Fatty Liver Support Protocol: A Resource for Practitioners


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by Fullscript’s Integrative Medical Advisory Team

Non-alcoholic fatty liver disease (NAFLD) is among the most common liver conditions in developed countries. (6)(13) One form of NAFLD, non-alcoholic steatohepatitis (NASH), occurs in approximately 20% of patients with NAFLD and affects 3 to 12% of adults living in the United States. (13)

practitioner examining a patient

NASH, a form of NAFLD, is characterized by a fatty liver, inflammation, and liver cell damage.

What is nonalcoholic steatohepatitis?

Nonalcoholic fatty liver disease (NAFLD) is a condition in which the body stores excess fat in the liver. Unlike alcoholic fatty liver disease, NAFLD is not caused by excess alcohol intake. There are two types of NAFLD, which include nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). (13)

While individuals with NAFL and NASH both present with a fatty liver, NASH is also characterized by hepatitis and liver cell damage (e.g., fibrosis). While it is still unclear as to why some individuals with NAFLD develop NAFL while others develop NASH, genetic susceptibility is believed to be a factor. (13)

Causes and risk factors

  • Causes and risk factors for both types of NAFLD include:
  • Overweight or obesity
  • Metabolic syndrome
  • Type 2 diabetes
  • Insulin resistance
  • High triglyceride and/or cholesterol levels
  • Certain health conditions in which your body improperly stores fat
  • Rapid weight loss
  • Certain toxins
  • Certain infections (e.g., hepatitis C)
  • Certain pharmaceutical medications (e.g., amiodarone, diltiazem, glucocorticoids methotrexate, etc.) (13)

Signs, symptoms, and complications

While individuals with NASH typically display few or no symptoms, (13) complications associated with the condition include cirrhosis, liver cancer, (5) and an increased risk of mortality from liver-related conditions and cardiovascular conditions. (6)

Integrative protocol for fatty liver support

Vitamin E

Vitamin E is a fat-soluble vitamin found primarily in nuts, seeds, and green leafy vegetables. (14) Vitamin E has been shown to have antioxidant, (6)(16) anti-inflammatory and anti-apoptotic properties. Due to its role in modulating the inflammatory response and cellular function, vitamin E may delay hepatic fibrosis and prevent cirrhosis. (16) Recently, studies have demonstrated the beneficial effects of vitamin E supplementation for individuals with NAFLD and NASH. (6)(16)

Recommended dosage:
800 IU, once per day, minimum 2 years (19)

Research findings:

  • Compared to control, vitamin E was shown to be effective in reducing fibrosis, AST, ALT, ALP, steatosis and inflammation (20)
  • As a result of its anti-inflammatory, anti-apoptotic, and antioxidant properties, vitamin E has been shown to improve enzyme levels and histology of the liver. For example, vitamin E increases lipid peroxyl radical scavenging, decreases COX2, and decreases caspases 9, 8, and 3. (16)

US: Search for Vitamin E in the Fullscript catalog.
CAN: Search for Vitamin E in the Fullscript catalog.

Milk thistle extract

Milk thistle has been used for centuries for its liver protective and antioxidant properties.

Milk Thistle (Silybum marianum)

Silybum marianum, commonly known as milk thistle, is a member of the Asteraceae family along with sunflowers and daisies. (21) Used as a medicinal plant for centuries, milk thistle was first grown in Europe and used for its hepatoprotective and antioxidant properties. (11) Silymarin, found primarily in the fruit and seeds of the milk thistle plant, contains a complex of active compounds, including silybin, a primary active constituent of milk thistle. (21) These compounds are believed to be responsible for the antioxidant, antiviral, anti-inflammatory, and hepatoprotective properties of milk thistle. (11)(21)

Recommended dosage:
70-140mg, two to three times per day, minimum 12 weeks (24)

Research findings:

  • Compared to a controlled regimen, significant reduction of AST and ALT levels were observed (2)(12)(24)
  • 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 (2)(12)(24)

US: Search for Milk Thistle in the Fullscript catalog.
CAN: Search for Milk Thistle in the Fullscript catalog.

Turmeric (Curcuma longa)

A member of the ginger family, turmeric is well known for its medicinal properties and its use as a culinary spice. Turmeric was traditionally used as a medicinal herb for its antioxidant, anti-inflammatory, antimicrobial, and anticancer properties. These effects have been primarily attributed to the actions of curcumin, a polyphenol and primary active constituent of the plant. Curcumin supplements are often found in combination with other ingredients that increase its bioavailability, such as piperine, an active constituent of black pepper. (10)

Research has shown that turmeric and curcumin may be effective in addressing a number of inflammatory conditions, such as cardiovascular disease, inflammatory bowel conditions, arthritis, psoriasis, diabetes, metabolic syndrome, cancer, and exercise-induced inflammation and muscle soreness. (8)(10) Curcumin has also demonstrated protective effects against chronic arsenic exposure, alcohol intoxication, and hepatic conditions. (8)

Recommended dosage:
500-1000mg, total per day, minimum 8 weeks (15)(18)

Research findings:

  • Curcumin has been shown to have protective effects through various mechanisms like PI3K/Akt and hepatic stellate cells activation, amelioration of the expression of Nrf2, SOD, CAT, GSH, GPx and GR, suppressing proinflammatory cytokines, lipid peroxidation products, PI3K/Akt and hepatic stellate cells activation (3)(7)
  • Reduction in ALT, AST and GGT levels was observed (3)(15)(18)

US: Search for Curcuma longa in the Fullscript catalog.
CAN: Search for Curcuma longa in the Fullscript catalog.

two pieces of Artichoke one cut in half

Artichoke may be effective in the treatment of NASH due to its lipid-lowering, bile-enhancing, antioxidant, and hepatoprotective effects.

Artichoke (Cynara scolymus)

Like milk thistle, Cynara scolymus, commonly known as artichoke, is a member of the Asteraceae family. Traditionally, artichoke was used in the treatment of certain conditions such as hyperlipidemia. (9) Modern research has demonstrated the lipid-lowering, bile-enhancing, antioxidant, and most significantly, hepatoprotective effects of artichoke. (1) Bioactive compounds identified in artichoke responsible for its antioxidant effects include luteolin, cynarin, caffeic acid, and chlorogenic acid. (9)

Recommended dosage:
600mg, once per day, minimum 2 months (15)

Research findings:

  • Artichoke leaf extract has been shown to have beneficial effects on liver enzymes ALT and AST (15)
  • Symptoms associated with NASH have been shown to be alleviated by artichoke leaf extract in addition to improving lipid levels and liver enzymes (17)

US: Search for Artichoke in the Fullscript catalog.
CAN: Search for Artichoke in the Fullscript catalog.

New and upcoming research

Reishi (Ganoderma lucidum)

A well known medicinal mushroom, Ganoderma lucidum has been used in China, Japan, and other Asian countries for over 2000 years. While Ganoderma lucidum is known as reishi in Japan, in China, it is known as lingzhi, the “herb of spiritual potency”. (22)(23) Traditional chinese medicinal applications of G. lucidum include the treatment and prevention of a number of conditions, including immune disorders, cancer, bronchitis, allergies, and hepatitis. It is believed that G. lucidum may play a role in the maintenance of blood glucose levels, modulation of the immune system, and hepatoprotection. (22) While the use of G. lucidum was previously largely based on cultural and anecdotal evidence, scientific studies are now emerging supporting its health benefits.

G. lucidum supplements and tea can be produced from the mycelia, spores, and fruit body of the mushrooms. (22)

Recommended dosage:
225mg, total per day, minimum 6 months (4)

Research findings:

  • Ganoderma lucidum was shown to reverse mild fatty liver to a normal condition (4)
  • Reduction in GOT and GPT levels was observed (4)

US: Search for Ganoderma lucidum in the Fullscript catalog.
CAN: Search for Ganoderma lucidum in the Fullscript catalog.

The bottom line

Management of NAFLD typically involves lifestyle modification, addressing the presence of metabolic syndrome, managing the complications of cirrhosis, and pharmaceutical intervention when necessary. (6) Several nutrients and botanicals, including vitamin E, turmeric, milk thistle, and artichoke, have demonstrated hepatoprotective properties and beneficial effects in treating NAFLD. A protocol using natural supplements can be used therapeutically on its own or as an adjunct to existing treatment. If you are not an integrative healthcare provider, we recommend speaking with one to find out whether these supplements are right for your wellness plan.


Disclaimer

The Fullscript Integrative 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.

  1. Ben Salem, M., Affes, H., Ksouda, K., Dhouibi, R., Sahnoun, Z., Hammami, S., & Zeghal, K.M. (2015). Pharmacological Studies of Artichoke Leaf Extract and Their Health Benefits. Plant Foods for Human Nutrition, 70(4), 441-53.
  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.
  3. Chai, L.J., Zhang, Y., Zhang, P.Y., Bi, Y.N., Yuan, X.M., Li, Y.H., … Zhou, K. (2018). The antiosteoporosis effects of zhuanggu guanjie pill in vitro and in vivo. BioMed Research International, 2018, 9075318.
  4. Chiu, H.F., Fu, H.Y., Lu, Y.Y., Han, Y.C., Shen, Y.C., Venkatakrishnan, K., … Wang, C.K. (2017). Triterpenoids and polysaccharide peptides-enriched Ganoderma lucidum: a randomized, double-blind placebo-controlled crossover study of its antioxidation and hepatoprotective efficacy in healthy volunteers. Pharmaceutical Biology, 55(1), 1041-1046.
  5. Diehl, A.M., & Day, C. (2017). Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. The New England Journal of Medicine, 377, 2063-2072
  6. Dyson, J.K., Anstee, Q.M., McPherson, S. (2015). Republished: Non-alcoholic fatty liver disease: A practical approach to treatment. Postgraduate Medical Journal, 91, 92-101.
  7. Farzaei, M.H., Zobeiri, M., Parvizi, F., El-Senduny, F.F., Marmouzi, I., Coy-Barrera, E., … Abdollahi, M. (2018). Curcumin in liver diseases: A systematic review of the cellular mechanisms of oxidative stress and clinical perspective. Nutrients, 10(7).
  8. Gupta, S.C., Patchva, S., & Aggarwal, B.B. (2013). Therapeutic roles of curcumin: Lessons learned from clinical trials. The AAPS Journal, 15(1), 195–218.
  9. Heidarian, E., & Rafieian-Kopaei, M. (2012). Protective effect of artichoke (Cynara scolymus) leaf extract against lead toxicity in rat. Pharmaceutical Biology, 51(9), 1104-1109.
  10. Hewlings, S.J., & Kalman, D.S. (2017). Curcumin: A review of its’ effects on human health. Foods, 6(10), 92.
  11. Karimi, G., Vahabzadeh, M., Lari, P., Rashedinia, M., & Moshiri, M. (2016). “Silymarin”, a promising pharmacological agent for treatment of diseases. Iranian Journal of Basic Medical Sciences, 14(4), 308–317.
  12. Loguercio, C., Andreone, P., Brisc, C., Brisc, M.C., Bugianesi, E., Chiaramonte, M., … Federico, A. (2012). Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Free Radical Biology and Medicine, 52(9), 1658-65.
  13. National Institute of Diabetes and Digestive and Kidney Disease. (2016). Symptoms & causes of NAFLD & NASH. Retrieve from https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/symptoms-causes
  14. National Institutes of Health. (2018). Vitamin E: Fact sheet for health professionals. Retrieved from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/
  15. 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.
  16. Perumpail, B.J., Li, A, A., John, N., Sallam, S., Shah, N.D., Kwong, W., … Ahmed, A. (2018). The role of vitamin E in the treatment of NAFLD. Disease, 6(4), 86.
  17. Radchenko, V.G., Seliverstov, P.V., Ledentsova, S.S., & Manyakov, A.V. (2016). Nonalcoholic steatohepatitis and biliary sludge in people with metabolic syndrome. Terapevticheskiĭ Arkhiv, 88(9), 78-83.
  18. 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, 30(9), 1540-8.
  19. Sanyal, A.J., Chalasani, N., Kowdley, K.V., McCullough, A., Diehl, A.M., Bass, N.M., … Robuck, P.R. (2010). Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. The New England Journal of Medicine, 362(18), 1675-85.
  20. Sato, K., Gosho, M., Yamamoto, T., Kobayashi, Y., Ishii, N., Ohashi, T., … 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), 923-30.
  21. Siegel, A.B., & Stebbing, J. (2013). Milk thistle: early seeds of potential. The Lancet Oncology, 14(10), 929–930.
  22. Wachtel-Galor, S., Yuen, J., Buswell, J.A., & Benzie, I.F.F. (2011). Ganoderma lucidum (lingzhi or reishi): A medicinal mushroom. In I.F.F. Benzie, & Wachtel-Galor, S. (Eds), Herbal Medicine: Biomolecular and Clinical Aspects.
  23. Wu, D., Deng, Y., Chen, L., Zhao, L., Bzhelyansky, A., & Li, S. (2017). Evaluation on quality consistency of Ganoderma lucidum dietary supplements collected in the United States. Scientific Reports, 7, 7792.
  24. Zhong, S., Fan, Y., Yan, Q., Fan, X., Wu, B., Han, Y., … Niu, J. (2017). The therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease: A meta-analysis (PRISMA) of randomized control trials. Medicine (Baltimore), 96(49), e9061.