1.

Introduction to Fossence (Fructo-Oligosaccharides – FOS)

1.1. What is FOSSENCE (Fructo-Oligosaccharide)?

FossenceTM is a short chain fructo-oligosaccharide (ScFOS) produced by TATA NQ, through a patented process of bio-
transformation of sucrose (cane sugar) by the action of enzymes from whole microbial cells (For further details please
refer to Application Patent number US8871476).

Fructo-oligosaccharides are oligomers of fructose (Fn) with one terminal glucose (G) moiety found at the non-reducing
end of the chain. The general formula could be GFn wherein the ‘n’ is the number of fructose moieties and it may
range between 2 and 4.

1.2. Fructooligosaccharides – Occurrence in nature

FOS is a natural oligosaccharide, which is present in substantial quantities in cane sugar. Other sources of FOS are
asparagus, artichokes, onions, honey, rye wheat, etc. (Becker et al. 1977; Shiomi and Izawa 1980; Darbyshire and
Henry 1981). Unfortunately the quantity of FOS reported in these is low (0.8-10% fresh basis). Even though chicory,
Jerusalem artichoke and dahlia report substantial quantity, the oligosaccharide derived from these has a high degree
of polymerization (DP).

1.3. Fructooligosaccharides - Processing and Production

FOS is derived enzymatically by bio-transforming sucrose. The enzyme used for the transformation is
ß-fructofuranosidase or fructosyltransferases. Enzymatically produced FOS are short-chained with 2-4 fructose units;
GF2 (1-Kestose), GF3 (Nystose) and GF4 (1ß- fructofuranosylnystose) with DP not exceeding 5. (Ganaie et al. 2014).
This enzymatically obtained FOS is known as short chain FOS (scFOS). ScFOS show higher fermentability and are
better utilized, compared to long chain oligofructoses, by bifidobacteria. (Rossi et al. 2005; Scott et al. 2014).

1.4. Fructooligosaccharides - Overview

1.4.1. What is Dietary Fiber and Classification of Dietary Fiber

The term dietary fibre was coined in 1953, but the health benefits of high fibre foods have been appreciated for
thousands of years. In 430 BC, Hippocrates described the laxative effects of coarse wheat in comparison with refined
wheat (Slavin 1987).

Different organizations define dietary fibre differently (Jones JM. 2014). Few of them are tabled below:

Organization Definition
Institute of Medicine Dietary fibre consists of non-digestible carbohydrates and lignin that are intrinsic and
intact in plants. "Added Fiber" consists of isolated, non-digestible carbohydrates that
have beneficial physiological effects in humans (Dietary Reference Intakes: Proposed
Definition of Dietary Fiber. Institute of Medicine (US), Panel on the Definition of Dietary
Fiber and the Standing Committee on the Scientific Evaluation of Dietary Reference
Intakes, National Academies Press.2001).
 Organization Definition
American Association Dietary fibre is the edible parts of plants or analogous carbohydrates that are resistant to
of Cereal Chemists digestion and absorption in the human small intestine, with complete or partial
fermentation in the large intestine. Dietary fibre includes polysaccharides, oligosaccharides,
lignin, and associated plant substances. Dietary fibres promote beneficial physiologic effects
including laxation, and/or blood cholesterol attenuation, and/or blood glucose attenuation
(Dietary fiber. American Association of Cereal Chemists. 2017).
Codex Alimentarius Dietary fiber means carbohydrate polymers with ≥10 monomeric units, which are not
Commission* hydrolyzed by the endogenous enzymes in the small intestine of humans (Jones JM. CODEX-
aligned dietary fiber definitions help to bridge the 'fiber gap'. Nutrition Journal, 2014;
13:34)
European Food Safety Non-digestible carbohydrates plus lignin, including all carbohydrate components occurring in
Authority (EFSA) foods that are non-digestible in the human small intestine and pass into the large intestine
Food Standards Dietary fibre means that fraction of the edible part of plants or their extracts, or synthetic
Australia and New analogues that a) are resistant to digestion and absorption in the, usually with complete or
Zealand (FSANZ) partial fermentation in the large intestine; and b) promote one or more of the following
2001 beneficial physiological effects a) laxation; b) reduction in blood cholesterol, c) modulation of
blood glucose

Classification of Dietary Fibre:

Dietary fibre can be divided into 4 clinically meaningful categories:

Type of Fiber Description

Insoluble, poorly Does not dissolve in water (no water-holding capacity); poorly fermented;
fermented can exert a laxative effect by mechanical irritation/stimulation of gut mucosa if
(eg, wheat bran) particles are sufficiently large and coarse; small smooth particles (eg, wheat bran
flour/bread) have no significant laxative effect; does not gel or alter viscosity and
thus does not provide other (gel- dependent) fiber health benefits.

Type of Fiber Description

 Soluble,non- viscous, Dissolves in water; no increase in viscosity; rapidly and completely fermented (once
readily fermented fermented, the fiber is no longer present in stool, rapid gas formation, increased
(eg, inulin, wheat flatulence, energy harvest [calorie uptake] from fermentation by-products); may alter
dextrin, oligosaccharides, the numbers of specific bacteria in the gut (eg, ‘‘prebiotic’’ effect); no laxative
resistant starches) effect at physiologic doses; does not gel or alter viscosity and thus does not provide
any of the gel- dependent fiber health benefits. Readily fermented fibers are part of
an emerging area of science relating to their effects on the gut microbiome, but to
date, the marketed fiber supplements have no established clinically meaningful health
benefits.
Soluble viscous/gel Dissolves in water, forms a viscous gel (eg, oatmeal), increases chyme viscosity to
forming, readily slow nutrient absorption and improve glycemic control, lowers elevated serum
fermented (eg, A-glucan cholesterol, readily fermented (gas formation, energy harvest [calorie uptake] from
[oats, barley], raw guar fermentation by-products), fermentation results in loss of gel and water holding
gum) capacity, and thus, no significant laxative effect and no retained gel to attenuate
diarrhea.
Soluble viscous/gel Dissolves in water; forms a viscous gel; increases chyme viscosity to slow nutrient
forming, non- fermented absorption and improve glycemic control, lowers elevated serum cholesterol; not
(ie, psyllium) fermented (no gas production, no calorie harvest from fermentation by-products);
because it is not fermented, it remains gelled throughout the large bowel, providing a
dichotomous ‘‘stool-normalizing’’ effect: softens hard stool in constipation
(relieves/prevents constipation) and firms/forms loose/liquid stool in diarrhea
(relieves/prevents diarrhea), and normalizes stool form in IBS (McRorie. 2015)

*Indigestible carbohydrates with degrees of polymerization (DP) between 3 and 9 were previously regarded as
oligosaccharides. AOAC official method for dietary fiber analysis (with DP 3 – 9) mostly cannot be precipitated by
alcohol and exhibit different desirable physiological activities as most dietary fibre do. CODEX published a new
definition of dietary fibre with short chain carbohydrates (DP 3 – 9) being included (de Menezes et al. 2013; Dai and
Chau 2017).
Fructo-oligosaccharides have degree of polymerization between 3 and 5 and hence can be considered as a
dietary fiber.

1.4.2. Fructooligosaccharides – As a Prebiotic

Ingestion of FOS impacts the microbial diversity in the gut, which harbors millions of bacteria. Being a dietary fibre,
FOS reaches the colon unchanged, where it then proceeds to have an impact on the intestinal microbiota. FOS is
fermented by saccharolytic bacteria in the intestine and it ultimately affects their composition. Supplementation of
FOS has been shown to increase the number of beneficial bacteria like Bifidobacterium and Lactobacillus and a
decrease in the load of pathogenic bacteria. (Tuhoy et al. 2014; Walsh et al. 2014)

The selective stimulation of growth of beneficial microorganisms (also called probiotics) in the gut is called a
‘prebiotic effect’ and substances triggering the prebiotic effect are called ‘prebiotics’ (Roberfroid MB. 2000; Slavin
2013). Prebiotics alter the bacteroidetes to firmicutes ratio and additionally enhance the growth of bifidobacterial
species and lactic acid bacteria (Delzenne et al. 2013).

The enhanced growth of probiotic bacteria in the gut have been shown to be associated with various health benefits
to the host. The dominant growth of beneficial bacteria results in the crowding out of pathogens and prevents their
attachment to the intestinal wall (Roberfroid MB. 2000).

The increase in the number of beneficial bacteria results in the production of short chain fatty acids (SCFA) like acetic,
propionic, and butyric acid. The net result of this is a decrease in the luminal pH which inhibits the growth of
pathogenic bacteria (Macfarlane and Macfarlane. 2012; Ríos-Covián et al. 2016).

1.4.3. Fructooligosaccharides - Low caloric value

Since FOS, upon entering the colon, is completely fermented into SCFAs and lactic acid along with the generation of
gases, there is a loss of energy (estimated to be 50% of the calorific value of the carbohydrate) for the host. Different
methods have proposed the calorific value between 1.5 – 2.2 kcal/g through radio respirometric method
(Hosoya et al.1988) and ileal intubation method (Molis et al. 1996).
Dietary carbohydrates, which are absorbed as hexose (glucose, fructose), have a caloric value of 3.9 kcal/g (16.3 kJ/g),
and their cellular metabolism produces approximately 38 mol ATP/mol. However, oligofructoses resist digestion and
are not absorbed in the upper part of the gastrointestinal tract. Upon reaching the colon, intact, they get hydrolyzed
and are extensively fermented by saccharolytic bacteria, thus producing short-chain carboxylic and lactic acids, as
electron sinks.

Depending on the degree of their colonic fermentation as well as the assumptions of the model used, their caloric
value varies between 0 and 2.5 kcal/g. Through the catabolism of the absorbed short-chain carboxylic and lactic acids,
they may produce up to 17 mol ATP/mol of fermented sugar moiety. Since the daily intake of these dietary fibers is
likely to remain relatively small (< 10% and probably often not > 5% of total daily calorie intake), it is of low
relevance, nutritionally, to give them a precise caloric value. On the basis of biochemical balance charts for
carbon atoms, metabolic pathways and energy yields to the host, the caloric value of a fructosyl residue in
oligofructose and chicory inulin has been calculated to be approximately 25-35% that of a fully digested and absorbed
fructose molecule. For the purpose of food labelling, it is recommended that oligofructose and chicory inulin, should
be given a caloric value of 1.5 kcal/g (6.3 kJ/g)" (Roberfroid M.B. 1999; Van Es 1987 and Hobbs 1988)
1.4.4. Fructo-oligosaccharides - Low Glycemic Index
The Glycemic Index (or GI) is a ranking of carbohydrates on a scale from
The amount of carbohydrate in the reference
0 to 100 according to the extent to which they raise blood sugar (glucose) and test food must be the same.
levels after eating. Foods with a high GI are those which are rapidly digested,
and test food must be the same.
absorbed and metabolised and result in marked fluctuations in blood sugar
(glucose) levels. Low GI carbohydrates are the ones that produce smaller
fluctuations in blood glucose levels.

Classification of Glycemic index:

Glycemic Index Level

Low 55 or less
Since FOS is a non-digestible carbohydrate that does not get converted
Medium 55 – 70
to glucose, the GI value for FOS (with purity as high as 95%) may be
High 70 and above considered as ZERO. Hence a LOW Glycemic Index. With purity as low as
55%, the GI is less than 20.

1.4.5. Fructooligosaccharides - General recommendations for Dosage

Recommendations for the doses for any intended effect are dependent on country specific regulations. However, for
specific health benefits, safe dose ranges have been shared under sections 2.1.4, 2.2.4, 2.3.4, 2.4.4, 2.5.4, 2.6.4, 2.7.4,
and 2.8.4.

1.4.6. Fructooligosaccharides - Tolerance, Safety and Toxicity Levels

Studies indicate that FOS is well tolerated by humans. However, high doses (e.g. 20g /day or higher), have shown to
increase gastrointestinal adverse effects such as abdominal pain, flatulence, borborygmic (rumbling noise made by
the movement of fluid and gas in the intestines), bloating and abdominal discomfort.

FOS has been widely used in various human intervention trials and generally recognized as safe for human
consumption. No human study has shown any adverse effect in terms of toxicity. Even in Wistar rats administered
(oral gavage) for a period of 90 days, no adverse toxicological effects were observed. The NOAEL (No Observed
Adverse Effect Level) for FOS was evaluated as ≥9000mg/kg body weight per day in Wistar rats under the test
conditions and doses employed (data not shared; data available on request).
________________________________________________________________________________________________

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