Low levels of EPA and DHA associated with depression
TAIPEI, TAIWAN. Major depressive disorder (MDD) is a serious illness that by 2020 is expected to be the second leading cause of disability, second only to heart disease. Numerous studies have been done to elucidate the possible connection between depression and blood levels of omega-3 and omega-6 long-chain polyunsaturated fatty acids (PUFAs), more specifically eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA). EPA and DHA are the main components of fish oils and there is evidence that societies with a high fish consumption tend to have a lower incidence of MDD. In addition, several, but not all, clinical trials have found that fish oil supplementation is as effective in treating MDD as is medication with standard antidepressants such as fluoxetine (Prozac).

A group of Chinese researchers report the results of a meta-analysis of 14 studies dealing with the association between depression and intake of long-chain PUFAs. Their main finding is that patients with depression have significantly lower levels of EPA and DHA and moderately lower levels of total omega-3 PUFAs than do non- depressed control subjects. The levels of AA and total omega-6 PUFAs were not significantly different between controls and patients. Limiting the analysis to patients diagnosed with major depressive disorder further strengthened the association between low levels of EPA and DHA and depression. NOTE: Fatty acid levels were measured in the phospholipid phase of cells or in serum cholesteryl esters.

The authors conclude that long-chain omega-3 PUFAs play an important role in the etiology of depression and suggest that this provides a rationale for using fish oils in the treatment of patients with depression.
Lin, PY, et al. A meta-analytic review of polyunsaturated fatty acid compositions in patients with depression. Biological Psychiatry, Vol. 68, 2010, pp. 140-47

Fish oil prevents atrial stunning
MELBOURNE, AUSTRALIA. Cardioversion and radiofrequency catheter ablation are often followed by a phenomenon known as atrial stunning. This condition involves a transient mechanical dysfunction of the left atrium and left atrial appendage (LAA) and is associated with an increased risk of post-procedure ischemic stroke, failure of improvement in cardiac output, decreased exercise tolerance, and an increased risk of arrhythmia recurrence. The degree of stunning can be measured with transesophageal echocardiography (TEE) and involves comparison of LAA emptying velocity (LAAEV), LAA emptying fraction (LAAEF), and the extent of the development of new or increased spontaneous echocardiographic contrast (SEC) after the procedure. SEC is defined as the appearance of swirling clouds of echodensity on the TEE.

A group of researchers at the University of Melbourne now report that supplementation with fish oil for at least 30 days prior to cardioversion or catheter ablation markedly reduces the extent of post-procedure atrial stunning. Their trial involved 49 patients scheduled for cardioversion of persistent atrial fibrillation (34 patients) or ablation of atrial flutter (15 patients). Only 18% had underlying heart disease, so 82% had lone AF or flutter. The patients were divided into a control group (26 patients) and a fish oil group in which 23 patients received 6 grams/day of natural fish oil [providing 1080 mg/day of eicosapentaenoic acid (EPA) and 720 mg/day of docosahexaenoic acid (DHA)] for a minimum of 30 days prior to their procedure. Due to scheduling problems fish oil supplementation was actually done for an average (mean) of 70 days. The researchers observed the following differences in LAAEV, LAAEF, SEC, and degree of atrial mechanical stunning when comparing results obtained immediately before the procedure with those obtained immediately after.

* New or increased presence of SEC

The researchers conclude that fish oil supplementation for a minimum of 30 days prior to procedures aimed at restoring sinus rhythm is highly effective in preventing post-procedure atrial mechanical stunning (82% reduction in risk). They speculate that reversion to sinus rhythm leads to an acute calcium deficiency implicated in a loss of contractile function. Fish oil is known to modulate L-type calcium channels to reduce fluctuations of concentration in heart cells.
Kumar, S, Sparks, PB, et al. Effects of chronic omega-3 polyunsaturated fatty acid supplementation on human atrial mechanical function after reversion of atrial arrhythmias to sinus rhythm. Heart Rhythm, Vol. 8, May 2011, pp. 643-49

Prescription fish oil does not prevent AF recurrence
WYNNEWOOD, PENNSYLVANIA. Fish oils (notably eicosapentaenoic acid and docosahexaenoic acid) have potent electrophysiological, autonomic nervous system modulating, and anti-inflammatory effects in atrial and ventricular tissue. Several trials have shown fish oil consumption to have beneficial effects on heart rate variability and to reduce sudden cardiac death in patients having experienced a heart attack. There is also substantial evidence that fish oil consumption helps reduce inflammation and plays an important role in preventing atherosclerosis, heart attack and ischemic stroke. Several smaller trials have also found that supplementation with from 1 to 1.7 grams/day of natural fish oil reduces AF recurrence in patients having undergone coronary bypass surgery, patients having undergone electrical cardioversion, and those with dual chamber pacemakers. The reduction in AF recurrence rate ranged from about 30% to about 60%.

Now a group of university-associated American cardiologists reports that prescription omega-3 fatty acid esters (Lovaza) is ineffective in preventing AF recurrence in paroxysmal and persistent afibbers. Their 6-month trial included 663 afibbers with confirmed paroxysmal (n=542) or persistent (n=121) AF and no substantial structural heart disease at time of enrolment from November 2006 to July 2009. The average age of the participants was 60 years, 56% were male, 90% were white Caucasians, and a large proportion of the group were obese (average BMI of 30.7). Almost half of the entire group (45%) were on statin drugs, 13% were taking an antiarrhythmic, and 39% were on ACE inhibitors or angiotensin II receptor blockers. All patients were in normal sinus rhythm at enrolment. After randomization, study participants were assigned to receive a placebo (corn oil) or Lovaza. Each 1-gram capsule of Lovaza contained approximately 465 mg of eicosapentaenoic acid and 375 mg of docosahexaenoic acid. Dosage was 8 grams/day of Lovaza or corn oil (placebo) for the first 7 days and then 4 grams/day thereafter through week 24.

At the end of 24 weeks, 48% of the paroxysmal afibbers in the placebo group had experienced one or more documented symptomatic atrial flutter or atrial fibrillation events. The corresponding number in the Lovaza group was 52%. In the persistent AF group, 33% of the placebo group experienced event(s) versus 50% in the Lovaza group. None of these differences were statistically significant. The researchers noted that the average heart rate during an episode was about 7 bpm lower in the Lovaza group than in the placebo group. They also observed an 11.5% larger drop in triglyceride levels and an 11.4% larger drop in the level of very low-density lipoprotein in the Lovaza group as compared to the placebo group at the end of the 24-week trial period.

Of particular interest is their comment that nearly half of the AF and flutter events occurred during the first 2 weeks of follow-up, suggesting that the effect of fish oil supplementation may not have rapid effects, even with high-loading doses. They conclude that Lovaza does not reduce recurrence rate among paroxysmal afibbers when given for a period of 24 weeks.
Kowey, PR, et al. Efficacy and safety of prescription omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation. Journal of the American Medical Association, Vol. 304, No. 21, December 1, 2010, pp. 2363-72

EPA improves cancer treatment
BARCELONA, SPAIN. Chemotherapy is associated with weight loss and decreased health-related quality of life (HRQOL). Spanish physicians report that providing patients undergoing chemotherapy with a nutritional supplement containing EPA (eicosapentaenoic acid), a main component of fish oil, is effective in preventing weight loss and deterioration of HRQOL. Their clinical trial included 11 patients with advanced (stage IV) colorectal cancer (CRC) who were going to receive chemotherapy (5-Fluorouracil + Oxaliplatin + Folinic acid or Capecitabine). The group was divided in half with 6 patients receiving standard nutritional counselling and 5 receiving standard nutritional counselling as well as a supplement containing 16 g protein, 6.1 g fat and 1 g EPA plus antioxidants. On average, the supplement group received 1.6 g/day of EPA. Height, weight and HRQOL were measured at baseline and after 12 weeks of treatment.

Although the sample size (11 patients) was too small to produce statistically significant differences between the two groups as far as overall HRQOL is concerned, there was a clear statistically significant difference in weight loss/gain between the two groups, with the supplement group gaining an average of 5 kg over the 12-week period as compared to an average loss of 1 kg in the control group. Both groups experienced a loss in physical functioning, but the loss was substantially greater in the control group. As far as social functioning is concerned, the supplement group experienced an average gain of 17 points, while the control group lost 14 points (on the GHS/QoL scale). Finally, the control group also experienced more fatigue and pain than did the supplement group and, while 4 of the 6 control patients experienced interruption in their chemotherapy schedule (due to toxicity) none of the patients in the supplement group did.

The researchers conclude that supplementation with EPA plus dietary counselling had a positive effect on weight maintenance, HRQOL and chemotherapy tolerability in advanced CRC patients. They recommend larger, randomized trials to confirm their findings.
Trabal, J, et al. Potential usefulness of an EPA-enriched nutritional supplement on chemotherapy tolerability in cancer patients without overt malnutrition. Nutricion Hospitalaria, Vol. 25, No. 5, September-October 2010, pp. 736- 40

Fish oils reduce exercise-induced muscle damage
URMIA, IRAN. It is well established that some forms of exercise result in acute inflammation and muscle damage. Eccentric exercises (exercises whereby the muscle under load is lengthened) such as stair stepping are particularly likely to induce inflammation, muscle soreness, injury, pain and edema. A group of German and Iranian sports medicine physicians report that supplementing with fish oils prior to, during, and following an eccentric exercise program markedly reduces biomarkers of inflammation and tissue injury.

Their study included 45 young, healthy, untrained male volunteers. All participants had blood samples drawn at baseline and were then assigned to one of three groups – fish oil group, placebo group or control group. Members of the fish oil group supplemented with a natural fish oil product providing 324 mg/day of EPA (eicosapentaenoic acid) and 216 mg/day of DHA (docosahexaenoic acid) for 30 days before the exercise session and also during the 48 hours following the end of the exercise. The placebo group received capsules containing a soybean/corn oil mixture, and the control group received no supplements for the 30 days + 48-hour period. The fish oil and placebo groups also received 100 IU of vitamin E to minimize oxidation of long-chain fatty acids.

The exercise session consisted of 40 minutes of bench stepping (knee height step, 50 cm on average, at a rate of 15 steps a minute), with 5 minutes of stepping, and 1 minute of rest between stepping periods. Blood samples were taken from all study participants immediately before the exercise session, immediately after, and 24 and 48 hours later. The samples were analyzed for the following markers of inflammation/muscle damage:

• Interleukin-6 (IL-6)
• Tumour necrosis factor alpha (TNF)
• Prostaglandin E2 (PGE)
• Lactate dehydrogenase (LDH)
• Creatine kinase (CK)
• Myoglobin (Mb)

There were no significant differences between groups in these markers either at baseline or immediately prior to the exercise session. However, levels of TNF, PGE and LDH in the fish oil group were substantially lower immediately post-exercise and at 24 and 48 hours than were levels in the placebo and control groups. Levels of IL-6, CK and Mb were substantially lower at 24 and 48 hours than were levels in the placebo and control groups. NOTE: There were no differences in inflammation marker levels between the placebo and control groups; however, these levels did increase after the exercise session.

The researchers conclude that fish oil supplementation taken before, during and following eccentric exercise provides potent anti-inflammatory protection and might serve as a potential agent to reduce exercise-induced muscle damage.
Tartibian, B, et al. Omega-3 fatty acids supplementation attenuates inflammatory markers after eccentric exercise in untrained men. Clinical Journal of Sport Medicine, Vol. 21, No. 2, March 2011, pp. 131-37