70 replies to this topic

[nupi]

Seems kind of daft to look at coronary mortality and thereby excluding the supposed positive effects on cancer from higher 25-OH-D levels...

[Hebbeh]

The article was not clearly written. I believe it was all cause mortality.

http://jcem.endojour...21/jc.2013-1185


Abstract


Context: Low serum calcidiol has been associated with multiple co-morbidities and mortality but no “safe” range has been found for the upper concentration.

Objective: To establish the upper threshold of serum calcidiol, beyond which there is an increased risk for acute coronary syndrome and/or mortality.

Design, Setting, and Participants: We extracted data for 1,282,822 Clalit Health Services members aged > 45 between July 2007 and December 2011. Records of mortality or acute coronary syndrome were extracted during the follow-up period. Kaplan Meier analysis calculated time to episode and Cox regression models generated adjusted hazard ratios for episode by calcidiol group (< 10, 10.1–20, 20.1–36 and > 36.1 ng/mL).

Outcome Measures: Acute coronary syndrome subsuming all-cause mortality.

Results: During the 54-month study period, 422,822 Clalit Health Services members were tested for calcidiol of which 12,280 died of any cause (905 with acute coronary syndrome) and 3,933 were diagnosed with acute coronary syndrome. Compared to those with 20–36 ng/ml, the adjusted hazard ratios among those with levels of < 10, 10–20 and > 36 ng/ml were 1.88 [CI: 1.80–1.96], 1.25 [CI:1.21–1.30] and 1.13 [CI:1.04–1.22], (P < 0.05) respectively.

Limitations: The study cohort comprised only 30% of the population, those tested for vitamin D. The small sample size of those with calcidiol > 36 ng/mL prevented further analysis of this group.

Conclusions: Vitamin D in the 20–36 ng/ml range was associated with the lowest risk for mortality and morbidity. The hazard ratio below and above this range increases significantly.

Edited by Hebbeh, 01 May 2013 - 12:00 PM.

[maxwatt]

Note the limitation above:

The small sample size of those with calcidiol > 36 ng/mL prevented further analysis of this group.

[Methos000]

Note the limitation above:

The small sample size of those with calcidiol > 36 ng/mL prevented further analysis of this group.

>Objective: To establish the upper threshold of serum calcidiol, beyond which there is an increased risk for acute coronary syndrome and/or mortality.


I'd say they failed to establish this. They made a good case for the dangers of lower D levels, though.

Edited by Methos000, 01 May 2013 - 02:53 PM.

[niner]

Note the limitation above:

The small sample size of those with calcidiol > 36 ng/mL prevented further analysis of this group.

>Objective: To establish the upper threshold of serum calcidiol, beyond which there is an increased risk for acute coronary syndrome and/or mortality.

I'd say they failed to establish this. They made a good case for the dangers of lower D levels, though.

I wouldn't call it a failure. They met the conventional test for statistical significance. They just weren't able to subdivide the >36ng/ml subset any further. They are reporting more or less the same results that Melamed published several years ago. I don't remember the size of his dataset, but these guys may have had a larger set. Melamed showed a mortality curve with a broad minimum around 36, while these guys make it sound like the curve has a sharper break at that point. I don't have access to the full paper, so I don't know exactly what they have. I suspect that the higher coronary RR's for the >36 set could be modified with vitamin K supplementation. I've been aiming for a 25-OH-D3 level of 30ng/ml lately, because of a family history of prostate cancer. I got my level checked recently, and noticed that the testing lab now labels <30ng/ml as "deficient". Their "normal" range is now 30-100. Previously, I think normal was 10-30. From one error to another...

[maxwatt]

Last month I tested at 36. For several years Quest and labcorp both have labeled 20 to 30 as "insufficiency", under 20 as "deficiency. I forget what their normal range is, but certainly not as high as 100! Which lab are you using?

FWIW, lab ranges are often bogus. For instance, thyroid TSH is considered "normal" by every lab in the country, even though the American Society of Endocrinologists has for a decade maintained that TSH levels greater than 3 indicate a hypothyroid condition that may require treatment. But few physicians can justify treatment to an insurance company unless the result is outside the testing lab range. So many victims of Hashimoto's Thyroiditis don't receive treatment until their thyroid is destroyed, or worse, the autoimmune condition progresses to type 1 diabetes.

Edited by maxwatt, 04 May 2013 - 10:46 AM.

[ta5]

25-OH-D >28.8 ng/ml is worse for bones. Best levels are 24-28.8 ng/ml.


J Bone Miner Res. 2014 Mar 27.
U-Shaped Association Between Serum 25-Hydroxyvitamin D and Fracture Risk in Older Men: Results from the Prospective Population Based CHAMP Study.
Bleicher K1, Cumming RG, Naganathan V, Blyth FM, Le Couteur DG, Handelsman DJ, Waite LM, Seibel MJ.
The aim of this population-based prospective observational study was to examine the relationship between serum levels of 25-hydroxyvitamin D (25OHD) and fracture risk in a cohort of 1662 community-dwelling men aged 70-97 years followed for a mean of 4.3 years. Data about mobility, muscle strength, balance, medication use, cognition, medical history, lifestyle factors, renal function and serum 25OHD were collected at baseline. Data on radiologically verified fractures were collected every 4 months. The relationship between fractures and serum 25OHD levels was analyzed using Cox's proportional hazard regression. We accounted for bone mineral density, falls, physical activity, sun exposure, season of blood draw, in addition to anthropometric and lifestyle factors, medical history, muscle strength, balance, medication and supplement use. There were 123 first incident fragility fractures. The relationship between baseline 25OHD and fracture risk was U-shaped, with increased fracture risk in men with either low or high serum 25OHD levels. In multivariate analysis, the risk of fracture was greatest in men with 25OHD levels in the lowest quintile (25OHD ≤ 36nmol/L; hazard ratio (HR) = 3.5 (95% confidence interval (CI): 1.7-7.0) and in men in the highest quintile (25OHD >72nmol/L; HR = 2.7, 95% CI: 1.4-5.4) compared to men in the 4th quintile (25OHD ≥60 to ≤72nmol/L). These associations were not explained by lower BMD, increased physical activity, falls' risk or other lifestyle or anthropomorphic factors. In community-dwelling older men, there appears to be a healthy target range for serum 25OHD concentrations. Thus, serum 25OHD levels too high and too low may be harmful in regards to fracture risk.
PMID: 24677358

[ta5]

Eur J Epidemiol. 2014 Mar 29.
Is vitamin D deficiency a cause of increased morbidity and mortality at older age or simply an indicator of poor health?
Schöttker B1, Saum KU, Perna L, Ordóñez-Mena JM, Holleczek B, Brenner H.
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
To assess whether vitamin D deficiency is a cause of increased morbidity and mortality or simply an indicator of poor health, we assessed (1) the cross-sectional and longitudinal association of vitamin D deficiency with self-rated health (SRH) and frailty and (2) the association of vitamin D deficiency with mortality, with and without control for SRH and frailty. Analyses were performed in 9,579 participants of the German, population-based ESTHER cohort (age-range at baseline: 50-74 years), with follow-ups after 2, 5 and 8 years (mortality: 12 years). During follow-up, 129 subjects newly reported poor SRH, 510 developed frailty and 1,450 died. In cross-sectional analyses, subjects with vitamin D deficiency had higher odds of a poor SRH and frailty but no association with SRH or frailty was observed in longitudinal analyses. The association of vitamin D deficiency with all-cause and several cause-specific mortalities was strong and unaltered by time-dependent adjustment for classic mortality risk factors, SRH and frailty. In conclusion, vitamin D deficiency may not cause frailty or poor general health but may nevertheless be a prognostic marker for mortality, independent of the individual's morbidity.
PMID: 24682834

[timar]

It is highly unlikely that those observational studies show any causal relation between high levels of vitamin D and increased disease/fracture/mortality risk. As I have explained before, there are some intriguing relations between vitamin D and cholesterol metabolism and certain genetic variants related to longevity. I'm quite confident that the right half of the U-shaped curve some studies show is mostly due to those genetic variants (e.g. ApoE4).

Edited by timar, 01 April 2014 - 04:52 PM.

[InquilineKea]

Couldn't Vitamin D actually increase IGF1 levels? Which could presumably accelerate aging?

 

http://www.ncbi.nlm....pubmed/24005315

 

Sure, there are some studies associating higher Vitamin D with longevity. But these are all in older people. We know that high IGF1 levels is bad when you're young, but that once you're older, IGF1 protects against muscle wasting. Couldn't a similar relationship exist for Vitamin D?

[smithx]

Couldn't Vitamin D actually increase IGF1 levels? Which could presumably accelerate aging?

 

That looks like a very good question.