The Effect of Weekly 50,000 IU Vitamin D3 Supplements on the Serum Levels of Selected Cytokines Involved in Cytokine Storm: A Randomized Clinical Trial in Adults with Vitamin D Deficiency

Bader, Dana A.; Abed, Anas; Mohammad, Beisan A; Aljaberi, Ahmad; Sundookah, Ahmad; Habash, Maha; Alsayed, Ahmad R.; Abusamak, Mohammad; Al-Shakhshir, Sami; Abu-Samak, Mahmoud

doi:10.3390/nu15051188

Cited by 6 publications

(5 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, it is crucial to prevent (intracellular) magnesium deficiency and provide sufficient amounts of other micronutrients and co-factors, allowing robust immune and metabolic functions. Because of the multiple biological and physiological benefits, the prompt administration of proper vitamin D dose supplements is necessary to prevent complications, ICU admissions, and death from infections [ 174 ]. Serum 25(OH)D concentration over 50 ng/mL is also necessary to overcome some cancers and reduce all-cause mortality.…”

Section: Discussionmentioning

confidence: 99%

Physiological Basis for Using Vitamin D to Improve Health

Wimalawansa

2023

Biomedicines

View full text Add to dashboard Cite

Vitamin D is essential for life—its sufficiency improves metabolism, hormonal release, immune functions, and maintaining health. Vitamin D deficiency increases the vulnerability and severity of type 2 diabetes, metabolic syndrome, cancer, obesity, and infections. The active enzyme that generates vitamin D [calcitriol: 1,25(OH)2D], CYP27B1 (1a-hydoxylase), and its receptors (VDRs) are distributed ubiquitously in cells. Once calcitriol binds with VDRs, the complexes are translocated to the nucleus and interact with responsive elements, up- or down-regulating the expression of over 1200 genes and modulating metabolic and physiological functions. Administration of vitamin D3 or correct metabolites at proper doses and frequency for longer periods would achieve the intended benefits. While various tissues have different thresholds for 25(OH)D concentrations, levels above 50 ng/mL are necessary to mitigate conditions such as infections/sepsis, cancer, and reduce premature deaths. Cholecalciferol (D3) (not its metabolites) should be used to correct vitamin D deficiency and raise serum 25(OH)D to the target concentration. In contrast, calcifediol [25(OH)D] raises serum 25(OH)D concentrations rapidly and is the agent of choice in emergencies such as infections, for those who are in ICUs, and for insufficient hepatic 25-hydroxylase (CYP2R1) activity. In contrast, calcitriol is necessary to maintain serum-ionized calcium concentration in persons with advanced renal failure and hypoparathyroidism. Calcitriol is, however, ineffective in most other conditions, including infections, and as vitamin D replacement therapy. Considering the high costs and higher incidence of adverse effects due to narrow therapeutic margins (ED50), 1α-vitamin D analogs, such as 1α-(OH)D and 1,25(OH)2D, should not be used for other conditions. Calcifediol analogs cost 20 times more than D3—thus, they are not indicated as a routine vitamin D supplement for hypovitaminosis D, osteoporosis, or renal failure. Healthcare workers should resist accepting inappropriate promotions, such as calcifediol for chronic renal failure and calcitriol for osteoporosis or infections—there is no physiological rationale for doing so. Maintaining the population’s vitamin D sufficiency (above 40 ng/mL) with vitamin D3 supplements and/or daily sun exposure is the most cost-effective way to reduce chronic diseases and sepsis, overcome viral epidemics and pandemics, and reduce healthcare costs. Furthermore, vitamin D sufficiency improves overall health (hence reducing absenteeism), reduces the severity of chronic diseases such as metabolic and cardiovascular diseases and cancer, decreases all-cause mortality, and minimizes infection-related complications such as sepsis and COVID-19-related hospitalizations and deaths. Properly using vitamin D is the most cost-effective way to reduce chronic illnesses and healthcare costs: thus, it should be a part of routine clinical care.

show abstract

Section: Discussionmentioning

confidence: 99%

Physiological Basis for Using Vitamin D to Improve Health

Wimalawansa

2023

Biomedicines

View full text Add to dashboard Cite

show abstract

“…These data would suggest that subjects with a history of adenoma should follow an anti-inflammatory diet and avoid unmotivated supplements [ 38 ]. Vitamin D supplementation has an effect on circulating cytokine and their modulation can be different based on the individual condition, being more pronounced in patients with inflammatory disorders compared to healthy subjects [ 39 , 40 ]. Furthermore, the trial by Fassio et al did not show significant differences among the different Vitamin D dosages.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Supplementation and Adherence to World Cancer Research Fund (WCRF) Diet Recommendations for Colorectal Cancer Prevention: A Nested Prospective Cohort Study of a Phase II Randomized Trial

et al. 2023

View full text Add to dashboard Cite

Vitamin D and a healthy diet, based on World Cancer Research Fund (WCRF) recommendations, are considered key elements for colorectal cancer (CRC) prevention. In a CRC case-control study, we observed that CRC cases were often significantly Vitamin D deficient while subjects following WCRF recommendations significantly decreased their risk of developing CRC. We conducted a randomized phase-II trial (EudraCT number-2015-000467-14) where 74 CRC patients showed differences in response to Vitamin D supplementation, 2000 IU in average per day, according to gender and microbiota. The aim of this nested study is to correlate Vitamin D (supplementation, serum level and receptor polymorphisms), circulating biomarkers, and events (polyp/adenoma, CRC relapse and other cancers) in concomitant to WCRF recommendation adherence. Vitamin D supplementation did not modulate circulating biomarkers or follow-up events. FokI and TaqI VDR were associated with 25-hydroxyvitamin D (25OHD) levels. Patients following the WCRF recommendations had significantly lower leptin, significantly lower IL-6 (only in females), and significantly lower risk of events (HR = 0.41, 95%CI: 0.18–0.92; p = 0.03; median follow-up 2.6 years). Interestingly, no WCRF adherents had significantly more events if they were in the placebo (p < 0.0001), whereas no influence of WCRF was observed in the Vitamin D arm. While one-year Vitamin D supplementation might be too short to show significant preventive activity, a healthy diet and lifestyle should be the first step for preventive programs.

show abstract

“…Relative studies showed that the levels of inflammatory cytokines, such as IL-6, IL-1, IL-18, and TNF-α, were significantly reduced with the vitamin D treatment group in SLE patients. On the other hand, vitamin D treatment upregulated IL-10 expression ( 33 , 34 ). A study found a positive correlation between elevated serum 25(OH)D and elevated IL-10.…”

Section: Discussionmentioning

confidence: 99%

The changes of Treg and Th17 cells relate to serum 25(OH)D in patients with initial-onset childhood systemic lupus erythematosus

Jiang,

Rong,

Zhang

2023

Front. Pediatr.

View full text Add to dashboard Cite

BackgroundT helper 17 (Th17) cells and regulatory T cells (Treg) are known to play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). Improving the balance between Treg and Th17 cells can be a promising new therapeutic target in SLE patients. Vitamin D has a significant impact on the immune inflammatory process and the immune cells involved in this process. The purpose of this study is to investigate the relationship between Th17, Treg, cytokines, and serum 25 hydroxyvitamin D [25(OH)D] in patients with initial-onset childhood SLE.MethodsA total of 82 children aged <18 years with initial-onset SLE were included, as well as 60 healthy subjects during the same period at the Pediatrics Department of the Second Hospital of Hebei Medical University. The chemiluminescence method was performed to detect serum 25(OH)D levels. Flow cytometry was used to evaluate Treg and Th17 cells. An enzyme-linked immunosorbent assay kit was used to evaluate plasma interleukin (IL)-23, IL-17, IL-10, IL-6, and tumor necrosis factor alpha (TNF-α) concentrations.ResultThe serum 25(OH)D levels in patients with initial-onset childhood SLE were significantly lower than those in the healthy controls. The proportion of lupus nephritis (LN) was higher in the vitamin D insufficiency group (71.4%) compared with the vitamin D sufficiency group (30.3%) (p < 0.05). The SLE disease activity index (SLEDAI) was higher in the vitamin D insufficiency group (median = 14) than that in the vitamin D sufficiency group (median = 9) (p < 0.05).The 25(OH)D level was positively correlated with the Treg ratio (r = 0.337, p = 0.002), and it was negatively correlated with the Th17 cell ratio (r = −0.370, p = 0.001). The serum 25(OH)D level had a negative correlation with IL-23 (r = −0.589, p < 0.001), IL-17(r = −0.351, p = 0.001), TNF-α (r = −0.283, p = 0.01), IL-6 (r = −0.392, p < 0.001), and IL-10 (r = −0.313, p = 0.004) levels.ConclusionThe serum 25(OH)D levels decreased in patients with initial-onset childhood SLE. There was a negative correlation between the serum 25(OH)D levels and SLEDAI. The serum 25(OH)D levels in patients with initial-onset childhood SLE were negatively correlated with the Th17 ratio and related cytokines, while positively correlated with the Treg ratio.

show abstract

The Effect of Weekly 50,000 IU Vitamin D3 Supplements on the Serum Levels of Selected Cytokines Involved in Cytokine Storm: A Randomized Clinical Trial in Adults with Vitamin D Deficiency

Cited by 6 publications

References 60 publications

Physiological Basis for Using Vitamin D to Improve Health

Physiological Basis for Using Vitamin D to Improve Health

Vitamin D Supplementation and Adherence to World Cancer Research Fund (WCRF) Diet Recommendations for Colorectal Cancer Prevention: A Nested Prospective Cohort Study of a Phase II Randomized Trial

The changes of Treg and Th17 cells relate to serum 25(OH)D in patients with initial-onset childhood systemic lupus erythematosus

Contact Info

Product

Resources

About