THE HEALTH | AUGUST , 2021

Vitamin D ( VitD ), as one of the central elements of our immune system , inexpensive and relatively safe side-effect profile molecule toxic only in extremely high doses , has captivated scientists ’ interest as one potential prophylactic since the onset of the Covid-19 pandemic .

The science behind VitD ’ s crucial immuno-modulating role is longestablished ( excellent reviews here : 1 , 2 , 3 ). Figure 1 summarises some technicalities important to this discussion .

The figure below shows VitD synthesis in our body from its inactive form ( D2 / D3 ) to active form through the process of subsequent hydroxylation in our liver and kidney .

The VitD helps our innate immune cells to produce beta-defensins and cathelicidins . These peptide nano-soldiers keep the first line of defence ( see Figure 1 ) immediately as a virus enters the body and until the adaptive immune response is activated ( which happens in about 7-10 days for the first infection or within 1-2 days in case of reinfection ). In other words , even before our B-cells start producing antibodies , betadefensins and cathelicidins , which can be produced in the right quantity only in VitD sufficiency , can significantly inhibit viral entry into the cells and its replication . Furthermore , a sufficient level of active VitD inhibits the production of proinflammatory cytokines ( IL-2 , IL-12 , INF- Gamma , IL-6 , IL-8 , IL-17 ) while upregulating anti-inflammatory cytokines ( IL-4 , IL-5 , IL-10 ) ( see Figure 1 for more insights ). In other words , VitD down-regulates our

SHAKEN , NOT STIRRED

BY DR RAIS HUSSIN

AND DR MARGARITA PEREDARYENKO

Figure 1 : Immunoregulation by Vitamin D immune system response towards the humoral pathway ( antibody production ), which is less inflammatory and therefore reduces the possibility of the cytokine storm .

The empirical evidence

VitD has other functions essential in fighting SARS-CoV-2 such as reinforcing physical barrier function in epithelial , intestinal , lung and corneal cells , inducing autophagy of the infected cells , which leads to reduced replication of virus — mechanism found to be suppressed by SARS-CoV-2 ( VitD here works similar to ivermectin less its side effects ), increasing surfactants that prevent alveolar collapse and many more .

The Malaysian health authorities have been looking into the VitD and SARS-CoV-2 association at the pandemic onset . However , no action was taken due to a lack of sufficient evidence at that time .

Nevertheless , to date , empirical evidence on the close association between SARS-CoV-2 and VitD multiplied many folds . To get a quick but robust overview of the empirical evidence , it is helpful to look at the most recent systematic meta-analytical studies , which are statistical studies on the large number of empirical studies pooled together .

The above systematic reviews of numerous studies now convincingly suggest that VitD deficiency defined as 25-OH D < 20 ng / mL is significantly associated with the risk of Covid-19 infection , the severity of its outcomes and mortality .

Although , like some authors rightfully pointed out , association does not imply causation , several clinical trials on VitD supplementation as a therapeutic intervention in SARS-CoV-2 management shed some light on the causal direction .

Two most recent meta-analytic studies looked into the existing observational , cross-sectional and even randomised clinical trials for VitD supplementation to SARS-CoV-2 patients and reported the following . The odds of Intensive Care Unit ( ICU ) admission , need for mechanical ventilation , and mortality were significantly lower in the VitD intervention group than in the placebo group . In all meta-analysed studies , there was inclusion of hypertension , diabetes and corticosteroid use patients . No side effects or adverse events related to VitD intervention is reported . The above meta-analytic studies did not include another more recent published clinical trial due to the timing of publication . This randomised clinical trial ( although single centre ) found that therapeutic improvement in serum VitD levels to 80 – 100 ng / ml has significantly reduced the inflammatory markers associated with Covid-19 with no side-effects .

Among the participants , hypertension and diabetes patients were present as well .

A compelling additional strategy to flatten the curve

The discussion of modes and doses used in any of the abovementioned clinical trials is intentionally left outside of this article . They are the purview of healthcare specialists and should not be motivation to self-treatment by the general public .

Overall , the convincing empirical results congruent with the well-established theory on VitD are there , but let ’ s take correct conclusions and corrective measures .

First of all , VitD sufficiency is not a silver bullet against SARS-CoV-2 severity , unlike vaccines . However , VitD deficiency should be recognised at least as a valid and important risk factor for SARS-CoV-2 infection and its severity .

Second , given the accumulated empirical evidence , VitD supplementation intervention in deficiency cases now sounds like a compelling additional strategy to flatten the curve . It is important to note that many studies indicated importance of early VitD intervention , at least immediately upon admission to the hospital as starting supplementation upon ICU admission could be too late .

Therefore , the healthcare authorities could consider making serum VitD deficiency screening standard operating procedure upon positive polymerase chain reaction test . Early VitD supplementation ( in the form of oral vitamin D3 or calcifediol ) can be considered for cases with VitD deficiency ( 25-OH D < 20 ng / mL ) and even its insufficiency ( 25-OH D < 30 ng / mL )— generally accepted thresholds in the medical literature . This proactive strategy may result in lower hospital admission and subsequent progression of severity while reliving our overwhelmed healthcare system .

Seek qualified medical advise first

Third , this is not in any measure a call for self-treatment ! VitD can be toxic in extremely large doses or even in only relatively large doses taken for a prolonged period . Furthermore , unsupervised VitD intake can be risky for people with cardiovascular issues , hypertension , and some other underlying health conditions because VitD primary function in our body is to maintain calcium and phosphate levels .

Therefore , unsupervised VitD intake may lead to calcification and other complications . VitD supplementation would also require intake of other essential minerals such as calcium , magnesium , vitamin K2 and others . Therefore , qualified medical assessment , advice and supervision on the mode of intake , correct dosage and duration is the absolute requirement .

Last but not least is the long-term takeaway . The airborne nature of SARS-CoV-2 has taught us that ignoring the state and standards of our ventilation and filtration systems nationwide is a ticking bomb . Now this virus is drawing our attention to the long-standing problem of VitD deficiency prevalence on the national scale , which to date seems to be not given the proper attention and intervention .

The fact that pandemic management has pushed more families to the poverty line should ring even louder alarm as VitD deficiency is well known to be prevalent in low-income individuals .

SARS-CoV-2 made our lives miserable in many ways . However , would we be able to appreciate the valuable lessons it taught us ? Remember that crisis management theory 99 per cent time talks about the value of being proactive ! — The Health

Rais Hussin and Margarita Peredaryenko are part of the research team at EMIR Research , an independent think tank focused on strategic policy recommendations based on rigorous research .