Vitamin D3 (VD3) is a fat-soluble vitamin that can accumulate in the body and lead to toxicity by increasing 25(OH) D levels when consumed in large amounts. Maintaining 25(OH) D levels greater than 30 ng/mL is crucial for overall health due to the significant role of vitamin D in the body. The most common causes of VD3 intoxication are manufacturing errors or self-administration. Currently, there is no definitive data on the dose and duration of VD3 consumption that leads to toxicity. The maximum daily doses of VD3 that can be tolerated without causing adverse effects are not established. The maximum recommended amount for long-term supplementation is 2,000 units per day. Vitamin D3 toxicity (VDT) can present in various scenarios, ranging from asymptomatic to gastrointestinal, and in severe cases with neuropsychiatric and life-threatening symptoms. We report the case of a 29-year-old man who presented with symptoms of VDT following an accidental overdose of VD3 over 2 weeks.

Results regarding the epidemiological association of vitamin D with lung (LCA) and prostate cancer (PCA) are controversial. This study tested whether serum 25-hydroxyvitamin D [25(OH)D] concentrations have interactive epidemiological associations with smoking, the number-one risk factor for LCA, and age, the number-one risk factor for PCA. Also, this study investigated whether the associations of 25(OH)D, smoking, age, alcohol consumption, body mass index, diet (the healthy Nordic diet score), and physical activity with incident LCA and PCA are multiplicative or additive. The study of association types makes it easier to select appropriate statistical methods. The Kuopio Ischaemic Heart Disease Risk Factor Study provided the data of 2578 men with 112 LCA and 300 PCA cases over 35 years by the end of 2019. Serum 25(OH)D did not associate with LCA and PCA or interact with smoking and age. The association of smoking with LCA was additive; 13 extra cases per 1000 men every 10 years. Age and alcohol consumption multiplicatively increased the hazard of LCA (hazard ratio, 95% confidence interval for age >50: 3.56, 1.82-6.17; drink per week: 1.01, 1.00-1.03), whereas adherence to healthy Nordic diet decreased it (per score point: 0.95, 0.89-1.00). The association of age >50 with PCA was additive; 2.5 extra cases per 1000 men every 10 years. To conclude, there was no epidemiological relationship of pre-diagnostic 25(OH)D concentrations with the incidence of LCA and PCA. The respective associations of smoking and age >50 with LCA and PCA were additive rather than multiplicative.

In the last few years, numerous studies have demonstrated that dietary modifications in the form of calory restriction exert beneficial effects in several clinical entities, including aging-related pathologies, autoimmune diseases and cancer. Both as preventive but also as therapeutic modalities, these dietary regimens can impact systemic metabolism, immune and hormonal responses, redox balance and gut microbiota, among others. In the field of oncology, the vast majority of experimental work has explored the role of restricted diets in the prevention of malignant tumors, mostly in carcinogenesis-induced models, with at least encouraging results; on the contrary, less research has been performed in the management of full-blown cancer with ketogenic diet or caloric restriction protocols. Herein, we are aiming to review the relevant preclinical and clinical studies to date that investigate the role of caloric restriction in the treatment of established cancer.

Background: The Human Immunodeficiency Virus (HIV) epidemic is still a public health concern. Micronutrient deficiencies can fasten the progression of this syndrome. Selenium and zinc are essential trace elements, which exert antioxidant and anti-inflammatory activities in HIV infection. The present overview aimed to evaluate the current knowledge from systematic reviews (SRs) of the effects of selenium and zinc supplementation in HIV patients to show the most updated and comprehensive summary of previous SRs. Methods: The current study was performed according to the guidelines of the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statements. To assess the quality of articles we used the Measurement Tool to Checklist Assess Systematic Reviews (AMSTAR). PubMed/Medline, Web of Science, Scopus, and EMBASE databases and Google Scholar web search engine were searched up until March 2022, using relevant keywords. Results: Among 3731 articles assessed, five and four studies met the inclusion criteria for selenium and zinc supplementation, respectively. Four studies found that selenium supplementation can be effective in delaying CD4 decline in HIV-infected patients. In four SRs, the dosage of selenium supplementation was 200 μg/day. Three studies, however, reported no significant effect of zinc supplementation on CD4 cell counts, and HIV viral load. The dosage of zinc supplementation ranged from 12 to 100 mg/day. The intervention duration ranged from 2 weeks to 18 months. Conclusion: In the present study, we identified some clinical evidence of a potential beneficial effect of selenium supplementation in HIV-infected patients.

Elevated homocysteine (Hcy) levels (≥15 μmol/L) in the elderly are frequently associated with a higher risk of cardiovascular disease and cognitive decline. Several studies have already shown an Hcy-lowering effect of B vitamin supplementation in cohorts deficient in these nutrients. The aim of this randomized, double-blinded 12-week intervention study was to investigate whether Hcy levels in healthy elderly subjects (75.4±4.5 years, n=133) could be lowered with a micronutrient supplement (i.e., 400 μg folic acid, 100 μg cobalamin). Difference in mean initial Hcy levels between intervention (17.6±7.1 μmol/L, n=65) and placebo group (18.9±6.1 μmol/L, n=68) was not significant. The prevalence of cobalamin and folate deficiency in the total study population was low: 27% had serum-cobalamin levels ≤150 pmol/L, 12% holo-transcobalamin (Holo-TC) levels ≤50 pmol/L, 13% low cobalamin status using the aggregated cobalamin marker 4cB12 and 10% red blood cell (RBC) folate ≤570 nmol/L. Nevertheless, the treated subjects still showed improved cobalamin and folate biostatus (serum cobalamin Δt12-t0: 63±48 pmol/L; Holo-TC Δt12-t0: 17±19 pmol/L; RBC folate Δt12-t0: 326±253 nmol/L) and Hcy levels (Δt12-t0: -3.6±5.7 μmol/L). The effects were statistically significant compared to the placebo group with p=0.005 (serum cobalamin), p=0.021 (Holo-TC), p=0.014 (RBC-folate) and p<0.001 (Hcy). The Hcy-lowering effect was dependent on the initial Hcy levels (p<0.001). Our findings suggest that elevated Hcy levels in elderly subjects can be lowered regardless of the initial cobalamin and folate biostatus.

Background: Previous observational epidemiological studies such as case-control studies and cohort studies have reported inconsistent results regarding the associations between seafood intake and the risk of thyroid cancer. Materials and methods: We searched PubMed and EMBASE in August 2021 using keywords related to seafood intake and thyroid cancer. A pooled odds ratio (OR) or relative risk (RR) with its 95% confidence interval (CI) was calculated. Results: We included 17 observational studies with 13 case-control studies and 4 cohort studies, which included 4,309 thyroid cancer patients among 599,161 participants. In the random effects model meta-analysis of all 17 studies, we found that there was no significant association between seafood intake (highest vs. lowest intake) and the risk of thyroid cancer (OR or RR, 1.01; 95% CI: 0.86 to 1.19; I2=51.4%). Although the associations were not statistically significant, subgroup meta-analyses by study design showed opposite findings: seafood intake decreased the risk of thyroid cancer in case-control studies (OR or RR, 0.94; 95% CI: 0.74 to 1.19; I2=60.6%; n=13) but increased in cohort studies (OR or RR, 1.14; 95% CI: 0.97 to 1.35; I2=0.0%; n=4). Conclusion: The current meta-analysis of observational epidemiological studies found that that overall, there was no significant association between seafood intake and the risk of thyroid cancer. However, given that cohort studies give us a higher level of evidence than case-control studies, further prospective cohort studies are warranted to confirm the association between them.

Background: Previous studies have shown that some dietary components may be implicated in the aetiology of postmenopausal osteoporosis. Objective: We examined the relationship between Dietary Inflammatory Index (DII®) and osteoporosis in postmenopausal women. Study design: Eight hundred and fifty postmenopausal women aged 50-65 years were randomly selected from 87 health care centers. Bone mineral density (BMD) was measured using the anterior-posteriorlumbar spine (L1-L4) and proximal femur neck through Hologic QDR 4500W(S/N 50266) dual-energy X-ray absorptiometry device. After checking inclusion and exclusion criteria and diagnosis of osteoporosis, 124 women with normal bone mineral density (normal-BMD) and 108 women with osteoporosis were selected. Demographic, anthropometric, physical activity, midwifery, and dietary intake questionnaires were completed. DII was calculated based on a valid and reliable 168-item semi-quantitative food frequency questionnaire using 37 (out of 45) food parameters. A Logistic regression model adjusted for confounders was applied to estimate osteoporosis's odds ratio (OR) based on modeling DII as a continuous and dichotomous variable. Results: In this study, DII scores ranged from -3.71 (the most anti-inflammatory score) to +4.16 (the most pro-inflammatory score). The median DII value among the osteoporosis group was 0.97, among the normal group it was -0.31, indicating a more pro-inflammatory diet for osteoporosis. There were positive associations between osteoporosis and DII based on both continuous (Adjusted OR=3.467, 95% confidence interval (CI): 2.280-5.272, P-value<0.001) and dichotomous (Adjusted OR: DII ≤-0.31 / >-0.31=0.248, 95% CI: 0.110-0.561, P-value=0.001) measures in modeling adjusted for age, BMI, post-menopausal years, parity, education, total energy intake, and physical activity. Conclusions: These data suggest a pro-inflammatory diet, as indicated by increasing the DII score, may be a risk factor for osteoporosis in postmenopausal Iranian women.

Apart from bone related effects, vitamin D has roles in immune modulation, hypertension, diabetes and cardiovascular diseases. Metabolic functions of vitamin D are mediated after binding with vitamin D receptor (VDR). VDR polymorphisms affect its physiological functions. Several VDR single nucleotide polymorphisms (SNPs) were reported previously. However, VDR polymorphisms causing influence on cardiovascular and metabolic disorders have not been investigated in the Pakistani population so far. Therefore, the present study was conducted to evaluate the role of VDR polymorphisms (rs2228570 and rs7975232) in the pathobiology of cardiometabolic disorders. In total, 400 cardiometabolic patients and 226 healthy control human adults were enrolled from Faisalabad, Pakistan. Biochemical parameters (serum glucose, liver function test, renal function test and lipid profile) were analyzed by standard kit methods. Genetic analysis was done by ARMS-PCR assay. Data was analyzed in SPSS v20. Regression analysis revealed that GG and AG genotypes of rs2228570 A>G polymorphism significantly increased the risk of hypertension in cardiovascular patients by 5.29 and 5.94 times respectively (GG: OR=5.29, 95% CI=1.63-17.2, p=0.005; AG: OR=5.94, 95% CI=1.70-20.7, p=0.005). However, rs7975232 C>A polymorphism was not correlated with cardiometabolic conditions. In conclusion, GG and AG genotypes of VDR SNP rs2228570 significantly contribute to hypertension in cardiovascular disease patients.

Background: The hypertriglyceridemic waist (HTGW) phenotype is characterized by concomitant increases in waist circumference (WC) and blood triglyceride levels (TG), which have been identified as a predictor of metabolic disorders. This study aimed to analyze associations between food consumption, exercise, and the CD36 gene rs1761667 G>A polymorphism with the HTGW phenotype in adult Mexicans. Methods: This cross-sectional study included a total of 255 participants (both genders, between 18-64 years of age). The HTGW phenotype was defined as WC >88 cm in women, WC >102 cm in men, and TG >150 mg/dL. Body composition was analyzed by electrical bioimpedance. Dietary intakes (macro and micronutrients) were evaluated through a validated 64-item food frequency questionnaire and a 24-h recall. Physical exercise was subjectively recorded asking the participants if they regularly performed some systematic exercise or sport of moderate intensity at least 150-300 minutes a week. Biochemical tests were determined by an automated system. A Taqman real-time assay was used to detect the rs1761667 (G>A) polymorphism of the CD36 gene. A multivariate logistic regression model was performed to analyze the variables potentially associated with the HTGW phenotype (adjusted for age, energy intake, and total fat mass). Results: Overall, 21.6% of the population presented the HTGW phenotype; compared to the HTGW-, also, they were older, had more body fat, higher glucose, cholesterol and insulin levels, and high blood pressure. Female sex (OR=2.92, 95% CI: 1.12-7.60, p=0.028), body mass index (OR=1.19, 95% CI: 1.07-1.32, p=0.001), total cholesterol (OR=1.01, 95% CI:1.00-1.02, p=0.039), daily consumption of sugary drinks (OR=6.94, 95% CI: 1.80-26.8, p=0.005), and the CD36 AG genotype (OR=3.81, 95% CI: 1.08-13.4, p=0.037) were positively associated with the HTGW phenotype, while performing exercise played a protective role (OR=0.23, 95% CI: 0.08-0.62, p=0.004). Overall, the model predicted the HTGW phenotype in 47% (R2=0.47, p≤0.001). Conclusion: The CD36 AG genotype, daily consumption of sugary drinks and sedentarism are risk factors for the HTGW phenotype in Mexicans.

Background and aims: Experimental studies showed that carotenoids had anti-carcinogenic properties, but epidemiological studies on the association between dietary carotenoids and esophageal squamous cell carcinoma (ESCC) risk were limited, and the findings were inconsistent. This study aimed to investigate the roles of intake of dietary carotenoids in the development of ESCC among a rural Chinese population. Methods: A population-based case-control study was conducted in Southwest China. A total of 915 incident ESCC cases and 925 community-based controls were included. A validated food frequency questionnaire with 76-item was adopted to collect information about dietary consumption. Intake of dietary calories and each carotenoid was calculated according to the China food composition tables. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by a logistic regression model, with adjustments for age, gender, body mass index, family cancer history, cigarette smoking, alcohol drinking, education, marital status, prudent pattern score, and total calories. Results: In comparison to the highest with lowest intake quartiles, intake of total carotenes (OR: 0.70, 95% CI: 0.52-0.96, Ptrend: 0.024), α-carotene (OR: 0.62, 95% CI: 0.46-0.83, Ptrend: 0.014), β-carotene (OR: 0.63, 95% CI: 0.46-0.86, P-trend: 0.005), and the sum of lutein and zeaxanthin (OR: 0.41, 95% CI: 0.29-0.56, Ptrend<0.001) was significantly associated with a decreased risk of ESCC after adjustment for confounders. Conclusions: The results indicated that a higher intake of total carotene, α-carotene, β-carotene, and the sum of lutein and zeaxanthin was associated with a lower risk of ESCC.