Fish oil - A friend or a foe?

Nowadays, we continue to struggle to live a healthy lifestyle by eating a balanced diet that ensures we achieve and maintain healthy body weight, as well as engaging in regular physical activity, quitting smoking, limiting alcohol use, and practising good sleep hygiene. Adoption of various healthy dietary practices such as reduced consumption of refined carbohydrates and simple sugars, the substitution of saturated and trans fats with unsaturated fats, and increased consumption of seafood (particularly species high in omega-3 fatty acids [n-3 FAs]) piqued the researchers' interest as well. [11]

Regular exercise and a heart-healthy diet continue to be the cornerstones of cardiovascular disease prevention. Thus, in this article, I would like to address the efficacy of omega-3 and omega-6 fatty acids derived from food or other formulations/supplements in hypertriglyceridemia.

Triglycerides (TG) are a type of fat that the body utilizes to store energy and provide energy to muscles; small amounts are also found in the blood. Too much fatty substance in the blood can accumulate inside arteries, forming plaque, which represents a substantial risk factor for atherosclerotic cardiovascular disease (acute coronary syndrome, myocardial infarction, stable or unstable angina, coronary artery disease, stroke, transient ischemic attack, carotid disease, peripheral artery disease and abdominal aortic aneurysm). [10,11]

Fig.1.- Atherosclerotic cardiovascular disease [12]

Hypertriglyceridemia, elevated plasma triglycerides (>200 mg/dl), is the result of an excess of triglyceride-rich lipoproteins of several different types, most commonly very-low-density lipoproteins (VLDLs) but other types of fatty substances, as well.??VLDL contains very little protein as the name implies and its main purpose is to distribute the triglyceride produced by your liver. A high VLDL cholesterol level can cause the buildup of cholesterol in your arteries and increases your risk of atherosclerotic cardiovascular disease. [10]

Screening tests are recommended by the Canadian Cardiovascular Society depending on age and risk factors for heart disease. Lipid/lipoprotein screening (fasting or nonfasting) is advised for men and women over the age of 40, as well as for anybody with one of the particular illnesses that may raise the risk of certain diseases. [10,11]

Fig.2. Triglyceride blood test technique [13]

The effectiveness of omega-3 fatty acids in lowering the triglycerides level

Prescription of omega-3 FDA-approved supplements (Lovaza, Vacepta) at 4g/day for patients with triglycerides between 200-499 mg/dL results in a 20% to 30% reduction in TG and no significant increase in LDL-C. [1,2,3] Increased consumption of omega-6 fats lowers serum total cholesterol but not other blood fat components or adiposity. [9]

In the case of TG level >500 mg/dl using FDA-approved omega-3 supplements, 4g/day results in >30 % drop in TG level, while DHA-containing agents may increase the LDL-C by 15% to 36%, but there is no increase in apo B. However, measuring LDL-C in the context of elevated triglycerides may be inaccurate. According to Skulas-Ray's literature reviews,??LDL-C increases proportionally to the degree of triglyceride reduction, not as a result of the prescription agent containing DHA. In the largest studies of 4 g/day EPA and DHA or EPA-only as adjuncts to statin therapy, non–HDL-C and apo B were modestly decreased, suggesting reductions in total atherogenic lipoproteins. [1,3]?

The effectiveness of omega-3 and omega-6 fatty acids in reducing cardiovascular risk

Omega-3 supplements were linked to lower cardiovascular outcomes in an updated meta-analysis of 38 randomized controlled trials published in Elsevier Journal 2021. Following the REDUCE-IT trial, several clinical guidelines recommended pure ethyl ester of EPA. However, two recent negative EPA + DHA trials, STRENGTH and OMEMI, have called into question the efficacy of omega-3 FAs in reducing atherosclerotic cardiovascular events. [4]

Previous research found no substantial cardiovascular benefit from low dose 1g/day omega-3 supplementation. According to the REDUCE-IT research, which used 4 g/day of Amarin's icosapent ethyl, a highly purified EPA ethyl ester, for patients with high triglycerides (135 to 499 mg/dL) and high cardiovascular risk, it was noticed a reduction of significant adverse cardiovascular events by 25% when added to a statin medication. Data from the STRENGTH and OMEMI studies, on the other hand, show that clinical success is not solely dependent on the use of a greater dose of n-3 FA. [3, 5, 6, 11]

According to the STRENGTH research, which was finished in 2020, the use of high-dose omega-3 fatty acids did not result in a substantial reduction in major adverse cardiovascular events. However, the omega-3 CA therapy group experienced a 67 % rise in atrial fibrillation, raising the question of whether utilizing any kind of omega-3 fatty acid formulation is as safe as we believe. The trial was stopped due to a low likelihood of clinical effect and a substantial increase in atrial fibrillation with omega-3 CA compared to placebo. Patients in the omega-3 CA group reported more gastrointestinal disorders that the placebo group (24.7% vs 14.7%). [7, 8, 11]

Fig.3. Atrial Fibrilation [14]

In terms of omega-6 supplements, according to a 2018 study published in PubMed, no evidence was discovered that increasing omega-6 fat intake improves cardiovascular outcomes other than MI, where 53 persons may need to increase omega-6 fat intake to prevent 1 person from getting MI. Although the benefits of omega-6 fats have yet to be demonstrated, increasing omega-6 fats in persons at high risk of MI may be beneficial. [9]

To summarise, the data do not support the use of omega-3 and omega-6 fatty acid formulations in high-risk patients to significantly reduce severe adverse cardiovascular events of hypertriglyceridemia.

I can't wait to use this information and educate my community. Also, remember that maintaining healthy body weight, eating a nutritious diet, engaging in regular physical activity (at least 150 minutes of moderate to strenuous aerobic activity per week), quitting smoking, limiting alcohol use, and practising excellent sleep hygiene are all important. Along with evidence of cardiovascular outcome benefits from the Mediterranean dietary pattern, other dietary patterns (Portfolio dietary pattern, Dietary Approaches to Stop Hypertension (DASH) dietary pattern, low-glycemic index/glycemic load dietary pattern, and plant-based dietary pattern, dietary patterns high in nuts/legumes/olive oil/fruits and vegetables/total fibre and whole grains) share important features. [11]

Fig.4. Healthy lifestyle features [15]

Resources:

1.?????https://www.ahajournals.org/doi/10.1161/CIR.0000000000000709

2.?????https://www.medpagetoday.com/cardiology/dyslipidemia/81701

3.?????https://www.tctmd.com/news/new-aha-guidance-omega-3-fatty-acids-high-triglycerides

4.?????https://www.thelancet.com/pdfs/journals/eclinm/PIIS2589-5370(21)00277-7.pdf

5.?????https://www.acc.org/latest-in-cardiology/articles/2021/03/02/12/59/how-should-clinicians-evaluate-the-use-of-omega-3-based-therapies

6.?????https://www.nejm.org/doi/full/10.1056/nejmoa1812792

7.?????https://jamanetwork.com/journals/jama/fullarticle/2773120?guestAccessKey=eb2eccec-6038-4a0f-a639-4ff557aaed60&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=111520

8.?????https://newsroom.clevelandclinic.org/2020/11/15/cleveland-clinic-led-trial-finds-high-doses-of-a-prescription-fish-oil-do-not-reduce-major-cardiac-events-in-high-risk-patients/

9.?????https://pubmed.ncbi.nlm.nih.gov/30488422/

10.?????https://www.healthlinkbc.ca/tests-treatments-medications/medical-tests/cholesterol-and-triglycerides-tests

11.?????https://www.onlinecjc.ca/article/S0828-282X(21)00165-3/fulltext

12. https://www.physio-pedia.com/Atherosclerosis

13. https://www.healthing.ca/diseases-and-conditions/triglyceride-level/

14. https://www.cdc.gov/heartdisease/atrial_fibrillation.htm

15. https://lamvascular.com/healthy-lifestyle-dallas/