Real world evidence on the characteristics of regular and intermittent users of a very-low calorie diet program and associations with measures of program success, health, and quality of life.

Background: Very low-calorie diet (VLCD) programs are readily available in Australia. However, there is a lack of real-world evidence describing the characteristics related to positive outcomes. Aims: To examine the demographic, eating, self-efficacy and program engagement characteristics of VLCD users in Australia, and the associations between user characteristics and program success, weight loss, quality of life (QOL) and health. Method: Cross-sectional data from Australian adults: regular users (n = 189: VLCD user ≥4 days/week for >4 weeks) and intermittent users (n = 111, VLCD user <4 weeks and/or <4 days/week). Self-reported data on demographics, VLCD program use, support, eating behavior, weight-related QOL, mental health, physical health, self-efficacy, and physical activity. Descriptive and inferential statistics were performed in R. Results: Compared to regular users, intermittent users reported lower percentage weight loss (15.1% ± SD 9.8 vs. 9.9% ± SD 6.8, relative to starting weight), fewer reported their VLCD program as very successful (44% vs. 35%), higher depressive symptom scores (8.7 ± SD 2.8 vs. 6.7 ± SD 5.1), and lower general self-efficacy (23.9 ± SD 4.7 vs. 29.4 ± SD 5.7), nutrition self-efficacy (11.9 ± SD 2.0 vs. 14.5 ± SD 3.1) and weight-related QOL scores (60.9 ± SD 22.2 vs. 65.0 ± SD 11.8; p < 0.001 for all). In regular users, older age and longer program duration were associated with greater total weight loss, support, and program success (p < 0.001 for all). In intermittent users, program success was greater when dietitian support was used (odds ratio [OR] 6.50) and for those with higher BMIs (OR 1.08, p < 0.001 for all). In both groups, more frequent support was associated with better weight-related QOL (p < 0.001). Conclusion: This study provides real-world evidence that regular VLCD users had greater success and weight loss than intermittent program users. These findings may be used to tailor and improve the delivery of VLCD programs in Australia and other countries with retail access to VLCDs.

The Impact of Gender-Affirming Hormone Therapy on Physical Performance.

CONTEXT: The inclusion of transgender people in elite sport has been a topic of debate. This narrative review examines the impact of gender-affirming hormone therapy (GAHT) on physical performance, muscle strength, and markers of endurance. EVIDENCE ACQUISITION: MEDLINE and Embase were searched using terms to define the population (transgender), intervention (GAHT), and physical performance outcomes. EVIDENCE SYNTHESIS: Existing literature comprises cross-sectional or small uncontrolled longitudinal studies of short duration. In nonathletic trans men starting testosterone therapy, within 1 year, muscle mass and strength increased and, by 3 years, physical performance (push-ups, sit-ups, run time) improved to the level of cisgender men. In nonathletic trans women, feminizing hormone therapy increased fat mass by approximately 30% and decreased muscle mass by approximately 5% after 12 months, and steadily declined beyond 3 years. While absolute lean mass remains higher in trans women, relative percentage lean mass and fat mass (and muscle strength corrected for lean mass), hemoglobin, and VO2 peak corrected for weight was no different to cisgender women. After 2 years of GAHT, no advantage was observed for physical performance measured by running time or in trans women. By 4 years, there was no advantage in sit-ups. While push-up performance declined in trans women, a statistical advantage remained relative to cisgender women. CONCLUSION: Limited evidence suggests that physical performance of nonathletic trans people who have undergone GAHT for at least 2 years approaches that of cisgender controls. Further controlled longitudinal research is needed in trans athletes and nonathletes.

Association between disordered eating and clinical outcomes following a surgical or endoscopic bariatric procedure: A real-world exploratory study.

Problem: Disordered eating, such as binge, graze, and emotional eating, has been strongly linked to weight gain. Improved understanding of disordered eating by adults who elect bariatric weight loss procedures in a real-world setting is required. Purpose: To determine the association between the number and type of disordered eating patterns (DEPs), as described by healthcare professionals during routine care without standardized assessment, with clinical outcomes in adults who elected a bariatric weight loss procedure. Method: An observational cohort study recruited laparoscopic sleeve gastrectomy (LSG) and endoscopic sleeve gastroplasty (ESG) patients. DEPs documented in the medical record during routine care were observed and tested for association with events (symptoms, side-effects, or adverse events), micronutrient deficiencies, weight loss, and attrition. Data were observed up to 12-month post-procedure. Results: 215 LSG and 32 ESG patients were recruited. The mean number of DEPs was 6.4 (SD: 2.1) and 6.4 (SD: 2.1) in the LSG and ESG cohorts, respectively. Night eating was associated with a higher number of events (p < 0.008) in the LSG cohort, and non-hungry eating was associated with a higher number of events in the ESG cohort (p < 0.001). ESG patients who had a surgical or medical event by 6-months post-procedure had mean 1.78 (95%CI: 0.67, 2.89) more DEPs (p = 0.004). DEPs were not associated with weight loss, micronutrient deficiencies, nor attrition. Conclusion: The treating healthcare team believed the LSG and ESG patients experienced a wide variety and high frequency of DEPs requiring multidisciplinary support. Non-hungry eating and night eating were associated with poorer outcomes following an LSG or ESG. Trial registration: The study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000332729).

Implications of gender-affirming endocrine care for sports participation.

Many transgender (trans) individuals utilize gender-affirming hormone therapy (GAHT) to promote changes in secondary sex characteristics to affirm their gender. Participation rates of trans people in sport are exceedingly low, yet given high rates of depression and increased cardiovascular risk, the potential benefits of sports participation are great. In this review, we provide an overview of the evidence surrounding the effects of GAHT on multiple performance-related phenotypes, as well as current limitations. Whilst data is clear that there are differences between males and females, there is a lack of quality evidence assessing the impact of GAHT on athletic performance. Twelve months of GAHT leads to testosterone concentrations that align with reference ranges of the affirmed gender. Feminizing GAHT in trans women increases fat mass and decreases lean mass, with opposite effects observed in trans men with masculinizing GAHT. In trans men, an increase in muscle strength and athletic performance is observed. In trans women, muscle strength is shown to decrease or not change following 12 months of GAHT. Haemoglobin, a measure of oxygen transport, changes to that of the affirmed gender within 6 months of GAHT, with very limited data to suggest possible reductions in maximal oxygen uptake as a result of feminizing GAHT. Current limitations of this field include a lack of long-term studies, adequate group comparisons and adjustment for confounding factors (e.g. height and lean body mass), and small sample sizes. There also remains limited data on endurance, cardiac or respiratory function, with further longitudinal studies on GAHT needed to address current limitations and provide more robust data to inform inclusive and fair sporting programmes, policies and guidelines.

Implementation of multiple statistical methods to estimate variability and individual response to training.

Multiple statistical methods have been proposed to estimate individual responses to exercise training; yet, the evaluation of these methods is lacking. We compared five of these methods including the following: the use of a control group, a control period, repeated testing during an intervention, a reliability trial and a repeated intervention. Apparently healthy males from the Gene SMART study completed a 4-week control period, 4 weeks of High-Intensity Interval Training (HIIT), >1 year of washout, and then subsequently repeated the same 4 weeks of HIIT, followed by an additional 8 weeks of HIIT. Aerobic fitness measurements were measured in duplicates at each time point. We found that the control group and control period were not intended to measure the degree to which individuals responded to training, but rather estimated whether individual responses to training can be detected with the current exercise protocol. After a repeated intervention, individual responses to 4 weeks of HIIT were not consistent, whereas repeated testing during the 12-week-long intervention was able to capture individual responses to HIIT. The reliability trial should not be used to study individual responses, rather should be used to classify participants as responders with a certain level of confidence. 12 weeks of HIIT with repeated testing during the intervention is sufficient and cost-effective to measure individual responses to exercise training since it allows for a confident estimate of an individual's true response. Our study has significant implications for how to improve the design of exercise studies to accurately estimate individual responses to exercise training interventions.HighlightsWhat are the findings? We implemented five statistical methods in a single study to estimate the magnitude of within-subject variability and quantify responses to exercise training at the individual level.The various proposed methods used to estimate individual responses to training provide different types of information and rely on different assumptions that are difficult to test.Within-subject variability is often large in magnitude, and as such, should be systematically evaluated and carefully considered in future studies to successfully estimate individual responses to training.How might it impact on clinical practice in the future?Within-subject variability in response to exercise training is a key factor that must be considered in order to obtain a reproducible measurement of individual responses to exercise training. This is akin to ensuring data are reproducible for each subject.Our findings provide guidelines for future exercise training studies to ensure results are reproducible within participants and to minimise wasting precious research resources.By implementing five suggested methods to estimate individual responses to training, we highlight their feasibility, strengths, weaknesses and costs, for researchers to make the best decision on how to accurately measure individual responses to exercise training.

Uncovering the effects of gender affirming hormone therapy on skeletal muscle and epigenetics: protocol for a prospective matched cohort study in transgender individuals (the GAME study).

INTRODUCTION: Gender affirming hormone therapy (GAHT) is increasingly used by transgender individuals and leads to shifts in sex hormone levels. Skeletal muscle is highly responsive to hormone activity, with limited data on the effects of GAHT on different human tissues. Here, we present the protocol for the GAME study (the effects of Gender Affirming hormone therapy on skeletal Muscle training and Epigenetics), which aims to uncover the effects of GAHT on skeletal muscle 'omic' profiles (methylomics, transcriptomics, proteomics, metabolomics) and markers of skeletal muscle health and fitness. METHODS AND ANALYSIS: This study is a prospective age-matched cohort study in transgender adults commencing GAHT (n=80) and age-matched individuals not commencing GAHT (n=80), conducted at Austin Health and Victoria University in Victoria, Australia. Assessments will take place prior to beginning GAHT and 6 and 12 months into therapies in adults commencing GAHT. Age-matched individuals will be assessed at the same time points. Assessments will be divided over three examination days, involving (1) aerobic fitness tests, (2) muscle strength assessments and (3) collection of blood and muscle samples, as well as body composition measurements. Standardised diets, fitness watches and questionnaires will be used to control for key confounders in analyses. Primary outcomes are changes in aerobic fitness and muscle strength, as well as changes in skeletal muscle DNA methylation and gene expression profiles. Secondary outcomes include changes in skeletal muscle characteristics, proteomics, body composition and blood markers. Linear mixed models will be used to assess changes in outcomes, while accounting for repeated measures within participants and adjusting for known confounders. ETHICS AND DISSEMINATION: The Austin Health Human Research Ethics Committee (HREC) and Victoria University HREC granted approval for this study (HREC/77146/Austin-2021). Findings from this project will be published in open-access, peer-reviewed journals and presented to scientific and public audiences. TRIAL REGISTRATION NUMBER: ACTRN12621001415897; Pre-results.

Biophysical evidence to support and extend the vitamin D-folate hypothesis as a paradigm for the evolution of human skin pigmentation.

OBJECTIVE: To test the "vitamin D-folate hypothesis for the evolution of human skin pigmentation." METHODS: Total ozone mapping spectrometer (TOMS) satellite data were used to examine surface UV-irradiance in a large (n = 649) Australian cross-sectional study population. Genetic analysis was used to score vitamin D- and folate-related gene polymorphisms (n = 22), along with two pigmentation gene variants (IRF4-rs12203592/HERC2-rs12913832). Red cell folate and vitamin D3 were measured by immunoassay and HPLC, respectively. RESULTS: Ultraviolet radiation (UVR) and pigmentation genes interact to modify blood vitamin levels; Light skin IRF4-TT genotype has greatest folate loss while light skin HERC2-GG genotype has greatest vitamin D3 synthesis (reflected in both TOMS and seasonal data). UV-wavelength exhibits a dose-response relationship in folate loss within light skin IRF4-TT genotype (305 > 310 > 324 > 380 nm). Significant vitamin D3 photosynthesis only occurs within light skin HERC2-GG genotype, and is maximal at 305 nm. Three dietary antioxidants (vitamins C, E, and ß-carotene) interact with UVR and pigmentation genes preventing oxidative loss of labile reduced folate vitamers, with greatest benefit in light skin IRF4-TT subjects. The putative photosensitiser, riboflavin, did not sensitize red cell folate to UVR and actually afforded protection. Four genes (5xSNPs) influenced blood vitamin levels when stratified by pigmentation genotype; MTHFR-rs1801133/rs1801131, TS-rs34489327, CYP24A-rs17216707, and VDR-ApaI-rs7975232. Lightest IRF4-TT/darkest HERC2-AA genotype combination (greatest folate loss/lowest vitamin D3 synthesis) has 0% occurrence. The opposing, commonest (39%) compound genotype (darkest IRF4-CC/lightest HERC2-GG) permits least folate loss and greatest synthesis of vitamin D3 . CONCLUSION: New biophysical evidence supports the vitamin D-folate hypothesis for evolution of skin pigmentation.

Vegetable content & variety of convenience cooking product recipes: an online audit of Australian supermarket products.

ABSTARCTMeal/recipe bases are low-cost and popular convenience cooking products, requiring limited preparation time and cooking skills. Back-of-pack recipes provided on these products could help encourage vegetable consumption; however, the vegetable content of these recipes has not been examined. Therefore, an audit was conducted of recipes provided on recipe/meal bases (n = 91) sold online at two Australian supermarkets. Recipes included 1.58 standard serves of vegetables per suggested serving on average, with 75% of recipes providing <2 standard serves of vegetables, and recipes had low vegetable variety. Beef-based recipes had more standard serves of vegetables per standard serving than those based on chicken (p = 0.02). 45% of products had recipes taking <25 minutes. These results provide new insights into the vegetable content of recipes provided on meal and recipe bases and how these recipes could be adjusted to increase vegetable intakes. Results serve as a baseline to track future improvements in these recipes.

Dimensions of hospital workplace violence: Patient violence towards the healthcare team.

AIMS AND OBJECTIVES: To investigate the cognitive dimensions nurses use when perceiving patient-to-healthcare provider workplace violence. BACKGROUND: The concept of workplace violence, especially with respect to healthcare settings, has been well documented. Healthcare workers are at particular risk for experiencing violence from their patients, though these incidents often go unreported. Experiencing violence in the workplace has been associated with numerous negative outcomes, including absenteeism, burnout and diminished quality of care. However, little emphasis has been placed on understanding the concept of violence itself, or why one type of violence might go unreported whilst another is readily communicated to officials. DESIGN: A card-sorting, multidimensional scaling design. METHODS: Thirty two nurses completed the card-sorting task. Using multidimensional scaling (MDS), 75 reported incidents of violence were considered. SPIRIT research reporting checklist followed. RESULTS: Nurses categorise patient violence in three dimensions: physical versus verbal, active versus threatening and more versus less severe. Implications for further research and intervention are discussed. CONCLUSIONS: Violence in the hospital workplace is a complex perception by the healthcare worker that cannot be captured by a single dimension. RELEVANCE TO CLINICAL PRACTICE: This study provides a theoretical framework for understanding the complexity of patient-to-provider violence in a hospital setting. It sheds light on why only a minority of such events are reported. This model can serve as a foundation for future research exploring interventions for hospital violence.

Correlations between Self-Reported Cooking Confidence and Creativity and Use of Convenience Cooking Products in an Australian Cohort.

BACKGROUND: Most Australians do not meet vegetable intake recommendations. Vegetables are most often consumed in evening meals. However, they often require preparation and therefore cooking skills. Convenience cooking products such as meal bases/concentrates and ready-made sauces are increasingly common and popular and may help address the barriers to vegetable consumption in terms of cost and time. These products also typically provide recipes, which include vegetables, and as such, may help address the barriers of cooking skills, confidence, and creativity. However, the relationships between the use of these products, cooking confidence, and cooking creativity remain unknown. METHODS: Australian adults were surveyed (snowball recruitment, n = 842) on their use of convenience cooking products (meal bases/recipe concentrates, simmer sauces, marinades, and other cooking sauces), cooking confidence (7 item scale) and creativity (6 item scale), and demographic information. RESULTS: Overall, 63.2% of participants reported using convenience cooking products. Those using these products had lower mean cooking skills confidence and creativity scores than those who did not, in all product categories assessed. Among users, those who reported "always" following the recipes provided had lower mean cooking confidence and creativity scores than those who followed the recipes less regularly. Conclusions: Therefore, improving the vegetable content of recipes provided with these products may be a tool to increase vegetable intake by users with lower cooking skills (confidence and creativity). This may complement traditional approaches such as education in improving vegetable intake.

Independent and Interactive Influences of Environmental UVR, Vitamin D Levels, and Folate Variant MTHFD1-rs2236225 on Homocysteine Levels.

Elevated homocysteine (Hcy) levels are a risk factor for vascular diseases. Recently, increases in ultraviolet radiation (UVR) have been linked to decreased Hcy levels. This relationship may be mediated by the status of UVR-responsive vitamins, vitamin D and folate, and/or genetic variants influencing their levels; however, this has yet to be examined. Therefore, the independent and interactive influences of environmental UVR, vitamin D and folate levels and related genetic variants on Hcy levels were examined in an elderly Australian cohort (n = 619). Red blood cell folate, 25-hydroxyvitamin D (25(OH)D), and plasma Hcy levels were determined, and genotyping for 21 folate and vitamin D-related variants was performed. Erythemal dose rate accumulated over six-weeks (6W-EDR) and four-months (4M-EDR) prior to clinics were calculated as a measure of environmental UVR. Multivariate analyses found interactions between 6W-EDR and 25(OH)D levels (pinteraction = 0.002), and 4M-EDR and MTHFD1-rs2236225 (pinteraction = 0.006) in predicting Hcy levels. The association between 6W-EDR and Hcy levels was found only in subjects within lower 25(OH)D quartiles (<33.26 ng/mL), with the association between 4M-EDR and Hcy occurring only in subjects carrying the MTHFD1-rs2236225 variant. 4M-EDR, 6W-EDR, and MTHFD1-rs2236225 were also independent predictors of Hcy. Findings highlight nutrient-environment and gene-environment interactions that could influence the risk of Hcy-related outcomes.

Distribution of variants in multiple vitamin D-related loci (DHCR7/NADSYN1, GC, CYP2R1, CYP11A1, CYP24A1, VDR, RXRα and RXRγ) vary between European, East-Asian and Sub-Saharan African-ancestry populations.

BACKGROUND: The frequency of vitamin D-associated gene variants appear to reflect changes in long-term ultraviolet B radiation (UVB) environment, indicating interactions exist between the primary determinant of vitamin D status, UVB exposure and genetic disposition. Such interactions could have health implications, where UVB could modulate the impact of vitamin D genetic variants identified as disease risk factors. However, the current understanding of how vitamin D variants differ between populations from disparate UVB environments is limited, with previous work examining a small pool of variants and restricted populations only. METHODS: Genotypic data for 46 variants within multiple vitamin D-related loci (DHCR7/NADSYN1, GC, CYP2R1, CYP11A1, CYP27A1, CYP24A1, VDR, RXRα and RXRγ) was collated from 60 sample sets (2633 subjects) with European, East Asian and Sub-Saharan African origin via the NCBI 1000 Genomes Browser and ALFRED (Allele Frequency Database), with the aim to examine for patterns in the distribution of vitamin D-associated variants across these geographic areas. RESULTS: The frequency of all examined genetic variants differed between populations of European, East Asian and Sub-Saharan African ancestry. Changes in the distribution of variants in CYP2R1, CYP11A1, CYP24A1, RXRα and RXRγ genes between these populations are novel findings which have not been previously reported. The distribution of several variants reflected changes in the UVB environment of the population's ancestry. However, multiple variants displayed population-specific patterns in frequency that appears not to relate to UVB changes. CONCLUSIONS: The reported population differences in vitamin D-related variants provides insight into the extent by which activity of the vitamin D system can differ between cohorts due to genetic variance, with potential consequences for future dietary recommendations and disease outcomes.

Environmental UVR Levels and Skin Pigmentation Gene Variants Associated with Folate and Homocysteine Levels in an Elderly Cohort.

Ultraviolet radiation (UVR) is a ubiquitous exposure which may contribute to decreased folate levels. Skin pigmentation mediates the biological effect of UVR exposure, but its relationship to folate levels is unexamined. Interactions may exist between UVR and pigmentation genes in determining folate status, which may, in turn, impact homocysteine levels, a potential risk factor for multiple chronic diseases. Therefore, independent and interactive influences of environmental UVR and genetic variants related to skin pigmentation (MC1R-rs1805007, IRF4-rs12203592 and HERC2-rs12913832) on folate (red blood cell (RBC) and serum) and homocysteine levels were examined in an elderly Australian cohort (n = 599). Genotypes were assessed by RT/RFLP-PCR, and UVR exposures were assessed as the accumulated erythemal dose rate accumulated over 4 months (4M-EDR). Multivariate analysis found significant negative associations between 4M-EDR and RBC folate (p < 0.001, ß = -0.19), serum folate (p = 0.045, ß = -0.08) and homocysteine levels (p < 0.001, ß = -0.28). Significant associations between MC1R-rs1805007 and serum folate levels (p = 0.020), and IRF4-rs12203592 and homocysteine levels (p = 0.026) occurred but did not remain significant following corrections with confounders. No interactions between 4M-EDR and pigmentation variants in predicting folate/homocysteine levels were found. UVR levels and skin pigmentation-related variants are potential determinants of folate and homocysteine status, although, associations are mixed and complex, with further studies warranted.

Early lifecycle UV-exposure calibrates adult vitamin D metabolism: Evidence for a developmentally originated vitamin D homeostat that may alter related adult phenotypes.

OBJECTIVES: Within the Developmental Origins of Adult Disease (DOHaD) model, early life environmental exposures can confer a long-term legacy on human health. This mechanism may be adaptive or maladaptive depending on lifestyle circumstances. This article examines the role of first trimester UV-exposure on late-life vitamin D levels, and potentially related adaptive and maladaptive phenotypes (height and osteoporosis respectively). METHODS: Six hundred and forty nine subjects were examined for vitamin D2 and D3 (HPLC) and height (stadiometer). Osteoporosis was assessed with an extensive medical history questionnaire. RESULTS: Solar irradiance over the first 90 days postconception correlated positively with late-life vitamin D3 (R2 = .0140; P = .0082; ß = .1075), but not vitamin D2 levels. It also correlated positively with female adult height (R2 = .170; P = .0103; ß = .1291) and negatively with the occurrence of female osteoporosis (P = .0495). All data were adjusted for age and gender as appropriate (unadjusted data also provided). From a contemporary perspective, vitamin D levels varied significantly according to season of blood sampling as might be predicted (P = .0009). CONCLUSIONS: Increased solar irradiance/UV exposure during the first trimester of pregnancy calibrates adult vitamin D metabolism, which is an important hormone in maintaining calcium balance. This may explain how very early lifecycle UV exposure can influence skeletal development (adult height) and modify risk for the skeletal degenerative disorder osteoporosis. The data demonstrate humans are tuned to the world (exposome) in ways we have not yet fully considered, and which are entrained at the earliest phase of the lifecycle.

Reply: "Comment on: The Vitamin D⁻Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas, Nutrients 2018, 10, 554".

We thank Elias and Williams for their interest in our review [...].

Vitamin D and folate: A reciprocal environmental association based on seasonality and genetic disposition.

OBJECTIVES: The purpose of this study was (1) to elucidate any reciprocal seasonal relationship that might exist between red cell folate (RCF) and serum vitamin D3 Levels; (2) to explore whether folate-related gene variants that influence/alter DNA-thymidylate and methyl group biosynthesis modify any associations detected in objective 1; and (3) to consider whether these processes might influence reproductive success consistent with the "folate-vitamin D-UV hypothesis of skin pigmentation" evolutionary model. METHODS: A large (n = 649) Australian cross-sectional study population was examined. Polymerase chain reaction (PCR)/Restriction fragment length polymorphism (RFLP) analysis was used to genotype C677T-MTHFR, C1420T-SHMT, T401C-MTHFD and 2R > 3R-TS. RCF was measured by chemiluminescent immunoassay and vitamin D2 and D3 by HPLC. RESULTS: RCF and photosynthesized vitamin D3 , but not RCF and dietary vitamin D2 , exhibit a significant reciprocal association in spring and summer. Three folate genes (C677T-MTHFR, C1420T-SHMT, and 2R > 3R-TS) strengthen this effect in spring, and another (T401C-MTHFD) in summer. Effects are seasonal, and do not occur over the whole year. CONCLUSIONS: Findings are consistent with what might be required for the "folate-vitamin D-UV hypothesis of skin pigmentation" model. It suggests genetic influence in provision of one-carbon units by 5,10-methylene-H4 folate, may be an important factor in what appears to be a clear seasonal relationship between vitamin D3 and folate status.

Photobiology of vitamins.

This review explores contemporary ideas about the relationship between light exposure and vitamin biology. Nutritional biochemistry has long recognized the relationship between vitamins A and D and light exposure, but in recent years other vitamins have also been implicated in photoresponsive biological mechanisms that influence health, well-being, and even evolutionary processes. Interactions between light and vitamins can modify genotype-phenotype relationships across the life cycle, providing a basis for interesting new explanations relevant to wide aspects of human biology. This review examines both well-established and emerging ideas about vitamin photobiology in the context of the following: (1) light responsiveness of vitamin D (photosynthesized in skin), vitamin A (linked to vision), and vitamin B3 (needed to repair genomic damage); (2) vulnerability of folate and vitamins B1, B2, B12, and D to ultraviolet (UV) light (all potentially degraded); (3) protective/filtering actions of carotenoids and vitamins C and E, which act as antioxidants and/or natural sunscreens, against UV light; (4) role of folate, carotenoids, and vitamins A, B3, C, D, and E in UV-related genomic regulation, maintenance, and repair; (5) role of folate and vitamins A, B2, B12, and D in a range of light-signaling and light-transduction pathways; and (6) links between folate and vitamin D and the evolution of UV light-adaptive phenotypes.

The Vitamin D⁻Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas.

Vitamin D is unique in being generated in our skin following ultraviolet radiation (UVR) exposure. Ongoing research into vitamin D must therefore always consider the influence of UVR on vitamin D processes. The close relationship between vitamin D and UVR forms the basis of the “vitamin D⁻folate hypothesis”, a popular theory for why human skin colour has evolved as an apparent adaption to UVR environments. Vitamin D and folate have disparate sensitivities to UVR; whilst vitamin D may be synthesised following UVR exposure, folate may be degraded. The vitamin D⁻folate hypothesis proposes that skin pigmentation has evolved as a balancing mechanism, maintaining levels of these vitamins. There are several alternative theories that counter the vitamin D⁻folate hypothesis. However, there is significant overlap between these theories and the now known actions of vitamin D and folate in the skin. The focus of this review is to present an update on the vitamin D⁻folate hypothesis by integrating these current theories and discussing new evidence that supports associations between vitamin D and folate genetics, UVR, and skin pigmentation. In light of recent human migrations and seasonality in disease, the need for ongoing research into potential UVR-responsive processes within the body is also discussed.