Target Health Blog

Vitamin D Levels Appear to Play a Role in COVID-19 Mortality

June 8, 2020


Calcium regulation in the human body. The role of active vitamin D (1,25-dihydroxyvitamin D, calcitriol) is shown in orange.
Graphic credit: by Mikael Haggstrom - All used images are in public domain., Public Domain; Wikipedia Commons

Vitamin D is a group of fat-soluble 1) _____ responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and multiple other biological effects. In humans, the most important compounds in this group are vitamin D3 (also known as cholecalciferol) and vitamin D2 (ergocalciferol). The major natural source of the vitamin is synthesis of cholecalciferol in the lower layers of skin epidermis through a chemical reaction that is dependent on 2) _____ exposure (specifically UVB radiation). Only a few foods, such as the flesh of fatty fish, naturally contain significant amounts of vitamin D. In the U.S. and other countries, cow's milk and plant-derived milk substitutes are fortified with vitamin D, as are many breakfast cereals. Mushrooms exposed to ultraviolet light contribute useful amounts of vitamin D. Dietary recommendations typically assume that all of a person's vitamin D is taken by mouth, as sun exposure in the population is variable and recommendations about the amount of sun exposure that is safe are uncertain in view of the skin cancer risk.

The active vitamin D metabolite 3) _____ mediates its biological effects by binding to the vitamin D receptor (VDR), which is principally located in the nuclei of target cells. The binding of calcitriol to the VDR allows the VDR to act as a transcription factor that modulates the gene expression of transport proteins (such as TRPV6 and calbindin), which are involved in calcium absorption in the intestine. The vitamin D receptor belongs to the nuclear receptor superfamily of steroid/thyroid hormone receptors, and VDRs are expressed by cells in most organs, including the brain, heart, skin, gonads, prostate, and breast. VDR activation in the intestine, bone, kidney, and parathyroid gland cells leads to the maintenance of calcium and phosphorus levels in the blood (with the assistance of parathyroid hormone and calcitonin) and to the maintenance of bone content.

One of the most important roles of vitamin D is to maintain skeletal 4) _____ balance by promoting calcium absorption in the intestines, promoting bone resorption by increasing osteoclast number, maintaining calcium and phosphate levels for bone formation, and allowing proper functioning of parathyroid hormone to maintain serum calcium levels. Vitamin D deficiency can result in lower bone mineral density and an increased risk of reduced bone density (osteoporosis) or bone fracture because a lack of vitamin D alters mineral metabolism in the body. Thus, vitamin D is also critical for bone remodeling through its role as a potent stimulator of bone resorption. The VDR regulates cell proliferation and differentiation. Vitamin D also affects the immune system, and VDRs are expressed in several white blood cells, including monocytes and activated T and B cells. In vitro, vitamin D increases expression of the tyrosine hydroxylase gene in adrenal medullary cells, and affects the synthesis of neurotrophic factors, nitric oxide synthase, and glutathione.

Vitamin D receptor expression decreases with age and findings suggest that vitamin D is directly related to muscle strength, mass and function, all being important factors to an athlete's performance. An estimated one 5) _____ people worldwide are either vitamin D insufficient or deficient.[24] A diet with insufficient vitamin D in conjunction with inadequate sun exposure causes vitamin D deficiency. Severe vitamin D deficiency in children causes rickets, a softening and weakening of bones, which is a rare disease in the developed world.  Vitamin D deficiency is found worldwide in the elderly and remains common in children and adults. Deficiency results in impaired bone mineralization and bone damage which leads to bone-softening diseases, including 6) _____ in children and osteomalacia in adults. Low blood calcifediol (25-hydroxy-vitamin D) can result from avoiding the sun. Being deficient in vitamin D can cause intestinal absorption of dietary calcium to fall to 15%. When not deficient, an individual usually absorbs between 60-80%.

Because it found mounting evidence for a benefit to bone health, the US Food and Drug Administration (FDA) has required manufacturers to declare the amount of vitamin D on nutrition facts labels, as “nutrients of public health significance“, since May 2016. By a proposed deadline extension, small manufacturers with less than $10 million in annual food sales will have to comply by January 1, 2021, while larger ones have to comply by January 1, 2020.[74] Manufacturers of single-ingredient sugars such as honey and maple syrup and certain cranberry products have until July 1, 2021, to make the changes.

Patients with severe Vitamin D 7) _____deficiency are twice as likely to experience major complications based on patient data from 10 countries. The study found a correlation between low vitamin D levels and hyperactive immune systems. Vitamin D strengths innate immunity and prevents overactive immune responses. The finding could explain several mysteries, including why children are unlikely to die from COVID-19. After studying global data from the novel 8) _____ (COVID-19) pandemic, researchers have discovered a strong correlation between severe vitamin D deficiency and mortality rates.

The research is available on medRxiv, a preprint server for health sciences.

The authors were inspired to examine vitamin D levels after noticing unexplained differences in COVID-19 mortality rates from country to country. Some people hypothesized that differences in healthcare quality, age distributions in population, testing rates or different strains of the coronavirus might be responsible. But the authors remained skeptical. By analyzing publicly available patient data from around the globe, it was discovered a strong correlation between vitamin D levels and cytokine 9) _____ - a hyperinflammatory condition caused by an overactive immune system - as well as a correlation between vitamin D deficiency and mortality. Thus not only does vitamin D enhance our innate immune systems, it also can prevent our immune systems from becoming dangerously overactive. This means that having healthy levels of vitamin D could protect patients against severe complications, including death, from COVID-19. The authors said that this correlation might help explain the many mysteries surrounding COVID-19, such as why children are less likely to die. Children do not yet have a fully developed acquired immune system, which is the immune system's second line of defense and more likely to 10) _____.

Sources: The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients. medRxiv, Posted April 30, 2020; Northwestern University. “Vitamin D levels appear to play role in COVID-19 mortality rates: Patients with severe deficiency are twice as likely to experience major complications;“; Wikipedia

ANSWERS: 1) secosteroids; 2) sun; 3) calcitriol; 4) calcium; 5) billion; 6) rickets; 7) deficiency; 8) coronavirus; 9) storm; 10) overreact

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