heart failure

Is Melatonin Safe?

by

What Is Peer Review?

Author: Dr. Stephen Chaney 

newspaper headlinesRecent headlines claim that long-term melatonin use may be risky. Specifically, the headlines claim that long term melatonin use may increase the risk of:

  • Heart failure by 90%.
  • Hospitalization for heart failure by almost 3.5-fold.
  • All-cause mortality by 2-fold.

Those statistics are frightening. But as Mark Twain said, “There are lies. There are damn lies, and then there are statistics.”

So, as someone who uses a melatonin supplement regularly, the claims about heart failure risk made me want to check out the study behind the headlines.

I set out to answer two questions:

  • Are the claims about melatonin use and heart failure risk true?
  • Are they significant?

How Was The Study Done?

clinical studyHere is what we know about the study:

  • The authors used a global data network of healthcare providers called the TriNetX Global Research Network and selected all patient records in the network of adults >18 who had a clinical diagnosis of insomnia.
  • They compared insomnia patients that had been prescribed melatonin for at least a year with non-melatonin users. Patients on heart failure drugs were excluded from the analysis.
  • Outcomes (new diagnosis of heart failure, hospitalization for heart failure, and all-cause mortality) were assessed 5 years after the patients were first prescribed melatonin.
  • A small subset of the two groups (414 in each group) were compared with respect to things like:
    • Demographics (things like age, sex, socioeconomic status, and income level).
    • Other diagnosed diseases.
    • Other medication use.
    • Healthcare utilization.
    • Blood and urine lab results.
    • Vitals (things like weight, height, blood pressure, heart rate, etc.

I said, “Here is what we know about the study” because this was not a published clinical study. It was a poster presented at a scientific meeting.

That means that a lot of details about design of the experiments and how the data were analyzed are missing. It also means the study has not gone through the peer review process that is required for publication in a scientific journal.

To help you understand why that is important, let me explain the peer review process.

What Is Peer Review?

SkepticPoster presentations at scientific meetings, like this one, have a couple of purposes:

  • They give graduate students and post-doctorate fellows a chance to learn how to present and defend their research. It also gives them a chance to form relationships with the leaders in their field who may become their next step up the career ladder.
  • They foster discussions with other experts in the field who may spot flaws or offer helpful suggestions for improving the research before submitting it for publication.

The ultimate goal, of course, is to get the research to the point where it is ready to be submitted to a high-quality, peer-reviewed scientific journal (It is still “publish or perish” in the academic world).

This is an area in which I have extensive experience, having published over 100 articles in peer reviewed journals during my career at the University of North Carolina. I was also a reviewer for hundreds of articles during my time at UNC.

Once the manuscript has been submitted to a peer-reviewed scientific journal, they send it to two or three peers (other experts in the same area of research). Some of the peers are your friends. Others are your competitors. In either case, their goal is to make sure the paper adheres to the highest scientific standards. They review the paper for:

  • Hypothesis to be tested: They ask, “Is the hypothesis credible and clearly stated?”
  • Experimental Design: They ask, “Are the experiments designed in such a way that they adequately test the hypothesis?”
  • Data Collection: They ask, “Was enough data gathered to test the hypothesis?” and “Were there gaps in the data that need to be filled?”
  • Statistical Analysis: They ask, “Was the statistical analysis of the data sufficient to test the hypothesis?” and “Were there any important controls missing from the data collected or the statistical analysis?”
  • Conclusions: They ask, “Are the conclusions of the authors adequately supported by the data collected and the statistical analysis?”

If the reviewers find defects in any of these areas, they have 3 options. They can:

  • Ask the authors to rewrite and resubmit the manuscript.
  • Ask the authors to perform additional experiments or use a more rigorous statistical method before resubmitting the manuscript.
  • Reject the manuscript.

Hopefully, this description helps you understand the power of the peer review process and why the lack of peer review for this study is significant.

I am not saying the claims in this poster presentation are inaccurate. I’m saying the headlines about them may be premature because the study has yet to be peer-reviewed.

What Did This Study Show? 

Question MarkThe abstract said that long-term (≥1 year) melatonin users had:

  • An 89% higher risk of developing heart failure.
  • A 3.44-fold higher risk of hospitalization for heart failure.
  • A 2.09-fold higher risk of all-cause mortality.

The authors concluded, “In a large, multinational real-world cohort rigorously matched on >40 baseline variables, long-term melatonin supplementation in insomnia was associated with an 89% higher hazard of incident heart failure, a three-fold increase in heart failure–related hospitalizations, and a doubling of all-cause mortality over 5 years. These findings challenge the perception of melatonin as a benign chronic therapy and underscore the need for randomized trials to clarify its cardiovascular safety profile.”

Is Melatonin Safe? 

The TruthAt the beginning of this article I said I wanted to answer two questions:

  • Are the claims about melatonin use and heart failure risk true?
  • Are they significant?

The first question (Are the claims about melatonin use and heart failure risk true?) is difficult to answer.

  • This is an abstract instead of a publication. That means I have no access to the data, statistical methods, and controls that went into the Author’s conclusions. So, I have no basis for analyzing the accuracy of the authors’ statements.
  • This has not gone through peer review. The conclusions of the authors may be modified or may be rejected based on peer review.

There are several questions I and others who have discussed this study would like to see answered. For example:

  • How can hospitalizations for heart failure be greater than the number of people with heart failure? Normally, between 20-80% (average = 45%) of people with congestive heart failure end up in the hospital. The discrepancy between hospitalizations and heart failure patients in this study suggests that:
    • Some hospitalizations were for another reason and were mischaracterized as being due to heart failure…or…
    • The same individual(s) were hospitalized multiple times during the 5-year follow-up.
    • In either case hospitalizations for heart failure would be overcounted.
  • How did they accurately distinguish between melatonin users and non-users since their study drew on data from both England and the United States?
    • In England, melatonin is only available by prescription, so the distinction is clear.
    • But in the United States a prescription is not required. Melatonin is infrequently prescribed. Most melatonin users obtain their melatonin over the counter and are not recorded in any database.
  • Were the controls sufficient?
    • The author’s conclusion states the data were “…matched on >40 baseline variables…”, but the Methods section states that only a small subset (414) of melatonin users were matched for those variables. That is less than 5% of the melatonin users in the study.
  • Are the data on the relationship between melatonin use and all-cause mortality accurate?
    • Again, the increase in all-cause mortality was greater than the number of melatonin users.
    • That suggests that the increase in all-cause mortality may be due to some characteristics of severe insomniacs who choose to take melatonin rather than to melatonin itself.

These are the kinds of questions that need to be answered during the peer review process and might alter the conclusions or prevent the study from being published.

  • So, the answer to the first question (Are the claims about melatonin use and heart failure risk true?) is, “We don’t know. The study has not gone through the peer review process and is unpublished.

Relative Risk Versus Absolute Risk 

ProfessorThe answer to the second question (Are the claims about melatonin use and heart failure risk significant) is much clearer. It has to do with the difference between relative risk and absolute risk.

Simply put:

  • Relative risk is the change in risk caused by an intervention (melatonin in this case) relative to the risk without the intervention.
    • Relative risk is generally used in describing the results of clinical studies because it gives much larger numbers and is, therefore, more newsworthy. It is more likely to generate the headlines you see and grab your attention.
  • Absolute risk is the actual change in risk that you experience.
    • This is the risk that matters to you.

With those simple definitions, let’s review the claims of this study:

  • The study said that long-term melatonin use increased the risk of heart failure by 90%. That sounds horrible, but it is an increase in relative risk!
    • To calculate the absolute increase in the risk of heart failure, you need to first ask what the baseline risk is in non-melatonin users. In this study it was 2.7%.
    • With that information, we can do some simple math. A 90% increase would increase the risk to 4.6%. 4.6% – 2.7% = 1.9%.
    • That means the absolute increase in risk caused by long-term melatonin use is less than 2%.
  • The study said that long-term melatonin use increases the risk of hospitalization 3.44-fold.
    • On average, 45% of heart failure patients are hospitalized. Since the risk of heart failure in this study was 2.7%, that means the baseline for hospitalization should be 45% of 2.7% or around 1.2%.
    • A 3.44-fold increase would increase that to 4.2% which means that the absolute risk of being hospitalized if you are a heart failure patient is around 3% (4.2% – 1,2%).
  • Finally, if the increase in all-cause mortality is solely caused by melatonin use (which is unclear), melatonin use increases mortality risk from 4.3% to 7.8%, for an absolute increase in risk of 3.5%.

In short, if the claims about melatonin use and heart failure are true (which is uncertain) the absolute increase in risk is very small for the average, healthy adult.

What Does This Study Mean For You? 

ConfusionIf you are an average, healthy adult you probably do not need to be concerned about the headlines linking melatonin use with heart failure.

  • It is not yet clear whether the claims are accurate.
  • And, if they are accurate, your increased risk is very small.

There are, however, some caveats.

  • If you suffer from severe, chronic insomnia you should consult your healthcare provider first.
    • Your insomnia may be caused by an underlying health condition.
    • Your healthcare provider may suggest more effective treatments. Some of these treatments may have more side effects than melatonin use, but it always useful to know what your choices are.
  • If you have been diagnosed with heart failure, you should avoid melatonin.

Finally, even though this study is very preliminary, there are also some individuals who may wish to consult with their healthcare provider before taking melatonin. These include people with conditions that increase the risk of heart failure such as coronary heart disease, heart attacks, diabetes, obesity, and high blood pressure.

The Bottom Line 

Recent headlines have suggested that long-term melatonin use substantially increases the risk of heart failure, hospitalizations due to heart failure, and premature death.

However, these headlines were based on an abstract of a poster presented at a scientific meeting. That means:

  • There is not adequate information available to analyze the data behind the claims.
  • The study has not yet gone through the peer review process, so we don’t know whether the claims are accurate.

Based on my evaluation of the available information, my analysis is:

If you are an average, healthy adult you probably do not need to be concerned about the headlines linking melatonin use with heart failure.

  • It is not yet clear whether the claims are accurate.
  • And, if they are accurate, your increased risk is actually very small.

For more information on the study and who should consult with their healthcare provider before using melatonin, 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.

_____________________________________________________________________________

My posts and “Health Tips From the Professor” articles carefully avoid claims about any brand of supplement or manufacturer of supplements. However, I am often asked by representatives of supplement companies if they can share them with their customers.

My answer is, “Yes, as long as you share only the article without any additions or alterations. In particular, you should avoid adding any mention of your company or your company’s products. If you were to do that, you could be making what the FTC and FDA consider a “misleading health claim” that could result in legal action against you and the company you represent.

For more detail about FTC regulations for health claims, see this link.

https://www.ftc.gov/business-guidance/resources/health-products-compliance-guidance

________________________________________________________________________

About The Author 

Dr. Chaney has a BS in Chemistry from Duke University and a PhD in Biochemistry from UCLA. He is Professor Emeritus from the University of North Carolina where he taught biochemistry and nutrition to medical and dental students for 40 years.

Dr. Chaney won numerous teaching awards at UNC, including the Academy of Educators “Excellence in Teaching Lifetime Achievement Award”.

Dr Chaney also ran an active cancer research program at UNC and published over 100 scientific articles and reviews in peer-reviewed scientific journals. In addition, he authored two chapters on nutrition in one of the leading biochemistry text books for medical students.

Since retiring from the University of North Carolina, he has been writing a weekly health blog called “Health Tips From the Professor”. He has also written two best-selling books, “Slaying the Food Myths” and “Slaying the Supplement Myths”. And most recently he has created an online lifestyle change course, “Create Your Personal Health Zone”. For more information visit https://chaneyhealth.com.

For the past 54 years Dr. Chaney and his wife Suzanne have been helping people improve their health holistically through a combination of good diet, exercise, weight control and appropriate supplementation.

 

The News About Omega-3s Just Got Better

by

What Does This Study Mean For You? 

Author: Dr. Stephen Chaney 

good newsA recent meta-analysis (AA Bernasconi et al, Mayo Clinic Proceedings, 96: 1365-1375, 2021) of randomized clinical studies with over 150,000 patients showed that omega-3s reduced the risk of heart attacks by 13% and fatal heart attacks by 35%. Another major clinical study (T Chao et al, Nutrition, Metabolism and Cardiovascular Disease, 34: 537-547, 2024) with 30,000 patients found that omega-3s reduced all-cause mortality by 10%, cardiovascular mortality by 18%, heart attacks by 33%, and sudden cardiac death by 33%.

In short, the evidence that omega-3s reduce the risk of heart attacks and other forms of cardiovascular disease keeps getting stronger. However, the effect of omega-3s on heart failure is not as clear. Some studies suggest that omega-3s reduce the risk of heart failure and heart failure deaths. But other studies find little or no effect.

That’s unfortunate because heart failure is responsible for 45% of cardiovascular deaths and 14% of all deaths in the United States. In 2023 6.7 million Americans had heart failure, and that number is expected to increase to 8.5 million in 2030.

But numbers don’t tell the whole story. It is the trend in heart failure deaths that is truly concerning. Heart failure deaths per 100,000 Americans decreased by 20% between 1999 and 2012. Then the trend abruptly reversed. By 2021 heart failure deaths per 100,000 people was greater than in 1999. And the increase in heart failure deaths shows no signs of slowing down.

Nobody knows what is causing this rapid increase in heart failure deaths. But clearly the miracles of modern medicine are not working. And because the clinical studies on omega-3s and heart failure risk have been confusing, omega-3s are not currently recommended for heart failure patients.

This study (M A Jawad et al, Mayo Clinic Proceedings, 99: 1895-1904, 2024) was designed to clear up the confusion about omega-3s and heart failure risk.

How Was This Study Done?

clinical studyThis utilized data from the UK Biobank study. The UK Biobank study is an ongoing study that enrolled 502,366 subjects, aged 40-69, from the United Kingdom between April 1, 2007, and December 31, 2010. It regularly collects environmental, lifestyle, and genetic data on these individuals and tracks their health outcomes.

Within the study 273,033 participants had their blood levels of omega-3s determined by mass spectrometry. These measurements were used to calculate the Omega-3 Index (% of membrane fatty acids that are omega-3s) of these participants.

Of these participants:

  • 271,794 did not have a heart failure diagnosis at the time the omega-3 levels were determined. This group was used to evaluate the effect of omega-3s on the risk of developing heart failure.
  • 1,239 had a heart failure diagnosis at the time the omega-3 levels were determined. This group was used to determine whether omega-3s reduced the risk of death in heart failure patients.
  • 20,000 from this group had a repeat measurement of omega-3 levels around 4 years after the first measurement to determine the consistency of omega-3 levels. On average the repeat measurements were slightly lower, but the differences were small.

These participants were followed for an average of 13.7 years.

  • A diagnosis of heart failure was based on international diagnosis standards.
  • Deaths were identified by using the central death registry in the United Kingdom.

The News About Omega-3s Just Got Better

Omega-3s And Heart DiseaseThe data were clear. When participants with an Omega-3 Index in the top 20% were compared to those with an Omega-3 Index in the bottom 20%:

  • The risk of developing heart failure during the 13.7-year follow-up period was reduced by 21%.

When participants with a heart failure diagnosis prior to omega-3 measurement were compared in the same manner:

  • All-cause mortality was reduced by 48%
  • Cardiovascular mortality was reduced by 43%.

When the investigators looked at the effect of omega-3 supplementation in this population:

  • The risk of developing heart failure was 5% lower for those who reported omega-3 supplement use. I will discuss the reason for the discrepancy between comparisons based on omega-3 supplement use and comparisons based on blood levels of omega-3s below.

The authors concluded, “Higher plasma levels of marine omega-3 fatty acids were associated with a lower incidence of heart failure. Furthermore, among patients with preexisting heart failure, higher omega-3 levels were associated with lower risks of all-cause mortality and cardiovascular mortality. These findings suggest that increasing plasma omega-3 levels, whether by diet or supplementation, could reduce both risk for development of heart failure and death in those with prevalent heart failure.”

What Are The Strengths And Weaknesses Of This Study?

strengths and weaknessesThis was a very large, very well-done study. There is the usual caveat for this type of study, namely that it looks at associations and cannot prove cause and effect. However, it would be impossible to perform a double blind, placebo-controlled study with that many people for almost 14 years.

And heart failure does not happen overnight. Studies of the size and length are required to show meaningful effects of diet and/or supplementation on health outcomes like heart failure are not feasible.

Another major strength of this study is that it measured blood levels of omega-3s and showed those blood levels were relatively stable over time rather than relying on participants remembering what they ate and/or what supplements they used.

  • In terms of supplement use, studies like this one simply ask whether omega-3 supplements were used. They do not ask what the dose was, how frequently they were taken, the form of the omega-3 supplement (fish oil, EPA-only, DHA-only), and whether they were consumed with food or not (which affects absorption).
  • Studies that rely on diet recall and/or supplement use also have another weakness, namely individual differences in the absorption and utilization of omega-3 fatty acids. Simply put, two individuals getting the same dose of omega-3s from diet and supplementation may have different levels of omega-3s in their cellular membranes.
  • The authors felt it was these differences that explained why they saw a much stronger and more accurate effect of omega-3s on heart failure when they based their comparison on blood levels of omega-3s rather than omega-3 supplement use.

In short, this study significantly strengthens the evidence that omega-3s reduce the risk of heart failure and improve survival for those with heart failure.

What Does This Study Mean For You?

confusionHere are the take-home lessons from this study:

As I said above, this study significantly strengthens the evidence that omega-3s reduce the risk of heart failure and improve survival for those with heart failure. That means:

  • Optimizing your intake of omega-3s may be a good strategy for reducing your risk of heart failure. More importantly, optimizing omega-3 intake may also be a good strategy for improving your survival if you have been diagnosed with heart failure.
  • The authors said, “Because omega-3 is a well-tolerated over-the-counter nutrient…it is perplexing why this safe and affordable therapy…has not been widely incorporated into guideline-directed medical therapy for heart failure. Omega-3s…should be considered as add-on therapy to the standard regimen in the prevention and treatment of heart failure.” I agree.

But what is the optimum intake of omega-3s? This is what the authors had to say about that:

  • The top 20% of participants in this study had a blood Omega-3 Index of >5.45%, but this is not necessarily optimal.
  • Previous studies have suggested that an Omega-3 Index of 8% is the optimal target for reducing the risk of death from other forms of heart disease, and the authors feel this is also the optimal target for reducing the risk of heart failure.
  • The average American has an Omega-3 Index of 4-5%, which is associated with a high risk of heart disease.
  • Previous studies have indicated that an average intake of 1.4 g/day of EPA + DHA is required to move from an Omega-3 Index of 4% to 8%.

But the key word here is “average”.

  • None of us are average. We all absorb and retain omega-3s with different efficiencies. Many people will do great with 1.4 g/day. But some may need more to achieve an Omega-3 of 8%. And others will need less.
  • That’s why I recommend that you request blood tests of your Omega-3 Index and use those to guide you to an optimal 8% rather than relying on dosage of omega-3 supplements or frequency of omega-3-rich fish consumption alone.
  • However, I recognize that Omega-3 Index determinations are expensive and not all doctor’s offices are equipped to provide them. On average, an intake of 1-2 g/day of EPA + DHA is safe and likely effective at reducing risk of heart failure and other forms of heart disease. But it may not be optimal for you.

The Bottom Line 

Previous studies have shown that an optimal intake of omega-3s is likely to reduce the risk of heart attacks and deaths from heart disease. But the news about omega-3s just got better. A recent study strengthened the evidence that omega-3s also reduce the risk of heart failure and improve survival for those with heart failure.

The authors concluded, “Higher plasma levels of marine omega-3 fatty acids were associated with a lower incidence of heart failure. Furthermore, among patients with preexisting heart failure, higher omega-3 levels were associated with lower risks of all-cause mortality and cardiovascular mortality. These findings suggest that increasing plasma omega-3 levels, whether by diet or supplementation, could reduce both risk for development of heart failure and death in those with prevalent heart failure.”

For more details on this study and what it means 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.

_______________________________________________________________________

My posts and “Health Tips From the Professor” articles carefully avoid claims about any brand of supplement or manufacturer of supplements. However, I am often asked by representatives of supplement companies if they can share them with their customers.

My answer is, “Yes, as long as you share only the article without any additions or alterations. In particular, you should avoid adding any mention of your company or your company’s products. If you were to do that, you could be making what the FTC and FDA consider a “misleading health claim” that could result in legal action against you and the company you represent.

For more detail about FTC regulations for health claims, see this link.

https://www.ftc.gov/business-guidance/resources/health-products-compliance-guidance

________________________________________________________________________

About The Author 

Dr. Chaney has a BS in Chemistry from Duke University and a PhD in Biochemistry from UCLA. He is Professor Emeritus from the University of North Carolina where he taught biochemistry and nutrition to medical and dental students for 40 years.  Dr. Chaney won numerous teaching awards at UNC, including the Academy of Educators “Excellence in Teaching Lifetime Achievement Award”. Dr Chaney also ran an active cancer research program at UNC and published over 100 scientific articles and reviews in peer-reviewed scientific journals. In addition, he authored two chapters on nutrition in one of the leading biochemistry text books for medical students.

Since retiring from the University of North Carolina, he has been writing a weekly health blog called “Health Tips From the Professor”. He has also written two best-selling books, “Slaying the Food Myths” and “Slaying the Supplement Myths”. And most recently he has created an online lifestyle change course, “Create Your Personal Health Zone”. For more information visit https://chaneyhealth.com.

For the past 45 years Dr. Chaney and his wife Suzanne have been helping people improve their health holistically through a combination of good diet, exercise, weight control and appropriate supplementation.

 

Are Omega-3 Supplements Safe?

by

The Flaws And Blind Spots In This Study

Author: Dr. Stephen Chaney

Pendulum
Pendulum

Has the omega-3 pendulum swung again? The recent headlines are downright scary. For example:

  • “Fish Oil May Increase the Risk of Stroke and Heart Conditions.”
  • “Fish Oil Supplements May Cause Harm, Study Finds. Is It Time to Ditch Them?”
  • “Fish Oil Supplements May Lead to Heart Problems”.
  • “Regular Use of Fish Oil Supplements Might Increase, Rather Than Lessen, The Risk of First Time Heart Disease and Stroke Among Those in Good Cardiovascular Health.”

Yikes! That sounds bad. Should we be thinking about giving up our omega-3 supplements?

But wait. Just a few weeks earlier we were reading headlines about the benefits and lack of side effects from omega-3 supplements. That’s confusing. Which headlines are correct?

To answer these questions:

  • I will point out the flaws and blind spots in the study.
  • I will strip away the hyperbole and put the headlines into perspective.

How Was The Study Done?

clinical studyThe investigators made use of data from the UK Biobank Study. The UK Biobank Study is a large, long-term study in the United Kingdom which was designed to investigate the contributions of genetic predisposition and environmental exposure [including diet and supplementation] to the development of disease.

The UK Biobank Study enrolled 502,461 participants, aged 40-69 years, between January 1st, 2006 and December 31st, 2010. Participants were followed from entry into the program until March 31st 2021, an average of 11.9 years.

The current study excluded any participants who had a diagnosis of atrial fibrillation, heart failure, heart attack, stroke, or cancer at entry into the study, leaving 415,737 participants.

The participants were:

  • 55% women.
  • Average age of 56 years, with 83.4% of them below 65 years old at entry into the study.
  • 94.5% white.

The study was designed in a unique manner, in that it was designed to test the effect of omega-3 supplements on 6 specific transitions:

  • Primary prevention. This measured the transition of healthy (no diagnosed heart disease) people to either atrial fibrillation, major cardiovascular events, or death.
  • Secondary prevention. This measured the transition from atrial fibrillation to either major cardiovascular events or death.
  • Tertiary prevention. This measured the transition from major cardiovascular events to death.
  • Major cardiovascular events were further broken down to heart attacks, stroke and heart failure.

Participants were asked whether they used fish oil supplements when they entered the study and were categorized as either regular users or non-users. [Note: The users were not asked the dose or brand of fish oil supplements they used.]

Deaths were obtained from the national death registry and disease diagnosis from the National Health Service.

Are Omega-3 Supplements Safe?

omega-3 fish oil supplementHere is what the study found.

Primary Prevention – For healthy individuals (defined as having no diagnosed heart disease) using omega-3 supplements for an average of 11.9 years:

  • Increased the risk of atrial fibrillation by 13%.
  • Did not affect the risk of major cardiovascular events and death were unaffected by omega-3 supplementation.
  • When major cardiovascular events were broken down to their component parts, omega-3 supplementation:
    • Decreased the risk of heart failure by 8%.
    • Increased the risk of stroke by 5% (this was just barely statistically significance).
    • Did not affect the risk of heart attack.

Secondary Prevention – For individuals with atrial fibrillation omega-3 supplementation:

  • Decreased the risk of major cardiovascular events by 9%.
  • Decreased the risk of death by 8%.
  • When major cardiovascular events were broken down into their component parts, omega-3 supplementation:
  • Decreased the risk of heart attacks by 15%.
  • Had no effect on the risk of stroke or heart failure.

Tertiary Prevention – For people who suffered major cardiovascular events during the study omega-3 thumbs upsupplementation:

  • Decreased the risk of death by 8%.

Since this is a very complex set of data, I have coded positive results in green and negative results in red.

And as if these complexities were not enough, when the investigators broke these effects down by population groups:

  • Omega-3 supplementation decreased the transition from healthy to death for men (7% decrease) and participants older than 65 (9% decrease).

I will discuss the significance of these observations below.

The authors concluded, “Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for [reducing] progression of cardiovascular disease from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death.”

In short, they were suggesting that omega-3 supplements should be avoided by the general population because they have no positive benefits and might increase the risk of atrial fibrillation and stroke. But omega-3 supplements may be useful for those who already have heart disease.

Some of the articles you may have read about the study repeated this message. Others just emphasized the negative aspects of the study.

But is this message accurate? Let me start by discussing the flaws, blind spots, and hidden data in this study. Then I will summarize the 3 key findings of the study and tell you what they mean for you.

The Flaws, Blind Spots, And Hidden Data In This Study

flawsFlaws: As I said above, there were two major flaws in the study.

Flaw #1: The study did not identify the dose of supplement used. This is important because the increased risk of atrial fibrillation and stroke is primarily seen in clinical trials using high dose omega-3 supplements.

Flaw #2: This was an association study which cannot prove cause and effect. However, the authors of this study reported it as showing that omega-3 supplement use caused atrial fibrillation and stroke – and all the news reports on the study have repeated that claim.

Flaw #3: Other experts have pointed out that the authors inflated the risks associated with omega-3 supplementation by reporting relative risk rather than absolute risk. Let me try to simplify the distinction.

The risk of atrial fibrillation was 4.24% in the non-supplement users and 4.80% in the omega-3 supplement users. That is an absolute increase in risk of 0.56% (4.80% – 4.24%). This is the increase in risk you actually experience. In contrast, 4.80% is 13% greater than 4.24%, which is how relative risk is calculated.

In response to the questions you are probably thinking:

  • Yes, this is a perfect example of the Mark Twain quote, “There are lies. There are damn lies. And then there are statistics.”
  • Yes, all the percentages reported in this study are based on relative risk and are, therefore, inflated. However, I do not have access to their data, so I cannot tell you the absolute risk associated with their other observations.

Blind Spots: In their paper the investigators recommended against the use of omega-3 supplements to prevent heart disease because their data showed:

  • No benefit of omega-3 supplementation for preventing major cardiovascular events and deaths in a healthy population.
  • But did suggest an increased risk of atrial fibrillation and stroke in that same population.

However, their blind spot was in underestimating the difficulty of showing the benefit of any intervention in a healthy population. The example I always use is statin drugs. Statin Drugs:

  • Dramatically reduce the risk of a second heart attack and/or death in people who have already had a heart attack.
  • Reduce the risk of heart attacks in people who are at high risk of heart attacks.
  • Cannot be shown to reduce the risk of heart attacks in a healthy population.

This study suggests that omega-3 supplements are no different. In this study, omega-3 supplements:

  • Reduced the risk of death in people who had already experienced a major cardiovascular event like a heart attack or stroke.
  • Reduced the risk of major cardiovascular events and death in people with atrial fibrillation, which puts them at high risk for a heart attack or stroke.
  • Could not be shown to reduce the risk of major cardiovascular events or deaths in a healthy population.

Hidden Data: There are some important data that were buried in the text and supplemental figures but were Skepticignored in the concluding remarks of this study and all the articles written about it. For example:

  • The original study and all articles written about the study reported that omega-3 supplementation increased the risk of stroke in otherwise healthy individuals but ignored the observation that omega-3 supplementation decreased the risk of heart failure in that same group.

The second example of hidden data likely represents another blind spot of the authors. They concluded that omega-3 supplementation had no benefit for healthy individuals without asking whether omega-3 supplements might benefit higher-risk subpopulations within this group. To help you understand this statement let me start by giving you some perspective.

As I said above, statin drugs cannot be shown to reduce the risk of heart attacks in a healthy population. But when you include people at high risk of heart disease with healthy people in the dataset, you start to see a reduced risk of heart attacks.

Similarly, with supplements you often see no benefits with the general population, which is what is usually reported in the media. But when you look at higher risk groups within that population, the benefits of supplementation emerge.

This study is no different:

  • For healthy individuals, omega-3 supplementation had no effect on deaths during the 12-year follow-up period.
  • However, omega-3 supplementation reduced the risk of death by 9% for both men and people ≥ 65. These represent two groups with elevated risk of heart disease within the otherwise healthy population.
  • Once again, these data were completely ignored.

What Does This Study Mean For You?

This study made 3 major points:

Point #1: Let me start with the one you’ve heard the most about. The risk of atrial fibrillation and stroke associated with omega-3 supplementation is real. We should not ignore it.

But what this study and most of the reports on the study didn’t tell you is that the risk is dose dependent. The risk is primarily seen with high doses of omega-3s. While no one has done a comprehensive dose response analysis, I can tell you that these side effects are:

  • Seldom reported in clinical studies at doses of 1 gm/day or less.
  • Sometimes reported in clinical studies at doses of ≥2 gm/day.
  • Frequently reported in clinical studies at doses of ≥4 gm/day.

However, atrial fibrillation and stroke occur in a very small percentage of omega-3 users, even at 4 gm/day. At this point we have no idea why some people are susceptible to these side effects and others are not. More research in this area is clearly needed.

Until we know more about who is at risk, my recommendation for people who are trying to reduce the risk of heart disease is to rely on something called the Omega-3 Index to determine your individual omega-3 needs rather than using high-dose omega-3 supplements.

  • The Omega-3 Index measures the amount of omega-3 fatty acids in your tissues. It is determined by the amount of omega-3s you consume and how you metabolize them, so it is individualized to you.
  • An Omega-3 Index of 4% is associated with a high risk of heart disease, while an Omega-3 Index of 8% is associated with a low risk of heart disease. There is no evidence that more than 8% provides additional benefit.
  • Most importantly, it only takes 1-1.6 gm/day of omega-3s to raise your Omega-3 Index from 4% to 8%. At these doses your risk of atrial fibrillation and stroke is extremely small.

For example, a recent meta-analysis of 29 studies with a total of 183,292 participants reported that people with an 8% Omega-3 Index had:

  • Decreased risk of ischemic stroke (stroke due to blood clots) with no detectable increased risk of hemorrhagic stroke (stroke due to bleeding), and…
  • No detectable increased risk of atrial fibrillation.

I recommend getting your Omega-3 Index determined, and if it is low, increasing your omega-3 intake to get it into the 8% range. Some people go from 4% to 8% more rapidly than others, so you may need to repeat the test several times to optimize your Omega-3 Index.

If your health professional doesn’t have access to the Omega-3 Index test, you can order it from https://omegaquant.com (I have no financial stake in this company, but I know it as a reputable source of the Omega-3 Index test).

Does The Professor Plan To Reduce His Intake Of Omega-3 Fatty Acids? Three weeks ago, I shared thatprofessor owl my wife and I have been taking around 3 gm/day of omega-3 supplements for the past 40 years. Now that the association of atrial fibrillation and stroke with high dose omega-3 intake has been firmly established, some of you may be wondering whether we plan to decrease our intake of omega-3 supplements.

The answer is, “No”. Remember that the increased risk of atrial fibrillation and stroke is only seen for a small subset of people taking high-dose omega-3 supplements. If we were part of that subset, we would likely have experienced one of those side effects by now.

However, if you are considering omega-3 supplementation for the first time, you don’t know whether you are part of that subset or not. So, my advice remains the same. Rely on optimizing your Omega-3 Index rather than high-dose omega-3 supplementation.

Point #2: Healthy individuals (those with no symptoms of heart disease) do not benefit from omega-3 supplementation. As I pointed out above, this ignores data from their study, namely.

  • Omega-3 supplementation reduced the risk of heart failure in healthy subjects.
  • Omega-3 supplementation reduced the risk of death in higher risk groups within the healthy population (namely men and people 65 and older).

Confusion Clinical StudiesAs I discussed above, this is a pattern seen with statin drugs and most nutritional supplements. Simply put, you can’t show any benefit of statin drugs or most nutritional supplements in a “healthy” population, but you can show benefit when you focus on higher risk individuals within the “healthy” population.

The problem, of course, is that most of us don’t really know whether we are “healthy” or not. For millions of Americans the first indication that they are at risk from heart disease is sudden death from a heart attack or stroke.

With that in mind, I will leave the decision about whether you want to supplement with omega-3s up to you. But if you decide to supplement, I recommend you optimize your Omega-3 Index rather than using a high dose omega-3 supplement.

Point #3: People with heart disease benefit from omega-3 supplementation. This recommendation is becoming non-controversial, so I won’t comment further other than to say high dose omega-3 supplements are probably not needed unless prescribed by your health professional.

The Bottom Line

You have been asking me about recent headlines saying that omega-3 supplements may increase rather than decrease the risk of heart disease. So, I analyzed the study behind the headlines. The study makes 3 claims:

  • Omega-3 supplements increase the risk of atrial fibrillation and stroke when taken by healthy people.
  • Omega-3 supplements are of no benefit for healthy individuals.
  • Omega-3 supplements are beneficial for people who have heart disease.

In the article above I review the flaws, blind spots, and hidden data in the article and discuss what it means for you.

For more details about this study and what it means 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.

 ______________________________________________________________________________

My posts and “Health Tips From the Professor” articles carefully avoid claims about any brand of supplement or manufacturer of supplements. However, I am often asked by representatives of supplement companies if they can share them with their customers.

My answer is, “Yes, as long as you share only the article without any additions or alterations. In particular, you should avoid adding any mention of your company or your company’s products. If you were to do that, you could be making what the FTC and FDA consider a “misleading health claim” that could result in legal action against you and the company you represent.

For more detail about FTC regulations for health claims, see this link.

https://www.ftc.gov/business-guidance/resources/health-products-compliance-guidance

 _______________________________________________________________________

About The Author 

Dr. Chaney has a BS in Chemistry from Duke University and a PhD in Biochemistry from UCLA. He is Professor Emeritus from the University of North Carolina where he taught biochemistry and nutrition to medical and dental students for 40 years.  Dr. Chaney won numerous teaching awards at UNC, including the Academy of Educators “Excellence in Teaching Lifetime Achievement Award”. Dr Chaney also ran an active cancer research program at UNC and published over 100 scientific articles and reviews in peer-reviewed scientific journals. In addition, he authored two chapters on nutrition in one of the leading biochemistry text books for medical students.

Since retiring from the University of North Carolina, he has been writing a weekly health blog called “Health Tips From the Professor”. He has also written two best-selling books, “Slaying the Food Myths” and “Slaying the Supplement Myths”. And most recently he has created an online lifestyle change course, “Create Your Personal Health Zone”. For more information visit https://chaneyhealth.com.

For the past 45 years Dr. Chaney and his wife Suzanne have been helping people improve their health holistically through a combination of good diet, exercise, weight control and appropriate supplementation.

Are Calcium Supplements Heart Healthy?

by

Should You Follow Your Doctor’s Advice About Calcium Supplementation?

Author: Dr. Stephen Chaney

Heart ConfusionAre calcium supplements good for your heart or bad for your heart? If you don’t know the answer to that question, don’t feel badly. You have every right to be confused. Some studies say that calcium supplements increase heart disease risk while others say they decrease heart disease risk. The headlines have veered between “killer calcium” and “beneficial calcium”.

The trend appears to be moving in a positive direction. In recent years most of the studies have suggested that calcium supplements either decrease heart disease risk or have no effect on heart disease risk.

However, the medical profession has been slow to take note of this trend. Most medical societies and health professionals have focused on earlier studies and are still recommending that their patients get calcium from food rather than from supplements. I will talk more about that recommendation below.

With this context in mind, this week I will review and discuss the results from the latest study (MG Sim et al, Heart, Lung and Circulation, 32: 1230-1239, 2023) on the effect of calcium supplementation on heart disease risk.

How Was This Study Done?

Clinical StudyThe authors of this study performed a meta-analysis of 12 double-blinded randomized clinical trials with 87,899 participants comparing the effect of a calcium supplement versus a placebo on heart disease outcomes (heart attack, stroke, heart failure, cardiovascular mortality, and all-cause mortality).

The studies included in this analysis:

  • Used calcium doses from 500 mg/day to 2,000 mg/day.
  • Used supplements with calcium coming from a variety of sources (calcium carbonate, calcium citrate, calcium gluconolactate, and tricalcium phosphate).
  • Ranged from 18 months to almost 12 years in length.
  • Were performed with population groups from a wide range of countries (United States, England, France, Australia, New Zealand, European Union, Denmark, and Thailand).
  • Included calcium supplements with and without vitamin D.
  • Were primarily (86% of participants) conducted with post-menopausal women. One small study (0.3% of participants) was conducted with non-osteoporotic men. The rest were conducted with mixed populations (men and women) diagnosed with colorectal adenoma.

Are Calcium Supplements Heart Healthy?

calcium supplementsThis is the largest meta-analysis performed to date of double-blind, placebo-controlled randomized clinical trials on the effect of calcium supplementation versus a placebo on heart disease outcomes. This study found no effect of calcium supplementation on:

  • Heart attack.
  • Stroke
  • Heart failure.
  • Cardiovascular mortality.
  • All-cause mortality.

This study also evaluated potential confounding variables and found no effect of calcium supplementation on heart disease risk for:

  • Calcium supplements with and without vitamin D.
  • Dosage of calcium in the supplements (The dosage ranged from 500 mg/day to 2,000 mg/day).
  • Females (I suspect the number of males in this study was too small to come to a statistically significant conclusion).
  • Duration of calcium supplementation ≤ 5 years (The shortest duration of calcium supplementation in these studies was 18 months).
  • Different geographical regions.

However, this meta-analysis reported considerable variation between studies included in the analysis. Simply put,

  • Some studies showed an increase in heart disease risk.
  • Some studies showed a decrease in heart disease risk.
  • Some studies showed no effect on heart disease risk.

What this analysis showed was that when you combine all the studies, the aggregated data is consistent with calcium supplementation having no effect on heart disease risk.

The authors concluded, “Calcium supplementation was not associated with myocardial infraction [heart attack], stroke, heart failure, and cardiovascular/all-cause mortality. Further studies are required to examine and understand these associations.

Should You Follow Your Doctor’s Advice About Calcium Supplementation?

Doctor With PatientAs I said above, most medical societies and health professionals have focused on earlier studies and are still recommending that their patients get calcium from food rather than from supplements. That may be the advice you are getting from your doctor.

Before you assume your doctor isn’t keeping up with the latest science and ignore his or her advice, we should ask why they are giving that advice. The top three reasons most medical societies give for recommending dietary sources of calcium are:

1) Some studies do show an increased risk of heart disease associated with calcium supplementation. The prime directive for health professionals is to do no harm. Yes, the average of all studies shows no effect of calcium supplementation on heart disease risk. But what if the studies showing increased risk are true for some of their patients? Those patients could be harmed. 

Are you someone who might be at increased risk for heart disease if you take calcium supplements. The short answer is we don’t know because previous studies have not asked the right questions. 

In my opinion, it is time to pause additional studies and meta-analyses on calcium supplementation and heart health until we have gone over existing studies with a fine-tooth comb to figure out why the results differ so wildly. For example, we need to ask whether the effect of calcium supplements on heart disease risk is influenced by things like:

    • Age or ethnicity of participants.
    • Other preexisting health conditions.
    • Other lifestyle factors (exercise is probably the most important, but others may be involved as well).
    • Diet context. For example, we already know that the effect of eggs and dairy on heart health is influenced by diet context. [I have covered this for eggs in a previous issue of “Health Tips From the Professor”.]
    • Other unanticipated variables.

Only when we have identified variables that might influence the effect of calcium supplements on heart disease risk, will the scientific community be able to design studies to identify the population groups who might be adversely affected by calcium supplementation.

This would allow health professionals to make informed decisions about which of their patients should avoid calcium supplementation and which of their patients would benefit from calcium supplementation. 

2) We really don’t need the recommended RDAs for calcium to build strong bones. The Healthy Bonerecommended RDAs for calcium are 1,000 mg/day for adults 19-50, 1,000 mg/day for men and 1,200 mg/day for women 51-70, and 1,200 mg/day for both men and women over 70. But do we really need that amount of calcium to build healthy bones? 

I have discussed this topic in detail in a previous issue of “Health Tips From the Professor”. Here are the key points:

    • The current RDAs are based on calcium needs for people consuming the typical American diet and following the typical American lifestyle. If that is you, the current RDAs probably apply.
    • However, strong bones are absolutely dependent on three things, adequate calcium, adequate vitamin D, and adequate weight-bearing exercise. Most recent studies of calcium supplementation and bone density include adequate vitamin D, but almost none of them include exercise. Previous studies have been inadequate.
    • The best calcium supplements contain certain nutrients besides vitamin D that optimize bone formation. I have listed those nutrients in the article cited above.
    • Our ability to use calcium to build strong bones is dependent on diet (something I call a bone-healthy diet) and lifestyle (something I call a bone-healthy lifestyle).
    • For more information on each of these points, read the article I referenced above.

In short, I agree that the current calcium RDAs may be too high for individuals consuming a bone-healthy diet and following a bone-healthy lifestyle. But the current calcium RDAs are likely accurate for people consuming the typical American diet and following the typical American lifestyle.

    • While we do not have a calcium RDA for populations following a bone healthy diet lifestyle, some studies suggest that 700-800 mg of calcium/day may be sufficient for this group.

3) Calcium from supplements is absorbed faster and gives higher blood level spikes than calcium from foods. That could be a problem because high blood levels of calcium are associated with calcification of our arteries, which is associated with increased heart disease risk. 

This is a theoretical concern, because high blood calcium levels from supplementation are transitory, while it is continuous high blood calcium levels that are associated with calcification of our arteries.

However, it is a plausible concern because most supplement companies design their calcium supplements based on how quickly they get calcium into the bloodstream rather than how effectively the calcium is utilized for bone formation. Here are my recommendations:

    • Choose a calcium supplement that provides RDA levels of vitamin D plus other nutrients shown to support strong bone formation.
    • Choose a calcium supplement supported by clinical studies showing it is effectively utilized for bone formation.

4) We should be getting our calcium from foods rather than supplements. dairy foods

While it is always easy for doctors to recommend that we get our nutrients from food rather than supplements, they need to ask whether we are getting those nutrients from our diet. For calcium the data are particularly sobering.

    • The average American gets around 740 mg of calcium/day from their diet. That is probably enough for the small percentage of Americans following a bone healthy diet and lifestyle. But it is 260-460 mg short of the 1,000-1,200 mg/day recommended for older adults with the typical American diet and lifestyle.
      • And for the average American, around 70% of their calcium intake comes from dairy foods.

       

      • So, Americans who are following a typical American diet and lifestyle and are restricting dairy may require 800-1,000 mg/day of supplemental calcium unless they carefully plan their diets to optimize calcium intake.

       

      • Finally, vegans average about 550 mg/day from their diet. That might be borderline even if they were following a bone healthy lifestyle.
    • In short, we cannot assume our diet will provide enough calcium for strong bones unless we include dairy foods and/or plan our diet very carefully. Some degree of supplementation may be necessary.

How Much Calcium Do You Need?

Questioning Woman

I have covered a lot of territory in this article, so let me summarize the four concerns of the medical community and answer your most important question, “Should you take calcium supplements?”

1) Calcium supplements may increase the risk of heart disease for some people.

That is true, but we have no idea at present who is at increased risk and who isn’t. So, we should minimize our risk by taking the precautions I describe below.

2) We don’t need RDA levels of calcium to build strong bones. That is probably true if you are one of the few people who follows a bone healthy diet and lifestyle, but it isn’t true if you follow the typical American diet and lifestyle.

  • The current RDAs of 1,000 – 1,200 mg/day are a good guideline for how much calcium you need if you follow the typical American diet and lifestyle.
  • If you a one of the few people who follow a bone healthy diet and lifestyle (For what that involves, read this article) you may only need 700-800 mg/day. But we don’t have clinical studies that can tell us what the actual RDA for calcium should be under those circumstances.

3) Calcium from supplements is absorbed faster and gives higher blood calcium spikes than calcium from foods. You may remember that the theoretical concern is that even short-term spikes of high blood calcium may lead to calcification of your arteries, which increases your risk of heart disease. So, the important question becomes, “What can we do to minimize these spikes in blood calcium levels?”

  • We should avoid calcium supplements that brag about how quickly and efficiently the calcium is absorbed. That could lead to calcium spikes. Instead, we should look for calcium supplements that are backed by clinical studies showing they are efficiently utilized for bone formation.
  • We should look for calcium supplements that include RDA levels of vitamin D and other nutrients that optimize bone formation. You will find more information on that in the same article I referenced above.
  • Some experts recommend that calcium supplements be taken between meals. But it is probably better to take them with meals because foods will likely slow the rate at which calcium is absorbed and reduce calcium spikes in the blood.
  • We are told to limit calcium supplements to less than 500 mg at any one time because calcium absorption becomes inefficient at higher doses. It might be even better to limit calcium to 250 mg or less at a time to reduce calcium spikes in the blood.

4) We should get calcium from foods rather than supplements.

  • Many Americans do not get enough calcium from diet alone, especially if they avoid dairy foods. So, some degree of calcium supplementation may be necessary. I have given some guidelines depending on your diet and lifestyle above.
  • The amount of supplemental calcium needed is relatively small. I do not recommend exceeding the RDA unless directed to by your health professional.

The Bottom Line 

Some studies say that calcium supplements increase heart disease risk while others say they decrease heart disease risk. The headlines veer between “killer calcium” and “beneficial calcium”.

The trend appears to be moving in a positive direction. In recent years most of the studies have suggested that calcium supplements either decrease heart disease risk or have no effect on heart disease risk.

However, the medical profession has been slow to take note of this trend. Most medical societies and health professionals have focused on earlier studies and are still recommending that their patients get calcium from food rather than from supplements.

A recent meta-analysis of 12 double-blinded randomized clinical trials with 87,899 participants comparing the effect of a calcium supplement versus a placebo on heart disease outcomes has just been published. This study found no effect of calcium supplementation on:

  • Heart attack.
  • Stroke.
  • Heart failure.
  • Cardiovascular mortality.
  • All-cause mortality.

The authors of the study concluded, “Calcium supplementation was not associated with myocardial infraction [heart attack], stroke, heart failure, and cardiovascular/all-cause mortality.

For more details and advice on whether you should follow your doctor’s recommendations for calcium supplementation 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.

 _____________________________________________________________________________

My posts and “Health Tips From the Professor” articles carefully avoid claims about any brand of supplement or manufacturer of supplements. However, I am often asked by representatives of supplement companies if they can share them with their customers.

My answer is, “Yes, as long as you share only the article without any additions or alterations. In particular, you should avoid adding any mention of your company or your company’s products. If you were to do that, you could be making what the FTC and FDA consider a “misleading health claim” that could result in legal action against you and the company you represent.

For more detail about FTC regulations for health claims, see this link.

https://www.ftc.gov/business-guidance/resources/health-products-compliance-guidance

____________________________________________________________________

About The Author

Dr. Steve ChaneyDr. Chaney has a BS in Chemistry from Duke University and a PhD in Biochemistry from UCLA. He is Professor Emeritus from the University of North Carolina where he taught biochemistry and nutrition to medical and dental students for 40 years.  Dr. Chaney won numerous teaching awards at UNC, including the Academy of Educators “Excellence in Teaching Lifetime Achievement Award”. Dr Chaney also ran an active cancer research program at UNC and published over 100 scientific articles and reviews in peer-reviewed scientific journals. In addition, he authored two chapters on nutrition in one of the leading biochemistry text books for medical students.

 

Which Supplements Are Good For Your Heart?

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How Should You Interpret This Study? 

Author: Dr. Stephen Chaney 

strong heartFebruary is Heart Health month. So, it is fitting that we ask, “What is the status of heart health in this country?” The American Heart Association just published an update of heart health statistics through 2019 (CW Tsao et al, Circulation, 145: e153-e639, 2022). And the statistics aren’t encouraging. [Note: The American Heart Association only reported statistics through 2019 because the COVID-19 pandemic significantly skewed the statistics in 2020 and 2021].

The Good News is that between 2009 and 2019:

  • All heart disease deaths have decreased by 25%.
  • Heart attack deaths have decreased by 6.6%.
  • Stroke deaths have decreased by 6%.

The Bad News is that:

  • Heart disease is still the leading cause of death in this country.
  • Someone dies from a heart attack every 40 seconds.
  • Someone dies from a stroke every 3 minutes.

Diet, exercise, and weight control play a major role in reducing the risk of heart disease. Best of all, they have no side effects. They represent a risk-free approach that each of us can control.

But is there something else? Could supplements play a role? Are supplements hype or hope for a healthy heart?

All the Dr. Strangeloves in the nutrition space have their favorite heart health supplements. They claim their supplements will single-handedly abolish heart disease (and help you leap tall buildings in a single bound).

On the other hand, many doctors will tell you these supplements are a waste of money. They don’t work. They just drain your wallet.

It’s so confusing. Who should you believe? Fortunately, a recent study (P An et al, Journal of the American College of Cardiology, 80: 2269-2285, 2022) has separated the hype from the hope and tells us which “heart-healthy” supplements work, and which don’t.

How Was This Study Done?

Clinical StudyThis was a major clinical study carried out by researchers from the China Agricultural University and Brown University in the US. It was a meta-analysis, which means it combined the data from many published clinical trials.

The investigators searched three major databases of clinical trials to identify:

  • 884 randomized, placebo-controlled clinical studies…
  • Of 27 types of micronutrients…
  • With a total of 883,627 patients…
  • Looking at the effectiveness of micronutrient supplementation lasting an average of 3 years on either…
    • Cardiovascular risk factors like blood pressure, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides…or…
    • Cardiovascular outcomes such as coronary heart disease (CHD), heart attacks, strokes, and deaths due to cardiovascular disease (CVD) and all causes.

[Note: Coronary heart disease (CHD) refers to build up of plaque in the coronary arteries (the arteries leading to the heart). It is often referred to as heart disease and can lead to heart attacks (myocardial infarction). Cardiovascular disease (CVD) is a more inclusive term that includes coronary heart disease, stroke, congenital heart defects, and peripheral artery disease.]

The investigators also included an analysis of the quality of the data in each of the clinical studies and rated the evidence of each of their findings as high quality, moderate quality, or low quality.

Which Supplements Are Good For Your Heart?

The top 3 heart-healthy supplements in this study were:

Omega-3s And Heart DiseaseOmega-3 Fatty Acids:

  • Increased HDL cholesterol and decreased triglycerides, both favorable risk factors for heart health.
  • Deceased risk of heart attacks by 15%, all CHD events by 14%, and CVD deaths by 7% (see definitions of CHD and CVD above).
  • The median dose of omega-3 fatty acids in these studies was 1.8 g/day.
  • The evidence was moderate quality for all these findings.

Folic Acid:

  • Decreased LDL cholesterol (moderate quality evidence) and decreased blood pressure and total cholesterol (low quality evidence).
  • Decreased stroke risk by 16% (moderate quality evidence).

Coenzyme Q10:

  • Decreased triglycerides (high quality evidence) and reduced blood pressure (low quality evidence).
  • Decreased the risk of all-cause mortality by 32% (moderate quality evidence).
  • These studies were performed with patients diagnosed with heart failure. Coenzyme Q10 is often recommended for these patients, so the studies were likely performed to test the efficacy of this treatment.

There were three micronutrients (vitamin C, vitamin E, and vitamin D) that did not appear to affect heart disease outcomes.

Finally, as reported in previous studies, β-carotene increased the risk of stroke, CVD mortality, and all-cause mortality.

In terms of the question I asked at the beginning of this article, this study concluded that:

  • Omega-3, folic acid, and coenzyme Q10 supplements represent hope for a healthy heart.
  • Vitamin C, vitamin E, and vitamin D supplements represent hype for a healthy heart.
  • β-carotene supplements represent danger for a healthy heart.

But these conclusions just scratch the surface. To put them into perspective we need to dig a bit deeper.

How Should You Interpret This Study?

Question MarkIn evaluating the significance of these findings there are two things to keep in mind.

#1: This study is a meta-analysis and meta-analyses have both strengths and weaknesses.

The strength of meta-analyses is that by combining multiple clinical studies they can end up with a database containing 100s of thousands of subjects. This allows them to do two things:

  • It allows the meta-analysis to detect statistically significant effects that might be too small to detect in an individual study.
  • It allows the meta-analysis to detect the average effect of all the clinical studies it includes.

The weakness of meta-analyses is that the design of individual studies included in the analysis varies greatly. The individual studies vary in things like dose, duration, type of subjects included in the study, and much more.

This is why this study rated most of their conclusions as backed by moderate- or low-quality evidence. [Note: The fact that the authors evaluated the quality of evidence is a strength of this study. Most meta-analyses just report their conclusions without telling you how strong the evidence behind those conclusions is.]

#2: Most clinical studies of supplements (including those included in this meta-analysis) have two significant weaknesses.

  • Most studies do not measure the nutritional status of their subjects prior to adding the supplement. If their nutritional status for a particular nutrient was already optimal, there is no reason to expect more of that nutrient to provide any benefit.
  • Most studies measure the effect of a supplement on a cross-section of the population without asking who would be most likely to benefit.

You would almost never design a clinical study that way if you were evaluating the effectiveness of a potential drug. So, why would you design clinical studies of supplements that way?

With these considerations in mind, let me provide some perspective on the conclusions of this study.

Coenzyme Q10:

This meta-analysis found that coenzyme Q10 significantly reduced all-cause mortality in patients with heart failure. This is consistent with multiple clinical studies and a recent Cochrane Collaboration review.

Does coenzyme Q10 have any heart health benefits for people without congestive heart failure? There is no direct evidence that it does, but let me offer an analogy with statin drugs.

Statin drugs are very effective at reducing heart attacks in high-risk patients. But they have no detectable effect on heart attacks in low-risk patients. However, this has not stopped the medical profession from recommending statins for millions of low-risk patients. The rationale is that if they are so clearly beneficial in high-risk patients, they are “probably” beneficial in low-risk patients.

I would argue a similar rationale should apply to supplements like coenzyme Q10.

Omega-3s:

This study found that omega-3 reduced both heart attacks and the risk of dying from heart disease. Most previous meta-analyses of omega-3s and heart disease have come to the same conclusion. However, some meta-analyses have failed to find any heart health benefits of omega-3s. Unfortunately, this has allowed both proponents and opponents of omega-3 use for heart health to quote studies supporting their viewpoint.

However, there is one meta-analysis that stands out from all the others. A group of 17 scientists from across the globe collaborated in developing a “best practices” experimental design protocol for assessing the effect of omega-3 supplementation on heart health. They conducted their clinical studies independently, and when their data (from 42,000 subjects) were pooled, the results showed that omega-3 supplementation decreased:

  • Premature death from all causes by 16%.
  • Premature death from heart disease by 19%.
  • Premature death from cancer by 15%.
  • Premature death from causes other than heart disease and cancer by 18%.

This study eliminates the limitations of previous meta-analyses. That makes it much stronger than the other meta-analyses. And these results are consistent with the current meta-analysis.

Omega-3s have long been recognized as essential nutrients. It is past time to set Daily Value (DV) recommendations for omega-3s. Based on the recommendations of other experts in the field, I think the DV should be set at 500-1,000 mg/day. I take more than that, but this would represent a good minimum recommendation for heart health.

folic acidFolic acid:

As with omega-3s, this meta-analysis reported a positive effect of folic acid on heart health. But many other studies have come up empty. Why is that?

It may be because, between food fortification and multivitamin use, many Americans already have sufficient blood levels of folic acid. For example, one study reported that 70% of the subjects in their study had optimal levels of folates in their blood. And that study also reported:

  • Subjects with adequate levels of folates in their blood received no additional benefit from folic acid supplementation.
  • However, for subjects with inadequate blood folate levels, folic acid supplementation decreased their risk of heart disease by ~15%.

We see this pattern over and over in supplement studies. Supplement opponents interpret these studies as showing that supplements are worthless. But a better interpretation is that supplements benefit those who need them.

The problem is that we don’t know our blood levels of essential nutrients. We don’t know which nutrients we need, and which we don’t. That’s why I like to think of supplements as “insurance” against the effects of an imperfect diet.

Vitamins E and D:

The situation with vitamins E and D is similar. This meta-analysis found no heart health benefit of either vitamin E or D. That is because the clinical studies included in the meta-analysis asked whether vitamin E or vitamin D improved heart health for everyone in the study.

Previous studies focusing on patients with low blood levels of these nutrients and/or at high risk of heart disease have shown some benefits of both vitamins at reducing heart disease risk.

So, for folic acid, vitamin E, and vitamin D (and possibly vitamin C) the take-home message should be:

  • Ignore all the Dr. Strangeloves telling you that these vitamins are “magic bullets” that will dramatically reduce your risk of heart disease.
  • Ignore the naysayers who tell you they are worthless.
  • Use supplementation wisely to make sure you have the recommended intake of these and other essential nutrients.

β-carotene:

This meta-analysis reported that β-carotene increased the risk of heart disease. This is not a new finding. Multiple previous studies have come to the same conclusion.

And we know why this is. There are many naturally occurring carotenoids, and they each have unique heart health benefits. A high dose β-carotene supplement interferes with the absorption of the other carotenoids. You are creating a deficiency of other heart-healthy carotenoids.

If you are not getting lots of colorful fruits and vegetables from your diet, my recommendation is to choose a supplement with all the naturally occurring carotenoids in balance – not a pure β-carotene supplement.

The Bottom Line 

The Dr. Strangeloves in the nutrition space all have their favorite heart health supplements. They claim their supplements will single-handedly abolish heart disease (and help you leap tall buildings in a single bound).

On the other hand, many doctors will tell you these supplements are a waste of money. They don’t work. They just drain your wallet.

It’s so confusing. Who should you believe? Fortunately, a recent study has separated the hype from the hope and tells us which “heart-healthy” supplements work, and which don’t.

This study was a meta-analysis of 884 clinical studies with 883,627 participants. It reported:

  • Omega-3 supplementation deceased risk of heart attacks by 15% and all cardiovascular deaths by 7%.
  • Folic acid supplementation decreased stroke risk by 16%.
  • Coenzyme Q10 supplementation decreased the risk of all-cause mortality in patients with heart failure by 32%.
  • Vitamin C, vitamin E, vitamin D did not appear to affect heart disease outcomes.
  • β-carotene increased the risk of stroke, CVD mortality, and all-cause mortality.

For more details on this study and what it means 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.

Omega-3s And Congestive Heart Failure

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We Have Been Asking The Wrong Questions 

Author: Dr. Stephen Chaney

Confusion Clinical StudiesToday’s Health Tip is a follow-up to the article I published last month on omega-3s and heart disease risk. In that article I pointed out the reasons why studies of the effect of omega-3s and heart disease risk have been so confusing.

One of the reasons is that many of the studies have been asking the wrong questions.

  • They were asking whether omega-3s reduced the risk of heart disease for everyone. Instead, they should have been asking who benefited from omega-3 supplementation.
  • They were asking whether omega-3s reduced the risk of all forms of heart disease combined. Instead, they should have been asking whether omega-3s reduced the risk of specific kinds of heart disease.

I also discussed a large clinical trial, the VITAL study, that was designed to answer those two questions.

The study I will describe today (L Djoussé et al, JACC Heart Failure, 10: 227-234, 2022) mined the data from the VITAL study to evaluate the effect of omega-3 supplementation on congestive heart failure, a form of heart disease that was not discussed in the VITAL study.

Everything You Need To Know About Congestive Heart Failure

Congestive Heart FailureCongestive heart failure is a killer. The term congestive heart failure simply means that your heart no longer pumps blood well. The initial symptoms are relatively non-specific and include things like.

  • Shortness of breath.
  • Fatigue and weakness.
  • Reduced ability to exercise.
  • Rapid or irregular heartbeat.
  • Persistent cough or wheezing.

However, as it progresses, the symptoms get much worse. Fluid builds up in your tissues.

  • Fluid buildup in your legs, ankles, and feet can make it difficult to walk.
  • Fluid buildup in your lungs makes it difficult to breathe. In advanced stages it can feel like you are drowning in a room full of air.

According to the CDC:

  • 4 million Americans have congestive heart failure (CHF).
    • It leads to ~380,000 deaths/year.
  • 83% of patients diagnosed with CHF will be hospitalized at least once.
    • 67% will be hospitalized two or more times.
  • CHF costs >$30 billion per year in health care costs and lost wages.

The risk of congestive heart failure is not spread evenly across the American population. Black Americans and Americans with type 2 diabetes are at increased risk.

According to the Framingham Heart Study:

  • Type 2 diabetes increases the risk of CHF 2-fold in men and 5-fold in women. The reasons are not entirely clear. However:
    • High blood sugar is thought to either damage cells in heart muscle, weakening it, or damage small blood vessels within the heart, making it more difficult for the heart to pump blood.
    • Some diabetes drugs that lower blood sugar also appear to increase the risk of congestive heart failure.

According to the CDC:

  • Black Americans are 2-fold more likely to develop CHF than White Americans. Again, the reasons are not clear. However:
    • Some experts feel it could be due to the higher incidence of untreated high blood pressure in Black Americans.

In summary:

  • Congestive heart failure is a serious disease. Its symptoms affect your quality of life, and it can lead to hospitalizations and death.
  • Black Americans and Americans with type 2 diabetes are at higher risk of developing congestive heart failure.

How Was The Study Done?

The VITAL study, from which these data were extracted, was a placebo-controlled clinical trial designed to measure the effects of 1,000 mg omega-3 supplementation on the risk of developing heart disease. It enrolled 25,871 Americans aged 55 years or older and followed them for an average of 5.3 years.

The participants enrolled in the VITAL study represented a cross-section of the American population. Most were at low risk of heart disease, but there were subsets of the study group who were at higher risk of heart disease. A strength of the VITAL study was that it was designed so the high-risk subgroups could be evaluated separately.

The current study utilized data from the VITAL study to look at the effect of omega-3 supplementation on hospitalizations due to congestive heart failure. It also evaluated the effect of type 2 diabetes and race on the risk of hospitalizations.

Omega-3s And Congestive Heart Failure

Omega-3s And Heart DiseaseWhen the investigators looked at the whole population, most of whom were at low-risk of congestive heart failure, they did not see any effect of omega-3 supplementation on the risk of hospitalizations due to congestive heart failure.

However, when they looked at high risk groups, the story was much different.

In patients with type-2 diabetes:

  • Omega-3 supplementation reduced the risk of the initial hospitalization for congestive heart failure by 31%
  • Omega-3 supplementation reduced the risk of multiple hospitalizations due to congestive heart failure by 47%.

The effect of omega-3 supplementation on hospitalizations was greatest for the Black participants in the study.

In the words of the authors, “Our data show beneficial effects of omega-3 fatty acid supplements on the incidence of heart failure hospitalizations in participants with type 2 diabetes but not in those without type 2 diabetes, and such benefit appeared to be stronger in Black participants with type 2 diabetes.”

We Are Asking The Wrong Questions

ScientistAs I said above, there is so much confusion about the effect of omega-3s on heart disease because we scientists have been asking the wrong questions:

  • We have been asking whether omega-3s reduce the risk of heart disease for everyone. Instead, we should have been asking who benefits from omega-3 supplementation.
  • We have been asking whether omega-3s reduced the risk of all forms of heart disease combined. Instead, we should have been asking whether omega-3s reduced the risk of specific kinds of heart disease.

In my “Health Tip” last month I discussed a large clinical study, the VITAL study, that was specifically designed to answer the right questions. Like so many other studies it found that omega-3 supplementation did not significantly reduce the risk of all kinds of heart disease for everyone.

However, what it did find was more important than what it did not find:

  • When they looked at the effect of omega-3s on heart disease risk in high-risk groups, they found that major cardiovascular events were reduced by:
    • 26% in African Americans.
    • 26% in patients with type 2 diabetes.
    • 17% in patients with a family history of heart disease.
    • 19% in patients with two or more risk factors of heart disease.
  • When they looked at the effect of omega-3s on heart disease risk in people with low omega-3 intake, they found that omega-3 supplementation reduced major cardiovascular events by:
    • 19% in patients with low fish intake.
  • When they looked at the effect of omega-3s on the risk of different forms of heart disease, they found that omega-3 supplementation reduced:
    • Heart attacks by 28% in the general population and by 70% for African Americans.
    • Deaths from heart attacks by 50%.
    • Deaths from coronary heart disease (primarily heart attacks and ischemic strokes (strokes caused by blood clots)) by 24%.

In other words, when they asked the wrong questions, they got the wrong answer. If they had just looked at the effect of omega-3 supplementation on all forms of heart disease for everyone (like most other omega-3 studies), they would have concluded that omega-3s are worthless.

However, when they asked the right questions, they found that omega-3s were very beneficial for high-risk populations and for certain types of heart disease.

The current study utilized the same data to analyze the effect of omega-3 supplementation on hospitalizations due to congestive heart failure. And the results were similar.

If they had asked the wrong question, “Does omega-3 supplementation reduce congestive heart failure hospitalizations for everyone?”, they would have concluded that omega-3 supplementation was worthless.

However, instead they asked, “Does omega-3 supplementation reduce congestive heart failure hospitalizations for certain high-risk groups” and were able to show that omega-3 supplementation significantly reduced congestive heart failure hospitalizations for people with type 2 diabetes and for Blacks.

We need to change the paradigm for clinical studies of supplements. The old paradigm asks the wrong questions. If we really want to know the role of supplementation for our health, we need to start asking the right questions.

The Bottom Line

There is perhaps nothing more confusing to the average person than the “truth” about omega-3 supplementation and heart disease risk. Much of the confusion is because we have been asking the wrong questions:

  • We have been asking whether omega-3 supplementation reduces the risk of heart disease for everyone. Instead, we should have been asking who benefits from omega-3 supplementation.
  • We have been asking whether omega-3 supplementation reduces the risk of all forms of heart disease combined. Instead, we should have been asking whether omega-3 supplementation reduces the risk of specific kinds of heart disease.

A recent study on the effect of omega-3 supplementation on hospitalizations due to heart disease is a perfect example.

If they had asked the wrong question, “Does omega-3 supplementation reduce congestive heart failure hospitalizations for everyone?”, they would have concluded that omega-3 supplementation was worthless.

However, instead they asked, “Does omega-3 supplementation reduce congestive heart failure hospitalizations for certain high-risk groups” and were able to show that omega-3 supplementation significantly reduced congestive heart failure hospitalizations for people with type 2 diabetes and for Blacks.

We need to change the paradigm for clinical studies of supplements. The old paradigm asks the wrong questions. If we really want to know the role of supplementation for our health, we need to start asking the right questions.

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.

Health Tips From The Professor