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.

Is Saturated Fat Good for You?

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Though largely driven by misinterpretation of the science and cherry-picked population studies, the “Butter is Back” movement comes with very persuasive sound bites followed by arrogant punctuation marks. No wonder so many people hopped on board the bandwagon while looking back, pointing fingers and shouting “health professionals have been misleading us for decades!” Yet the flawed reasoning behind the pro-saturated fat movement comes with a hefty price tag – you could be making food choices that, over time, will increase your risk for cardiovascular disease and type 2 diabetes.

Here’s what I’ll cover in this article:

  • Why is there so much confusion about saturated fat?;
  • The science behind saturated fats, cardiovascular disease (diseases of the heart & blood vessels) and type 2 diabetes;
  • Best food choices for heart health.

Why is there so Much Confusion about Saturated Fat?

There are a few reasons for the confusion about saturated fat (fat that is solid at room temperature such as butter, shortening, coconut oil and the fat on meat) and misinterpretation of the science. First off, some people group all saturated fatty acids (saturated fatty acids make up saturated fat) together as a team. However, there are several types of saturated fatty acids. Some raise LDL cholesterol (the kind that contributes to clogged arteries and is a risk factor for cardiovascular disease) as well as HDL cholesterol (“good” cholesterol, the kind that removes bad cholesterol; SN: drugs that increase HDL do not lower risk of heart disease so there is some considerable debate regarding the role of HDL), others don’t raise LDL cholesterol and some we aren’t quite sure about. Secondly, using population-based studies alone to draw conclusions about saturated fat intake and heart disease is misguided.  These studies are not designed to determine cause and effect (that’s the job of well-designed clinical trials) plus, there are inherent issues with the methods used in many of these studies.  Nutrition research is not easy, especially in humans living their life (those not in a metabolic ward where all factors are controlled and measured including diet and physical activity).

Lastly, some research studies (and the media) take the results way out of context. So, here’s the lowdown based on sound science:

The Science Behind Saturated Fat, Cardiovascular Disease and Type 2 Diabetes

  • There is no dietary requirement for saturated fat. Your body can make all of the saturated fatty acids it needs.
  • Foods high in saturated fat typically increase total, HDL and LDL cholesterol. However, the impact dietary saturated fat has on increasing LDL-cholesterol (the kind that contributes to clogged arteries and an inflammatory cascade in arteries) may depend on the amount of polyunsaturated fat (PUFAs) in your diet (as well as the type of saturated fatty acids consumed).
  • In general, replacing saturated fat with polyunsaturated fat (and monounsaturated fat though there is less evidence for monounsaturated fat) reduces LDL and total cholesterol, both risk factors for cardiovascular disease.
  • saturated fat and cholesterolOverweight, obesity and insulin resistance may reduce the beneficial effects (lowered LDL cholesterol) generally noticed from a reduction in saturated fat intake. *If obese or overweight, losing excess body fat (regardless of the type of diet used to lose the weight) has powerful effects on lowering risk for cardiovascular disease, some cancers, and type II diabetes.
  • Food contains a complex mixture of compounds that may affect cholesterol and cardiovascular disease risk (it is not just the fat). The food “matrix” matters.
  • Many factors impact how a food affects cholesterol and blood lipids (fats) including fats eaten at the same time, overall diet, and carbohydrate intake (and type of carbohydrates consumed – high fiber vs. foods high in added sugar with few other nutrients).
  • There are individual, genetic differences in response to saturated fat intake – your cholesterol might shoot up after eating a diet containing a diet high in the type of saturated fatty acids that raise LDL cholesterol and I might be able to get away with this diet without a problem (blame your genetics or consider it an opportunity to open your taste buds to foods containing less saturated fat; particularly the kind that is artery clogging).
  • Certain saturated fatty acids, or a diet high in saturated fat, may increase risk for type 2 diabetes.

Best Choices for Heart Health

If you are overweight, focus on losing excess body fat. Even small amounts of fat loss will improve health and risk factors for cardiovascular disease. If you have high total and LDL cholesterol, swap foods high in saturated fat for foods high in polyunsaturated fat (liquid oils, nuts, seeds, olives, avocados). Minimize your intake of foods high in added sugars and refined, white flour, carbohydrates. Instead, choose higher fiber carbohydrates as often as possible.

Don’t get sucked into the media headlines written by journalists who could sell ice to an eskimo. Butter isn’t back (for good health anyway). The bulk of your fat intake should still come from foods that are higher in polyunsaturated and monounsaturated fats. However, food is a complex matrix of compounds and therefore, some foods higher in saturated fat may have little to no impact on cholesterol and therefore fit into your diet while contributing to your vitamin and mineral needs and providing plant-based compounds important for good health.

References

Tholstrup T, Hoy CE, Andersen LN, Christensen RD, Sandstrom B. Does fat in milk, butter and cheese affect blood lipids and cholesterol differently? J Am Coll Nutr 2004;23:169–76.

Nestel P. Effects of Dairy Fats within Different Foods on Plasma Lipids. J Am Coll Clin Nutr 2008, 27(6): 735S–740S.

Hodson L, Skeaff CM, Chisholm WA. The effect of replacing dietary saturated fat with polyunsaturated or monounsaturated fat on plasma lipids in free-living young adults. Eur J Clin Nutr 2001; 55(10):908-15

Soerensen KV et al. Effect of dairy calcium from cheese and milk on fecal fat excretion, blood lipids, and appetite in young men. Am J Clin Nutr 2014;99(5):984-91.

 

Pros and Cons of Grain Brain, Wheat Belly and the Paleo Diet

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Diet books are tempting. They tell you the reason you’re overweight, what foods are “toxic” and how to get rid of them while strolling down the yellow brick road to lasting weight loss and good health. But there’s one main issue – many of these books aren’t based on scientific evidence but instead theories that are pulled out of thin air. “But my neighbor lost 50 lbs. following Paleo!” Well your neighbor cut out potato chips, beer and fried food in the process so of course he lost weight. The Paleo diet just gave him a convincing (even if scientifically inaccurate) reason to cut these foods out.

All of these diets have some pros and cons which I expand upon in this TV segment I did for Fox 5 and below the video:

https://www.youtube.com/watch?v=KQyfQ5hf_Qc&feature=youtu.be

Gluten is a protein formed from other proteins (gliadins and glutenins; any single wheat plant may produce > 100 gliadins and > 50 glutenins) naturally found in wheat foods when wheat flour is mixed with water (the mechanical action of mixing plus the water are necessary). Other proteins that are similar to gluten are found in barley (hordiens) and rye (secalins). Gluten gives dough it’s tough elastic structure and contributes to the light and fluffy texture of baked goods. If it sounds complex, it is but here are the important points:

  • Wheat today doesn’t have more gluten (or create more gluten when mixed with water) than varieties from 70 years ago unless the manufacturer adds vital wheat gluten back to the food itself (J Plant Reg 2012;6(1)).
  • Wheat breeding is complex and focuses on creating varieties of wheat that meet what food makers and consumers are looking for – a flaky pie crust or nice soft wheat bread for instance.
  • Gluten isn’t an easy to digest protein (there are many foods we eat that are not completely broken down) but, this isn’t a problem for most people – only those with celiac disease, wheat allergy and non-celiac gluten sensitivity (which might not be due to gluten alone but instead FODMAPs).

Paleo: What You Need to Know

The Paleo diet is based on one main principle: if we eat like our hunter-gatherer ancestors who lived between 2.6 million to 10,000 years ago, before the start of the agricultural revolution, we will avoid modern diseases such as heart disease as well as infections.

This diet is based on grass-produced meats, fish/seafood, fresh fruits and vegetables, eggs, nuts and seeds and “healthful” oils. Everything else is off limits.

Paleo’s Glaring Oversights:

  • there was no one single Paleo diet – diets varied based on region and time period (check out Christina Warinner’s TED talk on this)
  • In several regions, well over 10,000 years ago and possibly even a few million years ago, people ate grains and legumes.
  • Examination of mummies tells us that all people from this time period had clogged arteries.
  • The fruits, vegetables and meats we have today look nothing like what our ancestors ate (ex: fruit were small, tough and bitter).
  • Our ancestors hunted and gathered food – in other words, their daily lives included physical activity (both strength training which builds muscle and bone and aerobic exercise).

Paleo – What’s Good:

  • The Paleo diet cuts out our top sources of calories in the US including alcohol, desserts and sugar sweetened beverages.
  • It’s loaded with protein which will keep you full for a longer period of time after eating and help you build muscle.
  • Plenty of fruits and vegetables!

Paleo – What’s Bad:

  • No legumes (peas, beans, lentils and peanuts) – legumes are rich in fiber, potassium, magnesium (some), iron (some), antioxidants and more.
  • No grains. Grains provide a good bit of the fiber in the average American diet in addition to folate, other vitamins and antioxidants.
  • No dairy – our top source of bone building calcium and vitamin D. Now, I know what some self proclaimed nutrition experts will say here – people in Africa (or insert other country here) don’t consume much calcium and they don’t have as many cases of osteoporosis as we do in the U.S. Go to Africa, conduct dietary recalls (to see what they are indeed eating) and then follow a group of women around for several days. The women I met from Africa a few years ago were big and strong thanks to farm work (in their particular country the women do all the farming). They walked (far) with buckets of water on their head daily (fantastic way to build bone density in the spine!). I don’t know any females in the U.S. who get near the bone building activity these women are getting on a daily basis. So, this is far from a valid comparison. (SN: I haven’t even bothered to research the incidence of osteoporosis here vs. Africa because I’d be comparing a largely sedentary desk-sitting population to one with different genetics that also gets bone building activity for hours each day).

Diet magic? Follow anything that makes you cut calories and you’ll lose weight. Eat more protein and you’ll tend to lose more fat than muscle.