Polyunsaturated fatty acids of the n-6 and n-3 series: effects on postprandial lipid and apolipoprotein levels in healthy men

OBJECTIVE: The present study was carried out to determine effects of test meals of different fatty acid compositions on postprandial lipoprotein and apolipoprotein metabolism. DESIGN: The study was a randomized, single blind design. SETTING: The study was carried out in the Clinical Investigation Unit of the Royal Surrey County Hospital. SUBJECTS: Twelve male normal subjects with an average age of 22.4 +/- 1.4 years (mean +/- SD) were selected from the student population of the University of Surrey; one subject dropped out of the study because he found the test meal unpalatable. INTERVENTIONS: The subjects were given three evening test meals on three separate occasions, in which the oils used were either a mixed oil (rich in saturated fatty acids and approximated the fatty acid intake of the current UK diet), corn oil (rich in n-6 fatty acids), or fish oil (rich in n-3 fatty acids) 40 g of the oil under investigation were incorporated into a rice-based test meal. Triacylglycerol-rich lipoproteins-triacylglycerol (TRL-TAG), TRL-cholesterol (TRL-cholesterol), plasma-TAG, plasma cholesterol (T-C), and serum apolipoprotein A-I and B (apo A-I and B) responses were measured. Postprandial responses were followed for 11 h. RESULTS: Postprandial plasma-TAG responses, calculated as incremental areas under the response curves (IAUC) were significantly reduced following the fish oil meal [365.5 +/- 145.4 mmol/l x min (mean +/- SD)[ compared with the mixed oil meal (552.0 +/- 141.7 mmol/l x min) (P < 0.05) and there was a strong trend towards the same direction in the TRL-TAG responses. In all instances, plasma-and TRL-TAG showed a biphasic response with increased concentrations occurring at 1h and between 3 and 7h postprandially. TRL-cholesterol, T-C, and serum apo A-I and B responses to the three meals were similar. CONCLUSIONS: The findings support the view that fish oils decrease postprandial lipaemia and this may be an important aspect of their beneficial effects in reducing risk of coronary heart disease (CHD). Further work is required to determine the mechanisms responsible for this effect.

Pretranslational regulation of the expression of the lipoprotein lipase (EC 3.1, l.34) gene by dietary fatty acids in the rat

Although there have been a number of studies of effects of diet and hormones on lipoprotein lipase (EC 3.1.1.34; LPL) activity and levels of LPL mRNA (Raynolds et al. 1990), there have been no studies which have investigated effects of different dietary fatty acids on LPL gene expression. In the present study male Wistar Albino rats were pair-fed diets containing 50 g fat/kg of different fatty acid composition for 2 weeks. The diets fed were (1) a mixed oil (450 g saturated fatty acids, 420 g monounsaturated fatty acids, 130 g polyunsaturated fatty acids/kg; n 8), (2) maize oil (n 8), or (3) fish oil (n 8). Animals were killed, RNA was extracted from liver and perirenal and epididymal fat pads, and analysed by ‘Northern methodology’. Samples were hybridized to a human cDNA probe for LPL (Gotoda et al. 1989). Two transcripts were identified in epididymai and perirenal adipose tissue which were approximately 3·7 and 1·7 kb in size. The results suggested that (1) fish oil-fed animals had significantly greater production of LPL mRNA in epididymai adipose tissue compared with maize oil-fed animals (P < 0·05), (2) maize oil-fed animals had significantly greater production of LPL mRNA in perirenal fat compared with the other dietary groups (P < 0·05), (3) expression in the liver was not significant. Rats fed on a fish oil diet had significantly reduced plasma triacylglycerol concentrations compared with the mixed-oil group (P < 0·05), but there were no significant differences in plasma cholesterol. The differences in LPL could not be explained directly by the changes in plasma immunoreactive-insulin and glucose-dependent insulinotrophic polypeptide levels in the three groups.

Effects of n-3 fatty acids on postprandial triacylglycerol and hormone concentrations in normal subjects

The present study reports results from two investigations to determine effects of a 6-week period of moderate n-3 fatty acid supplementation (2.7 g/d) on fasting and on postprandial triacylglycerol and metabolic hormone concentrations in response to standard test meals. In the first study postprandial responses were followed for 210 min after an early morning test meal challenge; in the second study responses to an evening test meal were followed during the evening and overnight for a total period of 12 h. In both studies postprandial triacylglycerol responses to the test meals were significantly reduced after compared with before fish-oil supplementation. In the second study the triacylglycerol peak response seen between 200 and 400 min in subjects studied before supplementation with fish oils was almost completely absent in the same subjects after 6 weeks of n-3 fatty acid supplementation. Analysis of fasting concentrations of metabolites and hormones was carried out on the combined data from the two studies. There were no significant differences in total, low-density-lipoprotein- or high-density-lipoprotein-cholesterol concentrations during fish-oil supplementation, although there was considerable individual variation in cholesterol responses to the supplement. Concentrations of Apo-B and Apo-A1 were unchanged during supplementation with fish oils. Fasting and early morning postprandial GIP concentrations were lower in subjects taking fish oils, possibly due to acute effects of fish-oil capsules taken on the evening before the studies. In both studies fasting insulin and glucose and postprandial insulin concentrations remained unchanged following fish-oil supplementation. The results do not support the view that triacylglycerol-lowering effects of n-3 fatty acids are due to modulation of insulin secretion mediated via the enteroinsular axis. Further studies are required to determine the precise mechanism by which fish oils reduce both fasting and postprandial triacylglycerol concentrations.

Trans fatty acids insulin resistance and diabetes

The possible relationship between consumption of trans fatty acids (TFAs) and risk of insulin resistance or development of diabetes mellitus type II has been considered by a number of human and animal studies over the past decade. This review evaluates the evidence, and concludes that there is limited evidence for a weak association at high TFA intakes, but very little convincing evidence that habitual exposure as part of a standard western diet has a significant contribution to risk of diabetes or insulin resistance. The possibility of increased risk for individuals with particular genotypes (such as the FABP2 Thr54 allele) is of interest, but further work would be required to provide sufficient evidence of any association.

Dietary monounsaturated fatty acids and haemostasis

Diets high in monounsaturated fatty acids (MUFA) are increasingly being recommended as a highly-effective cholesterol-lowering strategy in populations at risk of CHD. However, the need for a re-appraisal of the benefits of diets rich in MUFA became apparent as a result of recent studies showing that meals high in olive oil cause greater postprandial activation of blood coagulation factor VII than meals rich in saturated fatty acids. The present review evaluates the evidence for the effects of MUFA-rich diets on fasting and postprandial measurements of haemostasis, and describes data from a recently-completed long-term controlled dietary intervention study. The data show that a background diet high in MUFA has no adverse effect on fasting haemostatic variables and decreases the postprandial activation of factor VII in response to a standard fat-containing meal. Since the same study also showed a significant reduction in the ex vivo activation of platelets in subjects on the high-MUFA diet, the overall findings suggest that there is no reason for concern regarding adverse haemostatic consequences of high-MUFA diets.

Dietary fatty acids and human health

A considerable amount of evidence has accumulated to support the view that the very long chain omega 3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) have beneficial cardiovascular and anti-inflammatory properties and that levels of their consumption are insufficient in most Western diets. More recently, attention has been given to the possibility that the precursor omega-3 PUFA, alpha linolenic acid (ALNA), may share some of the beneficial actions of EPA/DHA on human health. Further research into the metabolism and physiological actions of ALNA, and comparisons with EPA/DHA, is needed before conclusions regarding the optimal amounts and types of omega-3 PUFA for human health can be defined. Conjugated linoleic acid (CLA), which arises as a metabolic by-product of rumen hydrogenation and which is found in foods of animal origin, has been proposed to possess potent health promoting properties, but much of this research has been conducted in experimental animals. There is an urgent need for complementary studies in human volunteers, to confirm the putative anti-carcinogenic, anti-atherogenic, anti-lipogenic and immuno-suppressive properties of CLA.

Genetic predisposition influences plasma lipids of participants on habitual diet, but not the response to reductions in dietary intake of saturated fatty acids

Objective: SNPs identified from genome wide association studies associate with lipid risk markers of cardiovascular disease. This study investigated whether these SNPs altered the plasma lipid response to diet in the ‘RISCK’ study cohort. Methods: Participants (n = 490) from a dietary intervention to lower saturated fat by replacement with carbohydrate or monounsaturated fat, were genotyped for 39 lipid-associated SNPs. The association of each individual SNP, and of the SNPs combined (using genetic predisposition scores), with plasma lipid concentrations was assessed at baseline, and on change in response to 24 weeks on diets. Results: The associations between SNPs and lipid concentrations were directionally consistent with previous findings. The genetic predisposition scores were associated with higher baseline concentrations of plasma total(P = 0.02) and LDL (P = 0.002) cholesterol, triglycerides (P = 0.001) and apolipoprotein B (P = 0.004), and with lower baseline concentrations of HDL cholesterol (P < 0.001) and apolipoprotein A-I (P < 0.001). None of the SNPs showed significant association with the reduction of plasma lipids in response to the dietary interventions and there was no evidence of diet-gene interactions. Conclusion: Results from this exploratory study have shown that increased genetic predisposition was associated with an unfavourable plasma lipid profile at baseline, but did not influence the improvement in lipid profiles by the low-saturated-fat diets.

Chronic disease risk associated with different dietary saturated fatty acids

This chapter compares the risks of chronic disease, and cardiovascular disease in particular, associated with consumption of different saturated fatty acids. Emphasis is placed on the effects of stearic acid as this has potential to replace trans fatty acids in certain manufactured food products. The chapter first reviews the effects of individual saturated fatty acids on blood lipids, including cholesterol, as these are commonly used as markers of disease risk. It then looks directly at evidence in relation to health outcomes. Finally, recent evidence specifically on the effect of stearic acid relative to other fatty acids, including trans fatty acids, is summarised.

DHA-rich fish oil reverses the detrimental effects of saturated fatty acids on postprandial vascular reactivity

Background: Experimental elevation of nonesterified fatty acids (NEFAs) impairs endothelial function, but the effect of NEFA composition is unknown. Objective: The objective was to test the effect of acute elevation of NEFAs enriched with either saturated fatty acids (SFAs) or SFAs with long-chain (LC) n−3 (omega-3) PUFAs on vascular function measured via flow-mediated dilatation (FMD), laser Doppler iontophoresis (LDI), and digital volume pulse (DVP). Design: In 59 subjects (30 men and 29 women), repeated oral fat feeding of either palm stearin (SFA) or palm stearin with DHA-rich fish oil (SFA + LC n−3 PUFA) was performed on 2 separate occasions with continuous heparin infusion to elevate NEFAs for a duration of 60 to 240 min. Vascular function was measured at baseline and at the end of NEFA elevation; venous blood was collected for measurement of lipids and circulating markers of endothelial function. Results: NEFA elevation during consumption of the SFA-rich drinks was associated with a marked impairment of FMD, whereas consumption of SFAs + LC n−3 PUFAs improved FMD response, with a mean (±SEM) difference of 2.06 ± 0.29% (P < 0.001). Positive correlations were found with percentage weight of LC n−3 PUFAs in circulating NEFAs and change in FMD response [Spearman's rho (rs) = 0.460, P < 0.001]. LDI measures increased during both treatments (P ≤ 0.026), and there was no change in DVP indexes. Conclusions: The composition of NEFAs can acutely affect FMD. The beneficial effect of LC n−3 PUFAs on postprandial vascular function warrants further investigation but may be mediated by nitric oxide–independent mechanisms. This trial is registered at clinicaltrials.gov as NCT01351324.