Obesity, Weight Loss and Exercise

Western society is characterized by a sedentary lifestyles and obesity has reached epidemic proportions at all ages. Today’s average person lives in a nutritional environment and has adopted a non-active lifestyle that differs from what our genetic makeup requires. Specifically, the present Western diet is deficient in omega-3 fatty acids with a ratio of omega-6 to omega-3 fatty acids of as high as 20:1 instead of 1:11,2. Human beings evolved on a diet in which there was a balance between the omega-6 and omega-3 fatty acids, both of which influence cellular metabolism and gene expression.

Key Points:

1. Omega-3 fatty acids increase fat break-down and reduce fat storage.
2. Omega-3 fatty acids lead to higher weight loss and greater decreases in BMI.
3. Omega-3 fatty acids reduce obesity.
4. Exercise, omega-3 fatty acids and diet restriction work in synergy to improve weight loss.
5. Omega-3 fatty acids improve heart parameters during exercise by reducing heart rate and improving oxygen delivery to the heart.
6. Omega-3 fatty acids reduce exercise induced asthma/bronchoconstriction.
7. Omega-3 fatty acids promote recovery from exercise and exercise induced inflammation.

Human Obesity Studies on Omega-3 Fatty Acids
Omega-3 fatty acids influence the balance between energy intake and expenditure; and reduce body weight and fat deposition in animal models. They inhibit key enzymes responsible for fat/lipid synthesis, such as fatty acid synthase and stearoyl-CoA desaturase-1, enhance lipid oxidation (fat-breakdown) and thermogenesis, while preventing free fatty acids from entering adipocytes for lipogenesis (fat storage)3. Therefore, omega-3 fatty acids: EPA and DHA exhibit an "anti-obesity" effect. Recently, a study was conducted to compare the effect of omega-3 and a low calorie diet, or just dieting for weight reduction in 20 obese women. Higher weight loss, a larger decrease in BMI, and a significant decrease in hip circumference loss were seen in the group which was given omega-3. Higher beta-hydroxybutyrate activity was seen in the omega-3 group which suggested higher lipid break down (ketogenesis) and higher fatty acid oxidation and a significant negative correlation was seen between BMI change and the omega-3 fatty acid DHA4. In another study, omega-3 fatty acid intake modulated satiety, and led to feelings of fullness in overweight and obese volunteers during weight loss5. Furthermore, in young, overweight men, the inclusion of either lean, fatty fish, or fish oil as part of an energy-restricted diet resulted in approximately 1 kg more weight loss after four weeks, than did a similar diet without seafood or supplement of marine origin. These results suggested that the addition of seafood to a nutritionally balanced energy-restricted diet boosts weight loss6.

Animal Research for Obesity and Omega-3
The possible involvement of intestinal lipid metabolism in the development of obesity has also been investigated. Mori et al. (2007)7 examined the effect of fish oil ingestion on intestinal lipid metabolism in relation to obesity. When diet-induced obesity-prone C57BL/6J mice were fed a 30% fat diet with 8% fish oil for five months, body weight gain was significantly reduced compared with mice fed a 30% triacylglycerol (TG) diet without fish oil. In addition to modulating messenger RNA (mRNA) levels in the liver, fish oil ingestion for two weeks affected the intestinal mRNA levels of lipid metabolism-related genes, i.e. at the genetic level; there was an increase in fat-breakdown. Fish oil ingestion also affected lipid metabolism-related enzyme activity; fatty acid beta-oxidation, omega-oxidation in the small intestine of mice fed the 8% fish oil diet. In short, omega-3 increased the amount of fat break-down and therefore diminished the amount of fat in mouse intestine. These findings suggest that an upregulation of intestinal lipid metabolism (fat-break-down) is associated with the anti-obesity effect of fish oil7.

The effect of omega-3 PUFAs on obesity has also been assessed in Otsuka Long-Evans Tokushima fatty (OLETF) rat. In these animals, omega-3 prevented and/or alleviated obesity-related disorders through the suppression of fatty acid synthesis (fat production), enhanced fatty acid beta-oxidation (fat break-down), and increased serum adiponectin levels8. Omega-3 fatty acids have been shown to reduce adiposity in animals fed a high-fat diet and EPA/DHA limits the development of obesity and reduces adipose tissue. Weight gain induced by composite high-fat diet in C57BL/6J mice was limited when the content of EPA/DHA was increased from 1 to 12% (wt/wt) of dietary lipids. Accumulation of adipose tissue was reduced9. In another study, supplementation with fish oil reduced the increase in adipose tissue weight after a high lard diet in rats10.

Obesity and Inflammation
Lipid metabolism, obesity and inflammation are intimately related. Fasting plasma triglycerides, acute phase proteins and BMI were studied in 159 healthy men and the effect of 6 g/d fish oil for 12 weeks on the former two parameters studied. Possession of genotypes associated with raised inflammatory stress strengthened the association between fasting plasma triglycerides and C-reactive protein. It was determined that the ability of fish oil to exert a lipid-lowering, anti-inflammatory effect in healthy men is influenced by BMI and possession of the LT-alpha+252 A allele11. Gunnarsdottir et al. assessed the effects of fish oil consumption on blood lipid concentration during weight loss. Three hundred and twenty-four men and women, aged 20-40 years with a body mass index of 27.5 to 32.5 were randomized to one of four groups: sunflower oil, salmon diet (3 x 150 g week), or fish oil (EPA + DHA capsules). In their study, a weight-loss diet including oily fish resulted in greater triglyceride reduction than did a diet without fish or fish oil12.

Degree of Obesity
Omega-3 fatty acids are also able to modulate the intensity of obesity. Scaglioni and colleagues13 assessed whether plasma levels of long-chain polyunsaturated fatty acid are associated with the degree of obesity in children with 67 normolipidaemic obese children, aged 8-12 years, and 67 normal weight children matched for age/sex. Obesity was defined in accordance with the International Obesity Task Force. BMI z-scores were calculated, fasting blood samples were analyzed for insulin, and glucose, lipid profile and fatty acid levels were determined. In obese children, a low amount of omega-3 fatty acids and a low ratio of omega-3 to omega-6 fatty acids were associated with a higher BMI z-score. It was concluded that in obese children, plasma fatty acid profile may be associated with the degree of obesity13.

Omega-3 Fatty Acids and Exercise Contribute to Weight Loss
Omega-3 fatty acids work in synergy with exercise to promote weight loss. Hill et al., in 200714 examined the individual and combined effects of omega-3 fatty acid supplements and regular exercise on body composition and cardiovascular health. Overweight volunteers with high blood pressure, cholesterol, or triacylglycerols were randomly assigned to one of the following interventions: fish oil, fish oil and exercise, sunflower oil (control), or sunflower oil and exercise. Subjects consumed 6 g tuna fish oil/day (approximately 1900 mg omega-3 fatty acids) or 6000 mg sunflower oil/day. The exercise groups walked three days/week for 45 minutes. Plasma lipids, blood pressure, arterial function and body composition were assessed at 0, 6, and 12 weeks. Fish oil supplementation lowered triacylglycerols, increased HDL cholesterol, and improved endothelium dependent arterial vasodilation. The interaction of different dietary fatty acids and exercise on body-weight regulation, adiposity, and metabolism was assessed in male Wistar rats born to dams fed high fat diets made with fish oil, soybean oil, or palm oil. Rat pups were fed diets similar to their mothers and were divided randomly into exercise (swimming) or sedentary control groups when they were nine weeks old. Exercise lasted for six weeks and twenty-four hours after the last exercise period fasted rats were killed by decapitation. Chemical analyses and body composition analysis were conducted. The results demonstrated that different fatty acids have different effects on body weight, composition, and metabolism. Soybean oil-fed rats gained the most weight and fat. Exercise reduced body weight of fish oil and palm oil fed rats, but soybean oil-fed rats were still heavier and fatter than other rats15. Both fish oil and exercise independently reduced body fat which suggested that an increased intake of omega-3 fatty acids could be a useful in adjunct to exercise programs aimed at improving body composition and decreasing cardiovascular disease risk16.

Exercise or physical activity and athletics are associated with lower risk for cardiovascular disease (CVD), hypertension, obesity, and diabetes16-23. Exercise lowers blood pressure and decreases the overall risk for CVD by lowering triglycerides, raising high-density lipoprotein (HDL), and decreasing low-density lipoprotein (LDL) cholesterol. In the athletic setting, omega-3 fatty acids are essential for overall health of the athlete. Both omega-3 fatty acids and exercise increase fatty acid oxidation, omega-3 fatty acids increase the production of endogenous antioxidant enzymes; exercise and omega-3 fatty acids increase sensitivity to insulin and prevent hyperglycemia and finally, omega-3 fatty acids increase oxygen delivery to the heart muscle.

Improvements in Physiological Parameters While Exercising
Omega-3 fatty acids are beneficial for the improvement of heart parameters during exercise, help promote muscle recovery by reducing inflammation and reduce the incidence of exercise induced bronchoconstriction. Walser et al., (2008)24 tested the hypothesis that dietary supplementation with EPA (3 g/day) + DHA (2 g/day) would be beneficial in the change in heart parameters during exercise. Twelve healthy subjects received EPA/DHA and nine subjects received safflower oil as a control. Both groups performed 20 minutes of bicycle exercise (ten minutes each at low and moderate work intensity) before and after EPA/DHA or safflower oil treatment. Mean arterial pressure, heart rate, stroke volume, cardiac output and systemic vascular resistance were assessed before exercise and during both workloads. EPA/DHA augmented increases in stroke volume and cardiac output and tended to attenuate decreases in systemic vascular resistance during the moderate workload whereas safflower oil treatment had no effects. The observed increases in stroke volume and cardiac output with EPA/DHA supplementation imply that these fatty acids can increase oxygen delivery during exercise, which may have beneficial clinical implications for individuals with cardiovascular disease and reduced exercise tolerance. In another study, the effects of fish oil supplementation and exercise were investigated in healthy, previously sedentary males, ages 19-34. Thirty-two subjects were assigned to four groups: control, fish oil, exercise, fish oil and exercise. The fish groups consumed 4000 mg/day of omega-3 fatty acids. The exercise groups performed aerobic exercise for one hour three times per week for ten weeks with pre- and post- values obtained for cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, maximal oxygen consumption, ventilatory anaerobic threshold, percent body fat, and dietary composition of macronutrients and polyunsaturated to saturated fat (P:S) ratio. Maximum oxygen consumption was greater for the exercise groups (exercise and fish oil exercise) as compared to the control group. Ventilatory anaerobic threshold was significantly greater with fish oil, exercise, and their combination compared to control. This data indicates an improvement in aerobic metabolism from aerobic exercise, alone or in combination with fish oil, compared to controls25.

Omega-3 fatty acids enhance exercise-induced increases in brachial artery diameter and blood flow during rhythmic exercise, whereas safflower oil rich in omega-6 fatty acids have no effect. Treatment with 5000 mg (2 g/d DHA and 3 g/d EPA) of omega-3 fatty acids enhanced brachial artery blood flow and conductance during exercise26. In another study 18 white men with a history of myocardial infarction and ejection fractions were randomized to placebo or omega-3 fatty acids (585 mg DHA and 225 mg EPA) for two, four-month periods in a crossover design. At the end of each period, heart rate, heart rate variability, and rate of heart rate recovery after exercise were determined, as were effects on arterial compliance, blood pressure, cardiac function, and fasting serum levels of lipids and inflammatory markers. Omega-3 fatty acids decreased heart rate at rest from 73+/-13 to 68+/-13 beats/minute and improved 1-minute heart rate recovery after exercise. Heart rate variability in the high-frequency band increased, but no change was noted in overall heart rate variability27.

Exercise Induced Bronchoconstriction
Exercise-induced asthma/bronchoconstriction occurs in up to 90% of individuals with asthma and approximately 10% of the general population without asthma. It describes a condition in which vigorous physical activity triggers acute airway narrowing with heightened airway reactivity resulting in reductions in forced expiratory volume. It is more prevalent in elite athletes compared with non-elite athletes and the general population. Exercise-induced bronchoconstriction is characterized by asthma-like symptoms such as: wheezing, chest tightness, abnormal breathlessness, coughs and sputum production. Although the mechanisms responsible for bronchial hyperactivity after exercise in asthmatics have been extensively investigated28,39, exercise-induced bronchoconstriction in elite athletes is less understood and most likely involves many mechanisms. It has been suggested that transient dehydration of the airways activates the release of inflammatory mediators, such as histamine, neuropeptides, and omega-6 metabolites, leukotrienes, and prostaglandins from airway cells, resulting in bronchial smooth muscle contraction.

Treatment of exercise-induced bronchoconstriction relies heavily on the use of pharmacological medications; however, there is accumulating evidence that a dietary excess of omega-6 fatty acids, and a dietary deficiency of antioxidant vitamins and omega-3 fatty acids, can modify severity. The modification of these dietary factors has the potential to reduce the incidence and prevalence of this disease30. Indeed, dietary fish oil supplementation has been shown to have a markedly protective effect on suppression of exercise-induced bronchoconstriction in elite athletes; an effect which can likely be attributed to the anti-inflammatory properties of EPA and DHA. Repetitive high-intensity exercise itself may contribute to the development of exercise-induced bronchoconstriction by releasing inflammatory cytokines31. Recent evidence with airway remodeling in cross-country skiers, the inability of pharmacologic agents to treat some forms of exercise-induced bronchoconstriction32, strongly suggests that the pathology of exercise-induced bronchoconstriction is quite different from asthma. In a randomized, double-blind, crossover study 16 asthmatic patients with documented exercise induced bronchoconstriction (asthma) were given 3.2 g EPA + 2.0 g DHA or placebo daily and were tested for pulmonary function and proinflammatory eicosanoid metabolites both before and after exercise for three weeks. Fish oil improved pulmonary function to below the diagnostic exercise induced bronchoconstriction threshold, reduced bronchodilator use and diminished concentrations of inflammatory eicosanoid metabolites when compared to the normal and placebo diets. The authors concluded that fish oil supplementation may present a potentially beneficial non-pharmacologic intervention for asthmatic subjects with exercise induced bronchoconstriction33.

In another study three weeks of fish oil supplementation (3.2 g EPA and 2.2 g DHA per day) reduced the fall in forced exporatory volume (FEV1) at 15 minutes post exercise by almost 80% in conjunction with a greater than 20% reduction in bronchodilator use in 10 non-atopic elite athletes with exercise induced asthma. In addition, the increase in tissue phospholipid omega-3 concentration was coincident with a significant suppression of urinary and blood eicosanoids (LTE4, 9, PGF2, and LTB4 respectively) and proinflammatory cytokines (TNF-alpha and IL-6)34.

Omega-3 and Physiological Recovery from Exercise
The immune system of athletes is affected by intensity and duration of exercise. Exhausting activities tend to produce adverse changes in immune parameters such as total leukocytes, number of natural killer cells, lymphocyte count, helper-to-suppressor cell ratio, proliferative response to a mitogen, and others35. Furthermore, during exercise, there is an increase in the generation of superoxide radicals in the lipid bilayers of muscle mitochondria, and trauma to the muscles16. Unaccustomed eccentric exercise causes muscle damage that presents as delayed soreness, strength and range of motion loss, swelling, and increased passive stiffness. These symptoms reduce the ability to exercise and might be harmful if further exercise is continued36. Excessive radical formation and trauma during high-intensity exercise leads to a state of inflammation that is made worse by the increased amounts of omega-6 found in the Western diet.

The effects of placebo or a dietary supplement containing mixed tocopherols, flavonoids, and the omega-3 fatty acid DHA on exercise-induced markers of cell damage and the inflammatory mediators C-reactive protein (CRP) and interleukin-6 (IL-6) in 40 healthy, nonsmoking, untrained males for 14 days was investigated37. Blood samples were collected on day 0 (baseline), day 7 (eccentric exercise-induced injury), day 10, and day 14. Eccentric arm curl exercise was used to induce an acute phase injury response as evidenced by significant increases in creatine kinase, lactate dehydrogenase, and pain, as well as a decreased range of motion three days after the exercise. There were significant group differences for IL-6 and C-reactive protein and the authors concluded that exercise-induced inflammation, evaluated by changes in IL-6 and C-reactive protein, were significantly reduced by the omega-3 fatty acid containing dietary supplement.

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