Friday, May 31, 2013

FDA Expands Advice on Statin Risks

FDA Expands Advice on Statin Risks

FDA Expands Advice on Statin Risks - (JPG)
Get this hi-resolution art on Flickr1.





On this page

If you’re one of the millions of Americans who take statins to prevent heart disease, the Food and Drug Administration (FDA) has important new safety information on these cholesterol-lowering medications.

FDA is advising consumers and health care professionals that:

  • Routine monitoring of liver enzymes in the blood, once considered standard procedure for statin users, is no longer needed. Such monitoring has not been found to be effective in predicting or preventing the rare occurrences of serious liver injury associated with statin use.
  • Cognitive (brain-related) impairment, such as memory loss, forgetfulness and confusion, has been reported by some statin users.
  • People being treated with statins may have an increased risk of raised blood sugar levels and the development of Type 2 diabetes.
  • Some medications interact with lovastatin (brand names include Mevacor) and can increase the risk of muscle damage.

This new information should not scare people off statins, says Amy G. Egan, M.D., M.P.H., deputy director for safety in FDA’s Division of Metabolism and Endocrinology Products (DMEP). “The value of statins in preventing heart disease has been clearly established,” she says. “Their benefit is indisputable, but they need to be taken with care and knowledge of their side effects.”

FDA will be changing the drug labels of popular statin products to reflect these new concerns. (These labels are not the sticker attached to a prescription drug bottle, but the package insert with details about a prescription medication, including side effects.)

The statins affected include:

  • Altoprev (lovastatin extended-release)
  • Crestor (rosuvastatin)
  • Lescol (fluvastatin)
  • Lipitor (atorvastatin)
  • Livalo (pitavastatin)
  • Mevacor (lovastatin)
  • Pravachol (pravastatin)
  • Zocor (simvastatin).

Products containing statins in combination with other drugs include:

  • Advicor (lovastatin/niacin extended-release)
  • Simcor (simvastatin/niacin extended-release)
  • Vytorin (simvastatin/ezetimibe).

Liver Injury Called Rare

FDA has found that liver injury associated with statin use is rare but can occur. Patients are advised to consult their health care professional if they have symptoms that include unusual fatigue, loss of appetite, right upper abdominal discomfort, dark urine or yellowing of the skin or whites of the eyes.

Statins work in the liver to reduce the production of cholesterol, a waxy substance that can form plaque on the walls of the arteries and keep the heart from getting the blood it needs.

Egan explains that there had been signals in early clinical trials of possible liver damage tied to statin use, so health care professionals were advised to regularly test their patients’ liver enzyme levels. However, she says, such damage is rare, and the tests are not effective at predicting or preventing who will develop this rare side effect.

So FDA is now recommending that liver enzyme tests be performed before statin treatment begins and then as needed if there are symptoms of liver damage.


Reports of Memory Loss

FDA has been investigating reports of cognitive impairment from statin use for several years. The agency has reviewed databases that record reports of bad reactions to drugs and statin clinical trials that included assessments of cognitive function.

The reports about memory loss, forgetfulness and confusion span all statin products and all age groups. Egan says these experiences are rare but that those affected often report feeling “fuzzy” or unfocused in their thinking.

In general, the symptoms were not serious and were reversible within a few weeks after the patient stopped using the statin. Some people affected in this way had been taking the medicine for a day; others had been taking it for years.

What should patients do if they fear that statin use could be clouding their thinking? “Talk to your health care professional,” Egan says. “Don’t stop taking the medication; the consequences to your heart could be far greater.”


The Risk of Diabetes

Diabetes occurs because of defects in the body’s ability to produce or use insulin—a hormone needed to convert food into energy. If the pancreas doesn't make enough insulin or if cells do not respond appropriately to insulin, blood sugar levels in the blood get too high, which can lead to serious health problems.

A small increased risk of raised blood sugar levels and the development of Type 2 diabetes have been reported with the use of statins.

“Clearly we think that the heart benefit of statins outweighs this small increased risk,” says Egan. But what this means for patients taking statins and the health care professionals prescribing them is that blood-sugar levels may need to be assessed after instituting statin therapy,” she says.


The Potential for Muscle Damage

Some drugs interact with statins in a way that increases the risk of muscle injury called myopathy, characterized by unexplained muscle weakness or pain. Egan explains that some new drugs are broken down (metabolized) through the same pathways in the body that statins follow. This increases both the amount of statin in the blood and the risk of muscle injury.

FDA is revising the drug label for Lovastatin to clarify the risk of myopathy. The label will reflect what drugs should not be taken at the same time, and the maximum lovastatin dose if it is not possible to avoid use of those other drugs.

Patients and health care professionals should report negative side effects from statin use to FDA’s MedWatch Adverse Event Reporting Program6.

This article appears on FDA's Consumer Update page7, which features the latest on all FDA-regulated products.

February 27, 2011

Association of Apolipoprotein B and NMR Spectroscopy–Derived LDL Particle Number with Outcomes

Association of Apolipoprotein B and Nuclear Magnetic Resonance Spectroscopy–Derived LDL Particle Number with Outcomes in 25 Clinical Studies              

  1. G. Russell Warnick4
BACKGROUND: The number of circulating LDL particles is a strong indicator of future cardiovascular disease (CVD) events, even superior to the concentration of LDL cholesterol. Atherogenic (primarily LDL) particle number is typically determined either directly by the serum concentration of apolipoprotein B (apo B) or indirectly by nuclear magnetic resonance (NMR) spectroscopy of serum to obtain NMR-derived LDL particle number (LDL-P).
CONTENT: To assess the comparability of apo B and LDL-P, we reviewed 25 clinical studies containing 85 outcomes for which both biomarkers were determined. In 21 of 25 (84.0%) studies, both apo B and LDL-P were significant for at least 1 outcome. Neither was significant for any outcome in only 1 study (4.0%). In 50 of 85 comparisons (58.8%), both apo B and LDL-P had statistically significant associations with the clinical outcome, whereas in 17 comparisons (20.0%) neither was significantly associated with the outcome. In 18 comparisons (21.1%) there was discordance between apo B and LDL-P.
CONCLUSIONS: In most studies, both apo B and LDL-P were comparable in association with clinical outcomes. The biomarkers were nearly equivalent in their ability to assess risk for CVD and both have consistently been shown to be stronger risk factors than LDL-C. We support the adoption of apo B and/or LDL-P as indicators of atherogenic particle numbers into CVD risk screening and treatment guidelines. Currently, in the opinion of this Working Group on Best Practices, apo B appears to be the preferable biomarker for guideline adoption because of its availability, scalability, standardization, and relatively low cost.
Read the complete article here.

Thursday, May 30, 2013

Salt intake What of Nuns? - Kendrick

Salt intake – What of Nuns?

Excess salt intake is one of the great issues in preventative medicine. Last year I watched a bus go by, with an advert for reducing salt plastered all over the side. Some restaurants have taken salt cellars off their tables, to protect customers. Many foodstuffs now have their salt content clearly labeled, with high salt content given a red sticker.

Given all of this you would think, would you not, that the case for excess salt consumption causing cardiovascular disease had been made beyond even the slightest possibility of doubt. One of the arguments in support of the dangers of salt consumption (the one that I am looking at in this article), comes from the native peoples living in the Amazon

The Amazon is an extremely low salt environment, and the average salt consumption of those living there is at very low. Several studies have found that the tribes people living in the Amazon have very low blood pressure which does not increase with age. They also have very little in the way heart disease and strokes.

Primitive societies who ingest little or no salt have no hypertension1

Proof, the anti-salt lobby cry, that it is excess salt intake that causes our blood pressure to rise dangerously.

Or is it? When presented with ‘proof’ like this I tend to look for contradiction, rather than confirmation. Are there, I wondered, other populations that fail to demonstrate a rise in blood pressure with age, that do not have a low salt consumption. My attention was drawn to nuns, living in Italy.

‘The powerful effect of psychosocial and acculturating influences on population blood pressure trends seems to be confirmed, through longitudinal observations, in the nuns in a secluded order. After initial observations had been made on culture, body form, blood pressure, diet, and other variables in 144 nuns and 138 lay women, included as a control group, a 30-year follow-up study was undertaken. Most striking were opposite trends noted between the two groups in blood pressure trend. During the follow-up period, blood pressure remained remarkably stable among the nuns. None showed an increase in diastolic blood pressure over 90 mm Hg.’

So, nuns do not develop high blood pressure as they age. What happened to the control women in this study?

‘By contrast, the control women showed the expected increase in blood pressure with age. This resulted in a gradually greater difference (delta>30/15 mm Hg) in systolic and diastolic blood pressure between the two groups, which was statistically significant.’

No difference in diet or salt consumption, yet one population developed the ‘normal’ Western rate of hypertension whilst the other did not. What did the authors of this thirty yearlong study think was the reason for this finding?

‘In conclusion, it seems reasonable to attribute much of the difference in blood pressure and cardiovascular events, to the different burden in psychosocial factor and to the preserved peaceful lifestyle of the nuns2.’

Now I do not know for sure if those living in the Brazilian rain forests have managed to preserve a traditional peaceful lifestyle – but it seems a reasonable assumption to make.

However, the main point I am trying to make here is that you do not need a low salt diet in order to prevent hypertension. You can find populations with a normal salt diet who do not develop hypertension either.

What factor, or factors, appears to link these two populations? The factor appears to be living a preserved peaceful lifestyle. This would suggest that stress is the cause of hypertension and cardiovascular disease, and not salt. Whilst association cannot prove causation, a lack of association disproves it.

1: Freis ED. The role of salt in hypertension. Blood Pressure 1992; 1: 196-200.
2: Timio M, et al: ‘Blood pressure in nuns in a secluded order: A 30-year follow-up.’ Miner Electrolyte Metab. 1999 Jan-Apr;25(1-2):73-9

JAMA on salt HERE.
Read the complete article here.
Another article here.

Salt guidelines raised ... as Canadian experts cite existing targets as ‘not feasible’

More data in the Salt Wars - Aug 14, 2014; http://www.medpagetoday.com/Cardiology/Hypertension/47203

An article by Marion Nestle - http://www.foodpolitics.com/2014/08/its-salt-arguments-again-new-research-arguments-over-public-health-recommendations-and-issues-of-conflicts-of-interest/

Are We Over-Treating High Blood Pressure? - Peter Lipson

Forbes is not my usual go-to for my medical posts here but I thought this was an article worthy of note. Here is a small quote from the article. Please read the complete

Are We Over-Treating High Blood Pressure?
By: Peter Lipson,

Heath argues that this is too aggressive, and that we over-treat people whose BPs run in the 140-160/90s range. She bases her opinion on a recent review published by the Cochrane Collaboration, an evidence-based medicine group that keeps an eye on such things. The review included data from four studies (they use fairly strict selection criteria).

Cochrane’s conclusions were fairly clear: when data from the four studies were analyzed,  the treatment of mild hypertension did not prevent important outcomes such as heart attack and stroke, but did cause side-effects.

At what level to treat high blood pressure is a hugely important question, given it’s impact on the nation’s health. As I said above, we’re talking about people who don’t already have other heart risks, and we’re talking about whether or not to commit them to long-term treatment. We’re also talking about patients who have not been able to bring their pressures down through proper diet and exercise (which, unfortunately, is a whole lot of people).

So what evidence is there to treat so-called low risk people with mild high blood pressure?

Read the complete article here.

Tuesday, May 28, 2013

Is salt really so bad for you? - Fenster

Is salt really so bad for you?

Decades of science show NO conclusive evidence that cutting back on dietary sodium reduces cardiovascular morbidity

(Credit: This piece originally appeared on Pacific Standard.
Pacific Standard No salt, low salt, salt free, heart-healthy salt substitution–any added salt will hurt your constitution. It reads like some bizarre, Seussian tale. Excepting that we’ve heard it not from the good Dr. Geisel but from the medical community and public health advocates everywhere. We watch as celebrity chefs take the salt elimination cooking challenge to prepare an “improved healthy” cuisine. Self-anointed “experts” cadge, coax, and cajole us to decrease our salt, or, more specifically, sodium intake. If that doesn’t work then the specter of heart attacks and strokes is unleashed upon us, along with a dash of fire and brimstone for good measure. It is, after all, clearly in our best personal and the greater public interest.
The hypothesis is sound and the supporting data is impeccable, right?

The theory goes as follows: Salt acts to make us retain fluid. When we retain more fluid it increases our blood pressure (albeit temporarily). Increased blood pressure is hypertension. Hypertension is a risk factor for cardiovascular disease like heart attacks and stroke. Heart attacks and strokes are bad. Therefore, hypertension is bad. Thus, sodium must be bad; A causes B which causes C, therefore A causes C. Get rid of A and you get rid of C—simple basic arithmetic, no? Reduce sodium intake and you will reduce blood pressure and thus reduce the incidence of stroke and heart attack. Reducing sodium intake is good—simple, effective, and undeniably the prevailing conventional wisdom these days.

Except… one thing is missing.

The conclusive data—or any data-that definitively shows that cutting back on dietary sodium reduces mortality or significantly reduces cardiovascular morbidity. For over half a century, starting in the 1960s, there has been a vehement and salty exchange just out of public earshot involving respected scientists on both sides of this line. But with the advent of an aggressive public policy to reduce dietary sodium intake for presumed public health benefit and studies emerging suggesting negative consequences of a low-sodium diet, the clamor of dissension is heating up.
JAMA on salt HERE.
Read the complete article here.

Here is an article from The Kennebec Journal on the division regarding the salt controversy. Here are a couple of quotes:

"Four months after an Institute of Medicine report said reducing salt to the lowest recommended level doesn't improve health and may harm it, the U.S. Centers for Disease Control and Prevention said they disagree. In an article published Monday in the American Journal of Hypertension, the CDC and New York City health officials said getting Americans to eat less salt remains a key objective with the potential to save thousands of lives."


"Lowering sodium to the extent required to lower blood pressure has a variety of other effects," including some that boost heart attacks, strokes and death, he said. "It's just not that simple. The message from the evidence is we don't know."

Here is another article from Food Politics by Marion Nestle.
Another article on salt here.

More data in the Salt Wars - Aug 14, 2014; http://www.medpagetoday.com/Cardiology/Hypertension/47203

An article by Marion Nestle - http://www.foodpolitics.com/2014/08/its-salt-arguments-again-new-research-arguments-over-public-health-recommendations-and-issues-of-conflicts-of-interest/

Wednesday, May 22, 2013

DHA: the crucial omega-3 - Davis

DHA: the crucial omega-3  

Of the two omega-3 fatty acids that are best explored, EPA and DHA, it is likely DHA that exerts the most blood pressure- and heart rate-reducing effects. Here are the data of Mori et al in which 4000 mg of olive oil, purified EPA only, or purified DHA only were administered over 6 weeks:

□ indicates baseline SBP; ▪, postintervention SBP; ○, baseline DBP; •, postintervention DBP; ⋄, baseline HR; and ♦, postintervention HR.

In this group of 56 overweight men with normal starting blood pressures, only DHA reduced systolic BP by 5.8 mmHg, diastolic by 3.3 mmHg.

While each omega-3 fatty acid has important effects, it may be DHA that has an outsized benefit. So how can you get more DHA? Well, this observation from Schuchardt et al is important:

DHA in the triglyceride and phospholipid forms are 3-fold better absorbed, as compared to the ethyl ester form (compared by area-under-the-curve). In other words, fish oil that has been reconstituted to the naturally-occurring triglyceride form (i.e., the form found in fresh fish) provides 3-fold greater blood levels of DHA than the more common ethyl ester form found in most capsules. (The phospholipid form of DHA found in krill is also well-absorbed, but occurs in such small quantities that it is not a practical means of obtaining omega-3 fatty acids, putting aside the astaxanthin issue.)

So if the superior health effects of DHA are desired in a form that is absorbed, the ideal way to do this is either to eat fish or to supplement fish oil in the triglyceride, not ethyl ester, form. The most common and popular forms of fish oil sold are ethyl esters, including Sam’s Club Triple-Strength, Costco, Nature Made, Nature’s Bounty, as well as prescription Lovaza. (That’s right: prescription fish oil, from this and several other perspectives, is an inferior product.)

What sources of triglyceride fish oil with greater DHA content/absorption are available to us? My favorites are, in this order:

Ascenta NutraSea
CEO and founder, Marc St. Onge, is a friend. Having visited his production facility in Nova Scotia, I was impressed with the meticulous methods of preparation. At every step of the way, every effort was made to limit any potential oxidation, including packaging in a vacuum environment. The Ascenta line of triglyceride fish oils are also richer in DHA content. Their NutraSea High DHA liquid, for instance, contains 500 mg EPA and 1000 mg DHA per teaspoon, a 1:2 EPA:DHA ratio, rather than the more typical 3:2 EPA:DHA ratio of ethyl ester forms.

Pharmax (now Seroyal) also has a fine product with a 1.4:1 EPA:DHA ratio.

Nordic Naturals has a fine liquid triglyceride product, though it is 2:1 EPA:DHA.

By Dr. William Davis
Read the complete article here.

Monday, May 20, 2013

Dietary Fats and Health - Lawrence

Dietary Fats and Health

Glen D. Lawrence*  Department of Chemistry and Biochemistry, Long Island University, Brooklyn, NY


Although early studies showed that saturated fat diets with very low levels of PUFAs increase serum cholesterol, whereas other studies showed high serum cholesterol increased the risk of coronary artery disease (CAD), the evidence of dietary saturated fats increasing CAD or causing premature death was weak. Over the years, data revealed that dietary saturated fatty acids (SFAs) are not associated with CAD and other adverse health effects or at worst are weakly associated in some analyses when other contributing factors may be overlooked. Several recent analyses indicate that SFAs, particularly in dairy products and coconut oil, can improve health. The evidence of ω6 polyunsaturated fatty acids (PUFAs) promoting inflammation and augmenting many diseases continues to grow, whereas ω3 PUFAs seem to counter these adverse effects. The replacement of saturated fats in the diet with carbohydrates, especially sugars, has resulted in increased obesity and its associated health complications. Well-established mechanisms have been proposed for the adverse health effects of some alternative or replacement nutrients, such as simple carbohydrates and PUFAs. The focus on dietary manipulation of serum cholesterol may be moot in view of numerous other factors that increase the risk of heart disease. The adverse health effects that have been associated with saturated fats in the past are most likely due to factors other than SFAs, which are discussed here. This review calls for a rational reevaluation of existing dietary recommendations that focus on minimizing dietary SFAs, for which mechanisms for adverse health effects are lacking.
Read the complete article from Advances in Nutrition here.

Thursday, May 16, 2013

“Carnitine Causes Heart Disease” - Colpo

As Usual, an excellent read from none other than Anthony Colpo, independent researcher, physical conditioning specialist, and author. His wit, wisdom, and ability to analyse tomfoolery in topics re diet and medical that otherwise seem scientifically sound make this article required in my opinion. And while I do not really like some of his choice of words, I choose not to be offended. So here it is - Read it and smile and enjoy the unabashed logic Anthony brings.
Bullshit Study of the Year: “Carnitine Causes Heart Disease”

Warning: This article contains language some folks would consider naughty. If you are deeply offended by words that start with “Sh…” and rhyme with “git”, you should close this page immediately and go back to reading Better Homes and Gardens.
If ever you needed proof the world is heavily populated by utter morons, all you’d need to do is examine a recent study appearing in Nature Medicine, wonder how supposedly educated people could ever contrive such utter rubbish, then marvel at the ease with which this pseudoscientific slop has been uncritically soaked up by media outlets and individuals all around the world.

I’m talking, of course, about the current “Carnitine in Red Meat Causes Heart Disease!” nonsense doing the rounds in the mainstream media, that preeminent source of misinformation that plays a key role in keeping the general population as dumbed down, confused and distracted as possible.
The Plain Facts, Whether You Like Them or Not

Before I begin tearing apart this joke of a ‘study’, I want to make a couple of things perfectly clear:
–Carnitine does NOT cause heart disease.

–No-one -I repeat NO-ONE – has ever shown red meat nor supplemental carnitine to cause heart disease in human beings. Not the ‘researchers’ responsible for the appalling Nature Medicine paper, and not anyone else.
So what’s with this latest study? Where do the researchers get off making such idiotic claims?


If you earnestly believe this stuff causes heart disease, my condolences. Life must be tough without a brain.

How to Make Headlines With Complete and Utter Garbage in 3 Easy Steps

The only kind of study equipped to support a fantasmagorical claim like “Carnitine Causes Heart Disease!” is a randomized controlled trial (RCT) in which you take a bunch of volunteers, randomly assign them to two groups, then assign one group to take carnitine supplements and the other a placebo. You would then let the study run long enough for people to start dying from heart disease (if the participants had preexisting CVD, this will generally happen a lot sooner). After several years (or less if one group showed a huge advantage over the other, in which case you would be ethically obliged to end the trial early) you would tally up the data.

By the way, if this trial was intended to examine the effects of carnitine on CVD incidence and mortality in human beings – as opposed to rats, mice, pigs, or Mongolian Gerbils – then it must meet another absolutely essential requirement: The participants of the trial must be human beings.
“No shit Anthony!“, you say? Hey, you’d be amazed at how many highly-decorated researchers apparently can’t tell the fundamental differences between a rodent and an adult Homo sapien. And that includes the authors of the Nature Medicine paper, as we’ll discuss shortly.

If the data from your human RCT showed more people in the carnitine group died of heart disease and your trial was a meticulously conducted endeavour pretty much free of confounding factors, dodgey researcher behaviour, or untoward influence from parties with a vested financial interest in the results, then and only then could you justify the claim “Carnitine Causes Heart Disease!” Even then, for the finding to be accepted as gospel fact by the scientific community at large, your research would need to be replicated and validated by other researchers.

So conducting such a carefully controlled trial must be what the Nature Medicine paper authors did, right? After all, they sound pretty damn confident that “Carnitine Causes Heart Disease!”
They did nothing of the sort.

Instead, they engaged in an exercise known as PIM (Pseudoscientific Intellectual Masturbation).
To be a good PIM-artist really isn’t that difficult. All you need, along with seemingly impressive credentials, is to serve up the right mix of shady inferences, dodgey extrapolations and ridiculous but tantalizingly sensationalist conclusions. Write a good press release, and you can be assured the shocking ignorance of most health reporters and the public’s eternal gullibility and faith in authority will do the rest.

The title of the paper, which Nature Medicine posted on its website on April 7 ahead of print, is Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Again, we can see the authors aren’t mincing their words – as far as they’re concerned, they’ve conclusively established a causal role for carnitine in the pathogensis of heart disease.
In their dreams, baby.

Why This Study is a Load of Bollocks

The very first line of the study’s text reads:

“The high level of meat consumption in the developed world is linked to CVD risk, presumably owing to the large content of saturated fats and cholesterol in meat1,2. However, a recent meta-analysis of prospective cohort studies showed no association between dietary saturated fat intake and CVD, prompting the suggestion that other environmental exposures linked to increased meat consumption are responsible3.”

See the numbers “1″, “2″ and “3″ at the end of the first and second sentences? These are citation numbers referring to the studies allegedly confirming what those sentences are saying. So let’s take a look at these studies.

Sudy “1″ can be found here. It was the Nurses’ Health Study and, yes, the researchers claimed that red meat intake was associated with a higher risk of CVD and diabetes. This was not an RCT but an epidemiological study, which means it was a load of uncontrolled, confounder-prone slop. As I have explained many times before, epidemiological studies are hopelessly subject to innumerable confounding factors over which the researchers have absolutely no control (and don’t give me this bollocks about “multivariate analyses”, which is simply an abbreviated way of saying “sophisticated mathematical chicanery that convinces epidemiologists they have god-like powers and can endow their work the same kind of robust validity seen with carefully conducted RCTs”).

So what I want you all to do now is open the PDF for the NHS paper and scroll down to pages 11 and 12 to view Table 1, which contains the baseline characteristics of the participants (to avoid contorting your neck, right click on the table and select “Rotate Clockwise”). Remember what I said about these garbage epidemiological studies being hopelessly prone to confounders? The NHS is a textbook classic example – we can clearly see that as red meat consumption went up, so too did smoking rates, trans fat intake, and history of angina/diabetes/blood pressure. And as red meat intake increased, levels of physical activity decreased.

In other words, subjects in the higher red meat quintiles clearly lived unhealthier lives and possessed several other unhealthy traits totally unrelated to red meat intake.

Here’s a few facts for our red meat-hating brethren in the epidemiology community to ponder:

–The primary source of trans fats are refined vegetable fats (you know, the same fats our idiotic health authorities told us were “heart healthy”, then quietly backed away from when mounting evidence showed otherwise).

–Smoking, meanwhile, involves ingestion of noxious gases from nicotine-containing products, primarily cigarettes. In my four-plus decades on this crazy blue ball called Earth, I’ve yet to see someone roll a topside steak, light it up, and draw on it like a Marlboro. In other words, red meat has nothing to do with smoking, and to blame the effects of the latter on the former is sheer idiocy.

–Any claim that red meat intake causes physical inactivity is similarly absurd. In fact, given its high concentrations of B-vitamins, creatine, iron, and carnitine (critical for energy production, idiotic statements about CHD from clueless researchers notwithstanding), we would reasonably expect red meat intake to facilitate, rather than impede, strenuous exercise.

–There is no reliable evidence whatsoever to support any notion that angina, diabetes and high blood pressure are caused by red meat intake. They are, however, promoted by smoking, inactivity, and trans fat intake, all of which increased among the NHS subjects along with rising red meat intakes. These ailments are also strongly linked to such factors as high refined carbohydrate intakes, stress, ambient pollution, and high bodily iron stores – none of which were reported in Table 1.

So yes, in the NHS, red meat was indeed “associated” with higher rates of CHD, but in the same way a woman who unwittingly marries a serial killer is “associated” with violent crime. The latter is not responsible for her husband’s murderous behaviour, and the former is in no way responsible for the otherwise unhealthy behaviour of its most voracious consumers.

So why would people who consume more red meat exhibit generally unhealthier lifestyle and dietary habits?

It’s simple. People who care less about their health, and ignore exhortations to avoid trans fats/smoking/inactivity are also more likely to ignore recommendations to avoid or limit red meat consumption. And so red meat is eaten in higher amounts among these subjects, allowing dodgey epidemiologists who think health research is all about clever statistical shenanigans to create “associations” between red meat and all sorts of health ailments. They then pronounce these associations as causal rather than statistical, blatantly ignoring one of the most fundamental rules of good science:


Health-conscious people, by the way, will also be more likely to eat poultry compared to red meat, which is why this source of animal flesh was associated with a lower risk of CVD in the NHS.
There’s one more thing I’d like to point out about the NHS paper. If you look at the “Body Mass Index” scores among the various quintiles of red meat consumption, they are pretty much identical. But scroll down to the “Calories” data, and you’ll see that as red meat intake increases, so too does the self-reported calorie intake. So what we are supposed to believe from this hogwash is that people who eat less red meat maintain the same level of overweight as people who eat higher amounts, despite eating 700 less calories per day!

You’d have to be Gary Taubes to believe bullshit like that.

So if the self-reported calorie intakes are way off the mark, what else in the NHS data is wildly inaccurate? Who knows. Like I said, it’s just a mass of totally uncontrolled, dubiously reported (a single dietary questionnaire every four years) and hopelessly confounder-prone data, ripe for dredging and misinterpretation by those happy to accept weak statistical odds ratios as physiological fact.

Anyway, let’s leave the bad joke that is the NHS red meat paper and move onto reference “2″. Before I discuss this paper, I want to reiterate that the Nature Medicine paper authors cite it in support of their claim “high level of meat consumption in the developed world is linked to CVD risk“.

The reality is it showed nothing of the sort, as you can see for yourself by clicking here. This paper was a meta-analysis examining the pooled data from not one, not two, but 20 epidemiological studies dealing with red meat and CVD and/or diabetes risk. Yessirree, a genuine all-you-can-eat epidemiological extravaganza encompassing data for some 1,218,380 individuals and 23,889 CHD, 2280 stroke, and 10,797 diabetes cases.

And what did it find? “Red meat intake was not associated with CHD…or diabetes mellitus”. Nor was it associated with stroke.

Processed meat intake was associated with a 1.42 and 1.19 increased risk of CHD and diabetes, respectively, but not stroke. Whether this is because of an unhealthy consumer phenomenon similar to the one we saw for red meat in the NHS, or a genuine detrimental effect of processed meat, or whether we should just ignore the results period because 1.42 and especially 1.19 are pathetically weak hazard scores considering the confounder-prone source, is an entirely different discussion. What matters here is that, despite the massive data-dredging opportunity it presented, the most massive analysis to date found no relationship between red meat and heart disease.

But the Nature Medicine authors cite it as showing that red meat is associated with CHD. Why would they say this when it is patently untrue? The NM paper has 23 listed contributors from a mix of institutions including Cleveland Clinic, University of California–Los Angeles, Cleveland State University, Perelman School of Medicine at the University of Pennsylvania, Wake Forest School of Medicine in North Carolina, Children’s Hospital Oakland Research Institute in Oakland, California.

Are we to seriously believe none of these 23 researchers read the meta-analysis in its entirety?

Are we to seriously believe none of them saw the words “Red meat intake was not associated with CHD“?

So why have they cited the meta-analysis in support of a statement patently at odds with its findings?

It gets worse.

Study “3″ can be found here. This study did not deal specifically with red meat intake; rather, it examined the relationship between CVD and saturated fats in general (i.e. not just from red meat, but other meats, dairy products, etc). This was also a meta-analysis, incorporating epidemiological data for 347,747 subjects, 11,006 of whom developed CHD or stroke. Contrary to decades of dedicated anti-saturate brainwashing, there was no relationship between saturated fat intake and CHD, stroke or CVD risk.

Now, I need you to re-read the first 2 sentences of the Nature Medicine paper – c’mon, humour me, it’s important:

“The high level of meat consumption in the developed world is linked to CVD risk, presumably owing to the large content of saturated fats and cholesterol in meat1,2. However, a recent meta-analysis of prospective cohort studies showed no association between dietary saturated fat intake and CVD, prompting the suggestion that other environmental exposures linked to increased meat consumption are responsible3.”

Did you notice the subtle but very dodgey sleight of hand performed by our anti-carnitine crew? The first sentence claims an association between meat intake and cardiovascular disease, but the second sentence claims this relationship is not explained by saturated fat intake. Despite having red meat squarely in their sights, they’ve also carefully slotted the word “meat” into the sentences rather than “red meat”, so they can technically claim study “2″ in support, even though it only found an association for processed meat (red meat by far is the richest source of carnitine; the carnitine content of processed meat varies widely due to its use of various meats, fillers and often high fat content; white meat contains negligible amounts).

So the reality is one of the studies allegedly showing a relationship between red meat intake and CVD was hopelessly confounded by other unrelated factors, while the much larger and all-encompassing meta-analysis showed no relationship of red meat – irrespective of its saturated fat content – with CVD. Yet the authors falsely claim otherwise, then lead into the saturated fat argument to pave the way for their carnitine hypothesis.

In other words, their carnitine hypothesis is based on a false premise. They go on to claim that carnitine may be the real explanation for the relationship between red meat and CVD, but there is no relationship between red meat and CVD!

So the underlying assumption upon which they build their carnitine theory is utter rubbish. I’m sure you guys don’t need me to remind you what happens to elaborate structures built on quicksand…

Up, Up and Away With TMA
Not to be deterred by the small matter of their thesis being built on a blatant falsehood, the Cleveland Clinic-led researchers then go searching for an alternative culprit to explain their mystical relationship between red meat and CVD.

They settle on a rather unusual choice, a substance known as trimethylamine, or TMA for short.
What the bleep is trimethylamine, I can hear you all asking?

Trimethylamine belongs to a group of organic compounds known as amines, and has a pungent, fishy, ammonia-like odor. TMA is formed naturally during the decomposition of plants, fish and animal products, and is ingested in foods such as fish, or from foods containing TMA precursors such as trimethylamine oxide (TMAO), choline, and L-carnitine, which are metabolized to TMA by enterobacteria.

TMA is the substance mainly responsible for the funky smell imparted by rotting fish. It is present in the plasma and urine of humans, and can also contribute to the less-than-pleasant aromas arising from some infections, bad breath and vaginal odors.

Sounds pretty gross, but TMA is present in every one of us after we eat foods containing TMA precursors. Conversion back to TMAO is the major fate of most TMA in our bodies, and considerable variability exists among humans in the efficiency of this process.

In a nutshell, what the authors of the Nature Medicine paper are saying is that when we eat red meat, the carnitine in that meat gets converted to TMA by microbes in our gut. That much is straightforward, concurs with what we already know about carnitine and TMA, and pretty much falls into the category of “Um, yeah, so what?”

It’s what the authors claim next that strains the boundaries of credulity. They claim that this newly formed TMA goes on to cause heart disease by promoting uptake of cholesterol into the artery walls.
For crying out loud…


The evidence absolving cholesterol of any causative role in atherosclerosis from heart disease is so abundant I was able to fill an entire book with it. And the best that any of my critics have been able to muster in response is to accuse me of being a money-hungry profiteer who resides out in left field (hi Dr Gholke, Pee Pee, Janet, et al!) In other words, they cannot even begin to factually refute the points I raise in the book.

Here are the facts:

–The campaign against saturated fats and cholesterol was born in 1953 after a shameless researcher by the name of Ancel Keys plotted the total fat intake and CHD mortality for six countries on a graph. By doing so, he was able to show a strong linear positive association between the two; as fat intake went up, so too did CHD mortality. But what he didn’t mention in his paper was that data for twenty-two countries was available at the time, and he’d simply chosen the six countries that best supported his thesis and flippantly ignored the rest. Depending on which six countries Keys chose, he could have shown fat intake was completely unrelated to CHD mortality, or he could even have shown that as fat intake went up, CHD mortality went down. Key’s research was patently fraudulent, but his driven, domineering manner and his position on the American Heart Association’s nutrition advisory panel saw to it that his shambolic findings eventually became official public policy. The anti-fat theory promptly morphed into the anti-cholesterol theory, and initially saw the heavy promotion of polyunsaturated fats as ‘healthier’ substitutes for saturated fats.

The above is now common knowledge, so why do so many researchers and health authorities keep up with the anti-cholesterol sham when from the very outset it was based on a fraud?

–Autopsy studies have repeatedly shown no relationship between blood cholesterol levels and atherosclerosis. Some of these studies observed recently deceased people with very low cholesterol levels but severely atherosclerotic arteries.

–Decades of dietary intervention trials have completely failed to lower coronary mortality, despite the fact that blood cholesterol levels were indeed lowered in the intervention groups.

–The most successful dietary intervention trial ever conducted, the Lyon Diet Heart Study, slashed mortality rates among those assigned to an omega-3, antioxidant-rich “Mediterranean” diet, even though cholesterol levels between the diet and control groups remained identical throughout the study.

–Statin drugs, those overhyped and inherently toxic agents that nonetheless have shown CHD mortality reductions in some population groups, only work because they possess a whole host of effects aside from mere cholesterol-lowering. This is why they’ve been able to deliver meager mortality reductions where their predecessors, the fibrates, were able to deliver none. In one particularly telling study- which, ironically, was published in Nature Medicine – researchers took the popular lovastatin and completely disabled its cholesterol-lowering abilities, then found it still possessed potent anti-inflammatory effects.

These are just a few of the contradictions to the untenable cholesterol hypothesis of heart disease that I discuss in The Great Cholesterol Con (you know, the book I allegedly wrote while residing out in “left field” and has since apparently made me millions of dollars, which of course is why I’m sitting here on a Saturday morning writing this article when I’d much rather be sipping Frangelico in the Caribbean or doing my darndest to destroy the gearbox on a brand new Lamborghini*).

I also debunked the “LDL Cholesterol is Bad Cholesterol!” bollockery in a Journal of American Physicians article that you can freely access here (for a Spanish version, click here).

I will repeat: Cholesterol does not cause heart disease. Cholesterol is an essential component of your cell membranes, and if someone were to suck all of the cholesterol out of your body you’d promptly collapse on the floor into a pile of mush, hair and bones.

Because of its key role in providing structural integrity to cell membranes, cholesterol constitutes an important repair substrate for our bodies. The lipid hypothesists wank on and on about how atherosclerotic plaques have been observed to contain cholesterol, but big deal. They’ve also been observed to contain white blood cells, calcium, the allegedly heart-healthy omega-6 fatty acid linoleic acid, fibrous tissue, and more. Now, if someone came along and said we should all go on diets or take drugs that lower our white blood cell count in order to fight heart disease, they’d be roundly ridiculed and laughed at. Ditto if they said we should eat diets or take drugs that destroy fibrous tissue or deplete our body of calcium. But when someone comes along and makes the equally ridiculous claim that we should eat Spartan diets and take powerful drugs in order to lower our blood cholesterol, they make the cover of Time magazine, receive awards for their monumental contribution to furthering human ignorance cardiovascular science, take up lucrative positions at “lipid clinics” where they can further research the non-existent relationship between cholesterol and CHD while the rest of us work real jobs, and receive lucrative honoraria from drug companies to boot!

I just love the way this shit works. Not.

The bottom line is that cholesterol, just like most other components of atherosclerotic plaque, is in the plaque as part of the body’s attempt to repair a damaged section of artery. Cholesterol does not cause heart disease, no more than police officers and paramedics cause the accident scenes they attend – they’re there to deal with the mess after the accident already happened.

Cholesterol’s importance in the repair process may be a key reason why heart attack patients presenting to the emergency ward suffering heart attack and displaying high cholesterol levels are far more likely to survive the ordeal than those presenting with low cholesterol levels. Yeah, I know, you probably never heard this and it goes against all your anti-cholesterol brainwashing, but it’s true[1-4].
So as it turns out, the Nature Medicine anti-meat/anti-carnitine paper is now based on two utterly false premises. In addition to the “meat causes heart disease” fantasy, the researchers have also added the fairy tale about cholesterol causing heart disease to their repertoire of dodgey working assumptions.

Guys, can I stop here? Seriously, the idiocy is killing me!

Huh? What’s that? You want me to keep going? Something about never leaving a job half-done? And you want to hear more about this TMA charade?

Ah, bugger. Alright, on we go…

TMA = Too Many Assumptions [of a Most Untenable Nature]
Okay, so we’re now up to the bit where the researchers fed some volunteers carnitine supplements as part of their TMA gig. Before I describe what happened, I just have to share the following passage from p.2 of their paper with you:

“Given the similarity in structure between l-carnitine and choline (Fig. 1a), we hypothesized that dietary l-carnitine in humans, like choline and phosphatidylcholine, might be metabolized to produce TMA and TMAO in a gut microbiota–dependent fashion and be associated with atherosclerosis risk. To test this hypothesis, we initially examined data from our recently published unbiased small-molecule metabolomics analyses of plasma analytes and CVD risks.

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).”

Due to the heavy use of gobbledegook, many of you won’t have a clue what all that means, but those of you familiar with both science-speak and the dodgey behaviour of statisticians are no doubt smiling one of those deep, knowing smiles right now. What they are essentially saying, in plain English, is this:

“We came up with this bright idea that carnitine might be converted to TMA and that this might increase CVD risk. So to see if this had any validity, we pulled out the data from a recent analysis we did linking itty bitty chemical substances to CVD risk. As it turns out, there were no substances with the same key characteristics as l-carnitine that were associated with CVD risk, which effectively sent our thesis down the toilet.


However, we weren’t going to give up that easily, because if we could somehow support our thesis it could get us some kick-ass coverage in the media! Hey, nothing like another headline-grabbing paper to keep those research funds flowing in!

So what we then did was pretty much the research equivalent of donning beer goggles in order to make an ugly woman attractive enough to sleep with: We dramatically loosened up our criteria until we finally found a substance that had similar characteristics to l-carnitine and delivered us the statistically significant association we needed to proceed with our charade. Gotta love statistics! With enough TLC, you can massage and bend those numbers any way you want, baby!”

So after gettin’ jiggy with the “metabolomic” data and finding the flabby, dateless, gap-toothed association they were after – not with carnitine mind you, but with a substance that kinda sorta was a little bit like carnitine – they then proceeded with the clinical phase of their caper.

To get this phase rolling, they fed five omnivorous subjects an 8-ounce sirloin steak, corresponding to an estimated 180 mg of l-carnitine, together with a capsule containing 250 mg of isotope–labeled l-carnitine. They then observed modest post-meal increases in carnitine and TMAO.

Then, to examine the role of gut microbes in TMAO formation from dietary l-carnitine, they placed the same volunteers on oral broad-spectrum antibiotics to suppress intestinal microbiota and then performed a second l-carnitine “challenge”. After the week-long treatment with the antibiotics, they noted near complete suppression of detectable TMAO in the subjects’ blood and urine.

Nothing outlandish there.

Then they rounded up some more omnivores and also found themselves a bunch of vegans and vegetarians. They found fasting baseline TMAO levels were significantly lower among the vegans and vegetarians. In a subset of these individuals, they performed another carnitine challenge (but with no steak, only supplements) and found the vegans and vegetarians had a markedly reduced capacity to synthesize TMAO from the supplemental carnitine. Vegans and vegetarians also had significantly higher post-challenge plasma concentrations of carnitine compared to the omnivores, indicating they were unable to metabolize the carnitine as effectively. Given that carnitine plays a key role in cellular energy production, this is hardly worth bragging about, but as you’ll soon learn the researchers carry on like this is in fact a wonderful thing.

The next sections of the paper deal with the researchers fishing through some of the subjects’ faeces to determine the concentrations of choline, carnitine, TMAO and gut bacteria. This task, which I’m guessing they assigned to the junior members of the team, found certain types of bacteria were associated with plasma TMAO levels and being omnivorous or vegetarian/vegan. This in turn suggests that your usual diet will have an effect on both the bacterial composition of your gut and your ability to synthesize TMA and TMAO from dietary l-carnitine.

Again, nothing particularly outlandish.

Return of the Bollocks
It doesn’t take long, however, for things to start going downhill again. After some mice experiments which I’ll discuss later, the researchers put their epidemiological costumes back on and examined the relationship of fasting plasma concentrations of l-carnitine with CVD risk in 2,595 subjects undergoing elective cardiac evaluation. Among this sample, they observed a positive association with plasma carnitine and coronary artery disease, peripheral artery disease and overall CVD.

A look at the supplementary data soon reveals why: As plasma carnitine levels rose, so too did the patients’ age, rate of smoking, and pre-existing CAD and CVD. Yessir, the same old unhealthy-lifestyle-meets-red-meat phenomenon that has confounded so many other epidemiological studies is again at work here.

What a joke.

After the usual overrated adjustment for a limited range of “traditional CVD risk factors”, only the highest quartile of plasma carnitine showed an increased ‘risk’ of any note.

From this terribly slanted epidemiological study, they also examined the relationship between plasma carnitine and 3-year risk for composite of adverse cardiac events (death, myocardial infarction, stroke and revascularization). Again, only the highest quartile of carnitine concentration was associated with this composite endpoint, after adjustments for several CVD risk factors.

After further adjustment for plasma TMAO concentration and a larger number of accompanying comorbidities (e.g. extent of CAD, ejection fraction, medications and estimated renal function), the significant relationship between carnitine and the composite endpoint was completely abolished. For example, in patients exhibiting high plasma carnitine but low TMAO, the relative risk was actually reduced (0.80 adjusted hazard ratio) when compared to patients with low levels of both.
I guess that kinda got left out of the press release…

In patients with high levels of carnitine and TMAO, the HR was 2.1. But what does that prove? Absolutely nothing, except that high levels of carnitine and TMAO were associated with a higher risk of composite CVD endpoints in a sample of 3,000 patients. Exactly why they were associated with higher risk is anyone’s guess; Was it causal or, as per the situation with cholesterol, an after-the-fact association? This study is simply not equipped to tell us that, although I am here to tell you without a shadow of a doubt that carnitine does not cause heart disease. I’ll present the evidence for that assertion in uno momento, but for now let’s look at the next section of the study.

More Mouseshit
After the epidemiological entree, the researchers serve up their main course. Yep, this is where they roll out the mice and feed them either their usual chow diet or the same fare plus supplemental l-carnitine. The mice fed carnitine, of course, go on to develop more ‘atherosclerosis’ than those fed standard chow. I say “of course” because it hardly takes a brain surgeon to figure what is going to happen when researchers showing strong signs of a predetermined agenda take a special strain of a herbivorous animal and feed it large amounts of a substance it has never evolved to properly metabolize. Plant foods contain bugger all carnitine – the only meaningful source is animal flesh. So when you take an animal that has never developed the mechanisms to efficiently metabolize carnitine, it’s hardly surprising that pathological changes might occur after carnitine feeding.
This is the very same reason why feeding cholesterol – also found only in animal foods – has repeatedly produced ‘atherosclerosis’ in herbivorous lab animals over the years, but has completely failed to induce atherosclerosis in carnivorous animals. The former never evolved to efficiently metabolize cholesterol, while the latter did so on a daily basis. Dogs, for example, simply will not show any pathological changes in their arteries after being fed cholesterol unless you surgically remove their thyroids (again, I discuss this all in detail in The Great Cholesterol Con).

Now once again, let’s all stop and engage in one of those reflective moments where you angle your head slightly upwards and to the side and look like you’re deep in philosophical thought. But instead of pondering life’s deeper mysteries, I want you to simply ask yourself this:

If cholesterol feeding cannot induce atherosclerosis in meat-eating animals no matter how hard researchers try, why keep up the charade? Why the $#@% rip out the thyroid glands of man’s best friend? If they need to disfigure such beautiful and loyal creatures, shouldn’t that in itself tell them the cholesterol theory is utter bullshit? At what point do these researchers finally acknowledge reality, give up the cholesterol wank, and go searching for the real causes of heart disease?!
And you thought I was being overly misanthropic when I said the world was full of morons…
Anyways, back to our carnitine-fed mice. Did I mention that these were Apoe−/− mice?
What the bleep are Apoe−/− mice, I hear you asking?

Apoe−/− mice are specially bred mice that spontaneously develop ‘atherosclerotic lesions’ on a standard chow diet. If they develop arterial plaque like there’s no tomorrow on mice chow, what do you think is going to happen when they are supplemented an essentially foreign substance like carnitine?


When the mice were given an oral antibiotic “cocktail” to wipe out their intestinal flora, in addition to l-carnitine, they showed marked reductions in plasma TMA and TMAO concentrations and no increase in atherosclerosis.

But so what? This still doesn’t change the fact that they are likely to metabolize carnitine very differently to humans. Proof of this comes from the researchers’ own initial studies with mice. This is where they gave them carnitine then cut them open to examine the bacterial compsition of their intestinal tract. They found “several bacterial taxa whose proportion was significantly associated (some positively, others inversely) with dietary l-carnitine and with plasma TMA or TMAO concentrations”.


“…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”.

In other words, my contention that this strain of mice metabolizes carnitine differently than humans is not just theoretical musing – it’s a plain fact.

Not fussed by yet another self-contradiction to their untenable anti-carnitine theory, the researchers continue on with their mice shenanigans. Rather than admitting their results have little real life applicability to humans, they instead seek to find a “mechanism” for the carnitine-induced atherosclerosis seen in the Apoe−/− mice.

They observed that both carnitine and choline inhibited what is known as reverse cholesterol transport, which basically refers to the removal of cholesterol from tissues into the bloodstream and back to the liver. To understand why this is significant, we have to ponder for a moment the grade-school mentality towards cholesterol that dominates the medical and science fields nowadays. When the cholesterol theory first started showing signs of self-contradiction many moons ago, researchers quickly went into salvage mode by claiming it wasn’t just total cholesterol that mattered, but the ratio of LDL:HDL. They labelled LDL the “bad” cholesterol because it took cholesterol to the tissues. I guess the fact that our tissues sorely need cholesterol and we’d be royally screwed if they didn’t get it never crossed their minds. Bottom line, appearing on the cover of Time magazine or receiving Nobel prizes in no way guarantees you have a clue what you’re on about. There is nothing “bad” about LDL – it serves a vital function in our bodies and we’d be in a really bad place without it.
But let’s continue on…

Next, they dubbed HDL the “good” cholesterol because that was the lipoprotein that carried cholesterol away from the tissues and back to the liver where it was broken down into bile.
And so was born the ridiculously simplistic good cholesterol/bad cholesterol charade, which like the total cholesterol theory is a complete and utter wank. Studies have repeatedly shown that LDL does not cause atherosclerosis nor heart disease, something I discuss at length in my LDL paper.

So researchers then latched onto the oxidized LDL theory, again using the childishly simplistic logic that the higher your LDL, the higher your oxidized LDL.

And again, it was complete nonsense. While oxidized LDL may indeed be harmful, it has no relationship with your levels of total or LDL cholesterol. Rather, poor antioxidant status and disordered blood sugar control are the main culprits. Again, I discuss this in my LDL paper which you can access free of charge thanks to the good folks at JPANDS right here.

Oh, and remember how the researchers also observed that the nutrient choline inhibited reverse cholesterol uptake? Well, notice how they remain silent about that, and focus their hate campaign on carnitine which, unlike choline, is found mainly in red meat?

What they would be well aware of, but have chosen to ignore, is that carnitine-containing red meat is hardly the only food that raises TMA levels nor does it even come close to being the food that causes the greatest spike in TMA levels.

Guess which food causes the greatest hike in TMA levels?


Yep, heart-healthy fish.

Thanks to a condition known as trimethylaminuria, whose unfortunate sufferers experience ‘‘fish-odour syndrome’’, numerous researchers have investigated the potential TMA-raising effects of choline and choline precursors and, more recently, actual foods.

Some especially insightful findings come from scientists at the Imperial College in London, who examined the urine of healthy male volunteers fed 30 different foods. Not all at once, of course. Instead, on separate occasions the volunteers consumed a 227 g serving of the foodstuff under investigation along with a standardized breakfast.

Beef ingestion resulted in negligible amounts of urinary TMA: a mere 20µg trimethylamine/g food, less than that seen for bread, carrots, cauliflower, cabbage, mushroom, peas, and potatoes. Lamb, by far the richest dietary source of carnitine, returned a score of 16.4µg.

In stark contrast, prawns, mackeral and cod delivered urinary TMA levels of 948, 679, and 1335µg trimethylamine/g food, respectively!

A previous paper by the same researchers also reported combined urinary levels of TMA+TMAO and found similar results. Beef and lamb produced lower urine levels of TMA+TMAO than the overwhelming majority of vegetables, all fish and seafood products, cheese, and eggs.

This previous paper also reported the effect of oral ingestion of betaine (1.76 g), carnitine (2.97 g), choline (2.10 g), creatinine (1.70 g), lecithin (11.65 g) and TMAO (1.67 g) on six separate occasions. Betaine, creatinine, and lecithin all failed to raise urinary TMA+TMAO levels. TMAO, not surprisingly, produced the highest levels, followed by choline. Carnitine, meanwhile, was converted to TMA+TMAO at only half the rate of choline (30.6% vs 62.9%, respectively).

Now let’s get back to the Nature Medicine paper. The researchers wanked on and on about red meat, but made no effort to investigate other foods, even though many other foodstuffs have already been documented to produce much higher TMA and TMAO increases than red meat. Based on the results of previous research, if we are going to make the extraordinary claim that carnitine-rich red meat causes heart disease due to its effects on TMA/TMAO levels, then for the sake of consistency we also need to claim that a far higher risk is posed by choline, most vegetables and all seafood.

Such a claim, of course, would be ridiculous. So the researchers simply ignored the inconvenient choline, vegetable and seafood data, and went about constructing a case against red meat.
Can you say preconceived agenda?

Summing It All Up So Far
So what we have is a study which used misrepresented epidemiology, blatant cherry-picking and a singles bar attitude to metabolomics as a springboard to validate what strongly looks like a preconceived agenda to implicate red meat and carnitine in the pathogenesis of heart disease.
This validation rests heavily on studies with a genetically modified strain of a herbivorous creature that is 0.001 the size of adult humans who follow omnivorous diets and have done so for millions of years. Despite the stark differences between the two species, this idiotic comparison is now being used to claim carnitine causes heart disease and to scare people away from both red meat and carnitine.

In further justification of their absurd theory, the researchers cite the allegedly lower CVD risk enjoyed by vegetarians and vegans. I recently explained in detail why the claim vegetarian/vegan diets confer protection against heart disease is yet another example of anti-science at its finest, propagated by people with an anti-meat agenda:

Vegetarian Diets Reduce Heart Disease? Nonsense!

The researchers even cite the Lyon Diet Heart Study in support of their theory, noting the subjects were instructed to eat less red meat. Yes, but they were also instructed to eat more fruits and vegetables and supplied with a special omega-3-rich spread. Blood testing showed both their serum antioxidant and omega-3 levels were increased; no such information was available for carnitine or TMA/TMAO.

The sad reality is that the Nature Medicine paper is one of the most poorly conceived pieces of rot I’ve had the misfortune of reading in a long, long time.

Ah, the good old days. When men were men, worked real jobs instead of playing with their statistics, and beat fresh carcasses in their pursuit of physical excellence.

Why Carnitine is Your (Very Good) Friend
Okay, I think we’ve well established that the methodology and reasoning in the Nature Medicine paper is dodgier than a drug-dealing loan-shark who also dabbles in used car sales.
What we’re now going to do is examine even more evidence the Nature Medicine researchers blatantly ignored – evidence not only showing carnitine does not cause cardiovascular disease, but may in fact benefit it.

I must say, I was shocked when I first heard about the current anti-carnitine hate campaign. I’ve read a lot about this amino acid over the years and have only ever been able to discover good things about it. So why on Earth were they picking on this beautiful, energy-providing amino acid, I wondered?
Like cholesterol, there is nothing “bad” about carnitine. Like cholesterol, it performs crucial functions in the body and if someone were to shove a carnitine-specific vacuum up your keester and completely suck this crucial amino acid from your body, you’d find yourself in a whole heap of trouble, real quick.

Carnitine is found in nearly every cell in your body, and plays a critical role in energy production. And when I say critical, I really do mean critical. It transports fatty acids into the “engines” of your cells – the mitochondria – so they can be oxidized to produce energy. Some very unfortunate folks suffer from a condition known as primary carnitine deficiency, a genetic disorder that interferes with cellular carnitine transport. This condition usually manifests itself by five years of age, and common symptoms include cardiomyopathy (which in turn increases the risk of heart failure), skeletal-muscle weakness, and hypoglycemia.

Carnitine also transports toxic compounds generated during energy production out of the mitochondria to prevent their accumulation. Yep, carnitine is one hell of a compound; it fuels your cellular engines and cleans them at the same time. The physiological equivalent of BP Ultimate, if you will.

Thanks to its critical role in fat-derived energy production, carnitine is concentrated in tissues like skeletal and heart muscle where fatty acids constitute a vital fuel source.

While muscles also rely heavily on carbohydrate (save me the “fat adaptation” speech, oh ye flabby low-carbers who bonk ten minutes into a strenuous ride), the heart relies primarily on fatty acids even when you consume a high-carb diet.

Are you beginning to see why I hold the anti-carnitine authors and the screwball journalists who uncritically soaked up their nonsense with such contempt? If the world listens to these maniacs and embarks on an anti-carnitine campaign, we will much more likely see an increase in heart disease, rather than a decrease. Not to mention a marked decline in overall health and well being.
Bold claim?

Not at all.

The Evidence they Ignored
We discussed how the researchers chose a specially bred strain of mice to prove their point that carnitine promotes atherosclerosis. Having obtained the results they were after, they then engage in some highly questionable extrapolation to incriminate carnitine as doing the same thing to humans.
Well, guess what? This was hardly the first time researchers had fed carnitine to herbivorous animals.
And guess what else? Yep, they obtained results starkly different to those reported in the Nature Medicine paper. Not surprisingly, that paper does not so much as mention these conflicting studies.

Here are just a few:
Spanish researchers took mice bred to be especially prone to obesity and fed them a high-fat diet for nine weeks, during which time they suffered reduced cardiac output, worsening arterial function, deteriorating glycemic control, and decreased tissue production of nitric oxide (the gas that helps keep your arteries supple and elastic). During the subsequent four weeks, they divided the mice into 2 groups. One group continued to receive plain water, while the other group’s drinking water was supplemented with carnitine (200 mg/kg/day). The carnitine-enhanced water improved cardiac output, arterial function, insulin resistance and increased nitric oxide levels. Plain water had no effect.
Egyptian researchers deliberately made rabbits hypercholesterolemic by feeding them cholesterol (again, unlike humans they aren’t equipped to properly process cholesterol, and dietary ingestion quickly raises their blood levels). They then made them carnitine deficient, and observed severe atherosclerotic lesions, intimal plaques and foam cell formation. Daily administration of L-carnitine (250 mg/kg), for 28 days, completely prevented the progression of atherosclerotic lesions in both aorta and coronary arteries.

Italian researchers similarly found that rabbits on a cholesterol-enriched diet who were supplemented with l-carnitine experienced a “decrease of plaque cell proliferation and severity of aortic atherosclerotic lesions.”[5]

So even in other strains of mice and in rabbits, other researchers have found no adverse effect of carnitine and in fact have found beneficial effects!

But that’s in animals. What cardiovascular effects does supplemental carnitine have in humans?

The Italians: Not Just Hot Curvy Babes and Hot Curvy Cars
The Italians have performed a lot of research on both l-carnitine and acetyl-l-carnitine, and their work is crying out to be replicated by other groups (of course, if carnitine were a patentable drug, this replication would have happened long ago). As far back as the 1970s and 1980s, they had reported l-carnitine improved exercise tolerance, reduced infarct size in heart attack patients, and reduced post-cardiac event mortality at one and six months.

Inspired by these early results, in 1992 Italian researchers published the results of a carnitine intervention trial involving 160 recent heart attack victims. This was a non-blinded trial in which patients were randomly assigned to 4 grams daily of carnitine in addition to their usual medication, or to a group which received their usual medication but no supplemental carnitine. After one year, there were ten deaths in the control group (8 due to cardiovascular causes) but only one in the carnitine group (due to thromboembolism).

In addition to greatly lowered mortality risk, the patients in the carnitine group also enjoyed improvements in heart rate and blood pressure, and a reduction of angina attacks, rhythm disorders, and signs of impaired heart muscle contractility[7].

Another group of Italian researchers took thirty-eight elderly patients suffering heart failure, and randomly assigned them to receive either l-carnitine or placebo in addition to their usual medical care. The dose was 1g twice daily, for 45 days. Those receiving carnitine experienced greater ECG improvements and a marked reduction in their daily digitalis requirement. No adverse reactions to carnitine were observed in any of the patients[8].

These were small, short studies; to see if they could be replicated in a larger, double-blind trial, a larger Italian study was commenced. This study, published in 2005, aimed to determine the effect of L-carnitine in patients presenting to cardiology units with heart attack. In those receiving carnitine, the amino acid was delivered at a dose of 9 grams intravenously for the first 5 days, then then 4 grams per day orally for the next 6 months. The researchers had originally planned to include 4,000 patients with acute anterior myocardial infarction, but lower than expected numbers of eligible patients meant only 2,330 patients participated.

During the first 5 days, patients receiving the high-dose IV carnitine enjoyed a significantly lower rate of mortality. During the remainder of the study, this advantage dissipated; at 6 months, the carnitine group showed a non-significant 14% relative reduction in the combined occurrence of death and heart failure, and a non-significant 12% lower overall mortality.

Disappointing, but hardly supportive of idiotic claims that “Carnitine Causes Heart Disease!”
Hopefully researchers will keep studying the cardiovascular effects of carnitine, and hopefully not in isolation but in conjunction with other critical and potentially synergistic nutrients such as taurine, CoQ10 and even creatine. All of which, by the way, are only found in animal products (hmmm, I wonder how long will it take for some nutty research crew to come out and claim they are also bad for your heart…)

There’s been a whole bunch of studies examining the effect of effect of carnitine on walking distance in patients with peripheral arterial disease. Researchers at Adelaide’s Flinders University recently conducted a review of this research and found “Most trials demonstrated a small or modest improvement in walking performance with administration of PLC [propionyl-l-carnitine] or l-carnitine. These findings were largely independent of level or quality of evidence, while there was some evidence that intravenous administration was more effective than oral administration and those with severe claudication may achieve greater benefits than those with moderate claudication.”
They also noted in their conclusion, “Routine carnitine supplementation in the form of PLC may therefore be a useful adjunct therapy for management of intermittent claudication.”[9]
Carnitine has also been shown to benefit, of all things, erectile dysfunction. Yep, researchers recruited a bunch of aging Italian ex-Stallions and then randomized them to either 4 grams daily of carnitine (2g acetyl-l-carnitine + 2g propionyl-l-carnitine), 160mg testosterone undecanoate, or placebo for 6 months. During the six months of the study, the carnitine combo proved significantly more effective than testosterone undecanoate in improving “nocturnal penile tumescence“, which is science-speak for nighttime boners. Carnitine was also significantly more effective for improving scores on the International Index of Erectile Function (yes, they have an international index for this kind of thing).

A year later, the same researchers published the results of another study involving patients who underwent prostatectomy. They compared sildenafil, sildenafil plus the aforementioned carnitine mix, or placebo. The carnitine+sildenafil group scored significantly better than sildenafil-only patients for erectile function, sexual intercourse satisfaction, orgasm, and general sexual well-being. Only the carnitine+sildenafil group had a significantly increased percentage of patients with a positive intracavernous injection test (please don’t ask me to describe what that involves…)
A more recent Italian study examined supplementation with propionyl-L-carnitine, L-arginine and niacin and sexual performance among men presenting to an erectile dysfunction clinic. After three months of treatment, a small but statistically significant improvement in total and individual items of the International Index of Erectile Function was found. Analyses of global assessment questions answered by the patients revealed the nutrient trio improved erections in 40% of cases, with a partial response occurring in up to 77% of subjects enrolled.

L-carnitine: Critical for your ticker, good for your pecker too!

In Closing…
If I haven’t convinced you by now that the study behind the current carnitine hating is complete and utter horseshit, then nothing will. For the rest of you that haven’t recently undergone a lobotomy, it’s important you start standing up to this kind of rot. This is serious business folks. Googling around, I see this study has received immense worldwide coverage while very few rebuttals have been posted, despite the fact it is patently absurd nonsense.

In recent times there seems to be an intensifying of research efforts, no matter how ridiculous, aimed at vilifying perfectly natural and wholly nutritious animal foods (see my article on the atrocious anti-egg research of Canadian trio Spence et al here, and the recent claim that vegetarian diets reduce heart disease here).

I’m not sure what the endgame is here. Some folks out there are convinced this growing anti-animal food crusade is part of some wider conspiracy, something I’m simply not placed to endorse nor refute. And while some of you are no doubt snickering and making jokes about tin foil hats, I will point out the following: Anyone who’s read Marvin Harris’ truly brilliant Cannibals and Kings will know this would hardly be the first time in history the powers-that-be have instigated and nurtured efforts to vilify certain types of meat in order to fulfill ulterior motives.

Regardless of whether or not a bunch of wealthy oligarchical assholes are covertly trying to manipulate our perceptions of certain foods, I sincerely doubt garden-variety research teams are a knowing part of any such agenda. Far more likely and ubiquitous explanations are the power of conformity, the desire for recognition, and financial gain.

In the “Contributions” section of the Nature Medicine paper (which can be viewed by clicking here and scrolling down) we learn “S.L.H. [co-author Stanley Hazen] conceived of the idea, helped design the experiments, provided the funding for the study and helped draft and critically revise the manuscript”.

Scrolling further down and taking a quick look at the competing financial interests of the authors reveals the usual links to drug companies and research outfits that profit handsomely from the cholesterol sham:

“Z.W. [Zeneng Wang] and B.S.L. [Bruce Levinson] are named as co-inventors on pending patents held by the Cleveland Clinic relating to cardiovascular diagnostics and have the right to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics from Liposciences. W.H.W.T. received research grant support from Abbott Laboratories and served as a consultant for Medtronic and St. Jude Medical. S.L.H. [Stanley Hazen] and J.D.S. are named as co-inventors on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics patents. S.L.H. has been paid as a consultant or speaker by the following companies: Cleveland Heart Lab., Esperion, Liposciences, Merck & Co. and Pfizer. He has received research funds from Abbott, Cleveland Heart Lab., Esperion and Liposciences and has the right to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics from Abbott Laboratories, Cleveland Heart Lab., Frantz Biomarkers, Liposciences and Siemens.”
But my eyebrows were raised when I read about “patents” and “royalty payments…relating to cardiovascular diagnostics”. So I jumped onto Google and promptly discovered the following patent application: “TRIMETHYLAMINE-CONTAINING COMPOUNDS FOR DIAGNOSIS AND PREDICTION OF DISEASE

The applicant is seeking a patent for TMA tests that will purportedly determine whether people are at risk of developing CVD, diabetes, insulin resistance, metabolic syndrome, or fatty liver.
The applicant/owner of the patent is none other than The Cleveland Clinic Foundation, and the listed inventors are, lo and behold, Stanley Hazen, Bruce Levison, and Zeneng Wang.

And so we now see a potentially very lucrative income stream for these researchers if their carnitine/red meat/TMA/heart disease charade gains traction. Again, this kind of information gets left out of the hyperbolic fanfare accompanying the release of these types of studies, and it’s left up to people like me – you know, living out here in “left field” sipping Dom Pérignon in our jaccuzzis, being pampered by half our supermodel harems while the other half washes our collection of exotic supercars out on our imported Italian marble driveways - to point out the absurdities and blatant conflicts of interest in these intelligence-assaulting studies.

Folks, stand up to stupid…it really isn’t that hard.

Otherwise, in 20 years time, billions of your (and your children’s) taxpayer dollars are going to be handed over to clueless researchers attempting to uncover the ‘paradox’ of why red meat consumption has dramatically diminished yet heart disease still remains our number one killer, along with an ‘unexplained’ increase in anemia and chronic fatigue…

Related and Recommended Reading:

*Please note AnthonyColpo.com does not condone reckless driving on public roads. If the author was wealthy enough to own and thrash a Lamborghini, he would most assuredly do it on a racetrack. Or in a muddy paddock. Now that would be fun. Or maybe the giant car park next to Bunnings at…uh, never mind.

Disclosure Statement: The author of this article has absolutely no relationship, financial or otherwise, with the meat, dairy, or egg industries. The author does, however, eat red meat on a regular basis because it makes him feel much more energetic, rosy-cheeked and downright manly compared to that terribly misguided period long, long ago where he obtained most of his protein from fish and chicken.
1. Onder G, et al. Serum cholesterol levels and in-hospital mortality in the elderly. American Journal of Medicine, Sep, 2003; 115 (4): 265-271.
2. Horwich TB, et al. Cholesterol levels and in-hospital mortality in patients with acute decompensated heart failure. American Heart Journal, Dec, 2008; 156 (6): 1170-1176.
3. Stachon A, et al. Prognostic Significance of Low Serum Cholesterol after Cardiothoracic Surgery. Clinical Chemistry, 2000; 46 (8): 1114–1120.
4. Spinar et al. Baseline characteristics and hospital mortality in the Acute Heart Failure Database (AHEAD) Main registry. Critical Care, 2011; 15: R291.
6. Spagnoli LG, et al. Propionyl-L-carnitine prevents the progression of atherosclerotic lesions in aged hyperlipemic rabbits. Atherosclerosis, Apr 7, 1995; 114 (1): 29-44.
7. Davini P, et al. Controlled study on L-carnitine therapeutic efficacy in post-infarction. Drugs Under Experimental And Clinical Research, 1992; 18: 355-365.
8. Ghidini O, et al. Evaluation of the therapeutic efficacy of L-carnitine in congestive heart failure. International Journal of Clinical Pharmacology, Therapy and Toxicology, Apr, 1988; 26 (4): 217-220.
9. Delaney CL, et al. A systematic review to evaluate the effectiveness of carnitine supplementation in improving walking performance among individuals with intermittent claudication. Atherosclerosis. 2013 Mar 15. pii: S0021-9150(13)00179-2. doi: 10.1016/j.atherosclerosis.2013.03.004. [Epub ahead of print]

Anthony Colpo is an independent researcher, physical conditioning specialist, and author of The Fat Loss Bible and The Great Cholesterol Con. For more information, visit TheFatLossBible.net or TheGreatCholesterolCon.com
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