Alina Carmen Porojnicu

Addressing the health benefits and risks, involving vitamin D or skin cancer, of increased sun exposure

Solar radiation is the main cause of skin cancers. However, it also is a main source of vitamin D for humans. Because the optimal status of vitamin D protects against internal cancers and a number of other diseases, a controversy exists: Will increased sun exposure lead to net health benefits or risks? We calculated the relative yield of vitamin D photosynthesis as a function of latitude with a radiative transfer model and cylinder geometry for the human skin surface. The annual yield of vitamin D is 3.4 and 4.8 times larger below the equator than in the U.K. and Scandinavia, respectively. In populations with similar skin types, there are clear latitude gradients of all major forms of skin cancer, indicating a north–south gradient in real sun exposure. Surprisingly, the incidence rates of major internal cancers also increase from north to south. However, the survival prognosis also improves significantly from north to south. Reasons for these findings are discussed in view of the role of vitamin D. In Norway, melanoma rates increased by a factor of 6 from 1960 to 1990, while the prognosis improved in the same period. After 1990, melanoma rates have remained constant or even decreased in age groups <50 years, whereas the prognosis has not improved further. These data, together with those for internal cancers and the beneficial effects of an optimal vitamin D status, indicate that increased sun exposure may lead to improved cancer prognosis and, possibly, give more positive than adverse health effects.

Estimated benefit of increased vitamin D status in reducing the economic burden of disease in western Europe.

Vitamin D has important benefits in reducing the risk of many conditions and diseases. Those diseases for which the benefits are well supported and that have large economic effects include many types of cancer, cardiovascular diseases, diabetes mellitus, several bacterial and viral infections, and autoimmune diseases such as multiple sclerosis. Europeans generally have low serum 25-hydroxyvitamin D [25(OH)D] levels owing to the high latitudes, largely indoor living, low natural dietary sources of vitamin D such as cold-water ocean fish, and lack of effective vitamin D fortification of food in most countries. Vitamin D dose-disease response relations were estimated from observational studies and randomized controlled trials. The reduction in direct plus indirect economic burden of disease was based on increasing the mean serum 25(OH)D level to 40 ng/mL, which could be achieved by a daily intake of 2000-3000 IU of vitamin D. For 2007, the reduction is estimated at euro187,000 million/year. The estimated cost of 2000-3000 IU of vitamin D3/day along with ancillary costs such as education and testing might be about euro10,000 million/year. Sources of vitamin D could include a combination of food fortification, supplements, and natural and artificial UVB irradiation, if properly acquired. Additional randomized controlled trials are warranted to evaluate the benefits and risks of vitamin D supplementation. However, steps to increase serum 25(OH)D levels can be implemented now based on what is already known.

Ultraviolet Radiation and Malignant Melanoma

Essential features of the epidemiology and photobiology of cutaneous malignant melanoma (CMM) in Norway were studied in comparison with data from countries at lower latitudes. Arguments for and against a relationship between ultraviolet radiation (UV) from sun and sun beds are discussed. Our data indicate that UV is a carcinogen for CMM and that intermittent exposures are notably melanomagenic. This hypothesis was supported both by latitude gradients, by time trends and by changing patterns of tumor density on different body localizations. However, even though UV radiation generates CMM, it may also have a protective action and/or an action that improves prognosis. The same may be true for a number of internal cancers. There appears to be no, or even an inverse latitude gradient for CMM arising on non-UV exposed body localizations (uveal melanoma). Furthermore, CMM prognosis was gradually improved over all years of increasing incidence (up to 1990), but during the last 10 to 15 years, incidence rates decreased and prognosis was not further improved. While CMM incidence rates are twice as high in South Norway as in North Norway, the ratios of death rates to incidence rates are higher in the North, where the annual UV fluences are lower. Death- and incidence rates in Australia and New Zealand fully support this. Comparisons of skin cancer data from Norway and Australia/New Zealand indicate that squamous cell carcinoma and basal cell carcinoma are mainly related to annual solar UVB fluences, while UVA fluences play a larger role for CMM.

Season of diagnosis is a predictor of cancer survival. Sun-induced vitamin D may be involved : A possible role of sun-induced vitamin D

The calcidiol level in a group of Norwegians (14,000 individuals, age range 16-80) was found to be highest in late summer. The seasonal variation was larger for young than for old persons. The calcitriol concentration was practically constant throughout the year. Younger persons had less calcidiol and more calcitriol than older persons, indicating that the conversion of calcidiol to calcitriol is more efficient in younger persons. A seasonal variation of prognosis of cancer (colon-, breast-, prostate- cancer and Hodgkin lymphoma) was found. The survival is highest for summer and autumn diagnosis, corresponding to maximal calcidiol levels. Thus, calcidiol may act synergistically with traditional treatment modalities. In view of these calcitriol and calcidiol data, the seasonal variation of cancer survival may be related to the calcidiol gradient, indicating that this Vitamin D metabolite may be more important than believed so far.

Influence of narrowband UVB phototherapy on vitamin D and folate status

Please cite this paper as: Influence of narrowband UVB phototherapy on vitamin D and folate status. Experimental Dermatology 2010; 19: e67–e72.

Serum 25-Hydroxyvitamin D Is a Predictor of Serum 1,25-Dihydroxyvitamin D in Overweight and Obese Patients

Recent research suggests that 1,25-dihydroxyvitamin D [1,25(OH)(2)D], a steroid hormone that regulates calcium homeostasis, may also play a role in the development and progression of cancer, multiple sclerosis, cardiovascular, and other diseases. Decreased serum 1,25(OH)(2)D concentrations are often observed in overweight and obese patients. However, little is known about the factors that may influence 1,25(OH)(2)D renal synthesis, because it is generally accepted that serum 1,25(OH)(2)D concentration is strictly regulated by parathyroid hormone and serum concentrations of calcium and phosphorus. In this study, the associations among serum 1,25(OH)(2)D, serum 25-hydroxyvitamin D [25(OH)D], and body composition were analyzed in 1779 patients with excess body weight registered in a Metabolic and Medical Lifestyle Management Clinic in Oslo, Norway. According to our results, serum 25(OH)D, adiposity, age, season of blood sampling, and gender directly influence serum 1,25(OH)(2)D (r = 0.33; P < 0.001), with serum 25(OH)D being the strongest predictor for serum 1,25(OH)(2)D. The 1,25(OH)(2)D concentrations were 25.4 pmol/L (95% Cl: 19.3-31.5; P < 0.001) lower in the lowest 25(OH)D quartile to compared with highest quartile. A seasonal variation was observed for both vitamin D metabolites. Thus, our results suggest that in patients with excess body weight, serum 1,25(OH)(2)D concentrations were associated with 25(OH)D and varied during the year. Therefore, it may also be valuable to measure both serum 25(OH)D and 1,25(OH)(2)D for the evaluation of vitamin D status in overweight and obese persons.

Sun beds and cod liver oil as vitamin D sources

The objective of this study was to (1) to determine the contribution of moderate sun bed exposure to serum 25(OH)D(3) levels; (2) to estimate the decay time of a high 25(OH)D(3) level obtained by sun bed exposure; and (3) to evaluate if the recommended ingestion of vitamin D is sufficient to maintain the 25(OH)D(3) concentration obtained by sun bed exposure. Ten volunteers (20-35 y.o.), skin type I and II, living in Olso, Norway were whole body exposed twice per week to the radiation of a commercial and approved sun bed (Life Sun S 100 W, Wolff System), starting with 0.5 MED (minimal erythema dose) and escalating to up to 1 MED per exposure for 4 weeks. After that, half of the volunteers were given a daily supplement of 200 IU vitamin D in the form of cod liver oil capsules, while the other half of the persons received no supplements. Erythema did not occur at any time and a slight pigmentation was seen in most of the volunteers after the sun bed exposures. Serum level of 25(OH)D(3) increased by about 40% on the average. The initial serum 25(OH)D(3) level was different among the volunteers (40-100 nmol/L). Within eight weeks after the last exposure the 25(OH)D(3) level decreased to the initial value in all volunteers irrespective of vitamin D supplementation or not.

Sun Exposure and Cancer Survival in Norway: Changes in the Risk of Death with Season of Diagnosis and Latitude

Epidemiological and experimental studies suggest that derivatives of vitamin D may improve prognosis of a number of cancer types. Sun is our most important source of vitamin D. Seasonal variations and latitudinal gradients of calcidiol (the marker of vitamin D status) have been reported. We wanted to investigate if season and latitude play any role for survival from seven different cancer types in Norway. Seasonal and geographical variations of vitamin D were estimated by calculations and were compared with clinical data. For the survival analyses, 249373 cancer patients were followed for three years after diagnosis and the risk of death was analyzed separately for summer- and winter diagnosis, as well as for two geographical regions with different UV exposures. We found a 15-25% better survival for patients diagnosed during summer and a slight beneficial effect for residents of the high UV region for some of the cancer forms investigated. Based on our results we suggest that calcidiol concentration at the time of cancer diagnosis is related to survival and discuss briefly ways to improve the vitamin D levels in the general population.

Obesity and increased risk of cancer: Does decrease of serum 25-hydroxyvitamin D level with increasing body mass index explain some of the association?

Low levels of vitamin D and excess body weight are both factors associated with increased risk of cancer. The increased risk seems to be proportional to the increase in BMI, and to decrease in serum 25-hydroxyvitamin D (25(OH)D) level. Our earlier investigations suggest that serum 25(OH)D levels decrease with increasing BMI. Although the connection between cancer risk, BMI and vitamin D status might be arbitrary, it has not been discussed in the literature so far. In this study, we analyze data published in current meta-analysis, prospective studies, and systematic reviews on cancer-specific risk attributed to high BMI and low vitamin D status. The contribution of low 25(OH)D levels associated with high BMI to increased cancer risk was calculated for 13 vitamin-D-sensitive cancers with a focus on colorectal and breast cancer as the most frequently studied vitamin-D-sensitive cancer types. Our study suggests that a low vitamin D status may explain at least 20% of the cancer risk attributable to high BMI. The contribution of low 25(OH)D to the increased cancer risk with increasing BMI may be different for different cancer types. Thus, we find 40% for breast cancer, and 26 and 75% for colorectal cancer in men and women, respectively.

Seasonal variation of 1,25-dihydroxyvitamin D and its association with body mass index and age

Under most normal conditions the serum level of 1,25-dihydroxyvitamin D is constant throughout the year, due to tight biochemical regulation. In contrast to this, the level of 25-hydroxyvitamin D is variable through the year, being largest in late summer, due to photosynthesis in the skin. The vitamin D status is usually assessed by measuring the level of the latter vitamin D derivative, rather than that of the presumably most active derivative 1,25(OH)2 vitamin D.We here show that for persons with a high body mass index (BMI) there is a significant seasonal variation, not only of 25(OH) vitamin D, but also of 1,25(OH)2 vitamin D. The variation seems to be largest for those with the poorest vitamin D status. Furthermore, there seems to be a correlation between the levels of the two vitamin D metabolites, indicating that the regulation of 1,25(OH)2 vitamin D is not always tight, notably in persons with high BMI.