Animal Proteins, TMAO and Heart Disease in Dogs
As the understanding of canine heart disease deepens, attention has turned toward the role of diet, particularly animal proteins, in the development of heart conditions such as myxomatous mitral valve disease (MMVD), dilated cardiomyopathy (DCM), and congestive heart failure (CHF). Central to this discussion is Trimethylamine (TMA), a compound metabolised into Trimethylamine N-oxide (TMAO), which has been implicated in the progression of these heart diseases. This article explores the connections between TMAO and canine heart disease, examining the evidence from scientific research, and discussing dietary strategies to mitigate these risks. We will also address the impact of raw versus cooked animal proteins and the role of animal fats in TMAO production.
Table of Contents
Introduction
Are Heart Diseases Increasing in Prevalence in Dogs?
- Epidemiology of Canine Heart Disease
- Breed Predisposition and Age Factors
What Are the Most Common Heart Diseases in Dogs?
- Myxomatous Mitral Valve Disease (MMVD)
- Dilated Cardiomyopathy (DCM)
- Congestive Heart Failure (CHF)
What are the Primary Causes of Heart Disease in Dogs?
- Genetic Factors
- Environmental and Lifestyle Factors
- Dietary Contributions
- Biochemical Overview
- Sources of TMA in the Canine Diet
What Foods Contain Trimethylamine (TMA)?
- High TMA-Producing Foods
- Impact of Diet on TMA Levels
What is Trimethylamine N-oxide (TMAO)?
- Metabolic Pathway of TMAO Production
- Role of Gut Microbiota
How is Trimethylamine N-oxide (TMAO) Produced?
- The Process of Oxidation in the Liver
- Influence of Gut Microbiota Composition
What is the Physiological Impact of TMAO in Dogs?
- Endothelial Dysfunction and Inflammation
- Cholesterol Metabolism Alteration
How Does TMAO Contribute to the Development of Myxomatous Mitral Valve Disease (MMVD)?
- Mechanisms of TMAO-Induced Valve Degeneration
- Evidence from Canine Studies
How Does TMAO Contribute to the Development of Dilated Cardiomyopathy (DCM)?
- Impact on Cardiac Muscle Function
- Role of TMAO in Cardiac Fibrosis
How Does TMAO Contribute to the Development of Congestive Heart Failure (CHF)?
- Fluid Retention and Cardiac Output
- Exacerbation of Existing Heart Conditions
Is TMAO Production Affected by the State of the Animal Protein – Raw or Cooked?
- Differences in TMA Production from Raw vs. Cooked Proteins
- Research Findings on Protein State and TMAO Levels
Do Animal Fats Increase the Production of TMAO?
- Relationship Between Dietary Fats and TMAO Production
- Impact on Heart Disease Risk
What are the Best Ways to Reduce the Production of TMAO in Dogs?
- Dietary Modifications
- Probiotic Supplementation
What Foods Reduce the Production of TMAO?
- Plant-Based Protein Alternatives
- High-Fiber Foods and Their Benefits
What are the Best Diets to Reduce the Development of Heart Conditions and Disease in Dogs?
- Designing a Heart-Healthy Canine Diet
- Long-Term Dietary Strategies
Introduction
Heart disease is a growing concern in the canine population, mirroring trends observed in human health. As veterinary science advances, so too does our understanding of the factors that contribute to these conditions. Among these factors, diet has emerged as a crucial element, particularly in relation to the consumption of animal proteins. Central to this discussion is Trimethylamine (TMA), a compound found in certain foods that is metabolized in the body to form Trimethylamine N-oxide (TMAO). TMAO has been implicated in the progression of various heart conditions, including myxomatous mitral valve disease (MMVD), dilated cardiomyopathy (DCM), and congestive heart failure (CHF) in dogs. This article provides an in-depth exploration of the scientific evidence linking TMAO to heart disease in dogs, examining how diet influences TMAO production and discussing strategies to reduce these risks.
Are Heart Diseases Increasing in Prevalence in Dogs?
Epidemiology of Canine Heart Disease
Heart disease has become increasingly prevalent in dogs, with an estimated 10% of all dogs suffering from some form of cardiovascular condition. The rise in heart disease cases is particularly noticeable in older dogs, as improvements in veterinary care have extended canine lifespans. Additionally, certain breeds are genetically predisposed to heart disease, which further contributes to the observed increase.
Study reported early MMVD (Type 1) in 9% of one-year-old dogs. Types 1 and 2 MMVD were recognisable only at necropsy and were found in 35% of dogs less than 5 years of age however, the lesions were thought to have clinical significance in less than 3% of the dogs. In dogs 9 years old and older, 97% had type 3 or 4 MMVD lesions which were considered clinically significant in 40% of the animals. Whitney Cardiovascular pathology. J Small Anim Pract. 1967; 8459–465) Other studies also confirmed the age effect on prevalence of the disease. Jones and Zook reported that the prevalence varied from 5% in dogs less than 1 year old to 75% in dogs 16 years old. (1) Similar age-related data were reported by Detweiler and Das and Tashjian in their studies. (2, 3)
Breed Predisposition and Age Factors
Small breeds, such as Cavalier King Charles Spaniels, are especially prone to developing myxomatous mitral valve disease (MMVD), while large breeds like Dobermans and Great Danes are more susceptible to dilated cardiomyopathy (DCM). Age is another critical factor, with the risk of heart disease increasing significantly in dogs over the age of seven.
What Are the Most Common Heart Diseases in Dogs?
Myxomatous Mitral Valve Disease (MMVD)
MMVD is the most prevalent heart condition in dogs, particularly affecting small breeds. It involves the progressive degeneration of the mitral valve, which leads to valve leakage (mitral regurgitation) and ultimately heart failure. This condition is characterised by a gradual worsening of heart function over time, often leading to congestive heart failure (CHF).
The two most common types of acquired heart disease include myxomatous mitral valve disease (MMVD), affecting 75% of dogs (4); and dilated cardiomyopathy (DCM), affecting approximately 16% of all heart diseased dogs. The prevalence of congenital heart disease in dogs varies between 0.46% to 1.6%.
Dilated Cardiomyopathy (DCM)
DCM primarily affects large breed dogs and is characterised by the dilation and weakening of the heart’s ventricles, which impairs the heart’s ability to pump blood efficiently. As the disease progresses, it can lead to arrhythmias, congestive heart failure, and sudden death. Recent studies have also highlighted a potential link between diet, particularly grain-free diets, and an increased risk of DCM.
Congestive Heart Failure (CHF)
CHF is not a disease itself but rather the end stage of many heart conditions, including MMVD and DCM. It occurs when the heart is no longer able to pump blood effectively, leading to fluid accumulation in the lungs (pulmonary oedema) or abdomen (ascites). CHF is a critical condition that requires immediate medical intervention to manage symptoms and prolong the dog’s life.
What are the Primary Causes of Heart Disease in Dogs?
Genetic Factors
Genetics play a significant role in the development of heart disease in dogs. Breeds like Cavalier King Charles Spaniels are predisposed to MMVD, while Dobermans are at higher risk for DCM. These genetic predispositions mean that some dogs are born with an increased risk of developing heart disease, regardless of other factors.
Environmental and Lifestyle Factors
Aside from genetics, environmental and lifestyle factors also contribute to the development of heart disease. Obesity, lack of exercise, and poor diet can all increase the risk of heart disease in dogs. Dogs that are overweight are more likely to develop heart conditions due to the added strain on their cardiovascular system.
Dietary Contributions
Emerging evidence suggests that diet plays a crucial role in the development of heart disease. Specifically, diets high in animal proteins, including carnitine, phosphatidylcholine, betaine, and trimethyl lysine have been linked to an increased production of TMA and subsequently TMAO, which are associated with cardiovascular conditions. (5, 6, 7) Understanding the dietary factors that contribute to TMAO production is essential for preventing heart disease in dogs.
What is Trimethylamine (TMA)?
Biochemical Overview
Trimethylamine (TMA) is a nitrogenous compound produced by the gut microbiota during the digestion of certain nutrients, particularly those found in animal products. TMA is a precursor to TMAO, which is implicated in the development of heart disease. The production of TMA in the gut is influenced by the types of bacteria present, as well as the diet.
Sources of TMA in the Canine Diet
TMA is primarily produced is a microbial metabolite produced from the bacterial metabolism of nitrogenous compounds such as carnitine, phosphatidylcholine, betaine, and l-carnitine, which are found in high amounts in meat, dairy, fish, and eggs (Karlin et al., 2019 and Marie Evans et al 2023):
- Red Meat: High in carnitine and choline, which are metabolised to TMA by gut bacteria. (8)
- Eggs: Particularly rich in choline, which also leads to TMA production. (9, 10)
- Fish: Especially cold-water species, which naturally contain high levels of TMAO. (10)
- Dairy Products: Contain carnitine and lecithin, another precursor to TMA.
What Foods Contain Trimethylamine (TMA)?
High TMA-Producing Foods
Foods that are high in choline, lecithin, and carnitine are the primary sources of TMA. These include:
- Red Meat: Beef, lamb, and pork.
- Eggs: Particularly egg yolks.
- Fish: Cod, haddock, and other cold-water species.
- Dairy Products: Cheese, butter, and other full-fat dairy products.
Impact of Diet on TMA Levels
The consumption of these foods leads to increased levels of TMA in the gut, which is then converted to TMAO in the liver. High levels of TMAO have been linked to an increased risk of heart disease in both humans and dogs. (11, 12)
What is Trimethylamine N-oxide (TMAO)?
Metabolic Pathway of TMAO Production
TMAO is produced when TMA, absorbed from the gut, is transported to the liver, where it undergoes oxidation by the enzyme flavin-containing monooxygenase (FMO). The resulting TMAO is then released into the bloodstream, where it exerts various physiological effects, many of which are linked to cardiovascular health.
Role of Gut Microbiota
The composition of the gut microbiota plays a crucial role in the production of TMA, and therefore TMAO. Certain bacterial species, such as those from the Firmicutes phylum, are more efficient at converting dietary choline, lecithin, and carnitine into TMA. This microbial activity is influenced by diet, with diets high in animal proteins promoting the growth of TMA-producing bacteria. (13, 14)
References:
- Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., Dugar, B., … & Hazen, S. L. (2011). Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature, 472(7341), 57-63.
How is Trimethylamine N-oxide (TMAO) Produced?
The Process of Oxidation in the Liver
Once TMA is produced in the gut, it is absorbed into the bloodstream and transported to the liver. In the liver, TMA is oxidised to TMAO by the enzyme flavin-containing monooxygenase 3 (FMO3). This process is highly efficient, meaning that even small amounts of dietary TMA can lead to significant increases in TMAO levels.
Influence of Gut Microbiota Composition
The production of TMA in the gut is influenced by the types of bacteria present. Diets high in animal proteins tend to promote the growth of bacteria that are proficient in TMA production. Conversely, diets rich in plant-based foods tend to support a more diverse microbiota that is less efficient at producing TMA, thereby reducing TMAO levels.
References:
- Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., Dugar, B., … & Hazen, S. L. (2011). Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature, 472(7341), 57-63.
- Tang, W. H., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., … & Hazen, S. L. (2013). Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. New England Journal of Medicine, 368(17), 1575-1584.
What is the Physiological Impact of TMAO in Dogs?
Endothelial Dysfunction and Inflammation
TMAO has been shown to induce endothelial dysfunction, which is a critical factor in the development of cardiovascular diseases. Endothelial cells line the blood vessels and are essential for maintaining vascular health. TMAO promotes inflammation within these cells, leading to increased expression of adhesion molecules and the recruitment of inflammatory cells, which can result in atherosclerosis. (15, 16, 17)
Cholesterol Metabolism Alteration
TMAO has a significant impact on cholesterol metabolism, promoting the accumulation of cholesterol in the arterial walls, which can lead to atherosclerosis. This alteration in cholesterol metabolism is one of the key ways in which TMAO contributes to the development of cardiovascular diseases, including those seen in dogs. (18, 19)
How Does TMAO Contribute to the Development of Myxomatous Mitral Valve Disease (MMVD)?
Mechanisms of TMAO-Induced Valve Degeneration
TMAO contributes to the development of MMVD by promoting inflammation and oxidative stress within the mitral valve. This leads to the progressive degeneration of the valve tissues, resulting in mitral regurgitation. Over time, this condition worsens, leading to congestive heart failure if left untreated.
Evidence from Canine Studies
Recent studies in canine models have shown a direct correlation between elevated TMAO levels and the severity of MMVD. These studies suggest that reducing TMAO levels through dietary interventions may slow the progression of MMVD in susceptible breeds. (20, 21, 22)
References:
- Li, X. S., Obeid, S., Klingenberg, R., Gencer, B., Mach, F., Räber, L., … & Tang, W. H. (2021). Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes: a prognostic marker for incident cardiovascular events beyond traditional risk factors. European Heart Journal, 42(10), 947-956.
How Does TMAO Contribute to the Development of Dilated Cardiomyopathy (DCM)?
Impact on Cardiac Muscle Function
TMAO has been shown to impair the energy metabolism of cardiac muscle cells, leading to reduced contractile function and the development of DCM. This impairment is particularly detrimental in breeds already predisposed to DCM, such as Dobermans and Great Danes. (23)
Role of TMAO in Cardiac Fibrosis
In addition to its effects on muscle function, TMAO also promotes cardiac fibrosis, a condition in which the heart muscle becomes stiffened due to the excessive deposition of extracellular matrix proteins. This fibrosis further impairs heart function, exacerbating the symptoms of DCM and leading to heart failure. (24, 25)
References:
- Karlin, E. T., Mohri, M., & Tang, W. H. (2019). Gut microbiota and cardiovascular disease: the role of TMAO. Nature Reviews Cardiology, 16(2), 96-108.
How Does TMAO Contribute to the Development of Congestive Heart Failure (CHF)?
Fluid Retention and Cardiac Output
TMAO has been linked to altered kidney function, leading to increased fluid retention. In dogs with pre-existing heart conditions, this can exacerbate the symptoms of CHF by increasing the volume of fluid that the heart must pump, which it may not be able to do effectively. (26, 27)
Exacerbation of Existing Heart Conditions
Through its effects on endothelial function, cholesterol metabolism, and fibrosis, TMAO directly contributes to the worsening of heart conditions that lead to CHF. Dogs with elevated TMAO levels are more likely to experience severe CHF symptoms and have a poorer prognosis.
References:
- Li, X. S., Obeid, S., Klingenberg, R., Gencer, B., Mach, F., Räber, L., … & Tang, W. H. (2021). Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes: a prognostic marker for incident cardiovascular events beyond traditional risk factors. European Heart Journal, 42(10), 947-956.
Is TMAO Production Affected by the State of the Animal Protein – Raw or Cooked?
Differences in TMA Production from Raw vs. Cooked Proteins
The state of animal protein—whether raw or cooked—can influence the production of TMA, and consequently TMAO. Cooking animal proteins often reduces the availability of choline and carnitine, the precursors to TMA, thereby potentially lowering TMAO production. However, some studies suggest that the cooking process can also create compounds that may increase TMA production in the gut.
Research Findings on Protein State and TMAO Levels
Studies have shown mixed results regarding the impact of cooking on TMAO levels. Some research indicates that raw diets may lead to higher TMAO production due to the presence of more bioavailable precursors, while other studies suggest that certain cooking methods might increase the formation of other compounds that enhance TMA production.
References:
- Tang, W. H., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., … & Hazen, S. L. (2013). Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. New England Journal of Medicine, 368(17), 1575-1584.
- He, R., Chen, L., & Liu, Y. (2017). The effect of cooking on the bioavailability of choline from food: a review. Journal of Food Science, 82(11), 2540-2547.
Do Animal Fats Increase the Production of TMAO?
Relationship Between Dietary Fats and TMAO Production
Animal fats, particularly those high in saturated fats, have been linked to increased TMAO production. This is due to their influence on the composition of the gut microbiota, promoting the growth of TMA-producing bacteria. High-fat diets have been shown to increase the levels of these bacteria, leading to higher TMAO production. (28, 29, 30)
Impact on Heart Disease Risk
Diets high in animal fats not only increase TMAO production but also contribute to other risk factors for heart disease, such as obesity and hyperlipidaemia. Reducing the intake of animal fats may therefore be beneficial in lowering TMAO levels and reducing the overall risk of heart disease in dogs. (41)
What are the Best Ways to Reduce the Production of TMAO in Dogs?
Dietary Modifications
One of the most effective ways to reduce TMAO production in dogs is through dietary modifications. This includes reducing the intake of foods high in choline, lecithin, and carnitine, such as red meat, eggs, and fish. Instead, focus on plant-based protein sources and high-fibre foods that support a healthy gut microbiota.(31, 32, 33, 34)
Probiotic Supplementation
Probiotics can also help reduce TMAO production by promoting a more balanced gut microbiota that is less efficient at producing TMA. Specific strains of probiotics have been shown to reduce the levels of TMA-producing bacteria, thereby lowering TMAO levels. (35, 36)
What Foods Reduce the Production of TMAO?
Plant-Based Protein Alternatives
Plant-based proteins, such as those found in lentils, beans, and soy products, are excellent alternatives to animal proteins. These foods do not contribute to TMA production and can help reduce TMAO levels in the body. (37, 38)
High-Fibre Foods and Their Benefits
High-fibre foods, such as vegetables, fruits, and whole grains, support a healthy gut microbiota that is less efficient at producing TMA. These foods also promote overall cardiovascular health by reducing cholesterol levels and supporting healthy digestion. (39, 40)
What are the Best Diets to Reduce the Development of Heart Conditions and Disease in Dogs?
Designing a Heart-Healthy Canine Diet
A heart-healthy diet for dogs should be low in TMAO-producing foods and high in nutrients that support cardiovascular health. This comprehensive approach includes not only managing macronutrient intake but also incorporating specific functional foods that promote a healthy gut microbiome, which is crucial for cardiovascular health.
Reducing Animal Protein Intake
Focus on limiting or replacing red meat, eggs, and certain fish with plant-based protein sources. Foods like lentils, chickpeas, quinoa, and tofu are excellent alternatives that do not contribute to TMAO production. These options provide high-quality protein without the precursors that lead to TMAO formation, thereby reducing the risk of heart disease.
Incorporating Omega-3 Fatty Acids
Omega-3 fatty acids, found in seaweed and algae, flaxseed, hemp seeds and chia seeds, have anti-inflammatory properties and can help protect the heart. Omega-3s are also known to support endothelial function and reduce the risk of arrhythmias.
High-Fibre Diet
A diet rich in dietary fibre supports a healthy gut microbiome, reducing the number of TMA-producing bacteria. Include vegetables like broccoli, spinach, and carrots, along with whole grains like brown rice, barley, and oats, which are beneficial for cardiovascular health. Fibre not only aids in digestion but also serves as a prebiotic, feeding beneficial gut bacteria that are essential for producing short-chain fatty acids (SCFAs), which have protective effects on the heart.
Incorporating Prebiotics, Probiotics, and Postbiotics
- Prebiotics: Prebiotics are non-digestible fibres that promote the growth of beneficial bacteria in the gut. Foods such as chicory root, garlic, and dandelion greens are excellent sources of prebiotics. These fibres nourish gut bacteria, leading to the production of SCFAs, which can lower inflammation and improve cardiovascular health.
- Probiotics: Probiotics are live beneficial bacteria that can be added to the diet to improve gut health. Strains such as Bacillus velezensis, Lactobacillus acidophilus and Bifidobacterium species are commonly included in dog diets and have been shown to improve gut flora balance, reduce gut permeability, and indirectly support cardiovascular health by modulating inflammation and immune function.
- Postbiotics: Postbiotics are by-products of probiotic bacteria and include compounds like SCFAs, peptides, and proteins that have health benefits. They play a role in reducing inflammation, enhancing gut barrier function, and supporting overall metabolic health. Incorporating postbiotics, either through specific supplements or by ensuring a diet rich in prebiotics and probiotics, can help lower the risk of heart disease.
References: Bonza: Best Herbs for Dogs Health, Bonza: Dog Food with Prebiotics, Probiotics, and Postbiotics.
Incorporating Beneficial Herbs
Certain herbs have been shown to support both gut health and cardiovascular function:
- Hawthorn Berry: Known for its cardiovascular benefits, hawthorn berry helps improve blood circulation, strengthens the heart muscle, and can aid in managing blood pressure. It also has antioxidant properties that support overall health.
- Turmeric: A potent anti-inflammatory herb, turmeric contains curcumin, which can help reduce systemic inflammation and support heart health. Turmeric also promotes a healthy gut microbiome by acting as a prebiotic.
- Ginger: Ginger has both anti-inflammatory and antioxidant properties, which help support cardiovascular health. It also aids digestion and can reduce nausea, making it a valuable addition to a heart-healthy diet.
Low-Fat Diet
Reducing the intake of saturated fats found in animal products can help lower TMAO levels and decrease the risk of heart disease. Instead, opt for healthier fats from sources like olive oil, avocados, and nuts. These fats are rich in monounsaturated and polyunsaturated fatty acids, which are beneficial for heart health. They also help reduce LDL cholesterol levels and support overall cardiovascular function.
References: The integration of these dietary elements—prebiotics, probiotics, postbiotics, and herbs—into a canine diet is supported by research showing their positive effects on gut and heart health. These functional foods help maintain a balanced microbiome, reduce systemic inflammation, and support cardiovascular health in dogs, making them an essential part of a heart-healthy diet plan.
Long-Term Dietary Strategies
For long-term heart health, it’s essential to maintain a consistent diet that supports cardiovascular function and overall well-being. Regularly incorporating the following into your dog’s diet can help prevent the onset of heart disease:
- Regular Monitoring: Work with your veterinarian to monitor your dog’s heart health and adjust their diet as necessary, especially as they age or if they belong to a breed predisposed to heart disease.
- Balanced Nutrition: Ensure your dog’s diet is balanced and provides all the necessary vitamins, minerals, and nutrients needed for overall health. Supplementing with specific nutrients like taurine (especially in breeds prone to DCM) may be beneficial under veterinary guidance.
- Avoiding Processed Foods: Minimise or eliminate highly processed dog foods that may contain hidden TMAO precursors or unhealthy fats. Opt for whole, natural foods whenever possible.
Conclusion
As heart disease continues to affect a growing number of dogs, understanding the impact of diet—specifically the role of TMAO—becomes increasingly important. While genetic predisposition and age are significant factors in the development of heart disease, the influence of diet cannot be ignored. Animal proteins, particularly those high in choline, lecithin, and carnitine, contribute to the production of TMA, which is then metabolised into TMAO, a compound linked to the development of serious heart conditions such as MMVD, DCM, and CHF.
Reducing the intake of TMAO-producing foods, incorporating plant-based proteins, and focusing on a diet rich in fibre and healthy fats can significantly reduce the risk of heart disease in dogs. By making informed dietary choices and working closely with veterinarians, dog owners can help their pets live longer, healthier lives free from the burden of cardiovascular disease.
