During the last decade, our scientific knowledge of the pleiotropic biological effects of vitamin D metabolites and their relevance to human health has expanded widely. Beyond the well-known key role of vitamin D in calcium homeostasis and bone health, it has been shown that vitamin D deficiency is associated with a broad variety of independent diseases, including several types of cancer, and with increased overall mortality. Moreover, recent findings have demonstrated biological effects of the vitamin D endocrine system that are not mediated via activation of the classical nuclear vitamin D receptor (VDR) by binding with high affinity to its corresponding ligand, the biologically active vitamin D metabolite 1,25-dihydroxyvitamin D (1,25(OH)₂D). In contrast, many of these new biological effects of vitamin D compounds, including regulation of the circadian clock and many metabolic functions, are mediated by other vitamin D metabolites, including 20-hydroxyvitamin D and 20,23-dihydroxyvitamin D, and involve their binding to the aryl hydrocarbon receptor (AhR) and retinoid-orphan receptor (ROR). In most populations, including the German population, UVB-induced cutaneous vitamin D production is the main source for fulfilling the human body’s requirements of vitamin D. However, this causes a dilemma because solar or artificial UVR exposure is associated with skin cancer risk. In addition to UVB-induced vitamin D production in skin, in humans, there are two other possible sources of vitamin D: from diet and supplements. However, only a few natural foods contain substantial amounts of vitamin D, and in most populations, the dietary source of vitamin D cannot fulfill the body´s requirements. Because an increasing body of evidence has convincingly demonstrated that vitamin D deficiency is very common worldwide, it is the aim of this paper to (i) give an update of the vitamin D status in a population with a western diet, namely, the German population, and to (ii) develop strategies to optimize the vitamin D supply that consider both the advantages as well as the disadvantages/risks of different approaches, including increasing vitamin D status by dietary intake, by supplements, or by UVB-induced cutaneous synthesis of vitamin D. Full article

Epidermolysis bullosa (EB) is a group of conditions characterized by severe fragility of the skin that causes recurring blistering. The recessive dystrophic subtype of EB (RDEB) has a strong impact on the nutritional status. We evaluated the resting energy expenditure (REE) and presence of protein catabolism in patients with RDEB. REE was assessed in 10 subjects (7 females; age range 4–33 years) by indirect calorimetry and using a predictive equation. Nitrogen balance was calculated by protein intake and 24 h urinary urea excretion estimations. An assessment of body surface area (BSA) with infected and non-infected skin lesions was applied to the nitrogen balance burn equation that was adapted to EB. The REE values predicted by the equation were consistently lower than the ones measured, except for two subjects. All subjects recorded high protein and energy intake, with protein intake being higher than 4 g protein/kg/day for five subjects. Even so, protein catabolism was observed in six subjects, three of whom had infected wounds. This study raises the hypothesis that the clinical and nutritional risks of people with RDEB are associated with an increased REE and negative nitrogen balance, which reinforces the importance of nutritional support. Full article

Vitamin D is well known for its effects on calcium and mineral metabolism. However, vitamin D effects on bone turnover markers (BTMs), which are used together with bone mineral density (BMD) to evaluate bone health, are less clear. We therefore examined vitamin D effects on BTMs (beta-cross laps (CTX) and osteocalcin (OC)) and BMD in a post-hoc analysis of a randomized controlled trial (RCT). This is a post-hoc analysis of the Graz Vitamin D&TT-RCT, a single-center, double-blind, randomized placebo-controlled trial conducted between December 2012 and November 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. A total of 200 healthy men with serum 25-hydroxyvitamin D (25(OH)D) levels <75 nmol/L participated in the trial. Subjects were randomized to receive 20,000 IU of vitamin D3/week (n = 100) or placebo (n = 100) for 12 weeks. Outcome measures were BTMs, BMD, and trabecular bone score (TBS). A total of 192 men (mean age and 25(OH)D: 43 (±13) years and 54.9 (±18.3) nmol/L, respectively) completed the study. We found no significant treatment effect on BTMs, BMD, or TBS (p > 0.05 for all). In middle-aged healthy men, vitamin D treatment for 12 weeks had no significant effect on BTMs or BMD. Full article

Sebum content, skin hydration and acidic skin pH are major factors in maintaining skin health. Various nutrients are reported to influence skin health, but the effect of dietary patterns (DPs) on skin health is unclear. In this study, we considered the DPs associated with these three skin health parameters in 84 healthy adults aged 19–37 years. Dietary intake was assessed using a food frequency questionnaire (FFQ) and skin health parameters were determined on the forehead of each subject. Among the four DPs extracted from the FFQ, DP2, characterized by a high intake of cereals, potatoes and starch, saccharides and fish and shellfish, was negatively associated with skin hydration. DP3, characterized by a high intake of potatoes and starch, seeds and nuts, fruits and eggs, was positively associated with acidic skin pH only before adjusting for potential confounders. On the other hand, DP4, characterized by a low intake of beans, and a high intake of meats, dairy products and beverages and alcohol, was negatively associated with acidic skin pH and positively associated with sebum content. The data stratified by sex revealed a negative association between skin hydration and DP2 in males and a negative association between sebum content and DP3 and a positive association between sebum content and DP4 in females. In conclusion, we demonstrated that specific DPs were associated with sebum content, skin hydration and pH in healthy Korean adults and that those associations were affected by sex. Full article

The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes CYP2R1 (rs12794714, rs10741657) and DHCR7/NADSYN1 (rs12785878, rs11234027), were combined in two allelic scores. Cox proportional hazards regression models were used with the ratio estimator and the delta method for calculating the hazards ratio (HR) and standard error of genetically determined 25(OH)D effect on all-cause mortality. We included 10,501 participants (50.1% females, 67.1±10.1 years) of whom 4003 died during a median follow-up of 10.4 years. The observed adjusted HR for all-cause mortality per decrease in 25(OH)D by 20 nmol/L was 1.20 (95% CI: 1.15–1.25). The HR per 20 nmol/L decrease in genetically determined 25(OH)D was 1.32 (95% CI: 0.80–2.24) and 1.35 (95% CI of 0.81 to 2.37) based on the two scores. In conclusion, the results of this MR study in a combined sample from three European cohort studies provide further support for a causal relationship between vitamin D deficiency and increased all-cause mortality. However, as the current study, even with ~10,000 participants, was underpowered for the study of the effect of the allele score on mortality, larger studies on genetics and mortality are needed to improve the precision. Full article

Ultraviolet (UV) light, a major risk factor for external skin photoaging, induces oxidative stress in skin. UV causes a breakdown of skin homeostasis by impairing the extracellular matrix and inducing cell death. Tectorigenin, a constituent of leopard lily (Belamcanda chinensis L.) rhizome, has been reported to possess antioxidant, hair-darkening, and anti-inflammatory activities; however, the effect of tectorigenin on UV-B-induced skin damage is unknown. Here, we investigated the anti-skin-damage effects of tectorigenin against UV-B-stimulated oxidative stress in human keratinocytes. We irradiated HaCaT cells with UV-B (25 mJ/cm²), followed by treatment with tectorigenin for 24 h. We found that tectorigenin decreased the levels of intracellular reactive oxygen species by increasing the expression of anti-oxidative enzymes, such as glutathione and catalase. Furthermore, tectorigenin inhibited apoptosis by reducing caspase-3- and Bcl-2-associated protein-X levels, and increasing Bcl-2 protein levels. Tectorigenin also decreased matrix metalloproteinase-1 levels and increased type 1 collagen levels, thus preventing collagen degradation. These data demonstrate that tectorigenin exerts anti-skin-damage effects in human keratinocytes by attenuating UV-B-induced hyper-oxidation, apoptosis, and collagen degradation. Full article

Nutrigenomics studies how environmental factors, such as food intake and lifestyle, influence the expression of the genome. Vitamin D₃ represents a master example of nutrigenomics, since via its metabolite 1α,25-dihydroxyvitamin D₃, which binds with high-affinity to the vitamin D receptor, the secosteroid directly affects the epigenome and transcriptome at thousands of loci within the human genome. Vitamin D is important for both cellular metabolism and immunity, as it controls calcium homeostasis and modulates the response of the innate and adaptive immune system. At sufficient UV-B exposure, humans can synthesize vitamin D₃ endogenously in their skin, but today’s lifestyle often makes the molecule a true vitamin and micronutrient that needs to be taken up by diet or supplementation with pills. The individual’s molecular response to vitamin D requires personalized supplementation with vitamin D₃, in order to obtain optimized clinical benefits in the prevention of osteoporosis, sarcopenia, autoimmune diseases, and possibly different types of cancer. The importance of endogenous synthesis of vitamin D₃ created an evolutionary pressure for reduced skin pigmentation, when, during the past 50,000 years, modern humans migrated from Africa towards Asia and Europe. This review will discuss different aspects of how vitamin D interacts with the human genome, focusing on nutritional epigenomics in context of immune responses. This should lead to a better understanding of the clinical benefits of vitamin D. Full article