R: CONCISE REVIEWS/HYPOTHESES IN FOOD SCIENCE
Food Security and Cardioprotection: The Polar Lipid Link
Direct inquiries to author Zabetakis (E-mail: email@example.com).
The projected increase in world population and therefore demand for food in the foreseeable future pose some risks on how secure is the food production system today. Millions of people are threatened by malnutrition, cardiovascular diseases (CVDs), diabetes, and obesity. This is a multidimensional challenge: the production of food needs to be increased but also the quality of food needs to be improved so less people suffer from undernourishment and CVDs. This hypothesis paper addresses this problem by critically evaluating recent developments on the role of food components against CVDs, presenting recent insights for assessing the nutritional value of food and suggesting novel approaches toward the sustainable production of food that would, in turn, lead to increased food security. The issue of the sustainability of lipid sources and genetically modified crops is also discussed from a food security point of view.
Today, almost 30 y after the study of the 7 countries (Keys and others 1984), there are still some questions on why some cohorts had coronary heart disease (CHD) at low frequencies but high levels of serum cholesterol. Today, cardiovascular diseases (CVDs), although preventable, remain the top global cause of death and stroke (Roger and others 2012) and the focus of this hypothesis paper is on suggesting ways to increase food functionality against CVDs in a sustainable way. The prevention of CVDs and atherosclerosis, in particular, is a major objective of research in life sciences and the focal point of this article (that is, how specific food components participate in the atherosclerotic mechanism(s) involved and how we can ensure sustainable production of these components).
More specifically, in this hypothesis paper, the issues of food security and cardioprotection are addressed using an interdisciplinary approach. The term “food security” has 2 dimensions: first, it implies that food is available, accessible, and affordable in sufficient quantity and quality. Second, it implies an assurance that this state of affairs can reasonably be expected to continue; or in other words, that it can be sustained (FAO 1996).
The recent developments on the role of food against CVDs, and thus, cardioprotection, are critically evaluated and some novel approaches are suggested toward the sustainable production of food with improved cardioprotective properties. Using a food security approach, some research avenues of improving the quality of produced food against CVDs while assuring that this production is sustainable are proposed.
Atherosclerosis could be defined as a chronic inflammatory condition caused by the deposition of cholesterol and other cellular constituents in the intima of large and medium arteries (Ross 1993) that can lead to an acute clinical event through plaque rapture and thrombosis. In atherosclerosis, platelet activating factor (PAF) (Demopoulos and others 1979) plays a crucial role (Demopoulos and others 2003).
Modern research in life sciences focuses on assessing the biological activities of food components against CVDs and structurally elucidating the food components with such specific cardioprotective properties. This approach should give valuable molecular and biological insights on the role of specific food in preventing atherosclerosis, and thus, providing cardioprotection (Zabetakis and others 2013).
The role of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) against CVDs and other human biological functions has been studied quite extensively in the past (Table 1). According to United Kingdom's Natl. Health System (NHS 2011), consumption of oily fish has been linked to higher levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and a subsequent favorable cardiovascular prognosis.
Table 1. Studies on the impact of omega-3 PUFAs
|Consumption of oily fish||Assessing increased levels of omega-3 PUFAs (EPA and DHA)||Favorable cardiovascular prognosis||He and others 2004; Whelton and others 2004; Konig and others 2005; USDA 2012|
|Consumption of oily fish at least once a week||Assessing the impact of fish intake to CHD and SCD||50% lower incidence of CHD and SCD||Albert and others 1998; He and others 2004; Whelton and others 2004; Konig and others 2005|
|Supplementation of omega-3 PUFAs (EPA and DHA) to adults||Meta-analysis of 20 studies on 68.680 patients||Omega-3 PUFAs were not statistically significantly associated with CVDs||Rizos and others 2012|
|Supplementation of omega-3 PUFAs (EPA and DHA)||Review paper summarizing evidence of clinical and animal studies||Omega-3 PUFAs may be linked to cognitive enhancement but further, better designed studies are needed||Luchtman and Song 2013|
|Supplementation of omega-3 PUFAs (EPA and DHA)||Assessing the risk of developing ovarian cancer||Neither higher intake of these PUFAs nor the ratio of omega-3 to omega-6 PUFAs was associated with this risk||Ibiebele and others 2012|
|Supplementation of omega-3 PUFAs||Influence the production of serum cytokine production and thus depressive symptoms||Omega-3 PUFAs can reduce inflammation in overweight, sedentary middle-aged and older adults||Kielcolt-Glaser and others 2012|
|Omega-3 PUFAs of marine origin||Their role on morbidity of and mortality from CVDs||The impact of omega-3 PUFAs on morbidity of, and mortality from, CVDs is not consistent; further research is needed||Calder and Yaqoob 2012|
Mechanistically, though, it is not clear how omega-3 PUFAs work. Their postulated mechanism in preventing atherosclerosis could be through lowering the levels of triacylglycerol, preventing arrhythmias, decreasing platelet aggregation, or lowering blood pressure. A possible proarrhythmic effect has been reported but there are still some mechanistic uncertainties obstructing in clarifying their beneficial effects and therefore proving or disproving that there are any clear health benefits of dietary intake of omega-3 PUFAs (Saravanan and others 2010).
Fish Omega-3 PUFAs and Food Security
In order to deliver increased food security while providing nutritional food, we need to improve the management of resources (for example, water, fertilisers, wild fish stocks, pesticides, and so on). More specifically, in aquaculture, there is a clear “paradox” that questions how sustainable the production of fish feeds is today: high amounts of fish oil (FO) are required to produce fish feed. The diminishing levels of available wild fish worldwide combined with the fact that aquacultured carnivorous species require large amounts of wild fish in their feed create an emerging necessity to identify and valorize alternative lipid sources with high nutritional value for (aquacultured) fish and thereafter humans. The use of such sources could ensure the sustainable production of fish feeds, and thus aquacultured fish, and subsequently increase aquatic food security and sustainability (Nasopoulou and others 2011; Nasopoulou and Zabetakis 2012).
The genetic modification of plants in order to produce oils with higher levels of either the precursors of omega-3 and omega-6 fatty acids or these fatty acids themselves has also been studied. These modifications have focused on C 18 Δ6-desaturated fatty acids (such as γ-linolenic and stearidonic acid), omega-6-long-chain PUFAs (such as arachidonic acid), and omega-3-long-chain PUFAs (often referred to as “fish oils”) (such as EPA and DHA) and they have been recently revised (Haslam and others 2012). This research approach is based on the assumption that omega-3 and omega-6 PUFAs have considerable nutritional value, and thus efforts have focused on enhancing the bioformation of these molecules in the “designer” oils (after genetic modification).
Undoubtedly, omega-3 PUFAs are required in fish feeds in order to ensure satisfactory fish growth and health. However, because of the somewhat overrated role of omega-3 PUFAs against CVDs (Rizos and others 2012), numerous fish nutritional studies have focused on ensuring that fish contains high levels of these acids; these studies have recently been reviewed (Nasopoulou and Zabetakis 2012). However, under the light of recent evidence that omega PUFAs have less nutritional value than previously considered (see Omega-3 PUFAS section above and Rizos and others 2012), genetic engineering and fish nutritional approaches need to address these 2 food security issues: a) are high levels of omega-3 PUFAs in fish feeds and thus fish needed? and b) are there any other food components with strong activities against CVDs?
Transgenic plants could be beneficial in reducing our dependency on fish oil but environmental, allergenic, toxicological, and molecular studies on their impact to the environment and also humans should also be conducted before rendering them as food secure sources. Recent evidence on the toxic and genotoxic effects of Roundup (Yadav and others 2013) and on the synergistic effects between pesticide stress and predator cues (Janssens and Stoks 2013) has risen some doubts on the sustainability of our approach using transgenic plants and glyphosate-based herbicides. There is a clear need for a deeper assessment of the uptake and effects of glyphosate to the ecosystems in our quest to develop sustainable weed management strategies (Helander and others 2012). In a recent review article, glyphosate has been suggested to suppress cytochrome P450 enzymes and the biosynthesis of amino acid biosynthesis by the gut microbiome; these biochemical actions have been linked to a number of diseases, such as gastrointestinal disorder, obesity, diabetes, CVDs, and cancer (Samsel and Seneff 2013).
On the contrary, there are some promising and mostly sustainable lipid sources: vegetable oils (VOs). The use of VO in animal and fish feeds has some strong sustainable advantages (for example, low water dependency, sustainability, less affected by climate change) (Nasopoulou and Zabetakis 2012). Olive pomace (OP) and olive pomace oil (OPO) are natural by-products of olive oil production, which contain microconstituents with atheroprotective (substances) activity such as PAF inhibitors and phenolic/polyphenolic molecules with antioxidant and other pleiotropic actions (Table 2). Considerable research has been carried out on olive oil by-products and fish with regard to their capacity to prevent atherosclerosis. Recently, the possibility of partially replacing fish oil in gilthead sea bream and sea bass grow-out diet with lipids obtained from OP and OPO has been studied and it was found that the incorporation of OP in fish feed results in an increase of the fish cardioprotective properties (Nasopoulou and others 2011).
Table 2. Studies on the impact of polar lipids.*
|Polar lipids of red and white wine||In vitro study using washed rabbits’ platelets||Inhibition of platelet aggregation||Fragopoulou and others 2002|
|Polar lipids of yoghurt||In vitro study using washed rabbits’ platelets||Inhibition of platelet aggregation||Antonopoulou and others 1996|
|Polar lipids of fish||In vitro study using washed rabbits’ platelets and in vivo study in hyperlipidemic rabbits||Inhibition of platelet aggregation and reduction of the thickness of atherosclerotic lesions in hypercholesterolaemic rabbits||Rementzis and others 1997; Nomikos and others 2006; Nasopoulou and others 2007; Nasopoulou and others 2010|
|Polar lipids of olive oil||In vitro study using washed rabbits’ platelets and in vivo study in hyperlipidemic rabbits||Inhibition of platelet aggregation and reduction of the thickness of atherosclerotic lesions in hypercholesterolaemic rabbits||Karantonis and others 2006a; Tsantila and others 2007|
|Polar lipids of OP||in vivo study in hyperlipidemic rabbits||Reduction of the thickness of atherosclerotic lesions in hypercholesterolaemic rabbits and regression of the already formed atherosclerotic lesions||Tsantila and others 2007; Tsantila and others 2010|
|Traditional Greek Mediterranean meals, rich in lipid PAF inhibitors with in vitro action||Dietary intervention study||Reduction of platelet activity in healthy subjects and in patients suffering from type 2 diabetes mellitus||Antonopoulou and others 2006; Karantonis and others 2006b|
|Mediterranean wild plants||Dietary intervention study in metabolic syndrome patients||Different lipid microconstituents, which act as PAF and/or adenosine diphosphate (ADP) inhibitors in vitro, contribute to the observed variation in their postprandial antiaggregatory action||Fragopoulou and others 2012|
Food Polar Lipid Components: CVDs and Food Security
Lipid microconstituents of specific foods that constitute important ingredients of the Mediterranean diet have been found to exert in vitro important biological activities, namely, anti-inflammatory and antithrombotic activities by inhibiting PAF actions (Zabetakis and others 2013). PAF is the most potent inflammatory lipid mediator, a well-recognized agonist of platelet aggregation that plays a crucial role in atherosclerosis. These lipid microconstituents could thus inhibit the onset of atherosclerosis and the development of CVDs. Such lipids have been found in a wide range of food and all these studies are summarized in Table 2. In all these studies where polar lipids have been used, the polar lipid fraction under study has been isolated using the experimental procedure, as described by Nasopoulou and others (2007).
In order to lower our dependency on FO and thus increase food security, our concept is to enrich the fish feeds with fractions of OP: the novel functional fish (fed with OP) has been found to contain more antiatherogenic compounds thereby protecting the consumer from the development of CVDs (Nasopoulou and others 2011). In the case of OP and OPO, these lipid sources have been used as they have been obtained from a local olive oil plant without any further extraction or fractionation.
By valorizing a by-product of the olive industry (that is, OP) and using it as a raw ingredient for the fish feed industry, the dual benefits of reduced pollution and sustainable productivity could be achieved. The strong cardioprotective activities of the OP-enriched fish, despite its lower levels of omega-3 PUFAs as opposed to the conventional one, show that we may not need to have high levels of PUFAs in food in order to achieve high nutritional value; this result should open new research avenues both for feeds and food production and human nutrition (Nasopoulou and others 2011). Having in mind that food security should be evaluated in conjunction with poverty worldwide, the valorization of low cost by-products rich in polar lipids beneficial against CVDs should provide a new route for sustainable food production.
Evaluation of Current Knowledge and Novel Research Approaches
CVDs are multifactor diseases and a single reduction in low density lipoprotein cholesterol and triacylglycerols can provide neither a satisfactory biochemical/nutritional explanation nor an effective protection of human health. Healthy eating patterns could lower cardiovascular risk factors and they can thus have a beneficial effect against atherosclerosis and CVDs. From this point of view, omega-3 PUFAs that demonstrate their beneficial effect mainly through reducing plasma cholesterol and triacylglycerol levels (Shearer and others 2012) or by inhibiting some of the individual stages of atherogenesis (Weber and others 1991; Mori and others 1997; Sneddon and others 2006) can neither explain satisfactorily the findings of the 7 countries study (Keys and others 1984) nor address the corresponding questions mentioned above. Additionally, supplementing omega-3 PUFAs has not lowered the risk of the development of CVDs (Rizos and others 2012).
It could be thus suggested that from a biochemical point of view, atherosclerosis is not primarily associated to cholesterol and triacylglycerol levels, since in several in vivo studies, using experimental animals, the development of atherosclerotic lesions was not influenced by the levels of cholesterol and triacylglycerol levels but by the action of polar lipids that acted as PAF inhibitors (Karantonis and others 2006a; Tsantila and others 2007, 2010; Nasopoulou and others 2010). Some additional conclusions could be drawn by evaluating studies correlating the structure of compounds (with cardioprotective properties) to their biological activity: dietary phospholipids and glycolipids exhibit beneficial effects against CVDs and these polar lipid classes could be thus studied and further valorized in producing novel functional food, health supplements, and even drugs (Karantonis and others 2003; Küllenberg and others 2012). The evaluation of such studies could help in identifying novel research approaches amalgamating nutritional questions (toward the production of food with higher cardioprotective properties) with sustainability issues (that is, low dependency on fish oil, water, and fertilizers).
Today, the biggest challenge for food scientists, technologists, and nutritionists working toward the secure production of food is to create sustainable procedures that allow current and future generations to have unlimited access to nutritious food. Innovative biochemical, technological, and nutritional approaches are required that combine thoughtful resource management with the ultimate aim being that the final produce (food in agriculture and fish in aquaculture) can satisfy the human population's needs in terms of quantity but also meet the customers’ nutritional requirements. The role of lipids (polar lipids and PUFAs) and their use in feed and food production needs to be readdressed under the light of the most recent epidemiological and nutritional facts. The approach needs to be interdisciplinary: the availability of raw ingredients (for example, fish oil and vegetable oils), the sustainable production of feeds, and the nutritional value of the final food produce need to be taken into account when designing new food policies.
Today, in the developed countries, the problems of overproduction and waste of food, obesity, CVDs, and diabetes occur, while famine and malnutrition exist in the developing countries. Water and soil pollution, climate change, and the subsequent increasing scarcity of drinkable/fit for irrigation purposes water, the rational use of cultivated land and the sustainable use of fertilizers and energy render the secure food production a complex task. Some views on how approaching this task by linking the sustainable food production to cardioprotection are given in this hypothesis paper.