The authors note that "covid-19 and NCDs share a common set of underlying risk factors, including deprivation, obesity, older age, and ethnicity" and highlight, " Non-communicable diseases (NCDs) such as obesity, diabetes, heart disease, stroke, cancer, chronic respiratory diseases, and mental health disorders". All those risk factors and diseases have a parameter in common: the secosteroid hormone D3 better known as the sunshine vitamin. Deficiency of D3, defined as sub-physiological ( 25(OH)D3 100 to 150 nmol/L ) is global. The risk factors listed above are all accompanied by either low D3 or low responsivity to D3. The list of NCDs are also known to be influenced by D3 status or mechanistically.
To this scientist, conditioned to seek causal explanations, the failure of medical researchers to follow up these glaringly obvious clues is astonishing. For a compendium of research papers organised by disease see: https://vitamindwiki.com/. There is no shortage of failed D3 RCTs for most of those diseases. But extensive cell/molecular studies (1000s pa) support important roles for D3 amongst the several hundred genes that 1,25(OH)D3 promotes. There lies a big clash. It seems likely that something is amiss with the RCTs. Indeed there is: dose. Most RCTs use doses approved as safe by their national D3 advisory panel, and those doses are too low to reach physiological 25(OH)D3. Dose-ranging studies are rarely used. But there is an abundance of observational evidence that physiological and higher doses are beneficial in a range of diseases, safely.https://www.preprints.org/manuscript/202005.0265/v1 This important review emphasises the role D3 plays in COVID and summarises the safety of higher doses of D3 that should be embraced by future RCTs.
An RCT however big that fails to attain physiological 25(OH)D3 is not only wasted resource but adds another nail in the D3 coffin, because an outcome of "no observed effect" then becomes accepted as indicating "no role for D3", despite abundant cell/molecular evidence to the contrary. My conclusion is that badly designed RCTs for D3 - and the vast majority are - are dangerous to health.
A single dose RCT is an abuse of science, no biologist would pass the most perfunctory referee with a dose-response curve with one point on it. But amongst RCTs one dose is commonplace and held up as the Gold Standard. Nonsense.
Rapid Response:
Twin epidemics or just one ?
Dear Editor
The authors note that "covid-19 and NCDs share a common set of underlying risk factors, including deprivation, obesity, older age, and ethnicity" and highlight, " Non-communicable diseases (NCDs) such as obesity, diabetes, heart disease, stroke, cancer, chronic respiratory diseases, and mental health disorders". All those risk factors and diseases have a parameter in common: the secosteroid hormone D3 better known as the sunshine vitamin. Deficiency of D3, defined as sub-physiological ( 25(OH)D3 100 to 150 nmol/L ) is global. The risk factors listed above are all accompanied by either low D3 or low responsivity to D3. The list of NCDs are also known to be influenced by D3 status or mechanistically.
To this scientist, conditioned to seek causal explanations, the failure of medical researchers to follow up these glaringly obvious clues is astonishing. For a compendium of research papers organised by disease see: https://vitamindwiki.com/. There is no shortage of failed D3 RCTs for most of those diseases. But extensive cell/molecular studies (1000s pa) support important roles for D3 amongst the several hundred genes that 1,25(OH)D3 promotes. There lies a big clash. It seems likely that something is amiss with the RCTs. Indeed there is: dose. Most RCTs use doses approved as safe by their national D3 advisory panel, and those doses are too low to reach physiological 25(OH)D3. Dose-ranging studies are rarely used. But there is an abundance of observational evidence that physiological and higher doses are beneficial in a range of diseases, safely.https://www.preprints.org/manuscript/202005.0265/v1 This important review emphasises the role D3 plays in COVID and summarises the safety of higher doses of D3 that should be embraced by future RCTs.
An RCT however big that fails to attain physiological 25(OH)D3 is not only wasted resource but adds another nail in the D3 coffin, because an outcome of "no observed effect" then becomes accepted as indicating "no role for D3", despite abundant cell/molecular evidence to the contrary. My conclusion is that badly designed RCTs for D3 - and the vast majority are - are dangerous to health.
A single dose RCT is an abuse of science, no biologist would pass the most perfunctory referee with a dose-response curve with one point on it. But amongst RCTs one dose is commonplace and held up as the Gold Standard. Nonsense.
There is an alternative, and eventually this protocol that puts causation first and foremost will succeed, as it has with providing a causal role of D3 status in COVID: https://www.medrxiv.org/content/10.1101/2020.05.01.20087965v3
Seen from the viewpoint of D3 the authors' twin epidemics reduce to just one: the pandemic of D3 deficiency.
Competing interests: No competing interests