Someone raised the question - is vitamin D supplementation ever a good idea?
TA: "JoAnn Mason (sic), probably the foremost expert on this ..."
I thought I'd look at what JoAnn Manson, as a member of the VITAL study team, had to report.
[1] "Vitamin D supplementation for five years, with or without omega 3 fatty acids, reduced autoimmune disease by 22%"
Note: intervention was "Vitamin D (2000 IU/day) or matched placebo"
"25 871 participants were enrolled and followed for a median of 5.3 years. ...
"For the vitamin D arm, 123 participants in the treatment group and 155 in the placebo group had a confirmed autoimmune disease (hazard ratio 0.78 ...".
[2] "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.
"... 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 ...)" 38% risk reduction.
3. Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium journals.plos.org/plosone/a...
4. Effects of Vitamin D and Omega-3 Fatty Acids Co-Supplementation on Inflammatory Factors and Tumor Marker CEA in Colorectal Cancer Patients Undergoing Chemotherapy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial – PubMed pubmed.ncbi.nlm.nih.gov/324...
5. Prostate Cancer News, Reviews & Views: Vitamin D has no effect on prostate cancer, heart disease, or bone mineral density. prostatecancer.news/2018/07...
7. Does testosterone mediate the relationship between vitamin D and prostate cancer? A systematic review and meta-analysis protocol | Systematic Reviews | Full Text systematicreviewsjournal.bi...
11. Circulating vitamin D level and mortality in prostate cancer patients: a dose–response meta-analysis ncbi.nlm.nih.gov/pmc/articl...
12. Vitamin D May Reduce Prostate Cancer Metastasis by Several Mechanisms Including Blocking Stat3 ncbi.nlm.nih.gov/pmc/articl...
13. Vitamin D levels and the risk of prostate cancer and prostate cancer mortality – PubMed pubmed.ncbi.nlm.nih.gov/331...
14. Physiologic serum 1,25 dihydroxyvitamin D is inversely associated with prostatic Ki67 staining in a diverse sample of radical prostatectomy patients – PubMed pubmed.ncbi.nlm.nih.gov/307...
15. Apoptosis Induction by 1α,25-Dihydroxyvitamin D3 in Prostate Cancer 1 Supported by the International Union Against Cancer [International Cancer Technology Transfer (ICRETT) and American Cancer Society Beginning Investigator (ACSBI) awards], Molecular Cancer Therapeutics mct.aacrjournals.org/conten...
Just in case people don't go to the link, let's read exactly what is said by the authors in "A Secondary Analysis of VITAL" (the Randomized Clinical Trial cited by TA, seemingly as support for the hypothesis that D3 supplementation is pointless, with respect to cancer):
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."
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."
And:"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)."
We have a ton of papers that reported increased PCa mortality in obese men. Visceral fat is hormonally active; it's not just excess weight. It seems that increasing visceral fat erodes any protection conferred by vitamin D.
{BMI is used as a surrogate for visceral fat in many studies, but one can be lean outside & fat inside - particularly on a high-carb/low fat diet.}
In addition, while 2,000 IU vitamin D3 is a nice addition to our 25-D3 reservoir, any protection is due to 1,25-D3. Ideally, we should control for calcium & phosphorus/phosphates, which can affect 1,25-D3 availability.
Much of the recent discussion on Vit D is about the risk of developing cancer (epidemiology) including this one, it seems to me. Does not address whether D3 supplementation is beneficial or harmful as an adjunct to treatment of APC, which of course we all here already have. No final answer on that, but it appears that Vit D3 supplementation is beneficial if low on tests. Or if on Zometa or Xgeva for bone protection (which I advocate for all on ADT if their dentition is good, regardless of BMD on DEXA scan. Our total risk for bone metastasis and serious sequelae leading to painful death is ultimately much much higher than the 1-2%risk of ONJ. Better to be ahead of it.)Otherwise, very high D3 supplementation may or may not be harmful and probably of limited benefit. If taking more than 400-800 IU/day probably better to use with Vitamin K-2 supplementation. That’s my take for now.
As I mentioned recently, an early event in PCa is the downregulation of the enzyme that prostatic cells use to convert inactive 25-D3 to active 1,25-D3, and the upregulation of the enzyme used to clear 1,25-D3. Which would explain why D3 might be important for survival, rather than prevention, but only if there is 1,25-D3 in circulation.
In terms of the optimum level of the 25-D3 reservoir, it has often puzzled me why it matters whether the level is 32, 50 or 75. One thing we know is that the primary purpose of 25-D3 is for serum calcium homeostasis. The 1,25-D3 in circulation is produced by the kidneys for calcium control - not for the use of peripheral tissue. It appears that when the reservoir is low - as it must often be during Nordic winters, say - peripheral tissue is prevented from tapping in to the 25-D3 reservoir.
Vitamin D might be the most common supplement used by men with PCa, but I think most have no understanding that PCa cells can't use it. We must rely on kidney production of 1,25-D3. Fructose can prolong production. When calcium or phosphorus/phosphates are high, the kidneys are too busy dumping excess amounts to be able to generate 1,25-D3.
Are there any studies that address the nuances? Unfortunately, only the maligned epidemiological studies.
Calcitriol (1,25 dihydroxy -cholecalciferol) is the form after 1 hydroxylation in the kidneys and has the full spectrum of effects. It is used for renal failure diálisis patients to maintain Calcium.I took high dose Rocaltrol (one brand) along with docetaxel chemo back in 2007. Don’t know if it made a difference, but I’m still here! Recall that Tomasz Beer at OHSU did clinical trial with it but did not meet outcome standard.
Interesting to test D3 levels and 1,25 diHO-D levels simultaneously in APC patients with normal kidneys.
When I was diagnosed there was tremendous interest in calcitriol analogs. Hundreds were tested with the aim of finding one that did not dangerously mess with calcium homeostasis,.
Meanwhile, I came across a paper that noted that fructose could cause calcitriol exposure to be increased by several hours. The only reason to buy fructose as a sweetener, IMO.
As I mentioned on another thread, D3 supplementation might be a good idea in general for those at very northern latitudes, at least during the roughly 5-7 months of the year when your body may be literally unable to produce it, regardless of how much sun exposure you get. (Those eating large amounts of oily fish or fortified food and drink would be "supplementing" via diet, but diet is not always a reliable source.)
For those hoping to source their D3 from the sun, realize also that the low-angle exposures of early morning or early evening also fail to give to adequate UVB, just as northern winters do. Optimal sun-angle times for good skin exposure are thought to be roughly 10am - 3pm. For many, it only takes about ten minutes to generate the equivalent of 10,000 iu.
[But rarely, some people just don't produce it well... a study of young Honolulu sunbathers managed to find a few with low serum D status!]
The ability to generate adequate D3 from UV sunlight also decreases, sometimes dramatically, both with 1) an individual's age, and 2) an individual's darkness of skin pigment... it also decreases in smoggy/smoky environments, as found in some big cities.
Amazed that you intentionally withheld info to make your point. What I wrote in my report is this:
Chandler et al. reported on an updated analysis of the VITAL RCT. They looked at whether Vitamin D supplementation affected the risk of developing metastatic or fatal cancer among people who were cancer-free at baseline. With a median intervention period of 5.3 years, there was almost no chance of finding metastatic or fatal prostate cancer in men who were prostate cancer-free at baseline (In the ProtecT trial, 10-year prostate cancer survival among men initially diagnosed with localized prostate cancer was 99%, and metastasis-free survival was 96%.) Because the metastasis-free and cause-specific survival with prostate cancer are so long when starting from a "no cancer" diagnosis, the authors looked for the effect on other cancers, excluding prostate cancer. They found:
•there were no significant differences due to Vitamin D on the incidence of any cancer
•there were no significant differences due to Vitamin D on the metastatic spread across all cancers
•there were no significant differences due to Vitamin D on all-cancer mortality
• Adding together metastases and fatalities due to all cancers, the difference (2.1% vs 1.7%) was statistically significant, especially after the first two years
•The reduction was only statistically significant among those with a normal body-mass index (<25)
• For prostate cancer patients, there were only 6 (out of 12,927) such cases among those who got Vitamin D and 14 (out of 12,924) such cases among those who got the placebo - not significantly different. Presumably, they were missed at diagnosis or had a rare virulent type of PCa.
There is only one nasty post that I can see. I believe it is meant for me, but I don't understand it.
I went through Manson's D3 writings this morning since she apparently is "probably the foremost expert". There were over 50 papers & I was looking for a case for D3 other than PCa. Didn't find much. I posted right away. I had no time to withhold anything.
Seems that Darryl has removed the nastier accusation. I hope that a lot of guys got to read it first.
After his derogatory mouse comment last week, I don't expect civility from that quarter.
0030 hours--was checking emails and yesterday's posts just showed up. Odd that those in balmy regions who wear little clothing and eat oily fish and fish as their main source of protein never had rampant prostate cancers in their populations. I'll read a bit and run it by my onco, the head of the genitourinary department at the hospital and my conventional/alternative doc.
A check of the Blue Zones shows long summers except for Sardinia, however, in Nicoya Peninsula, Costa Rica summer never ends. All close to the sea or on the sea except for Loma Linda which is about 40 miles inland. Fish consumption.
For those of us who want to sunbathe for Vitamin D, there is an app called Dminder that tracks your position, altitude, age, cloudiness, skin exposure and more. Free with paid upgrade,cheap.Also Sparta sells a Vitamin D lamp designed for those with short gut syndrome who cannot absorb enough D from diet. The citizen scientist Ivor Cummins has one . Not cheap.
There is a literature developing of the benefits of sunlight other than Vitamin D.
There is also an association of low D levels and metabolic syndrome.
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