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.

The Ketogenic Diet Craze: Fat-Filled Lies, Part 1

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ketogenic diPicture this: a thick, juicy, tender eventeak grilled to perfection with melted butter glazed on top, gently dripping down the sides. Lying next to the steak there’s a side of dark green asparagus sautéed in coconut oil and dusted with a sprinkle of sea salt. Could a diet loaded with fat help you lose diet-resistant body fat that’s been taunting the seams of your dress pants and poking through buttons on your shirt? Will eating fat turn you into an all-star athlete? This is part 1 of a 2 part series on the ketogenic diet.

Here is what I will cover in this blog post:

  • What is the ketogenic diet?
  • Adverse health effects.

Here is what I will cover in tomorrow’s blog on this topic:

  • The issue with ketogenic research studies.
  • Is the ketogenic diet superior for losing fat?
  • How will the ketogenic diet affect muscle?
  • How will the ketogenic diet impact athletic performance?

What is the Ketogenic Diet?

For nearly a century, epileptic patients have used ketogenic diets to control seizures when common medications provide no relief. Scientists aren’t sure why following a ketogenic diet decreases the incidence and severity of seizures but it works.

The ketogenic diet contains – 80-90% of calories from fat, 15% from protein and 5% from carbohydrate (1, 2). Food choices may include heavy cream, bacon, eggs, non-starchy vegetables, mayonnaise and sausage while fruits, starchy vegetables, breads, pasta, cereal and other carbohydrate-rich foods are not allowed.

During the first several days on a ketogenic diet, your body’s limited supply of carbohydrate stored in liver and muscle tissue decreases dramatically. As a result, you will feel like you have mono – exhausted, with headaches and easy exercise will feel like you’re climbing Mount Everest (3). Once your stored carbohydrate has dwindled, ketones, formed from the breakdown of dietary fat, become the primary source of energy for brain and body. Ketogenic means “ketone forming.” It takes at least seven days to reach nutritional ketosis and several weeks to fully adapt to the diet (12). If you aren’t in nutritional ketosis (as measured by blood, urine or breath ketones; ketone levels > 0.5 mmol/L), then you aren’t following a ketogenic diet, you are on a low carbohydrate diet.

Adverse Health Effects from the Ketogenic Diet

Much of the research on adverse effects comes from studies in epileptic children since they have been on the diet for long periods of time. These studies show soon after starting a ketogenic diet, blood cholesterol levels and artery stiffness increase (4, 5). High total and LDL cholesterol are risk factors for cardiovascular disease (diseases of the heart and blood vessels). When arteries are stiff, they cannot expand as well in response to changes in blood pressure. Think of this like a garden hose when you turn up the water pressure, your hose either expands or the water bursts out of the space between the faucet and the hose. When arteries cannot open widely to accommodate increases in blood flow, blood pressure increases leading to microscopic tears on artery walls, development of scar tissue and the perfect surface for plaque buildup (6). Blood cholesterol levels returned to normal in patients who went off the diet and in those who stayed on it, they returned to normal after 6 to 12 months. Artery stiffness returned to normal after 24 months on a ketogenic diet.5 Studies in obese patients suggest ketogenic diets improve blood sugar and blood cholesterol levels over time, either due to the diet, weight loss from the diet, a combination of the two or carbohydrate restriction (7, 8). Lose weight, regardless of what you eat and blood cholesterol, blood pressure, inflammation, blood sugar and many other disease risk factors will improve.

Ketogenic diets are typically low in calcium, vitamin D, potassium, magnesium, folic acid and fiber. There are several potential consequences associated with consistently low intake of each of these micronutrients including softening of the bones, decreased bone density, muscle damage, muscle weakness or spasms, and abnormal heart rhythm. However, with careful planning, a fiber supplement, multivitamin and under the guidance of a physician who may prescribe potassium and sodium supplements (blood sodium could drop to dangerously low levels while on this diet), nutrient needs can be met. Also, to prevent constipation when on a ketogenic diet, a fiber supplement may be necessary along with more water / fluid intake then you are used to.

Here are some other potentially bad side effects from following a high fat diet:

  • Harm to your Brain. Studies in mice show a high fat diet, even when followed for as little as two months leads to chronic inflammation, sedentary immune cells in the brain – these cells typically act like janitors picking up trash and infectious compounds but when they become sedentary they stop doing their job, leading to cognitive impairment (9). Does this happen in humans and resolve over time? We don’t know.
  • Mad Bacteria in Your Gut. A diet with no probiotics (healthy bacteria) and low in prebiotics (certain types of fiber that the healthy bacteria much on for food keeping them happy) will likely change the composition of bacteria in your gut so you have more harmful and less beneficial bacteria.
  • Leaky Gut. High saturated fat meals increase bacterial toxins (endotoxins) in the intestines and intestinal permeability. In other words: leaky gut (10, 11). If you are on this diet, consider opting for foods lower in saturated fat and higher in unsaturated fats (liquid oils, avocado, nuts, seeds, olives).
  • Free radicals in overdrive? If you can’t eat a number of colorful foods including blueberries, beets, corn, oranges, and more, chances are you won’t get a wide array of antioxidant compounds to quench free radicals (compounds that are important for good health but can wreck your body when they aren’t tamed by antioxidants) as well as other plant-based compounds that keep your arteries, muscles and other parts of your body healthy. Will your body adapt? We don’t know at this time.

Are the side effects and potential negative side effects worth it if you can lose weight on this diet? Stay tuned for tomorrow’s post on how the ketogenic diet impacts body fat and athletic performance.

References

1 Freeman JM, Freeman JB, Kelly MT. The ketogenic diet: a treatment for epilepsy. 3rd ed. New York, NY: Demos Health; 2000.

2 Paoli A, Bianco A, Damiani E, Bosco G. Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases. BioMed Research International 2014, Article ID 474296, 10 pages, 2014.

3 White AM, Johnston CS, Swan PD et al. Blood ketones are directly related to fatigue and perceived effort during exercise in overweight adults adhering to low-carbohydrate diets for weight loss: a pilot study. J Am Diet Assoc 2007;107(10):1792-6.

4 Tanakis M, Liuba P, Odermarsky M, Lundgren J, Hallböök T. Effects of ketogenic diet on vascular function. Eur J Paediatr Neurol 2014;18(4):489-94.

5 Coppola G, Natale F, Torino A et al. The impact of the ketogenic diet on arterial morphology and endothelial function in children and young adults with epilepsy: a case-control study. Seizure 2014;23(4):260-5.

6 Cecelja M, Chowienczyk P. Role of arterial stiffness in cardiovascular disease. JRSM Cardiovascular Disease 2012;1(4):1-10.

7 Dashti HM, Mathew TC, Hussein T, Asfar SK, Behbahani A, Khoursheed MA, Al-Sayer HM, Bo-Abbas YY, Al-Zaid NS. Long-term effects of a ketogenic diet in obese patients. Exp Clin Cardiol 2004; 9(3): 200–205.

8 Volek JS, Feinman RD. Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction. Nutr Metab (Lond) 2005;2:31.

9 Hao S, Dey A, Yu X, Stranahan AM. Dietary obesity reversibly induces synaptic stripping by microglia and impairs hippocampal plasticity. Brain Behav Immun 2016 Jan;51:230-9.

10 Mani V, Hollis JH, Gabler NK. Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemia. Nutr Metab (Lond) 2013; 10: 6.

11 Lam YY, Ha CW, Campbell CR, Mitchell AJ, Dinudom A, Oscarsson J, Cook DI, Hunt NH, Caterson ID, Holmes AJ, Storlien LH. Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice. PLoS One 2012;7(3):e34233.

12 Paoli, A, Grimaldi K, D’Agostino D, Cenci L, Moro T, Bianco A, Palma A. Ketogenic diet does not affect strength performance in elite artistic gymnasts. J Int Soc Sports Nutr 2012;9:34.

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.

 

Is Coffee Good for You?

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CoffeeDrinking coffee will leave you dehydrated and geeked out on caffeine. For several decades we’ve been warned about America’s favorite beverage. Yet these dire warnings were largely based on assumptions rather than actual science. A growing body of evidence suggests your morning Cup O’ Joe may be good for you! Here’s a look at the latest research.

What’s in a Coffee Bean?

Coffee beans are actually seeds from coffee cherries. They are picked, dried, and roasted turning them from green to those familiar aromatic brown beans we know and love. It’s ironic that a beverage made from seeds has gotten such a bad rap. Green coffee beans are naturally rich in antioxidants including chlorogenic acids, compounds that are readily absorbed in the human body, have antibacterial and anti-inflammatory actions and are associated with many health benefits including a reduction in cardiovascular disease, type II diabetes and Alzheimer’s disease. Antioxidants protect plants from disease and pests. Some antioxidants also protect human cells from harm. Roasted coffee beans are loaded with antioxidants (contrary to popular belief, they are not destroyed during roasting) and scientists are slowly uncovering the metabolic fate of each type antioxidant as well as the potential health benefits associated with regular coffee intake.

Potential Health Benefits

A National Institutes of Health study published in 2012 found older adults who drank caffeinated or decaffeinated coffee were less likely to die from heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections. Those who drank over 3 cups per day had a 10% lower risk of death compared to those who did not drink coffee. Though this study only showed an association between coffee consumption and a decreased risk of death, it provided some reassurance to people who couldn’t seem to give up their favorite beverage. Studies published over the past three years lend strength to the relationship between regular coffee intake and a decreased risk of certain diseases.

Heart Health
A study published in the British Medical Journal’s publication Heart, examined diet and artery health in over 25,000 Korean men and women. Those who drank 3 to 5 cups of coffee per day were 19% less likely to have the first signs of atherosclerosis,  plaque buildup on artery walls, compared to those who were not coffee drinkers. Lower intakes were not associated with a reduction in plaque buildup. Drawbacks to this study: diet was examined at one point in time and study subjects were asked to recall their coffee intake over the previous year (people generally don’t recall their food / drink intake with great accuracy). Also, keep in mind this study showed an association between coffee intake and artery health, it doesn’t prove that coffee reduces plaque buildup on artery walls or that it can prevent cardiovascular disease. More research is needed to understand how coffee intake could potentially support heart health.

Cancer
A recently published study found individuals previously treated for stage III colon cancer who were regular coffee drinkers, consuming at least 4 cups of caffeinated coffee per day, had a 42% lower risk of recurrence of colon cancer and 33% lower risk of dying from the disease. This study found an association between coffee intake and decreased risk of colon cancer recurrence.

Research on coffee intake and risk of various cancers is mixed with some showing it is protective and others suggesting it may increase risk. Keep in mind there are many potential factors that impact cancer risk and risk of cancer recurrence with a sedentary lifestyle, high body fat and alcohol intake strongly associated with increased risk of certain types of cancer. Fruit and vegetable intake is associated with a decreased risk of some types of cancers. As for your Cup O’ Joe, time and more research, will tell us how America’s favorite beverage fits in the picture.

Should You Increase Your Coffee Intake?

All of these studies on regular coffee consumption include higher intakes. No benefits are noted for lower intakes – one to two cups per day. Keep in mind that some people should avoid or be cautious with caffeine intake including kids, teens, people with anxiety disorders, glaucoma, heartburn or cardiovascular disease. Also, pregnant women should avoid higher intakes of caffeine – more than 3 cups of coffee per day (regular sizes cups). Now about the caffeine – regular intake of moderate amounts of caffeine will not dehydrate you.

If you drink coffee in moderation, enjoy it! Don’t increase your intake based on these studies or start drinking if you aren’t a regular coffee consumer. Future research will tell us more about the many naturally occurring compounds in coffee, their actions in the body and the potential link between coffee and disease risk.

References
Heart 10.1136/heartjnl-2014-306663
New Eng J Med 2012;366:1891-1904.
J Nutr 2008;138(12):2309-15.
Mol Nutr Food Res 2005;49:274–84.
J Agric Food Chem. 2006;54:8738–43.
Am J Epidemiol 2002;156:445–53.
Biol Pharm Bull 2006;29:2236–4
Pest Manag Sci 2003 Apr;59(4):459-64.
J Clin Oncol 2015 Aug 17. [Epub ahead of print]