Wednesday, December 10, 2008

Another Study on Vitamin D

Here is yet another abstract of Vitamin D status as it seems to be all the rage now (and for good reason).
Be sure to check out my earlier post on Vitamin D and Muscle Strength HERE.

A vitamin D nutritional cornucopia: new insights concerning the serum 25-hydroxyvitamin D status of the US population

Anthony W Norman1

It is generally agreed that the serum concentration of 25-hydroxyvitamin D [25(OH)D] in healthy persons is the best indicator of the vitamin D status of patients with vitamin D–related disease states (1). The report by Looker et al (2) in this issue of the Journal provides a cornucopia of new insights into the vitamin D nutritional status of US citizens from 1988 through 2004. In particular, this report compares serum 25(OH)D concentrations of 20 289 participants in the National Health and Nutrition Examination Survey (NHANES) 2000–2004 with those of 18 158 participants in NHANES III (1988–1994). For the first time, results were reported for children 1–11 y old, pregnant women, and the Mexican American population.

The most important finding in the report is that the mean serum 25(OH)D concentrations of persons ≥12 y old fell by {approx}5–20 nmol/L between 1988–1994 and 2000–2004. Assay changes, which were unrelated to changes in 25(OH)D status, accounted for a portion of this apparent difference between the 2 study groups; nevertheless, at the end of the complex analysis, there still was a significant (7.1 nmol/L) reduction in 25(OH)D concentrations in males (except Mexican Americans) but not in most female groups. This result is potentially disturbing if it represents the beginning of the downward trend in serum 25(OH)D concentrations that has been seen over the past 10–15 y. It will therefore be essential to repeat this study after another decade.

The vitamin D cornucopia that Looker et al provided contains a variety of other novel and important observations. These include differences in 25(OH)D status 1) by ethnicity and sex in non-Hispanic whites, non-Hispanic blacks, and Mexican Americans; 2) by age group (1–5, 6–11, 12–19, 20–49, 50–69, or ≥70 y old); 3) by season (November–March or April–October); and 4) by pregnancy status. In addition, a second vitamin D cornucopia can be found under "Supplementary data" in the current online issue. This material contains extensive data on 4 topics: 1) a comparison of 25(OH)D assay methods; 2) seasonal variations in serum 25(OH)D by race-ethnicity in persons ≥12 y old; 3) the prevalence of serum 25(OH)D concentrations < 25 nmol/L (an indication of nutritional vitamin D deficiency); and 4) the prevalence of serum 25(OH)D3 concentrations below selected thresholds by age, sex, and race-ethnicity.

Some readers may be troubled by 2 technical aspects of the study by Looker et al. A potentially confounding problem is that there was an evolution in 25(OH)D assay methodology between the first study in 1988–1994 and the second study in 2000–2004. Possible assay differences were assessed by repeating measurements of the 25(OH)D concentrations in 150 stored serum samples from NHANES III with the samples from the 2000–2004 samples. Looker et al used sophisticated statistical techniques to tease out the shift in the mean serum 25(OH)D concentrations between the 2 decades that was due to changes in assay methods. This problem was recently discussed in detail (3). However, there still is a need for significant improvements in 25(OH)D assays so that consistent and precise assay results may be obtained over multiyear periods.

The second potential concern relates to the protocol used in NHANES; that is, the serum samples were collected in the US southern latitudes (<35 °N) only in November–March and in the US northern latitudes (>35 °N) only in April–October. Thus, the magnitude of the seasonal fall in 25(OH)D concentrations in the winter in the northern latitudes is underestimated, as is the increase in concentrations in the summer in the southern latitudes. Ideally, in a study focusing on serum 25(OH)D concentrations, there should be no bias of the time of the year for the latitude at which the serum samples were collected. These same concerns also apply to the involvement of the vitamin D endocrine system with the disease process of cancer. Epidemiologic studies have suggested a direct link between greater sunlight (ultraviolet B light) production of vitamin D3 in populations living at lower latitudes and lower incidences of breast, colon, prostate, and ovarian cancers and non-Hodgkin lymphoma (4). Other studies have shown that persons with low serum concentrations of 25(OH)D (ie, <8 nmol/L) had a higher incidence of cancer (5), which reinforces the need to improve vitamin D nutritional status.

The study by Looker et al is particularly important, given the current concerns about the appropriate recommendations for the daily intake of vitamin D3 (6, 7). The current adequate intake allowance of vitamin D, recommended in 1997, is considered by many scientists to be too low and to be focused only on vitamin D's actions on calcium and bone issues (1). However, over the past decade, new evidence has shown that there are 5 additional physiologic systems in which the vitamin D receptor and its cognate steroid hormone, 1{alpha},25-dihydroxyvitamin D3 [1{alpha},25(OH)2D3], generate biological responses (8). These are the immune, pancreas, heart-cardiovascular, muscle, and brain systems; the control of the cell cycle and thus of the disease process of cancer is also involved. Acting through the vitamin D receptor, the steroid hormone 1{alpha},25(OH)2D can produce a wide array of favorable biological effects that collectively are projected to contribute to the improvement of human health. The sphere of influence of the vitamin D endocrine system, updated to include physiologic systems beyond calcium and bone, is shown in Figure 1Go.

FIGURE 1. Summary of the vitamin D endocrine system. Target organs for the steroid hormone 1{alpha},25-dihydroxyvitamin D3 [1{alpha},25(OH)2D3] are defined by the presence of the vitamin D receptor (VDR); ≥37 tissues are known to possess the VDR (8). The paracrine production of 1{alpha}, 25(OH)2D3 is known to occur in at least 10 tissues (8). New evidence shows that 5 additional physiologic systems (immune, pancreas, heart-cardiovascular, muscle, and brain systems) and the traditional intestinal-bone calcium system are responsible for producing biological vitamin D–related responses that are important to good health.

The size of the NHANES study group is large, and one of its greatest values is that it provides the opportunity for study of the nutritional status of major ethnic groups in the US population. The 25(OH)D data from a properly diverse study group will allow appropriate health-care decisions to be made for each ethnic subgroup. It is essential that the next chapter of the NHANES process will include appropriate measurements and evaluations to provide insight into the 25(OH)D nutritional status of all 6 of the physiologic systems that make up the vitamin D endocrine system.

Conclusion: The report of Looker et al should be required reading for all nutritionists, clinicians, and vitamin D aficionados who are decision makers with regard to 25-hydroxyvitamin D assays, vitamin D nutritional policy, and the care of patients with vitamin D–related diseases.