Potentially important in various health issues from cancer to dementia and anti-aging, methylene blue (MB) is the new hot subject for improving mitochondrial performance and cellular power.
Methylene blue a synthetic dye
Methylene blue is a synthetic dye first made over 150 years ago. It is a diaminophenothiazine and was used to dye paper, wool, silk, and cotton textiles. It was incorporated into the medicines of psychiatric patients so that Doctors could see from their urine that they had taken their pills!
For this reason it is also used sometimes during surgery to see if there are leaks!
Methylene blue and malaria
In a more purified form, it is used in medicine, it has been used for various purposes. For example, it was the first compound used for the treatment of malaria starting with soldiers in World War 1. A 2018 study in the Lancet showed that within two days of usage, it had killed all the parasite in the host, and therefore a further mosquito bite could not pick up the parasite and pass it on (1).
Methylene blue is an anti-infective agent - for bacteria or viruses - and can help in detoxification.
Methylene blue and blood disorders
It was also used to treat methemoglobinemia - a rare blood disorder that affects how red blood cells deliver oxygen throughout your body (2). It has also been used to treat cyanide poisoning.
Methylene blue, mitochondria and anti-aging
Methylene blue is also a mitochondria-targeting antioxidant with a low redox value allowing it to convert rapidly between reduced and oxidised forms. As long ago as 1907, German biochemist Paul Ehrlich described MB as a 'Magic Bullet' because it could both recognise and then target cells with impaired mitochondrial function.
Mitochondria produce their energy in the form of ATP, via a system called 'Oxidative Phosphorylation'. ATP production has been shown to increase in the presence of Methylene blue. However, mitochondria also produce Reactive oxygen species (e.g. Hydrogen peroxide) and cause oxidative stress in cells. Methylene Blue reduces the ROS levels and thus cellular oxidative stress.
Methylene blue can thus be used for both mitochondrial repair and for mitochondrial energy production. These features could benefit you if you had chronic fatigue, fibromyalgia and/or even long Covid.
On YouTube, one American Doctor (Paul Anderson) sees it as ‘an indirect mitochondrial primer’, increasing the respiratory ATP chain inside the mitochondria. Anderson believes it can also protect organs such as the Kidneys when patients are having chemotherapy. It is cell protective and DNA protective. Everybody is saying the same thing!
One study showed it had enormous potential for skin care (3).
The potent ROS scavenging efficacy, when used in cultured human skin fibroblasts derived from healthy donors and from patients with progeria, showed that MB was extremely effective in stimulating skin fibroblast proliferation and delaying cellular senescence. As we age, Reactive Oxygen Species (ROS) decrease collagen synthesis and increase collagen breakdown. Methylene blue is very effective at blocking ROS.
These anti-aging properties have been examined in other contexts, for example, MB can neutralise the free radical nitric oxide (NO), and regulate the NO-cyclic guanosine monophosphate signaling pathway. One study showed it slowed aging because it enhanced the key mitochondrial pathways (4).
Methylene blue and autophagy
A natural process of cellular regeneration in the body is called autophagy. When parts of a cell have been damaged, or if pathogens are present, autophagy is like having a workman come in to fix the problems and even recycle used parts. But autophagy can go wrong. Methylene blue is soluble in both water and organic solvents and can enter cells, their nuclei, mitochondria and even the workmen, called 'lysosomes'. Methylene blue seems able to correct failing autophagy (5).
Methylene blue and neurodegenerative diseases
These properties of correcting aging have prompted scientists to study the benefits of Methylene blue with the brain. It crosses the blood brain barrier easily, and has been shown to reduce tau protein aggregation and the ‘tangles’ (tauopathies) the protein creates; it also improves energy metabolism. These actions are of particular interest for the treatment of all neurodegenerative diseases (6).
Methylene blue is being explored for its potential to treat dementia, including Alzheimer's disease. Studies have also shown that Methylene blue can improve cognitive function in patients after just six months of treatment.
If used early in the disease, it may protect the brain and enhance its function while reducing levels of toxic chemicals that may accumulate in the brain - there is a comprehensive review of its potential benefits with dementia and Alzheimer’s (7).
In strokes, MB enhanced autophagic signaling cascades (p53-AMPK-TSC2-mTOR). MB induced neuroprotection, at least in part, by enhancing autophagy and reducing apoptosis (8).
Photobiomodulation, or PBM, uses red light of different frequencies to treat depression and other neuropsychiatric disorders including anxiety, insomnia, mild cognitive impairment, Parkinson’s disease, Alzheimer’s disease, traumatic brain injury, and even stroke. Using Methylene blue at the same time as Red light Therapy seems to create stronger benefits. The treatments work synergistically and PBM has been shown in its own right to be cytoprotective, reducing oxidative stress. Together, MB donates electrons and PBM contributes photons to the electron transport chain, resulting in a super increase in ATP production (9).
Methylene blue and cancer
Methylene blue is not officially approved for the prevention or treatment of cancer.
However, its ability to cross cell membranes easily, target cancer cells, enhance mitochondrial function, (which goes wrong in cancer), and inhibit tumour growth has led to studies with cancer and it does seem to have the potential to disrupt the energy systems of cancer cells and cause apoptosis (cell death). The research on strokes (8) showed that Methylene blue could enhance p53, a protein often found to be low in cancer patients. p53 is a tumour suppressor protein, and Guardian of the Mitochondrial Genome. It needs to be at high levels to protect against cancer.
Methylene blue certainly makes cancer cells more responsive to treatment. In the laboratory it increased the effectiveness of carboplatin with ovarian cancer cells. In research by Zhenhua Chen at the Jinzhou Medical University in China, MB also increased the performance of chemotherapy drugs with TNBC.
It also seems to be a photosenitiser and helped Photodynamic Therapy (PDT) achieve improved results with colorectal cancer and melanoma (10).
Side effects of Methylene Blue
Higher doses have shown some evidence of toxicity. According to a review of the current evidence the conclusions showed that 13 of 14 of the reported cases of Central Nervous System toxicity were serotonin toxicity that met the Hunter Serotonin Toxicity Criteria.Data showed that an intravenous dose of only 0.75 mg/kg caused a problem.
Please remember that methylene blue started its life in 1876 as a synthetic dye. Methylene blue is interesting. It comes in two forms - Industrial grade and Lab grade - it’s the latter you want.
Either way, it can be contaminated with heavy metals. You must buy pharmaceutical grade methylene; but don’t be surprised if your urine or faeces turn blue.
Would I take it every day for 6 months? Well I know the new US Health and Human Services Secretary Robert F. Kennedy Jnr was seen putting vivid blue drops of a liquid in his fizzy water on a plane, but I would be a little more cautious.
I do anyway take 50 mg CoQ10 for mitochondrial support. If I had cancer, or early Alzheimer's, dementia or Parkinson's, I would certainly consider Methylene blue but in modest doses.
Go to: What is TUDCA?
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References
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Efficacy and safety of primaquine and methylene blue for prevention of Plasmodium falciparum transmission in Mali: a phase 2, single-blind, randomised controlled trial; Prof Alassane Dicko et al; The Lancet, Infectious Diseases, Vol 18, issue 6; June 2018
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"NCI Dictionary of Cancer Terms". National Cancer Institute. 2 February 2011. Retrieved 21 December 2019.
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Anti-Aging Potentials of Methylene Blue for Human Skin Longevity. Xiong, ZM., O’Donovan, M., Sun, L. et al.Sci Rep 7, 2475 (2017). https://doi.org/10.1038/s41598-017-02419-3
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Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways. Atamna, H. et al. Faseb j 22, 703–712, doi:10.1096/fj.07-9610com (2008).
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Mitochondrial dysfunction and oxidative stress mediate the physiological impairment induced by the disruption of autophagy.Wu, J. J. et al. Aging (Albany NY) 1, 425–437, doi:10.18632/aging.100038 (2009)
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Methylene blue upregulates Nrf2/ARE genes and prevents tau-related neurotoxicity; Cliona Stack et al; Human Molecular Genetics, Volume 23, Issue 14, 15 July 2014, Pages 3716–3732, https://doi.org/10.1093/hmg/ddu080
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Exploring Methylene Blue and Its Derivatives in Alzheimer's Treatment: A Comprehensive Review of Randomized Control Trials; Muhammad Usman Hashmi et al; Cureus. 2023 Oct 9;15(10):e46732. doi:10.7759/cureus.4673
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The Effects of Methylene Blue on Autophagy and Apoptosis in MRI-Defined Normal Tissue, Ischemic Penumbra and Ischemic Core; Zhao Jiang et al; PLoS One. 2015 Jun 29;10(6)
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Protection against neurodegeneration with low-dose methylene blue and near-infrared light. Gonzalez-Lima F, Auchter A. Frontiers in Cellular Neuroscience 2015;9.
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Methylene blue in anticancer photodynamic therapy: systematic review of preclinical studies Frontiers in Pharmacol., 28 September 2023 Sec. Pharmacology of Anti-Cancer Drugs Volume 14 - 2023