Project description:BackgroundKlotho is a hormone that emerges as an antiaging biomarker. However, the influence of the dietary pattern's inflammatory potential on serum Klotho levels in human populations, especially in a general adult population, remains unknown. This study aimed to evaluate the relationship between the dietary inflammatory index (DII) and serum Klotho concentrations in individuals living in the United States. METHODS : From the 2007-2016 National Health and Nutrition Examination Survey database, data of participants who completed the full 24-h dietary history and underwent serum Klotho testing were analyzed. The association between DII and serum Klotho concentrations was estimated using multivariable linear regression models. We also conducted segmented regression model to examine the threshold effect of DII on serum Klotho concentrations.ResultsA total of 10,928 participants were included, with a median serum Klotho concentration of 805.20 pg/mL (IQR: 657.58 - 1001.12) and a median DII of 1.43 (IQR: - 0.16 - 2.82). Multivariable regression showed that participants with high DII scores were associated with low serum Klotho concentrations; when classifying DII into quartiles, after full adjustment, participants in DII quartiles 3 and 4 showed a decrease in Klotho levels (25.27 and 12.44 pg/ml, respectively) compared with those in the lowest quartile (quartile 1) (95% CI: - 41.80, - 8.73 and - 29.83, 4.95, respectively; P for trend = 0.036). The segmented regression showed that the turning point value of DII was - 1.82 (95% CI: - 2.32, - 0.80). A 1-unit increase in DII was significantly associated with lower Klotho levels by - 33.05 (95% CI: - 52.84, - 13.27; P = 0.001) when DII ranges from - 5.18 to - 1.82; however, the relationship was not significant when DII ranges from - 1.82 to 5.42 (P > 0.05). Furthermore, stratified analyses indicated that the observed associations between DII and serum Klotho concentration were stronger among those aged ≥ 56 years, those with normal weight, and those without chronic kidney disease (P for interaction = 0.003, 0.015, and 0.041, respectively).ConclusionsIn summary, we indicated that there was a dose-response relationship between DII and serum Klotho concentrations, suggesting that adhering to an anti-inflammatory diet has beneficial effects on aging and health by increasing the serum Klotho concentration.
Project description:BackgroundKlotho has anti-oxidative and anti-inflammatory properties. However, little is known about whether high Klotho concentrations were associated with reduced hyperlipidemia risk and improved plasma lipid levels.MethodsParticipants with complete data on serum Klotho and plasma lipid concentrations from the 2007-2016 National Health and Nutrition Examination Survey were included. Weighted regression models were fitted to explore the association of Klotho concentrations with hyperlipidemia risk and plasma lipid levels while restricted cubic spline models were applied to explore the dose-response relationship. Additionally, we assessed the mediating effects of C-reaction protein (CRP) on the foregoing association.ResultsIndividuals in the fourth and fifth quintile of serum Klotho had an adjusted odds ratio (OR) of 0.77 (95%CI: 0.65, 0.93) and 0.67 (95%CI: 0.65, 0.93) for hyperlipidemia. Doubling of serum Klotho concentrations was associated with decreased hyperlipidemia risk (OR = 0.81; 95%CI: 0.68, 0.95) and triglyceride levels (13.25 mg/dL; 95%CI: 4.02, 22.47), with a monotonic dose-response relationship. Individuals in the fourth and fifth quintile of serum Klotho had a 0.07 (95%CI: 0.002, 0.13), 0.08 (95%CI: 0.02, 0.15) and 0.05 (95%CI: -0.03, 0.12) mg/dL decreased CRP levels, with a marginally significant trend (Ptrend = 0.05).ConclusionsHigher Klotho concentrations were associated with reduced hyperlipidemia risk and triglyceride levels. Klotho supplementation maybe a promising method to intervene and prevent hyperlipidemia, but the underlying mechanism should be further explored.
Project description:The wide spectrum of vitamin D activity has focused attention on its potential role in the elevated burden of disease in a northern Canadian First Nations (Dené) cohort. Vitamin D insufficiency, and gene polymorphisms in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) have been implicated in susceptibility to infectious and chronic diseases. The objectives of this study were to determine the contribution of vitamin D from food, and measure the serum concentrations of 25-hydroxyvitamin D(3) (25-OHD(3)) and VDBP in Dené participants. Single nucleotide polymorphisms (SNPs) associated with the dysregulation of the innate immune response were typed and counted. Potential correlations between the SNPs and serum concentrations of 25-OHD(3) and VDBP were evaluated. Venous blood was collected in summer and winter over a one-year period and analyzed for 25-OHD(3) and VDBP concentrations (N?=?46). A questionnaire was administered to determine the amount of dietary vitamin D consumed. Sixty-one percent and 30% of the participants had 25-OHD(3) serum concentrations <75 nmol/L in the winter and summer respectively. Mean vitamin D binding protein concentrations were within the normal range in the winter but below normal in the summer. VDBP and VDR gene polymorphisms affect the bioavailability and regulation of 25-OHD(3). The Dené had a high frequency of the VDBP D432E-G allele (71%) and the Gc1 genotype (90%), associated with high concentrations of VDBP and a high binding affinity to 25-OHD(3). The Dené had a high frequency of VDR Fok1-f allele (82%), which has been associated with a down-regulated Th1 immune response. VDBP and VDR polymorphisms, and low winter 25-OHD(3) serum concentrations may be risk factors for infectious diseases and chronic conditions related to the dysregulation of the vitamin D pathway.
Project description:We systematically investigated the association of 48 SNPS in four vitamin D metabolizing genes [CYP27A1, GC, CYP27B1 and CYP24A1] with serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels and the association of these SNPS and an additional 164 SNPS in eight downstream mediators of vitamin D signaling [VDR, RXRA, RXRB, PPAR, NCOA1, NCOA2, NCOA3 and SMAD3] with prostate cancer risk in the 749 incident prostate cancer cases and 781 controls of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. 25(OH)D (all cases and controls) and 1,25(OH)(2)D (a subset of 150 controls) levels were measured by radioimmunoassay and SNP data were genotyped as part of a genome-wide scan. Among investigated SNPS, only four tag SNPS in GC, the major serum 25(OH)D carrier, were associated with 25(OH)D levels; no SNPS were associated with 1,25(OH)(2)D levels. None of the 212 SNPS examined were associated with cancer risk overall. Among men in the lowest tertile of serum 25(OH)D (<48.9 nmol/l), however, prostate cancer risk was related to tag SNPS in or near the 3' untranslated region (UTR) of VDR, with the strongest association for rs11574143 [odds ratio (95% confidence interval) for risk allele carriers versus wild-type: 2.49 (1.51-4.11), P = 0.0007]; the genotype associations were null among men in tertile 2 and tertile 3. Results from the most comprehensive evaluation of serum vitamin D and its related genes to date suggest that tag SNPS in the 3' UTR of VDR may be associated with risk of prostate cancer in men with low vitamin D status.
Project description:PurposeAlcohol consumption is an established breast cancer risk factor, though further research is needed to advance our understanding of the mechanism underlying the association. We used global metabolomics profiling to identify serum metabolites and metabolic pathways that could potentially mediate the alcohol-breast cancer association.MethodsA cross-sectional analysis of reported alcohol consumption and serum metabolite concentrations was conducted among 211 healthy women 25-29 years old who participated in the Dietary Intervention Study in Children 2006 Follow-Up Study (DISC06). Alcohol-metabolite associations were evaluated using multivariable linear mixed-effects regression.ResultsAlcohol was significantly (FDR p < 0.05) associated with several serum metabolites after adjustment for diet composition and other potential confounders. The amino acid sarcosine, the omega-3 fatty acid eicosapentaenoate, and the steroid 4-androsten-3beta,17beta-diol monosulfate were positively associated with alcohol intake, while the gamma-tocopherol metabolite gamma-carboxyethyl hydroxychroman (CEHC) was inversely associated. Positive associations of alcohol with 2-methylcitrate and 4-androsten-3beta,17beta-diol disulfate were borderline significant (FDR p < 0.10). Metabolite set enrichment analysis identified steroids and the glycine pathway as having more members associated with alcohol consumption than expected by chance.ConclusionsMost of the metabolites associated with alcohol in the current analysis participate in pathways hypothesized to mediate the alcohol-breast cancer association including hormonal, one-carbon metabolism, and oxidative stress pathways, but they could also affect risk via alternative pathways. Independent replication of alcohol-metabolite associations and prospective evaluation of confirmed associations with breast cancer risk are needed.
Project description:BackgroundMany studies have suggested that the serum concentrations of vitamin A (VA) and vitamin E (VE) influence preeclampsia (PE) risk in pregnant women. However, few studies have assessed whether dietary intake and serum concentrations of VA and VE are correlated with PE risk.MethodsA 1:1 matched case-control study was conducted to explore the association between the dietary intake and serum concentrations of VA and VE and the risk of PE in pregnant Chinese women. A total of 440 pregnant women with PE and 440 control pregnant women were included in the study. Dietary information was obtained using a 78-item semi-quantitative food frequency questionnaire. Serum concentrations of VA and VE were measured by liquid chromatography-tandem mass spectrometry.ResultsCompared with the lowest quartile, the multivariate-adjusted odds ratios [95% confidence interval (CI)] of the highest quartiles were 0.62 (95% CI: 0.40-0.96, P trend = 0.02) for VA, 0.51 (95% CI: 0.33-0.80, P trend =0.002) for β-carotene, and 0.70 (95% CI: 0.45-1.08, P trend = 0.029) for retinol. Additionally, for serum VA and VE concentrations, the multivariate-adjusted odds ratios (95% CI) were 2.75 (95% CI: 1.24-6.13, P trend = 0.002) and 11.97 (95% CI: 4.01-35.77, P trend < 0.001), respectively. No significant association was seen between VE intake and PE risk.ConclusionsDietary VA intake was negatively correlated with PE risk, and serum VA and VE concentrations were positively correlated with PE risk among pregnant Chinese women.
Project description:BackgroundVitamin A deficiency is a public health problem in sub-Saharan Africa. Pro-vitamin A biofortified (yellow) cassava has the potential to contribute significantly to improve vitamin A status, especially in populations that are difficult to reach with other strategies.ObjectivesThe study aimed at determining the efficacy of biofortified cassava to improve vitamin A status of Nigerian preschool children.MethodsAn open-label randomized controlled trial was conducted in southwestern Nigeria. In total, 176 preschool children (aged 3-5 y) were randomized into 2 parallel arms comprising an experimental group (n = 88), fed foods prepared from biofortified (yellow) cassava, and a control group (n = 88), fed foods prepared from white cassava, twice a day, 6 d a week for 93 d.ResultsA total of 159 children completed the trial (yellow cassava group, n = 80; white cassava group, n = 79). Children consumed 221 and 74 µg/d retinol activity equivalents from intervention foods in the yellow and white cassava groups, respectively. The treatment effect on serum retinol concentrations at the end of the feeding trial was 0.06 µmol/L (95% CI: 0.004, 0.124 µmol/L), after adjustment for baseline retinol concentrations, inflammation, and asymptomatic malaria status. No significant treatment effects were detected for serum β-carotene (adjusted effect: 3.9%; 95% CI: -0.6%, 8.6%) and gut permeability (adjusted effect: 0.002; 95% CI: -0.089, 0.092), but a significant effect was detected for hemoglobin concentrations (adjusted effect: 3.08 g/L; 95% CI: 0.38, 5.78 g/L).ConclusionsDaily consumption of β-carotene from biofortified cassava improved serum retinol and hemoglobin concentrations modestly in Nigerian preschool children. This study was registered with clinicaltrials.gov as NCT02627222.
Project description:BackgroundThe effects of soy isoflavones on prostate cancer may be concentration-dependent. The impact of soy supplementation on isoflavone concentrations in prostate tissues and serum remain unclear.ObjectiveTo assess and compare concentrations of soy isoflavones in prostate tissue and serum among 19 men with prostate cancer who had elected to undergo radical prostatectomy.MethodsParticipants were randomized to receive either daily soy supplements (82 mg/day aglycone equivalents) or placebos for 2 weeks (14 days) prior to surgery. Serum samples were obtained at the time of the surgery. Isoflavone concentrations were measured by HPLC/ESI-MS-MS.ResultsThe median (25th, 75th percentile) total isoflavone concentration in the isoflavone-supplemented group was 2.3 micromol/L (1.2, 6.9) in the prostate tissue and 0.7 micromol/L (0.2, 1.2) in the serum. Total isoflavone concentrations in this group were an average of approximately 6-fold higher in prostate tissue compared to serum; the tissue versus serum ratio was significantly lower for genistein than daidzein, 4-fold versus 10-fold, P = 0.003. Tissue and serum levels of isoflavones among the placebo group were negligible with a few exceptions.ConclusionsThe findings from the present study suggest that prostate tissue may have the ability to concentrate dietary soy isoflavones to potentially anti-carcinogenic levels.
Project description:BackgroundThe role of Klotho as a multifunctional protein in anemia is unclear. This study aimed to determine the association between anemia and serum Klotho concentrations in middle-aged and elderly populations.MethodsIn this cross-sectional study, we used data collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. A total of 13,357 individuals who received serum Klotho measurements, biochemical tests, and demographic surveys were analyzed. Multivariate linear regression models adjusting for covariates were used to investigate the associations between anemia and serum Klotho.ResultsMultivariable regression showed that serum Klotho correlates positively with hemoglobin and red blood cells and inversely with red cell distribution width. After adjusting for all covariates, compared with Q4, there was a significantly increased risk of anemia in serum Klotho quartiles 1 to 2 (OR=1.54, 95% CI:1.21-1.95, P=0.002; OR=1.30, 95% CI:1.02-1.64, P=0.042,respectively). Segmented regression showed that for every 100 pg/mL increase in serum Klotho <9.746 pg/mL, the risk of anemia was reduced by 10.9%, and this reduction was significant (P<0.001). Furthermore, stratified analyses yielded a stronger association between reduced anemia and high levels of Klotho in men and those with diabetes (P< 0.05 for interaction). However, this association was not found to be significantly altered by chronic kidney disease.ConclusionsIn summary, we indicated that low serum Klotho is associated with an increased likelihood of anemia using a nationally representative sample of middle-aged and older adults.