Tag Archive for: omega-3 fatty acids

Obesity and Prenatal Omega-3s: Premature Conclusions

/in /by

Women frequently ask about prenatal supplementation, and omega-3 fatty acids are always part of prenatal recommendations; that’s why this study attracted my attention. Did they come to the right conclusions? I think the best place to begin is by reading the conclusion statement of the abstract, and then examine the data from the paper to see if it supports those conclusions.

Here we go:

“In this randomized clinical trial, children of mothers receiving omega-3 fatty acid supplementation had increased BMI at age 10 years, increased risk of being overweight, and a tendency of increased fat percentage and higher metabolic syndrome score. These findings suggest potential adverse health effects from n-3 long-chain polyunsaturated fatty acid supplementation during pregnancy and need to be replicated in future independent studies.”

Problems with the Conclusions

The difference in body weight was two pounds, with the fish oil group weighing more than the placebo group; neither group was classified as being overweight by international standards. With height being equal, that automatically meant that the BMI would be higher in the fish oil group. However, both groups would be classified as underweight based on standards for children five to ten years old. The implication was the omega-3 group might be overweight. They were not; in fact they were closer to normal weight than the lighter kids. The increased risk of being overweight isn’t supported by the data presented.

Related to the higher metabolic syndrome score, the researchers calculated the score using an algorithm that considered waist circumference, systolic BP, negative HDL cholesterol, the log of triglycerides, and the Homeostatic Model Assessment for Insulin Resistance or HOMA-IR for short. There was a difference of 3/10 of an inch in waist circumference, with the omega-3 group being slightly larger. There was no difference in triglyceride levels, and the omega-3 group had a higher HDL cholesterol level than the control group. There was no difference in systolic blood pressure between the groups. That leaves us with the HOMA-IR calculation.

Typically, serum insulin would be used in the calculation to determine the HOMA-IR number. They didn’t collect insulin data, so they used another indicator of insulin levels in calculating the HOMA-IR. The problem is that that algorithm was based on 21 adult subjects; it was never validated with a larger group or for use in children. I question its use, but for argument’s sake, let’s say it doesn’t matter.

The Real Problem

The real problem that I have is with the remark about a tendency towards increased percent body fat. When they assessed body composition at 10 years of age, they used bioelectrical impedance analysis (BIA). I worked on comparing methods of body composition analysis when I was a graduate student, so I can tell you from experience that underwater weighing is the gold standard for any group (and, yes, I’ve underwater weighed 10-year-olds). Specifically, there are two factors that are always concerning with BIA:

  • The algorithm is 95% dependent on height and weight. A two-pound difference in body weight in children could impact the calculation, even if the actual body composition was the same.
  • BIA is sensitive to fluid levels of the body. It assesses total body water and calculates fat mass by making an assumption about the water content of the remaining tissues. It’s not the best way to assess body fat in a major study such as this.

The Bottom Line

How?!!!

We hear that a lot when our grandson plays a videogame. When something happens that he doesn’t anticipate or understand, he yells “How?!!!” and that’s what I’m thinking right now. The most frustrating part of this research paper is their conclusion that omega-3 supplementation in the last trimester of pregnancy may result in adverse effects to the children.

How? How would supplementing with omega-3 fatty acids cause the offspring to have an increased risk of being overweight or obese? They did not provide any comment on how that could occur.

As it stands now, we really don’t know much more about omega-3 supplementation in the third trimester of pregnancy other than the kids whose mothers took omega-3 fatty acid had fewer serious asthma and allergy symptoms; because the incidence of asthma and allergies are rising steadily, that may be the most important observation from this study so far.

As for body composition? Not so much. This study will continue until the subjects are adults, so maybe further testing will yield more conclusive results.

What are you prepared to do today?

        Dr. Chet

Reference: AJCN. 2024. doi.org/10.1016/j.ajcnut.2023.12.015

Research Update: Omega-3s and Lung Function

/in /by

Lung function declines as we age; depending on how we treat our lungs, our habits can determine the rate of decline. Working in toxic situations (or even worse, smoking cigarettes) can accelerate the decline. That’s why a recent study that examined blood levels of omega-3 fatty acids and measures of lung function found that our diet has an impact on lung function. Let’s look at this study.

Increases in Omega-3 Levels Prevent Decline

Of the two studies reported in the paper, I’ll stick to the longitudinal study, although both demonstrated the positive impact of omega-3s on lung function. A couple definitions first.

  • Forced expiratory volume 1 (FEV1) is the amount of air that one can forcefully breathe out in one second. The normal range is 2,500 to 3,250 milliliters.
  • Forced vital capacity (FVC) is the amount breathed out after a normal exhalation. The normal range is 3,700 ml to 4,800 ml.

One more thing: in this study, the mean rate of lung function decline was 36.8 mL per year for FEV1 and 35.8 mL per year for FVC.

Researchers examined a pooled group of studies that were part of the National Heart, Lung, and Blood Institute Pooled Cohorts Study. Studies were chosen because of the repeated measurements of both lung function and plasma phospholipid omega-3 fatty acids. The study found that higher omega-3 fatty acid levels were associated with less decline in lung function for 15,063 participants. The omega-3 that provided the most benefit was the omega-3 fatty acid DHA. In plain English, the more the DHA levels increased over time, the more the decline in lung function was prevented. I know that sounds funny to say it “prevented decline” but to say that it improved lung function would be incorrect.

The Questions

In both studies, nutritional information wasn’t collected, or if it was collected, it wasn’t used in the statistical analyses performed. The assumption seems to be that seafood and plants were the primary sources of omega-3 fatty acids, and that may be true. But it raises a question about the potential for using omega-3s in dietary supplements. Would the same response occur in reducing the risk of chronic kidney disease as it did for the loss of lung function?

It also raises another question. Many studies on the benefits of omega-3 supplements on heart health and other organs are often less than overwhelming. Could it be that there is a nutrient or nutrients in fish that, together with omega-3s, could contribute to benefits? Or could it be there’s a factor that helps with digestion, absorption, and utilization in the actual form of omega-3s used as supplements? We don’t know at this time.

The Bottom Line

While the benefits of omega-3s, specifically DHA, were small, the fact that they prevented decline over years contributes to aging with a vengeance. I think having a diet that includes the regular intake of fatty fish is the key to a healthy lifestyle, and I still think regular use of fish oil supplements may prove to be beneficial as the research continues. I’ll keep you posted.

What are you prepared to do today?

        Dr. Chet

References:
1. Am J Respir Crit Care Med. 2023 Jul 20. doi: 10.1164/rccm.202301-0074OC
2. BMJ 2023;380:e072909. doi: 10.1136/bmj-2022-0729092

Research Update: Omega-3s and Chronic Kidney Disease

/in /by

Two recently published articles examined the link between omega-3 fatty acids from fish and two conditions; let’s begin with a study on fish consumption and chronic kidney disease (CKD). By definition, CKD is the loss of kidney function over time. The kidneys are the major blood filtering system, so continued decline can impact the entire body.

Researchers selected 19 studies from 12 countries to perform a meta-analysis. The key variables were measurement of omega-3 fatty acid levels and types—EPA, DHA, and DPA from seafood, plus ALA from plant sources—together with the estimated glomerular filtration rate (eGFR). The researchers identified 25,570 participants that met the criteria and were included in the analysis.

Over a median of 11.3 years of follow-up, 4,944 (19.3%) developed CKD. Higher levels of total seafood omega-3s were associated with a lower CKD risk. In comparing categories of omega-3 levels, subjects with total seafood omega-3 level in the highest quintile had a 13% lower risk of developing CKD compared with those in the lowest quintile. The association appeared consistent across subgroups by age, eGFR, and diagnosis of hypertension, diabetes, and coronary heart disease at baseline.

While this was an observational study, there appeared to be an inverse relationship between blood levels of omega-3s from seafood sources and the development of CKD. Do we know if this included supplementation with omega-3s? That wasn’t assessed in this study. We’ll look at another recent study on omega-3s on Saturday and ask the big question.

What are you prepared to do today?

        Dr. Chet

Reference: BMJ 2023;380:e072909. doi: 10.1136/bmj-2022-0729092

Should People with CVD Take Omega-3s?

/in /by

Last time, I talked about some research that hasn’t been done to definitively know whether DHA contributes to arrhythmias or not, but I implied that there may be one issue that may have contributed to this latest study. Let’s talk about research bias.

Research Bias

Some of the researchers who examined the data from the longitudinal study I talked about on Tuesday were also involved in at least one of the clinical trials on Vascepa, the pharmaceutical form of EPA-only omega-3s. I know what you’re thinking: somehow they intentionally manipulated data so that it seemed DHA was bad. I wouldn’t assume that, because these are good scientists. However, there has to be an inherent bias—beliefs that set up space in your brain and affect your actions without you realizing it. Another way of stating this would be that you find what you look for. It would be very difficult to examine any data involving EPA, DHA, and cardiovascular disease and withhold bias. I don’t believe it was intentional, but I also believe that it could have influenced the results to some degree.

The INtermountain Healthcare Biological Samples Collection Project and Investigational Registry (INSPIRE for short) is not a randomized clinical trial; it’s an observational study. I’ve already talked about the data that are missing on diet, supplementation, and exercise. In addition, it’s a big stretch to suggest that 10 years after samples were taken during an angiographic procedure that the same distribution of EPA-DHA was maintained.

Prior Research

Let’s think about the studies from last week: they were test-tube studies. Those are the foundation you must build before you start doing animal testing; only after that do you get to human testing. One research group also did a study on rodents which demonstrated proof of possible benefit. Have we had that type of research on EPA and DHA as it relates to cardiovascular disease? I did find some.

There have been studies examining how omega-3s may positively affect heart rhythms. In studies on rodents and dogs, DHA but not EPA showed clear benefits on reducing atrial fibrillation and other forms of cardiovascular disease.

But when you examine research on humans, the data are conflicting. By that I mean that some studies show that higher DHA intake and/or levels are associated with the reduction of arrhythmias. Other more recent research shows that it may not. There’s simply not enough information to make a decision.

The Bottom Line

At this point, you have to be thinking “What the heck am I supposed to do?” I think that we stand in an area of research where we have to “reserve judgment,” or maybe it would be better to say to “reserve condemnation.” We just don’t have enough data to make an informed decision either way. I’ve illustrated some of the things that need to be answered as it relates to omega-3 intake, but there are many more questions.

So I’ll leave you with this. If you have had no signs or symptoms of cardiovascular disease, no matter your age, you can most likely continue taking the same omega-3 supplements you always have been. If you have had a heart attack with damage to the muscle tissue, that seems to be where the problem lies, but it isn’t the same for every person. I would have a discussion with your cardiologist before deciding whether to take just EPA or to continue taking combinations of EPA and DHA; that’s the prudent thing to do.

But as you make that decision, consider all the other benefits of omega-3s. A search for “omega-3” at drchet.com yields several pages of results. Very rarely in life do we have simple decisions to make; it’s always a balancing act between competing objectives and imperfect information, and this is another one of those situations.

What are you prepared to do today?

        Dr. Chet

References:
1. J Am Coll Cardiol. 2021 May, 77 (18_Supplement_1) 1453.
2. Vascul Pharmacol. 2016 Jul;82:11-9. doi: 10.1016/j.vph.2016.03.007.
3. Can J Physiol Pharmacol. 2016 Mar;94(3):309-23. doi: 10.1139/cjpp-2015-0300.
4. Circulation: Arrhythmia and Electrophysiology. 2012;5:978–983.

Omega-3s and Heart Disease

/in /by

In addition to the research papers on omega-3s I talked about last week, another paper was presented at the American College of Cardiology in May that suggests EPA seems to reduce cardiovascular disease (CVD), while DHA seems to neutralize the benefits. Let’s take a look at this recent study to see what they found.

I haven’t seen the data, just press releases of varying lengths; I’ve written the authors but haven’t heard back yet. The problem with this recent study is that it’s a retrospective examination of a large group of people. The data are part of an ongoing study (much like the All Of Us study in which I’m a volunteer) that secured blood and tissue samples of volunteers; the researchers use that data as well as access to the volunteers’ medical records. In this case, they assessed the EPA and DHA levels of the blood samples and the CVD events that occurred in a random sample of the volunteers over the years. That’s how they determined that the EPA was beneficial in reducing CVD and as DHA levels rose, the benefits were negated.

The primary problem is that the blood samples are a snapshot of one day in the life of the volunteers. We have no idea if they took dietary supplements or if they happened to eat a lot of fish or a lot of nuts and other foods with omega-3s. No other dietary data, no supplement data, no exercise data—all things that we know are related to the development of cardiovascular disease. I think there’s a significant factor at play in this data analysis, and I’ll give you that observation in Saturday’s memo.

What are you prepared to do today?

        Dr. Chet

Reference: Press Release: Warning: Combination of Omega-3s in Popular Supplements May Blunt Heart Benefits. Intermountain Medical Center May 17, 2021

Omega-3s May Kill Tumors

/in /by

As exciting as Tuesday’s Memo might have been on omega-3s and superbugs, today’s Memo probably tops that. Before we get too excited, it’s important to remember that this was another test-tube study. That’s fine; that’s how research into any topic begins, but it still has to be proven in human trials.

Researchers in Belgium exposed tumors to various types of polyunsaturated fatty acids including omega-3s and omega-6s. This is the important part: as they made the medium more acidic, the tumors preferentially used fatty acids as fuel. The tumor cells started to implode via a process called ferroptosis. Literally, it means “iron cell death.” What seems to happen is that as the tumor becomes more acidic, it can’t store the fat as well. That creates free radicals, and the tumor cells are destroyed from the inside out. The fish-oil DHA was the most effective at killing tumor cells.

What does this mean for us? Nothing yet, but in another study, when mice were given DHA, their tumors developed more slowly. Remember, what happens in tumors may not happen in the body because actual tumors may have developed a more sophisticated defense system. Then there’s the matter of causing acidity—not necessarily easy to do systemically or targeting just the cancer. But just as with the superbugs, it gives us a reason to take our fish oil with EPA and DHA. And of course, there are other potential benefits to the body as well. Fish burps seem a small price to pay for all this protection, right?

How about the recent research on DHA and atrial fibrillation? I’ll tackle that issue in next week’s Memos. It comes down to scientists asking the correct question.

What are you prepared to do today?

        Dr. Chet

Reference: Cell Metabolism. https://doi.org/10.1016/j.cmet.2021.05.016.

Omega-3s: New Weapon Against Superbugs?

/in /by

One of the biggest concerns with hospitalization is catching an antibiotic-resistant bacterial infection. It happened to my father-in-law about 15 years ago, and it was a serious infection requiring over a week in the hospital. He survived, but more superbugs are still around and have gotten worse.

Researchers in Australia examined one such superbug to see how it responds to exposure to omega-3 fatty acids from fish oil. This was a test-tube study and the paper isn’t published online yet, so I can’t check the methodology. What they have reported is that one such superbug, Acinetobacter baumannii, doesn’t seem to discriminate between the fats that it consumes in the hosts’ body. The omega-3s seem to make the bacteria susceptible to a greater variety of antibiotics.

Remember, this is a test-tube study; not everything that works in a test tube works in a human body. Human trials will take some time if those scientists and others can replicate this research. What it means to us right now is that the fish oil we’ve been taking all these years may have benefits we never even considered. I’ll cover another such benefit on Saturday.

Wednesday night at 9 E.T. is the Insider Conference Call. Topics on the docket are more info on omega-3s and cardiovascular disease, plus collagen and skin health. You can still participate by becoming an Insider before 8 p.m. Wednesday.

What are you prepared to do today?

        Dr. Chet

Reference: mBio. DOI: 10.1128/mBio.01070-21

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

/in /by

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

/in /by

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

/in /by

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