Does Carnitine Increase Heart Disease Risk?

Written by Dr. Steve Chaney on . Posted in Food and Health, Issues, Supplements and Health

Carnitine: Dr. Jekyl or Mr. Hyde?

Author: Dr. Stephen Chaney

Heart HealthIt’s both interesting and confusing when one Journal article appears talking about the dangers of a particular supplement and just a couple of weeks later another article appears talking about the benefits of that same supplement – especially when the conclusions of both articles are misrepresented in the media.

But that’s exactly what has just occurred with the supplement L-carnitine. Media reports of the first article trumpeted the headline “Cleveland Clinic study links L-carnitine to increased risk of heart disease”. Media reports of the second article featured the headline “Mayo Clinic review links L-carnitine to multiple health heart benefits”. As you might suspect, neither headline was completely accurate. So let me help you sort out the confusion about L-carnitine and heart health

What is Carnitine?

But first let me give you a little bit of background about L-carnitine. L-Carnitine is an essential part of the transport system that allows fatty acids to enter the mitochondria where they can be oxidized and generate energy. So it is an essential nutrient for any cell that has mitochondria and utilizes fatty acids as an energy source.

L-carnitine is particularly important for muscle cells, and the hardest working muscle cells in our body are those that pump blood through our hearts. So when we think of L-carnitine we should think of heart health first.

But that doesn’t mean that L-carnitine is an essential nutrient. In fact, our bodies generally make all of the L-carnitine that we need. There are some metabolic diseases that can prevent us from making L-carnitine or utilizing L-carnitine efficiently. People with those diseases benefit from L-carnitine supplementation, but those diseases are exceedingly rare.

There is some evidence that supplemental L-carnitine may be of benefit in individuals suffering from congestive heart failure and other diseases characterized by weakened heart muscles. Other than that there is little evidence that supplemental L-carnitine is beneficial for healthy individuals.

Does Carnitine Increase Heart Disease Risk?

fatty steakLet’s look at the first study (Koeth et al, Nature Medicine, doi:10.1038/nm.3145, April 7, 2013) – the one that purportedly linked L-carnitine to increase risk of heart disease. The authors were trying to gain a better understanding of the well-established link between red meat consumption and cardiovascular disease risk. The classical explanation of this link has been the saturated fat and cholesterol content of the red meat.

However, several recent studies have questioned whether saturated fat and cholesterol actually increase the risk of cardiovascular disease (see last week’s article “Are Saturated Fats Good For You?”)

Since red meat is also high in L-carnitine, the authors hypothesized that it might be the L-carnitine or a metabolite of the L-carnitine that was associated with increased risk of heart disease in people consuming red meat.

The authors honed in on a metabolite of L-carnitine called trimethylamine-N-oxide or TMAO that is produced by bacteria in the intestine and had been previously shown to accelerate atherosclerosis in mice. They developed what they called an L-carnitine challenge. Basically, they gave their subjects an 8 ounce sirloin steak, which contains about 180 mg of L-carnitine, and measured levels of L-carnitine and TMAO in the blood one hour later and the urine 24 hours later. [I’m guessing they didn’t have much trouble finding volunteers for that study.]

When the subjects were omnivores (meaning meat eaters) they found a significant increase in both L-carnitine and TMAO in their blood and urine following the L-carnitine challenge. When they put the same subjects on broad-spectrum antibiotics for a week to wipe out their intestinal bacteria and repeated the L-carnitine challenge, they found an increase in L-carnitine but no increase in TMAO. This simply confirmed that the intestinal bacteria were required for the conversion of L-carnitine to TMAO.

Finally, because previous studies have shown that omnivores and vegetarians have very different populations of intestinal bacteria, they repeated their L-carnitine challenge in a group of vegans and found that consumption of the same 8 ounce sirloin steak by the vegans did not result in any significant increase in TMAO in either their blood or urine.

Armed with this information, the authors measured L-carnitine and TMAO concentrations in the fasting blood of 2595 patients undergoing cardiac evaluation in the Cleveland Clinic. They used an established protocol to assess the three-year risk for major adverse cardiac events in the patients they examined. They observed a significant association between L-carnitine levels and cardiovascular event risks, but only in subjects who also had high blood levels of TMAO.

Now it’s time to compare what the headlines said to what the study actually showed. The headlines said “L-carnitine linked to increased risk of heart disease”. What the study actually showed was that there were two things that were required to increase the risk of heart disease – L-carnitine and a population of intestinal bacteria that converted the L-carnitine to TMAO.

The major source of L-carnitine in the American diet is red meat, and habitual red meat consumption is required to support a population of intestinal bacteria that is capable of converting L-carnitine to TMAO. So the headlines should have read “red meat consumption linked to increased risk of heart disease”. But, of course, that’s old news. It doesn’t sell subscriptions.

Does Carnitine Decrease Heart Disease Risk?

Heart AttackThe second study (DiNicolantonio et al, Mayo Clinic Proceedings, dx.doi.org/10.1016/j.mayocp.2013.02.007) was a meta-analysis. It reviewed 13 clinical studies involving 3629 people who had already had heart attacks and were given L-carnitine or a placebo after the heart attack.

In evaluating the results of this study it is useful to remember that a heart attack generally kills some of the heart muscle and weakens some of the surviving heart muscle. When the data from all of the studies was combined the authors reported a 27% reduction in all cause mortality, a 65% reduction in arrhythmias, and a 40% reduction in angina. However, there was no reduction in a second heart attack or the development of heart failure.

So perhaps the headlines describing this study were a little closer to being on target, but they failed to mention that these effects were only seen in people who had already suffered a heart attack and had weakened heart muscles. They also failed to mention that there was no decreased risk of a second heart attack or congestive heart failure.

The Bottom Line:

1)     The first study should be considered preliminary. It needs to be confirmed by other studies. If it is true, it is not ground breaking. It merely gives us a fuller understanding of why red meat consumption may be linked to increased risk of heart disease and gives you yet another reason to minimize red meat consumption.

The study does raise the possibility that use of L-carnitine supplements may increase your risk of heart disease if you eat red meat on a regular basis, and that this same risk may not be associated with L-carnitine supplementation if you are a vegan. But the study did not directly test that hypothesis, and much more research is required before I would give it any weight.

2)     The second study suggests that if you have already had a heart attack, you may want to consult with your physician about whether L-carnitine supplementation might be of benefit. Once again, this study is not ground breaking. We already knew that L-carnitine supplementation was helpful for people with weakened heart muscle. This study merely confirmed that.

Contrary to what the headlines suggested, this study provides no guidance about whether L-carnitine supplementation has any heart health benefits in people without pre-existing heart disease – and the bulk of existing literature suggests that it does not.

3)     Finally, I realize that the major use of L-carnitine in the US market is in sports supplements purported to increase strength and endurance. The literature on that is decidedly mixed, but that’s another subject for another time.

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.

Tags: , , ,

Trackback from your site.

Comments (2)

  • Linda Dietz

    |

    Thank you once again for clearing up the confusing messages we receive from the press-usually on slow news days! Then hearing from the expert doctors on these shows further confuses the issues.

    Your well written and clear articles are such a blessing to us — so helpful to have your articles to send when someone has questions we can’t answer as well as you.

    Reply

Leave a comment

Recent Videos From Dr. Steve Chaney

READ THE ARTICLE
READ THE ARTICLE

Latest Article

The Truth About Vitamin D

Posted December 11, 2018 by Dr. Steve Chaney

Does Vitamin D Reduce Risk Of Heart Disease & Cancer?

Author: Dr. Stephen Chaney

 

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

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

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

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

How Was The Study Designed?

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

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

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

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

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

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

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

Does Vitamin D Reduce The Risk Of Cancer?

 

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

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

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

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

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

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

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

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

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

 

Does Vitamin D Reduce The Risk Of Heart Disease?

 

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

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

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

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

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

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

 

What Is The Truth About Vitamin D?

 

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

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

What Does This Study Mean For You?

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

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

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

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

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

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

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

 

The Bottom Line

 

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

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

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

 

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

 

UA-43257393-1