Effect of Dried Moringa Seeds on Non-alcoholic Fatty Liver Disease - A randomized clinical trial

Introduction

The liver is the largest solid organ, weighs approximately 1500g and one of the most important organ that has many vital functions such as metabolism of nutrients and excretion of waste metabolites. Hepatocytes represent 60 % of the liver‘s cells and about 80 % of the liver‘s total cell mass. Most of the liver‘s synthetic and metabolic capabilities stem from the work of hepatocytes.

Functions of Liver:

The liver has many important functions like secretion of bile, metabolism of bilirubin, vascular and hematologic functions, metabolism of nutrients, metabolic detoxification and storage of minerals and vitamins, it has hemostatic functions, synthesizes prothrombin, fibrinogen, and clotting factors. It is a storage of minerals and vitamins which stores certain vitamins and minerals, including iron and copper. The liver can store vitamins B12 and D for several months and vitamin A for several years. The liver also stores vitamins E and K and has immunologic functions as the liver contain cells involved in adaptive and innate immunity (Ozougwu, J. C. (2017).

Prevalence of Liver disease accounts for a significant burden of disease and costs worldwide. Currently the major cause of acute liver disease is viral hepatitis, while alcohol and viral hepatitis are the main causes of chronic liver disease. It accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1 million due to viral hepatitis and hepatocellular carcinoma. Approximately 2 billion adults are obese or overweight and over 400 million have diabetes; both of which are risk factors for non-alcoholic fatty liver disease and hepatocellular carcinoma (Asrani, S. K.,et al. (2019).

Background:

Nonalcoholic fatty liver disease (NAFLD) is a dynamic chronic liver disease that develops in close association with metabolic irregularities. Between 2016 and 2019, the global prevalence among adults was reported as 38% and among children and adolescents it was about 10% (Younossi, Z. M., et al. 2023). Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the major health concern worldwide. These two diseases have similar pathological spectra, ranging from simple steatosis to hepatitis to cirrhosis and hepatocellular carcinoma with basic differences only in their etiology. The incidence and prevalence of NAFLD is on the rise with each passing decade. Presently, 25%-35% and 5%-15% of the general population of Western and Asian countries, respectively, are affected by this disease. This proportion is even higher in people with type 2 diabetes (60%-70%) and in those who are obese or morbidly obese (75%-92%) compared to the general population. Although most people with excessive alcohol or calorie intake display abnormal fat accumulation in the liver (simple steatosis), a small percentage develops progressive liver disease.

Despite understanding much of the pathophysiology of both diseases, there is still no effective treatment for either disease. The focus of treatment for NAFLD is on weight loss, exercise and the use of insulin sensitizers. Removal of the cause would be the most efficient way of treating both diseases (Singh, S., Osna, N. A., & Kharbanda, K. K. (2017).

Diet in Fatty Liver: The relationship between nutrients/food/meals, dietary patterns and NAFLD has been widely studied in the last decade. Research into the role of nutrition for the management of NAFLD patients is a major challenge. This is particularly important because lifestyle modifications including diet, exercise and weight loss have been found to be effective in controlling NAFLD. The long-term effects of calorie-restricted diets result in an improvement in several features of NAFLD (Berná, G., & Romero‐Gomez, M. (2020). Despite several adverse outcomes, no pharmacological treatments currently exist to treat nonalcoholic steatohepatitis, the progressive form of NAFLD. Therefore, the main treatment is the pursuit of a healthy lifestyle for both children and adults, which includes a diet rich in fruits, nuts, seeds, whole grains, fish and chicken and avoiding overconsumption of ultra-processed food, red meat, sugar-sweetened beverages and foods cooked at high heat (Younossi, Z. M., et al. 2023).

Moringa seeds: Moringa oleifera seeds are a promising resource for food and non-food applications, due to their content of monounsaturated fatty acids with a high monounsaturated/saturated fatty acids (MUFA/SFA) ratio, sterols and tocopherols, as well as proteins rich in sulfated amino acids. All parts of the Moringa tree (leaves, seeds, roots and flowers) are suitable for human and animal consumption. The seeds have attracted scientific interest as M. oleifera seed kernels contain a significant amount of oil (up to 40%) with a high-quality fatty acid composition (oleic acid > 70%) and, after refining, a notable resistance to oxidative degradation. Its properties make it suitable for both human consumption and commercial purposes. Indeed, Moringa oil could be a good substitute for olive oil in the diet as well as for non-food applications.

Chemical Characteristics of Seeds: Apart from the oil, the seed has high protein content, on average 31.4%, whereas carbohydrate, fibre and ash contents are 18.4%, 7.3% and 6.2%, respectively. Thus, the defatted seeds provide an economical source of protein for use as a food supplement to traditional diets to increase protein intake, also seeds have a high content of methionine and cysteine, close to that reported for milk and eggs with free of trypsin inhibitor and urease activity, confirming the high protein digestibility (93%).

Benefits of Moringa seeds and Medicinal Uses of Moringa Seeds: In addition to their macronutrient, several studies have found good antioxidant activity and have isolated phytochemical compounds that, because of their biological properties, can be used as nutraceutical molecules. The total phenolic content of seeds has been found to be in the range of 4581–4953 mg/100 g, similar to leaf amounts. The flavonoids are represented by catechin, epicatechin, quercetin and kaempferol, present mainly in the bound form, also contains important bioactive compounds including alkaloids, glucosinolates, isothiocyanates and thiocarbamates.

Folk medicine uses raw or crushed seeds as a decoction for treating stomach pain, ulcers, poor vision, joint pain and for aiding digestion. The seed extract has been found to possess good antimicrobial activity against numerous bacterial and fungal species. For this reason, some authors have speculated the use of these phytochemicals as an alternative to traditional therapies as they can be pharmacologically effective with low or no side effects. The seeds’ antimicrobial activity is also related to the presence of a short cationic protein. This protein causes bacterial cell damage through rapid flocculation and the fusion of cell inner and outer membranes. One study done on rats, reported that M. oleifera seeds possess hepatoprotective, anti-inflammatory and anti-fibrotic properties against CCl4-induced liver damage and fibrosis.

Purpose of this study:

Thus we have seen that non-alcoholic fatty lever disease (NAFLD) is widely spread all over the world and diet has a very important role to recover from it. The seeds of M. oleifera contain numerous phytochemical compounds with pharmacological activity. However, this activity is reported in the literature only for animal and cellular models, there has been no study of their pharmacological activity in humans. Despite the relatively diffuse use of Moringa seeds and their oil in traditional medicine, no pharmacological activity study has been conducted on humans. Therefore, we will conduct a clinical trial with nutrition intervention by dried moringa seeds powder in Non-alcoholic Fatty Liver patients with the purpose to see any recovery in NAFLD.