Methylene Blues: When Biohackers Choose Petroleum Over Plants

Written by Sayer Ji on August 28, 2025. Posted in Current News

It sounds like something out of a Victorian dye factory: a coal tar-derived petroleum dye from the 19th century being ingested by modern health enthusiasts

Yet that is precisely the paradox of methylene blue (MB). Discovered in 1876 by German chemists for coloring textiles¹, MB is an aniline-derived synthetic (i.e. a brown, oily petroleum-derived product) that today finds itself touted as a ‘nootropic’ and ‘mitochondrial booster’ in certain biohacker circles.

Wellness influencers have promoted its electric-blue drops for enhanced cognition and cellular energy. But behind the trendy blue tongue photos lies an unsettling truth: if we’d reject coal tar dyes in our food or skincare, why would we welcome them into our brain?

Picture a health-conscious individual swirling a vial of brilliant blue solution and downing it for “brain fuel.” The liquid’s vivid hue comes from the same industrial dye class once used to stain cloth.

Methylene blue owes its lineage to petrochemical coal-tar chemistry, a far cry from the natural herbal tonics one might expect of holistic health. The irony is rich: a community that rightfully shuns artificial food coloring is embracing a synthetic dye as a supplement.

How did we get here? Proponents argue MB can enhance mitochondrial function and even act as a neuroprotective agent. But emerging evidence paints a far less rosy picture.

Methylene Blue: From Antidote to “Nootropic” Fad

Methylene blue has a long history in medicine, primarily as an emergency antidote and diagnostic tool. In clinical settings, MB is used to treat methemoglobinemia (a life-threatening inability of blood to carry oxygen), to manage ifosfamide-induced neurotoxicity, as a last-resort therapy in vasoplegic shock, and as a surgical dye for imaging².

These uses leverage MB’s pharmacological actions — it can accept and donate electrons in cells, inhibit nitric oxide (NO) signaling (raising blood pressure), and assist in restoring hemoglobin function².

In other words, MB is deployed as a “lesser evil” in acute crises, where its benefits may outweigh risks for a short period. It was never designed to be a daily cognitive enhancer.

Despite this, a trend has emerged: some biohackers now take microdoses of MB regularly, hoping to boost brain energy metabolism. This off-label use was spurred by early studies suggesting MB might support mitochondrial respiration or memory under certain conditions. However, translating a chemical antidote into a wellness supplement is a dubious leap.

MB received an FDA black-box warning in 2011 due to dangerous interactions with common antidepressants; it can trigger potentially fatal serotonin syndrome when combined with SSRIs³.

Far from being a harmless vitamin, MB is a potent monoamine oxidase inhibitor at higher doses³ — effectively a drug that modulates brain chemistry. Before anyone adds this blue dye to their smoothie, it’s crucial to examine the science of its safety.

The Dark Side of Methylene Blue: What Science Reveals

Enthusiasts claim methylene blue “powers up” mitochondria and neurons. But peer-reviewed research and case reports reveal serious liabilities:

Neurotoxicity and Electrophysiological Disruption

In vitro studies have shown that MB can damage neurons and impair their electrical function at surprisingly low concentrations. Mouse sensory neurons exposed to MB in the micromolar range suffered dose-dependent toxicity — by 10 µM, many neurons lost their neurites (branches) and degenerated⁴.

What does this 10 µM threshold actually mean for your brain?

To understand the implications, let’s break down the numbers. A concentration of 10 µM (micromolar) equals approximately 3.2 micrograms per milliliter of fluid — or about 0.003 milligrams per milliliter.

At this seemingly minuscule concentration, neurons in laboratory studies begin to malfunction dramatically. They lose their ability to communicate properly with other cells, their branches (dendrites and axons) wither away, and eventually the cells die altogether⁴.

This is particularly concerning when you consider that many methylene blue supplements recommend doses of 0.5–4 mg. While we can’t directly equate a supplement dose to brain tissue concentration (due to variables like absorption rates, blood-brain barrier penetration, and individual metabolism), the forensic evidence of blue-green brain staining at autopsy proves that MB does accumulate in neural tissue⁵.

Think of it this way: if your morning coffee started killing brain cells after just a few sips rather than requiring massive overdose, you’d reconsider that daily cup. Yet that’s essentially what these studies reveal about methylene blue — the margin between its promoted “nootropic” dose and documented neurotoxic effects is alarmingly narrow.

Electrophysiological recordings from nerve cells treated with MB revealed even more troubling effects. The neurons showed diminished electrical currents and blunted action potentials⁴.

In essence, MB makes it harder for neurons to fire properly, slowing their signals and reducing their ability to generate the electrical impulses that underlie all brain function. These findings align with earlier reports in brain tissues and gut neurons showing that MB exposure leads to neuronal loss and altered membrane properties⁴.

The take-home point: the same chemical that might prop up a failing mitochondrion in emergency medicine can, at concentrations easily achievable through supplementation, poison the neuron itself.

What’s marketed as “brain fuel” operates on a razor’s edge between enhancement and harm — and the science suggests we’re playing with fire when we treat this industrial dye as a daily vitamin.

Bioaccumulation in Brain and Organs

One of the most striking (and unsettling) illustrations of MB’s impact comes from forensic medicine. Pathologists performing autopsies on patients who received MB have noted a bizarre phenomenon: the brain (and sometimes heart) emerges stained an eerie blue-green color⁵.

A 2024 study titled “Fifty shades of green and blue: autopsy findings after administration of xenobiotics“ reported that systemic methylene blue use before death led to dark blue-green discoloration of organs, especially the brain⁵. In multiple cases, patients treated with MB for shock or poisoning were found on autopsy to have vivid blue-green brains⁵.

This occurs because MB (a lipophilic cation) readily penetrates the brain and gets reduced to a colorless form in vivo — but upon exposure to air post-mortem, it oxidizes back to blue, revealing its presence dramatically⁵,⁶. The images (published by forensic teams) are jarring: a human brain with turquoise-blue hues infiltrating the tissue.

As one Substack commenter quipped, “If this is what methylene blue in the brain post-mortem looks like, what is it doing while you’re alive?” In living patients, that dye is presumably lodging in neurons and glia.

MB’s half-life is ~5-6 hours in plasma⁸, but its affinity for certain tissues means residues can linger — indeed, it is known to tint the urine blue or green as it slowly clears⁵. The autopsy data prove that MB crosses the blood-brain barrier and accumulates, which should give any neurohacker pause.

Suppressed Brain Blood Flow and Metabolism

Paradoxically, the very outcome biohackers desire — enhanced brain energy and perfusion — may be undermined by MB in healthy individuals. A placebo-controlled study published in 2023 examined acute MB administration in humans using advanced neuroimaging⁷.

The researchers expected MB to boost cerebral oxygen consumption (based on test-tube studies of mitochondrial enzymes), but instead found the opposite. MB reduced global cerebral blood flow (CBF) in healthy volunteers by a significant degree, at doses of 0.5–1 mg/kg i.v.⁷

It also decreased the brain’s metabolic rate of oxygen (CMRO₂) — meaning the brain was using less oxygen — compared to baseline⁷. In parallel experiments, rats given MB showed a drop in cerebral glucose metabolism⁷.

These effects were dose-dependent and consistent across species. The authors concluded that MB at clinically relevant doses can exert an inhibitory effect on brain energy metabolism in normal brains⁷.

The likely mechanism is related to MB’s strong inhibition of nitric oxide signaling². By scavenging NO and blocking guanylate cyclase, MB causes blood vessels to constrict². Less blood flow means less oxygen and glucose delivered to brain tissue.

In a diseased brain with mitochondrial dysfunction, a small MB dose might act as an electron shuttle and improve efficiency (a hormetic effect). But in a healthy brain, those same doses appear to overshoot into a metabolic suppression.

So while anecdotes claim mental clarity on MB, the hard data show that in healthy humans MB can decrease cerebral perfusion and metabolism⁷ — hardly a biohacking win.

Serotonin Syndrome and Neurochemical Chaos

MB’s biochemical actions are wide-ranging, and that breadth comes with risks. At higher systemic doses, MB and its metabolites inhibit monoamine oxidase (particularly MAO-A)³,⁴. This means MB can amplify serotonin levels in the brain — dangerously so if combined with other serotonergic agents.

The FDA’s black-box warning on MB is there for good reason: cases of serotonin syndrome (a life-threatening toxic state) have occurred when MB was given to patients on antidepressants³.

Symptoms can include high fever, muscle rigidity, agitation, and seizures — a medical emergency. For example, in one published case, a cancer patient treated with MB for ifosfamide-induced encephalopathy developed severe serotonin syndrome and had to be admitted to intensive care³.

MB was the trigger that, combined with an SSRI in the patient’s regimen, sent serotonin signaling into overdrive. Several deaths have been reported after the combination of an MAOI (like MB in this context) with an SSRI².

Even on its own, MB’s serotonergic toxicity can manifest as confusion, neuromuscular hyperactivity (tremors, clonus), and autonomic instability².

This is not a gentle compound — it acts on neurotransmitter systems in ways that are not fully predictable, especially outside a controlled medical setting. For anyone self-medicating with MB, the message is clear: you are tinkering with a drug that can push the brain’s serotonin network into chaos if misused.

Pro-oxidant and Cytotoxic Effects

While often billed as an “antioxidant” or mitochondrial protectant, MB can also promote oxidative stress under certain conditions. Research shows that MB increases production of superoxide (a reactive oxygen species) when it inhibits NO signaling². The result can be heightened inflammatory activity and cellular damage.

In ischemic tissues, for example, MB has been noted to exacerbate injury at high doses by impairing microcirculation⁶. An animal study found that large doses of MB during endotoxemia actually worsened hypotension and heart function, whereas low doses had the opposite effect⁶. This highlights MB’s narrow therapeutic window.

On a cellular level, MB exposure has been linked to apoptosis and necrosis of tissue. Cases exist of local tissue death: for instance, a mere 1% MB injection (intravenous) causing skin necrosis at the site², or mucosal ulceration from submucosal MB use².

These are extreme outcomes, but they underscore that MB is fundamentally a toxin — it kills microbes (and can kill cells) by generating oxidative stress.

Even its beneficial actions (like treating methemoglobinemia) rely on its pro-oxidant chemistry to some extent, as it cycles between oxidized and reduced forms. Thus, using MB chronically might expose the body to continuous low-grade oxidative stress.

Indeed, countries such as Canada have classified MB as harmful for general consumer use due to risks like skin irritation and inflammatory reactions².

A “Last Resort” Drug, Not a Daily Tonic

Perhaps the most salient point is context. MB’s role in medicine is as an antidote or diagnostic stain — essentially, a tool to be used sparingly when needed. It is not approved as a daily prophylactic supplement.

As a 2022 toxicology review bluntly stated, the basic toxicological characteristics of MB remain inadequately studied, and its clinical use is “controversial” given reports of severe adverse effects that *”could significantly exceed any possible benefits”².

In other words, even in critical care where MB might be indicated, doctors must weigh its toxicity heavily.

There are no long-term studies on healthy people taking methylene blue regularly. What we do know comes from short-term emergency use and lab studies — and much of that knowledge waves red flags.

MB can cause hemolytic anemia in people with G6PD enzyme deficiency, for example, and can spike blood pressure or precipitate arrhythmias.

The precautionary principle would dictate that we don’t blithely experiment on ourselves with such a compound, certainly not when safer alternatives exist. As the toxicology review concluded, the clinical use of MB without robust safety data “conflicts with the standards of safe use” in medicine².

All this underscores a key ethical point for the natural health community: If we chastise pharmaceutical drugs for their side effects and demand rigorous safety evidence, should we not hold methylene blue to the same standard?

This is taken from a long document. Read the rest here substack.com

Header image: VeryWell Health

Please Donate Below To Support Our Ongoing Work To Defend The Scientific Method

PRINCIPIA SCIENTIFIC INTERNATIONAL, legally registered in the UK as a company incorporated for charitable purposes. Head Office: 27 Old Gloucester Street, London WC1N 3AX. 

Trackback from your site.