Low Dose Methylene Blue

Anyone here have any experiences taking low dose methylene blue for longevity?

I have used it. I was initially reluctant because it just seems so out there. I don’t use it often or much but everything I read seems to endorse it. I took it today but only 2 drops in a half glass of water. My interest is in prevention of Alzheimer’s. I also do Red LIght Therapy and it seems that the combination of Methylene Blue and Red Light exposure (head and face) is beneficial for the brain. I haven’t experienced any side effects. I drink it from a straw to try to bypass my teeth as much as possible as it can stain teeth.

I have taken Meth Blue on and off for the past 2 years or so. Up to 20 drops in small amount of water weeks at a time with some powdered vitamin C that’s supposed to contribute to its power (per the popular book). I experienced no ill effects, but at the same time, no discernible positive effects. I think it’s a question of blind faith in hoping it will pay off in the end.

What is your dosage and how did you arrive at that dosage.

Hello Horace,

My name is Brandon. I am on the clinical team at Healthspan. Thank you so much for your important question. Methylene blue is considered safe from 0.5-4.0mg/kg body weight [1]. Methylene blue works on a hormetic principle, meaning its benefits follow a U-shaped curve, where low doses can enhance health while higher doses may diminish or even reverse those effects. Recent interest and focus on methylene blue is exciting as it is likely to advance our understanding of this agent for many health and longevity applications in humans. From our comprehensive review of the research literature we noted many potential benefits associated with methylene blue including improvements in energy production, reduced reactive oxygen species, anti-bacterial, anti-viral, and improvement in cognitive function, including mood. We also noted some instances of side effects.

For healthy individuals in pursuit of longevity benefits we encourage a conservative gradual dosing approach beginning at 5mg 5 out of 7 days per week. There is some research that suggests lower dose ranges might be advantageous for clinical conditions. Interestingly, there have been studies in which “placebo” low-dose may have similar beneficial effects according to two randomized control trials [2,3]. In these trials the low dose targets that were suggested 0.15-0.3mg/kg body weight [2] and utilized were 8mg/day [3].

Dose increase with Healthspan is possible up to 25mg 5 out of 7 days per week. This is something that the clinical team would help individuals navigate based upon their specific goals and a more complete understanding of other lifestyle habits or agents involved in their longevity pursuit. As always, in an effort to provide guidance that is safe and effective while mitigating risk we have concluded that lower dose methylene blue may be the best way to optimize for benefits and minimize for risks.

Refs:

  1. Xue, H., Thaivalappil, A., & Cao, K. (2021). The Potentials of Methylene Blue as an Anti-Aging Drug. Cells, 10(12), 3379.
  2. Alda, M., McKinnon, M., Blagdon, R., Garnham, J., MacLellan, S., O’Donovan, C., Hajek, T., Nair, C., Dursun, S., & MacQueen, G. (2017). Methylene blue treatment for residual symptoms of bipolar disorder: randomised crossover study. The British journal of psychiatry : the journal of mental science, 210(1), 54–60.
  3. Gauthier, S., Feldman, H. H., Schneider, L. S., Wilcock, G. K., Frisoni, G. B., Hardlund, J. H., Moebius, H. J., Bentham, P., Kook, K. A., Wischik, D. J., Schelter, B. O., Davis, C. S., Staff, R. T., Bracoud, L., Shamsi, K., Storey, J. M., Harrington, C. R., & Wischik, C. M. (2016). Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer’s disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet (London, England), 388(10062), 2873–2884.

@Horace, our team did a write-up on the neuroprotective mechanisms of methylene blue.

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I have begun Meth Blue about 2 months ago. 4 drops in small amount of water each day has improved my stamina throughout the day for certain.. I used to struggle to make it through the day without a nap. But not anymore. Also more alert, more organized and accomplish more in a given day than before. I’m an 84 yr old female..

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Hey Brandon.. thank you for the great information!! So, I’m on the subscription for the MB.. my dose went from 5mg to 10mg. Is this by design or mistake? What is not considered low dose anymore?

Hey there!

Can you please shoot me an email so we can connect and walk through your subscription privately? brandon@gethealthspan.com

To answer your question about low-dose, though:

Our dosing protocol for Methylene Blue (MB) is based on a combination of scientific evidence, clinical experience, and risk-benefit analysis to ensure both safety and efficacy. While studies have investigated a wide range of MB doses—some using higher doses in acute clinical settings—our approach is designed for long-term, sustainable use with mitochondrial and cognitive health in mind. While studies have investigated a wide range of MB doses considered safe between 0.5-4.0mg/kg body weight many of these investigations using higher doses are in acute clinical or emergent settings our approach is designed for long-term, sustainable use with mitochondrial and cognitive health in mind. Based upon our current understand of the research we support low dose <0.5mg/kg.

Our physicians prescribe Methylene Blue starting at 10 mg, with a recommended range of 5 mg to 25 mg per day. The rationale for this dosing is based on the concept of hormetic (biphasic) dose response, meaning that lower doses may be more effective for mitochondrial support, cognitive enhancement, and neuroprotection than higher doses, which can introduce oxidative stress.

At low doses, MB acts as an electron donor, improving mitochondrial efficiency, ATP production, and oxygen utilization. It also functions as an antioxidant, neutralizing excess reactive oxygen species (ROS) without disrupting the body’s natural balance. At higher doses, MB shifts from being an antioxidant to a pro-oxidant, increasing ROS production, which can potentially cause cellular stress. This is useful in high-dose medical applications (such as treating methemoglobinemia, infections, or depression), but not necessarily beneficial for long-term mitochondrial and cognitive health.

Our protocols follow a 5-days-on, 2-days-off cycle to prevent tolerance and adaptation – continuous daily use of MB can lead to diminished effects over time as the body adapts. Cycling allows for a reset period, maintaining long-term efficacy. Additionally, while MB is an effective mitochondrial support compound, excessive or continuous dosing may overload the system, leading to oxidative stress rather than protection. Some individuals find MB to be highly energizing, which can be beneficial during workdays but may feel excessive on rest days. The weekend break helps the body regulate its response to MB, preventing overstimulation.

Many published studies on Methylene Blue focus on high-dose, short-term use for acute medical conditions (e.g., methemoglobinemia, sepsis, major depressive disorder). These studies often involve one-time intravenous (IV) doses or daily high-dose regimens for a short duration. In contrast, our protocol is designed for long-term mitochondrial and cognitive support, prioritizing safety, sustainability, and neuroprotection. By keeping doses within the 10-25 mg range and following a cycling strategy, we aim to optimize MB’s benefits while reducing potential risks associated with excessive oxidative stress, overstimulation, and long-term adaptation.

Doses of MB ≥30 mg can indeed shift from antioxidant to pro-oxidant, and this has been observed in both animal studies and cell models — and the risk is dose-dependent. As I mentioned above, at low doses, MB acts as an alternative electron carrier in the mitochondrial electron transport chain (ETC), reducing oxidative stress. At high doses, MB becomes saturated in its redox cycle. It can accept electrons but not recycle efficiently, which leads to ROS accumulation (such as superoxide or hydrogen peroxide). To illustrate, high-dose MB (≥10 mg/kg) caused oxidative DNA damage and neuronal apoptosis in rodent brains. This was associated with increased lipid peroxidation, a hallmark of oxidative injury.

MB can induce mild oxidative stress that triggers adaptive antioxidant responses (hormesis), but above a threshold (~30 mg in humans), and the system may tip toward cellular damage. High doses are also more likely to interfere with cytochrome systems in the liver and monoamine oxidase activity, compounding toxicity risks.

These are the main reasons our MB protocol tops out at the 25mg/day, 5 days per week dose :nerd_face: