Methylene Blue - Should I or Shouldn't I ?
Methylene blue has gotten alot of press lately, and as usual most people ask, "is it good or bad?".
There are 3 key things that methylene blue has been shown to do:
It is a great electron donor (so it reduces the demand on NAD/NADPH) - this helps facilitate the mitochondrial electron transport chain and mitochondrial biogenesis, and its a great 'reducer', like vitamin c. Methyleneblue treatment, significantly increases the cellular NAD + /NADH ratio and NAD + content. [3]
It stimulates or activates SIRT1 - a key gene in regulating a number of genes such as NFKB, and a series of anti oxidant genes. [1,2,4]
It inhibits iNOS / NOS2 [5].
In that vein, G6PD status is an important consideration, noted in existing research as well.
"But known or suspected glucose-6-phosphate dehydrogenase (G6PD) deficiency is a relative contraindication to the use of methylene blue because G6PD is the key enzyme in the formation of NADPH through pentose phosphate pathway and G6PD-deficient individuals generate insufficient NADPH to efficiently reduce methylene blue to leukomethylene blue, which is necessary for the activation of the NADPH-dependent methemoglobin reductase system. So, we should be careful using methylene blue in methemoglobinemia patient before G6PD levels." [6]
Proposed Treatment For Covid
"The only drug known to inhibit the excessive production of reactive species and cytokines is methylene blue, a low-cost dye with antiseptic properties used effectively to treat malaria, urinary tract infections, septic shock, and methaemoglobinaemia. We propose testing methylene blue to contrast Covid-related acute respiratory distress syndrome, but particularly suggest testing it early in Covid infections to prevent the hyper-inflammatory reaction responsible for the serious complications of the disease. Methylene blue inhibits the formation of superoxide anion (ROS precursor) by blocking the xanthine oxidase pathway; it counteracts the synthesis of nitric oxide (RNS precursor) by direct inhibition of NO-synthase, and inhibits cytokine expression via attenuation of NF-kB signaling. "[4]
For those with upregulated iNOS it appears worthy of consideration and research for you. Similar for those who struggle to activate SIRT1, perhaps one of the most important genes along with iNOS in terms of post viral malaise, and Chronic Fatigue. Also, given its role as a great electron donor and reducing agent, it like Vitamin C can help recycle both methylfolate and BH4 (tetrodydrobiopterin) - both critical in Chronic Fatigue and upregulated iNOS.
In a later blog post focused on Ferroptosis, i will explain why Methyl Blue may be helpful to stop Ferroptosis - an important process in cell death. Only a few things can stop or block Ferroptosis, BH4, CoQ10, and GPX4, while on the flip side iNOS is a key actor. Methyl Blue can play a part in an intervention program for this issue as well to both shut down iNOS, and preserve BH4. [7]
References
[1] SIRT1 activation by methylene blue, a repurposed drug, leads to AMPK-mediated inhibition of steatosis and steatohepatitis. Seo Young Shin a 1, Tae Hyun Kim a 1, Hongmin Wu a, Young Hee Choi b, Sang Geon Kim. European Journal of Pharmacology; Volume 727, 15 March 2014, Pages 115-124; European Journal of Pharmacology Pulmonary, gastrointestinal and urogenital pharmacology. https://doi.org/10.1016/j.ejphar.2014.01.035
[2] Methylene blue alleviates experimental autoimmune encephalomyelitis by modulating AMPK/SIRT1 signaling pathway and Th17/Treg immune response. Jueqiong Wang, Congying Zhao, Peng Kong, Guanyun Bian, Zhe Sun, Yafei Sun, Li Guo, Bin Li. Journal of Neuroimmunology. Volume 299, 15 October 2016, Pages 45-52. Journal of Neuroimmunology. https://doi.org/10.1016/j.jneuroim.2016.08.014
[3] Pyrroloquinoline Quinone, a Redox-Active o-Quinone, Stimulates Mitochondrial Biogenesis by Activating the SIRT1/PGC-1α Signaling Pathway. Kazuhiro Saihara†, Ryosuke Kamikubo†‡, Kazuto Ikemoto§Orcid, Koji Uchida*‡, and Mitsugu Akagawa*†Orcid. Biochemistry 2017, 56, 50, 6615–6625. Publication Date:November 29, 2017. https://doi.org/10.1021/acs.biochem.7b01185. Copyright © 2017 American Chemical Society
[4] Methylene blue in covid-19. Giulio Scigliano a, Giuseppe Augusto Scigliano. Medical Hypotheses. Volume 146, January 2021, 110455. Medical Hypotheses. https://doi.org/10.1016/j.mehy.2020.110455
[5] Methylene Blue Attenuates iNOS Induction Through Suppression of Transcriptional Factor Binding Amid iNOS mRNA Transcription. Chao Huang, Lijuan Tong, Xu Lu, Jia Wang, Wenjuan Yao, Bo Jiang, Wei Zhang. First published: 03 March 2015 https://doi.org/10.1002/jcb.25132. Journal of Cellular Biochemistry, Volume116, Issue8. August 2015. Pages 1730-1740
[6] Blue cures blue but be cautious. Pranav Sikka, V. K. Bindra,1 Seema Kapoor,2 Vivek Jain,3 and K. K. Saxena. Journal List J Pharm Bioallied Sci v.3(4); Oct-Dec 2011 PMC3249703. J Pharm Bioallied Sci. 2011 Oct-Dec; 3(4): 543–545. doi: 10.4103/0975-7406.90112. PMCID: PMC3249703. PMID: 22219589
[7] Journal of Amino Acids Vol. 2015, Article ID 973548, http://dx.doi.org/10.1155/2015/973548