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Plasma 25-hydroxyvitamin d is associated with markers of the insulin resistant phenotype in nondiabetic adults. Liu E, Meigs JB, Pittas AG, McKeown NM, Economos CD, Booth SL, Jacques PF. J Nutr. 2009 Feb;139(2):329-34. Epub 2008 Dec 23. PMID: 19106328 doi:10.3945/jn.108.093831 After adjusting for age and sex, plasma 25(OH)D was positively associated with ISI(0,120), plasma adiponectin, and HDL cholesterol and inversely associated with plasma triacylglycerol, but these associations were no longer significant after further adjustment for BMI, waist circumference, and current smoking status. 25(OH)D and 2-h post-OGTT glucose were not associated. Among adults without diabetes, vitamin D status was inversely associated with surrogate fasting measures of insulin resistance. These results suggest that vitamin D status may be an important determinant for type 2 diabetes mellitus.

Vitamin D receptor (VDR) gene polymorphisms and haplotypes, interactions with plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and prostate cancer risk. Mikhak B, Hunter DJ, Spiegelman D, Platz EA, Hollis BW, Giovannucci E. Prostate. 2007 Jun 15;67(9):911-23. PMID: 17440943 DOI: 10.1002/pros.20570 RESULTS No association was found between these SNPs or their associated haplotypes and all PC subtypes except that haplotype 2 (A-f-b) with Cdx2 A, Fok1 f, and Bsm1 b alleles and haplotype 3 (A-F-B) with Cdx2 A, Fok1 F and Bsm1 B alleles compared to the most common haplotype (A-F-b), were associated with reduced risk of aggressive PC (high stage or Gleason sum 7; P = 0.02), both with two alleles suspected of being low risk. Carriers of the variant Cdx2 A allele who were deficient in plasma 25-hydroxyvitamin D (15 ng/ml) compared to non-carriers with normal 25-hydroxyvitamin D, had a lower risk of total and poorly differentiated PCs (Gleason sum 7) (P for interaction = 0.02 and 0.04, respectively). Plasma 1,25-dihydroxyvitamin D deficiency (26 pg/ml) was associated with a threefold risk of poorly differentiated PC (P for interaction = 0.01) when comparing carriers of the Cdx2 A allele to non-carriers with normal 1,25-dihydroxyvitamin D. CONCLUSION In this population of men, none of the VDR polymorphisms studied was associated with susceptibility to PC. Carriers of the variant Cdx2 A allele with low plasma 25-hydroxyvitamin D may experience a reduction in risk of total and poorly differentiated prostate cancers compared to non-carriers with adequate 25-hydroxyvitamin D.

Plasma 25-hydroxyvitamin D levels and risk of incident hypertension among young women. Forman JP, Curhan GC, Taylor EN. Hypertension. 2008 Nov;52(5):828-32. Epub 2008 Oct 6. PMID: 18838623 doi: 10.1161/HYPERTENSIONAHA.108.117630 Women in the lowest compared with highest quartile of plasma 25(OH)D had an adjusted odds ratio for incident hypertension of 1.66 (95% CI: 1.11 to 2.48; P for trend=0.01). Compared with women with sufficient levels, those with vitamin D deficiency (<30 ng/mL; 65.7% of the study population) had a multivariable odds ratio of 1.47 (95% CI: 1.10 to 1.97). Plasma 25(OH)D levels are inversely and independently associated with the risk of developing hypertension.

Relationships between 25-Hydroxyvitamin D Levels and Plasma Glucose and Lipid Levels in Pediatric Outpatients. Johnson MD, Nader NS, Weaver AL, Singh R, Kumar S. J Pediatr. 2009 Nov 17. [Epub ahead of print] PMID: 19926097 Conclusions Low 25(OH) D levels in children and adolescents are associated with higher plasma glucose and lower HDL concentrations.

Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of incident ovarian cancer. Tworoger SS, Lee IM, Buring JE, Rosner B, Hollis BW, Hankinson SE. Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):783-8. PMID: 17416771 doi: 10.1158/1055-9965.EPI-06-0981 Overall, our results do not suggest that plasma vitamin D levels are associated with risk of ovarian cancer. However, we observed significant associations in some subgroups, which should be evaluated further in other studies because increasing vitamin D intake is an easy preventive measure to adopt.

Plasma calcidiol, season, and serum parathyroid hormone concentrations in healthy elderly men and women. Dawson-Hughes B, Harris SS, Dallal GE. Am J Clin Nutr. 1997 Jan;65(1):67-71. PMID: 8988915 Plasma calcidiol and serum PTH concentrations were inversely related, with PTH rising slowly as calcidiol concentrations declined below 110 nmol/L (95 CI: 60, 168 nmol/L). More than 90% of the men and women had calcidiol concentrations below this value in the wintertime. The high prevalence of lower wintertime calcidiol values may increase risk of bone loss in elderly men and women.

"I discussed in my last post how Dr Vieth has a model of tissue 1,25(OH)2D synthesis and degradation in which the level of active substance is pretty well independent of blood vitamin D level, provided the level is either rising or stable. I think it is also worth pointing out that he is talking, hypothetically, about tissue 1,25(OH)2D, not plasma level... As we know, almost nothing is known about tissue 1,25(OH)2D control. By Vieth's hypothesis tissue 1,25(OH)2D is OK so long as there is at least SOME vitamin D present in plasma and the level dose not vary too much. Obviously there is a level below which you can have as much of the enzyme for converting vitamin D to the active form as you like, if there is no vitamin D in your blood you can't make any 1,25(OH)2D in your tissues, or in your kidneys for export to your blood to control calcium levels. At the lower extremes we have rickets and osteomalacia. These are clear cut, unarguable markers of vitamin D deficiency, in the absence of confounding factors (there are a few)."

Association between plasma 25-hydroxyvitamin D and breast cancer risk. Crew KD, Gammon MD, Steck SE, Hershman DL, Cremers S, Dworakowski E, Shane E, Terry MB, Desai M, Teitelbaum SL, Neugut AI, Santella RM. Cancer Prev Res (Phila Pa). 2009 Jun;2(6):598-604. Epub 2009 May 26. PMID: 19470790 In summary, these results add to a growing body of evidence that adequate vitamin D stores may prevent breast cancer development. Whereas circulating 25-OHD levels of >32 ng/mL are associated with normal bone mineral metabolism, our data suggest that the optimal level for breast cancer prevention is ≥40 ng/mL. Well-designed clinical trials are urgently needed to determine whether vitamin D supplementation is effective for breast cancer chemoprevention.

In conclusion, genetic variations of DBP are associated with insulin resistance in Japanese with normal glucose tolerance, which might contribute to the development of type 2 diabetes. Variations in vitamin D-binding protein (group-specific component protein) are associated with fasting plasma insulin levels in Japanese with normal glucose tolerance. Hirai M, Suzuki S, Hinokio Y, Hirai A, Chiba M, Akai H, Suzuki C, Toyota T. J Clin Endocrinol Metab. 2000 May;85(5):1951-3. PMID: 10843180

Plasma 25-hydroxyvitamin D levels in young children undergoing placement of tympanostomy tubes.\nLinday LA, Shindledecker RD, Dolitsky JN, Chen TC, Holick MF.\nAnn Otol Rhinol Laryngol. 2008 Oct;117(10):740-4.\nPMID: 18998501

Li H, Stampfer MJ, Hollis JBW, Mucci LA, Gaziano JM, et al. (2007) A Prospective Study of Plasma Vitamin D Metabolites, Vitamin D Receptor Polymorphisms, and Prostate Cancer. PLoS Med 4(3): e103 doi:10.1371/journal.pmed.0040103

A nested case control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer. Wu K, Feskanich D, Fuchs CS, Willett WC, Hollis BW, Giovannucci EL. J Natl Cancer Inst. 2007 Jul 18;99(14):1120-9. Epub 2007 Jul 10. PMID: 17623801

Plasma vitamin D and 25OHD responses of young and old men to supplementation with vitamin D3. Harris SS, Dawson-Hughes B. J Am Coll Nutr. 2002 Aug;21(4):357-62. PMID: 12166534 Conclusions: There appears to be no age-related impairment among men in the absorption or metabolism of 20 µg/day of vitamin D3 taken orally for at least eight weeks.

Circulating 25-hydroxyvitamin d levels and survival in patients with colorectal cancer. Ng K, Meyerhardt JA, Wu K, Feskanich D, Hollis BW, Giovannucci EL, Fuchs CS. J Clin Oncol. 2008 Jun 20;26(18):2984-91. PMID: 18565885 DOI: 10.1200/JCO.2007.15.1027 Conclusion Among patients with colorectal cancer, higher prediagnosis plasma 25(OH)D levels were associated with a significant improvement in overall survival. Further study of the vitamin D pathway and its influence on colorectal carcinogenesis and cancer progression is warranted.

Vitamin D and breast cancer. Bertone-Johnson ER. Ann Epidemiol. 2009 Jul;19(7):462-7. Epub 2009 Feb 20. Review. PMID: 19230714 Though the relationship between vitamin D and breast cancer remains unclear, a growing body of evidence suggests that vitamin D may modestly reduce risk. A large number of in vitro studies indicate that vitamin D can inhibit cell proliferation and promote apoptosis and cell differentiation in breast tumor tissue. Results from analytic studies of sunlight exposure and dietary intake have been inconsistent but together generally support a modestly protective role of vitamin D, at least in some population subgroups. Studies using blood vitamin D metabolites to assess vitamin D status may be less prone to misclassification than those of diet and sunlight exposure. Overall, the two prospective and four case-control studies of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D tend to support a protective effect in older women. The relationship between common vitamin D receptor polymorphisms and risk remains unclear. Many questions about this relationship clearly remain, including the utility of assessing vitamin D through diet and sunlight exposure, the relationship between plasma metabolites, and the potential modifying effects of age, menopausal status and tumor characteristics. Given that vitamin D status is modifiable, additional prospective studies are necessary to determine if vitamin D may have important potential for breast cancer prevention.

The Diet-Heart Hypothesis: Subdividing Lipoproteins Two posts ago, we made the rounds of the commonly measured blood lipids (total cholesterol, LDL, HDL, triglycerides) and how they associate with cardiac risk. It's important to keep in mind that many things associate with cardiac risk, not just blood lipids. For example, men with low serum vitamin D are at a 2.4-fold greater risk of heart attack than men with higher D levels. That alone is roughly equivalent to the predictive power of the blood lipids you get measured at the doctor's office. Coronary calcium scans (a measure of blood vessel calcification) also associate with cardiac risk better than the most commonly measured blood lipids. Lipoproteins Can be Subdivided into Several Subcategories In the continual search for better measures of cardiac risk, researchers in the 1980s decided to break down lipoprotein particles into sub-categories. One of these researchers is Dr. Ronald M. Krauss. Krauss published extensively on the association between lipoprotein size and cardiac risk, eventually concluding (source): The plasma lipoprotein profile accompanying a preponderance of small, dense LDL particles (specifically LDL-III) is associated with up to a threefold increase in the susceptibility of developing [coronary artery disease]. This has been demonstrated in case-control studies of myocardial infarction and angiographically documented coronary disease. Krauss found that small, dense LDL (sdLDL) doesn't travel alone: it typically comes along with low HDL and high triglycerides*. He called this combination of factors "lipoprotein pattern B"; its opposite is "lipoprotein pattern A": large, buoyant LDL, high HDL and low triglycerides. Incidentally, low HDL and high triglycerides are hallmarks of the metabolic syndrome, the quintessential modern metabolic disorder. Krauss and his colleagues went on to hypothesize that sdLDL promotes atherosclerosis because of its ability to penetrate the artery wall more easily