In the past weeks, two important papers have been published which were intended to advance the understanding of the role of carnitine in human health (or disease). The one, which appears to suggest carnitine is potentially harmful, you might already know about; the other, which shows the repeated benefit of carnitine, you may not have heard about (yet). We will attempt to synthesize the information in these two papers (along with some background information) to see if we can come to a reasonable understanding of the role of carnitine as a dietary supplement. A brief “Final Point” can be found at the end.

First of all, for those less familiar with carnitine; it is an amino acid-like compound which our bodies can synthesize from the amino acids lysine and methionine. Natural sources of carnitine come primarily from red meat and dairy, although lesser amounts can be found in a variety of foods such as fish, nuts, tempeh and avocados.  Its main biological function is to help transport acyl-groups from fatty acids into mitochondria where they can be used as energy for the cell (via beta-oxidation).  As a dietary supplement, L-carnitine has been used primarily for heart conditions, male fertility, sperm health, weight loss and energy.

The first paper we will discuss was published in Nature Medicine from the prestigious group at the Cleveland Clinic. This was an ambitious project and paper- covering a wide range of experiments in both human and animal subjects. The title itself is a bit provocative: “Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis”, immediately tying this research with red meat consumption and risk for heart disease. Needless to say it has set off a number of debates- some of which I will point you to throughout the rest of this brief discussion.

What they reported was essentially that certain bacteria in our gut can convert carnitine (and other compounds) into a molecule called TMA (trimethylamine), which can be further converted by our liver to TMAO (trimethylamine oxide). TMAO has been shown in other studies to increase the risk for atherosclerosis. Further, they found that in vegetarians (at least those they tested) conversion of carnitine (from beef or supplements) was not converted to TMA because the bacteria required for the conversion are not abundant enough to allow for this conversion. No TMA- no conversion to TMAO- and therefore a reduced atherosclerotic risk (-or so the logic is assumed). They also showed that in a large number of patients coming in for voluntary cardiac evaluation- those with the highest levels of blood carnitine had a higher calculated risk for certain cardiovascular events. The researchers also conducted several studies in mice which were fed carnitine and they found consistent changes in the gut microbiota- allowing for selectively more carnitine to TMA conversion.

The paper, at first, seems to be airtight and quite convincing; until you really begin to look at the details of each experiment and the broader question of the role of TMAO in the diet. Since there is an extremely detailed discussion of these issues and critiques of this paper at the Weston Price Foundation Website online (not for the scientific faint of heart), I will just give you the gist of it here.

  • To focus on “red meat” and carnitine in particular as notable substrates for the generation of TMAO in humans is odd when previous studies have shown that serum TMAO is much higher in subjects after the consumption of numerous vegetable and greatly increased (up to 100X) when consuming certain types of seafood. The authors even say “An analyte with identical molecular weight and retention time to L-carnitine was not in the top tier of analytes that met the stringent P value cutoff for association with CVD. However, a hypothesis-driven examination of the data using less stringent criteria (no adjustment for multiple testing) revealed an analyte with the appropriate molecular weight and retention time for L-carnitine that was associated with cardiovascular event risk (P=0.04).”[emphasis added] One might ask why their hypothesis-driven examination focused on a relatively low TMAO inducing agent with no association with CVD which happens to be in red meat.
  • Much of the data between vegetarian and omnivore subjects were dependent on few, and in some cases, single individuals. Apparently convincing vegetarians to consume meat was more challenging than they initially figured. Some of this data is, at best, hypothesis generating- but is far from conclusive. These issues are further complicated since the gender of the vegetarian and the omnivore were different and there is known sex-based differences in the enzyme activities which form TMAO in humans. Since diet is very important to the formation of the human gut bacteria environment, I don’t doubt there may be significant differences in the microbiota between vegetarians and omnivores/carnivores- even in their ability to convert carnitine into TMA. It may also be that other beneficial compounds made by these same organisms would be absent or diminished in vegetarians- limiting other benefits derived from carnitine.
  • The mouse studies, again, are very interesting and should be the basis of future studies but the ability to translate these results to humans is very tenuous at best. By anyone’s calculations, the amount of carnitine given to these mice greatly exceeds the doses which could be consumed by humans eating meat or by supplementation. Likewise, the changes in microbiota in mice which resulted from carnitine consumption is difficult to contextualize since as the authors tell us “Notably, a direct comparison of taxa associated with plasma TMAO concentrations in humans versus in mice failed to identify common taxa. These results are consistent with prior reports that microbes identified from the distal gut of the mouse represent genera that are typically not detected in humans” I am guessing we will see follow-up studies in humans.
  • Finally, the authors report two relationships between blood carnitine levels and risk for cardiovascular disease. In one data set- they report that the predicted risk is higher at the highest blood level of carnitine; however when they actually correlated fasting carnitine levels with known major adverse cardiac events over a 3-year period (adjusted for comorbidities and traditional risk factors) there was no increased incidence of events (see discussion on Mayo Clinic paper below).

Again- further details on these and other finer points can be found at the Weston Price Foundation’s online discussion of this paper for those interested. The Cleveland Clinic group has certainly illuminated us on the role of intestinal microbiota in the conversion of food substances and potential health outcomes (this is likely to be a huge area of future research on bioactives in food and supplement in the next decade) – but this data is not sufficient yet to demonstrate that red meat or the carnitine it delivers contributes to the risk of heart disease in humans.

Now, on to the second big carnitine paper from last week (the one you may not have heard about yet). This paper was published in the Mayo Clinic Proceedings and is a systematic review and meta-analysis of a number of clinical trials published since the mid-1980’s using L-carnitine as a supplement. Specifically, since myocardial carnitine levels are quickly diminished during ischemic events (like an MI), they looked at only those studies which used L-carnitine supplements (compared to placebo) in individuals with a previous acute myocardial infarction (AMI). The studies that met their criteria looked at outcomes like all-cause mortality, ventricular arrhythmias, myocardial reinfarction, heart failure or angina. In all, 13 studies met there criteria for evaluation which included 3629 patients. In their statistical analysis, L-carnitine consumption was associated with a 27% reduction in all-cause mortality, a 65% reduction in ventricular arrhythmias, and a 40% reduction in angina symptoms compared to placebo in these post-AMI patients. A non-statistical trend toward reduced risk was seen with both heart failure and myocardial reinfarction.

As anyone who has reviewed meta-analysis data can tell you, these types of analysis are far from definitive evidence for (or against) a particular therapy. Different doses were used, different routes of administration and slightly different outcomes measured always makes the pooling of data from experiments performed over several decades for statistical analysis less than perfect; this study is no exception. Also, like many other dietary supplement trials-many of those selected for this meta-analysis were small trials.

Individually, while many of these studies did not reach statistical significance for some of the outcome measurements, in nearly every case, the benefit clearly favored carnitine over the placebo. Pooling the data increases the statistical significance, but it did not change the clear benefit from these studies. In fact, only one measurement in a single study (a 1995 study looking at reinfarction) showed a benefit for the placebo group (albeit non-statistical) which was enough to prevent the overall benefit in the pooled data for this measurement.

As always they suggest (and we agree) that more studies (larger, better) be performed to assess the role of L-carnitine as a supplement for post-AMI patients (and other cardiovascular outcomes). What we can say from these data is there appears to be no harm in using L-carnitine in patients for secondary prevention of cardiovascular disease- and a strong likelihood of benefit. Certainly, future studies will likely address TMAO production in light of the Cleveland Clinic study above. It may be possible to discover a relationship between certain intestinal microbiota which enhance or diminish the use of L-carnitine as a bioactive agent.

While I don’t have time to add more here- check these recent papers for more about the use of carnitine (as a supplement):

Final Point: Q&A

Q: Should we avoid or limit the use of L-carnitine in foods or supplements in order to avoid the potential risk for cardiovascular disease?

A: There is no evidence that avoiding carnitine will reduce CVD. If we are convinced that the formation of TMAO is a leading cause of atherosclerosis (I’m not yet), the conversion from carnitine to TMAO is a minor contributor even at extremely high supplemental (or dietary) levels; furthermore, individuals with cardiovascular disease appear (from the Mayo Clinic paper) to be protected from secondary events when using supplemental carnitine; a finding which shows that higher doses are more protective.

Q: Is Red Meat Bad for your health?

A: This is a much bigger topic than we can cover here and, of course, very controversial. Our position is that the majority of the risks associated with meat can be attributed to processed meat consumption, certain cooking methods for meat (frying, charring etc.) and the fact that many people who eat meat also have a wide-range of poor eating patterns (low fruit and vegetable consumption, low consumption of good fats, increased use of potatoes, breads and refined sugars etc.). Within the background of a prudent diet (like the Mediterranean diet), red meat, poultry and fish should not increase risk for chronic disease.

Q: Are there probiotics that can be taken which will reduce/eliminate the conversion of carnitine or other substances to TMA in our GI tract?

A: We don’t know yet. Certainly this type of research will be conducted in the future as the role of probiotics in a wide-range of health conditions are being explored. My guess is that we will, over the next decade or so, find specific blends of probiotics which may sufficiently modulate the GI microbiota to compensate for many disease-related conditions.

 [Image courtesy of piyato /]

Probiotics foods have been enjoyed for centuries, and recently more and more research has been confirming the many health benefits that the billions of friendly bacteria in our guts impart, as well as the role they play in treating gastrointestinal diseases. Since IBD is the result of an unbalanced gut microbiome, health practitioners are increasingly using probiotics as part of treatment protocols for Crohn’s and Colitis – in an effort to rebalance gut flora and help reduce the damaging inflammatory process characteristic of these disease.

According to a new study on childhood obesity, when it comes to the size of kids’ lunch plate, size does matter. Among 2nd graders who served themselves lunch, those using bigger plates served themselves approximately 90 calories more on average than those using the smaller plates and bowls, about 80% of the time. The kids served themselves an average 239 calories more on days when offered a one piece food, such as nuggets for lunch, rather than a shapeless meal like pasta. Since it is generally recommended that children serve themselves at mealtimes, researchers suggested that using smaller dishware at home may be a good strategy to achieve more appropriate kid-portion sizes.

Proponents of eating organic now have the results of a new study to support the health benefits associated with their preference for chemical free produce. In the study of fruit flies, those fed extracts of organically grown vegetables were found to have longer lifespans and better fertility than those fed conventionally grown produce.

A few important comments about this study; first, this was a study using fruit flies. Keep in mind that because their life cycle is so short, the accumulated benefits are seen much sooner. So the subtle benefit of added nutrition or the lack of life-sapping chemicals occurs within the time frame of these types of experiments. I believe many of the same benefits occur in humans- but they are difficult to measure with so many other variables over a lifetime. (I should also add that if you frequently keep organic produce sitting on your counter- you might have a swarm of fruit flies in a few days!) – TGG.

Your chances of death may depend on the county you live in, according to a new National Survey, but the reasons for the startling findings boil down to lifestyle factors. Healthy eating habits, smoking, and the environment, including quality of local parks and water were all key components of the ratings. Some of the worst scoring counties in the Survey included: Lake in CA, New Haven in CT, Baltimore City in MD and Menominee in WI – check out the article to see how your county scored!


For many years, the relationship between serum vitamin D levels and Parkinson’s disease (PD) has been studied. For instance, in a long-term cohort study, PD incidence was 3 times higher in persons with the lowest serum vitamin D concentration (lowest quartile vs. highest quartile). Along with other neurological disorders, the particular functions of vitamin D seem to play a role in the protection against PD (for further details- see links at the bottom of this article). The obvious question for the clinician and patient is simple: will supplementing vitamin D change the outcome or have clinically meaningful benefits when given to a patient with PD?

Well, just a few weeks ago, such an experiment was published in the American Journal of Clinical Nutrition. The study was conducted in Japan where patients with PD were given either vitamin D3 or placebo for 12 months. The dose they used was 1,200 IU vitamin D3 per day and all patients were also on the drug Levadopa. The researchers used two different rating scales to determine the changes in the severity of PD over the 12 month trial period. As you would expect, patients given vitamin D saw a great improvement in their serum vitamin D levels (48% were considered deficient at baseline).

When the patients were tested for changes (from baseline) in their PD assessment, those given vitamin D saw no change or even a slight improvement, while those given placebo saw a significant deterioration of their PD condition. They also looked at the effect of vitamin D and placebo based on a specific variant of the vitamin D receptor (VDR) gene known to influence PD. Those patients with the gene variant that makes them more vulnerable to vitamin D-related issues (in this case the TT variant of the FokI allele) had a much more robust response to the vitamin D supplementation than patients with the other variants (CT, CC). Since vitamin D is already known to improve balance and muscle strength, the authors cannot be absolutely positive that all the measured benefits were neurological in nature, but since they are influenced by genetic variations in the vitamin D receptor- we can be fairly certain these changes are related to the supplementation of vitamin D. There were no safety issues and no apparent increase in hypercalcemia at these doses.

Since 1,200 IU (or more) of vitamin D3 is safe in nearly every patient. We believe that every patient, regardless of their PD status, should be tested for their serum D levels and supplemented with adequate levels of vitamin D3. This data should compel physicians with PD patients, to be even more urgent in those patients.

Check out our general Vitamin D recommendations in our White paper Section

Links to additional articles:

After the 10 year trial that most thought (and many hoped) would result in the debunking of IV Chelation therapy for cardiovascular disease, JAMA has published the initial results of The Trial to Assess Chelation Therapy (TACT). The publication is free to download here.

The primary end point was a composite of death from any cause, reinfarction, stroke, coronary revascularization, or hospitalization for angina. The composite of cardiovascular death, reinfarction, or stroke was a pre-specified secondary end point. TACT was a “2×2” factorial trial where patients received 40 weekly infusions of EDTA or placebo and a high dose vitamin and mineral supplement or placebo. Because of the unique challenges created by recruiting patients for the trial, the normal p=value for statistical significance of <0.05 was dropped to a p<0.036 (a more stringent level of statistical significance). The 5-year estimate of reaching the primary end point shows that those given the EDTA chelation had a 18% lower risk (Hazard Ratio 0.82) which met the stringent level of statistical significance (p=0.035). The expectant lukewarm conclusion by authors was that the therapy “modestly reduced the risk of adverse cardiovascular outcomes, many of which were revascularization procedures. These results provide evidence to guide further research but are not sufficient to support the routine use of chelation therapy for treatment of patients who have had an MI.”

It should be mentioned that in the sub-group analysis, they saw much greater benefits in patients with diabetes (risk reduction of 39%, p=0.002) or with previous anterior MI (risk reduction of 37%, p=0.003) when given EDTA.

Not only did JAMA publish this paper, they published an interesting editorial to accompany its publication. While the typical editorial discusses the implications of new data or some clinical perspective regarding the publication, this editorial basically apologized to the JAMA reader for even publishing the TACT trial at all. After all, they are concerned that if JAMA is publishing this (positive) trial of EDTA chelation therapy it might be misconstrued as an endorsement. They wanted to avoid the certain avalanche of comments from readers who were already convinced that EDTA chelation is merely snake-oil in a bag. You might imagine that the editorial would have been much different (and unapologetic) had the primary end-point only reached a p=0.037! Here is the editorial for your reading pleasure [Free Online].

Also: Unpublished Data from TACT presented in San Francisco at the American College of Cardiology meeting earlier in March shows an even stronger clinical and statistical benefit when comparing patients receiving both EDTA and vitamin/mineral therapy compared to those receiving only placebo. A news story can be found here.

Dr. Rangaswamy at Scripps Conference

Dr. Guilliams is heading to The Scripps Conference on Dietary Supplements this week. He and a colleague, Dr. Nagmani Rangaswamy, will be presenting a poster reviewing the immune-modulating effects of mushroom-derived ingredients. There is a new white paper on the same subject posted in the “whitepapers” section, if you are interested in this topic. The Scripps conference is a great way to get the latest information on the use of dietary supplements for clinical use, including mechanisms and actions, regulatory issues and therapeutic considerations. Here is a link in case you want to add it to your calendar for next year.

Losing weight is always difficult, but what if extra fat may be the body’s only defense from dangerous fat-soluble toxins?  Remember the adage: “The solution to pollution is dilution”- we attempt to dilute poisons to reduce their concentration and therefore, their toxic effects. In the case of fat-soluble toxins, many compounds actually trigger the body to produce fat as a protective storage for these additional toxins. This keeps the toxins away from sensitive tissues and cells, but increases body fat and weight which can lead to other serious concerns.

Two things you should think about if you are a clinician or a patient. If you are attempting to lose a lot of weight quickly and you have never considered a detoxification program you should be aware that massive fat reduction will put additional strain on the liver and gall bladder as additional toxins will be released from fat stores and moved into the liver and other tissue. The toxins will also be working to tell your body to produce more fat to re-dilute the toxins. Losing weight slowly while changing the diet to include helpful liver cleansing foods is much healthier. Consider doing a medically appropriate detoxification program after you have lost 10-15 lbs to blunt this affect. Or, consider doing a detoxification program as the start to your weight-loss program.

Below are some links to recent papers which shows the links of certain toxins to obesity and weight-loss- and several showing how pollutants increase risk for diabetes. Some food for thought for the New Year.

I have often suggested that taking a walk a short time after eating a meal is a good way to improve overall glycemic control by directly impacting the post-prandial (after-meal) effects of glucose and insulin. A new study from Mayo Clinic has done a great job of showing how large an impact this might actually have. In order to get this data, however, they required volunteers (healthy controls and Type 1 diabetic subjects) to wear special suits and monitors that recorded their every move and calorie expended for three days in a laboratory/clinic setting.


I will focus my attention on the control subject for this report. These subjects were normal weight (avg. BMI-25.6) and in their late 30’s (5 men, 7 women). Before testing the effects of walking on post-prandial glucose, they first recorded the energy expenditure of these subjects based on their activity- something that is important to note.


At rest (Basal metabolic rate/BMR):     0.84 kcal/h/kg

Standing                                               1.17 (40% increase over BMR)

Walking 1 mph                                                2.41 (186% increase over BMR)

Walking 2 mph                                                3.08 (266% increase over BMR)

Walking 3 mph                                                4.02 (378% increase over BMR)


Notice how much more energy is expended just when they begin to walk even at 1 mph, compared to being sedentary. For me, this data alone made the paper worth reading and another confirmation of why I am planning to install my new treadmill desk soon! Now back to the rest of the data.


Each of the 3 meals they consumed for the 3 days was virtually identical and contained 33% of their daily caloric needs. Meals consumed at 7 AM, 1 PM and 7 PM were 30% carbohydrate, 40% fat and 40% protein (no food was permitted outside these meals). Each day, one of the meals was followed by complete sedentary activity (lying in bed for 6 hours) and the other two meals were followed by bouts of walking (averaging 90-95 minutes before the next meal). While these activity levels seem a bit extreme, the metabolic differences were quite dramatic. When measuring the glucose excursion for 270 minutes after these meals, the amount was over twice us much (113% higher) when the subjects had no physical activity, compared to when they were walking (at only 1.2 mph!).


What does this mean for the average person? Well, the total distance walked after these meals was actually less than 2 miles. Most people can walk this in 40 minutes (at 3 mph) which is much more practical with a busy schedule. But more to the point, it tells us that any amount of physical activity, especially after a meal, improves glucose tolerance and reduces the level of blood glucose after eating. These numbers are likely to be even more striking in patients with insulin resistance eating higher carbohydrate meals than those tested here (i.e. the average American).


Think about how you can change your regular eating habits to allow for a walk afterward, or perhaps schedule your physical household chores to be accomplished right after eating supper so you can avoid plopping down on the couch or in front of the computer for several hours of sitting.


Here are some other similar recent studies you might find interesting: