36 Great Ideas from Cardiometabolic Function: The Intersection Among Neurology, Endocrinology, and Immunology

On April 21-22, 2023, Personalized Lifestyle Medicine Institute, in collaboration with Lifestyle Matrix Resource Center, hosted healthcare practitioners at Cardiometabolic Function: The Intersection Among Neurology, Endocrinology, and Immunology. The live conference provided expert insights on cardiometabolic health, technological advancements and clinical applications for practitioners.

The speakers covered conditions ranging from hyperuricemia and Alzheimer’s disease to polycystic ovary syndrome and non-alcoholic fatty liver disease. The field of cardiometabolic health faces many challenges and opportunities for innovation, and understanding the interplay between organ systems, genetics, lifestyle and environment is invaluable to clinicians and the future of functional medicine.

Here are key takeaways from the event, organized by presentation and speaker.

Day 1 | April 21, 2023

The Clinical Connection Among Metabolic Fitness, Immunity and Cardiometabolic Disease

Jeffrey Bland, PhD

• Dr. Bland emphasized that “biomarkers are used to prognose rather than diagnose disturbances in the immune-endocrine-nervous system network related to cardiometabolic disorders.”
• Technological advancements have provided us with opportunities to reexamine cardiometabolic syndromes and improve personalization with clinical tools like metabotyping and the Immuno-Identity™ Questionnaire.
• Although stress, emotions and psychosocial factors are often relegated to the “soft” sciences, they send hard signals that mechanistically influence cardiometabolic disorders. Dr. Bland highlighted a study that suggested: “The stress response is a major driver of IBS symptoms.”¹  

What Do Dementia, Depression and Adiposity Have in Common?

Austin Perlmutter, MD

• The emerging field of neurometabolism is central to understanding mental and cognitive health. Microglial state activation, which is mediated by metabolism, may contribute to neuroinflammation, and inflammation may drive depression in some patient subgroups.
• Decreases in cerebral glucose metabolism in Alzheimer’s disease are associated with disease severity,² and brain insulin is linked to neuroplasticity, memory and learning.
• Dr. Perlmutter encouraged rethinking fat as a metabolic organ that regulates physiology.³ Adipocyte plasticity is, in turn, regulated by the browning or whitening of adipose tissue, sleep, exercise, and dietary components, such as those found in supplemental cinnamon oil, quercetin, curcumin, and fish oil.

Uric Acid as an Independent Marker of Metabolic Syndrome

David Perlmutter, MD

• Dr. Perlmutter traced the legacy of the uricase mutation in hominoid evolution back to its possible role as a food scarcity survival adaptation during the Middle Miocene cooling and extinction period.⁴ 
• Both the uricase mutation and fructose increase serum uric acid (SUA) levels. For every 1 mg/dL increase in SUA, the risk of developing metabolic syndrome increases by 30%.⁵ Elevated uric acid levels inhibit nitric oxide bioavailability and are associated with ischemic stroke, Alzheimer’s disease and cognitive deterioration.⁶
• Dr. Perlmutter concluded his presentation with five key supplements he recommends for patients with elevated uric acid levels: quercetin, luteolin, DHA, vitamin C and Chlorella vulgaris, a species of green microalga.

Insulin: When Things Go Wrong and No One Notices

Elizabeth Boham, MD, MS, RD

• When evaluating your patients for potential insulin resistance (IR), Dr. Boham recommended using the ABCDs of nutrition assessment: anthropometrics, biomarkers, clinical indicators, and diet and lifestyle indicators. She demonstrated applying this strategy through in-depth explorations of IR case studies.
• Three useful biomarkers and clinical indicators of IR, non-alcoholic fatty liver disease (NAFLD), and polycystic ovary syndrome (PCOS) include the HOMA-IR score, waist-hip ratio and hyperandrogenism.
• Dr. Boham also recommended the green Mediterranean diet, which contains additional polyphenol-rich green plants, for patients with IR and related conditions. An 18-month trial demonstrated 39% hepatic fat reduction amongst participants following the green Mediterranean diet compared to a 20% reduction in those following the traditional Mediterranean diet.⁷ 

Dysautonomia: An Emerging Post-Pandemic Problem

Shilpa P. Saxena, MD

• According to the CDC, nearly one in five American adults who have had COVID-19 reported symptoms of long COVID.⁸ Infection-associated dysautonomia may be directly caused by the action of the virus on autonomic nervous system structures, or it may be an indirect consequence of post-infectious immune-mediated processes.⁹
• While the COMPASS score is frequently used for dysautonomia diagnosis, Dr. Saxena remarked that it is “clunky.” She instead recommended using heart rate variability, heart rate and blood pressure as key clinical indicators. Learn more about this topic from her contributions to the recently updated CM Vitals Program.
• Dr. Saxena outlined her functional medicine approach to treating dysautonomia as a five-pronged strategy incorporating mitochondrial support, endothelial health, vagal tone, inflammation and psychosocial factors. She emphasized that it is essential to reengage your patients’ parasympathetic ventral vagal complex and improve their heart rate variability.¹⁰

Patterns, Connections and Clinical Pearls: Stress, Sleep and Diet

Shilpa P. Saxena, MD

• When similar lifestyle and environmental patterns act upon unique genetic codes, a phenotypic array of cardiometabolic disorders, such as NAFLD, PCOS or type 2 diabetes, can arise. According to Dr. Saxena, these conditions are not simply comorbidities; the conditions an individual develops are mediated by genetics and epigenetics. As such, cardiometabolic syndrome demands semi-standardized personalization for treatment.
• Adverse childhood experiences are strongly associated with the development of cardiovascular disease.¹¹ Dr. Saxena suggested asking the following question to gently probe whether a history of trauma may be contributing to a patient’s stress or other symptoms: Did you like going home when you were a child?
• Dr. Saxena shared three clinical pearls: meet your patients where they are, assess their readiness to change and help them feel empowered. One way to empower your patients is to give them easy wins at the beginning of treatment, like offering the option to either add or remove a simple dietary choice.

Day 2 | April 22, 2023

The Story of the Glycocalyx

Michael Twyman, MD

• The endothelial glycocalyx (EGX) is a SMART barrier: selective, micro-thin, antioxidant, regulator and transducer. Key takeaways from Dr. Twyman’s presentation include that the EGX prevents circulating blood components from sticking to vessel walls, regulates vascular inflammation and coagulation, and sends signals to the endothelium to produce nitric oxide.
• Damage to the EGX precedes endothelial dysfunction and its downstream cardiovascular health effects. Functional medicine providers can intervene early by testing for free glycosaminoglycans (GAGs) in urine, which can indicate EGX damage.¹²
• The EGX is fragile but resilient and can recover from damage in some cases. Strategies for repairing the EGX include reducing lipid levels, decreasing inflammation and replacing fundamental EGX components, like hyaluronic acid or precursor molecules for GAG synthesis.

Nitric Oxide: Beyond Hypertension

Nathan Bryan, PhD

• Dr. Bryan presented three main contributors to aging and chronic disease that are modified by nitric oxide: telomere shortening,¹³ mitochondrial dysfunction,¹⁴ and loss of stem cell function and repair.¹⁵ 
• Dr. Bryan speculated that disruptions to environmental and human nitrogen cycles might be to blame for inadequate nitric oxide synthesis in the population. Studies in mice have shown that restoring nitric oxide production reduces the atherogenic effects of a high-cholesterol diet and supplemental nitrite restored nitric oxide homeostasis.¹⁶
• Moderate physical exercise and leafy green vegetables may help restore nitric oxide production. Although L-arginine is a precursor to nitric oxide, multiple studies have demonstrated it may be harmful to administer as a supplement to patients.¹⁷

Cardiometabolic Physiology as a Health Barometer

Thomas G. Guilliams, PhD

• Throughout his talk, Dr. Guilliams encouraged providers to stop chasing biomarkers and risk calculators to prevent cardiometabolic disease. Instead, he suggested preventative therapeutic strategies to build resiliency and reserve capacity in patients.
• Carbohydrate-last meal patterns and post-meal walks decrease postprandial glucose and blunt peak glucose, which are key targets for glycemic control in type 2 diabetes.^18,19 
• In keeping with the motifs of the conference, Dr. Guilliams highlighted the importance of reducing inflammation and managing hyperglycemia because both drive EGX damage. Berberine may ameliorate EGX degradation caused by low shear stress.

Getting Results: Where Medicine and Lifestyle Collide

Cheng Ruan, MD

• Dr. Ruan reiterated the importance of empowering patients through a culture of empathy and compassion. However, more importantly, providers must help themselves first through self-compassion in order to then help others better, especially when nearly 60% of providers are experiencing burnout.²⁰ As the saying goes, put your oxygen mask on first.
• He also encouraged practitioners to leverage innovation to improve outcomes and expand care. Advancements in telemedicine can increase touchpoints with patients, which are associated with better health outcomes. Wearable devices with real-time monitoring, like continuous glucose monitors, can help patients engage with their health and improve their behavior.
• Dr. Ruan highlighted the creation of 13 new CPT codes for mental and behavioral health that clinicians should be aware of for reimbursement purposes.²¹ These codes are related to remote therapeutic monitoring devices for cognitive behavioral therapy.

Patterns, Connections and Clinical Pearls: Hormones, Infections and Genetics

Regina S. Druz, MD, MBA, MS, FACC

• Dr. Druz called attention to the alarming statistics showing that 70% of heart failure admissions are preventable yet see 50% mortality rates at the five-year mark.²² She called for practice model innovations in cardiology to improve prevention, particularly advances in precision and personalization utilizing technology.
• Patients with heart failure are in a state of myocardial IR,²³ and studies indicate SGLT2 inhibitors and mild ketosis improve cardiovascular outcomes.²⁴ 
• For these patients, multiple paths are available to achieve beneficial ketosis, including mild intermittent fasting and diets high in plant-derived proteins. Before prescribing ketosis, however, practitioners should investigate monogenic risks for hypercholesterolemia genes.

The Top 5 Nutrients to Level Up Your Cardiometabolic Protocols

Shilpa P. Saxena, MD

• In the closing presentation for the conference, Dr. Saxena laid out her overall approach to her cardiometabolic cases. She urged prioritizing lifestyle therapies in all cases and incorporating nutraceuticals most of the time. 
• All three of Dr. Saxena’s presentations contained quality clinical pearls aimed at improving patient compliance and outcomes. For example, when encouraging lifestyle changes, Dr. Saxena suggested treating your guidelines like an actual prescription by writing them on a prescription pad. Print other important information, like handouts or lab results, on heavy paper and then insert them into sheet protectors. This “medical theatre” communicates the importance of lifestyle to patients.
• Nutraceutical therapies can be further segmented into foundational and targeted support. Dr. Saxena recommended vitamin K2/D3, magnesium, essential fatty acids and probiotics for foundational cardiometabolic support. 

References

1. Groeger D, Murphy EF, Tan HTT, Larsen IS, O'Neill I, Quigley EMM. Interactions between symptoms and psychological status in irritable bowel syndrome: An exploratory study of the impact of a probiotic combination. Neurogastroenterol Motil. 2023;35(1):e14477. doi:10.1111/nmo.14477

24. Selvaraj S, Kelly DP, Margulies KB. Implications of Altered Ketone Metabolism and Therapeutic Ketosis in Heart Failure. Circulation. 2020;141(22):1800-1812. doi:10.1161/circulationaha.119.045033