By Eric Cressey

It’s time to pick up where I left off last month in Part I.  To “reset” the stage, I’ll just say that fish oil is good because it helps with:

Crohn’s Disease:

• Belluzzi et al (1996) found that 2.7 g of fish oil per day for one-year significantly reduced the incidence of relapse in Crohn’s patients in remission. Thirty-nine of the patients received the fish oil, while 39 others received a placebo; the relapse rate was 41% lower in the former group. Regression analysis indicated that the positive effects of fish oil were independent of patient age, sex, previous surgery history, disease duration, and smoking status (34).

Ulcerative Colitis:

• Barbosa et al (2003) hypothesized that omega-3 fatty acids from fish oil tend to exert their anti-inflammatory effects in ulcerative colitis via decreases in plasma oxidative stress, acting as free radical scavengers (35).
• In a study of eighteen patients with active ulcerative colitis (characterized by diarrhea and rectal inflammation; ain’t that a pretty picture?), four months of 5.4 g combined EPA and DHA supplementation (vs. placebo) led to significantly “reductions in rectal dialysate leukotriene B4 levels, improvements in histologic findings, and weight gain (36).” English translation: their rectums looked, felt, and performed better.

Asthma:

• Nagakura et al (2000) found that ten months of EPA and DHA supplementation lessened asthma symptoms and acetylcholine sensitivity in 29 children with severe bronchial asthma (in collaboration with a controlled environment and diet) (37).
• Three weeks of 5.4 g combined EPA and DHA markedly blunted exercise-induced asthma in ten elite athletes and improved post-exercise pulmonary function significantly (38).

Cystic Fibrosis:

• In a study of thirty cystic fibrosis patients that received EPA and DHA supplementation as 1.3% of their total calories for eight months, researchers noted significant decreases in markers of inflammation. Subtle improvements in forced expiratory volume (a measure of pulmonary function) were noted as well. Furthermore, in comparison with the previous eight-month period, the patients (collectively) required much fewer days (392 vs. 721) of antibiotic therapy during the eight months on EPA and DHA (39).

Chronic Obstructive Pulmonary Disease (COPD):

• Shahar et al (1994) examined the relationship between dietary omega-3 fatty acid intake and COPD in 8,960 smokers, finding that combined EPA and DHA intake was “inversely related to the risk of COPD in a quantity-dependent fashion (40).” In other words, if you’re going to smoke, you might as well complement that metallic cough with some fish breath; it’ll probably protect you from COPD down the road.
• Romieu and Trenga (2001) observed that “data also suggest that omega-3 fatty acids may have a potentially protective effect against airway hyperreactivity and lung function decrements” in both children and adults (41).

Sickle Cell Anemia:

• In patients with sickle cell disease, omega-3 fatty acid supplementation at 0.1 g/kg per day “reduced the frequency of pain episodes requiring presentation to the hospital from 7.8 events during the preceding year to 3.8 events/year.” Conversely, subjects receiving dietary olive oil (the control group) experienced 7.1 pain events/year, only slightly less than the 7.6 event average from the previous year. This reduction in pain episodes was likely attributable to the effects of EPA and DHA on reducing prothrombotic activity (42).
• A study of Nigerian children found that omega-3 fatty acid concentrations were 40-50% lower in the phospholipid membranes of children with sickle cell disease than in those of healthy children. The researchers noted that “the phospholipids of the children with SCD are less fluid relative to those of their healthy counterparts. (43)”

Menstrual Symptoms:

• In a Danish study, low intakes of omega-3 fatty acids were correlated with more severe menstrual symptoms. Dysmenorrhea correlations were also observed in low omega-3: omega-6 ratios and vitamin B12 deficiencies. The body utilizes omega-3s to create type-3 prostaglandins that are less “aggressive” than those formed from other fatty acids. The net result of utilizing omega-3s as raw materials appears to be milder symptoms. Prostaglandins act like hormones, controlling uterine contractions and pains (44).

Vision/Eye problems (glaucoma):

• Ninety days of DHA with vitamins E and B significantly improved computerized visual field (CVF) and retinal contrast sensitivity in thirty chronic glaucoma patients. The researchers concluded that such a supplement merits inclusion in an intervention to prevent the progression of glaucoma-related damage (45).

Multiple Sclerosis:

• Cunnane et al (1989) found that in comparison with their healthy counterparts, MS patients had lower omega-3 fatty acids in their plasma (46).
• As a follow-up, Gallai and colleagues (1995) found that omega-3 supplementation in MS patients led to decreases in proinflammatory eicosanoids, indicating potential for fish oil in modulating some immune function decrements associated with MS (47).

Prenatal and postpartum support:

• Supplementation with DHA between the 24th and 28th week of pregnancy significantly increased (by roughly six days on average) the duration of gestation. Birth weight, length, and head circumference all increased slightly as well (48).
• A study of Norwegian children found that “use of cod liver oil in the first year of life was associated with a significantly lower risk of type 1 diabetes.” Regression analysis implied that this effect was independent of the oil’s vitamin D content, and was likely due to the omega-3 fatty acids in the oil (49).
• Malcolm et al (2003) noted an association between “the DHA status of infants at term and early postnatal development of the pattern-reversal VEP [visual evoked potential], indicating that DHA status itself may influence maturation of the central visual pathways” in infants. These assertions were based on results seen in a trial of one hundred women that received either fish oil capsules or a placebo (50).
• Uauy and colleagues (2003) found not only that long chain polyunsaturated fatty acid supplementation in newborns improved visual acuity at four months, but also there was “a significant relation between the total DHA equivalents provided and effectiveness (51).” In other words, more was better (to a certain point, of course). This effect is likely due to effects on physical properties of the membranes, neurotransmitters, and modulation of gene expression in the retina and brain (52).
• Because of the crucial role of essential fatty acids as structural components of all cell membranes, profound implications can be seen at the “brain, retina and other neural tissues are particularly rich in long-chain polyunsaturated fatty acids (LC-PUFA) (52).”
• Uauy et al (2001) asserted that “light sensitivity of retinal rod photoreceptors is significantly reduced in newborns with n-3 fatty acid deficiency, and that docosahexaenoic acid (DHA) significantly enhances visual acuity maturation and cognitive functions (52).” Furthermore, “DHA also has significant effects on photoreceptor membranes and neurotransmitters involved in the signal transduction process; rhodopsin activation, rod and cone development, neuronal dendritic connectivity, and functional maturation of the central nervous system (52).” It beats feeding potato chips to your kids, doesn’t it?
• Data from Dunstan et al (2003) suggests that there may be a role for omega-3 fatty acids in the prevention of allergic disease. In a study of 83 atopic pregnant women receiving fish oil or placebo, the researchers noted that infants from the fish oil group had significantly less severe atopic dermatitis at age one, although no difference in the frequency of the disease was apparent between groups (53).
• Williams and colleagues (1995) described preeclampsia (affecting pregnant women) as “a systemic disease characterized by diffuse endothelial dysfunction, increased peripheral vascular resistance, coagulation abnormalities, antioxidant deficiency, persistent elevations of maternal leukocyte-derived cytokines, and hyperlipidemia (54).” These researchers conducted a study to examine the relationship between omega-3 fatty acid intake and preeclampsia. Women with the lowest omega-3 levels were 7.6 times more likely than those with the highest levels to have preeclampsia-related complications during their pregnancies. Moreover, “a 15% increase in the ratio of omega-3 to omega-6 fatty acids was associated with a 46% reduction in risk of preeclampsia (54).”

Psoriasis:

• Psoriatic lesions are characterized by increased concentrations of arachidonic acid. EPA exerts an anti-inflammatory effect that likely works to counteract the pro-inflammatory effects of arachidonic acid and its metabolites. In a study of 83 patients with chronic plaque-type psoriasis, researchers found that omega-3 fatty acid infusions were superior to omega-6 infusions (the placebo) “with respect to change in severity of psoriasis per body area, change in overall erythema, overall scaling and overall infiltration, as well as change in overall assessment by the investigator and self-assessment by the patient (55).”
• Grimminger et al (1993) observed that high dose intravenous omega-3 fatty acid supplementation exerted a rapid beneficial effect on inflammatory skin lesions in twenty patients hospitalized with acute guttate psoriasis. These effects were most likely mediated through eicosanoid metabolism regulation (56).

Photosensitivity:

• Hydroa vacciniforme ?also known as photosensitivity ? is a serious skin disorder characterized by blistering (especially on the face) after even the slightest amount of sun exposure; it affects primarily children. In a small study, Rhodes and White reported that three months of fish oil supplementation reduced erythemal sensitivity to UVA and UVB (two types of ultraviolet radiation), and yielded modest improvements in overall symptoms (57).

Diabetes/Insulin Resistance:

• Increased oxidative stress is a hallmark of type 2 diabetes. Jain et al (2002) sought to determine the effects of very low dose omega-3 fatty acid supplementation (0.6 g combined EPA and DHA) on type 2 diabetics. Even at such a low dose, they found that the patients in the omega-3 group exhibited significantly greater improvements in glycemic status, blood pressure, lipid profiles, and reductions in markers of oxidative stress as compared to a placebo group of type 2 diabetics (58).
• It’s well established that the various types of fatty acids are clearly involved in the onset of chronic conditions (such as insulin resistance and obesity) characterized by inflammation. In overweight subjects, higher concentrations of saturated fats and omega-6 and lower concentrations of omega-3 fatty acids are significantly associated with higher concentrations of circulating interleukin-6 (IL-6), a marker of inflammation. Interestingly, though, these associations are not apparent in lean subjects (59).
• In a 14-year study of 84,204 female nurses ages 34-59, the risk of type 2 diabetes was significantly positively associated with high consumptions of trans fatty acids and cholesterol, whereas the condition was negatively associated with omega-3 and omega-6 polyunsaturated fatty acids. The investigators estimated that “replacing 2% of energy from trans fatty acids isoenergetically with polyunsaturated fat would lead to a 40% lower risk” of type 2 diabetes (60). I guess it’s time to replace the doughnuts in the nurses’ lounge with canned salmon. Or, you could contact Krispy Kreme about introducing the chocolate frosted sardine filled doughnut!
• Chicco et al (1996) found that low-dose fish oil supplementation in rats led to significant reductions in blood lipids and plasma insulin levels without changes in glucose tolerance. The investigators hypothesized that because no changes in pancreatic insulin content were apparent, the lower insulin levels may have been due to improvements in peripheral insulin sensitivity (61).
• Unfortunately, studies attempting to demonstrate these effects in humans have been less impressive (62-64). In spite of the fact that omega-3 consumption in the form of fish increased HDL cholesterol and improved overall dyslipidemia in overweight patients, Mori et al (1999) found no independent effect of fish consumption on glucose or insulin (62). Others have come to similar conclusions with actual fish oil supplementation (63,64).

Resting Metabolic Rate:

• Eric Noreen has done extensive work examining the effect of fish oil on resting metabolic rate (RMR). At the 2003 American College of Sports Medicine Annual Conference, Noreen presented the results of a study that compared RMR in subjects supplemented with 9g of safflower oil (predominately omega-6), 3, 6, or 9g of 60% concentrated fish oil. The fish oil groups saw daily RMR increases of 141 to 448 calories, whereas the safflower group’s RMR actually decreased. As an added bonus, the fish oil group also lost a little bit of fat mass while gaining some lean body mass. (65)

Body Composition Regulation and Leptin:

• Leptin is a hormone released by adipocytes that has a great impact on body fat levels. In simple terms, the amount of leptin present in one’s body serves as feedback to the brain about whether one is okay as far as nutritional status is concerned. As you get leaner, leptin levels drop; as you get pudgier, they go up. These are important responses, as high leptin concentrations are associated with decreased hunger and food intake and increased energy expenditure, all of which are important factors in getting and staying lean.
• Unfortunately, as you get leaner, leptin levels drop as your body essentially senses starvation-like conditions; this decrease makes it difficult to get and stay lean. Fish oil may be able to help with this problem, as rats fed high omega-3 diets demonstrate up-regulation in plasma leptin concentrations significantly above what is predicted based on body fat levels (66,67).
• In an overfeeding study of rats with 42% of their energy intakes as fish oil, safflower oil, olive oil, or beef tallow, the fish oil group had the greater lean body mass gains and the lowest fat mass gains (68). In other words, if you’re going to stuff yourself, be sure to include some fish oil in the feast.

Psychological Disorders:

• Maes et al (1999) observed that there is a significant deficiency in omega-3 fatty acids serum phospholipids and red blood cell membranes in major depression. Furthermore, the deficiency is likely a result of abnormal omega-3 metabolism in depressed patients and may continue in spite of treatment with antidepressants (69). As such, fish oil treatment may serve as an important adjunct to ? or even a replacement for – traditional antidepressant therapy
• Hibbeln and Salem (1995) proposed that low concentrations of polyunsaturated fatty acids may be related to increased risks of suicide, depression, alcoholism, and post-partum depression (70).
• Four out of five trials of EPA in the treatment of schizophrenia have demonstrated significant reduction in patient episodes of severe mania and depression following supplementation (71).
• In an eight-week study of 28 clinically depressed patients receiving either 9.6 g omega-3 fatty acids per day or a placebo, there were significant decreases in scores on the Hamilton Rating Scale for Depression, an evaluative tool on which high scores indicate more severe feelings of depression (72).
• Zanarini and Frankenburg (2003) studied the effects of 1 g/day ethyl-EPA (or placebo) on thirty females with borderline personality disorder. The ethyl-EPA supplement proved “to be superior to placebo in diminishing aggression as well as the severity of depressive symptoms (73).”
• Attention-deficit/hyperactivity disorder (ADHD) may be related to an abnormality in polyunsaturated fatty acid metabolism. As such, both Richardson and Puri (2000) and Kidd (2000) have proposed that omega-3 fatty acid supplementation may have merits in the treatment of this condition, although more research is warranted in this regard (74,75).

The Response to Stress:

• Here’s one for the Type A folks out there. Delarue et al (2003) studied seven subjects on two occasions separated by three weeks. In the first session, these seven individuals were subjected to mental stress in the form of mental arithmetic and the Stroop task, and measures of sympathoadrenal activation (plasma cortisol, catecholamines, energy expenditure, and adipose tissue lipolysis) were taken thirty minutes after the stress. After this mental stress challenge, each subject supplemented with 7.2 g fish oil/day for three weeks, at which point they took the battery of tests again. In this second session, plasma epinephrine, cortisol, energy expenditure, and plasma non-esterified fatty acids concentrations, were all significantly lower than in the initial session. The investigators therefore concluded that omega-3 fatty acid supplementation “inhibits the adrenal activation elicited by a mental stress, presumably through effects exerted at the level of the central nervous system (76).” It appears that omega-3 fatty acids are able to partially inhibit the pro-inflammatory response to psychological stress (77). Ever get a racing heart or high blood pressure before a test, presentation, or job interview? Fish oil may be just what you need to get mellow!

Migraine Headaches:

• In a study of 27 adolescents with chronic migraines, supplementation with fish oil led to reductions of 87% in headache frequency, 74% in headache duration, and 78% in headache severity compared to a period prior to the study. Interestingly, olive oil (the placebo) produced similar results, although they were not quite as favorable (78).

Epilepsy:

• Many anticonvulsant medications for epileptics have highly undesirable side effects. In light of the profound roles of omega-3 fatty acids in immune and nervous system activities, Rabinovitz and colleagues (2004) compared the effects of carbamazepine (CBZ) and SR-3, a compound with a 1:4 omega-3: omega-6 ratio, on seizure control efficiency, and protection against cognitive impairment and cortisol elevation in rats. While the two treatments were equally effective in controlling seizures, SR-3 proved to be superior on the latter two measures (79). Treating epilepsy with omega-3 compounds is certainly a new frontier, so more research is warranted (especially in human subjects) to determine its true efficacy.

Chronic Fatigue Syndrome (CFS):

• The exact cause of CFS remains to be determined, but there is speculation that it could involve abnormalities at the immune, neuroendocrine, and autonomic levels. Because fish oil inhibits the production of certain pro-inflammatory substances, many experts believe that it holds great potential in the treatment of CFS. Research is ongoing (80).

Fibromyaglia:

• Several experts predict a role for omega-3 fatty acids in the treatment of fibromyalgia; anecdotal evidence supports this assertion, and further research is certainly warranted on this front (81).

Cirrhosis:

• In chronic liver disease, widespread inflammation can cause the liver to become fibrotic. In light of the known anti-inflammatory benefits of omega-3 fatty acids, Hayashi et al (1999) studied the effect of EPA and DHA supplementation on four patients with hepatitis B infection, one with hepatitis C virus cirrhosis, and one with alcohol-related cirrhosis. Subtle reductions were observed in globulin (a marker of liver pathology) with simultaneous increases in HDL cholesterol and various apolipoproteins (protective agents against hepatitis-related liver disease) (82).

Closing Thoughts

If you aren’t taking fish oil, you’re an idiot. Seriously. Okay, I’ll leave you with a bit more practical wisdom instead. The typical fish oil capsule you’ll encounter is 1000 mg fish oil; we, however, are more concerned with the EPA and DHA content of that 1000 mg. In most cases, you’ll find 180 mg EPA and 120 mg DHA per capsule. A good rule of thumb (especially based on the results of the clinical trials) is to consume 3-6 g combined EPA and DHA per day; at this capsule size, you’d need 10-20 capsules per day. For this reason, liquid fish oil is a great alternative.

A small percentage of people will suffer from fish burps with the EPA/DHA supplementation; if you’re one of those individuals, I recommend you take all your fish oil with your last meal of the day. That way, if you have salmon belches, they’ll be in your sleep! Another alternative is to just eat fatty fish every day, but that can get old very quickly!

Finally, be patient! Read the finer details of all of the studies that I’ve outlined and you’ll realize that the majority of them were at least 6-8 weeks in duration (usually longer). Your body needs time to make good use of these healthy raw materials, so count on a few months before you see noticeable results if you have one of the aforementioned conditions. For the rest of you, you probably won’t notice much, but I guarantee that you’ll be healthier in the long run.

References (continued)

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