INULINE

CAS Number: 9005-80-5
Chemical Formula: C6nH10n+2O5n+1

Inuline are a group of naturally occurring polysaccharides produced by many types of plants, industrially most often extracted from chicory.
The inuline belong to a class of dietary fibers known as fructans. 

Inuline is used by some plants as a means of storing energy and is typically found in roots or rhizomes. 
Most plants that synthesize and store Inuline do not store other forms of carbohydrate such as starch. 

In the United States in 2018, the Food and Drug Administration approved Inuline as a dietary fiber ingredient used to improve the nutritional value of manufactured food products.
Using Inuline to measure kidney function is the "gold standard" for comparison with other means of estimating glomerular filtration rate.

Inuline is a natural active ingredient. 
Chemically, Inuline is a fructose polymer partly terminated by glucose monomers. 
Produced naturally by numerous plants, Inuline is an outstanding moisturizing active ingredient.

Uses of Inuline:

Harvesting and Extraction of Inuline:
Chicory root is the main source of extraction for commercial production of inulin. 
The extraction process for Inuline is similar to obtaining sugar from sugar beets.

After harvest, the chicory roots are sliced and washed, then soaked in a solvent (hot water or ethanol).
The Inuline is then isolated, purified, and spray dried. 
Inuline may also be synthesized from sucrose.

Processed foods of Inuline:
Inuline received no-objection status as generally recognized as safe (GRAS) from the US Food and Drug Administration (FDA), including long-chain Inuline as GRAS.
In the early 21st century, the use of Inuline in processed foods was due in part to Inuline adaptable characteristics for manufacturing.

Inuline is approved by the FDA as an ingredient to enhance the dietary fiber value of manufactured foods.
Inuline flavor ranges from bland to subtly sweet (about 10% of the sweetness of sugar/sucrose). 

Inuline can be used to replace sugar, fat, and flour. 
This is advantageous because Inuline contains 25–35% of the food energy of carbohydrates (starch, sugar).

In addition to being a versatile ingredient, Inuline provides nutritional advantages by increasing calcium absorption and possibly magnesium absorption, while promoting the growth of intestinal bacteria.
Chicory Inuline is reported to increase absorption of calcium in young women with lower calcium absorption and in young men.

In terms of nutrition, Inuline is considered a form of soluble fiber and is sometimes categorized as a prebiotic.
Conversely, Inuline is also considered a FODMAP, a class of carbohydrates which are rapidly fermented in the colon producing gas.
Although FODMAPs can cause certain digestive discomfort in some people, they produce potentially favorable alterations in the intestinal flora that contribute to maintaining health of the colon.

Due to the body's limited ability to process fructans, Inuline has minimal increasing impact on blood sugar, and may potentially have use in managing blood sugar-related illnesses, such as metabolic syndrome.

Medical:
Inuline and its analog sinistrin are used to help measure kidney function by determining the glomerular filtration rate (GFR), which is the volume of fluid filtered from the renal (kidney) glomerular capillaries into the Bowman's capsule per unit time.
While Inuline is the gold standard for measuring the GFR, Inuline is rarely used in practice due to the expense and difficulty in conducting the test.

Inuline requires intravenous (IV) access for the infusion of Inuline as well as up to twelve blood samples taken from the patient over the course of four hours.
In the United States, creatinine clearance is more widely used to estimate GFR.

Inuline enhances the growth and activities of bacteria or inhibits growth or activities of certain pathogenic bacteria.
Research has linked Inuline to several health benefits, such as helping control diabetes, aiding weight loss and improving digestive health.
A 2017 systematic review of clinical trial results showed that dietary supplementation with Inuline reduced biomarkers of metabolic syndrome.

Diet and Side Effects of Inuline:
The side effects of Inuline dietary fiber diet, which may occur, usually in sensitive persons, are:

Intestinal discomfort, including flatulence, bloating, stomach noises, belching, and cramping
Diarrhea
Inflammation - Inuline can cause an allergy-related type of inflammation in the gut and lungs
Anaphylactic allergic reaction (rare) – Inuline is used for GFR testing, and in some isolated cases has resulted in an allergic reaction, possibly linked to a food allergy response.

Industrial use of Inuline:
Nonhydrolyzed Inuline can also be directly converted to ethanol in a simultaneous saccharification and fermentation process, which may have potential for converting crops high in Inuline into ethanol for fuel.

Benefits of Inuline:
Composed of fructose oligosaccharides, 100% vegetable, Inuline is moisturizing and softening.
Inuline has the power to retain water in the skin tissue and therefore maintains hydration and a soft and silky touch. 
The skin is plumped up and moisturized.

Biochemistry of Inuline:
Inuline are polymers composed mainly of fructose units (fructans), and typically have a terminal glucose. 
The fructose units in Inuline are joined by a β(2→1) glycosidic bond. 

The molecule is almost exclusively linear, with only a few percent branching.
In general, plant Inuline contain between 2 and 70 fructose units  or sometimes as high as 200,  but molecules with less than 10 units are called fructo-oligosaccharides, the simplest being 1-kestose, which has two fructose units and one glucose unit. 
Bacterial Inuline is more highly branched (more than 15% branching) and contains on the order of tens or hundreds of subunits. 

Inuline are named in the following manner, where n is the number of fructose residues and py is the abbreviation for pyranosyl:
Inuline with a terminal glucose are known as alpha-D-glucopyranosyl-[beta-D-fructofuranosyl](n-1)-D-fructofuranosides, abbreviated as GpyFn.
Inuline without glucose are beta-D-fructopyranosyl-[D-fructofuranosyl](n-1)-D-fructofuranosides, abbreviated as FpyFn.

Hydrolysis of Inuline may yield fructo-oligosaccharides, which are oligomers with a degree of polymerization (DP) of 10 or less.

Calculation of glomerular filtration rate:
Inuline is uniquely treated by nephrons in that Inuline is completely filtered at the glomerulus but neither secreted nor reabsorbed by the tubules. 
This property of Inuline allows the clearance of Inuline to be used clinically as a highly accurate measure of glomerular filtration rate (GFR) — the rate of plasma from the afferent arteriole that is filtered into Bowman's capsule measured in ml/min.

Inuline is informative to contrast the properties of Inuline with those of para-aminohippuric acid (PAH). 
PAH is partially filtered from plasma at the glomerulus and not reabsorbed by the tubules, in a manner identical to inulin. 

PAH is different from Inuline in that the fraction of PAH that bypasses the glomerulus and enters the nephron's tubular cells (via the peritubular capillaries) is completely secreted. 
Renal clearance of PAH is thus useful in calculation of renal plasma flow (RPF), which empirically is (1-hematocrit) times renal blood flow. 
Of note, the clearance of PAH is reflective only of RPF to portions of the kidney that deal with urine formation, and, thus, underestimates the actual RPF by about 10%.

The measurement of GFR by Inuline or sinistrin is still considered the gold standard. 
However, Inuline has now been largely replaced by other, simpler measures that are approximations of GFR. 
These measures, which involve clearance of such substrates as EDTA, iohexol, cystatin C, 125I-iothalamate (sodium radioiothalamate), the chromium radioisotope 51Cr (chelated with EDTA), and creatinine, have had their utility confirmed in large cohorts of patients with chronic kidney disease.

For both Inuline and creatinine, the calculations involve concentrations in the urine and in the serum. 
However, unlike creatinine, Inuline is not naturally present in the body. 
This is an advantage of Inuline (because the amount infused will be known) and a disadvantage (because an infusion is necessary).

Chemical structure and properties of Inuline:
Inuline is a heterogeneous collection of fructose polymers. 
Inuline consists of chain-terminating glucosyl moieties and a repetitive fructosyl moiety, which are linked by β(2,1) bonds. 

The degree of polymerization (DP) of standard Inuline ranges from 2 to 60. 
After removing the fractions with DP lower than 10 during manufacturing process, the remaining product is high-performance inulin.
Some articles considered the fractions with DP lower than 10 as short-chained fructo-oligosaccharides, and only called the longer-chained molecules inulin.

Because of the β(2,1) linkages, Inuline is not digested by enzymes in the human alimentary system, contributing to Inuline functional properties: reduced calorie value, dietary fiber, and prebiotic effects. 
Without color and odor, Inuline has little impact on sensory characteristics of food products. 

Oligofructose has 35% of the sweetness of sucrose, and Inuline sweetening profile is similar to sugar. 
Standard Inuline is slightly sweet, while high-performance Inuline is not. 

Inulines solubility is higher than the classical fibers. 
When thoroughly mixed with liquid, Inuline forms a gel and a white creamy structure, which is similar to fat. 

Inulines three-dimensional gel network, consisting of insoluble submicron crystalline Inuline particles, immobilizes a large amount of water, assuring Inuline physical stability.
Inuline can also improve the stability of foams and emulsions.

Metabolism in vivo:
Inuline is indigestible by the human enzymes ptyalin and amylase, which are adapted to digest starch. 
As a result, Inuline passes through much of the digestive system intact. 

Only in the colon do bacteria metabolise inulin, with the release of significant quantities of carbon dioxide, hydrogen, and/or methane. 
Inulin-containing foods can be rather gassy, in particular for those unaccustomed to inulin, and these foods should be consumed in moderation at first.

Inuline is a soluble fiber, one of three types of dietary fiber including soluble, insoluble, and resistant starch. 
Soluble fiber dissolves in water to form a gelatinous material. 
Some soluble fibers may help lower blood cholesterol and glucose levels.

Because normal digestion does not break Inuline down into monosaccharides, Inuline does not elevate blood sugar levels and may, therefore, be helpful in the management of diabetes. 
Inuline also stimulates the growth of bacteria in the gut.

Inuline passes through the stomach and duodenum undigested and is highly available to the gut bacterial flora. 
This makes Inuline similar to resistant starches and other fermentable carbohydrates.

Some traditional diets contain over 20 g per day of Inuline or fructo-oligosaccharides. 
The diet of the prehistoric hunter-forager in the Chihuahuan Desert has been estimated to include 135 g per day of inulin-type fructans.
Many foods naturally high in Inuline or fructo-oligosaccharides, such as chicory, garlic, and leek, have been seen as "stimulants of good health" for centuries.

Due to Inuline resistance to digestive enzymes, Inuline resists absorption during Inuline transit through the upper gastrointestinal tract. 
After reaching the large intestine, Inuline is converted by colonic bacteria to a gel known as a prebiotic, a food ingredient that is highly nourishing to gut microflora. 

As of 2013, no regulatory authority had permitted health claims in the marketing of prebiotics as a class. 
Inulin's health effects had been studied in small clinical trials, which showed that Inuline causes gastrointestinal adverse effects such as bloating and flatulence, does not affect triglyceride levels or development of fatty liver, may help prevent traveler’s diarrhea, and may help increase calcium absorption in adolescents.

Origin and history of Inuline:
Inuline is a natural storage carbohydrate present in more than 36,000 species of plants, including agave, wheat, onion, bananas, garlic, asparagus, Jerusalem artichoke, and chicory. 
For these plants, Inuline is used as an energy reserve and for regulating cold resistance.

Because Inuline is soluble in water, Inuline is osmotically active. 
Certain plants can change the osmotic potential of their cells by changing the degree of polymerization of Inuline molecules by hydrolysis. 
By changing osmotic potential without changing the total amount of carbohydrate, plants can withstand cold and drought during winter periods.

Inuline was discovered in 1804 by German scientist Valentin Rose. 
He found “a peculiar substance” from Inula helenium roots by boiling-water extraction.

In the 1920s, Irvine used chemical methods such as methylation to study the molecular structure of Inuline, and he designed the isolation method for this new anhydrofructose.
During studies of renal tubules in the 1930s, researchers searched for a substance that could serve as a biomarker that is not reabsorbed or secreted after introduction into tubules.

Richards introduced Inuline because of Inuline high molecular weight and Inuline resistance to enzymes.
Inuline is used to determine glomerular filtration rate of the kidneys.

Natural Sources of Inuline:
Plants that contain high concentrations of inulin include:
Agave (Agave spp.)
Banana and plantain (Musaceae)
Burdock (Arctium lappa)
Camas (Camassia spp.)
Chicory (Cichorium intybus)
Coneflower (Echinacea spp.)
Costus (Saussurea lappa)
Dandelion (Taraxacum officinale)
Elecampane (Inula helenium)
Garlic (Allium sativum)
Globe artichoke (Cynara scolymus, Cynara cardunculus var. scolymus)
Jerusalem artichoke (Helianthus tuberosus)
Jicama (Pachyrhizus erosus)
Leopard's bane (Arnica montana)
Mugwort root (Artemisia vulgaris)
Onion (Allium cepa)
Wild yam (Dioscorea spp.)
Yacón (Smallanthus sonchifolius)

Identifiers of Inuline:
CAS Number: 9005-80-5
ChEMBL: ChEMBL1201646
ChemSpider: none
DrugBank: DB00638
ECHA InfoCard: 100.029.701
KEGG: D00171
PubChem CID: 24763
UNII: JOS53KRJ01
CompTox Dashboard (EPA): DTXSID70872610

Properties of Inuline:
Chemical formula: C6nH10n+2O5n+1
Molar mass: Polymer; depends on

Molecular Weight: 586.7
XLogP3-AA: 1.5
Hydrogen Bond Donor Count: 3
Hydrogen Bond Acceptor Count: 10
Rotatable Bond Count: 9
Exact Mass: 586.32541643
Monoisotopic Mass: 586.32541643
Topological Polar Surface Area: 133 Ų
Heavy Atom Count: 42
Complexity: 1080
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 10
Undefined Atom Stereocenter Count: 3
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes

Pharmacology of Inuline:
ATC code: V04CH01 (WHO)

Synonyms of Inuline:
Inuline
Anthraniloyllycoctonine
Anthranoyllycoctonine
Monoanthraniloyllycoctonine
(+)-Anthranoyllycoctonine
O(sup 14)-Methyldelectine
Swatinine B
Lycoctonine, monoanthranilate (ester)
O14-Methyldelectine
BRN 0072684
Lycoctonine, anthraniloyl-
22413-78-1
Aconitane-7,8-diol, 4-(((2-aminobenzoyl)oxy)methyl)-20-ethyl-1,6,14,16-tetramethoxy-, (1-alpha,6-beta,14-alpha,16-beta)-
4-21-00-02879