Methylene blue is a synthetic dye that has been shown to have antiviral properties against a range of viruses, including HIV, hepatitis C virus (HCV), Zika virus, and SARS-CoV-2 (the virus that causes COVID-19). The exact mechanism of action by which methylene blue exerts its antiviral effects is not fully understood, but there are several proposed mechanisms based on existing research.
a. Antiviral Properties of Methylene Blue
One proposed mechanism is that methylene blue can inhibit viral entry into host cells by preventing the fusion of the viral envelope with the cell membrane. This mechanism has been demonstrated in the case of HIV, where methylene blue was shown to block the fusion of the virus with the host cell membrane by interfering with the viral envelope glycoprotein.
Methylene blue was found to inhibit viral replication by blocking the activity of the viral RNA-dependent RNA polymerase. Methylene blue can raise lysosomal pH and interfere with low pH-dependent viral processes, such as uncoating and membrane fusion, which could contribute to its antiviral activity.
In addition to its direct antiviral effects, methylene blue has been shown to have broad-spectrum antimicrobial properties, which could help to prevent secondary bacterial infections that often occur in viral infections. Methylene blue can inhibit the growth of a wide range of bacteria, including Staphylococcus aureus and Escherichia coli, by disrupting their membrane potential and inhibiting their energy metabolism.
b. Enhancing Immune Response with Methylene Blue
Methylene blue has also been shown to have immunomodulatory effects, which could contribute to its antiviral activity. The methylene interferes with macrophages and prevents the cytokine storm in lungs. It has been found to stimulate the production of cytokines, which are essential for the immune response to viral infections. Overall, the antiviral mechanism of methylene blue appears to involve a combination of inhibiting viral entry into host cells, interfering with viral replication, and stimulating the immune response.
c. Methylene Blue in COVID-19 Clinical Trials
There were several ongoing clinical trials investigating the use of methylene blue as a treatment for COVID-19. These trials were mainly in the early phases, such as Phase 1 and Phase 2, and were being conducted in various countries around the world
There is some research suggesting that methylene blue may have antiviral properties that could be effective against COVID-19. One study published in the Journal of Medical Virology in 2021 found that methylene blue inhibited the replication of SARS-CoV-2 in vitro, which means it prevented the virus from multiplying in laboratory conditions.
In a medical center, 80 patients with severe COVID-19 were assigned in a random manner to receive oral methylene blue with standard care or standard care only. The addition of methylene blue in the protocol of COVID-19 treatment enhanced the oxygen saturation levels and improved respiratory distress in severe cases of COVID-19, shortened hospital stay, and reduced mortality.
A trial in 2020 for the application of MB in the COVID-19 treatment. The intervention consisted of an injectable mixture methylene blue, vitamin C, N-acetyl cysteine (MCN). 4 out of 5 patients responded well to the MCN treatment and increased the survival rate of the patients. The therapeutic effect of MCN can be attributed to the macrophage activation cycle leading to oxidative stress and “cytokine storm”. The additional benefit of this protocol is the use of economical drugs approved by the FDA for other diseases.
d. Potential Synergistic Effects with Other COVID-19 Treatments
1. Antiviral activity: Methylene blue has been shown to have antiviral activity against a range of viruses, including SARS-CoV-2.
2. Immune modulation: COVID-19 can cause an overactive immune response known as a cytokine storm, which can lead to severe lung damage and other complications. Methylene blue has been shown to modulate the immune response by interfering with macrophages and preventing cytokine storms in the lungs.
3. Oxygenation: COVID-19 can cause respiratory distress and low oxygen levels in severe cases. Methylene blue has been shown to improve oxygenation in the blood by facilitating the release of oxygen from hemoglobin.
4. Treatment of methemoglobinemia: Methemoglobinemia is a potential side effect of methylene blue, but it can also be used as a treatment for methemoglobinemia caused by other substances.
e. Future Implications of Methylene Blue in Pandemic Response
Methylene Blue can be termed as a “rescue magic bullet” for COVID-19 treatment. The use of Methylene Blue in novel dosage forms like an anti-COVID mouthwash may also be beneficial. It was reported that there is an increased risk of acute myocarditis in the Covid-19 patients. Treatment with Methylene Blue and light influences a number of coagulation factors. In addition, approximately 30% of anti-hemophilic factor has been lost. A study by wang et al. reported that the addition of heparin to Methylene Blue solution resulted in 3.7-fold higher Methylene Blue dimerization, indicating that heparin aids Methylene Blue aggregation.
Treating Methemoglobinemia with Methylene Blue
a. What is methemoglobinemia?
It’s a blood disorder where abnormal amount of methemoglobin is produced. Hemoglobin (the protein that carries oxygen in red blood cells) is oxidized to methemoglobin and cannot bind oxygen properly. This can cause cyanosis (bluish coloration of the skin and lips), shortness of breath, fatigue, or death.
Methemoglobinemia can occur as side effect of high doses of methylene blue, as it acts as an electron acceptor and converts normal hemoglobin to methemoglobin. However, this risk is generally low when methylene blue is used in therapeutic doses
ِb. How Methylene Blue works as a treatment
Methylene blue can act as reducing agent and convert methemoglobin back to hemoglobin. However, in cases where methemoglobinemia is caused by high doses of methylene blue, the use of methylene blue as treatment is contraindicated.
Exploring Methylene Blue’s Potential in Pain Management
a. Methylene Blue’s Mechanism of Action in Pain Relief
Methylene blue, acting as a non-opioid analgesic, influences various pain pathways, blocking pain signals, reducing inflammation, and impacting the activity of pain-related chemicals in our brains. By inhibiting nitric oxide production, methylene blue can help reduce pain and inflammation and vasoconstriction. In addition, Methylene blue may contribute to pain reduction by hindering nerve connection to tissues. Indeed, it can make affected nerve fibers or neurons incapable of sensing pain.
b. Neuropathic Pain and Methylene Blue
Growing evidences have revealed that Methylene blue functions to restore abnormal vasodilation and notably it is implicated even in pain relief. A small study of patients with chronic neuropathic pain found that intravenous administration of methylene blue resulted in significant reductions in pain intensity and improved quality of life. For osteoarthritis and colitis, Methylene blue reduces inflammation by suppressing nitric oxide production, and ultimately relieves pain.
c. Postoperative Pain Management with Methylene Blue
Methylene blue has been found to have unique analgesic property through temporary disruption of sensory nerve conduction. Its analgesic properties are thought to be related to its ability to block certain pain receptors in the body which play a role in the transmission of pain signals.
d. Methylene Blue in Chronic Pain Conditions
Physicians began to inject methylene blue into degenerated disks to relieve pain in patients with chronic discogenic low back pain (CDLBP), and some of them achieved remarkable outcomes. They believed that methylene blue has a capacity to mitigate pain in the patients by blocking nerve conduction or destroying nerve endings around the painful disks that may be vascularized and extensively innervated owing to disk degeneration.
e. Clinical Trials and Emerging Research on Methylene Blue for Pain Management
One study found that methylene blue injections were effective in reducing pain in patients with chronic low back pain. Another study found that topical application of methylene blue reduced pain and inflammation in patients with herpes zoster (shingles). A study published in the journal Pain Practice in 2015 found that intravenous administration of methylene blue in patients undergoing abdominal surgery resulted in reduced postoperative pain scores compared to placebo.
Conclucion
Methylene Blue has caught attention as a potential treatment for COVID-19. It shows promise in fighting the virus by hindering its replication and blocking viral enzymes. Not only that, but methylene blue also has anti-inflammatory properties that can help calm down the exaggerated immune response seen in severe cases. On another note, methylene blue has a longstanding role in pain relief. With its ability to tackle multiple pain mechanisms, methylene blue brings hope for easing different types of pain, from nerve-related discomfort to inflammatory conditions.
References:
- Behavioral, Physiological and Biochemical Hormetic Responses to the Autoxidizable Dye Methylene Blue
- Repurposing methylene blue in the management of COVID-19: Mechanistic aspects and clinical investigations
- Clinical effectiveness and prospects of methylene blue: A systematic review
- Methylene Blue Application to Lessen Pain: Its Analgesic Effect and Mechanism
