Tag Archive for: fish oil

Omega-3s and A-Fib: More Analysis Required

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I hope that you took the time to review the paper on atrial fibrillation as well as the research letter on omega-3s and atrial fibrillation. If you haven’t, especially the primer on A-fib, please do it. It’s a serious condition that requires attention if you have it; in most cases, fixing it is surprisingly simple.

The research letter included five studies. I decided to look at each of those research papers individually to see how each trial was conducted, especially on the populations used in those experiments. Here’s what I found.

The Subjects

The subjects in the studies had several characteristics in common. First, they were, on average, in their mid 60s and older. Second, they had already had a myocardial infarction (heart attack) or were at high risk for cardiovascular disease due to factors such as obesity, hypertension, elevated triglycerides, and others. Third, most were taking multiple medications.

They definitely were not healthy and free of disease. The potential for a cardiac event increases if you’ve already had a cardiac event. On top of that, in the trials that used prescription fish oils, the attempt was to lower triglycerides in those patients who were taking a maximal dose of statins. There may be some interaction that hasn’t been identified yet between very high doses of omega-3s, equal to or greater than four grams, and statin medications or other pharmaceuticals the patients were taking to control blood pressure, heart rate, etc.

In short, this does not apply to everyone. In fact, in the concluding statement of the research letter, the researchers state that physicians should be cautious when prescribing high-dose omega-3s in patients with high triglycerides and an increased risk of cardiovascular disease.

Additional Analyses

As I alluded to in the prior paragraphs, I think the analysis should include factors such as exercise, diet, and especially prescription medications. It may be that the number of subjects might not be able to be broken down by statin intake, beta blocker intake, or ace inhibitors, but I think that it should at least be examined to see if there’s any trend.

Also, the data could be separated into those people who’ve had a heart attack and those that haven’t, even though they may have significant risk factors for cardiovascular disease. After a heart attack, there may be morphological changes such as damage to nerve conduction or the buildup of scar tissue that could impact how omega-3s impact the heart itself.

Are all of these possible? I would think it would be with over 150,000 subjects from all the studies included in the meta-analysis.

Two More Things

I still have not found a single nutritionist involved in any of this research. When you look at prior studies that seemed to benefit heart rhythms, it’s DHA omega-3, not EPA, which is the factor related to better heart rhythms.

Take a look at the map that’s in the primer on atrial fibrillation. It applies to those on Medicare who are 65 and older, but there’s an amazing and obvious trend. I’m even going to give it a name; I’ll tell you that next Tuesday. The only clue that I’ll give you is to think maps and what they’re typically used for.

The Bottom Line

While interesting, the Research Letter on the update of omega-3s in relation to atrial fibrillation leaves more questions than answers. So far, it applies only to people over 65 with high triglycerides and other risk factors for cardiovascular disease. If you already take omega-3 fatty acids, there’s probably no reason to stop, but it’s a discussion you should have with your physician.

It’s also obvious that if you do have high triglycerides, you can work on changing that by changing your diet first. Reducing refined carbohydrates is the key; eating more vegetables helps as well.

It always comes back to this: eat better. Eat less. Move more.

What are you prepared to do today?

        Dr. Chet

References:
1. European Heart Journal – CVD Pharm. 2021 doi:10.1093/ehjcvp/pvab008
2. Curr Atheroscler Rep. 2020. https://doi.org/10.1007/s11883-020-00865-5
3. Atrial Fibrillation Primer. https://www.cdc.gov/heartdisease/atrial_fibrillation.htm

Research Update on Omega-3s and A-Fib

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A recent research letter to The European Heart Journal caught my attention. This was a continuing meta-analysis of data linking the use of omega-3 fatty acids to atrial fibrillation. The result of the original analysis in 2020 and the additional studies that were examined in the current meta-analysis led to the conclusion that there’s an increased risk of atrial fibrillation for those who take omega-3 fatty acids. That seemed surprising to me because prior research suggests that there’s a reduced risk of fibrillation in those that use omega-3 fatty acids.

To quote Vince Lombardi, “What the heck is going on around here!”

The concern by the research group seems to be focused on the current recommendations for high-dose prescription fish oil for elevated triglycerides. The problem is that the original meta-analysis that included 14 studies did not just use prescription fish oil; it used fish oil from dietary supplements as well. While the current update seemed to focus on the prescription omega-3s, it also used margarines enhanced with vegetarian-sourced omega-3s.

What are we supposed to do? Dig deeper. Do the results apply to everyone? No. Are there other potential problems with these studies? Yes, and I’ll cover those on Saturday. Until then, if you want a primer on atrial fibrillation, read the link in Reference 3; pay close attention to the map. You can also read the Research Letter by checking out reference 1; it’s open access.

What are you prepared to do today?

        Dr. Chet

References:
1. European Heart Journal – CVD Pharm. 2021 doi:10.1093/ehjcvp/pvab008
2. Curr Atheroscler Rep. 2020. https://doi.org/10.1007/s11883-020-00865-5
3. Atrial Fibrillation Primer. https://www.cdc.gov/heartdisease/atrial_fibrillation.htm

The Bottom Line on Omega-3s

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When you consider the research studies I reviewed last week and this week on omega-3 fatty acids, they may seem confusing. The reason is that in both of those studies, they were looking at very specific outcomes. In last Thursday’s memo, it was changes in the quantity of specific cytokines, chemicals that are inflammatory in nature. In the study from Tuesday, it was for reduction of cardiac events. There are other ways that omega-3s can contribute to health, and I thought a little review would be in order.

Cellular Membranes

Cells seem to work better when they contain omega-3 fatty acids. Remember, a cell has an exterior wall of a lipid bilayer. If the diet contains a high amount of saturated fat, a high amount of saturated fat becomes part of that lipid bilayer. If the diet contains more omega-3 fatty acids, whether by eating fish or by taking a dietary supplement, the cell membranes contain a higher proportion of omega-3 fatty acids. While the mechanisms are not known, the cells seem to function better when they contain more omega-3s.

Let me give you a couple of examples. Nerve tissue seems to function better when there’s a high amount of DHA in the bloodstream; DHA supplementation seems to be beneficial for nerve problems such as migraine headaches, depression, and Parkinson’s disease. It’s not a cure, but somehow the omega-3s become integrated into those nerve cells and they work better. The same holds true for the eyes; vision is dependent on the nervous system to operate properly, and high DHA appears to benefit eye health as well.

Hormone Control

The study I reviewed last Thursday focused on one type of inflammatory chemicals called the cytokines, but there are other pro-inflammatory hormones that may be better controlled with both high EPA and DHA supplementation. Cortisol is a known stress hormone. In times like we’re experiencing now and for those who are overweight or obese, cortisol levels are higher; that may be due to the increased presence of saturated fat. If omega-3s become part of triglycerides, the potential for inflammatory hormones such as cortisol can be decreased.

There’s also the possibility that persistent use of both EPA and DHA reduces atherosclerotic plaque, the hard layer of fat that builds up in arteries, or it may prevent cholesterol from being manufactured in the first place. While it’s too long of a process to explain in a Memo, our bodies make cholesterol two carbon molecules at a time. When there’s a higher amount of saturated fat, the process can speed along unabated; but when there’s a high percentage of omega-3 fatty acids present, the process gets interrupted. We don’t know the mechanisms; we just know omega-3s help.

The Bottom Line

Those are some of the possible ways omega-3 fatty acids are used for our health. Undoubtedly there are many more that haven’t been discovered or haven’t been examined in enough clinical trials at this point. The most important thing for you and me is to make sure that either we eat several servings of fatty fish per week or we take up to four grams of high EPA-DHA omega-3 supplements every day—let the science work it out later. Our job is to provide our body with nutrients that are beneficial.

What are you prepared to do today?

        Dr. Chet

Omega-3s and Cardiac Events

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There was another study this week on omega-3 fatty acids. While the study I talked about last Thursday was small with only 21 subjects, this trial contained over 13,000 subjects from 675 hospitals and clinical centers all around the world. In this five-year study, one of the omega-3 fish oil medications was being tested to see if it would reduce cardiac events such as heart attacks, stroke, and death when compared with subjects taking a corn-oil placebo. The study was stopped early when it was clear there were going to be no significant differences in any of the outcomes that were being studied. In other words, the prescription fish oil did not reduce cardiovascular disease events.

While that may seem disappointing, there are some factors that most likely impacted the outcome and a couple that may have but could not be tested.

The Subject Pool

The subjects in this clinical trial had significant risk for CVD; they were required to have established coronary artery disease or significant risk factors to be included in the clinical trial. Those risk factors included being a type 1 or type 2 diabetic, with at least one additional risk factor including chronic smoking, hypertension, hs-CRP higher than two mg/L, moderately increased protein loss, or being older with similar factors as the diabetics.

The Data Not Collected

In reading the study, there were three criteria that came to mind that could have impacted the outcome if the corresponding data had been collected and considered in the statistical analysis. I emailed the relevant author and got the answers.

1. Were data collected on exercise habits of the subjects? No.

2. Were nutritional data collected on the subjects? No.

3. Was the form of omega-3 used, a highly purified carboxylic acid form, assessed as to how the metabolism impacts the omega-3s’ mechanism of action? No.

It seems to me that if the data could be analyzed on exercisers versus sedentary as well as using nutritional factors, even just daily caloric intake, there may have been significant results. As for the form of omega-3s, the CA form is highly absorbed and doesn’t require a fat in the diet to assist with that process. There might have been something else that happens during metabolism that normally assists in the risk reduction. We just don’t know.

The Bottom Line

The authors acknowledge that this subject pool was at high risk for cardiac events. One explanation is that the progression of disease may have already been too advanced and could have impacted the efficacy of the medication. For people with less established CVD, the omega-3s might have been more effective.

Many in the medical field wrote about the failure of omega-3s in medication or supplement form to prove that they have any impact on CVD events or mortality. I think they’re wrong. The one outcome they never test is the quality of life. Granted, it’s difficult to assess but if people can live their lives even 10% better, regardless of CVD events, that seems worth it. Paula and I are still taking our omega-3 supplements; in fact Riley takes one, too, even though he’s only five and we’re not concerned about his heart. Whether you’re worried about your heart or not, omega-3s have many benefits. This study shows no reason why you or I should stop taking them.

What are you prepared to do today?

        Dr. Chet

Reference: JAMA. 2020;324(22):2268-2280. doi:10.1001/jama.2020.22258

Can Omega-3s Reduce Inflammation?

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Omega-3 fatty acids have been in the science news this week. In this Memo, I’ll take a look at a small study that examined the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on specific markers of inflammation in 21 subjects between 50 and 75 who had elevated levels of inflammation. Researchers had subjects follow a particular regimen: take three grams of either DHA or EPA for 10 weeks, cease all omega-3s for 10 weeks, and then take three grams of the other omega-3.

The study showed both omega-3s were effective; they just worked differently, and I can’t explain that without getting technical. It seemed that DHA reduced specific cytokines such as TNF-alpha, IL-6, and IL-10 to a greater degree than did EPA. One of the ways that may have happened was a reduction or replacement of the proinflammatory omega-6 arachidonic acid. The important point is this: however they worked and although they worked in different ways, both DHA and EPA were effective in reducing the inflammatory response in this small study.

Could adding high-DHA fish oil supplements to the diet reduce cytokine production in every case? Specifically, could it potentially have some benefit for the cytokine storm that’s associated with severe cases of COVID-19? We don’t know that yet because that specific research hasn’t been done. But since there are so many other well-documented benefits of omega-3s, make sure you regularly eat fatty fish or take fish oil supplements with DHA and EPA. It’s always a good bet.

What are you prepared to do today?

        Dr. Chet

Reference: DOI:https://doi.org/10.1016/j.atherosclerosis.2020.11.018

The Bottom Line on Cats and Dogs and Supplements

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One of my all-time favorite movie lines is by Bill Murray’s character in the original Ghostbusters. He goes on a rant about the coming plague of ghosts and says “…dogs and cats living together…” It’s the delivery more than the words, but it still makes me laugh. I often blurt it out when people talk about all the things that could go wrong if X happens.

I decided to search the literature for specific supplements that can benefit cats and dogs, whether they live together or not. There’s no research on multivitamins-multiminerals per se, although there’s some info on the use of vitamins and minerals as additives to food.

Cats and Supplements

There are two primary areas of research on supplements in cats. The first is the amino acid taurine and the other is joint issues. The lack of taurine in a cat’s diet can result in compromised immune systems, eye problems including blindness, deafness, cardiomyopathy and heart failure, and reproductive issues. Researchers have found that taurine supplementation can increase the taurine level in a cat’s cardiac tissue. One more thing: soy interferes with taurine absorption or utilization, so make sure that the food you feed your cat is soy-free.

The other issue is joint problems such as arthritis. In research on cats, the same blends used in humans that consist of glucosamine, chondroitin, Boswellia, and fish oil help alleviate pain as assessed by owner and veterinarian pain evaluations.

Dogs and Supplements

The big issue with dogs is joint problems such as osteoarthritis. Research shows that the same nutrients recommended for cats and humans are appropriate for dogs: glucosamine, chondroitin, Boswellia, and fish oil. When it comes to amino acids, dogs require 10 essential amino acids to be healthy. While they can get that from vegetarian protein, research shows that dogs can smell it when meals don’t contain all the essential amino acids and will avoid them. That’s some sniffer dogs have!

In the category of interesting research, the amino acid l-arginine together with antioxidants has been shown to benefit dogs with memory issues. Also medium-chain triglycerides are being tested in epileptic dogs to see if the supplement can help reduce seizures. Maybe a teaspoon of coconut oil every day can benefit these dogs—there’s no harm in it while waiting for the research to be completed.

The Bottom Line

We love our cats and dogs and want them to being as healthy as they can be. Targeted supplementation for specific issues is certainly warranted, and it’s probably good to use the same recommendations for us humans and for our best friends: eat better, eat less, and move more. You’ll both be healthier for it!

What are you prepared to do today?

        Dr. Chet

References:
1. Vet Med Sci. 2019 Aug;5(3):325-335. doi: 10.1002/vms3.1822.
2. J Nutr. 1995 Nov;125(11):2831-7. doi: 10.1093/jn/125.11.2831.
3. Am J Vet Res. 1992 Feb;53(2):237-41.

Research Update on Fish Oil Supplements

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Researchers performed a meta-analysis of studies that examined EPA and DHA as dietary supplements to see if there was a reduction in CVD events and mortality. In this study, researchers included 40 studies with 135,267 participants. While they examined many different variables, including whether EPA was better than DHA and whether they could find the best combination or ratio, almost every analysis they ran demonstrated benefits for those who use fish oil supplements: a 13% decrease in the risk of a heart attack, a 10% decrease in any coronary heart disease event, and a 35% reduction in the risk of a fatal heart attack.

For me, the most significant finding was that there was a dose-response effect of taking fish oil supplements. In other words, CVD events decreased with higher intake of fish oil supplements.

The Problems with the Prescription Study

There were three issues with the EVAPORATE study I talked about in Thursday’s Memo. First, there was a significant loss of subjects. Most of the loss was in the experimental group, which reduced the number of subjects from 40 to 31.

Second, they did not compare the prescription fish oil with an equivalent amount of fish oil dietary supplement, whether it contained DHA or not, which seems to be a glaring omission to me.

Finally, the study was funded by the manufacturer; several of the researchers had a relationship with the pharmaceutical manufacturer as well. That doesn’t mean anything shady was going on, but it does put in question the conclusions that can be drawn about the significance of the entire clinical trial.

The Problem with the Fish Oil Supplement Study

The primary problem with the fish oil supplement study is that it was a meta-analysis. Even though that method is becoming popular, and even though by all accounts the researchers tried their best in selecting the correct studies for inclusion, there’s always the specter that they may have left out some studies. To their credit, they re-ran the analysis without several of the clinical trials and did get slightly different findings. However, it did not change the outcomes related to heart attacks or coronary heart disease events.

The study was funded by Global Organization for EPA and DHA Omega-3s. Just as with the pharmaceutical study, there’s an inherent bias implied. In both cases though, if the funding organizations didn’t sponsor the research, who would? There are only so many research dollars available, and many dollars are being siphoned off to fund urgent COVID-19 studies.

The Bottom Line

I think that these studies establish that fish oil is beneficial to reduce CVD events and reduce disease progression. Because there appears to be a dose-response relationship to fish oil and the reduction of CVD risk, the higher amount of fish oil a person takes, up to four grams, the better the potential outcomes.

Which one is better: prescription versus supplements? Until there’s a study that directly compares prescription fish oil to fish oil supplements, I don’t believe it matters; both studies we reviewed demonstrate benefits. The key is that if you have been diagnosed with CVD, you should take fish oil. Talk it over with your physician first and then get going. Your heart will love you for it. And don’t forget to eat better and move more as well.

What are you prepared to do today?

        Dr. Chet

References:
1. European Heart Journal (2020) 00, 1–8 doi:10.1093/eurheartj/ehaa652
2. https://doi.org/10.1016/j.mayocp.2020.08.034

Research Update on Prescription Fish Oil

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Let’s begin by taking a look at the prescription fish oil supplement medication. To review, this is a 100%-EPA fish oil that received FDA approval in December of 2019. The amount prescribed for people with high triglycerides is four grams of highly processed fish oil per day. Data from the REDUCE-IT trial suggested that there was a 25% decrease in mortality in the experimental group compared with the control group.

The current trial was called the EVAPORATE trial: Effect of Vascepa on Improving Coronary Atherosclerosis in People with High Triglycerides Taking Statin Therapy. The study began with 80 men and women, ages 30-85, with greater than 20% blockage in at least one of their coronary arteries, elevated triglycerides, and taking statin therapy; 68 subjects completed the 18-month study. The primary endpoint was to see if there was any reduction in plaque buildup in the coronary arteries.

The subjects in the prescription fish oil group saw a 17% decrease in overall arterial plaque; there was a plaque increase in the placebo group. The researchers did not track cardiovascular events or mortality in this study. We’ll take a look at the OTC fish oil supplement study on Saturday as well as determine the clinical significance of each trial.

What are you prepared to do today?

        Dr. Chet

References:
1. European Heart Journal (2020) 00, 1–8 doi:10.1093/eurheartj/ehaa652
2. https://doi.org/10.1016/j.mayocp.2020.08.034

Research Update: Fish Oil and Heart Disease

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The prescription fish oil Vascepa has been approved since December of last year. The fish oil medication was originally intended for those who had a family history of high triglycerides of 500 mg/dl or greater. In the approval process, the recommendation was lowered to those whose triglycerides were at least 150 mg/dl and who were taking a statin medication. But the research hasn’t stopped.

Research on Vascepa as well as over-the-counter (OTC) fish oil supplements continues. From the pharmaceutical perspective, more research on the use of the medication could result in an increase in the potential applications of this pharmaceutical. From the dietary supplement perspective, research may help establish the efficacy of using fish oil dietary supplements instead of the prescription medication

Last week within one day of each other, studies on prescription fish oil and fish oil supplements were published that both demonstrated significant benefits. We’ll review those studies the rest of the week and see if we can find out whether fish oil dietary supplements match up with pharmaceutical fish oil. If you want a preview of the studies, check the references below; they’re both open access.

What are you prepared to do today?

        Dr. Chet

References:
1. European Heart Journal (2020) 00, 1–8 doi:10.1093/eurheartj/ehaa652
2. https://doi.org/10.1016/j.mayocp.2020.08.034

It’s Official: Prescription Fish Oil

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The U.S. Food and Drug Administration approved the prescription fish oil Vascepa for expanded use on Friday, December 13. The approval for the medication is for the secondary prevention of cardiovascular disease in patients under the following conditions:

  • Triglycerides above 150 mg/dl for everyone with diagnosed CVD and taking a statin medication.
  • Diabetes and two or more additional risk factors for CVD along with taking a statin medication.

The modifiable risk factors for CVD include smoking, obesity, high cholesterol, hypertension, and sedentary living. Remember from our prior series, secondary prevention may help reduce the risk of CVD symptoms developing.

My concerns are the same as they were before. Triglycerides less than 250 mg/dl can be resolved by diet and exercise in most people. Because the mechanism of action is unknown as to how the prescription works, there’s no reason to think that reducing triglycerides by lifestyle change won’t work as well as the prescription; the clinical trial didn’t track this data.

Speaking of lifestyle change, keep in mind the website specials on the Optimal Performance program as we get ready for the New Year. The Basic Meal Plan will teach you how to change your diet to reduce triglyceride levels if your levels are too high.

What are you prepared to do today?

        Dr. Chet

References:
1. http://bit.ly/36EbsYK
2. N Engl J Med 2019;380:11-22. DOI: 10.1056/NEJMoa1812792.