Vitamin D and recent research indicates profound outcomes

[Mike41]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061380/

[Dean Pomerleau]

Recent? The meta-analysis you point to [1] is from 2014. Recent randomized control trials of vitamin D supplements haven't found significant benefits in subjects who weren't deficient in vitamin D to start with [2].

--Dean 

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[1] Schöttker B, Jorde R, Peasey A, Thorand B, Jansen EH, Groot Ld, Streppel M, Gardiner J, Ordóñez-Mena JM, Perna L, Wilsgaard T, Rathmann W, Feskens E, Kampman E, Siganos G, Njølstad I, Mathiesen EB, Kubínová R, Pająk A, Topor-Madry R, Tamosiunas A, Hughes M, Kee F, Bobak M, Trichopoulou A, Boffetta P, Brenner H; Consortium on Health and Ageing: Network of Cohorts in Europe and the United States. Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ. 2014 Jun 17;348:g3656. doi: 10.1136/bmj.g3656. PMID: 24938302; PMCID: PMC4061380. 

 

[2] 1. Nutrients. 2022 Jan 12;14(2):303. doi: 10.3390/nu14020303.

Critical Appraisal of Large Vitamin D Randomized Controlled Trials.

Pilz S(1), Trummer C(1), Theiler-Schwetz V(1), Grübler MR(1), Verheyen ND(2), 

Odler B(3), Karras SN(4), Zittermann A(5), März W(6)(7)(8).

 

As a consequence of epidemiological studies showing significant associations of 

vitamin D deficiency with a variety of adverse extra-skeletal clinical outcomes 

including cardiovascular diseases, cancer, and mortality, large vitamin D 

randomized controlled trials (RCTs) have been designed and conducted over the 

last few years. The vast majority of these trials did not restrict their study 

populations to individuals with vitamin D deficiency, and some even allowed 

moderate vitamin D supplementation in the placebo groups. In these RCTs, there 

were no significant effects on the primary outcomes, including cancer, 

cardiovascular events, and mortality, but explorative outcome analyses and 

meta-analyses revealed indications for potential benefits such as reductions in 

cancer mortality or acute respiratory infections. Importantly, data from RCTs 

with relatively high doses of vitamin D supplementation did, by the vast 

majority, not show significant safety issues, except for trials in critically or 

severely ill patients or in those using very high intermittent vitamin D doses. 

The recent large vitamin D RCTs did not challenge the beneficial effects of 

vitamin D regarding rickets and osteomalacia, that therefore continue to provide 

the scientific basis for nutritional vitamin D guidelines and recommendations. 

There remains a great need to evaluate the effects of vitamin D treatment in 

populations with vitamin D deficiency or certain characteristics suggesting a 

high sensitivity to treatment. Outcomes and limitations of recently published 

large vitamin D RCTs must inform the design of future vitamin D or nutrition 

trials that should use more personalized approaches.

 

DOI: 10.3390/nu14020303

PMCID: PMC8778517

PMID: 35057483 [Indexed for MEDLINE]

 

 

[Saul]

9 hours ago, Dean Pomerleau said:

but explorative outcome analyses and 

meta-analyses revealed indications for potential benefits such as reductions in 

cancer mortality or acute respiratory infections. Importantly, data from RCTs 

with relatively high doses of vitamin D supplementation did, by the vast 

majority, not show significant safety issues, except for trials in critically or 

severely ill patients or in those using very high intermittent vitamin D doses. 

The recent large vitamin D RCTs did not challenge the beneficial effects of 

vitamin D regarding rickets and osteomalacia, that therefore continue to provide 

the scientific basis for nutritional vitamin D guidelines and recommendations. 

  --  Saul

[Ron Put]

I think I've posted this before, but now I am reevaluating my supplementation with vitamin D based on it:

Low levels of vitamin D are also linked to longevity:
 

Levels of 25-hydroxyvitamin D in familial longevity: the Leiden Longevity Study

See also this:

https://www.snpedia.com/index.php/rs2060793

[mccoy]

I've reported this a while ago: my levels of vitamin D3, measured after a summer of daily exposure to natural UV rays (sunrays at hours around noon), was 32 ng/ml (I hope the units are right). The body did not produce more, even if it plausibly had the possibility. At first I was disappointed. But afterwards, I reasoned, perhaps that indicates that higher concentrations were not optimal for me?

[corybroo]

1 hour ago, mccoy said:

At first I was disappointed. But afterwards, I reasoned, perhaps that indicates that higher concentrations were not optimal for me?

Quite reasonable, I think.  The same is true for carrots and vitamin A.   Is it possible to get an overdose of vitamin A from eating carrots?

If you do want to overdose, use supplements.  Hypervitaminosis A

[Mike41]

4 hours ago, mccoy said:

I've reported this a while ago: my levels of vitamin D3, measured after a summer of daily exposure to natural UV rays (sunrays at hours around noon), was 32 ng/ml (I hope the units are right). The body did not produce more, even if it plausibly had the possibility. At first I was disappointed. But afterwards, I reasoned, perhaps that indicates that higher concentrations were not optimal for me?

Interesting I had the same experience several years ago and my levels were in the same range as yours. But where I live it’s not possible 6 months out of the year and so I supplement 1000 mg from late October until March. A test in February showed I maintained the summer levels doing that

[Ron Put]

This might give a clue as to some of the correlations often sited. It makes sense to me at first listen:
 

 

[InquilineKea]

I had 69 ng/mL.. Mult5iply by 2.5 for nmol/L

I've been drinking lots of almond milk lately, some supplementation with Vitamin D.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388383/

Quote

 

A minority of studies (n = 3) reported higher mortality associated with very high 25(OH)D (Figure 2C) [17,19,20]. In the CopD study, increased all-cause mortality was observed for both low and high 25(OH)D, and the lowest risk was at 50–60 nmol/L [17]. However, this study utilized a general practice database, and was therefore unable to adjust for confounders other than age, sex, and season, and the median follow-up was only three years. In addition, relatively few participants (1.0%) had 25(OH)D concentrations >140 nmol/L, (versus 8.3% with 25(OH)D ˂ 10 nmol/L) [17]. In the Uppsala Longitudinal Study of Adult Men, there was a U-shaped association, with higher mortality for the lowest 10% (<46 nmol/L, HR = 1.43, 95% CI 1.11–1.84) and the highest 10% of 25(OH)D (>93 nmol/L, HR = 1.27, 95% CI 0.97–1.66) versus the 10^th–90^th percentiles [20]. There was also a U-shaped relationship in the Newcastle 85+ study, but the increased risk for high 25(OH)D was only evident for women (RR for 25(OH)D ≥ 75 versus 25–74 nmol/L = 1.72, 95% CI 1.19–2.51) [19]. Further, this relationship differed depending on how 25(OH)D was categorized, and seemed to be mainly ascribed to women taking vitamin D supplements. When categorized as season-specific quartiles, the increased mortality risk (RR = 1.51, 95% CI 1.06–2.14) observed for the highest 25% versus the middle 50% of 25(OH)D was attenuated when restricted to women not taking vitamin D-containing supplements/prescribed medication (RR = 1.32, 95% CI 0.76–2.28). Using predefined cut-offs of >50 compared with 30–50 nmol/L, the corresponding HRs were 1.42 (95% CI 0.98–2.06) and 1.09 (95% CI 0.64–1.87), respectively. For men, neither low nor high 25(OH)D was associated with mortality [19]. Vitamin D supplementation is more likely to be recommended to elderly women than men [71]. A possible explanation for the U-shaped association in some studies could be that people with very high 25(OH)D were taking vitamin D supplements due to poor health, leading to a spurious association between high 25(OH)D concentrations and mortality [71]. Another possible explanation is that people with very high 25(OH)D concentrations have lower concentrations of the active vitamin D metabolite 1,25(OH)₂D [72], which might in itself be associated with mortality [73,74]. Therefore, the results from these studies should be interpreted with caution.

Initial analyses of data from the Third National Health and Nutrition Examination Survey (NHANES III) suggested a “reverse J-shaped” association between 25(OH)D and all-cause mortality (albeit based on sparse data at low and high extremes of the 25(OH)D distribution), with a strong inverse association below 40 nmol/L, and a weak increased risk above 120 nmol/L [21]. However, after the standardization of 25(OH)D measurements to the National Institute of Standards and Technology reference measurement procedures, the shape of the association was different, with no increased nor decreased mortality risk at high 25(OH)D concentrations (>100 nmol/L) [75]. Below 40 nmol/L, the all-cause mortality risk increased with decreasing 25(OH)D, while above 40 nmol/L, the risk appeared to plateau. The radioimmunoassay used in NHANES III seemed to overestimate 25(OH)D [15], particularly at high concentrations (above about 102 nmol/L) [75]. After standardization, few individuals had 25(OH)D ≥ 120 nmol/L, and the association at very high concentrations could not be estimated [75], highlighting the importance of scrutinizing assay validity when interpreting results. Other studies that have examined very high concentrations of 25(OH)D compared with levels consistent with vitamin D sufficiency (generally around 50–75 nmol/L) have not found increased mortality for high 25(OH)D [50,57,76], and these findings are supported by meta-analyses [2,3,4].

 

 

Edited February 27 by InquilineKea

[Sibiriak]

On 10/10/2022 at 1:17 AM, Ron Put said:

This might give a clue as to some of the correlations often site

 

Thanks.   I did  a lot of research on Vit D a few years back and, as I tend to  do,  reached certain tentative conclusions and more or less dropped the issue.

Regarding evidence of Vit D--> bone loss / hypercalciuria  discussed in the video,  I  would have liked to see Vit. k2 brought into the discussion.

In any case, I think it's probably  impossible to identify an ideal  25(OH)D level for  all individuals.  

Personally, I  get less sun exposure than I would  like (my California surfing  days are  over), and  I've found I  need to supplement modestly to avoid sinking below  30 ng/ml.

.

 

Edited February 27 by Sibiriak

[IgorF]

The topic is a complicated thing and there is no simple scheme to follow or answer yes/no or build a decision tree that will be reliable etc. After reading few books and many articles on the topic all I know from it - I have to read more and more or stick to some own scheme and don't care about any study published until it will be a part of medical textbooks.

When I discovered that my serum calcium is on the high norm (and sometimes slightly higher) I started to search the answers and found that it is not easy to answer on such thing, even with a lot of analyses (almost any available in the lab, several times). When I started to wonder if I do not produce more PTH than it is ok I visited an endocrinologist with all the things I had and he told - ok, do 5kU of soluble vit D with fatty food for a few weeks and measure the things again, if they will be the same - let's investigate it deeper. Don't think yet about scary things like surgery for glands etc.

And my calcium was a bit lower afterwards, as well as captured PTH in the same probes. So I changed to d3+k2 instead of pure d3 and did some more tests. With k2 added it started to look even better. Before deciding about k2 addition I did a test and saw it less than low normal.

My calcium intake during all these studies was 0.6-1.1 g daily, some from animal sources. I think this is not enough and that was a part of the puzzle.

Finally I discovered that I have to run d3 supplementation 10 months per year at the place I do live now, k2 - just daily because I don't have it in my diet and possible conversions from high k1 intake seems unreliable.

Daily calcium intake from non-animal sources should be at least 1.6 g/day in my case, but that topic worse a separate long discussion.

To have serum d3 levels at 40-50 ng/ml (preferably higher side) and PTH at the same 40-50 but pg/ml (preferably at lower side) I have to supplement with ~4kU daily so I am doing 8kU every second day (because I have a big bottle of 8kUs). These values are consistent with all I read about caucasians' requirement to have a recommended ~50 g/ml in the serum test.

Other ancestries - the requirements are different, people should research their situation on their own.

The next very important thing - serum levels achieved with supplements are not the same as levels achieved from its natural way of production. Serum precursors are not distributed to all the potential consumers but there is no solution so far for this.

So in other words - if it seems your PTH is too high and calcium also - you either have not enough calcium intake or are not efficient with reuptake - d3+k2 supplementation can help with this and also can fill some stores for d which could be very important when a challenge will happen (like covid or other similar things). But a natural way of achieving the same (if possible) will work better - the tissues that are "expecting" to get inplace vit d from UV-helped reactions will also get it, they can't do it from circulating serum version. Also there are some doubts that supplemented d3 is protective against viral-originated challenges but so far there is no really good data on such things, we only sure that those who faces the challenge with depleted stores for d have more chances for serious troubles, so it is better to be on a safer side perhaps.

 

Br,

Igor