Vitamin D is useful in preventing and treating Covid-19 infections. In light of new scientific evidence, Scotland and Britain have begun to distribute it free of charge to at-risk populations. The Group of 61–so many Italian doctors and academics believe in following the British example–publishes an open letter. (1) GIFT(Great Italian Food Trade) and Égalité Onlus join this appeal. Reasons to follow.
Covid-19, the role of vitamin D in preventing and treating Covid-19 infections
At the dawn of the SARS-CoV-2 pandemic declaration, two physicians at the Turin Academy of Medicine-Giancarlo Isaia and Enzo Medico, professors of geriatrics and histology, respectively-were the first to intuit the possible role of vitamin D in preventing and treating infections. (2) Recall, in this regard, the list of foods with the highest vitamin D contents and recommendations for daily exposure to sunlight. (3)
The favorable role of vitamin D has been reaffirmed in a number of studies published in international scientific journals (4,5,6). The governments of Scotland and Great Britain have therefore decided on its free distribution to the most at-risk sections of the population. The Scottish government distributes it to 2.7 million people at higher COVID-19 risk (elderly and residents in RSAs, ethnic groups most susceptible to vitamin deficiencies). (7) An operation that the House of Commons considers to have ”
low-cost, zero-risk, and potentially highly effective
‘(low-cost, zero-risk, potentially highly effective action). A recent study by the Royal Society of London in turn explains that ‘it seems there is nothing to loose and potentially much to gain.’ (8)
Italy, prescription ban
AIFA (Italian Drug Agency)-despite scientific evidence on the crucial functions of vitamin D (3)-has banned its prescription, as it turns out, at the end of 2019. (4) Outside of only cases of severe insufficiency (serum levels of 25OHD < 20 ng/mL).
The elderly population in Italy, however, is largely deficient in vitamin D. (9) And they are the first lethal target of the virus, as unfortunately we continue to observe with the daily death statistics. Nevertheless, only a small circle of physicians seems accustomed to reading the scientific literature.
Hypovitaminosis D and mortality from Covid-19
PubMed collects about 300 scientific papers on correlations between vitamin D levels and Covid-19. Retrospective studies and meta-analysis (10,11). Confirming the presence of hypovitaminosis D in the majority of COVID-19-infected patients, especially those with a severe form and higher mortality (OR 3.87) associated with it (12,13).
Paradoxically, the mainstream media has instead given wide coverage to the only study that denies the usefulness of Vitamin D (mostly cholecalciferol) administration to COVID-19 patients. A work not yet published, awaiting peer-review (review among experts in the relevant scientific field), moreover conducted on patients at a very advanced stage of the disease. (14) It is undoubtedly better to prevent.
Clinical evidence
Clinical evidence on the usefulness of vitamin D in counteracting COVID-19 is summarized by the authors of the open letter as follows:
– A 6-week observational study of 154 patients shows the prevalence of hypovitaminosis D (<20 ng/mL) in 96.82%(2020) of the subjects then admitted to the ICU, (15)
– A randomized trial of 76 oligosymptomatic patients revealed that subjects treated with high doses of calcifediol were corrected to ICU admission in minimal proportion (2%, 1/50) compared to untreated patients (50%, 13/26) in untreated patients, (16)
– A retrospective study of more than 190,000 patients found that there was a significant correlation between the low percentage of disease-positive individuals and higher circulating levels of 25OHD, (17)
– In 77 elderly subjects hospitalized for COVID-19, the probability of survival to disease, estimated with the Kaplan-Meier curve, was significantly correlated with the administration of cholecalciferol, taken in the previous year at a dose of 50,000 IU per month, or 80,000-100,000 IU for 2-3 months, or 80,000 IU at the time of diagnosis. (18)
– In PCR-positive patients for SARS-CoV-2, vitamin D levels were significantly lower (p=0.004) than those of PCR-negative patients (a finding later confirmed by other work in terms of faster viral clearance and recovery for those with higher blood levels of vitamin D), (19)
– A clinical trial of 40 asymptomatic or paucisymptomatic patients showed disease negativity in 62.5 percent (10/16) of patients treated with high doses of cholecalciferol (60,000 IU/day for 7 days), compared with 20.8 percent (5/24) of patients in the control group. A significant reduction in plasma fibrinogen levels was also found in treated patients. (20)
The doses of vitamin D recommended by the Group of 61
Based on the results, the ‘Group of 61’ Italian physicians and academics make the following remarks:
– vitamin D appears to be most effective against COVID-19-both because of the rate of negativity and because of the benign evolution of the disease in case of infection-when administered with prevention goals, especially in elderly, frail, and institutionalized individuals. (21) Albeit pending further controlled studies,
– in the preventive setting, the optimal minimum plasma target of 25(OH)D to be achieved is estimated to be 40 ng/mL. (22) To reach this level, high doses of cholecalciferol, also related to the patient’s basal levels, up to 4000 IU/day, should be administered (23)
– in therapeutic settings, randomized studies indicate the usefulness of a single bolus administration of 80,000 IU of cholecalciferol (No. 4, Annweiler G et al.), or calcifediol (0.532 mg on Day 1, 0.266 mg on Day 3, Day 7, and then once a week) (No. 2, Castillo ME et al.), or again 60000 IU of cholecalciferol for 7 days, with the goal of achieving 50 ng/mL of 25(OH)D. (20)
Open letter. The appeal of the Group of 61
The Group of 61 – the 61 physicians and academics who signed the open letter 3.12.20 – therefore calls for ‘a serious investigation into the matter.’ In particular:
1) The activation of a consensus conference and/or a state-sponsored and supported randomized controlled clinical trial on the therapeutic efficacy of Vitamin D in symptomatic or oligosymptomatic patients. Applying one of the following patterns:
– Oral cholecalciferol 60,000 IU/day for 7 consecutive days,
– Cholecalciferol in oral single administration 80,000 (in elderly patients),
– calcifediol 0.532 mg (106 drops) on day 1 and 0.266 mg (53 drops) on days 3 and 7 and then in weekly single administration,
2) The preventive administration of oral cholecalciferol (up to 4000 IU/day) to individuals at risk of infection (elderly, frail, obese, health care workers, relatives of infected patients, individuals in closed communities). In this context, the use of vitamin D, even at high doses, has no major side effects (14), it is still useful to correct a situation of specific general population deficiency, especially in the winter period, regardless of SARS-CoV-2 infection.
Sharing knowledge
The document-attached in footnote 1-is prepared by the working group of the Turin Academy of Medicine, coordinated by its president, Prof Giancarlo Isaia, professor of Geriatrics, and Antonio D’Avolio, professor of Pharmacology at the University of Turin, and composed of 61 physicians from many Italian cities.
Already sent to national and regional health authorities, it can be shared by emailing the Turin Academy of Medicine (accademia.medicina@unito.it).
For more news and scientific data on how to strengthen the immune system through diet, please refer to Volume I-People of the Covid-19 trilogy , abc at https://www.greatitalianfoodtrade.it/covid-19-abc-volume-i-persone_1
Marta Strinati and Dario Dongo
Notes
(1) The full text of the document dated 3.12.20, in ANNEX, also contains the list of subscribers,
(2) Isaiah, G., Physician, E. (2020). Associations between hypovitaminosis D and COVID-19: a narrative review. Aging Clin Exp Res 32, 1879-1881 . https://doi.org/10.1007/s40520-020-01650-9
(3) Dario Dongo, Andrea Adelmo Della Penna. The potential of vitamin D in the prevention and treatment of Covid-19. GIFT (Great Italian Food Trade). 3/30/20, https://www.greatitalianfoodtrade.it/salute/il-potenziale-della-vitamina-d-nella-prevenzione-e-trattamento-di-covid-19
(4) Marta Strinati, Dario Dongo. Vitamin D, scientific evidence on anti Covid-19 role. But the NHS blocks prescriptions. GIFT (Great Italian Food Trade). 8.7.20. https://www.greatitalianfoodtrade.it/salute/vitamina-d-prove-scientifiche-sul-ruolo-anti-covid-19-ma-il-ssn-blocca-le-prescrizioni
(5) Marta Strinati. Covid-19, new evidence on the benefits of vitamin D. GIFT (Great Italian Food Trade). 6.9.20, https://www.greatitalianfoodtrade.it/salute/covid-19-nuove-evidenze-sui-benefici-della-vitamina-d
(6) Dario Dongo, Andrea Adelmo Della Penna. Vitamin D, immune system, and Covid-19. New scientific evidence. GIFT (Great Italian Food Trade). 9/29/20, https://www.greatitalianfoodtrade.it/salute/vitamina-d-sistema-immunitario-e-covid-19-nuove-evidenze-scientifiche
(7) Mattha Busbi. Covid: UK government requests guidance on vitamin D use. The Guardian. 11/14/20, https://www.theguardian.com/world/2020/nov/14/covid-uk-government-requests-guidance-on-vitamin-d-use
(8) George Griffin, Martin Hewison, Julian Hopkin, Rose Kenny, Richard Quinton, Jonathan Rhodes, Sreedhar Subramanian, David Thickett (2020). Vitamin D and COVID-19: evidence and recommendations for supplementation. Royal Society Open Science, December 2020, Volume 12, Issue 7. doi: https://doi.org/10.1098/rsos.201912
(9) Isaiah, G., Giorgino, R., Rini, G.B. et al. (2003). Prevalence of hypovitaminosis D in elderly women in Italy: clinical consequences and risk factors. Osteoporos Int 14, 577-582. doi: https://doi.org/10.1007/s00198-003-1390-7
(10) Meltzer DO, Best TJ, Zhang H, Vokes T, Arora V, Solway J. Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results. JAMA Netw Open. 2020;3(9):e2019722. doi:10.1001/jamanetworkopen.2020.19722
(11) Marcos Pereira, Alialdo Dantas Damascena, Laylla Mirella Galvão Azevedo, Tarcio de Almeida Oliveira & Jerusa da Mota Santana (2020). Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis. Critical Reviews in Food Science and Nutrition, doi: 10.1080/10408398.2020.1841090
(12) Kohlmeier M. Avoidance of vitamin D deficiency to slow the COVID-19 pandemic . BMJ Nutrition, Prevention & Health 2020;3:doi:10.1136/bmjnph-2020-000096
(13) Dieter De Smet, MD, Kristof De Smet, MD, Pauline Herroelen, MSc, Stefaan Gryspeerdt, MD, Geert A Martens, MD, PhD, Serum 25(OH)D Level on Hospital Admission Associated With COVID-19 Stage and Mortality, American Journal of Clinical Pathology, https://doi.org/10.1093/ajcp/aqaa252
(14) Igor H. Murai et al. (2020). Effect of Vitamin D3 Supplementation vs Placebo on Hospital Length of Stay in Patients with Severe COVID-19: A Multicenter, Double-blind, Randomized Controlled Trial. medRxiv 2020.11.16.20232397. doi: https://doi.org/10.1101/2020.11.16.20232397
(15) Jain, A., Chaurasia, R., Sengar, N.S. et al. (2020). Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers. Sci Rep 10, 20191. https://doi.org/10.1038/s41598-020-77093-z
(16) Marta Entrenas Castillo et al. (2020). Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study. The Journal of Steroid Biochemistry and Molecular Biology, Volume 203, 2020, 105751, ISSN 0960-0760, https://doi.org/10.1016/j.jsbmb.2020.105751
(17) Kaufman HW, Niles JK, Kroll MH, Bi C, Holick MF (2020). SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS ONE 15(9): e0239252. https://doi.org/10.1371/journal.pone.0239252
(18) Annweiler, G.; Corvaisier, M.; Gautier, J.; Dubée, V.; Legrand, E.; Sacco, G.; Annweiler, C., on behalf of the GERIA-COVID study group (2020). Vitamin D Supplementation Associated with Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study. Nutrients 2020, 12, 3377. https://doi.org/10.3390/nu12113377
(19) D’Avolio, A.; Avataneo, V.; Manca, A.; Cusato, J.; De Nicolò, A.; Lucchini, R.; Keller, F.; Cantù, M. 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2. Nutrients 2020, 12, 1359 . https://doi.org/10.3390/nu12051359.
(20) Rastogi A, Bhansali A, Khare N, et al. (2020). Short-term, high-dose vitamin D supplementation for COVID-19 disease: a randomized, placebo-controlled, study (SHADE study) Postgraduate Medical Journal. doi: 10.1136/postgradmedj-2020-139065)
(21) Mamtha Balla et al. (2020) Back to basics: review on vitamin D and respiratory viral infections including COVID-19. Journal of Community Hospital Internal Medicine Perspectives, 10:6, 529-536. doi: 10.1080/20009666.2020.1811074
(22) Maghbooli Z, Sahraian MA, Ebrahimi M, Pazoki M, Kafan S, Tabriz HM, et al. (2020). Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection. PLoS ONE 15(9): e0239799. https://doi.org/10.1371/journal.pone.0239799
(23) Arboleda John F., Urcuqui-Inchima Silvio (2020). Vitamin D Supplementation: A Potential Approach for Coronavirus/COVID-19 Therapeutics? Frontiers in Immunology. Volume 1, 1523. doi: 10.3389/fimmu.2020.01523
Professional journalist since January 1995, he has worked for newspapers (Il Messaggero, Paese Sera, La Stampa) and periodicals (NumeroUno, Il Salvagente). She is the author of journalistic surveys on food, she has published the book "Reading labels to know what we eat".
Dario Dongo, lawyer and journalist, PhD in international food law, founder of WIISE (FARE - GIFT - Food Times) and Égalité.
