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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Do Omega-3s Lower Blood Pressure in Young, Healthy Adults?

Posted August 14, 2018 by Dr. Steve Chaney

What Is The Omega-3 Index And Why Is It Important?

Author: Dr. Stephen Chaney

 

Do omega-3s lower blood pressure in healthy adults?

omega-3s lower blood pressure young adultsThe literature on the potential health benefits of omega-3s is very confusing. That’s because a lot of bad studies have been published. Many of them never determined the omega-3 status of their subjects prior to omega-3 supplementation. Others relied on dietary recalls of fish consumption, which can be inaccurate.

Fortunately, a much more accurate measure of omega-3 status has been developed and validated in recent years. It’s called the Omega-3 Index. Simply put, the Omega-3 Index is the percentage of EPA and DHA compared to 26 other fatty acids found in cellular membranes. Using modern technology, it can be determined from a single finger prick blood sample. It is a very accurate reflection of omega-3 intake relative to other fats in the diet over the past few months. More importantly, it is a measure of the omega-3 content of your cell membranes, which is a direct measure of your omega-3 nutritional status.

A recent extension of the Framingham Heart Study reported that participants with an Omega-3 Index >6.8% had a 39% lower risk of cardiovascular disease than those with an Omega-3 Index <4.2% (WS Harris et al, Journal of Clinical Lipidology, 12: 718-724, 2018 ). Although more work needs to be done, an Omega-3 Index of 4% or less is generally considered indicative of high cardiovascular risk, while 8% or better is considered indicative of low cardiovascular risk. For reference, the average American has an Omega-3 Index in the 4-5% range. In Japan, where fish consumption is much higher and cardiovascular risk much lower, the Omega-3 Index is in the 9-11% range.

Previous studies have suggested that omega-3 fatty acids lower blood pressure to a modest extent. Thus, it is not surprising that more recent studies have shown an inverse correlation between Omega-3 Index and blood pressure. However, those studies have been done with older populations, many of whom had already developed high blood pressure.

From a public health point of view, it is much more interesting to investigate whether it might be possible to prevent high blood pressure in older adults by optimizing omega-3 intake in a young, healthy population, most of whom had not yet developed high blood pressure. Unfortunately, there were no studies looking at that population. The current study was designed to fill that gap.

 

How Was The Study Done?

omega-3s lower blood pressure young healthy adultsThe current study (M.G. Filipovic et al, Journal of Hypertension, 36: 1548-1554, 2018 ) was based on data collected from 2036 healthy adults, aged 25-41, from Liechtenstein. They were participants in the GAPP (Genetic and Phenotypic Determinants of Blood Pressure) study. Participants were excluded from the study if they had been diagnosed with high blood pressure and were taking medication to lower their blood pressure. They were also excluded if they had heart disease, chronic kidney disease, other severe illnesses, obesity, sleep apnea, or daily use of non-steroidal anti-inflammatory medications.

Blood samples were collected at the time of their enrollment in the study and frozen for subsequent determination of Omega-3 Index. Blood pressure was also measured at their time of enrollment in two different ways. The first was a standard blood pressure measurement in a doctor’s office.

For the second measurement they were given a wearable blood pressure monitor that recorded their blood pressure over 24 hours every 15 minutes during the day and every 30 minutes while they were sleeping. This is considered more accurate than a resting blood pressure measurement in a doctor’s office because it records the variation in blood pressure, while you are sleeping, while you are exercising, and while you go about your everyday activities.

 

Do Omega-3s Lower Blood Pressure In Young, Healthy Adults?

omega-3s lower blood pressure young adults equipmentNone of the participants in the study had significantly elevated blood pressure. The mean systolic and diastolic office blood pressures were 120±13 and 78±9 respectively. The average Omega-3 Index in this population was 4.6%, which is similar to the average Omega-3 Index in the United States.

When they compared the group with the highest Omega-3 Index (average = 5.8%) with the group with the lowest Omega-3 Index (average = 4.6%):

  • The office measurement of systolic and diastolic blood pressure was decreased by 3.3% and 2.6% respectively
  • While those numbers appear small, the differences were highly significant.
  • The 24-hour blood pressure measurements showed a similar decrease.
  • Blood pressure measurements decreased linearly with increasing Omega-3 Index. [In studies of this kind, a linear dose-response is considered an internal validation of the differences observed between the group with the highest Omega-3 Index and the group with the lowest Omega-3 Index.]

The authors concluded: “A higher Omega-3 Index is associated with statistically significant, clinically relevant, lower systolic and diastolic blood pressure in normotensive, young and healthy individuals. Diets rich omega-3 fatty acids may be a strategy for primary prevention of hypertension.”

 

What Does This Mean For You?

omega-3s lower blood pressure young adults questionPerhaps I should first comment on the significance of the relatively small decrease in blood pressure observed in this study.

  • These were young adults, all of whom had normal or near normal blood pressure.
  • The difference in Omega-3 Index was rather small (5.8% to 4.6%). None of the participants in the study were at the 8% or above that is considered optimal.
  • Liechtenstein is a small country located between Switzerland and Spain. Fish consumption is low and omega-3 supplement consumption is rare.

Under these conditions, even a small, but statistically significant, decrease in blood pressure is remarkable.

We should think of this study as the start of the investigation of the relationship between omega-3 status and blood pressure. Its weakness is that it only shows an association between high Omega-3 Index and low blood pressure. It does not prove cause and effect.

Its strength is that it is consistent with many other studies showing omega-3 fatty acids lower blood pressure. Furthermore, it suggests that the effect of omega-3s on blood pressure may also be seen in young, healthy adults who have not yet developed high blood pressure.

Finally, the authors suggested that a diet rich in omega-3s might reduce the incidence of high blood pressure by slowing the age-related increase in blood pressure that most Americans experience. This idea is logical, but speculative at present.

However, the GAPP study is designed to provide the answer to that question. It is a long-term study with follow-up examinations scheduled every 3-5 years. It will be interesting to see whether the author’s prediction holds true, and a higher Omega-3 Index is associated with a slower increase in blood pressure as the participants age.

 

Why Is The Omega-3 Index Important?

 

The authors of this study said: “The Omega-3 Index is very robust to short-term intake of omega-3 fatty acids and reliably reflects an individual’s long-term omega-3 status and tissue omega-3 content. Therefore, the Omega-3 Index has the potential to become a cardiovascular risk factor as much as the HbA1c is for people with diabetes…” That is a bit of an overstatement. HbA1c is a measure of disease progression for diabetes because it is a direct measure of blood sugar control.

In contrast, Omega-3 Index is merely a risk factor for cardiovascular disease. However, if it is further validated by future studies, it is likely to be as important for predicting cardiovascular risk as are cholesterol levels and markers of inflammation.

However, to me the most important role of Omega-3 Index is in the design of future clinical studies. If anyone really wants to determine whether omega-3 supplementation reduces cardiovascular risk, high blood pressure, diabetes or any other health outcome they should:

  • Start with a population group with an Omega-3 Index in the deficient (4-5%) range.
  • Supplement with omega-3 fatty acids in a double blind, placebo-controlled manner.
  • Show that supplementation brought participants up to an optimal Omega-3 Index of 8% or greater.
  • Look at health outcomes such as heart attacks, cardiovascular deaths, hypertension, stroke, or depression.
  • Continue the study long enough for the beneficial effects of omega-3 supplementation to be measurable. For cardiovascular outcomes the American Heart Association has stated that at least two years are required to obtain meaningful results.

These are the kind of experiments that will be required to give definitive, reproducible results and resolve the confusion about the health effects of omega-3 fatty acids.

 

The Bottom Line

 

An accurate measure of omega-3 status has been developed and validated in recent years. It’s called the Omega-3 Index. Simply put, the Omega-3 Index is the percentage of EPA and DHA compared to 26 other fatty acids found in cellular membranes.

Although more work needs to be done, an Omega-3 Index of 4% or less is generally considered indicative of high cardiovascular risk while 8% or better is considered indicative of low cardiovascular risk.

Previous studies have shown an inverse correlation between Omega-3 Index and blood pressure. However, these studies have been done with older populations, many of whom had already developed high blood pressure.

From a public health point of view, it is much more interesting to investigate whether it might be possible to prevent high blood pressure in older adults by optimizing omega-3 intake in a young, healthy population, most of whom had not yet developed high blood pressure. Until now, there have been no studies looking at that population.

The study described in this article was designed to fill that gap. The participants in this study were ages 25-41, were healthy, and none of them had elevated blood pressure.

When the group with the highest Omega-3 Index (average = 5.8%) was compared with the group with the lowest Omega-3 Index (average = 4.6%):

  • Both systolic and diastolic blood pressure were decreased
  • Blood pressure measurements decreased linearly with increasing Omega-3 Index.

The authors concluded: “A higher Omega-3 Index is associated with statistically significant, clinically relevant, lower systolic and diastolic blood pressure in normotensive, young and healthy individuals. Diets rich omega-3 fatty acids may be a strategy for primary prevention of hypertension.”

Let me translate that last sentence into plain English for you. The authors were saying that optimizing omega-3 intake in young adults may slow the age-related increase in blood pressure and reduce the risk of them developing high blood pressure as they age. This may begin to answer the question “Do omega-3s lower blood pressure in young, healthy adults?”

Or even more simply put: Aging is inevitable. Becoming unhealthy is not.

For more details, 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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