Is TMAO from Fish, Meat and Eggs Harmful?

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In another confusing nutrition story that should be titled “is there anything left for us to eat?” recent research threw a curveball. Fish, a staple of the Mediterranean diet, as well as meat and eggs may be doing more harm than good thanks to a compound called trimethylamine-N-oxide (TMAO). TMAO is found in fish and produced in the body after eating meat and eggs. TMAO is linked to greater risk for heart attack, stroke and death; yet the research isn’t crystal clear. Is it time to give up fish meat and eggs or ignore the recent media headlines?

This post will cover:

  • TMAO: More than a Gut Reaction—What gives us higher TMAO levels?
  • TMAO and health?
  • The bottom line

TMAO: More than a Gut Reaction

Blood levels of TMAO are ~ 50 times higher after eating fish compared to eggs or beef. The human body absorbs intact TMAO like the kind found in fish, easily. However, the human body’s production of TMAO, after eating foods containing the essential nutrient choline (found in eggs and meat) and the compound l-carnitine (found in meat and pork and in much smaller quantities in chicken breast and dairy products), depends on the makeup of bacteria in your gut, kidney functioning and genetics.

In one study, regular meat eaters produced more TMAO than a vegetarian did after eating steak (which contains ~ 180 mg of l-carnitine). After wiping out their gut bacteria with antibiotics, the carnivores didn’t produce any TMAO after consuming 250 mg l-carnitine. The makeup of gut bacteria in the habitual meat eaters was presumably responsible for greater TMAO production compared to the vegetarian, yet this was a small study and we don’t know anything else about the participants’ diet. Was it the meat that altered gut bacteria or something else in their diet? After all, a steady diet of red meat may mean double cheeseburgers on white bread with regular servings of French fries and soda on the side. This isn’t exactly the diet you want for promoting good bacteria in your gut.

Another study found blood levels of TMAO were greater in those with a less diverse makeup of microbes and greater amounts of a less healthy type of bacteria (firmicutes), compared to one that is healthy (bacteroidetes). A diet higher in saturated fat will promote this environment.

While bacteria seem to influence TMAO production from l-carnitine, l-carnitine also influences the makeup of gut bacteria. A study in mice found those with their gut bacteria wiped out thanks to antibiotics produced a different makeup of bacteria in the gut after consuming l-carnitine while also doubling the risk of plaque buildup in their arteries.

Higher TMAO levels come from:

  • Eating fish
  • Less diverse array of gut bacteria and increased levels of bad versus good bacteria
  • Consuming l-carnitine (mouse study)

TMAO and Health

A few human studies found higher blood levels of TMAO were associated with greater risk for heart disease. However, all research isn’t pointing in the same direction. One study in over 300 patients found blood TMAO levels were not associated with heart attack or heart disease over the course of eight years, following the initial test for TMAO. However, TMAO levels were higher in those with diabetes, patients with metabolic syndrome and those with declining kidney functioning. Another study examined over 800 people between the age of 33 and 55 and found blood TMAO levels were not associated with clogged arteries, insulin resistance (this comes before type 2 diabetes) and inflammatory markers or negative changes in blood lipids suggesting TMAO levels might not contribute significantly to the progression of clogged arteries. However, this study shows TMAO levels were significantly lower than in previous research, showing an association between TMAO and heart disease.

TMAO is considered a risk factor for cardiovascular disease. In those with type 2 diabetes, higher TMAO levels are associated with greater risk for death, heart attack, heart failure and unstable angina (chest pain). Also, higher levels of circulating TMAO are associated with higher risk of death in those with chronic kidney disease and greater risk of certain cancers. Yet, there are several confounding factors. Fish is the primary culprit for higher acute circulating TMAO levels, yet fish-based diets are associated with reduced risk for heart disease. Also, levels of TMAO are dependent upon disease state and the makeup of gut bacteria. Therefore, at this time it isn’t entirely clear which came first – does TMAO cause disease or does TMAO increase due to disease?

The Bottom Line

The story on TMAO isn’t crystal clear, so there’s no reason to avoid fish, meat and eggs in an effort to decrease TMAO levels. All three of these foods are good sources of several nutrients important for health. Though processed red meats are linked to higher risk of colorectal and stomach cancers, when cooked appropriately (lower, moist heat for example) red meat can fit into a healthy diet and deliver important nutrients including iron, zinc and vitamin B12. Eggs are an economical source of protein and contain many nutrients and compounds that contribute to health including two antioxidants important for eyesight.

Though there is no reason to completely avoid these foods, you can alter your diet to help diversify gut bacteria and also increase the amount of good versus bad bacteria. Probiotic rich foods such as yogurt and kefir with live and active cultures, miso soup, tempeh and other fermented foods contain good bacteria. Fiber-rich plant foods (fruits, vegetables, legumes) are important food sources for bacteria to thrive in your body.

Disclosure: this post was sponsored by USFRA. All views are my own and backed by research.

References
Koeth RA, Wang Z, Levison BS et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 2013 Apr 7.

Cho CE, Caudill MA. Trimethylamine-N-Oxide: Friend, Foe, or Simply Caught in the Cross-Fire? Trends Endocrinol Metab 2016 Nov 4. [Epub ahead of print]

Cho CE, Taesuwan S, Malsheva OV, Bender E, Tulchinsky NF, Yan J, Sutter JL, Caudill MA. Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: A randomized controlled trial. Mol Nutr Food Res 2016 Jul 5.

Carnitine. Health Professional Fact Sheet, NIH. https://ods.od.nih.gov/factsheets/Carnitine-HealthProfessional/

Mueller DM, Allenspach M, Othman A, Saely CH, Muendlein A, Vonbank A, Drexel H, von Eckardstein A. Plasma levels of trimethylamine-N-oxide are confounded by impaired kidney function and poor metabolic control.Atherosclerosis 2015;243(2):638-44.

Meyer KA, Benton TZ, Bennett BJ, Jacobs DR Jr., Lloyd-Jones DM, Gross MD, Carr JJ, Gordon-Larsen P, Zeisel SH. Microbiota-Dependent Metabolite Trimethylamine N-Oxide and Coronary Artery Calcium in the Coronary Artery Risk Development in Young Adults Study (CARDIA). J Am Heart Assoc. 2016 Oct 21;5(10). pii: e003970.

Does Meat Cause Cancer?

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According to a report released today, processed meat is carcinogenic (cancer causing – see the definition below for more detail). After considering more than 800 studies examining the association between meat and cancer, the World Health Organization’s International Agency for Research on Cancer (IARC) Working Group classified processed meats as Group 1, carcinogenic. They based this on convincing evidence from population based studies that eating processed meats causes colorectal cancer. Yet the results aren’t as crystal clear as they seem.

What is Red Meat and Processed Meat?

Red meat – unprocessed mammalian muscle meat – beef, pork, veal, lamb, mutton, horse or goat meat, including minced or frozen meat

Processed meat – meat that is transformed through salting, curing, fermenting, smoking or other processes to preserve the meat and enhance flavor. Processed meats can include other meats or meat byproducts such as blood. Hot dogs, sausages, corn beef, beef jerky and canned meat are all examples of processed meat.

Carcinogenic – compounds that are carcinogenic “do not cause cancer at all times, under all circumstances. Some may only cause cancer in people who have a certain genetic makeup. Some of these agents may lead to cancer after only a very small exposure, while others might require intense exposure over many years,” states the American Cancer Society.

What they Found

Processed Meat:
Though they considered 800 studies, their conclusions were drawn upon 18 cohort studies (this is when scientists follow a group of people that don’t have the disease – in this case cancer – over time to see who does and who doesn’t develop cancer). Twelve of the 18 studies reported positive associations between processed meat consumption and colorectal cancer. Six out of 9 case-control studies (where they look at the diet of people with cancer and compare it to the diet of people without cancer) reported a positive association and a meta-analysis (statistical approach to combining results from several studies) of 10 cohort studies reported a statistically significant dose-response relationship with an 18% increase in risk for every 50 gram (1.5 oz. or about the size of ½ of a deck of cards) of processed meat eaten daily. Yet Dr. Kurt Straif, Head of the IARC Monographs Programme stated “for an individual, the risk of developing colorectal cancer because of their consumption of processed meat remains small, but this risk increases with the amount of meat consumed.” Recent estimates suggest approximately 34,000 cancer deaths per year can be attributed to diets high in processed meats.

Red Meat:
The Working Group classified red meat as “probably carcinogenic to humans” while stating there is “limited evidence in human beings for the carcinogenicity of the consumption of red meat.” If those two statements sound like they contradict each other, here’s why:

The largest body of data they found was from 14 cohort studies (where they follow a group of people that don’t have the disease – in this case cancer – over time to see who does and who doesn’t develop cancer). Seven of the 14 studies showed higher consumption of red meat (as compared to lower consumption of red meat) was positively associated with colorectal cancer. Seven out of 15 case-control studies (where they look at the diet of people with cancer and compare that to the diet of people without cancer) found higher consumption of red meat was positively associated with colorectal cancer compared to lower intake of red meat. “No association was seen in  several high quality studies.” The author suggests that bias and confounding couldn’t be ruled out (other diet and lifestyle variables may have affected the results.

What Makes Processed Meat Carcinogenic?

When meat, fish, or poultry (chicken, turkey, ducks, geese) are cooked over high temperatures, chemical compounds that are known or suspected carcinogens (cancer causing) including N-nitroso-compounds (NOC), polycyclic aromatic hydrocarbons (PAH), advanced glycation end products (AGEs) and heterocyclic aromatic amines (HCA) are formed. High and dry heat including frying, grilling and barbecuing are the worst combination for the production of these chemicals. The 2-page report mentions some of these compounds as “mechanistic evidence” supporting their conclusions while also stating that we don’t know how cancer risk is increased by processed and red meat. (The full report won’t come out for several months).

N-nitroso-compounds (NOC) are found in nitrate-cured meats, smoked foods (fish or meat), malt in beer and whiskey production, pickled vegetables and foods stored under humidity leading to fungi that generate nitrosamines.

Polycyclic aromatic hydrocarbons (PAH) are formed when fat and juices from meat grilled over an open flame drip onto the fire, resulting in flames, and PAHs adhering to the surface of the meat. Smoking meats also leads to the formation of PAHs. PAHs are also found in air pollution.

Advanced glycation end products (AGEs) are harmful compounds formed during dry heat cooking. Though many foods contain AGEs, meats fried or cooked over dry heat have significantly more AGEs than any other food. AGEs accumulate in the human body, affect cell functioning and may contribute to insulin resistance, type 2 diabetes and, as the name implies, aging.

Heterocyclic aromatic amines (HCA) are formed when amino acids, sugars and creatine react at high temperatures. When meat, fish, pork and poultry are cooked at higher temperatures for a longer period of time, more HCAs are formed.

HCAs and PAHs must be metabolized by specific enzymes (a process called bioactivation) before they can damage DNA. Yet the activity of these enzymes varies between people and therefore, one’s risk of developing cancer due to HCA and PAH exposure depends on how they metabolize these compounds.

What this Report Does Not Tell Us

IARC Working Groups examine if exposure to a specific food or compound could cause cancer but does not tell us how likely we are to get cancer. Also, there are many known human carcinogens (UV light – including the UV light in those LEDs lights used to set gel nails, alcohol, the mineral oil you use on wood cutting boards and more) – some many cause cancer after little exposure while others take a lifetime of exposure. Many factors influence the development of cancer including age, gender, family history, and other lifestyle factors (tobacco and alcohol use, weight, diet, physical activity).

How Much Processed & Red Meat is Too Much?

Cancer is a complex disease and no single food causes, cures or prevents cancer. However, as stated by the American Institute for Cancer Research (AICR):

  • A modest amount of red meat does not raise colorectal cancer risk.
  • Eating more than 18 ounces of cooked red meat per week increases the risk of  colorectal cancer.
  • Eating small amounts of processed meat regularly increases risk (of colorectal cancer).

AICR recommends avoiding processed meats and eating no more than 18 ounces of red meat per week (3 oz. = about the amount in a deck of cards). I also suggest making potentially better choices (see the infographic below and the 2nd to last paragraph of this blog post). What about HCAs, PAHs and other compounds? Here’s how you can decrease your intake of these compounds:

cooking meat
Where does meat processed without nitrates fit in? We don’t know. If they are processed without nitrates then they should  presumably contain few to no NOCs making them a better choice than meats processed with nitrates. However, I couldn’t find a single study comparing the compounds in meats produced without nitrates to their counterparts produced with nitrates.

If you aren’t preparing your food at home, take a close look at how it was prepared and cooked so you can minimize your intake of these compounds. If you don’t plan on cutting out processed meats, at the very least, limit your intake of sausage, ham, bacon, hot dogs, pepperoni, pastrami, bologna, corned beef, deli/luncheon meats, salami, nitrite-treated meat or meat products as well as meat preserved by smoking, curing or salting, all of which could increase your risk of cancer.

Disclosures: None, I have no connection to any red meat commodity boards, stock in red or processed meat companies (though I should look up the shorts or consider buying on a dip) or emotional connection to cows, pigs, horses, red or processed meats 🙂

References:
National Cancer Institute. 
American Institute for Cancer Research
Medline Plus.
Nutr Cancer 2008;60(2):131–144.
J Food Sci 2008;73(6):T100-5.
Cancer Sci 2010;101(2):508-16.
Cancer Epidemiol Biomarkers Prev 2012;21(6):905-15.
Int J Cancer 2014;134(1):125-35.
J Am Diet Assoc 2010;110(6):911-16.
Curr Diab Rep 2014;14(1):453.
Ann N Y Acad Sci 2005;1043:533-44.

Putting a Fork in Forks Over Knives

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The war over good food, bad food grew larger when Forks Over Knives hit the movie theaters in 2011. Forks Over Knives, which means “use a dinner fork instead of going under the knife (surgery for chronic diseases)” contained some good information, some misleading information and left a lot of gaps in the research. So here are my good and bad impressions of this documentary.

The entire film was devoted to the supposed evils of animal based proteins. That’s right, all animal protein is bad. They didn’t distinguish between fish, red meat, packaged meats, turkey breast, free-range eggs, low fat dairy or any other type of animal protein. Instead, they lumped them into one large category of food you should avoid at all costs while adopting a plant-based diet. Go Vegan or Go Home!

Now don’t get me wrong, I’m in favor of a diet loaded with fruits and vegetables but I’m first and foremost realistic and research-based. In the words of my friend and amazing colleague Sally Hara, I can work within almost anyone’s food religion unless it is absurd and harmful to them. But, I will move clients in the right direction based their lifestyle, goals, medical history and training program.

That being said here are the gaping holes I found in this documentary:

China study – this study and others like it cannot prove cause and effect. Being longitudinal studies, they cannot answer the question “ does eating meat cause disease.” The film also failed to talk about any confounding variables. Were any other factors tied to disease – such as, obesity?

All animal proteins are bad. There are so many things wrong with this statement that I’m not sure where to begin. But, first and foremost, since I’m a fan of people being functional into old age, preventing osteoporosis and sarcopenia (the gradual loss of muscle mass with age), I know the power of protein and high quality protein – the kind that is easy to digest and gives muscle tissue the amino acids it needs. Which proteins are on the top the list? Dairy, whey, casein (both are dairy proteins), eggs and soy. In fact, if you are an athlete, mix and match these and you may get even better results according to ground-breaking research presented last month (pick up the June 2012 copy of Physique 3D for my article on this study).

Protein also keeps you satiated so you eat less – add protein to every meal and you may find over time that weight management is easier. Sure, they talked about stretch receptors in your stomach, but there’s more to satiety than just how full your stomach is (ask anyone on a fruit and vegetable fast, because the people who have done this tell me they are hungry all the time!). You will stay full for a longer period if you add a good quantity of protein to that veggie rich meal. And I’m not talking a measly 12 grams. Aim for 30 grams at each main meal (unless you are on a protein restricted diet for some reason).

What about colon cancer and meat? Valid point. But, it’s red meat, and possibly just the way you cook it that is the issue.

You Can Build a Strong Body on a Vegetarian Diet

In an attempt to tell us you can build a healthy, strong body on a vegan diet, the filmmakers gave us two examples, one was the firefighter son of one of the featured physicians. The other, UFC fighter Mac Danzig. I’ve worked with vegetarian athletes, including one who is at the top of his sport but he includes BCAA supplements, whey and eggs in his diet and I’m willing to bet that Mac adds BCAAs at a minimum. Can you perform well and get all the nutrients you need on a vegan diet? Possibly but, it depends on your sport, your body and your training. Check out Tony Gonzalez’s trial of veganism here.

Last I’ll leave you with the reaction of one of my friends after seeing this movie “those two physicians look emaciated. Do you think if they actually consumed some animal protein they may look healthier and have more muscle on their bodies?” Yep, I sure do.

In summary, I’m all in favor of adding fruits, vegetables and whole grains. Most of us do not get enough of these every day. I also think a vegetarian diet can be healthy if done correctly. However, this movie left glossed over the science (but, pay attention to what Connie Diekman says in it) and left many some very important points.

If you’ve watched Forks Over Knives, I’d love to hear your impression of this documentary!