Epigenetic drift causes modification in gene expression during aging and a myriad of physiological changes that are mostly undesirable, remove youthful phenotype and are related to biological decay and disease onset. The epigenome is considered a stable regulator of genetic expression. Moreover, evidence is now accumulating that commonly available compounds found in foods can influence the epigenome to embrace a more youthful and therefore, more disease resistant state. Here we explore the correlation between nutriment and the epigenetic regulation through various types of alimentation. The aim is not to discuss specific chemicals involved in disease onset. Instead, we offer a brief glance at pathogens and offer a practical pathway into epigenetic regulation, hypothesizing that epigenetic drift might be attenuated by several foods able to drive a more youthful and disease resistant phenotype.

Non-alcoholic fatty liver disease (NAFLD) is considered as one of the most common causes of chronic liver disease. It includes a group of conditions associated with fat deposition in liver cells. Also, NAFLD is strongly associated with obesity and insulin resistance (IR). Until now, there is no pharmacological treatment validated for this disease. Fasting, nutritional intervention, and weight loss can be considered the first line in treating hepatic steatosis. This review is based on the scientific evidence showing the results of these interventions in the past years. The results include fasting and nutritional support for NAFLD treatment in humans. In clinical trials and cohort studies, an increase in hepatic fat content was correlated with a weight loss of at least 7% and a diet resembling the Mediterranean diet (MD) improving hepatic biomarkers and histological regression of NAFLD. Fasting is a dietary approach known to improve the lipid profile in healthy and obese populations by decreasing overall cholesterol, triglycerides, LDL, and increasing HDL. Bariatric surgery helps improve liver fat content in patients with serious health problems due to overweight.

Studies showed that vitamin D (25-hydroxyvitamin D) level in the human blood circulation could be affected by exogenous estrogen exposure. This study aims to explore the relationships between urinary phytoestrogens metabolites and serum total 25(OH)D in general population, urinary phytoestrogens metabolites (daidzein, enterodiol, enterolactone, equol, genistein and o-desmethylangolensin). Totally 2,609 adults ≥6 y old from the 2009–2010 National Health and Nutrition Examination Surveys (NHANES) were recruited into the cross-sectional analyses and information including demographic, socioeconomic, examinations and laboratory test were collected. All analyses were performed using Stata13.0, one-way analysis of variance and multivariable regression were utilised according to data characteristics, respectively. It showed that age, race, education level, body mass index (BMI), and sampling season had significant effects on serum 25(OH)D level (all p<0.001). In the whole population, urinary enterodiol and equol were significantly positively associated with serum total 25(OH)D level (β=0.86, 95%CI=0.08–1.65, p<0.05; β=1.68, 95%CI=0.91–2.45, p<0.001). Equol was also found significantly positively correlated with total 25(OH)D in both female and male separately (β=1.69, 95%CI=0.51–2.87, p<0.05; β=1.66, 95%CI=0.63–2.69, p<0.05). Phytoestrogen concentrations in the urinary and 25(OH)D levels in the serum had proved a positive correlation in our study, which provide theoretical basis and reference for the dietary nutrient intake in the population.

Sunlight exposure and oral supplementation are the key strategies to increase serum 25-hydroxyvitamin D [25(OH)D] concentration. We aimed to determine elevation in serum 25(OH)D levels by comparing sunlight exposure and oral vitamin D supplementation in vitamin D-deficient participants who chose the treatment strategy by shared decision-making. We enrolled 197 participants aged ≥19 y who had vitamin D deficiency (serum 25(OH)D<20 ng/mL). Participants selected their treatment method through shared decision-making by preference: sunlight exposure or 1,000 IU oral vitamin D3 supplementation daily. Changes in serum 25(OH)D concentration and duration of sunlight exposure were evaluated after 3 mo. Among 197 participants, 26 (13%) selected sunlight exposure and 171 (87%) selected oral vitamin D supplementation. Seasonal distribution of participants and follow-up rate after 3 mo were not significantly different. There was no significant increase in mean serum 25(OH)D levels in the sunlight exposure group. Conversely, the mean serum 25(OH)D level increased by 11 ng/mL after 3 mo in the oral vitamin D supplementation group. The duration of mean sunlight exposure per day during the study period was not significantly different between the groups. Oral supplementation with 1,000 IU vitamin D3 daily significantly increased serum 25(OH)D levels in vitamin D-deficient participants after 3 mo, while sunlight exposure did not. This study suggests that oral supplementation is more effective than sun exposure in increasing vitamin D levels in the Korean population. Therefore, new recommendations on maintaining adequate vitamin D levels are needed in the Korean population.

Colorectal cancer is the main leading cause of death from cancer worldwide. Protective effects of vitamin B1 on colorectal cancer have been observed in some epidemiological studies. A systematic review and meta-analysis of observational studies evaluated the association of intake of vitamin B1 with the incidence of colorectal cancer. Relevant studies were identified in MEDLINE via PubMed (published up to September 2020). We extracted data from articles on vitamin B1 and used a multivariable-adjusted odds ratio (OR) and a random-effects model for analysis. We found seven articles meeting the inclusion criteria (1 of cohort studies and 6 case-control studies) and a total of 6,184 colorectal cancer cases were included in this meta-analysis. The multivariable-adjusted OR for pooled studies for the association of roughly the same high dose level versus the lowest vitamin B1 intake and the risk of colorectal cancer was 0.76 (95% confidence interval ([95%CI]: 0.65, 0.89). This meta-analysis studied the relationship between vitamin B1 and colorectal cancer. We found vitamin B1 intake was inversely associated with the risk of colorectal cancer. However, further research and large sample studies need to be conducted to better validate the result.

In cholestatic liver diseases, coagulopathy is induced by malabsorption of vitamin K. Supplementation of vitamin K has previously been shown to prevent coagulopathy. In this study, we tested the efficacy of a newly invented micellized vitamin K2 (m-vitK2) in treating coagulopathy, using a rat bile duct ligation (BDL) model. Experiment 1: m-vitK2 (0.3 mg/kg) or m-vitK2 (0.3 mg/kg) mixed with taurocholic acid (TA) (10 mg/body) was orally administrated every day for 7 d from the fourth day after BDL (n=6 for each). Experiment 2: To evaluate absorption, m-vitK2 (0.3 mg/kg) with or without TA (10 mg/body) was orally administered on the fourth day after BDL and compared with the untreated control BDL (n=2 for each). These data were compared with sham-operated (n=6) and untreated control BDL rats (n=6). The m-vitK2 recovered prothrombin time (PT) in Experiment 1 (control 42.7±5.7 s vs. m-vitK2 24.0±9.3 s, p<0.05). Experiment 2 demonstrated that the mixture of m-vitK2 and TA enhanced absorption compared to m-vitK2 alone. Moreover, in Experiment 1, m-vitK2 mixed with TA completely recovered PT (control 42.7±5.7 s vs. m-vitK2+TA 14.9±1.2 s, p<0.01). Micelle sizes decreased with the m-vitK2 and TA treatment (m-vitK2 86.3±5.6 nm vs. m-vitK2+TA 71.9±4.7 nm, p<0.05). Orally administered, newly invented m-vitK2 recovered coagulopathy even under obstructive jaundice. TA decreased the mean micelle size and improved m-vitK2 absorption.

Sodium nitrite (NaNO₂) is a widely used food additive. The present study compared the outcomes from intakes of dietary NaNO₂ and a high-fat diet (HFD), and assessed their combined effects on inflammatory gene expression in the immune tissues of the mouse. In experiment I, mice were fed a standard low-fat diet (LFD) without or with NaNO₂ (0.02 and 0.08%, w/w) for 11 wk. In experiment II, mice were fed an LFD without or with NaNO₂ (0.02%) or HFD without or with NaNO₂ (0.02%) for 11 wk. Inflammatory gene expression in the immune tissues was then measured. NaNO₂ consumption and HFD feeding each resulted in increased splenic mRNAs for cell markers of neutrophils (Ngp, NE, Ly6g, Mpo) and eosinophils (Epo, Ear6), and an S100 family member (S100A8). In contrast, NaNO₂ consumption and HFD feeding each resulted in decreased splenic mRNAs for cell markers of macrophages (Emr1, Itgax, CD68, CD206, Dectin-1, TLRs 4, 6, and 7), T- (CD3, CD4), NK- (CD56) and B-cells (CD20, CD40), pro- and anti-inflammatory cytokines (TNF-α, IL-6, IL-1β, IFN-γ, IL-18, IL-10, TGF-β), interleukin receptor antagonists (IL1ra, IL6ra) and cell adhesion molecules (ICAM-1, VCAM-1). However, dietary NaNO₂ combined with HFD feeding caused no further decrease in these transcript levels compared with dietary NaNO₂ alone. These NaNO₂- or HFD-induced modifications were less profound in the liver and abdominal adipose tissues than in the spleen. These findings indicate that dietary NaNO₂ has similar modulatory effects to HFD feeding on splenic inflammatory genes.

The association of homocysteine metabolism-related nutrients along with renal function to homocysteine levels is not well known in patients with type 2 diabetes mellitus (T2DM). We investigated the relevance of kidney function, albuminuria, and nutritional factors to serum homocysteine in T2DM patients. This cross-sectional study enrolled 149 T2DM patients (96 men and 53 postmenopausal women), and patient characteristics and laboratory data including kidney-related data [glomerular filtration rate (eGFR), urinary albumin excretion (UACR), uric acid] and metabolism parameters (hemoglobin A1c and lipids) were collected from the medical record and serum levels of vitamin B12, folic acid, zinc, homocysteine and UACR were also acquired. In total subjects, serum levels of homocysteine, vitamin B12, and folic acid were within reference intervals, but zinc levels were close to lower limits of its reference interval. A multivariate-adjusted analysis showed that gender (β=−0.259, p<0.001), uric acid (β=0.267, p<0.001), eGFR (β=−0.188, p=0.001), log UACR (β=0.190, p=0.002), log folic acid (β=−0.259, p<0.001), log vitamin B12 (β=−0.224, p<0.001) and zinc (β=−0.169, p=0.006) were correlated to log homocysteine. In multiple regression analysis by gender, these correlations were found similarly in men, but neither log folic acid nor zinc showed correlations with log homocysteine in women. The present study suggests that renal function parameters and the certain nutritional factors have a possible influence on serum homocysteine, in T2DM patients including diabetes kidney disease.

CYP24A1 regulates serum vitamin D (VD) levels by inactivating 25(OH)₂D₃, which is the precursor of the active form of VD [1α,25(OH)₂D₃], and CYP24A1 expression is controlled by multiple calcemic factors such as 1α,25(OH)₂D₃, calcium, and phosphate. A major phosphaturic factor, FGF23, has also been identified as a regulator of serum VD levels by affecting renal CYP24A1 gene expression; however, its effect on CYP24A1 in extrarenal cells remains largely unstudied. Therefore, the direct effect of FGF23 on CYP24A1 was examined in a human keratinocyte cell line (HaCaT). In this cell line, significant induction of CYP24A1 gene expression by 1α,25(OH)₂D₃ was seen within 4 h by qRT-PCR, and this was mediated by the VD receptor, as shown in a mutant cell line genetically deficient in this receptor. However, FGF23 treatment up to 12 h did not induce CYP24A1 expression, although the expected activation of the downstream MAPK signaling pathway was seen. High calcium and phosphate treatments were also ineffective in inducing CYP24A1 gene expression. Furthermore, a luciferase assay showed no activation of a VD-sensitive proximal CYP24A1 promoter in response to the calcium and phosphate treatments, suggesting that the effect of FGF23 on dermal CYP24A1 gene expression is indirect. From these findings, we speculate that CYP24A1 gene regulation by FGF23 occurs mainly in renal cells, but not in extrarenal cells, at least not in keratinocytes.