Polyunsaturated Fatty Acids: Health Impacts - Journal Repository

European Journal of Nutrition & Food Safety 6(3): 111-131, 2016, Article no.EJNFS.2016.016 ISSN: 2347-5641

SCIENCEDOMAIN international www.sciencedomain.org

Polyunsaturated Fatty Acids: Health Impacts Mahyara Markievicz Mancio Kus-Yamashita1*, Jorge Mancini Filho2, Brent Mcdonald3, Graziela Ravacci4, Marcelo M. Rogero5, Raul Dias Santos4, Dan Waitzberg4, María Soledad Reyes6, Shlomo Yehuda7, Juergen Gierke8, Hector Cori9, Tatiana Pires10 and Franco Maria Lajolo2 1

Adolfo Lutz Institute, Brazil. Faculty of Sciences Pharmaceutics, University of São Paulo, Brazil. 3 Nutritional Lipids, DSM, Canada. 4 Faculty of Medicine, University of São Paulo, Brazil. 5 Faculty of Public Health, University of São Paulo, Brazil. 6 University of Chile, Chile. 7 Bar Ilan University, Israel. 8 Human Nutrition, BASF, Germany. 9 Department of Nutrition Science, Latin America at DSM Nutritional Products, Chile. 10 Regulatory Affairs at Herbalife, Brazil. 2

Authors’ contributions This work was carried out in collaboration between all authors. All authors read and approved the final manuscript. Article Information DOI: 10.9734/EJNFS/2016/23018

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Grey Literature

Received 10 November 2015 Accepted 23rd June 2016 Published 12th July 2016

ABSTRACT In order to encourage discussions on "polyunsaturated fatty acids" and health, the Brazilian branch of the International Life Sciences Institute (ILSI) promoted the XII International Workshop Series on Foods with Functional Properties and/or Health Claims (28-29 November 2013) which consolidated knowledge, presented scientific advances, and promoted exchange of experiences on "Polyunsaturated Fatty Acids: Health Impacts". Various topics were addressed at this meeting including: nutritional needs and consumption issues; impact on chronic diseases: cardiovascular diseases and cancer; influence on gene expression; immunological system and inflammation; sources of these fatty acids; benefits during pregnancy and childhood; cost and benefit of supplementation; and regulations (legislation). In general terms, the event presented evidence of the benefit of polyunsaturated fatty acids on cardiovascular diseases, pregnancy, breastfeeding, and infant development, as well as possible influence on gene expression, contributing to their relationship with the immunological system and, therefore, inflammatory processes. The _____________________________________________________________________________________________________ *Corresponding author: Email: [email protected];

Kus-Yamashita et al.; EJNFS, 6(3): 111-131, 2016; Article no.EJNFS.2016.016

recommendations of consumption and/or supplementation with these fatty acids are specific to particular groups and still require further studies. With respect to regulations in terms of legislation, each country/authority recommends different content properties and/or health claims. The event generated prospects for research fields, development, and regulation of polyunsaturated fatty acids in the scientific community and industries. Keywords: Polyunsaturated fatty acids; docosahexaenoic acid; arachidonic acid; eicosapentaenoic acid; benefits of health.

1. INTRODUCTION Polyunsaturated fatty acids (PUFA) contain more than one unsaturation in their molecules and due to this feature they have the potential to be beneficial to health. The most studied fatty acids are the essential, namely: linoleic acid (LA) and α-linolenic acid (ALA); and those considered long-chain fatty acids: eicosapentaenoic acid (EPA); docosahexaenoic acid (DHA); and arachidonic acid (AA), which can be divided into two classes, omega-3 (w-3, n-3): ALA, DHA, and EPA, and omega-6 (w-6, n-6): LA and AA. The "XII International Workshop Series on Foods with Functional Properties and/or Health Claims for Polyunsaturated Fatty Acids: Impacts on Health" held in São Paulo, Brazil, on 28 and 29 November 2013, addressed the effect of these fatty acids on health, since there may be controversial evidence regarding some topics and scientific discussions of great value. The goal of the event was to consolidate the knowledge and scientific advances in recent studies addressing the relationship between PUFAs and health. The topics presented were: (a) Overview: what they are and how they function in the body; (b) nutritional needs, dietary reference intakes (DRI) and consumption; (c) natural/industrial sources; (d) gene expression and nutrigenomics; (e) cardiovascular diseases and diabetes; (f) cancer; (g) importance and benefits associated with DHA in pregnancy and childhood; (h) balance between omega-3/omega6 and aging; (i) effects of omega-3 fatty acids (EPA and DHA) on inflammation biomarkers; (j) cost and benefit of interventions with omega-3; (k) regulatory status in Brazil and in the world. Representatives of academia, industry and regulatory agencies, and experts from Brazil, Chile, Israel, the United States and the United Kingdom participated in the event. The workshop was coordinated by Professor Franco Lajolo from the University of São Paulo, São Paulo, Brazil.

2. OVERVIEW Fatty acids participate in various processes in the body, such as the characterization of lipids and

plasma levels. They have action on inflammatory processes, the hepatic lipid metabolism, and adipose tissue. PUFAs have their importance related to their melting point and chemical structure (carbon chain folding, location of methylene carbon, and number of double bonds), and may exert different functions in the body [1,2]. In the 1900s (industrial revolution), there was increase in the consumption of fat and oils, which are essentially composed of saturated fatty acids (SFA) and PUFAs of the omega-6 series. On the other hand, there was a decrease in the consumption of PUFAs of the omega-3 series. This imbalance was associated with circulatory problems [3,4]. Omega-3 and omega-6 PUFAs are essential for the body and compete for desaturase and elongase enzymes originating differentiated series of eicosanoids (prostacyclin, thromboxane, and leukotrienes), which will have specific functions in each tissue type, namely: production and inhibition of platelet aggregation; anti-inflammatory, chemotactic, and vasodilator effect; and uptake of cholesterol from the tissues. It is worth mentioning that polyunsaturated and trans fatty acids may interfere in the mechanism of these enzymes and inactivate the eicosanoids. The vast majority of the eicosanoids derived from omega-6 fatty acids have proinflammatory and proarrhythmic effects and induce fever, pain, bronchoconstriction, proaggregating effect, and vasoconstriction. Eicosanoids derived from omega-3 fatty acids have anti-inflammatory, antiarrhythmic and anti-aggregation effects, and decreased oxidative stress [5,6,7]. The main PUFAs representative of the omega-3 fatty acids are: ALA; EPA; and DHA, and of the omega-6 fatty acids are: LA and AA [4,8]. Omega-3 PUFAs have proven to be beneficial for health. In cardiovascular cases, they inhibit platelet aggregation (anti-thrombotic effect), stimulate vessel dilation, have anti-inflammatory effect, reduce chemotaxis of leukocytes, inhibit

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Table 1. Recommended values for adults (aged >18 years) according to the Food and Agriculture Organization, 2011 [15]

the synthesis of triacylglycerides in the liver by inhibiting the secretion of smaller VLDL particles which become larger LDL particles (atherogenic), stimulate the reverse transport of this cholesterol favouring its capture to the liver and its elimination through the bile duct [9]. These fatty acids have great significance in brain development, especially during pregnancy and early life, and they are incorporated into the retina. DHA has active participation in the following brain processes: synaptogenesis; neuronal migration; and neurogenesis. Its importance is related to fluidity in the cell membranes of the central nervous tissue and rods and cones in the retina. It increases light sensitivity of photoreceptors; facilitates the movement of neurons from the ventricular to the peripheral zone (neurogenesis), stimulates preand postnatal development of glia cells, and stimulates synaptogenesis in preformed neurons [10].

3. NUTRITIONAL REFERENCE CONSUMPTION SURVEY)

NEEDS, DIETARY INTAKES, AND (FAMILY BUDGET

The increased consumption of saturated fats is associated with cardiovascular diseases, which are the leading cause of death in the world (30% of worldwide mortality) [11]. The nutritional recommendations including PUFAs have been advocated by many guidelines, such as Dietary Guidelines for Americans, [12] American Heart Association, [13] and Brazilian Society of Cardiology [14]. These recommendations are based on epidemiological evidence mainly related to cardiovascular diseases. According to the Dietary Guidelines for Americans, [12] consumption of 200 g of fish per week—i.e., about 250 mg of EPA + DHA—shows moderate evidence of cardiovascular disease prevention. According to the recommendations of the Food and Agriculture Organization, [15] there is compelling evidence that saturated fatty acids lead to increased LDL cholesterol and the total cholesterol/HDL cholesterol ratio compared with monounsaturated fatty acids (MUFA) or cisPUFAs. Still, saturated fatty acids increase LDL cholesterol; however, they have no effect on the total cholesterol/HDL cholesterol ratio compared with carbohydrates [15].

Type of fat Total fat (% of calories) Saturated fat (% of calories) Monounsaturated fat Polyunsaturated fat (% of calories) n-6 polyunsaturated fat (% of calories) n-3 polyunsaturated fat (% of calories) Trans fat (% of calories)

Recommendation 20 - 35% 7-10% *

Per difference 6 -11% 2.5 - 9% 0.5 - 2% 14 g ALA a day reduces inflammatory markers. ALA supplementation decreases the levels of inflammatory markers in dyslipidemic individuals. The consumption of food rich in ALA can reduce the risk of cardiovascular diseases. There is no evidence that ALA supplementation reduces cardiovascular risk. The consumption of omega-3 PUFAs from vegetable origin as part of a healthy diet can be recommended to reduce cardiovascular risk, although the real benefit of this recommendation is controversial and the evidence is not conclusive. Clinical studies have shown that supplementation with 2 to 4 g of EPA/DHA per day can decrease triglycerides levels by up to 25 to 30%; however, it can increase LDL cholesterol by up to 10%. A meta-analysis of 36 randomized clinical trials with fish oil supplementation (average dose of 3.7 g/day) showed reduction of 3.5 mmHg in systolic blood pressure and 2.4 mmHg in diastolic blood pressure. Reduction of adrenergic tone and systemic vascular resistance are proposed mechanisms. In some cross-sectional and cohort studies, dietary consumption of marine omega-3 PUFAs has been associated with lower plasma levels of inflammatory markers. Supplementation with marine omega-3 PUFAs (2-4 g/day) should be recommended for severe hypertriglyceridemia (>500 mg/dL) with risk of pancreatitis refractory to nonpharmacological measures and drug treatments.

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•

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At least two fish meals per week, as part of a healthy diet, should be recommended to decrease cardiovascular risk. This recommendation is particularly targeted at high-risk individuals, such as those who have already suffered myocardial infarction. Supplementation with marine omega-3 PUFAs (about 1 g/day) can be recommended to reduce cardiovascular risk in low- to moderate-risk individuals who do not consume two fish meals per week; although the real benefit of this recommendation is controversial. Supplementation with marine omega-3 PUFAs (about 1 g/day) may be recommended to reduce cardiovascular risk in high-risk individuals, such as survivors of myocardial infarction or systolic failure; although the real benefit of this recommendation is controversial. The benefit seems to be minor or null when the patients receive optimized treatment— according to current recommendations— and have their risk factors well controlled.

Fatty acid consumption in Brazil is similar to the Mediterranean-style diet, due to the consumption of soya oil and grains. The 2008-2009 Family Budget Survey [16] does not specify the consumption of fatty acids, but only food expenses. The 2002-2003 Family Budget Survey [17] found that the consumption of oils and fats had reduced in comparison to 2008-2009, [16] the main being soya and olive oils. In the case of olive oil, consumption increases according to the increase of family income. It was also found increased consumption of meat and animal food products [16,17].

4. NATURAL/INDUSTRIAL OMEGA-3

SOURCES

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Due to scientific evidence of the benefits of omega-3 PUFAs—brain and visual development in children, immunity, eye health, heart health, cognitive development, inflammation, and cancer—consumption can achieve around 1.3 3 million m /year, considering the current world population and the recommendation for supplementation between 250 and 500 mg/day [18,20]. Marine microorganisms are the main source for consumption and production of encapsulated fish oil. Fish consume these microorganisms and accumulate fatty acids. On the other hand, these

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microorganisms can be genetically modified with plant genes, fungi, or animals and they produce oil. Fish can be consumed or have their oil extracted. Oils are encapsulated and can be consumed or used for food and drinks enrichment [2,1]. The current scenario demonstrates that fish oil production is declining and other sources are being used in addition to fish, such as algae and microorganisms. Approximately one third of fish products are oil and the species used are mainly anchovy and tuna. The difficulty in using these sources is due to different concentrations of omega-3 PUFAs in each fish species, as well as their individual amount [19,20]. According to the predictions for mass supplementation, there will be a difference of 3 0.77 million m /year that should be provided. The 3 production only reaches 533,000 m /year and the demand of the population would be 1.3 million 3 m /year. Currently, consumption is only 200,000 m3/year and this number has been increasing every year [19,21]. Other possible sources are being commercially evaluated for extraction of oil rich in omega-3 PUFAs from fish and shrimp. Other sources, such as zooplankton, algae, fungi, and plants genetically modified are being developed. Each source has its own peculiarity: fish is the largest source with variety of quality and quantity. As a result of new emerging technologies for oil extraction, fatty acids are found in different forms (phospholipids, triacylglycerides), with highest concentration of >90%, and have the ability to ensure the nutritional demand; shrimp: consumed in the diet has high levels of DHA and omega-3 PUFAs found in various forms and concentrations; however, the demand in the market is relatively small; zooplankton: commonly known as "krill"—successful in the United States and Australia—is original from Antarctica and serves as food for whales. It is particularly found in the form of phospholipids and is the best bioavailable source with EPA/DHA levels of