Methylene Blue

Methylene Blue is Neuroprotective

Neurons (brain cells) have extraordinarily high energy requirements but are unable to store energy. Millions of mitochondria are needed in each neuron in order to keep up with energy demand - and these cells are exquisitely susceptible to any disruption in mitochondrial function.

In fact it appears that mitochondrial dysfunction underlies almost all, if not all, neurodegenerative diseases. Fortunately methylene blue is uniquely capable of rescuing impaired mitochondrial function. It has even been documented to improve memory and executive function in healthy subjects.

Furthermore, many potentially therapeutic molecules cannot cross the blood brain barrier and ultimately reach the mitochondria. However, methylene blue readily crosses the blood brain barrier and preferentially accumulates in the brain.

Acute Brain Injury

Ifosfamide Encephalopathy

Methylene blue has an established track record in addressing acute brain injury.  It has been used for decades as a potentially life saving treatment of encephalopathy caused by a cancer drug called ifosfamide.  This can occur in up to thirty percent of patients treated with this drug and symptoms include incoherence, hallucinations, coma and death. Methylene blue can prevent and reverse these symptoms.

Strokes and Traumatic Brain Injury

Animal studies indicate that methylene blue may be of great benefit for acute (immediately after) and chronic (recovery phase) outcomes in strokes. In both instances brain scans and functional assessments demonstrated methylene blue limited the extent of brain damage and expedited recovery.

Similar findings were made in animal models of traumatic brain injury where methylene blue was found to reduce neuro-inflammation and limit the size of damaged brain tissue.

Psychiatric Disorders

Methylene blue has also been shown to have a beneficial effect on psychosis, depression and anxiety.

Psychosis

The phenothiazine class of drugs often used to treat psychosis are actually derivatives of methylene blue so it’s no surprise that methylene blue has similar actions.

Anxiety and Depression

Reduced levels of serotonin and melatonin are associated with depression, anxiety and poor sleep respectively. Methylene blue inhibits an enzyme called monoamine oxidase which leads to an increase in these compounds in the brain.

Methylene blue therefore echoes the effects of Prozac and other drugs that boost serotonin levels. It has mildly positive effects on depression and anxiety along with insomnia without many of the potential side effects (agitation, dizziness, blurred vision, erectile dysfunction and severe withdrawal symptoms).

As discussed above, the dangers of using methylene blue along with these drugs may have been significantly over stated. Nevertheless we still exercise caution in this regard.

Alzheimer’s and Other NEURODEGENERATIVE Diseases

Mitochondrial Dysfunction is a Key Disease Process

Alzheimer’s disease is a progressive degenerative disorder which, until recently, was considered to be irreversible. This debilitating disorder is characterized by the formation of amyloid plaques, neurofibrillary tangles and death of brain cells.

Methylene blue has been demonstrated to reverse all of these key disease processes.  However it appears that plaque formation and neurofibrillary tangles are really the aftermath of the disease process as opposed to the cause. Focusing soley on these changes is akin to focusing on the ashes as opposed to identifying the cause of a fire and putting it out.

Mitochondrial dysfunction appears to be a common and prominent pathological feature across a wide range of neurodegenerative disorders including Alzheimer’s disease, Parkinsons disease, Huntingtons disease and amyotrophic lateral sclerosis (ALS).

The role of methylene blue in promoting and rescuing mitochondrial function, reducing oxidative stress and reducing neuro inflammation, along with its ability to access the brain makes it an ideal candidate for these neurodegenerative diseases.

Lab Studies

Many lab studies and animal models of Alzheimer’s and other neurodegenerative diseases indicate that methylene blue holds great promise for addressing these conditions.

Clinical Evidence

A clinical study demonstrated that the methylene blue derivative used arrested disease progression in mild to moderate Alzheimer’s disease with an 81% reduction in cognitive decline over 1 year. The same group subsequently conducted a larger phase 3 trial. However the results were inconclusive most likely due to the use of a control group which also received methylene blue but at a much lower dose than the active treatment group. (The control group were also administered methylene blue because otherwise the blue urine in the active group would have been a dead giveaway!)

The trial results did not meet the predicted outcomes due to the fact that both groups showed improvement and there wasn’t a substantial difference in response between the active and control groups.

According to world renowned neuroscientist Dr. Gonzalez-Lima, these results were not surprising because methylene blue exhibits a biphasic dose response: the dose needs to be high enough but not too high in order to achieve benefit. Nevertheless the fact that the control group on low dose methylene blue showed improvements is very encouraging!

A Holistic Approach is Essential

Although methylene blue is a promising means of targeting Alzheimer’s disease, it is more likely to be effective if combined with synergistic modalities synergistic modalities such as photobiomodulation (light therapy), molecular hydrogen therapy and addressing some of the recognized root causes of this complex disease which is critically important. Some of these important factors are outlined below:

Nutrient Deficiencies

Although studies examining the use of these supplement in isolation do not consistently show benefit, there is strong evidence that a combination of omega-3 fatty acids, vitamin B and vitamin D can significantly reduce the risk of Alzheimer’s disease. According to Professor David Smith from Oxford University, studies confirmed a 73% reduction in brain shrinkage in patients with early cognitive impairment who were given vitamin B supplements but only if they had pre-existing adequate levels of omega-3. This response was not seen if the same vitamin B supplements were given in the context of low omega-3 levels.

Insulin Resistance in the Brain: Type 3 Diabetes

In addition to these nutrient deficiencies, the metabolic shift that takes place in Alzheimer’s disease means that the brain cells cannot process carbohydrates and refined sugars - sometimes referred to as type 3 diabetes. Fortunately the brain can utilize ketones as an alternative energy substrate - hence the recommendation of a ketogenic diet to prevent and treat Alzheimer’s disease.


The Gut-Brain Axis
There is now overwhelming evidence that the gut microbiome can have a profound influence on disease processes in every organ including the brain.

Changes in the composition of the gut microbiome, a shift in the substances produced by these gut microbes and increased levels of bacterial endotoxins have been repeatedly documented in Alzheimer’s patients. However it wasn’t clear if these changes play a causative role or if they are a result of the disease.

A landmark study published in 2023 shed light on this important question. They found that if the gut microbiome was transplanted from persons with Alzheimer’s to normal mice, the mice would then exhibit features of Alzheimer’s disease, whereas transplants from healthy donors did not. Furthermore, the degree of changes closely correlated with the degree the affected donor.

Methylene Blue Provides Hematologic Support

Methemoglobinemia

Hemoglobin has the critically important function of binding inhaled oxygen and carrying it to the tissues. Methemoglobin is an oxidized form of hemoglobin which has a greatly diminished capacity to bind oxygen. Methylene blue rapidly transforms methemoglobin to the correct configuration of hemoglobin, thereby reversing this dangerous disorder. It is a first line treatment for methemoglobinemia and all modern hospitals are therefore obligated to keep this life saving drug available at all times. Unfortunately it is not utilized for many other conditions where the evidence is equally as strong.

Vasoplegic Shock

Methylene blue is also used for vasoplegic syndrome following cardiac surgery and septic shock. These conditions result in dangerously low blood pressure as a result of almost complete loss of blood vessel tone (ability of vessel walls to constrict).

Nitric oxide is a key molecule which leads to relaxation of the vessel walls. Methylene blue normalizes the blood pressure by inhibiting guanylate cyclase which is a component of the nitric oxide signaling pathway. As it doesn’t directly inhibit nitric oxide it rescues vasoplegic shock without completely inhibiting this important molecule.

Methylene Blue for Cancer

Methylene blue can potentially target cancer by several mechanisms either as an adjunctive measure along with standard cancer therapies or even as a standalone treatment.

Leveraging the Warburg Effect

One of ways that methylene blue can target cancer is via the Warburg effect. This phenomenon was originally proposed one hundred years ago, but is now being increasingly recognized and investigated by leading oncology researchers. Warburg noted cancer cells exhibit a shift in metabolic processes compared to normal cells. This difference can be leveraged to selectively destroy cancer cells. Methylene blue is one of the agents which can facilitate this approach, alone or more effectively in concert with other agents.

Photodynamic Therapy

Methylene blue is also activated by intense red light in a process referred to as photodynamic therapy (PDT). PDT produces a burst of oxidative compounds which can selectively damage cancer cells and infectious organisms. Normal cells are relatively resistant to this effect.

PDT has several advantages over standard chemotherapy. Chemotherapy is highly toxic to both normal and cancerous cells, and if the response is inadequate, a different chemotherapeutic agent must be administered. In contrast, PDT causes minimal toxicity by specifically targeting cancer cells and can be safely repeated multiple times to achieve the desired response.

Methylene Blue Boosts Effects of Other Cancer Therapies

Many tumors exhibit low oxygen levels which is thought to promote tumor growth, metastasis and increased resistance to many types of cancer treatments. Methylene blue can significantly increase oxygen levels in thereby increasing response to other cancer therapies.

Supportive Therapy

Methylene blue also plays a supportive role for patients undergoing cancer treatment as it offers two much needed benefits: increased energy and reduced inflammation.

A Holistic Approach is Essential

In much the same way as Alzheimer’s disease, targeting cancer with methylene blue is far more likely to be successful if nutrient deficiency, metabolic dysfunction and sources of underlying inflammation are addressed. Of particular importance is vitamin D levels as deficiency significantly limits the ability of the immune system to control cancer initiation, growth and spread.