Comparative Study Randomized Controlled Trial

Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial.

Authors: Stephen J Nicholls, A Michael Lincoff, Michelle Garcia...

IMPORTANCE

It remains uncertain whether the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce cardiovascular risk.

OBJECTIVE

To determine the effects on cardiovascular outcomes of a carboxylic acid formulation of EPA and DHA (omega-3 CA) with documented favorable effects on lipid and inflammatory markers in patients with atherogenic dyslipidemia and high cardiovascular risk.

DESIGN, SETTING, AND PARTICIPANTS

A double-blind, randomized, multicenter trial (enrollment October 30, 2014, to June 14, 2017; study termination January 8, 2020; last patient visit May 14, 2020) comparing omega-3 CA with corn oil in statin-treated participants with high cardiovascular risk, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL-C). A total of 13 078 patients were randomized at 675 academic and community hospitals in 22 countries in North America, Europe, South America, Asia, Australia, New Zealand, and South Africa.

INTERVENTIONS

Participants were randomized to receive 4 g/d of omega-3 CA (n = 6539) or corn oil, which was intended to serve as an inert comparator (n = 6539), in addition to usual background therapies, including statins.

MAIN OUTCOMES AND MEASURES

The primary efficacy measure was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization.

RESULTS

When 1384 patients had experienced a primary end point event (of a planned 1600 events), the trial was prematurely halted based on an interim analysis that indicated a low probability of clinical benefit of omega-3 CA vs the corn oil comparator. Among the 13 078 treated patients (mean [SD] age, 62.5 [9.0] years; 35% women; 70% with diabetes; median low-density lipoprotein [LDL] cholesterol level, 75.0 mg/dL; median triglycerides level, 240 mg/dL; median HDL-C level, 36 mg/dL; and median high-sensitivity C-reactive protein level, 2.1 mg/L), 12 633 (96.6%) completed the trial with ascertainment of primary end point status. The primary end point occurred in 785 patients (12.0%) treated with omega-3 CA vs 795 (12.2%) treated with corn oil (hazard ratio, 0.99 [95% CI, 0.90-1.09]; P = .84). A greater rate of gastrointestinal adverse events was observed in the omega-3 CA group (24.7%) compared with corn oil-treated patients (14.7%).

CONCLUSIONS AND RELEVANCE

Among statin-treated patients at high cardiovascular risk, the addition of omega-3 CA, compared with corn oil, to usual background therapies resulted in no significant difference in a composite outcome of major adverse cardiovascular events. These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in high-risk patients.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT02104817.

Topics: Adult; Cardiovascular Diseases; Cholesterol; Corn Oil; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Female; Heart Disease Risk Factors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertriglyceridemia; Male; Middle Aged; Treatment Outcome; Triglycerides

PubMed: 33190147
DOI: 10.1001/jama.2020.22258

Review

Authors: Mingke Tian, Yuchen Bai, Hongyu Tian...

With population and economic development increasing worldwide, the public is increasingly concerned with the health benefits and nutritional properties of vegetable oils (VOs). In this review, the chemical composition and health-promoting benefits of 39 kinds of VOs were selected and summarized using Web of Science as the main bibliographic databases. The characteristic chemical compositions were analyzed from fatty acid composition, tocols, phytosterols, squalene, carotenoids, phenolics, and phospholipids. Health benefits including antioxidant activity, prevention of cardiovascular disease (CVD), anti-inflammatory, anti-obesity, anti-cancer, diabetes treatment, and kidney and liver protection were examined according to the key components in representative VOs. Every type of vegetable oil has shown its own unique chemical composition with significant variation in each key component and thereby illustrated their own specific advantages and health effects. Therefore, different types of VOs can be selected to meet individual needs accordingly. For example, to prevent CVD, more unsaturated fatty acids and phytosterols should be supplied by consuming pomegranate seed oil, flaxseed oil, or rice bran oil, while coconut oil or perilla seed oil have higher contents of total phenolics and might be better choices for diabetics. Several oils such as olive oil, corn oil, cress oil, and rice bran oil were recommended for their abundant nutritional ingredients, but the intake of only one type of vegetable oil might have drawbacks. This review increases the comprehensive understanding of the correlation between health effects and the characteristic composition of VOs, and provides future trends towards their utilization for the general public's nutrition, balanced diet, and as a reference for disease prevention. Nevertheless, some VOs are in the early stages of research and lack enough reliable data and long-term or large consumption information of the effect on the human body, therefore further investigations will be needed for their health benefits.

Topics: Humans; Rice Bran Oil; Plant Oils; Corn Oil; Coconut Oil; Cardiovascular Diseases

PubMed: 37687222
DOI: 10.3390/molecules28176393

Review

Authors: Yuqing Zhang, Tahir Mahmood, Zhenhai Tang...

This study was conducted to investigate the effects of naturally oxidized corn oil on the inflammatory reaction and intestinal health of broilers. Total 450, one-day-old Arbor Acres male broilers were randomly divided into 5 treatments with 6 replicate cages (15 birds in each replicate cage). The dietary treatment array consisted of the varying ratio of nonoxidized corn oil to naturally oxidized corn oil from 0:100, 25:75, 50:50, 75:25, and 100:0, respectively. The experimental period was 42 d. Serum, jejunum, and contents of cecum samples were taken at the age of 42 d of broilers. The results showed no significant difference in the body weight gain (BWG) with a different proportion of oxidized corn oil compared with the 0% oxidized oil group on d 42. The feed intake (FI), the concentration of immunoglobulin G (IgG), interferon-γ (IFN-γ), and interleukin-10 (IL10) in serum showed a significant quadratic response with the increase of oxidized oil concentration on d 42. The serum's concentration of IgG, IFN-γ, and IL-10 reached the highest value at 75% oxidized corn oil. In addition, the mRNA expression levels of interleukin-1β (IL-1β), IFN-γ, nuclear factor kappa B (NF-κB), tumor necrosis factor α (TNF-α), and myeloid differentiation factor-88 (MyD88) in the jejunum were significantly affected by different proportions of oxidized corn oil, and the gene expression levels were highest at 75% oxidized corn oil on d 42. The mRNA expression of Bcl2-associated X (Bax) in the jejunum showed a significantly quadratic curve with the increase of oxidized oil concentration, and its gene expression was the highest after adding 50% oxidized corn oil according to the regression equation on d 42. The villus height/crypt depth and goblet cells of jejunum decreased linearly with the increasing proportion of oxidized corn oil and reached the lowest point after adding 100% oxidized corn oil on d 42. The β diversity showed the remarkable differentiation of microbial communities among 5 groups, and the microbial community of the 0% oxidized oil group was significantly separated from that of 75 and 100% oxidized oil groups in the cecum. Taken together, these results showed that a low dose of naturally oxidized corn oil is not harmful to the growth of broilers, while a high dose of oxidized corn oil will trigger the inflammatory response and adversely affect the gut health of broilers.

Topics: Animals; Chickens; Corn Oil; Diet; Eating; Male; Microbiota; Randomized Controlled Trials as Topic

PubMed: 34788712
DOI: 10.1016/j.psj.2021.101541

Authors: Erika Kwek, Chi Yan, Huafang Ding...

Repeated reuse of frying oil raises health concerns due to the accumulation of oxidative products after each frying cycle. Gut microbiota is integral in lipid metabolism and immune regulation. The present study was designed to investigate the effects of thermally-oxidized corn oil and lard on gut microbiota in relation to atherosclerosis, inflammatory cytokines, and plasma lipids. Male Golden Syrian hamsters were randomly divided into four groups and fed one of four diets containing fresh corn oil (CF), oxidized corn oil (CO), fresh lard (LF), and oxidized lard (LO), for six weeks. CO and LO were prepared by deep-frying potatoes in corn oil or lard for seven days. Results indicated that oxidized oil and lard caused the loss of species diversity and richness of gut microbiota. Feeding CO and LO also reduced the body and adipose tissue weights, associated with genus and . Plasma triacylglycerols significantly increased by 51% in the CO and 35% in the LO group compared with that in their CF and LF counterparts, respectively. CO could also affect the abundance of specific bacteria genera: and . In addition, CO and LO could adversely remodel gut composition and affect intestinal production of short-chain fatty acids, pro-inflammatory biomarkers (LPS and IL-6), anti-inflammatory biomarker IL-10, and atherosclerotic progression. It was concluded that frying oil could adversely modulate the gut microbiota and exacerbate the atherosclerosis at least in a hypercholesterolemia hamster model.

PubMed: 36139806
DOI: 10.3390/antiox11091732

Authors: Keqing Jiang, Shibang Lu, Dongxiao Li...

BACKGROUND

Nonalcoholic steatohepatitis (NASH) is an advanced form of chronic fatty liver disease, which is a driver of hepatocellular carcinoma. However, the roles of the C5aR1 in the NASH remain poorly understood. Here, we aimed to investigate the functions and mechanisms of the C5aR1 on hepatic inflammation and fibrosis in murine NASH model.

METHODS

Mice were fed a normal chow diet with corn oil (ND + Oil), a Western diet with corn oil (WD + Oil) or a Western diet with carbon tetrachloride (WD + CCl) for 12 weeks. The effects of the C5a-C5aR1 axis on the progression of NASH were analyzed and the underlying mechanisms were explored.

RESULTS

Complement factor C5a was elevated in NASH mice. C5 deficiency reduced hepatic lipid droplet accumulation in the NASH mice. The hepatic expression levels of TNFα, IL-1β and F4/80 were decreased in C5-deficient mice. C5 loss alleviated hepatic fibrosis and downregulated the expression levels of α-SMA and TGFβ1. C5aR1 deletion reduced inflammation and fibrosis in NASH mice. Transcriptional profiling of liver tissues and KEGG pathway analysis revealed that several pathways such as Toll-like receptor signaling, NFκB signaling, TNF signaling, and NOD-like receptor signaling pathway were enriched between C5aR1 deficiency and wild-type mice. Mechanistically, C5aR1 deletion decreased the expression of TLR4 and NLRP3, subsequently regulating macrophage polarization. Moreover, C5aR1 antagonist PMX-53 treatment mitigated the progression of NASH in mice.

CONCLUSIONS

Blockade of the C5a-C5aR1 axis reduces hepatic steatosis, inflammation, and fibrosis in NASH mice. Our data suggest that C5aR1 may be a potential target for drug development and therapeutic intervention of NASH.

Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; Toll-Like Receptor 4; Corn Oil; Mice, Knockout; Liver; Fibrosis; Hepatitis; Liver Cirrhosis; Disease Models, Animal; Inflammation; Signal Transduction; Liver Neoplasms; Macrophages; Mice, Inbred C57BL

PubMed: 37227481
DOI: 10.1007/s00535-023-02002-w

Randomized Controlled Trial

Authors: Hideaki Kashima, Ayumi Honma, Saori Kamimura...

Consumption of 2,4-decadienal (2,4-DD) delays gastric emptying (GE) rate in animals. Oil heating produces 2,4-DD and other aldehydes. Here we examined whether heated oil affects GE rate and food intake in humans, and whether it is mediated by 2,4-DD. In the first experiment, 10 healthy volunteers consumed 240-g pumpkin soup with 9.2 g of heated (HO) or non-heated corn oil (CO). Subsequently, 17 participants consumed pumpkin soup containing 3.1 g of either heated corn oil (HO), 1 mg 2,4-DD + non-heated corn oil (2,4-DD), or non-heated corn oil (CO). Sixty minutes following pumpkin soup, cod roe spaghetti was provided, and then energy intake was determined. To evaluate GE rate, C breath test (Experiment 1) and ultrasonography (Experiments 1 and 2) were used. The results from the Experiment 1 confirmed that consumption of heated corn oil reduced GE rate. Experiment 2 showed a delayed GE rate in HO and 2,4-DD trials compared with CO trial ( < 0.05). Energy intake was approximately 600-650 kJ lower in HO and 2,4-DD trials compared with CO trial ( < 0.05). These findings suggest that 2,4-DD, either formed by oil heating or added to food, contributes to suppressing GE rate and energy intake.

Topics: Aldehydes; Breath Tests; Corn Oil; Cross-Over Studies; Cucurbita; Eating; Energy Intake; Female; Food Additives; Gastric Emptying; Healthy Volunteers; Hot Temperature; Humans; Male; Ultrasonography; Young Adult

PubMed: 33920888
DOI: 10.3390/nu13041304

Authors: YoonHa Kim, Mi-Ja Kim, JaeHwan Lee...

Corn oil was heated using an infrared cooker, an air fryer, and a cooking oven at similar temperatures, and oxidative stability and physicochemical properties including moisture content, temperature change, the profile of headspace volatiles, formaldehyde and acetaldehyde of the heated oils were compared. Corn oil heated using the air fryer showed the lowest degree of oxidation, followed by that heated using the infrared cooker and the cooking oven. However, the content of headspace volatiles in 120 min heated oil using the infrared cooker was higher by 2.57 and 5.37 times than that in oil heated using the cooking oven and the air fryer, respectively. The profiles of formaldehyde and acetaldehyde in oils showed patterns inconsistent with those of headspace volatile and oxidation parameters. Generally, the air fryer-treated oil underwent slow lipid oxidation, whereas oil from the infrared cooker had more volatiles and imparted odor to foods.

PubMed: 36060572
DOI: 10.1007/s10068-022-01127-7

Authors: Basma Damiri, William S Baldwin

We previously made a RNAi-based cytochrome P450 2b (Cyp2b)-knockdown (Cyp2b-KD) mouse to determine the in vivo role of the Cyp2b subfamily in xenobiotic detoxification. Further studies reported here indicate a role for Cyp2b in unsaturated fatty-acid (UFA) metabolism and in turn obesity. Mice were treated intraperitoneally (i.p.) with 100 μL corn oil as a carrier or the potent Cyp2b-inducer 3,3',5,5'-Tetrachloro-1,4-bis(pyridyloxy)benzene (TCPOBOP (TC)) dissolved in corn oil. Surprisingly, female Cyp2b-KD mice but not male mice showed increased liver lipid accumulation. Male Cyp2b-KD mice had higher serum triacylglycerols, cholesterol, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) than wildtype (WT) mice; females had higher cholesterol, LDL, and HDL. Thus, Cyp2b-KD mice are unable to clear a high bolus dose of corn oil, potentially because the Cyp2b-KD mice were unable to metabolize the UFA in the corn oil. Therefore, WT and Cyp2b-KD mice were housed for 35 weeks and necropsies performed to test whether Cyp2b-KD mice develop age onset obesity. Cyp2b-KD mice exhibited a significant increase in body weight caused by an increase in white adipose tissue deposition relative to WT mice. Serum cholesterol, triacylglycerol, LDL, and VLDL were significantly greater in 35-week-old Cyp2b-KD males compared to WT males; only serum triacylglycerol and LDL were higher in females. In conclusion, changes in Cyp2b expression led to perturbation in lipid metabolism and depuration in Cyp2b-KD mice. This suggests that Cyp2b is more than a detoxification enzyme, but also involved in the metabolism of UFA, as Cyp2b-KD mice have increased the body weight, fat deposition, and serum lipids.

Topics: Aging; Animals; Body Weight; Corn Oil; Cytochrome P-450 Enzyme System; Fatty Acids, Unsaturated; Female; Injections, Intraperitoneal; Lipid Metabolism; Lipids; Male; Mice; Mice, Inbred Strains; Mice, Knockout; Obesity

PubMed: 30421529
DOI: 10.1002/lipd.12095

Authors: Jaume Sempere-Torregrosa, Jose Miguel Ferri, Harrison de la Rosa-Ramírez...

The present work analyzes the influence of modified, epoxidized and maleinized corn oil as a plasticizing and/or compatibilizing agent in the PLA-PHB blend (75% PLA and 25% PHB wt.%). The chemical modification processes of corn oil were successfully carried out and different quantities were used, between 0 and 10% wt.%. The different blends obtained were characterized by thermal, mechanical, morphological, and disintegration tests under composting conditions. It was observed that to achieve the same plasticizing effect, less maleinized corn oil (MCO) is needed than epoxidized corn oil (ECO). Both oils improve the ductile properties of the PLA-PHB blend, such as elongation at break and impact absorb energy, however, the strength properties decrease. The ones that show the highest ductility values are those that contain 10% ECO and 5% MCO, improving the elongation of the break of the PLA-PHB blend by more than 400% and by more than 800% for the sample PLA.

PubMed: 36236152
DOI: 10.3390/polym14194205

Gut microbiota contributes to bisphenol A-induced maternal intestinal and placental apoptosis, oxidative stress, and fetal growth restriction in pregnant ewe model by regulating gut-placental axis.

Authors: Hao Zhang, Xia Zha, Bei Zhang...

BACKGROUND

Bisphenol A (BPA) is an environmental contaminant with endocrine-disrupting properties that induce fetal growth restriction (FGR). Previous studies on pregnant ewes revealed that BPA exposure causes placental apoptosis and oxidative stress (OS) and decreases placental efficiency, consequently leading to FGR. Nonetheless, the response of gut microbiota to BPA exposure and its role in aggravating BPA-mediated apoptosis, autophagy, mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and OS of the maternal placenta and intestine are unclear in an ovine model of gestation.

RESULTS

Two pregnant ewe groups (n = 8/group) were given either a subcutaneous (sc) injection of corn oil (CON group) or BPA (5 mg/kg/day) dissolved in corn oil (BPA group) once daily, from day 40 to day 110 of gestation. The maternal colonic digesta and the ileum and placental tissue samples were collected to measure the biomarkers of autophagy, apoptosis, mitochondrial dysfunction, ERS, and OS. To investigate the link between gut microbiota and the BPA-induced FGR in pregnant ewes, gut microbiota transplantation (GMT) was conducted in two pregnant mice groups (n = 10/group) from day 0 to day 18 of gestation after removing their intestinal microbiota by antibiotics. The results indicated that BPA aggravates apoptosis, ERS and autophagy, mitochondrial function injury of the placenta and ileum, and gut microbiota dysbiosis in pregnant ewes. GMT indicated that BPA-induced ERS, autophagy, and apoptosis in the ileum and placenta are attributed to gut microbiota dysbiosis resulting from BPA exposure.

CONCLUSIONS

Our findings indicate the underlying role of gut microbiota dysbiosis and gut-placental axis behind the BPA-mediated maternal intestinal and placental apoptosis, OS, and FGR. The findings further provide novel insights into modulating the balance of gut microbiota through medication or probiotics, functioning via the gut-placental axis, to alleviate gut-derived placental impairment or FGR. Video Abstract.

Topics: Humans; Pregnancy; Sheep; Female; Animals; Mice; Placenta; Gastrointestinal Microbiome; Fetal Growth Retardation; Dysbiosis; Corn Oil; Oxidative Stress; Mitochondrial Diseases; Benzhydryl Compounds; Phenols

PubMed: 38365714
DOI: 10.1186/s40168-024-01749-5