Fish oil, insulin sensitivity, insulin secretion and glucose tolerance in healthy people: Is there any effect of fish oil supplementation in relation to the type of background diet and habitual dietary intake of n-6 and n-3 fatty acids?

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Abstract

Aim

To evaluate whether a moderate supplementation of long-chain n-3 fatty acids is able to modulate insulin sensitivity, insulin secretion, β-cell function and glucose tolerance in healthy individuals consuming a diet rich in either saturated or monounsaturated fat, also in relation to their habitual dietary intake of n-6 and n-3 fatty acid.

Methods and results

One hundred and sixty-two healthy individuals were randomly assigned to follow either one of two isoenergetic diets for 3 months, one rich in monounsaturated fats and the other rich in saturated fats. Within each group there was a second randomisation to fish oil (n-3 fatty acids 3.6 g/day) or placebo. At the beginning and at the end of the treatment periods insulin sensitivity (SI), first phase insulin response (FPIR) and glucose tolerance (KG-value) were evaluated by the intravenous glucose tolerance test (IVGTT).

Fish oil did not have any effect on SI, FPIR, KG-value and disposition index in either diet. Even after dividing subjects according to the median value of n-6/n-3 ratio of serum phospholipids at baseline, there was no change in SI (Δ SI 0.42 ± 0.34 on fish oil vs 0.14 ± 0.23 on placebo for those with n-6/n-3 <4.85; −1.03 ± 0.47 on fish oil vs −0.27 ± 0.32 on placebo for those with n-6/n-3 >4.85) (M ± SE), FPIR (Δ FPIR 135.9 ± 78.9 vs 157.2 ± 157.5 pmol/L; 38.8 ± 181.7 vs 357.1 ± 181.7 pmol/L), KG-value (Δ KG 0.14 ± 0.15 vs 0.12 ± 0.11; −0.32 ± 0.16 vs 0.15 ± 0.15) or disposition index (Δ disposition index 1465.4 ± 830.4 vs 953.8 ± 690.0; −1641.6 ± 1034.3 vs 446.6 ± 905.1). Considering the 75th percentile of n-6/n-3 ratio (5.82) the results on insulin sensitivity, insulin secretion and disposition index were confirmed, while, in this more extreme situation, n-3 fatty acid supplementation induced a significant deterioration of KG-value (p = 0.02).

Conclusions

In healthy individuals a moderate supplementation of fish oil does not affect insulin sensitivity, insulin secretion, β-cell function or glucose tolerance. The same is true even when the habitual dietary intake of n-6 and n-3 fatty acids is taken into account.

Introduction

The beneficial effects of both short and long-chain n-3 fatty acids on insulin action in animals are well documented [1], [2], [3], [4]. In rats, for instance, n-3 fatty acids are able to completely revert the insulin resistance induced by a high saturated fat diet [5]. Much less consistent are the data in humans. The majority of intervention studies described in the literature – most of which are dated and not perfectly controlled – show no effect on insulin sensitivity [6], [7], [8], [9], [10], [11]. On the other hand, prospective studies have shown an inverse association between intake of n-3 fatty acids and incidence of type 2 diabetes, again suggesting a possible role of these fatty acids in modulating insulin action [12], [13], [14]. In an attempt to explain the lack of effects of fish oil intervention studies in humans, many possibilities have been considered: 1) fish oil may be able to modulate insulin action more than revert an established insulin resistance; therefore the beneficial effects may be evident in healthy people and not in diabetic patients – in whom studies have mostly been performed; 2) fish oil may be more active as part of a diet rich in saturated fat, completely or partially reverting the negative effects of the fatty acids on insulin action, as happens in animals [5]; and 3) a different habitual intake of n-6 and n-3 polyunsaturated fatty acids might condition the effects of fish oil on insulin sensitivity through different possible mechanisms, such as competition for the same enzymes and/or transcriptional factors, production of eicosanoids with different anti-inflammatory potency and different membrane fluidity [15], [16], [17].

On the other hand, the possible effects of long-chain n-3 fatty acids on insulin secretion and β-cell function represent a more neglected area of research, although they may account for the relationship between these fatty acids and the incidence of type 2 diabetes. While animal studies have shown that both the length and the degree of unsaturation of fatty acids have different effects on insulin secretion [18], [19] and that acute supplementation with long-chain n-3 reverts the insulin hypersecretion induced by saturated fatty acids [20], very little is known about this aspect in humans.

Therefore, the aim of our study was to evaluate a large sample of healthy individuals in a study of adequate duration, to ascertain whether a moderate supplementation of long-chain n-3 fatty acids is able to modulate: 1) insulin sensitivity, insulin secretion and β-cell function with a diet rich in either saturated or monounsaturated fat; and 2) insulin sensitivity, insulin secretion and β-cell function in relation to the n-6/n-3 fatty acid ratio of the habitual diet.

Furthermore, since some old studies reported a negative effect of high-dose fish oil supplementation on glucose tolerance and glucose control in diabetic patients [21], [22], [23], we also evaluated the effects of fish oil on glucose tolerance in relation to different types of diet (SAFA vs MUFA) and to the different n-6 and n-3 habitual intake in our population of healthy individuals.

Section snippets

Study design

The design of the study has previously been reported in detail [24], [25]. It was a multicentre controlled dietary study performed in five different centres (Kuopio, Aarhus, Naples, Wollongong and Uppsala) with a duration of 90 days. The participants were randomised to a diet containing a high proportion of saturated fatty acids (SAFA) diet or a monounsaturated fatty acid (MUFA) diet. Within the two groups there was a second randomisation allocating the participants to supplementation with

Results

The baseline parameters of subjects randomised to the four intervention groups were on average similar (Table 1). In particular, age, BMI, baseline insulin sensitivity index (SI), FPIR, disposition index and KG were similar in the n-3 fatty acids supplementation and placebo groups with both the SAFA and MUFA diets. All subjects completed the study. Compliance to dietary intervention was satisfactory, as described previously [24], [25]. Compliance to n-3 intake was evaluated by the analysis of

Discussion

This study shows very clearly that a moderate supplementation of fish oil has no effect on insulin action, insulin secretion or β-cell function in healthy volunteers, independent of the fatty acid composition of the diet (rich in saturated or monounsaturated fat) and the serum phospholipids n-6/n-3 ratio – taken as an index of the habitual dietary intake of n-6 and n-3 fatty acids.

The results on insulin action are relevant because, given the adequate size and duration of the study, they show

Acknowledgements

Food for the study was kindly supplied by MD Foods, Denmark; Carlshamns mejeri AB, Svenka Nestlé AB and Van der Bergh Foods AB, Sweden; Eridania and Beghin-Say, Belgium and Meadow Lea Foods, Australia. Pikasol capsules were supplied by Lube A/S, Denmark. The study was supported by the Swedish Council for Forestry and Agricultural Research, Health Research Council Academy of Finland, The Danish Medical Research Council, Helga and Peter Kornings Foundation and The International Olive Oil Council.

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