Red Light Therapy and Methylene Blue May Promote Brain Health

By Mitchell Liester and June Winsor

A new therapy is showing promise for the treatment of mental illness and neurodegenerative disorders. This treatment, which consists of a blue dye and red light, may improve disorders ranging from depression to Alzheimer’s disease. The two components of this treatment are methylene blue (MB) and red light therapy, also known as photobiomodulation (PBM).

Methylene blue

Source: Amanda Slater / Wikimedia Commons, Creative Commons Attribution-Share Alike 2.0 Generic

Methylene blue

MB is a U.S. Food and Drug Administration-approved medication that is inexpensive and safe to use. However, this agent didn’t start out as a medicine. Developed in 1876, MB was first used as a dye for textiles. In 1907, the German biochemist Paul Ehrlich described MB as a “Magic Bullet” due to its ability to recognize and target cells with impaired mitochondrial function. This blue dye was also administered to soldiers during World War I after it was found to be effective in treating malaria. In the early 20th century, MB was used as an antidote for cyanide poisoning, and today it is employed as a treatment for a blood disorder known as methemoglobinemia.

More recently, MB has been suggested to treat a wide range of disorders including COVID-19, Alzheimer’s disease, depression, anxiety, and schizophrenia. Additionally, MB has been shown to improve memory in humans even when no underlying neuropsychiatric disorder is present. So, how does MB work?

Mitochondria are cellular organelles that produce most of the energy cells need to function. This energy is created in the form of ATP through a process known as oxidative phosphorylation. Mitochondrial production of ATP, which is decreased in individuals who are depressed, increases following treatment with MB, thereby increasing cellular energy.

In addition to increasing ATP production, mitochondria also produce reactive oxygen species (ROS), such as hydrogen peroxide. Excess levels of ROS produce oxidative stress, which damages lipids and proteins and oxidizes mitochondrial DNA. Methylene blue regulates ROS levels and thereby reduces oxidative stress.

Chronic stress inhibits oxidative phosphorylation and damages parts of the brain including the hippocampus, cortex, and hypothalamus. Individuals with depression have been found to have higher levels of mitochondrial oxidative damage. Such damage produces inflammation, which plays a critical role in depression. MB, which crosses the blood-brain barrier, improves neuronal function and brain health. MB also upregulates brain-derived neurotrophic factor (BDNF), which stimulates neuroplasticity.

MB has been demonstrated to improve symptoms of depression. In a study of individuals with severe depression, 15 mg of MB daily significantly improved depressive symptoms. A second study, which involved a six-month double-blind crossover design, examined the effects of 195 mg of MB daily on depression and anxiety in individuals with bipolar disorder. This study found both depression and anxiety improved with MB treatment, and manic symptoms remained low throughout the study. A third study compared 15 mg versus 300 mg of MB daily in 17 individuals with bipolar disorder. This study found individuals treated with the higher dose were significantly less depressed. No difference in manic symptoms was observed. In a fourth study, MB was demonstrated to be effective for treatment-resistant bipolar disorder. Among 19 individuals with bipolar disorder, 14 improved after taking 100 mg of MB orally two or three times daily.

Photobiomodulation

Source: Collab Media / Pexels

Photobiomodulation

Photobiomodulation (PMB) treatment employs red light (400–720 nm) or near-infrared light (700–1000 nm) to stimulate healing, increase mitochondrial function, improve blood flow, and enhance tissue oxygenation. Also known as low-level light laser therapy (LLLT), PBM reduces swelling, increases antioxidants, decreases inflammation, regulates the brain’s immune system, and protects against cell death as well as tissue damage and cellular injury. In addition, PBM has been suggested to treat depression and other neuropsychiatric disorders including anxiety, insomnia, mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, and stroke. PBM also enhances cognitive functioning in people who do not suffer from neuropsychiatric disorders.

Several possible mechanisms of action have been proposed to explain PBM’s beneficial effects. These include increased cellular energy (via enhanced production of ATP), vasodilation, and stimulation of cell signaling pathways. PBM also reduces oxidative stress and triggers the release of BDNF. PBM is also cytoprotective, which means this treatment protects cells that are at risk of dying.

PBM exhibits a biphasic dose response. Whereas lower doses work well, higher doses often produce fewer benefits and can even be damaging.

Studies have found certain wavelengths of red light can penetrate the skull and reach the brain. Several factors influence how deeply the light penetrates the brain including the wavelength of the light. However, it may not be necessary to penetrate the skull as PBM exposure to other parts of the body also produces beneficial neurocognitive effects.

Therapy Essential Reads

The Transformative Power of Questions in Psychotherapy

The Fascinating History of Animal-Assisted Therapy

Combination therapy with methylene blue and photobiomodulation

Physicians and scientists have been exploring the combined use of MB and PBM to treat a wide variety of medical conditions ranging from COVID-19 to neuropsychiatric conditions such as Kleine-Levin syndrome. Together, MB and PBM have a synergistic relationship wherein MB donates electrons and PBM contributes protons to the electron transport chain, resulting in an increase in ATP production. The increase in mitochondrial and overall cellular activity, function, and respiration protects against neurodegeneration. These two interventions share common cellular mechanisms such as enhanced energy production, low-dose hormetic dose responses, reduction in oxidative stress, and upregulation of BDNF. All of these mechanisms serve to protect neurons from degeneration.

Risks and contraindications

Side effects with MB are generally mild. One of the most common effects is a change in the color of urine to bluish-green. MB should not be taken with medications that include or increase serotonin such as SSRIs, SNRIs, MAOIs, and TCAs. This combination can trigger a dangerous rise in serotonin levels, known as serotonin syndrome when MB is taken at doses greater than 5 mg/kg. Also, MB should not be used by pregnant women nor should it be given to infants. In addition, MB should not be used by individuals with a genetic disorder known as glucose-6-phosphate dehydrogenase deficiency. Risks with PBM are minimal but include skin irritation and eye damage when used at high levels. The use of protective glasses or goggles may be recommended when using red light therapy.

Future implications

At least one-third of people who suffer from depression do not respond to conventional antidepressant medications. Combined treatment with MB and PBM offers hope for these individuals. Additionally, future studies may discover additional therapeutic applications for this safe and effective treatment.

June Winsor

Source: June Winsor

June Winsor has a Bachelor's Degree of Science in business management. She is an independent researcher exploring alternative healing methods including indigenous healing practices. She has studied with Mayan healers in Guatemala; Achuar Shamans in the Amazon rainforest of Ecuador; medicine men and women in regions of Mexico including Nayarit, Guanajuato, El Tecolote, San Luis Potosi; and a Genseki Sensei in Shikoku, Japan.