New look at previous RCT shows reduced cancer(including PCa) mortality with vitamin D3

Skim to read main points in bold if too long:
I'm not certain, but apparently the first headline associated with this Randomized Control Trial (when 1st released) would have been that D supplementation is of no significant benefit against cancer? I think this is from the original study:

https://www.acc.org/latest-in-cardiology/clinical-trials/2018/11/08/22/42/vital
"The VITAL trial showed that supplementation with either n–3 fatty acid at a dose of 1 g/day or vitamin D3 at a dose of 2000 IU/day was not effective for primary prevention of CV or cancer events among healthy middle-aged men and women over 5 years of follow-up...............".

But for some reason they are taking another look at the data, and using a different primary end point(I find that often something being studied is of benefit, but maybe not for whatever the authors chose as the PRIMARY end point, so it ends up being declared of no significant benefit)
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7675103/
"JAMA Netw open. 2020 Nov; 3(11): e2025850.
Published online 2020 Nov 18. doi: 10.1001/jamanetworkopen.2020.25850
PMCID: PMC7675103
PMID: 33206192
Effect of Vitamin D3 Supplements on Development of Advanced Cancer
A Secondary Analysis of the VITAL Randomized Clinical Trial..................................

Question

Does vitamin D3 supplementation reduce the risk of developing advanced (metastatic or fatal) cancer among adults without a diagnosis of cancer at baseline?
Findings

In this secondary analysis of a randomized clinical trial with 25 871 patients, supplementation with vitamin D3 reduced the incidence of advanced (metastatic or fatal) cancer in the overall cohort, with strongest risk reduction in individuals with normal weight and no reduction among individuals with overweight or obesity.
Meaning

These findings suggest that vitamin D3 may reduce the risk of developing advanced cancer among adults without a diagnosis of cancer at baseline; this protective effect is apparent for those who have normal but not elevated body mass index...........................................................

Objective

To follow up on the possible reduction in cancer death in the Vitamin D and Omega-3 Trial (VITAL) with an evaluation of whether vitamin D reduces the incidence of advanced (metastatic or fatal) cancer and an examination possible effect modification by body mass index.
Design, Setting, and Participants

VITAL is a randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial of vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d). This multicenter clinical trial was conducted in the United States; participants included men aged 50 years or older and women aged 55 years or older who were free of cancer and cardiovascular disease at baseline. Randomization took place from November 2011 through March 2014, and study medication ended on December 31, 2017. Data for this secondary analysis were analyzed from November 1, 2011, to December 31, 2017.
Interventions

Vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d) supplements.
Main Outcomes and Measures

For the present analysis, the primary outcome was a composite incidence of metastatic and fatal invasive total cancer, because the main VITAL study showed a possible reduction in fatal cancer with vitamin D supplementation and effect modification by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) for total cancer incidence reduction for individuals with normal BMI, but not for individuals with overweight or obesity. Secondary analyses included examination of BMI (<25, 25 to < 30, and ≥30) as effect modifiers of the observed associations............................................................

Results

Among 25 871 randomized VITAL participants (51% female; mean [SD] age, 67.1 [7.1] years), 1617 were diagnosed with invasive cancer over a median intervention period of 5.3 years (range, 3.8-6.1 years). As previously reported, no significant differences for cancer incidence by treatment arm were observed.

However, a significant reduction in advanced cancers (metastatic or fatal) was found for those randomized to vitamin D compared with placebo (226 of 12 927 assigned to vitamin D [1.7%] and 274 of 12 944 assigned to placebo [2.1%]; HR, 0.83 [95% CI, 0.69-0.99]; P = .04).

When stratified by BMI, there was a significant reduction for the vitamin D arm in incident metastatic or fatal cancer among those with normal BMI (BMI<25: HR, 0.62 [95% CI, 0.45-0.86]) but not among those with overweight or obesity (BMI 25-<30: HR, 0.89 [95% CI, 0.68-1.17]; BMI≥30: HR, 1.05 [95% CI, 0.74-1.49]) (P = .03 for interaction by BMI).

Conclusions and Relevance

In this randomized clinical trial, 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............".

So, among normal BMI folks, this RCT of 2000 IU Vitamin D reduced metastatic or fatal cancer by 38%( 17% reduction for entire cohort, regardless of BMI).

I would like to add that in my opinion, since "medicines" are usually dosed on a mg/kg basis, that being obese(high BMI) would be the equivalent of getting less vitamin D. If they weigh more, they probably need more, of whatever it might be. Just as if when working if I had given a 100 lb lady just enough(and no more) dose of propofol that might have laid her out, the same dose given to a 200 or 300 lb man might have just made them very drowsy.

Enjoy!

Post Edited (BillyBob@388) : 11/26/2020 7:43:42 AM (GMT-7)

BTW, if it might be of interest to more of us here, there are results specifically for prostate cancer mortality. You need to scroll down to table 2 to see them. This was a BIG study, over 12,000 in each group. The number of PCa events(not certain if this was being diagnosed as "advanced" or just mortality or either/both? ) for the D group was 192 vs 219. (88%). Total cancer deaths were 83% compared to placebo. Remember, this was "only" 2000 IU/day.

"Because prostate cancer was associated with a lower but nonsignificant reduction in incidence with vitamin D supplementation (HR, 0.88; 95% CI, 0.72-1.07; P = .19) and was the largest contributor to total cancer incidence, we conducted sensitivity analyses excluding metastatic /fatal prostate cancer. Results were similar (HR, 0.85; 95% CI, 0.71-1.02; P = .08). Case numbers for the site-specific HRs for breast, prostate, colorectal, and lung mortality are too small to be interpreted (eTable 2 in Supplement 2)........
When stratified by BMI, there was a significant reduction for the vitamin D3 arm in incident metastatic or fatal cancer among those with normal BMI (BMI <25: HR, 0.62; 95% CI, 0.45-0.86), but not among those with overweight or obesity (BMI 25 to <30: HR, 0.89; 95% CI, 0.68-1.17; BMI ≥30: HR, 1.05; 95% CI, 0.74-1.49; P = .03 for interaction) (Table 3). There was a stepwise decrease in effect size of the association of vitamin D treatment with metastatic cancer and cancer mortality by each higher BMI subgroup..........."

The reduction in mortality for the non obese (BMI <25) was 38% ( HR .62). Unfortunately, I can not find a figure for specific PCa mortality that is adjusted for BMI.

Buddy Blank said...
Thanks Bill, appreciate your researching this for us. Happy Thanksgiving!

Happy Thanksgiving, Buddy, and to all the HWPC brothers as well! ( LOL, I caught just before hittin send, I had written(or auto correct got me) "Nappy Thanksgiving"!

Cigafred said...
The H and N keys are not far apart. Thanks for all the work that you share with us.

Thanks, Cigafred! They are close together!

Since all D taker saw a benefit, and all got 2000IU/day, but only the normal BMI folks saw a significant benefit, wouldn't that imply, but not prove, that the higher weight folks were not getting enough D to help significantly? That 2000 was not enough to significantly help the higher weight folks?

One of the first things they taught me back in anesthesia school in the dark ages(1979) was the starting dose for Pentathol (you could always give more if needed, but you couldn't take too much back) was 3 to 4 mg/kg. So the average 70 Kg(154lb) adult was going to need between 210 and 280 mg to get them adequately asleep, all other things being equal, which they rarely were. (gender, health, other drugs taken all entered into it). By the same token, a 300 pounder was going to need over 500 mg. Otherwise, the big guy was NOT going to be adequately asleep. (personally, I always found those dose calculations to be a bit on the low side, as did many of my coworkers)

Thus I have no doubt that 2000 IU/day of D would have a much stronger affect(whatever it might accomplish, good or bad, if anything) on a 150 lb person compared to a 300 lb person. Same with all medications or supplements, or even food amounts. And indeed, we see exactly that in this study: a relatively small amount(IMO) of supplementation has a measurably better effect on the skinnier people.

Not saying this applies to this study at all, but there is a thing known a "the tiny parachute effect". (affect?) 100 people jump out of a plane with 10" diameter parachutes. All die. Conclusion: parachutes show no benefit for people who jump out of airplanes. Many a study has been influenced by the tiny parachute affect.