L-Lysine for Canker Sores — Does It Actually Work?

TL;DR

Nobody has run a controlled trial of L-lysine for canker sores. The studies that get cited in forums and supplement marketing were all done on cold sores, which are a herpes virus infection and a completely different disease. Even for cold sores, the results are mixed: a few small trials found fewer outbreaks, others found nothing, and a 2015 Cochrane review of cold sore prevention found no preventive effect from lysine (Chi et al., 2015 — PMID: 26252373). For canker sores, the only direct evidence is a small 1994 case series with no comparison group. Lysine is cheap and generally safe at normal doses, so trying it won't hurt most people. But if you're going to spend money on one supplement for canker sores, vitamin B12 is the one with a placebo-controlled trial behind it.

Where the Lysine Idea Came From

The lysine recommendation started with cold sores in the 1970s.

Herpes simplex virus needs the amino acid arginine to replicate. In lab experiments, adding lysine (which competes with arginine) slowed the virus down. Researchers reasoned that lysine supplements might do the same thing in people, and they started testing it on cold sore patients.

Canker sores got pulled into this because, for a long time, a lot of people (including some clinicians) assumed canker sores and cold sores were related. They look superficially similar, they both show up in the mouth, and both recur. So advice for one bled into the other, and lysine became a standard canker sore recommendation without anyone testing it on canker sores.

They aren't related. Cold sores are caused by a virus. Canker sores are caused by the immune system attacking the lining of your mouth, and there's no virus involved for lysine to slow down. If you're not sure which one you have, see Canker Sore vs. Cold Sore.

What the Cold Sore Research Actually Found

It's worth looking at the cold sore studies, because they're the entire basis for lysine's reputation. They're small, they're old, and they disagree with each other.

• Griffith et al., 1978: 45 people with herpes infections took lysine and reported faster recovery and fewer recurrences (Griffith et al., 1978 — PMID: 640102). There was no control group, so there's no way to know how many would have improved anyway.
• Milman et al., 1980: A placebo-controlled crossover trial in 65 people taking 1 gram a day. No overall effect on how often cold sores came back, and no effect on healing time (Milman et al., 1980 — PMID: 6153847).
• DiGiovanna & Blank, 1984: A double-blind trial in 21 people. No benefit (DiGiovanna & Blank, 1984 — Arch Dermatol).
• McCune et al., 1984: In 41 people, 1,248 mg a day reduced how often cold sores came back. Half that dose did nothing, and neither dose made outbreaks heal faster (McCune et al., 1984 — PMID: 6435961).
• Thein & Hurt, 1984: Over 12 months in 26 people, 1 gram a day led to fewer lesions, and the benefit showed up in people whose blood lysine levels rose above a certain threshold (Thein & Hurt, 1984 — PMID: 6438572).
• Griffith et al., 1987: A placebo-controlled trial in 52 people taking 1 gram three times a day for six months. The lysine group had about 2.4 fewer outbreaks, and they were milder and healed faster (Griffith et al., 1987 — Dermatologica).

So a couple of the better trials were positive, a couple were negative, and the effect seemed to depend on dose. When a Cochrane review pooled the evidence on cold sore prevention in 2015, it found no preventive effect from lysine (Chi et al., 2015 — PMID: 26252373).

That's the strongest evidence lysine has, and it's for a different disease.

What the Canker Sore Research Found

Very little. The one study we could find that looked at lysine for canker sores was a small case series published in a general dentistry journal in 1994, which reported on lysine for both canker sores and cold sores (Wright, 1994 — Gen Dent). A case series means a dentist gave lysine to patients and reported what happened. There was no placebo group and no blinding, which matters a lot with canker sores, because they come and go on their own. Almost anything you try during a bad stretch will look like it worked when the stretch ends.

We could not find any randomized, placebo-controlled trial of lysine for recurrent aphthous stomatitis (the medical name for recurring canker sores).

Why the Mechanism Doesn't Carry Over

Even if lysine works for cold sores, there's no reason to expect it to work for canker sores.

The whole theory is antiviral. Lysine is supposed to compete with arginine so the herpes virus can't replicate as easily. Canker sores have no virus. They happen when T-cells, a type of immune cell, attack the cells lining the mouth. The things that seem to make people more prone to that attack are genetics, nutrient deficiencies like low B12, iron, zinc, and folate, SLS in toothpaste, stress, and minor injuries to the mouth. Arginine isn't part of that picture as far as anyone has shown.

You'll sometimes see people say that high-arginine foods like chocolate and nuts trigger their canker sores. That might be true for some individuals, but it hasn't been studied, and chocolate and nuts are also common triggers for other reasons (nuts are abrasive, and chocolate is a frequently reported food trigger in general). If you suspect a particular food, testing it directly makes more sense than taking a supplement to counteract it. See Foods That Cause Canker Sores.

So Why Do People Say It Works?

A lot of people on Reddit and in reviews swear by lysine for canker sores. There are a few reasonable explanations that don't involve lysine doing anything to canker sores.

They have cold sores, not canker sores. Intraoral herpes (herpes inside the mouth, usually on the gums or the roof of the mouth) gets mistaken for canker sores all the time. If that's what someone actually has, lysine is at least aimed at the right disease.

Canker sores come in waves. Most people with recurring canker sores have bad months and quiet months. People usually start a new supplement during a bad month. When the quiet stretch arrives, the supplement gets the credit.

They changed other things at the same time. People who start taking lysine are often also switching toothpaste, eating differently, or sleeping more. Any of those could be the real reason.

None of this means nobody has ever been helped. It means individual experience can't tell you whether lysine works, which is exactly why controlled trials exist.

Is Lysine Safe?

At typical supplement doses, yes, for most people.

A 2020 review of human studies covering more than 3,000 participants suggested no adverse effects up to about 6 grams a day, with stomach upset being the main problem at higher doses (Hayamizu et al., 2020 — J Nutr). That's well above the 1–3 grams a day people usually take.

The one serious problem in the literature is a case report of a woman who developed kidney damage (Fanconi syndrome and interstitial nephritis) after taking lysine long-term (Lo et al., 1996 — Am J Kidney Dis). It's a single case, but if you have kidney disease, talk to your doctor before taking amino acid supplements.

Lysine can also increase calcium absorption, so anyone with a history of high calcium or calcium-based kidney stones should check with a doctor first.

If You Want to Try It Anyway

Plenty of people will try lysine regardless of what the research says, and at normal doses the downside is mostly the cost. If you're going to do it, do it in a way that gives you a real answer:

• Dose: 1 gram a day is typical. The cold sore trial that worked used about 1.25 grams a day; the one that used 3 grams a day was also positive.
• Duration: Give it at least three months. Canker sores vary so much from month to month that anything shorter is noise.
• Track it: Write down the date of every new sore for the three months before you start and the three months after. If you don't have a "before" record, you won't be able to tell if anything changed.
• Change one thing at a time. If you start lysine and switch toothpaste the same week, you won't know which one helped.

If you get both cold sores and canker sores, there's a little more reason to try it, since at least the cold sore side has some trial evidence. Just know that the evidence is mixed even there.

What Has Better Evidence

If you have frequent canker sores and want to try a supplement, this is how the options compare:

The B12 trial is the one to know about. People took 1,000 mcg of B12 under the tongue every night, and the benefit showed up regardless of their starting B12 level. See Vitamin B12 for Canker Sores.

For the full ranking, see Best Supplements for Canker Sore Prevention.