In truth, vitamin D is both a supplement/drug that can be orally dosed, and an endogenous hormone that can go up and down based on UV exposure and additional dietary intake. The predominantly negative population based supplementation (regardless of baseline D25) RCTs done to date have hopefully proven that population based supplementation with conservative D3 dosing isn’t very effective. [RCTs= randomized controlled trials, ASCO= American Society of Clinical Oncology and is considered a standard-bearer (along with NCCN) for the best in clinical oncology care]
Clearly targeted supplementation is a superior approach from the patient perspective as it offers more precise dosing with D3 based on actual weight and change in D25 desired with the physician, followup options in cases of major lifestyle changes, and with a vitamin D25 test costing $48-58 for walk-in friendly professional labs like Labcorp or Quest (in the United States) it is one of the most cost-effective tests for quality of life in integrative oncology care.
No RCT exists to question the wisdom of targeted supplementation. And that’s where academic cancer centers have to recognize D25 is a vitality sign for cancer patients, and ignoring the severe levels of deficiency particularly in black, hispanic, asian, native american populations is particularly a health care policy that is putting all ethnic minority and obese patients at higher risk for fatigue, foggy brain and conventional therapy toxicity at minimum, and likely worse cancer mortality if they don’t end up getting bone weakening agents (apparently the only reason per ASCO to check a D25 at all).
The formula for vitamin D3 dosing is not a mystery that we have to use population based dosing algorithms to treat patients with a deficiency, which is the cognitive error of using IOM or Endocrine Society Guidelines (mostly informed by population-based supplementation RCTs) to replace a known deficiency. The formula for rapid replacement for patients ages 18-88 (https://pubmed.ncbi.nlm.nih.gov/20139241/) is Delta25D(in nmol/L not ng/ml) desired=0.025x(dose per kg body weight). An online calculator to skip the conversions is available here (which also provides maintenance doses).
On Reddit, the vitamin D community likes to use a U.S.-friendlier formula (Weight in kg X 100 IU/day) to calculate appropriate maintenance doses, which at least is concordant with observational cohorts and a more “clinically comfortable” approach for patients without deficiency symptoms, but the author prefers knowing D25 and using more rapid replacement protocols in the context of cancer care because there might be only one chance to help the patient feel the benefit and reinforce its importance throughout the continuum of their care.
One of the ironies of the vitamin D RCTs done to date is that their greatest weakness is complete ignorance of D3 “drug pharmacokinetics” (lipid solubility) which requires “massive” (relative to what most doctors are used to prescribing) dosing based on the BMI/weight. My greatest adjustment in the first few years of practicing vitamin D3 replacement for all deficient patients before starting conventional therapy when I worked at CTCA was being comfortable with 10,000 IU – 25,000 IU/d!
But for those following the hierarchy of evidence as bible and still believe the RCTs of population based supplementation as gospel of truth that treating a vitamin D deficiency is not worthwhile, consider this then. If you are a clinical research investigator like me and you receive a study protocol asking if you would be interested in studying Drug X which on phase I studies requires BMI adjusted dosing, but the phase II protocol only wants to test the drug at a fixed dose that a priori you already know is not going to work for over 75% of the population due to how low the dose is and the predominantly white Caucasian population tested (least at risk for vitamin D deficiency), you would question the sanity of the investigator, and never work with that company again. These are the “amateur hour” RCTs that are keeping you from understanding how important vitamin D replacement therapy is for those who are low.
So ironically, vitamin D which has always been “reframed” as a drug by the medical literature as a justification to ignore all the other evidence I reviewed in my last blog and free chapter, and therefore requires RCT evidence to justify replacing a deficiency before starting conventional therapy for cancer…has never been appropriately studied as a weight-based drug. There is no RCT that has actually looked at an a priori logical weight based replacement schedule to make sure those who need the D3 the most actually get the right amount. That is the study we need if we want to get the high quality evidence others are waiting for to best understand vitamin D as a drug AND endogenous hormone.
One criticism that is valid since there is not a lot of research on fatigue and vitamin D specifically: how do we know the fatigue studies with vitamin D wasn’t placebo effect? Including myself? I’ll address that question in the next blog. Thanks for reading!
Four shots from Antelope Canyon, AZ – the beauty and yin yang of the life-sustaining and cell-damaging qualities of sunlight
Leave a Reply