Vitamin D status and ill health: a systematic review

Autier, Philippe; Boniol, Mathieu; Pizot, Cécile; Mullie, Patrick

doi:10.1016/s2213-8587(13)70165-7

Cited by 1,005 publications

(923 citation statements)

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“…The Baltimore Longitudinal Study of Aging has found that 25(OH)D is positively correlated with leftventricle wall thickness and there is a relationship between 25(OH)D and left-ventricle concentric remodelling (13) . Hypertension was also linked in the study to left-ventricle hypertrophy and low 25(OH)D. According to the argument of Autier et al (1) and Bolland et al (2) , these low 25(OH)D levels are the consequence of ill health that is associated with heart pathology by reverse causality. However, experiments with young rats show that deprivation of vitamin D causes cardiac hypertrophy, left-chamber alterations and systolic dysfunction, which follow on from cardiac inflammation, fibrosis and apoptosis (14) .…”

Section: Diseases Caused By Low Vitamin D That May Not Be Corrected Imentioning

confidence: 84%

“…Indeed, this same mechanism may explain the association of low vitamin D levels with other nervous system diseases and with autoimmune diseases which Autier et al (1) choose to explain by 'reverse causation'. DeLuca et al concluded that vitamin D is a candidate in influencing susceptibility to several psychiatric and neurological diseases with the strength of evidence varying for schizophrenia, autism, Parkinson's disease, amyotrophic lateral sclerosis and Alzheimer's disease, while being especially strong for MS (20) .…”

Section: Diseases Caused By Low Vitamin D That May Not Be Corrected Imentioning

confidence: 93%

“…6. Scientific evidence ignored (19) by Autier et al (1) and Bolland et al (2) suggests that the incidence of MS in the UK might be halved by a major programme of supplementation in pregnancy, childhood and early life that could lower the incidence to that in southern Europe. Virtual eradication may not be impossible if sufficiently comprehensive public health measures could be organised.…”

Section: Harms Consequent Upon False Inference Of Reverse Causationmentioning

confidence: 99%

“…

AbstractTwo recent studies published in The Lancet (Autier et al (2013) 76-89 and Bolland et al (2014) Lancet Diabetes Endocrinol 2, 307-320) have concluded that low levels of vitamin D are not a cause but a consequence of ill health brought about by reduced exposure to the sun, an association known as 'reverse causality'. The scientific evidence and reasoning for these conclusions are examined here and found to be faulty.

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mentioning

confidence: 99%

“…A statistical test has very precise conditions and can never prove the null hypothesis to be true for all or different conditions. Autier et al (1) insist that, to be reliable, claims of benefit from increases in 25-hydroxyvitamin D (25(OH)D, the usual proxy for vitamin D status) 'must be supported by evidence from randomised controlled trials' and not by evidence coming only from observational studies. In this submission I argue that clinical trials cannot be and are not in fact a reliable method of establishing causation of disease except in special circumstances.…”

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confidence: 99%

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Controlled trials of vitamin D, causality and type 2 statistical error

Gillie

2014

Public Health Nutr.

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Two recent studies published in The Lancet (Autier et al. (2013) 76-89 and Bolland et al. (2014) Lancet Diabetes Endocrinol 2, 307-320) have concluded that low levels of vitamin D are not a cause but a consequence of ill health brought about by reduced exposure to the sun, an association known as 'reverse causality'. The scientific evidence and reasoning for these conclusions are examined here and found to be faulty. A null result in a clinical trial of vitamin D in adults need not lead to a conclusion of reverse causation when low vitamin D is found in observational studies of the same disease earlier in life. To assume an explanation of reverse causality has close similarities with type 2 statistical error.Lancet Diabetes Endocrinol 2,

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Section: Diseases Caused By Low Vitamin D That May Not Be Corrected Imentioning

confidence: 84%

Section: Diseases Caused By Low Vitamin D That May Not Be Corrected Imentioning

confidence: 93%

Section: Harms Consequent Upon False Inference Of Reverse Causationmentioning

confidence: 99%

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confidence: 99%

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Controlled trials of vitamin D, causality and type 2 statistical error

Gillie

2014

Public Health Nutr.

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Effect of High-Dose Vitamin D₃on Hospital Length of Stay in Critically Ill Patients With Vitamin D Deficiency

Amrein

Schnedl

Höll

et al. 2014

JAMA

413

407

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Effect of a Single High Dose of Vitamin D₃ on Hospital Length of Stay in Patients With Moderate to Severe COVID-19

Murai

Fernandes

Sales

et al. 2021

JAMA

456

520

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IMPORTANCEThe efficacy of vitamin D 3 supplementation in coronavirus disease 2019 remains unclear.OBJECTIVE To investigate the effect of a single high dose of vitamin D 3 on hospital length of stay in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThis was a multicenter, double-blind, randomized, placebo-controlled trial conducted in 2 sites in Sao Paulo, Brazil. The study included 240 hospitalized patients with COVID-19 who were moderately to severely ill at the time of enrollment from June 2, 2020, to August 27, 2020. The final follow-up was on October 7, 2020.INTERVENTIONS Patients were randomly assigned to receive a single oral dose of 200 000 IU of vitamin D 3 (n = 120) or placebo (n = 120). MAIN OUTCOMES AND MEASURESThe primary outcome was length of stay, defined as the time from the date of randomization to hospital discharge. Prespecified secondary outcomes included mortality during hospitalization; the number of patients admitted to the intensive care unit; the number of patients who required mechanical ventilation and the duration of mechanical ventilation; and serum levels of 25-hydroxyvitamin D, total calcium, creatinine, and C-reactive protein. RESULTSOf 240 randomized patients, 237 were included in the primary analysis (mean [SD] age, 56.2 [14.4] years; 104 [43.9%] women; mean [SD] baseline 25-hydroxyvitamin D level, 20.9 [9.2] ng/mL). Median (interquartile range) length of stay was not significantly different between the vitamin D 3 (7.0 [4.0-10.0] days) and placebo groups (7.0 [5.0-13.0] days) (log-rank P = .59; unadjusted hazard ratio for hospital discharge, 1.07 [95% CI, 0.82-1.39]; P = .62). The difference between the vitamin D 3 group and the placebo group was not significant for in-hospital mortality (7.6% vs 5.1%; difference, 2.5% [95% CI, -4.1% to 9.2%]; P = .43), admission to the intensive care unit (16.0% vs 21.2%; difference, -5.2% [95% CI, -15.1% to 4.7%]; P = .30), or need for mechanical ventilation (7.6% vs 14.4%; difference, -6.8% [95% CI, -15.1% to 1.2%]; P = .09). Mean serum levels of 25-hydroxyvitamin D significantly increased after a single dose of vitamin D 3 vs placebo (44.4 ng/mL vs 19.8 ng/mL; difference, 24.1 ng/mL [95% CI, 19.5-28.7]; P < .001). There were no adverse events, but an episode of vomiting was associated with the intervention.CONCLUSIONS AND RELEVANCE Among hospitalized patients with COVID-19, a single high dose of vitamin D 3 , compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D 3 for treatment of moderate to severe COVID-19.

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Vitamin D status and ill health: a systematic review

Cited by 1,005 publications

References 59 publications

Controlled trials of vitamin D, causality and type 2 statistical error

Controlled trials of vitamin D, causality and type 2 statistical error

Effect of High-Dose Vitamin D₃on Hospital Length of Stay in Critically Ill Patients With Vitamin D Deficiency

Effect of a Single High Dose of Vitamin D₃ on Hospital Length of Stay in Patients With Moderate to Severe COVID-19

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Vitamin D status and ill health: a systematic review

Cited by 1,005 publications

References 59 publications

Controlled trials of vitamin D, causality and type 2 statistical error

Controlled trials of vitamin D, causality and type 2 statistical error

Effect of High-Dose Vitamin D3on Hospital Length of Stay in Critically Ill Patients With Vitamin D Deficiency

Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19

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Product

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Effect of High-Dose Vitamin D₃on Hospital Length of Stay in Critically Ill Patients With Vitamin D Deficiency

Effect of a Single High Dose of Vitamin D₃ on Hospital Length of Stay in Patients With Moderate to Severe COVID-19