Side effects of L-lysine
L-lysine is usually considered one of the safest amino acid supplements, and for moderate doses this is largely true. However, the medical literature describes cases of kidney damage, there are rare hereditary conditions in which lysine is contraindicated, and gastrointestinal complaints occur fairly often. The editorial team has gathered what is known about the side effects of lysine and the limits of safe intake.
General safety profile
Lysine is an essential amino acid that people obtain daily from food, mainly from meat, fish, dairy products and legumes. The daily requirement of an adult, according to the WHO/FAO/UNU estimate (2007), is about 30 mg/kg of body weight, that is, roughly 2 g for a person weighing 70 kg.
Lysine supplements add a few more grams to this amount, and some studies of herpes used even higher doses. A systematic review by Hayamizu and co-authors (2019) analyzed clinical data on oral lysine intake and concluded that at the doses studied, roughly up to 6 g per day, no serious side effects were observed in adults.
The US Institute of Medicine has not established an official tolerable upper intake level for lysine due to a lack of data. Therefore the safety limit is defined only by the doses that have been studied, and beyond them there are no reliable data.
Flodin's review (1997) on the pharmacology and toxicology of lysine also describes it as a substance of low toxicity, while emphasizing that the data come mainly from animal models and small clinical observations.
The most common adverse reactions
The most common complaints are related to digestion. They are dose-dependent and appear more often when large amounts are taken on an empty stomach.
- Nausea and stomach discomfort:the most common complaint, especially when taking several grams at once.
- Abdominal pain and cramps:usually pass after reducing the dose.
- Diarrhea:described at high doses.
- Reactions to excipients:dyes, flavorings, tablet fillers.
Such reactions are, as a rule, transient and not dangerous for a healthy person. Taking it with food and dividing the daily amount into several doses helps to reduce them.
Lysine is most often sold in the form of the hydrochloride. The acidic part of the salt may additionally irritate the stomach lining in sensitive people, so if you are prone to heartburn it is better not to take tablets on an empty stomach.
Allergic reactions to the amino acid itself are described extremely rarely. If a rash, itching or swelling appears, intake should be stopped and a doctor consulted: the cause may be other components of the product.
Kidneys: cases of damage and experimental data
The most serious risk described in the literature is related to the kidneys. Lo and co-authors (1996) reported a clinical case of Fanconi syndrome and tubulointerstitial nephritis in a patient who had taken lysine for a long time. After discontinuation, kidney function partially recovered.
This is an isolated case, and it does not allow the conclusion that lysine harms the kidneys of every person. However, it shows that in some people prolonged intake of high doses may be accompanied by damage to the kidney tubules.
In animal studies, very high doses of lysine also caused changes in kidney function, which is consistent with the fact that the kidneys play a key role in the reabsorption of cationic amino acids. The significance of these data for humans at moderate doses is uncertain.
Therefore, people with chronic kidney disease or a reduced glomerular filtration rate are not advised to take lysine supplements without consulting a nephrologist. Healthy people on prolonged intake would be wise to periodically monitor basic indicators of kidney function.
| Potential risk | Level of evidence | Who it concerns |
|---|---|---|
| Gastrointestinal disorders | Clinical studies | High doses, intake on an empty stomach |
| Damage to the kidney tubules | Isolated clinical cases, animal data | Prolonged intake of high doses, kidney disease |
| Change in calcium metabolism | Physiological study | People with impaired calcium metabolism |
| Competition with arginine | Transport physiology | Prolonged intake of large doses |
| Metabolic crisis in hereditary diseases | Clinical description of the disease | Lysinuric protein intolerance |
Metabolic interactions and risk groups
Calcium.Civitelli and co-authors (1992) showed that lysine increases calcium absorption in the intestine and reduces its loss in the urine. For healthy people this is not a problem, but people with hypercalcemia, a tendency to calcium stones, or those taking large doses of calcium and vitamin D should discuss lysine intake with a doctor.
Arginine.Lysine and arginine use shared transporters in the intestine and kidneys. Large doses of lysine could theoretically reduce the availability of arginine. It is precisely on this antagonism that the hypothesis of the benefit of lysine in herpes is built, but for other body systems it may be undesirable.
Lysinuric protein intolerance.This is a rare hereditary disease in which the transport of lysine, arginine and ornithine in the intestine and kidneys is impaired. It is accompanied by disorders of the urea cycle, hyperammonemia and damage to many organs (Sebastio et al., 2011). Lysine supplements are not prescribed to such patients without the decision of a metabolic specialist.
Pregnancy, breastfeeding, childhood.There are insufficient studies of the safety of lysine supplements in these groups, so in the absence of medical indications it is better to avoid them or take them only on a doctor's recommendation.
How to reduce the risk of side effects
The first rule is not to exceed the doses used in clinical studies, and to remember that the diet already provides a significant amount of lysine. For most purposes there is no need to go beyond a few grams per day.
The second is to take the supplement with food and divide the daily amount into several doses. This reduces stomach irritation and the peak concentration of the amino acid in the blood.
The third is not to take lysine for years just in case. If the supplement is used for a specific purpose, for example during periods of frequent herpes flare-ups, its effect should be assessed together with a doctor and intake should not be continued without need.
The fourth is to choose products from manufacturers with transparent composition and independent quality control. For athletes who undergo doping testing, this is also protection against the risk of supplements being contaminated with foreign substances.
Editorial conclusions
At the doses studied in clinical work, lysine is well tolerated by healthy adults; the most common side effects are nausea, abdominal pain and diarrhea.
The most serious described risk is kidney damage with prolonged intake, known from isolated clinical cases and animal data.
People with kidney disease, lysinuric protein intolerance, disorders of calcium metabolism, pregnant women and children should take lysine only on a doctor's recommendation.
We also recommend the materials How to take L-lysine: dosage, timing, duration, L-lysine: what it is and how it works and The benefits of L-lysine for athletes: the evidence base.
References
- Hayamizu K, Oshima I, Fukuda Z, et al. Safety assessment of L-lysine oral intake: a systematic review. Amino Acids. 2019;51(4):647–659.
- Flodin NW. The metabolic roles, pharmacology, and toxicology of lysine. J Am Coll Nutr. 1997;16(1):7–21.
- Lo JC, Chertow GM, Rennke H, Seifter JL. Fanconi's syndrome and tubulointerstitial nephritis in association with L-lysine ingestion. Am J Kidney Dis. 1996;28(4):614–617.
- Civitelli R, Villareal DT, Agnusdei D, et al. Dietary L-lysine and calcium metabolism in humans. Nutrition. 1992;8(6):400–405.
- Sebastio G, Sperandeo MP, Andria G. Lysinuric protein intolerance: reviewing concepts on a multisystem disease. Am J Med Genet C Semin Med Genet. 2011;157C(1):54–62.
- World Health Organization, Food and Agriculture Organization, United Nations University. Protein and amino acid requirements in human nutrition. WHO Technical Report Series 935. Geneva: WHO; 2007.
- Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: National Academies Press; 2005.
Andriy Melnyk
A strength-sports coach and author of programs for beginner and intermediate levels. Writes about training planning.
