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Merlin et al., Afr., J. Complement Altern Med. (2020) 17 (2): 29-36
https://doi.org/10.21010/ajtcam.v17i2.3
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MORINGA OLEIFERA LEAF POWDER FOR TYPE 2 DIABETES: A PILOT CLINICAL TRIAL
Lassana Sissoko1,2, Nouhoum Diarra2, Ibrahim Nientao3, Beth Stuart4, Adiaratou Togola1, Drissa
Diallo1,2, Merlin Luke Willcox4*
1Département de Médecine Traditionnelle, Institut National de Recherche en Santé Publique, BP 1746,
Bamako, Mali. 2l’Université des Sciences, des Techniques et des Technologies de Bamako, Bamako,
Mali., 3ONG Santé Diabète Mali, Bamako, Mali., 4School of Primary Care, Population Sciences and
Medical Education, University of Southampton, Aldermoor Health Centre, Aldermoor Close,
Southampton SO16 5ST, UK.
*Corresponding author’s E-mail: M.L.Willcox@soton.ac.uk
Abstract
Background: Moringa oleifera Lam. (Moringaceae) leaves are commonly used for diabetes in Mali. This pilot clinical
study aimed to evaluate its effect on post-prandial blood glucose in preparation for a larger trial.
Methods: Diabetic patients and non-diabetic healthy volunteers (35 each) were asked to fast for 13 hours on three
occasions. Blood glucose was measured before and after eating 100g of white bread (at 30, 60, 90, 120, 150 and 180
minutes). On their second and third study visits, they were given 1g and 2g respectively, of M. oleifera leaf powder, 30
minutes after eating the bread. The mean paired reduction in blood glucose at each time interval and the incremental
area under the curve were calculated.
Results: Ingestion of Moringa powder had no effect on blood glucose in non-diabetic participants, but in diabetic
patients, it lowered blood glucose at 90 minutes. There was a trend towards lower incremental area under the curve
when diabetic patients took 2g of Moringa. No side-effects were reported by any participant.
Conclusions:Moringa oleifera leaf powder reduced post-prandial glycaemia in diabetic patients. A larger study is
needed to define the optimal dose and to assess whether this translates into longer-term benefits.
Key words: Moringa oleifera; Type 2 diabetes; clinical trial
List of Abbreviations: 95% CI = 95% Confidence Interval, AUC = Area Under the Curve, BMI = Body Mass Index
HbA1c = Haemoglobin A1c, IC50 = Inhibitory Concentration 50%, NIHR = National Institute of Health Research
mmol/l = millimoles per litre, SD = Standard Deviation, SGLT-1 = sodium glucose transporter-1
Introduction
The prevalence of diabetes in Mali has increased six-fold from 0.27% in 2002-3 to 1.8% in 2017 (95% CI 1.4-
4.2%) in adults aged 20-79 years (International Diabetes Federation, 2017; Liu et al., 2012). Diabetes was the second
most common reason for admission to the two university teaching hospitals in Bamako (Mali), and was also
responsible for 40% of general medical consultations in 1996 (Santé Diabète Mali, 2012). A survey of 100 diabetic
patients at Gabriel Touré University Hospital in 2006-7 showed that 71% of patients had a monthly income of less than
US$100, but the average yearly treatment costs for diabetes were US$1169 (Sanogo et al., 2015). This has been
confirmed in a later study which found that total annual healthcare-associated costs for diabetic patients were $1127
compared to $308 for non-diabetic control patients, in a sample of 500 diabetic patients and 500 controls in Mali
(Bermudez-Tamayo et al., 2017). A further survey of 100 type 2 diabetic patients attending the University Hospital
clinic in 2009 found that 65% were not complying with their medications; in 57% of cases this was due to cost, and in
20% due to poor access to medicines (Sanogo et al., 2013). In rural areas, financial barriers to accessing medications
are even greater; most of the population in Mali cannot easily access modern medicines and prefer to use herbal
medicine as the first line.
Article History
Received: March 8th 2020
Revised Received: March 28th 2020
Accepted: Sept. 17th 2020
Published Online: Nov. 18th 2020
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Many herbal medicines are used for the treatment of diabetes, and the most widely-used modern antidiabetic
medicine (metformin) is derived from guanidine and galegine, active compounds of the Western herbal remedy Galega
officinalis (Simmonds and Howes, 2006). Moringa oleifera Lam. (Moringaceae) is widely used in the tropics as a
herbal remedy for diabetes. In Bangladesh, an ethnobotanical survey showed that M. oleifera was one of the plants
most frequently cited by traditional healers across 15 districts (Kadir et al., 2012). In South Africa, 17% of Bapedi
healers of Limpopo district use the raw seeds and leaves, cooked for 5-10 minutes, to treat diabetes mellitus (Semenya
et al., 2012). In Senegal, M. oleifera was used by nearly 66% of diabetic patients interviewed at a university teaching
hospital (Dièye et al., 2008). The most popular use of M. oleifera is as medicine for treating diabetes and regulating
blood pressure through the consumption of the fresh or dried leaves. These uses are common knowledge throughout
Senegal (Yousefian, 2012), and have also been reported in Nigeria (Popoola and Obembe, 2013). In Ugandan rural
communities, the use of Moringa leaves to treat diabetes mellitus was cited by 90% of respondents (Kasolo et al.,
2010).
M. oleifera, commonly referred to as the “drumstick tree” because of its large seed-pods (figure 1), is native to
the western sub-Himalayan regions of India, Pakistan, Bangladesh and Afghanistan, but has been cultivated for food
and medicine in tropical Asia, sub-Saharan Africa, Latin America and the Caribbean (Fahey, 2005; Jahn et al., 1986;
Morton, 1991). The consumption of the leaves, pods and flowers as food is very common. In West Africa, the leaves
and sometimes the flowers, are eaten in a peanut sauce, whereas the immature pods are not frequently consumed but
rather pressed for oil and used as medicine (Yousefian, 2012). In India, the immature pods are cooked in curries as
vegetables, the mature pods are used in soups and stews and the drumstick pulp is used in various dishes (Pandey et al.,
2011). The leaves are also widely used as vegetable, condiment and in salads. The leaves are rich in protein, essential
amino acids, iron, copper, calcium, Vitamin C and carotenoids (Fahey, 2005; Fuglie, 2002) so have been promoted as a
nutritional supplement for malnourished children, lactating women and people with osteoporosis (Pandey et al., 2011).
Therefore, various non-governmental organisations and governments have supported large scale planting of
Moringa (Hirt and Lindsey, 2008; Thurber and Fahey, 2009; Yousefian, 2012). As would be expected for a food, M.
oleifera leaves are non-toxic. This has been confirmed by laboratory experiments. The aqueous extract of M. oleifera
leaves was administered orally to 30 male Wistar rats and even at doses of 2000 mg/kg, no mortality ensued (Adedapo
et al.,2009 ). Sub-acute toxicity was assessed by administering daily doses of up to 1600 mg/kg to male rats, and no
signs of serious toxicity were observed on biochemical or haematological tests, or on histopathology of the organs
(Adedapo et al., 2009). The safety of M. oleifera leaves has been confirmed in other studies (Isitua and Ibeh, 2013).
Figure 1: Moringa oleifera tree (Photo: Merlin Willcox)
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In vitro studies
A water extract of dried Moringa leaf strongly inhibited the activity of intestinal sucrase (IC50 0.98mg/ml) and
weakly inhibited the activity of maltase and pancreatic α-amylase (22.3% and 5.3% respectively, at 5mg/ml). It also
inhibited the activity of pancreatic cholesterol esterase (IC50 4.34 mg/ml) (Adisakwattana and Chanathong, 2011).
A methanol extract at a concentration of 250 µg/ml inhibited α-amylase activity by 68% (Leone et al., 2018).
Moringa oleifera water, ethanol and methanol extracts have a dose-dependent α-D-glucosidase inhibition activity
(Togola, 2014). Moringa leaf contains a high concentration of quercetin-3-glucoside (Q3G) (Ndong et al., , 2007)
which competitively inhibits sodium (Na+) dependent mucosal uptake of glucose via SGLT-1 (sodium glucose
transporter-1) in the small intestine (Cermak et al., 2004).
In vivo studies
Several studies in diabetic rats have shown that M. oleifera leaf extracts have antidiabetic properties. An
ethanolic leaf extract of M. oleifera was one of the most potent among 30 hypoglycaemic medicinal plants from
indigenous folk medicines for lowering blood glucose level in alloxan-induced diabetic albino rats (Kar et al., 2003).
M. oleifera leaf tablets reduced blood glucose by 54.4%, compared to 40% in those who received
glibenclamide, while the negative control groups had an increased blood glucose level with time (Momoh et al.,2013).
M. oleifera leaf powder significantly improved glucose tolerance and lowered fasting plasma glucose in
diabetic rats (Jaiswal et al.,2009). M. oleifera significantly decreased postprandial blood glucose levels in both Wistar
and Goto-Kakizaki (GK) rats (Ndong et al., 2007). This study suggests that M. oleifera leaves increase glucose
tolerance, though the effect was greater in GK rats than in Wistar rats.
Other parts of the plant also have antidiabetic properties: an alcoholic bark extract prevented dexamethasone-
induced insulin resistance in peripheral tissues of rats (Sholapur and Patil, 2013). A methanol extract of the pods
reduced blood sugar levels in diabetic rats (Gupta et al., 2012) and a hydroalcoholic flower extract had significant
activity against hyperglycemia in diabetic rats (Sunilkumar, 2011).
Clinical studies
There have been three clinical trials to study the hypoglycaemic effect of Moringa leaf in diabetic patients.
The first studied the effect of 50g of cooked leaves on post-prandial blood glucose after a standard meal, compared to
bitter gourd and curry leaves, in six type 2 diabetic patients who were not taking any medication (William et al., 1993).
The meal including Moringa leaves was followed by a significantly reduced incremental area under the
glucose curve, unlike the other two vegetables, suggesting that Moringa does indeed have hypoglycaemic properties
over and above the reduction in glycaemic index seen with any vegetable or fibre in the diet. The insulin levels were
not raised compared to the other foods, suggesting that the mechanism of action is not an increase in insulin secretion.
A second trial measured HbA1c and post-prandial blood glucose levels after three months in 30 patients with
type 2 diabetes who took a Moringa leaf tablet after breakfast and after dinner every day, in addition to sulphonylureas,
compared to 30 control patients without Moringa (Giridhari et al., 2011). The experimental group had a significant
reduction of HbA1c (from 7.8% to 7.4%) and in postprandial blood glucose, whereas there was no significant change in
the control group.
More recently, a trial in 17 diabetic patients found that 20g of dried Moringa leaf powder significantly reduced
post-prandial glucose in diabetic patients after eating a standard meal, but that this significantly reduced the
acceptability of the meal due to the bitter taste (Leone et al., 2018). The authors, therefore, recommended trials with
lower doses of Moringa. All these trials are small and have methodological flaws, so there is a need for better evidence
on the effectiveness and optimal dosage of Moringa leaf powder in diabetic patients.
Aims and Objectives
We aimed to conduct a pilot study of the effect of Moringa oleifera leaf powder on postprandial blood glucose
in diabetic patients and non-diabetic controls. The objectives were to test whether it was possible to recruit and retain
patients to such a study, and to inform sample size calculation for a definitive study. This study was approved by the
Institut National de Recherche en Santé Publique in Mali.
Materials and Methods
Preparation of plant material
The youngest leaves (at the tips of the branches) were harvested early in the morning at the start of the rainy
season in June 2014, in Bamako district (Mali). The plant was identified by the Head Botanist of the Department of
Traditional Medicine (Seydou Dembélé), and a voucher specimen has been deposited in its herbarium (Number
1391/DMT). The leaves were washed with tap water, dried in the shade, then pounded and sifted to give a fine powder.
The powder was stored in hermetically sealed glass jars and kept in a dry area. The dose was determined by
32
weighing the dose normally given by traditional healers – this was approximately one gram. We decided to test this,
and double this dose, to look for a dose-response effect.
Participants
We recruited 70 participants (35 with diet-controlled type 2 diabetes, and 35 non-diabetic) from Bamako and
Kati. Diabetic patients were excluded if they were pregnant, if they had any cardiac, respiratory, renal or liver disease;
if their fasting blood glucose was <7.0 mmol/l, if their post-prandial glucose was <11.0 mmol/l, or if they had any
allergy to Moringa leaf powder. Non-diabetic participants were recruited from among the relatives of the diabetic
patients, and from the staff of local schools.
Study procedures
Participants came on three occasions, at least 15 days apart. On all occasions, they were asked to fast for 13
hours before the test. Participants were weighed, and body mass index was calculated. Fasting blood glucose was
measured with a hand-held glucometer (Infopia Element, USA), following which the patient ate 100 g of white bread,
with water. On the first occasion, nothing else was administered, and blood glucose was measured again 30, 60, 90, 120,
150 and 180 minutes after eating the bread. On the second occasion, participants were given 1g of Moringa oleifera
leaf powder with 75 ml water, 30 minutes after eating the bread (after the first post-prandial measurement of blood
glucose). On the third occasion, they took 2 g of Moringa oleifera leaf powder with 75 ml in the same way.
Patients were asked about any symptoms.
Analysis
Data was recorded on paper forms, and then entered into a database using Epi-info version 3.5.4 (CDC,
Atlanta, USA). After completing data entry, data were exported and analysed using SPSS 20 (IBM). A paired t-test
was used to compare mean post-prandial blood glucose at 60, 90 and 120 minutes, with and without different doses of
Moringa. The results were analysed separately for the patients with diabetes, and the healthy controls. The primary
outcome measure was defined as the mean paired difference in blood glucose at 90 minutes, with and without Moringa
at the two different doses.
As a secondary outcome measure, positive incremental area under the curve was calculated for all glucose
measurements from baseline to 180 minutes in accordance with FAO/WHO’s ‘Joint Guidelines on glycaemic index
testing of foods’ and the International Standard ‘ISO 26642/2010: Food Products – determination of the glycaemic
index (GI) and recommendation for food classification’. Repeated measures ANCOVA was used to compare
treatments across time-points, recognising that responses were clustered within individual participants. This analysis
was carried out in Stata v14.
Sample size for a definitive study was calculated using NQuery, assuming 90% power, and using the
difference in the positive incremental area under the curve and standard deviation estimated during this pilot study.
Ethical issues
The research followed guidelines of the Declaration of Helsinki and Tokyo. The protocol received ethical
approval from the ethics committee of the National Institute for Public Health Research (INRSP) in Bamako, Mali
(decision No 12/13 CE-INRSP, 6th November 2013). The study was explained to participants, who were given an
information sheet and allowed an opportunity to ask questions. If they agreed to participate, they were asked to sign a
consent form. Participants were compensated for the time and travel to each appointment.
Results
Participants
Baseline characteristics are summarised in Table 1. The diabetic group was on average slightly older, included
more women, and had a higher BMI than the non-diabetic group. It was feasible to recruit and retain patients to this
study.
Table 1: Baseline characteristics of participants
Diabetic (n=35)
Non-diabetic (n=35)
Mean age in years (SD)
45.8 (10.6)
50.1 (11.6)
Number of women (%)
25 (71%)
14 (40%)
Mean BMI (SD)
29.6 (4.4)
24.5 (3.8)
No of obese patients, BMI>30 (%)
18 (51%)
3 (9%)
Mean baseline fasting glucose,
mmol/l (SD)
9.1 (2.7)
5.4 (0.7)
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Effect of Moringa on blood glucose
In diabetic patients, blood glucose was on average about 1mmol/l lower after ingesting Moringa than it was
after eating the same meal without Moringa (Table 2 and Figure 3). The difference reached statistical significance at 90
minutes when the dose was 1g, and at 120 mins when the dose was 2 g. In non-diabetic participants, there was no
significant difference in blood glucose, except in the group that took 2 g, at 60 minutes; this reduction was lower than
in diabetic patients (0.58 mmol/l). No side-effect was reported by any participant.
Table 2: Mean paired difference in blood glucose (mmol/l) at different time intervals after eating 100g white bread
without Moringa, compared to white bread 100 g with Moringa 30 minutes later (* p<0.05, paired t-test)
Group
Dose of
Moringa
60 mins (95% CI)
90 mins (95% CI)
120 mins (95% CI)
Non-
diabetic
1 g
0.07 (-0.57 to 0.72)
-0.03 (-0.55 to 0.50)
0.11 (-0.31 to +0.52)
2 g
0.58 (0.19 to 0.98)*
0.17 (-0.31 to 0.66)
0.15 (-0.32 to + 0.61)
Diabetic
1 g
0.70 (-0.39 to 1.78)
1.26 (0.07 to 2.46)*
0.76 (-0.26 to +1.80)
2 g
1.04 (-0.21 to 2.29)
1.04 (- 0.18 to 2.27)
1.25 (0.24 to 2.26)*
Time (minutes)
Figure 3: Observed mean blood glucose in non-diabetic and diabetic patients taking different doses of Moringa. (DM=
Diabetic; ND = Non-Diabetic)
There were no significant differences between the control and Moringa treatments in the positive incremental
area under the curve (AUC) for the whole study population controlling for age, sex, BMI and whether the participant
was diabetic (Table 3). There was a trend towards a dose-response effect, with a larger reduction for diabetic patients
who took 2 g of Moringa compared to when they took no Moringa (by 92 mmol min/l) but this difference was not
statistically significant.
Blood glucose (mmol/l)
34
Table 3: Positive incremental area under the curve (mmol min/l)
The sample size calculation, using a simple crossover design to detect a difference between 2 g of Moringa
oleifera leaf powder and control, for a difference in the positive incremental area under the curve of 92 and a standard
deviation of 360, suggests that a full study would require 82 diabetic patients.
Discussion
Principal findings
We were able to recruit and retain diabetic patients to a trial examining the effect of Moringa oleifera leaf
powder on post-prandial glucose. We were able to collect the primary outcome measure (post-prandial glycaemia,
measured from a finger prick); administration of Moringa appears to reduce the post-prandial rise in blood glucose in
diabetic patients but not in healthy controls. The duration of effect may be greater and longer after taking 2 g of
Moringa oleifera leaf powder than after taking 1g. A larger study of 82 diabetic patients is needed to confirm this effect.
No adverse effects were reported.
Strengths and limitations
This was a small pilot study, and because of logistical difficulties, healthy volunteers were not perfectly
matched by age and sex to the diabetic patients. We used glucometers rather than venous blood samples to measure
glucose, because of limited resources and practical considerations. Nevertheless it is unlikely that these factors could
have caused the observed differences in blood glucose. Moringa leaf powder was administered 30 minutes after the
bread, but in future studies it would be better to administer it at the same time as the food (which is the traditional
practice, and which would fit with the putative mechanism of action). It would also be good to escalate the dose further
beyond 2 g to evaluate whether there would be a larger and more significant effect, while maintaining acceptability.
In future studies it would be better to use the positive incremental area under the curve as the primary outcome
measure.
Implications
This pilot study supports the results of previous research which also show that M. oleifera leaf powder lowers
blood glucose. It is particularly interesting that this effect only seemed to occur in diabetic patients. Future studies are
needed to confirm this, to study whether a larger dose would have a greater effect, and to evaluate the effect of its daily
use over a period of several months, on glycated haemoglobin. It would also be interesting to evaluate its effect on
blood cholesterol, since preclinical studies suggest that M. oleifera may also have cholesterol-lowering effects (Ghasi et
al., 2000). Diabetic patients are at increased risk of cardiovascular disease, and cholesterol is a major risk factor for this.
M. oleifera leaves are primarily a food, part of the normal diet in many tropical countries, so are particularly
interesting as a potential dietary intervention for patients with diabetes, because it is possible to increase the dose
significantly with no risk of toxicity. Giving the leaf powder in capsules could avoid the issue with acceptability of the
taste. While awaiting results of further research, there would be no harm in encouraging diabetic patients to incorporate
M. oleifera into their daily diet (if they do not already do so).
Conclusions
Moringa oleifera leaf powder, administered 30 minutes after a food bolus, seemed to reduce post-prandial
blood glucose in diabetic patients only, but not in non-diabetic volunteers. A definitive trial would need 82 diabetic
patients to demonstrate whether there is a statistically significant difference in the area under the curve. Further
research is also needed to assess whether this translates into reductions in HbA1c after use of Moringa for three or more
months, and reductions in long-term complications of diabetes.
Group
Mean positive incremental area
under the curve (SD)
Difference compared to
control (95% CI)
Non-diabetics
Control
222.77 (108.29)
1 g Moringa
301.29 (453.67)
78.52 (-51.54, 208.59)
2 g Moringa
221.82 (125.28)
-0.94 (-131.01, 129.12)
Diabetics
Control
552.79 (344.47)
1 g Moringa
549.83 (318.29)
-2.96 (-121.70, 115.77)
2 g Moringa
461.41 (414.88)
-91.38 (-210.11, 27.35)
35
Acknowledgements
The authors are grateful to all the patients who participated in this trial, and to Ms Emma Weisbord for helping
to conduct a preliminary literature review which contributed to the background section. This work was funded by the
European Union Research Directorate through the MUTHI project, FP7 Grant Agreement No.: 266005. The salary of
Dr Merlin Willcox is funded by NIHR Academic Clinical Lectureship, under grant CL-2016-26-005.
Declaration of Conflict of Interest: The authors have declared no conflicts of interest.
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