N-Acetyl Cysteine (NAC) and benefits for patients with Non-Alcoholic Fatty Liver Disease (NAFLD)

Natural Treatments for Non Alcoholic Fatty Liver Disease (NAFLD)

What is "NAC?"

N-Acetylcysteine (NAC) is a compound known for its role as a precursor to glutathione, a key antioxidant that mitigates oxidative stress. It is a remarkable compound, quite 'natural' and present in human physiology.

Of note, it is particularly important in the control and/or treatment of many liver and pancreatic disease states and conditions.

Non Alcoholic Fatty Liver Disease (NAFLD)

Recent research highlights its potential benefits in the treatment of non-alcoholic fatty liver disease (NAFLD), a common liver disorder characterized by the accumulation of fat in hepatocytes without significant alcohol consumption. Below, the benefits of NAC in NAFLD management are discussed in detail.

Why do you care? Well, fatty liver can lead directly to cirrhosis of the liver.

The Benefits of NAC in the treatment of control of NAFLD

1. Reduction of Oxidative Stress

Oxidative stress is a hallmark of NAFLD, contributing to liver damage and progression to non-alcoholic steatohepatitis (NASH). NAC, by replenishing intracellular glutathione levels, reduces oxidative stress, thereby protecting hepatocytes from damage. Studies indicate that improved antioxidant capacity can halt or even reverse the progression of fatty liver

disease.

2. Anti-Inflammatory Properties

Inflammation plays a pivotal role in the progression of NAFLD to NASH. NAC has demonstrated anti-inflammatory effects through the inhibition of pro-inflammatory cytokines like TNF-alpha and IL-6. This property helps mitigate liver inflammation, reducing the risk of fibrosis and cirrhosis.

3. Improved Insulin Sensitivity

NAFLD is closely associated with insulin resistance, a condition that exacerbates hepatic fat accumulation. NAC has been shown to enhance insulin sensitivity by reducing oxidative stress and inflammation in insulin-responsive tissues, including the liver, thereby addressing one of the root causes of NAFLD.

4. Lipid Metabolism Regulation

Dysregulated lipid metabolism contributes significantly to NAFLD. NAC influences lipid profiles by decreasing serum triglycerides and low-density lipoprotein (LDL) levels while increasing high-density lipoprotein (HDL) levels. These changes help reduce hepatic steatosis and improve overall liver health.

5. Fibrosis Prevention

Advanced NAFLD often leads to liver fibrosis, a precursor to cirrhosis. NAC helps inhibit fibrogenesis by reducing oxidative stress and inflammation, two key drivers of fibrosis. Furthermore, it modulates hepatic stellate cell activity, which is responsible for extracellular matrix deposition during fibrosis.

6. Hepatoprotective Effects in Drug-Induced Liver Injury

Many patients with NAFLD have co-existing conditions requiring pharmacological interventions, which may exacerbate liver damage. NAC is widely recognized for its hepatoprotective role in drug-induced liver injury, particularly in acetaminophen toxicity, suggesting its utility in protecting the liver from additional insults in NAFLD.

7. Enhanced Mitochondrial Function

Mitochondrial dysfunction is a critical factor in NAFLD progression. NAC improves mitochondrial bioenergetics by maintaining glutathione levels, reducing reactive oxygen species (ROS), and enhancing ATP production. This restoration of mitochondrial function can halt liver damage and promote recovery.

8. Synergistic Effects with Other Therapies

When used in combination with lifestyle changes or pharmacological treatments, NAC enhances their efficacy. For instance, its antioxidant properties can augment the effects of vitamin E or pioglitazone, common treatments for NAFLD, providing a more comprehensive therapeutic approach.

9. Safety and Tolerability

NAC has a favorable safety profile, even at high doses, making it a viable long-term treatment option for NAFLD. Its minimal side effects and wide availability add to its appeal as an adjunctive therapy for managing the condition.

10. Potential Role in Advanced Stages of NAFLD

While most treatments focus on early-stage NAFLD, NAC has shown promise in addressing advanced stages, including NASH and early fibrosis. Its broad mechanism of action, targeting oxidative stress, inflammation, and fibrogenesis, makes it a versatile option for comprehensive liver health management.

General References

What can I do to reduce the severity of NAFLD?

NAC 500 mg is most frequently recommended to my patients, to be taken 3 times daily. Breakfast, Dinner and Bed time.

N-acetyl cysteine for NAFLD
To it, I frequently add L-Theanine 200 mg at bed time, to treat subclinical hepatitis and elevated liver enzymes.

L-Theanine for non alcoholic Fatty liver disease
Reduced Glutathione, 250 mg twice daily, taken only after trying the NAC and L-theanine

Reduced Glutathione for NAFLD — Glutathione for NAFLD

REFERENCES:

1. Angulo, P. (2002). Nonalcoholic fatty liver disease. New England Journal of Medicine, 346(16), 1221-1231.

2. Day, C. P., & James, O. F. W. (1998). Steatohepatitis: A tale of two "hits". Gastroenterology, 114(4), 842-845.

3. Sanyal, A. J., et al. (2001). Oxidative stress and hepatic apoptosis in non-alcoholic fatty liver disease. Journal of Clinical Investigation, 108(7), 1071-1078.

4. Pessayre, D., et al. (2005). Mitochondria in steatohepatitis. Seminars in Liver Disease, 25(1), 41-54.

5. Nagy, L. E. (2003). Recent insights into the role of the innate immune system in the development of alcoholic liver disease. Experimental Biology and Medicine, 228(8), 882-890.

6. Polyzos, S. A., et al. (2010). Nonalcoholic fatty liver disease: The pathogenetic roles of insulin resistance and adipocytokines. Current Molecular Medicine, 10(6), 579-588.

7. Younossi, Z. M., et al. (2016). Global epidemiology of NAFLD-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology, 64(1), 73-84.

8. Brunt, E. M., et al. (1999). Nonalcoholic steatohepatitis: A proposal for grading and staging the histological lesions. American Journal of Gastroenterology, 94(9), 2467-2474.

9. Chalasani, N., et al. (2018). The diagnosis and management of nonalcoholic fatty liver disease. Practice Guidelines, AASLD.

10. Marí, M., et al. (2006). Mitochondrial glutathione, a key survival antioxidant. Antioxidants & Redox Signaling, 8(7-8), 1373-1385.