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.

Natural Treatments for Non Alcoholic Fatty Liver Disease (NAFLD)

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.

Natural Treatments for Non Alcoholic Fatty Liver Disease (NAFLD)

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?

1. 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

   
   
   
   

2. 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

   
   

3. Reduced Glutathione, 250 mg twice daily, taken only after trying the NAC and L-theanine

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.

David S. Klein, MD Functional Medicine Physician

David S. Klein, MD FACA FACPM

David S. Klein, MD, FACA, FACPM

1917 Boothe Circle

Longwood, Florida 32750

Tel: 407-679-3337

Fax: 407-678-7246

Why Are Elevated Uric Acid Levels Linked to an Increased Risk of Heart Attack?

Uric Acid can cause Heart Attack

Why is Uric Acid level important enough that I should read this? How does Uric Acid Cause Heart Disease & Heart Attack?

In short, modest elevations in uric acid level put you, your family, and your friends at increased risk of developing preventable heart disease, heart attack and sudden death.

1. Have you ever wondered why some of your acquaintances have suddenly had heart attacks or dropped dead without much notice that they had heart disease?

2. Have you ever wondered why heart disease occurs without having particularly high cholesterol levels?

If this gets your attention, please read on........

Uric acid, a byproduct of purine metabolism, has been increasingly recognized as a potential contributor to cardiovascular diseases, including heart attacks. Elevated serum uric acid (SUA) levels, also known as hyperuricemia, have long been associated with gout, but emerging evidence suggests a significant link between hyperuricemia and adverse cardiovascular outcomes. This relationship is particularly concerning given the increasing prevalence of hyperuricemia worldwide.

Hyperuricemia has been implicated in the development of endothelial dysfunction, which plays a critical role in the initiation and progression of atherosclerosis—a major precursor to myocardial infarction. At relatively modest concentrations, Uric Acid crystalizes and these small crystals can damage the inner lining of the arteries, destroying the lining called the Glycocalyx.

Elevated uric acid levels can induce oxidative stress and inflammation in endothelial cells, impairing nitric oxide bioavailability and promoting vascular stiffness. These mechanisms establish a direct pathophysiological link between uric acid and cardiovascular risk (Becker & Jolly, 2006).

What Uric Acid level seems to be the threshold for causing heart disease? This is where the fun begins.

Numerous epidemiological studies have shown a correlation between elevated SUA levels and an increased risk of coronary artery disease and heart attacks. A meta-analysis of over 16 studies involving more than 200,000 participants found that individuals with hyperuricemia had a 20-40% higher risk of coronary heart disease compared to those with normal SUA levels (Li et al., 2014).

The risk of heart disease increases and the risk of serious damage begins at the level of 5.5 mg/dl. This is well below the level seen as 'high' or consistent with Gout. (please see my other Blog on Uric Acid for the data & reference)

This association remained significant even after adjusting for traditional cardiovascular risk factors such as hypertension, diabetes, and hyperlipidemia.

The role of uric acid as an independent risk factor for heart attacks has been debated, partly because hyperuricemia often coexists with other metabolic disorders. For instance, hyperuricemia is frequently associated with hypertension, insulin resistance, and obesity, all of which are established cardiovascular risk factors (Feig et al., 2008). While these conditions may confound the relationship, experimental evidence supports a direct role for uric acid in cardiovascular pathophysiology.

Uric acid has also been linked to the activation of the renin-angiotensin-aldosterone system (RAAS) and increased production of inflammatory cytokines, further exacerbating cardiovascular risk. Elevated SUA levels can lead to renal microvascular damage, promoting hypertension—a well-known risk factor for myocardial infarction (Mazzali et al., 2001). This interaction highlights the systemic impact of hyperuricemia on cardiovascular health.

Clinical studies have suggested that reducing uric acid levels through pharmacological interventions, such as allopurinol or febuxostat, may mitigate cardiovascular risk. For instance, a randomized controlled trial found that allopurinol improved endothelial function and reduced arterial stiffness in patients with hyperuricemia (Kanbay et al., 2011). While these findings are promising, further research is needed to confirm the cardiovascular benefits of uric acid-lowering therapy.

Gender differences in the relationship between uric acid and cardiovascular risk have also been observed. Women, particularly premenopausal women, appear to have a weaker association between hyperuricemia and heart attacks compared to men, possibly due to the uricosuric effects of estrogen. However, postmenopausal women show a similar risk profile to men, underscoring the complex interplay between sex hormones and uric acid metabolism (Chen et al., 2015).

Hyperuricemia has also been associated with the formation of microvascular thrombi, which can contribute to acute coronary syndromes. Uric acid crystals can activate the NLRP3 inflammasome, leading to the release of interleukin-1β and subsequent inflammatory cascades that destabilize atherosclerotic plaques (Martinon et al., 2006). These processes further elucidate the mechanistic link between uric acid and myocardial infarction.

Despite the growing evidence, some experts argue that uric acid may serve more as a marker of cardiovascular risk rather than a causative factor. This perspective emphasizes the need for well-designed longitudinal studies and clinical trials to disentangle the complex relationship between SUA levels and heart attacks (Kuwabara et al., 2018).

In conclusion, elevated uric acid levels are strongly associated with an increased risk of heart attack through multiple mechanisms, including endothelial dysfunction, oxidative stress, and inflammation. While hyperuricemia is often intertwined with other cardiovascular risk factors, it may also independently contribute to myocardial infarction.

Addressing hyperuricemia through lifestyle modifications and pharmacological interventions could potentially reduce cardiovascular risk, but further research is essential to validate these strategies.

What can I realistically do to address this potential problem?

1. Get your uric acid level checked regularly. At my practice, Stages of Life Medical Institute, we check our patients every 3 to 6 months.

   
   

2. Maintain your level below 5.4

   
   

3. My preferred medication is Allopurinol. Starting dosage is 100 mg tablet, 2 in the morning. Titrate the dosage upward after subsequent blood work confirms the level and suggests a change, usually an increase in dosage.

   
   

4. Eat sensibly. Go to your favorite search engine and read about what foods are good for patients with gout, and you are well on your way to getting this under control.

   
   

5. In my practice, I have found that the CRP levels, used to look for inflammation decrease substantially when the uric acid levels are lowered below 4.2 mg/dl.

   
   

References

1. Becker, M. A., & Jolly, M. (2006). Hyperuricemia and associated diseases. Rheumatic Disease Clinics of North America, 32(2), 275-293.

2. Li, M., Hou, W., Zhang, X., Hu, L., Tang, Z., & Wang, C. (2014). Hyperuricemia and risk of stroke: a systematic review and meta-analysis of prospective studies. Atherosclerosis, 232(2), 265-270.

3. Feig, D. I., Kang, D. H., & Johnson, R. J. (2008). Uric acid and cardiovascular risk. New England Journal of Medicine, 359(17), 1811-1821.

4. Mazzali, M., Hughes, J., Kim, Y. G., et al. (2001). Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension, 38(5), 1101-1106.

5. Kanbay, M., Ozkara, A., Selcoki, Y., et al. (2011). Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearance, and proteinuria in patients with normal renal functions. International Urology and Nephrology, 39(4), 1227-1233.

6. Chen, L., Zhu, W., & Chen, Z. (2015). Gender and age specific prevalence of hyperuricemia and its associated risk factors in Chinese adults: A longitudinal study. BMC Public Health, 15(1), 537.

7. Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006). Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature, 440(7081), 237-241.

8. Kuwabara, M., Niwa, K., Nishi, Y., et al. (2018). Relationship between serum uric acid levels and cardiovascular disease risk factors in a Japanese cohort. Journal of Cardiology, 71(3), 283-288.

9. Borghi, C., & Cicero, A. F. G. (2016). Serum uric acid and cardiovascular risk: state of the art and future perspectives. Current Cardiology Reports, 18(2), 118.

10. Gagliardi, A. C., Miname, M. H., & Santos, R. D. (2009). Uric acid: A marker of increased cardiovascular risk. Atherosclerosis, 202(1), 11-17.

David S. Klein, MD FACA FACPM

David S. Klein, MD, FACA, FACPM

1917 Boothe Circle

Longwood, Florida 32750

Tel: 407-679-3337

Fax: 407-678-7246

Unveiling the Mysteries: The Profound Healing Potential of Berberine Unveiled. Lower Blood Sugar, naturally!

Stages of LIfe Vitamins, pharmaceutical grade supplements

How does Berberine lower blood sugar and reduce triglycerides & cholesterol?

Berberine, a bioactive compound extracted from various plants, has intrigued the health and wellness community for its impressive healing properties.

Berberine is an isoquinoline alkaloid derived from the roots and stem bark of the Berberis L. plant. It is an antihyperglycemic drug that inhibits the efficiency of disaccharidases, reducing glucose transport through the intestinal epithelium.

This golden yellow alkaloid has been used in traditional medicine for centuries, especially in Chinese and Ayurvedic practices. With increasing interest in herbal remedies, berberine is being regarded as a powerful natural healer. In this post, we explore berberine's numerous benefits, mechanisms of action, and practical applications.

What is Berberine?

Berberine is a natural compound chiefly found in plants like Berberis vulgaris (barberry), Coptis chinensis (Chinese goldthread), and Hydrastis canadensis (goldenseal).

Important to note, is that the amount of the alkaloid varies from species to species, variety to variety. This unique bioactive agent has garnered a reputation for its varied pharmacological effects, with roots in traditional medicine due to its antimicrobial, anti-inflammatory, and blood sugar-regulating properties.

The extraction process of Berberine from natural sources.

Many health enthusiasts consider berberine one of the most potent natural supplements for various conditions, such as type 2 diabetes and high cholesterol. Its diverse composition enables it to influence several physiological pathways, making it a versatile compound for boosting health.

How Does Berberine Work?

Berberine's effectiveness stems from its ability to influence multiple cellular pathways. Primarily, it activates an enzyme called AMP-activated protein kinase (AMPK), crucial for maintaining energy balance and metabolic regulation. By triggering AMPK, berberine enhances glucose absorption in cells and boosts fat metabolism, which is particularly beneficial for people with insulin resistance.

Research shows that berberine can modify the gut microbiota, which is important for metabolic health. For example, a study found that berberine increased the levels of beneficial bacteria by 34%, promoting better digestion and nutrient absorption that supports overall health.

Health Benefits of Berberine

Blood Sugar Regulation

Berberine's ability to manage blood sugar is one of its most significant benefits. Studies indicate that berberine can lower fasting blood glucose levels by approximately 20% and improve insulin sensitivity by around 30%. For individuals with type 2 diabetes, these effects can be transformative, providing a natural approach to blood sugar control.

Cholesterol and Heart Health

In terms of heart health, berberine appears to improve lipid profiles significantly. Research has shown it can reduce total cholesterol levels by 22%, LDL (bad) cholesterol by 25%, and triglycerides by 30%, while increasing HDL (good) cholesterol by 15%. These changes suggest that incorporating berberine might lower the risk of cardiovascular diseases.

Weight Management

The association between berberine and weight management is gaining ground. Studies show that when combined with a healthy diet and exercise, berberine can help reduce body weight by as much as 5% over a three-month period. This effect results from its ability to enhance fat metabolism and curb fat storage.

Antimicrobial and Anti-Inflammatory Properties

Berberine is well-known for its antimicrobial properties, proving effective against a range of pathogens, including bacteria and fungi. For instance, it has been shown in laboratory settings to inhibit Staphylococcus aureus, a common bacterium responsible for various infections.

Its anti-inflammatory effects are equally remarkable. Chronic inflammation can contribute to health issues like arthritis and heart disease. Berberine's ability to reduce inflammation markers by 20% in some studies showcases its potential in alleviating chronic conditions.

Practical Applications of Berberine

Supplementation

Berberine comes in several forms, including capsules and tinctures. A common recommendation for optimal supplementation ranges from 500 mg to 1500 mg daily, often split into multiple doses. Initiating a supplementation plan should always be done in consultation with a healthcare provider to tailor it to individual health needs.

Berberine 500 mg Capsules

Dietary Sources

Including berberine-rich foods can complement supplementation. Foods derived from barberry or goldenseal are good choices, although the concentration of berberine is generally lower than in supplement form, which may necessitate additional supplementation for desired health effects. Basically, it is impractical to obtain sufficient berberine from ordinary food sources.

Lifestyle Interventions

To enhance the efficacy of berberine, integrating a holistic approach to health is essential. Adopting a balanced diet, engaging in regular physical activity, and managing stress significantly amplifies its positive impacts. Activities like yoga, meditation, and prioritizing sleep can further support overall wellness.

Safety and Considerations

Berberine is typically safe for most people, yet it can interact with certain medications like blood thinners and diabetes treatments. Side effects, including gastrointestinal discomfort such as bloating or constipation, may occur, more commonly, the consumer will initially experience loosening of their bowel movements. Weight loss can be expected, although it tends to be modest, at first.

As with all interventions of this nature, it is best to consult with your healthcare professional before starting any new supplement is advisable to ensure it aligns well with your health circumstances.

Embracing the Power of Berberine

Berberine is an intriguing compound with significant healing potential. Its abilities to regulate blood sugar, improve cholesterol levels, aid in weight management, and combat infections position it as an essential ingredient in contemporary health practices. As research continues to illuminate its benefits, incorporating berberine into a balanced lifestyle may enhance overall health.

By understanding the healing characteristics of berberine, individuals can take informed steps toward natural remedies that support their well-being. Through thoughtful supplementation, dietary adjustments, and lifestyle improvements, we can unlock the numerous advantages berberine offers, enriching our journey toward better health.

More to come! Berberine may decrease the incidence of cancer, and interestingly, it may assist in prolonging survival if you happen to suffer from cancer.

David S. Klein, MD and the Stages of Life Team

David Stephen Klein, MD, FACA, FACPM

1917 Boothe Circle

Longwood, Florida 32750

407-679-3337

www.suffernomore.com