Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide, with the global burden of CVD nearly doubling between 1990 and 2019 (from approximately 271 to more than 523 million cases) and projected to continue rising. Conventional CVD risk assessment and management strategies typically focus on lipid parameters, blood pressure regulation, glycemic control, and lifestyle modifications, such as diet and physical activity. While these factors are essential, they may not fully address an important and often overlooked contributor to cardiovascular health — mitochondrial function. Mitochondria, commonly referred to as the “powerhouses of the cell”, are organelles responsible for generating most of the cellular energy in the form of adenosine triphosphate (ATP). The heart is one of the most energy-demanding organs in the body, relying on continuous mitochondrial ATP production to sustain normal function. Consequently, even subtle impairments in mitochondrial efficiency may compromise cardiac performance, underscoring mitochondrial health as an integral component of overall cardiovascular function. 

The Role of Mitochondria in Cardiovascular Health

Mitochondria serve as the primary source of energy in the heart, with the majority of myocardial ATP generated through oxidative phosphorylation — the final step of mitochondrial energy metabolism. During this process, electrons derived from the reduced forms of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH₂) are transferred through the mitochondrial electron transport chain, creating a proton gradient that drives ATP synthesis. Because the heart has minimal ATP reserves and would deplete its energy supply within seconds without continuous ATP production, mitochondria function as indispensable energy engines that sustain normal cardiac activity.

Beyond their role in energy production, mitochondria are essential for supporting the function, survival, and homeostasis of cardiomyocytes — the specialized contractile cells within the heart’s muscular layer responsible for generating the force needed to pump blood throughout the body. Cardiomyocytes have the highest ATP demand of all cardiac cell types and are correspondingly rich in mitochondria. These cells rely on precisely regulated calcium fluxes to coordinate excitation-contraction coupling (ECC), the process that links electrical signaling to mechanical contraction during each heartbeat. Mitochondria play a central role in ECC by responding to intracellular calcium signals and by actively taking up calcium through specialized channels such as the mitochondrial calcium uniporter (MCU). In doing so, mitochondria also function as calcium buffers, limiting excessive cytosolic calcium accumulation and protecting cardiomyocytes from calcium overload, which may otherwise contribute to arrhythmias or heart failure. In addition, mitochondria support redox homeostasis by generating reactive oxygen species (ROS) at controlled levels that participate in intracellular signaling. At low concentrations, mitochondrial ROS can activate adaptive signaling pathways that promote cardiac resilience and function, a phenomenon referred to as hormesis.

Under normal physiological conditions, mitochondrial ROS production serves important signaling functions. However, when mitochondrial function is compromised, excessive ROS generation, impaired ATP synthesis, and excessive cytosolic calcium may contribute to endothelial dysfunction, myocardial impairment, and increased CVD risk. Mitochondrial dysfunction has been associated with a broad spectrum of cardiovascular conditions, including ischemic injury, cardiomyopathy, and heart failure. One of the primary mechanisms may involve impaired mitochondrial bioenergetics, in which reduced ATP production compromises both systolic and diastolic cardiac function, contributing to diminished cardiac output, exercise intolerance, and heart failure. Additionally, excessive ROS generated by dysregulated mitochondria may contribute to endothelial dysfunction, vascular inflammation, plaque instability, and atherosclerotic lesion progression.

In addition to impaired energy production and oxidative stress, mitochondrial dysfunction may also affect substrate utilization within the heart. Since cardiomyocytes rely primarily on fatty acid oxidation for energy, impaired β-oxidation may lead to lipid accumulation, lipotoxicity, and reduced metabolic flexibility, thus increasing CVD risk. Mitochondrial damage may also activate apoptotic pathways and pro-inflammatory signaling, contributing to cardiomyocyte loss, adverse cardiac remodeling, and progression toward heart failure.

What are some nutrients that can support mitochondrial and cardiovascular health?

• Coenzyme Q10 (CoQ10) is a critical component of the mitochondrial electron transport chain, facilitating electron transfer from complexes I and II to complex III, thereby supporting ATP synthesis. As a lipid-soluble molecule, CoQ10 can integrate into mitochondrial membranes, where it not only functions as an electron carrier but also plays an important role in supporting the mitochondrial membrane structure. In addition to its role in energy production, CoQ10 may also promote a healthy antioxidant status by helping mitigate excessive ROS, which are commonly observed in CVD. CoQ10 exists in two biologically active and interconvertible forms: ubiquinone (oxidized) and ubiquinol (reduced). Ubiquinone primarily supports mitochondrial ATP production through its role as an electron acceptor, while ubiquinol promotes a healthy antioxidant status by mitigating oxidative stress and supporting redox balance. 
• L-Carnitine, the biologically active form of carnitine, is a conditionally essential nutrient that plays an important role in energy production and fatty acid metabolism by transporting long-chain fatty acids into mitochondria for β-oxidation — a critical energy pathway in cardiac tissue. Given the heart’s reliance on fatty acids as its primary fuel source, adequate L-carnitine availability is fundamental to cardiac bioenergetics. A systematic review and meta-analysis of 13 controlled trials (n = 3629) found that L-carnitine was associated with a reduction in ventricular arrhythmias, angina, and all-cause mortality in patients experiencing an acute myocardial infraction. Another systematic review of 13 meta-analyses suggests that L‑carnitine supplementation may help support lipid metabolism and improve lipid profiles, including reductions in total cholesterol, triglycerides, and low‑density lipoprotein cholesterol (LDL‑C), and increases in highdensity lipoprotein cholesterol (HDL‑C).
• Magnesium is a required cofactor for hundreds of enzymatic reactions, including those involved in mitochondrial ATP synthesis. It supports normal mitochondrial function, including electron transport and ATP production, and helps regulate intracellular calcium levels. These magnesium‑dependent processes support vascular tone, cardiac excitability, and heart rhythm. Conversely, magnesium deficiency has been associated with arrhythmia, impaired cardiovascular function, hypertension, impaired glucose tolerance, and increased cardiovascular risk.
• Nicotinamide adenine dinucleotide (NAD⁺) is a central coenzyme in mitochondrial redox reactions and cellular energy metabolism. NAD⁺ levels decline with aging, metabolic stress, and many chronic pathological conditions, which may contribute to impaired mitochondrial function and reduced cellular resilience. NAD⁺ precursors, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have been shown to support NAD⁺ status and mitochondrial function, including mitochondrial biogenesis, mitophagy, antioxidant responses, and overall energy production. 

Cardiovascular health is closely related to efficient cellular energy metabolism, with mitochondrial function playing a central role in supporting cardiac performance, vascular integrity, and metabolic resilience. Prioritizing mitochondrial health through targeted dietary strategies and evidence-based nutritional supplementation may play a role in proactively supporting long-term cardiovascular health at a foundational level. 

Learn more about mitochondrial and cardiovascular health: 

CoQ10 Helps Promote Mitochondrial Function

The Latest on Nicotinamide Riboside for Optimal Energy and Cellular Health

Fueling Mitochondria for Illness Recovery

Supporting Cellular Energy Production and NAD+ Status with Nicotinamide Riboside (NR)

L-Carnitine for Energy Production and Beyond

By Antonia Toupet, PhD