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Condition

Chronic Liver Disease

Chronic liver disease is long-lasting liver damage, where inflammation and scarring gradually interfere with filtering blood and making bile. S-adenosylmethionine has the most research behind it, but a review found no clear difference in bilirubin, while liver cell content went up with TUDCA in one small study. That study involved only five people, so the evidence overall is limited.

Sources: PMID 25774783; PMID 8541578

Supplements studied
4
Graded outcomes
4
Trials
1
People studied
7,066

Evidence by supplement

  • Strong
  • Moderate
  • Limited
  • Very limited

4 supplements

TUDCA

TUDCA: outcomes studied for Chronic Liver Disease
GradeOutcomeEffectSizeStudiesPeopleStudies list
Liver Cell Content

Small Increase

Improves (the measure goes up)Small effect1 study5 people

Studies that measured liver cell content

Liver EnzymesChanges; see studies4 studies5 people

Studies that measured liver enzymes

and 1 more on the TUDCA page

Vitamin D

Vitamin D: outcomes studied for Chronic Liver Disease
GradeOutcomeEffectSizeStudiesPeopleStudies list
All-Cause Mortality

No effect

NoneNo effect1 study4,084 people

Studies that measured all-cause mortality

InsulinChanges; see studies3 studies4,084 people

Studies that measured insulin

Insulin ResistanceImproves (the measure goes down)1 study4,084 people

Studies that measured insulin resistance

Liver EnzymesChanges; see studies1 study4,084 people

Studies that measured liver enzymes

High-density lipoprotein (HDL)Improves (the measure goes up)4,084 people
Liver FatImproves (the measure goes down)4,084 people
Liver FibrosisImproves (the measure goes down)4,084 people
TriglyceridesImproves (the measure goes down)4,084 people

S-adenosylmethionine

  • Bilirubin
  • Depression Symptoms: improves
  • Osteoarthritis Symptoms: improves
S-adenosylmethionine: outcomes studied for Chronic Liver Disease
GradeOutcomeEffectSizeStudiesPeopleStudies list
Bilirubin

No effect

NoneNo effect1 study1,558 people

Studies that measured bilirubin

Depression SymptomsImproves (the measure goes down)6 studies1,558 people

Studies that measured depression symptoms

and 3 more on the S-adenosylmethionine page

Osteoarthritis SymptomsImproves (the measure goes down)6 studies1,558 people

Studies that measured osteoarthritis symptoms

and 3 more on the S-adenosylmethionine page

Liver EnzymesChanges; see studies1 study705 people

Studies that measured liver enzymes

ItchingImproves (the measure goes up)1,558 people

Resveratrol

  • Bilirubin
  • Liver Enzymes: changes; see studies
Resveratrol: outcomes studied for Chronic Liver Disease
GradeOutcomeEffectSizeStudiesPeopleStudies list
Bilirubin

No effect

NoneNo effect208 people
Liver EnzymesChanges; see studies2 studies714 people

Studies that measured liver enzymes

Key findings

  • Liver Cell ContentTUDCAImproves (the measure goes up)
  • All-Cause MortalityVitamin D
  • BilirubinS-adenosylmethionine

The Chronic Liver Disease protocol

2 primary supplements · 4 supporting supplements

  • Silymarin (Milk Thistle)420 mg daily (standardized to 70–80% silymarin)
  • S-Adenosyl-L-Methionine (SAMe)1,200 mg daily in divided doses

See the full protocol

Studies cited

27 studies from PubMed

  1. Role of Vitamin D Supplementation in Chronic Liver Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Nutr Rev · PMID 40644459
  2. Vitamin D supplementation for prevention of mortality in adultsCochrane Database Syst Rev · PMID 21735411
  3. Vitamin D Supplementation Affects the Beck Depression Inventory, Insulin Resistance, and Biomarkers of Oxidative Stress in Patients with Major Depressive Disorder: A Randomized, Controlled Clinical TrialJ Nutr · PMID 26609167
  4. Effect of vitamin D3 supplementation on insulin resistance and β-cell function in prediabetes: a double-blind, randomized, placebo-controlled trial.Am J Clin Nutr · PMID 31559433
  5. Efficacy of vitamin D supplementation on glycaemic control in type 2 diabetes: An updated systematic review and meta-analysis of randomized controlled trials.Diabetes Obes Metab · PMID 39355942
  6. Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trialAm J Clin Nutr · PMID 21715514
  7. A multicenter, randomized, double-blind trial comparing the efficacy and safety of TUDCA and UDCA in Chinese patients with primary biliary cholangitis.Medicine · PMID 27893675
  8. Ursodeoxycholic and tauro-ursodeoxycholic acids for the treatment of primary biliary cirrhosis: a pilot crossover study.Aliment Pharmacol Ther · PMID 9146783
  9. Tauroursodeoxycholic acid for treatment of primary biliary cirrhosis. A dose-response study.Dig Dis Sci · PMID 8674405
  10. Tauroursodeoxycholic acid for the treatment of HCV-related chronic hepatitis: a multicenter placebo-controlled studyHepatogastroenterology · PMID 9840118
  11. Does tauroursodeoxycholic acid (TUDCA) treatment increase hepatocyte proliferation in patients with chronic liver diseaseItal J Gastroenterol · PMID 8541578
  12. S-adenosyl-L-methionine for the treatment of chronic liver disease: a systematic review and meta-analysisPLoS One · PMID 25774783
  13. S-adenosylmethionine (AdoMet) supplementation for treatment of chemotherapy-induced liver injuryAnticancer Res · PMID 14981985
  14. Efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients: A systematic review and meta- analysis.Prog Neuropsychopharmacol Biol Psychiatry · PMID 38423354
  15. S-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with depression: An updated systematic review and meta-analysis.Gen Hosp Psychiatry · PMID 38199136
  16. S-adenosyl methionine (SAMe) for depression in adultsCochrane Database Syst Rev · PMID 27727432
  17. S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: efficacy and effects of histamine and carnitine as moderators of responseJ Affect Disord · PMID 24856557
  18. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trialAm J Psychiatry · PMID 20595412
  19. S-Adenosylmethionine for osteoarthritis of the knee or hip.Cochrane Database Syst Rev · PMID 19821403
  20. S-adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease.Evid Rep Technol Assess · PMID 12899148
  21. S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. [ISRCTN36233495]BMC Musculoskelet Disord · PMID 15102339
  22. Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint diseaseAm J Med · PMID 3318442
  23. Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis: an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patientsClin Ther · PMID 20110025
  24. Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritisJ Fam Pract · PMID 12019049
  25. S-Adenosyl-Methionine improves depression in patients with Parkinson's disease in an open-label clinical trialMov Disord · PMID 11104210
  26. Efficacy of resveratrol supplementation on liver enzymes in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysisComplement Ther Med · PMID 33271299
  27. Effects of resveratrol supplementation on liver enzymes: A systematic review and meta-analysis of randomised controlled trials.Int J Clin Pract · PMID 32869460

Supplement stack for Chronic Liver Disease