Article from Townsend Letter
Novel Ways to Support Cardiac Energetics
by Chris D. Meletis, ND

Aging is inevitable, yet we have some governance over our biological age versus our chronological age. Never is this more true than in regards to our heart health. For example, the prevalence of myocardial infarctions (heart attacks) roughly increases with mean age, but increased body mass index also plays a vital role in increased heart disease risk.1  Other factors, many of which are under the control of patients, also impact heart health, such as exercise and diet. However, other factors are not as well recognized that play a role in the health of cardiovascular systems. In this article, I will address some of these lesser-known factors involved in heart health, particularly those often neglected when evaluating and treating patients with cardiovascular concerns.

Sleep Apnea and Heart Health

An individual can often live weeks without food, days without proper hydration, yet merely moments without air. Ensuring good oxygenation during exercise, rest, and sleep is a foundation to adequate energy production and recovery and consequently to heart health. Whether an individual seeks peak exercise performance goals or generalized wellness, quantifying sufficient pulmonary function and competency is of paramount importance.

Furthermore, simple pulse oximetry, spirometry, and home sleep apnea testing can save countless lives from cardiac events. There is a strong connection between obstructive sleep apnea, high blood pressure, and other cardiovascular problems. Organic acid profile (OAP) testing can detect the presence of sleep apnea by measuring analytes that may point to the presence of hypoxia, including lactate and pyruvate-lactate ratios, succinate, fumarate, malate, methylmalonate, and vanilmandelate.

Yet, despite the heart’s need for oxygen, screening for sleep apnea often escapes even the savviest functional medicine provider. Functional medicine providers can suspect the presence of apnea by examining a patient’s history. For example, does it include orthodontic work, mouth-breathing during early childhood, asthma, tongue-to-jaw ratio, soft and hard palate anatomy, and much more? It’s also important to remember that not all patients with sleep apnea are obese or overweight.

The reality is that compromised energy production by myocardial tissue is a critical contributor to most forms of cardiac disease. An organic acid profile test can determine if this energy production by myocardial tissue is compromised.

Hydration and Heart Health

One factor not often considered in cardiovascular health is drinking plenty of water. Drinking less than ideal amounts of water or liquid or becoming dehydrated through exercise, heat stress, or diuretic use, known as hypohydration, has long been known to weaken mental and physical performance, but recent evidence has emerged that indicates low liquid intake may also harm the cardiovascular system.2 Evidence suggests that the ideal amount of water intake may equal about a half-gallon within 24 hours, although this can vary from person to person.3Observational studies have associated habitual low water intake with an increased risk of adverse cardiovascular events.2

Hypohydration and cardiovascular disease are linked to impaired vascular function and blood pressure regulation.2 Hypohydration may lead to reduced endothelial function, increased sympathetic nervous system activity, and a worsening of orthostatic tolerance,2 the displacement of blood into appropriate vessels when arising from a lying to standing position. There’s an indication that drinking water at night can reduce the nocturnal rise in blood viscosity and discourage a morning occurrence of cerebral infarction.4

The Heart Is Integrated with Other Bodily Systems

The human heart is an amazing organ. It pumps on average 103,680 times a day, with a sustained pulse of 72 beats per minute throughout a 24-hour period of time. The heart is perfusing the trillions of cells that comprise the human frame via approximately 60,000 miles of blood vessels. This process requires monumental quantities of ATP to sustain this level of repetitive contractility. Yet we must realize the heart is more than a mechanical wonder—its  complexity and intricacies with other organs are highly integrated.

Indeed, a healthy gastrointestinal tract is essential for the assimilation of the biochemical substrates and nutritional co-factors to sustain this energetic demand of the heart. In turn, a healthy mind is critical as well to control deleterious cardiac impacts such as imbalanced sympathetic/parasympathetic pathways.

Happiness Is Linked to Heart Health

There is a definite link between cardiac health and mental health. Depression is a risk factor for the development of cardiovascular disease and points to a worse outcome in heart patients.5

Our ability to process and mindfully mitigate the impact of exogenous stressors that can burden the cardiovascular system depends on one’s mindset and thoughts. In a world of stress, sorrow, and sadness, guarding one’s heart literally and figuratively serves as a prime directive for longevity and happiness. As Emily Dickinson once said, “If I can stop one heart from breaking, I shall not live in vain.”  As documented in the scientific literature, there is a risk of dying of a broken heart. Takotsubo cardiomyopathy (broken heart syndrome) presents with the weakening of the left ventricle arising from severe emotional or physical stress.6 Our mental health is therefore critical to our cardiovascular health. 

Food Sensitivities and the Cardiac Inflammatory Response 

It’s often underrecognized the role that diet plays in our happiness. Yet, our mental health is linked to the food we eat and if the food we eat is sabotaging our mental health, then our cardiovascular system will suffer. Often, in regards to cardiac health, we only think about eating too much fat or sugar. But what about food sensitivities?

A 2018 article in the journal Nutrients discusses the role of IgG food reactivity and depression.7 An inflamed brain impacts our ability to process life events and disrupts neurotransmitter production, sympathetic tone, and inflammation of the circulatory vasculature.7 Exploring the contribution of food sensitivity and allergies relative to cardiac risk is paramount not only from a mental health impact but also the role of shifts in the complement pathway and innate immunity on pro-inflammatory status. Inflammation is a major contributor to heart disease8 and anything that puts our bodies in a state of inflammation—including food sensitivities—can harm the vascular system.

Furthermore, patients who tested positive for food intolerances to fructose, sugar cane, and sugar beet had an increased incidence of insulin resistance,9 a condition that is an important component of metabolic syndrome, which is associated with an increased risk of heart disease. A gene that promotes insulin resistance was common in these sugar-intolerant subjects.9

Ensuring that the foods patients eat are not causing an inflammatory response that can harm the cardiovascular system is critical to promoting vascular health. Testing patients for food sensitivities, food allergies, and gluten reactivity is essential to empower them to eat right for their unique biochemistry and immunology to promote cardiovascular and whole-body health.

Is Your Heart Getting Enough Energy?

Without continuous energy production, it is estimated that the cardiac muscles will run out of ATP in 2 to 10 seconds.10 So, how can we measure cardiac energy metabolism? In clinical practice, employing an organic acid profile (OAP), a simple urine test, can offer significant clinical insights for those seeking to gain perspective into cardiac energy metabolism, including fatty acids, glucose, lactate, ketones (β-hydroxybutyrate), pyruvate, and amino acid utilization.10

Quantifying the metabolic energy pathways that fuel the heart and other life-sustaining functions throughout the body would seem to embody the very foundation of functional medicine testing. Any and all tissues within the body—including the heart—can only manifest their full genetic potential with optimal energy production and reserves. This very point leads me as a clinician to perform OAP testing on a variety of patients with a wide array of presenting maladies.

The adult heart harnesses energy production via mitochondrial oxidative phosphorylation (95%) and glycolysis (5%).Forty to sixty percent of mitochondrial ATP production is generated from the oxidation of fatty acids, with the remainder arising from the oxidation of pyruvate from glucose and lactate, ketone bodies, and amino acids.10 Among the numerous organic acid profile analytes that offer insights relative to cardiac energetics include beta-hydroxybutyrate, adipate, suberate, ethylmalonate, methylsuccinate, succinate, alpha-ketoisocaproate, alpha-ketoisovalerate, alpha-keto-beta-methylvalerate, and methylmalonate. Analyzing each of these analytes on an organic acid profile can indicate whether the heart is getting enough energy. The levels and ratios will vary depending on each analyte, related analyte, and dietary habits.

All of the analytes of an organic acid profile test must be looked at through a clinical lens of diet, lifestyle, exercise, and other individual factors. If levels of analytes are high or low relative to the classical bell-shaped curve on these analytes on an organic acid profile test, there is either an under-fueling via substrate in the case of low levels or insufficient metabolic processing of organic acid analytes.

Diet and some other factors can affect some of these analytes. For example, a keto diet or high-fat diet or diabetes can alter the analyte beta-hydroxybutyrate. In the case of other analytes such as adipate, suberate, and other fatty acid analytes, they can be shifted due to excess fueling of a pathway or insufficient co-factors to allow for proper metabolism, and in the case of this discussion, the fueling of the citric acid cycle or electron transport chain.

Furthermore, analytes can be abnormal either due to overt mitochondriopathy or subclinical mitochondrial dysregulation, which will directly or indirectly place sufficient cardiac energetics in peril.

Specific analytes may also potentially identify hypoxia. The organic acid profile analytes that may point to the presence of hypoxia include the following:

Fueling the Heart for Optimal Performance

I have developed a deep appreciation for the role of nicotinamide adenine dinucleotide (NAD+) in various aspects of health, including heart health. NAD+ is an essential coenzyme involved in multiple metabolic pathways. More than 500 enzymes are created, sustained, and uniquely maintained by NAD+ and are therefore NAD+ dependent. Boosting NAD+ levels is an effective way to treat a wide variety of pathophysiological conditions. I have found that the best way to enhance levels of NAD+ is to supplement with nicotinamide riboside (NR), one of the most studied NAD+ precursors. Mounting scientific evidence from animal and human studies has validated NR’s health benefits in several cardiovascular, neurodegenerative, and metabolic disorders.11

Functional medicine providers must not become myopic and focus on just one condition or organ system. Instead, it is the entirety of patients that is important. If a nutrient can support biochemistry, healthy aging, and cellular performance in all the trillions of cells in the human body, is that not the perfect fit? Such is the case with NR. I tell my patients it’s like the saying, “A rising tide lifts all boats.” So, too, NR improves all aspects of health.

Nevertheless, having acknowledged the importance of NR’s role in the body as a whole, we will zoom in on its role in cardiovascular health and related conditions. Mitochondrial dysfunction disrupts NAD+ homeostasis, which leads to the development of cardiac hypertrophy and heart failure.11

NAD exists in its oxidized form (NAD+) and its reduced form (NADH). The NAD+/NADH ratio is important as this is what dictates how well the cell can make adenosine triphosphate (ATP), the fuel our cells use to produce energy. The heart has a high energy demand and requires the ongoing production of large amounts of ATP.10 In heart failure, the NAD+/NADH ratio shifts,12 which affects cardiac vulnerability to stress.11Supplementation with NR normalizes the NAD+/NADH ratio and protects the heart from adverse cardiac remodeling while also triggering antioxidant gene expression.13 By improving NAD+ homeostasis, NR can stop the decline in cardiac function and therefore protect against heart failure.11

There is an association between cardiovascular problems, and inflammation, and NR may have a role to play in reducing this inflammatory response. In humans with stage D heart failure, NR supplementation protected the mitochondria of peripheral blood mononucleated cells, leading to a lower inflammatory response.14 Another human study in 12 aged men found that NR lowered levels of circulating inflammatory cytokines and exhibited anti-inflammatory effects.15

Animal research indicates that increasing NAD+ levels also improve metabolic disorders linked to cardiovascular diseases such as type-2 diabetes and metabolic syndrome.11,16 Furthermore, increasing NAD+ levels is important in non-alcoholic fatty liver disease (NAFLD),11 a condition associated with increased cardiomyopathy, atherosclerosis, and arrhythmias.17

Conclusion

There are often several factors that are neglected when evaluating the heart health of patients. I tell my patients in regard to the heart, “There is no single organ that is more tangibly physical and yet metaphysical at the very same moment.” Ignoring this fact is why mental health aspects of cardiovascular problems are often under appreciated. 

Other neglected factors include determining if a patient has sleep apnea, proper hydration, the role of food sensitivities in inflammation of the circulatory vasculature, and the use of an organic acid profile test to evaluate whether the heart is getting enough energy. Finally, increasing levels of NAD+ through supplementation with nicotinamide riboside is critical for cardiovascular health and cardiac energy metabolism.

6 Ways to Improve Cardiac Energetics

Test for Sleep Apnea
Drink Enough Water
Support Mental Health
Test for Food Sensitivities (Linked to Circulatory System Inflammation)
Order an organic acid profile
Support healthy levels of NAD+  (Levels Decrease with Aging and During Stress)

References:

  1. Frenzel A, et al. The aging human body shape. NPJ Aging Mech Dis. 2020;6:5.
  2. Watso JC, Farquhar WB. Hydration Status and Cardiovascular Function. 2019;11(8).
  3. Armstrong LE, Johnson EC. Water Intake, Water Balance, and the Elusive Daily Water Requirement. Nutrients. 2018;10(12).
  4. Kurabayashi H, et al. A glass of water at midnight for possible prevention of cerebral infarction. 1991;22(10):1326-1327.
  5. Kemp DE, et al. Heart disease and depression: don’t ignore the relationship. Cleve Clin J Med. 2003;70(9):745-746, 749-750, 752-744 passim.
  6. Dawson DK. Acute stress-induced (takotsubo) cardiomyopathy. Heart. 2018;104(2):96-102.
  7. Karakula-Juchnowicz H, et al. The Food-Specific Serum IgG Reactivity in Major Depressive Disorder Patients, Irritable Bowel Syndrome Patients and Healthy Controls. Nutrients. 2018;10(5).
  8. Lopez-Candales A, et al. Linking Chronic Inflammation with Cardiovascular Disease: From Normal Aging to the Metabolic Syndrome. J Nat Sci. 2017;3(4).
  9. Pompei P, et al. A Clinical Evidence of a Correlation Between Insulin Resistance and the ALCAT Food Intolerance Test. Altern Ther Health Med. 2019;25(2):22-38.
  10. Lopaschuk GD, et al. Cardiac Energy Metabolism in Heart Failure. Circ Res. 2021;128(10):1487-1513.
  11. Mehmel M, Jovanović N, Spitz U. Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Nutrients. 2020;12(6).
  12. Lee CF, Tian R. Mitochondrion as a Target for Heart Failure Therapy- Role of Protein Lysine Acetylation. Circ J. 2015;79(9):1863-1870.
  13. Diguet N, et al. Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy. Circulation. 2018;137(21):2256-2273.
  14. Zhou B, et al. Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure. J Clin Invest. 2020;130(11):6054-6063.
  15. Elhassan YS, et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD(+) Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Rep. 2019;28(7):1717-1728.e1716.
  16. Trammell SA, et al. Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice. Sci Rep. 2016;6:26933.
  17. Stahl EP, et al. Nonalcoholic Fatty Liver Disease and the Heart: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73(8):948-963.

Author Bio:

Chris D. Meletis, ND, is an educator, international author, and lecturer. His mission is “Changing the World’s Health One Person at a Time.” Dr. Meletis has authored 18 books and over 200 national scientific journal articles, including Natural Health,  Alternative and Complementary Therapies, Townsend Letter for Doctors and Patients, Life Extension, Natural Pharmacy, NDNR, and PubMed.gov.

Dr. Meletis served as Dean of Naturopathic Medicine and Chief Medical Officer for 7 years for the National College of Naturopathic Medicine (now the National University of Natural Medicine). The American Association of Naturopathic Physicians awarded him the 2003 Physician of the Year. He has a deep passion for helping the underprivileged and spearheaded the creation of 16 free natural medicine healthcare clinics in the Portland metropolitan area of Oregon.

Consult your doctor before using any of the treatments mentioned in this article.

Reprinted with permission from the May 2022 Townsend Letter, and Chris D. Meletis, ND.

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