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Disappearing Vitamin D?
Abstract & commentary
By Ralph R. Hall, MD, FACP, FACSM, Professor of Medicine Emeritus, University of Missouri, Kansas City School of Medicine. Dr. Hall reports no financial relationship relevant to this field of study.
Synopsis: Plasma concentrations of 25-hydroxyvita-min D [25(OH)D] decrease after an inflammatory insult such as knee surgery and, therefore, are unlikely to be a reliable measure of 25(OH)D status in patients with evidence of a significant inflammatory response.
Source: Reid D, et al. The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty. Am J Clin Nutr 2011;93:1006-1111.
Studies indicate that low plasma 25-hydroxyvitamin d [25(OH)D] is associated with a range of disease processes, many of which are inflammatory. However, many other lipid-soluble vitamins decrease during the systemic inflammatory response, and this may confound the interpretation of plasma 25(OH)D.
The objective was to examine whether plasma 25(OH)D concentrations change during evolution of the systemic inflammatory response. Patients (n = 33) who underwent primary knee arthroplasty had venous blood samples collected preoperatively and postoperatively beginning 6-12 hours after surgery and each morning for 5 days for the measurement of 25(OH)D, vitamin D-binding protein, C-reactive protein, and albumin. A final sample was collected at 3 months.
Preoperatively, most patients were 25(OH)D deficient (< 50 nmol/L) and had secondary hyperparathyroidism. Age, sex, body mass index, season, medical history, and medication use were not associated with significant differences in preoperative plasma 25(OH)D concentration. By day 2 there was a large increase in C-reactive protein concentration (P < 0.001) and a significant decrease in 25(OH)D of 40% (P < 0.001). C-reactive protein, 25(OH)D, and calculated free 25(OH)D had not returned to preoperative concentrations by day 5 postoperatively. At 3 months, 25(OH)D and free 25(OH)D remained lower (20% and 30%, respectively; P < 0.01).
The authors concluded that plasma concentrations of 25(OH)D decrease after an inflammatory insult and, therefore, are unlikely to be a reliable measure of vitamin D status in subjects with evidence of a significant systemic inflammatory response.
The decrease in 25(OH)D during the immediate post- operative period is perplexing. The authors examined various possibilities (i.e., fluid balance, seasonality, associations with vitamin D binding protein), but found no explanation for the significant drop in plasma vitamin D concentrations. It is noteworthy that they have previously demonstrated decreases in other fat-soluble vitamins.1
Another possibility that was explored was that the turnover and cellular uptake might have increased. However, that would appear unlikely given that the half life of vitamin D stores is around 3 weeks. There is evidence that vitamin D can be actively taken up by macrophages.2
The patients were all vitamin D deficient preoperatively. There is no evidence that they received treatment during the ensuing 3 months; therefore one would expect the plasma levels to still be low. One would presume that because the 3-month level is lower than the preoperative level that this is not due to worsening vitamin D deficiency. It would be helpful to know the diet, sun exposure, and vitamin D intake of each patient to fully understand the 3-month 25(OH)D levels.
An abstract describing the effect of the normalization of low vitamin D status and the restoration of statin tolerance in vitamin D deficient patients adds to the intrigue.
Gal et al studied 68 hypercholesterolemic patients who were unable to tolerate statins because of myositis-myalgia. The patients had low vitamin D levels of less than 32 ng/mL. While the patients were not receiving statins, 50,000 units of vitamin D were given twice weekly for 3 weeks and then continued once weekly. After 3 weeks, patients were started on statins and were reassessed after 3 months on vitamin D and statins.
After 3 months, 62 of the 68 patients now tolerated statins well and were asymptomatic without myositis-myalgia. In the 62 patients, the mean vitamin D rose from 22 to 43 ng/mL (P = 0.0001), and LDL cholesterol fell from a mean of 162 to 99 mg/dL.3
Because we have only the information in the abstract, we do not know whether the vitamin D levels were assessed during the period the patients were having myositis-myalgia or after they had become asymptomatic.
The careful study by Reid et al and the clinical trial by Gal et al provide important clues to the role of vitamin D in systemic inflammatory processes. There is obviously more to know.
1. Gray A, et al. The relationship between the acute changes in the systemic inflammatory response, lipid soluble antioxidant vitamins and lipid peroxidation following elective knee arthroplasty. Clin Nutr 2005;24:746-750.
2. Lee P, et al. Vitamin D deficiency in critically ill patients. N Engl J Med 2009;360:1912-1914.
3. Gal A, et al. Normalization of serum vitamin D in hypercholesterolemic, vitamin D deficient patients, previously statin intolerant. Am Fed for Med Research 2011;59:714.