Heart disease is a significant global health concern, affecting millions of lives each year. In the United States, heart disease is a leading cause of death, claiming a life every 33 seconds. While traditional risk factors such as diet, exercise, and genetics have a significant impact on the development of heart disease, emerging research suggests an intriguing link between gut health and cardiovascular well-being. The human gut, home to trillions of microbes, influences various aspects of our health, including immune function, metabolism, and inflammation. As the connection between gut and heart health has become more well-understood, it has opened the door for new preventative and treatment strategies focusing on the gut-heart axis.
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Understanding the Heart-Digestive Connection
This gut-heart connection is an emerging concept recognizing the interconnectedness of the gastrointestinal and cardiovascular systems and their bidirectional influence on each other's function. Digestive symptoms are common in individuals with heart disease. These symptoms can include abdominal pain, bloating, constipation, diarrhea, and indigestion. Reduced blood flow to the digestive organs, often seen in heart conditions, can result in ischemia, leading to abdominal discomfort Medications prescribed for heart diseases, such as diuretics and beta-blockers, may contribute to GI side effects, including changes in bowel habits. Fluid retention associated with heart failure can lead to abdominal bloating (70, 79).
Gastrointestinal (GI) diseases, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), gastritis, and non-alcoholic fatty liver disease (NAFLD), have been linked to the development of cardiovascular diseases, including coronary artery disease (CAD), peripheral artery disease (PAD), and hypertension. The association between these conditions can be explained, at least in part, by the gut microbiome’s influence on inflammatory and metabolic pathways.
The Role of Gut Microbiota in Heart Disease
The gut microbiome is a community of microorganisms, primarily bacteria, but also including fungi, viruses, and archaea, that reside within the gastrointestinal tract. Its impact on human health extends beyond just digestive function, also influencing immune responses, systemic inflammation, and metabolism. Dysbiosis, or disruptions in the composition of the microbiome, and impaired gut barrier function have emerged as factors linked to the development and advancement of cardiovascular diseases.
About 70% of immune cells are located in the gut where they interact with the microbial organisms that reside there, which affects how our immune system develops and functions. Some organisms promote the development of immune cells called regulatory T cells, which help to control immune responses and can prevent excess inflammation, while others stimulate the activity of immune cells involved in promoting inflammation. Furthermore, gut microbes also influence gut barrier function. Dysbiosis promotes intestinal permeability, or leaky gut, allowing potentially potentially harmful substances, such as undigested food particles and toxins, to enter the bloodstream, triggering immune responses and inflammation. Systemic inflammation induces endothelial dysfunction and plays a critical role in both the development and progression of heart disease.
The microorganisms in the gut also produce metabolites, including short-chain fatty acids (SCFAs) such as butyrate, acetate, and propionate. SCFAs have anti-inflammatory properties and also regulate insulin sensitivity, blood pressure, and lipid metabolism, positively impacting endothelial function. Additionally, gut bacteria produce trimethylamine N-oxide (TMAO) through the metabolism of dietary compounds like choline and carnitine. TMAO may promote heart disease by influencing cholesterol metabolism and promoting endothelial inflammation, the formation of foam cells, and the development of arterial plaques. Bile acid composition is influenced by the gut microbiome, with primary bile acids being metabolized into secondary bile acids in the colon. Reabsorbed secondary bile acids activate receptors involved in immune responses and lipid metabolism.
The gut microbiome has the potential to either promote or impede cardiovascular health through its effects on inflammation and metabolism. A diverse and well-balanced microbiome can protect against heart disease through its production of advantageous compounds like SCFAs. Conversely, an imbalanced or dysbiotic microbiome may have negative consequences, increasing the production of potentially inflammatory compounds like TMAO. Disturbances in the gut microbiome have been linked to a number of cardiovascular diseases including heart failure, atherosclerosis, hypertension, coronary artery disease, and myocardial infarction (heart attack).
Functional Medicine Lab Assessments for Gut and Heart Health
Recognizing the importance of the gut-heart axis, functional medicine tests reveal potential links between gastrointestinal issues and cardiovascular risk. Armed with this information, healthcare providers can create personalized treatment strategies that address the root causes of heart disease related to gastrointestinal dysfunction, such as dysbiosis, inflammation, and nutritional deficiencies.
Comprehensive Stool Analysis
The GI Effects Comprehensive Profile by Genova Diagnostics is a stool test that analyzes the microbiome's diversity and composition to assess for any dysbiosis. It also measures metabolites, such as SCFAs, and inflammatory markers like calprotectin. Zonulin, available as an optional add-on, is a possible indication of intestinal permeability when elevated.
Intestinal Permeability Screen
Cyrex’s Array 2, or Intestinal Antigenic Permeability Screen, measures biomarkers related to intestinal barrier function. Antibodies to components of the intestinal barrier, such as zonulin and tight junction proteins, or lipopolysaccharide (LPS), a bacterial endotoxin, are indicative of intestinal permeability.
CardioMetabolic Panel
The CardioMetabolic Profile by Doctor’s Data evaluates risk factors for cardiovascular disease, such as lipids and inflammatory markers, as well as metabolic factors associated with metabolic syndrome and type II diabetes. Metabolic syndrome and diabetes are associated with an increased risk of cardiovascular disease. Early detection of metabolic syndrome or diabetes through these panels allows for timely intervention and management, helping to mitigate the risk of cardiovascular complications.
TMAO
Boston Heart Diagnostics offers a single-marker test measuring TMAO in the blood. Individuals with high TMAO levels are at an increased risk of major cardiovascular events, such as heart attack, stroke, and death, a risk that persists independently of other common risk factors (49, 82).
Nutritional Evaluation
Conditions such as dysbiosis and intestinal permeability are associated with nutritional insufficiencies (3, 35). Nutrients function synergistically within the body, acting as cofactors to support the functions of various body systems, including cardiovascular and metabolic pathways. Insufficient intake of certain nutrients such as vitamin A, magnesium, selenium, and vitamin D are commonly seen in heart failure patients. Furthermore, low vitamin D levels are associated with an increased risk of cardiovascular disease and magnesium levels are inversely associated with the incidence of coronary heart disease, hypertension, and type 2 diabetes.
SpectraCell’s Micronutrient Test analyzes the level of 31 vitamins, minerals, and other nutrients to identify any nutritional insufficiencies. By measuring intracellular levels, it offers insights into how well the body is absorbing and utilizing nutrients at the cellular level.
Organic Acids
Metabolic processes in the body produce organic acids as by-products, which can then be measured in the urine. The Organic Acids test (OAT) by Mosaic Diagnostics provides insights into intestinal health by detecting issues like yeast or bacterial overgrowth. It also offers valuable information about nutritional status and mitochondrial function. Citric acid cycle intermediates, when elevated, can be a sign of mitochondrial dysfunction and oxidative stress. Cardiac tissue has a high concentration of mitochondria and mitochondrial dysfunction and oxidative stress are thought to contribute to cardiovascular diseases.
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The Impact of Lifestyle Factors
Lifestyle factors play a significant role in both digestive wellness and heart health. The foods we consume directly influence risk factors for heart disease, such as inflammation and lipid levels. The Western diet is characterized by excessive consumption of processed foods, red meat, sweetened beverages, and processed carbohydrates, and low intake of fruits and vegetables. This type of dietary pattern has been associated with changes to microbiome composition and an increased risk of cardiovascular and gastrointestinal diseases.
During stress, the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis are activated resulting in the release of catecholamines and hormones, like cortisol. Stress is associated with the development of various GI diseases, including IBD, IBS, ulcers, and gastroesophageal reflux disease (GERD). Stress affects multiple facets of gastrointestinal function including motility, visceral sensitivity, intestinal barrier function, microbiome composition, and mucosal blood flow. Stress and cortisol also affect lipid levels, blood sugar metabolism, inflammation, and blood pressure, all of which are important factors in the development of heart disease (44, 84, 86). Research has linked emotional stress to an increased risk of subsequent cardiovascular events, including myocardial infarction and heart failure (83).
Sedentary behavior and physical activity are major modifiable risk factors for heart disease, but 50% of adults in the United States reported spending more than 9.5 hours per day being sedentary. Physical activity regulates lipid levels, blood pressure, inflammation, and blood sugar and insulin levels, promoting optimal heart health.
Adequate sleep is an important part of maintaining optimal health, but one-third of US adults do not get the recommended 7-9 hours of sleep each night. Poor sleep contributes to heart disease risk factors such as inflammation, obesity, and high blood pressure. It can also negatively impact other aspects of individuals' lifestyles, like dietary choices. Short sleep durations of less than 7 hours are associated with an increased risk of coronary events.
Nutritional Strategies for Supporting Digestive and Heart Health
Anti-inflammatory dietary strategies stand out as powerful tools in supporting the gut-heart axis. By emphasizing whole, nutrient-dense foods and minimizing foods such as high-fat red and processed meats, ultra-processed foods, refined grains, sugary foods and beverages, and excessive amounts of alcohol, these types of diets can help reduce inflammation. Incorporating a variety of colorful fruits and vegetables rich in phytonutrients and antioxidants can also combat inflammation and oxidative stress. High-fiber foods, such as fruits, vegetables, whole grains, and legumes, help to manage cholesterol levels and act as prebiotics, supporting microbiome diversity and abundance. Heart-healthy fats, such as those found in avocados, nuts, and olive oil, can promote cardiovascular health by improving lipid profiles. Furthermore, omega-3 fatty acids, found in foods like fatty fish, walnuts, and flaxseeds, demonstrate positive effects on both digestive and heart health. Omega-3s possess anti-inflammatory properties, balance lipid profiles, modulate microbiome composition, and help maintain optimal barrier function, promoting optimal gastrointestinal and cardiovascular health (46, 76, 85).
The Mediterranean diet stands out as a well-researched dietary regimen for protecting against heart disease. This diet emphasizes a rich array of whole foods, incorporating an abundance of fruits, vegetables, whole grains, legumes, nuts, and seeds. Higher adherence to traditional Mediterranean diet principles is associated with improvements in risk factors, as well as lower rates of cardiovascular diseases and mortality. The Mediterranean diet also improves microbiome composition and reduces gastrointestinal inflammation. The Institute for Functional Medicine’s (IFM) CardioMetabolic Food Plan is a modified Mediterranean diet strategy designed specifically for individuals with cardiometabolic risk factors or disease. It follows the basic tenets of the Mediterranean diet with an additional emphasis on specific therapeutic foods and phytonutrients for particular conditions, which help to reduce specific cardiometabolic risk factors like high blood pressure, LDL cholesterol oxidation, and blood sugar.
Integrative Therapies and Supplement Use
Integrative treatments, such as dietary interventions, probiotics, herbal supplements, and mind-body practices, for heart disease consider the interconnectedness of gastrointestinal and cardiovascular health. By addressing factors such as microbiome balance, inflammation, and stress, integrative treatments aim to harmonize the gut-heart axis.
Probiotics
Probiotics are live microorganisms, primarily beneficial bacteria, used to improve microbiome composition and diversity. Outside of the benefits on digestive function, probiotic supplementation can also confer advantages to cardiovascular function by reducing cholesterol levels, inflammation, and TMAO production. Strains of Lactobacillus and Bifidobacterium, specifically, have been well-studied in reducing cardiovascular risk factors and improving heart disease treatment.
Turmeric
Turmeric, or Curcuma longa, contains an active compound called curcumin, which has been studied for its potential therapeutic properties. It is utilized in the treatment of both GI and cardiovascular issues due to its anti-inflammatory and antioxidant properties. In the gut, curcumin regulates microbiome composition, modulates inflammation, and supports intestinal barrier function (29, 38). Curcumin has been used as a treatment in inflammatory conditions, such as IBD and ulcers, as well as conditions such as IBS. Curcumin’s antioxidant properties restore endothelial function and its anti-inflammatory properties reduce inflammatory markers, such as interleukin-6 (IL-6) and c-reactive protein (CRP), which are associated with increased risk of heart disease (26).
Curcumin has poor bioavailability when taken orally, which has prompted the formulation of supplements that combine it with other ingredients, such as piperine or phospholipid complexes, to enhance its absorption and efficacy. Doses ranging from 200 mg to 8 grams daily have been used in research studies.
Omega-3 Fatty Acids
Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fatty fish, support various processes that optimize heart health. These essential fatty acids reduce inflammation, balance lipid levels, and reduce blood pressure. They also support the gut microbiome. The American Heart Association recommends eating 2 servings (6 ounces) of fatty fish per week to help reduce heart disease and stroke risk. In individuals with specific risk factors for heart disease, like hyperlipidemia or hypertension, higher doses of omega-3 fatty acids supplements might be recommended ranging from 2-4 grams daily (2).
Mind-Body Practices
Mind-body practices, including techniques like meditation, yoga, and deep breathing, promote a relaxation response, activating the parasympathetic nervous system and mitigating the chronic stress-induced activation of the SNS and HPA axis. The resulting reduction in catecholamines and stress hormones not only contributes to better gut health but also improves heart health by lowering blood pressure and reducing heart rate.
Challenges and Considerations in Treatment
Managing digestive health in patients with heart disease poses unique challenges, considering potential interactions between medications and the presence of comorbidities. Some cardiovascular medications may have gastrointestinal side effects. Additionally, comorbidities such as diabetes or kidney disease may complicate the treatment of heart disease (4). To navigate these challenges, a collaborative and holistic approach is essential. Healthcare providers should prioritize clear communication between specialists, ensuring a comprehensive understanding of the patient's medications and conditions. Focusing on modifiable lifestyle factors, such as diet, physical activity, and stress management, can help to reduce the risk of cardiovascular disease and other common comorbidities without the risks of side effects associated with medications or risk of negative interactions with other treatments (33).
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Digestive Wellness for Patients with Heart Disease: Key Takeaways
Recognizing the importance of the gut-heart axis, a functional medicine approach is effective in managing digestive wellness for patients with heart disease. Advanced diagnostics dive deeper into aspects of the digestive system, such as microbiome composition and intestinal permeability, to understand root causes affecting both digestive and cardiovascular health. By emphasizing the interconnectedness of these two systems and creating tailored treatment plans for each individual’s unique needs, healthcare practitioners pave the way for more effective, holistic care that promotes enduring well-being in patients with heart disease.
Lab Tests in This Article
References
- Anderson, S. (2022, May 19). 6 preventable risk factors associated with heart attacks. Rupa Health. https://www.rupahealth.com/post/5-things-to-do-after-a-heart-attack
- Are you getting enough omega-3 fatty acids?. American Heart Association. (2023, July 5). https://www.heart.org/en/news/2023/07/05/are-you-getting-enough-omega-3-fatty-acids
- Barone, M., D’Amico, F., Brigidi, P., & Turroni, S. (2022). Gut microbiome–micronutrient interaction: The key to controlling the bioavailability of minerals and vitamins? BioFactors, 48(2), 307–314. https://doi.org/10.1002/biof.1835
- Bell, D. S., McGill, J. B., & Jerkins, T. (2023). Management of the ‘wicked’ combination of heart failure and chronic kidney disease in the patient with diabetes. Diabetes, Obesity and Metabolism, 25(10), 2795–2804. https://doi.org/10.1111/dom.15181
- Blake, K. (2023a, May 22). Anti inflammatory diet 101: What to eat and avoid plus specialty labs to monitor results. Rupa Health. https://www.rupahealth.com/post/anti-inflammatory-diet
- Blake, K. (2023b, July 17). What is the cardiometabolic food plan?. Rupa Health. https://www.rupahealth.com/post/what-is-the-cardiometabolic-food-plan
- Canyelles, M., Borràs, C., Rotllan, N., Tondo, M., Escolà-Gil, J. C., & Blanco-Vaca, F. (2023). Gut microbiota-derived Tmao: A causal factor promoting atherosclerotic cardiovascular disease? International Journal of Molecular Sciences, 24(3), 1940. https://doi.org/10.3390/ijms24031940
- Cardiovascular diseases. World Health Organization. (n.d.). https://www.who.int/health-topics/cardiovascular-diseases#tab=tab_1
- Cascino, T. M., & Hummel, S. L. (2018). Nutrient deficiencies in heart failure: A Micro problem with macro effects? Journal of the American Heart Association, 7(17). https://doi.org/10.1161/jaha.118.010447
- Chen, J., Sun, Y., Fu, T., Lu, S., Shi, W., Zhao, J., Li, S., Li, X., Yuan, S., & Larsson, S. C. (2023). Risk of incident cardiovascular disease among patients with gastrointestinal disorder: A prospective cohort study of 330751 individuals. European Heart Journal - Quality of Care and Clinical Outcomes. https://doi.org/10.1093/ehjqcco/qcad059
- Chiang, J. Y., Ferrell, J. M., Wu, Y., & Boehme, S. (2020b). Bile acid and cholesterol metabolism in atherosclerotic cardiovascular disease and therapy. Cardiology Plus, 5(4), 159–170. https://doi.org/10.4103/2470-7511.305419
- Christie, J. (2022, December 13). 95% of American’s aren’t getting enough fiber: How many grams should we be consuming per day? Rupa Health. https://www.rupahealth.com/post/95-of-americans-arent-getting-enough-fiber-how-many-grams-of-fiber-should-we-be-consuming-per-day
- Cloyd, J. (2022, December 8). Inflammatory bowel disease: Treatments for IBD flares and remission. Rupa Health. https://www.rupahealth.com/post/inflammatory-bowel-disease-ibd-treatments-for-flares-and-remission
- Cloyd, J. (2023, February 21). A functional medicine GERD protocol. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-gerd-protocol
- Cloyd, J. (2023, February 28). A functional medicine protocol for leaky gut syndrome. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-protocol-for-leaky-gut-syndrome
- Cloyd, J. (2023, March 8). Bile acids 101: Testing, interpreting, treatment. Rupa Health. https://www.rupahealth.com/post/stool-bile-acids-101
- Cloyd, J. (2023, April 10). A functional medicine hypertension protocol. Rupa Health. https://www.rupahealth.com/post/functional-medicine-hypertension-protocol
- Cloyd, J. (2023, April 13). A functional medicine protocol for peptic ulcers. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-protocol-for-peptic-ulcers
- Cloyd, J. (2023, May 1). A functional medicine protocol for coronary artery disease. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-protocol-for-coronary-artery-disease
- Cloyd, J. (2023, May 17). A functional medicine constipation protocol: Testing, nutrition, and supplements. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-constipation-protocol-testing-nutrition-and-supplements
- Cloyd, J. (2023, July 28). A functional medicine diarrhea protocol: Comprehensive lab testing, therapeutic diet, and supplements. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-diarrhea-protocol-comprehensive-lab-testing-therapeutic-diet-and-supplements
- Cloyd, J. (2023, October 18). The 6 most important uses of omega-3s for your health. Rupa Health. https://www.rupahealth.com/post/the-6-most-important-uses-of-omega-3s-for-your-health
- Cloyd, J. (2023, December 4). Omega-3 fatty acids in cardiovascular health: A functional medicine guide. Rupa Health. https://www.rupahealth.com/post/omega-3-fatty-acids-in-cardiovascular-health-a-functional-medicine-guide
- Cloyd, J. (2023, December 5). Inflammation and heart disease: A functional medicine approach to prevention and treatment. Rupa Health. https://www.rupahealth.com/post/inflammation-and-heart-disease-a-functional-medicine-approach-to-prevention-and-treatment
- Cloyd, K. (2023, December 20). Interpreting oxidative stress markers. Rupa Health. https://www.rupahealth.com/post/interpreting-oxidative-stress-markers
- Cox, F. F., Misiou, A., Vierkant, A., Ale-Agha, N., Grandoch, M., Haendeler, J., & Altschmied, J. (2022). Protective effects of curcumin in cardiovascular diseases—impact on oxidative stress and mitochondria. Cells, 11(3), 342. https://doi.org/10.3390/cells11030342
- DeCesaris, L. (2022, June 6). What is gut dysbiosis? 7 signs to watch for. Rupa Health. https://www.rupahealth.com/post/how-your-gut-bacteria-affects-your-overall-health
- DePorto, T. (2022, December 9). Functional medicine lab tests for heart disease. Rupa Health. https://www.rupahealth.com/post/worried-about-heart-disease-ask-your-provider-for-these-6-specialty-labs-at-your-next-appointment
- Di Meo, F., Margarucci, S., Galderisi, U., Crispi, S., & Peluso, G. (2019). Curcumin, gut microbiota, and neuroprotection. Nutrients, 11(10), 2426. https://doi.org/10.3390/nu11102426
- Diorio, B. (2023, January 17). Why most functional medicine practitioners say no to alcohol. Rupa Health. https://www.rupahealth.com/post/why-most-functional-medicine-practitioners-say-no-to-alcohol
- Diorio, B. (2023, April 7). Could your patients benefits from the phytonutrient spectrum food plan?. Rupa Health. https://www.rupahealth.com/post/could-your-patients-benefits-from-the-phytonutrient-spectrum-food-plan
- Duan, F., Wu, Q., Zuo, Y., Yang, H., Dai, F., & Wang, L. (2021). Effects of mind-body exercise on cardiopulmonary function, blood pressure, and quality of life in CHD patients. Medicine, 100(9). https://doi.org/10.1097/md.0000000000025042
- Elwood, P. C., Longley, M., Greene, G., Morgan, G., Watkins, J., Pickering, J., Watkins, A., Protty, M., Bayer, A., & Gallacher, J. (2020). Better than any pill—and no side effects! healthy lifestyles, statins, and aspirin. Lifestyle Medicine, 1(1). https://doi.org/10.1002/lim2.4
- Endothelial dysfunction: Symptoms, causes & treatments. Cleveland Clinic. (n.d.). https://my.clevelandclinic.org/health/diseases/23230-endothelial-dysfunction
- Farré, R., Fiorani, M., Abdu Rahiman, S., & Matteoli, G. (2020). Intestinal permeability, inflammation and the role of nutrients. Nutrients, 12(4), 1185. https://doi.org/10.3390/nu12041185
- Flaxman, N. (1941). Gastro-intestinal manifestations of heart disease. American Journal of Digestive Diseases, 8(1), 10–13. https://doi.org/10.1007/bf02999385
- Fu, Y., Wang, Y., Gao, H., Li, D., Jiang, R., Ge, L., Tong, C., & Xu, K. (2021). Associations among dietary omega-3 polyunsaturated fatty acids, the gut microbiota, and intestinal immunity. Mediators of Inflammation, 2021, 1–11. https://doi.org/10.1155/2021/8879227
- Ghosh, S. S., He, H., Wang, J., Gehr, T. W., & Ghosh, S. (2018). Curcumin-mediated regulation of intestinal barrier function: The mechanism underlying its beneficial effects. Tissue Barriers, 6(1). https://doi.org/10.1080/21688370.2018.1425085
- Greenan, S. (2021, November 5). A functional medicine approach to IBS. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-approach-to-ibs
- Gupta, S. C., Patchva, S., & Aggarwal, B. B. (2012). Therapeutic roles of Curcumin: Lessons Learned From Clinical Trials. The AAPS Journal, 15(1), 195–218. https://doi.org/10.1208/s12248-012-9432-8
- Heart disease facts. Centers for Disease Control and Prevention. (2023, May 15). https://www.cdc.gov/heartdisease/facts.htm
- Henein, M. Y., Vancheri, S., Longo, G., & Vancheri, F. (2022). The role of inflammation in cardiovascular disease. International Journal of Molecular Sciences, 23(21), 12906. https://doi.org/10.3390/ijms232112906
- Hijová, E. (2023). Benefits of biotics for cardiovascular diseases. International Journal of Molecular Sciences, 24(7), 6292. https://doi.org/10.3390/ijms24076292
- Inoue, K., Horwich, T., Bhatnagar, R., Bhatt, K., Goldwater, D., Seeman, T., & Watson, K. E. (2021). Urinary stress hormones, hypertension, and cardiovascular events: The multi-ethnic study of Atherosclerosis. Hypertension, 78(5), 1640–1647. https://doi.org/10.1161/hypertensionaha.121.17618
- Jafarzadeh, E., Shoeibi, S., Bahramvand, Y., Nasrollahi, E., Maghsoudi, A. S., Yazdi, F., KarkonShayan, S., & Hassani, S. (2022). Turmeric for treatment of irritable bowel syndrome: A systematic review of population-based evidence. Iranian Journal of Public Health. https://doi.org/10.18502/ijph.v51i6.9656
- Jain, A. P., Aggarwal, K. K., & Zhang, P.-Y. (2015). Omega-3 fatty acids and cardiovascular disease. European Review for Medical and Pharmacological Sciences, 19(3), 441–445.
- Khakham, C. (2023, March 7). Top medical evidence supporting curcumin’s health benefits. Rupa Health. https://www.rupahealth.com/post/top-medical-evidence-supporting-curcumins-health-benefits
- Kheiri, B., Abdalla, A., Osman, M., Ahmed, S., Hassan, M., & Bachuwa, G. (2018). Vitamin D deficiency and risk of cardiovascular diseases: A narrative review. Clinical Hypertension, 24(1). https://doi.org/10.1186/s40885-018-0094-4
- Koeth, R. A., Wang, Z., Levison, B. S., Buffa, J. A., Org, E., Sheehy, B. T., Britt, E. B., Fu, X., Wu, Y., Li, L., Smith, J. D., DiDonato, J. A., Chen, J., Li, H., Wu, G. D., Lewis, J. D., Warrier, M., Brown, J. M., Krauss, R. M., … Hazen, S. L. (2013). Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature Medicine, 19(5), 576–585. https://doi.org/10.1038/nm.3145
- Konturek, P. C., Brzozowski, T., & Konturek, S. J. (2011). Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. PubMed, 62(6), 591–599. https://pubmed.ncbi.nlm.nih.gov/22314561
- Lavie, C. J., Ozemek, C., Carbone, S., Katzmarzyk, P. T., & Blair, S. N. (2019). Sedentary behavior, exercise, and Cardiovascular Health. Circulation Research, 124(5), 799–815. https://doi.org/10.1161/circresaha.118.312669
- Lewis, C. V., & Taylor, W. R. (2020). Intestinal barrier dysfunction as a therapeutic target for cardiovascular disease. American Journal of Physiology-Heart and Circulatory Physiology, 319(6). https://doi.org/10.1152/ajpheart.00612.2020
- Lin, Y., Liu, H., Bu, L., Chen, C., & Ye, X. (2022). Review of the effects and mechanism of curcumin in the treatment of inflammatory bowel disease. Frontiers in Pharmacology, 13. https://doi.org/10.3389/fphar.2022.908077
- LoBisco, S. (2022, December 14). How to build a healthy microbiome from birth. Rupa Health. https://www.rupahealth.com/post/building-a-healthy-microbiome-from-birth
- Maholy, N. (2023, March 9). Integrative medicine protocol for reversing type 2 diabetes. Rupa Health. https://www.rupahealth.com/post/integrative-medicine-protocol-for-reversing-type-2-diabetes
- Maholy, N. (2023, April 14). How to reduce stress through mind-body therapies. Rupa Health. https://www.rupahealth.com/post/how-to-reduce-stress-through-mind-body-therapies
- Maholy, N. (2023, May 23). A functional medicine treatment protocol for metabolic syndrome: Testing, nutrition, and supplements. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-treatment-protocol-for-metabolic-syndrome-testing-nutrition-and-supplements
- Maholy, N. (2023, June 29). The role of probiotics and prebiotics in Gut Health: An integrative perspective. Rupa Health. https://www.rupahealth.com/post/the-role-of-probiotics-and-prebiotics-in-gut-health-an-integrative-perspective
- Martínez-González, M. A., Gea, A., & Ruiz-Canela, M. (2019). The Mediterranean diet and Cardiovascular Health. Circulation Research, 124(5), 779–798. https://doi.org/10.1161/circresaha.118.313348
- Matthews, C. E., Carlson, S. A., Saint-Maurice, P. F., Patel, S., Salerno, E. A., Loftfield, E., Troiano, R. P., Fulton, J. E., Sampson, J. N., Tribby, C., Keadle, S. K., & Berrigan, D. (2021). Sedentary behavior in U.S. adults: Fall 2019. Medicine & Science in Sports & Exercise, 53(12), 2512–2519. https://doi.org/10.1249/mss.0000000000002751
- Meo, F., Margarucci, S., Galderisi, U., Crispi, S., & Peluso, G. (2019). Curcumin, gut microbiota, and neuroprotection. Nutrients, 11(10), 2426. https://doi.org/10.3390/nu11102426
- Miller, D. B., & O’Callaghan, J. P. (2002). Neuroendocrine aspects of the response to stress. Metabolism, 51(6), 5–10. https://doi.org/10.1053/meta.2002.33184
- Mind-body techniques for IBS relief. Rupa Health. (2023, March 16). https://www.rupahealth.com/post/mind-body-techniques-for-ibs-relief
- Mousa, W. K., Chehadeh, F., & Husband, S. (2022). Microbial dysbiosis in the gut drives systemic autoimmune diseases. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.906258
- Nagai, M., Hoshide, S., & Kario, K. (2010). Sleep duration as a risk factor for cardiovascular disease- A review of the recent literature. Current Cardiology Reviews, 6(1), 54–61. https://doi.org/10.2174/157340310790231635
- Nagpal, R., Shively, C. A., Register, T. C., Craft, S., & Yadav, H. (2019). Gut microbiome-mediterranean diet interactions in improving host health. F1000Research, 8, 699. https://doi.org/10.12688/f1000research.18992.1
- Nesci, A., Carnuccio, C., Ruggieri, V., D’Alessandro, A., Di Giorgio, A., Santoro, L., Gasbarrini, A., Santoliquido, A., & Ponziani, F. R. (2023). Gut microbiota and cardiovascular disease: Evidence on the metabolic and inflammatory background of a complex relationship. International Journal of Molecular Sciences, 24(10), 9087. https://doi.org/10.3390/ijms24109087
- Ohira, H., Tsutsui, W., & Fujioka, Y. (2017). Are short chain fatty acids in gut microbiota defensive players for inflammation and atherosclerosis? Journal of Atherosclerosis and Thrombosis, 24(7), 660–672. https://doi.org/10.5551/jat.rv17006
- Peoples, J. N., Saraf, A., Ghazal, N., Pham, T. T., & Kwong, J. Q. (2019). Mitochondrial dysfunction and oxidative stress in heart disease. Experimental & Molecular Medicine, 51(12), 1–13. https://doi.org/10.1038/s12276-019-0355-7
- Philpott, H. L., Nandurkar, S., Lubel, J., & Gibson, P. R. (2013a). Drug-induced gastrointestinal disorders. Frontline Gastroenterology, 5(1), 49–57. https://doi.org/10.1136/flgastro-2013-100316
- Philpott, H. L., Nandurkar, S., Lubel, J., & Gibson, P. R. (2013). Drug-induced gastrointestinal disorders. Frontline Gastroenterology, 5(1), 49–57. https://doi.org/10.1136/flgastro-2013-100316
- Physical Activity And Your Heart: Benefits. National Heart Lung and Blood Institute. (n.d.). https://www.nhlbi.nih.gov/health/heart/physical-activity/benefits
- Prucksunand, C., Indrasukhsri, B., Leethochawalit, M., & Hungspreugs, K. (2001). Phase II clinical trial on effect of the long turmeric (Curcuma longa Linn) on healing of peptic ulcer. PubMed, 32(1), 208–215. https://pubmed.ncbi.nlm.nih.gov/11485087
- Rahman, Md. M., Islam, F., -Or-Rashid, Md. H., Mamun, A. A., Rahaman, Md. S., Islam, Md. M., Meem, A. F., Sutradhar, P. R., Mitra, S., Mimi, A. A., Emran, T. B., Fatimawali, Idroes, R., Tallei, T. E., Ahmed, M., & Cavalu, S. (2022). The gut microbiota (microbiome) in cardiovascular disease and its therapeutic regulation. Frontiers in Cellular and Infection Microbiology, 12. https://doi.org/10.3389/fcimb.2022.903570
- Rippe, J. M. (2018). Lifestyle Strategies for Risk Factor Reduction, prevention, and treatment of cardiovascular disease. American Journal of Lifestyle Medicine, 13(2), 204–212. https://doi.org/10.1177/1559827618812395
- Seethaler, B., Lehnert, K., Yahiaoui-Doktor, M., Basrai, M., Vetter, W., Kiechle, M., & Bischoff, S. C. (2023). Omega-3 polyunsaturated fatty acids improve intestinal barrier integrity—albeit to a lesser degree than short-chain fatty acids: An exploratory analysis of the randomized controlled Libre Trial. European Journal of Nutrition, 62(7), 2779–2791. https://doi.org/10.1007/s00394-023-03172-2
- Sleep and sleep disorders. Centers for Disease Control and Prevention. (2022, September 7). https://www.cdc.gov/sleep/index.html
- Sleep disorders and heart health. American Heart Association. (2023b, August 17). https://www.heart.org/en/health-topics/sleep-disorders/sleep-and-heart-health
- Sundaram, V., & Fang, J. C. (2016). Gastrointestinal and liver issues in heart failure. Circulation, 133(17), 1696–1703. https://doi.org/10.1161/circulationaha.115.020894
- Sweetnich, J. (2023, February 17). 6 health benefits of Prebiotics. Rupa Health. https://www.rupahealth.com/post/6-health-benefits-of-prebiotics
- Sweetnich, J. (2023, February 22). How stress affects our gut health. Rupa Health. https://www.rupahealth.com/post/how-stress-affects-our-gut-health
- Tang, W. H. W., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., Wu, Y., & Hazen, S. L. (2013). Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. New England Journal of Medicine, 368(17), 1575–1584. https://doi.org/10.1056/nejmoa1109400
- Tawakol, A., Ishai, A., Takx, R. A., Figueroa, A. L., Ali, A., Kaiser, Y., Truong, Q. A., Solomon, C. J., Calcagno, C., Mani, V., Tang, C. Y., Mulder, W. J., Murrough, J. W., Hoffmann, U., Nahrendorf, M., Shin, L. M., Fayad, Z. A., & Pitman, R. K. (2017). Relation between resting amygdalar activity and cardiovascular events: A longitudinal and cohort study. The Lancet, 389(10071), 834–845. https://doi.org/10.1016/s0140-6736(16)31714-7
- Tolmay, C. M., Malan, L., & Van Rooyen, J. M. (2012). The relationship between cortisol, C-reactive protein and hypertension in African and causcasian women : The POWIRS study. Cardiovascular Journal of Africa, 23(2), 78–84. https://doi.org/10.5830/cvja-2011-035
- Vijay, A., Astbury, S., Le Roy, C., Spector, T. D., & Valdes, A. M. (2020). The prebiotic effects of omega-3 fatty acid supplementation: A six-week randomised intervention trial. Gut Microbes, 13(1). https://doi.org/10.1080/19490976.2020.1863133
- Wang, W., Ren, H., Tian, Q., Tang, C., & Meng, W. (2019). Effects of occupational stress on blood lipids, blood sugar and immune function of doctors. Iranian Journal of Public Health. https://doi.org/10.18502/ijph.v48i5.1798
- Weinberg, J. L. (2022, November 16). What is the Mediterranean diet?. Rupa Health. https://www.rupahealth.com/post/4-science-backed-health-benefits-of-the-mediterranean-diet
- Weinberg, J. L. (2022, December 19). How short chain fatty acids affects our mood, digestion, and metabolism. Rupa Health. https://www.rupahealth.com/post/how-short-chain-fatty-acids-affects-our-mood-digestion-and-metabolism
- Weinberg, J. L. (2023, June 1). A functional medicine non alcoholic fatty liver disease (NAFLD) protocol: Testing, nutrition, and supplements. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-non-alcoholic-fatty-liver-disease-nafld-protocol-testing-nutrition-and-supplements
- Weinberg, J. L. (2023, December 26). The gut-heart connection: Functional medicine’s approach to cardiovascular health. Rupa Health. https://www.rupahealth.com/post/the-gut-heart-connection-functional-medicines-approach-to-cardiovascular-health
- Widmer, R. J., Flammer, A. J., Lerman, L. O., & Lerman, A. (2015). The Mediterranean diet, its components, and cardiovascular disease. The American Journal of Medicine, 128(3), 229–238. https://doi.org/10.1016/j.amjmed.2014.10.014
- Wiertsema, S. P., van Bergenhenegouwen, J., Garssen, J., & Knippels, L. M. (2021). The interplay between the gut microbiome and the immune system in the context of infectious diseases throughout life and the role of Nutrition in Optimizing Treatment Strategies. Nutrients, 13(3), 886. https://doi.org/10.3390/nu13030886
- Wu, H., & Chiou, J. (2021). Potential benefits of probiotics and prebiotics for coronary heart disease and stroke. Nutrients, 13(8), 2878. https://doi.org/10.3390/nu13082878
- Wu, J., Xun, P., Tang, Q., Cai, W., & He, K. (2017). Circulating magnesium levels and incidence of coronary heart diseases, hypertension, and type 2 diabetes mellitus: A meta-analysis of prospective cohort studies. Nutrition Journal, 16(1). https://doi.org/10.1186/s12937-017-0280-3