Methylene blue offers a wide range of benefits, including producing anti-aging effects, improving cognitive function, and reducing mortality and morbidity. It also plays a role in enhancing mood, aiding in the treatment of conditions like methemoglobinemia and malaria, improving skin health, and contributing to the fight against infectious diseases and cancer, making it a versatile and valuable compound in various medical applications.
Methylene blue, also known as methylthioninium chloride, is a synthetic dye that has been widely used for various purposes, including as a stain in histology and microbiology. Beyond its traditional applications, methylene blue has found its way into the realm of health and medicine due to its unique properties.
Methylene blue was first prepared in 1876 by Heinrich Caro, a German chemist. This medication has a variety of medical and industrial applications. It is on the List of Essential Medicines by the World Health Organization (WHO), which means that it is considered to be an essential medication for a basic health system.
Methylene blue exerts its effects through several mechanisms due to its unique chemical properties. It interacts with various cellular components, leading to a range of potential benefits:
Numerous studies provide empirical evidence supporting the potential anti-aging effects attributed to methylene blue:
According to studies, methylene blue has demonstrated the potential to enhance cognitive function via several important mechanisms:
Research indicates that methylene blue has been found to lower both mortality and morbidity rates in individuals affected by a range of medical conditions:
Research studies have demonstrated that methylene blue has shown positive effects on mood:
Methemoglobinemia is a medical condition characterized by elevated levels of methemoglobin, a modified form of hemoglobin containing ferric iron, in the blood. Hemoglobin, responsible for transporting oxygen in red blood cells, is normally in a ferrous iron state, allowing efficient oxygen binding and release to body tissues. However, in methemoglobin, the iron is oxidized to its ferric state, preventing effective oxygen exchange. At lower levels, one might experience difficulty breathing, nausea, and increased pulse rate, while higher levels can lead to symptoms progressing to lethargy, stupor, declining consciousness, cardiac arrhythmias (abnormal heart rhythms), and even death.
Treatment of methemoglobinemia frequently involves the use of reducing agents, including methylene blue, which is converted to leukomethylene blue (LB). LB acts as a potent reducing agent, facilitating the reduction of ferric iron back to ferrous iron within the methemoglobin molecule. This conversion effectively restores hemoglobin’s ability to transport oxygen, thus remedying the symptoms associated with methemoglobinemia and improving oxygen delivery to body tissues.
Research findings indicate that methylene blue demonstrates therapeutic efficacy in the treatment of methemoglobinemia:
Malaria is a mosquito-borne infectious disease caused by parasites of the Plasmodium genus and characterized by symptoms like fever, chills, and anemia. Numerous studies have indicated that methylene blue serves as an effective antimalarial agent, demonstrating its potential in the field of malaria treatment:
Methylene blue has been recognized for its potential anti-aging effects on the skin. Emerging research suggests that the compound’s antioxidant properties and ability to enhance cellular energy production may contribute to improved skin health and appearance:
According to research findings, methylene blue has exhibited the potential to combat a diverse range of infections:
According to research studies, methylene blue has shown potential in combating cancer and contributing to cancer treatment strategies.
Methylene blue is used for the treatment of the following conditions:
There are certain situations in which the use of methylene blue is contraindicated, meaning it should be avoided due to potential risks or interactions. Contraindications for methylene blue include:
Always consult a healthcare provider before using methylene blue, especially if you have any preexisting medical conditions, are taking dietary supplements, non-prescription drugs and other medicines, or are unsure about its suitability for your specific situation.
When it comes to using methylene blue as a treatment, there are two main ways it can be given: intravenous and oral. Intravenous (IV) methylene blue means the substance is injected directly into the bloodstream using a needle, while oral methylene blue is taken by swallowing a pill or liquid.
Intravenous methylene blue is often used in more critical situations or medical settings. It can quickly reach the bloodstream, making it a faster-acting option. This method is commonly used to treat conditions like methemoglobinemia (a blood disorder) or to support certain medical procedures. Because methylene blue injection goes directly into the bloodstream, it can have more immediate effects. However, methylene blue must be injected intravenously very slowly over a period of several minutes to avoid having too much of the compound in one place, which could cause more methemoglobin to form.
On the other hand, oral methylene blue involves taking the substance through the digestive system, like other medications. It is usually used for less urgent situations or chronic conditions. The effects might take longer to appear compared to the IV form because the body needs time to process and absorb the substance through the digestive tract.
Both methods have their own advantages and considerations, and the choice between intravenous and oral methylene blue depends on the specific condition being treated, the desired speed of action, and the overall health of the patient. Always follow the guidance of a health care professional on which form of treatment is best for your situation.
Methylene blue side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on methylene blue. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of methylene blue.
The side effects of methylene blue can vary depending on whether it’s injected or taken orally. Methylene blue injection might cause local discomfort at the injection site, temporary urine discoloration (blue staining of the urine), an allergic reaction, and skin sensitivity. When taken orally, it could lead to gastrointestinal discomfort, nausea, and possibly discolored stool. Seek medical attention immediately if you experience any untoward signs and symptoms or other side effects.
The dosage of methylene blue can vary depending on the condition being treated. For conditions like methemoglobinemia, a single dose of 1-2 milligrams per kilogram of body weight is often used. However, it’s important to follow the guidance of a medical professional for the correct dosage.
This medication is used for various purposes, including microbiology staining, potential cognitive enhancement, support for mitochondrial function, antioxidant properties, and as an adjunct in antimicrobial therapies.
Like other medicines, this medication can be safe when used appropriately and under medical guidance of a health care professional. However, improper use or excessive consumption can lead to side effects and potential harm. For instance, methylene blue is known to have the potential to induce hemolytic anemia in individuals with a deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD). It can also cause drug interactions when used together with certain medicines for depression or anxiety.
Methylene blue’s potential benefits include enhancing cognitive function, supporting mitochondrial health, providing antioxidant effects, aiding in microbial control, and assisting in studying microscopic organisms.
This medication can be toxic if consumed at high doses. It’s important to use any form of methylene blue, including the dye, with proper caution and guidance of a health care professional.
When used appropriately and under medical supervision, methylene blue is generally considered safe for humans. However, individual reactions and conditions can vary.
Yes, this medication has the potential to increase oxygen levels. The way methylene blue works is by changing the oxidized form of hemoglobin (Fe3+) back to its normal form (Fe2+). This helps hemoglobin pick up more oxygen and carry it to the body’s tissues, improving oxygen delivery.
The duration of methylene blue’s effects in the body can vary based on factors such as dosage, individual metabolism, and the purpose for which it’s used. It’s best to follow medical guidance.
This medication is used for staining in microbiology, potential cognitive enhancement, supporting mitochondrial function, providing antioxidants, and aiding antimicrobial therapies.
When used properly and under medical supervision, methylene blue is generally considered safe for humans. However, individual responses may differ.
Methylene blue may offer benefits such as cognitive enhancement, support for mitochondria, antioxidant effects, microbial control, and the ability to stain microscopic samples.
The common name for methylene blue is methylthioninium chloride.
Methylene blue’s effects on the body include potential cognitive enhancement, support for cellular energy production, antioxidant activity, and assistance in microbial control.
Using methylene blue daily should be done under medical guidance, as excessive or prolonged use might lead to adverse effects. It’s important to follow recommended dosages and usage patterns.
Methylene blue’s anti-inflammatory effects have been explored in research, but its precise impact on inflammation can vary and further studies are needed.
Some studies have suggested that methylene blue might have a protective effect on the liver, but its overall impact depends on various factors and requires more research.
Methylene blue can be used for staining in microbiology, potential cognitive enhancement, supporting mitochondrial function, providing antioxidant effects, and aiding antimicrobial therapies.
Potential benefits of methylene blue include cognitive enhancement, support for mitochondria, antioxidant effects, microbial control, and its use as a stain in research.
Methylene blue can detect various biological substances and cellular structures when used as a stain in microbiological and histological research.
Methylene blue can stain bacterial cells, making them more visible under a microscope. It’s also been explored for its potential antimicrobial properties.
Individuals with certain medical conditions, such as certain types of glucose-6-phosphate dehydrogenase deficiency, and those on specific medications should avoid methylene blue. Consultation with a healthcare professional is advised to prevent potential adverse effects of the following medications. During the consultation period, it is recommended to tell your doctor if you smoke, drink alcohol, take over the counter medications, or use illegal drugs to avoid any potential interactions.
Avoid taking this medicine with the following medications:
Using methylene blue daily should be approached cautiously and under medical guidance to prevent potential adverse effects. It’s important to follow recommended usage instructions.
The effects of methylene blue can vary depending on its purpose and dosage. It’s not meant for recreational use, and any effects should be discussed with a healthcare provider.
Methylene blue is used in medicine for various purposes, including treating methemoglobinemia, acting as a diagnostic stain, and potentially offering neuroprotective effects.
Methylene blue is commonly employed as a stain in histology and microbiology to enhance contrast and visibility of cellular structures.
Methylene blue helps to turn the abnormal “rusty” form of blood (methemoglobin) back into the normal red form that can carry oxygen effectively.
Methylene blue has shown promise in potentially mitigating neurodegenerative conditions by influencing mitochondrial function and reducing oxidative stress.
Methylene blue has been investigated for its potential to enhance memory and cognitive function, possibly through its effects on mitochondrial function and neurotransmitter systems.
Methylene blue has been explored as a potential mood regulator due to its effects on mitochondrial function and interactions with neurotransmitter systems.
Methylene blue is used in various industries, including textiles, as a dye and colorant, and in analytical chemistry as an indicator.
In analytical chemistry, methylene blue serves as a redox indicator, undergoing color changes that signal the endpoint of titrations.
Methylene blue is used in photodynamic therapy as a photosensitizer that, when activated by light, produces reactive oxygen species to target and destroy cancer cells.
Methylene blue can interact with certain medications, particularly those affecting serotonin levels, potentially leading to a condition known as serotonin syndrome.
Methylene blue’s properties make it a candidate for applications in nanomedicine and drug delivery, potentially aiding in targeted therapy.
Methylene blue has demonstrated antimicrobial effects against various bacteria, fungi, and parasites, suggesting its potential as an antimicrobial agent.
Methylene blue has been found to influence mitochondrial function by promoting electron transport and enhancing cellular energy production.
Ifosfamide-induced encephalopathy is a neurological condition associated with the use of ifosfamide chemotherapy.
Yes, methylene blue is commonly used in histological staining to enhance the visualization of cellular structures under a microscope.
Methylene blue can inhibit the reuptake of serotonin, potentially leading to increased serotonin levels and affecting mood and other physiological processes.
Methylene blue can be administered through various routes, including oral, intravenous, and topical application, depending on the intended medical use.
Methylene blue’s mechanisms of action include its roles as a redox agent, mitochondrial enhancer, and potential modulator of neurotransmitter systems.
Methylene blue’s effects on neurotransmitters and mitochondrial function have led to investigations into its potential as an adjunctive treatment for depression.
Methylene blue’s diverse properties open up possibilities for future applications in areas such as neuroprotection, cancer therapy, and drug delivery.
Methylene blue exhibits antioxidant properties by reducing oxidative stress and potentially contributing to cellular protection.
Methylene blue’s influence on mitochondrial function and neurotransmitter systems may contribute to its impact on cognitive function and memory enhancement.
Yes, methylene blue is used as a redox indicator in analytical chemistry to signal the endpoint of titrations.
Methylene blue is used in aquaculture to treat fungal and bacterial infections in fish, providing a safe environment for aquatic organisms.
Methylene blue’s color change in response to redox reactions makes it useful as an indicator in redox titrations.
Methylene blue’s photodynamic properties have led to its investigation as a potential agent for cancer treatment through targeted cell destruction.
Methylene blue should be used with caution, considering potential interactions with medications and its adverse effects.
Methylene blue’s properties suggest it could play a role in drug delivery systems, potentially enhancing targeted therapies.
Methylene blue’s impact on neurotransmitter systems and mitochondrial function has led to its exploration as a potential treatment for mood disorders.
Drawbacks of methylene blue therapy include potential interactions with medications and adverse effects such as serotonin syndrome.
Methylene blue’s diverse mechanisms of action make it a candidate for combination therapies in various medical applications.
Methylene blue offers distinct staining capabilities compared to other dyes, making it valuable in specific histological and microbiological contexts.
Methylene blue has been shown to enhance mitochondrial function by promoting electron transport and cellular energy production.
Yes, methylene blue is used in veterinary medicine to treat various conditions, including fish parasites and cyanide poisoning.
Methylene blue’s antioxidant properties contribute to its role in mitigating oxidative stress and protecting cells from damage.
Methylene blue interacts with neurotransmitter systems by affecting serotonin reuptake and potentially influencing mood and cognitive function.
Methylene blue’s impact on neurotransmitters and mitochondrial function may lead to mood-enhancing effects.
Methylene blue’s photodynamic properties make it a candidate for targeting and destroying cancer cells through light activation.
Methylene blue’s potential neuroprotective effects have sparked interest in its application for neurodegenerative disease treatment.
Challenges in methylene blue therapy include optimizing dosages, understanding potential interactions, and managing adverse effects.
Methylene blue enhances mitochondrial electron transport, potentially leading to increased cellular energy production.
Future research on methylene blue may uncover new applications and further elucidate its mechanisms of action.
Yes, methylene blue’s diverse properties make it versatile and applicable in various fields, from medicine to industry.
Pharmacokinetics and organ distribution of intravenous and oral methylene blue
This study aimed to understand the pharmacokinetics and organ distribution of intravenous (i.v.) and oral methylene blue, used to prevent ifosfamide-induced encephalopathy in cancer patients. The researchers measured methylene blue concentration in blood after i.v. and oral doses in volunteers, and in various tissues in rats. I.v. administration showed a multiphasic time course with a 5.25-hour half-life. Oral administration resulted in much lower blood levels. Co-administration with mesna didn’t affect distribution. Urinary excretion was moderately higher for i.v. administration. In rats, intraduodenal administration led to higher intestinal and liver concentrations but lower blood and brain levels than i.v. administration. The differences in organ distribution account for distinct pharmacokinetics, suggesting i.v. methylene blue might be more effective if targeting the central nervous system, while oral and i.v. forms could be equally effective in the liver.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/10952480/
Methylene blue (MB) holds therapeutic potential for various human conditions, especially in neurodegenerative diseases. Its beneficial effects are linked to mitochondrial function, where it can donate electrons to cytochrome c independently of complex I and III through an “alternative electron transport” process. This counters the harmful effects of inhibitors on these complexes. Recent debate concerned MB’s effects on complex III-inhibited mitochondria, with new evidence suggesting MB can enhance bioenergetic parameters like respiration and membrane potential by reducing cytochrome c in mitochondria treated with complex III inhibitors. Unusual respiratory responses and consistent outcomes across rodent species underscore MB’s impact, reflecting its distribution across mitochondrial compartments and indicating its role in influencing mitochondrial metabolism.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920423/.
Recent research suggests that low-dose methylene blue (MB), known for its antioxidant and metabolic-enhancing properties, could potentially counteract neural damage caused by neurotoxins. In a study involving rats infused with the neurotoxin rotenone, MB was examined for its effects. Results showed that MB reduced the size of rotenone-induced anatomical lesions and prevented decreases in cytochrome oxidase activity and oxidative stress in the striatum and related motor regions. It also maintained functional connectivity in motor circuits and partially prevented behavioral asymmetries caused by rotenone. This study highlights MB’s potential as a protective intervention against neural damage associated with oxidative stress and energy deficits in the brain.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765788/.
In the past two decades, numerous neuroprotective approaches, including agents targeting oxidative stress, ion channels, and inflammation, have been investigated for treating neurological disorders, but none have shown efficacy in clinical trials. This study highlights methylene blue (MB) as an alternative electron carrier that bypasses complex I/III blockage in mitochondria by accepting electrons from NADH and transferring them to cytochrome c. A derivative of MB lacking its redox center showed no impact on mitochondrial complexes. MB increased oxygen consumption and decreased anaerobic glycolysis in neuronal cells, displaying protective effects at low concentrations against various insults in vitro. Animal models demonstrated MB’s remarkable capacity to mitigate impairments in Parkinson’s disease and cerebral ischemia-reperfusion injury, suggesting a novel strategy for neuroprotection in conditions linked to mitochondrial dysfunction.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091255/.
Methylene blue (MB) and similar compounds have been utilized for a century in clinical settings to treat various ailments. Recent research demonstrates that MB extends the lifespan of human fibroblasts in culture by over 20 population doublings, primarily by delaying cellular aging. This effect is achieved through improved mitochondrial function, indicated by increased mitochondrial complex IV levels and enhanced oxygen consumption. MB also counters premature senescence caused by oxidative stressors like H2O2 and cadmium, while prompting the production of antioxidant enzymes. The interplay between MB and its reduced form, MBH2, within mitochondria appears crucial for its protective impact, potentially by minimizing mitochondrial-generated oxidative stress. This suggests MB might have utility in mitigating age-related mitochondrial dysfunction and even in addressing complex IV decline in conditions like Alzheimer’s disease.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/17928358/.
This paper presents the first comprehensive exploration of methylene blue’s memory-enhancing and neuroprotective mechanisms in vivo. These mechanisms hold significant potential for a novel neurobiological strategy to enhance regular memory and address memory loss and neurodegeneration linked to mitochondrial dysfunction. Unlike conventional drug-receptor interactions, methylene blue’s impact relies on distinctive metabolic pathways, exhibiting a hormetic dose-response pattern with contrasting effects at low and high doses. At lower doses, methylene blue acts as a mitochondrial electron transporter, displaying remarkable antioxidant and cell respiration-boosting attributes that adaptably influence nervous system function. Notably, the memory-enhancing impacts are linked to memory consolidation improvement within specific neural networks. Moreover, methylene blue’s application at low doses demonstrates efficacy in safeguarding against mitochondrial dysfunction-associated neurodegeneration, owing to its unique self-oxidizing property and broad effects on various tissue oxidases. The findings underscore the potential of low-dose methylene blue as a safe and promising avenue for memory enhancement and the management of conditions marked by oxidative stress, memory loss, and neurodegeneration.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265679/.
Chronic cerebral hypoperfusion, linked to mild cognitive impairment and Alzheimer’s disease risk, impacts mitochondrial function and memory consolidation. Enhancing mitochondrial function with drugs could potentially treat cerebral hypoperfusion-related cognitive issues. Methylene blue (MB), which crosses the blood-brain barrier and aids mitochondrial electron transport at low doses, has shown memory enhancement and neuroprotection. Rats with bilateral carotid occlusion or sham surgery were treated with MB or saline daily for a month, undergoing various behavioral tests. Carotid occlusion rats performed poorly in the visual water maze test, but daily MB improved their visual learning and memory deficits. MB could offer cognitive benefits for chronic cerebral hypoperfusion conditions like mild cognitive impairment, vascular dementia, and Alzheimer’s disease, as indicated by this pioneering study.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/25079810/.
Methylene blue (MB) is a well-established drug with a history of use for malaria, methemoglobinemia, and carbon monoxide poisoning. Its recent resurgence in interest stems from its role in mitochondria, where it enhances mitochondrial activity and reduces oxidative stress. Additionally, MB exhibits potent neuroinflammation mitigation. Mitochondrial dysfunction plays a pivotal role in neurodegenerative disorders, making MB a promising therapy. In both in vitro and in vivo studies, MB has demonstrated efficacy in mitigating neurodegeneration and associated behaviors in models of stroke, Alzheimer’s, Parkinson’s, and traumatic brain injury. This review highlights MB’s potential for neuroprotection, focusing on its impact on mitochondrial function, neurogenesis, and age-related cognitive decline.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826781/.
Methylene blue, a well-established drug with complex pharmacology, boasts a multitude of clinical applications due to its diverse mechanisms of action. Notably, it has demonstrated antidepressant, anxiolytic, and neuroprotective properties in both animal and human studies, largely attributed to its stabilizing influence on mitochondrial function and its dose-dependent impact on reactive oxygen species generation. As a result, methylene blue shows promise as a proof-of-concept treatment for organic/neurodegenerative disorders and as a general neuroprotective agent. In psychiatry, its century-long history includes successful applications in treating psychotic and mood disorders and enhancing memory during fear-extinction training. Particularly encouraging outcomes have emerged from short- and long-term use in bipolar disorder, where methylene blue has delivered antidepressant and anxiolytic effects without inducing manic episodes. Long-term usage has led to improved stability and reduced residual symptoms, although caution is advised due to its monoamine oxidase A inhibitory effect.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/31144270/.
In a phase II clinical trial aimed at evaluating methylene blue (MB) as a potential Alzheimer’s disease (AD) therapy, noteworthy improvements in cognitive function were observed in AD patients after 6 months of MB treatment. However, the specific mechanisms of MB’s action concerning AD pathology remained unclear, as no prior preclinical mammalian studies had been published. To uncover MB’s effects on AD pathology and its mechanism of action, we conducted experiments using a mouse model (3xTg‐AD) that replicates age-related Aβ and tau accumulation along with cognitive decline. Our findings reveal that chronic dietary MB treatment reduces Aβ levels and enhances learning and memory in 3xTg‐AD mice. The mechanism underlying MB’s impact on Aβ pathology appears to involve increased Aβ clearance, demonstrated by the enhanced chymotrypsin- and trypsin-like activities of brain proteasomes induced by MB. This study marks the first report of MB’s ability to augment proteasome function and ameliorate AD-like pathology in vivo, providing compelling support for MB’s potential as an AD treatment and offering insight into its mechanism of action.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2992595/.
Mitochondrial dysfunction is a central factor in hepatic encephalopathy (HE), resulting in altered cytochrome c-oxidase (CCO) enzyme activity and reduced brain metabolism. In an HE animal model, we investigated the effects of intracranial methylene blue (MB) administration and transcranial photobiomodulation (PBM), both targeting CCO, on cognitive recovery. Rats were divided into five groups: sham-operated + saline (SHAM + SAL), HE + SAL, SHAM + MB, HE + MB, and HE + PBM. PBM involved daily transcranial exposure to 670 ± 10 nm LED light (9 J/cm2) for 7 days, while the MB and SAL groups received accumbens injections (2.2 μg/0.5 μL). Cognitive improvement was observed in the HE group treated with MB, accompanied by reduced CCO activity in the prefrontal cortex, dorsal striatum, and dorsal hippocampus. Comparing MB and PBM, both improved HE-related memory deficits, but PBM led to a more generalized decrease in CCO activity in the prefrontal and entorhinal cortices, dorsal striatum, and hippocampus compared to MB. These findings suggest that CCO alteration contributes to mitochondrial dysfunction and reduced brain metabolism in HE, and both MB and PBM can mitigate these effects.
You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S0166432821000516.
Methylene Blue (MB), introduced to biology by Ehrlich in the 19th century, has since found diverse applications in medicine and biology. Currently, it serves as the primary treatment for methemoglobinemias, is commonly used to address ifosfamide-induced encephalopathy, and is a standard diagnostic tool in surgical procedures. Recent research indicates potential benefits of MB in Alzheimer’s disease and memory enhancement. While the modulation of the cGMP pathway is considered its primary mechanism, newer studies highlight its multiple cellular and molecular targets. MB’s distinctive physicochemical properties, including its planar structure, redox chemistry, ionic charges, and light spectrum characteristics, largely dictate its biological effects and clinical applications. This review explores these physicochemical attributes and MB’s impact on various cellular and molecular targets, particularly in the context of the nervous system.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005530/.
Methylene blue USP (MB) is a drug approved by the FDA and used in hospitals to treat specific types of poisoning and blood-related issues. Recent research on animals has shown that it might improve brain responses and memory, even in small amounts. However, we don’t fully understand how it affects the human brain.
To learn more, we gave healthy adults a low dose of MB or a placebo, without them knowing which one. We then used brain scans while they did tasks and while their brains were at rest, both before and after taking MB or the placebo. The results were interesting: when people took MB, blood flow in a brain network connected to tasks decreased during a task, and different parts of the brain that are related to how we perceive things and remember them became more connected when the brain was resting. This suggests that even a small amount of MB can change how our brains work when we’re doing things and when we’re not.
These findings are important because they show that MB could have potential benefits for brain function, and we need to look into this more, especially in different groups of people and those with brain-related conditions.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018244/.
This paper emphasizes brain mitochondrial respiration as a key therapeutic target for enhancing neuroprotection and cognitive function. It suggests that advancing brain mitochondrial respiration should be a crucial focus in research and treatment not only for Alzheimer’s disease (AD) but also for various cognitive impairment and neurodegenerative conditions. Three distinct approaches for enhancing brain mitochondrial respiration are proposed: (a) pharmacological intervention using low-dose USP methylene blue to boost mitochondrial respiration and promote memory improvement and neuroprotection, (b) photobiomodulation through transcranial low-level light/laser therapy using near-infrared light with similar neurometabolic mechanisms as methylene blue, and (c) nutrition intervention to enhance mitochondrial respiration by increasing dietary ketone bodies. These interventions aim to improve oxidative energy metabolism while reducing the pro-oxidant tendencies of the nervous system, representing a promising bioenergetics-driven strategy for addressing cognitive impairment and neurodegeneration in AD and related neuropsychological disorders.
You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S0006295213007417?via%3Dihub.
Phase II clinical trials with Methylene blue (MB) have demonstrated cognitive improvements in Alzheimer’s disease (AD) patients, aligning with its known antioxidant and mitochondrial protective properties. Recent findings also indicate MB’s capacity to reduce amyloid beta (Aβ) levels in AD models. Since Aβ can induce mitochondrial dysfunction through its interaction with the mitochondrial enzyme amyloid-binding alcohol dehydrogenase (ABAD), implicating a direct link between Aβ toxicity and AD-related mitochondrial dysfunction, this study aimed to investigate whether MB’s protective effects involve ABAD regulation. The study shows that MB enhances cell viability, reduces reactive oxygen species levels, and notably decreases Aβ oligomers in a lipopolysaccharide (LPS) mouse model. Furthermore, MB treatment reduces ABAD levels, and it has the potential to modulate both ABAD levels and function, as seen in the restoration of estradiol levels in mouse brains. These findings shed new light on potential mechanisms through which MB may act in AD.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/25601181/.
This paper delves into the neuroprotective effects of low-dose methylene blue and near-infrared light, emphasizing their shared cellular mechanism of action centered on stimulating mitochondrial respiration. Low-dose methylene blue, upon systemic administration, preferentially enters neuronal mitochondria and forms an electron cycling redox complex that enhances the mitochondrial electron transport chain, promoting energy metabolism and neuronal survival. Conversely, low-level near-infrared light, applied transcranially, delivers photons to cortical neurons, accepted by cytochrome oxidase, thereby increasing cellular respiration and cerebral blood flow. These interventions show promising potential for safeguarding against various neurodegenerative disorders, underpinned by their common cellular mechanisms, including energy transfer, hormetic dose-responses, and enhanced oxidative metabolic energy production, ultimately shielding nervous tissue from degeneration.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428125/.
In a prospective, double-blinded clinical trial approved by the institutional review board, twenty-six participants were administered either a low dose of methylene blue or a placebo. Functional MR imaging showed increased neural activity in the bilateral insular cortex during sustained attention tasks and in the prefrontal, parietal, and occipital cortex during short-term memory tasks after methylene blue administration. Additionally, methylene blue led to a 7% improvement in memory retrieval. These findings suggest that low-dose methylene blue can enhance neural activity related to sustained attention, short-term memory, and memory retrieval in the healthy human brain.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084971/.
Methylene blue (MB) has garnered increased scientific interest in its potential to slow down Alzheimer’s disease (AD) progression. MB, known for its inhibitory effects on the cGMP pathway, also impacts various cellular and molecular factors linked to AD development. It has demonstrated the ability to reduce amyloid plaques and neurofibrillary tangles, partially restore mitochondrial function and cellular metabolism, and influence neurotransmitter systems such as cholinergic, serotonergic, and glutamatergic, all implicated in AD pathogenesis. These multifaceted effects of MB are believed to underpin its potential benefits, leading to the exploration of novel MB-based AD treatments. This review summarizes MB’s actions on neurotransmitter systems and diverse cellular and molecular targets in relation to AD.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/19433072/.
Methylene blue, a compound previously recognized for its potential neuroprotective qualities in experimental neurodegenerative disease models, has posed intriguing questions about its underlying mechanisms. While prior research has highlighted the various roles of macroautophagy in maintaining cellular balance and its protective effects during myocardial ischemia, our current study reveals that methylene blue shields HT22 hippocampal cells from serum deprivation-induced death by promoting macroautophagy. Remarkably, inhibition of macroautophagy reverses methylene blue’s neuroprotective effects. Furthermore, our investigation indicates a dose-dependent activation of 5′ adenosine monophosphate-activated protein kinase (AMPK) signaling, rather than inhibition of the mammalian target of rapamycin signaling, at 12 and 24 hours following methylene blue treatment. Notably, the inhibition of AMPK blocks methylene blue-induced macroautophagy. Supporting our in vitro findings, we observed macroautophagy induction in the cortex and hippocampus of methylene blue-treated mouse brains. In summary, our study suggests that methylene blue’s neuroprotection is, at least partially, mediated through macroautophagy activation via the AMPK signaling pathway.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3642497/.
The study aimed to assess methylene blue’s effectiveness in treating ifosfamide-induced encephalopathy. Data were collected from MEDLINE (1966-August 2005) and International Pharmaceutical Abstracts (1971-August 2005) using specific search terms. The analysis revealed several case reports and one retrospective chart review detailing methylene blue’s use for this condition, but no controlled clinical trials were identified. Methylene blue showed promise in rapidly alleviating encephalopathic symptoms in some patients, often within 10 minutes of administration, yet its overall efficacy was modest in most cases. Notably, patients who didn’t receive methylene blue also experienced symptom resolution within a similar timeframe, suggesting the possibility of spontaneous recovery from ifosfamide-induced encephalopathy. Consequently, while methylene blue could be considered as a treatment option, particularly for severe cases, its true utility remains uncertain due to the lack of controlled clinical trials and the potential for spontaneous symptom improvement.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/16391008/
The discovery of nitric oxide as a mediator in cardiac postoperative vasoplegia has prompted the investigation of inhibitory drugs like methylene blue, which have shown promise in isolated cases. This study aimed to assess the incidence and prognosis of postoperative vasoplegic syndrome and evaluate the impact of intravenous methylene blue on mortality. In total, 638 cardiac surgery patients were enrolled, with 8.8% meeting vasoplegia criteria, resulting in a higher mortality rate (10.7% vs. 3.6%). Patients treated with methylene blue exhibited reduced morbidity and mortality (0% vs. 21.4%), and the syndrome’s duration was shorter (less than 6 hours vs. over 48 hours in some cases). In conclusion, vasoplegic postoperative syndrome affected 8.8% of patients, leading to poorer outcomes, but methylene blue administration significantly improved mortality rates.
You can read the full article at https://www.annalsthoracicsurgery.org/article/S0003-4975(03)01510-8/fulltext.
In the challenging realm of pediatric medicine, where shock resistant to conventional treatments poses grave risks to young patients, the potential role of methylene blue remains a largely uncharted territory. Our mission was to delve into this unexplored domain, gathering and summarizing existing literature while shedding light on the practices of physicians when it comes to employing methylene blue as a lifesaving measure for children in refractory shock. Our systematic search combed through databases from their inception up to 2019, unveiling 24 pertinent studies that, despite their limited quantity and sometimes questionable quality, hinted at the safety and efficacy of methylene blue in elevating mean arterial blood pressure among pediatric patients enduring refractory shock of various origins. Simultaneously, we probed the minds of U.S.-based pediatric critical care physicians through an electronic survey, revealing a striking schism: 40% reported using methylene blue, while 43% had never contemplated its use. The reasons for this divide were multifaceted, spanning from a lack of familiarity with the drug to uncertainties about dosing and insufficient empirical backing. This duality of practice patterns underscores the pressing need for rigorous studies to definitively assess methylene blue’s safety and efficacy in the treatment of pediatric shock, ultimately guiding physicians towards more informed and effective clinical decisions.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/32453920/.
This systematic review and meta-analysis aimed to assess the efficacy and safety of methylene blue (MB) in vasodilatory shock patients. After analyzing 15 studies involving 832 patients, it was found that MB, when administered alongside vasopressors, significantly lowered mortality rates and reduced vasopressor requirements. MB also improved hemodynamics by increasing mean arterial pressure, heart rate, and peripheral vascular resistance, while lowering the incidence of renal failure and lactate levels. No serious side effects were observed. Further research is needed to validate these results, but concomitant MB and vasopressor administration appears promising for vasodilatory shock management.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552293/.
This prospective, open-label, single-dose study aimed to investigate the acute effects of methylene blue (MB), an inhibitor of the L-arginine nitric oxide pathway, in six patients with severe septic shock treated in the medical ICU of a university hospital. The study found that MB increased mean arterial pressure, mean pulmonary artery pressure, systemic vascular resistance index, and pulmonary vascular resistance index while decreasing PaO2/FIO2 without significant changes in other hemodynamic parameters. The effects on oxygenation may limit its use in patients with adult respiratory distress syndrome. The study suggests that MB induces vasoconstriction in septic shock patients, and larger studies are needed to assess its impact on patient outcomes.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/8750129/.
This open-label, nonrandomized clinical trial investigated the role of nitric oxide in circulatory changes in human septic shock. Nine consecutive patients with septic shock were studied in an intensive care unit. After initial resuscitation, they received a 20-minute infusion of 2 mg/kg of methylene blue, an inhibitor of nitric oxide action. The results showed that methylene blue temporarily increased mean arterial pressure and cardiac index, along with changes in vascular resistance and arterial compliance. Oxygen delivery and uptake also improved. These findings suggest that nitric oxide may contribute to the circulatory alterations seen in septic shock after initial resuscitation.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/7634806/.
In this single-center randomized controlled trial, researchers investigated the potential benefits of methylene blue (MB) as an early adjunctive therapy for septic shock. They randomized 91 patients with septic shock according to Sepsis-3 criteria into two groups: MB and placebo. The study found that MB, when initiated within 24 hours, significantly reduced the time to vasopressor discontinuation, increased vasopressor-free days at 28 days, and shortened ICU and hospital stays without adverse effects. While days on mechanical ventilation and mortality rates were similar, these findings suggest the potential of MB as an adjuvant therapy, warranting further investigation in larger randomized clinical trials.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10010212/.
This single-center randomized controlled trial aimed to investigate the potential benefits of early adjunctive methylene blue (MB) in septic shock patients. Among the 91 participants, with 45 in the MB group and 46 in the placebo group, MB administration initiated within 24 hours significantly reduced the time to vasopressor discontinuation, increased vasopressor-free days at 28 days, and led to shorter ICU and hospital stays without adverse effects. Days on mechanical ventilation and mortality rates were similar between the groups. These findings support the need for further research on MB’s role in septic shock through larger randomized clinical trials.
You can read the abstract of this article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10010212/.
Methylene blue (MB) has been utilized to raise blood pressure in septic shock by affecting guanylate cyclase and nitric oxide synthase activity. This case series involving six septic shock patients within 72 hours of diagnosis aimed to demonstrate the benefits of MB in the early phase of septic shock. After fluid replacement, norepinephrine, and vasopressin, patients received a loading dose of MB followed by a 48-hour maintenance dose. Results showed a reduction in vasopressor dose and lactate levels after the loading dose of MB, with sustained effects during the maintenance phase. Interleukin 6 and interleukin 8 levels, initially elevated during septic shock, progressively decreased following MB infusion, suggesting a role for MB in reducing inflammation. While these findings are promising, further studies are needed to confirm their validity.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9875988/.
In this retrospective observational historical control-matched study, the objective was to assess the efficacy of methylene blue (MB) as an alternative treatment for vasoplegia after cardiopulmonary bypass (CPB). Patients who received MB for post-CPB vasoplegia from 2010 to 2015 were compared to historical controls from 2004 to 2009. The study included 28 matched patients in each group, and findings revealed that MB administration led to a significantly quicker improvement in vasoplegia (Ti), reduced mortality at day 30, decreased cardiac surgical Intensive Care Unit (CSICU) morbidity, and shorter hospital stays. The use of MB was associated with rapid hemodynamic recovery, reduced reliance on vasopressors, lower ICU mortality, decreased incidence of renal failure, and shorter length of stay post-cardiac surgery.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879859/.
Stroke is a major global health concern, and low-dose methylene blue (MB), known for its safe use in treating methemoglobinemia and cyanide poisoning, was investigated for its potential neuroprotective effects in rats with permanent middle cerebral artery occlusion. Serial MRI assessments showed that MB notably extended the perfusion-diffusion mismatch, mildly improved blood flow in underperfused areas, and sustained ATP production. However, it did not alter the final infarct volume, and there were no dose-dependent effects observed. These findings suggest that MB may offer neuroprotection by maintaining ATP production and enhancing blood flow in at-risk brain tissue, making it a promising candidate for clinical stroke trials due to its established safety profile.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907336/.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/18451123/.
This study explored the mechanisms underlying the antidepressant effects of methylene blue (MB). While previous research suggested that MB might work by inhibiting nitric oxide-induced stimulation of N-methyl-D-aspartate receptors, this study investigated additional mechanisms. It found that MB and related redox dyes, including toluidine blue O (TBO), thionine (TN), brilliant cresyl blue (BCB), and toluylene blue (TB), acted as reversible competitive inhibitors of monoamine oxidase type A (MAO-A) and monoamine oxidase type B (MAO-B), with a strong preference for MAO-A. These dyes also increased the levels of N-acetylserotonin (NAS) and melatonin in the pineal gland, consistent with the stimulation of melatonin biosynthesis observed with selective MAO-A inhibition. Furthermore, these dyes exhibited antidepressant-like activity in frogs, indicating a potential role of MAO-A inhibition in mediating the clinical antidepressant effect of MB through NAS stimulation and melatonin production.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/18077577/.
Methylene blue (MB), a thionine dye, is known for its potent inhibition of monoamine oxidase (MAO) A, contributing to its antidepressant effects and its potential for serotonin toxicity (ST) when combined with serotonergic drugs. This study explored the MAO inhibition properties of five MB analogues: neutral red, Nile blue, new methylene blue, cresyl violet, and 1,9-dimethyl methylene blue. Like MB, these analogues exhibited specific MAO-A inhibition, with cresyl violet, Nile blue, and 1,9-dimethyl methylene blue showing even greater potency than MB. Nile blue also demonstrated strong MAO-B inhibition. These findings suggest that non-thionine MB analogues, such as cresyl violet and Nile blue, should be considered as potential high-potency MAO-A inhibitors with a risk of ST, similar to phenothiazines like MB, in pharmacological studies.
You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S0041008X17301400.
Methylene blue is a versatile and well-established drug with a range of clinical applications, driven by its multifaceted mechanisms of action. Notably, it has demonstrated antidepressant, anxiolytic, and neuroprotective properties supported by both animal and human studies. Its capacity to stabilize mitochondrial function and regulate reactive oxygen species production holds significant promise in treating organic/neurodegenerative disorders and providing neuroprotection. In psychiatry, methylene blue has been used successfully for over a century, proving effective in treating psychotic and mood disorders and enhancing memory in fear-extinction training. Notably, it has shown promise in the short- and long-term management of bipolar disorder, offering antidepressant and anxiolytic benefits without the risk of inducing manic episodes. While generally well-tolerated, caution is advised due to its inhibitory effect on monoamine oxidase A.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/31144270/.
In a double-blind crossover study, low-dose methylene blue (15 mg, ‘placebo’) and an active dose (195 mg) were investigated in bipolar disorder patients already receiving lamotrigine treatment. Over a 6-month trial, the active dose of methylene blue significantly alleviated depression symptoms measured by the Montgomery-Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression, as well as reducing anxiety symptoms assessed by the Hamilton Rating Scale for Anxiety. Mania symptoms remained stable, and although methylene blue had no significant effect on cognitive symptoms, it was well-tolerated with mild and temporary side effects. These findings suggest that methylene blue, as an adjunctive treatment, can improve residual depression and anxiety symptoms in bipolar disorder patients.
You can read the full article at https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/methylene-blue-treatment-for-residual-symptoms-of-bipolar-disorder-randomised-crossover-study/D3ACE2C595AADA7AF7410A8EF7BAF6D5.
Methylene Blue (MB) has a wide range of medical applications, including its established use in treating methemoglobinemias and ifosfamide-induced encephalopathy. Recently, MB has gained attention for its potential as an antimalarial agent and as a treatment for neurodegenerative conditions like Alzheimer’s disease. Notably, MB has shown antidepressant and anxiolytic properties in pre-clinical models and has demonstrated promise in clinical trials for schizophrenia and bipolar disorder. It functions as an inhibitor of monoamine oxidase A (MAO-A), a known target for antidepressant effects, and it also inhibits nitric oxide synthase (NOS) and guanylate cyclase, which are relevant in mood and anxiety disorders. Furthermore, MB’s ability to restore mitochondrial function and mitigate redox imbalances contributes to its therapeutic potential. The use of MB in depression alongside neurodegenerative disorders like Alzheimer’s and Parkinson’s disease is a promising approach. Analogues of MB with similar properties may offer novel multi-target strategies for treating depression, potentially with fewer adverse effects.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/28762173/.
Methylene blue (MB) boasts a wide range of medical applications, with particular interest in its antidepressant-like effects in animals and potential for mood disorder treatment in clinical trials. While its antidepressant properties may arise from various mechanisms, including modulation of the nitric oxide cyclic guanosine monophosphate (NO-cGMP) cascade, mitochondrial respiration enhancement, and antioxidant effects, MB is also a potent inhibitor of monoamine oxidase (MAO) A. This dual nature, while beneficial for antidepressant effects, has raised concerns about adverse effects like serotonin toxicity. To address this, a study synthesized five new MB analogues with lower MAO-A inhibitory activity and found that these analogues exhibited antidepressant-like properties in rats without affecting locomotor activity. These results suggest that these novel MB analogues may provide effective antidepressant compounds with reduced MAO-A-related adverse effects, offering potential as a new class of antidepressants.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/29976053/.
In a 3-week trial, a daily dose of 15 mg of methylene blue was compared to a placebo for the treatment of severe depressive illness. The study was carefully designed to minimize both placebo response bias and observer bias. Results indicated that patients who received methylene blue showed significantly greater improvement compared to those on placebo. This suggests that a daily dose of 15 mg of methylene blue may be a potent antidepressant, warranting further clinical evaluation.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/3555627/.
Methylene blue, a centuries-old medicinal treatment, is primarily known for countering acquired methemoglobinemia (MetHB). Recently, it has gained recognition for its effectiveness in treating ifosfamide neurotoxicity and refractory vasoplegic shock, expanding its applications beyond MetHB. Methylene blue’s mechanism of action, rooted in its oxidizing properties, will be explored in this review, along with its use in acquired MetHB and ifosfamide neurotoxicity. The review will also assess its role in critically ill pediatric and adult patients with refractory vasoplegic shock, along with discussions on dosing and potential adverse effects.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/34463662/.
Methemoglobinemia is a rare condition characterized by the conversion of divalent ferro‐iron in hemoglobin (Hb) to ferri‐iron in methemoglobin (MetHb). It can arise from inherited or acquired factors, with acquired forms being more common, often linked to exposure to substances causing Hb oxidation. Inherited forms stem from autosomal recessive CYB5R3 gene variants or autosomal dominant globin gene variants, collectively known as HbM disease. This review is based on a systematic literature search and offers recommendations for key signs, diagnosis methods, clinical management across different age groups, and therapeutic approaches for methemoglobinemia. The recommendations were achieved through a consensus reached by an expert panel with over 75% agreement on all questions.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291883/.
This review aims to provide insights into the acquired and hereditary causes of methemoglobinemia, recommend sensitive diagnostic tests, and equip critical care clinicians with the knowledge to promptly identify and manage methemoglobinemia cases. The review methodology involved searching internet sources for relevant articles, encompassing case reports, case series, observational, longitudinal, and surveillance studies. Common methemoglobinemia culprits include oxidizing reactions triggered by substances like cocaine-derived anesthetics (e.g., benzocaine, lidocaine), antibiotics (e.g., dapsone, sulfonamides), and gases (e.g., nitric oxide). Furthermore, the review underscores the superior capability of CO-oximetry compared to standard pulse oximetry for methemoglobinemia detection. Lastly, it highlights effective treatment options, including intravenous administration of methylene blue, ascorbic acid, and riboflavin. The manuscript offers comprehensive insights into the occurrence and management of methemoglobinemia.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467467/.
Malaria remains a significant cause of illness and death, particularly in sub-Saharan Africa, where progress in reducing the malaria burden has stagnated since 2015. Historically, success in malaria control was attributed to widespread use of insecticide-treated mosquito nets and the introduction of artemisinin-based combination therapy (ACT). However, resistance to artemisinins and ACT has emerged in Southeast Asia, posing a threat to global malaria control efforts. To combat this, researchers have proposed adding a third antimalarial drug (triple therapy) to standard ACT. Two promising triple therapy regimens are currently under investigation in clinical trials in Southeast Asia. Additionally, the addition of a single dose of the gametocytocidal drug primaquine (PQ) to standard ACT has been shown to reduce the transmission of drug-resistant parasites. While concerns about PQ’s potential for hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency have limited its use, a low dose of PQ is now recommended by the World Health Organization (WHO) for uncomplicated falciparum malaria, even without G6PD testing. However, concerns about PQ’s toxicity remain, necessitating further investigation of alternative drugs. Methylene blue (MB), a versatile medical dye, has a long history of use, including as an antimalarial drug since 1891. Recent research has highlighted MB’s potential as a partner drug for ACT, given its efficacy against various malaria parasites, strong gametocytocidal effects, and synergy with artemisinin derivatives. Clinical studies have demonstrated the effectiveness and safety of MB in malaria treatment, with high cure rates and minimal adverse events. MB’s impact on gametocytes of P. falciparum has been confirmed in clinical trials. Although MB may cause urine discoloration and mild gastrointestinal side effects, it has not been associated with serious adverse events, making it a viable alternative to PQ for inclusion in combination therapies. MB has the potential to enhance malaria treatment, reduce transmission, and mitigate the risk of artemisinin and ACT resistance. Further research is needed to optimize MB formulations and conduct multicountry phase III studies to validate its efficacy and safety in diverse endemic regions and populations, especially considering the various types of G6PD deficiency. The development of MB-based combination therapy is considered highly cost-effective in the context of global health efforts to combat malaria.
You can read the full article at https://www.tandfonline.com/doi/full/10.1080/14787210.2019.1634545.
Developing safe, effective, and affordable drug combinations to combat malaria in Africa is a public health priority. Methylene blue (MB) shares similarities in its mode of action with chloroquine (CQ) and has demonstrated selective inhibition of Plasmodium falciparum glutathione reductase. In 2004, an uncontrolled dose-finding study was conducted with the MB-CQ combination in 435 young children suffering from uncomplicated falciparum malaria in Burkina Faso, where CQ monotherapy had shown a high clinical failure rate in 2003. During the study, three serious adverse events (SAE) were recorded, with one likely attributable to the study medication. Analysis showed no dose-specific effects on safety, and by day 14, the overall clinical and parasitological failure rates were 10% and 24%, respectively. While MB appears to have antimalarial efficacy, the CQ-MB combination was found to be ineffective for treating malaria in Africa.
You can read the full article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1617109/
Methylene blue (MB) was the first synthetic antimalarial to be discovered and was used during the late 19th and early 20th centuries against all types of malaria. MB has been shown to be effective in inhibiting Plasmodium falciparum in culture, in the mouse model and in rhesus monkeys. MB was also shown to have a potent ex vivo activity against drug-resistant isolates of P. falciparum and P. vivax. In preclinical studies, MB acted synergistically with artemisinin derivates and demonstrated a strong effect on gametocyte reduction in P. falciparum. MB has, thus, been considered a potentially useful partner drug for artemisinin-based combination therapy (ACT), particularly when elimination is the final goal. The aim of this study was to review the scientific literature published until early 2017 to summarise existing knowledge on the efficacy and safety of MB in the treatment of malaria.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979000/.
Methylene blue has intrinsic antimalarial activity and it can act as a chloroquine sensitizer. In addition, methylene blue must be considered for preventing methemoglobinemia, a serious complication of malarial anemia. As an antiparasitic agent, methylene blue is pleiotropic: it interferes with hemoglobin and heme metabolism in digestive organelles, and it is a selective inhibitor of Plasmodium falciparum glutathione reductase. The latter effect results in glutathione depletion which sensitizes the parasite for chloroquine action.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/14962363/.
Untreated malaria can rapidly progress to severe forms within 24 hours, and drug resistance poses a global threat to malaria control efforts, necessitating the development of new chemotherapy approaches. This study contributes novel data on the use of methylene blue (MB) in combination therapy with common antimalarial drugs, including mefloquine (MQ) and amodiaquine (AQ), for the treatment of malaria and cerebral malaria. Using a C57BL6/J mouse model, Plasmodium berghei ANKA infection was initiated on Day 0, and treatment commenced on Day 3 when parasitemia reached nearly 1%, involving AQ, MQ, or MB alone or in combination with AQ or MQ. Late-stage treatment with AQ, MQ, or MB alone failed to prevent cerebral malaria. However, MB-based combination therapies remained effective even when initiated late. Significant differences in survival rates were observed, with MB-AQ providing complete protection against cerebral malaria, while MB-MQ demonstrated partial protection. These findings suggest that MB in combination with AQ holds promise as a candidate for preventing cerebral malaria.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9611243/.
Oxidative stress is the major cause of skin aging that includes wrinkles, pigmentation, and weakened wound healing ability. Application of antioxidants in skin care is well accepted as an effective approach to delay the skin aging process. Methylene blue (MB), a traditional mitochondrial-targeting antioxidant, showed a potent ROS scavenging efficacy in cultured human skin fibroblasts derived from healthy donors and from patients with progeria, a genetic premature aging disease. In comparison with other widely used general and mitochondrial-targeting antioxidants, we found that MB was more effective in stimulating skin fibroblast proliferation and delaying cellular senescence. The skin irritation test, performed on an in vitro reconstructed 3D human skin model, indicated that MB was safe for long-term use, and did not cause irritation even at high concentrations. Application of MB to this 3D skin model further demonstrated that MB improved skin viability, promoted wound healing and increased skin hydration and dermis thickness. Gene expression analysis showed that MB treatment altered the expression of a subset of extracellular matrix proteins in the skin, including upregulation of elastin and collagen 2A1, two essential components for healthy skin. Altogether, our study suggests that MB has a great potential for skin care.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449383/.
Methylene blue (MB) is a century-old medicinal compound and laboratory dye, recently recognized for its potent antioxidant properties in combating ROS-induced cellular aging in human skin. Leveraging MB’s molecular structure and light absorption characteristics, this study investigates its potential as a sunscreen active ingredient for UV radiation protection. The research demonstrates that MB treatment reduces DNA damage and cell death caused by UVB irradiation in primary human keratinocytes. Compared to Oxybenzone, a commonly used chemical sunscreen ingredient with known ecological risks, MB exhibits superior UVB absorption capability at the same concentrations and effectively prevents UVB-induced DNA damage while clearing UVA-induced cellular ROS. Importantly, unlike Oxybenzone, MB-containing seawater does not adversely affect the growth of the coral species Xenia umbellata. This study suggests that MB holds promise as a coral reef-friendly sunscreen active ingredient, offering broad-spectrum protection against both UVA and UVB radiation.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163870/.
This study aimed to evaluate the efficacy and side effects of intradermal methylene blue injection in the perianal skin of patients suffering from chronic refractory idiopathic pruritus ani (IPA). Ten IPA patients, unresponsive to standard treatments and care, received intradermal injections of 1% methylene blue solution into the itching perianal area. Symptoms resolved within 4 weeks in all cases, with numbness and tattooing disappearing within 3-4 weeks. No skin necrosis or anaphylaxis occurred during the study, and while anal itching recurred in 8 patients, 4 noted milder symptoms upon recurrence, while 6 out of 10 patients reported significant improvement or resolution of pruritus ani. The procedure showed a 20% success rate within a 60-month follow-up period, demonstrating positive effects on IPA with mild sensory side effects.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/22669483/.
SARS-CoV-2 infection generally begins in the respiratory tract where it can cause bilateral pneumonia. The disease can evolve into acute respiratory distress syndrome and multi-organ failure, due to viral spread in the blood and an excessive inflammatory reaction including cytokine storm. Antiviral and anti-cytokine drugs have proven to be poorly or in-effective in stopping disease progression, and mortality or serious chronic damage is common in severely ill cases. The low efficacy of antiviral drugs is probably due to late administration, when the virus has triggered the inflammatory reaction and is no longer the main protagonist. The relatively poor efficacy of anti-cytokine drugs is explained by the fact that they act on one or a few of the dozens of cytokines involved, and because other mediators of inflammation – reactive oxygen and nitrogen species – are not targeted. When produced in excess, reactive species cause extensive cell and tissue damage. 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.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728423/.
The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), responsible for COVID-19, was declared a pandemic by the World Health Organization in March 2020. This virus primarily infects the respiratory tract, particularly the lungs, sometimes progressing to acute respiratory distress syndrome and multi-organ failure. Current COVID-19 treatments involve antiviral and anti-cytokine drugs, but their efficacy is limited as they can’t simultaneously inhibit free radical and cytokine production. Methylene blue (MB) has recently garnered attention as a potential treatment. MB, a well-established therapeutic agent with FDA approval for other conditions, offers the added benefit of affordability and safety when used at low doses (< 2 mg/kg). This review explores MB’s applicability in COVID-19 management, delving into its mechanisms and detailing relevant clinical studies, thereby examining its potential role in COVID-19 treatment.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352658/.
In December 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, leading to coronavirus disease 2019 (COVID-19). Currently, there is no recommended antiviral treatment against SARS-CoV-2, necessitating the urgent search for effective antiviral drugs. Methylene blue, known for its in vitro antiviral activity in photodynamic therapy and its antibacterial, antifungal, and antiparasitic properties, exhibited significant in vitro activity against SARS-CoV-2 at very low micromolar concentrations, with an EC50 (median effective concentration) of 0.30 ± 0.03 μM and an EC90 (90% effective concentration) of 0.75 ± 0.21 μM at a multiplicity of infection (MOI) of 0.25. These values are lower than those obtained for hydroxychloroquine (1.5 μM and 3.0 μM) and azithromycin (20.1 μM and 41.9 μM). Methylene blue concentrations in human blood support its potential as a promising drug for COVID-19 treatment, warranting further in vivo evaluation in animal models and prospective clinical studies to confirm its effectiveness.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566888/.
Local antiviral photodynamic inactivation (PDI) has the potential to reduce viral load in the nose and throat during early-phase COVID-19 infections. In this study, low-dose methylene blue (MB) was explored as a photosensitizer, and LED light was used instead of a laser. Initial experiments with BCoV-infected cells showed that 0.001% MB sensitizer, combined with LED irradiation for 2.5 or 10 minutes, resulted in a significant reduction in viral load (logarithmic reduction factor ≥ 5.29). In contrast, dark conditions with MB sensitizer alone showed residual viruses. In SARS-CoV-2 experiments with VERO E6 infected cells, a minimum concentration of 0.0001% MB and a minimum radiation intensity of 20,000 lx led to a 99.99% reduction in intracellular and extracellular viruses after one minute of exposure. These findings suggest a potential PDI therapy option for early-phase COVID-19 using MB and LED light.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635689/.
This prospective, double-blind, randomized study compared the efficacy and safety of two urinary antiseptic combinations, methenamine 120mg + methylene blue 20mg (Group A) and acriflavine 15mg + methenamine 250mg + methylene blue 20mg + Atropa belladonna L. 15mg (Group B), in treating recurrent cystitis. Both groups showed improvement in UTI symptoms assessed by the UTISA questionnaire after 3 days of treatment, with no significant difference in efficacy. However, Group A had fewer treatment-related adverse events compared to Group B, indicating that the combination of methenamine + methylene blue resulted in a more favorable safety profile.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751791/.
Methylene blue, an FDA and EMA approved drug known for its safety, demonstrates broad-spectrum virucidal activity, particularly when exposed to UV light. This study investigated its effectiveness against influenza virus H1N1 and SARS-CoV-2, both as a preventive and therapeutic measure. Methylene blue displayed antiviral activity at low micromolar concentrations, even without UV activation, suggesting its potential for clinical trials as a preventive or therapeutic agent against these infections. The drug’s mechanisms of action, including genomic RNA degradation, were also explored, emphasizing its multifaceted antiviral properties.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275569/.
Current methods for identifying infected tissue in periprosthetic joint infection (PJI) are insufficient. This prospective study assessed the use of methylene blue-guided surgical debridement as a novel technique in PJI. Sixteen total knee arthroplasty patients with PJI underwent this procedure, and samples from methylene blue-stained and unstained tissues were analyzed using various methods. The results showed that more bacteria and higher neutrophil counts were observed in methylene blue-stained tissue, suggesting its potential as a visual guide for surgical debridement in PJI treatment. Clinical success, defined as infection eradication and infection-free survival, was also evaluated, with some patients experiencing new infections at follow-up.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/28811108/.
Candida albicans is a well-known cause of infections, particularly in immunocompromised individuals, with manifestations ranging from superficial to systemic. This study investigated the antifungal mechanism of Methylene blue (MB) against C. albicans and clinical isolates. The research demonstrated MB’s efficacy against C. albicans, including non-albicans species, and revealed that its antifungal action was not reliant on major drug efflux pumps but likely involved mitochondrial inhibition, as evidenced by increased sensitivity on non-fermentable carbon sources. MB also disrupted membrane integrity, reduced ergosterol levels, and inhibited the transition from yeast to hyphal forms, a significant virulence attribute in Candida infections. Overall, this study highlights MB as a promising antifungal agent for combating Candida infections.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780517/.
The contamination of blood products with hepatitis C virus (HCV) poses a risk of liver diseases. To combat this, pathogen reduction methods like methylene blue (MB) plus visible light and shortwave ultraviolet (UVC) light irradiation have been developed to inactivate viruses in plasma and platelet concentrates (PCs). Previous studies only used model viruses for HCV, but this research employed a cell culture-derived HCV infection system. The results show that both MB plus light and UVC irradiation effectively inactivated HCV in plasma and PCs, with HCV being more sensitive to these methods than the model virus, bovine viral diarrhea virus (BVDV). This suggests that these pathogen reduction technologies have the potential to significantly reduce transfusion-transmitted HCV infections.
You can read the abstract of this article at https://pubmed.ncbi.nlm.nih.gov/22905868/.
Methylene blue, an FDA-approved drug, has been identified as a potent and broad-spectrum antiviral against Zika virus (ZIKV) and Dengue virus (DENV) in both in vitro and in vivo studies. This research revealed that methylene blue can effectively disrupt the interactions between the viral protease NS3 and its co-factor NS2B, inhibit viral protease activity, hinder viral growth, protect mini-brain organoids from ZIKV infection, and reduce viremia in a mouse model. Its antiviral mechanism encompasses both entry and post-entry steps, reducing virus production and inhibiting processed NS3 protein production. With its established safety profile, methylene blue presents a promising therapeutic option for managing flavivirus infections, particularly ZIKV, and other related pathogens.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646565/.
Photodynamic therapy involves delivery of a photosensitising drug that is activated by light of a specific wavelength, resulting in generation of highly reactive radicals. This activated species can cause destruction of targeted cells. Application of this process for treatment of microbial infections has been termed “photodynamic antimicrobial chemotherapy” (PACT). In the treatment of chronic wounds, the delivery of photosensitising agents is often impeded by the presence of a thick hyperkeratotic/necrotic tissue layer, reducing their therapeutic efficacy. Microneedles (MNs) are an emerging drug delivery technology that have been demonstrated to successfully penetrate the outer layers of the skin, whilst minimising damage to skin barrier function. Delivering photosensitising drugs using this platform has been demonstrated to have several advantages over conventional photodynamic therapy, such as, painless application, reduced erythema, enhanced cosmetic results and improved intradermal delivery. The aim of this study was to physically characterise dissolving MNs loaded with the photosensitising agent, methylene blue and assess their photodynamic antimicrobial activity. Dissolving MNs were fabricated from aqueous blends of Gantrez® AN-139 co-polymer containing varying loadings of methylene blue. A height reduction of 29.8% was observed for MNs prepared from blends containing 0.5% w/w methylene blue following application of a total force of 70.56 N/array. A previously validated insertion test was used to assess the effect of drug loading on MN insertion into a wound model. Staphylococcus aureus, Escherichia coli and Candida albicans biofilms were incubated with various methylene blue concentrations within the range delivered by MNs in vitro (0.1–2.5 mg/mL) and either irradiated at 635 nm using a Paterson Lamp or subjected to a dark period. Microbial susceptibility to PACT was determined by assessing the total viable count. Kill rates of >96%, were achieved for S. aureus and >99% for E. coli and C. albicans with the combination of PACT and methylene blue concentrations between 0.1 and 2.5 mg/mL. A reduction in the colony count was also observed when incorporating the photosensitiser without irradiation, this reduction was more notable in S. aureus and E. coli strains than in C. albicans.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695826/.
Bartonella henselae, a Gram-negative bacterium transmitted through cat scratches and ectoparasites, can lead to various clinical diseases in humans, including local lymphadenopathy and severe conditions like persistent bacteremia and endocarditis. The current treatment for persistent B. henselae infections faces challenges regarding effectiveness. To address this, the study evaluated 14 antibiotics and 25 antibiotic combinations against stationary phase and biofilm-recovered B. henselae cells. Notably, ciprofloxacin, gentamicin, and nitrofurantoin showed high activity, while clofazimine and miconazole performed poorly. Combinations like azithromycin/ciprofloxacin, azithromycin/methylene blue, rifampin/ciprofloxacin, and rifampin/methylene blue effectively eliminated stationary phase B. henselae within a day, and methylene blue and rifampin displayed strong activity against biofilm B. henselae after 6 days. These findings hold promise for developing more effective treatments for persistent Bartonella infections in the future.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149919/.
Photodynamic therapy (PDT) is gaining traction in breast cancer treatment due to its localized selectivity and reduced toxicity compared to radiotherapy and chemotherapy. PDT involves using photosensitizer drugs loaded into various nanomaterials along with light exposure. However, a key challenge with PDT is the limited capacity of nanomaterials to encapsulate anticancer drugs at high doses, resulting in reduced treatment efficacy. This study proposes the use of poly(N-isopropylacrylamide) (PNIPAM) microgels for encapsulating methylene blue, an anticancer drug, for potential breast cancer treatment in the MCF-7 cell line. The research involved developing biocompatible microgels based on PNIPAM and its anionically functionalized counterpart (PNIPAM-co-PAA) for drug encapsulation. The findings suggest that core PNIPAM microgels outperformed core/shell PNIPAM-co-PAA microgels in drug loading and retention, leading to enhanced photodynamic efficacy against MCF-7 cells.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988338/.
Heat shock proteins 70 (Hsp70) and 90 (Hsp90) are vital for the survival and proliferation of lung cancer cells. This study compared the anticancer potential of methylene blue (MB), an Hsp70 inhibitor, novobiocin (NB), a known Hsp90 inhibitor, and their combination. In vitro, MB showed lower cell viability compared to NB, and the combination of MB and NB further reduced cell viability. MB was more potent than NB in inhibiting cancer cell growth. In vivo, MB effectively inhibited Hsp70, reduced tumor biomarkers, and improved lung histopathology in a lung carcinogenesis mouse model induced by benzo[a]pyrene. These findings highlight MB’s significant anticancer activity via Hsp70 inhibition in lung cancer.
You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S0753332218343944.
Breast cancer remains a significant cause of mortality in women, often due to incomplete primary treatment efficacy in eliminating all cancer cells, leading to recurrence. Photodynamic therapy (PDT), which involves visible light activation in the presence of methylene blue (MB) and oxygen, presents a promising adjunct therapy to chemotherapy and surgery. In this study, MB-PDT demonstrated varying cell-killing potential among different breast cell lines, with malignant cells being more susceptible than non-malignant ones. The cell death mechanisms induced by MB-PDT appeared to involve alternative pathways rather than classical apoptosis. This research highlights the potential of MB-PDT as an effective adjunct therapy to enhance the eradication of microscopic residual disease in breast tumors, reducing the risk of recurrence.
You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28298203/.
Oral mucositis is a distressing complication of cancer therapy, often causing severe pain and negatively impacting patients’ oral health, nutrition, and overall quality of life. This retrospective study assessed the efficacy and safety of methylene blue (MB) oral rinse in relieving oral pain associated with mucositis in cancer patients who did not respond to conventional treatments. The analysis included 281 patients with various cancer types, and the results demonstrated a significant reduction in pain scores after MB oral rinse treatment. Most patients achieved pain relief within the first few doses, with minimal adverse effects reported. This study suggests that MB oral rinse is an effective and safe option for managing refractory oral mucositis pain in cancer patients.
You can read the full article at https://jnccn.org/view/journals/jnccn/19/5/article-p521.xml.
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