Laser therapy for mitochondrial dysfunction

The use of low-level laser therapy (LLLT) across three different wavelengths simultaneously is an exciting new development for treating mitochondrial dysfunction.

When the laser light contains wavelengths from the red-green-violet portions of the spectrum, all phases of the mitochondrial energy generation process are stimulated.

How mitochondria make energy

Every cell in the body — except red blood cells — contains many mitochondria. These tiny powerhouses generate cellular energy through adenosine triphosphate (ATP), which powers nearly all of the body’s essential functions. Cells that need more energy, such as those in the heart, liver, muscles and brain, contain more mitochondria. Liver cells contain one to 2,000 mitochondria per cell; each heart cell contains about 5,000 mitochondria. In addition to the intracellular mitochondria, free-floating mitochondria circulate in the bloodstream.¹

The process of converting glucose to ATP occurs within each mitochondrion’s folded inner membrane. It begins when glucose from the cell enters the mitochondrion through the structure’s outer membrane. The glucose is then metabolized in the mitochondrial matrix by the citric acid cycle (the Krebs cycle) into breakdown products (chiefly pyruvate). These products then move into the inner membrane of the mitochondrion and the process of converting them to ATP begins.

Through a series of redox reactions, the nutrients are moved along an electron transport chain (ETC) through five protein components. At each of the first four stages along the chain, the process produces free energy that finally drives the phosphorylation of adenosine diphosphate (ADP) to ATP in the fifth and final complex of the chain, ATP synthase.

In the end, one glucose molecule has been converted to 36 to 38 molecules of ATP, along with carbon dioxide and water as byproducts.

Mitochondrial dysfunction: Disrupting energy production

When mitochondrial energy production moves smoothly, the body has ample energy for normal functions, growth and adaptation. However, when the process is disrupted, mitochondrial dysfunction sets in. Energy levels drop, oxidative stress increases, cell signaling is disrupted and inflammation occurs. The lowered ATP levels can lead to fatigue, hypersensitivity and chronic pain.² Chronically impaired mitochondrial function can even lead to fatal organ failure.³

Mitochondrial dysfunction occurs when the mitochondria aren’t working efficiently. Fundamental causes of mitochondrial dysfunction include:

Oxidative stress. Energy production within the mitochondria generates high levels of free radicals, particularly reactive oxygen species (ROS), which can overwhelm antioxidant levels, leading to damage from oxidative stress, impaired function and inflammation.

Viral illness. Mitochondrial dysfunction caused by viral illness is a significant underlying cause of chronic illness, including long COVID. Viruses can damage the mitochondria’s delicate internal structures and lead to increased production of free radicals and the cascade of damage this causes. The mitochondria can no longer produce energy efficiently, leading to chronic and often severe fatigue.

Environmental factors. Exposure to environmental toxins, such as heavy metals, pesticides and certain drugs, can disrupt the integrity of the outer and inner mitochondrial membranes. They can also interfere with enzyme activity and damage mitochondrial DNA replication and repair mechanisms. Standard OTC and prescription non-steroidal anti-inflammatory drugs, including aspirin, ibuprofen, indomethacin and diclofenac, can inhibit the electron transport chain and impair mitochondrial function.

Age-related changes. Overall mitochondrial function declines with age, partly from the accumulated damage of oxidative stress and decreased efficiency of repair mechanisms. Age-related mitochondrial dysfunction contributes to age-related diseases and declines in overall cellular function.⁴

Sedentary lifestyle. Lack of physical activity leads to lower production of oxidative enzymes, more damage from free radicals and reduced electron transport chain activity.

Metabolic disorders. Prediabetes, diabetes, obesity and metabolic syndrome can impair mitochondrial function by disrupting glucose breakdown, damaging the mitochondrial membranes and increasing oxidative stress and free radical damage.

Cell danger response

When the mitochondria become dysfunctional from age, lifestyle and metabolic disorders, all systems in the body, including the immune system, operate at suboptimal levels. A poor lifestyle that leads to suboptimal mitochondrial function also leads to chronic low-level inflammation, which causes further mitochondrial dysfunction and a self-perpetuating loop of fatigue and additional damage. If a viral illness such as COVID or RSV is added to the already dysfunctional system, the immune system is less equipped to fight it.

When illness strikes, the mitochondria enter the cell danger response (CDR) mode. CDR is defined as “the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical or biological threats that exceed the cellular capacity for homeostasis. ”⁵

In CDR, mitochondrial activity switches from energy production to cell defense in the cell to support the immune system. In other words, the mitochondria downregulate and divert their energy to the immune system.

When the mitochondria switch over to cellular energy production that favors immune defense, little energy is left for other functions. This is the underlying cause of fatigue that usually accompanies any illness. Healthy mitochondria have enough reserve to continue generating energy, although at a reduced level, during an illness. When the mitochondria function well, energy levels return to normal after the body fights off infection.

However, in some cases, the danger response in the mitochondria doesn’t switch off. The cells can’t turn off the danger response until they receive signals from the adaptive immune system telling them the danger is past. If the signal isn’t given or received, CDR remains active and blocks the return to homeostasis and normal energy levels.

CDR can be modulated with an anti-inflammatory diet, exercise and stress management. Supplements that can help include vitamin D and zinc to support immune function and adaptogens, such as ashwagandha. Also essential are prebiotics and probiotics for a healthy gut microbiome.

Low-level laser therapy for mitochondrial dysfunction

The electron transport chain in the mitochondria uses high-energy electrons and hydrogen ions to convert ADP into ATP.⁶

Because the process is so energetic, nonthermal laser light can stimulate it and improve the function and stability of the mitochondria by delivering highly energetic photons of energy into the cell. When photons of visible light energy from a non-thermal laser strike certain atoms in the inner membrane of the mitochondria, where the electron transport chain occurs, the energy may push an electron from that atom to a higher energy level, where an electron acceptor in the electron transport chain can pick it up.

Photons in the visible laser light spectrum are believed to affect complexes I, II, III and IV of the electron transport chain. Some wavelengths used in low-level laser therapy are particularly effective at different points along the electron transport chain. Using the correct wavelengths is critical to achieving an excellent therapeutic response.

Laser light in the 400- to 450-nm (violet) range stimulates complexes I and II. Complex I is the electron transport chain’s largest and most complicated complex.⁷ The reactions here are rate-limiting; any dysfunction at this point will affect energy production as it moves through the downstream complexes. Laser therapy using the violet wavelength supplies sufficient photonic energy to trigger the needed electron jumps to make complexes I and II function more efficiently.⁸

Complex III is stimulated by laser light in the 500- to 560-nm (green) range. Laser light in this range can stimulate the processes related to oxidative phosphorylation at the ATP synthase complex, the final step in the production of ATP.⁹

Complex IV is stimulated only by laser light in the 600- to 670-nm (red) range.

By stimulating the activity of the ETC complexes, the rate-limiting mechanism for ATP is restored, and ATP production within the mitochondria is increased. In addition, the free-floating mitochondria in the bloodstream absorb photon energy and disperse throughout the body, allowing photon energy to have a systemic effect on sites away from the laser application site.

Restoring mitochondrial function

When mitochondria become dysfunctional, their normal function can often be restored with a combination of lifestyle changes, nutritional supplements and low-level laser therapy.

Numerous studies have shown exercise is a highly effective way to improve mitochondrial function. Exercise helps enhance mitochondrial health by increasing the activity of the genes that produce mitochondrial proteins and enzymes and decreasing oxidative stress. In overweight, sedentary people, exercise increases the total number of mitochondria in muscle cells and increases the production of mitochondrial oxidative enzymes, accompanied by improvements in insulin resistance.¹⁰ Exercise to improve mitochondrial function is also valuable for fighting many chronic diseases, including heart failure and peripheral artery disease. Improved mitochondrial function from exercise may also play a critical role in preventing cognitive impairment and Alzheimer’s disease and in maintaining muscle mass in older adults.¹¹

Supplements

The production of ATP in mitochondria relies on several enzymes and coenzymes to function correctly. In the cell, glycolysis and the Krebs cycle need the coenzyme nicotinamide adenine dinucleotide (NAD) to complete the reactions and break down glucose before it enters the inner membrane of the mitochondrion. Complex I also requires NAD to function properly. NAD+ is the oxidized form of NAD; NADH is the reduced form. Within the mitochondria, they are the two sides of the redox reactions that shuttle electrons along the electron transport chain. Individuals may be low on NAD because of low intake of niacin, a B vitamin that is a crucial precursor needed for NAD production. Normal age-related decline can also lead to low NAD levels.

In complex II, ubiquinone (CoQ10) is needed to move the free electrons to the next electron transport chain phase. CoQ10 levels may be low in individuals taking statin drugs and in those with heart failure; levels also decline with age.

The following supplement protocol is recommended to support optimal mitochondrial function:

B vitamins: 60 mg/day
CoQ10: 300 mg/day
Acetyl-L-carnitine: 1,000 mg/day
NMN (nicotinamide mononucleotide), a precursor to NAD: 200 mg/day
Alpha-lipoic acid (ALA): 600 mg/day
NAC/liposomal glutathione: 500 mg/day
Magnesium: 200 mg/day
Zinc: 40 mg/day
Selenium: 200 mcg/day
Vitamin C: 2,000 mg/day

Low-level laser therapy

Low-level laser therapy using a red-green-violet nonthermal laser can help stimulate energy production within the mitochondria. These wavelengths target the entire mitochondria electron transport chain, particularly the high-photon energy green and violet wavelengths. The key to their effectiveness is the photobiomic energy the wavelengths transmit to the cells and their mitochondria.

Laser light in the red-green-violet wavelengths activates photoreceptor molecules at every point along the mitochondrial electron transfer chain. The photobiomic effect is particularly effective for impacting the enzyme cytochrome c oxidase production in complex IV.¹² When the electron flow in the mitochondria is limited or completely blocked, the effect is like a kink in a hose: Nothing gets through. The photobiomodulation impact of red-green-violet laser light unkinks the hose and restores the energy flow.

Final thoughts

Evidence-based research supports the use of low-level laser therapy for treating chronic musculoskeletal pain. A recent study shows high photo energy wavelengths in the green and violet spectrum are highly effective in reducing chronic neck and shoulder pain. This study provided substantial support for the first Food and Drug Administration clearance for the combined application of green and violet lasers.¹³ Other research suggests red-green-violet laser therapy can be helpful for a range of different disorders related to mitochondrial dysfunction, including chronic fatigue and traumatic brain injuries.

ROBERT G. SILVERMAN, DC, DACBN, DCBCN, MS, CCN, CNS, CSCS, CIISN, CKTP, CES, HKC, FAKTR, is a doctor of chiropractic, clinical nutritionist, national/international speaker, author of Amazon’s #1 bestseller Inside-Out Health, and founder and CEO of Westchester Integrative Health Center. He graduated magna cum laude from the University of Bridgeport College of Chiropractic and has a master’s degree in human nutrition. The ACA Sports Council named Silverman Sports Chiropractor of the Year in 2015. He is on the advisory board for Functional Medicine University and is a seasoned health and wellness expert on the speaking circuits and in the media. A thought leader in his field and practice, he is a frequently published author in peer-reviewed journals and other mainstream publications and was the principal investigator in two Level 1 laser FDA studies. His new book, Amazon best-seller Immune Reboot, was released in December 2022. For more information, visit drrobertsilverman.com.

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