Mending the Mitochondria: Lipid Replacement Therapy for Chronic Fatigue Syndrome

At the very heart of it chronic fatigue syndrome is characterized by impaired mitochondria function. These cellular powerhouses function to create energy for the cell in the form of ATP. Many note that in CFS chronic oxidative stress and inflammatory mediators contribute to mitochondrial dysfunction and loss (1). A vicious cycle is created in which free radicals overwhelm the delicate mitochondrial membrane producing even more highly reactive free radicals.

Electrons leak out of membranes disrupting the electrochemical gradient necessary to form ATP—a phenomenon called “leaky mitochondria.” Leaky mitochondrial membranes promote progressive functional loss linked to a number of chronic illnesses (2). Repair mechanisms such as antioxidant enzymes and transporters are hindered, leaving dilapidated machinery unable to meet the body’s energy demands (3).

Several studies in CFS and fibromyalgia show evidence of increased markers of free radical damage; including DNA oxidation and lipid oxidation (1). These markers are measured through blood or as urine organic acid metabolites. Excessive nitric oxide is also observed indicating changes in cytokines as the cycle of free radical damage ensues (1).

Microbial byproducts generated from dysbiosis may also damage the mitochondria. Excessive hydrogen sulfide produced from microbe overgrowth in the small intestine (SIBO) can damage mitochondrial complexes in a dose-dependent manner similar to the action of cyanide (2).

Supplementation with mitochondrial supports are widely utilized by CFS and FM patients. Critical nutrients like alpha-lipoic acid, co-enzyme Q10, NADH, and L-carnitine are well documented as efficacious for mitochondrial health and energy production (4). Individual research surrounding these nutrients has its drawbacks, however. One may presume that these interventions work best together and may not have substantial effects in isolation.

Nutrients used for Mitochondrial Support

  • Vitamins

    • Vitamin B1, B2, B3, B6, vitamin C

  • Minerals

    • Magnesium, calcium, zinc, copper

  • Metabolites

    • Creatine

  • Cofactors

    • CoQ10, alpha-lipoic acid, NADH, nicotinomide riboside

  • Transporters

    • L-carnitine, phospholipids (glycerophosphocholine & phosphatidylserine)

From Leaky Mitochondria to Leaky Brain

The brain utilizes oxygen for ATP production more than any other body tissue. As a result, free radical production is abundant in the brain. This is further complicated by the fact that neural tissue is rich in polyunsaturated fats which are easily oxidized promoting free radical damage. Brain mitochondria house inferior antioxidant defenses compared to the greater cell, with neural mitochondrial damage 10-100 times more likely than nuclear DNA (3). Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, dementia, and ALS are now believed to stem from mitochondrial damage of neural tissues.

Neuroinflammation was recently documented in a study using advanced imaging techniques in ME/CFS patients. A substantial difference in an inflammatory marker produced by astrocytes and microglia was found to be 45%–199% higher in ME/CFS patients than in healthy controls (6). Those with the greatest neuroinflammation also experienced the worst cognitive symptoms. This small study further suggests that mitochondrial damage of neural tissue perpetuates the illness.

New research in the field of neuroplasticity tells us that neural tissue is dynamic and able to repair from oxidative damage. Brain-derived growth factors and neural stem cells can be stimulated by certain nutrients to help repair damaged neuronal mitochondria and cell membranes. Curcumin, L-carnitine, and glycerophosphocholine (GP) studies show these three nutrients can stimulate neuroplasticity via growth factor promotion (6). The lipid phosphatidylserine (PS) is directly linked to mitochondrial support as it is the precursor to phosphatidylethanolamine (PE), the most abundant lipid of the mitochondrial membrane.

Lipid Replacement Therapy

Earlier this year I had the pleasure of hearing Dr. Garth Nicolson present new research in the arena of mitochondrial health. His team developed a mitochondrial membrane phospholipid combining antioxidants and lipid transporters. This combined lipid replacement therapy (LRT) taken orally replaces damaged membrane phospholipids with undamaged lipids, ensuring proper function of cellular and mitochondrial membranes (4). To be effective, LRT must deliver high concentrations of undamaged membrane lipids to reverse damage and restore function of oxidized cellular membranes. Special formulations are required for these lipids to survive ingestion and the digestive processes.

Lipid replacement therapy with NT factor is an option for repairing damaged mitochondrial membranes.

His team redeveloped the supplement NT Factor and studied its effects in several clinical trials. In a 12 week cross-over study in individuals with chronic fatigue syndrome and fibromyalgia, supplementation resulted in a 35.5% reduction in fatigue and 26.8% increase in mitochondrial function. After a 12-week washout period (supplement discontinued), fatigue increased and mitochondrial function decreased toward control levels (4).

Similar improvements were found in a cohort of patients with unspecified fatigue. A two-month trial of 58 patients with various non-specified fatigue conditions (including CFS, FM, cancer, GWI, autoimmune disease) were supplemented with ATP Fuel, a combined lipid replacement and antioxidant product. After 8 weeks, 30% experienced reduced fatigue and 28% experienced improved cognition (5).

My Experience Using LRT

Impressed with Nicolson’s results, I naturally tried LRT for myself. A single dose of NT Factor (Allergy Research Group) provided me a sustained boost in energy and mental clarity. A similar effect was had using ATP Fuel (Researched Nutritionals), with the need to lower the dose as energy was a little too much. On a regular basis I utilize glycerophosphocholine and phosphatidylserine (Brain Vitale, Designs for Health) for mental clarity. Collectively these nutrients have erased my brain fog, severe memory deficits, and aphasia (difficulty finding words).

When used in conjunction with other effective CFS/FM therapies, LRT is a valuable addition to improve clinical outcomes. Undoing the vicious cycle of free radical damage and inflammatory cytokines through diet and intermittent fasting can slow mitochondrial decline. Taken together, periodic LRT can effectively restore damaged cellular membranes and promote energy production.

Disclaimer: I am not affiliated with these or any supplement companies. These products are sold through the FullScript store and the RN Shop (e-mail for password)..


1  Maes, M. & Morris, G. (2014) Mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways. Metab Brain Dis. 29(1):19-36.

2  Vasquez, A. (2014) Mitochondrial medicine arrives to prime time in clinical care: nutritional biochemistry and mitochondrial hyperpermeability ("leaky mitochondria") meet disease pathogenesis and clinical interventions. Altern Ther Health Med. 20 Suppl 1:26-30.

3  Kidd, PM. (2005) Neurodegeneration from mitochondrial insufficiency: nutrients, stem cells, growth factors, and prospects for brain rebuilding using integrative management. Altern Med Rev. 10(4):268-93.  

4  Nicolson, GL. (2005) Lipid Replacement to Reduce the Adverse Effects of Cancer Therapy. Pathology Oncology Research. 11(3):139-144.

5  Nicolson, GL. (2014) Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements. Alternative Therapies. 20 Suppl 1:18-25.

6  Nakatomi Y., et al (2014) Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study. J Nucl Med. [Epub ahead of print]