Omega 3 and diabetes, ASCEND study reveals benefits and useful dosages

Omega 3s, allies of cardiovascular health, could protect against the risks of diabetes. A new study helps to understand when and in what doses to take them, and what benefits to expect 

Is it worth taking Omega 3 to protect the heart and arteries from the risks inherent in diabetes? Years of research have shown the importance of these fats for heart health; a new study helps to understand when and in what doses they should be taken and what benefits can be expected from this supplementation. 

Published in the New England Journal of Medicine and conducted at the University of Oxford in the United Kingdom, the study in question involved more than 15 thousand patients with diabetes, monitoring their health for an average of as much as 7.4 years. About half of the patients were asked to take an Omega 3 capsule every day; the other half, however, were made to take olive oil.

From published data it would seem that in the absence of cardiovascular problems for those living with diabetes, taking Omega 3 or olive oil would not make a difference. However, a closer analysis reveals benefits in terms of reducing deaths from vascular causes. Moreover, the benefits of Omega 3 intake may be more pronounced with adequate doses of these essential fatty acids.

• Diabetes and cardiovascular risk
• Omega 3 and cardiovascular risk
• Omega 3 and diabetes: the study
• The importance of patients' nutritional status
• Omega 3 against diabetes: a viable way forward

Diabetes and cardiovascular risk

Cardiovascular disease is one of the leading causes of death for people living with type 1 diabetes, and in this respect the heart of those who develop type 2 diabetes cannot consider themselves untroubled either: this form of diabetes is also associated with an increased incidence of cardiovascular problems and mortality from heart and artery disease. 

Most of the studies on the subject have been conducted precisely on patients with type 2 diabetes and have led to estimates of an increase in coronary artery disease and ischemic stroke ranging between 2 and 4 times; in contrast, the increase in mortality is estimated to vary between 1.5 and 3.6 times. Added to this is the fact that type 2 diabetes is a major risk factor for heart failure, peripheral arterial insufficiency, and microvascular complications-all issues that adversely affect both quality and life expectancy, so much so that in the presence of diabetes the latter is reduced by 4 to 8 years. Underlying this increased cardiovascular risk are well-known problems:

• hypertension, which is associated with insulin resistance. It is not uncommon for diabetes to be associated precisely with hypertension, and this combination doubles cardiovascular risk;
• increased triglycerides and LDL(Low Density Lipoproteins, the so-called "bad cholesterol") and HDL(High Density Lipoproteins, the "good" cholesterol) levels below desirable standards. This set of factors is characteristic of a problem associated with insulin resistance, called atherogenic dyslipidemia, which in the presence of diabetes is called diabetic dyslipidemia.

Omega 3 and cardiovascular risk

For their part, the Omega 3 have attracted the interest of researchers precisely because of their link to cardiovascular health. The first studies revealing their heart-healthy properties now date back nearly 50 years, when it was observed that in Greenland Eskimo populations, heavy consumers of fish rich in these fatty acids, the incidence of atherosclerosis was significantly reduced. The large body of scientific work conducted since then has allowed the European Food Safety Authority (the Efsa) to conclude that Omega 3 is legitimate to attribute several health properties to, including:

• the ability to contribute to normal heart function and to maintain normal blood pressure and triglycerides, characteristic of the two Omega 3s found in fish: eicosapentaenoic acid(EPA) and docosahexaenoic acid(DHA);
• the ability to help maintain normal cholesterol values, inherent in the precursor of EPA and DHA, alpha-linolenic acid(ALA).

For these reasons, the prospect of protecting the heart and arteries of those living with diabetes with an approach based on Omega 3 intake seems entirely reasonable.

Omega 3 and diabetes: the study

The one conducted by the Oxford researchers is not the first study to test the hypothesis that Omega 3 intake may help combat cardiovascular risk associated with diabetes. In patients with type 2 diabetes, for example, EPA intake (compared to taking a placebo) was associated with a significant reduction in triglycerides and non-HDL cholesterol. 

In contrast, this new study shows a lower incidence of death from vascular causes among participants who took Omega 3 compared with those who took the olive oil placebo. The difference (196 cases versus 240) is statistically significant. However, the authors of this new trial themselves suggest that additional benefits could be obtained by modifying the dosage of Omega 3 administered to patients. In this case, the researchers limited themselves to having the patients take 840 mg of EPA+DHA per day, but pointed out that "triglyceride levels may be reduced by administration of higher doses of Omega 3 fatty acid supplements than those used in our study (typically, 2 to 4 grams per day)." 

In general, randomized clinical trials published in the scientific literature have shown that supplementation with Omega 3 helps to significantly reduce triglyceride levels and that its effect increases both with the duration of treatment and as the dose of Omega 3 increases. Unfortunately, this study did not plan to measure participants' blood triglyceride levels, but its authors point out that "it is possible that a reduction in triglyceride levels may produce beneficial effects in some patients with diabetes." In addition, there is another factor to consider: the ratio of EPA to DHA intake. 

This new study involved the administration of 460 mg EPA and 380 mg DHA, corresponding to an EPA/DHA ratio of 1.2. Previously published analyses, however, have shown that the reduction in triglycerides observable in patients with type 2 diabetes is most significant when this ratio is at least 1.5; the same seems to be true in the case of cholesterol. 

All this suggests that treatments based on the administration of higher doses of Omega 3 and characterized by a higher EPA/DHA ratio in turn may be associated with significant cardiovascular health benefits for those living with diabetes.

The importance of patients' nutritional status

When analyzing the results, it is then important to consider the nutritional status of the patients. Experts involved in the study published in the New England Journal of Medicine stated that participants who took Omega 3 had an Omega 3 Index (an indicator of the amount of EPA and DHA in the blood) quite high, "close to what we would consider a baseline level for a protective effect." In other words, this study may have involved patients who actually did not need to take the Omega 3 they were given because they already had enough. In fact, most of the participants, if they had not taken Omega 3, would not have been at high risk of dealing with a serious vascular event in the next 5 years: 40.4% were classified as low risk (less than 5%), 42.3% as moderate risk (between 5 and 10%), and only a much smaller 17.2% as high risk (equal to at least 10%). 

Intake of food-derived omega-6s may also have made a difference. Very abundant in modern Western diets, if taken in too high doses these fatty acids can contribute to endangering heart health. That is why it is also important to assess the ratio of Omega 3 to Omega 6 intakes-about which, unfortunately, the Oxford researchers' study gives no indication.

Omega 3 against diabetes: a viable way forward

The evidence therefore suggests that Omega 3 supplementation could provide real benefits to those living with diabetes, and that what may make a difference in the effect achieved is the health condition of the person taking them, the dose of Omega 3 taken, and the EPA/DHA ratio. In other words, in cases where there may be a real need, the intake of appropriate amounts of Omega 3 seems to be potentially useful even in cases of diabetes. For the time being, let's remember that according to Efsa to help the body maintain triglycerides and blood pressure in the normal range, 2 and 3 grams of EPA+DHA per day, respectively, are needed. In contrast, 250 mg per day is sufficient to help the heart function well. Finally, 2 grams of ALA per day are needed to keep cholesterol in the normal range.    

Sources: American Heart Association. Cardiovascular Disease and Diabetes. https://goo.gl/mM1NXr. 09/25/18 ASCEND Study Collaborative Group. Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus. N Engl J Med. 2018 Aug 26. doi: 10.1056/NEJMoa1804989 Casaccia Bertoluci M and Zorzanelli Rocha V. Cardiovascular risk assessment in patients with diabetes. Diabetol Metab Syndr. 2017; 9: 25. doi: 10.1186/s13098-017-0225-1 Chen C et al. Effects of Omega-3 Fatty Acid Supplementation on Glucose Control and Lipid Levels in Type 2 Diabetes: A Meta-Analysis. PLoS One. 2015 Oct 2;10(10):e0139565. doi: 10.1371/journal.pone.0139565 Dyerberg J and Bang HO. Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet. 1979 Sep 1;2(8140):433-5 European Commission. EU Register of nutrition and health claims made on foods. https://goo.gl/faHW7R. 09/25/18 Lee SI et al. Cardiovascular disease and type 1 diabetes: prevalence, prediction and management in an aging population. Ther Adv Chronic Dis. 2015 Nov; 6(6): 347-374. doi: 10.1177/2040622315598502 Schultz H. Omega-3s fail to prevent heart events in trial on diabetics; experts question baseline levels, dosing. Nutraingredients-usa.com. 28-Aug-2018 Tajuddin N et al. Prescription omega-3 fatty acid products: considerations for patients with diabetes mellitus. Diabetes Metab Syndr Obes. 2016 Apr 19;9:109-18. doi: 10.2147/DMSO.S97036 Tenenbaum A andFisman EZ. Omega-3 polyunsaturated fatty acids supplementation in patients with diabetes and cardiovascular disease risk: does dose really matter? Cardiovasc Diabetol. 2018 Aug 28;17(1):119. doi: 10.1186/s12933-018-0766-0 Image: Pixabay