Reverse Nonalcoholic Fatty Liver Damage

Most people have never heard of NAFLD.

Yet nearly one in four adults in the U.S. has nonalcoholic fatty liver disease (NAFLD).^1-4

In the long term, NAFLD can cause fibrosis (scarring) of the liver, significantly impairing normal liver function.^5-7

Advanced scarring, known as cirrhosis, is irreversible and can lead to liver failure.

The only treatment at that point is a liver transplant.⁸

Normal ways to address NAFLD include diet and lifestyle changes, and weight loss.

Innovative approaches include the medication metformin and certain nutrients.

Specific probiotics can now be added to this list.

In two clinical trials of people with NAFLD, a carefully designed blend of probiotics and a prebiotic decreased a marker of liver damage and reduced levels of fibrosis (scarring) from moderate or almost severe to normal.^9,10

These findings suggest that the probiotic-prebiotic blend not only stopped the progression of the liver disease, but even reversed existing liver damage.

What Is Nonalcoholic Fatty Liver Disease?

Fat accumulation and inflammation in the liver can lead to chronic liver damage, scarring, and eventual liver failure.

In the past, alcohol abuse and viral hepatitis were the leading causes of chronic liver disease and death from liver cirrhosis.

NAFLD is now the number one chronic liver disease, and cause of liver cirrhosis deaths, in the United States.^11,12

Back in the 1980s, experts first started to report on a newly recognized phenomenon: fat accumulating in the liver with no connection to alcohol intake or viral infection.¹³

The earlier phases of this condition are now referred to as nonalcoholic fatty liver disease (NAFLD), which accounts for about 75% of all chronic liver disease in the U.S.¹⁴ It affects roughly 25% of adults, both in the U.S. and across the world.^4,11

When the disease becomes more severe, it is called nonalcoholic steatohepatitis (NASH). At this point, it can lead to liver cirrhosis, which is severe scarring of and damage to the liver.²

This damage to the liver is irreversible and can lead to complete liver failure.⁸

NAFLD Smolders Before Symptom Onset

NAFLD is common in obese adults, with around 50%-90% showing signs of fatty liver as the disease advances.¹⁵

But fatty liver disease can affect anyone with a metabolic disease such as metabolic syndrome or type II diabetes.¹⁶

In its early phases, NAFLD rarely causes specific signs or symptoms.¹⁷

Symptoms of early-stage NAFLD may include:¹⁷

• Abdominal (belly) weight gain
• Increase in cholesterol
• Hypertension
• Pain in the upper right abdomen
• Persistent tiredness/fatigue
• Binge eating

By the time major NAFLD symptoms manifest, significant scarring and hardening of the liver have already been inflicted. Symptoms of a more advanced disease may include:¹⁸

• Abdominal swelling (ascites)
• Swollen lower legs (edema)
• Enlarged blood vessels beneath the skin’s surface
• Enlarged spleen
• Red palms
• Yellowing of the skin and eyes (jaundice)

At advanced stages, NAFLD causes damage to the brain, vasculature, and other essential tissues.

An Interesting Finding

Researchers noted that fatty liver and liver damage are often seen in patients suffering from gastro-intestinal conditions, including inflammatory bowel and celiac disease.^19,20

One thread that ties together metabolic disorders and nonalcoholic fatty liver disease is an unhealthy gut microbiota or microbiome.

The gut microbiota or gut flora is the population of different types of microorganisms—primarily bacteria—that naturally inhabit our gut.

A healthy, diverse microbiota is thought to promote health, but an unhealthy one is associated with the opposite.^21,22

The Gut-Liver Connection

Here’s why the connection between gut health and liver health is so strong:

Most of the blood draining from the gastrointestinal tract (or gut) travels directly to the liver before entering general circulation.

This means that potentially harmful microorganisms, toxins, and other substances travel first to the liver after leaving the intestines.

An unhealthy mix of microorganisms in the gut also leads to inflammation in the intestines and what’s known as "leaky gut."²³ That causes more and more microorganisms and toxic compounds to make their way directly to the liver.

The result of this toxic flow from the intestines causes oxidative stress and chronic inflammation, which contribute to nonalcoholic fatty liver disease and long-term liver damage.

Animal studies have shown that worsening of the gut microbiota can worsen fatty liver, while increasing beneficial bacteria can improve the health of the liver.^24,25

As a result, improving the health of the microbiota and the gut with probiotics has become a major target of research into fighting fatty liver disease.

A Probiotic-Prebiotic Combination

Despite over four decades of research, there are still no medications approved by the U.S. Food and Drug Administration (FDA) to treat fatty liver disease.

Treatment is usually weight loss, through a combination of a healthy diet and exercise.

While weight loss is often crucial, scientists designed a blend of microorganisms they believed would favorably impact the liver, reducing risk and severity of nonalcoholic fatty liver disease (NAFLD).

In two clinical trials, a specific probiotic formulation has shown promising results for improving liver health.^9,10

This formula is a blend of seven different probiotic strains:

• Lactobacillus casei PXN® 37,
• Lactobacillus rhamnosus PXN® 54,
• Streptococcus thermophilus PXN® 66,
• Bifidobacterium breve PXN® 25,
• Lactobacillus acidophilus PXN® 35,
• Bifidobacterium longum PXN® 30, and
• Lactobacillus bulgaricus PXN® 39.

To provide maximum benefits, probiotics need to thrive and outcompete harmful bacteria.

For this reason, scientists combined these probiotics with fructooligosaccharide (FOS), a form of dietary fiber found in many plants. FOS serves as a prebiotic, a nutrient that "feeds" healthy bacteria.

With this extra energy source, the healthy bacteria are better equipped to survive and improve liver function and heal the liver.

Combating Fatty Liver: The First Study

Two human trials evaluated the use of this probiotic-prebiotic combination on subjects with a diagnosis of nonalcoholic fatty liver disease.

In the first, overweight and obese adults with NAFLD were randomized to receive the probiotic-prebiotic blend or a placebo for 28 weeks.⁹

At the study’s start, every subject had elevated liver enzyme levels in the blood, evidence of ongoing liver damage.

Over the course of the study, enzyme levels in the placebo group didn’t change. But those receiving the probiotic blend had multiple liver enzymes fall into the normal range.

In addition, all subjects at the start of the study had above normal levels of fibrosis in the liver, as identified by a specialized ultrasound technology specifically designed to assess liver fibrosis and fattiness. On average, this scarring was moderate to almost severe.

The group receiving the probiotic-prebiotic blend dropped their fibrosis scores all the way into the normal range. The placebo group had no significant change by the end of the study.

These findings suggest that the probiotic-prebiotic blend stopped the progression of liver disease and reversed liver damage that was already present.

Combating Fatty Liver: The Second Study

The second study had a similar design, but enrolled adults with NAFLD who were not overweight or obese.¹⁰

The findings echoed those from the first study. Evidence of ongoing liver damage was reduced significantly in those receiving the probiotic-prebiotic blend, and fibrosis scores dropped into the normal range.²⁶

In a further benefit, in both studies the group taking the probiotic-prebiotic blend had a substantial decline in C-reactive protein blood levels. C-reactive protein is a marker of systemic inflammation, indicating that overall inflammation was reduced.

This probiotic-prebiotic blend offers a way to lessen or even reverse the damage done by nonalcoholic fatty liver disease.

Summary

Nonalcoholic fatty liver disease affects roughly a fourth of the adult population in the U.S.

This progressive liver condition can lead to liver cirrhosis and liver failure, requiring a transplant. It is also a major contributor to the development of liver cancer.

Research has found a link between the microbiome and liver health.

Two clinical studies confirm that a specially formulated blend of seven probiotics and a prebiotic can help stop the progression of NAFLD and reverse the damage already done.

If you have any questions on the scientific content of this article, please call a Life Extension Wellness Specialist at 1-866-864-3027.

References

1. Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016 Jul;64(1):73-84.
2. Available at: https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/definition-facts. Accessed February 11, 2022.
3. Estes C, Razavi H, Loomba R, et al. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2018 Jan;67(1):123-33.
4. Alkhouri N, Scott A. An Update on the Pharmacological Treatment of Nonalcoholic Fatty Liver Disease: Beyond Lifestyle Modifications. Clin Liver Dis (Hoboken). 2018 Apr;11(4):82-6.
5. Calzadilla Bertot L, Adams LA. The Natural Course of Non-Alcoholic Fatty Liver Disease. Int J Mol Sci. 2016 May 20;17(5):774.
6. Musso G, Gambino R, Cassader M, et al. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011 Dec;43(8):617-49.
7. Noureddin M, Vipani A, Bresee C, et al. NASH Leading Cause of Liver Transplant in Women: Updated Analysis of Indications For Liver Transplant and Ethnic and Gender Variances. Am J Gastroenterol. 2018 Nov;113(11):1649-59.
8. Available at: https://www.uptodate.com/contents/cirrhosis-beyond-the-basics. Accessed October 2, 2019.
9. Eslamparast T, Poustchi H, Zamani F, et al. Synbiotic supplementation in nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled pilot study. Am J Clin Nutr. 2014 Mar;99(3):535-42.
10. Mofidi F, Poustchi H, Yari Z, et al. Synbiotic supplementation in lean patients with non-alcoholic fatty liver disease: a pilot, randomised, double-blind, placebo-controlled, clinical trial. Br J Nutr. 2017 Mar;117(5):662-8.
11. Available at: https://medlineplus.gov/fattyliverdisease.html. Accessed February 17, 2022.
12. Paik JM, Golabi P, Biswas R, et al. Nonalcoholic Fatty Liver Disease and Alcoholic Liver Disease are Major Drivers of Liver Mortality in the United States. Hepatol Commun. 2020 Jun;4(6):890-903.
13. Ludwig J, Viggiano TR, McGill DB, et al. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980 Jul;55(7):434-8.
14. Hassan K, Bhalla V, El Regal ME, et al. Nonalcoholic fatty liver disease: a comprehensive review of a growing epidemic. World J Gastroenterol. 2014 Sep 14;20(34):12082-101.
15. Divella R, Mazzocca A, Daniele A, et al. Obesity, Nonalcoholic Fatty Liver Disease and Adipocytokines Network in Promotion of Cancer. Int J Biol Sci. 2019;15(3):610-6.
16. Godoy-Matos AF, Silva Junior WS, Valerio CM. NAFLD as a continuum: from obesity to metabolic syndrome and diabetes. Diabetol Metab Syndr. 2020 2020/07/14;12(1):60.
17. Available at: https://www.liverhealthuk.com/post/2017/07/16/early-signs-of-non-alcoholic-fatty-liver-disease-nafld. Accessed February 21, 2021.
18. Available at: https://www.mayoclinic.org/diseases-conditions/nonalcoholic-fatty-liver-disease/symptoms-causes/syc-20354567. Accessed February 21, 2022.
19. Chao CY, Battat R, Al Khoury A, et al. Co-existence of non-alcoholic fatty liver disease and inflammatory bowel disease: A review article. World J Gastroenterol. 2016 Sep 14;22(34):7727-34.
20. Reilly NR, Lebwohl B, Hultcrantz R, et al. Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease. J Hepatol. 2015 Jun;62(6):1405-11.
21. Park JW, Kim SE, Lee NY, et al. Role of Microbiota-Derived Metabolites in Alcoholic and Non-Alcoholic Fatty Liver Diseases. Int J Mol Sci. 2021 Dec 31;23(1).
22. Vallianou N, Christodoulatos GS, Karampela I, et al. Understanding the Role of the Gut Microbiome and Microbial Metabolites in Non-Alcoholic Fatty Liver Disease: Current Evidence and Perspectives. Biomolecules. 2021 Dec 31;12(1).
23. Tripathi A, Debelius J, Brenner DA, et al. The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol. 2018 Jul;15(7):397-411.
24. Burz SD, Monnoye M, Philippe C, et al. Fecal Microbiota Transplant from Human to Mice Gives Insights into the Role of the Gut Microbiota in Non-Alcoholic Fatty Liver Disease (NAFLD). Microorganisms. 2021 Jan 19;9(1).
25. Safari Z, Gerard P. The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD). Cell Mol Life Sci. 2019 Apr;76(8):1541-58.
26. Available at: https://www.mskcc.org/pdf/cancer-care/patient-education/understanding-your-fibroscan-results. Accessed February 17, 2022.
27. Magosso E, Ansari MA, Gopalan Y, et al. Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: a randomised placebo-controlled clinical trial. Nutr J. 2013 Dec 27;12(1):166.
28. Pervez MA, Khan DA, Ijaz A, et al. Effects of Delta-tocotrienol Supplementation on Liver Enzymes, Inflammation, Oxidative stress and Hepatic Steatosis in Patients with Nonalcoholic Fatty Liver Disease. Turk J Gastroenterol. 2018 Mar;29(2):170-6.
29. Pervez MA, Khan DA, Slehria AUR, et al. Delta-tocotrienol supplementation improves biochemical markers of hepatocellular injury and steatosis in patients with nonalcoholic fatty liver disease: A randomized, placebo-controlled trial. Complement Ther Med. 2020 Aug;52:102494.
30. Dajani AI, Abuhammour A. Agents for the treatment of fatty liver disease: focus on essential phospholipids. Drugs & Therapy Perspectives. 2021;37(6):249-64.
31. Maev IV, Samsonov AA, Palgova LK, et al. Effectiveness of phosphatidylcholine as adjunctive therapy in improving liver function tests in patients with non-alcoholic fatty liver disease and metabolic comorbidities: real-life observational study from Russia. BMJ Open Gastroenterol. 2020;7(1):e000368.
32. Maev IV, Samsonov AA, Palgova LK, et al. Effectiveness of phosphatidylcholine in alleviating steatosis in patients with non-alcoholic fatty liver disease and cardiometabolic comorbidities (MANPOWER study). BMJ Open Gastroenterol. 2020;7(1):e000341.
33. Cacciapuoti F, Scognamiglio A, Palumbo R, et al. Silymarin in non alcoholic fatty liver disease. World J Hepatol. 2013 Mar 27;5(3):109-13.
34. Federico A, Trappoliere M, Tuccillo C, et al. A new silybin-vitamin E-phospholipid complex improves insulin resistance and liver damage in patients with non-alcoholic fatty liver disease: preliminary observations. Gut. 2006 Jun;55(6):901-2.
35. Loguercio C, Andreone P, Brisc C, et al. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Free Radic Biol Med. 2012 May 1;52(9):1658-65.
36. Zhong S, Fan Y, Yan Q, et al. The therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease: A meta-analysis (PRISMA) of randomized control trials. Medicine (Baltimore). 2017 Dec;96(49):e9061.
37. Millea PJ. N-acetylcysteine: multiple clinical applications. Am Fam Physician. 2009 Aug 1;80(3):265-9.
38. Bajt ML, Knight TR, Lemasters JJ, et al. Acetaminophen-induced oxidant stress and cell injury in cultured mouse hepatocytes: protection by N-acetyl cysteine. Toxicol Sci. 2004 Aug;80(2):343-9.
39. de Oliveira CP, Simplicio FI, de Lima VM, et al. Oral administration of S-nitroso-N-acetylcysteine prevents the onset of non alcoholic fatty liver disease in rats. World J Gastroenterol. 2006 Mar 28;12(12):1905-11.
40. Mehta K, Van Thiel DH, Shah N, et al. Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants. Nutr Rev. 2002 Sep;60(9):289-93.