Abstract (Summary) There is a need to increase the options for vitamin D fortification. We have developed a method to fortify hard cheese with vitamin D. Our aim was to characterize the bioavailability of vitamin D from fortified cheeses. Eighty adults were randomized to weekly servings of fortified Cheddar cheese (DC) (34 g; n = 20); fortified low-fat cheese (DLF) (41 g; n = 10); liquid vitamin D supplement (1 mL), taken with food (DS +) (n = 20) or without food (DS-) (n = 10); placebo cheddar cheese (n = 10); or placebo supplement (n = 10). The treatments contained 28,000 IU cholecalciferol (vitamin D3), equivalent to 4000 IU (100 µg/d). The primary outcome was the comparison of vitamin D bioavailability, as measured by the serum 25-hydroxyvitarnm D [25(OH)D] response, between fortified cheeses and supplement. In the placebo groups, initial 25(OH)D, 55.0 ± 25.3 nmol/L, declined over the 8-wk winter protocol, to 50.7 ± 24.2 nmol/L (P = 0.046). In the vitamin D-treated groups, the mean increases in 25(OH)D over 8 wk were: 65.3 ± 24.1 (DC), 69.4 ± 21.7 (DLF), 59.3 ± 23.3 (DS +), and 59.3 ± 19.6 nmol/L (DS-); these changes differed from the placebo groups (P < 0.0001) but not from one another (P = 0.62). Compared with baseline, serum parathyroid hormone decreased with both fortification (P = 0.003) and supplementation (P = 0.012). These data demonstrate that vitamin D is equally bioavailable from fortified hard cheeses and supplements, making cheese suitable for vitamin D fortification Discussion Our results show that vitamin D is bioavailable from fortified cheddar and low-fat cheese. The change in 25(OH)D from baseline to 8 wk was significantly greater in the subjects consuming fortified cheddar or low-fat cheese compared with those consuming the placebo. Furthermore, the fortified cheeses produced a change in 25(OH)D that did not differ from vitamin D supplement, demonstrating that vitamin D is equally bioavailable from fortified cheese and supplement. These findings are similar to those of Natri et al. (52), who showed that bread fortified with cholecalciferol increases serum 25(OH)D as effectively as a supplement. We also found that differences in the fat content of the fortified cheeses did not affect vitamin D bioavailability. The increases in serum 25(OH)D did not differ between subjects consuming fortified regular-fat cheddar cheese, comprised of -33% fat, or fortified low-fat cheese, comprised of -7% fat. These observations are consistent with those of Tangpricha et al. (53) in which peak serum vitamin D concentrations did not differ significantly after the ingestion of vitamin D in whole milk, skim milk, or corn oil on toast. We also did not observe any significant changes in serum 25(OH)D between subjects consuming vitamin D supplemented with food and those consuming it without food. We conclude that taking a vitamin D supplement together with food also does not alter its bioavailability All of the differences in the mean change in 25(OH)D among vitamin D-treated groups were less than one-half of what the present study had been powered to detect. For example, the largest difference in 25(OH)D response between treatment groups was 10 nmol/L (DLF compared with DS-). If this difference were true, an appropriately powered experiment to confirm this 10-nmol/L difference would require 2 groups of 71 study subjects (50). An efficacy difference requiring this large a sample size would not be clinically relevant. Taken together, our results demonstrate that vitamin D bioavailability is equivalent from the various methods for providing vitamin D that we tested. Serum and urine calcium concentrations are the classic safety indices for vitamin D excess and those remained unchanged by the intervention. None of the subjects reported any untoward side effects. Ingestion of vitamin D from fortified cheese and vitamin D supplements lowered PTH concentrations over the period of 8 wk. Other markers of bone and mineral metabolism, including serum and urine phosphate, serum ALP, and serum CTX were not affected by the consumption of fortified cheese or vitamin D supplement. These bone variables should be expected to improve with vitamin D supplementation, but this would be more likely to occur in an older population than the one we studied. The results confirm previous reports of the safety and efficacy of vitamin D supplementation at doses ≥4000 ID/d (14,54,55). We designed our study so that the vitamin D would be consumed once per week instead of daily, because the expected improvement in adherence to the protocol (56) would minimize variability. We achieved a 98% adherence to dose intake. Our weekly dosing protocol delivered 28,000 IU of cholecalciferol per weekly serving, which is equivalent to a daily vitamin D intake of 4000 IU. Weekly dosing with vitamin D is consistent with basic pharmacology. Suitable dosing intervals usually approximate the half-life of the administered agent (57). Depending on how it is characterized (tracer kinetics or decline upon discontinuation of input), serum 25(OH)D has a half-life of between 2 wk and 2 mo (48). Thus, weekly supplementation with cholecalciferol is effective and appropriate (48). The amount of vitamin D fortification we used for this study protocol was substantially higher than what would be added to foods. A more conventional dose would have been 100-400 IU vitamin D/30-50 g serving of cheese, the usual fortification level permitted by North American food regulations. However, Johnson et al. (58) demonstrated that in elderly subjects, daily consumption of fortified processed cheese containing 600 IU of vitamin D for 2 mo did not produce a detectable increase in serum 25(OH)D. Their results were surprising, because they provided the adequate intake of vitamin D for the elderly (> 70 y) (49), which should have produced a measurable change, at least in theory. Nevertheless, their findings are consistent with previous reports that suggest that 600 IU vitamin D/d is insufficient to increase serum 25(OH)D in the elderly (1,54,55). In contrast to Johnson et al. (58), we studied a younger population, fortified different types of cheeses, and administered a higher dose of cholecalciferol (equivalent to 4000 lU/d). The higher vitamin D intake was chosen to produce a rise in serum 25(OH)D that would increase the statistical power to detect possible differences in bioavailability among our treatment groups. Ingestion of 4000 lU/d cholecalciferol from fortified cheese or supplement safely increased the vitamin D status of our subjects, ensuring a serum 25(OH)D concentration of ≥75 nmol/L in over 90% of the vitamin D-treated subjects, and significantly decreased mean PTH levels. We would not expect a lower dose to produce as effective a rise in 25(OH)D as that here. Even so, a daily dose of 400 IU vitamin D can improve vitamin D status, as was shown with vitamin D-fortified bread (52). In conclusion, we found that fortified cheese enhances vitamin D status as effectively as a supplement. The extension of vitamin D fortification to cheese and other such foods that are widely distributed, frequently consumed, and exhibit good bioavailability Js an inexpensive and effective approach for increasing the availability of vitamin D in the diet. This will improve vitamin D intakes in the population and could help to bring about the public health benefits that many experts are now proposing may result from a greater consumption of vitamin D. |
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