Several widely publicized clinical trials in the past weeks and months purport that the use of omega-3 fatty acids, especially those from supplemental fish oil, has no therapeutic value or are even potentially harmful to consume. This short communication [pdf of this article] is written to help put these reports within the context of the studies’ own limitations and also the broader fish oil research that has gone virtually unreported during the same time. 

Let’s begin with the most recent study purporting to link fish oil with prostate cancer risk. The report was published online in the J. of the National Cancer Institute (Online Abstract) and soon afterward, headlines such as Men who take fish oil omega-3 supplements at 71% higher risk of prostate cancer: study”[1] began floating around the internet, print and national television. One would assume by such headlines that this study was specifically designed to look at prostate cancer risk in men consuming fish oil supplements- it was not. In fact, this study didn’t even look at fish oil (or even dietary fish) consumption in these subjects!

Instead, this report was a secondary analysis of data collected from the previously concluded SELECT (Selenium and Vitamin E Cancer Prevention Trial) trial, which recruited men over 50 with no history of prostate cancer who were then randomized to receive vitamin E, selenium, a combination of vitamin E plus selenium, or placebo and followed for prostate cancer incidence (NCI’s SELECT Website). The data from this report is considered a case-cohort design, attempting to find an association between plasma phospholipid fatty acid levels in case subjects (those diagnosed with prostate cancer during the length of the trial) and compare those with study cohorts (similar subjects within the trial not diagnosed with prostate cancer during the length of the trial). It is important to note that the original vitamin E/selenium study was not designed to detect the association between plasma phospholipids and cancer risk and patients were not asked about their fish or fish oil supplement use at either the start or the length of the trial.

Nevertheless, they report that higher levels of 3 specific omega-3 fatty acids (EPA,DHA,DPA- combined) as a percent of plasma phospholipid fatty acids- were associated with a higher incidence of prostate cancer during the SELECT trial.  While the authors are much more cautious in their direct indictment of omega-3 supplementation within their publication (since they have no data related to supplementation), one of the authors said in a press release “We’ve shown once again that use of nutritional supplements may be harmful” Here are a few reasons these conclusions and statements are unwarranted and misrepresent the data.

  • The fatty acid levels reported here represent only a single blood draw taken at the start (baseline) of each participant’s entry into the study, often years before a prostate cancer diagnosis was assigned to the subject. Since plasma phospholipid fatty acid content fluctuates with dietary intake on a day to day basis, a single time point may only reflect dietary habits within the previous week prior to the blood draw and may have no correlation to long-term omega-3 intake or blood levels.
  • While the omega-3 fatty acid differences between groups were statistically different, they were not clinically significant. That is, the omega-3 levels reported would be considered “average” in all subject groups and the largest difference in the levels reported between groups could have been achieved with very low omega-3 consumption in a few weeks’ time.(see endnote #2)[2]
  • The authors admit that because of the high cost of phospholipid testing, that only case subjects diagnosed through 2007 (and their cohorts) were originally to be tested. But since “new finding” of associations between fatty acids and prostate cancer came to light- more subjects with high-grade cancer were analyzed in the 8th and 9th year of the trial. This highly unusual change in data set would have been disallowed in most other peer-review settings. The original data set was not published.
  • In almost all cases of associative data, a number of variables are used to adjust the data. Typically these adjustments include most variables that might influence risk. While these data were adjusted for education, diabetes, family history of prostate cancer and the SELECT intervention assignment; these data were not adjusted for the most striking variables that affect risk in this population- age, race, BMI and PSA levels- information which may have nullified these statistical associations. How these reviewers ignored this most obvious adjustment and permitted the data to be reported without these adjustments is baffling.

Omega-3 associated with lower prostate cancer, breast cancer, CHD and total mortality.

Beyond the specific conclusion of this study is the broader epidemiological and scientific question of plausibility. The authors readily admit that there is no plausible scientific explanation for how long-chain fatty acids like EPA and DHA could actually cause prostate cancer. There is also the inconvenient fact that several people groups which consume high levels of omega-3 fatty acids and have plasma phospholipids much higher than the participants in this study have extremely low incidence of prostate cancer (i.e. Japan). More importantly, studies that specifically look at fish and fish oil consumption show a dramatic decrease in prostate cancer risk in older men, seeing a slightly higher risk associated only with salted and smoked fish intake. [3] Other large meta-analysis have shown that even when overall prostate cancer incidence may be unaffected by omega-3 intake, prostate cancer mortality is dramatically lower in individuals with higher intake of marine omega-3 fatty acids.[4]

In fact, in a highly under-reported study published this year in the Annals of Internal Medicine, plasma phospholipid omega-3 fatty acids (much like the SELECT data above) were associated with lower total mortality- especially related to CHD deaths.[5] However, in this study the plasma phospholipid fatty acid difference between the highest and lowest groups were highly clinically relevant (200-300% difference), as compared to the clinically irrelevant differences in the SELECT trial data (6% difference-see endnote #2).

Lost in all this has been another significant report published in the British Medical Journal which associates the intake of fish and marine omega-3 fatty acids with a reduced risk for breast cancer.[6] This meta-analysis of 21 independent prospective cohort studies showed an overall 14% reduction in the relative risk for breast cancer related to marine omega-3 fatty acids. This risk reduction was associated with both the consumption of fish and fish oil, as well as tissue biomarker analysis (i.e. plasma phospholipids). They even suggested a “dose-response” relationship which suggested that the risk of breast cancer was reduced by 5% for each 100mg/day of marine omega-3 consumed.


When the data from the subcohort of the SELECT trial is analyzed and placed alongside the growing epidemiological, interventional and mechanistic data (see below) – the purported relationship between consuming omega-3 fatty acids (in the diet or through dietary supplements) with an increased risk of prostate cancer cannot be supported. Furthermore, since this study did nothing to ascertain the consumption of fish or omega-3-containing supplements in these subjects, it makes the sensationalized media reports about this study even more disturbing. In addition, the fact that the association data was not adjusted for the most obvious factors (such as PSA levels, race, BMI and age) leaves us unsure that there is any association at all; and leaves many others to suppose that strong bias may be at play here. We find it quite telling that one of the key authors of the trial is quoted in the DailyMail as saying ‘There is not really a single example of where taking a supplement lowers chronic disease risk.’ [7] On the contrary, we believe the current overall scientific evidence suggests that consumption of omega-3 fatty acids from fish oil supplements is not only safe at a wide-range of doses, but has proven efficacy in reducing risk for a wide-range of chronic conditions.                                                                                                                     

Recent animal or basic research on omega-3 fatty acids and prostate cancer


[2] For instance, the greatest difference between DHA levels in these subjects was reported as 0.18% (2.91% in the no cancer group and 3.09% in the high-grade cancer group, difference P=0.009). For comparison, other studies have shown that fish oil intake equivalent to a single serving of fish per week can raise DHA levels 0.63%, and do so in about 12 days. (AJCN 2012; 96:748). As Duffy MacKay, VP of Science & Regulatory Affairs at the Council for Responsible Nutrition said about the most recent study, these difference in omega-3 levels “literally could have occurred if somebody ate a fish sandwich on their way to get their blood drawn” 

[3] Consumption of Fish Products across the Lifespan and Prostate Cancer Risk PLoS One. 2013; 8(4): e59799).

[4] Fish consumption and prostate cancer risk: a review and meta-analysis. Am J Clin Nutr. 2010 Nov;92(5):1223-33

[5] Plasma phospholipid long-chain ω-3 fatty acids and total and cause-specific mortality in older adults: a cohort study. Ann Intern Med. 2013 Apr 2;158(7):515-25.

[6] Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies. BMJ. 2013 Jun 27;346:f3706

Coenzyme Q-10 has been used as a dietary supplement for a variety of uses over the past few decades. Among its many therapeutic benefits, are those related to heart failure symptoms and mortality. This past week the results of a large clinical trial were presented at a congress of the European Society of Cardiology Heart Failure Association. That study (Q-SYMBIO) showed that 300mg of daily CoQ-10 supplementation for 2 years had a highly significant effect on major adverse cardiovascular events (50% reduction) and all-cause mortality (>45% reduction).  Here is a news reports about this study.

Since the full paper has not been published, it is difficult to assess the nuances of the data- something that has invited many to discount the potential benefits of these study results. The cautious, but optimistic conclusion of the study authors is that “CoQ10 should be considered as a part of the maintenance therapy of patients with chronic heart failure.”

*- Remember- Statin therapy reduced serum CoQ-10

Here are some more recent studies using CoQ-10 you might be interested in-


I was recently reminded of how impressive berberine can be after recently hearing a clinician’s story. The particular patient had Type 2 diabetes and this clinician had been treating him for 15 years. Consistently his glycated hemoglobin was above 9% (aim: to be below 7%). Historically, the patient had been taking 2 grams of Metformin, then recently these meds were lowered to 1 g and berberine was added. Within one month, his glycated hemoglobin was 6.7%. Obviously, this is a single case and other factors may have been involved- lthough the clinician was convinced berberine was a major factor in these results.

We have been following the growing research related to use of the alkaloid compound berberine for almost a decade now and wanted to give a short update for those interested in using this dietary supplement as part of their healthcare protocol for managing glucose, lipids or related cardiovascular outcomes.

Berberine for glucose management in Type 2 Diabetes

Most of the excitement related to the use of berberine for diabetic patients comes from a paper published in early 2010 (Metabolism 59(20)) where a group of Type 2 diabetic patients were given either metformin 1.5 g/d (n=26), rosiglitazone 4 mg/d (n=21) or berberine HCl 1g/day (n=-50) and followed for 2 months. The remarkable results showed drops in fasting blood glucose and glycated hemoglobin for berberine which matched both metformin and rosiglitazone- while only the berberine group saw a statistical drop in TG levels. Furthermore, they followed this study by testing 1g/day of berberine HCl in type 2 diabetic patients who had either hepatitis B or C to detect whether these same outcomes could be confirmed in these patients and what affect berberine may have on liver enzymes in these patients. They found similar benefits in both blood glucose and TG levels as in the non-hepatitis patients, but also a statistical improvement in both AST and ALT enzyme levels.

One of the critiques of this (and most) berberine studies is that they have nearly all been performed in China- on Chinese subjects and most of the published trials are in Chinese- making the data difficult to assess and translate (both linguistically and clinically) into practice here in the US. A recent meta-analysis of these Chinese studies has recently been published (in English) and is available for download online (Evidence-Based Complementary and Alternative Medicine Volume 2012). While showing a consistent positive benefit for berberine in a wide-range of Chinese subjects (14 trials, 1068 subjects), the authors also conclude that many of these trials were poorly conducted and the need for a large, well-controlled and randomized clinical trial is critical. Nonetheless, they found berberine generally safe- listing GI discomfort and constipation (berberine is traditionally used to treat diarrhea in China) as side-effects to treatment in a small number of patients.

Berberine for lipid-altering effects or related cardiovascular outcomes

Years before the glucose-related outcomes were being published, researchers in China had described lipid-altering effects using berberine. Some of these trials are now being performed outside of China in Caucasian subjects. Most recently was a study done at the University of Pavia (Italy) in 144 subjects with low cardiovascular risk (Expert Opin Biol Ther 2013). After a 6-month run-in period of diet and physical activity, patients were randomly given either placebo or berberine (500 mg- twice per day) for 3 months. Patients were taken off their experimental therapy for 2 months (wash-out), and then placed back on berberine or placebo for an additional 3 months. Not only was berberine deemed safe in these individuals, but subjects consuming berberine had reduced total cholesterol, LDL-cholesterol and TG, and increased HDL-cholesterol. All of these benefits were diminished during the washout period but returned once back on berberine.

A small pilot study, done also in Caucasian subjects, was performed here in the US (U. of South Dakota and South Dakota State University) which explored the lipid-lowering effect of berberine (Phytomedicine 2012). Sixteen obese subjects were given berberine (500 mg- 3 times per day) for 12 weeks. As a pilot study, there was no control group. After 12 weeks they saw a modest loss in body weight (avg. 5 lbs/subject) and a significant reduction in total cholesterol (-12.2%) and triglyceride levels (-23%). 2 subjects stopped the protocol due to GI complaints- which may have been due to the higher dose (1.5 grams) over other studies using only 1 gram.

A review and meta-analysis of the Chinese studies looking at the lipid altering effects of berberine is also online (Planta Medica Abstract-2013)

Other Recent Human Studies using berberine

Potential for berberine/drug interactions

“CONCLUSIONS: Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.”

Animal or Mechanism studies of interest

One of the most impressive aspects of the recent berberine studies is the vast number of animal, tissue and mechanistic studies which have been emerging in the past few years. Listed below is just a few recent studies related to metabolic pathways and outcomes. I will only highlight one particular study because it is a fascinating relationship between a nutraceutical agent, the gut microbiome and human physiology.

One of the main historical uses for berberine (Coptis chinensis and its extracts) within Traditional Chinese Medicine is for intestinal infections and diarrhea. This has led some to wonder if consuming berberine regularly for cardiometabolic outcomes might promote an imbalance within the gut bacteria (microflora). As it turns out, the answer might be yes, but in a very helpful way. In a study published in PLoS ONE (Full Article Free online), researchers show that the prevention of obesity and insulin resistance which occurs in rats fed a high-fat diet are partially mediated by changes to the gut microflora. This mechanism adds to the long list of known metabolic influences that berberine has on metabolic pathways and links to the growing evidence we now have of the relationship between obesity and gut microflora in humans. While the paper is quite technical, it gives some interesting background information and highlights the type of research that will continue to be done to decipher the benefits of berberine and other nutraceutical agents. It also shows us that some agents have activities which don’t even require absorption to result in a clinical outcome.

Here are more studies on berberine that might interest you:






Many of you are aware that strontium, a mineral closely related to calcium, has been used in humans in several forms as a bone-building agent. In Europe, the compound strontium ranelate (a salt that uses ranelic acid) is available as a drug (Protos/Protelos). In the US, FDA has not approved strontium ranelate as a drug, but various forms of strontium are available as dietary supplements (most commonly strontium citrate).  Our goal here is not to discuss the widely published efficacy of strontium ranelate, but simply to update you on some interesting and recent studies concerning the related compound strontium citrate; in particular, two studies which address the ability of strontium citrate to deliver similar levels of strontium to bones (I have included links to a number of very remarkable recent studies about strontium ranelate at the end for you to follow if interested).

The first is an animal study (in rats) that is similar to many of the studies which first showed (and are still showing) the various ways in which strontium modifies bone structure and prevents bone fractures. What makes this study interesting for our discussion is that it was a head- to-head study between the citrate and ranelate versions of strontium. Rats were given an equivalent amount of strontium (either as citrate or ranelate) or placebo starting at 19 weeks and followed for another 8 weeks. Researchers could measure the amount of strontium incorporated into the bones of the rats using a custom X-Ray fluorescence spectrometer. Post-mortem analysis of several bones was also performed using the same techniques.

What they found was very simple and straight-forward, strontium provided from citrate salts incorporated into bones just as well (or maybe even better) than the strontium provided from ranelate. As it turns out, they had to re-adjust the data because the strontium content of the strontium citrate was higher than they originally figured- and when they made the adjustment, the two were virtually identical (see figure below). Even though it was predicted (by us and others) that the citrate form is essentially equivalent in its ability to deliver strontium to bone tissue- this study goes a long way to confirm this fact, albeit in an animal model.

The second study is actually a very unique case-study of an osteoporotic women who decided to take strontium citrate and allow researchers at McMaster’s University to follow her bone strontium levels for nearly 3 years (this was an earlier report from the some of the same researchers who performed the rat study above). The subject was 68 years of age and had no history of supplementing strontium in any form prior to the study. She began supplementing  with strontium citrate pills which provided 340 mg of elemental strontium (as citrate) per pill; taking 2 per day for a total of 680 mg of strontium per day. Using X-Ray fluorescence, researchers measured the changes in strontium levels in her finger and ankle bones. Not only did her bone strontium levels statistically increase after just 5 days, but it continued to increase until it reached a plateau after 1 year (at least in the finger). However, in the ankle, strontium was continuing to accumulate even after 2.5 years of strontium intake. In both cases, the majority of the increase occurs in the first 3-6 months.

The constraints of such a case-report being used for a wide conclusion are obvious, although there has never been a reason to believe that strontium as a citrate salt would perform in a manner different than strontium as a ranelate salt in this, or any, subject. Even so, we take this limited data for what it is worth. Beyond that, the X-ray fluorescence technique described in this paper could open up more opportunities to study the dynamics of strontium accumulation in bone, as this diagnostic technique results in much less radiation than a traditional DEXA scan. [Email communication with the author of the study does confirm they have repeated this analysis in many more subjects and this data will be published in the near future].

Of course, we would like to see more data generated, perhaps a clinical trial similar to those done with strontium ranelate performed using strontium citrate. Finding someone to fund such a trial while no one holds a patent for strontium citrate (or even an exclusive) is daunting- since such a trial would need to have a large number of subjects and be at least 2-3 years long. I do know of a researcher who is willing to do the study if the money is available…any takers?

A full whitepaper on the role of strontium as a bone-building agent will be available in the Whitepapers section soon. Also see The Standard Vol. 6 No. 2 for a discussion of other related nutrients that can be used to support osteoporosis.

Recent Studies of Interest:


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 /]

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: