Jason Wild 

Background: NAFLD is an increasingly prevalent disease worldwide and costs the United States alone $100M annually². It has recently been renamed to metabolic associated fatty liver disease (MAFLD) and defines a spectrum of liver disease that range from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH^)2,3. The pathogenesis of NAFLD is explained by a concept known as the multiple hit model which states that many different variables combine to cause disease in patients². Researchers believe that NAFLD develops in a two-step process, the first step being the deposition of fat onto the liver and the second being oxidative stress on the liver³. This oxidative stress can lead to cirrhosis, or the formation of non-functional scar tissue on the liver. In the clinic, NAFLD patients can present with fatigue, splenomegaly and right upper quadrant pain³. Often, NAFLD patients will also have closely related metabolic diseases such as type II diabetes mellitus (T2DM) and cardiovascular disease³. The gold standard for diagnosing NAFLD is through a liver biopsy, however, patients can also be diagnosed through abnormal liver function tests and a detailed history and physical³. Unfortunately, there is not yet an FDA approved treatment for NAFLD; however, current therapeutic approaches include lifestyle intervention (diet, exercise, etc.), pharmaceuticals, bariatric surgery and gut microbiome alterations^2,4.

Objective: In this narrative review, we explored some of the current therapeutic approaches to treating patients with NAFLD.

Search Methods: An online search in the PubMed database was conducted from 2018 to 2024 using the keywords “NAFLD” and “MedDiet”.

Results: Five individual studies investigating the effects of different diet interventions and pharmaceutical agents on patients with metabolic disease were used. Extra virgin olive oil (EVOO) and nitrate supplementation was shown to increase levels of nitrate fatty acids and anti-inflammatory mitochondrial enzyme heme-oxygenase 1 (HO-1) in mice⁵. Essential oil supplementation of thyme and oregano was shown to increase levels of short chain fatty acids (SCFAs) and decrease levels of pro-inflammatory proteins and LDL-cholesterol in mice⁶. Omega-3 poly-unsaturated fatty acids (n-3-PUFAs) were shown to decrease levels of gamma glutamyl transferase (GGT) and improve patients lipidomic profiles by increasing the levels of both omega-3 triacylglycerdes and phospholipids in human NAFLD patients⁷. The Mediterranean Diet (MedDiet) was shown to improve outcomes for patients with NAFLD by diminishing intrahepatic fat contents for subjects that adhered to the MedDiet¹. Ipragliflozin, an SGLT-2 inhibitor that promotes glucose excretion, was also shown to diminish NASH in patients who previously had the condition⁸. The pharmaceutical agent significantly reduced ballooning and fibrosis in NASH patients as well⁸.

Conclusions: Studies have found promising results in patients with metabolic disorders who adhere to the lifestyle interventions and pharmaceutical agents discussed above; however, more extensive research needs to be done in order to further solidify the current findings and continue to discover more effective, efficient ways to treat NAFLD.

Works Cited:

1. Montemayor S, Mascaró CM, Ugarriza L, et al. Adherence to Mediterranean Diet and NAFLD in Patients with Metabolic Syndrome: The FLIPAN Study. Nutrients. 2022;14(15):3186. Published 2022 Aug 3. doi:10.3390/nu14153186
2. Nassir F. NAFLD: Mechanisms, Treatments, and Biomarkers. Biomolecules. 2022;12(6):824. Published 2022 Jun 13. doi:10.3390/biom12060824
3. Pouwels S, Sakran N, Graham Y, et al. Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC Endocr Disord. 2022;22(1):63. Published 2022 Mar 14. doi:10.1186/s12902-022-00980-1
4. Raza S, Rajak S, Upadhyay A, Tewari A, Anthony Sinha R. Current treatment paradigms and emerging therapies for NAFLD/NASH. Front Biosci (Landmark Ed). 2021;26(2):206-237. Published 2021 Jan 1. doi:10.2741/4892
5. Sánchez-Calvo B, Cassina A, Mastrogiovanni M, et al. Olive oil-derived nitro-fatty acids: protection of mitochondrial function in non-alcoholic fatty liver disease. J Nutr Biochem. 2021;94:108646. doi:10.1016/j.jnutbio.2021.108646
6. Sánchez-Quintero MJ, Delgado J, Martín Chaves L, et al. Multi-Omics Approach Reveals Prebiotic and Potential Antioxidant Effects of Essential Oils from the Mediterranean Diet on Cardiometabolic Disorder Using Humanized Gnotobiotic Mice. Antioxidants (Basel). 2023;12(8):1643. Published 2023 Aug 20. doi:10.3390/antiox12081643
7. Šmíd V, Dvořák K, Šedivý P, et al. Effect of Omega-3 Polyunsaturated Fatty Acids on Lipid Metabolism in Patients With Metabolic Syndrome and NAFLD. Hepatol Commun. 2022;6(6):1336-1349. doi:10.1002/hep4.1906
8. Takahashi H, Kessoku T, Kawanaka M, et al. Ipragliflozin Improves the Hepatic Outcomes of Patients With Diabetes with NAFLD. Hepatol Commun. 2022;6(1):120-132. doi:10.1002/hep4.1696