A restricted cubic spline approach to assess the association between high fat fish intake and red blood cell EPA + DHA content
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.
References (58)
Fish and n-3 fatty acids for the prevention of fatal coronary heart disease and sudden cardiac death
Am J Clin Nutr
(2008 Jun)- et al.
Fish consumption and depression: the Northern Finland 1966 birth cohort study
J Affect Disord
(2004 Nov 1) Biomarkers of fat and fatty acid intake
J Nutr
(2003 Mar)- et al.
The omega-3 index: a new risk factor for death from coronary heart disease?
Prev Med
(2004 Jul) - et al.
Comparison of the effects of fish and fish-oil capsules on the n-3 fatty acid content of blood cells and plasma phospholipids
Am J Clin Nutr
(2007 Dec) - et al.
Very-long-chain n-3 fatty acids as biomarkers for intake of fish and n-3 fatty acid concentrates
Am J Clin Nutr
(1996 Sep) - et al.
Lipid and fatty acid composition of fish and seafood consumed in France: CALIPSO study
J Food Compost Anal
(2008) - et al.
Dietary exposure and biomarkers of arsenic in consumers of fish and shellfish from France
Sci Total Environ
(2009 Mar 1) - et al.
Methylmercury exposure assessment using dietary and biomarker data among frequent seafood consumers in France CALIPSO study
Environ Res
(2008 May) - et al.
Studies on the extraction of phospholipids from erythrocyte membranes in the rat
Clin Chim Acta
(1993 Oct 15)
Dietary fish intake and plasma phospholipid n-3 polyunsaturated fatty acid concentrations in men and women in the European Prospective Investigation into Cancer-Norfolk United Kingdom cohort
Am J Clin Nutr
Fish intake and serum fatty acid profiles from freshwater fish
Am J Clin Nutr
Comparison between plasma and erythrocyte fatty acid content as biomarkers of fatty acid intake in US women
Am J Clin Nutr
Smoking, gender, and dietary influences on erythrocyte essential fatty acid composition among patients with schizophrenia or schizoaffective disorder
Biol Psychiatry
EPA and DHA in blood cell membranes from acute coronary syndrome patients and controls
Atherosclerosis
Red blood cell docosahexaenoic acid and eicosapentaenoic acid concentrations are positively associated with socioeconomic status in patients with established coronary artery disease: data from the Heart and Soul Study
J Nutr
n-3 fatty acids and serum lipoproteins: human studies
Am J Clin Nutr
Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: an 18-month controlled study
J Lipid Res
Inclusion of 10% fish oil in mixed medium-chain triacylglycerol-long-chain triacylglycerol emulsions increases plasma triacylglycerol clearance and induces rapid eicosapentaenoic acid (20:5n-3) incorporation into blood cell phospholipids
Am J Clin Nutr
Persistent changes in the fatty acid composition of erythrocyte membranes after moderate intake of n-3 polyunsaturated fatty acids: study design implications
Am J Clin Nutr
Erythrocyte eicosapentaenoic acid versus docosahexaenoic acid as a marker for fish and fish oil consumption
Prostaglandins Leukot Essent Fatty Acids
Omega-3 fatty acid containing diets decrease plasma triglyceride concentrations in mice by reducing endogenous triglyceride synthesis and enhancing the blood clearance of triglyceride-rich particles
Clin Nutr
Protective effect of zinc supplementation on blood antioxidant defense system in rats exposed to cadmium
J Trace Elem Med Biol
Dietary factors protective against breast cancer in Japanese premenopausal and postmenopausal women
Int J Cancer
Lipids as determinants of cell function and human health. Proceedings of the 6th congress of the International Society for the Study of Fatty Acids and Lipids (ISSFAL). Brighton, United Kingdom, 26 June–1 July 2004
Lipids
Avis de l’Agence française de sécurité sanitaire des aliments relatif à l’actualisation des apports nutritionnels conseillés pour les acides gras
n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits
Am J Clin Nutr
Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee
Circulation
Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease
Circulation
Cited by (9)
Low long chain omega-3 fatty acid status in middle-aged women
2017, Prostaglandins Leukotrienes and Essential Fatty AcidsCitation Excerpt :In previous studies in Germany, where the LC n-3 PUFA status in the erythrocyte membrane was measured in both genders, a low omega-3 index (>4−6%) was prevalent [17,25,27,28]. Thus, our results are in line with these previously published results and with the findings of other European countries [25], such as France [29]. In contrast, extrapolated data showed moderate omega-3 index values (>6−8%) in other European countries, such as Sweden and Finland, and high omega-3 values (>8%) in Denmark and Norway [25].
Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults
2016, Progress in Lipid ResearchCitation Excerpt :Although some studies had multiple reasons for exclusion, each study was classified into only one exclusion category. A total of 298 studies were included [5,6,14,16–310] and a total of 626 studies were excluded (Supplementary Table S2). Extracted data was sorted into categories of blood fraction analyzed and included plasma total lipids, plasma phospholipid, erythrocytes and whole blood.
Antioxidant-rich phytochemicals in miracle berry (Synsepalum dulcificum) and antioxidant activity of its extracts
2014, Food ChemistryCitation Excerpt :Therefore, the antioxidant capability of miracle berry was superior to many other recognised antioxidant-rich fruits in scavenging free radicals. Fish oil is abundant in EPA (C20:5) and DHA (C22:6) fatty acids, which are two long chain unsaturated omega-3 fatty acids and have been recommended for promoting cardiovascular health (Sirot et al., 2012). However, due to the high degree of unsaturation, the incorporation of EPA and DHA in food could increase the tendency for lipid oxidation.
Relationship between diet and plasma long-chain n-3 PUFAs in older people: Impact of apolipoprotein e genotype
2013, Journal of Lipid ResearchCitation Excerpt :However, that sample was very small (n = 25) and their fish consumption was not reported. Our results do not compare directly with those of another French study (45) which was conducted among 382 adult high seafood consumers who had a very high intake of EPA and DHA combined (1,220 mg/day on average), which is not representative of the general population. In contrast to the present study, the authors found that at intakes >200 g per week of EPA+DHA, i.e., 28.6 g/day, their concentration in erythrocyte membranes no longer increased suggesting a ceiling effect in the relationship.
Seaweeds as a functional ingredient for a healthy diet
2020, Marine DrugsUS family physicians overestimate personal ω-3 fatty acid biomarker status: Associations with fatty fish and ω-3 supplement intake
2018, Current Developments in Nutrition