Critique of the U-shaped serum 25-hydroxyvitamin D level-disease response relation

Figures & data

Table 1 Previous reports showing a U-shaped serum 25(OH)D level dose-disease response relation

	Quantile*
Disease outcome	1	2	3	4	5	Reference
Colorectal cancer	11.5	23	29.5	37	50	7
	1.00	0.48	0.25	0.21	0.73
Prostate Cancer (OR)	<7.6	8–15.6	16–23.6	24–31.6	>32	1
	2.6 (1.1–6.2)	1.2 (0.8–1.9)	1.0	1.1 (0.7–2.8)	1.4 (0.7–2.7)
	<14.8	14.8–18.8	18.8–24.0	>24.0		16
	1.00	0.88 (0.48–1.61)	0.59 (0.31–1.11)	0.89 (0.49–1.62)
Pancreatic cancer	<12.8	12.8–16.4	16.4–20.4	20.4–26.2	>26.2	10
	1.00	1.30 (0.70–2.40)	2.12 (1.15–3.90)	1.50 (0.81–2.76)	2.92 (1.56–5.18)
	<18.4	18.4–24.1	24.1–27.8	27.8–32.9	>32.9	17
	1.00	0.97 (0.47–1.98)	0.86 (0.40–1.84)	0.84 (0.39–1.80)	1.45 (0.66–3.19)
Esophageal cancer	<7.8	7.8–12.8	12.8–19.5	>19.5		11
	1.00	0.87 (0.64–1.17)	0.85 (0.63–1.16)	1.30 (0.97–1.73)
Esophageal squamous dysplasia	<9.6	9.6–13.2	13.2–19.3	>19.3		12
	1.00	1.43 (1.00–2.06)	1.47 (1.04–2.12)	1.86 (1.35–2.62)
CVD	<10	10–15	>15			8
	2.63 (1.57–4.38)	1.80 (1.05–3.08)	1.00
All-cause mortality rate	<17.8	17.8–24.3	24.4–32.1	>32.1		9
	1.26 (1.08–1.46)	1.06 (0.89–1.24)	(0.93 (0.79–1.10)	1.00

* [25(OH)D, OR] (ng/mL; OR, 95% CI).

Table 2 Summary of data showing that the U-shaped serum 25(OH)D level-disease outcome does not apply for cardiovascular disease and all-cause mortality rates

Disease outcome	Hazard or rate ratio for serum 25(OH)D levels					Reference
	7*	10*	20*	30*	40*
CVD (hazard ratio)	2.21	1.97	1.49	1.24	1.06	9, 49–53
All-cause mortality rate ratio	1.93	1.90	1.38	1.15	1.00	16

* ng/mL.

Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008; 117:503 - 511

 PubMed Web of Science ®Google Scholar

Tuohimaa P, Tenkanen L, Ahonen M, Lumme S, Jellum E, Hallmans G, et al. Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in Nordic countries. Int J Cancer 2004; 108:104 - 108

 PubMed Web of Science ®Google Scholar

Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 2007; 85:1586 - 1591

 PubMed Web of Science ®Google Scholar

Chen W, Dawsey SM, Qiao YL, Mark SD, Dong ZW, Taylor PR, et al. Prospective study of serum 25(OH)-vitamin D concentration and risk of oesophageal and gastric cancers. Br J Nutr 2007; 97:123 - 128

 Web of Science ®Google Scholar

Lim U, Freedman DM, Hollis BW, Horst RL, Purdue MP, Chatterjee N, et al. A prospective investigation of serum 25-hydroxyvitamin D and risk of lymphoid cancers. Int J Cancer 2009; 124:979 - 986

 PubMed Web of Science ®Google Scholar

Abnet CC, Chen W, Dawsey SM, Wei WQ, Roth MJ, Lie B, et al. Serum 25(OH)-vitamin D concentration and risk of esophageal squamous dysplasia. Cancer Epidemiol Biomarkers Prev 2007; 16:1889 - 1893

 PubMed Web of Science ®Google Scholar

Vieth R. How to optimize vitamin D supplementation to prevent cancer, based on cellular adaptation and hydroxylase enzymology. Anticancer Res 2009; 29:3675 - 3684

 PubMed Web of Science ®Google Scholar

Melamed ML, Michos ED, Post W, Astor B. 25-Hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med 2008; 168:1629 - 1637

 PubMed Web of Science ®Google Scholar

Stolzenberg-Solomon RZ, Vieth R, Azad A, Pietinen P, Taylor PR, Virtamo J, et al. A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers. Cancer Res 2006; 66:10213 - 10219

 PubMed Web of Science ®Google Scholar

Semba RD, Houston DK, Bandinelli S, Sun K, Cherubini A, Cappola AR, et al. Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults. Eur J Clin Nutr 2010; 64:203 - 209

 PubMed Web of Science ®Google Scholar

Cannell JJ, Hollis BW. Use of vitamin D in clinical practice. Altern Med Rev 2008; 13:6 - 20

 PubMed Web of Science ®Google Scholar