Woodman RJ, Mori TA, t al. Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Am J Clin Nutr, 2002; 76: 1007-1015.

BACKGROUND: n-3 Fatty acids lower blood pressure, improve lipids, and benefit other cardiovascular disease risk factors. Effects on glycemia in patients with type 2 diabetes are uncertain.

OBJECTIVE: We determined whether purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have differential effects on glycemic control, including insulin sensitivity and stimulated insulin secretion; 24-h ambulatory blood pressure; and serum lipids in type 2 diabetic patients with treated hypertension.

DESIGN: In a double-blind, placebo-controlled trial of parallel design, 59 subjects were randomly assigned to consume 4 g EPA, DHA, or olive oil/d for 6 wk while continuing to consume their usual diet.

RESULTS: Thirty-nine men and 12 postmenopausal women with a mean (+/- SE) age of 61.2 +/- 1.2 y completed the study. In comparison with the change from baseline in fasting glucose in the olive oil group, fasting glucose in the EPA and DHA groups increased 1.40 +/- 0.29 mmol/L (P = 0.002) and 0.98 +/- 0.29 mmol/L (P = 0.002), respectively. Neither EPA nor DHA had significant effects on glycated hemoglobin, fasting insulin or C-peptide, insulin sensitivity or secretion, or blood pressure. Serum triacylglycerols in the EPA and DHA groups decreased 19% (P = 0.022) and 15% (P = 0.022), respectively. There were no significant changes in serum total, LDL, or HDL cholesterol, although HDL(2) cholesterol in the EPA and DHA groups increased 16% (P = 0.026) and 12% (P = 0.05), respectively. HDL(3) cholesterol decreased 11% (P = 0.026) with EPA supplementation.

CONCLUSIONS: EPA and DHA had similar benefits on lipids but adverse effects on short-term glycemic control in hypertensive diabetic patients. The overall implications for cardiovascular disease require long-term evaluation.

Hu F, Cho E, et al. Fish and Long-Chain -3 Fatty Acid Intake and Risk of Coronary Heart Disease and Total Mortality in Diabetic Women. Circulation 2003;107:1852-1857.

Background Although several prospective cohort studies have found an inverse association between fish consumption and risk of coronary heart disease (CHD) or sudden cardiac death in the general population, limited data are available among diabetic patients.

Methods and Results We examined prospectively the association between intake of fish and -3 fatty acids and risk of CHD and total mortality among 5103 female nurses with diagnosed type 2 diabetes but free of cardiovascular disease or cancer at baseline. Between 1980 and 1996 (45 845 person-years of follow-up), we documented 362 incident cases of CHD (141 CHD deaths and 221 nonfatal myocardial infarctions) and 468 deaths from all causes. Compared with women who seldom consumed fish (<1 serving/mo), the relative risks (RRs) (95% CI) of CHD adjusted for age, smoking, and other established coronary risk factors were 0.70 (0.48 to 1.03) for fish consumption 1 to 3 times per month, 0.60 (0.42 to 0.85) for once per week, 0.64 (0.42 to 0.99) for 2 to 4 times per week, and 0.36 (0.20 to 0.66) for 5 or more times per week (P for trend=0.002). Higher consumption of fish was also associated with a significantly lower total mortality (multivariate RR=0.48 [0.29 to 0.80] for 5 times per week [P for trend=0.005]). Higher consumption of long-chain -3 fatty acids was associated with a trend toward lower incidence of CHD (RR=0.69 [95% CI 0.47 to 1.03], P for trend=0.10) and total mortality (RR=0.63 [95% CI, 0.45 to 0.88], P for trend=0.02).

Conclusions A higher consumption of fish and long-chain -3 fatty acids was associated with a lower CHD incidence and total mortality among diabetic women

Deyhim F, Olivarez O. The Beneficial Effect of Arctic Omega Liquid and Pro Omega Liquid on Glucose Uptake and Cell Livability in L6 Muscle Cell Line. Diabetes,2006;55(1):A382.

Previous research has shown that populations eating a lot of fish containing omega-3 fatty acids have lower rates of type 2 diabetes compared with those eating less fish.

The objective of the present study was to evaluate whether saponified fish oil influences glucose uptake and survival rate of L6 muscle cells. The L6 rat muscle cells were grown to confluence in either low (5 mM) or high (25 mM) glucose media for seven days in the presence of either 3 µg/ml or 30 µg/ml saponified Arctic Omega Liquid (863 mg omega-3), Pro Omega Liquid (1601 mg omega-3g), ProDHA (580 mg omega-3) and ProEFA Liquid (706 mg omega-3 + 83 mg GLA) for the final 24 hours of incubation.

After 24 hours of incubation with varied doses of saponified fish oil, cells were exposed to 2-deoxy-glucose, 14C glucose, or 3H-palmitate in the presence of insulin (1000 nm). Also, superoxide anion production and cell livability were assessed.
14C glucose incorporation to glycogen, glucose uptake and palmitate uptake per gram protein, and cell livability significantly decreased (P<0.05), while superoxide anion production significantly increased (P<0.05) after exposure to 25 mM glucose compared to 5 mM glucose media.

Despite a numerical dose response, saponified arctic omega liquid, pro omega liquid, and ProDHA significantly increased (p<0.05) while ProEFA numerically improved glucose uptake. The fish oil examined in this study did not (P>0.1) affect 14C glucose incorporation to glycogen, palmitate uptake, or superoxide anion production. Saponified arctic omega liquid exhibited a numerical improvement in cell livability compared to pro omega liquid and a significant (P<0.05) enhancement in cell livability compared to ProDHA and ProEFA. Saponified Pro Omega liquid exhibited a numerical improvement in cell livability compared to Pro-DHA and a significant (P<0.05) enhancement in cell livability compared to Pro-EFA.

In conclusion, the potential benefit of fish oil on glucose uptake and cell livability depends on the concentration of omega-3 taken up by the L6 muscle cells.

The Sikh population, and potentially other Asian groups, could significantly reduce their risk of heart disease by increasing the amount of oily fish they eat, according to research released by the Food Standards Agency today.

In the UK, the risk of heart disease among Indian Asians is currently around twice the UK average.

The study, by the University of Reading, found that Sikh men and women consumed less of the fatty acids found mainly in fish oil, and more of those found in vegetable oils, than UK white men and women.

After a moderate intake of fish oil (4g per day for 12 weeks), the levels of beneficial fatty acids in the body increased in the Sikh group to levels similar to the white men and women studied. Results also showed that taking fish oil supplements reduced the risk of heart disease by changing levels of fats in the blood.

Dr Peter Sanderson, Nutrition Scientist at the Agency, said: This new research shows that Sikh men and women in the UK, who are at significantly higher than average risk of heart disease, have a low intake of fish. They therefore do not get the protective health benefits of fatty acids found in fish, especially oily fish.

'Eating at least two portions of fish a week, one of which should be oily fish such as salmon or mackerel, could significantly help reduce the risk of heart disease in Asian communities.

In the UK, admission to hospital with heart attack is about double the average in the Asian population, and early death from heart disease is 46% higher for Asian men and 51% higher for Asian women than the UK average.

Diabetes, which is associated with abnormal blood-fat levels, is also four times more likely in the Asian population, and diabetes is known to be linked to an increased risk of heart disease.

Source: http://www.food.gov.uk/news/newsarchive/oilyfish_sikhheartdiseaserisk

Das UN. Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how? Prostaglandins Leukot, Essent Fatty Acids 2000;63(6):351-362.

Low rates of coronary heart disease was found in Greenland Eskimos and Japanese who are exposed to a diet rich in fish oil.

Suggested mechanisms for this cardio-protective effect focused on the effects of n-3 fatty acids on eicosanoid metabolism, inflammation, beta oxidation, endothelial dysfunction, cytokine growth factors, and gene expression of adhesion molecules; But, none of these mechanisms could adequately explain the beneficial actions of n-3 fatty acids.

One attractive suggestion is a direct cardiac effect of n-3 fatty acids on arrhythmogenesis.

N-3 fatty acids can modify Na+ channels by directly binding to the channel proteins and thus, prevent ischemia-induced ventricular fibrillation and sudden cardiac death.

Though this is an attractive explanation, there could be other actions as well.
N-3 fatty acids can inhibit the synthesis and release of pro-inflammatory cytokines such as tumor necrosis factoralpha (TNFalpha) and interleukin-1 (IL-1) and IL-2 that are released during the early course of ischemic heart disease.
These cytokines decrease myocardial contractility and induce myocardial damage, enhance the production of free radicals, which can also suppress myocardial function.

Further, n-3 fatty acids can increase parasympathetic tone leading to an increase in heart rate variability and thus, protect the myocardium against ventricular arrhythmias.
Increased parasympathetic tone and acetylcholine, the principle vagal neurotransmitter, significantly attenuate the release of TNF, IL-1beta, IL-6 and IL-18.

Exercise enhances parasympathetic tone, and the production of anti-inflammatory cytokine IL-10 which may explain the beneficial action of exercise in the prevention of cardiovascular diseases and diabetes mellitus.

TNFalpha has neurotoxic actions, where as n-3 fatty acids are potent neuroprotectors and brain is rich in these fatty acids.

Based on this, it is suggested that the principle mechanism of cardioprotective and neuroprotective action(s) of n-3 fatty acids can be due to the suppression of TNFalpha and IL synthesis and release, modulation of hypothalamic-pituitary-adrenal anti-inflammatory responses, and an increase in acetylcholine release, the vagal neurotransmitter.

Thus, there appears to be a close interaction between the central nervous system, endocrine organs, cytokines, exercise, and dietary n-3 fatty acids.

This may explain why these fatty acids could be of benefit in the management of conditions such as septicemia and septic shock, Alzheimer's disease, Parkinson's disease, inflammatory bowel diseases, diabetes mellitus, essential hypertension and atherosclerosis.

PMID: 11133172