Authored by Dr.Dr.Ir. Vincent van Ginneken*
Abstract
There are currently two main directions with regard to nutritional supplements with PUFAs. The first research school recommends enriching the diet with the essential fatty acid (EFA) obtained from vegetable sources, the C18 lipid omega-3 molecule α-linolenic acid and then via the elongase/ desaturase activity naturally in omega-3 Eicosapentaenoic acid (EPA) and omega-3 Docosahexaenoic acid (DHA). The second research school says that the diet should be immediately enriched with EPA and DHA, obtained directly from fish oil. Here we want to investigate the controversies about the possible use of these FAs as preventive / curative instruments against the development of CVDs to combat the current pandemic of heart disease through nutritional intervention. We calculated from the [product] / [precursor] ration in the Cholesteryl (ChE) fraction the enzymatic activity of elongase/desaturase activity of the heart muscle of a juvenile high-fat-induced C57bl6 mouse model, which model we previously used in CVD studies. The main conclusion is that the omega-3 route from α- linolenic acid to EPA and DHA does not exist enzymatically in the heart and that the best strategy for preventing CVDs is direct diet enrichment with EPA and DHA. Because CVDs are currently the number one cause of death in the US and the WHO predicts that especially in the coming decades developing countries will be affected by this pandemic of CVDs. Research should focus on the underlying mechanism of omega-3 PUFA protection.
Keywords: Cardiovascular diseases; Heart; Metabolic syndrome; LC-MS; Lipidomics; Essential fatty acid (EFA); α-linolenic acid; Elongase/ desaturase activity; Eicosapentaenoic acid (EPA); Docosahexaenoic acid (DHA); Fish oil; C57bl6 mouse model
Introduction
Very recently, in the Lancet of October 7, 2019 [1], the WHO published projections about the pandemic of cardiovascular disease (CVDs) that currently plague the world population, resulting in 2030 with 22.2 million deaths a year [2]. In the past three decades, numerous epidemiological and observational studies have been published on the prevention of CVD and the benefits of diet enrichment with polyunsaturated fatty acids (PUFAs) [3]. There are currently two main directions with regard to nutritional supplements with PUFAs. The first research school recommends enriching the diet with the essential fatty acid (EFA) obtained from vegetable sources, the C18 lipid omega-3 molecule α-linolenic acid and then via the elongase/desaturase activity naturally in omega-3 Eicosapentaenoic acid (EPA) and omega-3 Docosahexaenoic acid (DHA) [4]. The second research school says that the diet should be immediately enriched with EPA and DHA, obtained directly from fish oil [5]. Here we want to investigate the controversies about the possible use of these FAs as preventive / curative instruments against the development of CVDs to combat the current pandemic of heart disease through nutritional intervention. We calculated from the [product] / [precursor] ration in the Cholesteryl (ChE) fraction the enzymatic activity of elongase/desaturase activity of the heart muscle of a juvenile high-fat-induced C57bl6 mouse model, which model we previously used in CVD studies [6,7]. The main conclusion is that the omega-3 route from α-linolenic acid to EPA and DHA does not exist enzymatically in the heart and that the best strategy for preventing CVDs is direct diet enrichment with EPA and DHA. Because CVDs are currently the number 1 cause of death in the US [8] and the WHO predicts that especially in the coming decades developing countries will be affected by this pandemic of CVDs [1]. Research should focus on the underlying mechanism of omega-3 PUFA protection.
Epidemiology Versus Lipidomics Enzymatic Conversion
Currently, more than 1/3 of the world’s population is obese (Body Mass Index, BMI> 30) [9]. As a result, cardiovascular disease and stroke are currently the largest killer in the US. Every year more than 2 million Americans suffer from a heart attack or stroke and more than 800,000 die. CVDs are the leading cause of death in the United States and the biggest cause of lower life expectancy among black African Americans [10]. The confluence of many westernizing factors has led to a worldwide increase in fat consumption in the US, which is partly due to an increased consumption of fast food. Total added fat intake increased from 57 to 66 pounds / person from 1980 to 1997 [11]. Thus, there is a close link between obesity morbidity and fat consumption as shown in (Figure 1) for the US.
We recently conducted a study to systematically identify the cause of cardiovascular disease (CVD) related to the high-fat diet (HFD) in a juvenile insulin resistant (IR) C57bl6 mouse model [7] according to a system biology [12] Lipidomics-based approach [13]. We have used LC-MS techniques to determine the 7 most important lipid classes: the lyso-phosphatidylcholines (LPC), phosphatidylcholines (PC), Sphingomyelins (SPM), Diacylglycerols (DG), phosphatidylethanolamines (PE), Triacylglycerols (TG) and Cholesteryl -esters (ChE) as previously performed [6,7]. The HFD had an extremely high TG content of 633.4% increase based on lard (P <0.0001***). Effects of the high-fat diet can be seen on the heart muscle, where the TG level increased by 278% (P≤ 0.029*) compared to the control chow diet, resulting in lipo-toxicity related to hypoxic disorders. So, our main conclusion in that recent study was that lipo-toxicity due to excessive TGs accumulation, resulting in hypoxic disorders, was the leading cause of CVD [7]. From various studies there are indications that increasing the amount of polyunsaturated fatty acids (PUFAs) that we eat can lower our cholesterol levels in the blood and give us less chance of cardiovascular disease, especially if PUFAs are eaten instead of saturated fats, e.g. fats from animal dairy sources such as meat and cheese [14,15]. From such epidemiological studies, hard statements such as: “Replacing 5% of energy intake from dairy fat with equivalent energy intake from polyunsaturated fatty acids (PUFA) has been linked to a 24% lower risk of cardiovascular disease (CVD)”, have been made [16].
But it is our perception, interpretation, and major disadvantage of such epidemiological studies - based primarily on systematic review and meta-analysis of prospective cohort studies - that there are many confusing factors that can ‘fail’ the outcomes and conclusions of such a study. Secondly, PUFAs is a large hub of fatty acids (FAs) (Figure 2), starting with the two essential fatty acids (EFAs) LA and ALA which then end up with a complex enzyme conversion pattern in the elongase-desaturase array important ‘fish oils’ EPA and DHA. LA and ALA are of vegetable origin, while EPA and DHA are obtained from fish oil or fish capsules. The most evidence for the benefits of PUFAs is obtained from Eicosapentaenoic acid (C20: 5, ω-3; EPA) and Docosahexaenoic acid (C22: 6, ω-3; DHA), the ‘fish oil’ such as fat with long chain acids (FAs) in this family. However, there is some epidemiological support for an advantage of the EFA α-linolenic acid (C18: 3, ω-3; ALA), the plant-based precursor of EPA for CVDs [17]. The American Heart Association (AHA) has currently approved the use of ω-3 PUFAs in a dose of approximately 1 g / day of combined DHA and EPA, either in the form of fatty fish or fish oil supplements (in capsules or liquid form) in patients with documented coronary artery disease (CHD) [5]. In the past three decades, numerous epidemiological and observational studies have been published on the benefits of CVDs from omega-3 PUFAs, to mention a few studies: [18-20]. Because cardiovascular diseases and strokes are number 1, it is important to have clear guidelines at the population level with regard to supplementing the diet with PUFAs.
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