ABSTRACT
Cytokine storm during severe COVID-19 infection increases the risk of mortality in critically ill patients in the intensive care unit. Multiple therapeutic proposals include, for example, anti-inflammatory and immunosuppressive agents, selective inhibitors of key pro-inflammatory receptors, and key enzymes necessary for viral replication. Unfortunately, safe and effective therapy remains an elusive goal. An alternative anti-inflammatory approach vis á vis omega-3 fatty acids, which yields less pro-inflammatory mediators by altering eicosanoid metabolism, has been proposed. Although theoretically promising, enteral tube delivery or oral capsules containing specific doses of omega-3 fatty acids take precious time (7 days to 6 weeks) to be incorporated in plasma cell membranes to be most effective, making this route of administration in the acute care setting an unfeasible therapeutic approach. Parenteral administration of precise doses of omega-3 fatty acid triglycerides in an injectable emulsion can greatly accelerate the incorporation and potential therapeutic effects (within hours), but at present, there is no commercially available product designed for this purpose. We describe a potential formulation that may address this deficiency, while recognizing that the high incidence of hyperlipidemia that occurs during severe COVID-19 infection must be recognized as a complicating factor, and, therefore, caution is advised.
Subject(s)
COVID-19 , Fatty Acids, Omega-3 , Humans , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Intensive Care Units , Cell Membrane , Fatty Acids, Omega-3/therapeutic useABSTRACT
Inflammation in arterial walls leads to coronary artery disease (CAD). We previously reported that a high omega-3 fatty index was associated with prevention of progression of coronary atherosclerosis, a disease of chronic inflammation in the arterial wall. However, the mechanism of such benefit is unclear. The two main omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are precursors of specialized pro-resolving lipid mediators (SPMs)-resolvins and maresins-which actively resolve chronic inflammation. To explore whether SPMs are associated with coronary plaque progression, levels of SPMs and proinflammatory mediators (leukotriene B4 [LTB4 ] and prostaglandins) were measured using liquid chromatography-tandem mass spectrometry in 31 statin-treated patients with stable CAD randomized to either EPA and DHA, 3.36 g daily, or no EPA/DHA (control). Coronary plaque volume was measured by coronary computed tomographic angiography at baseline and at 30-month follow-up. Higher plasma levels of EPA+DHA were associated with significantly increased levels of two SPMs-resolvin E1 and maresin 1-and 18-hydroxy-eicosapentaenoic acid (HEPE), the precursor of resolvin E1. Those with low plasma EPA+DHA levels had a low (18-HEPE+resolvin E1)/LTB4 ratio and significant plaque progression. Those with high plasma EPA+DHA levels had either low (18-HEPE+resolvin E1)/LTB4 ratios with significant plaque progression or high (18-HEPE+resolvin E1)/LTB4 ratios with significant plaque regression. These findings suggest that an imbalance between pro-resolving and proinflammatory lipid mediators is associated with plaque progression and potentially mediates the beneficial effects of EPA and DHA in CAD patients.
Subject(s)
Eicosapentaenoic Acid/analogs & derivatives , Eicosapentaenoic Acid/blood , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Leukotriene B4/blood , Plaque, Atherosclerotic/drug therapy , Prostaglandins/blood , Aged , Docosahexaenoic Acids/blood , Female , Humans , Male , Middle AgedSubject(s)
COVID-19/therapy , Critical Illness/therapy , Docosahexaenoic Acids/therapeutic use , Eicosapentaenoic Acid/therapeutic use , Fat Emulsions, Intravenous/chemistry , Fish Oils/therapeutic use , Parenteral Nutrition , COVID-19/complications , Critical Care , Emulsions , Humans , Inflammation/etiology , Inflammation/prevention & control , Research DesignABSTRACT
BACKGROUND: Dietary strategies can aid in the management of critically ill patients. Very-low-carbohydrate diets have been shown to improve glucose control and the inflammatory response. We aimed to determine the effects of a eucaloric ketogenic diet (EKD) enriched with ω-3 fatty acids (O3KD) on glucose levels and inflammation in mice with endotoxemia. METHODS: Adult mice were fed 1 of 3 diets (control diet [CD], EKD, or O3KD). After 4 weeks, each group received saline or Escherichia coli lipopolysaccharide (LPS) (5 mg/kg) intraperitoneally during the postprandial (PPP) or postabsorptive (PAP) periods. Blood glucose was measured at 0, 15, 30, 60, 90, 120, 180, and 240 minutes. Serum tumor necrosis factor (TNF)-α and interleukin (IL) 6 were measured by enzyme-linked immunosorbent assay. Distribution of serum fatty acids was determined by gas liquid chromatography. Hepatic expression of genes involved in inflammation, as well as glucose and lipid metabolism, were determined by quantitative polymerase chain reaction. RESULTS: During the PPP, glucose curves were comparable among the experimental groups. During the PAP, EKD showed a more pronounced increase in glucose levels at the first hour after LPS challenge compared with the CD-LPS group. During the PAP, IL6 was lower in O3KD-LPS compared with CD-LPS and EKD-LPS groups. These differences disappeared in the PPP. Similarly, TNF-α was lower in the O3KD-LPS group compared with the EKD-LPS group. The O3KD significantly increased the serum levels of the ω-3 eicosapentaenoic and docosahexaenoic acids and decreased the ω-6 arachidonic acid. CONCLUSION: An O3KD leads to reduced inflammation and maintains glucose homeostasis in mice with endotoxemia.
Subject(s)
Blood Glucose/analysis , Diet, Ketogenic , Endotoxemia/diet therapy , Endotoxemia/physiopathology , Fatty Acids, Omega-3/administration & dosage , Inflammation/prevention & control , Animals , Escherichia coli , Inflammation/blood , Interleukin-6/blood , Lipopolysaccharides/administration & dosage , Male , Mice , Mice, Inbred C57BL , Tumor Necrosis Factor-alpha/bloodABSTRACT
BACKGROUND AND AIMS: Higher blood levels of the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been associated with fewer cardiovascular events and lower mortality in prospective studies. Our aim was to determine a target level of EPA and DHA to prevent progression of coronary artery plaque. METHODS: 218 subjects with stable coronary artery disease on statins were randomized to high-dose EPA and DHA (3.36 g daily) or no omega-3 for 30 months. Coronary plaque volume was measured by coronary computed tomographic angiography. Plasma phospholipid levels of EPA, DHA and total fatty acids were measured by gas chromatography mass spectrometry. The omega-3 fatty acid index was calculated as EPA+DHA/total fatty acid. RESULTS: Mean (SD) age was 62.9 (7.8) years; mean (SD) LDL-C level 78.6 (27.3) mg/dL and median triglyceride level 122â¯mg/dL. Subjects assigned to EPA and DHA had increased plasma EPA and DHA levels variably from 1.85% to 13.02%. Plasma omega-3 fatty acid index ≥4% prevented progression of fibrous, noncalcified, calcified and total plaque in nondiabetic subjects whereas those in the lowest quartile (<3.43%) had significant progression of fibrous, calcified and total plaque. No difference was observed in diabetic subjects. CONCLUSIONS: EPA and DHA added to statins prevented coronary plaque progression in nondiabetic subjects with mean LDL-C <80â¯mg/dL, when an omega-3 index ≥4% was achieved. Low omega-3 index <3.43% identified nondiabetic subjects at risk of coronary plaque progression despite statin therapy. These findings highlight the importance of measuring plasma levels of omega-3 fatty acids early and at trial conclusion. Targeting an omega-3 index ≥4% maximizes cardiovascular benefit.
Subject(s)
Coronary Artery Disease/blood , Coronary Artery Disease/drug therapy , Docosahexaenoic Acids/blood , Eicosapentaenoic Acid/blood , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Plaque, Atherosclerotic/blood , Aged , Coronary Artery Disease/complications , Coronary Artery Disease/prevention & control , Disease Progression , Docosahexaenoic Acids/physiology , Eicosapentaenoic Acid/physiology , Female , Humans , Male , Middle Aged , Plaque, Atherosclerotic/complications , Plaque, Atherosclerotic/prevention & controlABSTRACT
Iron deficiency and anaemia after metabolic surgery, potentially modifiable nutritional complications, are becoming an increasing cause for concern as prevalence increases with time and there is limited evidence supporting the effectiveness of the current guidelines for prophylactic oral iron supplementation and treatment for deficiency. Abnormalities in iron nutrition predisposing to deficiency are common in severely obese patients, and the low-grade systemic inflammation, also common to these patients, reduces the effectiveness of oral iron supplementation. The surgical procedures result in alterations of foregut anatomy and physiology, which limit iron absorptive capacity and daily food intake. These alterations and the limited effects of oral iron supplementation explain the high prevalence of postoperative iron deficiency and anaemia. This review outlines current mechanisms concerning the pathogenesis of disordered iron nutrition in patients with severe obesity, current gaps in knowledge, and opportunities for quality improvement.
Subject(s)
Anemia, Iron-Deficiency/etiology , Bariatric Surgery/adverse effects , Iron/metabolism , Obesity/surgery , Humans , Nutritional Status , Postoperative Complications/etiologyABSTRACT
BACKGROUND: Poor physical function impairs fitness and exercise and is associated with worse cardiovascular outcomes and all-cause mortality. Joint pain and stiffness limit physical function. OBJECTIVE: To determine if eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation improves physical function and exercise in coronary artery disease (CAD) patients. METHODS: A total of 291 subjects with stable CAD were randomized to either Lovaza (1.86 g of EPA and 1.5 g of DHA daily) or no Lovaza (control) for 1 year. Change in pain, stiffness, and physical function was assessed by the Western Ontario and McMaster Universities Arthritis Index. Minutes of exercise per week were recorded, and musculoskeletal events were reported. RESULTS: Mean age (standard deviation) was 63.3 (7.6) years. In the intention-to-treat analysis, compared with controls, those on Lovaza had better physical function (mean difference, -11.0%, 95% confidence interval [CI] -18.5% to -3.5%, P = .004), better total Western Ontario and McMaster Universities Arthritis Index scores (mean difference, -9.8%, 95% CI -16.6% to -3.0%, P = .005), more exercise per week (135 minutes vs 197 minutes, respectively, P = .028), and less joint replacement (11 vs 1, respectively, P = .002). Pain and stiffness showed a trend toward significance (P = .06). The per-protocol analysis also showed less stiffness compared with controls (mean difference, -11.5%, 95% CI -22.9% to -0.1%, P = .048). CONCLUSION: High-dose EPA and DHA may benefit CAD patients by preserving physical function, increasing amount of exercise, and reducing joint replacement. EPA and DHA may be a safe preventative strategy against musculoskeletal symptoms in CAD patients.
Subject(s)
Coronary Artery Disease/drug therapy , Docosahexaenoic Acids/therapeutic use , Eicosapentaenoic Acid/analogs & derivatives , Exercise , Aged , Arthroplasty, Replacement , Blood Cell Count , C-Reactive Protein/analysis , Coronary Artery Disease/pathology , Dietary Supplements , Eicosapentaenoic Acid/therapeutic use , Female , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
Protein sparing therapies were developed to mitigate the harms associated with protein-calorie malnutrition and nitrogen losses induced by either acute illness or hypocaloric diets in patients with obesity. We review the development of protein sparing therapies in illness and obesity with a focus on the pioneering contributions of George Blackburn, MD, PhD. He recognized that protein-calorie malnutrition is a common and serious clinical condition and developed new approaches to its treatment in hospitalized patients. His work with stable isotopes and with animal models provided answers about the physiological nutritional requirements and metabolic changes across a spectrum of conditions with varying degrees of stress and catabolism. This led to improvements in enteral and parenteral nutrition for patients with acute illness. Blackburn also demonstrated that lean body mass can be preserved during weight loss with carefully designed very low calorie treatments which became known as the protein sparing modified fast (PSMF). We review the role of the PSMF as part of the comprehensive management of obesity.
Subject(s)
Nutritional Sciences/history , Obesity/metabolism , Obesity/therapy , Protein-Energy Malnutrition/therapy , Proteins/metabolism , Acute Disease/therapy , Animals , History, 20th Century , History, 21st Century , HumansABSTRACT
BACKGROUND: Although statins reduce cardiovascular events, residual risk remains. Therefore, additional modalities are needed to reduce risk. We evaluated the effect of eicosapentaenoic acid and docosahexaenoic acid in pharmacologic doses added to statin treatment on coronary artery plaque volume. METHODS AND RESULTS: A total of 285 subjects with stable coronary artery disease on statins were randomized to omega-3 ethyl-ester (1.86 g of eicosapentaenoic acid and 1.5 g of docosahexaenoic acid daily) or no omega-3 (control) for 30 months. Coronary plaque volume was assessed by coronary computed tomographic angiography. Mean (SD) age was 63.0 (7.7) years; mean low-density lipoprotein cholesterol ≤80 mg/dL. In the intention-to-treat analysis, our primary endpoint, noncalcified plaque volume, was not different between groups (P=0.14) but approached significance in the per protocol analysis (P=0.07). When stratified by age in the intention-to-treat analysis, younger omega-3 subjects had significantly less progression of the primary endpoint, noncalcified plaque (P=0.013), and fibrous, calcified and total plaque. In plaque subtype analysis, controls had significant progression of fibrous plaque compared to no change in the omega-3 ethyl-ester group (median % change [interquartile range], 5.0% [-5.7, 20.0] versus -0.1% [-12.3, 14.5], respectively; P=0.018). Among those on low-intensity statins, omega-3 ethyl-ester subjects had attenuation of fibrous plaque progression compared to controls (median % change [interquartile range], 0.3% [-12.8, 9.0] versus 4.8% [-5.1, 19.0], respectively; P=0.032). In contrast, those on high-intensity statins had no difference in plaque change in either treatment arm. CONCLUSIONS: High-dose eicosapentaenoic acid and docosahexaenoic acid provided additional benefit to statins in preventing progression of fibrous coronary plaque in subjects adherent to therapy with well-controlled low-density lipoprotein cholesterol levels. The benefit on low-intensity statin, but not high-intensity statin, suggests that statin intensity affects plaque volume. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01624727.
Subject(s)
Coronary Artery Disease/drug therapy , Coronary Vessels/diagnostic imaging , Docosahexaenoic Acids/administration & dosage , Eicosapentaenoic Acid/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Plaque, Atherosclerotic/drug therapy , Administration, Oral , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Computed Tomography Angiography , Coronary Angiography , Coronary Artery Disease/blood , Coronary Artery Disease/diagnosis , Coronary Vessels/drug effects , Disease Progression , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Lipoproteins, LDL/blood , Male , Middle Aged , Plaque, Atherosclerotic/blood , Plaque, Atherosclerotic/diagnosis , Risk Factors , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: Parenteral nutrition associated liver disease (PNALD) is a deadly complication of long term parenteral nutrition (PN) use in infants. Fish oil-based lipid emulsion has been shown in recent years to effectively treat PNALD. Alternative fat sources free of essential fatty acids have recently been investigated for health benefits related to decreased inflammatory response. We hypothesized that the addition of medium-chain triglycerides (MCT) to a purified fish oil-based diet would decrease the response to inflammatory challenge in mice, while allowing for sufficient growth and development. MATERIALS/METHODS: Six groups of ten adult male C57/Bl6 mice were pair-fed different dietary treatments for a period of twelve weeks, varying only in fat source (percent calories by weight): 10.84% soybean oil (SOY), 10% coconut oil (HCO), 10% medium-chain triglycerides (MCT), 3% purified fish oil (PFO), 3% purified fish oil with 3% medium-chain triglycerides (50:50 MCT:PFO) and 3% purified fish oil with 7.59% medium-chain triglycerides (70:30 MCT:PFO). An endotoxin challenge was administered to half of the animals in each group at the completion of dietary treatment. RESULTS: All groups demonstrated normal growth throughout the study period. Groups fed MCT and HCO diets demonstrated biochemical essential fatty acid deficiency and decreased IL-6 and TNF-α response to endotoxin challenge. Groups containing PFO had increased inflammatory response to endotoxin challenge, and the addition of MCT to PFO mitigated this inflammatory response. CONCLUSION: These results suggest that the addition of MCT to PFO formulations may decrease the host response to inflammatory challenge, which may pose potential for optimized PN formulations. Inclusion of MCT in lipid emulsions given with PN formulations may be of use in therapeutic interventions for disease states resulting from chronic inflammation.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Dietary Fats, Unsaturated/therapeutic use , Dietary Supplements , Disease Models, Animal , Fish Oils/therapeutic use , Non-alcoholic Fatty Liver Disease/prevention & control , Triglycerides/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Deficiency Diseases/etiology , Deficiency Diseases/prevention & control , Dietary Fats, Unsaturated/administration & dosage , Dietary Fats, Unsaturated/adverse effects , Dietary Supplements/adverse effects , Emulsions , Fatty Acids, Essential/adverse effects , Fatty Acids, Essential/deficiency , Fatty Acids, Essential/therapeutic use , Fish Oils/adverse effects , Fish Oils/chemistry , Lipopolysaccharides , Liver/immunology , Liver/metabolism , Liver/pathology , Male , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Parenteral Nutrition, Total/adverse effects , Triglycerides/administration & dosage , Triglycerides/adverse effects , Triglycerides/chemistry , Weight GainABSTRACT
OBJECTIVE: Essential fatty acids (EFA) are necessary for growth, development, and biological function, and must be acquired through the diet. While linoleic acid (LA) and alpha-linolenic acid (ALA) have been considered the true EFAs, we previously demonstrated that docosahexaenoic acid (DHA) and arachidonic acid (AA) taken together as the sole source of dietary fatty acids can prevent biochemical essential fatty acid deficiency (EFAD). This study evaluates the effect of varying dietary ratios of DHA:AA in the prevention and reversal of biochemical EFAD in a murine model. METHODS: Using a murine model of EFAD, we provided mice with 2.1% of daily caloric intake in varying DHA:AA ratios (1:1, 5:1, 10:1, 20:1, 200:1, 100:0) for 19 days in association with a liquid high-carbohydrate fat-free diet to evaluate the effect on fatty acid profiles. In a second experiment, we evaluated the provision of varying DHA:AA ratios (20:1, 200:1, 100:0) on the reversal of biochemical EFAD. RESULTS: Mice provided with DHA and AA had no evidence of biochemical EFAD, regardless of the ratio (1:1, 5:1, 10:1, 20:1, 200:1, 100:0) administered. Biochemical EFAD was reversed with DHA:AA ratios of 20:1, 200:1, and 100:0 following 3 and 5 weeks of dietary provision, although the 20:1 ratio was most effective in the reversal and stabilization of the triene:tetraene ratio. CONCLUSION: Provision of DHA and AA, at 2.1% of daily caloric intake in varying ratios can prevent biochemical evidence of EFAD and hepatic steatosis over the short-term, with a ratio of 20:1 DHA:AA most effectively reversing EFAD.
Subject(s)
Arachidonic Acid/pharmacology , Docosahexaenoic Acids/pharmacology , Fatty Acids, Essential/deficiency , Animals , Diet , Diet, Fat-Restricted , Dietary Carbohydrates/pharmacology , Dietary Fats/pharmacology , Fatty Acids, Nonesterified/blood , Fatty Acids, Nonesterified/metabolism , Fatty Acids, Unsaturated/metabolism , Female , Growth/drug effects , Liver/enzymology , Liver/metabolism , Liver/pathology , Male , Mice , Mice, Inbred C57BLABSTRACT
This study examined whether purified fish oil (PFO) supplemented to an essential fatty acid deficient (EFAD) diet meets EFA needs in rats. The EFAD diet contained 10% hydrogenated coconut oil (HCO). A similar diet contained 7% HCO and 3% PFO which also provided 2.84% arachidonic acid (AA), 52.50% eicosapentaenoic acid (EPA) and 35.73% docosahexaenoic acid (DHA) but no linoleic acid (LA) or alpha linolenic acid (ALA). A 10% soybean oil control diet provided ample LA and ALA. After 4 weeks of feeding, blood glucose, plasma triglyceride and phospholipid fatty acid profiles, C-reactive protein (CRP), TNF and IL-6 were determined after saline or LPS injection. EFAD developed with the HCO diet with triene:tetraene ratios in plasma phospholipids >.20, which remained <.02 with the control and HCO+PFO diets. Mead acid levels significantly increased by a factor of 10 with the HCO diet compared to the AIN and HCO+PFO diets and were significantly lowest with the HCO+PFO diet. 18:1 n9 levels were significantly higher in plasma phospholipids and triglycerides with the HCO diet. CRP levels were significantly highest with the control diet and significantly lowest with the HCO diet. LPS significantly increased 18:1 n9 and cytokines, and decreased AA and plasma glucose in all diets and significantly increased plasma triglycerides and decreased plasma glucose in controls. Providing AA, EPA and DHA in EFAD prevents EFAD over the short-term as reflected in Mead acid production, triene:tetraene ratio, and de novo lipogenesis and may reduce the inflammatory response to LPS.
Subject(s)
Fish Oils/administration & dosage , Animals , Blood Glucose/analysis , Body Weight , C-Reactive Protein/analysis , Eating , Interleukin-6/blood , Linoleic Acid/analysis , Male , Phospholipids/blood , Rats , Rats, Sprague-Dawley , Triglycerides/blood , Tumor Necrosis Factor-alpha/blood , alpha-Linolenic Acid/analysisABSTRACT
This study examined fatty acid profiles, triene-tetraene ratios (20:3n9/20:4n6), and nutritional and inflammatory markers in rats fed an essential fatty acid-deficient (EFAD) diet provided as 2% hydrogenated coconut oil (HCO) alone for 2 weeks or with 1.3 mg of arachidonic acid (AA) and 3.3 mg of docosahexaenoic acid (DHA) (AA + DHA) added to achieve 2% fat. Healthy controls were fed an AIN 93M diet (AIN) with 2% soybean oil. The HCO and AA + DHA diets led to significant reductions of linoleic acid, α-linolenic acid, and AA (20:4n6) and increases in Mead acid (20:3n9) in plasma and liver compared with the AIN diet; but the triene-tetraene levels remained well within normal. However, levels of 20:3n9 and 20:4n6 were lower in liver phospholipids in the AA + DHA than in HCO group, suggesting reduced elongation and desaturation in ω-9 and -6 pathways. The AA + DHA group also had significantly lower levels of 18:1n9 and 16:1n7 as well as 18:1n9/18:0 and 16:1n7/16:0 than the HCO group, suggesting inhibition of stearyl-Co A desaturase-1 activity. In response to lipopolysaccharide, the levels of tumor necrosis factor and interleukin-6 were significantly lower with HCO, reflecting reduced inflammation. The AA + DHA group had higher levels of IL-6 and C-reactive protein than the HCO group but significantly lower than the AIN group. However, in response to endotoxin, interleukin-6 was higher with AA + DHA than with AIN. Feeding an EFAD diet reduces baseline inflammation and inflammatory response to endotoxin long before the development of EFAD, and added AA + DHA modifies this response.
Subject(s)
Arachidonic Acid/pharmacology , Diet , Docosahexaenoic Acids/pharmacology , Endotoxins/toxicity , Fatty Acids, Essential/deficiency , Animals , C-Reactive Protein/metabolism , Eating , Fatty Acids/metabolism , Inflammation/pathology , Interleukin-6/metabolism , Lipid Metabolism/physiology , Male , Nutritional Status , Phospholipids/metabolism , Rats , Rats, Sprague-Dawley , Weight Gain/physiologyABSTRACT
OBJECTIVES: Essential fatty acids are important for growth, development, and physiologic function. α-Linolenic acid and linoleic acid are the precursors of docosahexaenoic and arachidonic acid, respectively, and have traditionally been considered the essential fatty acids. However, the authors hypothesized that docosahexaenoic acid and arachidonic acid can function as the essential fatty acids. METHODS: Using a murine model of essential fatty acid deficiency and consequent hepatic steatosis, the authors provided mice with varying amounts of docosahexaenoic and arachidonic acids to determine whether exclusive supplementation of docosahexaenoic and arachidonic acids could prevent essential fatty acid deficiency and inhibit or attenuate hepatic steatosis. RESULTS: Mice supplemented with docosahexaenoic and arachidonic acids at 2.1% or 4.2% of their calories for 19 days had normal liver histology and no biochemical evidence of essential fatty acid deficiency, which persisted when observed after 9 weeks. CONCLUSION: Supplementation of sufficient amounts of docosahexaenoic and arachidonic acids alone without α-linolenic and linoleic acids meets essential fatty acid requirements and prevents hepatic steatosis in a murine model.
Subject(s)
Arachidonic Acid/administration & dosage , Dietary Supplements , Docosahexaenoic Acids/administration & dosage , Fatty Acids, Essential/deficiency , Fatty Liver/prevention & control , Animals , Coconut Oil , Disease Models, Animal , Energy Intake , Mice , Mice, Inbred C57BL , Plant Oils/administration & dosageABSTRACT
BACKGROUND: Total parenteral nutrition (PN), including fat administered as a soybean oil-based lipid emulsion (SOLE), is a life-saving therapy but may be complicated by PN-induced cholestasis and dyslipidemia. A fish-oil-based lipid emulsion (FOLE) as a component of PN can reverse PN-cholestasis and has been shown to improve lipid profiles. OBJECTIVE: The objective was to describe changes in the fatty acid and lipid profiles of children with PN-cholestasis who were treated with a FOLE. DESIGN: Lipid and fatty acid profiles of 79 pediatric patients who developed PN-cholestasis while receiving standard PN with a SOLE were examined before and after the switch to a FOLE. All patients received PN with the FOLE at a dose of 1 g · kg(-1) · d(-1) for ≥1 mo. RESULTS: The median (interquartile range) age at the start of the FOLE treatment was 91 (56-188) d. After a median (interquartile range) of 18.3 (9.4-41.4) wk of receiving the FOLE, the subjects' median total and direct bilirubin improved from 7.9 and 5.4 mg/dL to 0.5 and 0.2 mg/dL, respectively (P < 0.0001). Serum triglyceride, total cholesterol, LDL, and VLDL concentrations significantly decreased by 51.7%, 17.4%, 23.7%, and 47.9%, respectively. CONCLUSIONS: The switch from a SOLE to a FOLE in PN-dependent children with cholestasis and dyslipidemia was associated with a dramatic improvement in serum triglyceride and VLDL concentrations, a significant increase in serum omega-3 (n-3) fatty acids (EPA and DHA), and a decrease in serum omega-6 fatty acids (arachidonic acid). A FOLE may be the preferred lipid emulsion in patients with PN-cholestasis, dyslipidemia, or both. This trial is registered at clinicaltrials.gov as NCT00910104.
Subject(s)
Bilirubin/blood , Cholestasis/drug therapy , Dietary Fats/administration & dosage , Fat Emulsions, Intravenous/administration & dosage , Fish Oils/therapeutic use , Lipids/blood , Parenteral Nutrition , Cholestasis/blood , Cholestasis/etiology , Female , Fish Oils/pharmacology , Humans , Infant , Infant, Newborn , Male , Parenteral Nutrition/adverse effects , Short Bowel Syndrome/therapy , Soybean Oil/adverse effectsABSTRACT
INTRODUCTION: It appears that enteral nutrition is more likely to produce hypoglycemia during intensive insulin therapy than is total parenteral nutrition. POINT OF VIEW: Although this consequence may in part be the result of frequent discontinuation of feeding or to variability of gastrointestinal absorption of nutrients, there are also distinct physiological differences between total parenteral nutrition and enteral nutrition that are more likely to be responsible, including much higher serum insulin responses to total parenteral nutrition than with enteral nutrition that approach submaximal response levels and direct appearance of administered glucose into the systemic circulation with total parenteral nutrition at rates that approximate usual postabsorptive rates and that avoid first-pass hepatic clearance. CONCLUSIONS: These factors may make total parenteral nutrition more efficacious, at least initially, with intensive insulin therapy and may justify setting a higher limit for glucose control when enteral feeding is principally used.
Subject(s)
Hyperglycemia/drug therapy , Hypoglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Parenteral Nutrition, Total , Humans , Hypoglycemia/etiologyABSTRACT
This study compared the effects of total parenteral nutrition (TPN) by central vein with or without fat provided at maintenance energy requirement on fatty acid metabolism, de novo lipogenesis, and the risk of hepatic and systemic inflammation in rats. Study 1 was conducted in 2 groups: high glucose (HG), where fat-free TPN was given at maintenance levels of 180 kcal/(kg d), and low glucose (LG), where fat-free TPN containing 30% fewer calories at 126 kcal/(kg d) was provided by reducing 54 kcal/(kg d) from parenteral glucose. Study 2 contained 3 TPN groups: 1 LG group at 126 kcal/(kg d) and 2 groups at 180 kcal/(kg d) with 30% of total calories (54 kcal/[kg d]) either from soybean or fish oil emulsion. In both studies, animals fed a chow diet ad libitum were included. Plasma and hepatic triglyceride and phospholipid fatty acid profiles, enzymes indicating hepatic injury, and C-reactive protein levels (CRP) reflecting systemic injury were measured. In study 1, evidence of de novo lipogenesis was noted in LG and was more prominent in HG with elevation of CRP in HG. In study 2, de novo lipogenesis was reduced by adding either fat to LG to achieve maintenance energy levels. Moreover, adding fat as soybean oil but not fish oil significantly increased plasma and hepatic triglyceride and also elevated aspartate aminotransferase and CRP levels, reflecting inflammation. Thus, in rats, either hypocaloric feeding as glucose-based TPN or TPN provided at maintenance energy levels with the addition of fish oil limits hepatic lipid accumulation and prevents the evidence of hepatic and systemic injury found with maintenance level TPN as glucose only or glucose plus soybean oil.
Subject(s)
Dietary Fats/administration & dosage , Dietary Fats/metabolism , Glucose/administration & dosage , Glucose/metabolism , Inflammation/metabolism , Parenteral Nutrition, Total , Animals , Aspartate Aminotransferases/analysis , C-Reactive Protein/analysis , Caloric Restriction , Fatty Acids/blood , Fish Oils/administration & dosage , Fish Oils/metabolism , Lipogenesis/physiology , Liver/chemistry , Liver/enzymology , Male , Phospholipids/blood , Rats , Rats, Sprague-Dawley , Soybean Oil/administration & dosage , Soybean Oil/metabolism , Triglycerides/bloodSubject(s)
Fatty Acids, Omega-3 , Fish Oils , Animals , Dietary Fats , Dietary Fats, Unsaturated , Heart , Humans , PhysiciansABSTRACT
BACKGROUND: A relative dietary ω-3 fatty acid deficiency exists in Western diets, and this deficiency may be associated with some chronic diseases. The aim of the present study was to supplement yogurt with docosahexaenoic acid and assess whether this fatty acid could be incorporated into plasma lipids. METHODS: We developed a stable emulsion of docosahexaenoic acid that was incorporated into yogurt. Twelve healthy volunteers agreed to consume 1 serving daily that contained 600 mg of docosahexaenoic acid. RESULTS: After 3 weeks of supplementation, plasma phospholipid docosahexaenoic acid content increased significantly, by 32%, in parallel with a 16% rise in total ω-3 fatty acids. This result was associated with a significant 7% decline in phospholipid arachidonic acid. CONCLUSIONS: Fortification of ordinary foods with docosahexaenoic acid is a potentially attractive method of increasing ω-3 fatty acid content of plasma lipids, and might even lower arachidonic acid concentrations.