Impact of the omega-3 to omega-6 polyunsaturated fatty acid ratio on cytokine release in human alveolar cells

Background: ω‐3 polyunsaturated fatty acids (PUFAs) and ω‐6 PUFAs have opposing influences on inflammation. The objective was to determine whether lipopolysaccharide (LPS)–induced cytokine release by human alveolar cells was affected by changes in the ω‐3/ω‐6 ratio of cell membranes induced by different supplies of PUFAs. Methods: After LPS challenge, PUFAs were added to alveolar cells as docosahexaenoic acid (DHA, ω‐3) and arachidonic acid (AA, ω‐6) in 4 different DHA/AA ratios (1:1, 1:2, 1:4, and 1:7), and the effects on cytokine release were measured. Results: The supply of 1:1 and 1:2 DHA/AA ratios reversed the baseline predominance of ω‐6 over ω‐3 in the ω‐3/ω‐6 PUFA ratio of cell membranes. The release of proinflammatory cytokines (tumor necrosis factor α, interleukin‐6, and interleukin‐8) was reduced by 1:1 and 1:2 DHA/AA ratios (P < .01 to P < .001) but increased by 1:4 and 1:7 DHA/AA ratios (P < .01 to P < .001) vs control. The 1:1 and 1:2 ratios increased the release of anti‐inflammatory interleukin‐10 (P < .001). The balance between proinflammatory and anti‐inflammatory cytokines showed an anti‐inflammatory response with 1:1 and 1:2 ratios and a proinflammatory response with 1:4 and 1:7 ratios (P < .001). Conclusions: This study showed that proinflammatory cytokine release was dependent on the proportion of ω‐3 in the ω‐3/ω‐6 ratio of alveolar cell membranes, being reduced with the supply of a high proportion of DHA and increased with a high proportion of AA, respectively. These results support the biochemical basis for current recommendations to shift the PUFA supply from ω‐6 to ω‐3 in nutrition support of patients with acute lung injury.     

Liver Disease,Systemic Inflammation,and Growth Using a Mixed Parenteral Lipid Emulsion,Containing Soybean Oil,Fish Oil,and Medium Chain Triglycerides,Compared With Soybean Oil in Parenteral Nutrition–Fed Neonatal Piglets

Background: The optimal parenteral lipid emulsion for neonates should reduce the risk of intestinal failure–associated liver disease and inflammation, while supporting growth and development. This could be best achieved by balanced content of ω‐6 and ω‐3 polyunsaturated fatty acids (PUFAs). Using a neonatal piglet model of parenteral nutrition (PN), we compared a 100% soy oil–based emulsion (ω‐6:ω‐3 PUFA: 7:1) with a mixed lipid emulsion comprising 30% soy oil, 30% medium‐chain triglycerides, 25% olive oil, and 15% fish oil (ω‐6:ω‐3 PUFA: approximately 2.5:1) with regard to liver disease, inflammation, and fatty acid content in plasma and brain. Method: Neonatal piglets, 3–6 days old, underwent jugular catheter insertion for isonitrogenous, isocaloric PN delivery over 14 days. The IL group (n = 8) was treated with Intralipid; the ML group (n = 10) was treated with the mixed lipid (SMOFlipid). Bile flow, liver chemistry, C‐reactive protein (CRP), and PUFA content in plasma phospholipids and brain were compared. Results: Compared with the IL group, ML‐treated piglets had increased bile flow (P = .008) and lower total bilirubin (P = .001) and CRP (P = .023) concentrations. The ω‐6 long‐chain PUFA content was lower in plasma and brain for the ML group. The key ω‐3 long‐chain PUFA for neonatal development, docosahexaenoic acid (DHA), was not different between groups. Conclusion: The mixed lipid, having less ω‐6 PUFA and more ω‐3 PUFA, was able to prevent liver disease and reduce systemic inflammation in PN‐fed neonatal piglets. However, this lipid did not increase plasma or brain DHA status, which would be desirable for neonatal developmental outcomes.     

Effects of the ω‐6:ω‐3 Fatty Acid Ratio of Fat Emulsions on the Fatty Acid Composition in Cell Membranes and the Anti‐Inflammatory Action

Background: This study investigated the effects of parenterally administered fish oil (FO) on the fatty acid composition in rats to determine the optimal ω‐6:ω‐3 polyunsaturated fatty acid (PUFA) ratio of fat emulsions to achieve an anti‐inflammatory effect. Methods: Male Sprague‐Dawley rats were infused a parenteral nutrition (PN) solution containing fat emulsions with different ω‐6:ω‐3 PUFA ratios. The fatty acid content of phospholipids in the membranes of splenocytes was analyzed by gas chromatography (experiment 1). In addition, the amounts of leukotriene (LT) B₄ and LTB₅ released from peritoneal polymorphonuclear leukocytes (PMNs) were measured by high‐performance liquid chromatography (experiment 2). Results: In experiment 1, after infusion of the fat emulsion containing FO, the ω‐3 PUFA content in cell membranes rose to 70% of the peak value on day 1 and nearly reached a plateau on day 3. The highest ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) was achieved by administrating a PN solution with the smallest ω‐6:ω‐3 PUFA ratio. In experiment 2, a larger amount of LTB₅ was released from Ca‐ionophore‐stimulated PMNs taken from rats given a larger quantity of FO. The ratio of LTB₅:LTB₄ released from PMNs correlated positively with the EPA:AA ratio in the membranous phospholipid and in serum. Conclusions: The ω‐3 PUFAs were readily incorporated into the cell membrane within 3 days of infusion with the fat emulsion. The EPA:AA ratio in membranous phospholipid in PMNs was positively correlated with the LTB₅:LTB₄ production ratio and was a good indicator of anti‐inflammatory effects.     

Dietary ω‐6/ω‐3 Polyunsaturated Fatty Acid Ratios Affect the Homeostasis of Th/Treg Cells in Mice With Dextran Sulfate Sodium–Induced Colitis

Background: This study evaluated the effect of different dietary ω‐6/ω‐3 polyunsaturated fatty acid (PUFA) ratios on modulating helper T (Th) and regulatory T (Treg) lymphocytes in mice with dextran sulfate sodium (DSS)–induced colitis. Methods: There were 3 control and 3 colitis groups. Mice were fed for 24 days with diets with soybean oil (S), a mixture of soybean oil and low fish oil content (LF), or high fish oil content (HF). The ratio of ω‐6/ω‐3 PUFA in the LF diet was 4:1, and that in the HF diet was 2:1. The control groups drank distilled water while colitis groups were provided 2% DSS in drinking water during days 15–19. All mice drank distilled water from days 20–24 for recovery and were sacrificed on day 25. Results: Colitis resulted in higher blood Th1, Th2, and Th17 and lower Treg percentages. Also, plasma haptoglobin and proinflammatory chemokines were elevated in colon lavage fluid. Colitic groups with fish oil had lower inflammatory mediators in the plasma and colon lavage fluid. Furthermore, the percentages of blood Th1, Th2, and Th17 cells were lower, whereas Treg cell percentages were higher than those in the soybean oil group. The colitis group with an ω‐6/ω‐3 PUFA ratio of 2:1 had more pronounced effects than the group with a ratio of 4:1. Conclusions: Diets with an ω‐6/ω‐3 PUFA ratio of 2:1 or 4:1 regulate the Th/Treg balance and attenuate inflammatory mediator production in colitis. Compared with the ω‐6/ω‐3 PUFA ratio of 4:1, the ratio of 2:1 was more effective in reducing inflammatory reactions in DSS‐induced colitis.     

Evolution of Lipid Profile,Liver Function,and Pattern of Plasma Fatty Acids According to the Type of Lipid Emulsion Administered in Parenteral Nutrition in the Early Postoperative Period After Digestive Surgery

Background: The metabolic effects of intravenous lipid emulsions (ILEs) used in parenteral nutrition (PN) depend on their fatty acid composition. Methods: Subjects in this prospective and randomized double‐blind study were 28 adult patients post digestive surgery. PN was started after surgery and lasts for 5 days. Randomly, patients receive 1 of 4 different ILEs: medium‐chain triglycerides/long‐chain triglycerides (soybean oil; MCT/LCT), olive/soybean oil (oleic), long‐chain triglycerides (soybean oil; LCT), and structured lipid. On days 0 and 6, serum liver function tests were analyzed for cholesterol, triglycerides, lipoproteins, and serum fatty acids. Results: No differences were found in the 4 groups according to their gender, age, body mass index, diagnosis, baseline white blood cell, C‐reactive protein, glucose levels, and other study parameters. Differential significant changes were not observed in any of the hepatic function parameters or plasmatic lipid levels between the groups. A significant decrease was observed in cis monounsaturated fatty acids (MUFAs) and a significant increase in ω‐6 polyunsaturated fatty acids (PUFAs) andω ‐3 PUFA values in LCT and structured groups compared with MCT/LCT and oleic groups, and a tendency for a decrease in trans fatty acids in the oleic and structured groups was found. Conclusions: All ILEs administered were safe and well tolerated. The changes in serum fatty acids reflected the pattern of fatty acids administered with different ILEs. The group receiving the olive oil emulsion achieved a fatty acid composition of serum lipids that could offer major therapeutic or biological advantages.     

Effect of intravenous omega-3 fatty acid infusion and hemodialysis on fatty acid composition of free fatty acids and phospholipids in patients with end-stage renal disease

Background: Patients treated with hemodialysis (HD) have been reported to have decreased levels of ω‐3 polyunsaturated fatty acids (PUFAs) in plasma and cells. The aim of this study was to investigate the effect of ω‐3 PUFAs administered intravenously during HD, as well as the effect of HD treatment, on the fatty acid composition of plasma free fatty acids (FFAs), plasma phospholipids, and platelet phospholipids. Methods: Forty‐four HD patients were randomized to groups receiving either a single dose of a lipid emulsion containing 4.1 g of ω‐3 PUFAs or placebo (saline) administered intravenously during HD. Blood was drawn immediately before (baseline) and after (4 hours) HD and before the next HD session (48 hours). Fatty acid composition was measured using gas chromatography. Results: The increase in ω‐3 FFAs was greater in the ω‐3 PUFA group compared with the placebo group, whereas the increase in total FFAs was similar between the 2 groups. In the ω‐3 PUFA group, ω‐3 PUFAs in plasma phospholipids were higher after 48 hours than at baseline, and in platelet phospholipids, ω‐3 PUFAs increased after 4 hours. In the placebo group, no changes were observed in ω‐3 PUFAs in plasma and platelet phospholipids. Conclusions: Intravenous ω‐3 PUFAs administered during HD caused a transient selective increase in ω‐3 FFA concentration. Furthermore, ω‐3 PUFAs were rapidly incorporated into platelets, and the content of ω‐3 PUFAs in plasma phospholipids increased after 48 hours.     

UK recommendations for dietary fat: should they be reassessed in light of the recent joint FAO/WHO recommendations?

In 2008, the Food and Agricultural Organization (FAO)/World Health Organization (WHO) reviewed its recommendations on dietary fat and fatty acids in light of the growing evidence base on dietary fatty acids and health outcomes. These new FAO/WHO recommendations are considerably broader than the current UK recommendations, in that the FAO/WHO report makes separate recommendations for adults and children and sets ranges of intake for n‐3 and n‐6 polyunsaturated fatty acids (PUFAs) based, not only on prevention of deficiency, but also on their role in contributing to optimum and long‐term health. The key recommendation of this report is that saturated fatty acids (SFAs) should be limited to 10% of dietary energy intake and, compared with the UK recommendations, there is a stronger emphasis on replacing excess dietary SFAs with PUFAs (both n‐3 and n‐6) because of convincing evidence that this dietary exchange reduces low density lipoprotein cholesterol and the risk of coronary heart disease. It may therefore be timely to consider the need for a modification of the UK dietary guidelines on dietary fat and fatty acid intake to take account of the growing evidence base for the potential benefit of replacing SFAs with PUFAs.     

The health effects of dietary unsaturated fatty acids

• 2.1 The chemistry of fatty acids
• 2.2 Digestion, absorption and metabolism
• 2.3 Functions of unsaturated fatty acids

3 Unsaturated fatty acids in the UK diet

• 3.1 Sources of fat in the diet
• 3.2 Dietary recommendations for fat
• 3.3 Intakes of unsaturated fatty acids
• 3.4 Major contributors to unsaturated fatty acid intake
• 3.5 Trends in intake

4 Unsaturated fatty acids in health and disease

• 4.1 Unsaturated fatty acids and cardiovascular disease
• 4.2 Unsaturated fatty acids and diabetes
• 4.3 Unsaturated fatty acids and cancer
• 4.4 Unsaturated fatty acids and inflammatory conditions
• 4.5 Unsaturated fatty acids in fetal and infant development
• 4.6 Unsaturated fatty acids and cognitive function and behaviour
• 4.7 Emerging aspects of unsaturated fatty acids and health

5 Unsaturated fatty acids and public health

• 5.1 Labelling of unsaturated fatty acids
• 5.2 Are current UK recommendations adequate?
• 5.3 Opportunities to increase intake of long chain n‐3 PUFAs
• 5.4 Implications of optimising intakes of unsaturated fatty acids

6 Conclusions

Acknowledgements

References

Appendix 1

Summary Fat provides energy; indeed it is the most energy dense of all the macronutrients, with 1 g providing 37 kJ (9 kcal). However, the constituent parts of fat, fatty acids, are required by the body for many other functions than simply as an energy source, and there is an increasing awareness of the potential health benefits of specific types of fatty acids. Fatty acids are long hydrocarbon chains, with a methyl group at one end (the omega or n‐end) and an acid group at the other. Unsaturated fatty acids are hydrocarbon chains containing at least one carbon–carbon double bond; monounsaturated fatty acids contain one double bond, and polyunsaturated fatty acids (PUFAs) contain many double bonds. The position of the double bond relative to the omega end determines whether a PUFA is an n‐3 (omega 3) or an n‐6 (omega 6) fatty acid. Most fatty acids can be synthesised in the body, but humans lack the enzymes required to produce two fatty acids. These are called the essential fatty acids and must be acquired from the diet. In humans, the essential fatty acids are the n‐3 PUFA α‐linolenic acid and the n‐6 PUFA linoleic acid. Although humans can elongate dietary α‐linolenic acid to the long chain n‐3 PUFAs eicosapentaenoic acid and docosahexaenoic acid, the rate of synthesis may not be sufficient to meet requirements, and it is, therefore, recommended that good sources of these fatty acids, namely, oil‐rich fish, are also included in the diet. Fat is found in most food groups, and foods containing fat generally provide a range of different fatty acids, both saturated and unsaturated. In the UK, the major dietary sources of unsaturated fatty acids include meat & meat products, cereals & cereal products and potatoes & savoury snacks; primarily as a result of the vegetable oil used in processing. Recommended intakes of both total fat and the different types of fatty acids have been set for the UK population, and it is possible to monitor fat intake from the data collected in nationwide dietary surveys. As a population, we are not currently meeting these recommendations, so there is still scope for dietary change. In Western diets, n‐6 fatty acids are the predominant PUFAs, and this is in line with current dietary advice to consume a minimum of 1% energy as n‐6 PUFAs and 0.2% energy as n‐3 PUFAs. The balance of n‐3 and n‐6 PUFAs in Western diets has changed substantially over the last 100 years or so, and as the two families of PUFAs share a common metabolic pathway, concerns have been raised that this might be detrimental to health; what is becoming increasingly clear is that both n‐3 and n‐6 PUFAs have independent health effects in the body, and as intakes of the n‐6 PUFAs are within the guidelines for a healthy diet, concerns about the n‐6 to n‐3 ratio are driven by low intakes of n‐3 rather than high intakes of n‐6. Currently in adults n‐6 PUFAs contribute to 5.3% energy. Detecting associations between components of the diet and risk of various diseases is notoriously complex and in many cases, the evidence is still accumulating. Cardiovascular disease, characterised by hardening and narrowing of blood vessels and/or the development of blood clots, is one of the leading causes of mortality and morbidity worldwide. The type and total amount of dietary fat has a clear part to play in affecting an individual’s disease risk, yet the precise mechanisms by which unsaturated fatty acids reduce cardiovascular disease risk are still unclear. A number of mechanisms whereby dietary fatty acids could influence the progression of cardiovascular disease and its risk factors have been identified. These include effects on blood lipid concentrations, blood pressure, inflammatory response, arrhythmia and endothelial function, along with many other effects, both known and as yet undefined. A well‐established risk factor for cardiovascular disease is an elevated plasma low density lipoprotein (LDL) cholesterol concentration. Replacing saturated fatty acids with either monounsaturated fatty acids or n‐6 PUFAs reduces LDL (the ‘bad’) cholesterol, and so reduces the risk of developing the disease. Unsaturated fatty acids, such as linoleic acid or monounsaturated fatty acids, also slightly raise high density lipoprotein (HDL) (the ‘good’) cholesterol, which assists in the removal of triacylglycerols from the bloodstream. Interest in the health effects of the long chain n‐3 PUFAs found in fish oils is also increasing. There is strong supportive, but not yet conclusive, evidence that these fatty acids protect against fatal heart disease. On the basis of this conclusion, in 2004 the Scientific Advisory Committee on Nutrition advised the UK government to adopt the population‐wide dietary recommendation to eat at least two portions of fish per week, of which one should be oil‐rich, equivalent to 0.45 g of the long chain n‐3 PUFAs per day. In recent years, the potential health benefits of α‐linolenic acid has attracted attention, and evidence is mounting on the role that this n‐3 fatty acid may play in preventing the progression of cardiovascular disease, although it is currently unclear what, if any, association exists. Brain cells are especially rich in certain long chain PUFAs. This has led to the suggestion that dietary status of these long chain fatty acids might influence cognitive function and behaviour. Research in this field is still in its early stages, but there is a small amount of evidence to suggest improvements in cognitive function following fatty acid supplementation. In contrast, it is well established that pregnant women must have an adequate supply of the long chain n‐3 PUFAs before and throughout pregnancy and lactation to support normal growth, neurological development and cognitive function of the baby. As n‐6 PUFAs are more abundant in the diet, achieving an adequate intake is less problematic. However, this is not the case for the n‐3 PUFAs; increasing fish consumption beyond two servings of oil‐rich fish per week or relying on fish oil supplementation is not appropriate during pregnancy due to the potential problems associated with heavy metal contamination of fish, or the high vitamin A level in some fish oil supplements. Unsaturated fatty acids have also been associated with a number of other diseases and although the evidence is by no means conclusive, it is an area that is attracting a huge amount of interest. Dietary fat affects a number of different metabolic pathways, including those involved with glycaemic control, so the types and amounts of dietary fat may have a role to play in the management of type 2 diabetes. Unsaturated fatty acids may also be associated with a reduced risk of developing certain cancers, including cancers of the colon, breast and prostate, although currently the level of evidence is not deemed sufficient by authoritative bodies, such as the World Cancer Research Fund, World Health Organization and the Department of Health, to make any specific dietary recommendations. There are a number of inflammatory conditions, such as asthma, Crohn’s disease and arthritis, which could potentially be alleviated by dietary modification. The fatty acid composition of cell membranes can be altered by consumption of both n‐3 and n‐6 PUFAs, and this can result in reduced inflammatory activity. However, whether this effect brings about a significant reduction in clinical symptoms is still unclear. It is also important to note that there are concerns that the beneficial effects on certain disease outcomes are only observed with very high intakes of unsaturated fatty acids, which could realistically only be achievable by supplementation. Few nutritionists would be comfortable recommending supplement use as the only alternative to fish, as this can be expensive and goes against the idea that all the nutrients that our bodies require can be obtained from the food that we eat if the right choices are made. Unsaturated fatty acids are now a nutritional hot topic, and their presence in foods has attracted both public and industrial interest. There is currently no specific legislation to control the use of health claims relating to the fatty acid content of foods. However, a European Union (EU) Directive is expected imminently which will formally set down the criteria that a product will have to meet in order to make any nutrition or health claim. With regards to the current recommendations, those for the UK are in line with those around the world. However, as a population, we need to increase our consumption of long chain n‐3 PUFAs and decrease intake of saturated fatty acids. To facilitate this, food technologists are looking at ways in which the fatty acid profile of a food can be modified in order to bring dietary improvements without requiring a major change in dietary habits. However, public health messages surrounding the optimum intakes of fatty acids must be clear and consistent to ensure that a favourable change in the fatty acid profile of the UK diet occurs.     

Effects of ω‐3 Polyunsaturated Fatty Acids on the Homeostasis of CD4+ T Cells and Lung Injury in Mice With Polymicrobial Sepsis

Background: Sepsis is a common cause of death in critically ill patients. An overwhelming inflammatory response and imbalance of helper T (Th) cells and regulatory T (Treg) cells are thought to be involved in the progression of sepsis. ω‐3 Polyunsaturated fatty acids (PUFAs) were found to have anti‐inflammatory and immunomodulatory properties. This study investigated the effects of ω‐3 PUFAs on the balance of Th subsets, Treg cells, and the inflammatory response in septic mice. Methods: Mice were randomly assigned to soybean oil (SO) and fish oil (FO) groups. The 2 groups received an identical nutrient distribution except for the sources of the fat. The SO group was fed soybean oil, while part of the soybean oil was replaced by fish oil in the FO group. The FO group had an ω‐6/ω‐3 PUFA ratio of 2:1. After feeding the diets for 3 weeks, sepsis was induced by cecal ligation and puncture (CLP), and mice were sacrificed on days 0, 1, and 3. Results: Compared with the SO group, the FO group had lower inflammatory mediator levels in the plasma and peritoneal lavage fluid after CLP. Also, the FO group had lower Th1, Th2, and Th17 percentages and a higher Th1/Th2 ratio in blood. In lung tissues, neutrophil infiltration was reduced, whereas peroxisome proliferator–activated receptor γ expression was upregulated. Conclusions: A fish oil diet with an ω‐6/ω‐3 PUFA ratio of 2:1 may elicit more balanced Th polarization, alleviate inflammatory responses, and attenuate lung injury in CLP‐induced sepsis.     

Soybean and Fish Oil Mixture With Different ω‐6/ω‐3 Polyunsaturated Fatty Acid Ratios Modulates Dextran Sulfate Sodium–Induced Changes in Small Intestinal Intraepithelial γδT‐Lymphocyte Expression in Mice

Background: This study investigated the effect of different ω‐6/ω‐3 polyunsaturated fatty acid (PUFA) ratios on dextran sulfate sodium (DSS)–induced changes to small intestinal intraepithelial lymphocyte (IEL) γδT‐cell expression. Methods: Mice were assigned to 3 control and 3 DSS‐treated groups and were maintained on a low‐fat semipurified diet. One of the control (S) groups and a DSS (DS) group were provided with soybean oil; the other 2 control (Hω‐3 and Lω‐3) groups and 2 other DSS (DHω‐3 and DLω‐3) groups were fed either a soybean and fish oil mixture with a ω‐6/ω‐3 ratio of 2:1 or 4:1. After feeding the respective diets for 2 weeks, the DSS groups were given distilled water containing 2% DSS, and the control groups were given distilled water for 5 days. All groups were further provided distilled water 5 days for recovery, and the small intestinal IEL γδT‐cell subset was isolated for analysis. Results: DSS treatment resulted in a lower small intestinal IEL γδT‐cell percentage and higher messenger RNA (mRNA) expressions of Reg IIIγ, keratinocyte growth factor (KGF), and complement 5a receptor (C5aR) by IEL γδT cells. Fish oil administration enhanced the proportion of small intestinal IEL γδT cells. Compared with the DLω‐3 group, the DHω‐3 group had lower Reg IIIγ, KGF, and C5aR mRNA expressions and higher expression of peroxisome proliferator‐activated receptor (PPAR)–γ gene by small intestinal IEL γδT cells. Conclusions: Fish oil diets with a ω‐6/ω‐3 PUFA ratio of 2:1 were more effective than those with a ratio of 4:1 in improving DSS‐induced small intestinal injury, and activation of PPAR‐γ in IEL γδT cells may be associated with resolution of small intestinal inflammation.     

Types and amount of dietary fat and colon cancer risk: Prevention by omega-3 fatty acid-rich diets

Colorectal cancer is the second most common malignancy in the Western world including the United Sates. In recent years there is a strong upward trend in colon cancer risk in Japan mainly due to Americanization of Japanese food habits. Several epidemiological studies point to a strong association between nutrient composition of the diet and cancer of the colon. The role of types of dietary fat, especially saturated fats of animal origin, n−6- and n−3-rich polyunsaturated fatty acids (PUFAs) in the etiology of colorectal cancer has become increasingly apparent. Epidemiological studies indicate a positive association between the dietary intake of saturated fat and/or animal fat and colon cancer risk and an inverse relationship between the intake of fish and fish oil rich in n−3 PUFAs and colon cancer development. Although the evidence from case-control studies and international correlational studies is not totally consistent, these inconsistencies may have arisen, at least in part, from methodological limitations. Animal, model studies have unequivocally provided evidence that the colon tumor-promoting effect of dietary fat depends on its fatty acid composition and that high dietary n−3 PUFAs lacks colon tumor-promoting effect, as compared to diets high in n−6 PUFAs or saturated fats. Diets rich in n−3 PUFAs inhibit colon carcinogenesis through the modulation of colonicras-p21, cyclooxygenase-2, and inducible nitric oxide synthase activities and apoptosis. Gene expression analysis using DNA microarrays indicates that n−3 fatty acid, docosahexaenoic acid activates cyclin-dependent kinase inhibitors such as p21, p27, p57 and p19 and inactivates antiapoptotic Bcl-2 family of genes, and prostagland in family of genes. These results suggest that decreasing the intake of n−6 PUFAs and saturated fats and increasing that of n−3 PUFAs, particularly eicosapentaenoic acid and docosahexaenoic acid has the potential to be a major component of colon cancer control.     

The ω-3 and ω-6 fats in meals: a proposal for a simple new label

Objective

The ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) are separate essential dietary fatty acids that play a key role in many physiologic processes in higher animals. The content of these PUFAs is relatively well described for many individual food components. Our goal in this study was to analyze the PUFA content of whole meals and produce a simple measurement to estimate the intake of these fatty acids.

Methods

The fatty acid profile and macronutrient composition were determined for a range of fast food, cuisine (restaurant-prepared), and home-prepared whole meals commonly consumed by Australians.

Results

Across the different meals there was significant variation in protein (4-fold), fat (13-fold), and carbohydrate (23-fold) contents. With regard to the fatty acid profile, saturated and monounsaturated fatty acids made up approximately 80% of total fatty acids for most meals. The ω-6 PUFAs were substantially more abundant than ω-3 PUFAs for most meals. The balance of dietary ω-3 and ω-6 PUFAs is an important determinant of their metabolic effects within the body, and accordingly we calculated the percentage of the total PUFA comprised of ω-3 PUFAs and referred to this as the PUFA Balance. This parameter showed the greatest variation among the different meals (>45-fold).

Conclusion

The relative proportions of ω-3 and ω-6 PUFAs vary greatly across meals. PUFA Balance is a useful tool that will allow individuals to more easily monitor and balance their intake of ω-3 and ω-6 fats.     

Comparison between omega-3 and omega-6 polyunsaturated fatty acid intakes as assessed by a food frequency questionnaire and erythrocyte membrane fatty acid composition in young children

OBJECTIVE: We conducted a dietary validation study in youth aged 1-11 years by comparing dietary intake of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) as assessed by a parent-completed semiquantitative food frequency questionnaire (FFQ) over time to erythrocyte membrane composition of the same fatty acids. DESIGN: The study population included youth aged 1-11 years who were participants in the Diabetes Autoimmunity Study in the Young (DAISY), a longitudinal study in Denver, Colorado that is following a cohort of youth at risk for developing type I diabetes. Four hundred and four children who had erythrocyte membrane fatty acid data matched to an FFQ corresponding to the same time frame for a total of 917 visits (matches) were included. PUFA intake was expressed both as g/day (adjusted for total energy) and as percent of total fat intake. We used mixed models to test the association and calculate the correlation between the erythrocyte membrane estimates and PUFA intake using all records of data for each youth. RESULTS: Intakes of total omega-3 fatty acids (beta=0.52, P<0.0001, rho=0.23) and marine PUFAs (beta=1.62, P<0.0001, rho=0.42), as a percent of total fat in the diet, were associated with percent of omega-3 and marine PUFAs in the erythrocyte membrane. Intakes of omega-6 PUFAs (beta=0.04, P=0.418, rho=0.05) and arachidonic acid (beta=0.31, P=0.774, rho=0.01) were not associated. CONCLUSIONS: In these young children, an FFQ using parental report provided estimates of average long-term intakes of marine PUFAs that correlated well with their erythrocyte cell membrane fatty acid status.     

Nutrition Modulation of Cardiotoxicity and Anticancer Efficacy Related to Doxorubicin Chemotherapy by Glutamine and ω‐3 Polyunsaturated Fatty Acids

Background: Doxorubicin (DOX) has been one of the most effective antitumor agents against a broad spectrum of malignancies. However, DOX‐induced cardiotoxicity forms the major cumulative dose‐limiting factor. Glutamine and ω‐3 polyunsaturated fatty acids (PUFAs) are putatively cardioprotective during various stresses and/or have potential chemosensitizing effects during cancer chemotherapy. Methods: Antitumor activity and cardiotoxicity of DOX treatment were evaluated simultaneously in a MatBIII mammary adenocarcinoma tumor‐bearing rat model treated with DOX (cumulative dose 12 mg/kg). Single or combined treatment of parenteral glutamine (0.35 g/kg) and ω‐3 PUFAs (0.19 g/kg eicosapentaenoic acid and 0.18 g/kg docosahexaenoic acid) was administered every other day, starting 6 days before chemotherapy initiation until the end of study (day 50). Results: Glutamine alone significantly prevented DOX‐related deterioration of cardiac function, reduced serum cardiac troponin I levels, and diminished cardiac lipid peroxidation while not affecting tumor inhibition kinetics. Single ω‐3 PUFA treatment significantly enhanced antitumor activity of DOX associated with intensified tumoral oxidative stress and enhanced tumoral DOX concentration while not potentiating cardiac dysfunction or increasing cardiac oxidative stress. Intriguingly, providing glutamine and ω‐3 PUFAs together did not consistently confer a greater benefit; conversely, individual benefits on cardiotoxicity and chemosensitization were mostly attenuated or completely lost when combined. Conclusions: Our data demonstrate an interesting differentiality or even dichotomy in the response of tumor and host to single parenteral glutamine and ω‐3 PUFA treatments. The intriguing glutamine × ω‐3 PUFA interaction observed draws into question the common assumption that there are additive benefits of combinations of nutrients that are beneficial on an individual basis.     

ω-3 Fatty acids have no impact on serum lactate levels after major gastric cancer surgery

Background: Preoperative and intraoperative nutrition support in patients undergoing major surgery results in decreased incidence of morbidity and mortality. Studies investigating the role of ω‐3 fatty acids in these patients are increasing. Some are focused on perfusion at the cellular level. This study was undertaken to address the effect of postoperative administration of ω‐3 fatty acids on cellular hypoperfusion associated with major gastric surgery. Methods: Twenty‐six patients undergoing gastric cancer surgery were randomly assigned to receive parenteral nutrition (PN) supplemented with a combination of ω‐6 and ω‐3 fatty acids (Omegaven, 0.2 g/kg/d; Lipovenoes 10%, 0.6 g/kg/d) or with ω‐6 fatty acid (Lipovenoes 10%, 0.8 g/kg/d) for 5 days. Blood samples were taken preoperatively, postoperative day 1, and on the last day of PN therapy (day 5). Results: Patients receiving ω‐3 and ω‐6 fatty acids showed neither lower serum lactate levels nor lower rates of complications compared with patients receiving ω‐6 only. There were no statistically significant differences between the groups in other biochemical parameters, complications, or length of hospital stay or mortality. Conclusion: PN with ω‐3 fatty acid supplementation does not have a significant impact on cellular hypoperfusion and lactate clearance after major gastric surgery.     

Dietary Lipids in Early Development and Intestinal Inflammatory Disease

Inflammatory bowel diseases are life-long reoccurring inflammatory disorders of the gastrointestinal tract and have been increasing in incidence in recent decades, notably in the pediatric population. Although genetic predisposition remains an important factor, this increased incidence most likely reflects an environmental change. One potential contributor to this is the change in dietary fat intake, with dietary intake of n-6 polyunsaturated fatty acids (PUFAs) following a similar temporal pattern to the change in inflammatory bowel disease incidence. Dietary n-6 PUFAs comprise a major, modifiable, environmental factor known to promote a heightened inflammatory response through a number of pathways, including their role as precursors for synthesis of eicosanoids and their inhibitory effect on the synthesis of the n-3 PUFAs eicosapentanoic acid and do-cosahexanoic acid. The increase in n-6PUFA intake affects individuals of all ages, with fetal PUFA accretion and infant dietary PUFA intake from breast milk reflecting maternal dietary intake. A high level of n-6 PUFA in milk results in increased n-6 PUFA in colonicphospholipids and an exaggerated inflammatory response to chemically induced colitis. Conversely, during development, a diet low in n-6 PUFAs and high in n-3 PUFAs increases colonic n-3 fatty acids, attenuates the inflammatory response, and lowers colonic damage. High dietary n-6 PUFA intake may be an important environmental modifier that contributes to inflammatory bowel diseases.     

Maternal dietary PUFAs intake and human milk content relationships during the first month of lactation

Maternal dietary fatty acids (FFAs) intake and corresponding human milk composition relationships have been assessed throughout the first month of lactation in 34 lactating women consecutively enrolled. All mothers were on their habitual diet. Food records (95 items) were administered to the mothers, six-times during the first month of lactation (1 day after delivery, 4, 7, 14, 21, and 28 days after colostrum appearance) and referred to maternal dietary intake of the day before. Milk collected on day 1 was considered as colostrum, day 4 and 7 samples as transitional milk, and day 14, 21 and 28 samples as mature milk. Five gas chromatographic analyses were performed on each sample. Statistics were made using Friedman's and Pearson's test. Maternal dietary saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) were significantly related to the corresponding milk pattern in the phase of transitional milk (P<0.01), while total polyunsaturated (PUFAs) content was significantly related only to the mature milk (P<0.01); in this phase about 42% of the variations occurring in PUFAs milk content can be related to variation of maternal PUFAs dietary intake. The results in the present study provide evidence of the relationships between maternal diet and milk composition. The degree of correlation between maternal diet and PUFAs milk content increases throughout milk maturational process and reaches significance only in mature milk. This would imply that advancing lactation, milk PUFAs provision sources gradually shift from adipose tissue catabolism to maternal diet.     

Adipose tissue fatty acid composition and its relations to diet and plasma lipid concentrations in hemodialysis patients

Adipose tissue fatty acid composition, serum lipid profile, and dietary intake of 37 patients on maintenance hemodialysis were studied. In August 1982, 1984, and 1986, analyses were carried out in 15 normotriglyceridemic (NTG) and 22 hypertriglyceridemic (HTG; type IV hyperlipidemia) patients. No correlations were found between dietary intake of polyunsaturated fatty acids (PUFAs), ratio of polyunsaturated to saturated fatty acids (P-S ratio), and carbohydrate content on the one hand and serum lipid concentrations on the other in the two groups. Adipose tissue linolenic acid correlated negatively with serum cholesterol in both groups. Strong correlations were found between dietary intake of PUFAs and adipose tissue linoleic acid content, between PUFAs and the double-bond index, between P-S ratio and adipose tissue linoleic acid content, and between P-S ratio and the double-bond index. No significant differences in dietary intake or adipose tissue fatty acid composition were observed between NTG and HTG patients. Thus, no evidence was found for exogenous dietary influences on serum lipid concentrations. The adipose tissue linoleic acid content did reflect the dietary intake of PUFAs.     

Monounsaturated and omega-3 but not omega-6 polyunsaturated fatty acids improve hepatic fibrosis in hypercholesterolemic rabbits

OBJECTIVE: Although the influence of saturated fatty acids, monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), lipids, cholesterol levels, and other blood lipids has been established, few studies have examined the influence of these dietary lipids on the composition and histologic damage of organs in situations of hypercholesterolemia. Biliary lipids come from the liver, and this organ is essential in cholesterol homeostasis; thus, it may be helpful to evaluate the inter-relations among biliary, hepatic lipids, and hepatotoxic effects in situations of hypercholesterolemia with different dietary lipids. This study investigated whether administration of diets differing in fatty acid profiles (omega-3 PUFA, omega-6 PUFA, or MUFA) influence the content of biliary lipids, the lithogenic index of gallbladder bile, and the development of hepatic fibrosis in hypercholesterolemic rabbits. METHODS: Thirty rabbits were randomized to one of five groups. A control group received rabbit chow for 80 d. The remaining four groups received a 50-d diet that contained 3% lard and 13% cholesterol to provoke hypercholesterolemia. After this period, three groups were fed for another 30 d on a diet enriched with omega-6 PUFAs, MUFAs, and omega-3 PUFAs, respectively. Liver, bile, and plasma lipid compositions, lipid peroxidation in hepatic mitochondria, and histologic hepatic lesions were analyzed. RESULTS AND CONCLUSIONS: There was a beneficial effect of MUFA and omega-3 PUFA on hepatic fibrosis in hypercholesterolemic rabbits because both dietary fats led to recovery from hepatic lesions. However, because intake of omega-3 PUFA provoked lithogenic bile in rabbits, MUFA intake would be more advisable.     

ω‐3 Fatty Acids Reduce Chemotherapy‐Induced Hematological Toxicity by Bone Marrow Stimulation in Mice

Background: ω‐3 Fatty acids exert several benefits during chemotherapy, such as preventing intestinal mucosal damage and improving response to chemotherapy. However, little is known about the effect of ω‐3 fatty acids on chemotherapy‐induced hematological toxicities. Methods: Mice that had consumed either an ω‐3–rich or an ω–3‐poor diet for 2 weeks were intraperitoneally administered cisplatin. The resultant changes in blood cell count, bone marrow cell count, and cytokine levels in bone marrow supernatant were analyzed. The effect of ω‐3 fatty acids on human peripheral blood mononuclear cells (PBMCs) exposed to cisplatin was also examined. Results: Although peripheral blood cell counts decreased after cisplatin treatment in both groups of mice, the decrease in white blood cell count was significantly lower in mice that consumed the ω‐3–rich diet. The decrease in bone marrow cells after cisplatin treatment was also reduced in mice that consumed the ω‐3–rich diet. Levels of stem cell factor (SCF) and fibroblast growth factor 1 (FGF‐1) were significantly higher in bone marrow supernatants from mice that consumed the ω‐3–rich diet. The rate of apoptosis in PBMCs (after exposure to cisplatin) cultured in medium containing ω‐3 fatty acids was significantly lower than in PBMCs cultured in control medium. Conclusion: ω‐3–Rich diets reduced chemotherapy‐induced leukopenia in mice. This may be the result of increased numbers of bone marrow cells due to higher levels of SCF and FGF‐1 in the bone marrow.