XYLITOL: A SUGAR SUBSTITUTE FOR PATIENTS OF DIABETES MELLITUS

Abstract

India figures conspicuously around the world for rapid growing of diabetes at a high rate and every fifth diabetic in the world is found to be Indian. India is also termed as " Diabetic capital of world " with high prevalence of disease among South Indian population. Obesity, food insecurity, illiteracy, poor sanitation, poor glycemic control and dominance of communicable diseases are the main factors responsible for developing this disease at a fast rate among Indian people. The treatment approaches currently used against diabetes are use of oral drugs, amylin agonists, glucagon antagonists, protein tyrosine phosphatase inhibitors, salicylate derivatives and G protein coupled receptors. The currently used therapeutic approaches against diabetes are costly and resulting in various side effects like allergic reactions, swollen ankles, weight gain, abdominal pain and digestive disturbances. The use of natural alcoholic sugars like sorbitol, mannitol, xylitol, erythritol, maltitol and lactitol is another alternative treatment against diabetes for controlling sugar levels. Among various alcoholic sugars, xylitol is found to be most effective due to its unique properties, resulting in its wide use in many industrial applications. In addition, GRAS status has been given to xylitol by FDA, USA in 1986 and is approved to be safe for human consumption. Currently, most of the xylitol demand has been met by its chemical synthesis, which is costly and resulting in low product yield. The alternative approach for synthesis of xylitol is biotechnological methods using whole cells and enzymatic methods by utilizing various low cost agricultural wastes as raw materials to decrease its production cost and increasing product yield. The Government of India should

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Balwinder et al. World Journal of Pharmacy and Pharmaceutical Sciences
XYLITOL: A SUGAR SUBSTITUTE FOR PATIENTS OF DIABETES
MELLITUS
Yogita Lugani1, Simmi Oberoi2 and *Balwinder Singh Sooch1
1Enzyme Biotechnology Laboratory, Department of Biotechnology, Punjabi University,
Patiala-147002, Punjab, India.
2Department of Community Medicine, Government Medical College, Patiala-147001,
Punjab, India.
ABSTRACT
India figures conspicuously around the world for rapid growing of
diabetes at a high rate and every fifth diabetic in the world is found to
be Indian. India is also termed as „Diabetic capital of world‟ with high
prevalence of disease among South Indian population. Obesity, food
insecurity, illiteracy, poor sanitation, poor glycemic control and
dominance of communicable diseases are the main factors responsible
for developing this disease at a fast rate among Indian people. The
treatment approaches currently used against diabetes are use of oral
drugs, amylin agonists, glucagon antagonists, protein tyrosine
phosphatase inhibitors, salicylate derivatives and G protein coupled
receptors. The currently used therapeutic approaches against diabetes
are costly and resulting in various side effects like allergic reactions, swollen ankles, weight
gain, abdominal pain and digestive disturbances. The use of natural alcoholic sugars like
sorbitol, mannitol, xylitol, erythritol, maltitol and lactitol is another alternative treatment
against diabetes for controlling sugar levels. Among various alcoholic sugars, xylitol is found
to be most effective due to its unique properties, resulting in its wide use in many industrial
applications. In addition, GRAS status has been given to xylitol by FDA, USA in 1986 and is
approved to be safe for human consumption. Currently, most of the xylitol demand has been
met by its chemical synthesis, which is costly and resulting in low product yield. The
alternative approach for synthesis of xylitol is biotechnological methods using whole cells
and enzymatic methods by utilizing various low cost agricultural wastes as raw materials to
decrease its production cost and increasing product yield. The Government of India should
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
SJIF Impact Factor 6.647
Volume 6, Issue 4, 741-749 Review Article ISSN 2278 – 4357
Article Received on
01 Feb. 2017,
Revised on 21 Feb. 2017,
Accepted on 13 Mar. 2017
DOI: 10.20959/wjpps20174-8946
*Corresponding Author
Balwinder Singh Sooch
Enzyme Biotechnology
Laboratory, Department of
Biotechnology, Punjabi
University, Patiala-
147002, Punjab, India.

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Balwinder et al. World Journal of Pharmacy and Pharmaceutical Sciences
also need to focus on planning some projects on utilization of these agricultural wastes,
which are produced in huge amounts annually in India, for xylitol production to fulfill the
need of xylitol for Indian market.
KEYWORDS: Xylitol, Xylose, Diabetes, Xylitol, Agricultural waste, Sweetener, Alcoholic
sugar.
INTRODUCTION
Diabetes is a rapidly growing non communicable disease in India with prevalence of 69.2
million and it is rising day by day at a high rate.[1] This disease is found to be more prevalent
among the population of urban areas compared to rural one. Various studies indicate the high
prevalence of diabetes among people of South Indians than North Indians.[2] Obesity, food
insecurity, illiteracy, poor sanitation, poor glycemic control and dominance of communicable
diseases are the main factors responsible for this disease.[3-4] Currently, various therapeutic
approaches are available to control diabetes, however, these treatments are not cost effective
and associated with many side effects. The use of natural alcoholic sugars like sorbitol,
mannitol, xylitol, erythritol, maltitol and lactitol is another alternative strategy against
diabetes for controlling sugar levels. Amongst various alcoholic sugars, xylitol is found to be
most effective due to its unique properties like sweetening power similar to sucrose, its
metabolism independent to insulin, absence of maillard reaction, negative heat of dissolution,
anticariogenicity and antiketogenicity. The current paper summarizes the magnitude of
diabetes in India, need to control diabetes, treatments available for this disease, use of xylitol
as sugar substitute for diabetic patients, processes for xylitol production, global status and
safety issues of xylitol.
MAGNITUDE OF DIABETES: INDIAN SCENARIO
Diabetes is growing rapidly at an alarming rate in India and that is why India is being termed
as „diabetes capital of world‟.[5] Currently, the prevalence of this major non communicable
disease (NCD) in India is 69.2 million, which is expected to be rise at a rate of 78.5% (123.5
million) by the year 2040. From the world record with diabetic patients, every fifth diabetic
in the world is found to be an Indian.[1] The Atlas of Diabetes (2006) published by
International Diabetes Federation revealed the urgent need to follow the preventive steps
against this rapidly rising disease.[5] The incidence of diabetes varies with the geographical
distribution with one quarter in rural populations that of urban populations.2 The first national
study on prevalence of diabetes was done between 1972 and 1975 by Indian Council of

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Balwinder et al. World Journal of Pharmacy and Pharmaceutical Sciences
Medical Research (ICMR) and this disease was found to be highly prevalent in urban
population compared to rural population.[6] Previous studies conducted by Indian Council of
Medical Research (ICMR) proved the lower prevalence of this disease in population of North
India like Chandigarh, 0.12 million and Jharkhand, 0.96 million compared to other states like
Maharashtra, 9.2 million and Tamil Nadu, 4.8 million.[2] Similar trend of diabetes were
recorded in metropolitan cities located in different directions of India like Kolkata, 11.7%;
Kashmir Valley, 6.1%; New Delhi, 11.6%; Mumbai, 9.3%; South India: Chennai, 13.5%;
Hyderabad, 16.6% and Bangalore, 12.4% by National Urban Diabetes Survey.[7]
NEED TO CONTROL DIABETES
The major concern of rising diabetes was also noticed by the Government of India due to
rapid increase of this deadly disease, which has reached at epidemic range in some parts of
the country. This epidemic disease results in loss of national productivity and exchequer at
social level. There is an immediate need to generate awareness among people for early
detection, cost effective management and rehabilitation of diabetic patients.[8] The major
factors responsible for this disease are obesity, food insecurity, illiteracy, poor sanitation,
poor glycemic control and dominance of communicable diseases. It is clear from the world
record that diabetes is very prevalent among the people of India and thus it has become
important to control the spread of this disease at a large scale. Many previous studies on
diabetes also suggested the need for developing government policies, interventions and public
awareness programmed in India to overcome the spread of this disease in the future
generation.[9-10]
TREATMENTS AVAILABLE TO CONTROL DIABETES
Several oral drugs like biguanides, sulfonylureas, glinides, thiazolidinediones, amylin
agonists, glucagon antagonists, protein tyrosine phosphatase inhibitors, salicylate derivatives
and G protein coupled receptors are used to treat diabetes.[11] However, these treatments are
costly and associated with many side effects like allergic reactions, swollen ankles, weight
gain, abdominal pain and digestive disturbances. Several non-nutritive, high intensity sugar
alcohols like sorbitol, mannitol, xylitol, erythritol, maltitol and lactitol are available in the
market for diabetic people due to their low calorie value, low glycemic index with high rate
of controlling blood sugar levels.[12-13] The relative sweetness and nutritive value of various
polyol sugars is given in Table 1.

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Balwinder et al. World Journal of Pharmacy and Pharmaceutical Sciences
Table 1: Relative sweetness and nutritive value of various polyol sugars.
Sugar Alcohol
Relative sweetness
(Sucrose=1)
Nutritive value
Xylitol
1.0
2.4
Lactitol
0.4
2.0
Sorbitol
0.6
2.6
Erythritol
0.7
0.2
Mannitol
0.5
1.6
Maltitol
0.9
2.1
Isomalt
0.5
2.0
Hydrogenated starch hydrolysates
0.3
3.0
XYLITOL AS SUGAR SUBSTITUTE FOR DIABETIC PATIENTS
Xylitol is pentitol sugar (C5H12O5) with sweetening power similar to sucrose but with low
calorie content. This alcoholic pentose sugar is found naturally in many fruits and vegetables
like yellow plum, strawberries, raspberries, cauliflower and lettuce.[14] The glycemic index of
xylitol is low because it is not actively transported through intestinal tract. The high tolerance
of xylitol by diabetics is due to its metabolism in humans by two different pathways, such as
direct absorption (mainly in liver) and indirect metabolism by intestinal bacteria. Both of
these mechanisms of xylitol metabolism are independent to insulin and hence it acts as
promising ideal alternate sweetner for diabetics.[15] Xylitol controls blood glucose, lipid level
and weight control, which are the three important objectives for diabetes management. It is
poorly absorbed by the human digestive system and thus acts as a dietary soluble fiber to
maintain healthy gut flora. Xylitol acts as prebiotic and fermented by the bacteria of large
intestine into low calories short chain fatty acids. These fatty acids are absorbed by small
intestine into blood circulation where they act as source of energy for various metabolic
pathways.[13] Hence, this polyol sugar is very good supplement as sugar for diabetic patients.
PROCESSES FOR PRODUCTION OF XYLITOL
There are mainly three processes for the production of xylitol such as solid liquid extraction,
chemical synthesis and biotechnological methods. Currently, the industrial demand of xylitol
has been met through its synthesis by chemical hydrogenation of xylose at high temperature
and pressure in the presence of catalyst. However, there are many limitations associated with
this chemical process like high process cost, low product yield and hazardous effects on
environment.[16] In the process of solid liquid extraction, xylitol is recovered from the natural
sources (fruits and vegetables), but small percentage present in natural sources is major
hindrance to make this process economical.[17-18] Biotechnological methods are based on

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utilization of microorganisms or purified enzyme for the production of xylitol by utilizing
various agriculutural lignocellulosic waste materials derived from wood, grass, forestry
waste, agricultural residues and municipal solid wastes are center of attraction for researchers
now a days.[19] Candida guilliermondii and Candida tropicalis are two commonly used yeasts
for the production of high yield of xylitol.[20-21] Most of the previous research on production
of xylitol using biotechnological methods has been conducted with whole microbial cells
(mainly yeasts) and recombinant organisms and very little work has been reported with
purified xylose reducatse enzyme. Hence, researchers should focus on enzymatic production
involving recent techniques like protein engineering using bioinformatics tools needs to be
done for economical production of xylitol.
GLOBAL STATUS FOR USE OF XYLITOL
The global market of xylitol is increasing day by day and it is estimated to be USD 1 billion
by 2020.[22] In addition to substituent as sugar, there are various potential applications of
xylitol in different industrial sectors, such as food, pharmaceutical, odontological, cosmetics
and textiles.[23-27] The wide applications of xylitol are due to its unique properties like
sweetening power similar to sucrose, its metabolism independent to insulin, absence of
maillard reaction, negative heat of dissolution, anticariogenicity and antiketogenicity. The
products of xylitol available in the market are Epic-xylitol gums, B-FRESH gums, Tic Tac
“Silvers”, Xylitol (100% pure natural sweetener), Omnii “Theramints”.[28] The major xylitol
market share is dominated by chewing gums applications followed by confectionery and food
sectors. However, a small amount of xylitol is used in the pharmaceuticals and
nutraceuticals.[29] Moreover, most of the xylitol products have been manufactured by USA
and its demend in India is catered through imports. Therefore, there is an utmost need to
focus on biotechnological production of xylitol by utilizing various lignocellulosic waste as
raw materials. The Government of India should need to focus on planning some projects on
economical xylitol production to fulfill the need of xylitol for Indian market by involving
biological methods.
SAFETY ISSUES OF XYLITOL FOR DIABETICS
GRAS (Generally Recognized as Safe) status has been given to xylitol by FDA (Food and
Drug Administration) in 1986. Xylitol has shown very little toxicity issues through various
routes of administration with negative results for tetrogenicity, embryogenicity and
reproductive toxicity for mutagenicity and clastogenicity through in vivo and in vitro

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studies.[30-32] FDA (1986) approved xylitol to be safe for human consumption and joint
FAO/WHO Experts Committee on food additives also recommended safety levels of this
polyol sugar with no need of further toxicological studies. Many previous studies conducted
on rats and diabetic patients confirmed the safety levels of xylitol with no side effects in
relation to carbohydrate and fat metabolism.[33-36]
CONCLUSION
Diabetes is found to be an epidemic disease among the people of India resulting in loss of
national productivity and exchequer at social level. The major factors responsible for this
disease are obesity, food insecurity, illiteracy, poor sanitation, poor glycemic control and
dominance of communicable diseases. Several oral drugs, amylin agonists, glucagon
antagonists, protein tyrosine phosphatase inhibitors, salicylate derivatives and G protein
coupled receptors are used to treat diabetes. However, these treatments are costly and
associated with many side effects like allergic reactions, swollen ankles, weight gain,
abdominal pain and digestive disturbances. Therefore, there is an urgent need to develop
government policies, interventions and public awareness programmed in India to overcome
the spread of this disease in the future generation. As an alternate natural sweetener, xylitol
overcomes the spread of diabetes due to its metabolism independent to insulin. There are
many constrains towards the use of this polyol sugar mainly the cost factor. Therefore, some
biotechnological methods should be developed by utilizing low cost agrowaste material to
increase the yield of xylitol in cost effective manner for its utilization in therapeutic sector.
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