NAC vs Silymarin: what to choose and for whom

NAC and milk thistle stand side by side on the shelves of sports nutrition and health supplements. A person who wants to «help the liver» often does not know which jar to pick up. The editorial team examined the real usage scenarios and explains for whom each option is more appropriate, and when it is better not to spend money on either.

What exactly you want to get

The choice between NAC and silymarin depends on the goal. If a person wants to support antioxidant protection in a situation where glutathione may be depleted, the logic leads to NAC as a source of cysteine. If the goal is long-term intake of a plant agent with a mild profile for minor changes in liver tests, silymarin is more often discussed.

At the same time, both agents have limits. Neither treats viral hepatitis, dissolves gallstones, removes fat from the liver without weight loss or neutralises systematic alcohol consumption. Expectations of «cleansing the liver» or «restoring it in a month» have no scientific basis.

So before buying it is worth undergoing a basic examination: liver tests, ultrasound and, if needed, markers of viral hepatitis. If there are no abnormalities, the agent is most likely not needed. If there are, it is worth finding out their cause together with a doctor.

Below we look at the situations in which people most often think about NAC or silymarin, and explain what is known about each from studies.

Scenarios where NAC is more logical

Acute paracetamol poisoning.Here NAC is the standard of treatment, but only in hospital. The protocol, dose and duration are determined by the paracetamol level in the blood and the time since intake. Self-administration of NAC tablets at home does not replace emergency care, and a delay can cost the liver.

Mucolytic therapy.NAC has been used for decades to thin sputum in bronchopulmonary diseases. If a person is already taking it as prescribed by a doctor for this reason, an additional «liver» agent is usually not needed.

A wish to support glutathione synthesis.According to the review by Rushworth and Megson, the benefit of NAC is greatest where glutathione stores are lowered. Such a state is described, for example, in some chronic diseases and in older people. In a healthy young person with a full diet the effect may be minimal.

In studies NAC as a supplement was most often used at 600 mg one to two times a day; for mucolytic use the regimen is stated in the patient leaflet of the medicinal product. It is worth taking it with water, and people with a sensitive stomach - after food, to reduce the risk of nausea.

Scenarios where silymarin is considered

Minor changes in liver tests in fatty liver disease.Some studies described a decrease in enzymes, but according to the EASL-EASD-EASO guidelines the basis of treatment is weight loss and physical activity. Silymarin here can only be an addition to these measures, not a substitute.

A person wants a plant agent with a mild profile.Silymarin is well tolerated, and for those who consciously choose herbal preparations it is an acceptable option. However, it is worth remembering the conclusion of the Cochrane review: no convincing effect on hard endpoints in liver diseases has been proven.

Long-term intake of drugs that burden the liver.People sometimes add silymarin on their own «for protection» during long-term therapy. This should be done only after speaking with a doctor, since interactions with drugs are possible, and monitoring liver tests in such a situation matters more than any supplement.

In studies standardised extracts were used, most often with several intakes a day. In practice it is important to choose a product that states the content of silymarin or silibinin, not simply «milk thistle extract» without standardisation.

NAC, silymarin and training

In the sporting environment NAC is of interest not only as a «liver» agent but also as an antioxidant that potentially affects fatigue. Experimental studies with the administration of NAC showed changes in the redox state of muscle. But there is a flip side: excessive suppression of oxidative signals may in theory weaken adaptation to training, so constant intake of high doses of antioxidants is not recommended for athletes.

Silymarin has been little studied in sport, and there are no convincing data on an effect on strength, endurance or recovery. It is bought mainly with the liver in mind, not results in the gym.

The most important thing for athletes: neither agent protects against the hepatotoxicity of oral anabolic steroids. The review by Pope and co-authors (2014) and the LiverTox database describe liver injury from 17-alpha-alkylated androgens, and there is no evidence that NAC or silymarin prevents it. Taking «protection» does not make such substances safer.

Also remember that after hard training ALT and AST can rise because of muscle. Before «treating the liver», it is worth having repeat tests after a few days of rest and checking GGT and creatine kinase.

Contraindications, interactions and practical tips

Before taking either of the two agents it is worth taking individual limitations into account. The editorial team has gathered the most important ones:

• NAC: caution in bronchial asthma, peptic ulcer disease, a tendency to nausea; do not use as self-treatment if poisoning is suspected.
• NAC: a possible effect on the action of nitroglycerin (enhanced vasodilation and headache) - when taking nitrates, a doctor's consultation is needed.
• Silymarin: avoid in allergy to plants of the Asteraceae family.
• Silymarin: when taking drugs with a narrow therapeutic window, agree with a doctor because of a possible effect on drug metabolism.
• Both: pregnancy and breastfeeding - only on a doctor's recommendation.

Taking NAC and silymarin at the same time is theoretically possible, the mechanisms do not conflict, but there is no evidence that the combination gives more than each on its own. If there is no specific indication, it is better to choose one agent or take neither.

When choosing a product, pay attention to standardisation and the dosage per capsule, the presence of an independent analysis of the composition and the reputation of the manufacturer. For NAC it is important that the packaging is tightly closed: moisture and air promote oxidation.

And finally: if, while taking anything, yellowing, darkening of the urine, itching of the skin or pain in the right upper abdomen appear, intake should be stopped and a doctor consulted.

Editorial conclusions

NAC is the more logical choice where a substrate for glutathione is needed, and an indispensable agent in hospital in paracetamol poisoning. Silymarin can be considered a mild plant auxiliary agent without convincing evidence of effectiveness.

For most healthy people who train, a measurable benefit from either agent is unlikely. The foundation of liver health is moderation in alcohol, a normal weight and avoiding hepatotoxic substances.

For more on the mechanisms, read the article «NAC vs Silymarin: what is the difference». We also recommend the editorial pieces «UDCA vs Silymarin: what to choose and for whom», «TUDCA vs Essential phospholipids: what to choose and for whom» and the review on antioxidants and adaptation to training.

References

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2. Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther. 2014;141(2):150–159.
3. Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-Acetylcysteine — a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol. 2007;7(4):355–359.
4. Rambaldi A, Jacobs BP, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database Syst Rev. 2007;(4):CD003620.
5. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388–1402.
6. Pope HG Jr, Wood RI, Rogol A, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev. 2014;35(3):341–375.
7. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–.