ABSTRACT
Asthma may respond to dietary modification, thereby reducing the need for pharmacologic agents. This study determined the effectiveness of n-3 polyunsaturated fatty acid (PUFA) ingestion in ameliorating methacholine-induced respiratory distress in an asthmatic population. The ability of urinary leukotriene excretion to predict efficacy of n-3 PUFA ingestion was assessed. After n-3 PUFAs in ratios to n-6 PUFAs of 0.1:1 and 0.5:1 were ingested sequentially for 1 mo each; patient respiratory indexes were assessed after each treatment. Forced vital capacity (FVC), forced expiratory volume for 1 s (FEV1), peak expiratory flow (PEF), and forced expiratory flow 25-75% (FEF 25-75) were measured along with weekly 24-h urinary leukotriene concentrations. With low n-3 PUFA ingestion, methacholine-induced respiratory distress increased. With high n-3 PUFA ingestion, alterations in urinary 5-series leukotriene excretion predicted treatment efficacy. Elevated n-3 PUFA ingestion resulted in a positive methacholine bronchoprovocation dose change in > 40% of the test subjects (responders). The provocative dose to cause a 20% reduction (PD20) in FEV1, FVC, PEF, and FEF25-75 values could not be calculated because of a lack of significant respiratory reduction. Conversely, elevated n-3 PUFA ingestion caused some of the patients (nonresponders) to further lose respiratory capacity. Five-series leukotriene excretion with high n-3 PUFA ingestion was significantly greater for responders than for nonresponders. A urinary ratio of 4-series to 5-series leukotrienes < 1, induced by n-3 PUFA ingestion, may predict respiratory benefit.
Subject(s)
Asthma/diet therapy , Asthma/metabolism , Fatty Acids, Omega-3/therapeutic use , Leukotrienes/metabolism , Adult , Asthma/physiopathology , Biomarkers/urine , Bronchial Provocation Tests , Dose-Response Relationship, Drug , Fatty Acids, Omega-3/administration & dosage , Forced Expiratory Volume/drug effects , Forced Expiratory Volume/physiology , Humans , Leukotrienes/urine , Methacholine Chloride/pharmacology , Predictive Value of Tests , Respiration/drug effects , Respiration/physiology , Time Factors , Vital Capacity/drug effects , Vital Capacity/physiologyABSTRACT
This study assessed the effect of frequency of consumption of a diet containing 10 g fat/100 g, with a (n-3):(n-6) polyunsaturated fatty acid (PUFA) ratio of 0.5, on tissue fatty acid composition and eicosanoid synthesis in CD-1 mice. With greater (n-3) PUFA consumption frequency, hepatic and peritoneal cell (n-3) PUFA levels changed to 14.4 +/- 1.3 and 12.4 +/- 0.9 mol/100 mol, respectively, from 2.4 +/- 0.3 and 1.9 +/- 0.3 mol/100 mol in control animals consuming a diet without (n-3) PUFA. Hepatic and peritoneal cell (n-6) PUFA levels were reduced to 6.4 +/- 0.5 and 7.6 +/- 0.5 mol/100 mol, respectively, with daily (n-3) PUFA consumption, compared with 23.6 +/- 0.7 and 17.9 +/- 0.7 mol/100 mol in control animals. Prostaglandin E, 6-keto-prostaglandin F1 alpha, and 4-series sulfidopeptide leukotriene biosyntheses reflected frequency of (n-3) PUFA consumption, with daily (n-3) PUFA consumption reducing prostaglandin E, consumption of (n-3) PUFA every other day reducing 6-keto-prostaglandin F1 alpha, and (n-3) PUFA consumption every 3 d reducing leukotriene C4 and leukotriene E4. Leukotriene C5 and leukotriene E5 changed from undetectable in animals consuming the control diet to > 40% of total leukotriene production in animals consuming (n-3) PUFA daily. Daily to biweekly consumption of fish or fish oil [1.26-0.63 g/wk of (n-3) PUFA, 6-3% of energy] may be a means for changing eicosanoid production. Consumption of (n-3) PUFA less often than twice a week may not change eicosanoid synthesis.
Subject(s)
Fatty Acids, Omega-3/pharmacology , Fatty Acids, Unsaturated/analysis , Leukotrienes/biosynthesis , Liver/drug effects , Prostaglandins/biosynthesis , Administration, Oral , Animals , Chromatography, High Pressure Liquid , Fatty Acids, Omega-3/administration & dosage , Leukotrienes/analysis , Liver/metabolism , Male , Mice , Periodicity , Peritoneal Cavity/cytology , Weight Gain/drug effectsABSTRACT
Ingestion of modest amounts of n-3 polyunsaturated fatty acids (PUFA) (2.8% w/w) decreased plasma triglyceride levels in Syrian hamsters by 49%. This was associated with a 45% increase in hepatic carnitine palmitoyl transferase activity. Significantly, at this low level of n-3 PUFA intake, hepatic peroxisomal oxidation measured as CN- insensitive palmitoyl-CoA dependent NAD reduction was unaffected. Consumption of increasing amounts of dietary n-3 PUFA up to 2% (w/w) in hamster diets containing 15% fat, gradually decreased plasma triglycerides to 56% of the control levels. The diet induced changes in plasma triglyceride levels were highly correlated (r = -0.97, P less than 0.01) with changes in hepatic carnitine palmitoyl transferase activity. A gradual decrease up to 59% in hepatic phosphatidate phosphohydrolase activity with n-3 fatty acid consumption was also observed. The hypotriglyceridemic effects of moderate intakes of n-3 fatty acids are, therefore, associated with changes in key enzymes in hepatic triglyceride synthesis and mitochondrial oxidation, but not peroxisomal oxidation.
Subject(s)
Fatty Acids, Unsaturated/pharmacology , Triglycerides/blood , Animals , Carnitine O-Palmitoyltransferase/metabolism , Cricetinae , Dietary Fats/administration & dosage , Dietary Fats/pharmacology , Fatty Acids, Unsaturated/administration & dosage , Fatty Acids, Unsaturated/metabolism , Liver/metabolism , Male , Mesocricetus , Mitochondria, Liver/enzymology , Phosphatidate Phosphatase/metabolism , Triglycerides/metabolismABSTRACT
The effects of preformed dietary arachidonic acid (AA, 20:4n-6) on murine phospholipid fatty acid composition in tissues capable (liver) and incapable (peritoneal exudate cells, PEC) of desaturating and elongating linoleic acid (LA, 18:2n-6) to AA were investigated. The results were compared with those obtained on matched animals on LA diets by either substituting or supplementing dietary LA with AA. Modest amounts of AA ethyl ester (0.5 wt%) included in the diet significantly increased tissue phospholipid AA levels by 39% and 57% in the liver and in PEC, respectively. The changes were further enhanced when dietary LA and AA intakes were equivalent, i.e., 57% and 68% in liver and PEC, respectively. This enrichment was observed in all phospholipid classes analyzed, with the greatest impact on phosphatidylcholine. In addition, the doubling of dietary LA had little effect on tissue phospholipid AA levels. The data suggest that while the level of n-6 PUFA may have an important effect on tissue fatty acid composition, the type of n-6 PUFA in the diet could be of greater significance.
Subject(s)
Arachidonic Acid/pharmacology , Linoleic Acids/pharmacology , Liver/chemistry , Macrophages/chemistry , Phospholipids/chemistry , Animals , Dietary Fats, Unsaturated/pharmacology , Fatty Acids/analysis , Linoleic Acid , Liver/drug effects , Macrophages/drug effects , Male , Mice , Peritoneal Cavity/cytology , Peritoneal LavageABSTRACT
An incremental increase in the dietary (n-3):(n-6) polyunsaturated fatty acid (PUFA) ratio from 0 to 1.93 in diets containing 15% fat (wt/wt) decreased the total (n-6) PUFA content of phospholipids of the liver and peritoneal cells (macrophage) in mice from 43.1 and 33.6 mol/100 mol to 16.0 and 12.3 mol/100 mol with a concomitant increase of 27.6 and 16.1 mol/100 mol in (n-3) PUFA, respectively. Consumption of (n-3) PUFA increased hepatic (n-3) PUFA levels without changing total PUFA (46.35 vs. 46.87 mol/100 mol), whereas macrophage PUFA levels were decreased. The synthesis of sulfidopeptide leukotrienes (SP-LT) (LTC4 and LTE4) was progressively reduced by increasing dietary (n-3) PUFA, i.e., there was a reduction of 76% in mice fed a diet containing a (n-3):(n-6) PUFA ratio of 1.93 compared with the control diet. The 5-series SP-LT (LTC5 and LTF5) were produced in all animals consuming (n-3) PUFA and accounted for 62% of all SP-LT synthesized in mice fed the diet containing a 1.93 (n-3):(n-6) PUFA ratio. Synthesis of 6-keto-prostaglandin F1 alpha decreased 81% in mice fed a diet containing a (n-3):(n-6) PUFA ratio of 1.93 whereas prostaglandin E2 synthesis decreased 44% in mice fed diets with (n-3):(n-6) ratios ranging from 0.41 to 1.93.