SAD is believed to have a multifaceted etiology, with various hypotheses suggesting that sunlight deficiency and hormonal changes play significant roles. The condition is linked to neurotransmitters like dopamine, norepinephrine, and glutamate, although the exact pathophysiology is unclear. Disruptions in the body’s circadian rhythm due to reduced sunlight exposure during fall and winter are thought to be involved in the onset of winter-onset SAD. Additionally, alterations in melatonin and vitamin D levels due to seasonal changes can impact sleep patterns and mood regulation.

There are a number of theories as to how changes in sunlight exposure affect our health and well-being. More recent research is now revealing that red and near-infrared light, both being present in sunlight, could explain the associations between sunlight exposure and better health status. Body irradiation with red and near-infrared light, usually termed as photobiomodulation (PBM), has demonstrated beneficial effects in animal models of chronic diseases. Beyond this, preliminary evidence from random control trials suggest potential clinical benefit from PBM for chronic diseases. PBM has emerged as a potential, very popular, complementary approach for managing mental health conditions. In fact, a recent review looked at Fourteen studies published through July 2025, addressing conditions such as anxiety, depression, and seasonal affective disorder (SAD). They found that PBM showed therapeutic potential, with reported improvements in brain activity, reduced anxiety, and antidepressant effects. They concluded, “PBM appears to be a safe and promising complementary option for mental health, particularly for anxiety, depression, and SAD.”

One possible mechanism of PBMs beneficial effect on depression is its positive effect on mitochondria. Mitochondrial dysfunction might have a central role in the pathophysiology of depression. Depression is often characterized by lack of energy, concentration problems and fatigue. These symptoms might be partially explained by reduced availability of adenosine triphosphate (ATP) as a consequence of impaired mitochondrial functioning. A recent study investigated mitochondrial respiration in white blood cells, an established model to investigate the pathophysiology of depression. Their results suggest that the biomolecular pathophysiology of depressive symptoms are in part attributable to impaired energy supply due to mitochondrial dysfunction.

Additionally, there are several common causal factors for brain disorders (such as Alzheimer’s disease, traumatic brain injury, Parkinson’s disease, stroke and even depression). Mitochondrial dysfunction plays a central role in the induction of these causative factors which include oxidative stress, inflammation, transcriptional alterations, and excitotoxicity. Mitochondria contribute to the pathophysiology through decreased energy production and excessive production of reactive oxygen species (ROS) – free radicals. Research on mitochondrial dysfunction in brain diseases indicate that restoration of mitochondrial function may be a very important method for treating neurodegenerative brain disorders, including depression. Photobiomodulation and treatments utilizing methylene blue (MB) are two of the most widely studied approaches targeting mitochondrial respiration to improve mitochondria health and function.

Methylene Blue:

Methylene blue began in the late 19th century as a textile dye before quickly entering medicine as a microbial stain and early antimicrobial agent. Paul Ehrlich’s experiments in the 1880s–1890s established its first therapeutic uses, including malaria and urinary tract infections. Through the early 20th century it was used for infections and poisoning, but its mainstream role narrowed after World War II as newer drugs emerged. Interest was revived in the 2000s when integrative and alternative practitioners highlighted its mitochondrial effects, neuroprotective potential, and antimicrobial properties. This resurgence positioned methylene blue as a tool for cognitive enhancement, longevity, and cellular support.

Over the last couple of years, I have been using oral methylene blue treatments to help patients with chronic fatigue, depression and neurodegenerative conditions such as Parkinson’s disease and Alzheimer’s disease. We have just started using IV methylene blue in the clinic. Methylene blue is known for its antioxidant properties, which help combat oxidative stress in the body. It acts as a scavenger of harmful free radicals, protecting cells from damage. This makes it a valuable addition to integrative medicine protocols aimed at reducing inflammation, preventing chronic diseases and improving mitochondrial function by optimizing the electron transport chain. Methylene Blue IV Therapy can also help stimulate glucose metabolism as well as help increase NAD+ production by mitochondria and help improve mitochondrial respiration.

 

Physicians and scientists have been exploring the combined use of MB and PBM to treat a wide variety of medical conditions ranging from Long Covid to neuropsychiatric conditions such as Kleine-Levin syndrome. Together, MB and PBM have a synergistic relationship wherein MB donates electrons and PBM contributes photons to the electron transport chain, resulting in an increase in ATP production. The increase in mitochondrial and overall cellular activity, function, and respiration help prevent 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.

Combining MB with PBM can be very helpful to help increase mitochondrial function, improving symptoms of chronic fatigue, Seasonal Affective Disorder, depression, Parkinson’s Disease, Alzheimer’s Disease and overall cognitive performance. Benefits can be seen with one treatment, but 4 weekly treatments will provide the best support to jumpstart your mitochondria.

 

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. Therefore, everyone who wants to receive MB IVs must have a blood test to rule out this genetic deficiency. Risks with PBM are minimal but include skin irritation.

If you are interested in combining IV Methylene Blue together with Photobiomodulation adding near -infrared sauna at our clinic, or have questions, please give us a call.

 

Ageing Res Rev Epub 2020 May 25. . 2020 Aug:61:101089. doi: 10.1016/j.arr.2020.101089. Sunlight and health: shifting the focus from vitamin D3 to photobiomodulation by red and near-infrared light. Vladimir Heiskanen , Morgan Pfiffner , Timo Partonen

Transl Psychiatry (2014) 4, e397; doi:10.1038/tp.2014.44; Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression. A Karabatsiakis, C Böck, J Salinas-Manrique, S Kolassa, E Calzia, DE Dietrich and I-T Kolassa

Yang et al. Translational Neurodegeneration (2020) 9:19 https://doi.org/10.1186/s40035-020-00197-z; Mitochondria as a target for neuroprotection: role of methylene blue and photobiomodulation Luodan Yang, Hannah Youngblood, Chongyun Wu and Quanguang Zhang

Lasers Med Sci . 2025 Nov 29;40(1):502. doi: 10.1007/s10103-025-04738-8. Exploring photobiomodulation as a complementary approach for mental health: an integrative review Francisco J Cidral-Filho