The question, what is a “normal” nutritional vitamin D status, is currently a hotly debated topic. Historically, a “normal” nutritional vitamin D status has been defined as just about any circulating level of 25(OH)D in asymptomatic subjects (1
). Recently, attempts have been made to reevaluate this “normal” circulating level of 25(OH)D using biomarkers such as parathyroid hormone (6
), intestinal calcium absorption (5
), skeletal density (2
), glucose clearance (12
), and innate immune function (13
). Generally, these studies suggest that a minimum circulating level of 25(OH)D should be >80 nmol (32 ng/mL) (18
In the present study, we sought to investigate what circulating 25(OH)D levels would result in populations exhibiting no substrate limitations to the vitamin D-25-hydroxylase. To perform this, we chose two distinct populations. The first were individuals from a year-found sunny environment who spent a good deal of time outdoors. The second were a group of lactating women receiving a substantial daily oral dose of vitamin D3. Surprisingly, a study such as this previously had not been undertaken. There are several reasons for this. First, finding a group of sun-exposed individuals is not an easy task; in fact, we had to go to Hawaii to find them. Secondly, very few studies have been performed where subjects actually received adequate vitamin D3 supplementation to make them replete. Finally, it is very difficult and costly to measure circulating vitamin D3 and relate it to circulating 25(OH)D. The results of our study are far-reaching.
At a maternal intake of 6,400 IU vitamin D3/day, circulating vitamin D3 increased dramatically. Maternal circulating 25(OH)D also increase; however, the increase appeared to be limited and controlled (). A similar relationship was observed in the sun-exposed individuals (). In these individuals, sun exposure was greater than fifteen hours/week—although not all had total body exposure, some only hands, arms, and head. The data from our study suggests the following: The relationship between circulating vitamin D3 and 25(OH)D is not linear in either case; rather it appears saturable and controlled. This suggest either/or product-substrate inhibition of the vitamin D-25-hydroxylase. Optimal nutritional vitamin D status may occur when approaching equimolar concentrations of circulating vitamin D3 and 25(OH)D (>100 nmol). At this point, the Vmax of the enzyme appears to be achieved. It is important to note that as humans live today, the vitamin D-25-hydroxylase operates well below its Vmax because of chronic substrate (vitamin D) deficiency. Not a single other steroidal hormone system in the body is limited in this fashion since their starting point is cholesterol. When humans are sun- (or dietary-) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate availability.
This study also demonstrates that individuals can be vitamin D deficient with significant sun exposure if the skin area exposed is limited as was suggested several years ago (19
). Finally, whether one receives their vitamin D3
orally or through UV
exposure, the vitamin D-25-hydroxylase appears to handle it in an equivalent fashion with respect to maintaining circulating 25(OH)D levels. Thus, we believe that the relationship between circulating vitamin D and 25(OH)D may define adequate nutritional vitamin D status.