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.

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Comments (7)

  • EROCA

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    A share button would make it easier to show others.

    Reply

    • Dr. Steve Chaney

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      Dear Eroca,

      Good idea, but not sure how to make that happen. I will have to check with my IT guru.

      Dr. Chaney

      Reply

  • Joann Miley

    |

    This information really told the truth about omega 3’s and I totally feel that was the best explanation I have ever read.

    I sincerely thank you for your expertise and sharing this valuable information to us. I firmly believe the omega 3’s have been a benefit to me. Thank you, Keep up your excellent work.
    Joann Miley

    Reply

  • Joann Miley

    |

    thank you

    Reply

  • William Byrne

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    GREAT N/L information….all good stuff to keep us healthy and going. personally I love our “heart healthy” products…..especially now at almost 80, indeed I need a strong heart….one that can carry me through an intense match of tennis….one that can sustain my interest and need to exercise…or just a heart strong enough to take on the daily stresses of life in general. So yes…I LOVE THE OMEGAS as well as any Shaklee preparations related to HEART HEALTH.

    Reply

  • William Byrne

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    THE OMEGAS…WHY A LL THE CONTROVERSY??? ITS PROVEN ISN’T IT? INDEED QUALITY.. AND .HARVESTING OF THE CLEAN FISH ALL PLAY AN IMPORTANT ROLE IN RESULTS (OR NOT) WE RECEIVE FROM SUPPLEMENTING OUR DIET WITH FISH OIL. PERSONALLY I AM ALL FOR IT ESPECIALLY WHEN MY DOCTOR SAYS I AM IN GOOD SHAPE AND THAT I MAKE GOOD BLOOD. A LARGE PART, I BELIEVE, DUE TO CONSISTENCY BOTH WITH STRENGTH / AEROBIC EXERCISE AS WELL AS TAKING A GOOD QUALITY PURE OMEGA 3
    FOR MANY YEARS. RARELY MISSING MY OPPORTUNITY TO CONTINUE TO BUILD NEW HEART HEALTH. EVEN AT THE RIPE OLD AGE OF 79.

    Reply

    • Dr. Steve Chaney

      |

      Dear William,

      Yes. Omega-3s are part of the puzzle, but so is exercise and a good diet. Keep up the good work!

      Dr. Chaney

      Reply

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Latest Article

Does Magnesium Optimize Vitamin D Levels?

Posted February 12, 2019 by Dr. Steve Chaney

The Case For Holistic Supplementation

Author: Dr. Stephen Chaney

 

Does magnesium optimize vitamin D levels?

magnesium optimize vitamin dOne of the great mysteries about vitamin D is the lack of correlation between vitamin D intake and blood levels of its active metabolite, 25-hydroxyvitamin D. Many people who consume RDA levels of vitamin D from foods and/or supplements end up with low blood levels of 25-hydroxyvitamin D. The reason(s) for this discrepancy between intake of vitamin D and blood levels of its active metabolite are not currently understood.

Another great mystery is why it has been so difficult to demonstrate benefits of vitamin D supplementation. Association studies show a strong correlation between optimal 25-hydroxyvitamin D levels and reduced risk of heart disease, cancer, and other diseases. However, placebo-controlled clinical trials of vitamin D supplementation have often come up empty. Until recently, many of those studies did not measure 25-hydroxyvitamin D levels. Could it be that optimal levels of 25-hydroxyvitamin D were not achieved?

The authors of the current study hypothesized that optimal magnesium status might be required for vitamin D conversion to its active form. You are probably wondering why magnesium would influence vitamin D metabolism. I had the same question.

The authors pointed out that:

  • Magnesium status affects the activities of enzymes involved in both the synthesis and degradation of 25-hydroxyvitamin D.
  • Some clinical studies have suggested that magnesium intake interacts with vitamin D intake in affecting health outcomes.
  • If the author’s hypothesis is correct, it is a concern because magnesium deficiency is prevalent in this country. In their “Fact Sheet For Health Professionals,” the NIH states that “…a majority of Americans of all ages ingest less magnesium from food than their respective EARs [Estimated Average Requirement]; adult men aged 71 years and older and adolescent females are most likely to have low intakes.” Other sources have indicated that magnesium deficiency may approach 70-80% for adults over 70.

If the author’s hypothesis that magnesium is required for vitamin D activation is correct and most Americans are deficient in magnesium, this raises some troubling questions.

  • Most vitamin D supplements do not contain magnesium. If people aren’t getting supplemental magnesium from another source, they may not be optimally utilizing the vitamin D in the supplements.
  • Most clinical studies involving vitamin D do not also include magnesium. If most of the study participants are deficient in magnesium, it might explain why it has been so difficult to show benefits from vitamin D supplementation.

Thus the authors devised a study (Q Dai et al, American Journal of Clinical Nutrition, 108: 1249-1258, 2018 ) to directly test their hypothesis.

 

How Was The Study Designed?

magnesium optimize vitamin d studyThe authors recruited 180 volunteers, aged 40-85, from an ongoing study on the prevention of colon cancer being conducted at Vanderbilt University. The duration of the study was 12 weeks. Blood was drawn at the beginning of the study to measure baseline 25-hydroxyvitamin D levels. Three additional blood draws to determine 25-hydroxyvitamin D levels were performed at weeks 1, 6, and 12.

Because high blood calcium levels increase excretion of magnesium, the authors individualized magnesium intake based on “optimizing” the calcium to magnesium ratio in the diet rather than giving everyone the same amount of magnesium. The dietary calcium to magnesium ratio for most Americans is 2.6 to 1 or higher. Based on their previous work, they considered an “ideal” calcium to magnesium ratio to be 2.3 to 1. The mean daily dose of magnesium supplementation in this study was 205 mg, with a range from 77 to 390 mg to achieve the “ideal” calcium to magnesium ratio. The placebo was an identical gel capsule containing microcrystalline cellulose.

Two 24-hour dietary recalls were conducted at baseline to determine baseline dietary intake of calcium and magnesium. Four additional 24-hour dietary recalls were performed during the 12-week study to assure that calcium intake was unchanged and the calcium to magnesium ratio of 2.3 to 1 was achieved.

In short this was a small study, but it was very well designed to test the author’s hypothesis.

 

Does Magnesium Optimize Vitamin D Levels?

 

does magnesium optimize vitamin d levelsThis was a very complex study, so I am simplifying it for this discussion. For full details, I refer you to the journal article (Q Dai et al, American Journal of Clinical Nutrition, 108: 1249-1258, 2018).

The most significant finding was that magnesium supplementation did affect blood levels of 25-hydroxyvitamin D. However, the effect of magnesium supplementation varied depending on the baseline 25-hydroxyvitamin D level at the beginning of the study.

  • When the baseline 25-hydroxyvitamin D was 20 ng/ml or less (which the NIH considers inadequate), magnesium supplementation had no effect on 25-hydroxyvitamin D levels.
  • When the baseline 25-hydroxyvitamin D was 20-30 ng/ml (which the NIH considers the lower end of the adequate range), magnesium supplementation increased 25-hydroxyvitamin D levels.
  • When the baseline 25-hydroxyvitamin D level approached 50 ng/ml (which the NIH says may be “associated with adverse effects”), magnesium supplementation lowered 25-hydroxyvitamin D levels.

The simplest interpretation of these results is:

  • When vitamin D intake is inadequate, magnesium cannot magically create 25-hydroxyvitamin D from thin air.
  • When vitamin D intake is adequate, magnesium can enhance the conversion of vitamin D to 25-hydroxyvitamin D.
  • When vitamin D intake is too high, magnesium can help protect you by lowering 25-hydroxyvitamin D levels.

The authors concluded: “Our findings suggest that optimal magnesium status may be important for optimizing 25-hydroxyvitamin D status. Further dosing studies are warranted…”

 

What Does This Study Mean For You?

magnesium optimize vitamin d for youThis was a groundbreaking study that has provided novel and interesting results.

  • It provides the first evidence that optimal magnesium status may be required for optimizing the conversion of vitamin D to 25-hydroxyvitamin D.
  • It suggests that optimal magnesium status can help normalize 25-hydroxyvitamin D levels by increasing low levels and decreasing high levels.

However, this was a small study and, like any groundbreaking study, has significant limitations. For a complete discussion of the limitations and strengths of this study I refer you to the editorial (S Lin and Q Liu, American Journal of Clinical Nutrition, 108: 1159-1161, 2018) that accompanied the study.

In summary, this study needs to be replicated by larger clinical studies with a more diverse study population. In order to provide meaningful results, those studies would need to carefully control and monitor calcium, magnesium, and vitamin D intake. There is also a need for mechanistic studies to better understand how magnesium can both increase low 25-hydroxyvitamin D levels and decrease high 25-hydroxyvitamin D levels.

However, assuming the conclusions of this study to be true, it has some interesting implications:

  • If you are taking a vitamin D supplement, you should probably make sure that you are also getting the DV (400 mg) of magnesium from diet plus supplementation.
  • If you are taking a calcium supplement, you should check that it also provides a significant amount of magnesium. If not, change supplements or make sure that you get the DV for magnesium elsewhere.
  • I am suggesting that you shoot for the DV (400 mg) of magnesium rather than reading every label and calculating the calcium to magnesium ratio. The “ideal” ratio of 2.3 to 1 is hypothetical at this point. A supplement providing the DV of both calcium and magnesium would have a calcium to magnesium ratio of 2.5, and I would not fault any manufacturer for providing you with the DV of both nutrients.
  • If you are taking high amounts of calcium, I would recommend a supplement that has a calcium to magnesium ratio of 2.5 or less.
  • If you are considering a magnesium supplement to optimize your magnesium status, you should be aware that magnesium can cause gas, bloating, and diarrhea. I would recommend a sustained release magnesium supplement.
  • Finally, whole grains and legumes are among your best dietary sources of magnesium. Forget those diets that tell you to eliminate whole food groups. They are likely to leave you magnesium-deficient.

Even if the conclusions of this study are not confirmed by subsequent studies, we need to remember that magnesium is an essential nutrient with many health benefits and that most Americans do not get enough magnesium in their diet. The recommendations I have made for optimizing magnesium status are common-sense recommendations that apply to all of us.

 

The Case For Holistic Supplementation

 

magnesium optimize vitamin d case for holistic supplementationThis study is one of many examples showing that a holistic approach to supplementation is superior to a “magic bullet” approach where you take individual nutrients to solve individual problems. For example, in the case of magnesium and vitamin D:

  • If you asked most nutrition experts and supplement manufacturers whether it is important to provide magnesium along with vitamin D, their answer would likely be “No”. Even if they are focused on bone health, they would be more likely to recommend calcium along with vitamin D than magnesium along with vitamin D.
  • If your doctor has tested your 25-hydroxyvitamin D levels and recommended a vitamin D supplement, chances are they didn’t also recommend that you optimize your magnesium status.
  • Clinical studies investigating the benefits of vitamin D supplementation never ask whether magnesium intake is optimal.

That’s because most doctors and nutrition experts still think of nutrients as “magic bullets.” I cover holistic supplementation in detail in my book “Slaying The Supplement Myths.”  Other examples that make a case for holistic supplementation that I cover in my book include:

  • A study showing that omega-3 fatty acids and B vitamins may work together to prevent cognitive decline. Unfortunately, most studies looking at the effect of B vitamins on cognitive decline have not considered omega-3 status and vice versa. No wonder those studies have produced inconsistent results.
  • Studies looking at the effect of calcium supplementation on loss of bone density in the elderly have often failed to include vitamin D, magnesium, and other nutrients that are needed for building healthy bone. They have also failed to include exercise, which is essential for building healthy bone. No wonder some of those studies have failed to find an effect of calcium supplementation on bone density.
  • A study reported that selenium and vitamin E by themselves might increase prostate cancer risk. Those were the headlines you might have seen. The same study showed Vitamin E and selenium together did not increase prostate cancer risk. Somehow that part of the study was never mentioned.
  • A study reported that high levels of individual B vitamins increased mortality slightly. Those were the headlines you might have seen. The same study showed that when the same B vitamins were combined in a B complex supplement, mortality decreased. Somehow that observation never made the headlines.
  • A 20-year study reported that a holistic approach to supplementation produced significantly better health outcomes.

In summary, vitamins and minerals interact with each other to produce health benefits in our bodies. Some of those interactions we know about. Others we are still learning about. When we take high doses of individual vitamins and minerals, we create potential problems.

  • We may not get the full benefit of the vitamin or mineral we are taking because some other important nutrient(s) may be missing from our diet.
  • Even worse, high doses of one vitamin or mineral may interfere with the absorption or enhance the excretion of another vitamin or mineral. That can create deficiencies.

The same principles apply to our diet. I mentioned earlier that whole grains and legumes are among the best dietary sources of magnesium. Eliminating those two foods from the diet increases our risk of becoming magnesium deficient. And, that’s just the tip of the iceberg. Any time you eliminate foods or food groups from the diet, you run the risk of creating deficiencies of nutrients, phytonutrients, specific types of fiber, and the healthy gut bacteria that use that fiber as their preferred food source.

The Bottom Line

 

A recent study suggests that optimal magnesium status may be important for optimizing 25-hydroxyvitamin D status. This is one of many examples showing that a holistic approach to supplementation is superior to a “magic bullet” approach where you take individual nutrients to solve individual problems. For example, in the case of magnesium and vitamin D:

  • If you asked most nutrition experts and supplement manufacturers whether it is important to provide magnesium along with vitamin D, their answer would likely be “No.”  Even if they are focused on bone health, they would be more likely to recommend calcium along with vitamin D than magnesium along with vitamin D.
  • If your doctor has tested your 25-hydroxyvitamin D levels and recommended a vitamin D supplement, chances are he or she did not also recommend that you optimize your magnesium status.
  • Clinical studies investigating the benefits of vitamin D supplementation never ask whether magnesium intake is optimal. That may be why so many of those studies have failed to find any benefit of vitamin D supplementation.

I cover holistic supplementation in detail in my book “Slaying The Supplement Myths” and provide several other examples where a holistic approach to supplementation is superior to taking individual supplements.

In summary, vitamins and minerals interact with each other to produce health benefits in our bodies. Some of those interactions we know about. Others we are still learning about. Whenever we take high doses of individual vitamins and minerals, we create potential problems.

  • We may not get the full benefit of the vitamin or mineral we are taking because some other important nutrient(s) may be missing from our diet.
  • Even worse, high doses of one vitamin or mineral may interfere with the absorption or enhance the excretion of another vitamin or mineral. That can create deficiencies.

The same principles apply to what we eat. For example, whole grains and legumes are among the best dietary sources of magnesium. Eliminating those two foods from the diet increases our risk of becoming magnesium deficient. And, that’s just the tip of the iceberg. Any time you eliminate foods or food groups from the diet, you run the risk of creating deficiencies.

For more details about the current study and what it means to 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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