Vitamin D is an important nutrient for maintaining a healthy skeleton as it forms an integral part of the bone metabolism, calcium and phosphor homeostasis [1]. There are indications that vitamin D may have several other health benefits such as prevention or mitigation of cancer [2] and autoimmune diseases [3], reduction in hypertension [4], and prevention of influenza [5]. Anti-carcinogenic effects have been demonstrated in laboratory studies on animals at high doses, but evidence of causality has not been shown in humans, possibly due to too low vitamin D levels in the human population to produce a statistically significant effect [2]. Overall, vitamin D seems to have a positive regulatory effect on the immune system. Recent research indicates that vitamin D stimulates antimicrobial activity [6] and thus may mitigate certain types of infections. There are vitamin D receptors in many organs [7], and long-term vitamin D deficiency may induce a wide range of harmful biological effects. Despite this, only skeletal effects have to date been proven causal in a strict sense [8,9,10]. The existence of an optimal ultraviolet (UV) exposure and its level is a subject of ongoing debate [2,11,12,13,14,15]. Likewise, public recommendations on vitamin D dietary intake and food fortifications are under revision in many countries.

Worldwide studies have shown that vitamin D status is low across wide ranges of populations and age groups even at very moderate latitudes [16,17,18,19,20,21,22,23,24]. Extremely low vitamin D levels have been observed in individuals with darker skin [25,26,27]. It seems clear that casual vitamin D intake from UV exposure and diet are not adequate. Improved public consciousness in combination with revised policies regarding vitamin D can very likely improve public health at quite moderate costs.

The formation, intake and circulation of vitamin D are well described in the literature, and are outlined in Figure 1. Provitamin D (7-dehydrocholesterol, 7-DHC) is converted to previtamin D in the skin by exposure to UVB radiation. The previtamin D is then isomerized by body heat to form vitamin D₃. Vitamin D₃ is then transported by the blood to the liver, where it is converted to 25-hydroxyvitamin D (25(OH)D). In the kidneys, the formation of the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)₂D), is tightly regulated by the parathyroid hormone (PTH). 1,25-dihydroxyvitamin D is important for the uptake of calcium and mobilization of calcium stores. As mentioned above, many organs have receptors for vitamin D, and consequently vitamin D is important for many bodily functions. More recently, it was found that 1,25-dihydroxyvitamin D can be produced in tissue and cells, decoupling partly the production of 1,25-dihydroxyvitamin D and its effects from the renal functions and PTH, reviewed in [28]. Although the underlying processes of vitamin D synthesis and circulation is known, the quantitative relationship of UV exposure to humans and the resulting vitamin D production is inadequately described. This review summarizes the status of knowledge with respect to vitamin D synthesis in the human skin, and attempts to clarify the gaps of knowledge as an aid to future research in the area.

The fundamental processes of vitamin D synthesis and circulation in humans is well understood at a qualitative level (Figure 1). In vitro models [29,30,31] and experiments [32,33,34] describing photoconversion of provitamin D to previtamin D exist. Although they are not necessarily representative for the cutaneous and systemic conditions on a large human population level, they are useful qualitative indicators for how much vitamin D is produced under various solar conditions.

The factors affecting vitamin D synthesis from ultraviolet B (UVB) radiation have been discussed previously [35,36]. The effect of some influencing factors can be further explored by running the online facilities described in section 5 for user-specified conditions. The factors are therefore only discussed briefly below:

Holick and co-workers found that one full body UV exposure causing a slight pinkness in skin (one minimum erythemal dose, 1 MED) is equivalent to an oral intake of somewhere in the range 250–625 μg (10,000–25,000 IU) of vitamin D₃ [61,62,63]. This relationship has been confirmed by at least three other studies (see below), including outdoor solar exposure and on only parts of the body. A weakness of the laboratory experiments lies in the fact that the experiments made use of fixed broadband UV lamps. The lamp spectral characteristics are unclear, and assimilation to natural conditions is difficult due to uncertainties in vitamin D action spectrum. Furthermore, relevant laboratory experiments are generally done for very small cohorts in the literature, and this was also the case for these studies. On the basis of the results of Holick and co-workers above [64,65], a UV exposure of one-quarter of personal MED on one-quarter of skin area (hands, face and arms) yields a dietary equivalent vitamin D dose of about 1000 IU. The exposure times to obtain this recommended UV dose depend greatly on skin type, time and location [65] as well as ambient conditions and clothing [53]. The latter paper has resulted in a freely accessible internet page, which gives an estimate of how long exposure is required to obtain any vitamin D-effective dose from the sun under user-specified conditions (http://nadir.nilu.no/~olaeng/fastrt/VitD_quartMED.html). Limitations of the method have been previously discussed [53]. Beneficial exposure times for Australian cities have also been computed from measurements of UV erythemal doses [66]. They assume that one-third to one-sixth MEDs at 15% of the body yield the equivalent of the current officially recommended vitamin D dose of 200-600 IUs. Note that the relationship between erythemally weighted doses (or MEDs) and vitamin D effective doses with respect to solar zenith angle is not linear [67,68]. Therefore, the amount of MEDs can be misleading in terms of cutaneous vitamin D synthesis.

As mentioned above, at least three additional studies support the concept that one full-body exposure to sunlight can be equivalent to an oral vitamin D intake of 250 μg (10,000 IU) [69]. “Stamp [70] compared oral vitamin D to the effects of UV light treatment sessions (~1 MED) and found that the rise in 25(OH)D was the same in subjects treated with UV light as in those given 250 μg (10,000 IU) vitamin D/d. In a study of institutionalized elderly, Davie et al. [71] exposed 600 cm², ~5% of skin surface, to UV light treatments over a 2–3-month period and compared the resulting 25(OH)D concentrations with those achieved with oral vitamin D doses. They calculated a production of vitamin D in the skin equivalent to 0.045 nmol・d^-1・cm^-2 exposed skin. This is equivalent to 10.9 μg (435 IU) vitamin D/d for 600 cm² (5%) of skin surface. If these results for the elderly are extrapolated to total body surface area, it works out to 218 μg (8,700 IU) vitamin D/d that can be acquired by the elderly.” Chel et al. [72] obtained very similar results for a half MED exposure of 1000cm² (one-sixth of the body area) yielding the equivalent of 400 IU corresponding to 9,600 IU for a full body MED exposure. Note that it is well established that the elderly are less capable of synthesizing vitamin D in their skin (see above). Also, their starting 25-hydroxyvitamin D levels were generally quite low (25(OH)D < 25 nmol/L in Holick [61], patients requiring vitamin D treatments in Stamp [70], 25(OH)D~5.5–16.6 nmol/L in Davie et al. [71]. 25(OH)D < 30 nmol/L for Chel et al. [72]). Low vitamin D status yields higher sensitivity to vitamin D intake than normal [see below]. Furthermore, no vitamin D effective doses are given, only the number of MEDs is given as an approximate measure of UV radiation dose.

There are several studies on the separate effects of dietary intake and UVR exposure on serum 25-hydroxyvitamin D levels. However, there are markedly less studies on the effects on UVR exposure, probably due to a more complex experimental setup as well as ethical problems by exposing subjects with knowingly harmful UV radiation. An extensive list is given in tables 2 and 4 of Vieth [69] and Vieth [73]. Other studies include [33,74,75,76,77]. Davie [71] devised empirical formulas describing the effect of both dietary intake and UV radiation on the serum 25-hydroxyvitamin D levels based on results from 25 subjects. Devising exact, general formulas are not straightforward because the effect of vitamin D intake on vitamin D production depends on the initial 25(OH)D level. It seems that the effect of vitamin D intake and synthesis is enhanced when the initial vitamin D status is low [69,78,79]. A problem in making comparisons between in vivo studies on the effect of UVR exposure is that evaluation of the exact UV doses is complicated by variations in the surface area of skin exposed, skin type, starting levels of serum 25-hydroxyvitamin D, and frequency and duration of exposure. Furthermore, the spectra of the radiation sources are usually variable and inadequately specified, and computing comparable vitamin-D effective doses from the given information is not straightforward. Exact assimilation of the various studies is thus difficult.

Several journal papers have described the statistical relationships between vitamin D status and an incomplete set of indirect parameters (latitude, hours of exposure, etc.). Unfortunately, many of those extensive cohort studies do not contain adequate information to reconstruct the relevant UVR doses at a desirable accuracy.

It has been often claimed that adequate vitamin D is obtained after a few minutes of sun exposure. This is commonly true only when the sun is high and if the equivalent of 400 IU (corresponding to one spoonful of cod liver oil) is desired (Table 1, Figure 3). However, many research scientists advocate higher intake levels of vitamin D (1,000–4,000 IU). These amounts are usually not available from casual daily exposure (e.g., waiting for the bus to work). The gap between beneficial UV exposure to obtain desirable vitamin D and harmful exposure leading to erythema also narrows (i.e., desirable vitamin D effective dose approaches 1 MED [15]). For example, for normal summer clothing, the exposed skin (25.5%) needs to be sunburnt in order to produce 4,000 IU. The skin would then receive a UV dose associated with clearly elevated skin cancer risk.

A dramatic effect of seasonal and latitudinal changes of solar UV radiation on vitamin D synthesis was revealed by Webb et al. [80]. This work showed that from November to February, there was insufficient solar UVB to synthesize vitamin D in Boston, MA (USA), but by March, previtamin D was formed from 7-DHC in both solution and the skin. This observation, also known as the “vitamin D winter”, has been reported in other journal studies [81,82]. More moderate estimates of the extent of this “vitamin D winter” have been obtained; however, are based on simulations of UV radiation for clear atmospheric conditions (Figure 4) [83]. The vitamin D effective UV doses depend significantly on latitude and season [84,85]. Vitamin D production is generally seasonally dependent, being low during late winter with exception to some high-latitude coastal communities where diet seems to be the dominant source of vitamin D [86]. There seems to be slightly lower vitamin D levels in women probably due to more body fat [87]. Latitude, location, and time of year may also have health implications in regards to vitamin D, where several studies have associated development of various diseases, influenced by vitamin D deficiency, with geography and season, e.g. [88,89].

User-operated model simulations for vitamin D synthesis and effective doses are available online:

The user can insert their own atmospheric and surface conditions and calculate UV doses and exposure times for arbitrary times and locations. Note that the results from three online model simulations are not entirely consistent. This is due to the laboratory experiments forming the basis for the calculations of the online facilities. Tool 1 is based on comparison to in vitro experiments for low intensities of UV radiation. Tool 2 on the other hand is based on extrapolations from intense erythemal doses of young adults.

The combined effects of UV radiation and diet on vitamin D status should be explored more rigorously, both in laboratory environments and at the population level.