Following up on gjm’s comment (sorry I’m a little late commenting on this post—I came to it via Scott Alexander’s “Contra Hoffman” post), there was an interesting followup analysis of the cancer mortality effect in VITAL that concluded that “supplementation with vitamin D reduced the incidence of advanced (metastatic or fatal) cancer in the overall cohort, with the strongest risk reduction seen in individuals with normal weight.” https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2773074
This study is interesting because, among other things, it bridges the cancer “incidence” and cancer “mortality” questions by looking closely at “incidence” of advanced / metastatic cancer as well as cancer mortality. To address the “data mining” concern, cancer incidence and cancer mortality were both preregistered outcomes of VITAL—those of us who follow Vitamin D research and lean toward (rather than contra) Hoffman with respect to Vitamin D had expected the VITAL researchers to preregister cancer mortality as a primary outcome and cancer incidence as a secondary outcome, not just because mortality seems more important than incidence—both are important, of course—but also because the leading theories of Vitamin D’s physiological effects provide a mechanism for reducing cancer mortality whereas the mechanisms for reducing initial (not metastatic) cancer incidence are speculative if they exist at all. (Alas, in the VITAL preregistration cancer incidence was primary and mortality secondary. Still, they were both preregistered and not just something that popped out after looking for something of significance.) The discussion section in the JAMA article explains the issues in detail, and the studies cited in the “biological plausibility” section (“[a]n association between vitamin D supplementation and metastatic and fatal cancer is biologically plausible”) are worth reviewing.
Following up on gjm’s comment (sorry I’m a little late commenting on this post—I came to it via Scott Alexander’s “Contra Hoffman” post), there was an interesting followup analysis of the cancer mortality effect in VITAL that concluded that “supplementation with vitamin D reduced the incidence of advanced (metastatic or fatal) cancer in the overall cohort, with the strongest risk reduction seen in individuals with normal weight.” https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2773074
This study is interesting because, among other things, it bridges the cancer “incidence” and cancer “mortality” questions by looking closely at “incidence” of advanced / metastatic cancer as well as cancer mortality. To address the “data mining” concern, cancer incidence and cancer mortality were both preregistered outcomes of VITAL—those of us who follow Vitamin D research and lean toward (rather than contra) Hoffman with respect to Vitamin D had expected the VITAL researchers to preregister cancer mortality as a primary outcome and cancer incidence as a secondary outcome, not just because mortality seems more important than incidence—both are important, of course—but also because the leading theories of Vitamin D’s physiological effects provide a mechanism for reducing cancer mortality whereas the mechanisms for reducing initial (not metastatic) cancer incidence are speculative if they exist at all. (Alas, in the VITAL preregistration cancer incidence was primary and mortality secondary. Still, they were both preregistered and not just something that popped out after looking for something of significance.) The discussion section in the JAMA article explains the issues in detail, and the studies cited in the “biological plausibility” section (“[a]n association between vitamin D supplementation and metastatic and fatal cancer is biologically plausible”) are worth reviewing.