Purified fish oil eliminating linoleic and alpha linolenic acid meets essential fatty acid requirements in rats.

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.

Arachidonic acid and docosahexaenoic acid supplemented to an essential fatty acid-deficient diet alters the response to endotoxin in rats.

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.

Effects of glucose or fat calories in total parenteral nutrition on fat metabolism and systemic inflammation in rats.

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.

A simple method of supplementation of omega-3 polyunsaturated fatty acids: use of fortified yogurt in healthy volunteers.

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.

Effect of a fish oil-containing beverage on changes in plasma lipid fatty acids in patients with malabsorption.

BACKGROUND: The aim of this pilot study was to assess tolerance of a beverage containing ω-3 fatty acids (fish oil) in patients with malabsorption receiving chronic parenteral nutrition (PN). The authors wanted to determine whether fish oil could be absorbed and incorporated into plasma fatty acids and reduce markers of inflammation. METHODS: This was a small intervention study in home-dwelling PN-dependent patients with chronic malabsorption. Ten patients were provided a drink containing 1.5 g of fish oil per day for 12 weeks. Baseline and post-supplement serum fatty acid profiles were compared. RESULTS: Five of 10 patients withdrew from the study because of GI side effects, principally worsened diarrhea, associated with the supplement. Modest increases were found in 20:5ω-3, 22:5ω-3, and 22:6ω-3 levels in both phospholipids and triglycerides in plasma (all P < .05). In phospholipids, a reduced arachidonic acid level was seen (P = .02). These changes were not sufficient to effect improvements in serum tumor necrosis factor-alpha (TNFα), soluble TNF receptor, C-reactive protein, or interleukin-6. CONCLUSIONS: Some patients with severe malabsorption can absorb oral ω-3 fatty acid supplements and incorporate these fatty acids into serum phospholipids and triglycerides. However, side effects are very common, and no anti-inflammatory effect was found, presumably related to the modest level of fatty acid change.

Early development of essential fatty acid deficiency in rats: fat-free vs. hydrogenated coconut oil diet.

This study examined the effects of feeding an essential fatty acid deficient (EFAD) diet either without fat or with added hydrogenated coconut oil (HCO) on fatty acid profiles in rats. Both diets induced equivalent biochemical evidence of EFAD reflected by the triene/tetraene ratio in plasma phospholipids within 2 weeks. However, the HCO diet led to larger increases of 16:1n7 and 18:1n9 in muscle but smaller increases in fat tissue and plasma triglycerides than the fat-free diet, suggesting greater increases in hepatic de novo lipogenesis with the latter. In addition, the HCO diet led to larger decreases of some 18:3n3 metabolites, particularly 22:6n3, in muscle, fat and brain tissues than the fat-free diet, presumably related to lesser stimulation of elongation and desaturation. Thus, these secondary effects of an EFAD diet on fatty acid metabolism can be modified by the saturated fat in the diet while the primary impact of both diets on development of EFAD is unaffected.

Effect of a dietary intervention and n-3 fatty acid supplementation on measures of serum lipid and insulin sensitivity in persons with HIV.

BACKGROUND: Elevated serum triglyceride and low HDL-cholesterol concentrations have been reported in persons with HIV. OBJECTIVE: The effect of a dietary intervention plus n-3 (omega-3) fatty acid supplementation on serum triglycerides and markers of insulin sensitivity was investigated. DESIGN: Fifty-four persons with HIV and elevated serum triglycerides (>150 mg/dL) and/or abnormal Quantitative Insulin Sensitivity Check Index values (<0.35 but >0.30) were recruited for a dietary intervention in which total fat, type of fat, fiber, and glycemic load were controlled along with supplementation with n-3 fatty acids to achieve an intake of 6 g/d. The subjects were randomly assigned to an intervention or control group, and serum lipids, markers of insulin sensitivity, and serum phospholipid fatty acids were measured in both groups at baseline, 3 wk, and 13 wk. RESULTS: Triglycerides in the intervention group decreased from a median of 180 mg/dL (interquartile range: 141, 396) to 114 mg/dL (interquartile range: 84, 169) from baseline to 3 wk, whereas they remained stable in the control group (P = 0.003). Serum phospholipid fatty acids indicated a decrease in de novo lipogenesis and a decrease in arachidonic acid (% nmol; P

Supplementation of arachidonic acid plus docosahexaenoic acid in cirrhotic patients awaiting liver transplantation: a preliminary study.

BACKGROUND: In patients with cirrhotic liver diseases, supplementation of linoleic acid and alpha-linolenic acid often does not alter the levels of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), suggesting the necessity to directly provide these nutrients. METHODS: In a double-blind, placebo-controlled fashion, 9 cirrhotic patients listed for liver transplantation at Lahey Clinic Center were given daily supplementation with either 10 gel caps containing 500 mg of AA and 1000 mg of DHA (AA/DHA) or 250 mg of linolenic acid (LA) and 125 mg of oleic acid (OA; OA/LA) for 6 weeks. alpha-Tocopherol at 200 IU was provided daily. No other dietary prescription was made. Plasma fatty acid profiles were determined in triglyceride and phospholipids fractions. Plasma levels of C-reactive protein (CRP), tumor necrosis factor (TNF), interleukin 6 (IL-6), and soluble TNF receptor II (sTNFRII) were also measured. RESULTS: Four patients receiving OA/LA and 5 patients receiving AA/DHA completed the study without evidence of any adverse effects or intolerance. The supplementation of LA, AA, and DHA effectively raised their levels in either one or both plasma lipid fractions in this limited number of subjects. DHA plus AA also lowered 22:4omega-6, 22:5omega-6, and 22:5omega-3, suggesting that DHA reduced the elongation and desaturation of AA and EPA. CONCLUSIONS: It is feasible to improve the liver disease-associated deficiency of AA or DHA with modest intakes of AA and DHA. Whether this maneuver will affect the systemic inflammatory responsiveness and ultimately clinical outcome will require a large-scale and well-controlled intervention.

Liver and skeletal muscle lipids have differing fatty acid profiles in short-gut rats fed via parenteral nutrition.

BACKGROUND: In short-gut rats, we showed marked abnormalities in plasma lipid fatty acids using parenteral nutrition (PN) with lipid vs sham surgery rats. This suggests that either sensing or metabolism of parenteral lipid is abnormal in malabsorption. The goal of this study was to determine fatty acid profiles in skeletal muscle and liver in short-gut rats treated with PN compared with sham rats. METHODS: Sprague-Dawley rats underwent laparotomy and massive small bowel resection (or sham surgery). Rats (n = 32, 16 sham, 16 short gut) were randomly assigned to PN with lipid or fat-free PN. After 5 days, weight loss was similar in all groups, and mixed hindlimb skeletal muscle and liver were biopsied. RESULTS: We found marked differences between liver and skeletal muscle. In livers of short-gut animals, 22:4omega6, 22:5omega6, and 22:6omega3 were higher (all p < .05) than in sham. In skeletal muscle, short gut had no effect on fatty acid profiles. In liver, fat-free PN led to significant increases in 20:3omega6, 22:4omega6, 22:5omega6, 20:3omega9, 20:5omega3, 22:6omega3, and triene/tetraene ratio (all p < .05) compared with feeding PN with lipid, irrespective of short gut. In muscle, levels of the distal long-chain fatty acid metabolites and triene/tetraene ratio were minimally affected by nutrition. Serum glucose and insulin concentrations were similar in all 4 groups. CONCLUSIONS: Both the presence of short gut and type of PN led to increases in distal metabolites of fatty acids on omega:3 and omega:6 pathway in liver phospholipids but not in skeletal muscle during short-term PN feeding in rats.

Abnormal regulation of serum lipid fatty acid profiles in short gut rats fed parenteral nutrition with lipid.

Despite absence of essential fatty acid deficiency (EFAD), increases in arachidonic acid to linoleic acid ratios occur in serum phospholipid of patients treated with chronic total parenteral nutrition (TPN). The parenteral lipid component of TPN contains abundant linoleate; thus low phospholipid linoleate may reflect increased conversion to arachidonate. Arachidonic acid excess has been associated with a proinflammatory milieu through increased eicosanoid production and might contribute to the increases in inflammatory markers seen in home TPN patients. We investigated fatty acid metabolism in a rodent model of malabsorption. We hypothesized that short gut rats would metabolize parenteral lipid differently from intact rats. We performed laparotomy and 80% small bowel resection (or sham surgery) in rats. Sixteen sham and 16 short gut rats were randomly assigned to TPN with lipid or fat-free TPN. After 5 days, weight loss was similar in all groups. Analysis of serum phospholipids demonstrated that 20:3omega9 (eicosatrienoic acid) was relatively increased in fat-free TPN groups, irrespective of surgery type, as were distal very long chain omega3 class fatty acids, as anticipated. Uniquely, both nutrition (TPN/lipid v fat-free TPN) and surgery type (sham v short gut) were significant in determining arachidonic acid levels. Relatively elevated arachidonate occurred in both groups of fat-free rats, suggesting increased Delta6 and/or Delta5 desaturase activity, as expected. In contrast, giving TPN/lipid lowered arachidonate (suggesting appropriately downregulated desaturases) in sham animals, but not in short gut animals. Ratios of arachidonic and di-homo-gamma-linolenic to linoleic acids further suggested increased turnover of precursor omega6 to arachidonic acid in short gut rats given lipid compared with the other groups. These preliminary data show that intravenous (IV) lipid gave rise to serum lipid fatty acid profiles that differed in short gut and sham rats. The short gut rat may have a heightened hepatic desaturase activity, inappropriate for the quantity of linoleic acid provided parenterally. Therefore, the short gut rat is an appropriate model to study further arachidonic acid excess in home TPN patients.