Do Omega-3s Reduce Heart Disease Risk

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

Omega-3 Confusion

Author: Dr. Stephen Chaney

 This article includes updates as of October 2, 2018.  First, here is the earlier information.

do omega 3s reduce heart disease risk confusionDo omega-3s reduce heart disease risk?

Perhaps there is nothing more controversial in nutrition today than omega-3 fatty acids and heart disease risk. It is so confusing. One day you are told they reduce heart disease risk. The next day you are told they are worthless.

The controversy around omega-3s and heart disease risk is part of the larger controversy around supplementation. It is omega-3 supplements that are controversial, not omega-3-rich fish. Of course, that completely ignores the fact that many omega-3-rich fish are contaminated with PCBs and/or heavy metals.

Why is omega-3 supplementation so controversial? The problem is that proponents of omega-3 supplementation often seize on a single study as “proof” that everyone should supplement with omega-3s.  Opponents of omega-3 supplementation take the opposite approach. They pick studies showing that not everyone benefits from omega-3 supplementation as “proof” that nobody benefits. As usual, the truth is in between.

I have a section in my book, “Slaying The Food Myths,”  called “None of Us Are Average.” In that section I point out that clinical studies report the average results of everyone in the study, but nobody in the study was average.

For example, let’s say the study reported that (on average) there was no heart health benefit from omega-3 supplementation. That is what makes the headlines. That is what opponents of omega-3 supplementation cite as “proof” omega-3 supplementation doesn’t work.

However, some of the people in the study may have benefited from omega-3 supplementation, while others did not. Thus, the important question is not “Does everyone benefit from omega-3 supplementation?” It is “Who benefits from omega-3 supplementation?” and “Why do the results vary so much from study to study?”

Omega-3 Confusion

do omega 3s reduce heart disease risk rolesI have a chapter in my book called “What Role Does Supplementation Play?” which helps put this omega-3 controversy into perspective. I created the graphic on the left to answer the question “Who needs supplementation?”

The concept is simple. Poor diet, increased need, genetic predisposition, and pre-existing disease all increase the likelihood that supplementation will be beneficial. However, the benefit will be most obvious in the center of the diagram where two or more of these factors overlap.

Let’s take this concept and apply it to studies of omega-3 fatty acids and heart disease risk.  In particular, let’s use this concept to understand what I call “omega-3 confusion” – why some studies give negative results and others give positive results:

Poor Diet: Again, the concept is simple. You are most likely to see a benefit of omega-3 supplementation when the dietary intake of omega-3 fatty acids is low. Put another way, if the subjects in a study are already getting plenty of omega-3s from their diet, supplementing with omega-3s is unlikely to provide any benefit.

Until recently, dietary surveys were the standard method for assessing dietary omega-3 intake. However, dietary surveys can be inaccurate. The best of recent studies, measure the omega-3 levels in cellular membranes. The omega-3 levels at the beginning of the study reflect your diet. The omega-3 levels at the end of the study reflect how effective supplementation was at improving your omega-3 status. In short, this is the gold standard for omega-3 clinical studies. Subjects can lie about how many omega-3-rich foods they eat and whether they take their supplements, but the omega-3 levels in their cell membranes reveal the truth.

When you read the methods section, it turns out that most negative studies did not ask how much omega-3s their subjects were getting from their diet. Almost none of the negative studies measured omega-3 levels in cell membranes.

Increased Need: In terms of heart disease, we can think increased need as the presence of risk factors for heart disease such as:

  • Age
  • Obesity
  • Inactivity
  • Elevated cholesterol or triglycerides
  • Dietary factors like saturated fats and/or sugar and refined carbohydrates
  • Smoking

What does this mean in terms of clinical studies?

  • Studies in which most of the subjects have a poor diet, are over 65, and have multiple risk factors for heart disease are more likely to show a beneficial effect of omega-3s on heart disease risk.
  • Studies in which most of the subjects are young and healthy are unlikely to show a measurable benefit of omega-3s on heart disease risk. You would need to follow this population group 20, 30, or 40 years to demonstrate a benefit.

Genetic Predisposition: There is a lot we don’t know about genetic predisposition for heart disease. The only exception is family history. If you do omega 3s reduce heart disease risk geneticshave a family history of early heart disease, you can be pretty certain you are at high risk for heart disease. As you might suspect:

  • Studies focused on populations with genetic predisposition to heart disease are more likely to show a benefit of omega-3 supplementation.
  • Studies that just look at the general population without consideration of genetic predisposition to heart disease are less likely to show a benefit of omega-3 supplementation.

Disease: Diseases like diabetes and high blood pressure increase heart disease risk. And, of course, pre-existing heart disease, especially a recent heart attack, dramatically increase the risk of a subsequent heart attack or stroke. Studies focusing on subjects with diabetes have been inconsistent. However, studies focusing on patients with pre-existing heart disease are more clear-cut:

  • Studies focused on populations with pre-existing heart disease and/or a recent heart attack are more likely to show a benefit of omega-3 supplementation.
  • Studies that just look at the general population without consideration of genetic predisposition to heart disease are less likely to show a benefit of omega-3 supplementation.

Interestingly, the situation is very similar with statin drugs. As I reported in a recent issue  of “Health Tips From the Professor” on cholesterol lowering drugs, studies done with patients who had recently had a heart attack show a clear benefit of statin drugs, while studies with the general population show little or no benefit of statin drugs.

One More Factor: There is one more confounding factor that is somewhat unique to the omega-3-heart disease studies and, therefore, not included in the figure at the beginning of this section. Ethical considerations dictate that the placebo group in a double-blind, placebo controlled clinical study receive the “standard of care” for that disease. In the case of heart disease, the standard of care is 4-5 drugs which provide most of the same benefits as omega-3 fatty acids (although with many more side effects).

Thus, these studies are no longer asking whether omega-3s reduce heart disease risk. They are asking whether omega-3s have any additional benefits for heart disease patients already on 4-5 drugs. I have discussed this in more detail in a previous issue of “Health Tips From the Professor” on omega-3 and heart disease.

do omega 3s reduce heart disease risk conflicting studiesWhy Are Omega-3 Studies Conflicting? In summary, the likelihood that clinical studies show a beneficial effect of omega-3 fatty acids on heart disease risk is highly dependent on study design and the population group included in the study. Many of the studies currently in the scientific literature are flawed in one way or another. Once you understand that, it is obvious why there are so many conflicting studies in the literature.

Unfortunately, meta-analyses that combine data from many studies are no better than the individual studies they include in the analysis. It is the old “Garbage in – garbage out” principle.

What Does An Ideal Study Look Like? In my opinion, an ideal study to evaluate the effect of omega-3s on heart disease risk should (at minimum):

  • Determine omega-3 levels in cellular membranes as a measure of omega-3 status (dietary intake of omega-3s plus their utilization by the body). The percentage of omega-3 fatty acids in cell membranes is referred to as Omega-3 Index. Based on previous studies (W.S. Harris et al, Atherosclerosis, 262: 51-54, 2017, most experts consider an Omega-3 Index of 4% to be low and an Omega-3 Index of 8% to be optimal.
  • Focus on a population group at high risk for heart disease or include enough subjects in the study so that you can determine the effect of omega-3s on high risk subgroups.
  • Measure cardiovascular outcomes (heart attack, stroke, cardiovascular deaths, etc.).
  • Perform the study long enough so that you can accumulate a significant number of cardiovascular events.
  • Include enough subjects for a statistically significant conclusion.

Do Omega-3s Reduce Heart Disease Risk?

do omega 3s reduce heart disease riskMost of you have probably heard of the Framingham Heart Study. It was started in 1941 with a large group of residents of Framingham Massachusetts and surrounding areas. The data from this study over the years has shaped much of what we know about cardiovascular risk factors. The original participants have passed on, but the study has continued with their offspring, now in their 60s.

A recent study (W. H. Harris et al, Journal of Clinical Lipidology, doi: 10.1016/j.jacl.2018.02.010 ) with 2500 subjects in the Offspring Cohort of the Framingham Heart Study incorporates many of characteristics of a good omega-3 clinical study.

  • The average age of the subjects was 66. While none of the subjects enrolled in the study had been diagnosed with heart disease at the time the study began, this is a high-risk population. At this age a significant percentage of them would be expected to develop heart disease over the next few years.
  • The subjects did have other risk factors for heart disease. 13% of them had diabetes, 44% had high blood pressure, and 40% of them were on cholesterol medication. However, those risk factors were corrected for in the data analysis, so they did not influence the results.
  • The Omega-3 Index was measured in their red blood cell membranes at the beginning of the study.
  • The study was long enough (7.3 years) for cardiovascular disease to develop.

When they compared subjects with the highest Omega-3 Index (>6.8%) with those with the those with the lowest Omega-3 Index (<4.2%):

  • Death from all causes was reduced by 34%
  • Incident cardiovascular disease was reduced by 39% (Remember that none of the subjects had been diagnosed with heart disease at the beginning of the study. This terminology simply means that they received a new diagnosis of heart disease during the study.)
  • Cardiovascular events (primarily heart attacks) were reduced by 42%
  • Strokes were reduced by 55%.

There were two other interesting observations from the study:

  • There was no correlation between serum cholesterol levels and heart disease in this study.
  • The authors estimated that it would require an extra 1300 mg of omega-3s/day, either from a serving of salmon or from fish oil supplements, to bring the membrane Omega-3 Index from the lowest level in this study to an optimal level.

The authors cited three other recent studies performed in a similar manner that have come to essentially the same conclusion. These studies are not perfect. They are all association studies, so they do not prove cause and effect.

However, the authors concluded that Omega-3 Index should be measured routinely as a risk factor for heart disease and should be corrected if it is low.

The Bottom Line:

Perhaps there is nothing more controversial in nutrition today than omega-3 fatty acids and heart disease risk. It is so confusing. One day you are told they reduce heart disease risk. The next day you are told they are worthless.  I have discussed the reasons for the conflicting results and the resulting omega-3 confusion in the article above.

I shared a recent study that escapes many of the pitfalls of previous studies because it measures the Omega-3 Index of red blood cells as an indication of omega-3 status.

When the study compared subjects with the highest Omega-3 Index (>6.8%) with those with the those with the lowest Omega-3 Index (<4.2%):

  • Death from all causes was reduced by 34%
  • Incident cardiovascular disease was reduced by 39% (Remember that none of the subjects had been diagnosed with heart disease at the beginning of the study. This terminology simply means that they received a new diagnosis of heart disease during the study.)
  • Cardiovascular events (primarily heart attacks) were reduced by 42%
  • Strokes were reduced by 55%.

There were two other interesting observations from the study:

  • There was no correlation between serum cholesterol levels and heart disease in this study.
  • The authors estimated that it would require an extra 1300 mg of omega-3s/day, either from a serving of salmon or from fish oil supplements, to bring the membrane Omega-3 Index from the lowest level in this study to an optimal level.

The authors concluded that Omega-3 Index should be measured routinely as a risk factor for heart disease and should be corrected if it is low.

 

Are Omega-3s Worthless?

omega 3 and heart disease supplementsRecommendations from the medical industry changes often.  The following updates are in response to some of those changes concerning omega-3 and heart disease.  These updates were added on October 2, 2018.

The internet is abuzz with headlines saying things such as “Omega-3 Supplements Don’t Protect Against Heart Disease” and “Forget Omega-3s”. Are those headlines true? Should we throw our omega-3 supplements in the trash?

If the recent headlines are true, it is confusing, to say the least. In the late 90s and early 2000s we were being told of clinical studies showing that omega-3s reduced the risk of heart attack and stroke. At that time the American Heart Association was recommending omega-3 supplements for patients at high risk of heart attack or stroke. What has changed?

It turns out that a lot has changed. The design of clinical studies has changed dramatically in the past 10-15 years. I have covered the changing omega-3 story in detail in my upcoming book “Slaying The Supplement Myths.” Let me just summarize a few key differences between the year 2000 and today.

  • The definition of “high risk of heart attack and stroke” has changed dramatically since 2000. Clinical studies today include subjects who have a much lower risk of heart attack and stroke. That makes it more difficult to see any benefits of omega-3s.
  • Most studies do not measure the omega-3 status of their subjects. That means they do not know whether their patients were omega-3 deficient at the beginning of the study. It also means they have no objective measure of how faithfully the subjects took their omega-3 capsules.
  • We are asking a totally different question today than we were in the year 2000. It is considered unethical to withhold “standard medical care” from the control group. In 2000 the standard of care was one or two heart medications and often did not include a statin. Back then we were asking “Do omega-3s reduce the risk of heart attack and stroke?” Today, the standard of care is 3-5 heart medications, each of which provides some of the same benefits as omega-3s. Today we are asking the question “Do omega-3s provide any additional benefit for people who are already taking 3-5 heart medications?”

Let me start by analyzing a recent study that illustrates these points perfectly.

How Was The Study Done?

omega 3 and heart disease studyOn the surface the study appeared to be a well-designed study. The study (The ASCEND Study Collaborative Group, New England Journal Of Medicine, DOI: 10.1056/NEJMoa1804989, 2018 ) was conducted by scientists from the University of Oxford. They used a national diabetes registry and contacted general practitioners from all over England to identify 15,480 patients who had diabetes, but no evidence of heart disease and were willing to participate in the study. Participants were at least 40 (average age 63) and 60% male.

The participants were mailed a six month’s supply of capsules containing either 1 gram of omega-3s or olive oil as a placebo. Each 6 months the participants were mailed a questionnaire to report on whether they took the capsule daily and whether they had any adverse side effects. If they returned the questionnaire, they were given another 6 month’s supply of omega-3s or placebo. The patients were followed for an average of 7.4 years and “adverse vascular events” (simple definition: non-fatal and fatal heart attack or stroke) were recorded.

 

Omega-3 and Heart Disease?

omega 3 and heart disease no affectsThe authors of the study reported:

  • Omega-3 supplementation had no significant effect on either serious vascular events or death from any cause.

The authors concluded “These findings, together with results of earlier randomized trials involving patients with and without diabetes, do not support the current recommendations for routine dietary supplementation with omega-3 fatty acids to prevent vascular events.”

On the surface, this appears to be a strong study and the results were conclusive. What could go wrong? The answer is “Plenty.”

What Are The Weaknesses Of The Study?

omega 3 and heart disease flawsThe study contains multiple weaknesses that have been ignored by the medical community and the press.

Omega-3 Supplements Reduced Vascular Deaths In This Study. To begin with, the study showed that omega-3 supplementation reduced vascular deaths (simple definition: fatal heart attacks and stroke) by 18%. That observation was reported as a single sentence in the Results section of the paper but did not appear in either the Discussion or Abstract. It was also not reported in any of the media reports telling you that omega-3s are worthless. Perhaps it did not match the preconceived beliefs of the authors.

This Study Was Not Really Looking At High Risk Patients. The studies in the late 90’s and early 2000’s showing a significant effect of omega-3s on heart attack risk were done with truly high-risk patients. For example, the best of these studies looked at the effect of omega-3 supplementation in patients who had suffered a heart attack in the past 6 months. Those patients were at high risk of a second heart attack in the next 6-12 months. They were in imminent danger.

This study looked at patients with diabetes. They have a 2 to 3-fold risk of heart attack or stroke over the next decade. That’s a big difference. In addition, this study only looked at patients with diabetes AND no evidence of heart disease. Their risk of heart attack and stroke is substantially less. In fact, if you look at the data in the study, 83% of the participants in their study were at low to moderate risk of heart disease. Only 17% were at high risk.

To put that into perspective, it has only been possible to prove the effectiveness of statins when they are tested in patients who have already suffered a heart attack. In low risk populations, their benefit is almost negligible. You will find details about those studies in my new book “Slaying The Supplement Myths.

If you can’t prove statins are effective in low risk populations, why would you expect to be able to show omega-3s are effective in low risk populations.

omega 3 and heart disease optimumThe Subjects Were Already Getting Near Optimum Amounts of Omega-3s From Their Diet. The study analyzed the omega-3 index (a measure of omega-3 status) from a randomly selected subset of participants at the beginning and end of the study. They reported that the omega-3 index in their study participants increased from 7.1% at the beginning to 9.1% at the end, a 32% increase. They considered that to be a good thing because it showed that their participants were taking the omega-3 supplements faithfully.

However, let’s put that into perspective. An omega-3 index of 4% is associated with a high risk of heart disease. An omega-3 index of 8% is associated with a low risk of heart disease. It is considered optimum. With an omega-3 index of 7.1% at the beginning of the study, the subjects already had near optimum omega-3 status before the study even began.

If the subjects were already at near optimum omega-3 status, why would you expect additional omega-3 supplementation to be beneficial?

The Subjects Were On 3-5 Heart Medications. To discover this, you had to dig a little.  Something only a science-wonk like me is willing to do. The Results section reported that 35% of the subjects were taking aspirin and 75% were on a statin. You have to go to the Supplementary Data online to discover that most of the subjects were on 3-5 heart medications in addition to 1 or 2 medications for diabetes. That is somewhat curious because nobody in the study had any detectable cardiovascular disease.

To understand the significance of this observation, we look at what the drugs do. Aspirin prevents blood clot formation in our arteries, which is one of the main benefits of omega-3s. For reasons nobody understands, statins decrease inflammation, which is another major benefit of omega-3s. Most of the subjects were also taking a medicine to decrease blood pressure, another major benefit of omega-3s.

If subjects are already on 3-5 heart medications that duplicate the benefits of omega-3s, why would you expect omega-3 supplementation to be beneficial?

As I said before, we are now asking a totally different question than we were in the studies performed in the late 90s and early 2000s. Back then we were asking whether omega-3s reduced the risk of heart disease. Today we are asking whether omega-3s have any additional benefits for someone who is already on 3-5 heart medications. That question may be of interest to your doctors, but it is probably not the question most of you are interested in.

Even worse, every one of those drugs has documented side effects. For example, the same group that published this paper also examined the role of aspirin in reducing heart attacks in the same patient population and concluded that the befits of aspirin were “largely counterbalanced by the bleeding hazard [caused by aspirin use],” (The ASCEND Study Collaborative Group, New England Journal Of Medicine, DOI: 10.1056/NEJMoa1804988, 2018).  In contrast, they found no side effects in the group receiving 1 gram/day of omega-3s.

Garbage In Again, Garbage Out Again

do omega 3s reduce heart disease risk conflicting studiesTwo recent meta-analyses (T Aung et al,  JAMA Cardiology 3: 225-234, 2018  and Cochrane Database of Systematic Reviews ) have analyzed all the recent placebo-controlled studies and have concluded that omega-3s are of little or no use for reducing heart disease risk. However, those meta-analyses both suffered from what, in the computer programming world, is called “Garbage in. Garbage out.”

The meta-analyses included the studies from the late 90s and early 2000s, but the positive data from those studies was swamped out by all the recent negative studies, most of which suffered from the same flaws as the study I reviewed above. This is the “Achilles’ Heel” of meta-analysis. If they include flawed studies in their analysis, their conclusions will also be flawed. What the recent studies do tell us is that omega-3s are of little additional benefit if you are already taking multiple heart medications.

 

Don’t Throw The Baby Out With The Bathwater

The next time you visit your doctor you are likely to be told: “The evidence is in. We know that omega-3s don’t reduce the risk of heart attack.” Now you know the truth. What we can definitively conclude is that omega-3s offer little additional benefit if you are already taking multiple heart medications. As I said before, that question may be of interest to your doctor but is probably not the question you had in mind.

omega 3 and heart disease reduce blood pressureUnfortunately, because of the way clinical studies of omega-3 supplementation and heart disease risk are currently conducted, we may never have a definitive answer to whether omega-3s reduce heart disease risk for those of us who aren’t taking heart medications.

However, even if there is some controversy about omega-3s and heart disease risk, there are multiple other reasons for making sure that your omega-3 status is optimum. For example:

  • We know that omega-3s reduce triglycerides. This is non-controversial.
  • There is excellent evidence that omega-3s improve arterial health and reduce blood pressure.
  • There is good evidence that omega-3s reduce inflammation.

If they also reduce heart disease risk, consider that to be a side benefit.

The Bottom Line

A recent study has reported that that omega-3s do not reduce the risk of heart attack and stroke. However, the study suffered from multiple flaws.

  • Omega-3s reduced the risk of cardiovascular deaths in the study by 18%. That never got reported by the media.
  • The study was looking at subjects at relatively low risk of heart disease.

If you can’t even prove statins are effective in low risk populations, why would you expect to be able to show omega-3s are effective in low risk populations.

  • The subjects had near optimum omega-3 status before the study even began.

If the subjects were already at near optimum omega-3 status, why would you expect additional omega-3 supplementation to be beneficial?

  • The subjects were on 3-5 heart medications that provided many of the same benefits as omega-3s, but with side effects.

If subjects are already on 3-5 heart medications that duplicate the benefits of omega-3s, why would you expect omega-3 supplementation to be beneficial?

Two recent meta-analyses also concluded that omega-3s do not reduce the risk of heart disease. However, most of the studies in those meta-analyses suffered from the same flaws as the study I reviewed in this article. The meta-analyses are an excellent example of what computer programmers refer to as “Garbage in. Garbage out.”

The next time you visit your doctor you are likely to be told: “The evidence is in. We know that omega-3s don’t reduce the risk of heart attack.” Now you know the truth. What we can definitively conclude is that omega-3s offer little additional benefit if you are already taking multiple heart medications. That question may be of interest to your doctor, but that is probably not the question you had in mind.

Unfortunately, because of the way that clinical studies of omega-3 supplementation and heart disease risk are currently conducted, we may never have a definitive answer to whether omega-3s reduce heart disease risk for those of us who aren’t taking heart medications.

However, even if there is some controversy about omega-3s and heart disease risk, there are multiple other reasons for making sure that your omega-3 status is optimum. For example:

  • We know that omega-3s reduce triglycerides. This is non-controversial.
  • There is excellent evidence that omega-3s improve arterial health and reduce blood pressure.
  • There is good evidence that omega-3s reduce inflammation.

If they also reduce heart disease risk, consider that to be a side benefit.

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.

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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The Truth About Vitamin D

Posted December 11, 2018 by Dr. Steve Chaney

Does Vitamin D Reduce Risk Of Heart Disease & Cancer?

Author: Dr. Stephen Chaney

 

the truth about vitamin dYou have every right to be confused. One day you are told that vitamin D reduces your risk of heart disease and cancer. The next day you are told vitamin D makes has no effect on those diseases. You are told vitamin D is a waste of money. What should you believe?  What is the truth about vitamin D?

In mid-November a major clinical study called VITAL was published. It examined the effect of vitamin D and omega-3s on heart disease and cancer risk. Last week I wrote about the omega-3 portion of the study. This week I will cover the vitamin D portion of the study.

Once again, if you rely on the media for your information on supplementation, you are probably confused. Headlines ranged from “Vitamin D Is Ineffective For Preventing Cancer And Heart Disease to “Vitamin D Lowers Odds Of Cancer Death.” What is the truth?

The problem is that reporters aren’t scientists. They don’t know how to interpret clinical studies. What they report is filtered through their personal biases. That is why I take the time to carefully evaluate the clinical studies, so I can provide you with accurate information. Let me sort through the dueling headlines and give you the truth about vitamin D, cancer, and heart disease.

How Was The Study Designed?

the truth about vitamin d studyThe VITAL study (JE Manson et al, New England Journal of Medicine, DOI: 10.1056/NEJMoa1811403) enrolled 25,871 healthy adults (average age = 67) in the United States. The study participants were 50% female, 50% male, and 20% African American. None of the participants had preexisting cancer or heart disease. The characteristics of the study group were typical of the American population at that age, namely:

  • The average BMI was 28, which means that most of the participants were significantly overweight.
  • 7% of them had diabetes.

Study participants were given questionnaires on enrollment to assess clinical and lifestyle factors including dietary intake. Blood samples were taken from about 65% of the participants to determine 25-hydroxyvitamin D levels (a measure of vitamin D status) at baseline and at the end of the first year. The participants were given either 2,000 IU of vitamin D/day or a placebo and followed for an average of 5.3 years.

There were two important characteristics of the participants in this study that may have influenced the outcome.

  • The average 25-hydroxyvitamin D level of participants at the beginning of the study was 31 ng/ml (78 nmol/L). The NIH considers 20-50 ng/ml (50-125 nmol/L) to be the optimal level of 25-hydroxyvitamin D for most physiological functions. This means that study participants started in the middle of the optimal range with respect to vitamin D status.

[Note: The NIH defines the 20-50 ng/ml range as “adequate.”  However, I know many of my readers like to aim beyond adequate to reach what they consider to be “optimal.”  In the case of vitamin D, that might not be a good idea. The NIH considers anything above 50 ng/ml as associated “with potentially adverse effects.”  For that reason, I will refer to the 20-50 ng/ml range as optimal for this article. I wouldn’t want to encourage my readers to be aiming for above 50 ng/ml.]

  • Only 12.7% of participants had 25-hydroxyvitamin D levels below 20 ng/ml, which the NIH considers to be inadequate. The results with this group were not statistically different from the study participants with optimal vitamin D status, but it is not clear that there were enough people in this subgroup for a statistically valid comparison with participants starting with an optimal vitamin D status.
  • At the end of the first year, 25-hydroxyvitamin D levels in the treatment group increased to 42 ng/ml (105 nmol/L), which is near the upper end of the optimal range. Thus, for most of the participants, the study was evaluating whether there was a benefit of increasing vitamin D status from the middle to the upper end of the optimal range.
  • The study allowed subjects to continue taking supplements that contained up to 800 IU of vitamin D. While the authors tried to correct for this statistically, it is a confounding variable.

Does Vitamin D Reduce The Risk Of Cancer?

 

the truth about vitamin d and cancerYou may remember from last week that omega-3s were more effective for reducing heart disease risk than for reducing cancer risk. What is the truth about vitamin D and cancer risk?   The results are reversed for vitamin D, so I will discuss cancer first.

The study reported that vitamin D supplementation did not reduce a diagnosis of invasive cancer of any type, breast cancer, prostate cancer, or colon cancer during the 5.3-year time-period of this study. This was the result that was reported in the abstract and was what lazy journalists, who never read past the abstract, reported.

However, the rest of the study was more positive. For example, occurrence of invasive cancer of any type was reduced by:

  • 23% in African-Americans.
  • 24% in patients with a healthy body weight.

Several previous studies have suggested that vitamin D may be more effective at preventing cancer in people with a healthy body weight, but the mechanism of this effect is currently unknown.

Most previous studies have not included enough African-Americans to determine whether they respond more favorably to vitamin D supplementation. However, African-Americans have a higher risk of cancer, so this finding deserves follow-up.

In addition, when the study looked at deaths from cancer, the results were very positive. For example:

  • Cancer deaths during the 5.3-year study period were reduced by 17%.
  • The longer vitamin D supplementation was continued the more effective it became at reducing cancer deaths. For example,
  • When the authors excluded cancer deaths occurring during the first year of supplementation, vitamin D reduced cancer deaths by 21%.
  • When the authors excluded cancer deaths occurring during the first two years of supplementation, vitamin D reduced cancer deaths by 25%.

Finally, no side effects were noted in the vitamin D group.

 

Does Vitamin D Reduce The Risk Of Heart Disease?

 

the truth about vitamin d and heart diseaseThe VITAL study also looked at the effect of vitamin D on heart disease risk. What is the truth about vitamin D and heart disease?  The results from this study were uniformly negative. There was no effect of vitamin D supplementation on all major cardiovascular events combined, heart attack, stroke, or death from heart disease. Does that mean vitamin D has no role in reducing heart disease risk? That’s not clear.

The authors had a thought-provoking explanation for why the results were negative for heart disease, but positive for cancer. Remember that the participants in this trial started with a 25-hydroxyvitamin D level of 31 ng/ml and increased it to at least 42 ng/ml with vitamin D supplementation.

The authors stated that previous studies have suggested the 25-hydroxyvitamin D level associated with the lowest risk for heart disease is between 20 and 25 ng/ml. If that is true, most of the participants in this trial were already in the lowest possible risk for heart disease with respect to vitamin D status before the study even started. There would be no reason to expect additional vitamin D to further reduce their risk of heart disease.

In contrast, the authors said that previous studies suggest the 25-hydroxyvitamin D level associated with the lowest risk of cancer deaths is above 30 ng/ml. If that is true, it would explain why vitamin D supplementation in this study was effective at reducing cancer deaths.

However, previous placebo-controlled clinical studies have also been inconclusive with respect to vitamin D and heart disease. My recommendation would be to think of adequate vitamin D status as part of a holistic approach to reducing heart disease – one that includes a heart-healthy diet and a heart-healthy lifestyle – rather than a “magic bullet” that decreases heart disease risk by itself.

As for heart-healthy diets, I discuss the pros and cons of various diets in my book, “Slaying The Food Myths.”  As I discuss in my book, the weight of scientific evidence supports primarily plant-based diets that include omega-3s as heart healthy. As an example, the Mediterranean diet is primarily plant-based and is rich in healthy oils like olive oil and omega-3s. It is associated with reduced risk of both heart disease and cancer.

 

What Is The Truth About Vitamin D?

 

the truth about vitamin d signThere is a lot of confusion around the question of whether vitamin D reduces the risk of cancer. This study strengthened previous observation suggesting that vitamin D supplementation decreases cancer deaths. However, it is also consistent with previous studies that have failed to find an effect of vitamin D on cancer development. How can we understand this apparent discrepancy? The authors provided a logical explanation. They pointed out that:

  • Cancer development takes 20-30 years while this clinical study lasted only 5.3 years. That means that vitamin D supplementation only occurred at the tail end of the cancer development process. In fact, the cancer was already there in most of the patients in the study who developed cancer. It just had not been diagnosed yet. In the words of the authors: “Given the long latency for cancer development, extended follow-up is necessary to fully ascertain potential effects [of vitamin D supplementation].”
  • In contrast, none of the patients had been diagnosed with cancer when they entered the trial. That means that the patients were diagnosed with cancer during the 5.3-year study period. They were receiving extra vitamin D during the entire period of cancer treatment. Thus, the effect of vitamin D on reducing cancer deaths was easier to detect.

What Does This Study Mean For You?

the truth about vitamin d questionsVitamin D Is Likely To Decrease Your Risk Of Dying From Cancer: When you combine the results of this study with what we already know about vitamin D and cancer, the results are clear. Vitamin D appears to reduce your risk of dying from cancer. More importantly, the longer you have been supplementing with vitamin D, the greater your risk reduction is likely to be.

Vitamin D May Decrease Your Risk Of Developing Cancer: Association studies suggest that optimal vitamin D status is associated with decreased cancer risk, especially colon cancer risk. However, the long time for cancer development means that we may never be able to prove this effect through double-blind, placebo-controlled clinical trials.

Holistic Is Best: When you combine the VITAL study results with what we already know about vitamin D and heart disease, it appears that supplementing with vitamin D is unlikely to reduce your risk of developing heart disease unless you are vitamin D deficient. However, a holistic approach that starts with a healthy, primarily plant-based diet and makes sure your vitamin D status is adequate is likely to be effective.

The same is likely true for cancer. While the latest study suggests that vitamin D supplementation reduces your risk of dying from cancer, those vitamin D supplements are likely to be even more effective if you also adopt a healthy diet and lifestyle.

How Much Vitamin D Do You Need? The optimal dose of vitamin D is likely to be different for each of us. One of the things we have learned in recent years is that there are significant differences in the efficiency with which we convert vitamin D from diet and/or sun exposure into the active form of vitamin D in our cells. Fortunately, the blood test for 25-hydroxyvitamin D is readily available and is widely considered to be an excellent measure of our vitamin D status.

I recommend that you have your blood level of 25-hydroxyvitamin D tested on an annual basis. Based on the best currently available data, I recommend you aim for >20 ng/ml (50 nmol/L) if you wish to minimize your risk of heart disease and >30 ng/ml (75 nmol/L) if you wish to minimize your risk of cancer. If you can achieve those levels through diet and a multivitamin supplement, that is great. If not, I would recommend adding a vitamin D supplement until those levels are achieved.

Finally, you shouldn’t think of vitamin D as a magic bullet. If you are a couch potato and eat sodas and junk food, don’t expect vitamin D to protect you from cancer and heart disease. You should think of maintaining adequate 25-hydroxyvitamin D levels as just one component of a holistic approach to healthy, disease-free living.

 

The Bottom Line

 

There is a lot of confusion around the question of whether vitamin D reduces the risk of cancer and heart disease. A major clinical study has just been published that sheds light on these important questions. It reported:

  • Vitamin D did not decrease the risk of developing cancer during the 5.3-year study duration. The authors pointed out that cancer takes 20-30 years to develop, which means their study was probably too short to detect an effect of vitamin D on the risk of developing cancer.
  • Vitamin D did decrease the risk of dying from cancer, and the longer people were supplementing with vitamin D the bigger the protective effect of vitamin D was.
  • Vitamin D did not decrease the risk of heart disease. However, most study participants had a level of 25-hydroxyvitamin D that was optimal for reducing the risk of heart disease at the beginning of the study. There was no reason to expect that extra vitamin D would provide additional benefit.
  • With respect to both cancer and heart disease the best advice is to:
    • Get your 25-hydroxyvitamin D levels tested on an annual basis and supplement, if necessary, to keep your 25-hydroxyvitamin D levels in what the NIH considers to be an adequate range (20-50 ng/ml).
    • We do not have good dose response data for the beneficial effects of vitamin D on heart disease and cancer. However, according to this article, previous studies suggest you may want to am for 25-hydroxyvitamin D levels above 20 ng/ml to reduce the risk of heart disease and above 30 ng/ml to reduce your risk of cancer.
    • Consider vitamin D as just one component of a holistic approach to healthy, disease-free living.

For more details about the interpretation of these studies and what they mean for you, 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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