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The purpose of this study was to investigate in healthy humans the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake, alone or in combination with dL-alpha-tocopherol acetate (vitamin E) supplements on lipid peroxidation. Eighty men were randomly assigned in a double-blind fashion to take daily for 6 wk either menhaden oil (6.26 g, n-3 fatty acids) or olive oil supplements with either vitamin E (900 IU) or its placebo. Antioxidant vitamins, phospholipid composition, malondialdehyde (MDA), and lipid peroxides were measured in the plasma at baseline and week 6. At the same time, breath alkane output was measured. Plasma alpha-tocopherol concentration increased in those receiving vitamin E (P < 0.0001). In those supplemented with n-3 fatty acids, EPA and DHA increased in plasma phospholipids (P < 0.0001) and plasma MDA and lipid peroxides increased (P < 0.001 and P < 0.05, respectively). Breath alkane output did not change significantly and vitamin E intake did not prevent the increase in lipid peroxidation during menhaden oil supplementation. The results demonstrate that supplementing the diet with n-3 fatty acids resulted in an increase in lipid peroxidation, as measured by plasma MDA release and lipid peroxide products, which was not suppressed by vitamin E supplementation.

Background: In orally fed animals, infusion of cachectin/tumor necrosis factor (TNF) caused weight loss and muscular wasting, accompanied by anorexia. Despite muscle wasting, there were gains in weight and protein and DNA contents of the viscera, but no significant metabolic abnormalities. Methods: To observe the effect of cachectin/TNF on the nutritional-metabolic status, and without the confounding effect of anorexia, cachectin/TNF was infused into rats receiving total parenteral nutrition in sufficient amounts to induce weight gain in controls at the same rate as in orally fed rats. Results: TPN prevented loss of body weight, but cachectin-treated animals had reduced nitrogen retention and carcass weight. By contrast, there were gains in visceral protein levels, which in the liver was due to a marked proliferation of biliary epithelium. In addition, cachectin-treated animals receiving TPN developed hyperglycemia, hyperosmolality, diuresis, and dehydration. They also had azotemia and cholestasis. Conclusions: In the absence of the effects of anorexia, cachectin reduced nitrogen retention and caused metabolic and multisystem dysfunction, comparable with the effects of clinical sepsis.

Changes in brain metabolites, energy balance, resting metabolic rate, body composition, and organ histology were studied over 10 days in control (C), cachectin-infused (CIR), and pair-fed (PFR) (in relation to CIR) rats. The cachectin was continuously infused for the 10 days into the superior vena cava at the rate of approximately 100 micrograms.kg-1.day-1. The brain of the CIR had significantly more tryptophan and 5-hydroxyindole-3-acetic acid than C and PFR. The CIR rats were anorexic, hypermetabolic, relatively hyperglycemic, and had raised blood urea nitrogen with comparable creatinine levels when compared with similarly wasted PFR. They had significant loss of muscle mass, especially in muscles with a predominance of type II fibers. However they gained liver, heart, and lung mass. The loss of muscle mass could be ascribed to dietary deficiency, but the gain in visceral mass was associated with an increase in organ DNA and protein. Histology showed that there was cell proliferation in the liver, heart, and kidneys. The data are consistent with centrally mediated anorexia with nutritionally mediated muscle wasting but with visceral hypermetabolism, protein accumulation, and cell proliferation.

Cigarette smoke contains many xenobiotics, including oxidants and free radicals, which can increase lipid peroxidation. Recently, breath pentane output (BPO) has been recognized as a good indicator of lipid peroxidation. Vitamin E is known to be a potent free radical scavenger which can protect biological membranes against oxidative damage. We investigated the effect of vitamin E (dl-alpha-tocopherol) on lipid peroxidation in 13 healthy smokers. The results showed (1) smokers had increased BPO as compared with 19 healthy non-smokers (16.3 +/- 1.9 vs 5.8 +/- 0.5, pmol/kg body weight/min, p less than 0.001) although both groups had comparable plasma vitamin E and selenium concentrations, (2) supplementation with vitamin E (800 mg/day for 2 weeks) decreased BPO in smokers, and (3) the concentration of plasma selenium-dependent glutathione peroxidase was restored to normal in those smokers (five out of 13) in whom this was low initially. We conclude that a normal plasma concentration of vitamin E does not prevent this increase of lipid peroxidation in smokers but that substantial doses of vitamin E will significantly reduce this increased lipid peroxidation. If a major function of vitamin E is to protect lipids from peroxidation, then smokers have a conditioned insufficiency of vitamin E on a normal diet.

Background Oxidative stress is increased in patients with congestive heart failure and can contribute to the progressive deterioration observed in these patients. Increased oxidative stress is the result of either an increased production of free radicals or a depletion of endogenous antioxidants, such as vitamin E. Objective We aimed to determine whether vitamin E supplementation of patients with advanced heart failure would modify levels of oxidative stress, thereby preventing or delaying the deterioration associated with free radical injury. Design Fifty-six outpatients with advanced heart failure (New York Heart Association functional class III or IV) were enrolled in a double-blind randomized controlled trial for 12 wk. At a baseline visit and at 2 follow-up visits, blood and breath samples were collected for the measurement of indexes of heart function and disease state, including malondialdehyde, isoprostanes, and breath pentane and ethane. Quality of life was also assessed at baseline and after 12 wk of treatment. Results Vitamin E treatment significantly increased plasma concentrations of alpha-tocopherol in the treatment group but failed to significantly affect any other marker of oxidative stress or quality of life. In addition, concentrations of atrial natriuretic peptide (a humoral marker of ventricular dysfunction), neurohormonal-cytokine markers of prognosis, tumor necrosis factor, epinephrine, and norepinephrine were unchanged with treatment and were not significantly different from those in the control group. Conclusion Supplementation with vitamin E did not result in any significant improvements in prognostic or functional indexes of heart failure or in the quality of life of patients with advanced heart failure.

Background/Aims: After massive small bowel resection, malabsorbed carbohydrates reach the colon and undergo fermentation. This study investigates the role of colonic fermentation in rats with 80% small bowel resection on weight gain, nitrogen balance, body composition, and intestinal adaptation. Methods: Resected or transected rats were fed a liquid diet enterally for 16 days with or without 30 mg/kg metronidazole to reduce fermentation. Weight gain was monitored until the rats were killed. Carcass composition, short-chain fatty acids in cecal content, total nitrogen output, and intestinal mucosal dry weight, protein, and DNA were measured. Results: Resected rats without metronidazole had a significantly better weight gain, carcass protein, nitrogen balance, and mucosal dry weight, protein, and DNA compared with that of resected rats receiving metronidazole. There were no significant differences between the two transected groups. Conclusions: Decreasing colonic fermentation, measured by short-chain fatty acids in cecal content, reduced intestinal adaptation and nutritional recovery in rats with massive small bowel resection.

Congestive heart failure depletes the myocardium of carnitine, coenzyme Q10 (CoQ10), and taurine--substances known to influence mitochondrial function and cell calcium. We hypothesized that feeding patients a nutritional supplement that contained carnitine, CoQ10, and taurine would result in higher myocardial levels of these nutrients and improve left ventricular function.Forty-one patients who underwent aortocoronary artery bypass with an ejection fractionor =40% at referral were randomly assigned to a double-blind trial of supplement or placebo. Radionuclide ventriculography was performed at randomization and before surgery. Surgical myocardial biopsies, adjusted for protein content, were analyzed for carnitine, CoQ10, and taurine levels.The groups were well matched. Minor exceptions were supplement group versus placebo group for digoxin use (7 vs 0, respectively; P =.009) and age (62 +/- 11 years vs 69 +/- 5 years, respectively; P =.04). There were significantly higher levels in the treated group compared with the placebo group for myocardial levels of CoQ10 (138.17 +/- 39.87 nmol/g wet weight and 56.67 +/- 23.08 nmol/g wet weight; P =.0006), taurine (13.12 +/- 4.00 micromol/g wet weight and 7.91 +/- 2.81 micromol/g wet weight; P =.003), and carnitine (1735.4 +/- 798.5 nmol/g wet weight and 1237.6 +/- 343.1 nmol/g wet weight; P =.06). The left ventricular end-diastolic volume fell by -7.5 +/- 21.7 mL in the supplement group and increased by 10.0 +/- 19.8 mL in the placebo group (P =.037).Supplementation results in higher myocardial CoQ10, taurine, and carnitine levels and is associated with a reduction in left ventricular end-diastolic volume in patients with left ventricular dysfunction before revascularization. Because the risk of death for surgical revascularization is related to preoperative left ventricular end-diastolic volume, supplementation could improve outcomes.

Breath pentane, which evolves from the scission of omega-6 fatty acids, is a good index of lipid peroxidation. Breath pentane output, plasma alpha- and gamma-tocopherol (alpha- and gamma-toc), plasma selenium (Se), and selenium-dependent glutathione peroxidase (Se-GSHPx) were measured in 10 healthy volunteers before and after 10 days of oral supplementation with d-alpha-tocopheryl acetate (1000 IU/day). After supplementation with this vitamin E, we observed a significant increase in plasma alpha-toc, with a simultaneous decrease in gamma-toc. Breath pentane output was significantly decreased after supplementation (7.60 ± 0.82 vs. 5.04 ± 0.57 pmol.kg −1 .min −1 , p Interestingly, plasma Se-GSHPx increased significantly, although plasma Se was stable. These results showed that short-term supplementation with alpha-tocopherol may decrease breath pentane output, and by inference, diminish lipid peroxidation in normal subjects.

Eight patients with a short bowel resulting from intestinal resection and clinically stable for at least 6 mo were studied on two diets. Each diet was given for 5 days at a time and crossed over with the other. Both diets contained 20% of total calories as protein. The high-fat diet had 60% of calories as fat and 20% as carbohydrate. This ratio was reversed in the high-carbohydrate diet. Both diets were lactose free with low fiber. Fluid intake was kept constant. The results showed that there was no difference in the blood chemistry, stool, or ostomy volume, the zinc, calcium, and magnesium balances, urine volume, and electrolyte excretion between patients on the two diets. Bomb calorimetry showed that the total calories absorbed and excreted were comparable between the two diets. It was concluded that low-fat diets had no special benefit in the overall nutrition of the patient who has been in remission in regard to bowel disease for 6 mo or longer. Hence, dietary restriction is not recommended in these patients. However, this study did not resolve the question of the requirements and losses of fat-soluble vitamins in such patients when on a high-fat diet.

We studied the effect of intravenous lipid infusion on lipid peroxidation as measured by breath pentane. Pentane, plasma alpha-tocopherol (alpha-tox) and plasma gamma-tocopherol (gamma-toc), selenium, and Se-dependent glutathione peroxidase (Se-GSHPx) were measured in 10 normal control subjects and in 10 home parenteral nutrition (HPN) patients before and after infusion of 100 mL Nutralipid 10% over 30 min. Before infusion, breath pentane was significantly higher and alpha-toc was significantly lower in the HPN group than in the control subjects. These two measurements were significantly negatively correlated (r = -0.54, p less than 0.05). Pentane, alpha-toc, and Se-GSHPx were significantly increased in both groups after lipid was infused but were still significantly higher in HPN patients than in control subjects. Thus, infusion of a small amount of lipid rich in linoleic acid induced a significant increase in breath pentane, reflective of increased lipid peroxidation.

Pentane, which evolves from the reaction involving omega-6 fatty acids, is a good index of lipid peroxidation. We describe a method for measuring breath pentane excretion in adult humans. After a 4-minute washout period, expired air was analyzed by gas chromatography. Breath was passed through a cooled loop of alumina to adsorb, concentrate, and release, on heating, pentane. Pentane was analyzed by a Porasil-D column with a derived calibration curve. The mean excretion of pentane in 10 normal adults was 6.34 +/- 0.96 pmol X kg-1 X min-1 (mean +/- SEM) and was significantly higher in five patients with plasma vitamin E deficiency (15.39 +/- 1.84 pmol X kg-1 X min-1). There was a significant negative correlation between pentane output and plasma vitamin E levels (r = -0.66, p less than 0.01). Moreover, breath pentane excretion was significantly decreased after a 10-d supplementation with vitamin E in five normal subjects. We conclude that breath pentane output is a sensitive, noninvasive, functional test for assessing vitamin E status.

Because both vitamin E and selenium protect against lipid peroxidation, we evaluated the relationship between breath pentane, evolved from the peroxidation of linoleic acid, and plasma levels of alpha-tocopherol (vitamin E), Se, and Se-dependent glutathione peroxidase (Se-GSHPx). Nine home parenteral-nutrition (HPN) patients received added Se in intravenous solutions and were compared with 10 normal control subjects. The excretion of pentane (pmol.kg-1.min-1, means +/- SEM) in control subjects (6.34 +/- 0.96) was significantly lower than in HPN patients (15.02 +/- 1.12, p less than 0.001). alpha-Tocopherol (mumol/L), Se (mumol/L), and Se-GSHPx (U) values were, respectively, 18.13 +/- 1.70, 1.70 +/- 0.05, and 5.34 +/- 0.27 in control subjects and 10.21 +/- 1.66, 1.35 +/- 0.14, and 7.01 +/- 0.31 in HPN patients. All differences were statistically significant. Significant negative correlations were observed between plasma alpha-tocopherol levels and HPN duration and between pentane output and plasma alpha-tocopherol levels (r = -0.58, p less than 0.01). In HPN patients with reduced plasma alpha-tocopherol levels associated with increased pentane output, there is, inferentially, increased lipid peroxidation despite normal plasma Se and Se-GSHPx levels.

Eight patients with a short bowel resulting from intestinal resection and clinically stable for at least one year were studied for 10 days. The diet chosen was lactose-free with a low fiber content and contained 22% of total calories as protein, 32% as carbohydrate, and 46% as fat. Total fluid volume was kept constant, and all patients were in positive nitrogen balance. During the 10-day period, blood chemical concentrations, stool, and/or ostomy volume, urine volume, electrolyte excretion, and calorie and divalent cation absorption were measured. In addition it was determined that fluid restriction during meals did not affect these parameters. In these patients the absorptions of fat, carbohydrate, protein, and total calories were 54%, 61%, 81%, and 62%, respectively. Similarly the absorption of the divalent cations, calcium, magnesium, and zinc, were 32%, 34%, and 15%, respectively. We suggest that patients with short bowel syndrome, who have been stable for at least one year and who can tolerate oral diets, do not need to restrict fat or to separate fluids from solids during their meals. Furthermore, they should increase their oral intake to 35–40 kcal/kg ideal body weight in order to counteract their increased losses. The diet should contain 80–100 g protein/day in order to maintain a positive nitrogen balance and a large margin of safety. In addition, these patients may take oral supplementation of calcium, magnesium, and zinc to maintain divalent cation balance.

Copper metabolism and requirements in patients receiving total parenteral nutrition were studied in 28 patients with gastrointestinal diseases. During each of the 3 wk of the study period, each of 24 patients received in their total parenteral nutrition solutions, a daily dose of copper amounting to 0.25 mg, 1.05 mg, or 1.85 mg, in a random order. The other 4 patients received a fixed daily dose of 1 mg throughout the 3 wk. Increased losses of copper through the gastrointestinal tract occurred in patients with diarrhea or high-output stomas or fistulas. Patients with abnormalities of liver excretory functions had decreases in gastrointestinal copper losses. Urinary copper excretion was twice that of normal subjects. Copper infused in excess of the requirements was retained and not excreted. Plasma copper did not reflect the copper balance and cannot be used as a guide for copper supplementation. Copper requirements were found to be 0.3 mg/day in patients with normal amounts of gastrointestinal excretion. In the presence of diarrhea or increased fluid loss through gastrointestinal stomas or fistulas, the copper requirements for total parenteral nutrition are 0.4--0.5 mg/day.