Non-Alcoholic Fatty Liver Disease (NAFLD): Considering a Domino Effect
By Lily George, APRN, AGNP-C, Natural Health Center
Non-Alcoholic Fatty Liver Disease (NAFLD) is estimated to occur in about 25% of the U.S. population (and about 30% of the global population), and in 50-70% of individuals with type 2 diabetes (1,2,3). If that sounds like a lot to you, you might be wondering what NAFLD is, how it can be this common, and what we can do to help treat or even reverse NAFLD.
NAFLD is commonly referred to as a “spectrum,” meaning it starts with the development of too much fat in the liver, which can then progress to inflammation, then fibrosis (stiffening of the liver), then cirrhosis, and sometimes liver failure or cancer (4,5,6).
Additionally, the liver is understood to be the most regenerative organ in our body – up to 90% regenerative (7). And given that understanding, the goal of this feature is to review NAFLD in a way that hopefully empowers you to feel like you can take a negative domino effect and turn it into a positive one; to make changes before we get to cirrhosis (when it starts to become irreversible) or worse.
The premise I aim to build from is that we know the world of endocrinology relies on domino effects, and that we do have an ability to influence the domino effect.
Risk Factors for NAFLD
The risk factors below can help give an idea of the negative domino effect that can lead to NAFLD (4,5,6):
Type 2 diabetes (T2DM)
Metabolic syndrome
Obesity
Sedentary lifestyle
High fructose and high saturated fat diet
Smoking
Given that list, I view it as coming down to two main things: inflammation and insulin resistance, as all of the above include one or both of those. This means that focusing on inflammation or insulin resistance alone can lead to a positive domino effect. For example: improving insulin resistance alone can lead to sustainable weight loss, lower inflammation (insulin resistance contributes to inflammation), improve high blood pressure, and improve your cholesterol panel - which means a positive domino effect regarding outcomes with T2DM, metabolic syndrome, and obesity.
Focusing on healthy weight loss as a single intervention can lead to all of the same improvements listed above as well.
Signs and Symptoms of NAFLD
There aren’t usually obvious signs or symptoms for NAFLD, which makes it a sneaky domino effect (and usually allows the negative domino effect to occur in the first place). That’s why it’s getting more attention as something that we should be screening for more routinely (4).
Symptoms are more likely to occur if things progress past NAFLD into NASH (nonalcoholic steatohepatitis, which is when NAFLD becomes inflammatory), fibrosis, or further. Such symptoms may include fatigue, right upper quadrant discomfort, and changes in skin color and texture characteristic of insulin resistance (9).
Screening for NAFLD
So aside from understanding what things may lead to NAFLD, you may be wondering how we screen for it in a clinical setting?
We can start with non-invasive ways to determine risk, such as:
A FIB-4 score (based on your age, AST/ALT, platelets from routine labs)
A fibroscan (looks for stiffness of the liver)
An abdominal ultrasound that looks for excess fat in the liver (defined as greater than 5% of the liver) (4, 5, 6, 8, 10).
An initial work up includes rule out of other reasons for elevated liver enzymes. Confirmation of diagnosis of NAFLD comes from a liver biopsy (6).
Medications to Treat NAFLD
Currently, there are no medications approved specifically for the treatment of NAFLD, but because we know about the domino effect, we can work toward a positive outcome by using medications that target improvement of metabolic processes that we know contribute to NAFLD. These include medications such as:
GLP-1RAs like semaglutide (Ozempic, Wegovy)
GLP-1 RA+GIP Tirzepatide (Mounjaro)
DPP4 inhibitors
SGLT-2 inhibitors
Pioglitazone
Vitamin E 800IU (supplement) per day has also been shown to be effective (4, 5, 6, 11).
You generally need a diagnosis of T2DM or obesity to get the medications listed above; however, understanding that improving insulin resistance and inflammation are at the core of it helps a lot too. After all, the above medications are targeted to improve insulin resistance and help with weight loss (an inflammatory state).
Lifestyle and functional factors
There is really quite a bit to explore here; such factors can include exercising, reducing intake of processed sugar, fructose, and saturated fat, and promoting gut health.
Exercise is one of the most helpful things we can do to improve insulin resistance. Another is reducing sugar intake. This is a doubling of effort – so if you exercise daily and reduce your sugar intake, you’ll be improving your body’s response to the insulin it has circulating, while reducing overproduction of insulin that can occur due to excess sugar in the diet. One way could be to look at it as a re-calibration.
Reducing fructose and saturated fat are particularly important in the treatment of NAFLD. Fructose is metabolized differently than glucose is, and most fructose goes to the liver where it ends up being stored as fat (10). Saturated fat is understood to increase the triglyceride levels in your liver and contribute to the process of NAFLD overall (12). Reducing sucrose intake can also be helpful since it is made of glucose and fructose (13).
If you are wondering where to start, here are some common sources of fructose:
Processed foods: soda, candy, baked goods, cereal, salad dressings (14).
Natural sources of fructose: Fruit, fruit juices, some vegetables, honey (14).
The general recommendation is to start with reducing processed sources of fructose first. Natural sources are not a problem when not in excess.
Improving gut health can also promote lowering liver inflammation. Research has also been looking at how fructose may damage the gut lining, leading to inflammatory cells leaking out of the gut to the liver, both increasing the risk for NAFLD and worsening a current NAFLD process (15, 16).
And to wrap up, I came across a podcast by Dr. Kara Fitzgerald featuring Dr. Richard Rountree, ND, discussing a naturopathic approach to NAFLD. They discuss there is limited research linking small intestinal bacterial growth (SIBO) and NAFLD, and also discuss the following supplements that have been shown to be helpful in promoting liver health (8):
Sunfiber
Curcumin phytosome
NAC, liposomal glutathione
Vitamin E
Omega 3s
Berberine
Melatonin
Resveracell (combination product)
It’s important to note that this list is to provide options to look into, not required together all at once.
If you are concerned about NAFLD or would like to discuss a plan to help you reduce your risk and optimize your lifestyle for better health, please contact our team at the Natural Health Center in Anchorage today to schedule a visit.
About Lily George, Adult Nurse Practitioner
Lily George is an adult nurse practitioner at the Natural Health Center in Anchorage.
Born and raised in Alaska, Lily is passionate about improving access to endocrine care for Alaskans, while using an integrative medicine approach.
Learn more about Lily George or contact us to schedule an appointment.
Sources:
1. Lee, Y. H., Cho, Y., Lee, B. W., Park, C. Y., Lee, D. H., Cha, B. S., & Rhee, E. J. (2019). Nonalcoholic Fatty Liver Disease in Diabetes. Part I: Epidemiology and Diagnosis. Diabetes & metabolism journal, 43(1), 31–45. https://doi.org/10.4093/dmj.2019.0011
2. Amiri Dash Atan, N., Koushki, M., Motedayen, M., Dousti, M., Sayehmiri, F., Vafaee, R., Norouzinia, M., & Gholami, R. (2017). Type 2 diabetes mellitus and non-alcoholic fatty liver disease: a systematic review and meta-analysis. Gastroenterology and hepatology from bed to bench, 10(Suppl1), S1–S7.
3. American Liver Foundation. (2023, August 2) NASH Definition and Prevalence. Retrieved from https://liverfoundation.org/liver-diseases/fatty-liver-disease/nonalcoholic-steatohepatitis-nash/nash-definition-prevalence/#:~:text=It's%20estimated%20that%20about%2025,NAFLD%20have%20simply%20fatty%20liver.
4. Tangpricha, V. MD., Ph.D.; Cusi, K. MD, FACP, FACE; Isaacs, S. MD, FACP, FACE. (Hosts) (n.d.). 2022 AACE Nonalcoholic Fatty Liver Disease Clinical Practice Guideline. Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD). (No. 31) [Audio podcast episode]. AACE Podcasts. AACE. https://pro.aace.com/podcast/episode-31-2022-aace-nonalcoholic-fatty-liver-disease-clinical-practice-guideline
5. Hatipoglu, B. MD; Kashyap S., MD. (Hosts) (n.d.) Managing NAFLD and NASH in Primary Care and Endocrinology Clinical Settings. (No. 38). [Audio podcast episode]. In AACE Podcasts. AACE. https://pro.aace.com/podcast/episode-38-managing-nafld-and-nash-primary-care-and-endocrinology-clinical-settings?check_logged_in=1
6. Alexopoulos, A. MD; Basu, R. MD; Cusi, K. MD. (Hosts). (2023). Implementing Holistic Care NOW for NAFLD: A Case-Based Approach [online course, CME]. Endocrine Society. Retrieved from https://education.endocrine.org/Public/Catalog/Details.aspx?id=CiKyrG3FrSMN%2f2ewj%2fBYdQ%3d%3d&returnurl=%2fUsers%2fUserOnlineCourse.aspx%3fLearningActivityID%3dCiKyrG3FrSMN%252f2ewj%252fBYdQ%253d%253d
7. Reynolds, Sharon. (2021). Cells that maintain and repair the liver identified. Retrieved from https://www.nih.gov/news-events/nih-research-matters/cells-maintain-repair-liver-identified#:~:text=The%20liver%20has%20a%20unique,the%20liver%20isn't%20invincible
8. Fitzgerald, K., & Rountree, R. (Hosts). (n.d.) Non-Alcoholic Fatty Liver Disease: Dr. Robert Rountree shares his Expertise (and Powerpoint!) (No. 54) [Audio podcast episode]. In New Frontiers in Functional Medicine® with Dr. Kara Fitzgerald. Retrieved from https://www.drkarafitzgerald.com/2019/01/03/non-alcoholic-fatty-liver-disease-dr-robert-rountree/
9. Pouwels, S., Sakran, N., Graham, Y., Leal, A., Pintar, T., Yang, W., Kassir, R., Singhal, R., Mahawar, K., & Ramnarain, D. (2022). Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC endocrine disorders, 22(1), 63. https://doi.org/10.1186/s12902-022-00980-1
10. Roeb, E., & Weiskirchen, R. (2021). Fructose and Non-Alcoholic steatohepatitis. Frontiers in Pharmacology, 12. https://doi.org/10.3389/fphar.2021.634344
11. Lee, M. Y., Shin, E., Bae, J., Cho, Y., Lee, J. H., Lee, Y. H., . . . Cha, B. S. (2020). Dipeptidyl peptidase-4 inhibitor protects against non-alcoholic steatohepatitis in mice by targeting TRAIL receptor-mediated lipoapoptosis via modulating hepatic dipeptidyl peptidase-4 expression. Scientific Reports, 10(1). https://doi.org/10.1038/s41598-020-75288-y
12. Parks, E., Yki-Järvinen, H., & Hawkins, M. (2017). Out of the frying pan: dietary saturated fat influences nonalcoholic fatty liver disease. The Journal of clinical investigation, 127(2), 454–456. https://doi.org/10.1172/JCI92407
13. Jensen, T., Abdelmalek, M. F., Sullivan, S., Nadeau, K. J., Green, M., Roncal, C., Nakagawa, T., Kuwabara, M., Sato, Y., Kang, D. H., Tolan, D. R., Sanchez-Lozada, L. G., Rosen, H. R., Lanaspa, M. A., Diehl, A. M., & Johnson, R. J. (2018). Fructose and sugar: A major mediator of non-alcoholic fatty liver disease. Journal of hepatology, 68(5), 1063–1075. https://doi.org/10.1016/j.jhep.2018.01.019
14. Endocrine Society (2022). People who consume too much high fructose corn syrup could be at risk for NAFLD. [Press release]. https://www.endocrine.org/news-and-advocacy/news-room/2022/people-who-consume-too-much-high-fructose-corn-syrup-could-be-at-risk-for-nafld
15. Albhaisi, S., & Bajaj, J. S. (2021b). The influence of the microbiome on NAFLD and NASH. Clinical Liver Disease, 17(1), 15–18. https://doi.org/10.1002/cld.1010
16. Bryant, E. (2020). How high fructose may trigger fatty liver disease. NIH Research Matters. Retrieved from https://www.nih.gov/news-events/nih-research-matters/how-high-fructose-intake-may-trigger-fatty-liver-disease