Whole-person care is a person-centered approach to medicine. It goes beyond treating symptoms or isolated conditions, focusing on the interconnectedness of bodily systems and addressing a wide range of factors. These include biological makeup, behavioral habits, environmental factors, and a patient’s personal beliefs, values, and goals. By tailoring care to align with these unique aspects, healthcare providers can create highly personalized treatment plans that address not only physical health but also emotional and mental well-being.

This template aims to provide healthcare providers with practical suggestions for labs, supplements, and lifestyle strategies, helping them design personalized, whole-person care plans for patients looking to support mitochondrial health and function. 

Mitochondria are essential for cellular energy production, redox signaling, and metabolic regulation. Dysfunction in these organelles has been implicated in a wide range of health conditions, including chronic fatigue, neurodegenerative diseases, and cardiometabolic disorders. (Nicolson 2014)

Comprehensive lab testing evaluates markers of oxidative stress, inflammation, and micronutrient status—all of which influence mitochondrial integrity and performance. Identifying areas of imbalance can provide insight into the underlying causes of mitochondrial dysfunction and guide targeted, customized interventions.

Evidence-based supplements, including antioxidants and mitochondrial cofactors, support mitochondrial bioenergetics, enhance antioxidant defenses, and restore metabolic flexibility. Dosing strategies and clinical rationale included in this protocol are informed by scientific literature and mitochondrial medicine guidelines.

Lifestyle modifications are also foundational to mitochondrial health. Nutrition, exercise, stress, sleep, and toxic environmental exposures modulate mitochondrial function and oxidative balance. A comprehensive care plan should screen for and address lifestyle-related contributors to mitochondrial stress and implement sustainable practices that promote cellular resilience.

Labs

NutrEval® FMV

OMX® Organic Metabolomics

F2-Isoprostane/Creatinine Ratio

Ingredients

Carnitine

Dosing: 330–990 mg 2–3 times per day for eight weeks; 3 g per day is the usual maximum dose (Parikh 2009)(Gimenes 2015)

Supporting evidence:

• L-carnitine transports long-chain fatty acids into the mitochondrial matrix for β-oxidation and adenosine triphosphate (ATP) production. L-carnitine also facilitates the export of excess acyl groups as acylcarnitines, preventing the accumulation of toxic metabolites within the mitochondria. Metabolic inflexibility can be associated with states of carnitine deficiency. (Virmani 2022)
• Carnitine insufficiency/deficiency has been measured in up to 43.8% of patients with mitochondrial myopathies. (Campos 1993)(Hsu 1995) An open-label study administered carnitine to individuals aged 2–64 with mitochondrial myopathy and carnitine insufficiency (n=48). Supplementation helped normalize plasma carnitine levels in all patients after ten days. Additionally, muscle strength improved in 19 of 20 patients with muscle weakness, growth improved in four of eight patients with failure to thrive, and all eight patients with cardiomyopathy showed marked cardiac improvement. (Campos 1993)
• Supplementation with acetyl-L-carnitine has been shown to help restore mitochondrial content and function in aged animal models and humans, including increased cytochrome b content and improved oxidative phosphorylation, which translates to enhanced cellular energy states. (Hagen 2002)(Rosca 2009)
• A small double-blind, placebo-controlled crossover trial in patients with chronic progressive external ophthalmoplegia (n=12), a subtype of mitochondrial myopathy, demonstrated that L-carnitine supplementation helped improve aerobic capacity and exercise tolerance, as measured by increased time to exhaustion and higher oxygen consumption during constant work rate exercise testing. However, this study was limited by its small sample size and focus on a specific mitochondrial phenotype. (Gimenes 2015)
• Despite having limited clinical evidence supporting the use of L-carnitine in this population, the Mitochondrial Medicine Society recommends L-carnitine supplementation in patients with primary mitochondrial diseases and documented carnitine deficiency, and recommends regularly monitoring blood levels during therapy. (Parikh 2015)

B Vitamins

Dosing: Variable based on ingredients and formulation

Supporting evidence:

• B vitamins act as mitochondrial enzyme cofactors. Thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), and cobalamin (B12) are required for the activity of mitochondrial enzymes involved in the citric acid cycle and electron transport chain (ETC). Deficiency impairs ATP production and cellular communication, while supplementation can optimize enzymatic activity, mitochondrial energy metabolism, and overall mitochondrial health. (Depeint 2006)(Janssen 2019)(Palmieri 2022)
• Surveys of international prescribing practices confirm the widespread use of B vitamins among mitochondrial specialists based on mechanistic and biochemical rationale. (Neugebauer 2025)
• In a small open-label study in six patients with Kearns-Sayre syndrome (KSS), a mitochondrial myopathy, and cerebral 5-methyltetrahydrofolate (5-MTHF) deficiency, folinic acid—an immediate precursor of the biologically active 5-MTHF—was shown to normalize cerebral 5-MTHF concentrations in 50% of patients. Additionally, patients who received a higher dose of folinic acid showed improvements in neurological symptoms, including ataxia and tremor. (Quijada-Fraile 2014)
• In a case report, adding folinic acid and riboflavin to a folate-free dietary regimen improved neurological symptoms in a patient with mitochondrial complex I deficiency and cerebrospinal fluid (CSF) 5-MTHF deficiency. Combining these B vitamins with other supplements (coenzyme Q10 (coQ10), vitamin C, and vitamin E) helped further reduce seizure frequency, hypotonia, and ataxia. (Ramaekers 2007)
• Riboflavin supplementation has shown benefit for patients with primary mitochondrial diseases (PMDs) associated with complex I and II deficiencies. Positive clinical outcomes associated with supplementation include improved muscle strength, psychomotor development, energy, and cognitive function. (Bernsen 1993)(Ogle 1997)(Bugiani 2006)
• Thiamine is effective in pyruvate dehydrogenase complex deficiency and some cases of Leigh syndrome (a mitochondrial disorder), reducing lactate levels and improving neurological symptoms. (Mahoney 2002)(El-Hattab 2017)
• Vitamins B6 and B12 contribute to mitochondrial antioxidant defenses and regulate mito-nuclear communication (the bidirectional signaling between the mitochondria and nucleus to coordinate cellular function), reducing oxidative stress and supporting mitochondrial integrity beyond their classical cofactor roles. (Janssen 2019)(Schleicher 2023)(Mucha 2024)

CoQ10

Dosing: 100 mg three times daily for eight weeks (Dai 2011)

Supporting evidence:

• CoQ10, also known as ubiquinone, facilitates electron transport between complexes I/II and III of the ETC. Additionally, CoQ10 functions as a powerful antioxidant, protecting mitochondria from oxidative damage and supporting mitochondrial membrane integrity. (Sergi 2019)
• An in-vitro study demonstrated that CoQ10 deficiency may be a risk factor/indicator of mitochondrial dysfunction. Pretreatment with exogenous CoQ10 attenuated the deleterious effects of toxic hexavalent chromium on hepatocytes by reducing oxidative stress. (Zhong 2017)
• In a randomized controlled trial (RCT) in 30 patients with mitochondrial cytopathy, high-dose CoQ10 for 60 days attenuated the rise in lactate after exercise and modestly improved aerobic capacity. However, effects on muscle strength and resting lactate levels were limited. (Glover 2010)
• Smaller studies and case series report symptomatic benefits of CoQ10 supplementation in patients with various PMDs, particularly in slowing the progression of muscle weakness and reducing plasma lactate. (Bresolin 1990)(Gold 1996)(Chen 1997)
• Patients with ischemic left ventricular systolic dysfunction received CoQ10 (n=28) or a placebo (n=28) for eight weeks in a randomized, double-blind, placebo-controlled trial. Mitochondrial function was determined by the plasma lactate/pyruvate ratio (LP ratio). At the end of the trial, CoQ10-treated patients had significant increases in plasma CoQ10 levels and a significant reduction in LP ratio. This biochemical improvement correlated with a significant increase in brachial artery flow-mediated dilation (FMD), indicating enhanced endothelial function and a mechanistic link between mitochondrial function and vascular health. (Dai 2011)
• Despite limited large-scale trial data, the Mitochondrial Medicine Society recommends CoQ10 as a first-line supplement for mitochondrial disease, citing its safety profile and mechanistic rationale. (Parikh 2015)

Glutathione

Dosing: 500–1,000 mg per day for four weeks (based on pilot clinical data using liposomal formulations) (Sinha 2018)

Supporting evidence:

• Glutathione (GSH) is the principal mitochondrial antioxidant that directly neutralizes reactive oxygen species (ROS) generated by oxidative phosphorylation and maintains mitochondrial redox homeostasis. Deficiency in mitochondrial GSH (mGSH) leads to increased oxidative stress, mitochondrial dysfunction, and cell death. (Ribas 2014)(Marí 2020)(Chen 2024)
• GSH acts as a cofactor for mitochondrial glutathione peroxidase, detoxifying hydrogen peroxide and lipid hydroperoxides, and is essential for preventing mitochondrial membrane permeabilization and apoptosis. This distinguishes GSH from other antioxidants (e.g., vitamins C and E), which do not directly replenish mGSH pools. (Ribas 2014)(Marí 2020)(Chen 2024)
• In patients with mitochondrial disorders, whole blood GSH levels and the GSH/oxidized GSH (GSSG) ratio are significantly reduced, correlating with increased redox imbalance and disease severity. Restoration of GSH levels is proposed as a therapeutic target for improving mitochondrial function. (Enns 2014)(Enns 2017)
• In a one-month pilot study, daily oral supplementation with liposomal glutathione helped elevate systemic GSH stores, reduce oxidative stress biomarkers (including a 35% reduction in plasma 8-isoprostane), and enhance immune function in 12 healthy adults. (Sinha 2018)

Magnesium

Dosing: 200–400 mg elemental magnesium per day for at least six weeks; dose should be titrated to bowel tolerance, as diarrhea is a common limiting side effect (Costello 2023)

Supporting evidence:

• Magnesium is a cofactor for mitochondrial enzymes involved in oxidative phosphorylation and stabilizes ATP molecules. Deficiency impairs mitochondrial energy production and increases susceptibility to oxidative stress and inflammation, both of which are central to mitochondrial dysfunction. (Liu 2023)
• Experimental models of diabetes and heart failure demonstrate that magnesium supplementation helped restore mitochondrial ATP production, reduce mitochondrial ROS, repolarize mitochondrial membrane potential, and decrease mitochondrial calcium overload. These effects translated into improved cardiac diastolic function and reduced tissue injury in vivo. (Liu 2019)
• Magnesium stabilizes mitochondrial membranes and reduces cellular apoptosis and necrosis by promoting the binding and activity of mitochondrial hexokinase and creatine kinase and inhibiting the mitochondrial permeability transition pore (PTP) opening. This cytoprotective effect is particularly relevant in conditions with high intracellular calcium, which is antagonized by magnesium. (Golshani-Hebroni 2016)
• A recent systematic review and meta-analysis indicated that magnesium supplementation helps reduce systemic inflammation, as evidenced by lower C-reactive protein (CRP) levels, though direct antioxidant effects on mitochondrial biomarkers remain less conclusive. The anti-inflammatory action may indirectly support mitochondrial health by mitigating chronic inflammatory stress. (Cepeda 2025)

Lifestyle Recommendations

Nutrition

• Encourage a whole-foods, plant-centered diet—such as the Mediterranean diet—for daily intake of vegetables, legumes, whole grains, nuts, seeds, and extra-virgin olive oil, with moderate fish and poultry. This dietary pattern is rich in polyphenols, fiber, and healthy fats, supporting mitochondrial function and reducing inflammation and oxidative stress. (Kyriazis 2022)(Pollicino 2023)
• To ensure sufficient intake of mitochondrial-specific nutrients, counsel patients to eat foods high in:
  • • B vitamins (e.g., leafy greens, legumes, whole grains, and eggs)
    • Magnesium (e.g., nuts, seeds, whole grains, and leafy greens)
    • Omega-3 polyunsaturated acids (e.g., fatty fish, flaxseed, and walnuts)
    • Polyphenols (e.g., berries, dark chocolate, green tea, and olive oil)
    • Selenium (e.g., Brazil nuts, seafood, and eggs)
    • Vitamin C (e.g., citrus, bell peppers, and strawberries)
    • Zinc (e.g., oysters, legumes, nuts, and seeds) (Herbst 2014)(Wesselink 2019)
• Advise avoidance of ultra-processed foods, refined carbohydrates, and added sugars to prevent increased oxidative stress and impaired mitochondrial function. (Harlan 2023) 
• Discuss time-restricted eating or intermittent fasting as evidence-based dietary strategies that enhance mitochondrial biogenesis, autophagy, and ketone utilization. Fasting can activate adaptive cellular responses that increase antioxidant defenses, improve mitophagy, and reduce inflammation. Safety considerations include gradual implementation, close monitoring in patients with diabetes or those on glucose-lowering medications, and avoidance in pregnancy, underweight individuals, or those with a history of eating disorders. (Gouspillou 2013)(Mehrabani 2020) 
• A well-formulated ketogenic diet (high fat, moderate protein, very low carbohydrate) can enhance mitochondrial bioenergetics, increase mitochondrial biogenesis, and reduce oxidative stress. (Kyriazis 2022)(Guevara-Cruz 2024)

Movement and Exercise

• Exercise stimulates mitochondrial enzyme activity and cellular oxygen uptake, thereby increasing the number and size of mitochondria. (Huertas 2019)
• Recommend high-intensity interval training (e.g., cycling or treadmill) 3–5 days per week as the best form of exercise to stimulate mitochondrial biogenesis. (Robinson 2017)(Ruegsegger 2023)
• In addition to aerobic exercise, resistance training should be encouraged 2–3 times weekly to augment mitochondrial function and increase lean body mass. (Porter 2015)(Nilsson 2019)

Stress Management

• Chronic psychological stress induces sustained neuroendocrine and metabolic activation, leading to structural and functional recalibrations of mitochondria (“mitochondrial allostatic load”). (Picard 2018) Over time, this can lead to mitochondrial DNA damage, impaired biogenesis, increased membrane permeability, and increased ROS generation. (Allen 2021)
• Routinely screen for chronic psychological stress in patients with symptoms suggestive of mitochondrial dysfunction (e.g., fatigue, cognitive impairment, mood disorders, sleep disturbances).
• Recommend stress management programs and relaxation techniques to help reorient to stressful triggers and support the body during stressful times. 

Sleep

• Sleep deprivation and poor sleep quality significantly reduce mitochondrial numbers and induce mitochondrial structural abnormalities, leading to decreased ATP production. Additionally, increased ROS production and oxidative stress are consistently observed following sleep deprivation, with evidence of depleted antioxidant reserves and increased lipid peroxidation. (Wrede 2015)(Trivedi 2017) 
• Recommend that patients sleep for 7–9 hours per night. (Wrede 2015)
• Screen for sleep disorders, such as obstructive sleep apnea, which increase oxidative stress and can induce mitochondrial DNA damage. (Lacedonia 2015) 

Environmental Health

• Encourage patients to quit smoking, avoid exposure to secondhand smoke, and drink alcohol in moderation. (Cakir 2007) 
• Educate patients on sources of additional environmental toxins that can put additional physical stress on mitochondria, including pesticides, heavy metals, and air pollutants. (Reddam 2022)
• To minimize exposure to environmental toxins, encourage: 
  • • Consuming organic produce, especially those on the Environmental Working Group’s Dirty Dozen™ list
    • Storing food in glass, ceramic, or stainless steel containers, and avoiding microwaving food in plastic
    • Using nontoxic cookware instead of nonstick options
    • Using nontoxic cleaning agents and buying unscented personal care products (Metcalfe 2022)

Patient Resource

• Fueling Your Body’s Powerhouses