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How do omega-3 fatty acids reduce cholesterol at the molecular level?

How do omega-3 fatty acids reduce cholesterol at the molecular level?


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I have heard that omega-3 fatty acids found in fish are a good way to prevent/reduce cholesterol problems.

My question is how do omega-3 fatty acids do that: what are they doing on a chemical level to produce this effect? And is there any way to maximize this effect through other substances, that may work in concert with them?


I found this research paper (pdf) by D. Roger Illingworth, William S. Harris, and William E. Connor (Journal of the American Heart Association, 1984) that offers some help. Its abstract says:

Diets rich in omega-3 fatty acids derived from fish oils lower the plasma concentrations of low density lipoproteins (LDL) and very low density lipoproteins in humans. The present study was designed to examine the mechanism(s) by which diets enriched in omega-3 fatty acids reduce plasma LDL cholesterol levels in normal subjects.

In the Dicussion part, you will find your answer:

Reductions in the plasma concentrations of LDL in human subjects consuming diets rich in long-chain omega-3 fatty acids from fish oils or omega-6 fatty acids from vegetable oils may be due to a reduction in LDL synthesis, an increased fractional rate of catabolism of LDL, or a combination of both… The present study indicates that the hypocholesterolemic effects of long-chain omega-3 fatty acids present in fish oils results from a reduction in the rate of LDL apoprotein B synthesis and that such oils do not stimulate the fractional rate of catabolism of LDL. These observations imply that the incorporation of omega-3 fatty acids into cellular or lipoprotein lipids does not enhance the rate of receptor-mediated catabolism of LDL as has been observed with omega-6 fatty acids in vitro.

I could not find a paper on its exact mechanism, so I'd rather say that the process is still not clear. Yet, as the paper suggests, the main effects of omega-3 fatty acids are reducing LDL synthesis and/or increasing fractional rate of catabolism (FRC) of LDL.

A similar article can be found here:

Omega-3 fatty acids have been shown to lower triglycerides, which are a type of fat in the bloodstream. Experts aren't sure of the exact mechanism. Omega-3 fatty acids may also slow down the growth of plaques in the arteries and reduce inflammation throughout the body.

A number of studies going back years have shown the benefits of fatty fish. In an important review of studies, researchers found that getting daily omega-3 fatty acids from fish oil could lower triglyceride levels by 25%-30%. The results were published in The American Journal of Clinical Nutrition in 1997.

BUT, I would also like to point out that the question itself "omega-3 fatty acids found in fish are a good way to prevent/reduce cholesterol problems" seems to be a matter of debate because of articles like this:

New data presented this week provide clues as to why eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--both components of omega-3 fatty acids--have differential effects on LDL cholesterol.

Presenting the results of the laboratory study here at the National Lipid Association (NLA) 2011 Scientific Sessions, senior investigator Dr Preston Mason (Brigham and Women's Hospital, Boston, MA) said that EPA is an inhibitor of lipid oxidation at normal and elevated cholesterol levels in the presence and absence of DHA, while DHA seems to have no real effect on lipid peroxidation. This trial was one of a number of studies that attempted to address the clinical question as to why LDL-cholesterol levels increase in patients treated with the triglyceride-lowering omega-3 fatty acids. In his trial, Mason et al compared the effects of EPA and DHA--alone or in combination with statins--on lipid peroxidation in polyunsaturated fatty-acid- and cholesterol-enriched vesicles.


Omega-3 fatty acids and HDL. How do they work in the prevention of cardiovascular disease?

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) from marine origin have been strongly associated with cardiovascular protection, even at low doses ( < 1g/d). Despite the research performed in this promising area, basic aspects, such as the ideal doses and the mechanisms by which ω-3 PUFAs act, are not precisely defined. The best known biological property of ω-3 PUFAs is their hypotriglyceridemic effect, but other cardioprotective actions, such as reduction of arrhythmia susceptibility, antithrombotic, antiinflammatory and antioxidant effects, improvement of endothelial function, and delayed atherosclerosis development have received an increased interest in recent years. Some of these actions are also ascribable to high-density lipoproteins (HDL). Abundant epidemiological evidence links increasing HDL-cholesterol concentrations to cardiovascular protection. Recently, the protein cargo (proteome) of HDL particles has been attributed a key role in their functionality. In this review, we summarize the main effects of ω-3 PUFAs on HDL-cholesterol, HDL subfractions, and its main proteins, apolipoproteins (apo) AI and AII. The shared cardioprotective actions of ω-3 PUFAs and HDL are reviewed as well.


1. Background

Attention deficit hyperactivity disorder (ADHD) is a common child-onset neurodevelopmental disorder occurring in children, adolescents, and adults, with an estimated prevalence of 5 to 7 per cent across cultures [1]. ADHD tends to be more common in boys than girls and is highly heritable, with pre- and perinatal factors also being implicated, although its definite cause remains unknown [2]. Although the rate of ADHD declines with age, at least half of children with the disorder will go on to have symptoms in adulthood [3]. The condition can impact heavily on mental health and education, lead to antisocial behaviour and personal dysfunction, and increase mortality risk [4]. Medications used to treat ADHD typically include methylphenidate (MPH also, known as Ritalin), amphetamine, and atomoxetine which typically assume that there is a dopamine/norepinephrine deficit, although the aetiology of this condition is more complex [5]. Whilst MPH may ameliorate some comorbidities [6] it has been found to be ineffective in eliminating symptoms in 50 per cent of cases [7, 8]. Parents also appear to be concerned about the long-term effects of their children using medications such as MPH [9].

Long-chain polyunsaturated fatty acids (LCPUFA) and particularly omega-3 fatty acids have been under the spotlight for decades. They are key regulators of brain neurotransmission, neurogenesis, and neuroinflammation, all having an important role in the prevention and treatment of psychological and behavioural dysfunction disorders [10]. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are two fatty acids that are highly concentrated in the brain, exhibiting antioxidative, anti-inflammatory, and antiapoptotic effects, with these contributing to neuron protection [11].

The omega-6 fatty acid gamma linolenic acid (GLA) is also important in the generation of arachidonic acid (ARA) which is abundantly present in in the brain [12, 13]. A recent meta-analysis found that combinations of omega-3 and omega-6 fatty acids (EPA and GLA) helped to improve symptoms of inattention in children with ADHD [14]. Brain lipids within cell membranes also act as signalling mediums, supporting neurotransmitter function with omega-3 fatty acids thought to play a key role in this which may help in the prevention of anxiety disorders [15]. Laboratory research has also identified that omega-3 fatty acids may act in a similar way to 𠇊ntipsychotics,” possibly by acting on brain receptors and helping to restore oxidative balance [16].

Omega-3 deficiencies have been found to alter dopaminergic and serotonergic systems, potentially modifying cerebral receptors in specific regions of the brain [17]. EPA and DHA are regarded as 𠇎ssential fatty acids (EFAs)” that need to be obtained from food or supplement sources as they cannot be made in sufficient amounts by the human body [11]. The ratio of fatty acids (omega-6 : omega-3) which complete for the same enzyme pathways can also influence neurotransmission and prostaglandin formation, both of which are crucial in the maintenance of normal brain function [18, 19]. Furthermore, as the storage of the omega-3 fatty acids is limited, a continual exogenous supply is needed to obtain suitable levels [20].

A number of studies have measured LCPUFA status in individuals with ADHD. One study conducted on young adults (22.3 to 24.3 years) found the proportion of omega-3 fatty acids was significantly lower in the plasma phospholipids and red blood cells of ADHD participants compared with controls, whilst levels of saturated fatty acids were higher [21]. Another investigation found that whilst teenagers with ADHD consume similar amounts of omega-3 and omega-6 fatty acids to controls, their DHA status was significantly lower, indicating metabolic differences in fatty acid handling in those with ADHD [22]. Similarly, another trial showed that the proportions of saturated and polyunsaturated fatty acids were higher and lower, respectively, in paediatric patients with ADHD, compared with controls again indicating differences in lipid profiles [23]. Further meta-analytical evidence has concluded that children and young people with ADHD have elevated ratios of blood omega-6/3 indicating disturbances in fatty acid metabolism in these individuals [24].

Given that the human brain is nearly 60 per cent fat and the central role that EFAs have to play in the structure, synthesis, and functions of brain neurotransmitters [25], the present article evaluates evidence on whether LCPUFAs have a therapeutic role in the management of ADHD. Particular focus will be given on their potential effects in the management of ADHD along with their role as an adjunctive therapy.


Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association

Hypertriglyceridemia (triglycerides 200–499 mg/dL) is relatively common in the United States, whereas more severe triglyceride elevations (very high triglycerides, ≥500 mg/dL) are far less frequently observed. Both are becoming increasingly prevalent in the United States and elsewhere, likely driven in large part by growing rates of obesity and diabetes mellitus. In a 2002 American Heart Association scientific statement, the omega-3 fatty acids (n-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were recommended (at a dose of 2–4 g/d) for reducing triglycerides in patients with elevated triglycerides. Since 2002, prescription agents containing EPA+DHA or EPA alone have been approved by the US Food and Drug Administration for treating very high triglycerides these agents are also widely used for hypertriglyceridemia. The purpose of this advisory is to summarize the lipid and lipoprotein effects resulting from pharmacological doses of n-3 FAs (>3 g/d total EPA+DHA) on the basis of new scientific data and availability of n-3 FA agents. In treatment of very high triglycerides with 4 g/d, EPA+DHA agents reduce triglycerides by ≥30% with concurrent increases in low-density lipoprotein cholesterol, whereas EPA-only did not raise low-density lipoprotein cholesterol in very high triglycerides. When used to treat hypertriglyceridemia, n-3 FAs with EPA+DHA or with EPA-only appear roughly comparable for triglyceride lowering and do not increase low-density lipoprotein cholesterol when used as monotherapy or in combination with a statin. In the largest trials of 4 g/d prescription n-3 FA, non–high-density lipoprotein cholesterol and apolipoprotein B were modestly decreased, indicating reductions in total atherogenic lipoproteins. The use of n-3 FA (4 g/d) for improving atherosclerotic cardiovascular disease risk in patients with hypertriglyceridemia is supported by a 25% reduction in major adverse cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With EPA Intervention Trial), a randomized placebo-controlled trial of EPA-only in high-risk patients treated with a statin. The results of a trial of 4 g/d prescription EPA+DHA in hypertriglyceridemia are anticipated in 2020. We conclude that prescription n-3 FAs (EPA+DHA or EPA-only) at a dose of 4 g/d (>3 g/d total EPA+DHA) are an effective and safe option for reducing triglycerides as monotherapy or as an adjunct to other lipid-lowering agents.

Elevated plasma triglycerides are the result of an excess of triglyceride-rich lipoproteins of several different types, most commonly very-low-density lipoproteins (VLDLs) but also intermediate-density lipoproteins (or VLDL remnants), chylomicrons, or chylomicron remnants. The classification, epidemiology, and pathophysiology of elevated triglycerides were reviewed in depth in a 2011 American Heart Association (AHA) scientific statement, along with detailed discussion of diet and lifestyle treatment options, as well as a brief mention of medications. 1 The 2011 statement cited epidemiological evidence that a moderate elevation in triglycerides is often associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. More recent evidence from mendelian randomization studies has shown that elevated triglycerides associated with genetic variants may be a causal factor for ASCVD and possibly for premature all-cause mortality. 2–7

Fasting plasma triglyceride concentrations may be categorized as normal (<150 mg/dL*), borderline (150–199 mg/dL), high triglyceride (HTG 200–499 mg/dL), and very HTG (VHTG ≥500 mg/dL). 1,8 Risk of acute pancreatitis is increased in patients with VHTG, especially those with triglycerides ≥1000 mg/dL. 9 For VHTG, the primary goal of therapy is to reduce triglycerides to <500 mg/dL, 10 whereas there is no specific treatment goal for HTG. For all degrees of triglyceride elevation, treatment or elimination of secondary causes and intensive diet and lifestyle changes are recommended before direct pharmacotherapy. 11 Such changes include weight loss, increased physical activity, limited alcohol consumption, and adoption of various healthy dietary practices such as decreased consumption of refined carbohydrates and simple sugars, substitution of saturated and trans fats with unsaturated fats, and increased consumption of seafood (especially species high in omega-3 fatty acids [n-3 FAs]).

The 2002 AHA scientific statement on fish and n-3 FAs recommended increased dietary omega-3 intake plus dietary supplements to achieve 2 to 4 g/d n-3 FA (referring to the total amount of eicosapentaenoic acid [EPA] plus docosahexaenoic acid [DHA]) for triglyceride-lowering treatment (ie, medical management of HTG) under the supervision of a physician. (No prescription n-3 FAs were available at the time). 12 A recent AHA science advisory has addressed the use of n-3 FA supplementation to reduce ASCVD risk. 13 This advisory focuses specifically on the use of n-3 FA agents to treat HTG and VHTG.

Since 2004, several types of prescription n-3 FA agents have been approved by the US Food and Drug Administration (FDA) for the treatment of VHTG. The typical dose is four 1-g capsules daily, providing >3 g/d EPA+DHA. Dietary supplements containing n-3 FA are also widely available in a variety of chemical forms (triglycerides, phospholipid, free fatty acid, or ethyl esters). However, because these supplements are neither reviewed nor approved by the FDA, they are not indicated for triglyceride lowering in patients with any degree of triglyceride elevation.

FDA-approved prescription n-3 FA products include Lovaza and its generic (n-3-acid-ethyl esters [O3AEE] EPA 0.465 g and DHA 0.375 g/capsule), Omtryg (a similar O3AEE product but not clinically available), Vascepa (an ethyl ester product consisting of EPA without DHA, chemical term icosapent ethyl [IPE] EPA 0.98 g/capsule), and Epanova (n-3-carboxylic acid [O3CA] EPA 0.55 g and DHA 0.2 g/capsule, not clinically available). For ethyl ester agents (O3AEE and IPE), the EPA+DHA content is in ethyl ester form rather than free fatty acid. Therefore, the dose of free n-3 FA is slightly less (explained in No. 3 of the Appendix). For consistency with the majority of scientific publications, this advisory uses the convention of expressing grams per day of EPA+DHA as equivalent to the amount of grams per day of EPA+DHA ethyl esters, without adjustment for the ethyl ester moiety. More details on these products and a discussion of n-3 FA dietary supplements are presented in the Appendix.

The purpose of this advisory is to summarize available clinical evidence related to the effects of n-3 FA on plasma concentrations of triglycerides and other lipids and lipoproteins in individuals with elevated triglycerides. Summary information provided in this advisory is intended to inform healthcare providers about prescription n-3 FA newly approved since the 2002 AHA statement and to elaborate on the effects of n-3 FA as an adjunctive lipid-lowering therapy, particularly in combination with statins.

Modifiable Causes of Elevated Triglycerides Should be Addressed Before Pharmacotherapy Is Initiated

As extensively reviewed and discussed in the 2011 “Triglycerides and Cardiovascular Disease: A Scientific Statement From the American Heart Association” 1 (summarized in Table 1), several factors such as medications, genetics, health conditions, lifestyle, and diet can be significant contributors to elevations in triglycerides. Before triglyceride-lowering therapy is initiated, reversible secondary causes of HTG such as hypothyroidism or poorly controlled type 2 diabetes mellitus should be identified and treated. In addition, dietary factors that are established causes of triglyceride elevations such as excessive alcohol or sugar intake (or excessive total dietary fat in the case of severe VHTG or chylomicronemia) warrant intervention. When HTG or VHTG appears to be caused, at least in part, by the medications noted in Table 1, treatment options include eliminating or lowering the dose of the inciting agent (eg, dose reduction or elimination of a thiazide diuretic or a retinoid), substituting within the same drug class (eg, carvedilol in place of metoprolol for post–myocardial infarction cardioprotection), or switching to a different drug class (eg, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker in place of metoprolol for congestive heart failure).

Table 1. Clinical Conditions and Drugs Associated With HTG


The importance of the ratio of omega-6/omega-3 essential fatty acids

Several sources of information suggest that human beings evolved on a diet with a ratio of omega-6 to omega-3 essential fatty acids (EFA) of approximately 1 whereas in Western diets the ratio is 15/1-16.7/1. Western diets are deficient in omega-3 fatty acids, and have excessive amounts of omega-6 fatty acids compared with the diet on which human beings evolved and their genetic patterns were established. Excessive amounts of omega-6 polyunsaturated fatty acids (PUFA) and a very high omega-6/omega-3 ratio, as is found in today's Western diets, promote the pathogenesis of many diseases, including cardiovascular disease, cancer, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 PUFA (a low omega-6/omega-3 ratio) exert suppressive effects. In the secondary prevention of cardiovascular disease, a ratio of 4/1 was associated with a 70% decrease in total mortality. A ratio of 2.5/1 reduced rectal cell proliferation in patients with colorectal cancer, whereas a ratio of 4/1 with the same amount of omega-3 PUFA had no effect. The lower omega-6/omega-3 ratio in women with breast cancer was associated with decreased risk. A ratio of 2-3/1 suppressed inflammation in patients with rheumatoid arthritis, and a ratio of 5/1 had a beneficial effect on patients with asthma, whereas a ratio of 10/1 had adverse consequences. These studies indicate that the optimal ratio may vary with the disease under consideration. This is consistent with the fact that chronic diseases are multigenic and multifactorial. Therefore, it is quite possible that the therapeutic dose of omega-3 fatty acids will depend on the degree of severity of disease resulting from the genetic predisposition. A lower ratio of omega-6/omega-3 fatty acids is more desirable in reducing the risk of many of the chronic diseases of high prevalence in Western societies, as well as in the developing countries, that are being exported to the rest of the world.


Phytochemicals &Chemoprevention

You have heard of saturated fats (not good for you), and poly unsaturated fats (also called poly unsaturated fatty acids, generally good for you). Now you have to draw a further distinction between the types of Poly-Unsaturated Fatty Acids ( PUFA ). Some are very good for you, while some are not only not good for you in large amounts, they can be the cause of many of our modern ailments. Specifically, the wrong type of PUFA can aggravate cardiac disease, autoimmune and chronic inflammation diseases such as multiple sclerosis (MS), lupus, type-1 diabetes, psoriasis, rheumatoid arthritis, yes, even cancer. The research in this area is so compelling that even the FDA is finally getting out there with some concrete guidelines. Read on, many of the benefits to be gained by getting the right mix of PUFAs is directly applicable to us as CLL patients. Indeed, some of the recommendations reviewed in this article may be the simplest, cheapest, low risk, low toxicity things you can do that may make a significant difference in how CLL plays out in your case, in what kind of response you get to therapy, and in how much hassle you get from related problems such as autoimmune disease. Did I say there was no free lunch? This comes close.

The PUFA Family

There are two distinct groups of poly unsaturated fats (also called poly unsaturated fatty acids). One group is called omega-6 acids and the other group is called omega-3 acids . It is now pretty well established that man evolved on a diet with roughly equal amount of omega-6 and omega-3 fatty acids. Unfortunately, today this ratio for the food we eat is anywhere from 10 to 25 times as much omega-6 acids, compared to omega-3 acids. Western diets are so deficient in omega 3 fatty acids, and so abundant in omega-6 acids, relative to what is good for our bodies, that a significant health crisis has emerged as a consequence.

This important ratio is out of balance in most of our diets because of the change in our eating patterns, as well as changes in food production technology. Omega-6 fatty acids account for the majority of polyunsaturated fatty acids (PUFA) in the food supply. They are the predominant PUFA in all diets, especially Western diets, where most of the fat comes from grain-based oils (corn oil and sunflower oil) or oils from meat (lard). Omega-3 fatty acids, by contrast, are mainly present in cold water fish, and in some oils derived from seeds such as flax seed oil. Not all fish have equal amounts of omega-3 oils - I doubt "fish fingers" (fried in corn oil, no doubt) qualify as health food. Sorry, you guys who fancy fish and chips.

Here are some names and abbreviations you will see as you dig into this whole business of PUFA. The major omega-6 acids are linoleic acid ( LA ) and arachidonic acid ( AA ). The principal omega-3 acids are eicosapentanoic acid ( EPA ) and docosahexanoic acid ( DHA ), both from cold water "fatty" fish, and last but not least, alpha linolenic acid ( ALA ). There is another omega-6 acid that is actually beneficial, called gamma linolenic acid ( GLA ), that we will discuss in another article. I will be using these abbreviations all through this review - you can always scroll up and see which one is which if you get confused. This is the bullet point to remember: LA and AA are omega-6 acids, we get too much of them already. What we need more of are omega-3 acids EPA and DHA from fish oil, and ALA from fish oil as well as flax seed. Before you go from one end of the pendulum's arc to the other extreme, let me hasten to add both omega-3 and omega-6 are important components of practically all cell membranes. It is just that we are overdosing on omega-6 and not getting enough omega-3. Omega-3 and omega-6 fatty acids are not inter-convertible in the human body. When diets are supplemented with omega-3 fatty acids, the latter partially replace the omega-6 fatty acids in the membranes of practically all cells (red blood cells, platelets, cells lining your mouth and gut, monocytes, lymphocytes, granulocytes, nerve cells, retinal cells in your eyes, liver cells and even brain cells). Therefore, getting the right amount of each group of PUFAs influences just about every major organ and system in your body.

General Categories of Fats and Fatty Acids

The Polyunsaturated Fatty Acids

Chronic Inflammation and PUFAs

The first evidence of the important role of dietary intake of omega-3 acids in diseases due to chronic inflammation was derived from epidemiological observations. In a population of Greenland Eskimos compared with gender- and age-matched groups living in Denmark, the Eskimos (who lived almost exclusively on a daily diet of cold water fatty fish of various kinds, and therefore got a lot of omega-3 acids) had a low incidence of autoimmune disorders such as psoriasis, asthma and type-1 diabetes, and a complete absence of multiple sclerosis. Most of these diseases are characterized by inappropriate activation of T cells resulting in inflammation of and ultimately destruction of host tissues. Traditional Japanese people have a high dietary intake of long chain omega-3 acids as well, from seafood. Not coincidentally, according to many researchers, they also have a low incidence of myocardial infarction and chronic inflammatory or autoimmune disorders, when compared to Japanese people who have adopted Westernized dietary habits.

We have discussed the role played by chronic inflammation in CLL in earlier articles. If you have not read these, I strongly urge you to do so: Chronic Inflammation and What You Can Do About It, Role of Pulmonary Inflammation in CLL. Left untreated, chronic pulmonary inflammation can put you in the hospital and pneumonia is the most common cause of death in CLL patients. It is thought that competition between the omega-6 and omega-3 fatty acids occurs in prostaglandin formation. EPA, an omega-3 fatty acid for example, competes with AA, an omega-6 fatty acid, for prostaglandin and leukotriene synthesis. When we eat fish or fish oil, the EPA and DHA from fish or fish oil lead to decreased production of the prostaglandin E2 and a decrease in leukotriene B4 formation. This has the effect of decreasing overall inflammation, and making leukocytes less sticky and less able to migrate into the lymph nodes and bone marrow.

In recent months we have all watched with fascination as the car wrecks of Vioxx and Celebrex played out on our TV screens. For a number of years, both of these selective cyclo-oxygenase-2 (Cox-2) inhibitors were touted as miracle drugs that helped arthritis sufferers. There were tantalizing leads that suppressing Cox-2 had the beneficial effect of suppressing inflammation, which in turn helped control cancers of various kinds. Recent findings have put a damper on some of these hopes. We now learn that daily large doses of both of these drugs can cause a higher risk of heart problems. Although common NSAIDs such as aspirin can also inhibit COX (both Cox-1 and Cox-2) and are potent anti-inflammatory agents, chronic use of high doses of aspirin and the like can also have serious adverse effects such as GI tract bleeding. Increasing the intake of omega-3 fatty acids while decreasing the omega-6 fatty acids in the diet has some of the same beneficial effects as Cox suppression. Patients with rheumatoid arthritis and asthma have shown significant improvements upon eating roughly equal amounts of omega-3 and omega-6 fatty acids in their diet.

Abstracts:

J Am Coll Nutr. 2002 Dec21(6):495-505.

Omega-3 fatty acids in inflammation and autoimmune diseases.

The Center for Genetics, Nutrition and Health, Washington, DC

Among the fatty acids, it is the omega-3 polyunsaturated fatty acids (PUFA) which possess the most potent immunomodulatory activities, and among the omega-3 PUFA, those from fish oil-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--are more biologically potent than alpha-linolenic acid (ALA) . Some of the effects of omega-3 PUFA are brought about by modulation of the amount and types of eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways, transcription factor activity and gene expression. Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohn's disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB(4) produced by omega-6 fatty acids. There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.

PMID: 12480795
____________

Omega-3 fatty acids and inflammation

School of Medicine and Pharmacology--Royal Perth Hospital Unit, The University of Western Australia, Perth, Western Australia 6847, Australia.

Dietary omega-3 (n-3) fatty acids have a variety of anti-inflammatory and immune-modulating effects that may be of relevance to atherosclerosis and its clinical manifestations of myocardial infarction, sudden death, and stroke. The n-3 fatty acids that appear to be most potent in this respect are the long-chain polyunsaturates derived from marine oils, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) , and this review is restricted to these substances. A variety of biologic effects of EPA and DHA have been demonstrated from feeding studies with fish or fish oil supplements in humans and animals. These include effects on triglycerides, high-density lipoprotein cholesterol, platelet function, endothelial and vascular function, blood pressure, cardiac excitability, measures of oxidative stress, pro- and anti-inflammatory cytokines, and immune function. Epidemiologic studies provide evidence for a beneficial effect of n-3 fatty acids on manifestations of coronary heart disease and ischemic stroke, whereas
randomized, controlled, clinical feeding trials support this, particularly with respect to sudden cardiac death in patients with established disease. Clinically important anti-inflammatory effects in man are further suggested by trials demonstrating benefits of n-3 fatty acids in rheumatoid arthritis, psoriasis, asthma, and inflammatory bowel disorders. Given the evidence relating progression of atherosclerosis to chronic inflammation, the n-3 fatty acids may play an important role via modulation of the inflammatory processes.

PMID: 15485592
____________

Omega-3 and Cancer Therapy

Animal and human epidemiologic studies indicate that the ratio of omega-3 to omega-6 fatty acids in the diet is particularly important to the reduction of cancer risk. Do remember that it is not really the amount of omega-3 fats you consume that matters, it is the ratio of omega-3 to omega-6 fatty acids in the diet that is important. Several studies have shown, for example, that the risk of breast and prostate cancer decreases sharply when we eat roughly equal amount of the two types of PUFAs.

How do omega-3 fats help reduce cancer risk? As you should know by now "apoptosis" is programmed cell death, and normal cells are very obedient in quietly committing suicide when it is their time to do so. However, apoptotic pathways are frequently disrupted in cancers, including CLL. This means that CLL cells hang around too long, do not die on command. This is one of the reasons why they accumulate in such large numbers in your body. Anything we can do to re-train them to die on command is going to help the process of controlling the disease, slow down the its progression. Among the reasons for this malfunction in the apoptosis pathway is increased COX-2 expression, over-the-top angiogenesis and activation of the NF-kB pathway, all of which make the cells more resistant to death signals, as well as increase the rate at which the cancer cells proliferate. Among the beneficial things that omega-3 fats do for us is block NF-kB and COX-2 activation, which in turn would restore apoptosis and reduce proliferation. An important gene of the Bcl-2 family can block apoptosis in CLL cells. DHA from fish oil has been reported to inactivate Bcl-2 and increase apoptosis.

Yet another important mechanism by which omega-3 fats play a role as adjuvants to cancer therapy depends on their ability to generate reactive oxygen species (ROS). This is an important subject all on its own, and I would like to take a rain check today in order to do justice to it at a later date. If you are curious about the role played by ROS in cancer cell kill, you might get your motor running by reading an earlier article on Mitochondria (Target Mitochondrion). If you type the key words "Omega-3" "PUFA" and "Cancer therapy" into the PubMed search engine, you will get several hundred hits, giving you an idea of the importance of this area of research.

Over the last decade we have been taught to incorporate more heart-healthy fats in our diet, decrease our use of saturated fatty acids (Lard, butter fat, coconut oil etc) and substitute in their place safflower, corn and soybean oils for frying and baking uses. True, these vegetable oils contain much less of the bad saturated fats, but they also contain a very high amount of omega-6 and very little omega-3 fatty acids. This is not good, as we are just beginning to find out. Getting back to the drawing board, the use of canola (or olive oil as a second choice) instead of safflower, corn or soybean oil for frying and baking would reduce the consumption of omega-6 fatty acids. In addition, canola oil includes a significant amount of the good omega-3 fatty acids. Bottom line, the guidelines are shaking out like this: consumption of several servings per week of fatty, cold-water fish (see list below), switching to canola oil for daily cooking and baking, and perhaps a good supplement of fish oil to bring in additional amounts of DHA and EPA omega-3 fatty acids to the diet.

Abstracts:

J Nutr. 2002 Nov132(11 Suppl):3508S-3512S.

Omega-3 fatty acids to augment cancer therapy.

Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA

The results of animal studies have demonstrated that the consumption of omega-3 fatty acids can slow the growth of cancer xenografts, increase the efficacy of chemotherapy and reduce the side effects of the chemotherapy or of the cancer. Molecular mechanisms postulated to contribute to the multiple benefits of omega-3 fatty acids include 1) suppressing the expression of cyclooxygenase-2 in tumors, thus decreasing proliferation of cancer cells and reducing angiogenesis in the tumor 2) decreasing the expression of AP-1 and ras, two oncogenes implicated in tumor promotion 3) inducing differentiation of cancer cells 4) suppressing nuclear factor-kappaB activation and bcl-2 expression, thus allowing apoptosis of cancer cells and 5) reducing cancer-induced cachexia. It seems reasonable to assume that after appropriate cancer therapy, consumption of omega-3 fatty acids might slow or stop the growth of metastatic cancer cells, increase longevity of cancer patients and improve their quality of life.

PMID: 12421878
____________

J Nutr. 2004 Dec134(12 Suppl):3427S-3430S

(n-3) fatty acids and cancer therapy.

Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA

Supplementing the diet of tumor-bearing mice or rats with oils containing (n-3) (omega-3) or with purified (n-3) fatty acids has slowed the growth of various types of cancers, including lung, colon, mammary, and prostate. The efficacy of cancer chemotherapy drugs such as doxorubicin, epirubicin, CPT-11, 5-fluorouracil, and tamoxifen, and of radiation therapy has been improved when the diet included (n-3) fatty acids. Some potential mechanisms for the activity of (n-3) fatty acids against cancer include modulation of eicosanoid production and inflammation, angiogenesis, proliferation, susceptibility for apoptosis, and estrogen signaling. In humans, (n-3) fatty acids have also been used to suppress cancer-associated cachexia and to improve the quality of life. In one study, the response to chemotherapy therapy was better in breast cancer patients with higher levels of (n-3) fatty acids in adipose tissue [indicating past consumption of (n-3) fatty acids] than in patients with lower levels of (n-3) fatty acids.
Thus, in combination with standard treatments, supplementing the diet with (n-3) fatty acids may be a nontoxic means to improve cancer treatment outcomes and may slow or prevent recurrence of cancer. Used alone, an (n-3) supplement may be a useful alternative therapy for patients who are not candidates for standard toxic cancer therapies.

PMID: 15570049
____________

Official Guidelines on Omega-3 Fatty Acids

OK, now that we know omega-3 fatty acids are good for us, the next practical question is how much to take. Remember, too much of a good thing is not necessarily better. This is particularly true for CLL patients, who may have problems with low platelets that expose them to risk of easy bleeding. There is some research that shows excessive amounts of omega-3 acids may make bleeding problems worse. If your platelet counts are on the low side, I strongly urge you to consult with your physician before you embark on any heavy duty supplementation or dietary modification. Here is what the American Heart Association has to say about the level of omega-3 fatty acids you should have as part of a healthy diet, the recommendations are given below as an exact quote. This 2002 article is very detailed, and the full text is available free of charge. You have absolutely no excuse for not clicking on the this link to a full-text PDF version of the article from Circulation, the journal of the American Heart Association.

Recommendations for Intake of Omega-3 Fatty Acid

  • Patients without documented coronary heart disease: Eat a variety of (preferably oily) fish at least twice weekly. Include oils and foods rich in alpha linolenic acid (ALA), such as soybeans, canola, walnut and flaxseed and oils made from those beans, nuts and seeds.
  • Patients with documented coronary heart disease: Consume 1 g of eicosapentanoic and docosahexanoic acid (EPA and DHA) daily, preferably from oily fish. Supplements could be considered in consultation with a doctor.
  • Patients with hypertriglyceridaemia: Take 2-4 g of eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) daily, provided as capsules under a doctor's care.

American Heart Association&rsquos dietary guidelines recommend that healthy adults eat at least two servings of fish per week, particularly fish such as mackerel, lake trout, herring, sardines, albacore tuna and salmon. These fish contain two omega-3 PUFAs eicosapentaenoic and docosahexaenoic acids (EPA and DHA). A third kind of omega-3 fatty acid alpha-linolenic acid (ALA), comes from soybeans, canola, walnut and flaxseed and oils made from those beans, nuts and seeds. It is thought to be less potent than EPA and DHA from fish oils. Getting enough EPA and DHA from diet alone can be a little tough, unless you are really fond of eating fish. People who have elevated triglycerides may need as much as 2 to 4 grams of EPA and DHA per day, and the only reasonable method of getting this much EPA and DHA is by taking a fish oil supplement. Patients taking more than 3 grams of omega-3 fatty acids from supplements should do so only under a physician&rsquos care. The FDA has noted that high intakes could cause excessive bleeding in some people, and taking lots of omega-3 fatty acids without cutting back on some of the not so good omega-6 fatty acids can lead to increased LDL cholesterol, especially if you also happen to have high levels of unhealthy triglycerides to begin with. Moral of the story: the idea is not to add a lot more omega-3 oils to your diet without changing anything else, the idea is to cut back on some of the omega-6 fats and substitute omega-3 fats in their place. In practical terms, you might do this by switching from corn oil or olive oil to canola oil, which has much higher ALA. It might mean passing on meat and potatoes in favor of a nice piece of grilled salmon and side of veggies. And to get sufficient amount of EPA and DHA, you may have to resort to a supplement. Be warned: fish oil capsules can cause upset an stomach in some patients but taking them at meal time with food seems to make for less problems. Some patients also complain of fishy aftertaste. Oh well. Here is a table of the relative risk of various side effects.

Risk of Side Effects From Ingestion of Omega-3 Fatty Acids
American Heart Association Dietary Guidelines
Dosage GI Upset Clinical Bleeding Fishy Aftertaste Worsening Glycemia* Rise in LDL-C**
Up to 1 gm/day Very low Very Low Low Very Low Very Low
Up to 3 gm/day Moderate Very Low Moderate Low Moderate
> 3gm/day Moderate Low Likely Moderate Likey
* Usually only in patients with impaired glucose tolerance and diabetes
** Usually only in patients with hypertriglyceridemia.
Composition of Common Dietary Fats and Oils
American Heart Association Dietary Guidelines
Source Saturated PUFAs Monounsaturated
n-6 (LA) n-3 (ALA)
Canola 7 21 11 61
Safflower 10 76 7 16
Corn 13 57 1 29
Olive 15 9 1 75
Soybean 15 54 8 23
Peanut 19 33 1 48
Lard 43 54 1 2
Palm 51 10 1 39
Butterfat 68 3 1 28
Coconut 91 2 0 7

How to Select the Right Fish Oil Supplement or the Right Fish

Type in "Fish Oil" into Google search box and you will get thousands upon thousands of hits. I am not about to recommend a brand name to you, that is your business. But I will recommend that you do your homework, read the fine print on the label, and use a reputable company. Fish oil capsules should be sold in dark colored bottles since they decompose upon exposure to light for long periods of time. I also suggest you don't buy a year's worth of fish oil capsules at one time and you should look to buy from a store that does brisk business so that you are not likely to get stuck with something that has been sitting on the shelf from a couple of years ago. "Buyer beware" is a good thing to remember when shopping for food supplements. Some of the vendors make extraordinary claims for their products, you need to have a good BS detector to be able to walk away from such products. You need to look for the EPA and DHA content of the fish oil, this should be clearly spelled out on the bottle label. Typically, the garden variety fish oil capsules from Walgreen's weigh 1 gram (1,000 milligrams), and contain 180 milligrams of EPA and 120 milligrams of DHA for a total of 300 milligrams of omega-3 PUFAs. It is equally important to make sure that the capsules have no other goodies, such as vitamins A, E and C. It is possible to overdose quite quickly on Vitamins A and E, in your effort to get sufficient EPA and DHA. Look for fish oil that has none of this stuff added in. Furthermore, all three of these vitamins (A, E and C) are strong anti-oxidants, and they will interfere with the generation of ROS and killing of cancer cells. As I said above, ROS, fish oil, and cancer therapy is a whole interesting subject by itself, we will get to it in the next few days. Bottom line, look for plain vanilla fish oil, nothing extra added to it. Not only will you have a better handle on what you are getting, it will be lighter on your wallet too.

If your preference is to increase omega-3 acids by making changes in your diet as opposed to swallowing a capsule, you need to eat fish a lot more than you have been. Here is a list of fish that have high omega-3 fat content. The table gives grams of omega-3 PUFAs per 6-ounce serving.


Which Omega-3 is Better For Lowering Triglyceride Levels?

We get asked this question a lot, “Which omega-3 should I take in order to reduce my triglycerides?” Is there a difference between plant-based oils, like flaxseed, chia seed, hemp seed or even echium seed oil, and traditional fish oils? Our answer is a resounding YES!

There is currently little evidence that plant-based oils, like flaxseed, chia seed, hemp seed or echium seed oils, help to lower high triglyceride levels. This is because plant-source omega-3s do not contain EPA or DHA, the ‘long-chain’ omega-3 fatty acids that are present in fish oil, which have been shown to produce the triglyceride-lowering effects and anti-inflammatory effects in the body. Instead, these plant-based seed oils contain a ‘short-chain’ omega-3 called ALA (alpha-linolenic acid), which must be converted within the body to EPA, and then to DHA.

However, this conversion is problematic because this conversion is very inefficient. In fact, the body only converts ALA to EPA and then to DHA at an efficiency rate of approximately 5 to 10 percent and 2 to 5 percent, respectively. The bottom line is taking a plant-base omega-3 product that delivers only ALA is not the same as taking a animal/algae based omega-3 that naturally contains already formed EPA and DHA. And this news is even more important for men who are taking omega-3 to lower their triglycerides or reduce inflammation because scientific studies have determined that men have a very hard time converting ALA to EPA – in fact, women convert ALA to EPA 2.5 times more efficiently than men.

The GREAT news is that fish oil supplementation has been shown to lower triglyceride levels. As we stated above, this is because animal/algae-source omega-3, unlike plant-based omega-3s, naturally contain both EPA and DHA, so there’s no conversion process necessary, and they can be directly absorbed. This means that consuming animal/algae-source omega-3s (such as fish oil) offers greater health benefits, including lowering triglyceride levels.

But, buyer beware…Here are 4 things to check before purchasing a fish oil to lower triglycerides:

1. Only purchase fish oil supplements that are in the triglyceride form. Research study after research study concludes that EPA and DHA from triglycerides are absorbed at dramatically higher percentages over the cheaper and less efficient form called ethyl esters. One study showed the EPA and DHA from triglycerides being 340% and 271% better absorbed, respectively, compared to those consumed as ethyl esters. This is a very important point – don’t think that just because you are taking a fish oil supplement that you are getting the EPA and DHA you need to reduce your triglycerides and inflammation. To test your current fish oil to see if it is in the superior, highly absorbable triglyceride form, follow the directions in the quick video HERE. (You’ll be amazed by this at home test!)

2. Only purchase fish oil supplements that deliver adequate amounts of EPA & DHA. Just because your omega-3 supplement is from fish, krill or algae (3 sources that do contain EPA and DHA) that doesn’t mean that it contains beneficial quantities of EPA and DHA. In other words, it may not contain enough EPA and DHA to actually improve your health. Many omega-3 supplements advertise high levels of omega-3 (ALA), but upon closer examination only supply minimal levels of EPA and DHA. Omega-3 research shows that if you want to give yourself the best chance at achieving meaningful health benefits, your omega-3 supplement must contain high enough quantities of the two active components, EPA and DHA. A minimum of 1000 mg per day of EPA/DHA (not ALA) are required to begin to see benefits, and a clinical dose of 2500 mg per day of EPA/DHA is suggested for individual with high triglyceride levels or other inflammation related conditions. Read the labels carefully to insure that you are getting the beneficial quantities of both EPA and DHA—if the levels are low or are not listed move on. Higher concentrations save you money and require you to take fewer capsules.

3. Avoid oxidized fish oil supplements. Not only will this greatly reduce the fishy burps often associated with fish oil supplements, but it will also deliver higher levels of EPA and DHA! As oxidation occurs, the fish oil’s EPA and DHA content also decreases. Since the EPA and DHA molecules are the main workhorses of the omega-3 family, reduced EPA/DHA content means reduced efficacy of the oil. In a Spanish study, researchers divided 52 women into three different groups: one group that consumed less oxidized omega-3 capsules, one group that consumed highly oxidized omega-3 capsules, and a third group that received no capsules. After thirty days, they measured the women’s triglyceride and cholesterol levels. Only the women who received the less oxidized capsules had reduced triglyceride and cholesterol levels. This study also proved that, the women in the highly oxidized capsule group saw a negative impact on their cholesterol levels. The oxidized oil was not just less effective than the less oxidized oil it actually increased their cholesterol levels producing a negative health consequence for the women. Always ask to see the TOTOX results from the fish oil manufacturer. Read more on rancidity HERE.

4. Only purchase fish oil that is formulated to eliminate the competition between EPA & DHA. Let’s discuss perhaps the most important issue of all the fact that even if an omega-3 supplement were to deliver beneficial quantities of a triglyceride form animal/algae sourced omega-3 (containing both EPA and DHA), if the EPA and DHA are combined in the same dose, they reduce the absorption potential of each other due to inherent micronutrient competitions. This is because DHA has a relatively similar structure to EPA, which causes them to compete for the active absorption sites. Thus if EPA and DHA are at relatively equal levels in the omega-3 product they will compete for occupation of these active sites and reduce their overall activity. The purer the preparation of the EPA and DHA, or the more that these competitions are eliminated, the more likely is it be properly absorbed and utilized by the body. Scientists state that separating EPA and DHA and taking them at different times during the day will allow them to do their job more effectively.

Triglyceride Benefits Mirror Whole Body Benefits. To be clear, lowering one’s triglycerides levels are just one of the many benefits of EPA and DHA (numerous others are listed below.) Because of this an animal/algae sourced omega-3 product like fish oil, that naturally contains EPA and DHA always be deemed superior to plant-based oils for omega-3 content.

Fish oil has also been shown to have these additional health benefits:

  • Improve heart health
  • Ensure healthy baby
  • Increased Bone denisty
  • Intensify fat loss and increase muscle gain
  • Reduce cortisol
  • Enhanced athletic performance & recovery
  • Alleviate dry eyes
  • Prevent Alzheimer’s
  • Restore joint health & reduce arthritis
  • Reduce stress, anxiety & depression
  • Treat Crohn’s disease
  • Curtail ADHD
  • Reduce aggressive behavior

And it can also save lives and money! Research by the Lewin Group shows that daily supplementation of 1,800 mg of omega-3 fatty acids (containing beneficial quantities of EPA and DHA) could reduce more than 380,000 hospitalizations due to coronary heart disease (CHD) over a 5 year period and save an estimated $3.1 billion over that same five years in CHD-related hospital and physician expenses. Additionally, according to research published in The Lancet, a diet with a omega-6 to omega-3 ratio of 4:1 or less (1:1 is optimal) may reduce total mortality by up to 70% over 2 years.

EPA and DHA are micronutrients too!

As you know our main focus is helping you create and maintain a state of micronutrient sufficiency (i.e. vitamins, minerals, essential fatty acids, and amino acids) and omega-3s essential fatty acids are one of those micronutrients! Once we understood everything we just went over in this article we searched everywhere for an omega-3 supplement that was sourced form wild caught (non-GMO) fish, was delivered in a triglyceride form, contained beneficial quantities of EPA/DHA, had third party testing to assure it was free of heavy metals and toxins, had TOTOX scores proving it was not oxidized, and most importantly was formulated to eliminate the competition between EPA and DHA for absorption sites.

In the end we could not find a single omega-3 supplement that met our rigorous, but essential requirements so we decided to create one that did! We believe Origin Omega is the highest quality fish oil supplement available anywhere! Our triple strength formulation is the first and only omega-3 supplement that delivers 1520 mg of EPA/DHA in each daily serving, at two completely different times during the day to naturally eliminate the competition between EPA and DHA for absorption. (Take two AM servings and two PM servings per day for clinical benefits)


How do omega fatty acids break down triglycerides in the blood?

I think you might have some things confused but omega fatty acids make up triglycerides. A triglyceride is just a glycerol backbone with 3 fatty acids attached to it. The reason for that is because free fatty acids have detergent properties that is they would disturb the integrity of many structures in the tissue (like soap). When you ingest triglycerides, they get broken down by the pancreatic enzyme lipase in the small intestines so they could be absorbed. After absorption, the triglycerides are built again and packed into a lipoprotein called chylomicron to circle the body with the blood because they're hydrophobic. Heart, muscle, and fat cells make an enzyme called lipoprotien lipase and anchor it in the epithelium of the capillaries. Lipoprotein lipase cleaves the triglycerides inside the chylomicrons to fatty acids and glycerol. Free fatty acids then attach to a protein in the blood called albumin which delivers the free fatty acids to heart and muscle cells for energy metabolism or to fat cells for storage.

As /u/smith61969 said, omega fatty acids don't break down triglycerides. But omega-3 fatty acids are still thought to be good for heart health, because they do result in lower levels of triglycerides in the blood. This textbook available on PubMed states:

The lipid lowering effects of fish oil are mediated by two omega-3-fatty acids: eicosapentaenoic acid (C20:5n-3) (EPA) and docosahexaenoic acid (C22:6n-3) (DHA). Omega-3-fatty acids lower triglycerides by 10-50% but do not effect total cholesterol, HDL cholesterol, or Lp(a) levels. LDL cholesterol levels may increase with EPA + DHA treatment when the triglyceride levels are markedly elevated (>500mg/dl). EPA alone does not increase LDL cholesterol levels. Omega-3-fatty acids have few side effects, drug interactions, or contraindications. Despite numerous studies the effect of omega-3-fatty acids on cardiovascular outcomes is uncertain but additional studies are underway.

Mechanism Accounting for the Fish Oil Induced Lipid Effects

As noted above, the major effect of fish oil is to lower plasma triglyceride levels. The predominant cause of the reduction in plasma triglyceride levels is a decrease in the hepatic production and secretion of triglyceride rich lipoproteins


Omega-3 Fatty Acids and Heart Health

From University of Wisconsin Hospital and Clinics, Department of Internal Medicine (A.C.) and University of Michigan Frankel Cardiovascular Center (K.A.E.), Madison, WI.

From University of Wisconsin Hospital and Clinics, Department of Internal Medicine (A.C.) and University of Michigan Frankel Cardiovascular Center (K.A.E.), Madison, WI.

Introduction

Lifestyle intervention such as consistent aerobic exercise and a diet high in fruits and vegetables promotes cardiovascular health. A heart-healthy lifestyle decreases the risk of coronary heart disease and heart attack. Although it may seem intuitive that dietary fat is bad for the heart and that it must be avoided, certain unsaturated fats are heart healthy, and other saturated fats are not good for the heart. These heart-healthy unsaturated fats are known as omega-3 fatty acids. The 3 main omega-3 fatty acids that are beneficial for cardiovascular health are α-linoleic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA is primarily found in plant-based foods such as olive, soybean, canola, walnut, and flaxseed oils, and in walnuts and flaxseeds, as well. EPA and DHA are primarily found in marine-based foods that include the variety of fatty fish, such as tuna, salmon, mackerel, herring, trout, halibut, and cod. This Cardiology Patient Page will present the beneficial effects of omega-3 fatty acids on cardiovascular health, explain the possible mechanisms for these effects, and offer recommendations that can be implemented into a healthy lifestyle to further promote good cardiovascular health.

Beneficial Effects of Omega-3 Fatty Acids on the Heart

Several studies have shown that individuals who consumed fatty fish a few times per week had almost one-half the risk of death from coronary heart disease and almost one-third the risk of death from a heart attack in comparison with those who consumed no fish. 1 In 1 study, the risk of death from coronary heart disease was 21%, 29%, 31%, and 34% lower in those who consumed fish 1 to 3 times per month, once per week, 2 to 4 times per week, and >5 times per week, respectively, in comparison with those who consumed no fish. 2 Similarly, ALA consumption has also been shown to reduce the risk of death from coronary heart disease and from heart attack. Regarding omega-3 fatty acid supplement capsules, in the largest randomized controlled trial to date, consisting of 11 324 patients with coronary heart disease, those who took fish oil and ALA capsules daily had a 15% reduction in death, heart attack, and stroke incidence, a 20% reduction in death from any health-related cause, and a 45% reduction in sudden death from a heart attack in comparison with placebo over 3.5 years of follow-up. In addition, triglyceride levels decreased by 4%. 3 This suggests that consuming omega-3 fatty acids may reduce the risk of death from heart disease for both men and women. Omega-3 fatty acid consumption has also been shown to reduce resting blood pressure modestly and to decrease body fat levels, both of which can improve heart health.

How Do Omega-3 Fatty Acids Affect the Heart?

There are several potential mechanisms for the favorable effects of omega-3 fatty acids on overall cardiovascular health (Table 1). Omega-3 fatty acids lower triglyceride levels and increase high-density lipoprotein (ie, good cholesterol) levels. They may also decrease platelet aggregation, which can prevent the coronary arteries from occluding (occlusion would prevent or decrease blood flow to the heart). Aspirin also prevents platelet aggregation. Omega-3 fatty acids may decrease the chance of the heart having an abnormal rhythm. Omega 3- fatty acids may also increase compliance of arteries, decrease atherosclerosis through their effects on metabolism, and reduce inflammatory markers in the body. 4

Table 1. Possible Mechanisms of How Omega-3 Fatty Acids May Decrease Cardiovascular Disease

HDL indicates high-density lipoprotein.

Reprinted from Kris-Etherton et al 4 with permission of the publisher. Copyright © 2002, Circulation.

Recommendations

Many studies have shown that omega-3 fatty acids reduce cardiovascular disease and improve outcomes. Although it is unclear whether plant-derived omega-3 fatty acids (ie, ALA) or fish-derived omega-3 fatty acids (ie, DHA, EPA) are more important for the heart, both should be a part of a healthy diet. Evidence suggests that 0.5 to 1.8 g/d of combined EPA and DHA, either as fatty fish or through supplement capsules, is recommended 1.5 to 3 g/d of ALA is also beneficial, either through plant-based foods or supplement capsules. 4 Table 2 lists various food sources of omega-3 fatty acids and their omega-3 fatty acid content. The American Heart Association dietary guidelines recommend including at least 2 servings of fatty fish per week in a healthy diet. Including vegetable oils, such as soybean, canola, walnut, flaxseed, and foods such as walnuts and flaxseeds, all of which are good sources of ALA, is also recommended. 4 When possible, omega-3 fatty acids should be consumed through food sources. However, when this is not feasible, for vegetarians, and for convenience, consumption of high-quality omega-3 fatty acid capsules may also be beneficial. Patients should consult with their physicians before taking these supplements. It is important to know that any potential long-term adverse effects of these capsules are not yet known.

Table 2. Foods With Omega-3 Fatty Acids and Their Omega-3 Fatty Acid Content (Rough Estimates)

ALA indicates α-linoleic acid DHA, docosahexaenoic acid EPA, eicosapentaenoic acid.

Reprinted from Kris-Etherton et al 4 . Copyright © 2002, Circulation.


Intake Recommendations

The American Heart Association recommends eating two servings of fish every week. The best sources for EPA and DHA are salmon, herring, trout, mackerel and tuna. If you don't eat fish, the University of Massachusetts Medical School suggests taking daily fish oil supplements containing 0.8 to 1 gram of combined EPA and DHA. If your triglycerides are already high, you may need larger doses. Prescription fish oil in doses of 3 grams daily may lower triglycerides by 20 to 50 percent, according to the report published in "Biochimica et Biophysica Acta." Do not take this much fish oil without consulting your physician because the higher dose can cause side effects.