Increasing Vitamin D levels would help reduce Covid-19 deaths

Vitamin D modulates thousands of genes and many aspects of immune function, both innate and adaptive. The scientific evidence shows that:

Higher Vitamin D blood levels are associated with lower rates of SARS-CoV-2 infection.

Higher D levels are associated with lower risk of a severe case (hospitalisation, ICU, or death).

Intervention studies (including RCTs) indicate that Vitamin D can be a very effective treatment.

Many papers reveal several biological mechanisms by which Vitamin D influences Covid-19.

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Causal inference modelling, Hill’s criteria, the intervention studies and the biological mechanisms indicate that Vitamin D’s influence on Covid-19 is very likely causal, not just correlation.

Vitamin D is well known to be essential, but most people do not get enough. Two common definitions of inadequacy are deficiency <20ng/ml (50nmol/L), the target of most governmental organisations, and insufficiency <30ng/ml (75nmol/L), the target of several medical societies and experts. Too many people have levels below these targets. Rates of Vitamin D deficiency <20ng/ml exceed 33% of the population in most of the world, and most estimates of insufficiency <30ng/ml are well over 50% (but much higher in many countries). Rates are even higher in winter, and several groups have notably worse deficiency: the overweight, those with dark skin (especially far from the equator), and care home residents. These same groups face increased Covid-19 risk.

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It has been shown that 3875 IU (97mcg) daily is required for 97.5% of people to reach 20ng/ml, and 6200 IU (155mcg) for 30ng/ml, intakes far above all national guidelines. Unfortunately, the report that set the US RDA included an admitted statistical error in which required intake was calculated to be ~10x too low. Numerous calls in the academic literature to raise official recommended intakes had not yet resulted in increases by the time SARS-CoV-2 arrived. Now, many papers indicate that Vitamin D affects Covid-19 more strongly than most other health conditions, with increased risk at levels <30ng/ml (75nmol/L) and severely greater risk <20ng/ml (50nmol/L).1

Evidence to date suggests the possibility that the Covid-19 pandemic sustains itself in large part through infection of those with low Vitamin D, and that deaths are concentrated largely in those with deficiency. The mere possibility that this is so should compel urgent gathering of more Vitamin D data. Even without more data, the preponderance of evidence indicates that increased Vitamin D would help reduce infections, hospitalisations, ICU admissions and deaths.

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Decades of safety data show that vitamin D has very low risk: toxicity would be extremely rare with the recommendations here. The risk of insufficient levels far outweighs any risk from levels that seem to provide most of the protection against Covid-19, and this is notably different from drugs and vaccines. Vitamin D is much safer than steroids, such as dexamethasone, the most widely accepted treatment to have also demonstrated a large Covid-19 benefit. Vitamin D’s safety is more like that of face masks. There is no need to wait for further clinical trials to increase use of something so safe, especially when remedying high rates of deficiency/insufficiency should already be a priority.

Therefore, we call on all governments, doctors, and healthcare workers worldwide to immediately recommend and implement efforts appropriate to their adult populations to increase vitamin D, at least until the end of the pandemic.

Specifically to:

Recommend amounts from all sources sufficient to achieve 25(OH)D serum levels over 30ng/ml (75nmol/L), a widely endorsed minimum with evidence of reduced Covid-19 risk.

Recommend to adults Vitamin D intake of 4000 IU (100mcg) daily (or at least 2000 IU) in the absence of testing. 4000 IU is widely regarded as safe.

Recommend that adults at increased risk of deficiency due to excess weight, dark skin, or living in care homes may need higher intakes (eg, 2x). Testing can help to avoid levels too low or high.

Recommend that adults not already receiving the above amounts get 10,000 IU (250mcg) daily for 2-3 weeks (or until achieving 30ng/ml if testing), followed by the daily amount above. This practice is widely regarded as safe. The body can synthesise more than this from sunlight under the right conditions (eg, a summer day at the beach). Also, the NAM (US) and EFSA (Europe) both label this a “No Observed Adverse Effect Level” even as a daily maintenance intake.

Measure 25(OH)D levels of all hospitalised Covid-19 patients and treat w/ calcifediol or D3, to at least remedy insufficiency <30ng/ml (75nmol/L), possibly with a protocol along the lines of Castillo et al ‘20 or Rastogi et al ‘20, until evidence supports a better protocol.

Many factors are known to predispose individuals to higher risk from exposure to SARS-CoV-2, such as age, being male, comorbidities, etc, but inadequate Vitamin D is by far the most easily and quickly modifiable risk factor with abundant evidence to support a large effect. Vitamin D is inexpensive and has negligible risk compared to the considerable risk of Covid-19.

Signatories:

Dr. Karl Pfleger, PhD AI & Computer Science, Stanford. Former Google Data Scientist. Biotechnology Investor, AgingBiotech.info, San Francisco, CA, USA. (organizing signatory)

Dr. Gareth Davies, PhD Medical Physics, Imperial College, London, UK. Codex World’s Top 50 Innovator 2019. Independent Researcher. Lead author of “Evidence Supports a Causal Role for Vitamin D Status in COVID-19 Outcomes.” (organizing signatory)

Dr. Bruce W Hollis, PhD. Professor of Pediatrics, Medical University of South Carolina, USA

Dr. Barbara J Boucher, MD, FRCP (London). Honorary Professor (Medicine), Blizard Institute, Bart's & The London School of Medicine and Dentistry, Queen Mary University of London, UK. (significantly contributing signatory)

Dr. Ashley Grossman, MD FRCP FMedSci. Emeritus Professor of Endocrinology, University of Oxford, UK. Professor of Neuroendocrinology, Barts and the London School of Medicine. 2020 Endocrine Society Laureate Award.

Dr. Gerry Schwalfenberg, MD, CCFP, FCFP. Assistant Clinical Professor in Family Medicine, University of Alberta, Canada.

Dr. Giovanna Muscogiuri, MD PhD. Associate Editor, European Journal of Clinical Nutrition. Department of Clinical Medicine and Surgery, Section of Endocrinology, University "Federico II" of Naples, Naples, Italy.

Dr. Michael F. Holick, PhD MD. Professor Medicine, Physiology and Biophysics and Molecular Medicine, Director Vitamin D, Skin and Bone Research Laboratory, Boston University Medical Center, USA. (6000 IU) Disclosure: Consultant Biogena and speaker's Bureau Abbott Inc.

Dr. John Umhau, MD, MPH. CDR, USPHS (ret). President, Academy of Medicine of Washington, DC, USA. Ex-NIH: co-author of the first peer-reviewed report linking vitamin D deficiency with acute respiratory infection. (significantly contributing signatory)

Dr. Pawel Pludowski, MD, dr hab. Associate Professor, Biochemistry, Radioimmunology and Experimental Medicine, Children’s Memorial Health Institute, Warsaw, Poland. Chair, European Vitamin D Association (EVIDAS) [non-profit].

Dr. Cedric F. Garland, DrPH. Professor Emeritus, Department of Family Medicine and Public Health, University of California, San Diego, USA.

Dr. Jose M. Benlloch, Professor, Director of the Institute for Instrumentation on Molecular Imaging, CSIC-UPV, Valencia, Spain.

Dr. Samantha Kimball, PhD, MLT. Professor, St. Mary's University, Calgary, Alberta, Canada. Research Director, GrassrootsHealth Nutrient Research Institute [non-profit]. (significantly contributing signatory)

Dr. William B. Grant, PhD Physics, U. of California, Berkeley. Director at Sunlight, Nutrition, and Health Research Center [non-profit], San Francisco, CA, USA. Disclosure: Receives funding from Bio-Tech Pharmacal, Inc.

Dr. Carol L. Wagner, MD. Professor, Medical University of South Carolina, USA.

Dr. Paul Marik, MD, FCCP, FCCM. Chief of Pulmonary and Critical Care Medicine and Professor of Medicine, Eastern Virginia Medical School, Norfolk, VA, USA.

Dr. Morry Silberstein, MD. Associate Professor, Curtin University, Australia.

Dr. Vatsal Thakkar, MD. Founder, Reimbursify, NY, USA.  Former faculty, NYU and Vanderbilt.  Op-Ed writer on Vitamin D and COVID-19. (significantly contributing signatory)

Dr. Peter H Cobbold, PhD. Emeritus Professor, Cell Biology, University of Liverpool, UK.

Dr. Afrozul Haq, PhD. Professor Dept of Food Technology, Jamia Hamdard University, New Delhi, India.

Dr. Barry H. Thompson, MD, FAAP, FACMG. Clinical Associate Professor (Pediatrics), Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Dr. Reinhold Vieth, PhD, FCACB. Professor, Departments of Nutritional Sciences and Laboratory Medicine & Pathobiology, University of Toronto, Canada. Director (retired), Bone and Mineral Group Laboratory, Mt Sinai Hospital. Disclosure: Receives patent royalties from Ddrops (an infant vitamin D supplement).

Dr. Linda Benskin, PhD, RN, SRN(Ghana), CWCN, CWS, DAPWCA. Independent Researcher for Tropical Developing Countries and Ferris Mfg. Corp, Texas, USA. (significantly contributing signatory)

Jim O’Neill, CEO, SENS Research Foundation. Former principal associate deputy secretary of Health and Human Services, USA.

Dr. Eric Feigl-Ding, PhD. Epidemiologist & Health Economist. Senior Fellow, Federation of American Scientists. USA.

Rt Hon David Davis MP, Member of British Parliament, BSc Joint Hons Molecular Science / Computer Science, Warwick University, UK.

Dr. Susan J Whiting, PhD. Professor Emerita, University of Saskatchewan, Canada.

Dr. Richard Mazess. PhD. Emeritus Professor, University of Wisconsin, Madison, USA.

Dr. Helga Rhein, MD (retired). Sighthill Health Centre, Edinburgh, UK. (significantly contributing signatory)

Dr. Andrea Doeschl-Wilson, PhD. Professor of Infectious disease genetics and modelling, The Roslin Institute, University of Edinburgh, UK.

Dr. Ute-Christiane Meier, Dr med habil, PhD (Oxon), Dipl-Biol. Visiting lecturer, Institute of Psychiatry, Psychology & Neuroscience, King's College, London, UK and Privatdozentin, Ludwig Maximilian University of Munich, Germany. Disclosure: Patent 20160131666: "Biomarkers for inflammatory response."

Dr. Luigi Gennari, MD PhD. Full Professor, Internal Medicine, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.

Dr. Ased Ali, MBChB, PhD, FRCS. Consultant Urological Surgeon, Mid Yorkshire Hospitals NHS Trust, UK.

Dr. Pavel Kocovsky, PhD DSc FRSE FRSC. Professor Charles University, Prague, and Czech Academy of Sciences, Czech Republic.

Dr. Ace Lipson, MD. Endocrinologist. Clinical Professor, George Washington University, Washington, DC, USA.

Dr. Attila R Garami, MD, PhD Multidisciplinary Medical Sciences. Senior Biomarker Consultant, Switzerland.

Dr. David S Grimes, MD (retired), FRCP, University of Manchester, UK.

Dr. Larry Callahan, PhD. Chemist, FDA, Maryland, USA.

Dr. Jeanne M Marconi, MD, Pediatrics. Vice President of PM Pediatrics, New York, USA.

Dr. Spiros Karras, MD. Endocrinologist, Department of Endocrinology and Metabolism-Diabetes Center, 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece.

Dr. Joanna Byers, MBChB, University of Birmingham, UK.

Dr. Jaimin Bhatt, MBChB, MMed(Surgery) FRCS(Urol) FEBU. Consultant Urological Surgeon, Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, UK.

Dr. Christiane Northrup, MD. Obstetrician/Gynecologist.

Dr. Jörg Spitz, Dr. med. Academy of Human Medicine, Schlangenbad, Germany.

Dr. Naghmeh Mirhosseini, MD, PhD, MPH. Research Associate, School of Public Health, University of Saskatchewan, Canada..

Dr. Iacopo Chiodini, Associate Professor of Endocrinology, Dept. of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy. Head, Unit for Bone Metabolism Diseases and Diabetes, Istituto Auxologico Italiano, IRCCS, Milan, Italy.

Dr. David C Anderson, MD MSc FRCP FRCPE FRCPath. Retired Physician and Endocrinologist, Former Professor of Endocrinology, Manchester University, UK and Professor of Medicine, The Chinese University of Hong Kong.

Dr. Colin Bannon, MBChB. GP (retired), Devon, UK.

Dr. Patricia S. Latham, MD EdD. Professor of Pathology & Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

Dr. Teresa Fuller, MD PhD. Pediatrician, Owings Mills, MD, USA.

Dr. Omar Wasow, PhD, Harvard. Assistant Professor, Politics, Princeton University, NJ, USA.

Dr. Fabio Vescini, MD PhD. Endocrinology and Metabolism Unit, University-Hospital S. Maria della Misericordia, Italy.

Dr. Emily Grossman, PhD Molecular Biology, University of Manchester, UK. Science Author, Broadcaster and Educator.

Dr. David Carman, MBChB, University of Cape Town, South Africa.

Dr. Kalliopi Kotsa, Professor, Endocrinology-Diabetes, Dept of Medicine, Aristotle University, Thessaloniki, Greece.

Dr. Eva Kocovska, PhD, Queen Mary University of London, UK. Gillberg Neuropsychiatry Centre, University of Gothenburg, Sweden. Medical College, Prague, Czech Republic.

Dr. Benjamin Jacobs, MBBS MD MRCP(UK) FRCPCH. Royal National Orthopaedic Hospital, UK.

Dr. Joan Lappe, PhD RN FAAN. Professor, Creighton University, Omaha, Nebraska, USA.

Dr. Ronald A. Primas, MD FACP FACPM DABIHM CTH. New York, NY, USA.

Dr. Cristina Eller Vainicher, MD. Unit of Endocrinology, Fondazione Ca'Granda IRCCS OSpedale Maggiore Policlinico Milan, Italy. Head of the outpatients clinic for osteoporosis.

Dr. Matthias Gauger, MD. General Practitioner, Switzerland.

Dr. David Warwick, DDS. Dentist, Alberta, Canada. Published Researcher.

Dr. Sunil J. Wimalawansa, MD PhD MBA FRCP FRCPath FACE FACP DSc. Professor of Medicine, Endocrinology & Nutrition, Cardiometabolic & Endocrine Institute, New Jersey, USA.

Perry S. Holman. Executive Director, Vitamin D Society [non-profit], Canada.

Sharon McDonnell, MPH. Biostatistician, GrassrootsHealth Nutrient Research Institute [non-profit], Encinitas, CA, USA.

Mike Fisher. Founder, VitaminDassociation.org [non-profit]. Director of Research, Systems Biology Laboratory, UK.

Dr. Lina Zgaga, MD, PhD. Associate Professor of Epidemiology, Trinity College Dublin, University of Dublin, Ireland.

Dr. Irwin Jungreis, PhD, Harvard University. Research Scientist, Massachusetts Institute of Technology, Cambridge, MA, USA.

Dr. Jane Coad, PhD. Professor of Nutrition, Massey University, New Zealand.

Dr. Cedric Annweiler, MD PhD. Professor of Geriatric Medicine, School of Medicine, Health Faculty, University of Angers and Department of Medicine, Clinique de l’Anjou, Angers, France. Disclosure: occasional consultant for Mylan Laboratories Inc.

Dr. Salvatore Minisola, Full Professor of Internal Medicine, "Sapienza" Rome University, Italy.

Dr. Mats B. Humble, MD PhD. Psychiatrist (retired), Senior lecturer, Department of Medical Sciences, Örebro University, Sweden.

Dr. Andrea Fabbri, MD PhD. Professor of Endocrinology, Head Endocrinology Division, Ospedale CTO A. Alesini, University of Rome Tor Vergata, Rome, Italy.

Dr. Steve Jones, PhD FRS. Emeritus Professor of Human Genetics, Dept of Genetics, Evolution and Environment, University College London, UK.

Dr. Hermann Brenner, MD MPH. Professor of Epidemiology, Head of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.

Dr. Helder F. B. Martins, MD PhD (hon).Specialist & Emeritus Professor of Public Health. Former Minister of Health, Mozambique. Former WHO. Member, Mozambican Government COVID-19 advisory committee.

Dr. G. Siegfried Wedel, MD. Internist-Nephrologist (retired), Vierhöfen, Germany.

Dr. Robin Weiss, PhD FRCPath FMedSci FRS. Emeritus Professor of Viral Oncology, Division of Infection & Immunity, University College London, UK.

Dr. Giancarlo Isaia, Full Professor, University of Turini. President of the Academy of Medicine of Turin, Italy.

Dr. Susanne Bejerot, Professor, Örebro University, Sweden.

Dr. Antonio D'Avolio, Professor of Pharmacology, University of Turin, Italy.

Dr. Gustavo Duque, MD PhD FRACP FGSA. Chair of Medicine & Director of the Australian Institute for Musculoskeletal Science (AIMSS). The University of Melbourne and Western Health, Melbourne, Australia.

Dr. Giovanni Passeri, Associate Professor, Internal Medicine, Dep. of Medicine and Surgery, University of Parma, Parma, Italy.

Dr. Pankaj Kapahi, Professor, Buck Institute for Research on Aging, Novato, California, USA.

Dr. Giuseppe Poli, Emeritus Professor of General Pathology, University of Turin, Italy.

Dr. Patrick McCullough, MD. Chief of Medical Services, Summit Behavioral Healthcare, Cincinnati, Ohio USA.

Dr. Prashanth Kulkarni, MD DM FSCAI FACC. Consultant Cardiologist, Hyderabad, India.

Dr. Klaus Badenhoop, MD PhD. Professor, Division of Endocrinology & Diabetes, Department of Internal Medicine, Goethe-University Hospital, Frankfurt am Main, Germany.

Dr. José-María Sánchez-Puelles, Senior Researcher, CIB Margarita Salas, CSIC, Spain

Dr. Carmelinda Ruggiero, MD PhD. Professor of Geriatric Medicine, School of Medicine, University of Perugia, Italy. Head of the Orthogeriatric Unit, S Maria Misericordia Teaching Hospital, Perugia, Italy. Disclosure: Occasional consultant for UCB Pharma.

Dr. Jose Manuel Quesada Gomez, MD, PHD, Honorary Professor, University of Cordoba. Maimonides Research Institute, Cordoba. Spain.

Dr. Minisola Giovanni, President Emeritus of Italian Society for Rheumatology. Scientific Director of "San Camillo - Forlanini" Foundation, Rome, Italy.

Christine French, MS. Research Analyst at GrassrootsHealth Nutrient Research Institute [non-profit], Encinitas, CA, USA.

Dr. Patrizia Presbitero, MD. Clinical and interventional cardiology, Cardio Center, Humanitas Research Hospital Rozzano, Rozzano, Milan, Italy.

Dr. Ken Redcross, MD. Doctor and on-camera medical expert, New York, USA. Disclosure: scientific advisory board of the Organic & Natural Health Association.

Dr. Rajeev Venugopal, MBBS FRCS FACS DM. Consultant Plastic Surgeon/ Associate Lecturer in Surgery, University of the West Indies at Mona, Jamaica.

Dr. Gianluca Isaia, MD PhD. Geriatrician, Section of Geriatrics, Department of Medical Sciences, University of Turin, A.O.U. Città della Salute e della Scienza di Torino, Molinette, Turin, Italy.

Dr. Piero Stratta, Professor of Nephrology, University Piemonte Orientale, Italy.

Dr. Ben Schöttker, PhD. Scientist, Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg, Germany.

Dr. Roberto Fantozzi, MD. Full Professor of Pharmacology, University of Turin, Turin, Italy.

Dr. Sheryl L Bishop, PhD. Professor Emeritus, University of Texas Medical Branch, School of Nursing, Galveston, Texas, USA.

Dr. Wayne Jonas, MD. Professor of Family Medicine, Georgetown University. Former Director NIH Office of Alternative Medicine, USA.

Dr. Ferdinando Silveri, Medical Director of the Rheumatology Clinic of the Marche Polytechnic University, Ancona, Italy.

Dr. Vatsalya Vatsalya, MD. Department of Medicine, University of Louisville. National Institute on Alcohol Abuse and Alcoholism NIH, USA.

Dr. Rachel Nicoll, PhD. Medical researcher, Umeå University, Sweden.

Dr. Raimund von Helden, Dr med. Family medicine. Institute VitaminDelta, Lennestadt, Germany. Disclosure: Institute VitaminDelta sells consumer advice including on vitamin D for modest cost, but with no ties to other commercial interests.

Carole Baggerly, Founder & Director, GrassrootsHealth Nutrient Research Institute [non-profit], Encinitas, CA, USA.

Dr. Edward Gorham, PhD MPH. Adjunct Professor, University of California San Diego, School of Medicine, Dept of Family Medicine and Public Health, USA.

Dr. David Verhaeghen, MD, Anesthesiology, Algology and Pain Medicine, Aalst, Belgium.

Dr. Silvia Migliaccio, MD PhD. Associate Professor at University Foro Italico of Roma, Italy. Secretary of the Italian Society of Food Sciences.

Dr. Vítor Oliveira, MD, Internal Medicine, Brazil.

Dr. Djamel Deramchi, MD. Functional medicine. GrassrootsHealth Certified Vitamin D*practitioner and Coimbra Protocol Certified Doctor. France.