Omega-3 fatty Acids-Straight Up

GUJHS. 2003 Aug; Vol. 1, No. 1

Daina Slekys*

The interest in fish as a health protector sparked with the news of drastically low incidence of heart disease in the Eskimo population. 3 Researchers have begun to realize that, despite the Eskimo’s apparent high fat intake, the population has low incidence of cerebral vascular attack (CVA) and myocardial infarction.  A possible reason for this is that they eat predominately fish, sometimes up to 5 or 6 times a week.7 To see if this was, indeed, the missing link to reducing cardiac disease, epidemiological data was produced from other fish-eating populations, like the Bantu fishermen in Tazmania, for example.7European countries that tend to eat fish about 3 times per week, like the islands of Crete and northern Europe, have significantly lower numbers of cardiovascular disease than those that do not.15 In light of these facts, experiments exploded all over the world in order to discover if it is fish causing these effects and, if so, what exactly and how?   Numerous researchers have suggested that omega-3 oils are the beneficial constituent in fish that help prevent and treat cardiovascular disease, myocardial infarctions, and CVA.2,3,5,7,8,13,17,18,21

What are omega-3 fatty acids? Nomenclature and Structure

Omega-3 fatty acids are long-chain polyunsaturated fatty acids with median lengths of 22 carbon atoms.  Hydrocarbon chains have a hydrophobic methyl group at one end and a hydrophilic carboxyl group at the other end.  Specifically for omega oils, the methyl end is referred to as the “omega end” and the carboxyl terminus is known as the “delta end.” 14 Fatty acids differ by the number and location of double bonds and by the length of their hydrocarbon chain.  Fatty acids can be categorized as saturated, unsaturated, or polyunsaturated.

Figure 1.

There are two subdivisions of polyunsaturated fatty acids: Omega-3, also known as Alpha linolenic acid (ALA) and Omega-6, or linolenic acid (LA).  Omega-3 molecules have their first double bond at the third carbon (C-3) on the hydrocarbon chain (figure 1),10 whereas the omega-6 oils house their first double bond on C-6.  LA and ALA areessential fatty acids which are crucial to the body’s function and have to be introduced externally through the diet.  These are especially important because they are the predominant fatty chains in the human body.  Omega-3 oils can be elongated and de-saturated into eicosopentoic acid (EPA) and docasahexanoic acid (DHA) by the human body.  EPA and DHA are the major constituents of fish oil and  provide a general protection from cardiovascular disease and other major health problems, including asthma, depressive disorders, and stroke.1,2,3,9,11

Cardioprotective evidence

Fish oils are generally composed of omega-3 oil and vitamin E.  After much investigation, the omega oil component demonstrated to be the active ingredient.1,3 Vitamin E provides for more antioxidant properties, beneficiating skin health and organ durability, than cardioprotective properties.3 Omega-3 oil seems to effect platelet activity; a study on rats done by Leray Claude et al (2001)1 suggests that dietary ingestion of DHA and EPA in any amount results in hypocoagulation even after 1 week.  Studies have shown that intake of dietary omega-3 fatty acids is significantly inversely associated with low risks for cardiovascular disease and CVA.17,2 A study aimed at comparing the properties of vitamin E with omega-3 acids done by Patricia J. Rand et al (1999)3, had convincing results: while purified capsules of EPA and DHA reduced myocardial infarction among those with cardiovascular disease by at least 20%, Vitamin E pills showed absolutely no change.  Further investigations concluded that omega-3 oils are the primary and active ingredients as well.1

Studies researching the effect of omega 3 oils found that they have 3 major effects on cardiovascular disease: They suggest antiarrhythmic,1,4,10,11 hypolipidemic,1,4,7-11 and antithrombotic1,2,8-11,21 properties.  Sperling et al.(1993)16 showed in a controlled study that in fish eating populations, there was 48% less morbidity due to cardiac arrhythmias than in non-fish eating populations.  Certainly, such a drastic change in arrhythmia occurrence is clinically significant.

Levels of LDL cholesterol proteins were studied during the study by Santica et al (1999) to suggest that in a fish-eating group, LDL blood levels significantly decreased in comparison to the non fish-eating group7.  Since high LDL levels are associated with coronary heart disease, this hypolipidemic aspect is essential.

Thirdly, its antithrombotic effects were the subject of Klaus et al.’s (1999)6 research.  Omega-3 oils decreased thrombosis and relapse of myocardial infarction in cardiovascular patients by 29%6.  These effects marry to provide a well-rounded protection for the heart.

Consumption of fish omega oils, even in small amounts, have shown to decrease mortality in general cardiovascular patients8, in those with myocardial infarction6,8, and in all participants overall.6,8 One study observed a significant inverse association between fish intake and risk of stroke, primarily thrombotic stroke, after adjustment for cardiovascular risk factors and selected dietary variables.  Women who ate fish 2-4 times per week experienced a 48% decrease in stroke.2 This in mind, health care workers see the beneficial cardioprotective effects of fish and omega-3 oils as undeniable.

Possible biochemical and physiological mechanisms of action for EPA and DHA

Clinicians furthered their research to include the possible mechanisms by which omega-3 oils have hypolipidemic, anti-arrhythmic, and antithrombotic effects.  Omega-3 fatty acids have been shown to reduce endothelium dysfunction in cardiac patients14,16,6.  Many researchers attribute this to its potential affect on the sympathetic nervous system.8,13Omega-3 polyunsaturated fatty acids reduce endothelium dysfunction by reducing sympathetic overactivity8,13 and enhancing nitric oxide-mediated vasodilatation.  Ongoing studies involve its interaction with statins, antiplatelets, beta-blockers, or angiotensin-converting enzyme inhibitors better define the mechanism of action.  The decrease in sympathetic activity results in minimized arrhythmias.8,6,14,16 In another study by Klaus et al.(1999),6 inhibition of monocytic adhesion was noted with the addition of omega-3 oils to the diet.  Neutrophils were found to be less chemotactic in fish eaters as well.6,16Monocytes, macrophages, and neutrophils are key players in the mechanisms of inflammation, synthesizing and secreting a series of cytokines and growth factors influencing the inflammatory process at the site of a vascular lesion;6 Inhibiting them would reduce inflammation.  Certain platelet-derived growth factors stimulated by monocytes promote cytokine secretion, which release platelets and thus trigger clotting.  In this study, dietary ingestion of omega-3 acids decreased blood serum levels of monocytes, thereby decreasing the secretion of platelet derived growth factors that lead to clotting. Since platelet over activity is reason for thrombi in those with cardiovascular disease,2 omega-3 oils could decrease coagulation problems or thrombotic events8through this mechanism (figure 2).  Since platelets are intimately involved in the pathogenesis of arteriosclerosis, omega-3 oils are antithrombotic.6 This not only affects those with cardiac problems, but greatly reduces chances for stroke as well.2,24

 

Other mechanisms help to explain omega-3’s beneficial effects on the cardiac system.  Santica et al.(1999) showed that, although lipoprotein(a) levels are known to be largely linked genetically to apolipoprotein(a), fish eaters and those that ingested EPA/DHA capsules 3 times per week had significantly lower levels of lp(a) in their blood, 7regardless of familial background.  Obviously, omega oils have a drastic effect on decreasing lipid levels as well.  Since high lipid levels are precursors to cardiovascular disease, the hypolipidemic properties of omega-3 oils help to inhibit the disease’s progression

Figure 3: Omega-3 oils help to maintain integrity of cardiac muscle

Anti-arrhythmia in fish eating populations can be attributed to the fact that omega-3 oils prevent myocardial cells from losing calcium, which is needed for appropriate cardiac contraction13,21.

Figure 4: Overall cardioprotective effects of omega-3 acids

Other clinical implications of omega-3 oils

Besides cardioprotective activity, omega-3 oils have shown to be beneficial in other areas of health, including pre-mature infant health, asthma, bipolar and depressive disorders, dysmenorrhea and diabetes.4,9,11,15,19,20,22,23

Reduced rates of low birth weight in fish-eating northern Europeans continue in marked contrast with persistently higher rates of low birth weight in non-fish consuming populations.15 This fact prompted McGregor et al (2001)15 to study the effects of omega-3 oils on pregnancy outcome.  Fatty acids, including DHA and EPA, are actively transported across the placenta and incorporated to a major extent in the blood stream and fetal tissues, including neural tissues, especially in the latter part of pregnancy.23 Since imbalances in contemporary diets include those of omega-3 oils, babies in utero may not receiving sufficient amounts of the oil.  Consequently, mothers who do not eat fish have increased preterm parturition, preeclampsia, and impaired brain and retinal development.15,23

Omega-3 fatty acids also appear to effectively alleviate the symptoms of dysmenorrhea in a study done on adolescents.20 Since increased omega intake leads to increased incorporation of the oils into the uterus,15,20,23 less potent prostiglandins are produced, resulting in decreased myometrial contractions and uterine vasoconstriction.   The decreased clotting by omega-3 acids helps to reduce ischemia.20 A study done by Harel et al.(1996)20 suggests this factor in treating dysmenorrhea in adolescents.

Beyond gynecological and cardiovascular patients’ benefits, there is evidence that asthma sufferers may profit as well from omega-3 acids.  Children in Japan, although exposed to twice the smoke and air pollution than American children, have a 75% less prevalence of asthma.22

In addition, research suggests that depressive and bipolar disorders profit from omega-3 acid intake.9 Studies have reported that countries with high rates of fish oil consumption have low rates of depressive disorders.  Nemets et al.(2002)9 studied daily EPA intake (2g/day) among those with diagnosed depression and bipolar disorder.Twenty patients with a current diagnosis of major depressive disorder participated in a 4-week, parallel-group, double-blind addition of either placebo or E-EPA to ongoing antidepressant therapy. Seventeen of the patients were women, and three were men.  Highly significant benefits of the addition of the omega-3 fatty acid compared with placebo were found by week 3 of treatment, including a decrease of core depressive symptoms such as low mood, guilt feelings, worthlessness, and insomnia.9 With little improvement in the placebo group, these results are noteworthy and imply a degree of effect of omega-3 in the treatment of depression.  Stoll et al.(1999)11 launched a similar placebo-controlled trial and found the same results11.  Severus et al.(1999)19 expanded on the research and found that those with major depressive disorders had a significant depletion in red blood cell membrane omega-3 fatty acids.  In conclusion, there is suggestive evidence that omega-3s help depression.

Table 1: U.S. Recommentations10

With much information on the extent to which omega-3 fatty acids benefit the health of the human population, health care workers have started to implement them into their treatment protocols.  Egg yolks, liquid lecithin, chicken thighs, tofu, wheat grass, and flax oil are some sources of omega-3 oils besides fish12.  Even though fish have the densest form of fatty acids, the others are good alternatives.  While today, the US average (table 1) intake of omega-3 oils is about 1.6 grams per day, FDA recommendations suggest a minimum of 2.3 grams/ day (a 57% increase.)10 Two to three fish meals a week should suffice (table 2).

Table 2: Fish levels of omega-3 acids.10

In conclusion, there is enough evidence to suggest that omega-3 acids are salubrious.  Ingestion of fish regularly might not only help reduce cardiovascular disease, but also other seriously debilitating conditions, such as asthma and depression.

*Georgetown University School of Nursing and Health Studies, 3700 Reservoir Rd. NW, Washington, DC. 20057. slekysd@georgetown.edu

References:

  1. Leray, Claude et al. “Long Chain n-3 Fatty Acids specifically affect rat coagulation factors dependent on Vitamin K: relation to peroxidative stress.” Arteriosclerosis, Thrombosis, and Vascular Biology 21(3): Mar, 2001, pp.459-65.

2.   Hiroyasu, Iso et al. “Intake of Fish and Omega-3 Fatty Acids and Risk of Stroke in Women.” JAMA 285(3): Jan 17, 2001, pp. 1815-21.

  1. Rand, Patricia J. MD and Schooff, Michael MD. “Do Fish oils or Vitamin E reduce morbidity and mortality after MI?” The Journal of Family Practice48(11): Nov, 1999, pp. 847-8.
  2. Cerrato, Paul. “Omega-3 Fatty Acids: Nothing Fishy Here!” RN 62(8): Aug, 1999, pp.59-60.

5.   Robertson, Rose MD and Smaha, Lynn MD, PhD. “Can a Mediterranean-Style Diet Reduce Heart Disease?” Circulation 103(13): April, 2001, p.1821.

6.   Baumann, Klaus H et al. “Dietary Omega-3, Omega-6 and Omega-9 Unsaturated Fatty Acids and Growth Factor and Cytokine gene expression in Unstimulated and Stimulated monocytes.”  Arteriosclerosis, Thrombosis, and Vascular Biology 19(1): Jan,1999,pp.59-66.

  1. Marcovinam, Santica M et al. “Fish Intake, Independent of Apo(a) size, Accounts for Lower Plasma Lipoprotein(a) levels in Bantu fishermen of Tanzania: the Lugalawa study.” Arteriosclerosis, Thrombosis, and Vascular Biology 19(5): May, 1999,pp.1250-6.
  2. Buchner, Heiner C. MD et al. “N-3 Polyunsaturated Fatty Acids in Coronary Heart Disease.” The American Journal of Medicine 112(4): Mar, 2002, pp. 298-304.

9.   Nemets, Boris MD et al. “Addition of Omega-3 fatty acid to maintenance medication treatment for recruitment unipolar depressive disorder.” The American Journal of Psychiatry 159(3): Mar,2002, pp.477-9.

10. Harper, Charles MD et al. “The Fats of life.” Harper 161(8): Oct, 2001, pp.2185-92.

11. Stoll, Andrew L. MD et al. “Omega 3 fatty acids in Bipolar Disorder.” Archives of General Psychiatry 56(5): May, 1999, pp.407-12.

  1. “Dietary Sources of Long-Chain n-3 Polyunsaturated Fatty Acids.” JAMA275(11): Mar, 1996, p. 836.
  2. De Lorgeril, Michel MD. “Fish and N-3 Fatty Acids for the Prevention and Treatment of Coronary Heart Disease.” The American Journal of Medicine112(4): Mar, 2002, pp.316-9.

14. Holub, Bruce J. “Clinical Nutrition : 4. Omega-3 Fatty acids in cardiovascular care.” CMAJ 166(5): Mar, 2002, pp. 608-15.

15. McGregor, James A MDCM et al. “The Omega 3 Story: Nutritional prevention of preterm birth and other adverse pregnancy outcomes.” Obstetric and Gynecologic Survey56(6): May, 2001, pp.S1-S13.

16. Sperling, Richard et al. “Dietary Omega-3 Polyunsaturated Fatty Acids Inhibit Phosphoinositide Formation and Chemotaxis in neutrophils.” The Journal of Clinical Investigation 91(2): Feb, 1993, pp. 651-60.

17. HU, Frank MD et al. “Fish and Omega-3 Fatty Acid Intake and Risk of Coronary  Heart disease in Women.” JAMA 287(14): Apr, 2002, pp.1815-21

18. Rosenberg, Irwin. “Fish-Food to Calm the Heart.” The New England Journal of Medicine 346(15): Apr, 2002, pp.1102-3.

19.    Severus, Emanuel MD et al. “Omega-3 Fatty Acids-the missing link?” Archives of General Psychiatry 56(4): Apr, 1999, pp.380-1.

20.    Harel, Zeev MD et al. “Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents.” American Journal of Obstetrics and Gynecology 174(4): Apr, 1996, pp.1335-8.

21.    Albert, Christine M et al. “Blood levels of long-chain n-3 fatty acids and the risk of sudden death.” New England Journal of Medicine 346(15): Apr, 2002, pp.1113-8.

22.    Mermer, C and Mercola, J. “Omega-3s and Childhood asthma.” THORAX 57(3): Mar, 2002, p.281.

23.    Olsen, Sjurdur Frodi et al. “Low consumption of seafood in early pregnancy as a risk factor for preterm delivery.” BMJ 324(7335): Feb, 2002, p.447.

24.    Iso, Hiroyasu MD et al. “Linoleic acid, other fatty acids, and the risk of stroke.” Journal of the American Heart association 33(8): Aug, 2002, pp. 2086-93.