An Appraisal to Address Health Consequences of Vitamin D Deficiency With Food Fortification and Supplements: Time to Act!

A symposium entitled "Vitamin D in Prevention and Therapy" was held on May 4-5, 2022, in Homburg, Germany to discuss important new advances in the field, including identification of new vitamin D signaling pathways, of new biologic effects of vitamin D-compounds (e.g., on the microbiome), and convincing proof of the relevance of vitamin D deficiency for the risk and outcome of many chronic diseases, including cancer, cardio-vascular, auto-immune, metabolic, and infectious diseases. Concerning the COVID-19-pandemic, an inverse association between 25(OH)D serum concentrations and SARS-CoV-2-infections, morbidity, and mortality was shown. In relation to cancer, several meta-analyses recently demonstrated an association of vitamin D-supplementation with significantly decreased mortality rates, which presumably would reduce health care costs. Considering the impressive body of evidence and the high safety of oral supplementation and food fortification with vitamin D, it was concluded that there is now an urgent need to act. In many countries worldwide, health care authorities need to increase efforts to address vitamin D deficiency, e.g., via food fortification and/or supplementation with vitamin D, and/or promoting moderate UV-exposure. It was estimated that in many countries, vitamin D intakes of the order of appr. 1,000 IE (25 µg)/day would be needed to bring and/or keep the vast majority of people over a serum 25(OH)D threshold of 20 ng/ml (50 nmol/l), which would be difficult to obtain alone from food fortification. New developments in personalized medicine may represent helpful tools to identify populations at risk for vitamin D deficiency and their responsiveness to vitamin D treatment.

[Phototherapy for psoriasis; clearing lesions and maintaining lesion-free status]. / Lichttherapie bij psoriasis.

Since time immemorial, sunlight has been used to treat a wide variety of skin afflictions. Consequently, probably on the basis of patients' experience and consequent experimentation with lamps, phototherapy has become an important dermatological treatment, particularly for psoriasis. The active component in sunlight proved to be ultraviolet (UV) radiation. Optimized UV lamps (type TL01) are now routinely used for clearing psoriatic lesions, after which therapy is stopped due to potential carcinogenic effects. The lesions reappear after a few months. Daily home treatment with low-dose UV radiation is a possible one to keep patients lesion-free; this leads to a marked reduction in the need for topical medications. This maintenance therapy can provide adequate suppression of this chronic skin disease.

Insufficient Sun Exposure Has Become a Real Public Health Problem.

This article aims to alert the medical community and public health authorities to accumulating evidence on health benefits from sun exposure, which suggests that insufficient sun exposure is a significant public health problem. Studies in the past decade indicate that insufficient sun exposure may be responsible for 340,000 deaths in the United States and 480,000 deaths in Europe per year, and an increased incidence of breast cancer, colorectal cancer, hypertension, cardiovascular disease, metabolic syndrome, multiple sclerosis, Alzheimer's disease, autism, asthma, type 1 diabetes and myopia. Vitamin D has long been considered the principal mediator of beneficial effects of sun exposure. However, oral vitamin D supplementation has not been convincingly shown to prevent the above conditions; thus, serum 25(OH)D as an indicator of vitamin D status may be a proxy for and not a mediator of beneficial effects of sun exposure. New candidate mechanisms include the release of nitric oxide from the skin and direct effects of ultraviolet radiation (UVR) on peripheral blood cells. Collectively, this evidence indicates it would be wise for people living outside the tropics to ensure they expose their skin sufficiently to the sun. To minimize the harms of excessive sun exposure, great care must be taken to avoid sunburn, and sun exposure during high ambient UVR seasons should be obtained incrementally at not more than 5-30 min a day (depending on skin type and UV index), in season-appropriate clothing and with eyes closed or protected by sunglasses that filter UVR.

Low wintertime pre-diagnostic vitamin D status is associated with an increased risk of internal malignancies in kidney transplant recipients.

Low serum 25-hydroxyvitamin D (25OHD) concentrations have been associated with increased cancer risk, but the relative importance of seasonality, i.e. high summer concentrations versus low winter concentrations, is unclear. We investigated this issue in a high risk group: kidney transplant recipients with known increased risk of cancer and low vitamin D statuses. We examined the relationship between registered concentrations of 25OHD binned by quarter and subsequent risk of internal malignancy or cutaneous squamous cell carcinoma in 1112 kidney transplant recipients. Hazard ratios for internal malignancies were significantly increased with lower pre-diagnostic 25OHD concentrations in the first quarter of the year (January-March); a 1.4 fold increase (95%CI 1.1;1.7) per 10 nmol L-1 decrease in 25OHD. Except for women in April-June (1.3 (1.01;1.7) per 10 nmol L-1 decrease) pre-diagnostic 25OHD concentrations in the other quarters were not statistically significantly associated with internal malignancies. Higher 25OHD concentrations tended to be associated with the development of cutaneous squamous cell carcinomas, independent of the time of the year. Our study indicates that low wintertime 25OHD concentrations are associated with an increased risk of internal malignancies and that transplant recipients may benefit from wintertime vitamin D supplementation. Our findings need further corroboration, but suggest that the lowest concentrations of vitamin D, which occur in winter, are important for the risk of internal malignancies.

The risks and benefits of sun exposure 2016.

Public health authorities in the United States are recommending that men, women and children reduce their exposure to sunlight, based on concerns that this exposure will promote skin cancer. On the other hand, data show that increasing numbers of Americans suffer from vitamin D deficiencies and serious health problems caused by insufficient sun exposure. The body of science concerning the benefits of moderate sun exposure is growing rapidly, and is causing a different perception of sun/UV as it relates to human health. Melanoma and its relationship to sun exposure and sunburn is not adequately addressed in most of the scientific literature. Reports of favorable health outcomes related to adequate serum 25(OH)D concentration or vitamin D supplementation have been inappropriately merged, so that benefits of sun exposure other than production of vitamin D are not adequately described. This review of recent studies and their analyses consider the risks and benefits of sun exposure which indicate that insufficient sun exposure is an emerging public health problem. This review considers the studies that have shown a wide range health benefits from sun/UV exposure. These benefits include among others various types of cancer, cardiovascular disease, Alzheimer disease/dementia, myopia and macular degeneration, diabetes and multiple sclerosis. The message of sun avoidance must be changed to acceptance of non-burning sun exposure sufficient to achieve serum 25(OH)D concentration of 30 ng/mL or higher in the sunny season and the general benefits of UV exposure beyond those of vitamin D.

UV exposure inhibits intestinal tumor growth and progression to malignancy in intestine-specific Apc mutant mice kept on low vitamin D diet.

Mortality from colorectal cancer increases with latitude and decreases with ambient UV radiation. We investigated whether moderate UV dosages could inhibit intestinal tumor development and whether this corresponded with UV-induced vitamin D. FabplCre;Apc(15lox/+) mice, which develop intestinal tumors, and their parents were put on a vitamin D-deficient diet. Next to a control group, one group was vitamin D supplemented and another one group was daily UV irradiated from 6 weeks of age. Vitamin D statuses after 6 weeks of treatment were markedly increased: mean ± SD from 7.7 ± 1.9 in controls to 75 ± 15 nmol/l with vitamin D supplementation (no gender difference), and to 31 ± 13 nmol/l in males and 85 ± 17 nmol/l in females upon UV irradiation. The tumor load (area covered by tumors) at 7.5 months of age was significantly reduced in both the vitamin D-supplemented group (130 ± 25 mm(2), p = 0.018) and the UV-exposed group (88 ± 9 mm(2), p < 0.0005; no gender differences) compared to the control group (202 ± 23 mm(2)). No reductions in tumor numbers were found. Only UV exposure appeared to reduce progression to malignancy (p = 0.014). Our experiments clearly demonstrate for the first time an inhibitory effect of moderate UV exposure on outgrowth and malignant progression of primary intestinal tumors, which at least in part can be attributed to vitamin D.

The effects of a mid-winter 8-week course of sub-sunburn sunbed exposures on tanning, vitamin D status and colds.

Like UV irradiation, which generates vitamin D(3) in the skin, the hormonally active metabolite, 1,25-dihydroxyvitamin D(3), boosts innate immunity against viruses and bacteria. Epidemiologic studies have found high vitamin D levels to be associated with lower risk of infections of the upper respiratory tract (colds). We have therefore performed an intervention study in 105 young adults (ages 18-30 years; 91% female) over a mid-winter 8-week period (January-March 2010). The participants were randomised to 3 groups: (A) subjected to 3 times a week sub-sunburn sunbed exposure (n = 35), (B) daily vitamin D supplementation, @ 1000 IU (n = 37), and (C) a control group without any intervention (n = 33). The mean serum level of 25-hydroxyvitamin D (25(OH)D) dropped from 62 to 55 nmol l(-1) in group C, while these levels rose from 62 to 109 and from 58 to 93 nmol l(-1) in groups A and B, respectively (p < 0.001). The skin on the chest darkened significantly in group A (mean difference in lightness, L*, equalled -5.7, p < 0.001), correlating significantly, but weakly, with increases in 25(OH)D (3.3 nmol l(-1) per unit drop in L*, R(2) = 0.17, p = 0.014). The percentage of self-reported colds with proper signs and symptoms was only slightly and not significantly reduced in groups A and B in comparison to group C: 57 and 51 versus 67%, respectively. Hence, the sub-sunburn sunbed treatment was effective in tanning and increasing the 25(OH)D serum level, more so than 1000 IU per day, but had no appreciable effect on colds.