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Does it matter how often researchers test serum vitamin D?

Posted on: May 1, 2012   by  Dr William Grant

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The recent paper by Meng et al.1 found a Spearman correlation coefficient of 0.61 [95% confidence interval (CI), 0.56-0.66] for serum 25-hydroxyvitamin D [25(OH)D] concentration measurements five years apart. This was deemed acceptable for determining serum 25(OH)D-disease relations.

Meng JE, et al. Intraindividual variation in plasma 25-hydroxyvitamin D measures 5 years apart among postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2012 Apr.

It was recently shown that the linear fit to the Pearson or Spearman correlation coefficient vs. follow-up period from one to 14 years had a slope of -0.020/year (p=0.71)2. The value from(1) was 0.026 above the regression line fit. Long follow-up studies often find that hazard ratios (HRs) or relative risks (RRs) tend to no effect as follow-up time increases. A change of 0.017/year for HR was found for all-cause mortality rate2. Changes in RRs for breast and colorectal cancer incidence were 0.050/year and 0.033/year respectively3. For breast cancer incidence, only case-control studies (zero follow-up time) were reported to have significant inverse correlations with respect to serum 25(OH)D concentration3. For all-cause mortality rate, the HR extrapolated for zero follow-up time was 0.72 (95% CI, 0.50–1.03)2, giving a reduction 3.5 times higher than the standard result from the meta-analysis (0.92 [95% CI, 0.89–0.95]) 4.

Thus, the problem with using a single serum 25(OH)D concentration measurement from the time of enrollment in a cohort study with long follow-up times is that its usefulness decreases with increasing follow-up time. It appears to be the primary reason for the disagreement between ecological studies of ultraviolet-B (UVB) doses and cancer incidence and/or mortality rates and observational studies of serum 25(OH)D concentrations and cancer incidence5. Observational studies have reported inverse, no, direct, and U-shaped serum 25(OH)D-cancer incidence relations. In contrast, ecological studies have consistently found inverse correlations between indices of solar UVB doses and cancer incidence and/or mortality rates for 15 types of cancer and less consistent findings for nine types of cancer5.

It is strongly urged that in cohort studies, blood be drawn every two-to-three years so that additional serum 25(OH)D concentrations can be determined, and that any meta-analysis of health outcome with respect to serum 25(OH)D concentration include an analysis of the effect of follow-up time. Also, more credit should be given to case-control studies. Those with cancer generally are unaware of having cancer until so diagnoses.

References

1. Meng JE, Hovey KM, Wactawski-Wende J, Andrews CA, Lamonte MJ, Horst RL, et al. Intraindividual variation in plasma 25-hydroxyvitamin D measures 5 years apart among postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2012 Apr 20. [Epub ahead of print]

2. Grant WB. Effect of follow-up time on the relation between prediagnostic serum 25-hydroxyitamin D and all-cause mortality rate. Dermatoendocrinol. 2012;4(2) In press.

3. Grant WB. Effect of interval between serum draw and follow-up period on relative risk of cancer incidence with respect to 25-hydroxyvitamin D level; implications for meta-analyses and setting vitamin D guidelines. Dermatoendocrinol. 2011;3:199-204.

4. Schöttker B, Ball D, Gellert C, Brenner H. Serum 25-hydroxyvitamin D levels and overall mortality. A systematic review and meta-analysis of prospective cohort studies. Ageing Res Rev. 2012 Feb 16. [Epub ahead of print]

5. Grant WB. Ecological studies of the UVB-Vitamin D-cancer hypothesis; review. Anticancer Res. 2012:32:223-36.

3 Responses to Does it matter how often researchers test serum vitamin D?

  1. JBG

    This post is pretty hard for a lay person to sort out, even a one-time academic like me, though I think I get the final drift.

    Minor point, I think there is a word missing in this sentence (shown in brackets): It appears to be the primary reason for the disagreement between ecological [studies] of ultraviolet-B (UVB) doses and cancer incidence

    • Brant Cebulla

      Thanks John, we’ll correct it.

  2. Brant Cebulla

    For the lay person, here is the gist of what Dr. Grant is saying: In research, a 25(OH)D level becomes less and less useful the longer you wait to measure outcomes.

    About a month ago, a study came out that found no correlation between a 25(OH)D level drawn when kids were 9 years old and their school performance at age 14 years old. While this might be true, that vitamin D does not influence school performance, common sense begs to ask: what does a vitamin D level at 9 years old have to do with cognitive function 5 years later?

    More useful would have been a 25(OH)D level drawn the same day the kids took a standardized test.

    In observational cancer studies, Dr. Grant argues that correlations become slightly weaker the longer the follow up time.

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