Leber Hereditary Optic Neuropathy

Straight answers about LHON, with the evidence attached.

A rare inherited mitochondrial disorder that causes painless, rapid loss of central vision, usually in one eye first and then the other. This site collects what is actually known, grades how well each claim is supported, and links every statement to its source. Where the evidence is thin, it says so.

Start here What changed in 2026 What to avoid

Content last reviewed · previous review

What's New

Developments since the last review of this site, most recent first. Items that changed a previous recommendation are marked.

Summary

Written to be readable without a medical background.

The Science: Complex I & Penetrance

Why a single-letter change in mitochondrial DNA destroys central vision, and why most carriers never lose it.

Complex I in health and in LHON

Normal Complex I function

Complex I is the largest enzyme of the electron transport chain, built from around 45 subunits. Seven of its core subunits (ND1, ND2, ND3, ND4, ND4L, ND5 and ND6) are encoded by mitochondrial DNA rather than the cell nucleus.

It transfers electrons from NADH to ubiquinone (CoQ10) through a chain of iron–sulfur clusters and a flavin mononucleotide cofactor. That electron transfer is mechanically coupled to pumping protons across the inner mitochondrial membrane, building the electrochemical gradient that ATP synthase uses to make ATP. In a healthy enzyme, electrons move through efficiently and little leaks away.

What the mutations break

LHON mutations sit in three of those mtDNA-encoded subunits: ND1, ND4 and ND6. Each disrupts the machine differently, by blocking the quinone binding site, uncoupling electron transfer from proton pumping, or destabilising assembly of the enzyme itself.

The result is the same in the end. Less ATP is made, and electrons that cannot move forward cleanly leak at the flavin site to form superoxide. The resulting oxidative stress drives lipid peroxidation and mtDNA damage, and eventually pushes retinal ganglion cells into apoptosis.

Why the eye, and why central vision? The small, unmyelinated axons of the papillomacular bundle have the highest energy demand and the least reserve of any fibres in the optic nerve. They fail first.

Supplements & Therapeutic Strategies

Graded by how strong the evidence actually is, including options whose support is purely theoretical.

Options studied in LHON patients

Everything in this table has been formally tested in people who have LHON. "Studied" is not the same as "worked". Two of the four did not meet their primary endpoint, and the table says so. Coenzyme Q10 is deliberately not here: despite being the alternative most often suggested when idebenone is unavailable, it has never been tested in a controlled LHON trial, so it sits in the emerging section below.

Emerging & theoretical options

Preliminary evidence, mechanistic rationale, or no human data at all. These are included because readers deserve to know what is being discussed and what the actual basis for it is, not as recommendations. Read the grade before the mechanism.

Read this before the table below

Several entries are research compounds, not medicines. Doses shown are the doses used in the cited study, which in many cases means an animal study or a cell culture where no human dose exists at all. Compounds sold online as "research peptides" are not manufactured to medicinal standards, are not tested for purity, and are not legal to sell for human use in most jurisdictions. Nothing on this list should be started without a clinician who knows your full history.

Testosterone, Androgens & Males

Why male carriers are asked to be careful, and why the story is less settled than it is usually presented.

Caution for male LHON carriers

Supraphysiological testosterone, whether from replacement therapy pushed above the normal range or from anabolic steroid use, is associated with markedly increased cell death in laboratory models of LHON. Male carriers should not begin testosterone therapy without telling the prescriber about their LHON status.

What LHON Carriers Should Avoid

Ranked by risk, with the strength of the evidence stated for each entry.

Risk level

On the watchlist

Exposures that come up frequently in patient discussion but do not currently have evidence strong enough to justify an entry above. Listed so the absence is deliberate and visible rather than an oversight.

Recommended Actions

Practical, ordered by how often you need to think about it.

Clinical Studies

Completed and active trials, with what each one actually showed, including the ones that failed.

Preclinical pipeline

Work that has not reached human trials. Included because this is where the most interesting LHON science currently is, and because knowing something is still in mice is part of understanding it.

Medical & Scientific Literature

The sources behind this site. If a statement here matters to a decision you are making, read the source.

Topic

Additional Resources

Where to go next.