SEARCHNARRATIVE_REVIEWnutrition, micronutrients

narrative_review·nutrition, micronutrients, vitamins, endocrinology, clinical nutrition·PMC10295227

Physiological Basis for Using Vitamin D to Improve Health

Biomedicines · 1 author, 1 centre

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TL;DR

This narrative review explains the physiological roles of vitamin D and its metabolites, arguing that adequate serum 25(OH)D levels above 50 ng/mL are needed to reduce the risk and severity of numerous conditions, including infections, metabolic diseases, and cancer. The author concludes that vitamin D3 is the correct supplement for deficiency correction, while calcifediol is indicated for emergencies requiring a rapid increase in serum levels.

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This narrative review article synthesizes the physiological mechanisms and clinical applications of vitamin D. The author describes how the active enzyme CYP27B1 and vitamin D receptors (VDRs) are ubiquitous, allowing calcitriol to modulate over 1200 genes. The central argument is that serum 25(OH)D concentrations above 50 ng/mL are necessary to mitigate infections, sepsis, and cancer and reduce premature deaths. It critiques current low-dose public health recommendations as inadequate for non-musculoskeletal benefits. The author concludes that maintaining vitamin D sufficiency is a cost-effective strategy to reduce chronic diseases, infections, and healthcare costs.

STUDY TYPE

narrative_review

SPECIALTY

nutrition

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AI pipeline

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100% · A

ORIGINAL PAPER

PMC10295227

Physiological Basis for Using Vitamin D to Improve Health

Biomedicines

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ABSTRACT

Vitamin D is essential for life—its sufficiency improves metabolism, hormonal release, immune functions, and maintaining health. In contrast, 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) 2 D], CYP27B1 (1α-hydroxylase), and calcitriol 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 many metabolic and physiological functions. The administration of vitamin D 3 or its correct metabolites at proper doses and frequency for extended periods will achieve the intended benefits. The same principle applies to designing and conducting RCTs. Different tissues have varied thresholds for 25(OH)D concentrations. To mitigate conditions such as infections/sepsis and cancer and reduce premature deaths, levels above 50 ng/mL are necessary. Cholecalciferol (D 3 ) (not its metabolites) should be used to correct vitamin D deficiency and raise serum 25(OH)D to the target concentration. Calcifediol [25(OH)D], in contrast, increases serum 25(OH)D concentrations rapidly and boosts the immune system in one day. Thus, it is the agent of choice in emergencies such as infections, for those in ICUs, and insufficient hepatic 25-hydroxylase (CYP2R1) activity. Calcitriol is crucial to maintaining serum-ionized calcium concentration in persons with advanced renal failure and hypoparathyroidism. Since administered calcitriol does not enter immune cells, it is ineffective in other conditions, like infections; it should not be used 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) 2 D, should not be used for other conditions. Similarly, calcifediol costs 20 times more than D 3 : it should not be used 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. Standard diets have too little vitamin D. Maintaining the population’s vitamin D sufficiency (above 40 ng/mL) (and individuals above 50 ng/mL) with vitamin D 3 supplements and/or daily sun exposure is the most cost-effective way to reduce chronic diseases and sepsis, overcome viral epidemics and pandemics like COVID-19, and reduce healthcare costs. Furthermore, vitamin D sufficiency improves overall health, reduces absenteeism, improves productivity, 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, infections, and healthcare costs; thus, it should be a part of routine clinical care.

CITATION EXPORT

Sunil J. Wimalawansa. Physiological Basis for Using Vitamin D to Improve Health. Biomedicines. (2024). https://doi.org/10.3390/biomedicines11061542

AUTHORS

1 · 1 CENTRES

Sunil J. Wimalawansa

Medicine, Endocrinology & Nutrition, Cardio Metabolic Institute, (Former) Rutgers University, North Brunswick, NJ 08901, USA; [email protected]

EDITOR / REVIEWER

Małgorzata Żychowska, Jędrzej Antosiewicz