COMPARISON OF ACUTE EFFECTS OF SUCRALOSE, ASPARTAME AND ACESULFAME POTASSIUM ON PULSE, BLOOD PRESSURE, AND BLOOD GLUCOSE LEVELS IN YOUNG HEALTHY ADULTS

Abstract

Background: The use of non-nutritive sweeteners (NNSs) have
become increasingly popular, so their health benefits and potential
adverse effects should be evaluated. Methodology: This
nonrandomized case-control comparative study was done at Mohi udDin Islamic Medical College on 200 healthy undergraduate medical
students in October 2017 after approval from ethical committee. The
participants were equally divided into groups A, B, C and D. The
control group A was given 100 gm cellulose while participants of
group B, C and D were given 0.36 gm (5 mg/kg) sucralose, 10.8 gm
(150 mg/kg) aspartame and 3.24 gm (45 mg/kg) acesulfame potassium
respectively in a glass of 180 ml water. The arterial pulse, systolic and
diastolic pressures were measured at 0, 30, 60, 90 and 120 minutes.
The random blood glucose levels were checked at 0 and 120 minutes in
all the participants. Results: The random blood glucose levels showed
a non-significant difference (p>0.05) at 0 and 120 minutes within and between all the study groups. A significant difference (p<0.05) regarding the pulse rate at 60,
90 and 120 minutes was noticed between participants of group A and B with that of group C
and D. The systolic pressure in participants of group A showed a significant difference
(p<0.05) with that of group C and D at 60, 90 and 120 minutes, while the diastolic pressure at
0, 30, 60, 90 and 120 minutes between and within the groups was found to be non-significant
(p>0.05). Conclusion: The artificial sweetener use showed cardio-metabolic health effects
which require further evaluation, however, the effects on glucose metabolism is nonsignificant. Objectives: To see the acute effects of non-nutritive sweeteners on blood
pressure, pulse and blood glucose levels in young healthy individuals.
KEYWORDS: Non-nutritive-sweeteners, Pulse, Blood-pressure, Glucose

Full text

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Kazmi et al. World Journal of Pharmacy and Pharmaceutical Sciences
COMPARISON OF ACUTE EFFECTS OF SUCRALOSE, ASPARTAME
AND ACESULFAME POTASSIUM ON PULSE, BLOOD PRESSURE,
AND BLOOD GLUCOSE LEVELS IN YOUNG HEALTHY ADULTS
Dr. Syed Asif Jahanzeb Kazmi1*, Dr. Akbar Nawaz Khan2, Dr. Muhammad Naqib3 and
Dr. Tahir Ahmad Munir4
1MBBS, M Phil, PhD Scholar (Pharmacology) Associate Professor, Department of
Pharmacology, Combined Military Hospital (CMH) Institute of Medical Sciences,
Bahawalpur.
2MBBS, M Phil (Physiology) Associate Professor, Department of Physiology, Women
Medical and Dental College, Abottabad.
3MBBS, M Phil (Biochemistry) Associate Professor, Department of Biochemistry, Mohi-Ud-
Din Islamic Medical College, Mirpur, Azad Kashmir.
4MBBS, FCPS (Physiology) Professor, Department of Physiology, Mohi-Ud-Din Islamic
Medical College, Mirpur, Azad Kashmir.
ABSTRACT
Background: The use of non-nutritive sweeteners (NNSs) have
become increasingly popular, so their health benefits and potential
adverse effects should be evaluated. Methodology: This
nonrandomized case-control comparative study was done at Mohi ud-
Din Islamic Medical College on 200 healthy undergraduate medical
students in October 2017 after approval from ethical committee. The
participants were equally divided into groups A, B, C and D. The
control group A was given 100 gm cellulose while participants of
group B, C and D were given 0.36 gm (5 mg/kg) sucralose, 10.8 gm
(150 mg/kg) aspartame and 3.24 gm (45 mg/kg) acesulfame potassium
respectively in a glass of 180 ml water. The arterial pulse, systolic and
diastolic pressures were measured at 0, 30, 60, 90 and 120 minutes.
The random blood glucose levels were checked at 0 and 120 minutes in
all the participants. Results: The random blood glucose levels showed
a non-significant difference (p>0.05) at 0 and 120 minutes within and
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
SJIF Impact Factor 6.647
Volume 7, Issue 2, 60-69 Research Article ISSN 2278 – 4357
*Corresponding Author
Dr. Syed Asif Jahanzeb
Kazmi
MBBS, M Phil, PhD
Scholar (Pharmacology)
Associate Professor,
Department of
Pharmacology, Combined
Military Hospital (CMH)
Institute of Medical
Sciences, Bahawalpur.
Article Received on
23 November 2017,
Revised on 13 Dec. 2017,
Accepted on 04 Jan. 2018
DOI: 10.20959/wjpps20182-10859

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Kazmi et al. World Journal of Pharmacy and Pharmaceutical Sciences
between all the study groups. A significant difference (p<0.05) regarding the pulse rate at 60,
90 and 120 minutes was noticed between participants of group A and B with that of group C
and D. The systolic pressure in participants of group A showed a significant difference
(p<0.05) with that of group C and D at 60, 90 and 120 minutes, while the diastolic pressure at
0, 30, 60, 90 and 120 minutes between and within the groups was found to be non-significant
(p>0.05). Conclusion: The artificial sweetener use showed cardio-metabolic health effects
which require further evaluation, however, the effects on glucose metabolism is non-
significant. Objectives: To see the acute effects of non-nutritive sweeteners on blood
pressure, pulse and blood glucose levels in young healthy individuals.
KEYWORDS: Non-nutritive-sweeteners, Pulse, Blood-pressure, Glucose.
INTRODUCTION
The major contributing factor to rising obesity epidemic is excess consumption of energy-
dense foods and reduced physical activity.[1] while epigenetic changes, alterations of
microbiome, drugs, psychological issues, endocrine disruptors, chronic sleep deprivation, use
of artificial sweeteners and soft drinks also play major role in obesity.[2]
The health issues related to obesity, like maturity onset diabetes mellitus (type 2),
hypertension and heart diseases are not only seen in older but also increasing in the youth.
Most foods marketed towards children are sugar-laden, a common diet component and one of
the major contributing factors to obesity and dental diseases both in children and adults.[3]
Only in US billions of dollars are required to manage morbidity and mortality related to
obesity, which can be managed simply by dietary interventions. Numerous diets amidst quick
weight loss; one such product group is non-nutritive sweeteners (NNS).[4]
Nonnutritive or artificial sweeteners are used, instead of sugars, to flavor and sweeten foods,
beverages and the products used in oral care and in medications. They contain few or no
calories or nutrients and derived from plants, herbs, or even sugar itself. They have a greater
intensity of sweetness compared with sugar, so smaller quantities are needed in foods and
beverages. Currently NNS used as sweetener in food include sucralose, aspartame, saccharin,
acesulfame potassium, neotame, advantame, steviol glycosides, and Luo han guo extract.
These have been recognized safe for use in food by the US Food and Drug Administration
(FDA).[5]

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The NNSs effect energy balance and metabolism through strong activation of the
heterodimeric (T1R1 + T1R3) oral and extra-oral sweet taste receptors and effect hormonal
secretion, cognitive actions (like taste perception, reward learning and memory) and gut
microbiota.[6]
The sucralose was discovered during a collaborative research project of the Tate & Lyle
Company and the Queen Elizabeth College in 1980. Sucralose, a substituted chlorinated
disaccharide with a molecular weight of 400, is described as 4, 10, 6'-trichlorogalactosucrose.
On weight for weight basis, it is 600 times sweeter than that of sugar and is stable at high
temperature and low pH. The hydrolysis products (4-CG, 1-6 DCF) are more rapidly
absorbed than sucralose: 1, 6-DCF undergoes rapid conjugation with glutathione and
eliminated in the urine, while 4-CG is excreted intact in the urine. The FDA approved
sucralose in 1998 and was used as a non-caloric high intensity sweetener in foods and
beverages.[7]
Aspartame, an odorless white crystalline powder, derived from aspartic
acid and phenylalanine, was discovered by James M. Schlatter while working on an anti-ulcer
drug. It is about 200 times sweeter than sugar and is used in frozen desserts,
gelatins, beverages and chewing gum. On cooking or when metabolized, it breaks down into
its constituent amino acids but is stable in acidic condition.[8] Aspartame is one of the most
widely tested food ingredients to date but had shown cancer, neurological as well as
psychiatric side effects by various researchers.[9]
Currently it is found safe for consumption by regulatory bodies like UK Food Standards
Agency,[10] European Food Safety Authority (EFSA).[11]
https://en.wikipedia.org/wiki/Sugar_substitute - cite_note-19and by the Health Canada.[12]
Acesulfame potassium (C4H4KNO4S), a heat stable, white crystalline powder with
molecular weight of 201.24 g/mol. is as sweet as aspartame, but bitter aftertaste. Acesulfame
potassium is often blended with sucralose or aspartame (Ovaltine, carbonated drinks,
pharmaceutical products) and is widely used in diet, baking, protein shakes and chewable as
well as in liquid pharmaceutical products.[13] Its absorption is by interaction of S-O double
bond with metal hydroxide layers, degrade to acetoacetamide and excreted by the kidneys.
Acesulfame potassium aids patients with type 1 diabetes but labeled as anticonvulsants.

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https://en.wikipedia.org/wiki/Acesulfame_potassium - cite_note-Talevi,_Alan_2012-12. The
FDA expanded its approval for use in beverages in 1998 and as a general sweetener in
2003.[14]
The use of artificial sweeteners increase the risk for metabolic syndrome, type 2 diabetes,
hypertension and cardiovascular disease.[15] Presently, no definitive data regarding the acute
effects of NNS related to cardiometabolic effects is available, though the FDA had endorsed
the safety of these additives. Our study was aimed to see the acute effects of different non-
nutritive sweeteners on blood pressure, pulse and blood glucose levels in healthy individuals.
MATERIAL AND METHOD
This nonrandomized case control comparative study with done at Mohi ud-Din Islamic
Medical College AJK undergraduate medical students in October 2017, after approval from
institutional ethical committee and consent of inducted students after explaining the
procedure. A total of 200 students of class 2019 and 2020 were selected non-randomly and
were equally divided into 4 groups A, B, C and D (n-50). Participants with history of illness
related to heart, taking medication for hypertension, depression, anxiety, or having any
vascular diseases were excluded from the study.
Group A was taken as control, while students of group B, C and D were taken as cases.
Before collection of data all participants were seated in a hall for duration of two hours to
explain the methodology and to remove effect of any confounding factor on arterial pulse,
systolic and diastolic blood pressure (mental or physical stress).
At 0 times, the arterial pulse rate from radial artery, systolic and diastolic blood pressure from
brachial artery were measured in all the participants. The participants of group B, C and D
were given 0.36gm (5mg/kg) sucralose, 10.8 gm (150mg/kg) aspartame and 3.24gm (45
mg/kg) acesulfame potassium respectively with a glass of 180 ml of water, the dose of these
NNSs has 200 time more Sweetness compared to sugar and is 3 times of Acceptable Daily
Intake ADI.[16] while participants of group A were given 10 gm of cellulose, using a physical
balance electrically operated with 0.001mg precision. The arterial pulse, systolic and diastolic
blood pressure were also measured at 30, 60, 90 and 120 minutes.
The blood sugar levels were checked at 0 and then at 120 minutes in all the participants.

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Data Analysis
Data was analyzed by SPSS version 16. The quantitative data was presented as mean and
standard deviation. Difference between two groups was calculated using student t test. The
95% confidence interval was taken and p-value less than 0.05 was considered significant.
One way ANOVA was used to show the difference within the groups and between the
groups.
RESULTS
Table 1: acute effect of non-nutritive sweeteners on blood glucose levels, and pulse at
different time intervals.
Variables
Group A
(Control)
Group B
(Sucralose)
Group C
(Aspartame)
Group D
(Acesulfame)
P
value
A+B
P
value
A+C
P
value
A+D
P
value
B+C
P
value
B+D
P
value
C+D
Age
18.82±0.80
18.60±0.57
18.64±0.59
18.64±0.59
0.117
0.206
0.206
0.733
0.733
1.00
Glucose-0
132.98±5.95
132.88±5.86
132.52±5.75
132.76±5.78
0.933
0.695
0.852
0.757
0.918
0.836
Glucose 120 Min
134.82±7.24
134.4±5.86
134.96±7.33
135.42±6.83
0.775
0.924
0.671
0.705
0.476
0.746
Pulse 0
78.68±8.02
77.18±6.70
77.38±10.48
77.38±9.34
0.313
0.488
0.450
0.910
0.912
0.992
Pulse 30 min
79.44±6.85
77.98±17.38
83.32±9.98
83.38±8.98
0.582
0.026
0.015
0.063
0.054
0.975
Pulse 60 min
78.22±8.42
75.96±15.70
83.26±10.18
83.0±8.73
0.372
0.008
0.006
0.007
0.007
0.891
Pulse 90 min
78.40±12.14
75.78±15.82
82.28±9.89
83.96±8.83
0.355
0.083
0.010
0.016
0.002
0.373
Pulse 120 min
79.32±7.30
77.72±6.07
84.16±10.73
83.22±9.90
0.237
0.010
0.027
0.000
0.001
0.650
Table 2: Acute effect of non-nutritive sweetener at systolic and diastolic blood pressure
at different time intervals.
Variables
Group A
Control
Group B
Sucralose
Group C
Aspartame
Group D
Acesulfame
P value
A+B
P value
A+C
P value
A+D
P value
B+C
P value
B+D
P value
C+D
Systolic Pr-0 min
115.12±9.09
113.82±9.61
112.12±9.6
113.18±9.35
0.489
0.112
0.296
0.379
0.737
0.578
Systolic Pr-30 min
115.64±8.00
114.40±9.94
113.40±10.17
113.0±1.15
0.494
0.224
0.152
0.620
0.488
0.844
Systolic Pr-60 min
116.92±8.98
112.60±11.21
109.82±11.39
110.60±11.0
0.166
0.001
0.002
0.223
0.078
0.715
Systolic Pr-90 min
117.84±10.2
114.20±11.65
112.54±11.18
113.50±12.36
0.100
0.015
0.059
0.469
0.771
0.685
Systolic Pr-120 min
117.16±8.62
113.98±11.14
112.02±10.54
113.36±10.44
0.114
0.009
0.050
0.369
0.775
0.525
Diastolic Pr-0
75.56±6.17
75.20±7.47
73.70±7.27
74.60±6.91
0.793
0.171
0.466
0.312
0.678
0.527
Diastolic Pr-30 min
76.74±5.97
76.92±7.17
78.98±8,30
75.76±10.45
0.892
0.125
0.566
0.188
0.519
0.091
Diastolic Pr-60 min
76.64±6.37
75.32±6.65
74.96±5.93
76.00±5.19
0.314
0.176
0.583
0.776
0.570
0.354
Diastolic Pr-90 min
76.80±6.04
75.58±6.75
74.74±6.44
75.92±6.00
0.344
0.103
0.467
0.526
0.791
0.346
Diastolic Pr-120 min
77.00±5.77
76.32±6.49
76.12±7.98
77.90±8.99
0.581
0.424
0.553
0.353
0.316
0.918
Table 3: One way ANOVA between and within the groups.
Variables
Mean Square
Between group
Mean Square
Within group
F value
p value
Glucose 0
1.965
34.122
0.058
0.982
Glucose 120 min
10.200
52.695
0.194
0.901
Pulse – 0 min
23.980
70.651
0.313
0.816
Pulse 30min
376.620
132.479
2.843
0.039
Pulse 60 min
651.153
124.429
5.233
0.002
Pulse 90 min
478.173
146.171
3.271
0.022
Pulse 120 min
474.178
75.909
6.247
0.000
Systolic pressure 0
76.653
88.762
0.886
0.449

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Systolic pressure 30 min
69.353
92.396
0.751
0.523
Systolic pressure 60 min
503.138
114.738
4.385
0.005
Systolic pressure 90 min
268.093
129.672
2.067
0.043
Systolic pressure 120 min
237.473
104.726
2.268
0.040
Diastolic pressure 0
33.045
48.647
0.679
0.566
Diastolic pressure-30 min
156.978
47.966
3.273
0.122
Diastolic pressure-60 min
27.700
36.798
0.753
0.522
Diastolic pressure -90 min
36.333
39.946
0.910
0.437
Diastolic pressure-120 min
66.013
42.397
1.533
0.207
RESULTS
Table 1 shows acute effect of non-nutritive sweeteners on blood glucose levels and pulse at
different time intervals. The study groups showed a mean age of 18.64±0.66 years. A non-
significant difference was noticed regarding random blood glucose levels before (p – 0.933,
0.695, 0.852) and 120 minutes after (p - 0.775, 0.924, 0.671) ingestion of sucral (group B),
aspartame (group C) and acesulfame potassium (group D) compared to control group
respectively. A same trend of non-significant difference was noticed when random blood
glucose levels at 0 and 120 minutes in participants of group B were compared with that of
group C (p-0.757, 0.705) and group D (p-0.918, 0.476) respectively. Similarly the difference
for random blood glucose between group C and D was also non-significant at 0 and 120
minutes (p-0.836, 0.746) respectively. The pulse rate at 0 time between group A and B (p-
0.313), group A and C (p-0.488), group A and D (p-0.450) were non-significant. When the
heart rate at 30, 60, 90 and 120 minutes between control (group A) and the participants of
group B, (0.582, 0.372, 0.355, 0.237 respectively, was compared, it was found to be non-
significant. However, a statistically significant difference (p<0.05) was noticed when heart
rate at 30, 60, 90,and 120 minutes between participants of group A was compared with that of
group C and group D. A non-significant difference was seen when pulse rate at 0 and 30
minutes of group B was compared with that of group C (0.910, 0.063) and group D (p-0.912,
0.054) respectively, a same trend of non-significant (p-0.992, 0.975) at 0,and 30 minutes
pulse rate was present between participants of group C and D. When pulse rate at 60 90, and
120 minutes in participants of group B was compared with that of group C and D, a
significant difference was found (p<0.05), however, the difference was non-significant
(p>0.05) between participants of groups C and D at 30, 60,90 and 120 minutes.
Table 2 shows acute effect of non-nutritive sweetener at systolic and diastolic blood pressure
Systolic pressure at 0 and 30 minutes showed a non-significant difference between
participants of group A and that of B (0.489, 0.494), group C (0.112, 0.224) and D (0.296,

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Kazmi et al. World Journal of Pharmacy and Pharmaceutical Sciences
0.152) respectively. A same trend of non-significant difference was noticed when systolic
pressure at 60, 90 and 120 minutes of group A was compared with that of group B (0.166,
0.100, 0.114) respectively, however, the difference regarding systolic pressure at 60, 90 and
120 minutes was statistically significant (p<0.05) when participants of group A were
compared with that of group C and D. The difference for systolic blood pressure was non-
significant at 30, 60, 90 and 120 minutes between participants of group B and C (0.620,
0.223, 0.469, 0.369) respectively and between group B and group D (0.488, 0.078, 0.771,
0.775) respectively. A similar trend of non-significance for systolic pressure was noticed
between group C and D at 30, 60, 90 and 120 minutes (0.844, 0.715, 0.685, 0.525)
respectively.
The diastolic pressure at 0, 30, 60, 90 and 120 minutes between the control and the study
groups B, C and D was found to be non-significant (p>0.05). A same trend of non-significant
difference (p>0.05) was noticed when diastolic pressure between the participants of group B
were compared with that of group C and D. Similarly the diastolic pressure between groups C
and D showed a non-significant difference at different time intervals (o, 30, 60, 90 and 120
minutes).
The systolic pressure at 60, 90 and 120 minutes showed significant difference (p<0.05)
within and between the groups, however non-significant difference was seen at 0 and 30
minutes (0.449, 0.523) times respectively.
The diastolic pressure at different time intervals (0, 30, 60, 90 and 120 minutes) between and
within the groups were found to be non-significant (p>0.05).
Table 3 shows one way analysis of variance between and within the groups.
The glucose levels were non-significant within and between the groups at 0 and 120 minutes
(0.982, 0.901) respectively. The statistically significant difference (p<0.05) was noticed when
pulse rate at 30, 60, 90 and 120 minutes were compared within the group and between the
groups, however, the difference for pulse rate at 0 time was non-significant (p-0.816)
between and within the groups.
The ANOVA showed significant difference (p<0.05) between and within the groups
regarding systolic pressure at 60, 90 and 120 minutes, however, it was non-significant at 0

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and 30 minutes (p-0.499, 0.523) respectively. The diastolic pressure at 0, 30, 60, 90 and 120
minutes within and between the groups was non-significant (p>0.05).
DISCUSSION
Our results showed no effects on random blood glucose levels after taking the NNS
(sucralose, aspartame and Acesulfame potassium) in study groups compared to control group.
These results are consistence with Brown et al[17] who showed no significant effect on blood
glucose levels after oral consumption of NNSs without co-administration of glucose. The
Jing Ma et al[18] showed that when Sucralose was administered by intraduodenal infusion in
combination with glucose, there was no marked effect on blood glucose however,[19] GLP-1
was elevated in healthy as well as in patients with type 1 diabetes. In vivo, the expression of
sodium glucose transporter-1, Na+-glucose cotransporter and glucose absorption increases
after oral ingestion of sucralose.[20]
Our results showed significant raised levels of pulse and blood pressure in participants who were
given aspartame and acesulfame compared to control. These results are consistent with Kiritsy et
al[21] showed acute effects of aspartame on systolic blood pressure in spontaneously hypertensive
rats. Dagfinn et al[22] indicated that daily consumption of artificially-sweetened beverages
showed significantly increased risk of hypertension and vascular events, equal in magnitude
to daily consumption of sugar-sweetened beverages.
Aspartame, comprising half of the phenylalanine molecules, elevates blood and brain tyrosine
levels which being hydrolyzed to phenylalanine. The phenylalanine in turn converts to
catecholamine-dopamine, epinephrine and norepinephrine. The phenylalanine and
catecholamine might cause nerve damage in the brain, which in turn affects signaling
transmissions from brain to heart, causing arrhythmia or an irregular heart-beat, palpitations,
dizziness, fainting, weakness and shortness of breath. The conversion also results raised
blood pressure. Aspartame also has evidenced peripheral vasomotor features like Raynaud
phenomenon and the pulmonary hypertension.[23] The likelihood of pulmonary hypertension
induced by the vasoconstrictive effects of aspartame products.[22] Even sudden death among
previously well individuals including pilots, drivers and athletes is also reported to aspartame
and its breakdown products.[24]

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CONCLUSION
The effects of the NNSs on glucose metabolism are not clear, however, there is strong
clinical association between artificial sweeteners and cardiometabolic outcomes. There is a
need for further research to address the evidence gaps related to health effects of NNSs use.
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