6 replies to this topic

[Taiidan]

Methylene blue gets a bunch of attention for nootropic and neuroprotective effects. In researching potential dangers, I came across the following: https://pubs.asahq.o...-on-the-Central

 

Although it found evidence of clinical and experimental neurotoxic effects at higher than nootropic doses, there's also this finding: 

 

" Dose-response experiments in single cell neuronal cultures revealed that a 2-h-long exposure to MB at non-cell-death-inducing concentrations could still induce significant retraction of dendritic arbor."

 

"Most importantly, analysis of neuronal dendritic architecture revealed a significant remodeling of dendritic arbor, including retraction of dendrites as well as elimination of branching points at MB concentrations of 1 μm and greater "

"Given that even minor changes in neuronal morphology have been shown to exert a significant impact on neuronal responses to stimuli,43these results could have important functional consequences, and an essential next step should be to determine whether low concentrations of MB initiate reorganization of neuronal arbor in a more complex and physiologic environment."


This was a 2008 study. Anything to be concerned about here for lower neuroprotective/ nootropic doses? 

Edited by Taiidan, 02 March 2021 - 07:23 PM.

[ekaitz]

How much MB would you have to take to reach 1 μm plasma concentration?

Edited by ekaitz, 09 July 2022 - 06:59 PM.

[JohnBoyTheGreat]

How much MB would you have to take to reach 1 μm plasma concentration?

 

Somewhere I read that an oral dose of 0.05 mg/kg would result in 1 μm plasma concentration for most people.

[JohnBoyTheGreat]

While it may be that there are some neurotoxic effects of MB at extremely large doses, I have my doubts that MB has any significant neurotoxic effects at normal doses of 2mg/kg or even a bit higher.

 

The reason is that there is a large group of people who have taken large doses of MB for many, many years without ill effects. Those are people who have methemoglobinemia. No study which I have ever heard of has indicated that MB has affected their mental capacity in any way whatsoever--and this is a LIFETIME of taking methylene blue.

 

My own experience taking MB in doses of slightly less than 1mg/kg for extended periods of time (weeks and months) is that it only helps with memory, thinking, and energy. I've never noticed a negative side effect at that dose and none of my family members have ever noted anything. (Obviously, if my memory were worse, I might not know it, so I have made sure to keep my family in the loop.)

 

In fact, I'm in college again as an older adult, in my senior year in Computer Science. Methylene Blue has helped me tremendously. I consider it nothing short of a miracle.

[JohnBoyTheGreat]

I also want to point out that the study examined high doses of Methylene Blue of 7.5mg to 10mg per kg of human bodyweight.

 

The study fails to consider several reasons for their findings which would be significant. Low doses of MB reduce methemoglobinemia, which is when blood cells cannot properly carry oxygen (this is a very simplified description). However, high doses can cause methemoglobinemia, having exactly the opposite effect.

 

Low oxygen levels due to induced methemoglobinemia could account for the findings in the study.

Note that the doses in the study are several times higher than typical doses used for longevity or MB's nootropic effect. They are also intravenously dosed rather than orally, which makes a significant difference in the immediate plasma concentration of MB.

 

The study also noted that there was a relationship between the negative effects of MB on the brain and anti-depressants, which may have accounted for their findings: "It is important to note that less than 10% of patients receiving high-dose MB bolus developed encephalopathy, and an association between the concomitant use of serotonin reuptake inhibitors and the development of encephalopathy was observed."

 

They also note that their study was done on rats, not humans, and rats may certainly be more susceptible to the effects of MB than humans are.

 

Based upon the study and experience, I don't believe that MB has neurotoxic effects at oral dosages of up to 2mg to 4mg per kg. The amount used for a nootropic effect is much lower, so I don't believe there is anything to be concerned abotu.

 

As I may have mentioned, I take roughly 1mg/kg without any discernible negative side effects. There are plenty of positive benefits, however, so I would highly recommend Methylene Blue to practically anyone.

[dabbling123]

Well, reading through that paper, it leads me to the conclusion that most people are VASTLY overdosing MB and causing brain cell growth retardation or even cell-death.

 

According to the paper, a methylene blue concentration of 10 micromoles causes brain cell apoptosis:

 

 1.png   38.86KB   0 downloads

 

Furthermore, methylene blue at concentrations higher than 0.25 micromoles causes brain cell growth retardation:

 

 2.png   135.46KB   0 downloads

 

0.25 micromoles is 80 nanograms per ml:

 

 3.png   29.92KB   0 downloads

 

This is equivalent to 0.08 milligrams per litre:

 

 4.png   24.52KB   0 downloads

 

The brain has a volume of 1.5 litres, so the maximum amount of MB that can go in the brain (assuming even distribution) is 0.1mg at any one time.

 

1% MB solution (which seems to be most commonly advertised and sold) is 1mg per two drops, which seems to be what many people are taking - 10 TIMES stronger than the maximum level that does not cause brain cell growth retardation, and at the level that causes brain cell death.

 

Furthermore, MB preferentially goes to the brain, easily surpassing the blood brain barrier.

 

In anything more than micro-doses, this seems to be potentially really dangerous stuff, especially considering people are taking it long term.

Edited by dabbling123, 01 December 2023 - 12:18 AM.

[ekaitz]

100mg oral dose of MB results in 9 nmol/min/ml

 

Following oral administration, the area under the concentration–time curve was much lower (9 nmol/min/ml vs 137 nmol/min/ml)

 

https://link.springe...7/s002280000124