Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts.

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD). DESIGN: Pooled analysis. DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020. STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate. DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis. MAIN OUTCOME MEASURES: Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2. In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2 and <75% of baseline rate. RESULTS: 25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I2=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I2=0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I2=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (≥60 v <60 years), estimated glomerular filtration rate (60-89 v ≥90 mL/min/1.73 m2), hypertension, diabetes, and coronary heart disease at baseline. CONCLUSIONS: Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.

The FADS1 rs174550 Genotype Modifies the n-3 and n-6 PUFA and Lipid Mediator Responses to a High Alpha-Linolenic Acid and High Linoleic Acid Diets.

SCOPE: The fatty acid composition of plasma lipids, which is associated with biomarkers and risk of non-communicable diseases, is regulated by dietary polyunsaturated fatty acids (PUFAs) and variants of fatty acid desaturase (FADS). We investigated the interactions between dietary PUFAs and FADS1 rs174550 variant. METHODS AND RESULTS: Participants (n = 118), homozygous for FADS1 rs174550 variant (TT and CC) followed a high alpha-linolenic acid (ALA, 5 percent of energy (E-%)) or a high linoleic acid (LA, 10 E-%) diet during an 8-week randomized controlled intervention. Fatty acid composition of plasma lipids and PUFA-derived lipid mediators were quantified by gas and liquid chromatography mass spectrometry, respectively. The high-LA diet increased the concentration of plasma LA, but not its lipid mediators. The concentration of plasma arachidonic acid decreased in carriers of CC and remained unchanged in the TT genotype. The high-ALA diet increased the concentration of plasma ALA and its cytochrome P450-derived epoxides and dihydroxys, and cyclooxygenase-derived monohydroxys. Concentrations of plasma eicosapentaenoic acid and its mono- and dihydroxys increased only in TT genotype carriers. CONCLUSIONS: These findings suggest the potential for genotype-based recommendations for PUFA consumption, resulting in modulation of bioactive lipid mediators which can exert beneficial effects in maintaining health.

Serum Levels of Plasmalogens and Fatty Acid Metabolites Associate with Retinal Microangiopathy in Participants from the Finnish Diabetes Prevention Study.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes, and retinal microaneurysms (MA) are one of the first detected abnormalities associated with DR. We recently showed elevated serum triglyceride levels to be associated with the development of MA in the Finnish Diabetes Prevention Study (DPS). The purpose of this metabolomics study was to assess whether serum fatty acid (FA) composition, plasmalogens, and low-grade inflammation may enhance or decrease the risk of MA. Originally, the DPS included 522 individuals (mean 55 years old, range 40-64 years) with impaired glucose tolerance who were randomized into an intervention (n = 265) or control group (n = 257). The intervention lasted for a median of four years (active period), after which annual follow-up visits were conducted. At least five years after stopping the intervention phase of DPS, participants classified as MA negative (n = 115) or MA positive (n = 51) were included in the current study. All these participants were free of diabetes at baseline (WHO 1985) and had high-sensitive C-reactive protein (hs-CRP), serum FA composition, and selected lipid metabolites measured during the active study period. Among the markers associated with MA, the serum plasmalogen dm16:0 (p = 0.006), the saturated odd-chain FA 15.0 (pentadecanoic acid; p = 0.015), and omega-3 very long-chain FAs (p < 0.05) were associated with a decreased occurrence of MA. These associations were independent of study group and other risk factors. The association of high serum triglycerides with the MA occurrence was attenuated when these MA-associated serum lipid markers were considered. Our findings suggest that, in addition to n-3 FAs, odd-chain FA 15:0 and plasmalogen dm16:0 may contribute to a lower risk of MA in individuals with impaired glucose tolerance. These putative novel lipid biomarkers have an association with MA independently of triglyceride levels.

Cost-Effectiveness of Passion Fruit Albedo versus Turmeric in the Glycemic and Lipaemic Control of People with Type 2 Diabetes: Randomized Clinical Trial.

BACKGROUND: Robust evidence has related yellow passion fruit albedo and long turmeric to the metabolic and glycemic control of diabetes. AIM: To analyze the incremental cost-effectiveness of the flour made from yellow passion fruit albedo versus long turmeric merged with piperine in the glycemic and lipid control of individuals with type 2 diabetes. METHOD: Eighty-nine patients were enrolled in this randomized, placebo-controlled, clinical trial for 120 days. The first group was prescribed 500 mg capsules, three times a day, of yellow passion fruit albedo flour (FAMA). The second group was prescribed long turmeric capsules (500 mg), merged with piperine (5 mg) (CURPI), at fasting. The third group followed the standard advice recommendations, and ingested a placebo of carboxymethyl cellulose (500 mg) at fasting. RESULTS: The group using FAMA showed a higher reduction (-5.9%) of glycemia after fasting, compared to placebo (+9%), and CURPI (-3.2%) (p < 0.05). Regarding HbA1c, the study observed a significant and similar statistical reduction (-0.8%) in the intervention groups, in contrast with the placebo group (p < 0.05). The reduction in HOMA-IR in the CURPI group (-9.4%) was higher than the other groups (p < 0.05). The CURPI group also showed a higher reduction of serum triglyceride levels (-20.8%) compared to the placebo (-0.09%) and FAMA (+1.8%) (p < 0.05) groups. CONCLUSION: It was concluded that turmeric is the most cost-effective in comparison with yellow passion fruit albedo, because of its decrease in the levels of triglycerides and HOMA-IR, even when adjusted for confounding variables. On the other hand, HbA1c cost-effectiveness relation was similar.

Correction to: Liver DNA methylation of FADS2 associates with FADS2 genotype.

Following publication of the original article [1], the author reported the title of this article has been misspelled.

Liver DNA methylation of FADS2 associates with FADS2 genotype.

BACKGROUND: Non-alcoholic fatty liver disease has been associated with increased mRNA expression of FADS2 in the liver and estimated activity of delta-6 desaturase in serum, encoded by the FADS2 gene. Since DNA methylation in the FADS1/2/3 gene cluster has been previously linked with genetic variants and desaturase activities, we now aimed to discover factors regulating DNA methylation of the CpG sites annotated to FADS1/2 genes. METHODS: DNA methylation levels in the CpG sites annotated to FADS2 and FADS1 were analyzed from liver samples of 95 obese participants of the Kuopio Obesity Surgery Study (34 men and 61 women, age 49.5 ± 7.7 years, BMI 43.0 ± 5.7 kg/m2) using the Infinium HumanMethylation450 BeadChip (Illumina). Associations between DNA methylation levels and estimated delta-6 and delta-5 desaturase enzyme activities, liver histology, hepatic mRNA expression, FADS1/2 genotypes, and erythrocyte folate levels were analyzed. RESULTS: We found a negative correlation between DNA methylation levels of cg06781209 and cg07999042 and hepatic FADS2 mRNA expression (both p < 0.05), and with estimated delta-6 desaturase activity based on both liver and serum fatty acids (all p < 0.05). Interestingly, the methylation level of cg07999042 (p = 0.001) but not of cg06781209 (p = 0.874) was associated with FADS2 variant rs174616. CONCLUSIONS: Genetic variants of FADS2 may contribute to the pathogenesis of non-alcoholic fatty liver disease by modifying DNA methylation.

DNA methylation in obesity and type 2 diabetes.

To elucidate the mechanisms related to the development of type 2 diabetes (T2D) and other degenerative diseases at a molecular level, a better understanding of the changes in the chromatin structure and the corresponding functional changes in molecular pathways is still needed. For example, persons with low birth weight are at a high risk for development of T2D later in life, suggesting that the intrauterine environment contributes to the disease. One of the hypotheses is that epigenetic regulation, including changes in DNA methylation leading to modifications in chromatin structure, are behind metabolic alterations, e.g. leading to the phenomenon termed metabolic memory. Altered DNA methylation has been shown to affect healthy aging and also to promote age-related health problems. There is suggestive evidence that lifestyle changes including weight loss can have an impact on DNA methylation and consequently gene expression. In this review we provide an overview of human studies investigating DNA methylation in obesity and T2D and associated risk factors behind these diseases.

Gene expression of peripheral blood mononuclear cells as a tool in dietary intervention studies: What do we know so far?

Peripheral blood mononuclear cells (PBMCs) generally refer to monocytes and lymphocytes, representing cells of the innate and adaptive immune systems. PBMCs are a promising target tissue in the field of nutrigenomics because they seem to reflect the effects of dietary modifications at the level of gene expression. In this review, we describe and discuss the scientific literature concerning the use of gene expression at the mRNA level measured from PBMCs in dietary interventions studies conducted in humans. A search of literature was undertaken using PubMed (last assessed November 24, 2011) and 20 articles were selected for discussion. Currently, results from these studies showed that PBMCs seem to reflect liver environment and complement adipose tissue findings in transcriptomics. PBMC gene expression after dietary intervention studies can be used for studying the response of certain genes related to fatty acid and cholesterol metabolism, and to explore the response of dietary interventions in relation to inflammation. However, PBMC transcriptomics from dietary intervention studies have not resulted yet in clear confirmation of candidate genes related to disease risk. Use of microarray technology in larger well-designed dietary intervention studies is still needed for exploring PBMC potential in the field of nutrigenomics.