Physiological Basis for Using Vitamin D to Improve Health

Abstract

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.

Impact of vitamin D on ultraviolet-induced photoaging and skin diseases

“…Vitamin D imposes a plethora of beneficial biological actions by mediating numerous endocrine and peripheral target cell functions. Skin, the location where vitamin D 3 synthesis takes place, also benefits from the protective mechanisms of vitamin D in mitigating the impact of skin photoaging [5,17,19,35].…”

“…Calcitriol can also be generated within peripheral target cells, functioning as a localized cytokine and a signaling molecule. The active 1,25(OH) 2 D that gets circulated through the bloodstream exerts its biological actions by binding to the vitamin D receptor (VDR) in the tissues through genomic and non-genomic pathways [5]. The generation of calcitriol from sunlight exposure and dietary sources is illustrated in Figure 1.…”

“…Further, vitamin D improves muscle size, cell growth, strength, and neuromuscular performance [7]. In addition to these musculoskeletal effects, vitamin D exerts a pleiotropic effect by controlling multiple body systems including respiratory, reproductive, nervous, gastrointestinal, and renal systems [5]. It plays a key role in modulating the immune system, overcoming acute infections such as sepsis and COVID-19, and preventing autoimmunity [8].…”

“…UVB photons photolyze the precursor 7-dehydrocholesterol (DHC) in the skin to previtamin D 3 , which gets isomerized later to form vitamin D 3 [12,13]. The amount of vitamin D that gets synthesized depends on the melanin content of the skin, duration of sun exposure, intensity of sunlight, and the ability of the skin to generate vitamin D [3,5]. Due to increased UV absorption by melanin, more intense sun exposure is needed to produce vitamin D in darker skin [9].…”

Vitamin D and Periodontal Health: A Systematic Review

“…Vitamin D is an elemental membrane-associated protein for its nongenomic products (communication passageways) [ 67 - 69 ]. Multiple studies revealed that vitamin D is responsible for a broad range of physiological functions [ 50 , 70 , 71 ] because it regulates the expression of many genes and their biotic course [ 72 , 73 ]. It has been reported that Vitamin D exerts a straightforward influence on the epigenome and the manifestation of over 1000 genes in utmost hominoid tissues and cell categories [ 72 ].…”