Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.

To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.

The following protocols were developed using only A through C-quality evidence.

Class
Qualifying studies
Minimum requirements
A
Systematic review or meta-analysis of human trials
 
B
RDBPC human trials
2+ studies and/or 1 study with 50 + subjects
C
RDBPC human trials
1 study

Elevated liver enzymes may indicate hepatic pathology. The most common cause for liver enzyme elevations is non-alcoholic fatty liver disease (NAFLD). (18) NAFLD has a global prevalence of roughly 25% and is associated with comorbidities such as obesity, type 2 diabetes, hyperlipidemia, hypertension, and metabolic syndrome. (19) Having one of the comorbidities associated with NAFLD also increases risk of NAFLD. (18) A specific type of NAFLD is nonalcoholic steatohepatitis (NASH), which describes when there is also inflammation and/or liver damage with NAFLD. 

Treatment for NAFLD typically consists of lifestyle changes such as diet, exercise and weight loss. (8) When NAFLD is progressive, such as in the case of NASH, pharmacological intervention may be recommended. (8) Supplements offer a promising alternative for managing the elevations in liver enzymes and other aspects of NAFLD. 

The ingredients presented in the protocol below reflect research findings that demonstrate efficacy to support hepatic function.

Milk thistle (Silybum marianum)

70-140 mg, two to three times per day, minimum 12 weeks (20)

  • Compared to control, significant reduction of AST and ALT levels were observed (20)(9)(2) 
  • Demonstrated decrease in transaminases of NASH patients, which led to a revival of liver function in NASH patients, hence improving prognosis and progression of liver cirrhosis (20)(9)(2) 
  • Meta-analysis of eight randomized controlled trials found silymarin extract to decrease AST by 6.57 UI/L and ALT by 9.16 UI/L in patients with non-alcoholic fatty liver disease (NAFLD) (20)
  • When given Realsil, a silybin phytosome complex with phosphatidylcholine and vitamin E, normalization of body mass index (BMI) occured in 15% of the treatment group compared to 2.1% in the control; improved liver function also occurred as demonstrated by improved ALT, AST, and HOMA (9) 
  • Improved hepatic function as demonstrated by a decrease in ALT, AST, hepatic steatosis, and GGT (2)
Milk thistle in the Fullscript catalog

Vitamin E

800 IU, once per day, minimum 2 years (16)

  • A meta-analysis showed that, compared to control, vitamin E was shown to be effective in reducing fibrosis, AST, ALT, ALP, steatosis and inflammation (17) 
  • A review of trials supports the use of vitamin E on biomarkers and liver enzymes, likely due to its anti-inflammatory, anti-apoptotic and antioxidant properties (13
  • Lobular inflammation and hepatic steatosis improved accompanied by normalization and/or decrease in liver enzymes in nondiabetic patients with nonalcoholic steatohepatitis (NASH) (13)
  • Hepatic function improved as shown by a decrease in AST by 19.43 U/L, ALT by 28.91 U/L, alkaline phosphatase (ALP) by 10.39 U/L, steatosis by 0.54 U/L, and hepatocellular ballooning by -0.34 U/L in random effect model analysis; as well as a decrease in inflammation by .20 U/L when compared to control group in patients with NAFLD (17)
  • A systematic review and meta-analysis found that the use of vitamin E in adults with NAFLD significantly improved ALT and AST scores (1)
  • Treatment with vitamin E at a dose of 800 IU for 96 weeks, compared to placebo, significantly improved NASH by 43% and significantly improved markers of ALT and AST (16)
Vitamin E in the Fullscript catalog

Turmeric (Curcuma longa)

500-1000 mg, total per day, minimum 8 weeks (7)(12)(15)

  • As a result of its anti-inflammatory, anti-apoptotic, and antioxidant properties, turmeric (Curcuma longa) has been shown to improve enzyme levels and histology of the liver. For example, turmeric (Curcuma longa) increases lipid peroxyl radical scavenging, decreases COX2, and decreases caspases 9, 8, and 3 (3)(15)
  • Higher dosing of 1000 mg per day or more for at least 8 weeks was found to have superior effects as shown by a decrease in ALT by 11.36 IU/L and AST by 9.22 IU/L (10)
  • Mean deviation decreases in ALT by 7.31 U/L and AST by 4.68 UL/L were found in a pooled analysis of curcumin supplementation for less than 12 weeks (5)
  • Fermented turmeric powder decreased AST and ALT in patients with mild to moderately elevated ALT as well as decreased gamma-glutamyl transferase (GGT) (7)
  • Hepatic function improved as demonstrated by 75% of subjects having improved ultrasonic findings (4.7% in placebo), decreased AST and ALT (increased in placebo), and a more significant decrease in BMI and waist circumference in patients with grade 1-3 NAFLD (12)
  • Liver fat content improved in 78.9% of treatment group compared to 27.5% in placebo while BMI, total serum cholesterol, LDL, all decreased in patients with NAFLD (15)
Turmeric in the Fullscript catalog

Artichoke (Cynara scolymus)

600 mg, once per day, minimum 2 months (11)

  • Symptoms associated with NASH have been shown to be alleviated by artichoke leaf extract in addition to improving lipid levels and liver enzymes (14) 
  • Improved liver profile as shown by decreases in ALT and AST, improved AST:ALT ratio and AST to platelet ratio (APRI), increased hepatic flow, and decreased portal vein diameter and liver size (11)
  • Hepatic function improved as demonstrated by increase in biliary sludge elimination and decrease in pain syndrome for 87% of patients as well as decrease in dyspeptic manifestations of 65.2% of patients in patients with NASH and metabolic syndrome given chopytol from purified artichoke extract (14)
Artichoke in the Fullscript catalog

Vitamin D

50,000 IU once per week, 12 weeks (6) or 2100 IU per day, up to 48 weeks (4)

  • Improved liver function, inflammatory status, and metabolic profile shown by a decrease in HOMA-IR, ALT, and AST, serum CRP and increase in adiponectin in patients with NAFLD when given 50,000 IU once weekly for 12 weeks (6)
  • Serum levels for vitamin D improved while ALT and cytokeratin 18 fragments decreased in patients with NASH, elevated ALT, and low serum vitamin D when given 2100 IU per day for 48 weeks (4)
Vitamin D in the Fullscript catalog

Disclaimer

The Fullscript Medical Advisory Team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

View protocol on Fullscript
References
  1. Amanullah, I., Khan, Y. H., Anwar, I., Gulzar, A., Mallhi, T. H., & Raja, A. A. (2019). Effect of vitamin E in non-alcoholic fatty liver disease: a systematic review and meta-analysis of randomised controlled trials. Postgraduate Medical Journal, 95(1129), 601–611. https://pubmed.ncbi.nlm.nih.gov/31434683/ (A)
  2. Cacciapuoti, F., Scognamiglio, A., Palumbo, R., Forte, R., & Cacciapuoti, F. (2013). Silymarin in non alcoholic fatty liver disease. World Journal of Hepatology, 5(3), 109–113. https://pubmed.ncbi.nlm.nih.gov/23556042/ (C)
  3. Farzaei, M. H., Zobeiri, M., Parvizi, F., El-Senduny, F. F., Marmouzi, I., Coy-Barrera, E., Naseri, R., Nabavi, S. M., Rahimi, R., & Abdollahi, M. (2018). Curcumin in Liver Diseases: A Systematic Review of the Cellular Mechanisms of Oxidative Stress and Clinical Perspective. Nutrients, 10(7). https://pubmed.ncbi.nlm.nih.gov/29966389/ (A)
  4. Geier, A., Eichinger, M., Stirnimann, G., Semela, D., Tay, F., Seifert, B., Tschopp, O., Bantel, H., Jahn, D., Marques Maggio, E., Saleh, L., Bischoff-Ferrari, H. A., Müllhaupt, B., & Dufour, J.-F. (2018). Treatment of non-alcoholic steatohepatitis patients with vitamin D: a double-blinded, randomized, placebo-controlled pilot study. Scandinavian Journal of Gastroenterology, 53(9), 1114–1120. https://pubmed.ncbi.nlm.nih.gov/30270688/ (C)
  5. Goodarzi, R., Sabzian, K., Shishehbor, F., & Mansoori, A. (2019). Does turmeric/curcumin supplementation improve serum alanine aminotransferase and aspartate aminotransferase levels in patients with nonalcoholic fatty liver disease? A systematic review and meta-analysis of randomized controlled trials. Phytotherapy Research: PTR, 33(3), 561–570. https://pubmed.ncbi.nlm.nih.gov/30653773/ (A)
  6. Hussain, M., Iqbal, J., Malik, S. A., Waheed, A., Shabnum, S., Akhtar, L., & Saeed, H. (2019). Effect of vitamin D supplementation on various parameters in non-alcoholic fatty liver disease patients. Pakistan Journal of Pharmaceutical Sciences, 32(3 Special), 1343–1348. https://pubmed.ncbi.nlm.nih.gov/31551213/ (B)
  7. Kim, S.-W., Ha, K.-C., Choi, E.-K., Jung, S.-Y., Kim, M.-G., Kwon, D.-Y., Yang, H.-J., Kim, M.-J., Kang, H.-J., Back, H.-I., Kim, S.-Y., Park, S.-H., Baek, H.-Y., Kim, Y.-J., Lee, J.-Y., & Chae, S.-W. (2013). The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study. BMC Complementary and Alternative Medicine, 13, 58. https://pubmed.ncbi.nlm.nih.gov/23497020/ (B)
  8. Leoni, S., Tovoli, F., Napoli, L., Serio, I., Ferri, S., & Bolondi, L. (2018). Current guidelines for the management of non-alcoholic fatty liver disease: A systematic review with comparative analysis. World Journal of Gastroenterology: WJG, 24(30), 3361–3373. https://pubmed.ncbi.nlm.nih.gov/30122876/ (A) 
  9. Loguercio, C., Andreone, P., Brisc, C., Brisc, M. C., Bugianesi, E., Chiaramonte, M., Cursaro, C., Danila, M., de Sio, I., Floreani, A., Freni, M. A., Grieco, A., Groppo, M., Lazzari, R., Lobello, S., Lorefice, E., Margotti, M., Miele, L., Milani, S., … Federico, A. (2012). Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Free Radical Biology & Medicine, 52(9), 1658–1665. https://pubmed.ncbi.nlm.nih.gov/22343419/ (B)
  10. Mansour-Ghanaei, F., Pourmasoumi, M., Hadi, A., & Joukar, F. (2019). Efficacy of curcumin/turmeric on liver enzymes in patients with non-alcoholic fatty liver disease: A systematic review of randomized controlled trials. Integrative Medicine Research, 8(1), 57–61. https://pubmed.ncbi.nlm.nih.gov/30949432/ (A)
  11. Panahi, Y., Kianpour, P., Mohtashami, R., Atkin, S. L., Butler, A. E., Jafari, R., Badeli, R., & Sahebkar, A. (2018). Efficacy of artichoke leaf extract in non-alcoholic fatty liver disease: A pilot double-blind randomized controlled trial. Phytotherapy Research: PTR, 32(7), 1382–1387. https://pubmed.ncbi.nlm.nih.gov/29520889/ (B) 
  12. Panahi, Y., Kianpour, P., Mohtashami, R., Jafari, R., Simental-Mendía, L. E., & Sahebkar, A. (2017). Efficacy and Safety of Phytosomal Curcumin in Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial. Drug Research, 67(4), 244–251. https://pubmed.ncbi.nlm.nih.gov/28158893/ (C)
  13. Perumpail, B. J., Li, A. A., John, N., Sallam, S., Shah, N. D., Kwong, W., Cholankeril, G., Kim, D., & Ahmed, A. (2018). The Role of Vitamin E in the Treatment of NAFLD. Diseases (Basel, Switzerland), 6(4). https://pubmed.ncbi.nlm.nih.gov/30249972/ (A)
  14. Radchenko, V. G., Seliverstov, P. V., Ledentsova, S. S., & Manyakov, A. V. (2016a). [Nonalcoholic steatohepatitis and biliary sludge in people with metabolic syndrome]. Terapevticheskii arkhiv, 88(9), 78–83. https://pubmed.ncbi.nlm.nih.gov/27735918/ (C)
  15. Rahmani, S., Asgary, S., Askari, G., Keshvari, M., Hatamipour, M., Feizi, A., & Sahebkar, A. (2016). Treatment of Non-alcoholic Fatty Liver Disease with Curcumin: A Randomized Placebo-controlled Trial. Phytotherapy Research: PTR, 30(9), 1540–1548. https://pubmed.ncbi.nlm.nih.gov/27270872/ (C)
  16. Sanyal, A. J., Chalasani, N., Kowdley, K. V., McCullough, A., Diehl, A. M., Bass, N. M., Neuschwander-Tetri, B. A., Lavine, J. E., Tonascia, J., Unalp, A., Van Natta, M., Clark, J., Brunt, E. M., Kleiner, D. E., Hoofnagle, J. H., Robuck, P. R., & NASH CRN. (2010). Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. The New England Journal of Medicine, 362(18), 1675–1685. https://pubmed.ncbi.nlm.nih.gov/20427778/ (C)
  17. Sato, K., Gosho, M., Yamamoto, T., Kobayashi, Y., Ishii, N., Ohashi, T., Nakade, Y., Ito, K., Fukuzawa, Y., & Yoneda, M. (2015). Vitamin E has a beneficial effect on nonalcoholic fatty liver disease: a meta-analysis of randomized controlled trials. Nutrition , 31(7-8), 923–930. https://pubmed.ncbi.nlm.nih.gov/26059365/ (A)
  18. Vernon, G., Baranova, A., & Younossi, Z. M. (2011). Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Alimentary Pharmacology & Therapeutics, 34(3), 274–285. https://pubmed.ncbi.nlm.nih.gov/21623852/ (A)
  19. Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016). Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology , 64(1), 73–84. https://pubmed.ncbi.nlm.nih.gov/26707365/ (A)
  20. Zhong, S., Fan, Y., Yan, Q., Fan, X., Wu, B., Han, Y., Zhang, Y., Chen, Y., Zhang, H., & Niu, J. (2017). The therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease: A meta-analysis (PRISMA) of randomized control trials. Medicine, 96(49), e9061. https://pubmed.ncbi.nlm.nih.gov/29245314/ (A)