A restricted cubic spline approach to assess the association between high fat fish intake and red blood cell EPA + DHA content

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Abstract

Background and aims

Fish, especially fatty fish, are the main contributor to eicosapentaenoic (EPA) and docosahexaenoic (DHA) intake. EPA and DHA concentrations in red blood cells (RBC) has been proposed as a cardiovascular risk factor, with <4% and >8% associated with the lowest and greatest protection, respectively. The relationship between high fat fish (HFF) intake and RBC EPA + DHA content has been little investigated on a wide range of fish intake, and may be non-linear. We aimed to study the shape of this relationship among high seafood consumers.

Methods and results

Seafood consumption records and blood were collected from 384 French heavy seafood consumers and EPA and DHA were measured in RBC. A multivariate linear regression was performed using restricted cubic splines to consider potential non-linear associations. Thirty-six percent of subjects had an RBC EPA + DHA content lower than 4% and only 5% exceeded 8%. HFF consumption was significantly associated with RBC EPA + DHA content (P [overall association] = 0.021) adjusted for sex, tobacco status, study area, socioeconomic status, age, alcohol, other seafood, meat, and meat product intakes. This relationship was non-linear: for intakes higher than 200 g/wk, EPA + DHA content tended to stagnate. Tobacco status and fish contaminants were negatively associated with RBC EPA + DHA content.

Conclusion

Because of the saturation for high intakes, and accounting for the concern with exposure to trace element contaminants, intake not exceeding 200 g should be considered.

Introduction

Fatty fish (FF) intake may reduce the risk of coronary heart diseases (CHD), sudden cardiac death [1], some types of cancer [2], and depression [3]. The strength of the association and potential underlying mechanisms are still under debate. However, the protective effect of FF intake has mostly been ascribed to the intake of the n-3 long-chain polyunsaturated fatty acids (LC-PUFA) eicosapentaenoic (EPA) and docosahexaenoic (DHA).

Accordingly, national and international organizations have recommended intakes of fish and/or EPA + DHA, mainly based on cardiovascular effects. For instance the American Heart Association (AHA), the International Society for the Study of Fatty Acids and Lipids (ISSFAL) [4], and the French Food Safety Agency [5], agree on ∼500 mg EPA + DHA/d as a reference intake for cardiovascular health for the general population [6].

As regards fish, the UK Committee on Medical Aspects of Food Policy, the French National Nutrition and Health Program, the AHA, and the Health Council of the Netherlands have recommended consuming fish twice a week. More quantitatively, fish intake recommendation has been set at 8 ounces (∼227 g), with half or more from FF, or mostly from fish rich in EPA + DHA [7], [8].

EPA + DHA content of red blood cell (RBC) membranes is one of the best non-invasive biomarkers of the intakes [9]. Also known as “the omega-3 index”, it has been proposed as a risk factor for death from CHD, especially sudden cardiac death [10], [11]. A content of 8%, or more, provides the greatest protection, whereas a content lower than 4% has been associated with the greatest risk [10], [11].

The consumption of FF or fish-oil capsules [12] or n-3 LC-PUFA enriched foods [13], increases the RBC n-3 FA content. In 20 subjects with low baseline RBC n-3 FA contents, fish-oil supplementation (2.1 g/d EPA + DHA), increased RBC DHA and EPA, their content nearly reaching the 8% threshold [14]. Because RBC EPA + DHA reflects dietary intake, we aimed to investigate this relationship on a wide range of intakes, and finally assess what level of high fat fish (HFF) consumption enables to reach the 8% threshold.

To maximize the health benefit of EPA + DHA, the characterization of the relationship between HFF intakes and biomarkers is required. To our knowledge, studies on RBC n-3 FA and fish consumption were generally based on linear relationships [15], [16], [17], [18], [19]. However, a polynomial third-degree relationship between supplemented intake and plasma DHA content has been shown [20]. Therefore, we hypothesized that such a non-linear relationship may exist between HFF intakes and RBC EPA + DHA in heavy fish-consumers. The aim was to test this hypothesis and tentatively set the optimal intake level, among frequent seafood consumers.

Section snippets

Subjects

The Calipso study was conducted in 2004–2005 in French coastal areas, centered on four cities: Le Havre (Channel), Lorient (North Atlantic Ocean), La Rochelle (North Atlantic Ocean), and Toulon (Mediterranean Sea). Permanent residents (18–81) consuming seafood at least twice a week were recruited [21]. Subjects treated for diabetes, renal disease, or arterial hypertension, were excluded. The study aimed at assessing the EPA + DHA intake and contaminant exposure (including methylmercury (MeHg),

Population characteristics

Subjects were mostly female (74%). Mean (±standard deviation) age was 46 ± 14 y; 7% were obese (n = 27, BMI>30 kg/m2), 24% overweight (n = 93, BMI between 25 and 30 kg/m2), and 69% were never or ex-smokers (n = 264). Two individuals did not consume HFF, but other fishes. On average, 63% of other seafood consumed by the population were lean fish.

Fatty acid intakes

Mean total fish (P < 0.001) and other seafood (P < 0.001) intakes increased ∼8-fold from the first to the fourth quartile of HFF consumption (Table 1).

Discussion

Our main finding is that the optimal HFF intake in the studied population is ∼200 g since RBC EPA + DHA reached a plateau thereafter.

The proportions of individuals exceeding the 8% or 4% RBC EPA + DHA content (5% and 64%, respectively) were close to those observed in an American study [19] on the impact of frequent fish intake on RBC FA content (9% and 56%, respectively).

However, our results should be compared to others with caution. Most studies on fish consumption and biomarkers considered

Conclusion

Based on restricted cubic spline modeling, this work suggests a non-linear relationship between HFF intake and RBC EPA + DHA content in frequent fish-consumers. HFF intake increases RBC EPA + DHA until ∼200 g HFF/wk, and plateaus thereafter. However, this 200 g value needs to be confirmed in other populations. Intakes higher than 200 g seem not to be warranted, and may largely contribute to increase exposure to contaminants, including trace elements but also dioxins or polychlorobiphenyls. The

Conflict of interest

None of the authors had a personal or financial conflict of interest.

Acknowledgement

This study was supported by grants from the French Ministry of Agriculture and Fisheries.

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