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9 Toxicity andSafety Aspects ofInulin
189
10
Role ofInulin intheManagement
ofMetabolic Disorders
SanziaMehjabin
, Md.KhokonMiahAkanda
,
A.H.M.NazmulHasan
, andG.M.MasudParvez
Abstract
Globally, metabolic disorders have become major public health concerns, which
include cardiovascular diseases, type 2 diabetes, and obesity. Currently, studies
are investigating dietary supplements as therapeutic options for various diseases.
Inulin, a soluble ber in the diet, has been considered a possible remedy because
of its unique physical-chemical properties and potential health advantages. On
the other hand, inulin is found in plants like chicory roots, and it is known to have
benecial effects on glucose metabolism, insulin sensitivity, and lipid prole.
The ability to modulate gut microbiota composition and function is one mecha-
nism through which inulin may affect metabolic health. Furthermore, prebiotic
activities of inulin result in short-chain fatty acid production that inuences
energy metabolism and regulation of inammation. For this reason, clinical
research examining the impact of oral supplementation with inulin on metabolic
parameters has shown promise; hence, it can be used as a dietary therapy for
those who are at risk of or are already suffering from such conditions. Also,
understanding how these compounds work will help develop precise interven-
tions directed at enhancing metabolic well-being using this natural ingredient.
This chapter underlines the various aspects of inulin’s participation in metabolic
disorders with emphasis on its potential as a natural and easily available compo-
nent of our diet to promote metabolic health. Furthermore, the current investiga-
S. Mehjabin
Department of Pharmacy, Varendra University, Rajshahi, Bangladesh
M. K. M. Akanda (*) · A. H. M. Nazmul Hasan
Department of Pharmacy, University of Asia Pacic, Dhaka, Bangladesh
G. M. M. Parvez
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of
Georgia, Athens, GA, USA
190
tions are promising for knowledge upgradation regarding inulin’s mechanisms of
action that could be used in the prevention and management of metabolic
disorders.
Keywords
Inulin · Biopolymer · Metabolic disorders · Prebiotic · Obesity · Insulin sensitivity
Abbreviations
ACF Antecubital fossa
AMPK AMP-activated protein kinase
AOM Azoxymethane
CC Colon cancer
CCK Cholecystokinin
Cd36 Luster of differentiation 36
DMH Dimethylhydrazine
DP values Desmosomal protein
FDA Food and Drug Administration
FFAR Free fatty acid receptor
FOS Fructo-oligosaccharides
GIT Gastrointestinal tract
GLP Glucagon-like peptide-1
GOS Galacto-oligosaccharides
HDAC Histone deacetylases
HLA-B27 Human leukocyte antigen B27
IBD Inammatory bowel disease
IFNG Interferon gamma
IL Interleukin
KLF Kruppel-like factor
LDL Low-density lipoprotein
LSD Lysergic acid diethylamide
MAPK Mitogen-activated protein kinase
mPa.s. Millipascal-second
mRNA Messenger ribonucleic acid
NK cell Natural killer cell
pH Potential hydrogen
PomX Pomegranate extract
PYY Peptide YY
SCFA Short-chain fatty acids
T cell Thymus cell
TNF Tumor necrosis factor
S. Mehjabin et al.
191
10.1 Introduction
The problems of obesity, diabetes, and heart disease as metabolic disorders have
caused a lot of interest in studying natural substances and changing diets as possible
remedies. Among many substances drawing scientists’ attention is inulin, which is
a versatile, naturally occurring polysaccharide that can be used to treat these dis-
eases (Haque etal. 2016). In addition to other plants, inulin is derived from chicory
and found naturally. Inulin is a kind of fructan carbohydrate which can be traced in
many plant sources, including artichokes roots, dandelion, and chicory (Roberfroid
2002; Akanda et al. 2024). Inulin has unique structure characterized by binding
several fructose molecules through glycosidic bonds β (2-1), which renders it indi-
gestible in the upper gastrointestinal tract. This distinctive property has piqued the
interest of researchers, as inulin’s behavior in the digestive system presents a range
of physiological benets that extend beyond mere caloric content (Hsu and Bansal
2011). FDA authorized inulin as a dietary ber to improve food nutrition in 2018.
To compare glomerular ltration rate calculations, inulin is the “gold standard” for
renal function (Roberfroid 2007). Research conducted in the last few decades has
shown that inulin signicantly improves constipation, enhances mineral absorption,
lowers hyperlipidemia and hyperglycemia, regulates gut ora, and suppresses
inammation (Nair etal. 2010; Akanda etal. 2024). The purpose of this chapter is
to delve into the multifaceted role of inulin in the context of metabolic disorders. As
we navigate through the biochemical intricacies and physiological responses associ-
ated with inulin consumption, we aim to unravel its potential as a dietary adjunct in
the prevention and management of conditions such as insulin resistance, dyslipid-
emia, and inammation. Furthermore, the investigation into the effects of inulin on
the composition of the gut microbiota and its subsequent impact on metabolic health
introduces an extra level of intricacy to its function within the complex relationship
between diet and metabolic homeostasis.
10.2 Inulin: ADietary Fiber Overview
The dietary ber inulin is a fructan, which is a type of carbohydrate. It is naturally
occurring and can be found in a variety of plants, primarily in the roots and rhi-
zomes of certain vegetables, such as chicory root, Jerusalem artichoke, and dande-
lion greens. The human enzymes in the small intestine do not breakdown inulin
which means it passes intact to the colon, where it serves as a substrate for bene-
cial gut bacteria (Niness 1999). Due to its water solubility, the substance exhibits
osmotic activity. Certain plant species may adjust the osmotic potential of their cells
by hydrolyzing inulin molecules, therefore changing the polymerization level. By
manipulating osmotic potential in winter, plants are able to endure cold and drought
conditions without modifying the overall carbohydrate content (Boeckner et al.
2001). A German scientist named Valentin Rose identied inulin in 1804. Utilizing
boiling-water extraction, he discovered “a peculiar substance” in the roots of Inula
helenium (Irvine and Soutar 1920). During the 1920s, Irvine investigated the
10 Role ofInulin intheManagement ofMetabolic Disorders
192
molecular structure of inulin using chemical techniques such as methylation.
Additionally, he devised the isolation method for this novel anhydrofructose (Irvine
and Stevenson 1929). In the 1930s, researchers began investigating renal tubules in
an effort to identify a biomarker substance that, upon introduction into tubules,
would not be reabsorbed or secreted (Richards et al. 1934). Richards developed
inulin due to its elevated molecular weight and notable resistance to enzymatic deg-
radation. To ascertain the glomerular ltration rate of the kidneys, inulin is utilized
(Coulthard and Ruddock 1983). Inulin comprises a diverse array of fructose poly-
mers. The compound is composed of a repetitive fructosyl moiety and chain-
terminating glucosyl moieties that are connected via β (2,1) bonds. Optimal standard
inulin possesses a degree of polymerization between 2 and 60. High-performance
inulin remains, following the elimination of fractions with DP values below 10
throughout the manufacturing procedure. Certain articles categorized fractions with
DP values below 10 as short-chained fructo-oligosaccharides, while designating
inulin as the name given to the longer-chained molecules exclusively (Mehjabin
etal. 2024a). Due to the presence of β (2,1) linkages, inulin evades enzymatic diges-
tion within the human alimentary system, thereby enhancing its functional charac-
teristics: diminished caloric content, dietary ber, and prebiotic properties. In the
absence of color and odor, the impression on the sensory attributes of food products
is minimal. Oligofructose is 35% as sweet as sucrose and has a comparable sweet-
ening prole to sugar. High-performance inulin is not pleasantly sweet like regular
inulin. It has a greater solubility than conventional bers. When inulin is mixed
extensively with a liquid, it produces a white, creamy gel that resembles fat. The
insoluble submicron crystalline inulin particles in its three-dimensional gel network
immobilize large amounts of water. This ensures the material’s physical stability. It
is also capable of enhancing the stability of emulsions and foams (Franck 2002).
The majority of commercially available inulin is derived from chicory. A biannual
plant species, chicory is a member of the Asteraceae family. Chicory plants enter the
vegetative phase during their initial year of development, manufacturing solely
leaves, brous, taproots, and roots. The root stocks resemble oblong sugar beets in
miniature form (Bonnema etal. 2010). The synthesis of inulin occurs in two phases.
First, the unprocessed syrup is extracted and initially puried; in the second phase,
it is rened to produce a commercial product with a concentration greater than
99.5%. Advanced methods like supercritical carbon dioxide, ultrasound, pulsed
electric eld, and simultaneous ultrasonic/microwave are used to extract inulin.
These technologies aim to increase the yield of the puried nal product while
reducing energy consumption (Menegas etal. 2013). However, the conventional
approach to purication necessitates carbonation, prelimiting, liming, and utilizing
an elevated temperature range of 80–90°C in order to eliminate impurities from the
extracted uid (Furrie etal. 2005). Calcium ions introduced into claried juice or
inulin compounds in juice extracted undergoing hydrolysis may necessitate addi-
tional purication procedures (Kip etal. 2006). Reportedly, membrane-based tech-
nologies such as ultraltration and microltration can also facilitate these laborious
and time-consuming processes. The inulin produced, which has a DP spanning from
3 to 60, mimics the initial DP found in chicory. Long-chain inulin of superior
S. Mehjabin et al.
193
quality with a DP greater than 23 is also attainable (Chao and Priscilla 2009). As a
unique food component, inulin provides numerous signicant dietary advantages in
addition to specic industrial properties that facilitate its widespread utilization in
food applications (Roberfroid 2002). A nely split white material, chicory inulin is
characterized by enhanced clarity. Inulin has an abysmal avor and leaves no lasting
residue. While long-chain inulin does not possess a sweet taste, chicory inulin pro-
vides a sweetness level of approximately 10% in comparison to sucrose (Valluru
and Van den Ende 2008). Inulin exhibits similar properties to bulking agents; when
combined with articially produced sweeteners such as aspartame, acesulfame K in
high concentrations imparts a pleasant mouthfeel accompanied by a faint residue
(Franck 2002). Additionally, these mixtures may reveal a crucial quantitative sweet-
ness formula. At 25 °C, chicory inulin exhibits a moderate solubility in water,
approaching 10%. This characteristic allows for its precipitation-free addition to
aqueous solutions. Water between 50 and 100 degrees Celsius is recommended for
the formulation of inulin solution. Chicory inulin solutions have relatively low
viscosity e.g., at 10°C, a 5% solution exhibits 1.65mPa.s, while a 30% solution
demonstrates 100mPa.s. Water freezing and boiling points are barely affected by
inulin. The addition of 15% chicory inulin signicantly reduces the freezing point
by 0.5°C, demonstrating the importance of low pH, high temperature, and less dry
substance conditions for inulin hydrolysis. Highly acidic circumstances can par-
tially hydrolyze β-(2-1) bonds between fructose molecules (Nair etal. 2010). High
amounts of inulin (long-chain inulin >15% and typical chicory inulin >25%) cause
gelling characteristics and the formation of a gelling structure after shearing. A
rotor-stat mixer or homogenizer thoroughly dissolves inulin in water or another
liquid, creating a white creamy texture. This structure can easily replace fat in diets
up to 100% (Imeson 2010). However, it remains unaffected by pH (between 4 and
9). The concentration of inulin, the amount of total dry matter, shearing variables
(temperature, pressure time, pace), and the kind of shearing instrument used all have
a substantial inuence on inulin’s gelling property. Furthermore, cryo-electron
microscopy revealed that the three-dimensional structure of these inulin gels is
made up of inulin pieces that are typically submicron in size and insoluble in water
(Zimeri and Kokini 2002).
10.2.1 Natural Sources ofInulin
Inulin, a dietary ber, can be found in natural food sources and supplements.
Common sources include chicory root, Jerusalem artichoke, dandelion root, aspara-
gus, onions, leeks, garlic, bananas, agave plants, and dietary supplements. Inulin
can be added to smoothies, yogurt, and other beverages and fortied into food prod-
ucts like energy bars, granola bars, and cereals. However, it is important to consult
a healthcare provider before supplementing with inulin, especially if you have other
health conditions (Mensink et al. 2015; Parvez et al. 2016; Gupta et al. 2019).
Table 10.1 shows the amount of inulin (%) that is in some common foods
(Coussement 1999; Moshfegh etal. 1999).
10 Role ofInulin intheManagement ofMetabolic Disorders
194
Table 10.1 Inulin content
(%) in various foods
Plant part
Plant
Inulin content (%)
Tubercle Jerusalem artichoke 16–20
Root Chicory 15–20
Leaves Dandelion 12–15
Bulb Garlic 9–16
Leaves Goat’s beard 4–11
Root Yacon 3–19
Bulb Onion 2–6
Bulb Leek 3–10
Central
leaves
Artichoke 3–10
Cereal Wheat 1–4
Cereal Barley 0.5–1.5
Cereal Rye 0.5–1.0
Fruit Banana 0.3–0.7
Fig. 10.1 Health benets of inulin dietary ber
10.2.2 Dietary Fiber andIts Importance
Inulin, an organic soluble dietary ber, is naturally present in specic fructan-
containing plants. Due to the fact that it fuels benecial gut ora, it possesses prebi-
otic properties (Akanda and Hasan 2021). The various advantages inulin has on the
body and well-being are what make its presence vital in one’s diet shown in
Fig.10.1.
10.2.2.1 Prebiotic Activity
Prebiotics, which are dietary supplements, promote the development and activity of
specic gut microorganisms that are benecial to the host (Wilson and Whelan
S. Mehjabin et al.
195
2017). An ideal prebiotic ought to undergo selective fermentation by intestinal
microbiota while traversing the upper gastrointestinal tract, avoiding digestion. This
process promotes the proliferation of particular advantageous bacteria, including
Lactobacilli and Bidobacteria, which impart advantageous effects to the host
organism. Prebiotics come in several forms, the majority of which are carbohy-
drates. These include galacto-oligosaccharides (GOS), fructo-oligosaccharides,
pectins, resist-resistant starch, and inulin. Naturally, avanols generated from cocoa
are likewise considered prebiotics, but they are not categorized as carbohydrates
(Davani-Davari etal. 2019). One well-known prebiotic that is involved in control-
ling the human gut microbiota is inulin, which increases the number of Lactobacilli
and Bidobacteria, two types of benecial bacteria. Prebiotics also have a link to
the health advantages of controlling blood sugar and cholesterol, enhancing mineral
absorption, avoiding colon cancer, and relieving constipation. According to a recent
study, inulin may also have the capacity to alleviate symptoms of depression. In
summary, prebiotic inulin imparts signicant physiological advantages to the human
body through the regulation of intestinal microora (Legette etal. 2012; Mehjabin
etal. 2024b). A vast network of microorganisms comprises the human intestinal
ora, the majority of which acquire nutrients through the process of fermentation.
Principal fermenting agents include inulin, oligofructose, and resistant starch,
which are nondigestible and non-absorbed by the human body. Enzymes secreted
by the human body would not decompose them; rather, microorganisms would uti-
lize them once they have reached the large intestine undamaged. For optimal host
health, including inulin in one’s diet promotes fermentation in the intestines by
good bacteria, particularly Bidobacteria and Lactobacilli, which lowers colon pH
and short-chain fatty acids and restricts harmful bacteria growth. The term for this
phenomenon is the bidogenic effect or prebiotic effect, and our gut mucosa absorbs
short-chain fatty acids (Makki etal. 2018).
10.2.2.2 Improved Gut Health
By nourishing the benecial bacteria in the gut, inulin supports a healthy digestive
system. It helps regulate bowel movements, prevent constipation, and alleviate other
digestive issues. 500–1000 bacterial species coexist symbiotically with the human
body in intestine, with Firmicutes and Bacteriodetes constituting the most abundant
phyla (Sommer and Bäckhed 2013; Afroja etal. 2017). The majority of Firmicutes
are benecial bacteria, with Lactobacillus being the most prevalent. This bacterium
is capable of producing acetate and preserving health. Undoubtedly, inulin, in its
capacity as a prebiotic and dietary supplement, exerts a signicant inuence on the
regulation of intestinal ora. Recent research indicates that supplementing schizo-
phrenia mice with inulin substantially increased number of Bidobacterium. In con-
trast, it decreased the numbers of Akkermansia and Eubacterium ssicatena,
bringing their intestinal microbiota closer to that of healthy mice (Hills etal. 2019).
10.2.2.3 Anti-Inflammatory Effects
IBD is a chronic form of intestinal disease that causes abnormal immune responses
leading to bleeding from the rectum and weight loss as well as Crohn’s and
10 Role ofInulin intheManagement ofMetabolic Disorders
196
ulcerative colitis (Parvez and Akanda 2019). For IBD patients, treatment usually
involves immunomodulators and anti-inammatory drugs among other interven-
tions like surgery and endoscopy (Lee etal. 2018; Akter etal. 2020). This study
aimed to examine whether fructo-oligosaccharides (FOS) and inulin could be used
to mitigate colitis or manipulate gut microbiota, hence reducing inammation in
HLA-B27 transgenic rats. On the other hand, FOS increased Bidobacteria pointing
towards relieving chronic bowel inammation, while inulin increased total bacteria
including Bacteroides, Porphyromonas, and Prevotella species. They concluded
that FOS offered a better ability to modify colonic microora when applied in ani-
mal models than inulin for the purpose of decreasing colitis severity (Koleva etal.
2012). An investigation made by scientists recently discovered an interrelationship
between consumption of inulin on gut bacteria epithelial cells. SCFAs generated
during inulin fermentation induced alterations in the intestinal microbiota.
Furthermore, the histone deacetylases (HDAC) and SCFA-mediated G-protein-
coupled receptors not only regulate epithelial cell physiological processes and pre-
serve epithelial integrity but also mitigate the inammatory response in the
gastrointestinal tract (He etal. 2021). Undoubtedly, the immune response is intri-
cately linked to the production of inammatory factors. Study found that inulin
reduced inammatory factors in porcine whipworm Trichuris suis models. Inulin in
the colon upregulated Th2-related immune genes and downregulated Th1-related
pro-inammatory genes, while pigs given inulin and T. suis had the highest
Bacteroidetes-to-Firmicutes ratio (Myhill etal. 2020). This study suggests that both
substances potentially enhanced the immune response in a synergistic manner by
modulating the gut microora. In contrast, this result was precisely the opposite in
whipworm-infected mouse models (He etal. 2017). By impeding worm expulsion,
inulin exacerbated inammatory responses and imbalanced intestinal ora. It
appears that environmental factors signicantly inuence the anti-inammatory
properties of inulin. Therefore, it is imperative to contemplate the correlation
between the environment and diet prior to administering inulin for the purpose of
inammation relief (Myhill etal. 2020).
10.2.2.4 Relief fromDepression
One of the most prevalent illnesses globally, depression is an affective disorder that
arises from a multitude of contributing factors. At this time, the precise etiology of
depression remains elusive; however, it is indisputable that depression is intricately
linked to a variety of factors, encompassing psychological and physical aspects, as
well as heredity. Medications and psychotherapy are typical treatments for depres-
sion. Inulin and other prebiotics have been linked in recent research to cognitive
impairment, antidepressant, and antianxiety properties (Parvez etal. 2017; Sultana
etal. 2017). In 2015, a research endeavor was undertaken to examine the immediate
impacts of inulin on the temperament and cognitive functioning of humans.
Participants were requested to complete mood assessments via questionnaires prior
to and subsequent to inulin administration. Inulin improved mood, dyspepsia, and
appetite compared to placebo. Additionally, inulin increases memory (Smith etal.
2015). Yacon (Smallanthus sonchifolius) inulin-type oligosaccharides were shown
S. Mehjabin et al.