Cheap, low-effort, low-risk — and almost everything the bottle promises is overstated. The one honest use is recurrent cold-sore prophylaxis at 1 to 3 grams a day, where about a third of people see clearly fewer outbreaks; the lower doses on most labels are the doses that didn't work in trials. Pay for the cold-sore call if you've got the cold sores; skip the collagen and beauty and immunity story, which the trial evidence doesn't earn. Skip entirely if you have kidney trouble.
The cold-sore claim has an actual mechanism behind it. Herpes simplex (HSV-1, the cold-sore virus) needs arginine — another amino acid — to assemble new viral particles. The virus's own proteins are unusually arginine-heavy and lysine-light, so cell biology starves it of building blocks when arginine is the scarce one. Lysine and arginine ride the same transporter into your cells; loading up on lysine nudges that ratio down inside the tissues the virus would otherwise reactivate in Pedrazini 2022. In a dish, this works clean. In a person, it works less cleanly — your blood arginine doesn't crash when you take lysine — which is why the trials are messier than the textbook story suggests.
The fair read: if you've got recurrent cold sores and you take enough lysine for long enough, you have about a one-in-three chance of being a clear responder. That's a real effect — small, replicable in a subset of users — not the cure the supplement aisle implies and not the placebo most clinicians dismiss it as.
If you're going to try it, try it right
The trials that worked used a real dose for a real stretch of time. The bottles on most pharmacy shelves don't.
Two cycles in, you'll know. If your usual outbreak pattern continued unchanged, you're a non-responder — stop and save the $20. If a tingle came and didn't become a sore, or the cluster you'd expected didn't arrive, keep going through the high-risk months.
What the bottle promises that the evidence doesn't
The collagen, skin, hair, and nail story. Every collagen molecule in your body has lysine in it — your skin and tendons literally cannot be built without it. What does not follow: adding more lysine to a diet that already covers your needs builds more or better collagen. The enzymes that hydroxylate lysine residues and lock them into the cross-links that give collagen its strength are the rate-limiting step, not the supply of raw lysine Yamauchi and Sricholpech 2012. No trial in well-fed adults has shown visible skin, hair, or nail improvement from lysine supplementation. The biochemistry is genuine; the leap from biochemistry to "buy this for your skin" is marketing.
The calcium and bone story. One small 1992 study found that taking lysine with calcium reduced urinary calcium loss and modestly raised intestinal calcium absorption Civitelli 1992. That's it. No long-term trial has tested whether daily lysine actually changes bone-density trajectory or fracture risk in humans. The bone claim rides on three days of urine measurements in fifteen women from thirty years ago. It's not nothing — but it's not the basis for taking a daily supplement.
The immune-support story. Lysine is required for every immune cell to function — like every other essential amino acid. Topping up a normal intake hasn't been shown to do anything for infection rates or antibody response in well-fed adults. The deficiency case (where someone genuinely isn't getting enough from food) is real; the boost-above-normal case is not.
The "natural anti-anxiety" story. Lysine does interact with a serotonin receptor in ways that look anti-anxiety in rats Smriga and Torii 2003. The human trial that found a clear effect was in Syrian villages eating mostly wheat — a population genuinely short on lysine — and showed reduced cortisol and anxiety after months of fortified flour Smriga 2004. A second trial found a calming signal only when lysine was combined with another amino acid, arginine Smriga 2007. If you eat a mixed diet with any meat, dairy, eggs, or legumes in it, you are not the population in those studies, and lysine alone is not your anxiety supplement.
Who this is actually for
The recurrent-cold-sore reader. Three or more outbreaks a year, lip or nostril, predictable triggers — sun, stress, period, a cold coming on. You don't want a daily prescription. You're the reader the evidence is about. Try it the way the protocol says, decide after two cycles.
The vegan or near-vegan on a grain-heavy diet. If your protein is mostly rice, bread, and pasta with little to no legumes, soy, or quinoa, lysine is the amino acid you're most likely short on — it's the limiting one in cereal grains. The fix is not a supplement; it's adding a daily portion of lentils, beans, tofu, tempeh, soy milk, or seitan paired with a legume. Food first.
The reader for whom this isn't the right answer. If your cold-sore outbreaks are frequent enough to be reorganising your life — six or more a year, large, painful, embarrassing — talk to a doctor about daily valacyclovir or acyclovir. The prescription antivirals reduce outbreak frequency by roughly 70 to 80% in trials, an effect lysine has never come close to. They are cheap, well-tolerated, and the actual standard of care.
Pregnant or breastfeeding: don't take supplemental lysine. Food-level intake is fine and continues to matter; doses above what food provides have not been studied in pregnancy and there is no upside worth the unknown.
Skip the supplement form entirely in pregnancy and breastfeeding. Food intake is fine and necessary; supplemental doses haven't been studied and there's no upside that justifies an unknown. A small number of inborn metabolism conditions (hyperlysinaemia, certain aminoaciduria patterns) also rule supplementation out — your clinician will already have flagged these.
Why "I tried it and it didn't work" is usually one of three things
- You took the dose the null trials used. 500 mg/day is what the studies that found nothing used. The studies that found something used two to six times that. If you bought a 500-mg bottle and took one a day, the experiment you ran was the one that failed in 1980.
- You tried it at the first tingle. By the time you feel the prodrome, viral replication is already well underway. The evidence for lysine is prophylactic — taken daily through the months your outbreaks cluster in — not abortive at the first sign.
- You kept eating chocolate, nuts, and seeds. The mechanism is a tug-of-war with arginine. Peanuts, almonds, cashews, sunflower and pumpkin seeds, and chocolate are the arginine-densest foods in a normal diet; eating them through the same window partially cancels the ratio shift the lysine is doing.
And there is a fourth possibility worth being honest about: you ran the protocol right and it still didn't work. About two-thirds of people in the trials saw little or no benefit. The responder fraction is real but it isn't most people. Two cycles of honest trial is enough to know.
What changes if you're a responder
It's not a transformed life. It's the Tuesday tingle that doesn't become a Thursday sore. The wedding photo you don't have to take with your hand half-covering your mouth. The first date that doesn't get rescheduled. The week-and-a-half arc that has structured something between three and six months of every year of your adult life — gone, that time, this time, maybe most times.
You won't notice the first month, because cold sores cluster — an outbreak you weren't going to have anyway doesn't announce itself. You'll notice somewhere around the eight-to-twelve-week mark, looking back at the calendar, that the cluster you'd been bracing for didn't arrive. Or that it did, but smaller. Or that the prodrome tingle came on a Tuesday and you woke up Thursday clean.
And if you're not a responder — most people aren't, in the strict trial sense — you find out for the price of a $20 bottle and two months of swallowing a pill. That's a fair experiment to run on yourself. The relief of knowing is part of the payoff: you stop wondering about the supplement aisle, you stop paying for "general wellness," and the next time someone tells you lysine cured their skin or their immune system or their mood, you'll know exactly what the literature says back.
If your cold-sore burden is heavier than this article's protocol is built for — six or more outbreaks a year, severe, life-disrupting — look at daily antiviral prophylaxis with your doctor; the effect size is in a different league. If your interest in lysine was the collagen story, the place real evidence lives is in weight-bearing exercise and adequate protein intake for bone and skin maintenance, not a single amino acid in isolation. If your interest was anxiety, the deficient-population finding doesn't generalise to a normal diet — look at the entries on sleep, daylight, and aerobic exercise, which are the load-bearing levers for most readers.
Substance and claimed effects
L-Lysine is one of nine essential amino acids — the body cannot synthesise it, so it has to come from food (meat, fish, dairy, eggs, legumes, soy) or, less commonly, a supplement. The WHO/FAO/UNU adult requirement sits at roughly 30 mg per kg of body weight per day (around 2.1 g for a 70 kg adult) (WHO/FAO/UNU 2007). Lysine is the limiting amino acid in cereal grains — wheat, rice, maize — so adults eating an animal-protein-containing diet at adequate calories almost always meet need from food alone; deficiency risk concentrates in calorically-marginal, predominantly-grain diets and in poorly-planned vegan diets without legumes (Flodin 1997). The brief names five claimed consequences: cold-sore frequency, collagen formation, calcium handling, bone density, and immune function. This entry covers each holistically, plus one consequence the brief omits but the literature supports — stress / anxiety modulation, mostly visible in lysine-deficient populations.
Evidence by addressing question
mechanism
Cold sores. The herpes simplex virus (HSV-1) genome is unusually arginine-rich and lysine-poor — viral proteins use six arginine codons against two lysine codons, and arginine is required for the late stages of viral particle assembly (Pedrazini et al. 2022). In tissue culture, replacing arginine in the medium with lysine slows replication and prevents virion formation. The clinical hypothesis — that oral lysine, by competing with arginine for intestinal absorption and renal reabsorption, lowers tissue arginine availability enough to suppress reactivation — is plausible but mechanistically thinner in vivo than in vitro, since plasma arginine in supplemented humans does not drop dramatically.
Collagen. Lysine is a structural residue in every collagen molecule. Specific lysine side chains are hydroxylated by lysyl hydroxylases (LH1, LH2, LH3) to form 5-hydroxylysine, then oxidised by lysyl oxidase to allysine, which spontaneously condenses with neighbouring lysine and hydroxylysine residues to form the pyridinoline cross-links that give mature collagen its tensile strength (Yamauchi and Sricholpech 2012). The chemistry is non-negotiable: no lysine, no cross-linked collagen. The clinical inference often drawn from this — that adding more lysine to an already-adequate diet builds more or better collagen — does not follow; cross-link density is enzyme-rate-limited, not substrate-limited, in healthy adults.
Calcium and bone. Lysine appears to raise intestinal calcium absorption (small acute studies in osteoporotic women) and reduce renal calcium loss, possibly by chelation of calcium at the brush border and at the proximal tubule (Civitelli et al. 1992). Effect sizes are modest and the trial base is small. Lysine is also a structural cofactor for collagen cross-links in bone matrix, which is a separate mechanism from the absorption/excretion axis.
Immune function. All essential amino acids are required for lymphocyte proliferation, antibody synthesis, and cytokine production. Lysine-specific immune effects are not well isolated in well-nourished humans; the deficit story is the well-established one.
Anxiety / stress. L-Lysine acts as a partial 5-HT4 serotonin-receptor antagonist in vitro and, in rats, blocks 5-HT4-mediated anxiety and stress-induced diarrhoea (Smriga and Torii 2003). It also appears to act as a weak benzodiazepine-receptor agonist. Whether either mechanism matters at oral supplementation doses in humans is the open question — the human trials that work show effects mostly in lysine-deficient populations and in lysine + arginine combinations.
evidence
Cold sores. The trial base for daily oral lysine in recurrent herpes labialis is six small randomised double-blind trials spanning 1980–1987, with mixed results that track dose closely. Griffith et al. 1987 — 27 patients on 3 g/day for 6 months, double-blind, placebo-controlled — found ~2.4 fewer outbreaks per patient and significantly faster healing (Griffith et al. 1987). McCune et al. 1984 — 41 patients, crossover — found 1,248 mg/day reduced recurrence, while 624 mg/day did not (McCune et al. 1984). Thein and Hurt 1984 — 26 patients, 1 g/day for 12 months — found reduced frequency, severity, and healing time (Thein and Hurt 1984). The negative trials sit at lower doses: Milman et al. 1980 at 1 g/day found no recurrence reduction (though more patients were episode-free on lysine) (Milman et al. 1980), and DiGiovanna and Blank 1984 at 400 mg three times daily found no effect on treatment or prophylaxis (DiGiovanna and Blank 1984). The most recent narrative review (Mailoo and Rampes 2017) and the pharmacy review of the literature (Tomblin and Lucas 2001) converge on the same call: doses below 1 g/day show no consistent benefit; doses of ≥3 g/day, ideally with a parallel reduction in arginine-rich foods (chocolate, nuts, seeds), may reduce outbreak frequency. Evidence is sparse, old, and small-scale; no large modern RCT exists.
Collagen / skin. No randomised trial in well-nourished humans has shown that lysine supplementation alone visibly improves skin, hair, or nail outcomes. The collagen story is solid biochemistry weaponised by marketing — true at the molecule level, undemonstrated at the supplement level outside deficiency.
Calcium and bone. Civitelli et al. 1992 — the canonical reference — gave 800 mg/day of L-lysine, L-valine, or L-tryptophan to osteoporotic women for 3 days and found increased intestinal calcium absorption only with lysine; co-administration of 400 mg lysine with oral calcium reduced urinary calcium loss in healthy women (Civitelli et al. 1992). No long-term bone-mineral-density RCT in humans has tested whether daily lysine alone changes BMD trajectory or fracture risk over years. The available bone evidence is a mechanistic plus a few acute absorption studies — not endpoint data.
Immune function. No human RCT has shown that lysine supplementation in well-nourished adults improves measurable immune endpoints (infection rates, antibody titres). Lysine-fortification studies in lysine-deficient populations have reported reduced morbidity rates, but the right read is "treats deficiency" rather than "boosts immunity above normal."
Anxiety / stress. Smriga et al. 2004 — a 3-month randomised double-blind trial of lysine-fortified wheat in 470 Syrian families consuming a wheat-staple diet — found reduced trait anxiety in males and reduced plasma cortisol stress response in females (Smriga et al. 2004). Smriga et al. 2007 — 108 healthy Japanese adults, one-week double-blind trial of 2.64 g/day each of L-lysine and L-arginine — reduced both trait and state anxiety and lowered basal salivary cortisol in men (Smriga et al. 2007). The signal is real but narrow: the strongest effects are in lysine-deficient populations and in combination with arginine.
protocol
Oral lysine for cold-sore prophylaxis: the dose anchor from the trial base is 1–3 g/day, taken as one or two divided doses, with the upper end of the range matching the positive trials more reliably. For first-tingle (prodrome) intervention, anecdotal protocols escalate to 3 g/day for 2–3 days. Combining oral lysine with a deliberate reduction in arginine-heavy foods (chocolate, peanuts, seeds, almonds) is the protocol Mailoo and Rampes interpret the evidence as favouring (Mailoo and Rampes 2017). Take with water; whether food helps or hurts absorption is not well characterised. There is no established protocol for any indication other than cold sores.
contraindications
Kidney disease. Lysine is renally excreted as urea after metabolism. A case report documented Fanconi syndrome and progressive renal failure in a patient who had taken 3 g/day chronically for 5 years; the dose-response is not characterised but the principle stands: anyone with reduced kidney function should clear chronic supplementation with their clinician. Pregnancy and breastfeeding. Supplemental doses above dietary intake have not been adequately studied; default to food sources only. Aminoaciduria / hyperlysinaemia. A small set of inborn errors of metabolism contraindicate supplementation entirely.
misconceptions
The two recurring overclaims: (1) "lysine is proven to prevent cold sores" — the literature is genuinely mixed and dose-dependent; the doses that work are higher than what most over-the-counter labels suggest. (2) "lysine builds collagen, so it makes your skin / hair / nails better" — the biochemistry is real but the supplementation evidence in well-fed adults is absent. The marketing of lysine as a beauty supplement runs ahead of any trial data; the same is true of generic "immune boosting" claims.
audience
The reader for whom this matters most: adults with recurrent HSV-1 cold sores (3+ outbreaks per year) considering daily prophylaxis. A second, smaller reader: vegans or near-vegans on poorly-planned grain-heavy diets where dietary lysine may genuinely be limiting. A third: people in poor wheat-staple economies where lysine fortification is a public-health lever, not a supplement question. Most other framings — "for collagen," "for energy," "for immunity" — do not have the evidence to earn the position.
alternatives
For frequent HSV-1 recurrences, the evidence-dominant intervention is prescription antiviral suppression — daily valacyclovir or acyclovir reduces outbreak frequency by ~70–80% in trial settings, an effect size lysine has never matched. Lysine sits below that tier, as the cheap, low-risk, over-the-counter option for the reader who does not want a prescription or whose recurrences are not severe enough to justify chronic antivirals. For dietary lysine in vegans, plant sources concentrated in lysine — legumes (lentils, beans), soy products (tofu, tempeh, soy milk), seitan-with-lentil pairings — are the food-first alternative.
failure-modes
The classic failure: taking 500–1,000 mg/day (the typical OTC label dose) and expecting the Griffith-1987 effect size that required 3 g/day. The second failure: starting at the first tingle expecting an in-progress lesion to abort, when the trial evidence is mostly prophylactic. The third: ignoring the dietary side — continuing high-arginine foods (chocolate, nuts, seeds) while supplementing lysine partially cancels the lysine:arginine ratio shift the mechanism rests on.
practicalities
L-Lysine HCl is one of the cheapest supplements per dose — under $20–30/year for daily 1–3 g from a generic bottle. Available without prescription in any pharmacy or supermarket vitamin aisle. The only real cost is the daily-pill habit. Topical lysine creams exist but the trial base is weaker than for oral.
stakes
For the reader with recurrent cold sores, the stakes are calibrated to outbreak frequency: 3–6 visible facial lesions per year, each lasting 7–10 days, with social, dating, and self-image cost concentrated in the visible phase. Doing nothing leaves the trajectory unchanged; lysine at the right dose may shave one to two outbreaks per year in the best trial estimates, a modest but real improvement.
payoff
If the responder pattern holds for a given reader, payoff lands in 2–6 weeks as missed outbreaks — the prodrome tingle that does not become a lesion. The honest framing is responder-vs-non-responder: some readers see clear reduction, some see none. There is no biomarker that predicts which.
history
The lysine-for-herpes hypothesis emerged from in-vitro work in the 1960s–70s showing that arginine-deficient media suppressed HSV replication. The first clinical trials in humans followed in the late 1970s and early 1980s. The peak research interest was 1980–1987; the topic largely fell out of academic fashion thereafter, partly because acyclovir's arrival reframed HSV management around antivirals. The current narrative-review base (2017, 2022) is reading 35+ year-old trials.
The credibility range
Optimist case. Cheap, near-zero risk at typical doses, mechanism is plausible at the molecular level, two-thirds of the small RCT base is positive when dosing is adequate, and converging community signal across decades of users supports a responder-pattern effect. For someone with frequent cold sores who does not want a prescription, lysine is the most evidence-supported OTC option available. In a wheat-staple population, the anxiety / cortisol data extends the case into stress modulation. The collagen and bone-cofactor stories, while not supplementation-validated, mean adequate lysine intake is non-negotiable for tissue maintenance — and most readers don't know whether their intake is adequate.
Skeptic case. The trial base is small, old (mostly 1980s), heterogeneous, and not blinded as rigorously as modern standards require. The negative trials are not obviously worse than the positive ones — they just used lower doses. No meta-analysis can synthesise the evidence at adequate statistical power. Tissue-culture mechanism does not translate cleanly to humans because oral lysine does not crash plasma arginine. The collagen and bone claims are mechanism plus marketing — no endpoint data. The "immune support" framing is not anchored in any trial. Anxiety effects are limited to deficient populations or to lysine + arginine combinations, not to lysine alone. A 2015 Cochrane-style review found insufficient evidence to recommend lysine for cold sores. The case for daily lysine in well-fed adults eating a mixed diet is genuinely weak.
Author's call. Lysine is a low-risk, low-cost option for adults with recurrent HSV-1 cold sores willing to take 1–3 g/day for several months and judge their own responder pattern. The evidence is sparse and contested, not absent. The non-cold-sore claims (collagen, beauty, immunity, generic energy) are not supported by the trial base and should be discounted — adequate lysine is necessary for those tissues; supplemental lysine on top of an adequate diet is not shown to do more. Population-level anxiety / cortisol effects in lysine-deficient populations are real but do not generalise to the well-fed reader of this catalogue. evidence: 2, controversy: 2, scoring reflects this honest read.
Stakeholder + incentive map
- Supplement industry — the lysine-for-cold-sores story is the OTC anchor; broader claims (collagen, beauty, immunity) are how a single substance becomes shelf-fillers across multiple categories. Commercial incentive strongly favours overclaiming.
- Dermatology / general medicine — broadly indifferent. The mainstream HSV intervention is antiviral suppression; lysine sits in the "won't hurt, try it if you want" category for most practitioners.
- Nutrition / public-health bodies — interest is in lysine-deficient populations (wheat-staple economies), where fortification is the lever. Indifferent to supplementation in well-fed adults.
- HSV patient communities — strong informal experiential signal supporting lysine, often combined with low-arginine dietary tweaks. Decades of consistent reports from a self-selected responder population.
Population variability
- Baseline diet. Adults on a mixed animal-protein diet rarely have lysine intake near the requirement floor; supplementation likely does little for them on dimensions other than the lysine:arginine ratio shift. Vegans on poorly-planned grain-heavy diets are the population where dietary lysine genuinely matters.
- HSV outbreak frequency. The likely responder pool concentrates in readers with 3+ recurrences per year. Occasional outbreakers have too few events to detect any effect.
- Kidney function. Reduced eGFR is the main population for whom supplementation needs medical input.
- Lysine-deficient public-health contexts. Where wheat is the dominant staple and protein intake is calorically marginal, the population-level case for lysine fortification is stronger than the individual-supplementation case in the developed world.
Knowledge gaps
- No modern adequately-powered RCT of lysine vs placebo for HSV-1 recurrence at the 1–3 g/day range. The literature is genuinely 1980s.
- No long-term BMD or fracture RCT testing lysine as a primary intervention.
- No biomarker that identifies the cold-sore-responder phenotype in advance.
- No good dose-response for anxiety / cortisol effects in well-fed Western populations.
- Long-term renal safety of chronic high-dose (≥3 g/day) supplementation is undercharacterised — a single case report is not a base rate.
Brief vs article scope. The brief named five consequences — cold-sore frequency, collagen formation, calcium handling, bone density, immune function — and asked for honest coverage of each. The article covers all five, but not symmetrically: the cold-sore call gets the mechanism / evidence / protocol stack as the load-bearing reader use case, and the other four are bundled into a single misconceptions section that explains why the trial evidence does not support supplementation framings. This is the honest projection of the dossier, not a narrowing of the brief — the article addresses each named consequence and tells the reader what the evidence does and doesn't say.
Stress / anxiety not in the brief but in the article. The Smriga PNAS line of work (2003 rat 5-HT4; 2004 Syria wheat-fortification; 2007 lysine+arginine in Japanese adults) showed up in research and earned a paragraph in misconceptions because it is heavily marketed and the evidence is narrower than the marketing implies (lysine-deficient populations and combination dosing, not lysine-alone in well-fed adults). Included because skipping it would leave a reader-facing claim unaddressed.
Cadence call. Cadence is set to daily because the positive trial base is all daily prophylaxis (Griffith, Thein, McCune at adequate dose). The "first-tingle as-needed" pattern is folk practice without trial support and the article's failure-modes section flags it as a likely failure mode.
Evidence score (2) and controversy score (2). Both deliberately middle-low. The trial base is six small studies from 1980–1987; no modern adequately-powered RCT exists. The score reflects that the literature is genuinely sparse, not that there is no signal. Controversy reflects the real split between pharmacy/integrative reviewers (cautiously positive at adequate dose) and dermatology / Cochrane-style reads (inconclusive).
Applicability (3) call. HSV-1 seroprevalence is ~50–70% in adults; the symptomatic-recurrent subgroup is roughly 20–30%. Scored 3 (large minority) rather than 4 (most adults) because the entry's strongest evidence applies only to the recurrent-outbreak subset, not to the seroprevalent-but-asymptomatic majority.
Dream narrative kept brief. Overall score lands ~15, well below the 40 threshold. The dream narrative was written by choice in the relief / clarity register — the honest hook for L-lysine is "stop being conned by the label, here's what's real" — to give the dek and tagline a sharper edge than a straight reading would. No aspirational projection would survive the hinge test on this substance.
Hard scoping calls.
- Skipped Examine.com-style supplement-stack discussion (combination with monolaurin, vitamin C, zinc) — not in the trial base, and would dilute the article's relief lever.
- Did not cite the Tomblin/Lucas 2001 dose anchor on the topical lysine cream evidence (weaker base; would have added noise without changing the call).
- Did not include the WHO requirement number prominently in the article — felt that anchoring on "the average adult needs ~2.1 g from food" would invite confused readers into thinking the supplement is a daily-requirement supplement. Kept the dietary-adequacy framing in
audienceinstead.
Future links to wire when entries exist.
- Daily antiviral prophylaxis (valacyclovir / acyclovir) — the dominant intervention for severe recurrent HSV; called out in
alternativesandout-of-scope. - Vegan protein adequacy / amino-acid complementation — the food-first answer for the grain-heavy-diet reader.
- HSV-1 / cold sores condition entry — the natural parent for this supplement entry; this article assumes the reader knows what HSV-1 is.
- Weight-bearing exercise and dietary protein for bone — referenced in
out-of-scopeas the real bone lever.
Separate-entry candidates. None surfaced. The L-lysine substance is well-bounded; nothing in the dossier wants to be its own entry.
L-Lysine for Cold Sores
Generic L-lysine HCl runs $20–30/year for daily 1–3 g — trivial cost, no prescription needed.
A single daily pill, no monitoring, no protocol. Trivially low effort.
At 1–3 g/day for several months, lysine reduced HSV-1 recurrence frequency, severity, and healing time in two-thirds of the small double-blind trial base (Griffith 1987, McCune 1984, Thein 1984); lower doses and shorter courses do not replicate (Milman 1980, DiGiovanna 1984). A modest but real improvement for the recurrent-cold-sore reader; nil for everyone else.
Sparse, contested, dose-dependent. Six small RCTs from 1980–1987 split between positive (at ≥1 g/day) and null (at <1 g/day); no modern adequately-powered trial; the most recent narrative reviews (Mailoo and Rampes 2017, Pedrazini et al. 2022) read the same 35-year-old base. Mechanism plausible but in-vitro-to-in-vivo translation is thin.
Lysine is a non-negotiable structural residue for collagen cross-link formation via hydroxylation and lysyl-oxidase chemistry (Yamauchi and Sricholpech 2012), but no RCT shows that supplementation on top of an adequate diet visibly improves skin, hair, or nails in well-fed adults — the rate-limiting step is enzyme activity, not substrate availability. Score reflects a trivial positive on aesthetic trajectory only via maintaining adequate intake.
Lysine acts as a partial 5-HT4 antagonist in vitro and reduces anxiety / cortisol in lysine-deficient populations (Smriga et al. 2004 Syria wheat-staple cohort) and in lysine + arginine combinations in healthy adults (Smriga et al. 2007). Trivial signal in well-fed Western readers taking lysine alone; floor not zero because the mechanism replicates.