Medical research would seem to hinge on the brand-new therapies coming out of major research labs pouring millions of dollars into the latest and greatest. Research into using an “out-dated” therapy like methylene blue would seem a waste of time. It now appears that the glory of those days has passed as we move into a new era in which many major advances come by learning to apply older therapies, like methylene blue, to new challenges. While COVID fast-tracked this type of research, other commonplace yet challenging infections can also find great advancements in old therapies. Methylene blue has found a new use in treating some chronic tick born infections which conventional medicine has ignored and it is time to learn more about this oldie-but-goodie.
Known officially as methylthioninium chloride, ‘methylene blue’ is the nickname we use because we can actually spell it right first time through. For countless years, it has been used to treat a potentially fatal condition called methemoglobinemia by catalyzing a change in hemoglobin based iron otherwise incapable of transporting oxygen. In order to carry out this function, it has often been combined with ascorbic acid (vitamin C) and/or NAC (n-acetyl cysteine). Besides its major role in chemotherapy induced methemoglobinemia recovery, it can even help overcome the resistance of malaria to chloroquine therapy. If that were not enough to earn kudos, it can even donate electrons to our energy production change and improve ATP production.
With the need for more effective medications against infections that are developing resistance or were just difficult to treat in the first place, researcher dollars are going towards how to use old drugs in new ways. Several studies have compared the efficacy of multiple therapeutic regimens against Barrelia and Bartonella, the causes of Lyme and Cat Scratch disease respectively. In an article by Feng et al, Identification of Additional Anti-Persister Activity against Borrelia burgorferi from an FDA Drug library, Johns Hopkins researchers found that methylene blue lowered the colonies of Borrelia persisters by 60%. The persistent forms of Borrelia are likely responsible for much of the difficulty in fully eradicating Lyme disease.
When other researchers at Johns Hopkins compared a long list of therapies against Bartonella (Li et al 2019), they found that a single exposure to methylene blue lowered the stationary phase of Bartonella by 75-84%. The stationary phase is the non-growing life phase of the bacteria which is far harder to kill and thus a target for development of new therapies. This compared favorably to a number of other therapies currently used or being consider although it was in a petri dish, so this does not confirm it will work in real life. When they continue the experiment for a whole day of exposure, methylene blue cleared 100% in the petri dish.
From there, they began combining various combinations and looking at whether the therapies worked where biofilms were protecting the bacteria. These microscopic layers of bacterial created mucous prevent antibacterials from reaching the bartonella. By combining methylene blue with either azithromycin or clotrimazone orally (a common antifungal), the efficacy works well if continued for long enough.
Having seen potential benefits in our patients with tick borne illnesses, we can consider how to give this medication safely and effectively. Like many medications, methylene blue behaves differently at different concentrations in our systems. At the very least we want to keep the dose below 10mg/kg, where toxicity risk is minimal. Oral administration offers a safer and more controlled route than IV, as well as being faster, while still being well absorbed at a slow enough rate to be safe and effective. The pharmacokinetics (how the medicine concentration changes over time as the drug is metabolized in the body) requires a twice a day dosing, which is primarily excreted out the kidneys while penetrating most body tissues including the brain. While the FDA approved methylene blue for the treatment of methemoglobinemia up to 4mg per kg, the dosing for tick borne illnesses vary from 4mg twice a day to 50mg twice a day, often starting at the low end and working up.
There are always contraindications to most therapies and methylene blue is no exception. The medication should never be used during pregnancy and not if the patient’s kidneys are functioning below a GFR of 30. The medicine should not be combined with an MAO-Inhibitor (lists of these meds are available online) and should not be combined with amphetamines like for ADHD or street drugs. One lab test that should always be performed before starting is a test for G6PD (glucose 6 Phosphatase deficiency) as it can be fatal in those people. Beyond that, patients on this medication may find that their oxygen saturation may look lower on a pulse ox reading that it actually is, and their other providers should be made aware of this possibility.
As a side note, some may ask if they can buy the industrial grade methylene blue at a cheaper rate. As is often the case, cheaper is not usually better. The cheaper version of methylene blue may be contaminated with arsenic, aluminum, cadmium, or mercury.
Further patient education includes the cosmetic: letting patients know that their urine will be very blue while they are on this medication. This will resolve after medication is stopped, but careful toilet care should be advised as infrequent cleaning the toilet will result in a permanently stained toilet. Guys should avoid peeing on the carpet during this time. Topical application is possible if someone wants to turn into a Smurf, meaning you are blue for months. The ease of absorption means that the more costly liposomal formulation is not needed. If a child needs a dissolvable form, they will end up with a blue mouth for quite a while.
With these newer uses of such an older medicine like Bartonella, the future is bright for success in other infections. These include potential benefits with RNA viruses as well as bacteria like Staphylococcus aureus, Staphylococcus epidermidis, and Klebsiella pneumonia. Research into potential use for E. coli, Candida albicans, and others is underway. Some in functional medicine are trying it in Babesia duncani but not Babesia microti (another parasite transmitted by ticks).
Bibliography:
Feng, Jie et al. Identification of Additional Anti-Persister Activity against Borrelia burdorfer from an FDA Drug Library. Antibiotics. September 16, 2013.
Li et al. Identification of FDA-Approved Drugs with Activity against Stationary Phase Bartonella hensalae. Antibiotics. April 29, 2019.
Zheng, Xiaoyan et al. Effect of different drugs and drug combinations on killing stationary phase and biofilms recovered cells of Bartonella hensalae in vitro. BMC Microbiology. Open Access.
Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.
