Vitamin D & Mortality

New study below.

I do wish Scandinavians would stop doing vitamin D studies on their own populations. For goodness sake - go to the Mediterranean where some men manage to be D-sufficient year round. Why look at a population where the majority are deficient or insufficient for much or the year, & the rest are mostly at the low end of sufficiency.

We have had a series of studies that identify vitamin D as a risk factor for PCa. The "reverse J-shaped association" mentioned in the new paper. Typically, using quartiles of serum D (calcidiol), the lowest quartile would include severely deficient (<15 ng/mL), the second quartile wold be a mix of deficient (<20 ng/mL) & insufficient (<32 ng/mL), the third would be all insufficient & the top quartile would be mostly barely sufficient, for a great part of the year. Oddly, the 4th quartile has higher risk than the lowest in those studies. As though deficiency were protective.

One possible explanation is that men who feel that they are at increased risk for PCa, might be inclined to supplement. Education has been found to be a PCa risk factor - perhaps because of the number of working hours spent indoors. Education + poor D status due to indoor work might lead to supplementation.

Those studies looked at incidence, the new Norwegian/Swedish study looked at mortality. Edward Giovannucci (Boston) was also involved.

"In men with prostate cancer (n = 2282), there was a significant inverse association between {calcidiol} and total mortality after controlling for potential confounders" ("during more than two decades of follow-up from the blood sample collection")

25% extra mortality for D below 50 nmol/L. To convert nmol/L to ng/mL, divide by 2.5. So there was 25% excess mortality for those under 20 ng/mL - which happens to be the cutoff for deficiency. Big surprise - deficiency is not a good place to be, after all:

"In this study population, {calcidiol} was inversely associated with total mortality during more than two decades of follow-up, despite, as previous reported, high {calcidiol} was associated with increased risk of prostate cancer."

A nitpick - the word "high", used in the sentence above, has also been used in the studies I mentioned. It doesn't actually mean high, except in comparison with the lowest group. In the new study, here are the number of men by serum D range:

<12 ng/mL - 160 - severely deficient

12-<20 ng/mL - 1,141 - deficient

20-<28 ng/mL - 1,561 - insufficient

28-<36 ng/mL - 1,023 - insufficient/sufficient (cutoff for sufficiency is 32 ng/mL)

>=36 ng/mL - 494 - sufficient

Total = 4,379 men (~1095 per quartile)

As can be seen, 1,301 are deficient (<20 ng/mL), which places 206 deficient men in the 2nd quartile.

The 4th quartile likely contains some insufficient men.

Less than half of the 4th quartile was >=36 ng/mL.

"... few men in our study had very high concentration {1.1% had concentration ≥ 50 ng/mL and 6% had concentration ≥ 40 ng/mL}"

Deaths:

<12 ng/mL - 32.4%

12-<20 ng/mL - 30.1%

20-<28 ng/mL - 25.6%

28-<36 ng/mL - 26.3%

>=36 ng/mL - 24.1%

Too bad the data is insufficient to see what happens in the 50-100 ng/mL range.

-Patrick

FULL Text: journals.plos.org/plosone/a...

ncbi.nlm.nih.gov/pubmed/269...

PLoS One. 2016 Mar 17;11(3):e0151441. doi: 10.1371/journal.pone.0151441.

Long Term Association between Serum 25-Hydroxyvitamin D and Mortality in a Cohort of 4379 Men.

Meyer HE1,2,3, Støer NC2,4,5, Samuelsen SO2,4, Blomhoff R6,7, Robsahm TE8, Brustad M9, Giovannucci EL3,10, Bjørge T8,11.

Author information

1Department of Community Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

2Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.

3Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.

4Department of Mathematics, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.

5Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

6Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

7Division of Cancer, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway.

8The Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway.

9Department of Community Medicine, UIT The Artic University of Norway, Tromsø, Norway.

10Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.

11Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.

Abstract

OBJECTIVE:

A number of observational studies have shown an inverse association between circulating 25-hydroxyvitamin D and total mortality, but a reverse J-shaped association has also been reported. In a large nested case-control study, serum-25-hydroxyvitamin D (s-25(OH)D) was positively associated with incident prostate cancer. Based on the same study population, the primary aim of the present study was to investigate the association between s-25(OH)D and total mortality.

METHODS:

Men participating in population based health screenings during 1981-1991 and enrolled in a nested case-control study were followed throughout 2007 with respect to all-cause and cause-specific mortality. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards regression.

RESULTS:

In men with prostate cancer (n = 2282), there was a significant inverse association between s-25(OH)D and total mortality after controlling for potential confounders (HR = 1.25 (95% CI 1.05-1.50), s-25(OH)D <50 nmol/l versus s-25(OH)D ≥50 nmol/l). The corresponding figure among controls (n = 2147) was HR = 1.15 (95% CI 0.88-1.50) and in the total study population HR = 1.19 (95% CI 1.03-1.38). For cause-specific deaths, we found no significant associations.

CONCLUSIONS:

In this study population, s-25(OH)D was inversely associated with total mortality during more than two decades of follow-up, despite, as previous reported, high s-25(OH)D was associated with increased risk of prostate cancer.

PMID: 26986958 [PubMed - as supplied by publisher]

4 Replies

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  • I thought I would be able to decipher the foregoing, Patrick, but still do not have a clue what your conclusion actually is. Since most readers of posts are not scientists or having been educated in deciphering the information your provided, it would help if you could "dumb it down" to understandable for me and others. I am a proponent for 25-hydroxy Vitamin D level for prostate cancer patients to be maintained within a range of around 75ng/ml to 90nng/ml given that equipment to determine this level has been found to be about 20% off, with actual level 20% less than the reading.

  • Chuck & Joe,

    The message from the study authors is:

    (a) others have found normal D to be a risk factor for PCa incidence, & insufficiency/deficiency to be protective.

    (b) in contrast, we have found higher mortality in D-deficient men with PCa.

    (c) therefore, men with PCa should ignore the other studies & avoid deficiency.

    You can't get much else out of it. It is necessarily a childlike conclusion, because of the limitations of their data.

    I don't know how many men gave up on vitamin D when they read the original Scandinavian studies with their J-shaped risk curves.

    For many of us familiar with the Vitamin D Council, etc, the context is quite different. We think in terms of D being above 50. Only 1.1% of men in the study achieved that.

    More importantly, we tend to aim much higher than 50. Dr Myers once mentioned 100 as the upper limit target. He later came down to 75. I don't know what he recommends now. The point is that these Scandinavian studies muddy the water & are really irrelevant to men who have never been deficient & don't intend to be. It's as though someone did a a study of testosterone & PCa risk, but only used men with T<375.

    I aim for D at least 75. I take 7,000 IU every day & don't get much above 75 with that dose.

    It's been established that levels well above 100 are safe, but we have no reason to go that high. What we lack is a study that has a significant number of men scattered through the 50-100 range. Currently, such men are lost in studies that deal in quartiles & quintiles.

    The D we measure is a reservoir. In a sense, why should the level matter? As long as there is water in one's reservoir, there will be water for coffee in the morning. But there are indications that the body can restrict access to peripheral tissue when the D level falls significantly. The primary purpose of the reservoir, after all, is to ensure serum calcium homeostasis.

    It has also been said that, even with very high levels, an erratic intake of D might trigger conservation. So one should settle on a dose & stick with it.

    Apologies for being abstruse.

    If you had problems with the first post, there is more of the same in my second. It seems that the establishment has gotten behind the J-shaped curve. I find it very frustrating. My only reason for discussing these new studies is to try to reverse the harm that the Swedish J-curve may be doing.

    Best, -Patrick

  • now i am a wee bit confused. i am on 4,000 units of vitamin D per day and have prostate cancer. i think from what your saying it may be OK

  • I opt for (b) and (c). My opinion regarding appropriate level of 25-hydroxy Vitamin D here: tinyurl.com/748cx5c

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