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Sixty seconds on . . . vitamin D

BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m3872 (Published 05 October 2020) Cite this as: BMJ 2020;371:m3872

Rapid Response:

Vitamin D Mitigates COVID-19, Say 40+ Patient Studies (listed below) – Yet BAME, Elderly, Care-homers, and Obese are still ‘D’ deficient, thus at greater COVID-19 risk - WHY?

Dear Editor

Vitamin D reduces COVID-19; infection; severity; ICU admission and mortality: as clearly evidenced by; immune biology, observational and interventional studies, and wider considerations of; latitude, seasonal UVB exposure, and national supplementation policies: the uncertainty is the quantum: but studies suggest ‘D’ effects are likely large - 50% less infectivity – multiples lower ICU and mortality rate.

Vitamin D is a steroid hormone, also present in limited dietary sources. For most, the major ‘D’ source is skin exposure to UVB in sunlight, which waxes and wanes seasonally. Supplementation is the only other option. ‘D’ with 50 metabolites[1] is more bio-actively influential than appreciated. Sensible ‘D’ supplementation has a 100-year track-record.[2] Side-effects are minimal.

Dexamethasone in the same structural steroid family as ‘D’, shares common VDR (vitamin-D-receptor)[3] and related gene pathways,[4] is artificial, and in some circumstances mitigates against COVID-19, albeit with variable side-effects. Dexamethasone is clearly a useful adjunct.

‘D’ deficiencies are widespread globally,[5] and particularly in; BAME, African Americans, Elderly, Carehomers,[6, 7] (Reality-check ref.) and Obese Persons; groups also at high-risk of COVID-19. Regions with proactive Vitamin-D-policies, education, nutritional supplementation, and/or greater UVB exposure, have much lower COVID-19 infection and mortality; e.g. Finland, Norway, New Zealand and, Equatorial-Africa (despite poverty / high urban-multi-person-dwelling-occupation).

Appropriate vitamin D supplementation risks are small: rewards huge. Public policy application of Bradford-Hill risk / harm criteria, used for smoking, social-distancing and masks, would support[8] ‘D’ supplementation of at-risk groups, and ‘D’ testing of all COVID-19 hospital patients.

Parachute RCTs studies (Smith & Pell. J CBE[9] ) [10, 11] ; analogies for research situations of observable risk reduction, but limited viable ethical alternatives; incisively, with wry humour, highlight risks of overly focusing on para-RCT-centric research.

Patient-based-studies; four interventions [12-14, 85]; a retrospective examination of clinical practice[15]; and thirty-nine observationals,[16-50, 86] three more are questioned;[51-53] some are preprints. All consider, mixed-size pre-and -or-post-infection ‘D’ samples, and COVID-19 positive patients. All studies variously evidence mitigation of COVID-19 infectivity and/or severity, by ‘D’.

Additionally, Biobank-study ‘D’ data (all over 10-years-old),[54-56] showed positive associations before adjustment. Comorbidities adjusted for, are impacted by vitamin D levels,[57] making evaluation complex. EPIC vitamin D data had no date-limits.[58]

Latitudinal,[59] COVID-19 seasonality, and wider, studies, including of polymorphisms,[60] grow in number; including those referencing historic pandemics and influenzas[61]: Juzeniene is a stand-out.[62] Latitudinal studies[63, 64] are helpful, but limited by availability of current accurate population ‘D’ data.

An in-vitro study,[65] observes; “Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2.”

Numerous studies,[66] explain vitamin D’s central genetic evolutionary,[67, 68] and wider role, in immune modulation, through multiple various and diverse [69] pathways, including via peroxisomes and mitochondria. More generally, studies link low ‘D’ with negative wider health effects[70] including increased mortality.[71]

Early 2020 hypotheses linking COVID-19 infectivity / severity, to vitamin D, include; Grant,[72] Brown,[73] and Davies.[74] Helpful summaries include Benskin.[75]

The urgent need for major studies, has been raised in several BMJ Rapid Responses.[76-82]

Collectively, studies strongly suggest essential prohormone-and-nutrient vitamin D, is a far more effective potential basal COVID-19 treatment, than any additive pharmaceutical available to date. Pharmaceuticals and vaccines are ultimately appreciated adjuncts, to meeting essential evolutionary biological nutrient intake imperatives.

Immediately testing of all COVID-19 hospital patient admissions for vitamin D, and supplementing where necessary, according to established NICE guidelines,[83] would provide time for new protocol, RCT-clinical-trials.

Thus, there is every reason to ‘D’ test hospitalised COVID-19 patients. Arguably, not to do so, in light of study outcomes to date, risks negligence. Judges, if asked, may take a broad-view in weighing evidence.

Since late January 2020, a loose group, have requested major clinical studies of sufficient power, including in care-homes, and hospitals. I thank Cooper, Grant, Grimes, Lahore, Pfleger, Rhein, Shotwell, Sarkar, and others, for sharing.

However, high-level drive and funding, have been lacking, exacerbated by the Wellcome-Gates-Accelerator exclusion from funding of ‘D’. Consequentially, research establishments excluded ‘D’ trials, focusing instead on repurposing, and new drugs, including in care-home settings. ‘D’ studies would reduce the study patient pool: further, successful ‘D’ outcomes may reduce funding for long-shot studies.

‘D’ is a non-patentable product family, produced by evolution, for which humans can garner no credit, with limited financial drivers to satisfy eternal human-yearning for golden but elusive bonanzas.

Overall, if the depth of information, and number of studies on ‘D’, consistently pointing in the same direction, related to a new COVID-19 ‘drug’, with minimal side-effects, it would have been front-page-news. Additional clinical research would have been prioritised with determination and alacrity, and ‘D’ by now, licensed as a standard-treatment-protocol.

In terms of saving lives, mental health and economies, it is inconsequential whether deficiency is due to pre-existing low-levels at infection, or infection driven catabolism. IF the issue was dehydration, nobody would dream of saying, ‘withhold treatment until determination if dehydration was due to; fever, or low historic water intake pre-infection’.

Surely the simple steps, of ‘D’ supplementing, and/or testing-and-supplementing, of at least all COVID-19 patients, and high-risk-persons, should be implemented as a matter of urgency. Thought-provokingly hospital ‘D’ supplementation was standard practice in Daniel Drake Center for Post-Acute Care in Cincinnati for many years.[84]

Absent: authorities; redirecting resources and research-focus; changing public health and hospital testing and supplementation policies, to ones that fully recognise the often-discriminatory impact and extent of ‘D’ deficiency disease, particularly in high risk groups; and funding and driving of urgent further ‘D’ research; human-frailties dictate ‘D’ will be shuffled into the pending-tray; notwithstanding observed 50% ‘D’ related reductions in infection (Kaufman 190,000 patient-base),[27, 39, 41] and reductions in ICU patients by multiples (Castillo, Tan et al).[12, 17, 31, 45, 48]

Pragmatic recognition of the need to: supplement ‘D’ in; high risk groups, COVID-19 hospital patients, and more widely; eliminate the ‘social-injustice’[6, 7] of vitamin ‘D’ discrimination against; BAME, the Elderly, Carehomers and Obese; reduce infection, ICU pressures and mortality, so public fear: could provide a cheap resource-and-cost-saving basal treatment protocol, added to by vaccines, a ‘paradigm-shift’ enlightening bleak COVID-19 outlooks, empowering people, thus possible exit from D-deficient COVID-19 pandemic shadow-lands, steering a ‘D’ course to a brighter pastures.

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Competing interests: No competing interests

15 October 2020
Robert A Brown
Researcher
McCarrison Society
La Route de Mont Cochon, St Lawrence, Jersey. C.I.