Infections and Autoimmunity-The Immune System and Vitamin D: A Systematic Review

Sunil J Wimalawansa, Sunil J Wimalawansa

Abstract

Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)2D: calcitriol), play critical roles in protecting humans from invasive pathogens, reducing risks of autoimmunity, and maintaining health. Conversely, low 25(OH)D status increases susceptibility to infections and developing autoimmunity. This systematic review examines vitamin D's mechanisms and effects on enhancing innate and acquired immunity against microbes and preventing autoimmunity. The study evaluated the quality of evidence regarding biology, physiology, and aspects of human health on vitamin D related to infections and autoimmunity in peer-reviewed journal articles published in English. The search and analyses followed PRISMA guidelines. Data strongly suggested that maintaining serum 25(OH)D concentrations of more than 50 ng/mL is associated with significant risk reduction from viral and bacterial infections, sepsis, and autoimmunity. Most adequately powered, well-designed, randomized controlled trials with sufficient duration supported substantial benefits of vitamin D. Virtually all studies that failed to conclude benefits or were ambiguous had major study design errors. Treatment of vitamin D deficiency costs less than 0.01% of the cost of investigation of worsening comorbidities associated with hypovitaminosis D. Despite cost-benefits, the prevalence of vitamin D deficiency remains high worldwide. This was clear among those who died from COVID-19 in 2020/21-most had severe vitamin D deficiency. Yet, the lack of direction from health agencies and insurance companies on using vitamin D as an adjunct therapy is astonishing. Data confirmed that keeping an individual's serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L) (and above 40 ng/mL in the population) reduces risks from community outbreaks, sepsis, and autoimmune disorders. Maintaining such concentrations in 97.5% of people is achievable through daily safe sun exposure (except in countries far from the equator during winter) or taking between 5000 and 8000 IU vitamin D supplements daily (average dose, for non-obese adults, ~70 to 90 IU/kg body weight). Those with gastrointestinal malabsorption, obesity, or on medications that increase the catabolism of vitamin D and a few other specific disorders require much higher intake. This systematic review evaluates non-classical actions of vitamin D, with particular emphasis on infection and autoimmunity related to the immune system.

Keywords: 25(OH)D; epidemiology; morbidity; mortality; prevention; public health; treatment.

Conflict of interest statement

The author declares no conflict of interest. He received no funding for this work or assistance in professional writing for this review.

Figures

Figure 1
Figure 1
PRISMA flow chart. Selection path of reference to advances in knowledge of vitamin D with particular emphasis on infections, autoimmunity, and the immune system.
Figure 2
Figure 2
Relationships between vitamin D and a spectrum of non-skeletal diseases and disorders associated with vitamin D deficiency. The complicated relationships between beneficial 25(OH)D concentrations (sufficiency) and various organ systems in the body and diseases are depicted. Top panel (light green background)—vitamin D sufficiency: White ovals—mode of vitamin D generation/entry to the body. Yellow ovals—system dysfunction. Green ovals—endocrine functions of vitamin D (circulating 1,25(OH)2D: calcitriol) on calcium metabolism. Bottom panela (light yellow background)— vitamin D deficiency: Dark blue ovals—functional and pathophysiological relationships with tissues and organ systems. Light blue ovals—metabolic dysfunctions associated with hypovitaminosis D. Abbreviations: Ca++, calcium; FGF23, fibroblast growth factor-23; IR, insulin resistance; Mg++, magnesium; UV, ultraviolet rays. Arrows indicate increased (improved) or decreased incidence or severity (modified from Wimalawansa 2012 and 2016 [30,31]).
Figure 3
Figure 3
Major negative consequences are categorized into groups of chronic vitamin D deficiency.
Figure 4
Figure 4
Different diseases (and tissues) require different steady-state serum 25(OH)D concentrations to achieve improvement: the need for varied serum 25(OH)D concentrations to subdue various disease statuses is illustrated (modified from Wimalawansa, S.J. Steroid Biochemistry [31].
Figure 5
Figure 5
Illustration of the dose/25(OH)D concentrations achieved in the circulation vs. responses (clinical health benefits and potential risks). It also provides the basic pharmacodynamics of a typical nutrient, taking vitamin D as an example. When tissue sufficiency occurred, generally, there would not be additional benefits by raising the circulatory concentration by increasing the intake. However, there are exceptions in a small percentage; pharmacological doses are needed under medical guidance in less than 0.01% of the population to overcome resistance to achieve the desired clinical goals (indicated in the dashed blue line) [115].

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Source: PubMed

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