Effect of Fiber Supplementation on Systemic Inflammation and Liver Steatosis in Mice Fed with High-Carbohydrate Diets.

Background: High consumption of carbohydrates can trigger metabolic and inflammatory disorders in the body. Thus, the aim of this study was to evaluate the effect of fiber supplementation on inflammation and hepatic steatosis in mice fed high-carbohydrate diets. Methods: Swiss male mice were distributed into two control groups and two experimental groups that received isocaloric diet rich in starch (55%) or rich in fructose (55%). In the last 4 weeks of the experiment, the animals received 5% fructo-oligosaccharide (FOS) supplementation via gavage, or water in the control groups. After 16 weeks, biochemical analyses, inflammatory cytokines, and histology of the liver of the animals were performed. Results: The animals that received fructose had higher weight at the end of the experiment as well as liver weight, consumed more feed, had higher levels of tumor necrosis factor (TNF) and monocyte chemoattractant protein-1 (MCP-1), and a higher degree of hepatic steatosis when compared with the animals that received starch. However, the animals that received starch showed a higher inflammatory process. FOS supplementation was efficient in reducing liver weight and hepatic steatosis degree in animals fed with fructose diet but showed more degeneration of liver tissue and high levels of inflammatory cytokines. FOS reduced the levels of urea and total cholesterol in the starch-fed animals. Conclusions: Diets rich in carbohydrates such as starch and fructose cause deleterious effects in animals, and fiber supplementation can bring beneficial effects.

Rhus chinensis Mill. Fruits Ameliorate Hepatic Glycolipid Metabolism Disorder in Rats Induced by High Fat/High Sugar Diet.

Hepatic glycolipid metabolism disorder is considered as one of the key factors in the pathogenesis of many chronic diseases. The objective of this study was to investigate the protective effect and underlying mechanisms of Rhus chinensis Mill. fruits against hepatic glycolipid metabolic disorders in rats induced by a high fat/high sugar diet. Results showed that ethanol extract, especially at a dose of 600 mg/kg b.w., could effectively ameliorate glycolipid metabolic disorders in rats. The biochemical indexes, including CAT, GSH and HOMA-IR, were significantly improved by the administration of ethanol extract. Immunohistochemistry and Western blot analysis revealed that ethanol extract up-regulated the expression levels of PI3K/AKT, PPAR-α, and the phosphorylation of IRS1 and AMPK proteins, and down-regulated the expressions of SREBP-1 and FAS proteins in the liver, which are closely related to hepatic glycolipid metabolism. Those findings suggested that R. chinensis Mill. fruits could be developed as functional foods and/or nutraceuticals for preventing or controlling some chronic diseases related to hepatic glycolipid metabolism disorder.

Associations Between Macronutrients From Different Dietary Sources and Serum Lipids in 24 639 UK Biobank Study Participants.

[Figure: see text].

Diets with high carbohydrate contents were associated with refeeding hypophosphatemia: A retrospective study in Japanese inpatients with anorexia nervosa.

OBJECTIVE: Refeeding hypophosphatemia (RH) is a potentially fatal complication in patients with anorexia nervosa (AN), and its dietary preventive strategy is not well established. We aimed to examine the association between carbohydrate content in the diet and the occurrence of RH in inpatients with AN via retrospective medical chart review. METHOD: We performed a chart review to collect data of patients with AN hospitalized at the Department of Psychosomatic Medicine of the University of Tokyo Hospital between April 1, 2012, and February 29, 2020. Receiver operating characteristic (ROC) analysis was performed to determine the cutoff point of the percentage of carbohydrate content in the diet for the occurrence of RH. Multivariate logistic regression analysis was performed with occurrence of RH as the dependent variable and the carbohydrate content of more than the identified cutoff point as the independent variable adjusting for the risk factors for RH. RESULTS: The percentage of carbohydrate content that is higher than the cutoff point obtained from the ROC analysis (58.4%) was significantly associated with the occurrence of RH, even after adjusting for variables associated with RH in univariate logistic regression analysis (age and body mass index) as well as the average daily calorie intake (odds ratio, 5.37; 95% confidence interval, 1.60-18.1; p = .0066). DISCUSSION: We identified that diets with higher carbohydrate contents were associated with RH in inpatients with AN, even after adjusting for known risk factors. Our findings may promote the development of dietary preventive strategies against RH in inpatients with AN.

Synergistic Effects of Heat-Killed Kefir Paraprobiotics and Flavonoid-Rich Prebiotics on Western Diet-Induced Obesity.

The synergistic anti-obesity effect of paraprobiotic heat-killed lactic acid bacteria (HLAB) and prebiotics has not been studied. To determine the anti-obesity properties of prebiotic polyphenol-rich wine grape seed flour (GSF) and paraprobiotic HLAB, C57BL/6J mice were administered a high-fat and high-fructose diet (HFFrD) with 5% microcrystalline cellulose (CON), HFFrD supplemented with 2.5% GSF, HFFrD with orally administered HLAB, or HFFrD with a combination of GSF and orally administered HLAB (GSF+HLAB) for 8 weeks. Compared with the CON group, the GSF and HLAB groups both showed significant reductions in HFFrD-induced body weight gain and adipose tissue weights (p < 0.05). Interestingly, combined supplementation with GSF and HLAB revealed statistically significant synergistic effects on body weight gain, visceral adiposity, and plasma triacylglycerol concentrations (p < 0.05). The synergistic action was significantly related to a decreased adipocyte gene expression in fatty acid synthesis and inflammation metabolism. In conclusion, the combination of prebiotic GSF and paraprobiotic kefir HLAB is potentially useful, as natural food ingredients, in the prevention of obesity and obesity-related diseases, especially for immunocompromised individuals.

The protective effects of walnut green husk polysaccharide on liver injury, vascular endothelial dysfunction and disorder of gut microbiota in high fructose-induced mice.

This study aimed to investigate the protective effects of walnut green husk polysaccharide (WGHP) on liver injury, vascular endothelial dysfunction and disorder of gut microbiota in mice induced by high fructose (HF) diet. The chemical analysis results show that the walnut green husk polysaccharide is a low molecular weight acidic heteropolysaccharide, composed mainly of glucuronic acid, arabinose and galactose. Biochemical analysis showed that WGHP significantly improved glucose metabolism and lipid metabolism and decreased oxidative stress in HF-diet induced obesity mice. Histopathological observation of liver and cardiovascular aorta confirmed the protective effects of WGHP on hepatic steatosis and vascular endothelial dysfunction. Furthermore, 16S rRNA sequencing results demonstrated that WGHP reversed the disorders of gut microbiota caused by HF, decreased the relative abundance of Verrucomicrobia and increased the relative abundance of Deferribacteres at the phylum level, decreased the relative abundance of Akkermansia, Lachnoclostridium and norank_f__Muribaculaceae and increased the relative abundance of Prevotellaceae_UCG-001, Helicobacter, Alloprevotella and Allobaculum at the genus levels. Our results indicate that WGHP may act as a functional polysaccharide for protecting liver and cardiovascular in HF-fed mice.

Beneficial Effects of Isoflavones in the Kidney of Obese Rats Are Mediated by PPAR-Gamma Expression.

Several studies have demonstrated an important association between altered lipid metabolism and the development of kidney injury because of a high-fat diet. Fructose is also closely associated with renal injury. We opted for a combination of fructose and saturated fats in a diet (DH) that is a model known to induce renal damage in order to evaluate whether soy isoflavones could have promising use in the treatment of renal alterations. After two months of ingestion, there was an expansion of visceral fat, which was associated with long-term metabolic disorders, such as sustained hyperglycemia, insulin resistance, polyuria, dyslipidemia, and hypertension. Additionally, we found a decrease in renal blood flow and an increase in renal vascular resistance. Biochemical markers of chronic kidney disease were detected; there was an infiltration of inflammatory cells with an elevated expression of proinflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß), the activation of the renin-angiotensin system, and oxidative/nitrosative stress. Notably, in rats exposed to the DH diet for 120 days, the concomitant treatment with isoflavones after 60 days was able to revert metabolic parameters, renal alterations, and oxidative/nitrosative stress. The beneficial effects of isoflavones in the kidney of the obese rats were found to be mediated by expression of peroxisome proliferator-activated receptor gamma (PPAR-γ).

Is frequency of potato and white rice consumption associated with cardiometabolic risk factors in children and adolescents: the CASPIAN-V study.

BACKGROUND: This study evaluated the association of frequency of potato and rice consumption with cardiometabolic risk factors in children and adolescents. METHODS: This nationwide cross-sectional survey was conducted on 14,400 children and adolescents. Fasting blood was obtained from a sub-sample of 4200 randomly selected students. Physical examination and laboratory tests were conducted under standard protocols. Metabolic Syndrome (Mets) was defined based on the Adult Treatment Panel III criteria modified for the pediatric age group. The self-reported frequency consumption of white rice and potato was reported on a daily or non-daily basis. RESULTS: The participation rate for the whole study and for blood sampling were 99 and 91.5%, respectively. Overall, 49.4% of the participants were girls while 50.6% were boys. The frequency of daily consumption of white rice and potato was 84.4 and 21.3%, respectively. In the multivariable linear regression model, daily consumption of potato increased body mass index (ß: 0.05, SE: 0.20, p = 0.010), waist (ß: 0.63, SE: 0.24, p = 0.008), and hip circumferences (ß: 0.62, SE: 0.26, p = 0.019). Moreover, in the multivariable logistic regression, daily consumption of potato was significantly associated with an increased risk of overweight (OR: 1.21, 95% CI: 1.04-1.39, P = 0.012). The potato and rice consumption had no statistically significant association with other cardiometabolic risk factors. CONCLUSIONS: Daily consumption of potato was significantly associated with higher anthropometric measures, whereas rice consumption had no statistically significant association with cardiometabolic risk factors. Future research to examine the possible obesogenic effects of intake of potato on children and adolescents is recommended.

Investigation and Management of Stool Frequency and Consistency Associated With SGLT1 Inhibition by Reducing Dietary Carbohydrate: A Randomized Trial.

Treatment with licogliflozin, a dual sodium-glucose co-transporter (SGLT)1/2-inhibitor, is associated with increased stool frequency and loose stools, attributed to SGLT1 inhibition. To investigate the effect of carbohydrate content and supplements on licogliflozin-induced stools, a randomized, open-label, two-part (N = 24/part), three-period crossover study was carried out in overweight or obese adults. Significantly higher (P < 0.01) change from baseline in 3-day total number of bowel movements was observed following 3 days of licogliflozin treatment (50 mg q.d.) together with a 50% carbohydrate meal compared with a 25% and 0% carbohydrate meal. The number of stools with Bristol Stool Chart score of 6 or 7 was also significantly lower following a 0% carbohydrate meal. Supplementation with psyllium 6 g or calcium carbonate 1 g had no effect on stool changes following treatment. Licogliflozin was generally safe and well-tolerated. Loose stool associated with licogliflozin treatment and ingestion of meals can be managed by reducing the carbohydrate content of meals taken with licogliflozin.

Carrageenans from the Red Seaweed Sarconema filiforme Attenuate Symptoms of Diet-Induced Metabolic Syndrome in Rats.

Carrageenans are thickening and gelling agents that may provide health benefits. Iota (ι)-carrageenan, a linear sulfated polysaccharide, is produced by the red seaweed, Sarconema filiforme. This study investigated the potential of this seaweed as a functional food for the reversal of metabolic syndrome and possible mechanisms. Male Wistar rats were divided into four groups in a 16-week protocol: corn starch diet-fed rats (C); C rats supplemented with 5% S. filiforme for the last 8 weeks (CSF); high-carbohydrate, high-fat diet-fed rats (H); and H rats supplemented with 5% S. filiforme for the last 8 weeks (HSF). S. filiforme was produced in tank-based aquaculture yielding 27 g dry weight/day/m2 of culture area. H rats developed obesity, hypertension, dyslipidaemia, glucose intolerance, fatty liver and increased left ventricular collagen deposition. S. filiforme supplementation decreased body weight, abdominal and liver fat, systolic blood pressure, plasma total cholesterol concentrations, and plasma activities of alanine transaminase and aspartate transaminase. S. filiforme supplementation modulated gut microbiota without changing the Firmicutes to Bacteroidetes ratio. S. filiforme improved symptoms of high-carbohydrate, high-fat diet-induced metabolic syndrome in rats. Possible mechanisms include a reduced infiltration of inflammatory cells into organs as well as prebiotic actions in the gastrointestinal tract.

Protective effect of Polygonatum sibiricum Polysaccharide on D-galactose-induced aging rats model.

The polysaccharide of Polygonatum sibiricum (PSP)is one of the main active ingredients of Polygonatum Polygonatum in Liliaceae. It has anti-tumor, anti-aging, immune regulation, and anti-oxidative effects. Recent studies have shown that the Klotho gene and fibroblast growth factor-23 (FGF-23) have a common receptor, which is closely related to aging and highly expressed in kidney and meninges. Our study aimed to investigate the anti-aging effect of PSP on D-galactose-induced rats and its mechanism. D-galactose (120 mg Kg-1) and PSP (100 mg Kg-1) was used to intervene in rats, respectively. Then The changes of indexes of the natural aging-like model rats before and after PSP intervention were observed. We found that PSP could significantly improve the learning and memory abilities of rats and reverse the pathological changes of kidney tissues in rats. At the same time, PSP up-regulated the expression of Klotho mRNA and Klotho protein in the renal cortex, down-regulated the expression of FOXO3a mRNA and p-FOXO3a protein in renal tissue, and inhibited the expression of FGF-23 protein in the femur. Our studies suggest that PSP may play a role by regulating the Klotho-FGF23 endocrine axis, alleviating oxidative stress, and balancing calcium and phosphorus metabolism.

Consumption of Lactose, Other FODMAPs and Diarrhoea during Adjuvant 5-Fluorouracil Chemotherapy for Colorectal Cancer.

Chemotherapy-induced mucosal injury of the small intestine may interfere with the enzymes and transporters responsible for the hydrolysis and absorption of dietary carbohydrates causing diarrhoea, abdominal discomfort and pain. The aim of this study was to investigate the association between the consumption of foods rich in FODMAPs (fermentable oligo-, di- and monosaccharides and polyols) and gastrointestinal symptoms in patients receiving adjuvant therapy for colorectal cancer. The patients (n = 52) filled in a 4-day food diary at baseline and during therapy and kept a symptom diary. The intakes of FODMAP-rich foods were calculated as portions and the intakes were divided into two consumption categories. Patients with high consumption of FODMAP-rich foods had diarrhoea more frequently than those with low consumption (for lactose-rich foods the odds ratio (OR) was 2.63, P = 0.03; and for other FODMAP-rich foods 1.82, P = 0.20). Patients with high consumption of both lactose-rich and other FODMAP-rich foods had an over 4-fold risk of developing diarrhoea as compared to those with low consumption of both (OR, 4.18; P = 0.02). These results were confirmed in multivariate models. Conclusion: Consumption of lactose-rich foods results in an increased risk of diarrhoea during adjuvant therapy for colorectal cancer, especially when the consumption of other FODMAP-rich foods is also high.

Xanthophyll ß-Cryptoxanthin Inhibits Highly Refined Carbohydrate Diet-Promoted Hepatocellular Carcinoma Progression in Mice.

SCOPE: ß-Cryptoxanthin (BCX) can be cleaved by both ß-carotene 15,15'-oxygenase (BCO1) and ß-carotene 9',10'-oxygenase (BCO2), generating biological active vitamin A and apocarotenoids. We examined whether BCX feeding could inhibit diethylnitrosamine (DEN)-initiated, highly refined carbohydrate diet (HRCD)-promoted hepatocellular carcinoma (HCC) development, dependent or independent of BCO1/BCO2 activity. METHODS AND RESULTS: Two-week-old male wild-type (WT) and BCO1-/- /BCO2-/- double knockout (DKO) mice are given a single intraperitoneal injection of DEN (25 mg kg-1 body weight) to initiate hepatic carcinogenesis. At 6 weeks of age, all animals are fed HRCD (66.5% of energy from carbohydrate) with or without BCX for 24 weeks. BCX feeding increases hepatic vitamin A levels in WT mice, but not in DKO mice that shows a significant accumulation of hepatic BCX. Compared to their respective HRCD littermates, both WT and DKO fed BCX have significantly lower HCC multiplicity, average tumor size, and total tumor volume, and the steatosis scores. The chemopreventive effects of BCX are associated with increased p53 protein acetylation and decreased protein levels of lactate dehydrogenase and hypoxia-inducible factor-1α in tumors. CONCLUSION: This study suggests that BCX feeding may alleviate HRCD-promoted HCC progression by modulating the acetylation of p53, hypoxic tumor microenvironment, and glucose metabolism, independent of BCO1/BCO2.

Hydrogel Carbohydrate-Electrolyte Beverage Does Not Improve Glucose Availability, Substrate Oxidation, Gastrointestinal Symptoms or Exercise Performance, Compared With a Concentration and Nutrient-Matched Placebo.

The impact of a carbohydrate-electrolyte solution with sodium alginate and pectin for hydrogel formation (CES-HGel), was compared to a standard CES with otherwise matched ingredients (CES-Std), for blood glucose, substrate oxidation, gastrointestinal symptoms (GIS; nausea, belching, bloating, pain, regurgitation, flatulence, urge to defecate, and diarrhea), and exercise performance. Nine trained male endurance runners completed 3 hr of steady-state running (SS) at 60% V˙O2max, consuming 90 g/hr of carbohydrate from CES-HGel or CES-Std (53 g/hr maltodextrin, 37 g/hr fructose, 16% w/v solution) in a randomized crossover design, followed by an incremental time to exhaustion (TTE) test. Blood glucose and substrate oxidation were measured every 30 min during SS and oxidation throughout TTE. Breath hydrogen (H2) was measured every 30 min during exercise and every 15 min for 2 hr postexercise. GIS were recorded every 15 min throughout SS, immediately after and every 15-min post-TTE. No differences in blood glucose (incremental area under the curve [mean ± SD]: CES-HGel 1,100 ± 96 mmol·L-1·150 min-1 and CES-Std 1,076 ± 58 mmol·L-1·150 min-1; p = .266) were observed during SS. There were no differences in substrate oxidation during SS (carbohydrate: p = .650; fat: p = .765) or TTE (carbohydrate: p = .466; fat: p = .633) and no effect of trial on GIS incidence (100% in both trials) or severity (summative rating score: CES-HGel 29.1 ± 32.6 and CES-Std 34.8 ± 34.8; p = .262). Breath hydrogen was not different between trials (p = .347), nor was TTE performance (CES-HGel 722 ± 182 s and CES-Std: 756 ± 187 s; p = .08). In conclusion, sodium alginate and pectin added to a CES consumed during endurance running does not alter the blood glucose responses, carbohydrate malabsorption, substrate oxidation, GIS, or TTE beyond those of a CES with otherwise matched ingredients.

No Benefit of Ingestion of a Ketone Monoester Supplement on 10-km Running Performance.

PURPOSE: Preexercise ingestion of exogenous ketones alters the metabolic response to exercise, but effects on exercise performance have been equivocal. METHODS: On two occasions in a double-blind, randomized crossover design, eight endurance-trained runners performed 1 h of submaximal exercise at approximately 65% V˙O2max immediately followed by a 10-km self-paced time trial (TT) on a motorized treadmill. An 8% carbohydrate-electrolyte solution was consumed before and during exercise, either alone (CHO + PLA), or with 573 mg·kg of a ketone monoester supplement (CHO + KME). Expired air, HR, and RPE were monitored during submaximal exercise. Serial venous blood samples were assayed for plasma glucose, lactate, and ß-hydroxybutyrate concentrations. RESULTS: CHO + KME produced plasma ß-hydroxybutyrate concentrations of approximately 1.0 to 1.3 mM during exercise (P < 0.001), but plasma glucose and lactate concentrations were similar during exercise in both trials. V˙O2, running economy, respiratory exchange ratio, HR, and RPE were also similar between trials. Performance in the 10-km TT was not different (P = 0.483) between CHO + KME (mean, 2402 s; 95% confidence interval, 2204-2600 s) and CHO + PLA (mean, 2422 s; 95% confidence interval, 2217-2628 s). Cognitive performance, measured by reaction time and a multitasking test, did not differ between trials. CONCLUSIONS: Compared with carbohydrate alone, coingestion of KME by endurance-trained athletes elevated plasma ß-hydroxybutyrate concentrations, but did not improve 10-km running TT or cognitive performance.

Dietary advice to cardiovascular patients. A brief update for physicians.

It is important, in our opinion, to provide physicians with a brief update of scientifically-sound evidence in preventive nutrition, to be employed in their everyday practice, since the latest scientific and clinical advances in this area are generally not well known. Here, we review the most recent evidence in support of an optimal cardio-protective diet, and we identify the need to focus mainly on protective food which should be part of such diet, rather than on nutrients with negative effects to be limited (salt, saturated fats, simple sugars). We conclude that, to favor patient compliance, it is also necessary to underscore indications on the topics for which there is convincing and coherent literature, leaving other less-explored aspects to individual preferences.

Blueberry Leaf Polyphenols Prevent Body Fat Accumulation in Mice Fed High-fat, High-sucrose Diet.

Blueberry leaf is currently a popular dietary supplement. Effects of dietary blueberry leaf and its active components on body fat accumulation were examined. C57BL/6J mice were fed high-fat, high-sucrose diet with or without 3% blueberry leaf extract (BLEx) or 3% concentrated-polyphenolic BLEx (CP BLEx) for 8 weeks. Compared to mice fed a high-fat, high-sucrose diet without blueberry leaf, BLEx and CP BLEx significantly reduced body weight and adipose tissue weight gain. Adipocytes were also smaller and and liver lipid accumulatioin was significantly inhibited in mice fed either BLEx or CP BLEx. These effects tended to be more pronounced in mice fed CP BLEx compared to in mice fed BLEx. Together, results suggest that blueberry leaf inhibits body fat accumulation typically observed in mice fed a high-fat, high-sucrose diet, and that inhibition is attributable to polyphenolic components in leaf extracts.

Hypokalemic periodic paralysis - the importance of patient education.

Hypokalemic periodic paralysis (HOKPP) is a rare neuromuscular disorder caused by altered transport of cellular potassium that leads to significant muscle weakness of the extremities. Paralytic attacks are induced by a drop in the serum potassium level and they have been associated with specific triggers. This case describes a 21-year-old male who has had recurrent presentations of acute paralytic attacks following vigorous physical activity. At presentation, this patient exhibited flaccid paralysis of all skeletal muscles below the neck, but was alert and oriented with stable vital signs. The patient was found to have a potassium level of 2.1 mmol/L and an EKG demonstrating U waves (characteristic of hypokalemia). The patient was treated with potassium supplementation with resolution of symptoms. The mainstay of prevention of long term permanent muscle weakness is avoidance of triggers that can lead to hypokalemia. Through education on disease process and lifestyle modifications, we were able to end the cycle of recurrent hospital readmissions and the subsequent financial burden this generated for the patient and his family.

Antihyperlipidemic Activity of Ligularia fischeri Extract in Mice Fed a High-Carbohydrate Diet.

Ligularia fischeri, indigenous to eastern Asia, has been used as a traditional herbal medicine. Ligularia fischeri reportedly possesses a number of biological activities such as antimutagenic, antioxidant, antigenotoxic, and anti-inflammation. This study demonstrated the effects of ethanol extracts of Ligularia fischeri (ELF) on a high-carbohydrate diet (HCD)-induced hyperlipidemia in C57BL/6 mice. The mice were divided into six groups (n = 7/group) as follows: normal diet, HCD, or HCD+ELF (100, 200, 400, and 800 mg/kg/day), which were orally administered daily for 12 weeks. Various lipid parameters and histological changes in liver and fat tissue were compared among the treatment and control groups. ELF remarkably reduced body weight gain and attenuated hyperlipidemia by improving the plasma levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, atherogenic index, and cardiac risk factor. Moreover, ELF decreased the HCD-induced hepatic accumulation of lipid droplets and adipocyte hypertrophy. These regulatory effects of ELF appeared to be mediated through the phosphorylation of AMP-activated protein kinase, acetyl-CoA carboxylase, sterol regulatory element-binding protein-1c, and expression of fatty acid synthase. Taken together, these findings indicate a functional role for ELF in the regulation of HCD-induced obesity and hyperlipidemia.

Associations of Monounsaturated Fatty Acids From Plant and Animal Sources With Total and Cause-Specific Mortality in Two US Prospective Cohort Studies.

RATIONALE: Dietary monounsaturated fatty acids (MUFAs) can come from both plant and animal sources with divergent nutrient profiles that may potentially obscure the associations of total MUFAs with chronic diseases. OBJECTIVE: To investigate the associations of cis-MUFA intake from plant (MUFA-P) and animal (MUFA-A) sources with total and cause-specific mortality. METHODS AND RESULTS: We followed 63 412 women from the NHS (Nurses' Health Study; 1990-2012) and 29 966 men from the HPFS (Health Professionals Follow-Up Study; 1990-2012). MUFA-Ps and MUFA-As were calculated based on data collected through validated food frequency questionnaires administered every 4 years and updated food composition databases. During 1 896 864 person-years of follow-up, 20 672 deaths occurred. Total MUFAs and MUFA-Ps were inversely associated with total mortality after adjusting for potential confounders, whereas MUFA-As were associated with higher mortality. When MUFA-Ps were modeled to isocalorically replace other macronutrients, hazard ratios (HRs, 95% CIs) of total mortality were 0.84 (0.77-0.92; P<0.001) for replacing saturated fatty acids, 5% of energy); 0.86 (0.82-0.91; P<0.001) for replacing refined carbohydrates (5% energy); 0.91 (0.85-0.97; P<0.001) for replacing trans fats (2% energy), and 0.77 (0.71-0.82; P<0.001) for replacing MUFA-As (5% energy). For isocalorically replacing MUFA-As with MUFA-Ps, HRs (95% CIs) were 0.74 (0.64-0.86; P<0.001) for cardiovascular mortality; 0.73 (0.65-0.82; P<0.001) for cancer mortality, and 0.82 (0.73-0.91; P<0.001) for mortality because of other causes. CONCLUSIONS: Higher intake of MUFA-Ps was associated with lower total mortality, and MUFA-As intake was associated with higher mortality. Significantly lower mortality risk was observed when saturated fatty acids, refined carbohydrates, or trans fats were replaced by MUFA-Ps, but not MUFA-As. These data suggest that other constituents in animal foods, such as saturated fatty acids, may confound the associations for MUFAs when they are primarily derived from animal products. More evidence is needed to elucidate the differential associations of MUFA-Ps and MUFA-As with mortality.