Ruminants can recycle nitrogen (N) and phosphorus (P), which are essential for vital body processes. Reduced N- and P-intake in ruminants is desirable for economic and ecologic reasons. Simultaneous modulation of mineral homoeostasis and bone metabolism occurs in young goats. This study aimed to investigate potential effects of dietary N- and/or P-restriction on molecular changes in bone metabolism. The twenty-eight young male goats were fed a control diet, an N-reduced diet, a P-reduced diet or a combined N- and P-reduced diet for 6–8 weeks. The N-restricted goats had lower plasma Ca concentration and higher plasma osteocalcin (OC) and CrossLaps concentrations. The P-restricted goats had reduced plasma inorganic phosphate (Pi) concentrations and increased plasma Ca concentrations. Due to the initiation of a signalling pathway that inhibits the fibroblast growth factor 23 (FGF23) expression, this was lower with P-restriction. Consequently, lower Pi concentrations were the main factor influencing the reduction in FGF23. The changes in mineral homoeostasis associated with P-restriction led to a reduction in OC, bone mineral content and mineral density. Simultaneously, bone resorption potentially increased with P-restriction as indicated by an increased receptor activator of NF-κB ligand/osteoprotegerin (OPG) ratio and an increase in OPG mRNA expression. Additionally, the increased mRNA expression of the calcitonin receptor during P-restriction points to a higher number of osteoclasts. This study demonstrates an impairment of bone remodelling processes in young goats by N- or P-restriction. With P-restriction, bone mineralisation rate was potentially reduced and bone quality impaired, while with N-restriction, bone remodelling increased.

Calcium and vitamin D have well-established roles in maintaining calcium balance and bone health. Decades of research in human subjects and animals have revealed that calcium and vitamin D also have effects on many other organs including male reproductive organs. The presence of calcium-sensing receptor, vitamin D receptor, vitamin D activating and inactivating enzymes and calcium channels in the testes, male reproductive tract and human spermatozoa suggests that vitamin D and calcium may modify male reproductive function. Functional animal models have shown that vitamin D deficiency in male rodents leads to a decrease in successful mating and fewer pregnancies, often caused by impaired sperm motility and poor sperm morphology. Human studies have to a lesser extent validated these findings; however, newer studies suggest a positive effect of vitamin D supplementation on semen quality in cases with vitamin D deficiency, which highlights the need for initiatives to prevent vitamin D deficiency. Calcium channels in male reproductive organs and spermatozoa contribute to the regulation of sperm motility and capacitation, both essential for successful fertilisation, which supports a need to avoid calcium deficiency. Studies have demonstrated that vitamin D, as a regulator of calcium homoeostasis, influences calcium influx in the testis and spermatozoa. Emerging evidence suggests a potential link between vitamin D deficiency and male infertility, although further investigation is needed to establish a definitive causal relationship. Understanding the interplay between vitamin D, calcium and male reproductive health may open new avenues for improving fertility outcomes in men.

Obesity is associated with low vitamin D status, and the optimal supplement and dosage of cholecalciferol (vitamin D3) or calcidiol (25OHD) for individuals with obesity have been debated. We aimed to determine the effect of high-dose vitamin D3 supplementation on achieving adequate vitamin D levels among infertile men with normal weight v. obesity. Here, we present secondary end points from a single-centre, double-blinded, randomised clinical trial, comprising 307 infertile men randomised to active or placebo treatment for 150 days. Men in the active group initially received an oral bolus of 300 000 mg of vitamin D3, followed by daily supplementation with 1400 mg of vitamin D3 and 500 mg of calcium. Baseline BMI was listed as a predefined subgroup. At baseline, serum 25OHD was significantly higher in men with normal weight (BMI < 25 kg/m2) compared with men with overweight (BMI 25–30 kg/m2) and obesity (BMI > 30 kg/m2) (48 nmol/l v. 45 nmol/l and 39 nmol/l, respectively; P = 0·024). After the intervention, men with normal weight, overweight and obesity treated with vitamin D3 had a significantly higher serum 25OHD compared with corresponding placebo-treated men (BMI < 25 kg/m2: 92 nmol/l v. 53 nmol/l, BMI = 25–30 kg/m2: 87 nmol/l v. 49 nmol/l and BMI > 30 kg/m2: 85 nmol/l v. 48 nmol/l; P < 0·001 for all, respectively). In conclusion, we show that high-dose vitamin D3 supplementation to infertile men with obesity and low vitamin D status is sufficient to achieve adequate serum 25OHD levels.

This review discusses epigenetic mechanisms and the relationship of infertility in men and women in relation to parameters pertaining to nutrition. The prevalence of infertility worldwide is 8–12 %, and one out of every eight couples receives medical treatment. Epigenetic mechanisms, aging, environmental factors, dietary energy and nutrients and non-nutrient compounds; more or less energy intake, and methionine come into play in the occurrence of infertility. It also interacts with vitamins B12, D and B6, biotin, choline, selenium, zinc, folic acid, resveratrol, quercetin and similar factors. To understand the molecular mechanisms regulating the expression of genes that affect infertility, the environment, the role of genotype, age, health, nutrition and changes in the individual's epigenotype must first be considered. This will pave the way for the identification of the unknown causes of infertility. Insufficient or excessive intake of energy and certain macro and micronutrients may contribute to the occurrence of infertility as well. In addition, it is reported that 5–10 % of body weight loss, moderate physical activity and nutritional interventions for improvement in insulin sensitivity contribute to the development of fertility. Processes that pertain to epigenetics carry alterations which are inherited yet not encoded via the DNA sequence. Nutrition is believed to have an impact over the epigenetic mechanisms which are effective in the pathogenesis of several diseases like infertility. Epigenetic mechanisms of individuals with infertility are different from healthy individuals. Infertility is associated with epigenetic mechanisms, nutrients, bioactive components and numerous other factors.

The aim of the present study was to assess the seasonal relationship between serum 25(OH)D concentration, lean mass and muscle strength. This was a secondary data analysis of a subgroup of 102 postmenopausal women participating in the 2006–2007 D-FINES (Vitamin D, Food Intake, Nutrition and Exposure to Sunlight in Southern England) study. The cohort was assessed as two age subgroups: <65 years (n=80) and ≥65 years (n=22). Outcome measures included lean mass (DXA), muscle strength (handgrip dynamometry) and serum 25(OH)D concentration (enzymeimmunoassay). Derived outcomes included appendicular skeletal muscle mass (ASM) and relative appendicular skeletal muscle index (RASM). Sarcopenia status was assessed using the European Working Group on Sarcopenia in Older People 2018 criteria. Non-parametric partial correlation using BMI as a covariate was used to evaluate the study aims. There were no statistically significant associations between total lean mass, ASM or RASM and 25(OH)D in any group at any season. There was a trend for handgrip strength to be positively associated with serum 25(OH)D concentration. There was a trend showing a higher prevalence of sarcopenia in women ≥65 years. Sarcopenia status appeared transient for five women. In conclusion, the present study found no significant association between vitamin D status and functional indicators of musculoskeletal health, which were additionally not affected by season.

Vitamin D is both a nutrient and a neurologic hormone that plays a critical role in modulating immune responses. While low levels of vitamin D are associated with increased susceptibility to infections and immune-related disorders, vitamin D supplementation has demonstrated immunomodulatory effects that can be protective against various diseases and infections. Vitamin D receptor is expressed in immune cells that have the ability to synthesise the active vitamin D metabolite. Thus, vitamin D acts in an autocrine manner in a local immunologic milieu in fighting against infections. Nutrigenetics and nutrigenomics are the new disciplines of nutritional science that explore the interaction between nutrients and genes using distinct approaches to decipher the mechanisms by which nutrients can influence disease development. Though molecular and observational studies have proved the immunomodulatory effects of vitamin D, only very few studies have documented the molecular insights of vitamin D supplementation. Until recently, researchers have investigated only a few selected genes involved in the vitamin D metabolic pathway that may influence the response to vitamin D supplementation and possibly disease risk. This review summarises the impact of vitamin D supplementation on immune markers from nutrigenetics and nutrigenomics perspective based on evidence collected through a structured search using PubMed, EMBASE, Science Direct and Web of Science. The research gaps and shortcomings from the existing data and future research direction of vitamin D supplementation on various immune-related disorders are discussed.

Vitamin D (VD) plays a vital role in various physiological processes in addition to its classic functions on maintaining the balance of Ca and P metabolism. However, there still are gaps to understand in depth the issues on the precise requirement, metabolic processes and physiological functions of VD in fish. In this study, we investigated the effects of VD on the growth, intestinal health, host immunity and metabolism in turbot (Scophthalmus maximus L.), one important commercial carnivorous fish in aquaculture, through the supplementation of different doses of dietary VD3 (0, 200, 400, 800 and 1600 μg VD3/kg diet). According to our results, the optimal VD3 level in the feed for turbot growth was estimated to be around 400 μg/kg, whereas VD3 deficiency or overdose in diets induced the intestinal inflammation, lowered the diversity of gut microbiota and impaired the host resistance to bacterial infection in turbot. Moreover, the level of 1α,25(OH)2D3, the active metabolite of VD3, reached a peak value in the turbot serum in the 400 μg group, although the concentrations of Ca and phosphate in the turbot were stable in all groups. Finally, the deficiency of dietary VD3 disturbed the nutritional metabolism in turbot, especially the metabolism of lipids and glucose. In conclusion, this study evaluated the optimal dose of dietary VD3 for turbot and provided the evidence that VD has a significant impact on intestinal health, host immunity and nutritional metabolism in fish, which deepened our understanding on the physiological functions and metabolism of VD3 in fish.

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease associated with severe systemic inflammation. The optimal status of vitamins and microelements is considered crucial for the proper functioning of the immune system and necessary for successful recovery. Most patients with respiratory distress in COVID-19 are vitamin and microelement deficient, with vitamin D and Se deficiency being the most common. Anyway, various micronutrient supplements are widely and arbitrarily used for prevention or in the treatment of COVID-19. We aimed to summarise current knowledge about molecular and physiological mechanisms of vitamins (D, A, C, B6, B9 and B12) and microelements (Se, Zn, Cu and Fe) involved in the immune system regulation in consideration with COVID-19 pathogenesis, as well as recent findings related to their usage and effects in the prevention and treatment of COVID-19. In the early course of the pandemic, several, mainly observational, studies reported an association of some micronutrients, such as vitamin C, D and Zn, with severity reduction and survival improvement. Still, emerging randomised controlled trials showed no effect of vitamin D on hospitalisation length and no effect of vitamin C and Zn on symptom reduction. Up to date, there is evidence neither for nor against the use of micronutrients in the treatment of COVID-19. The doses that exceed the recommended for the general population and age group should not be used, except in clinical trials. Benefits of supplementation are primarily expected in populations prone to micronutrient deficiencies, who are, as well, at a higher risk of worse outcomes in COVID-19.

The ubiquity of vitamin D metabolising enzymes and vitamin D receptors in mammalian organisms suggests that vitamin D has pleiotropic effects. There are quite a few studies indicating the anticancer, cardioprotective and antidiabetic effects of vitamin D; however, the best-documented actions of vitamin D are the regulation of Ca–phosphate balance and its effect on immune function.

Vitamin D levels in organisms are modulated by many environmental and non-environmental factors. One potential factor that may influence vitamin D levels and effects is the sex of the individuals studied. This review focuses on the scientific evidence indicating different synthesis and metabolism of vitamin D in females and males, mainly from PubMed database sources. The article verifies the sex differences in vitamin D levels reported around the world. Moreover, the different effects of vitamin D on the musculoskeletal, cardiovascular, nervous and immune systems, as well as cancer in males and females, were discussed.

Most studies addressing sex differences in vitamin D levels and effects are observational studies with conflicting results. Therefore, carefully designed clinical trials and experiments on animal models should be carried out to determine the role of non-environmental factors that may differentiate vitamin D levels in females and males.

Renal fibrosis is common especially in the elderly population. Recently, we found that vitamin D deficiency caused prostatic hyperplasia. This study aimed to investigate whether vitamin D deficiency promotes renal fibrosis and functional impairment. All mice except controls were fed with vitamin D-deficient (VDD) diets, beginning from their early life. The absolute and relative kidney weights on postnatal week 20 were decreased in VDD diet-fed male pups but not in female pups. A mild pathological damage was observed in VDD diet-fed male pups but not in females. Further analysis showed that VDD-induced pathological damage was aggravated, accompanied by renal dysfunction in 40-week-old male pups. An obvious collagen deposition was observed in VDD diet-fed 40-week-old male pups. Moreover, renal α-smooth muscle actin (α-SMA), a marker of epithelial–mesenchymal transition (EMT), and Tgf-β mRNA were up-regulated. The in vitro experiment showed that 1,25-dihydroxyvitamin D3 alleviated transforming growth factor-β1 (TGF-β1)-mediated down-regulation of E-cadherin and inhibited TGF-β1-evoked up-regulation of N-cadherin, vimentin and α-SMA in renal epithelial HK-2 cells. Moreover, 1,25-dihydroxyvitamin D3 suppressed TGF-β1-evoked Smad2/3 phosphorylation in HK-2 cells. These results provide experimental evidence that long-term vitamin D deficiency promotes renal fibrosis and functional impairment, at least partially, through aggravating TGF-β/Smad2/3-mediated EMT in middle-aged male mice.

Studies show that vitamin D (vit-D) (25(OH)D), the bioactive metabolite (1,25(OH)2D3) and vit-D receptors (vit-D receptor; protein disulphide isomerase, family A member 3) are expressed throughout the brain, particularly in regions pivotal to learning and memory. This has led to the paradigm that avoiding vit-D deficiency is important to preserve cognitive function. However, presently, it is not clear if the common clinical measure of serum 25(OH)D serves as a robust surrogate marker for central nervous system (CNS) homeostasis or function. Indeed, recent studies report CNS biosynthesis of endogenous 25(OH)D, the CNS expression of the CYP group of enzymes which catalyse conversion to 1,25(OH)2D3 and thereafter, deactivation. Moreover, in the periphery, there is significant ethnic/genetic heterogeneity in vit-D conversion to 1,25(OH)2D3 and there is a paucity of studies which have actually investigated vit-D kinetics across the cerebrovasculature. Compared with peripheral organs, the CNS also has differential expression of receptors that trigger cellular response to 1,25(OH)2D3 metabolites. To holistically consider the putative association of peripheral (blood) abundance of 25(OH)D on cognitive function, herein, we have reviewed population and genetic studies, pre-clinical and clinical intervention studies and moreover have considered potential confounders of vit-D analysis.

There is growing evidence that suggests the association of vitamin D status with the development and progression of heart failure (HF). The objective of the present study is to assess the impact of concentration of serum 25-hydroxyvitamin D (25(OH)D) on cardiac prognosis in patients with HF. Between 1 January 2015 and 31 December 2016, we consecutively recruited patients with HF. Patients were followed prospectively for a median duration of 1 year. Serum concentration of 25(OH)D was measured with competitive chemiluminescent immunoassay. The endpoints were cardiac events, including CVD death and rehospitalisation for worsening HF. Univariate and multivariable adjustments were performed with Cox proportional-hazard regression analyses. The 25(OH)D concentration was obtained in 343 patients with a median value of 17·4 (interquartile range 12·6–23·4) ng/ml. There were 102 cardiac events, including forty-three deaths and fifty-nine rehospitalisations. Multivariate Cox hazard analysis found that the serum concentration 25(OH)D was independently associated with cardiac events (hazard ratio 0·93, 95 % CI 0·88, 0·97) and CVD mortality (hazard ratio 0·83; 95 % CI 0·77, 0·89) after adjustment for confounding factors. We divided the HF patients into four groups according to the 25(OH)D quartiles. Kaplan–Meier analysis found that the patients with lower serum 25(OH)D concentration had a higher risk of cardiac events or CVD mortality than those with high serum 25(OH)D concentration (log-rank test P < 0·001 and P = 0·032). Decreased serum concentrations of 25(OH)D were associated with cardiac prognosis and CVD mortality in a Chinese population with HF independent of other baseline HF markers.

Vitamin D receptor expression and associated function have been reported in various muscle models, including C2C12, L6 cell lines and primary human skeletal muscle cells. It is believed that 1,25-hydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, has a direct regulatory role in skeletal muscle function, where it participates in myogenesis, cell proliferation, differentiation, regulation of protein synthesis and mitochondrial metabolism through activation of various cellular signalling cascades, including the mitogen-activated protein kinase pathway(s). It has also been suggested that 1,25(OH)2D3 and its associated receptor have genomic targets, resulting in regulation of gene expression, as well as non-genomic functions that can alter cellular behaviour through binding and modification of targets not directly associated with transcriptional regulation. The molecular mechanisms of vitamin D signalling, however, have not been fully clarified. Vitamin D inadequacy or deficiency is associated with muscle fibre atrophy, increased risk of chronic musculoskeletal pain, sarcopenia and associated falls, and may also decrease RMR. The main purpose of the present review is to describe the molecular role of vitamin D in skeletal muscle tissue function and metabolism, specifically in relation to proliferation, differentiation and protein synthesis processes. In addition, the present review also includes discussion of possible genomic and non-genomic pathways of vitamin D action.

Reduced plasma vitamin D (VD) levels may contribute to excessive white adipose tissue, insulin resistance (IR) and dyslipidaemia. We evaluated the effect of chronic oral VD supplementation on adiposity and insulin secretion in monosodium glutamate (MSG)-treated rats. During their first 5 d of life, male neonate rats received subcutaneous injections of MSG (4 g/kg), while the control (CON) group received saline solution. After weaning, groups were randomly distributed into VD supplemented (12 µg/kg; three times/week) and non-supplemented (NS) rats, forming four experimental groups (n 15 rats/group): CON-NS, CON-VD, MSG-NS and MSG-VD. At 76 d of life, rats were submitted to an oral glucose tolerance test (OGTT; 2 g/kg), and at 86 d, obesity, IR and plasma metabolic parameters were evaluated. Pancreatic islets were isolated for glucose-induced insulin secretion (GIIS), cholinergic insulinotropic response and muscarinic 3 receptor (M3R), protein kinase C (PKC) and protein kinase A (PKA) expressions. Pancreas was submitted to histological analyses. VD supplementation decreased hyperinsulinaemia (86 %), hypertriacylglycerolaemia (50 %) and restored insulin sensibility (89 %) in MSG-VD rats, without modifying adiposity, OGTT or GIIS, compared with the MSG-NS group. The cholinergic action was reduced (57 %) in islets from MSG-VD rats, without any change in M3R, PKA or PKC expression. In conclusion, chronic oral VD supplementation of MSG-obese rats was able to prevent hyperinsulinaemia and IR, improving triacylglycerolaemia without modifying adiposity. A reduced cholinergic pancreatic effect, in response to VD, could be involved in the normalisation of plasma insulin levels, an event that appears to be independent of M3R and its downstream pathways.

SNP in the vitamin D receptor (VDR) gene is associated with risk of lower respiratory infections. The influence of genetic variation in the vitamin D pathway resulting in susceptibility to upper respiratory infections (URI) has not been investigated. We evaluated the influence of thirty-three SNP in eleven vitamin D pathway genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4, CYP27A1, LRP2, CUBN and VDR) resulting in URI risk in 725 adults in London, UK, using an additive model with adjustment for potential confounders and correction for multiple comparisons. Significant associations in this cohort were investigated in a validation cohort of 737 children in Manchester, UK. In all, three SNP in VDR (rs4334089, rs11568820 and rs7970314) and one SNP in CYP3A4 (rs2740574) were associated with risk of URI in the discovery cohort after adjusting for potential confounders and correcting for multiple comparisons (adjusted incidence rate ratio per additional minor allele ≥1·15, Pfor trend ≤0·030). This association was replicated for rs4334089 in the validation cohort (Pfor trend=0·048) but not for rs11568820, rs7970314 or rs2740574. Carriage of the minor allele of the rs4334089 SNP in VDR was associated with increased susceptibility to URI in children and adult cohorts in the United Kingdom.

The hypovitaminosis D kyphotic pig provides a reliable model to study the initiation of bone lesions caused by maternal vitamin D (D) deficiencies. Matrix metalloproteinases (MMP; specifically, MMP9 and MMP13) and vascular endothelial growth factor (VEGF) are important in endochondral ossification and are potentially regulated by D. Fibroblast growth factor 23 (FGF23) is interrelated with D homoeostasis and bone mineralisation. Relative mRNA expression of MMP9, MMP13, VEGF and FGF23 was measured in pig femur and vertebra. Sows (n 37) were fed diets with 0 (−D), 8·125 (+D) or 43·750 (++D) µg D3/kg throughout gestation and lactation. At weaning (3 weeks), pigs were fed diets with 0 (−D) or 7·0 (+D) µg D3/kg, each with 75 and 95 % (LCaP) or 150 and 120 % (HCaP) of the Ca and P requirements. Pigs at birth (n 27), 3 weeks (n 27) and after the nursery period (7 weeks; n 72) were euthanised for analysis. At 3 weeks, femur MMP9 expression of pigs produced by +D or ++D sows was reduced (P<0·05) to 0·5-fold and VEGF expression to 0·4-fold compared with pigs from –D sows. At 7 weeks, MMP9 expression was reduced (P<0·05) to 0·45-fold in femur and 0·58-fold in vertebra from pigs produced by +D or ++D sows compared with pigs from −D sows. Pig femur VEGF expression was reduced to 0·75-fold in pigs produced by ++D sows. MMP9 and VEGF mRNA expression offer potential markers for the initiation of bone lesions in the hypovitaminosis D kyphotic pig model.

Globally, an estimated 46 million people are currently living with dementia and this figure is projected to increase 3-fold by 2050, highlighting this major public health concern and its substantial associated healthcare costs. With pharmacological treatment yet to reach fruition, the emphasis on evidence-based preventative lifestyle strategies is becoming increasingly important and several modifiable lifestyle factors have been identified that may preserve cognitive health. These include good cardiovascular health, physical activity, low alcohol intake, smoking and a healthy diet, with growing interest in vitamin D. The aim of the present paper is to review the evidence supporting the potential roles of vitamin D in ageing and cognitive health in community-dwelling older adults. Furthermore, to describe the utility and challenges of cognitive assessments and outcomes when investigating vitamin D in this context. Evidence indicates that serum 25-hydroxyvitamin D (25(OH)D) may impact brain health. There is a biological plausibility from animal models that vitamin D may influence neurodegenerative disorders, through several mechanisms. Epidemiological evidence supports associations between low serum 25(OH)D concentrations and poorer cognitive performance in community-dwelling older populations, although an optimal 25(OH)D level for cognitive health could not be determined. The effect of raising 25(OH)D concentrations on cognitive function remains unclear, as there is a paucity of interventional evidence. At a minimum, it seems prudent to aim to prevent vitamin D deficiency in older adults, with other known common protective lifestyle factors, as a viable component of brain health strategies.

Maternal dietary vitamin D carry-over effects were assessed in young pigs to characterise skeletal abnormalities in a diet-induced model of kyphosis. Bone abnormalities were previously induced and bone mineral density (BMD) reduced in offspring from sows fed diets with inadequate vitamin D3. In a nested design, pigs from sows (n 23) fed diets with 0 (−D), 8·125 (+D) or 43·750 (++D) µg D3/kg from breeding through lactation were weaned and, within litter, fed nursery diets arranged as a 2×2 factorial design with 0 (−D) or 7·0 (+D) µg D3/kg, each with 95 % (95P) or 120 % (120P) of P requirements. Selected pigs were euthanised before colostrum consumption at birth (0 weeks, n 23), weaning (3 weeks, n 22) and after a growth period (8 weeks, n 185) for BMD, bone mechanical tests and tissue mRNA analysis. Pigs produced by +D or ++D sows had increased gain at 3 weeks (P<0·05), and at 8 weeks had increased BMD and improved femur mechanical properties. However, responses to nursery diets depended on maternal diets (P<0·05). Relative mRNA expressions of genes revealed a maternal dietary influence at birth in bone osteocalcin and at weaning in kidney 24-hydroxylase (P<0·05). Nursery treatments affected mRNA expressions at 8 weeks. Detection of a maternal and nursery diet interaction (P<0·05) provided insights into the long-term effects of maternal nutritional inputs. Characterising early stages of bone abnormalities provided inferences for humans and animals about maternal dietary influence on offspring skeletal health.

In many cells throughout the body, vitamin D is converted into its active form calcitriol and binds to the vitamin D receptor (VDR), which functions as a transcription factor to regulate various biological processes including cellular differentiation and immune response. Vitamin D-metabolising enzymes (including CYP24A1 and CYP27B1) and VDR play major roles in exerting and regulating the effects of vitamin D. Preclinical and epidemiological studies have provided evidence for anti-cancer effects of vitamin D (particularly against colorectal cancer), although clinical trials have yet to prove its benefit. In addition, molecular pathological epidemiology research can provide insights into the interaction of vitamin D with tumour molecular and immunity status. Other future research directions include genome-wide research on VDR transcriptional targets, gene–environment interaction analyses and clinical trials on vitamin D efficacy in colorectal cancer patients. In this study, we review the literature on vitamin D and colorectal cancer from both mechanistic and population studies and discuss the links and controversies within and between the two parts of evidence.