Omega-3 and Heart Disease Risk

Written by Dr. Steve Chaney on . Posted in Omega-3s and Heart Disease

Why Is There So Much Confusion About Omega-3 and Heart Disease Risk?

Author: Dr. Stephen Chaney

 

omega-3 heart diseaseConcerning omega-3 and heart disease, the pendulum keeps swinging. In the 1990’s several strong clinical studies showed that omega-3s reduced heart disease risk. In fact, a major clinical study in Italy, (Lancet 354: 447 – 455, 1999 , Circulation 105 : 1897 – 1903, 2002 ), found omega-3s to be just as effective as statin drugs for preventing heart attacks, but without any of the side effects of statins.

At that time, everyone was talking about the benefits of omega-3s in reducing heart disease risk. The American Heart Association recommended an intake of 500-1,000 mg/day of omega-3s for heart health. Some experts were recommending even more if you were at high risk of heart disease.

In the 2000’s the pendulum swung in the other direction. Several clinical studies found no benefit of omega-3s in reducing heart disease risk. Suddenly, experts were telling us that omega-3s were overrated. They were a waste of money. The American Heart Association kept their omega-3 recommendations for heart health, but put more emphasis on omega-3s for people with elevated triglycerides (where the benefits of omega-3s are non-controversial).

Suddenly regarding omega-3 and heart disease, the pendulum is swinging back again. A recent meta-analysis (Alexander et al, Mayo Clinic Proceedings, 92: 15-29, 2017) reported that omega-3s do appear to be beneficial at reducing heart disease risk. An editorial accompanying that article (O’Keefe et al, Mayo Clinic Proceedings, 92: 1-3, 2017) called the meta-analysis “the most comprehensive of its kind to date…” Those experts went on to say “…omega-3-fatty acid intake of at least 1 gram of EPA + DHA per day, either from seafood or supplementation (as recommended by the American Heart Association) continues to be a reasonable strategy.”

This was followed by publication of three clinical studies that came to essentially the same conclusion (Kieber et al, Atherosclerosis, 252: 175-181, 2016 ; Sala-Vila et al, Journal of the American Heart Association, In Press ; and Greene et al, American Journal of Cardiology, 117: 340-346, 2016 ).

Why is there so much confusion about omega-3 and heart disease? Let’s start by reviewing the recently published meta-analysis.

 

Do Omega-3s Lower Heart Disease Risk?

omega-3 lowers heart disease riskThis study (Alexander et al, Mayo Clinic Proceedings, 92: 15-29, 2017) combined the data from 18 randomized controlled trials with 93,000 patients and 16 prospective cohort studies with 732,000 patients. This was the largest meta-analysis on omega-3s and heart health performed to date. The results were as follows:

  • The combined data from the randomized controlled studies showed that omega-3 supplementation resulted in a non-significant 6% reduction in heart disease risk. This is similar to other recently published studies (more about that later).
  • However, when the investigators looked at high risk populations within the randomized controlled studies, the results were strikingly different.
    • In patients with elevated triglycerides, omega-3 supplementation caused a significant 16% reduction in heart disease risk.
    • In patients with elevated LDL cholesterol, omega-3 supplementation caused a significant 18% reduction in heart disease risk.
  • In addition, the combined data from the prospective cohort studies showed that omega-3 supplementation resulted in a significant 18% decrease in heart disease risk.

The authors concluded “[Our] results indicate that EPA + DHA may be associated with reducing heart disease risk, with greater benefits observed among higher-risk populations…”

 

Why Is There So Much Confusion About Omega-3s and Heart Disease Risk?

confusionThere are several major clinical studies in progress looking at the effect of omega-3s on heart health. Some experts predict that the confusion will be cleared up once they are published. I predict they will only add to the confusion. Let me explain why.

You’ve heard the old saying “Garbage in – garbage out.”  Proper design of clinical studies is essential. If a study is poorly designed, it provides incorrect information. When you analyze the previous clinical studies carefully, you find that many of them are flawed. Their results are, therefore, incorrect. My fear is that many of the ongoing clinical studies will contain the same flaws and will provide the same incorrect information.

Let’s look at the flaws, and why they provide incorrect information.

Flaw #1: Omega-3 supplementation will only be beneficial for people who are omega-3 deficient. The authors of the Mayo Clinic Proceedings editorial provided a useful analogy. They said: “Vitamin C bestows dramatic and lifesaving benefits to persons with scurvy, but is no better than placebo for persons who are replete with vitamin C.”

That means a well-designed study should measure omega-3 levels in red blood cells both prior to and at the end of the clinical study. The data analysis should focus on those individuals who started the study with low omega-3 status and whose omega-3 status improved by the end of the study. Unfortunately, few of the previously published studies have done that, and I am not confident that the ongoing studies have incorporated that into their experimental design.

Flaw #2: Omega-3 supplementation will be of most benefit for those people who are at highest risk for heart disease. This has been a recurrent pattern in the literature. Many of the clinical studies focusing on high-risk individuals have shown a beneficial effect of omega-3 supplementation on heart disease risk. Most of the studies focusing on the general population (most of which are of low risk for heart disease) have failed to show a benefit of omega-3 supplementation. The current meta-analysis is no exception. When they looked at the general population, there was a non-significant reduction in heart disease risk. However, when they looked at high-risk populations the beneficial effect of omega-3s was highly significant.

I can’t predict how the ongoing studies will analyze their data. If they focus on high-risk groups they are more likely to report a beneficial effect of omega-3s on heart health. If they only report on the results with the general population, they are likely to conclude that omega-3s are ineffective.

I do need to make an important distinction here. The inability to demonstrate a beneficial effect of omega-3 supplementation in the general population does not mean that there is no effect. It turns out to be incredibly difficult to demonstrate a beneficial effect of any intervention, including statins , in a healthy, low-risk population. Because of that, we may never know for sure about the relationship between omega-3 and heart disease. Do omega-3s reduce heart disease risk for the young and healthy. At the end of the day, you will need to make your own decision about whether omega-3s make sense to you.

omega-3 supplementationFlaw #3: Heart medications mask the beneficial effects of omega-3 supplementation. When the public hears about the results of a randomized controlled study they assume that the placebo group received no treatment and the omega-3 group was only receiving omega-3s. That is not how it works.  Medical ethics guidelines require that the placebo group receive the standard of care treatment – namely whatever drugs are considered appropriate for that population group.

That means that it has become very difficult to demonstrate that high-risk populations benefit from omega-3 supplementation. Back in the 90s, the standard of care for high risk patients was only one or two drugs. In those days, many studies were reporting beneficial effects of omega-3 supplementation in high risk populations. However, for the past 5-10 years the standard of care for high risk patients is 4-5 medications.

These are medications that reduce cholesterol levels, lower triglyceride levels, lower blood pressure, reduce inflammation, and reduce clotting time. In other words, the drugs mimic all the beneficial effects of omega-3s. (The only difference is that the drugs come with side-effects. The omega-3s don’t.) It is no coincidence that many of the recent studies have come up empty-handed.

The current studies are asking a fundamentally different question. In the 90s, clinical studies asked whether omega-3s reduced heart disease risk in high-risk patients. Today’s clinical studies are asking whether omega-3s provide any additional benefits for patients who are already taking multiple drugs. Personally, I think my readers are more interested in the first question than the second.

Once again, the current meta-analysis is perfectly consistent with this interpretation. The high-risk groups who clearly benefited from omega-3 supplementation were not ones with pre-existing heart disease or who had previously had a heart attack. They were the ones with elevated LDL cholesterol or triglycerides. They were patients who were, either not taking drugs for those risk factors, or patients for whom the drugs were ineffective.

Because subjects in future studies will be taking multiple medications, I predict that even those ongoing studies focusing on high-risk populations will come up empty-handed.

Now you understand why I started this section by saying that I predict many of the ongoing studies will provide incorrect results. I predict that you will see more headlines proclaiming that omega-3s don’t work. However, you won’t be swayed by those headlines because you now know the truth about the flaws in the clinical studies behind the headlines!

What Does This Mean For You?

omega-3 fish oilThe most recent meta-analysis and a careful evaluation of previous studies make two things clear:

  • If you are at high risk of heart disease, omega-3 supplementation is likely to reduce your risk.

We can divide risk factors for heart disease into those we know about, and those we don’t.

  • Risk factors we know about include previously diagnosed heart disease or heart attack, genetic predisposition, age, elevated LDL cholesterol levels, high triglycerides, high blood pressure, inflammation, obesity, metabolic syndrome and diabetes.
  • Unfortunately, there are also risk factors we don’t know about. For too many Americans the first sign of heart disease is sudden death – sometimes just after receiving a clean bill of health from their doctor.
  • If you are not getting enough omega-3s in your diet, omega-3 supplementation is likely to reduce your heart disease risk.

If you are young and healthy, the unfortunate truth is that we may never completely understand the relationship between omega-3 and heart disease. We may not know whether omega-3 supplementation reduces your risk of heart disease. However, I think the overall evidence is strong enough that you should consider adding omega-3s to your diet.

In short, I agree with the authors of the Mayo Clinic Proceedings editorial and the American Heart Association that omega-3-fatty acid intake of at least 1 gram of EPA + DHA per day, either from seafood or supplementation, is a prudent strategy for reducing heart disease risk.

 

The Bottom Line

  • There has been a lot of confusion about the role of omega-3s in reducing heart disease risk.
  • In the 90s, several clinical studies reported that omega-3 supplementation reduced heart disease risk. Most experts, including the American Heart Association, were recommending that most Americans would benefit from adding 500-1,000 mg of omega-3s to their daily diet.
  • In recent years, several clinical studies have reported that omega-3 supplementation has no effect on heart disease risk. [There were some important flaws in those studies, which I discuss in the article above]. Experts started saying that omega-3s were overrated. They were a waste of money.
  • The largest meta-analysis ever undertaken in this area of research has recently reported that omega-3 supplementation decreases risk of heart disease in high-risk population groups. Three subsequent clinical studies have come to essentially the same conclusion.
  • Other studies suggest that omega-3 supplementation is also likely to reduce heart disease risk in individuals with poor omega-3 status, and most Americans have poor omega-3 status.
  • We may never know whether omega-3 supplementation reduces heart disease risk if you are young and healthy. Simply put, not enough young & healthy people develop heart disease within the time-frame of a clinical study for the results to be statistically significant. For this group, the old saying about “An ounce of prevention…” just makes sense.
  • I agree with those experts who recommend at least 1,000 mg/day of omega-3s as a prudent strategy for reducing heart disease risk.
  • There are several major clinical trials in progress studying the efficacy of omega-3s for reducing heart disease risk. Some experts predict that the confusion will be cleared up once they are published. I predict they will only add to the confusion. I predict that many of those studies will show no benefit of omega-3 supplementation, and you will see more headlines proclaiming that omega-3s play no role in heart health. If you have read the article above, you won’t be swayed by those headlines because you will know the truth about the flaws in the studies behind the headlines.

 

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

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Is Our Microbiome Affected By Exercise?

Posted November 6, 2018 by Dr. Steve Chaney

Microbiome Mysteries

Author: Dr. Stephen Chaney

is our microbiome affected by exerciseIn a recent post,  What is Your Microbiome and Why is it Important,  of “Health Tips From The Professor” I outlined how our microbiome, especially the bacteria that reside in our intestine, influences our health. That influence can be either good or bad depending on which species of bacteria populate our gut. I also discussed how the species of bacteria that populate our gut are influenced by what we eat and, in turn, influence how the foods we eat are metabolized.

I shared that there is an association between obesity and the species of bacteria that inhabit our gut. At present, this is a “chicken and egg” conundrum. We don’t know whether obesity influences the species of bacteria that inhabit our gut, or whether certain species of gut bacteria cause us to become obese.

Previous studies have shown that there is also an association between exercise and the species of bacteria that inhabit our gut. In particular, exercise is associated with an increase in bacteria that metabolize fiber in our diets to short chain fatty acids such as butyrate. That is potentially important because butyrate is a primary food source for intestinal mucosal cells (the cells that line the intestine). Butyrate helps those cells maintain the integrity of the gut barrier (which helps prevent things like leaky gut syndrome). It also has an anti-inflammatory effect on the immune cells that reside in the gut.

However, associations don’t prove cause and effect. We don’t know whether the differences in gut bacteria were caused by differences in diet or leanness in populations who exercised regularly and those who did not. This is what the present study (JM Allen et al, Medicine & Science In Sports & Exercise, 50: 747-757, 2018 ) was designed to clarify.  Is our microbiome affected by exercise?

 

How Was The Study Designed?

is our microbiome affected by exercise studyThis study was performed at the University of Illinois. Thirty-two previously sedentary subjects (average age = 28) were recruited for the study. Twenty of them were women and 12 were men. Prior to starting the study, the participants filled out a 7-day dietary record. They were asked to follow the same diet throughout the 12-week study. In addition, a dietitian designed a 3-day food menu based on their 7-day recall for the participants to follow prior to each fecal collection to determine species of gut bacteria.

The study included a two-week baseline when their baseline gut bacteria population was measured, and participants were tested for fitness. This was followed by a 6-week exercise intervention consisting of three supervised 30 to 60-minute moderate to vigorous exercise sessions per week. The exercise was adapted to the participant’s initial fitness level, and both the intensity and duration of exercise increased over the 6-week exercise intervention. Following the exercise intervention, all participants were instructed to maintain their diet and refrain from exercise for another 6 weeks. This was referred to as the “washout period.”

VO2max (a measure of fitness) was determined at baseline and at the end of the exercise intervention. Stool samples for determination of gut bacteria and concentrations of short-chain fatty acids were taken at baseline, at the end of the exercise intervention, and again after the washout period.

In short, this study divided participants into lean and obese categories and held diet constant. The only variable was the exercise component.

 

Is Our Microbiome Affected By Exercise?

is our microbiome affected by exercise fitnessThe results of the study were as follows:

  • Fitness, as assessed by VO2max, increased for all the participants, and the increase in fitness was comparable for both lean and obese subjects.
  • Exercise induced a change in the population of gut bacteria, and the change was comparable in lean and obese subjects.
  • Exercise increased fecal concentrations of butyrate and other short-chain fatty acids in the lean subjects, but not in obese subjects.
  • The exercise-induced changes in gut bacteria and short-chain fatty acid production were largely reversed once exercise training ceased.

The authors concluded: “These findings suggest that exercise training induces compositional and functional changes in the human gut microbiota that are dependent on obesity status, independent of diet, and contingent on the sustainment of exercise.” [Note: To be clear, the exercise-induced changes in both gut bacteria and short-chain fatty acid production were independent of diet and contingent on the sustainment of exercise. However, only the production of short-chain fatty acids was dependent on obesity status.]

 

What Does This Study Mean For You?

is our microbiome affected by exercise gut bacteriaThere are two important take home lessons from this study.

  • With respect to our gut bacteria, I have consistently told you that microbiome research is an emerging science. This is a small study, so you should regard it as the beginning of our understanding of the effect of exercise on our microbiome rather than conclusive by itself. It is consistent with previous studies showing an association between exercise and a potentially beneficial shift in the population of gut bacteria.

The strength of the study is that it shows that exercise-induced changes in beneficial gut bacteria are probably independent of diet. However, it is the first study to look at the interaction between obesity, exercise and gut bacteria, so I would interpret those results with caution until they have been replicated in subsequent studies.

  • With respect to exercise, this may be yet another reason to add regular physical activity to your healthy lifestyle program. We already know that exercise is important for cardiovascular health. We also know that exercise increases lean muscle mass which increases metabolic rate and helps prevent obesity. There is also excellent evidence that exercise improves mood and helps prevent cognitive decline as we age.

Exercise is also associated with decreased risk of colon cancer and irritable bowel disease. This effect of exercise has not received much attention because the mechanism of this effect is unclear. This study shows that exercise increases the fecal concentrations of butyrate and other short-chain fatty acids. Perhaps, this provides the mechanism for the interaction between exercise and intestinal health.

 

The Bottom Line

A recent study has reported that:

  • Exercise induces a change in the population of gut bacteria, and the change was comparable in lean and obese subjects.
  • Exercise causes an increase in the number of gut bacteria that produce butyrate and other short-chain fatty acids that are beneficial for gut health.
  • These effects are independent of diet, but do not appear to be independent of obesity because they were seen in lean subjects but not in obese subjects.
  • The exercise-induced changes in gut bacteria and short-chain fatty acid production are largely reversed once exercise training ceases.

The authors concluded: “These findings suggest that exercise training induces compositional and functional changes in the human gut microbiota that are dependent on obesity status, independent on diet, and contingent on the sustainment of exercise.”

For more details and my interpretation of the data, read the article above.

 

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

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