Clinical Evidence of Moringa Leaves on Glycemic Control: A Review of Animal and Human Studies Volume 52- Issue 3

Amina Faheem¹, Sanaullah Iqbal¹* and Umer Faheem²

• ¹Department of Food Science and Human Nutrition, Faculty of Bio-Sciences, University of Veterinary and Animal Sciences [UVAS], Lahore, Pakistan
• ²Department of Marketing, Dr Hasan Murad School of Management [HSM], University of Management and Technology [UMT], Lahore, Pakistan

Received: August 14, 2023;   Published: August 22, 2023

*Corresponding author: Prof. Dr. Sanaullah Iqbal, email:sanaullah.iqbal@uvas.edu.pk

DOI: 10.26717/BJSTR.2023.52.008249

Abstract PDF

The incidence of type 2 diabetes has been increased substantially in the last two decades. Improving diet and lifestyle along with functional foods can prevent the increasing incidence of diabetes. Moringa is a functional food that contains flavonoids mainly quercetin, kaempferol and chlorogenic acid which are responsible for hypoglycemic effects. Moreover, moringa is gaining popularity regarding its health benefits as a super food among Asian population but the scientific evidence is still lacking. The present review aims to present the existing literature published regarding the role of moringa leaves in glycemic control in various animal models and human studies limited to time frame from 2007 to 2022. Numerous research had emphasized on the role of biologically active components present in moringa leaves in the prevention of various diseases such as non-insulin dependent diabetes mellitus. In the conducted studies, large number of animal trails has reported antihyperglycemic activity of moringa. In humans, there is limited evidence regarding hypoglycemic effect of moringa. It is difficult to reach a conclusion and hence, there is a need to conduct well designed clinical trials of appropriate duration regarding the effect of moringa leaf powder supplementation on glycemic control in humans.

Keywords: Moringa Oleifera; Moringa Leaf; Diabetes; Glycemic Control; Animal Models; Effect; Mechanisms

Abbreviations: ORAC: Oxygen Radical Absorbance Capacity; SGLT1: Sodium Glucose Linked Type 1 Transporters; ERK: Extracellular Signal-Regulated Kinase; ROS: Reactive Oxygen Species; MESH: Medical Subject Headings; GK: Goto-Kakizaki; STZ: Streptozotocin; HFD: High Fat Diet

Globally, diabetes mellitus is a major public health problem. There are two types of diabetes. Type 1 diabetes which is also known as insulin dependent diabetes is characterized by lack of insulin secretion due to autoimmune destruction of pancreatic beta cells. It accounts for 5 to 10% of all diabetic cases (Kharroubi and Darwish, [1]). Type 2 diabetes mellitus is also known as non-insulin dependent diabetes. Around 90 to 95% of diagnosed cases of diabetes are of type 2 diabetes. It is a chronic metabolic disorder characterized by insulin resistance, deficiency of insulin secretion from pancreas and increased plasma glucose levels. Type two diabetic individuals are at increased risk of developing serious complications such as dyslipidemia and cardiovascular complications leading to mortality and morbidity (Galicia-Garcia, et al. [2]). The incidence of type 2 diabetes has been increased substantially in the last two decades (Danaei, et al. [3]). Around 415 million people worldwide are living with diabetes. In developing countries, such as Pakistan, prevalence of diabetes mellitus is reported to be 17.1% around 148% higher than previously stated (IDF, [4]).

South Asians have increased risk for the development of non-communicable diseases such as diabetes and cardiovascular diseases. Due to urbanization, dietary patterns have shifted towards increased consumption of refined carbohydrates, sweets, desserts, sugary drinks, fat and animal foods with a decrease in the intake of fiber thus increasing the incidence of non-communicable diseases including diabetes (Faheem, et al. [5,6]). Improving diet and lifestyle along with functional foods can prevent the increasing incidence of diabetes. In recent years, functional foods have gained popularity regarding health benefits beyond basic nutritional value among South Asians (Alissa, et al. [7]). Numerous researches had emphasized on the role of biologically active components present in functional foods in the prevention of various diseases such as non-insulin dependent diabetes mellitus. Regular consumption of functional food can reduce the occurrence of diabetes mellitus by improving insulin sensitivity, lipid profile and antioxidant status of body. Moreover, functional foods are cost effective and without side effects as compared to pharmacological interventions (Alkhatib, et al. [8]).

Moringa Nutritional Composition

Moringa is also known as a drumstick tree among Asian population. Moringa is a functional food that has been widely used as a medical herb to treat hyperglycemia and diabetes (Leone, et al. [9]). Moringa tree have numerous nutritional as well as medicinal health benefits. Moringa is a miracle plant with extraordinary nutritional, therapeutic and antioxidant properties. It is an excellent source of protein, vitamins, minerals and phytochemicals, containing 92 nutrients, 46 anti-oxidants and 36 anti-inflammatory compounds. This composition makes it a “Super Food”. Many studies had shown that moringa leaves are a rich source of macronutrients, micronutrients and other bioactive components which are essential for proper functioning of the human body (Islam, et al. [10]). The leaves of moringa are consumed raw or as a powder, as they are rich in minerals (calcium, iron, potassium, and magnesium) as well as beta-carotene, b-complex vitamins, vitamin C and E, polyphenols and antioxidants (Falowo, et al. [11]). Chromium, magnesium and zinc present in moringa multiplies the effect of insulin to reduce blood sugar level. The B-vitamins, antioxidants and omega-3 fatty acids present aids in diabetes control. Being super anti-oxidant, moringa reduces oxidative stress and control free radicals. Free radicals are unstable compounds, produced during metabolism in body. These must be controlled otherwise damage cellular and mitochondrial membranes resulting oxidative stress, early aging and atherosclerosis / heart diseases. Moringa is the queen of anti-oxidants, has highest Oxygen Radical Absorbance Capacity (ORAC) value among plants. It has 46 different anti-oxidants which modulate enzymatic activity, facilitate detoxification and promote anti-tumoral activities. Moringa contains important flavonoids like catechins, polyphenols, beta-sitosterol, quercetin and vitamin K reduce that fat deposits in blood vessels and act as cardio-protector, preventing one the major complication associated with diabetes mellitus. It aids in wound healing due to presence of high amount of vitamin C. Due to vitamin A and plenty of anti- oxidants, Moringa not only reduce the rate of the aging process but also improves the condition of hair, skin as well as eyes. Thus, it also reduces the risk of diabetes complications such as retinopathy.

Mode of Action of Moringa Leaves in Improving Glycemic Control

Moringa leaf contains flavonoids mainly quercetin, kaempferol and chlorogenic acid which are responsible for hypoglycemic effects in different animal models. These compounds reduce the intestinal absorption of glucose by inhibiting sodium glucose linked type 1 transporters (SGLT1) present in the mucosa of small intestine (Singh, et al. [12]). Quercetin provides protection to beta cells (pancreas) from oxidative damage and stimulates insulin secretion via phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 pathway (Youl, et al. [13]). Existing evidence from studies has shown that chlorogenic acid in moringa decreases glycogenolysis and gluconeogenesis by inhibiting glucose-6-phosphate translocase (Mbikay,[14]). Epidemiological researches have reported certain insulin-like proteins in moringa that contribute to the hypoglycemic effect (Vargas- Sanchez, et al. [15]). The flavonoids and polyphenols present in moringa leaves exhibit hypoglycemic effects by inhibiting the activity of enzymes such as α-glucosidase and α-amylase which are responsible for the hydrolysis of starch (Adisakwattana, et al. [16]). Bioactive components present in moringa leaves such as kaempferol, gallic acid, quercetin, ellagic acid and chlorogenic acid, act as a protective agent against Reactive Oxygen Species (ROS). These compounds prevents proteins, lipids and DNA from free radical oxidation. These reactive oxygen species causes oxidative damage to beta cells and thus lead to insulin resistance (Sangkitikomol, et al. [17]). Considering the current evidence, moringa contains flavonoids and isothiocynates which are responsible for its anti-inflammatory effects (Xu, et al. [18]). (Figure 1) represents the role of active ingredients moringa leaves in glycemic control.

Figure 1

Search Strategy

This review of literature reviews all papers published regarding effect of moringa leaves on blood glucose levels. A thorough search was done using multiple databases and manual tracking of citations in selected articles was also performed. Google Scholar, PubMed, Science Direct, Cochrane Library, Food Science and Technology Abstracts, MEDLINE and Scopus were the search engines used to find articles limited to time frame 2007 to 2022. Boolean operators were used for more focused and productive search and to avoid unnecessary interruption.

Keyword and MeSH Terms

The search strategy followed departs from the more general aspects like the nutritional profile of moringa and progressively moves the focus of interest towards the main study object, which is hypoglycemic effect of moringa leaves in various animal models and human studies. The search involved the following key words: moringa oleifera, moringa leaf, diabetes, glycemic control, animal models, effect, and mechanisms. These keywords were also used as Medical Subject Headings (MeSH).

Inclusion and Exclusion Criteria

The present review included peer reviewed articles in the English language within time frame 2007 to 2022 fulfilling the criteria described below.

• Studies that used moringa leaf powder and moringa leaves extract as an intervention in humans.
• Studies that used moringa leaf powder and moringa leaves extract as an intervention in animal models.

Studies that used seeds, bark and parts other than leaves of moringa tree as a intervention. Studies which were not in English language and those with intervention period less than two days in different rodent models were excluded from the review. Editorials, letters, conference abstracts and unpublished studies were excluded.

This present systematic review was conducted according to the PRISMA guidelines. The flowchart of our literature search is shown in (Figure 2). A total of 200 articles were searched through multiple databases. After removal of duplicate articles, there were 65 articles screened for included in the review. Majority of studies were excluded because they failed to report plasma glucose levels. Therefore, the present review included 25 studies (20 in animal model and 5 in humans).

Figure 2

Clinical Evidence of Moringa on Glycemic Control

Recently, functional foods are gaining popularity regarding prevention of diabetes because of the bioactive components present in them and limited side effects as compared to pharmacological interventions (Abd El Latif, et al. [19]). Moringa leaves had been studied for antidiabetic, anti-inflammatory and antioxidant effects. Several animal trails have investigated moringa mechanism of action and its role in various disease models such as diabetes mellitus. Many animal trails have reported anti hyperglycemic effects of moringa. But there are few clinical trials regarding hypoglycemic effect of moringa in humans (Vargas-Sánchez, et al. [15]).

Clinical Trials in Humans

To investigate the effect of moringa on plasma glucose levels, ten healthy participants within the age group 20 to 40 years were selected. After every 2 weeks the selected participants received moringa leaf powder capsules at an increasing dosage of 1 gram, 2 gram and 4 grams. Insulin and blood glucose levels were measured at baseline and 0.5, 1, 1.5, 2, 4, and 6 hours after moringa capsule ingestion. The results concluded that there was no reduction in plasma glucose levels. The current study reported significant improvement in insulin levels of the subjects. Authors reported no negative effects after moringa ingestion (Anthanont, et al. [20]). A single oral dose of 500 mg moringa aqueous leaf extract was given to healthy volunteers. The study reported no significant reduction in blood glucose levels of the subjects after moringa ingestion. There was a significant improvement in antioxidant markers (Ngamukote, et al. [21)). A single oral dose of 20 g of moringa leaf powder supplemented with meal was given to diabetic patients. There was a specific meal for the participants comprising 80 gram of rice and 160 gram of camel meat stew. Authors reported significant reduction in blood glucose levels of the subjects at 90, 120 min and 150 min after moringa ingestion. Postprandial glucose response peaked earlier with lower increments at 90-, 120-, and 150-min. authors also reported significant reduction alpha amylase activity (Leone, et al. [9]). The three studies with single dose administration are shown in (Table 1).

Table 1: Human Studies with Single Dose Administration (Moringa Leaf Powder).

A study was conducted to evaluate the antihyperglycemic effect of moringa. Treatment group was administered 8 gram moringa leaves powder in three divided doses for one month. The study concluded significant reduction in fasting and post prandial plasma glucose levels of the subjects in experimental group receiving moringa supplementation. The authors reported no adverse effects after moringa ingestion (Kumari, et al. [22]). A randomized controlled clinical study was conducted to evaluate the effect of moringa leaf capsules and placebo in type 2 diabetes mellitus patients. There were 16 participants in both groups. Experimental group received 8 gram moringa leaf powder per day (4 gram moringa leaf powder capsules, twice daily) for one month. The results concluded that there was no significant reduction in fasting plasma glucose levels and HbA1C levels between groups. After moringa leaf powder ingestion, there were no changes reported in individuals’ creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. There was no adverse effect regarding consumption of moringa leaf powder (Taweerutchana, et al. [23]). These clinical trials of short duration are shown in (Table 2).

Table 2: Short Duration Human Trial of Moringa Leaf Powder (Only one month & HBA1c Parameter was not accurately measured).

Clinical Trials in Animals

A study conducted on diabetic male Goto-Kakizaki (GK) rats and nondiabetic male Wistar rats showed improved in plasma glucose levels after moringa leaf powder ingestion. The control groups orally received 2 gram/kg body weight of single dose of glucose. Experimental group received 200 mg moringa leaf powder per kg body weight with 2 gram/kg body weight of glucose solution. Plasma glucose levels were measured at 10, 20, 30, 45, 60, 90 and 120 min from the tail vein using blood glucose meter. Moringa leaf powder significantly reduced plasma glucose levels at 20, 30, 45 and 60 min in GK rats. Moringa significantly decreased stomach emptying (Ndong, et al. [24]). A three week supplementation of moringa leaf powder in metabolic syndrome induced wistar rats reported improvement in blood glucose level. 700 mg/kg/day of moringa leaf powder was administered orally via a gavage for 3 weeks. The present study reported significant reductions in abdominal circumference and in triglyceride levels. The authors reported no significant improvement in blood pressure and total cholesterol levels (Lopez, et al. [25]).

A clinical trial was conducted on thirty healthy male sprague dawley rats (180–200 g) to evaluate the effect of moringa leaf powder on blood glucose levels. Diabetes was induced by 150 mg/kg of alloxan monohydrate in rats. Experimental group received 50 mg/day of moringa leaf powder orally using cannula needle for 2 months. The diabetic group receiving moringa leaf powder reported increase in body weight and significant reductions in blood glucose levels as compared to control group (Villarruel-Lopez, et al. [26]). Studies regarding moringa leaves powder supplementation in animal model are represented in (Tables 3-6). Moringa aqueous extract was administered orally by a gavage at an increasing dosage of 100 mg, 200 mg, and 300 mg/kg body weight for three weeks in streptozotocin (STZ) induced diabetic rats. Different doses of moringa extract improved glycemic control in diabetic rats (Jaiswal, et al. [27]). A study conducted on diabetic rats showed reduction in fasting plasma glucose levels after moringa extract ingestion. Experimental group orally received 400mg of moringa extract for 28 days. Diabetes was induced by intraperitoneal dose of 100 mg/kg of alloxan monohydrate in rats. The control group was given distilled water without moringa extract. Moringa leaf extract significantly reduced cholesterol and glucose levels treatment group (Oyedepo, et al. [28]). Female alloxan-induced diabetic wistar rats at intraperitoneal dosage of 100 mg/kg body weight receiving moringa aqueous leaf extract showed significant reduction in glycemic levels together with improvement in lipid profile. In addition, also normalized the mRNA expression of gluconeogenic enzyme pyruvate carboxylase in hepatic tissues (Abd El Latif, et al. [19]).

Table 3: Clinical Trials of Moringa Leaf Powder in Animal Model.

Table 4: Macronutrients and Micronutrients in 100 Gram Dried Moringa Leaves.

Note: Nutritional Composition of Moringa Leaves (Dried).

Table 5: Phytochemical Analysis of Moringa Leaves.

Table 6: Clinical Trials of Moringa Leaf Extract in Animal Model.

A significant improvement in blood glucose levels was reported in male rats treated with moringa leaf extract (150 mg/kg of body weight for 21 days) with alloxan-induced diabetes at a intraperitoneal dose of 120 mg/kg. The authors also stated that moringa leaves possess potent antihyperglycemic activity (Fahmy, et al. [29]). A significant decrease in blood glucose levels was reported in male wistar rats treated with moringa methanolic leaf extract (300 mg/kg of body weight) with alloxan-induced diabetes at a intraperitoneal dose of 120 mg/kg. The authors also stated improvement in insulin levels and lipid profile in experimental group with moringa methanolic leaf extract as compared to control group (Olayaki, et al. [30]). A study conducted on diabetic rats showed significant reduction in blood glucose levels after moringa ethanol extract ingestion via oral gavage. Diabetes was induced by intraperitoneal dose of 40 mg/kg body weight of streptozotocin in male rats. Treatment group orally received 500 mg/kg of moringa extract for 14 days. Authors reported significant improvement in lipid profile in experimental group with moringa leaf extract. The ethanolic extract also improved islet of Langerhan’s in pancreas in treatment group. (Toma A, et al. [31]). A recent study reported significant improvements in glycemic levels in female wistar rats with streptozotocin (45 mg/kg, intraperitoneal) induced diabetes and in high-fat diet induced female diabetic mice, treated with moringa leaf extract. After diabetes induction, streptozotocin induced rats received 100 mg/kg of body weight of moringa leaf extract orally for 3 weeks. The diabetic mice were administered 200 mg/kg of body weight of moringa leaf extract. There was significant improvement in high density lipoprotein levels with significant reduction in total cholesterol and triglyceride levels in both diabetes induced mice and rats (Khan, et al. [32]).

Authors reported that forty-two days administration of 300 mg/ kg of body weight moringa ethanolic leaf extract along with sitagliptin (an oral hypoglycemic used for type 2 DM) reported significant reduction in fasting plasma glucose levels in alloxan-induced (intraperitoneal dose of 150 mg/kg) diabetic wistar rats. The study concluded no improvements in insulin levels diabetic rats treated with moringa extract (Olurishe, et al. [33). An oral dose of 250 mg/kg of body weight moringa aqueous leaf extract was given to 150mg/kg of alloxan-induced diabetic rats for 18 days. The study reported significant reduction in blood glucose levels after moringa ingestion. There was a significant improvement in antioxidant markers and normalized the expression of apoptotic, gluconeogenic, and glycogenic genes in hepatic tissue (Abdeldaim, et al. [34]). A study conducted on diabetic rats showed reduction in plasma glucose levels after moringa extract ingestion. Experimental group orally received 500mg of moringa extract was suspended in distilled. The control group was given equal volume of distilled water without moringa extract. Moringa leaf extract significantly reduced plasma glucose levels at 30 min in treatment group (Azad, et al. [35]). Previous researches had showed an antihyperglycemic effect of moringa in different animal models. Strongest hypoglycemic effects in diabetic models (animals) were reported at the doses between 200 and 300 mg/kg (Wang, et al. [36]). A recent study reported significant improvements in glycemic levels in rats with streptozotocin (55 mg/kg, intraperitoneal) induced diabetes treated with moringa leaf extract. After diabetes induction, streptozotocin induced rats received 250 mg/kg of body weight of moringa leaf extract orally for six weeks. High antioxidant capacities of moringa extract and improved serum biochemical markers (Omodanisi, et al. [37]).

A protein isolate (Mo-LPI) from moringa leaves was studied in 150 mg/kg of alloxan-induced diabetic mice. A single protein isolate dose of 300 and 500 mg/kg of body weight reported significant reduction blood glucose level in diabetic mice. The hypoglycemic effect of the extract was abolished after heating at 98 °C. The authors reported no significant improvement in insulin levels (Paula, et al. [38]). A study conducted on male diabetic rats showed reduction in blood glucose levels after moringa extract ingestion. Diabetes was induced by intraperitoneal dose of 145 mg/kg body weight of streptozotocin in male rats. Experimental group orally received 100mg/kg of moringa extract for 10 days. Authors reported significant improvement in glycemic control in treatment group with moringa leaf extract (Azevedo, et al. [39]). A ethyl acetate extract fraction from moringa leaves was studied in 55 mg/kg streptozotocin-induced diabetic mice. 200 mg/kg of body weight ethyl acetate extract fraction from moringa leaves for 30 days reported significant reduction blood glucose level in diabetic rats.Moringa extract reversed the manifestation of streptozotocin on` the levels of serum glucose & insulin, lipid profile, hepatic damage markers (Bamagous, et al. [40]).

Another study was conducted on thirty male rats to investigate the antihyperglycemic effect of moringa leaf extract. Diabetes was induced by 60 mg/kg of streptozotocin in rats. Experimental group received 50 mg/day of moringa leaf extract orally for 10 days. The diabetic group receiving moringa leaf extract reported significant reductions in blood glucose and cholesterol levels (Hidayati, et al. [41]). High fat diet (HFD) fed rats were administered 40 mg/kg of streptozotocin to induce type 2 diabetes. Treatment group received moringa leaf extract at an increasing dosage of 100 mg, 200 mg, and 400 mg/kg body weight. The study showed significant reduction in plasma glucose levels of the subjects in experimental group treated with moringa as compared to control group (Answer, et al. [42]). A four-week supplementation of moringa leaf extract in metabolic syndrome induced rats reported improvement in plasma glucose level. 1000 mg/kg/day of moringa leaf extract were administered orally for 4 weeks. The authors also reported significant improvement in insulin resistance and visceral fat after moringa supplementataion (Irfan, et al. [43-56]).

In the present review, many animal trials (twenty studies) had reported antihyperglycemic activity of moringa. All these studies reported significant improvement in blood glucose levels along with lipid profile. Strongest hypoglycemic effects in diabetic models (animals) were reported at the doses between 200 and 300 mg/kg. In humans, there is limited evidence regarding hypoglycemic effect of moringa. Only five studies are reported in humans. Three of them were with single dose administration and postprandial blood glucose measurement. Among them, only one study (20 g moringa leaf powder once with meal) reported significant improvement in post prandial blood glucose levels. The remaining were two clinical trials with 8-gram moringa leaf powder supplementation of short duration around one month. Secondly, the HbA1C parameter was not accurately measured in these two studies. Moreover, one study reported significant reductions in blood glucose level while the other study reported no significant improvement in glycemic control in diabetic patients. Hence, considering the current evidence, it is difficult to reach a conclusion that moringa can be used as an anti-hyperglycemic agent and there is a need to conduct a clinical trial of appropriate duration in humans.

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