Sunday, February 19, 2017

No Guts, No Glory: TMAO




Narrator, “Royal Tenenbaum bought the house on Archer Avenue in the winter of his 35th year. Over the next decade, he and his wife had three children, and then they separated.”
The whimsical and story book feel of the film Royal Tenenbaums (2001) tells the story of an estranged family and their sudden unexpected reunion one winter. The brilliance and accomplishments of the three Tenenbaum children were erased by decades of betrayal, failure, and disaster. This was generally considered to be their father’s fault. Royal Tenenbaum (Gene Hackman) is childish, manipulative, and happy-go-lucky character.

Royal fakes stomach cancer to get his family’s attention in an attempt to remedy his relationships with his children (Chas, Margot, and Richie) and win back his wife (Etheline Tenenbaum). Falling back to his old habits of deceit and trickery ends up bringing the entire Tenenbaum family back under one roof after 17 years.

The instrumental version of the Beatle’s hit, “Hey Jude” plays as an eagle (freed by a young Richie Tenenbaum) flies across the New York City scenery.


Narrator, “All memory of the brilliance of the young Tenenbaums had been erased by two decades of betrayal, failure and disaster.”


INTRODUCTION:
Recent studies have found a link between the type of foods ingested and absorbed in the alimentary canal to future cardiovascular risks. These studies revealed that levels of TMAO in a patients’ blood serum can predict future heart attacks, stroke, or even death. With a simple blood test, levels of TMAO can be measured. In general, blood is composed of water, ions, proteins, and cells (i.e. nutrients (glucose), waste (ammonium), hormones, and gasses. Albumin (maintains osmotic pressure), antibodies, and fibrinogen (functions in blood clotting) are some of the other components found in blood.

TMAO is a compound produced by the liver after intestinal bacteria digest certain nutrients such as L-carnitine (found in red meat) and lecithin (found in egg yolks, meats, and full-fat dairy products). Regardless of an individual’s diet, lecithin is found in everyone’s intestines because it is a component of bile. The gut microbes are filled with lecithin which then has the potential for rising levels of TMAO. The liver synthesizes bile that travels to the gall bladder where bile is stored and this bile functions to solubilize fats in the duodenum of the small intestine. Jejunum and ileum together make up the rest of the small intestine. This is where nutrients and fats are absorbed through the vili and microvilli located here.

The microvilli increase the surface area for absorption by the capillaries located underneath the villi so that the nutrients can reach the circulatory system into the rest of the body for fuel and energy. Next, is the large intestine or LI where water is reabsorbed, feces is stored, and where colonic bacteria (i.e. “E-Coli”) eats any leftovers and produces vitamin K (necessary for blood clotting). The final stop is the remaining waste from the food bolus.

Uzi Tenenbaum, “Who's your father?”
Chaz, “His name is Royal Tenenbaum.”
Ari, “You told us he was already dead.”
Chaz, “Yeah, well, now he's really dying.”

Heart disease is the number one killer of lives in the United States where it accounts for a total of 25% of deaths. In order of the most common to least, the top ten leading causes of death in America are: heart disease, cancer, chronic lower respiratory disease, accidents/ unintentional injuries, stroke (cerebro-vascular diseases), Alzheimer’s disease, Diabetes Mellitus, Influenza and Pneumonia, Kidney Disease (such as nephritis, nephrotic syndrome, and nephrosis), and lastly, suicide (intentional self-harm). Together this top ten list makes up for 75% of all deaths of US individuals. Heart is also the leading cause of death worldwide.

Over half of deaths in men stems from their animal based and saturated filled diets that are common in heart disease patients. Saturated fats are solid at room temperature (aka: “solid fats”) and are found in animals such as beef, pork, and chicken. The building blocks that make up a saturated fat are tightly packed bonds that make the overall fat solid at room temperature. Butter and fat found inside various meats are just some examples of saturated fats.

 Because their bonds are loosely packed allowing for an overall fluid like structure, unsaturated fats are known to be liquid at room temperature. These fats are also called oils, however compared to saturated fats these oils are made up of mainly monounsaturated and polyunsaturated fats. Plants such as olives, nuts, and seeds tend to carry unsaturated fats within them. They can also be derived from fish.

Eli, “I wish you'd've done this for me when I was a kid.”
Richie, “But you didn't have a drug problem then.”
Eli, “Yeah, but it still would've meant a lot to me.”

The ‘Bad Fats’ are saturated because they clog the walls of your arteries which over time will block blood flow that is necessary to keep the heart beating. The end result of these events are typically stroke, heart attack, and possibly death. Heart disease is a term used to describe several conditions, many of which are related to plaque buildup in the walls of the arteries.
Other types of heart problems include angina (a condition marked by severe pain in the chest, often also spreading to the shoulders, arms, and neck, caused by an inadequate blood supply to the heart), arrhythmias (condition in which the heart beats with an irregular or abnormal rhythm), and heart failure. The key to preventing death from heart disease is to protect the heart and know the warning signs and symptoms of a heart attack.


Eli, “[to Richie] I always wanted to be a Tenenbaum, you know?”
Royal, “[quietly] Me too, Me too.”
Eli, “It doesn't mean what it used to though, does it?”
BACKGROUND INFORMATION:
When tri-methyl-amine is oxidized, Trimethylamine-N-oxide or TMAO is produced. This organic compound has a chemical formula of (CH3)3NO and is found in the class of amine oxides. TMAO is a metabolite produced by the bacteria in the stomach. It is solid and colorless in appearance. This metabolite (substance in the body that is necessary to maintain life) is commonly found in animals such as saltwater fish, sharks, rays, mollusks, and other crustaceans. When TMAO decomposes to tri-methyl-amine (or TMA), it’s characteristic odor of seafood degrading that one usually smells when walking past the oceans or fish markets. TMAO can be synthesized from trimethylamine by treatment with hydrogen peroxide:

H2O2 + (CH3)3N → H2O + (CH3)3NO

TMAO is biosynthesized from tri-methyl-amine, which is derived from choline. As of recently, researchers have discovered TMAO’s potential in functioning as a biomarker for cardiovascular risk in patients. Preliminary studies have shown that TMAO is produced by the body when egg yolks and red meat are consumed showing a correlation to the risk of heart disease. Researchers believe that it affects the body’s metabolism of cholesterol, leading to enhanced development of plaque on blood vessel walls, and can increase risk of heart disease. Studies showed that people with high TMAO levels had higher risk for heart attack, heart disease, and stroke. Consumption of a heart-healthy diet has been shown to reduce TMAO levels.

Narrator, “Margot Tenenbaum was adopted at age 2. Her father had always noted this when introducing her.”
Royal, “[at a dinner party] This is my adopted daughter, Margot Tenenbaum.”
When choline and carnitine, found in egg yolks and red meats, are metabolized by intestinal bacteria in our stomachs which then cause the liver to increase the production of TMAO (Tri-methyl-amine-N-oxide). Increased blood levels of TMAO are also linked to increased risk of heart attack and stroke. TMAO’s have been found to predict the risks of cardiac problems in people who do not have the traditional risk factors or blood tests.

The metabolism of dietary phosphatidylcholine found in the gut flora is the source of circulating TMAO. These TMAO levels served as the very predictors of patients’ death, MI, and stroke. The relationship between the levels of TMAO revealed that TMAO is directly linked to high levels of cholesterol that accumulates in the artery walls. In other words, the higher TMAO levels the more likely that the patient’s artery walls narrow due to plaque buildup. This then, increases their risks of experiencing a heart attack, stroke, and even death.

Royal, “He saved my life, you know. Thirty years ago. I was knifed at a bazaar in Calcutta, and he carried me to the hospital on his back.”
Ari, “Who stabbed you?”
Royal, “[Royal motions to Pagoda again] He did. There was a price on my head, and he was a hired assassin. Stuck me in the gut with a shiv.”
RESEARCH:
A link that doesn’t involve the influence of cholesterol has been discovered. Studies concluded that nutrients generally found in eggs, beef, and other animal foods (or simply known as ‘dietary choline’) are metabolized by bacteria in our gut which then converts it by the liver into TMAO.

Researchers used the ‘choline challenge’ to support their findings. They had a group of participants consume two large hard-boiled eggs with an egg yolk (egg yolk was high in lecithin) and a capsule of synthetic heavy isotope-labeled lecithin. The results revealed an increase of isotope-labeled TMAO in their blood levels and a direct correlation of TMAO to cardiovascular disease. TMAO circulates the blood and is the catalyst for inflammation which damages arteries, increases cholesterol, and builds walls of plaque. TMAO in its high levels prevents the body from discarding LDL, the bad form of cholesterol.

*The isotope acts like a chemical “label” that allowed the researchers to track what happened to the choline after it was ingested. Their data did indeed show an increase in both labeled TMAO and total TMAO (in urine and blood) in the volunteers after they consumed the eggs and supplemental choline.

Tennis Match Commentator #1, “That's 72 unforced errors for Richie Tenebaum. He's playing the worst tennis of his life. What's he feeling right now, Tex Hayward?”
Tex Hayward, “I don't know, Jim. There's obviously something wrong with him. He's taken off his shoes and one of his socks and... actually, I think he's crying.”


Researchers monitored TMAO levels of the study’s participants and tracked the number of cardiac events. The primary focus of these studies were based on the very mechanisms that trigger certain foods when they are consumed, making contact with the bacteria found in the stomach. Antibiotics that were given to the participants of the study was to change the chemistry of the gut flora. When the group was given a meal with antibiotics (which are poorly absorbed by the body to suppress gut bacteria), no TMAO was detected in their blood levels.

These results indicate that gut microbes do in fact play a vital role in TMAO production. There are many foods that elicit a TMAO response, including green vegetables, halibut and cod. Further research is need to test whether the changes in gut flora affect TMAO production after eating cod, halibut, and other foods.

Another team of researchers conducted a study with L-Carnitine which is a nutrient that has a similar structure to TMAO results in heart attacks and stroke risks. Both studies discovered that both red meat and full-fat dairy products contribute to inflammation and development of arterial disease of in certain patients.

In a second study, Dr. Hazen’s group showed that increased levels of TMAO in the blood are associated with cardiovascular disease (CVD). The researchers followed roughly 4,000 adults for three years. At the end of the study period, those with the highest levels of TMAO 2.5 times increased risk for a major cardiovascular event (heart attack, stroke, or death) than those with the lowest levels during three years of follow-up.

TMAO still predicted risk even after adjustments were made for risk factors such as diabetes, high blood pressure, and diabetes. The specific mechanism of action (the foods' ability to elicit a TMAO response being dependent on certain gut bacteria). Those with elevated TMAO levels increased their risk for heart attacks or strokes and increased their risk of death from these events. Researchers suggest dietary interventions may mitigate these risks by reducing TMAO levels.
 Raleigh, “[after reading a private investigator's research on Margot's background, which reveals she's been a smoker since she was 12, she married a man in Jamaica at 19, has had numerous affairs and one-night stands with men and women, including Eli Cash] She smokes.”

CONTROVERSY: 
The super-food of the heart, eggs, protect us against heart disease. For most of my life, I have only been told that eggs are a great part of a healthy diet because they are a great source of protein and necessary nutrients. Eating eggs frequently may even lead to lower cholesterol, prevention of heart disease, and a formation of larger less dense LDL and HDL (which protect against atherosclerosis). Instances where individuals consumed up to four or more eggs a week, compared to those who do not consume eggs, had lower levels of total blood serum cholesterol. Overall, these individuals reflected a reduced risk of cardiovascular disease. 

However, now that eggs are being reported by recent studies that they have a significant impact on the levels of TMAO, I began questioning these findings as I’m sure many others did too. Is it possible that there are foods that could have a greater impact on TMAO levels than eggs?

In addition to vitamins E, B12, and folate, studies have indicated that eggs and dietary cholesterol are not significant factors in heart risk. Even though eggs appear to increase levels of TMAO, where TMAO is now being linked to heart disease, eggs themselves are not associated with heart disease. So, what is it about eggs that must be good or even beneficial for the heart? What element found in eggs protects us from the observed dangers of high levels of TMAO?


 [Royal's fake terminal illness has been exposed and he is being thrown out of the house]

Royal, “Look, I know I'm going to be the bad guy on this one, but I just want to say the last six days have been the best six days of probably my whole life.”

Narrator, “Immediately after making this statement, Royal realized that it was true.”




Almost all species of seafood (although they have lower amounts of choline than eggs) have tri-methyl-amine and TMAO. Health reports have identified that the consumption of seafood increases TMAO levels in the urine. More studies are needed to address the process of how fish have a greater impact on TMAO levels than eggs do. In addition, how do other choline-rich foods compare to TMAO levels over time? Although consuming foods that can increase these levels, the body itself eliminates TMAO quickly and efficiently through urination. With no data confronting these questions, it is questionable whether these dietary factors alone can explain chronic elevations in TMAO.

Epidemiological studies are key to see if people’s eating habits correlating with the risk of chronic disease. These type of studies focus on populations which are selected specifically for their red meat consumption or populations that eat a lot of eggs. These groups were then followed up on to see if they have many cases of heart disease. Contemporary meat eaters consume a quite different meat product than rural populations who grew their own meat a century ago. Because of these new discoveries and recent research reporting that eggs can also provoke bacteria to increase one’s risk of heart attack in addition to consuming meat.

Besides choline-rich foods, there are other factors that can increase TMAO levels in the body. A malfunction in the kidneys can prevent the body from clearing TMAO levels through urination. Then there are cases where individuals with the highest levels of TMAO averaged in glomerular filtration at about 69 mL/min. Generally speaking, GFR’s between 60 to 89 mL/min correlates to a reduced capacity to filter blood through the kidneys (National Kidney Foundation’s guidelines).



The activity of the enzyme Fmo3, that functions in converting trimethylamine to TMAO in the liver, is affected by genetic factors, iron/ salt overload, and various common pharmaceutical drugs used to treat arthritis, GERD, and infections. Patients diagnosed with diabetes and/or metabolic syndrome, express upregulated Fmo3 activity because of the body’s resistance to insulin and insulin deficiency.

Royal, “You know, Richie, this illness, this closeness to death... it's had a profound affect on me. I feel like a different person, I really do.”
Richie, “Dad, you were never dying.”
Royal, “But I'm going to live.”
CONCLUSION:
Further studies are needed to support the hypothesis that TMAO serum levels are associated with heart disease and that dietary choline is a major cause of increased TMAO. More evidence is needed for people to begin to avoid choline-rich foods like eggs, liver, beef and pork. Studies on the function of the microbiota will be critical to understanding the role of the microbiota in human homeostasis and disease pathogenesis.

Individuals with high levels of TMAO are strongly advised to change their lifestyles by converting to an all Mediterranean (plant) diet, participating in physical activities to lose weight and lowering blood pressure and cholesterol. The Mediterranean diet has been shown to directly reduce TMAO levels, improving the health of gut microbiota in addition to limiting red meat, eggs, and full-fat dairy products.
Royal Tenenbaum's epitaph: Royal O'Reilly Tenenbaum 1932-2001 Died Tragically Rescuing His Family From The Wreckage Of A Destroyed Sinking Battleship

Links:
*Please note! These images are not mine. They were found on various tumblr, pinterest, google image sites! If any are yours please let me know so that I can give you credit for them! Also the people in the images have no relation to the diseases, illnesses, or cancers I write about. Thanks so much & enjoy~

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