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7X less likely to go to ICU if COVID-19 ward gave calcifediol (semi-activated Vitamin D) – July 2021

Role of vitamin D in COVID-19: active or passive?

Bess Dawson-Hughes, MD. USDA Human Nutrition Research Center on Aging at Tufts University bess.dawson-hughes at tufts.edu


8 Wards in one hospital in Barcelona, Spain
All COVID-19 patients had 12-13 ng of vitamin D
The wards all shared standard of practice other than restoring Vitamin D levels
5 of the 8 wards gave their patients calcifediol
The patients of the calcifediol wards were 0.13 less likely to go to the ICU
And 1/2 as likely to die

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Amidst a raging pandemic, Nogues et al. developed and implemented a protocol to determine whether treatment with calcifediol compared with no calcifediol altered the course of 838 coronavirus disease-2019 (COVID-19) patients admitted to a hospital in Barcelona, Spain (1). This was not a classical randomized, controlled trial, but rather a real-world examination of outcomes of patients assigned (on a bed availability basis) to one of 8 COVID wards, 3 of which had chosen not to administer calcifediol and 5 that had chosen to do so. Other practices in the 8 wards were standardized. Some patients did not have serum 25(OH)D measurements upon admission for reasons related to staff availability.

The supplemented patients had significantly fewer transfers to the Intensive Care Unit (ICU) (adjusted odds ratio 0.13 [95% CI 0.07, 0.23]) and lower mortality rates (adjusted odds ratio 0.52 [95% CI 0.27, 0.99]) than the unsupplemented patients, findings that have important implications for the in-hospital management of COVID-19 patients globally.

Serum 25-hydroxyvitamin D [25(OH)D] was measured in 678 of the 838 patients upon admission to the hospital. It was notable that the median 25(OH)D level was 13 [interquartile values 8, 24] ng/ml in the calcifediol-treated group and 12 [8, 19] ng/ml in the untreated control group. How might we interpret the significance of these very low 25(OH)D levels at the time of hospitalization - was low 25(OH)D a predisposing factor to serious COVID-19 infection or was it a marker of inflammation associated with acute illness? The answer has implications for patient care.
A predisposing factor The patients’ values, measured in March - May of 2020, were far lower than those expected in the general population, even for the early spring when levels tend to be lowest in the Northern hemisphere. Barcelona has a similar latitude to Boston (41.4 vs 42.4 degrees N). In a cross-sectional study of older postmenopausal women not taking vitamin D supplements, mean 25(OH)D levels in Boston in March, April and May were 24, 27, and 31 ng/ml, respectively (2). These values are consistently higher than the median levels of 12 and 13 ng/ml reported by Nogues (1). Although the assays used by Nogues and Krall were not standardized to the same reference material, the values that Nogues et al. documented are much lower than expected, consistent with the concept that COVID-19 severe enough to require hospitalization occurred more frequently in the segment of the Barcelona population with low rather than representative 25(OH)D values. Although relevant evidence is inconsistent (3,4), it is plausible that vitamin D deficiency and insufficiency were a risk factor for severe COVID-19 infection requiring hospitalization.
A marker of severe illness An alternative explanation of the very low 25(OH)D values reported by Nogues et al. is worth considering. The patients may have had 25(OH)D levels that were representative of those in the Barcelona area prior to contracting COVID-19, but their COVID-19 illness caused these levels to decline precipitously. Acute illness with high levels of inflammation has been associated with very low 25(OH)D levels in several studies, including one conducted in Barcelona prior the COVID-19 epidemic (from Jan to November, 2015?) in which 135 patients were a variety of illnesses. These patients had a mean level of 11 ng/ml) (5), and non-survivors had a significantly lower level than survivors l 8.1 ng/ml. . . .

The robust positive response to supplementation observed by Nogues et al. would seem unlikely in patients who had low 25(OH)D levels solely on the basis of critical illness and is consistent with the notion that vitamin D deficiency/insufficiency is a contributing factor in the development and progression of COVID-19. If so, this would support the rationale not only . . . . .

A specific COVID-19-related guideline for vitamin D intake is premature; however, it does seem prudent during the pandemic to adhere to current vitamin D intake recommendations with greater attention and urgency. The National Academy of Medicine (NAM) recommendation of 800 IU per day of vitamin D for older adults is based on evidence that it benefits the skeleton (6) but evidence is expanding that this level of intake may also reduce risk of infection. In an individual participant data meta-analysis of trials conducted before the COVID-19 pandemic, Martineau et al. found that daily or weekly doses of vitamin D reduced risk of acute respiratory infections, with doses < 800 IU per day lowering risk by 20% and doses of 800-2000 IU per day lowering it similarly, by 19% (7). Moreover the benefit of supplementation appeared to be greater among those with 25(OH)D levels below 20 ng/ml than in those with higher 25(OH)D levels. The work of Nogues et al. extends current evidence, by adding COVID-19 to the list of infections that are likely mitigated by maintaining an optimal vitamin D status. Finally, as previously noted (8), the favorable effects of vitamin D on bone and muscle provide a strong rationale for maintaining vitamin D adequacy after hospital discharge in COVID-19 survivors who face an arduous rehabilitation process.

References in PDF

Biography from her website (July 2021)
Dr. Bess Dawson-Hughes, Senior Scientist and Director of the Bone Metabolism Team at the HNRCA, is internationally renowned for her research regarding bone health. As an endocrinologist, her research interests include metabolic bone disease, the acid-base balance of the diet, calcium and vitamin D nutrition, and prevention and treatment of osteoporosis. She currently serves as General Secretary of the International Osteoporosis Foundation and was past President and Trustee of the National Osteoporosis Foundation (USA). Dr. Dawson-Hughes has authored more than 450 peer-reviewed journal articles, book chapters, and reviews. Recently, she and her collaborators discovered that an alkaline diet is associated with greater lean tissue mass in older adults. The team also identified that low vitamin D levels in the body are associated with impaired cognitive function and that the absorption of vitamin D supplements is enhanced when taken with a meal. Dr. Dawson-Hughes’s current projects include researching the impact of supplemental vitamin D on vitamin D levels in the blood as well as bone material strength in people with normal blood sugar and elevated blood sugar. She is a Professor of Medicine at Tufts University School of Medicine and the Founding Director of the Center for the Advancement of Science in Space (CASIS) that develops and oversees research on the international space station. Dr. Dawson-Hughes is on the editorial boards of Bone, Osteoporosis International and Calcified Tissue International and is General Secretary for the International Osteoporosis Foundation. She has served as Associate Editor of the Journal of Bone and Mineral Research and as Principle Investigator of the NIH Osteoporosis and Related Bone Disease National Resource Center, Washington, D.C. Among her many awards, Dr. Dawson-Hughes has received the Bolton L. Corson Medal for Research from the Benjamin Franklin Institute, International Osteoporosis Foundation’s President's Award in 2012, NOF Lawrence G. Raisz Memorial Lecture Award in 2014, Thomson Reuters Highly Cited Scientist in 2014, and the International Institute for Nutrition and Bone Health Research Award in 2015.

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