addenbrooke's Cognitive Examination III (ACE); and Trail Making Test A and B (TMT‐A and TMT‐B). Baseline and 8‐week measurements of inflammatory markers, including interleukin 6 (IL‐6) and C‐reactive protein (CRP), were also collected.ResultsSignificant improvements were found in the vitamin D group for CFQ (coefficient −3.5, P = 0.024), DASS‐anxiety (−2.0, P = 0.011), and ACE (2.1, P = 0.012). No significant differences were observed in PSQI, DASS‐depression, TMT, IL‐6, or CRP levels. The incidence of adverse events was comparable between groups, with no serious adverse events reported.ConclusionHigh‐dose vitamin D supplementation may benefit patients with post‐COVID syndrome by reducing fatigue, alleviating anxiety, and improving cognitive symptoms, with minimal side effects.

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Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy

Cited by 3 publications

References 132 publications

Micronutrients at Supplemental Levels, Tight Junctions and Epithelial Barrier Function: A Narrative Review

Micronutrients at Supplemental Levels, Tight Junctions and Epithelial Barrier Function: A Narrative Review

Targeting the AMPK/Nrf2 Pathway: A Novel Therapeutic Approach for Acute Lung Injury

Effects of an 8‐week high‐dose vitamin D supplementation on fatigue and neuropsychiatric manifestations in post‐COVID syndrome: A randomized controlled trial

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