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PubMed1992

Management of non-insulin-dependent diabetes mellitus.

The initial management of non-insulin-dependent diabetes mellitus (NIDDM) should include patient education, dietary counselling and, when feasible, individualised physical activity. It is only when such measures fail that drug therapy should be considered. Dietary management of NIDDM includes a restriction in calories, and these should be appropriately distributed as carbohydrates, lipids and proteins. Supplementation of the diet with soluble fibre and supplementation with magnesium salts if hypomagnesaemia is demonstrated, is recommended. However, supplementation with fish oils or with fish oil-derived omega-3 fatty acids is not currently recommended. Oral drug therapies used in NIDDM include sulphonylurea derivatives, which are a first-line treatment in patients who are not grossly obese, metformin, which is the treatment of choice for obese patients, and alpha-glucosidase inhibitors such as acarbose, which are used mainly to reduce postprandial blood glucose peaks. These types of drugs can be used alone or in combination. Insulin therapy may be required to achieve adequate control of blood glucose levels in some patients. In several instances, it is suggested that insulin therapy be combined with sulphonylureas (essentially when residual insulin secretion is present), with metformin, or with alpha-glucosidase inhibitors. The treatment of disorders associated with NIDDM, such as obesity, hypertension or hyperlipidaemia, requires particular attention in diabetic patients, since some drugs can adversely affect glycaemic control. Oral drugs for the treatment of NIDDM include sulphonylurea derivatives used in first-line treatment in patients who are not grossly obese, metformin, which is often the treatment of choice for obese patients and, more recently, the alpha-glucosidase inhibitors, such as acarbose, which are effective in reducing the postprandial rise in blood glucose.

Acarbose↗
PubMed1976

Prostaglandins and polyunsaturated fatty acids in heart muscle.

1. Dietary lipids modify fatty acid composition of cardiac lipids. Polyunsaturated fatty acids replace less unsaturated fatty acids in phospholipds. 2. Mortality following isoproterenol-stimulation increase with decreasing amount of arachidonic acid in cardiac phospholipds. 3. In normal human heart muscle the ratio of essential, omega-6/nonessential, omega-3 fatty acids diminshes from age 17 to age 50 years. 4. In sudden cardiac death the ratio of prostaglandin substrate, C20:4, to prostaglandin inhibitor, C22:6, is frequently much higher than expected.

Age Factors↗
PubMed1979

Haemostatic function and platelet polyunsaturated fatty acids in Eskimos.

Death from cardiovascular disease is rare among Eskimos. Haemostasis was investigated in twenty-one Greeland Eskimos and twenty-one age and sex matched Danish controls. Platelet lipid analysis demonstrated that a high consumption of omega-3 polyunsaturated fatty acids (such as cis 5, 8, 11, 14, 17-eicosapentaenoic acid [C20:5]) by Eskimos increased the proportion of omega-3 polyunsaturated fatty acids in the platelets. The Eskimos had a significantly longer bleeding-time due to a reduction in platelet aggregation. It is suggested that C20:5 in the platelets is converted by the vascular-wall tissue to an anti-aggregatory prostacyclin. Partial dietary substitution of arachidonic acid by eicosapentaenoic acid may reduce the incidence of thrombotic disorders, including myocardial infarction.

Adult↗
PubMed2026

Vegan multinutrient supplementation significantly increases Omega-3 index and 25-OH-vitamin D status: a randomized, double-blind, placebo-controlled trial in healthy young vegans.

In this randomized, double-blind, placebo-controlled trial, 72 healthy vegan adults (aged 19-57 years) received a multinutrient supplement consisting of a vitamin and mineral supplement (providing 26 &#xb5;g vitamin D) and an omega-3 supplement administered in either a single dose (EPA 98.7 mg, DHA 171.0 mg, additional vitamin D 36 &#xb5;g, vitamin E 3.7 mg) or a double dose (EPA 197.4 mg, DHA 342.0 mg, additional vitamin D 72 &#xb5;g, vitamin E 7.4 mg) or placebo capsules for 4 months. Nutrient biomarkers were assessed at baseline and at the end of the intervention after 4 months. An analysis of covariance was employed to test for between-group differences (p < 0.05) and adjusted for multiple testing using the Bonferroni-Holm method. Compared to the control group, which showed on average a significant decline in both the omega-3-index and 25-hydroxyvitamin D, participants in both intervention groups demonstrated significant increase in these parameters (p < 0.001). Although the double dose group exhibited numerically greater increases in omega-3 index and vitamin D compared to the simple dose group, the differences between these dosing regimens were not statistically significant. As expected, vitamin E levels remained unchanged, reflecting its inclusion solely for antioxidative protection in the omega-3 supplement rather than as a critical nutrient in vegan diets. In conclusion, supplementation significantly improved omega-3 and vitamin D status in healthy vegans, with no significant benefit from doubling the dose. Although clinical endpoints were not evaluated, improved nutrient status may have potential implications for health. The study has been registered at the German Clinical Trials Register (DRKS00028151).

Humans↗
PubMed1975

Omega-1, Omega-2 and Omega-3 hydroxylation of long-chain fatty acids, amides and alcohols by a soluble enzyme system from Bacillus megaterium.

A soluble enzyme preparation from Bacillus megaterium, previously shown to hydroxylate free fatty acids to isomeric mixtures of Omega-1, Omega-2 and Omega-3 monohydroxy fatty acids in the presence of NADPH and O2, has now been shown to act also on fatty amides but not only hydrocarbons or fatty acid methyl esters. Using 14-C-labelled substrates, both the chain-length specificity and the positional specificity of hydroxylation was determined for fatty acids, alcohols and amides. The most active saturated fatty acid (pentadecanoic) was hydroxylated at a rate 10 times greater than the most active amide (myristamide) and 14 times faster than the most active alcohol (1-tetradecanol). Among the saturated fatty acids, the order of activity as hydroxylation substrates was C15 greater than C16 greater than C14 greater than C17 greater than C13 greater than C18 = C12. For amides the order was C14 greater than C12 greater than C15 greater than C16 while for alcohols it was C14 greater than C13 = C15 greater than C12 greater than C15. Four cis-monounsaturated fatty acids were also tested. Oleic, palmitoleic and cis-12-octadecenoic acids were more active than their saturated analogs but cis-5-tetradecenoate was less active than myristate. For all of the substrates mentioned above, with the possible exception of several unsaturated acids, the alkyl chains were monohydroxylated to give isomeric mixtures of the Omega-1, Omega-2 and Omega-3 derivatives. The distribution of these three isomers varied with chain-length and type of substrate but generally, the Omega-2 position was favored. The terminal methyl (Omega) group of these substrates was never hydroxylated and there did not appear to be significant hydroxylation of methylene carbons beyond the Omega-3 position. Based on the data presented here and in a previous paper, a model is proposed for the enzyme-substrate complex which involves hydrophobic binding and sequestering of the terminal methyl group of the substrate and electrostatic binding of the substrate's polar functional group.

Amides↗
PubMed1992

Effects of dietary fish oil on plasma high density lipoprotein. Electron spin resonance and fluorescence polarization studies of lipid ordering and dynamics.

Dietary fish oils are implicated in reducing the incidence of coronary heart disease, perhaps by altering the properties of plasma lipoproteins. The hypothesis that omega-3 polyunsaturated fatty acids (PUFA) in fish oils produce changes in lipid ordering and dynamics within high density lipoprotein (HDL), thereby potentially modifying cholesterol transport, is investigated here. Rabbits were fed a diet supplemented with either 10% (by weight) menhaden oil (MO), a fish oil rich in omega-3 PUFAs, or hydrogenated cottonseed oil for a period of 12 weeks. HDL was isolated by sequential flotation ultracentrifugation from plasma drawn every 2 weeks. Gas chromatography confirmed that the predominant omega-3 PUFAs of fish oils, eicosapentaenoic 20:5 and docosahexaenoic 22:6 acids, were only incorporated into the triglyceride, phospholipid, and cholesteryl ester constituents of lipoproteins from rabbits on the MO diet. ESR of 5- and 16-doxyl stearic acids demonstrates that molecular order and dynamics within the outer monolayer of HDL is virtually unaffected. In contrast, ESR of cholesteryl 12-doxyl stearate indicates order is less within the inner apolar core of the lipoprotein for the MO diet than for the hydrogenated cottonseed oil diet. Fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene supports this finding. The greater disorder detected within HDL from rabbits fed fish oil may result in an enhancement of cholesterol exchange between lipoproteins and between lipoproteins and cells, which may have anti-atherogenic ramifications.

Animals↗
PubMed1977

Protection against carbon tetrachloride-induced lipid peroxidation in the rat by dietary vitamin E, selenium, and methionine as measured by ethane evolution.

Dietary vitamin E, selenium (Se), and methionine were tested for their ability to inhibit carbon tetrachloride (CCL4)-induced lipid peroxidation. Peroxidation, in vivo, was monitored by the evolution of ethane, an autoxidation product of omega-3-unsaturated fatty acids. Weanling rats were fed a basal diet low in vitamin E, Se, and sulfur-containing amino acids, or diets individually supplemented with these factors. After 3 to 7 weeks, the rats were injected with CCL4 (ip) and ethane was collected for 9 hours. Cumulative ethane evolution was increased by CCl4 in all groups. Vitamin E, Se, and methionine reduced ethane evolution from CCl4-treated rats by 82%, 74%, and 60%, respectively. The toxicity of CCl4 was decreased in correlation with ethane evolution. Thus, methionine and Se, probably by maintaining intracellular glutathione and glutathione peroxidase, protected against CCl4-induced lipid peroxidation, as did vitamin E. Substitution of cod liver oil, which is rich in omega-3-unsaturated fat, for lard in the basal diet increased CCl4-induced ethane evolution six-fold. Relative inhibition by the dietary supplements was not changed. Thus, the feeding of cod liver oil greatly increased ethane production which facilitated the detection and measurement of lipid peroxidation in vivo.

Animals↗
PubMed1992

The effect of dietary n-3 fatty acids on in vivo platelet aggregation in the cerebral microcirculation.

Diets enriched in n-3 fish oil have been suggested to decrease coronary artery disease in part through their ability to decrease cyclooxygenase-dependent platelet aggregation. However little is known concerning the effect of n-3 fatty acids on in vivo platelet aggregation. The purpose of these experiments was to determine whether dietary n-3 fatty acids affect the rate at which platelet aggregation occurs in cerebral arterioles. Fish oil (200 mg eicosapentaenoic acid + 143 mg docosahexaenoic acid/kg), corn oil or water was given daily by gavage to mice (n = 30) for six weeks and then in vivo platelet aggregation was induced by the light plus dye method, which injuries the endothelium. Two additional groups of mice were acutely treated with saline or indomethacin (0.5 mg/kg, ip), with the latter serving as a positive control for therapeutic inhibition of platelet aggregation. Serum thromboxane B2 was analyzed by RIA. All fed groups gained weight equally. Serum thromboxane B2 was decreased by 40% in the fish oil group (p = 0.05 vs. corn oil, p = 0.07 vs. water). The mean (+/- SE) time to first aggregate in pial arterioles was 101 +/- 6, 91 +/- 6 and 101 +/- 9 seconds in the fish corn oil and water groups, respectively. Indomethacin significantly increased the time to first arteriolar aggregate by 35% (p < 0.002) and caused an 80% reduction in serum thromboxane. These studies show dietary fish oil produces a moderate reduction in serum TxB2 level and does not affect arteriolar platelet aggregation whereas indomethacin produces a drastic TxB2 reduction and significantly slows platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A low-sodium diet supplemented with fish oil lowers blood pressure in the elderly.

OBJECTIVE: To examine effects of dietary fish oil supplementation with sodium restriction on blood pressure in the elderly. DESIGN: In a double-blind dietary intervention lasting 4 weeks, parallel comparisons of blood pressure were made in volunteers assigned to one of four treatment groups: fish oil and low sodium; fish oil and normal sodium; sunflower oil and low sodium; or sunflower oil and normal sodium. SETTING: Subjects lived at home and attended our nutrition research clinic at fortnightly intervals for dietary counselling and blood pressure measurement. PARTICIPANTS: Health volunteers aged 60-80 years were sought by advertisement. A total of 114 men and women were enrolled in two cohorts; 106, with an initial mean blood pressure of 132/77 mmHg, satisfactorily completed the study. INTERVENTION: All subjects adopted a low-sodium diet and dietary changes were effected by double-blind administration of slow-release sodium chloride or placebo tablets, along with capsules containing either fish or sunflower oil. MAIN OUTCOME MEASURE: The primary measure was the within-subject change in blood pressure after 4 weeks of intervention in each dietary treatment group. RESULTS: Urinary sodium excretion in subjects on low-sodium diets decreased whilst potassium excretion was unaffected. Systolic blood pressure (SBP) fell in the group taking sunflower oil with low sodium, but there was only a transient fall in diastolic blood pressure (DBP). In those taking fish oil with normal sodium, the change in blood pressure was not significant, except after adjustment for initial blood pressure and weight changes. When fish oil was combined with low sodium, however, both SBP and DBP were substantially reduced; the reduction in DBP was significantly greater than in the other treatment groups. CONCLUSION: Dietary fish oil and sodium restriction can interact to lower DBP in the elderly.

Aged↗
PubMed1992

n-3 fatty acids: biochemical actions in cancer.

A number of reports indicate that fish n-3 PUFA inhibit the development, growth and progression of several experimental tumors. There emerges a pattern of complex and diverse biochemical actions of n-3 PUFA in different animal tumor models, from the studies undertaken to date to evaluate the underlying mechanisms. These findings, along with the recent epidemiological evidence of an inverse correlation between fish intake and incidence of some human cancers, makes it worthwhile to determine the role of n-3 PUFA in cancer.

Animals↗
PubMed1992

Dietary supplementation with fish oil in ulcerative colitis.

OBJECTIVE: To determine the efficacy of fish oil supplementation in patients with active ulcerative colitis. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, crossover trail with 4-month treatment periods (fish oil and placebo) separated by a 1-month washout. SETTING: Four gastroenterology divisions. PATIENTS: Twenty-four patients with active ulcerative colitis entered the study. Five dropped out, and one was noncompliant. Eighteen patients completed the study. All patients had active disease as manifested by diarrhea and rectal inflammation. INTERVENTIONS: Treatment with prednisone and sulfasalazine was continued. Fish oil supplementation consisted of 18 Max-EPA (eicosapentaenoic acid) capsules daily (eicosapentaenoic acid, 3.24 g; and docosahexaenoic acid, 2.16 g). Placebo supplementation consisted of 18 identical capsules containing isocaloric amounts of vegetable oil. MEASUREMENTS: Patients were evaluated at study entry and after each diet period. Evaluations included a review of symptoms, flexible sigmoidoscopy, rectal biopsy, and rectal dialysis to measure prostaglandin E2 and leukotriene B4 levels. RESULTS: Fish oil supplementation resulted in a significant decrease in rectal dialysate levels of leukotriene B4 from 71.0 to 27.7 pg/mL (average change, -43.3 pg/mL; 95% CI, -83 to -3.6). Significant improvements were seen in acute histology index (average change, -8.5 units from a baseline of 10.5 units; CI, -12.9 to -4.2) and total histology index (average change, -8.5 units from a baseline of 14.80; CI, -13.2 to -3.8) as well as significant weight gain (average weight gain, 1.74 kg, CI, 0.94 to 2.54). No significant changes occurred in any variable during the placebo period. Seven patients received concurrent treatment with prednisone. During the fish oil supplementation period, the mean prednisone dose decreased from 12.9 mg/d to 6.1 mg/d and rose from 10.4 mg/d to 12.9 mg/d during the placebo diet period (P greater than 0.20). CONCLUSIONS: Four months of diet supplementation with fish oil in patients with inflammatory bowel disease resulted in reductions in rectal dialysate leukotriene B4 levels, improvements in histologic findings, and weight gain.

Adult↗
PubMed1979

Lipid metabolism, atherogenesis, and haemostasis in Eskimos: the role of the prostaglandin-3 family.

In Eskimos coronary heart disease is a rarity. This can partly be explained by their favorable plasma lipid levels. An additional factor seems, however, to be that in Eskimo food polyunsaturated fatty acids of the omega-3 series replace those of the omega-6 series. C20:5, omega-3 can be converted by the vessel wall to an antiaggregatory substance, whereas it has no proaggregatory effect on platelets. Consistent with these findings Eskimos were found to have a nearly 2-fold longer bleeding time than Danes. Platelet aggregability, too, was markedly depressed when exposing platelets from Eskimos to ADP and collagen.

Adenosine Diphosphate↗
PubMed1976

Fatty-acid composition of rat brain lipids. Determined by support-coated open-tubular gas chromatography.

The nonhydroxy fatty acid composition of rat brain lipids (except gangliosides) was determined by support-coated open-tubular (SCOT) gas chromatography. Fatty acids of both odd and even chain lengths ranging from C14 to C26 were detected. Brain lipids contained 49% saturated, 29% monounsaturated, and 22% polyunsaturated fatty acids. Monoenoic fatty acids were mainly of the omega-9 and omega-7 series with minor amounts of omega-10 and amega-11 isomers. Dienes and trienes consisted of omega-6, amega-7, and omega-9 series. Tetraenes were of the omega-6 series. Small amounts of omega-6 and omega-3 pentaenes were detected. The most abundant polyunsaturated fatty acid was 22:6omega-3. The advantages of support-coated open-tubular columns over wall-coated open-tubular columns for the analysis of brain lipid fatty acids are discussed.

Animals↗
PubMed2026

Fatty acids and breast cancer: Epidemiology, subtype-specific metabolism, immune regulation, and clinical translation.

Fatty acids (FAs) are bioactive dietary and metabolic molecules that participate in membrane architecture, energy homeostasis, inflammatory signaling, gene regulation and immune function, all of which intersect with breast cancer (BC) risk, progression and treatment response. In this narrative review we integrate epidemiological, clinical, translational and mechanistic evidence on the role of FAs in BC. Saturated, monounsaturated, trans- and polyunsaturated FAs (PUFAs) are treated as distinct biological exposures rather than interchangeable measures of total fat intake. Similarly, evidence from dietary assessment, circulating biomarkers, erythrocyte membrane composition, adipose tissue stores and tumor lipid signatures is interpreted separately, because each captures exposure and biology at a different level. BC subtypes differ in FA synthesis, uptake, oxidation, storage and remodeling: luminal tumors are frequently linked to hormone-regulated lipogenesis, human epidermal growth factor receptor 2 (HER2)-positive tumors to growth-factor-driven lipid metabolism, and triple-negative tumors to exogenous FA uptake, inflammatory lipid mediators and ferroptosis-related vulnerabilities. FA-derived mediators also shape immune-cell polarization, cytokine signaling and the tumor microenvironment, and dietary FAs may reshape the gut microbiota; the fiber-derived short-chain FAs it produces, distinct from dietary FAs, likewise help regulate immune and inflammatory tone. Clinical data suggest possible roles for fat-quality modification and selected n-3 PUFA interventions, but findings are heterogeneous and not yet sufficient to support routine biomarker-guided precision onco-nutrition. Candidate biomarkers, such as erythrocyte n-6:n-3 composition, require prospective validation before clinical implementation. FA biology thus represents a modifiable but complex axis in BC prevention, tumor biology and supportive care.

Humans↗
PubMed1977

Hydrocarbon gases produced during in vitro peroxidation of polyunsaturated fatty acids and decomposition of preformed hydroperoxides.

Hydrocarbon gases have been used previously as an index of lipid peroxidation in vivo and in vitro. In vitro experiments are reported on the formation of hydrocarbon gases from peroxidizing omega-3 and omega-6 fatty acids. Hydrocarbon gases were not released during a 20-hr peroxidation phase but were released following the decomposition of hydroperoxides by addition of excess ascorbic acid. The major hydrocarbon gas products in iron, copper, or hematin catalyzed peroxidation systems were ethane or ethylene from linolenic acid, and pentane from linoleic acid and arachidonic acid. Calculations of the ratios of hydrocarbon gases formed were based on fatty acid decrease and/or change in diene conjugation and peroxide values. Depending on the fatty acid, catalyst, and calculation basis used, pentane formation was as high as 1.3 mol %, ethane 4.3 mol %, and ethylene 10.6 mol %.

Chemical Phenomena↗