What’s in the web for family physicians – vitamin D and its clinical implications

Wilbert WB Wong 王維斌，Alfred KY Tang 鄧權恩

HK Pract 2021;43:11-12

Vitamin D is a fat-soluble vitamin. It plays an important role in bone metabolism, anti-inflammatory and immune-modulating properties. Vitamin D is found naturally in only a few kinds of food such as fish-liver oils, fatty fishes, mushrooms, egg yolks, and liver. It is also produced when sunlight strikes the skin and then triggers vitamin D synthesis.

Low vitamin D levels are associated with increased overall and cardiovascular mortality, cancer incidence and mortality, and autoimmune diseases such as multiple sclerosis.

Vitamin D – fact sheet for health care professionals

The National Institues of Health had published a fact sheet on vitamin D deficiency intended for health professionals, last updated in October 2020. The expert committee of the Food and Nutrition Board (FNB) had identified some patient groups who are more prone to vitamin D inadequacy, namely breastfed infants, older adults, those with limited sun exposure, dark skin, those with conditions that limit fat absorption, and whose who are obese or have undergone gastric bypass surgery.

Besides, implications of vitamin D on different health issues, sources of vitamin D as well as health risks of excessive vitamin D and interactions with other medications are also outlined. There are also information on what kinds of food are rich in vitamin D.

Vitamin D and bone health: a practical clinical guideline for adult patient management. National Osteoporosis Society.

Vitamin D deficiency is common in the UK, particularly in older people with limited exposure to sunlight. The Royal Osteoporosis Society had issued a practical clinical guideline on vitamin D and bone health in 2020. It was primarily intended for health practitioners as an aid to patient management. The guideline had discussions on who should be tested for vitamin D deficiency, how vitamin D status should be assessed, and how the results should be interpreted. It also outlined what treatment regimens and follow up plans are available.

Vitamin D is important in the prevention of a lot of non-skeletal disorders such as autoimmune disease, cancer, mental health problems, and correcting vitamin D is essential in the treatment of osteoporosis and some other bone diseases. The guideline also suggested that people over 65, people who have low or no exposure to the sun, and people who have darker skin to check vitamin D status. People aged 65 years and over and people who are not exposed to much sun should also take a daily supplement of vitamin D.

Vitamin D deficiency guidelines in children

This is a guideline on Vitamin D deficiency in children developed by the Royal Children’s Hospital of Melbourne, last updated in September 2020. The guideline outlined management approaches to Vitamin D deficiency, from history taking, clinical assessment, management flowcharts, investigations and treatment. Background information and risk factors of vitamin D deficiency are well summarised.

The guideline also covered treatment approaches of vitamin D deficiency for different age groups, recommendations on dietary intake of calcium, food rich in calcium, and what to do for ongoing monitoring. Other information on the choice of different vitamin D preparations, and the risk of vitamin D toxicity are also emphasised.

Development of Vitamin D toxicity from overcorrection of vitamin D deficiency: a review of case reports

Owing to its wide therapeutic index, vitamin overdose is rare. In this report, cases of patients who had received high doses of vitamin D were reviewed and features of vitamin D toxicity were discussed. The clinical manifestations of vitamin D toxicity reported in these cases were usually consequence of the hypercalcemia and included nausea, vomiting, weakness, polyuria, nephrocalcinosis, and renal failure. Vitamin D toxicity can be caused by formulation, self administration, prescription errors, which had resulted in excessive dosing. A 25(OH)D level over 150 ng/mL is likely to be associated with toxicity and should be avoided at all costs. The highest daily intake of vitamin D that would pose no risk of adverse effects is not known.

Vitamin D supplements and prevention of cancer and cardiovascular disease

Supplemental vitamin D has been viewed in recent years as a potential strategy for preventing cancer and cardiovascular disease (CVD). The VITamin D and OmegA-3 TriaL (VITAL) is a randomised clinical trial of vitamin D and marine omega-3 fatty acid supplements in the primary prevention of cancer and cardiovascular disease (CVD). Existing data from laboratory studies, epidemiologic research, small primary prevention trials, and/or large secondary prevention trials strongly suggest that these nutritional agents may reduce risk for cancer or CVD, but large primary prevention trials with adequate dosing in general populations are lacking.

The article concluded that there was no reduction in incidence of invasive cancer and cardiovascular events with vitamin D supplementation. Rates of breast, prostate, and colorectal cancer did not differ significantly between the vitamin D and placebo groups. However, normal-weight participants had greater reductions in cancer incidence and mortality rates than those who were overweight or obese.

A basic review of the preliminary evidence that COVID-19 risk and severity is increased in vitamin D deficiency

The review was trying to explore whether vitamin D deficiency increased both COVID-19 rates and illness severity. Vitamin D deficiency is one factor which increases risk for COVID-19 infection and progression. The evidence strongly suggests that vtamin D deficiency is an easily modifiable risk factor and correcting it is potentially life-saving.

Researchers reported that the risk groups for severe COVID-19 match the risk groups for vitamin D deficiency. The immune system might be impaired by vitamin D deficiency, which would predispose sufferers to viral infections such as COVID-19. Vitamin D deficiency would also increase the activity of the X-linked “Renin-Angiotensin” System, making vitamin D deficient individuals more susceptible to COVID19's deadly “cytokine storm”. The groups who were at highest risk for severe COVID-19 included the elderly, male agenda, those who avoid sun exposure for cultural and health reasons, those who lived in institutions, the obese, and those who were suffering from hypertension, cardiovascular disease, or diabetes.

Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalised for COVID-19: A pilot randomised clinical study

SARS-CoV-2 infection can remain asymptomatic or cause modest symptoms. This pilot double blinded randomised control study suggested that administration of a high dose of a main metabolite of vitamin D endocrine system would significantly reduce the need for ICU treatment of patients requiring hospitalisation due to proven COVID-19. The vitamin D endocrine system might be involved in COVID-19 progression with reduction in the Acute Respiratory Distress Syndrome. The effect of calcifediol treatment on Intensive Care Unit Admission and Mortality rate among patients hospitalised for COVID-19 were evaluated.

It was found that administration of calcifediol significantly reduced the need for ICU treatment of patients requiring hospitalisation for COVID-19. The next COVIDIOL trial could be to evaluate calcifediol associated to dexamethasone. Dexamethasone, with its potent anti-inflammatory actions, have been recommended as the best available treatment in different centers around the world.