Non-Alcoholic Steatohepatitis (NASH) is a progressive form of liver disease that falls under the umbrella of Non-Alcoholic Fatty Liver Disease (NAFLD). Characterized by the accumulation of fat in the liver, inflammation, and liver cell damage, NASH can advance to more severe conditions such as cirrhosis or liver cancer if not managed properly. This article will systematically explore the causes, symptoms, diagnosis, pathophysiology and prevention strategies, and MIT homeopathy protocol for treatment of NASH.
The precise cause of NASH is not fully understood, but it is closely linked to metabolic syndrome, which includes conditions such as obesity, insulin resistance, high blood pressure, and abnormal cholesterol levels. Other risk factors include genetics, age, and certain medical conditions and medications.
In its early stages, NASH often presents with no noticeable symptoms. As the condition progresses, symptoms such as fatigue, weight loss, and pain in the upper right abdomen may appear. Advanced stages of NASH, leading to cirrhosis, can result in jaundice, swelling in the legs and abdomen, and confusion.
NASH is typically diagnosed through a combination of medical history review, blood tests, imaging studies, and sometimes a liver biopsy. Blood tests may indicate liver dysfunction, while imaging tests like ultrasound, CT scan, and MRI can show fat accumulation in the liver. However, a liver biopsy is the definitive method for diagnosing NASH, as it can assess the degree of inflammation and damage.
PATHOPHYSIOLOGY OF NON-ALCOHOLIC FATTY LIVER DISEASE
The pathophysiology of Non-Alcoholic Steatohepatitis (NASH) is complex and involves multiple pathways leading to liver damage. It is generally considered to evolve from Non-Alcoholic Fatty Liver Disease (NAFLD), a condition characterized by excessive fat accumulation in the liver (steatosis) in the absence of significant alcohol consumption. The progression from simple steatosis to NASH involves not only the accumulation of fat but also inflammation and hepatocyte injury, which can eventually lead to fibrosis, cirrhosis, or hepatocellular carcinoma.
A key player in the development of NASH is insulin resistance, which is often seen in conditions such as obesity and type 2 diabetes. Insulin resistance leads to an increased release of free fatty acids (FFAs) from adipose tissue into the bloodstream. The liver then takes up these FFAs, which contribute to the accumulation of fat within liver cells (hepatocytes). Additionally, insulin resistance impairs the liver’s ability to export fat, exacerbating fat accumulation.
As FFAs accumulate in the liver, they undergo esterification to triglycerides, which in themselves are not particularly toxic. However, not all FFAs are converted into triglycerides; some are shunted into alternative metabolic pathways, leading to the production of toxic lipid metabolites such as diacylglycerol (DAG), ceramides, and reactive oxygen species (ROS). These toxic metabolites can induce lipotoxicity, causing direct injury to hepatocytes, mitochondrial dysfunction, oxidative stress, and eventually apoptosis or necrosis of liver cells.
Diacylglycerol has its critical role in cellular physiology, acting as a precursor for glycerophospholipids and triglycerides, and as a signalling molecule in various intracellular signalling cascades. Dysregulation of DAG level is implicated in the pathogenesis of several diseases, including metabolic disorders and cancers, and liver diseases. Ceramide is a class of lipid molecules known as sphingolipids, which are critical components of cell membranes and play vital roles in regulating cellular functions, including cell signalling, differentiation, proliferation, and programmed cell death (apoptosis). Ceramides have been implicated in inflammatory processes, partly through their ability to modulate cytokine production. Elevated ceramide levels in tissues have been linked to insulin resistance, a hallmark of type 2 diabetes and metabolic syndrome. High levels of ceramides are associated with obesity, diabetes, and metabolic syndrome, contributing to insulin resistance and the development of cardiovascular diseases.
The injury to hepatocytes triggers an inflammatory response. Damaged hepatocytes release cytokines and chemokines that attract immune cells to the liver, including macrophages and T cells. These immune cells further release pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1β), perpetuating the cycle of inflammation and hepatocyte injury.
Oxidative stress plays a significant role in the progression from steatosis to steatohepatitis. The accumulation of toxic lipid metabolites leads to the production of ROS, which can damage cellular proteins, lipids, and DNA. Oxidative stress also contributes to the activation of stellate cells, which are central to the process of fibrogenesis.
The continuous cycle of hepatocyte injury and inflammation stimulates the activation of hepatic stellate cells, which transform into myofibroblast-like cells. These cells are responsible for the production of extracellular matrix proteins, leading to the deposition of collagen and other fibrous tissue in the liver. Over time, this fibrosis can progress to cirrhosis, characterized by the distortion of the liver’s architecture and impaired liver function.
Genetic predispositions and environmental factors also contribute to the pathogenesis of NASH. Variations in genes related to fat metabolism, inflammation, and fibrosis can influence an individual’s susceptibility to NASH. Environmental factors, including diet, physical activity, and gut microbiota composition, play a role in modulating these genetic risks.
The pathophysiology of NASH involves a multifactorial and complex interplay of metabolic dysregulation, lipotoxicity, inflammation, oxidative stress, and fibrosis. Understanding these underlying mechanisms is crucial for the development of targeted therapies and the management of NASH. Ongoing research continues to explore these pathways in greater depth, aiming to identify novel targets for intervention.
The development and progression of Non-Alcoholic Fatty Liver Disease (NAFLD) and its more severe form, Non-Alcoholic Steatohepatitis (NASH), are influenced by various metabolic pathways. The enzymatic activities within these pathways play a crucial role in the pathogenesis of these conditions. Here, we will explore some of the key enzymes and their kinetics involved in NAFLD and NASH, focusing on lipid metabolism, oxidative stress, and fibrosis.
SREBP-1c or Sterol Regulatory Element-Binding Protein 1c is transcription factor regulating the expression of genes involved in fatty acid and triglyceride synthesis. Insulin activates SREBP-1c, leading to increased lipogenesis in the liver. In conditions of insulin resistance, as often seen in NAFLD and NASH, there is an inappropriate activation of SREBP-1c, contributing to the accumulation of fat in the liver.
PNPLA3 is an enzyme involved in triglyceride hydrolysis in hepatocytes and adipocytes. Mutations in PNPLA3 impair its enzymatic activity, leading to increased triglyceride accumulation in liver cells.
CYP2E1 or Cytochrome P450 2E1 is an enzyme involved in the metabolism of fatty acids and generates reactive oxygen species (ROS) as byproducts. In NAFLD and NASH, the upregulation of CYP2E1 leads to oxidative stress, contributing to liver damage and the progression of the disease.
GPx or Glutathione Peroxidase and SOD or Superoxide Dismutase are antioxidant enzymes that help in neutralizing ROS. In NAFLD and NASH, the activity of these enzymes may be decreased, or overwhelmed by the excessive production of ROS, leading to oxidative stress and liver injury.
LOX (Lysyl Oxidase) enzyme plays a role in the cross-linking of collagen and elastin in the extracellular matrix, contributing to the fibrosis seen in advanced NASH. The activity of LOX is increased in liver fibrosis, promoting the accumulation of fibrous tissue.
MMPs are enzymes that degrade extracellular matrix components, while TIMPs inhibit MMPs. The balance between MMPs and TIMPs is crucial for the maintenance of liver architecture. In NASH, this balance is disturbed, often leading to an accumulation of extracellular matrix and progression of fibrosis.
The enzymatic kinetics in NAFLD and NASH can be influenced by several factors, including substrate availability, enzyme concentration, and the presence of activators or inhibitors. For instance, insulin resistance can alter the kinetics of enzymes involved in lipid metabolism by changing the levels of substrates and cofactors. Similarly, oxidative stress can affect the kinetics of antioxidant enzymes through modifications in their structure or expression levels.
The kinetics of these enzymes not only contribute to the development and progression of NAFLD and NASH but also represent potential targets for therapeutic intervention. Understanding the kinetics and regulation of these enzymes can help in designing strategies to modulate their activities, aiming to prevent or treat NAFLD and NASH.
ROLE OF ENZYMES IN NON-ALCOHOLIC FATTY LIVER DISEASE
Enzymes play pivotal roles in these pathways, and their activity can be modulated by different activators and inhibitors. Understanding these can provide insights into potential therapeutic targets for NASH. Here are some key enzymes involved in the causation of NASH, along with their activators and inhibitors:
Acetyl-CoA Carboxylase (ACC) and Fatty Acid Synthase (FAS) are crucial in fatty acid synthesis. Insulin and sterol regulatory element-binding proteins (SREBPs) activate ACC and FAS, leading to increased lipogenesis. AMP-activated protein kinase (AMPK) can inhibit ACC, reducing fatty acid synthesis. Dietary components like omega-3 fatty acids can also inhibit SREBPs.
Carnitine Palmitoyltransferase 1 (CPT1) is involved in the mitochondrial oxidation of long-chain fatty acids. Malonyl-CoA levels regulate CPT1, with decreased levels leading to CPT1 activation and increased fatty acid oxidation. Malonyl-CoA acts as a direct inhibitor of CPT1, reducing fatty acid oxidation.
Cyclooxygenase-2 (COX-2) and Lipoxygenases (LOX) are involved in the synthesis of pro-inflammatory mediators. Inflammatory cytokines can induce the expression of COX-2 and LOX. Nonsteroidal anti-inflammatory drugs (NSAIDs) can inhibit COX-2 activity. LOX inhibitors are being explored as potential therapies for inflammatory diseases.
Protein Kinase B (Akt) and Insulin Receptor Substrate (IRS) are Insulin Signalling Pathway Enzymes. Insulin activates Akt through the IRS, promoting glucose uptake and utilization. In the context of insulin resistance, a hallmark of NASH, the activity of IRS and Akt is impaired. Drugs that improve insulin sensitivity, such as metformin, can indirectly activate these enzymes.
Superoxide Dismutase (SOD), Catalase, and Glutathione Peroxidase (GPx) are key antioxidant enzymes. Antioxidant compounds like vitamin E, selenium (for GPx), and certain phytochemicals can enhance the activity of these antioxidant enzymes. Chronic oxidative stress can overwhelm these enzymes and inhibit their activity. Superoxide dismutase (SOD) is a critical antioxidant enzyme that protects the cell from oxidative stress by catalyzing the conversion of superoxide radicals (O2•-) into oxygen (O2) and hydrogen peroxide (H2O2). Inhibiting SOD can lead to an accumulation of superoxide radicals, resulting in increased oxidative stress and potential cellular damage. While the direct inhibition of SOD is generally not a therapeutic goal due to the protective role of this enzyme, understanding substances that can inhibit SOD is important for recognizing potential toxicities and the mechanisms of oxidative stress-related diseases. Increased oxidative stress from reduced SOD activity is implicated in the pathogenesis of numerous diseases, including neurodegenerative disorders, cardiovascular diseases, and cancer. Therefore, research often focuses on enhancing SOD activity to protect against oxidative stress-related damage.
Diethyldithiocarbamate (DDC) is a copper chelator that is known to inhibit Cu,Zn-SOD (SOD1). It binds to the copper ion in the active site of SOD1, preventing the enzyme from catalyzing the dismutation of superoxide radicals. Hydrogen Peroxide (H2O2) can inhibit SOD activity. Although SOD helps convert superoxide radicals into H2O2, excessive H2O2 can act as a feedback inhibitor. Cyanide can inhibit Cu,Zn-SOD by binding to the copper in the active site. However, cyanide’s high toxicity limits its relevance to experimental settings. Nitric Oxide (NO) can interact with superoxide to form peroxynitrite (ONOO-), a highly reactive and toxic molecule. This reaction competes with the dismutation reaction catalyzed by SOD, effectively reducing SOD activity in conditions of high NO levels. At high concentrations, fluoride ions can inhibit both Cu,Zn-SOD and Mn-SOD (SOD2) activities by interfering with the metal ion cofactors essential for their enzymatic activities.
The complex pathogenesis of NASH involves various enzymatic pathways that regulate lipid metabolism, oxidative stress, inflammation, and insulin sensitivity. Targeting these enzymes through activators or inhibitors presents a promising approach for treating NASH. Many current therapeutic strategies aim to modulate these pathways to reduce liver fat, mitigate inflammation and oxidative stress, and improve insulin sensitivity. Continued research into these enzymes and their regulators is critical for developing effective treatments for NASH.
As per MIT perspective, Molecular imprints of SOD inhibitors such as Diethyldithiocarbamate, Hydrogen peroxide, Potassium cyanide, Fluoric acid etc could be prepared using the process of homeopathic potentization, and could be used to enhance the activity SOD and prevent the harmful effects of superoxides.
ROLE OF METALLIC ELEMENTS IN NON-ALCOHOLIC FATTY LIVER DISEASE
The role of metallic elements in the context of Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) is intriguing, as these elements can significantly influence the pathogenesis and progression of these liver conditions through various mechanisms. Some metallic elements are essential for normal bodily functions, acting as cofactors for enzymes involved in metabolic processes, including those relevant to liver health. However, an imbalance, whether deficiency or excess, can contribute to the development and progression of liver diseases. Below, we explore the roles of several key metallic elements in NAFLD and NASH:
Iron overload is commonly observed in NAFLD and NASH patients and is associated with more severe liver damage and fibrosis. Excess iron can catalyze the formation of reactive oxygen species (ROS) through the Fenton reaction, leading to oxidative stress, lipid peroxidation, and liver injury. On the other hand, iron deficiency has also been noted in some NAFLD cases and might affect liver enzyme activities and metabolic functions.
Zinc is crucial for numerous enzymatic reactions and plays a vital role in maintaining cellular integrity and immune function. Zinc deficiency is prevalent among patients with liver disease and is linked to the progression of NAFLD to NASH. Zinc acts as an antioxidant and anti-inflammatory agent, and its deficiency may impair these protective mechanisms against liver damage.
Copper levels are intricately linked to liver health. Both copper deficiency and excess can be harmful. Copper is a cofactor for enzymes involved in antioxidant defenses (such as superoxide dismutase) and energy metabolism. Altered copper homeostasis can affect these processes, contributing to oxidative stress, inflammation, and metabolic disturbances seen in NAFLD and NASH.
Selenium is a component of selenoproteins, including glutathione peroxidase, an important enzyme in antioxidant defense mechanisms. Selenium deficiency can impair this defense system, leading to increased oxidative stress and inflammation, factors known to contribute to the development and progression of many metabolic diseases.
Elements like zinc and selenium are integral to the antioxidant defense system. Their deficiency can weaken this system, making the liver more susceptible to damage. Many metallic elements act as cofactors for enzymes regulating metabolic pathways. Dysregulation of these enzymes can contribute to the metabolic disturbances associated with NAFLD and NASH.
The balance of metallic elements is crucial for liver health. Both deficiencies and excesses of these elements can contribute to the pathogenesis and progression of NAFLD and NASH through mechanisms like oxidative stress, impaired antioxidant defense, and dysregulation of metabolic enzymes. Understanding these roles highlights the importance of monitoring and managing the levels of these metallic elements in individuals with or at risk of liver diseases. Further research into the precise mechanisms and therapeutic targeting of metal homeostasis may provide new avenues for the prevention and treatment of NAFLD and NASHMetallic elements involved in redox reactions (like iron and copper) can contribute to oxidative stress and lipid peroxidation, key mechanisms in liver injury in NAFLD and NASH. As per MIT view, molecular imprinted forms of Copper and Zinc will reduce the oxidative stress, an prevent lipid peroxidation, thereby reducing the chances of NAFLD and NASH.
ROLE OF PHYTOCHEMICALS IN NON-ALCOHOLIC FATTY LIVER DISEASE
Phytochemicals, the bioactive compounds found in plants, have attracted considerable attention for their health benefits, including their potential roles in the prevention and treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH). Unlike the factors that directly cause NAFLD and NASH, such as poor diet, sedentary lifestyle, insulin resistance, and genetic predisposition, phytochemicals primarily offer protective and therapeutic effects. Here, we explore the roles of various phytochemicals in influencing the pathophysiology of NAFLD and NASH:
Polyphenols are a diverse group of phytochemicals found in fruits, vegetables, tea, coffee, and wine. They have antioxidant, anti-inflammatory, and antifibrotic properties, which are beneficial in NAFLD and NASH. Resveratrol, found in grapes and berries, improves insulin sensitivity, reduces lipid accumulation in hepatocytes, and diminishes oxidative stress. Curcumin, from turmeric, has been shown to reduce liver inflammation and fibrosis in NASH through its potent antioxidant and anti-inflammatory actions. Silymarin, derived from milk thistle, is known for its hepatoprotective properties, improving liver function, and reducing liver fibrosis.
Flavonoids, present in fruits, vegetables, and certain beverages like tea and red wine, exert anti-inflammatory, antioxidant, and antidiabetic effects. Quercetin reduces lipid accumulation in the liver and inflammation. Epigallocatechin gallate (EGCG), a major component of green tea, has been shown to decrease liver fat content and inflammation.
Found in garlic and onions, Organosulfur Compounds, including allicin and diallyl sulfide, have been reported to possess hepatoprotective properties. They may help reduce liver enzyme levels, inhibit lipid synthesis, and promote antioxidant defenses.
Terpenoids, including saponins and limonoids found in various fruits and medicinal plants, have been shown to possess hepatoprotective, antioxidant, and anti-inflammatory effects. They could play a role in modulating lipid metabolism and enhancing insulin sensitivity.
Phytochemicals exert their beneficial effects on NAFLD and NASH through several mechanisms. Many phytochemicals influence lipid homeostasis by regulating the expression of genes involved in fatty acid synthesis and oxidation. Some phytochemicals improve insulin sensitivity, thereby reducing the hepatic fat accumulation associated with insulin resistance. Phytochemicals often have strong antioxidant properties, neutralizing reactive oxygen species (ROS) and reducing oxidative stress. They also modulate the activity of inflammatory pathways and cytokine production. By inhibiting stellate cell activation and the expression of pro-fibrotic genes, some phytochemicals can mitigate liver fibrosis, a critical step in the progression from NAFLD to NASH.
The intake of phytochemicals, through a diet rich in fruits, vegetables, and other plant-based foods, may offer protective benefits against the development and progression of NAFLD and NASH. These compounds target multiple pathogenic pathways involved in these liver diseases, including lipid metabolism, insulin resistance, oxidative stress, inflammation, and fibrosis. While the evidence supporting the role of phytochemicals is promising, further clinical research is needed to fully understand their therapeutic potential and to develop specific dietary or supplementation recommendations for individuals with or at risk for NAFLD and NASH.
While many phytochemicals are celebrated for their health benefits, including hepatoprotective effects, it is also important to recognize that not all phytochemicals are beneficial. Some can be harmful to the liver, especially when consumed in large quantities or under certain conditions. Pyrrolizidine Alkaloids (PAs) are found in certain plants belonging to the Boraginaceae, Asteraceae (Compositae), and Fabaceae families. These compounds can be hepatotoxic, causing veno-occlusive disease (VOD) or hepatic sinusoidal obstruction syndrome (HSOS), which leads to liver congestion, hepatomegaly, and sometimes severe liver damage. Herbal teas and supplements containing comfrey (Symphytum officinale), borage (Borago officinalis), and certain other herbs have been implicated.
Aflatoxins are mycotoxins produced by Aspergillus species of fungi, which can contaminate crops such as corn, peanuts, and tree nuts. Although not phytochemicals themselves, they are often discussed in the context of plant-based dietary risks. Aflatoxins are potent carcinogens and have been linked to an increased risk of hepatocellular carcinoma (HCC).
Found in the Aristolochia and Asarum genera, aristolochic acids have been associated with aristolochic acid nephropathy (AAN), which can lead to renal failure and urothelial cancer. These compounds can also cause liver damage and have been implicated in cases of herbal hepatotoxicity.
Safrole is a phytochemical found in sassafras and certain other plants. It was once used as a flavoring agent but is now recognized as a hepatocarcinogen, leading to its ban in commercially mass-produced foods and beverages in many countries.
Supplements containing Germander (Teucrium chamaedrys) have been associated with cases of hepatotoxicity. It is believed that the toxic effects are due to the presence of furan-containing diterpenes, which can induce liver damage.
The mechanisms by which these phytochemicals exert their toxic effects on the liver vary. Some phytochemicals can directly damage liver cells, leading to necrosis or apoptosis. The generation of reactive oxygen species (ROS) and the depletion of antioxidants can result in oxidative damage to cellular components. Interference with DNA repair and cell cycle control: Certain compounds can interfere with genomic stability, increasing the risk of mutations and cancer. Obstruction of sinusoidal blood flow: Compounds like pyrrolizidine alkaloids can cause occlusion of the small hepatic veins, leading to congestion and liver damage.
While phytochemicals offer numerous health benefits, it is crucial to be aware of those that can cause liver damage. This underscores the importance of moderation, cautious use of herbal supplements, and adherence to safety guidelines to minimize the risk of hepatotoxicity. Always consult healthcare professionals before starting any new supplement, especially if there is a pre-existing liver condition.
ROLE OF CHEMICAL DRUGS IN NON-ALCOHOLIC FATTY LIVER DISEASE
Chemical drugs, while designed to treat or manage specific health conditions, can sometimes have adverse effects on the liver, one of the body’s crucial organs for metabolizing and detoxifying substances. Hepatotoxicity from chemical drugs is a significant concern and can range from mild liver enzyme elevations to severe liver failure. Some drugs are known for their potential to cause liver damage, and their use is monitored closely.
Acetaminophen (Paracetamol) is a widely used over-the-counter pain reliever and fever reducer. While safe at recommended doses, overdose of acetaminophen is a leading cause of acute liver failure in the United States and other countries. Toxicity occurs because the drug’s metabolic pathways get overwhelmed, leading to accumulation of a toxic metabolite that causes liver cell damage.
Certain antibiotics are associated with liver damage. Amoxicillin/clavulanate (Augmentin) can cause liver inflammation and damage, typically reversible upon discontinuation. Macrolides such Erythromycin can cause acute liver injury.Tetracyclines can cause fatty liver (specially when given intravenously.
Some drugs used to treat epilepsy, such as valproate (Valproic acid) and carbamazepine, have been associated with hepatotoxicity. The risk may be higher in children, those on multiple antiepileptics, or individuals with certain metabolic disorders.
NSAIDs like diclofenac, ibuprofen, and naproxen can cause liver damage in some individuals. While less common than gastrointestinal side effects, NSAID-induced hepatotoxicity can range from mild liver enzyme elevations to fulminant hepatic failure.
Statins are cholesterol-lowering medications that occasionally cause liver enzyme elevations, which are usually temporary and mild. However, severe liver damage from statins is rare.
Isoniazid, rifampicin, and pyrazinamide, used to treat tuberculosis, can cause hepatotoxicity. The risk is higher when these drugs are used in combination, which is common in tuberculosis treatment.
Many drugs used in chemotherapy, such as methotrexate, azathioprine, and cisplatin, can cause various degrees of liver damage. Monitoring liver function tests during treatment is essential.
Used for muscle building and performance enhancement, anabolic steroids can cause liver damage, including the development of liver tumors.
The mechanisms by which drugs can cause liver injury include direct hepatocyte toxicity, immune-mediated liver injury, disruption of bile acid secretion leading to cholestasis, and mitochondrial damage. The liver injury can be predictable (dose-dependent) or idiosyncratic (not dose-dependent and often allergic in nature).
ROLE OF FOOD HABITS IN NON-ALCOHOLIC FATTY LIVER DISEASE
Food habits play a crucial role in liver health, influencing the risk of liver diseases such as Non-Alcoholic Fatty Liver Disease (NAFLD), Non-Alcoholic Steatohepatitis (NASH), cirrhosis, and liver cancer. The liver is pivotal in metabolizing nutrients, detoxifying harmful substances, and producing bile for digestion, making its health vital for overall well-being. Below are the effects of various food habits on liver health:
Foods rich in omega-3 fatty acids, like fish, nuts, and seeds, can reduce liver fat levels and inflammation, beneficial for those with NAFLD and NASH. A diet high in fibre from fruits, vegetables, and whole grains can aid in maintaining a healthy weight and reducing the risk of NAFLD. Regular, moderate coffee consumption has been associated with a lower risk of chronic liver disease and cirrhosis, likely due to its anti-inflammatory and antioxidant properties. Fruits and vegetables rich in antioxidants can help combat oxidative stress in the liver, protecting against liver cell damage.
Diets high in sugar and refined carbs can lead to obesity, insulin resistance, and the accumulation of fat in the liver, contributing to NAFLD and NASH. While not a food, alcohol consumption significantly affects liver health. Heavy and chronic drinking can lead to alcoholic liver disease, fatty liver, hepatitis, and cirrhosis. Consuming high levels of saturated fats (found in red meat, butter, and cheese) and trans fats (found in processed foods) can increase liver fat, contributing to liver disease. High salt intake can lead to hypertension and exacerbate liver damage, especially in those with existing liver conditions. Processed foods often contain additives and preservatives that can increase the liver’s workload, potentially leading to liver damage over time.
Poor dietary habits can lead to the accumulation of fat in the liver, causing NAFLD and progressing to NASH. Diets low in antioxidants can lead to oxidative stress, contributing to liver inflammation and damage. High intake of sugars and refined carbs can lead to insulin resistance, a key factor in the development of NAFLD. Consuming processed foods and excessive alcohol can increase the level of toxins the liver must process, potentially overwhelming its detoxification mechanisms.
Food habits have a direct and profound impact on liver health. Adopting a balanced diet rich in omega-3 fatty acids, fiber, and antioxidants while avoiding excessive alcohol, sugar, refined carbs, and unhealthy fats can support liver health and reduce the risk of liver diseases. For those with existing liver conditions, tailored dietary recommendations from healthcare professionals are crucial for managing their health.
ROLE OF VITAMINS IN NON-ALCOHOLIC FATTY LIVER DISEASE
Vitamins play a crucial role in maintaining liver health and preventing liver diseases. The liver is involved in the metabolism of vitamins, and adequate intake of certain vitamins is essential for liver function, detoxification processes, and protection against liver damage.
Vitamin A is vital for immune function, vision, cell growth, and organ function. The liver stores a significant amount of vitamin A, releasing it as needed. Excessive intake of vitamin A, particularly in supplement form, can lead to liver toxicity and cirrhosis, especially in adults with liver disease or those consuming alcohol excessively. Therefore, balance is key.
Vitamin D has anti-inflammatory and immune-modulating effects, which are beneficial for individuals with liver diseases. It also helps in managing insulin resistance, a contributor to NAFLD. Vitamin D deficiency is common in people with chronic liver disease, partly because the diseased liver can struggle to convert vitamin D into its active form.
Vitamin E is a powerful antioxidant that helps protect cells from oxidative stress, which can lead to liver inflammation and damage. Studies have shown that vitamin E supplementation can improve liver function in non-diabetic adults with NAFLD. It is important to consume vitamin E in recommended amounts, as high doses can have adverse effects, including bleeding risks.
Vitamin B12 and Folate (B9) are essential for DNA synthesis and repair. They play a role in homocysteine metabolism, high levels of which are associated with liver disease and damage. Niacin (B3) converts nutrients into energy and plays a role in DNA repair and stress responses. Excessive amounts, especially from supplements, can lead to liver toxicity. Riboflavin (B2), Pyridoxine (B6) and Thiamine (B1) are important for energy metabolism and the breakdown and elimination of toxins from the body. Thiamine, in particular, is critical for those with alcohol dependence to prevent Wernicke-Korsakoff syndrome, a brain disorder due to thiamine deficiency.
Vitamin C is an antioxidant that helps protect the liver from oxidative stress and supports the liver in detoxifying the body. It also aids in the absorption of iron, reducing the risk of iron overload, which can damage the liver. Vitamin C is generally safe, but excessive amounts can cause gastrointestinal distress and, in people with a history of kidney stones, could potentially increase the risk of stone formation.
Vitamin K is essential for blood clotting and bone metabolism. Liver disease can impair the body’s ability to use vitamin K effectively, leading to an increased risk of bleeding. Individuals with liver disease should monitor their vitamin K intake, especially if they are on anticoagulation therapy, as it can interact with medications.
Vitamins play various roles in supporting liver health, from antioxidative protection to energy metabolism and detoxification processes. Adequate intake through a balanced diet is crucial for liver health, although supplementation might be necessary in some cases, such as with vitamin D deficiency or specific B-vitamin requirements. However, it’s essential to approach supplementation cautiously, as excessive intake of certain vitamins, like A and E, can lead to adverse liver effects. Always consult healthcare professionals before starting any new supplement, particularly for individuals with existing liver conditions or those at risk of liver disease.
There is no specific medication in modern medicines approved for the treatment of NASH. Management focuses on controlling the underlying conditions that contribute to fat accumulation in the liver. This includes weight loss through diet and exercise, control of diabetes, and reduction of cholesterol levels. In some cases, medications may be prescribed to address these issues. For advanced stages of NASH, liver transplantation may be considered.
Preventing NASH involves addressing its risk factors: Consuming a balanced diet rich in fruits, vegetables, whole grains, and healthy fats can help manage body weight and reduce liver fat. Regular physical activity helps in weight management and can reduce liver fat. Managing conditions such as diabetes, hypertension, and cholesterol levels is crucial in preventing NASH. Even though NASH is a non-alcoholic liver disease, drinking alcohol can exacerbate liver damage.
Non-Alcoholic Steatohepatitis is a serious liver condition that requires attention and management to prevent progression to more severe liver diseases. Understanding the risk factors and adopting a healthy lifestyle are key in preventing and managing NASH. Early diagnosis and treatment are critical, emphasizing the importance of regular medical check-ups for those at risk. With ongoing research, it is hoped that more specific treatments for NASH will be developed in the future.
MIT APPROACH TO TREATMENT OF NON-ALCOHOLIC FATTY LIVER DISEASE
MIT or Molecular Imprints Therapeutics refers to a scientific hypothesis that proposes a rational model for biological mechanism of homeopathic therapeutics.
According to MIT hypothesis, potentization involves a process of ‘molecular imprinting’, where in the conformational details of individual drug molecules are ‘imprinted or engraved as hydrogen- bonded three dimensional nano-cavities into a supra-molecular matrix of water and ethyl alcohol, through a process of molecular level ‘host-guest’ interactions. These ‘molecular imprints’ are the active principles of post-avogadro dilutions used as homeopathic drugs. Due to ‘conformational affinity’, molecular imprints can act as ‘artificial key holes or ligand binds’ for the specific drug molecules used for imprinting, and for all pathogenic molecules having functional groups ‘similar’ to those drug molecules. When used as therapeutic agents, molecular imprints selectively bind to the pathogenic molecules having conformational affinity and deactivate them, thereby relieving the biological molecules from the inhibitions or blocks caused by pathogenic molecules.
According to MIT hypothesis, this is the biological mechanism of high dilution therapeutics involved in homeopathic cure. According to MIT hypothesis, ‘Similia Similibus Curentur’ means, diseases expressed through a particular group of symptoms could be cured by ‘molecular imprints’ forms of drug substances, which in ‘molecular’ or crude forms could produce ‘similar’ groups of symptoms in healthy individuals. ‘Similarity’ of drug symptoms and diseaes indicates ‘similarity’ of pathological molecular inhibitions caused by drug molecules and pathogenic molecules, which in turn indicates conformational ‘similarity’ of functional groups of drug molecules and pathogenic molecules. Since molecular imprints of ‘similar’ molecules can bind to ‘similar ligand molecules by conformational affinity, they can act as the therapeutics agents when applied as indicated by ‘similarity of symptoms. Nobody in the whole history could so far propose a hypothesis about homeopathy as scientific, rational and perfect as MIT explaining the molecular process involed in potentization, and the biological mechanism involved in ‘similiasimilibus- curentur, in a way fitting well to modern scientific knowledge system.
If symptoms expressed in a particular disease condition as well as symptoms produced in a healthy individual by a particular drug substance were similar, it means the disease-causing molecules and the drug molecules could bind to same biological targets and produce similar molecular errors, which in turn means both of them have similar functional groups or molecular conformations. This phenomenon of competitive relationship between similar chemical molecules in binding to similar biological targets scientifically explains the fundamental homeopathic principle Similia Similibus Curentur.
Practically, MIT or Molecular Imprints Therapeutics is all about identifying the specific target-ligand ‘key-lock’ mechanism involved in the molecular pathology of the particular disease, procuring the samples of concerned ligand molecules or molecules that can mimic as the ligands by conformational similarity, preparing their molecular imprints through a process of homeopathic potentization upto 30c potency, and using that preparation as therapeutic agent.
Since individual molecular imprints contained in drugs potentized above avogadro limit cannot interact each other or interfere in the normal interactions between biological molecules and their natural ligands, and since they can act only as artificial binding sites for specific pathogentic molecules having conformational affinity, there cannot by any adverse effects or reduction in medicinal effects even if we mix two or more potentized drugs together, or prescribe them simultaneously- they will work.
Based on the understanding evolving from above discussions regarding molecular mechanism of Fatty Liver Disease, this disease could be prevented or cured using homeopathic potentized forms of Insulin 30, 30, Cortisol 30, Adrenalin 30, Diacylglycerol 30, Ceramide 30, Tumour necrosis factor-alpha (TNF-α) 30, Interleukin 30, Selenium 30, Kali Cyanatum 30, Acid Fluoricum 30, Diethylcarbamate 30, Cuprum Met 30, Ferrum Met 30, Zincum Met 30, secale cor 30, Aristolochia Serpentaria 30 , Safrole 30, Teucrium 30, Acetaminophen 30, Valproic acid 30, Ibuprofen 30, Isoniazid 30, Methotrxate 30 etc. These drugs could be used as single medicines or as combinations of multiple remedies, as required by the case.
REDEFINING HOMEOPATHY 