Cohort study to evaluate the effect of combination Vitamin D, Magnesium and Vitamin B12 (DMB) on progression to severe outcome in older COVID-19 patients

Tan et al., Nutrition, doi:10.1016/j.nut.2020.111017, Jun 2020 (preprint)
Oxygen therapy 80% improvement lower risk ← → higher risk ICU admission 81% Vitamin D for COVID-19  Tan et al.  LATE TREATMENT Is late treatment with vitamin D + combined treatments beneficial? Retrospective 43 patients in Singapore Lower need for oxygen therapy with treatment (p=0.04) c19early.org Tan et al., Nutrition, June 2020 0 0.5 1 1.5 2+ RR
Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 126 studies, recognized in 18 countries.
Lower risk for mortality, ICU, hospitalization, progression, recovery, cases, and viral clearance.
No treatment is 100% effective. Protocols combine treatments.
6,300+ studies for 210+ treatments. c19early.org
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Observational study of 43 patients ≥50 years old, with 17 patients receiving vitamin D, magnesium, and vitamin B12 (DMB); and 26 control patients, showing a significantly lower need for oxygen therapy and ICU admission with treatment. DMB OR 0.20 [0.04-0.93] for oxygen therapy and/or intensive care support with multivariate analysis.
Cholecalciferol was used in this study. Meta analysis shows that late stage treatment with calcitriol / calcifediol (or paricalcitol, alfacalcidol, etc.) is more effective than cholecalciferol: 66% [47‑78%] lower risk vs. 42% [31‑52%] lower risk. Cholecalciferol requires two hydroxylation steps to become activated - first in the liver to calcifediol, then in the kidney to calcitriol. Calcitriol, paricalcitol, and alfacalcidol are active vitamin D analogs that do not require conversion. This allows them to have more rapid onset of action compared to cholecalciferol. The time delay for cholecalciferol to increase serum calcifediol levels can be 2-3 days, and the delay for converting calcifediol to active calcitriol can be up to 7 days.
This is the 1st of 126 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 155 septillion).
30 studies are RCTs, which show efficacy with p=0.0000032.
Important missing comments or errors? Let us know.
Study covers vitamin B12 and vitamin D.
risk of oxygen therapy, 80.5% lower, RR 0.20, p = 0.04, treatment 3 of 17 (17.6%), control 16 of 26 (61.5%), NNT 2.3, adjusted per study, multivariate.
risk of ICU admission, 80.9% lower, RR 0.19, p = 0.07, treatment 1 of 17 (5.9%), control 8 of 26 (30.8%), NNT 4.0, no adjusted result available.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Tan et al., 10 Jun 2020, retrospective, Singapore, peer-reviewed, 14 authors, dosage 1,000IU daily, this trial uses multiple treatments in the treatment arm (combined with magnesium and vitamin B12) - results of individual treatments may vary.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2025 Singapore United Kingdom Russia USA Sudan Angola Colombia Kenya Mozambique Pakistan Argentina Vietnam Peru Philippines Spain Brazil Italy France Japan China Uzbekistan Ethiopia Iran Ghana Mexico South Korea Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Ukraine Côte d'Ivoire Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR Singapore favored high-profit treatments.The average efficacy of treatments was moderate.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org November 2025 Singapore United Kingdom Russia USA Sudan Angola Colombia Kenya Mozambique Pakistan Argentina Vietnam Peru Philippines Spain Brazil Italy France Japan China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Ukraine Côte d'Ivoire Eritrea Malawi Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia Syria Singapore favored high-profit treatments.The average efficacy was moderate.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
Cohort study to evaluate the effect of vitamin D, magnesium, and vitamin B12 in combination on progression to severe outcomes in older patients with coronavirus (COVID-19)
Chuen Wen Tan, Liam Pock Ho, Shirin Kalimuddin, Benjamin Pei Zhi Cherng, Yii Ean Teh, Siew Yee Thien, Hei Man Wong, Paul Jie Wen Tern, Manju Chandran, Jason Wai Mun Chay, Chandramouli Nagarajan, Rehena Sultana, Jenny Guek Hong Low, Heng Joo Ng
Nutrition, doi:10.1016/j.nut.2020.111017
The aim of this study was to determine clinical outcomes of older patients with coronavirus (COVID-19) who received a combination of vitamin D, magnesium, and vitamin B 12 (DMB) compared with those who did not. We hypothesized that fewer patients administered this combination would require oxygen therapy, intensive care support, or a combination of both than those who did not. Methods: This was a cohort observational study of all consecutive hospitalized patients 50 y of age with COVID-19 in a tertiary academic hospital. Before April 6, 2020, no patients received the (DMB) combination. After this date, patients were administered 1000 IU/d oral vitamin D 3 , 150 mg/d oral magnesium, and 500 mcg/d oral vitamin B 12 upon admission if they did not require oxygen therapy. Primary outcome was deterioration leading to any form of oxygen therapy, intensive care support, or both. Results: Between January 15 and April 15, 2020, we identified 43 consecutive patients 50 y of age with COVID-19. Seventeen patients received DMB before onset of primary outcome and 26 patients did not. Baseline demographic characteristics between the two groups were significantly different by age. In univariate analysis, age and hypertension had a significant influence on outcome. After adjusting for age or hypertension separately in a multivariate analysis, the intervention group retained protective significance. Fewer treated patients than controls required initiation of oxygen therapy during hospitalization (17.6 vs 61.5%, P = 0.006). DMB exposure was associated with odds ratios of 0.13 (95% confidence interval [CI], 0.03À0.59) and 0.20 (95% CI, 0.04À0.93) for oxygen therapy, intensive care support, or both on univariate and multivariate analyses, respectively. Conclusions: A vitamin D / magnesium / vitamin B 12 combination in older COVID-19 patients was associated with a significant reduction in the proportion of patients with clinical deterioration requiring oxygen
References
Dai, Zhu, Manson, Song, Li et al., Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial, Am J Clin Nutr
Degnan, Taga, Goodman, Vitamin B12 as a modulator of gut microbial ecology, Cell Metab
Dhar, Mohanty, Gut microbiota and Covid-19-possible link and implications, Virus Res
Lau, Majumder, Torai, Saeg, Hoffman et al., Vitamin D insufficiency is prevalent in severe COVID-19, doi:10.1101/2020.04.24.20075838
Martineau, Jolliffe, Hooper, Greenberg, Aloia et al., Vitamin D supplementation to prevent acute respiratory tract infections: systemic review and meta-analysis of individual participant data, BMJ
Negi, Das, Pahari, Nadeem, Agrewala, Potential role of gut microbiota in induction and regulation of innate immune memory, Front Immunol
Pan, Mu, Yang, Sun, Wang et al., Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study, Am J Gastroenterology
Shechter, Merz, Paul-Labrador, Meisel, Rude et al., Oral magnesium supplementation inhibits platelet-dependent thrombosis in patients with coronary artery disease, Am J Cardiol
Verity, Okell, Dorigatti, Wiskill, Whittaker et al., Estimates of the severity of coronavirus disease 2019: a model-based analysis, Lancet Infect Dis
Zuo, Zhang, Lui, Yeoh, Li et al., Alterations in gut microbiota of patients with COVID-19 during time of hospitalization, Gastroenterology
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Late treatment
is less effective
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