Indian Journal of Traditional Knowledge

Vol. 16(4), October 2017, pp. 700-705

Clinical evaluation of efficacy and safety of appetizer syrup as appetite stimulant

in children with non-pathogenic anorexia
JLN Sastry1*, PS Tathed2, Rajiv K Rai3 & V Sasibhushan1
1Healthcare Research; 3Formulations Division, Dabur Research and Development Centre,

Dabur, India Limited, Plot No.22, Site IV, Sahibabad, Ghaziabad- 201 010, Uttar Pradesh, India;
2Department of Kayachikitsa, R A Podar Medical College (Ay), Worli, Mumbai- 400 025, Maharashtra, India

E-mail: j.sastry@mail.dabur
Received 04 March 2016, revised 19 January 2017

Anorexia, i.e., lack of desire to eat or loss of appetite is a common cause of parental concern in pre-school and school-
going children. Many herbs and herbal formulations have been traditionally used in India as ‘appetizers’ in children with non-
pathological anorexia and over 100 phyto-constituents are claimed to have appetite-stimulant effects, though efficacy and
safety of many of these formulations needs to be evaluated with well-controlled clinical trials. Appetizer syrup (Mfd: Dabur
India Limited) is an Ayurvedic polyherbal formulation proposed to stimulate appetite in children with non-pathogenic
anorexia. It comprises herbs such as Kismis (Vitis vinifera L.), Pipalli (Piper longum L.), Anar (Punica granatum L.), Amla
(Emblica officinalis Gaertn), etc., that are traditionally known to be useful in digestive impairment and are documented to
possess appetite stimulant and strength promoting properties. Present trial was a double-blind, randomized, placebo-controlled
parallel group clinical study to evaluate the efficacy and safety of Appetizer Syrup in children with non-pathogenic anorexia.
Results were assessed from baseline to study completion on basis of the appetite stimulating effects of the formulation and
the benefits secondary to appetite stimulation like changes in anthropometric measurements and academic performance.

Keywords: Non-pathogenic anorexia, Appetite stimulant, Children, Herbal, Ayurveda

IPC Int. Cl.8: A01D 7/03, A23L 29/30, A23L 33/125, A61K 36/00

Anorexia, i.e., lack of desire to eat or loss of appetite, and may not be suitable for prolonged use. Serotonin
is a common cause of parental concern in pre-school (5-HT) too is believed to have an inhibitory influence
and school-going children. A variety of factors, both over feeding behavior5. Recent times have seen a
physiological and psychological, determines one’s renewed interest of herbal and other complementary
hunger, desire to eat and satiety1, which may or may therapies in the management of various chronic
not be associated with an underlying intestinal or extra- diseases6. Traditional Medicines derived from
intestinal disease. Intermittent anorexia without any medicinal plants are used by about 60 % of the world’s
underlying cause (non-pathological anorexia) is population. Many herbs and herbal formulations have
common in childhood, which may adversely affect the been traditionally used in India as ‘appetizers’ in
childhood growth and development due to inadequate children with non-pathological anorexia and over 100
nutritional intake during an age of higher requirements. phyto-constituents are claimed to have appetite-
It is recognized that a diminished nutritional status may stimulant effects7-10, though efficacy and safety of
be a contributing factor for decreased immune many of these formulations needs to be evaluated with
function, delayed wound healing, and disturbed drug well-controlled clinical trials. Appetizer syrup (Mfd:
metabolism influencing prognosis2,3. Appetite Dabur India Limited) is an Ayurvedic polyherbal
stimulants such as megastore acetate (MA), formulation proposed to stimulate appetite in children
cyproheptadine hydrochloride (CH), cannabinoids, with non-pathogenic anorexia. It comprises of
anabolic and growth hormones and serotonin have ingredients such as Kismis, Pipalli, Anar, Amla, etc.,
been used to help overcome decreased appetite and that are traditionally known to be useful in digestive
malnutrition in children with various chronic impairment and are documented to possess appetite
illnesses3,4. Many of these have substantial side effects stimulant and strength promoting properties6,11-13.
————— Present trial conducted between the years 2004-2005
*Corresponding author was a double-blind, randomized, placebo-controlled
 SASTRY et al.: APPETIZER SYRUP IN CHILDREN WITH NON-PATHOGENIC ANOREXIA 701

parallel group clinical study conducted to evaluate the 2. Subjects with any chronic infection or significant
efficacy and safety of Appetizer Syrup (DRF/AY/4008) systemic disease.
in children with non-pathogenic anorexia. Results were 3. Subjects with known history of food allergies.
assessed from baseline to study completion basis of the 4. Subjects with dysphagia due to inflammatory
appetite stimulating effects of the formulation and the conditions of oral cavity (ulcers) or neuromuscular
benefits secondary to appetite stimulation like changes in dysfunction.
anthropometric measurements and academic 5. Subjects not willing to sign informed consent
performance. 6. Subjects not willing to come for follow-up as and
when required.
Aim
To evaluate the clinical efficacy and safety of a Methodology
polyherbal appetite stimulant - Appetizer syrup The study was conducted at RA Podar Ayurvedic
Hospital, Worli, Mumbai, Maharashtra with approval
Objectives from Institutional Ethics Committee of RA Podar
1. Evaluation of the primary effects of appetizer Medical College (Ayurveda), Worli, Mumbai
syrup on pattern of changes in rated hunger, (Approval Date & No: 07 August 2004 &
fullness and associated factors. NO/RAP/store/4784/2004). The study was registered
2. Evaluation of the secondary effects of this drug retrospectively with the CTRI, Clinical Trial Registry
appetizer syrup on growth, using anthropometric of India vide Reg. No/2015/12/006465.
parameters as indicators. Healthy male and female children in the age range
3. Evaluation of safety profile and identification of of 03-12 yrs, attending OPD Department of
adverse effects, if any, associated with use of any Kayachikitsa, RA Podar Ayurvedic Hospital, Mumbai
of the study products. were screened for eligibility. On screening/ baseline
visit, a written informed consent was obtained from
Material and methods
children’s parent/legally accepted guardian for their
Study product participation in the study. Assessment of inclusion and
Appetizer syrup was prepared using standard exclusion criteria was made. Screened subjects were
methodology for preparing syrups. Hot and cold administered a single oral dose of Albendazole 400 mg
infusions of herbs were used. The composition details one week before the enrollment. Thereafter, they were
of Appetizer syrup (Mfd: Dabur India Limited) are randomized to receive either appetizer syrup or the
given in Table 1. placebo syrup.
Study design
Blinding
Prospective double-blind, placebo-controlled,
For the purpose of blinding, the study drug was
randomized, parallel study
supplied in a pre-encoded syrup form along with a
Number of subjects similarly packed placebo formulation as- Group I–
A total of 100 children with complaints of reduced appetizer syrup (coded as 201) and Group II– placebo
appetite were recruited as per the inclusion/exclusion syrup (coded as 102).
criteria
Dosage and treatment schedule
Inclusion criteria Recruited subjects were randomized to receive
1. Male and female children in age range 3-12 yrs. either appetizer syrup or placebo syrup according to
2. History of poor appetite with or without reduced computer generated randomization list. Both the study
food intake. products were advised to taken orally at doses of 5 mL
3. Willingness to provide informed consent and to twice daily for 2 months.
come for regular follow-up evaluation as and when
required. Analysis
All enrolled cases were evaluated on day 0
Exclusion criteria (baseline), day 15 (±3 days), day 30 (±3 days) and day
1. Subjects with compromised renal and liver 45 (±3 days) for following efficacy and safety
function. parameters.
702 INDIAN J TRADIT KNOWLE, VOL 16, NO. 4, OCTOBER 2017

Table 1Composition details of appetizer syrup quantity of actives (in mg) used for preparing 5mL of ayrup
S.No. Name of Botanical name Quantity (mg)/ Benefits as per Ayurveda
Ingredient per 5 mL of syrup
1. Kismis Vitis vinifera L. 35 Agnimandya (Digestive Impairment)
2. Anar seed Punica grantum L. 35 Agnimandya (Digestive Impairment)
3. Elaichi Elettaria cardamomum (L.) Maton. 25 Deepana (Appetizer), Aruchi (Tastelessness)
4. Haritaki Terminalia chebula Retz. 25 Deepana (Appetizer), Aruchi (Tastelessness),
Udararoga (Diseases of Abdomen), Rasayana
5. Ajwain Trachyspermum ammi (L.) Sprague 25 Adhmana (Flatulance), Udararoga
(Diseases of Abdomen)
6. Jeera sveta Cuminum cyminum L. 25 Agnimandya (Digestive Impairment)
7. Chavya Piper retrofractum Vahl. 25 Pachan (Digestive), Adhamana (Flatulance)
8. Sowa Anethum sowa Roxb. 25 Deepan (Appetizer), Pachan (Digestive),
Adhamana (Flatulance), Sula (Pain)
9. Mulethi Glycyrrhiza glabra L. 25 Sheetal, Rasayana (Rejuvinator), Balya
(Strength promoter)
10. Palash seed Butea monosperma (Lam.) 25 Agnimandya (Digestive Impairment)
11. Mustak Cyprus rotundus L. 25 Deepan (Appetizer), Pachan (Digestive)
12. Guruchi Tinospora cordifolia (Thunb.) Miers 25 Agnimandya (Digestive Impairment)
13. Amla Dry Phyllanthus emblica L. 10 Deepan (Appetizer)
14. Dalchini Cinnamomum zeylanicum J.Presl 10 Ruchya (Appetite stimulant)
15. Pippali Piper longum L. 10 Deepana (Appetizer), Ruchya (Appetite Stimulant),
Udararoga (Diseases of Abdomen)
16. Sunthi Zingiber officinale Roscoe 10 Agnimandya (Digestive impairment), Adhaman
(Flatulance), Udararoga (Diseases of Abdomen)
17. Maricha Piper nigrum L. 10 Deepana (Appetizer), Ruchya (Appetite Stimulant)
18. Lavang Syzygium aromaticum (L.) 5 Deepana (Appetizer), Pachana (Digestive), Ruchya
Merrill & Perry (Appetite stimulant), Adhmana (Flatulance), Amlapitta
(Hyperacidity)
Contains Preservatives, Colours and other Permitted Excipients

Efficacy parameters academic performance and interest/ participation

a) Subjective evaluation during each visit, based on in extracurricular activities were recorded on a
history from parents and rating on a visual structured CRF.
analogue scale following parameters were
considered for efficacy evaluation: b) Secondary efficacy parameters: Following
anthropometric evaluation for selected growth
1. History regarding various food habits directly or parameters were recorded on follow up visits on
indirectly related to appetite, e.g. general desire to day 0, 15, 30 and 45.
eat, quantity of food intake, left over in the plate,
number of meals taken per day and range of food 1. Body weight (up to 100 g least value)
taken. 2. Linear height (up to 1cm least value)
2. History related to bowel habits (regularity and b) Safety parameter: Following safety parameters
consistency of stools) and sleep (sound/ disturbed were considered
& duration). Leading questions were asked in this
regard. 1. Recording of any undesirable experience since last
visit
3. Ratings for appetite related factors like hunger 2. Physical examination during each visit
rating, rating for abdominal fullness and satiety, 3. Following laboratory investigations on visit day
fatigue and general energy levels, were carried out 0 and 45 days – Liver function tests (LFT), Renal
on a visual analogue scale (VAS) as higher is the function tests (RFT), Complete blood counts
rating on VAS scale, better is the improvement. (CBC), Stool examination
4. Rating for the performance of various activities 4. Serious Adverse events (if any) were graded and
directly or indirectly related to poor appetite, like recorded according to their severity in clinical
 SASTRY et al.: APPETIZER SYRUP IN CHILDREN WITH NON-PATHOGENIC ANOREXIA 703

Table 2  Effect on various parameters (Mean ± SD of two groups over the time)
Variables Groups Visit 0 Baseline Visit 2 15 days Visit 2 30 days Visit 3 45 days
Weight Appetizer syrup 16.7±5.88 16.92±6.02 17.00±6.33 17.67±6.57
Placebo syrup 14.08±1.89 14.90±2.62 14.50±2.39 14.6±1.64
Height Appetizer syrup 113.56±19.70 113.56±19.70 113.57±19.69 113.69±19.65
Placebo syrup 108.83±8.38 108.83±8.38 108.83±8.38 109±8.29
Hunger rating Appetizer syrup 25.56±8.82 41.11±9.28 55.56±14.24 60±14.14
Placebo syrup 18.33±7.53 33.33±5.16 40±12.65 58.33±14.72
Abdominal fullness Appetizer syrup 17.78±8.33 34.44±18.10 51.11±12.69 45.56±14.24
Placebo syrup 18.33±9.83 30±6.32 35±8.37 23.33±8.16
Satiety Appetizer syrup 28.89±7.82 43.33±10.00 55.56±10.14 61.11±13.64
Placebo syrup 28.33±13.29 36.67±5.16 38.33±11.69 48.33±11.69
General desire to eat Appetizer syrup 26.67±10.00 44.44±11.30 57.78±15.63 64.44±17.40
Placebo syrup 26.67±10.33 41.67±7.53 51.67±14.72 58.33±4.08
Quality of food intake Appetizer syrup 24.44±7.26 44.44±10.14 53.33±15.00 64.44±19.44
Placebo syrup 21.67±4.08 36.67±5.16 40±16.73 51.67±18.35
General Energy level Appetizer syrup 56.67±21.21 65.56±20.07 75.56±13.33 77.78±14.81
Placebo syrup 58.33±14.72 66.67±13.66 75±5.48 78.33±4.08

research form. The study was conducted in two

parts. Part-1 of the study completed with the
evaluation of the subjects after visit 4. This would
give an idea regarding the appetite stimulating
effects of the formulation. Part-2 was for
evaluation of the benefits secondary to appetite
stimulation, like effects on anthropometric
measurements and academic performance; there
shall be one more follow- up at the end of two
months of treatment. Subjects were also followed
up after visit 4 for assessment of sustenance of
appetite stimulating effects. The benefits
secondary to appetite stimulation, like effects on
anthropometric measurements and academic Fig. 1Effect of the study drugs on hunger (HR)
performance, one more follow- up was done at the
end of two months of treatment. All the parameters after 60 days of study. Therefore, the
observations were documented in the case record efficacy of the study drug was concluded on the basis
forms and data was incorporated for independent of 45 days study period (Table 2). There was
statistical analysis. significant improvement in hunger in both the groups
at all the visits when compared to baseline at the end of
Results and discussion the study. In between group statistical analysis was not
The present study included 100 completed subjects done as there was significant difference observed at
falling in to the inclusion criteria. Both male and baseline in between groups (Fig. 1). The abdominal
female children between 3-12 yrs of age formed fullness showed significant improvement at all the
subjects in the present study. They were randomized in visits in group I and group II except at visit 3.
to two groups’ comprising 50 subjects each. The male Moreover, there was significant improvement
vs female ratio in group I and II was 57:43 and 52:48, observed in group I when compared to group II at visit
respectively. The mean average age of male children 2&3 (Fig. 2). Significant improvement in satiety was
was 10.32 (± 1.62) and that of female children was observed at all the visits in group I&II when compared
10.41 (±1.27) in group I while that in group II was to baseline. In between group analysis showed
11.03 (±3.61) and 10.94 (±2.78), respectively. There significant improvement in group I, when compared to
was no significant variation in the observational group II at all the visits (Fig. 3). General desire to eat
704 INDIAN J TRADIT KNOWLE, VOL 16, NO. 4, OCTOBER 2017

showed significant improvement in at all the visits in Appetizer syrup is an Ayurvedic polyherbal
group I&II when compared to baseline. In between formulation comprising ingredients such as Kismis
group analysis showed significant improvement in
group I, when compared to group II at visit 2&3 (Fig. 4).
There was significant change in food intake between
visits 0 to visit 3 in both the groups from baseline. In
between group statistical analysis was not done as there
was significant difference was observed between the
group I&II at baseline only (Fig. 5).
A significant improvement in general energy level was
observed between visits 0 to 3 in both the groups from
baseline. However, these scores were not significant
when group I is compared to group II (Fig. 6).
No adverse events were reported during the study.
Assessment of vitals like pulse, respiration and body
temperature did not show any significant difference
both within the group and between the groups. The
study drug was found to be safe in the given dosage and Fig. 4Effect of the study drugs on general desire to eat (GDE)
well tolerated by the subjects.

Fig. 2Effect of the study drugs on abdominal fullness (AF) Fig. 5Effect of the study drugs on quality of food intake (QF)

Fig. 3Effect of the study drugs on satiety Fig. 6Effect of the study drugs on general energy level (GEL)
 SASTRY et al.: APPETIZER SYRUP IN CHILDREN WITH NON-PATHOGENIC ANOREXIA 705

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