Fish oil supplementation and risk of dementia among diabetic patients: a prospective study of 16,061 older patients.

BACKGROUND: Although n-3 Polyunsaturated fatty acids (PUFAs) may benefit cognitive performance, the association of n-3 PUFA intake with dementia risk under dysglycemia has not been examined. We aimed to evaluate the relationship between fish oil supplement use or fish consumption and dementia risk among older patients with diabetes. METHOD: A total of 16,061 diabetic patients aged over 60 years were followed up in the UK Biobank. Fish oil supplements use (yes or no) was collected by the touch screen questionnaire. The diagnosis of dementia was ascertained by the UK Biobank Outcome Adjudication Group. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. RESULTS: A total of 337 cases of dementia were confirmed after a mean duration of 7.7 years (123,486 person-years) of follow-up. Habitual use of fish oil supplements showed a 24% lower dementia risk among older diabetic patients [HRs (95% CIs): 0.76 (0.60-0.98) (P = 0.031)] compared with non-users. Such inverse association was not modified by the APOE ε4 genotype. However, the consumption of both oily fish (≥2 times/week) and non-oily fish (≥2 times/week) had no significant association with dementia risk (p-trend = 0.271 and p-trend = 0.065) compared with non-consumers. CONCLUSION: In summary, fish oil supplementation may play a protective role in cognitive function across all APOE genotypes, while non-oily fish and oily fish consumption have no protective association among older diabetic patients.

Circulating fatty acids, genetic risk, and incident coronary artery disease: A prospective, longitudinal cohort study.

The role of fatty acids (FAs) in primary prevention of coronary artery disease (CAD) is highly debated, and the modification effect by genetic risk profiles remains unclear. Here, we report the prospective associations of circulating FAs and genetic predisposition with CAD development in 101,367 U.K. Biobank participants. A total of 3719 CAD cases occurred during a mean follow-up of 11.5 years. Plasma monounsaturated FAs (MUFAs) were positively associated with risk of CAD, whereas the risk was significantly lower with higher n-3 polyunsaturated FAs (PUFAs) and more reductions in risk were detected among TT carriers of rs174547. Furthermore, increased plasma saturated FAs (SFAs) and linoleic acid were related to a significant increase in CAD risk among participants with high genetic risk (genetic risk score > 90%). These findings suggest that individuals with high genetic risk need to reduce plasma SFAs levels for CAD prevention. Supplementation of n-3 PUFAs for CAD prevention may consider individuals' genetic makeup.

Association of Fish Oil Supplementation with Risk of Coronary Heart Disease in Individuals with Diabetes and Prediabetes: A Prospective Study in the UK Biobank.

This study aimed to explore the association between habitual intake of fish oil supplementation and the risk of developing CHD in patients with prediabetes and diabetes. Habitual use of fish oil was assessed by repeated questionnaires. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over a median follow-up of 11.6 years, 4304 and 3294 CHD cases were documented among 47,663 individuals with prediabetes and 22,146 patients with diabetes in the UK Biobank, respectively. After multivariable adjustment, the HRs (95% CI) of CHD were 0.91 (0.85-0.98) and 0.87 (0.80-0.95) for individuals utilizing fish oil supplementation compared with non-users among the participants with prediabetes and diabetes, respectively. Furthermore, we identified an inverse relationship between fish oil use and CHD incidence, which was significantly mediated by serum C-reactive protein (CRP) levels in individuals with prediabetes and by very-low-density lipoprotein cholesterol (VLDL-C) in patients with diabetes at baseline. The inverse associations were consistent in the analyses stratified by potential confounders. In conclusion, the consumption of fish oil supplements was linked to decreased serum CRP and VLDL-C levels and subsequent CHD risk among adults with prediabetes and diabetes. Our findings highlight the important role of the habitual intake of fish oil supplements in preventing CHD in individuals with impaired glucose metabolism.

Potato consumption, polygenic scores, and incident type 2 diabetes: An observational study.

Whether the consumption of different processed potatoes is detrimental to type 2 diabetes (T2D) is highly debated. This study aimed to assess the relations between potato consumption and the risk of T2D and whether the relationship was modified by the genetic predisposition to T2D. We included 174,665 participants from the UK Biobank at baseline. Potato consumption was evaluated using the 24-hour dietary questionnaire. The genetic risk score (GRS) was calculated based on 424 variants associated with T2D. After adjustment for demographic, lifestyle, and dietary factors, the consumption of total potatoes was significantly and positively associated with T2D risk [hazard ratio (HR) comparing two or more servings/day with non-consumers was 1.28 (95% CI: 1.13-1.45)]. HRs (95% CIs) of T2D for each 1-SD increment in boiled/baked potatoes, mashed potatoes, and fried potatoes were 1.02 (0.99-1.05), 1.05 (1.02-1.08), and 1.05 (1.02-1.09), respectively. There were no significant interactions between the consumption of total or different processed potatoes and overall GRS on T2D risk. Theoretically, replacing one serving/day of total potatoes with the same amount of non-starchy vegetables was related to a 12% (95% CI: 0.84-0.91) lower T2D risk. These results showed the positive associations of the consumption of total potatoes, mashed potatoes or fried potatoes and genetic risk with higher incident T2D. An unhealthy potato-based diet is associated with higher diabetes risk regardless of genetic risk.

Lifelong docosahexaenoic acid intervention ameliorates aging in the telomere-DNA-mitochondria axis in telomerase-deficient mice.

The health benefits of n-3 polyunsaturated fatty acids (PUFAs) in multiple age-related diseases are associated with telomere length. Telomerase is intimately related to inflammation and oxidative stress, but whether the underlying function of n-3 PUFAs on telomere maintenance is based on telomerase activation or related mechanisms remains unclear. Herein, we utilized late-generation (G4) telomerase-deficient (Terc-/-) mice to perform a lifelong docosahexaenoic acid (DHA) intervention to determine the potential of DHA in telomere maintenance and health promotion. Unfortunately, DHA failed to prolong mouse longevity in either intrinsic or premature aging. However, intriguingly, lifelong dietary DHA intervention slowed the aging phenotypes and profoundly attenuated telomere attrition in blood leukocytes and multiple tissues, consistent with decreased ß-galactosidase activity and other senescence hallmarks with no observed sex differences. Notably, DHA intervention alleviated telomere attrition-induced γ-H2AX accumulation dependent on poly (ADP-ribose) polymerase 1 (PARP1) recruitment, and further regulated mitochondrial dysfunction critically involved in the DNA damage response. Together with the improvement of mitochondria function, the blocked reactive oxygen species (ROS) accumulation and suppression of the nuclear factor-κB (NF-κB)/nucleotide-binding domain-like receptor protein 3 (NLRP3)/caspase-1 pathways partially indicated anti-oxidative and anti-inflammatory effects of DHA. These data revealed a regulatory paradigm involving DHA in the telomere-DNA-mitochondria feedback loop mediated by DNA damage response and inflammation in alleviating senescence, which may hold potential as a translatable intervention in telomere-related diseases during aging.

Metabolomics strategy comprehensively unveils the effect of catechins intervention on the biomarkers of exposure to acrylamide and biomarkers of cardiometabolic risk.

Polyphenolic antioxidants have been suggested to control the generation of acrylamide during thermal reactions. However, their role in protecting against the toxicity of acrylamide and the mechanism of action regarding profile alteration of biomarkers and metabolome remains unclear. A total of 65 adults were randomized into tea polyphenols (TP) and control groups and served with potato chips, which corresponded to an intake level of 12.6 µg/kg·bw of acrylamide, followed by capsules containing 200 mg, 100 mg or 50 mg TP, or equivalent placebo. Moreover, nontargeted urinary metabolomics analysis in acrylamide exposed rats was conducted using ultra-high performance liquid chromatography linked with a quadrupole-orbitrap high-resolution mass spectrometry. Our results showed that supplementation with catechins promoted the excretion of N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine in both humans and rats. We also found that epigallocatechin gallate (EGCG) or epicatechin (EC) intervention attenuated the ratio of hemoglobin adduct of glycidamide to hemoglobin adduct of acrylamide in rat blood. Metabolomics analysis revealed that EGCG/EC intervention regulated the differential expressed metabolites, including l-glutamic acid, 2-oxoglutarate, citric acid, and cysteinylglycine. Kyoto Encyclopedia of Genes and Genomes pathway analysis further showed acrylamide-induced metabolic disorders were improved after EGCG/EC supplementation by glycolipid metabolism (alanine, aspartate and glutamate metabolism, and d-Glutamine and d-glutamate metabolism) and energy metabolism (tricarboxylic acid cycle). Notably, the supplement use of EGCG prevented the cardiometabolic risk after exposure to acrylamide by mediating the phenylalanine and hippuric acid in phenylalanine metabolism. Here we showed the beneficial effect of catechins as major polyphenolic antioxidant ingredients on the toxicity of acrylamide by the changes in biomarkers from metabolic profile analysis based on human and animal studies. These findings shed light into the catechins as natural polyphenolic antioxidants that could be a therapeutic ingredient for preventing acrylamide-induced cardiometabolic toxicity.

Association of fish oil supplementation with risk of incident dementia: A prospective study of 215,083 older adults.

BACKGROUND & AIMS: Evidence linking the use of omega-3 PUFA supplements with incident dementia is scarce. We aim to assess the relationship between fish oil supplementation and incident dementia risk among older adults with different apolipoprotein E (APOE) genotypes in a large population-based cohort. METHODS: We included 215,083 participants (average age: 64.1 ± 2.9 y) without dementia at baseline from UK Biobank study. Fish oil use was assessed by a touch screen questionnaire at baseline. Dietary intake was assessed by a food frequency questionnaire. The APOE genotypes were determined by allele variations on rs429358 and rs7412 from genome-wide genotyping of blood samples. Dementia was diagnosed using the International Classification of Diseases (ICD-9 and ICD-10). Cox proportional hazards regression models were used to calculate the associations of fish oil supplement use with dementia risk. RESULTS: During an average 7.92 years of follow-up, 2054 participants were diagnosed with dementia. After multivariable adjustment for major risk factors, the use of fish oil supplements was significantly associated with a lower risk of all-cause dementia (p for trend = 0.004). Compared with non-users, the multivariable-adjusted hazard ratio (95% confidence interval) of dementia was 0.87 (0.79-0.96) for fish oil users. A marginal interaction was found between fish oil supplementation and APOE gene variants on the risk of dementia (p for interaction = 0.057). However, fish oil supplementation was not associated with the risk of any subtype of dementia, including Alzheimer's disease (AD), vascular dementia (VD), and frontotemporal dementia (FTD). CONCLUSIONS: Intake of fish oil supplements was associated with lower risk of all-cause dementia among 60-73 y elders. Our findings provide new population-based evidence for linking fish oil supplement use with dementia prevention.

Urinary non-targeted toxicokinetics and metabolic fingerprinting of exposure to 3-monochloropropane-1,2-diol and glycidol from refined edible oils.

The widespread presence of 3-monochloropropane-1,2-diol (3-MCPD) and glycidol in refined edible oils have raised food industrial and public health concerns, but their specific biomarkers of exposure and urinary metabolic pathways indicating nephrotoxicity remain largely unknown. Here, we unraveled the in vivo biotransformation of these two contaminants and revealed how they affect metabolic pathways in rats. Urine metabolomes in rats administered with glycidol or 3-MCPD were investigated using ultra-high performance liquid chromatography combined with a quadrupole-orbitrap high-resolution mass spectrometry. Compared to the currently acknowledged metabolite which is only 2,3-dihydroxypropyl mercapturic acid, we identified 8 and 4 new specific exposure biomarkers of glycidol and 3-MCPD, respectively, via mapping the glyceryl polymerization and glutathione and sulfur conjugation. The changes of metabolites in the surrounding metabolic network were investigated to further gain insight into their metabolic fates. Exposure to glycidol up-regulated citrate, isocitrate, ketoglutarate, malate, and pyruvate in the tricarboxylic acid cycle and glycolysis pathways, while 3-MCPD intake down-regulated these signal molecules in both pathways. Nonetheless, L-cysteine, proline, and arginine were significantly decreased by the effect of either glycidol or 3-MCPD. Our findings first map the urinary metabolomics of both contaminants from edible oils and advance the omics-level recognition for their observational health hazards.

Eicosapentaenoic and docosahexaenoic acids attenuate hyperglycemia through the microbiome-gut-organs axis in db/db mice.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been suggested to prevent the development of metabolic disorders. However, their individual role in treating hyperglycemia and the mechanism of action regarding gut microbiome and metabolome in the context of diabetes remain unclear. RESULTS: Supplementation of DHA and EPA attenuated hyperglycemia and insulin resistance without changing body weight in db/db mice while the ameliorative effect appeared to be more pronounced for EPA. DHA/EPA supplementation reduced the abundance of the lipopolysaccharide-containing Enterobacteriaceae whereas elevated the family Coriobacteriaceae negatively correlated with glutamate level, genera Barnesiella and Clostridium XlVa associated with bile acids production, beneficial Bifidobacterium and Lactobacillus, and SCFA-producing species. The gut microbiome alterations co-occurred with the shifts in the metabolome, including glutamate, bile acids, propionic/butyric acid, and lipopolysaccharide, which subsequently relieved ß cell apoptosis, suppressed hepatic gluconeogenesis, and promoted GLP-1 secretion, white adipose beiging, and insulin signaling. All these changes appeared to be more evident for EPA. Furthermore, transplantation with DHA/EPA-mediated gut microbiota mimicked the ameliorative effect of DHA/EPA on glucose homeostasis in db/db mice, together with similar changes in gut metabolites. In vitro, DHA/EPA treatment directly inhibited the growth of Escherichia coli (Family Enterobacteriaceae) while promoted Coriobacterium glomerans (Family Coriobacteriaceae), demonstrating a causal effect of DHA/EPA on featured gut microbiota. CONCLUSIONS: DHA and EPA dramatically attenuated hyperglycemia and insulin resistance in db/db mice, which was mediated by alterations in gut microbiome and metabolites linking gut to adipose, liver and pancreas. These findings shed light into the gut-organs axis as a promising target for restoring glucose homeostasis and also suggest a better therapeutic effect of EPA for treating diabetes. Video abstract.

Cooking oil/fat consumption and deaths from cardiometabolic diseases and other causes: prospective analysis of 521,120 individuals.

BACKGROUND: Increasing evidence highlights healthy dietary patterns and links daily cooking oil intake with chronic diseases including cardiovascular disease (CVD) and diabetes. However, food-based evidence supporting the consumption of cooking oils in relation to total and cardiometabolic mortality remains largely absent. We aim to prospectively evaluate the relations of cooking oils with death from cardiometabolic (CVD and diabetes) and other causes. METHODS: We identified and prospectively followed 521,120 participants aged 50-71 years from the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Individual cooking oil/fat consumption was assessed by a validated food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for mortality through the end of 2011. RESULTS: Overall, 129,328 deaths were documented during a median follow-up of 16 years. Intakes of butter and margarine were associated with higher total mortality while intakes of canola oil and olive oil were related to lower total mortality. After multivariate adjustment for major risk factors, the HRs of cardiometabolic mortality for each 1-tablespoon/day increment were 1.08 (95% CI 1.05-1.10) for butter, 1.06 (1.05-1.08) for margarine, 0.99 (0.95-1.03) for corn oil, 0.98 (0.94-1.02) for canola oil, and 0.96 (0.92-0.99) for olive oil. Besides, butter consumption was positively associated with cancer mortality. Substituting corn oil, canola oil, or olive oil for equal amounts of butter and margarine was related to lower all-cause mortality and mortality from certain causes, including CVD, diabetes, cancer, respiratory disease, and Alzheimer's disease. CONCLUSIONS: Consumption of butter and margarine was associated with higher total and cardiometabolic mortality. Replacing butter and margarine with canola oil, corn oil, or olive oil was related to lower total and cardiometabolic mortality. Our findings support shifting the intake from solid fats to non-hydrogenated vegetable oils for cardiometabolic health and longevity.

Mixed conjugated linoleic acid sex-dependently reverses high-fat diet-induced insulin resistance via the gut-adipose axis.

Conjugated linoleic acid (CLA) may prevent the development of obesity and metabolic disorders. However, the effects of CLA on inflammation and glucose metabolism are controversial. The underlying mechanisms governing the gut microbiota and sexual dimorphisms have also not been elucidated. The present study assessed the effect of CLA on glucose and lipid metabolism in established obesity and examined the mechanism of action based on gut microbiota. Four-week-old C57BL/6J mice were fed a high-fat diet (HFD) for 10 weeks to induce obesity. The diet-induced obese (DIO) mice were fed an HFD supplemented with mixed CLA (50% cis-9, trans-11 isomer and 50% trans-10, cis-12 isomers, 0.2% wt/wt) for 15 weeks. CLA supplementation remarkably reversed body weight in both sexes. CLA favored anti-inflammatory microbiota in male mice, mediating increased short-chain fatty acids and decreased lipopolysaccharide (LPS) production, which alleviated global inflammation and improved insulin sensitivity via inhibition of the TLR4-NF-κB pathway in adipose tissue. CLA promoted the growth of hydrogen sulfide-producing Desulfovibrio and the release of LPS in female mice, which aggravated adipose inflammation and insulin resistance. Although CLA impaired glucose metabolism in females, brown adipose tissue was significantly activated with browning of white adipose tissue in both sexes, which led to enhanced energy expenditure. Fecal transplantation from CLA-treated mice to DIO mice mimicked the sex-dependent phenotype. In conclusion, CLA decreased body weight and increased energy expenditure but sex-dependently modulated insulin resistance via the gut-adipose axis.

Current intake levels of potatoes and all-cause mortality in China: A population-based nationwide study.

OBJECTIVE: Current levels of potato consumption in relation to mortality in Chinese people remains unknown. The aim of this study was to investigate the intakes of total potatoes, fried potatoes, non-fried potatoes, and sweet potatoes as dietary carbohydrate sources in relation to all-cause mortality in the China Health and Nutrition Survey (CHNS). METHODS: Overall 14 117 participants ≥20 y of age were included, with a median follow-up of 14 y. The cumulative average consumption of potatoes and other foods were calculated and validated using weighing methods in combination with 3-d, 24-h dietary recalls at both household and individual levels. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models after multivariate adjustment. RESULTS: We documented 1007 deaths among the participants. The low and moderate intakes of total potatoes, fried potatoes, and non-fried potatoes were inversely associated with mortality. Compared with non-consumers, the intakes of total potatoes (HR, 0.48; 95% CI, 0.38-0.59), fried potatoes (HR, 0.44; 95% CI, 0.34-0.56), and non-fried potatoes (HR, 0.47; 95% CI, 0.37-0.61) at low consumption levels were most significantly related to lower mortality. Sweet potato consumption was inversely associated with mortality after full adjustment (HR, 0.82; 95% CI, 0.69-0.96) compared with non-consumers. Substituting grains and mixed beans for potatoes with equal amounts at high consumption levels strengthened the inverse associations. CONCLUSION: In the CHNS, current low and moderate, but not high levels of total potato and fried/non-fried potato consumption as well as sweet potato consumption were inversely associated with all-cause mortality among Chinese people.

Cooking Oil Consumption Is Positively Associated with Risk of Type 2 Diabetes in a Chinese Nationwide Cohort Study.

BACKGROUND: Evidence suggests that the relations between intakes of individual fatty acids and risk of type 2 diabetes (T2D) vary. However, associations between intakes of different cooking oils as sources of fatty acids and incident T2D remain largely unknown. OBJECTIVES: We aimed to evaluate relations between intakes of individual cooking oils and incident T2D in a nationwide Chinese cohort. METHODS: Overall 15,022 Chinese adults aged ≥20 y from the China Health and Nutrition Survey (CHNS) without self-reported T2D at entry in the 1997, 2000, 2004, 2006, or 2009 rounds were followed up until 2011. Consumption of various cooking oils/fats including lard, peanut oil, soybean oil, canola oil, sesame oil, and refined blended plant oil was assessed using 3-d 24-h records in each survey and the cumulative mean intake was calculated. Multivariable-adjusted Cox proportional hazards regression models were constructed to estimate the HRs of T2D. RESULTS: A total of 1014 cases were recorded after a median follow-up of 14 y. The intakes of animal and plant cooking oils/fats were both associated with higher T2D risk. Compared with nonconsumers, multivariable-adjusted HRs and 95% CIs for the highest tertiles were 1.31 (1.03, 1.67) for lard, 1.36 (1.10, 1.66) for peanut oil, 1.14 (0.91, 1.43) for soybean oil, 1.11 (0.87, 1.43) for canola oil, 1.02 (0.79, 1.32) for sesame oil, and 1.42 (1.12, 1.82) for refined blended plant oil. Substituting 1 tablespoon/d (8 g · 2000 kcal-1 · d-1) of soybean oil for the sum of lard, peanut oil, refined blended plant oil, and other plant oils was associated with a 3% (HR: 0.97; 95% CI: 0.95, 0.99) lower risk of T2D. CONCLUSIONS: Intakes of lard, peanut oil, and refined blended plant oil but not soybean oil, canola oil, and sesame oil are associated with higher T2D risk. Reducing the consumption of cooking oils in general may be protective against T2D among the Chinese population.This trial was registered at clinicaltrials.gov as NCT03259321.

Plant-sourced cooking oil consumption is associated with lower total mortality in a longitudinal nationwide cohort study.

BACKGROUND & AIMS: Evidence linking individual cooking oil consumption with total mortality is limited in China. The aim of this study was to examine the associations of intakes of plant-sourced and animal-sourced cooking oils with total mortality in a Chinese nationwide cohort. METHODS: We analyzed data from 14,305 adults aged ≥20 y at entry in the China Health and Nutrition Survey (CHNS). The 3-day 24-h dietary records were used to collect dietary information. Cox proportional hazards regression models were established to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause death. RESULTS: Overall 1006 deaths were documented during a median of 14 years (199,091 person-years) of follow-up. Multivariate-adjusted HRs (95% CIs) of total mortality via comparing the highest tertile of cooking oil consumption with no consumption were 0.86 (0.70-1.06) for lard, 0.59 (0.47-0.74) for peanut oil, 0.71 (0.54-0.93) for soybean oil, 0.76 (0.61-0.94) for canola oil, 0.71 (0.50-0.99) for salad oil, and 0.59 (0.44-0.79) for other plant cooking oils. Replacing animal cooking oils with 1 tablespoon/d of total plant cooking oils or other plant cooking oils was related to 4% or 17% lower total mortality, respectively, while consumption of peanut oil or salad oil in replacement of animal cooking oils had a marginal inverse association with total mortality. CONCLUSIONS: Intakes of plant-sourced cooking oils, including peanut oil, soybean oil, canola oil, salad oil, and other plant cooking oils and substituting plant cooking oils for animal cooking oils were associated with lower total mortality among general Chinese population (NCT03259321).

Eicosapentaenoic and Docosahexaenoic Acids Differentially Alter Gut Microbiome and Reverse High-Fat Diet-Induced Insulin Resistance.

SCOPE: To assess the individual effects of dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on insulin resistance (IR), gut microbiome, and gut metabolites in high-fat-diet-induced obese (DIO) mice. METHODS AND RESULTS: DIO mice are fed an either high-fat diet (HFD), EPA (1% w/w) enriched HFD, or DHA (1% wt/wt) enriched HFD for 15 weeks. Both EPA and DHA supplements reverse hyperglycemia and IR but do not affect body weight in DIO mice while DHA exhibits a more pronounced ameliorative effect in male mice. Both EPA- and DHA-enriched Lactobacillus and short-chain fatty acids (SCFAs)-producing species from Lachnospiraceae while reduced lipopolysaccharide (LPS)-producing Bilophila and Escherichia/Shigella. Compared with EPA, DHA-supplemented mice have more abundant propionic/butyric acid-producing bacteria, including Coprococcus, Butyricimonas synergistica, Bacteroides acidifaciens, and Intestinimonas, and less-abundant LPS-correlated species Streptococcus and p-75-a5. The shifts in gut microbiome co-occurred with the changes in levels of propionic/butyric acid, circulating LPS, and serotonin. Additionally, EPA/DHA supplementation attenuates adipose inflammation with upregulated glucose transporter 4 and Akt phosphorylation, indicating the improvement of insulin signaling. CONCLUSION: EPA and DHA differentially reverse IR and relieve adipose inflammation while modulating gut microbiome and SCFAs/LPS production, underscoring the gut-adipose axis as a primary target of EPA/DHA.

Current level of fish and omega-3 fatty acid intakes and risk of Type 2 diabetes in China.

Whether fish and marine omega-3 polyunsaturated fatty acid (PUFA) intakes are linked to type 2 diabetes (T2D) risk remains unclear in China. We aimed to assess the long-term associations in a nationwide cohort. Overall 15,100 Chinese adults, aged ≥20 years, were included from China Health and Nutrition Survey. The cumulative averages of fish and marine omega-3 PUFA intakes were evaluated based on 3-day 24-h records. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of T2D risk. Overall 1017 T2D cases were documented over a median of 14 years of follow-up. Compared with non-fish consumers, low and moderate fish consumption were associated with higher T2D risk whereas high fish consumption was not associated. Multivariable-adjusted HRs (95% CIs) for low and moderate fish consumption were 1.43 (1.09, 1.86) and 1.42 (1.07, 1.85) respectively in men, and were 1.58 (1.22, 2.02) and 1.39 (1.08, 1.83) respectively in women. In meat substitution analyses, low and moderate fish consumption was related to 55% and 69% higher T2D risk for men, and was associated with 68% and 54% higher T2D risk for women, respectively. Fried but not non-fried fish intake was associated with higher T2D risk. Intake of marine omega-3 PUFAs was dose-dependently associated with higher T2D risk for both men and women (P-trend<0.001). Overall low and moderate intakes of fish, especially fried fish, and marine omega-3 PUFAs were associated with higher T2D risk. Current level of fish and marine omega-3 PUFA consumption is not protective against T2D incidence among Chinese people.

Differential Anti-Adipogenic Effects of Eicosapentaenoic and Docosahexaenoic Acids in Obesity.

SCOPE: To assess the associations of plasma eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with body fat in a population-based sample and explore the mechanism of action based on browning of white adipose tissue (WAT) in high-fat-diet-induced obese (DIO) mice and 3T3-L1 adipocytes. METHODS AND RESULTS: Plasma EPA and DHA of 1719 adults in the National Health and Nutrition Examination Survey (2003-2004) are determined by gas chromatography mass spectrometry, while total body fat is measured by dual-energy X-ray absorptiometry. DIO mice are fed a high-fat diet supplemented with EPA or DHA (1% wt/wt) for 15 weeks and 3T3-L1 preadipocytes are treated with EPA or DHA during differentiation. Plasma DHA but not EPA is associated with lower body fat mass (ptrend < 0.0001), which persists in overweight/obese subjects (ptrend = 0.02). DHA supplementation reduces inguinal WAT and exhibits a more pronounced thermogenic effect than EPA in DIO mice. In vitro, the browning process is induced after 2-day and 6-day treatment with DHA and EPA, respectively. CONCLUSION: Plasma DHA but not EPA is inversely associated with body fat mass. The more potent anti-adipogenic effect of DHA than EPA may involve a better capability of inducing browning of WAT for DHA.

Dietary Fats in Relation to Total and Cause-Specific Mortality in a Prospective Cohort of 521 120 Individuals With 16 Years of Follow-Up.

RATIONALE: Evidence linking saturated fat intake with cardiovascular health is controversial. The associations of unsaturated fats with total and cardiovascular disease (CVD) mortality remain inconsistent, and data about non-CVD mortality are limited. OBJECTIVE: To assess dietary fat intake in relation to total and cause-specific mortality. METHODS AND RESULTS: We analyzed data of 521 120 participants aged 50 to 71 years from the National Institutes of Health-American Association of Retired Persons Diet and Health Study with 16 years of follow-up. Intakes of saturated fatty acids (SFAs), trans-fatty acids, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were assessed via food frequency questionnaires. Hazard ratios and 95%CIs were estimated using the Cox proportional hazards model. Overall, 129 328 deaths were documented during 7.3 million person-years of follow-up. In the replacement of carbohydrates, multivariable-adjusted hazard ratios of total mortality comparing extreme quintiles were 1.29 (95% CI, 1.25-1.33) for SFAs, 1.03 (1.00-1.05) for trans-fatty acids, 0.98 (0.94-1.02) for MUFAs, 1.09 (1.06-1.13) for animal MUFAs, 0.94 (0.91-0.97) for plant MUFAs, 0.93 (0.91-0.95) for PUFAs, 0.92 (0.90-0.94) for marine omega-3 PUFAs, 1.06 (1.03-1.09) for α-linolenic acid, 0.88 (0.86-0.91) for linoleic acid, and 1.10 (1.08-1.13) for arachidonic acid. CVD mortality was inversely associated with marine omega-3 PUFA intake ( P trend <0.0001), whereas it was positively associated with SFA, trans-fatty acid, and arachidonic acid intake. Isocalorically replacing 5% of the energy from SFAs with plant MUFAs was associated with 15%, 10%, 11%, and 30% lower total mortality, CVD, cancer, and respiratory disease mortality, respectively. Isocaloric replacement of SFA with linoleic acid (2%) was associated with lower total (8%), CVD (6%), cancer (8%), respiratory disease (11%), and diabetes mellitus (9%) mortality. CONCLUSIONS: Intakes of SFAs, trans-fatty acids, animal MUFAs, α-linolenic acid, and arachidonic acid were associated with higher mortality. Dietary intake of marine omega-3 PUFAs and replacing SFAs with plant MUFAs or linoleic acid were associated with lower total, CVD, and certain cause-specific mortality. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00340015.

Saturated Fatty Acid Intake Is Associated with Total Mortality in a Nationwide Cohort Study.

Background: Dietary intakes of total and specific types of saturated fatty acids (SFAs) in relation to total mortality remain largely unknown in China. Objective: We assessed the associations of total and individual SFA intakes with total mortality in a Chinese nationwide population. Methods: This prospective analysis included 7888 women and 6495 men, aged >20 y, from the China Health and Nutrition Survey (1989-2011). Cumulative mean of SFA intake was calculated based on 3 d of 24-h records in each round of the survey. Multivariable Cox proportional hazard models were used to estimate HR and 95% CI. Results: There were 1011 deaths during a median of 14 y of follow-up. In isocaloric nutrient density models that replace total carbohydrates, intakes of total SFAs and even-chain SFAs were associated with higher total mortality in women but not in men. Compared with the lowest quartiles, the HRs (95% CIs) in the highest quartiles were 1.65 (1.03, 2.62) for total SFAs (P-trend = 0.042) and 1.83 (1.13, 2.94) for even-chain SFAs (P-trend = 0.016) in women. Intake of odd-chain SFAs was associated with lower total mortality both in men [HR (95% CI): 0.64 (0.47, 0.87); P-trend = 0.01] and in women [HR (95% CI): 0.59 (0.42, 0.84); P-trend = 0.0013]. Moreover, intake of medium-chain SFAs was linked with lower total mortality in men [HR (95% CI): 0.64 (0.44, 0.93); P-trend = 0.013]. However, isocalorically replacing 1% of energy from unsaturated fatty acids with even-chain SFAs was associated with higher total mortality in men [HRs (95% CIs): 1.08 (0.97, 1.20) and 1.39 (1.20, 1.60) for replacing PUFAs and MUFAs, respectively]. Conclusions: Total SFA and even-chain SFA intake was associated with higher total mortality in women, whereas intake of odd-chain SFAs was related to lower total mortality in both sexes. This analysis of cohort was registered at clinicaltrials.gov as NCT03281512.

Polyunsaturated fatty acids intake, omega-6/omega-3 ratio and mortality: Findings from two independent nationwide cohorts.

BACKGROUND & AIMS: Polyunsaturated fatty acids (PUFA) have been reported to exert pleiotropic protective effects against various chronic diseases. However, epidemiologic evidence linking specific PUFA intake to mortality has been limited and contradictory. We aim to assess the associations between specific dietary PUFA and mortality among adults in China and America, respectively. METHODS: Participants from China Health and Nutrition Survey (CHNS, n = 14,117) and National Health and Nutrition Examination Survey [NHANES (n = 36,032)] were prospectively followed up through the year 2011. Cox regression models were used to investigate hypothesized associations. RESULTS: A total of 1007 and 4826 deaths accrued over a median of 14 and 9.1 years of follow-up in CHNS and NHANES, respectively. Dietary marine omega-3 PUFA was robustly associated with a reduced all-cause mortality [Hazard ratio (HR) comparing extreme categories: 0.74, 95% CI: 0.61-0.89; P < 0.001 for trend] in CHNS. Nevertheless, this inverse relationship was not observed in NHANES. The overall mortality was positively associated with the intake of α-linolenic acid (ALA) (HR comparing extreme quartiles: 1.23, 95% CI: 1.01-1.50; P = 0.054 for trend) in CHNS, whereas weak inverse associations of ALA (P = 0.035 for trend) and LA (P = 0.027 for trend) with all-cause mortality were found in NHANES. Increased dietary intake of arachidonic acid was consistently linked with reduced all-cause mortality both in NHANES and CHNS. Importantly, consuming PUFA at an omega-6/omega-3 ratio of 6-10 was associated with a lower risk of death in CHNS. CONCLUSIONS: Intakes of different specific PUFA show distinct associations with mortality and these relationships also vary between Chinese and US populations. These findings suggest maintaining an omega-6/omega-3 balance diet for overall health promotion outcomes (NCT03155659).