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Inulin and Oligofructose: Safe Intakes and Legal Status¹

Orafti, Aandorenstraat 1, 3300 Tienen, Belgium

	ABSTRACT

TOP ABSTRACT INTRODUCTION Safe intakes Legal status Labeling: ingredients list Analytical determination Nutrition labeling Health claims Future labeling REFERENCES

 
Inulin and oligofructose are a significant part of the daily diet of most of the world's population. Daily intakes for the U.S. and Europe have been estimated at up to 10 g, specifically 1–4 g for the 97th percentile in the U.S. Because both inulin and oligofructose are macroingredients, it is difficult to apply classical toxicology tests. Although some high dose animal tests have been performed, none have revealed any toxic effects. The safety of inulin and oligofructose for use in foods was evaluated by many legal authorities worldwide. As a result, both inulin and oligofructose are accepted in most countries as food ingredients that can be used without restrictions in food formulations. In the U.S., a panel of experts performed a generally accepted as safe (GRAS) Self-Affirmation Evaluation in 1992 and concluded similarly. At high doses, increased flatulence and osmotic pressure can cause intestinal discomfort. These doses vary widely from person to person and also depend on the type of food in which inulin or oligofructose is incorporated. With regard to labeling, both inulin and oligofructose are gradually being accepted as "dietary fibers" in most countries around the world. The mention of their "bifidogenic effect" on food labels has also been legally accepted in several countries.

KEY WORDS: • inulin • oligofructose • safety • labeling • acceptability

	INTRODUCTION

TOP ABSTRACT INTRODUCTION Safe intakes Legal status Labeling: ingredients list Analytical determination Nutrition labeling Health claims Future labeling REFERENCES

 
Inulin was defined by Rose in the early 1800s as the carbohydrate substance that he isolated from the root of Inula helenum (Rose 1804). We now know that it is present in a wide range of plants, including common vegetables and fruits (Van Loo et al. 1995 ). Inulin is a polydisperse substance based on fructose polymers (De Leenheer et al. 1994 ).

Today, only inulin from chicory roots is commercialized as a purified food ingredient. The chicory roots that are used are of the same species (Cichorium intybus) that has been used for many years to produce the coffee substitute. At the moment, no genetically modified organism-derived chicory roots are used.

Among the several commercial inulin types available, all have a very high purity; they differ with regard to their powder characteristics and carbohydrate composition (Table 1). Standard inulin, as it is extracted from chicory roots, always contains a small amount of sugars (up to 10%). These sugars are present in the root and are not a result of processing. Low sugar and high performance inulin are obtained by chromatographic or physical removal of the mono-, di- and oligosaccharide fractions.

Table 2

	Safe intakes

TOP ABSTRACT INTRODUCTION Safe intakes Legal status Labeling: ingredients list Analytical determination Nutrition labeling Health claims Future labeling REFERENCES

Both inulin and oligofructose are present in the daily diet of many of the world's populations (Van Loo et al. 1995 ). This presence is not a matter of trace amounts; several grams per day may be ingested through the normal diet (Table 3). This fact is the cornerstone of the safety evaluation of both inulin and oligofructose. On the one hand, it shows that mankind has been exposed to both substances for centuries. On the other hand, the fact that specific meals and even some diets can contain considerable amounts of inulin or oligofructose (up to 20 g) provides a history of exposure to such high amounts through the diet.

Use as food ingredient.

Inulin and oligofructose are macronutrients. They are used either as supplements to foods or as macronutrient substitutes. As supplements to foods, they are added mainly for their nutritional properties. Adding inulin or oligofructose increases the dietary fiber content of the food. Such additions are usually in the range of 3–6 g per portion, in extreme cases up to 10 g. In other applications, inulin or oligofructose are added to allow a specific nutritional claim such as that regarding the bifidogenic activity. In these foods, typical levels are 1–6%, leading to ~3–8 g per portion.

As macronutrient substitutes, inulin and oligofructose are used mainly to replace fat andsugars, respectively. The fat-replacing potential of inulin was discovered and patented by Orafti in 1992. Using a specific processing technique, inulin is combined with water to produce the same texture and mouthfeel as fat. This is possible only in water-based foods such as dairy products and table spreads, and not in dry foods such as most snacks, bakery and confectionery products. Typically, 1 g of fat is replaced by a 0.25 g of inulin. Consequently, fat replacement in most foods will lead to inulin concentrations of ~2–6 g per portion.

Oligofructose has technical properties that are comparable to those of sugar and glucose syrups, yet nutritionally speaking, it has totally different properties. The sweetness of (pure) oligofructose is ~30% compared with sugar. Consequently, it is difficult to use oligofructose alone as a sugar substitute; most often, it must be combined with intense sweeteners to obtain the desired sweetness level.

Further, the use of oligofructose (and inulin) is not possible in most soft drinks and fruit jams. In such acid foods with a long shelf life, both substances are slowly hydrolyzed into fructose. Therefore, oligofructose is used as a sugar substitute mainly in dairy products and bakery products, at levels that cause no intestinal discomfort. In practice, amounts of 2–6 g per portion are used frequently.

On the basis of these considerations, a committee of experts (Kolbye et al. 1992 ) concluded that even for a consumer at the 90th percentile, increased exposure to inulin and oligofructose is likely to be of negligible biological significance.

Toxicity studies.

The long history of mankind's safe use of inulin-containing foods is reflected by the fact that very little formal toxicity testing in laboratory animals has been reported on inulin or its oligosaccharide hydrolysis products.

A number of animal toxicity studies with Neosugar have been published. Neosugar has the same chemical structure as inulin, but has shorter chain length (up to four fructose units) and is produced by enzymatic synthesis from sucrose. No specific safety issues were raised in these studies (Clevenger et al. 1988 , Sleet and Brightwell 1990, Takeda and Niizato 1982 ).

Numerous publications in peer-reviewed clinical journals document careful studies with inulin and oligofructose in normal subjects and patients with disease states (Roberfroid 1993 ). These individuals of different ages have provided additional assurances of the safety of inulin and oligofructose. For example, inulin has been used to measure glomerular filtration rate by intravenous injection since 1931. This has become a standard procedure without a recorded history of toxic effects (Price et al. 1978 ). In addition, man's history of the food uses of inulin has not shown evidence of untoward effects. A committee of experts (Kolbye et al. 1992 ), based on a review of these studies, concluded, "There is no reason to believe the oligofructoses or their metabolites would have a toxic potential from expanded use in foods; on the contrary, recent findings document the beneficial nutritional effects of these purified, chemically identified, derivatives of inulin in the gastrointestinal tract of man."

Safety of the inulinase enzyme.

Oligofructose is produced from inulin by partial enzymatic hydrolysis (Norman and Hojer-Pedersen 1989 ). This process uses an inulinase enzyme isolated from the carbohydrase complex of Aspergillus niger. The enzyme was toxicologically tested by the producer and classified as safe for use in the production of foods.

Enzymes from Aspergillus niger are considered by JECFA² (Joint FAO/WHO Expert Committee on Food Additives) to represent no hazard to human health when used in the production of food. The JECFA evaluation resulted in "acceptable daily intake (ADI) not specified" (35th meeting, 1989). These enzymes are widely used in the food industry, e.g., for fruit juice production.

In the U.S., the carbohydrase complex of Aspergillus niger is covered by a generally regarded as safe (GRAS) Affirmation Petition (GRASP 3G0016) filed by the ad hoc Enzyme Technical Committee in 1973. The Authorities in Denmark have evaluated the safety of the inulinase and accepted the use of the enzyme for the production of oligofructose (1990). The Conseil Supérieur d'Hygiène Public in France has also evaluated and recommended the acceptance of the use of the enzyme for the production of, among others, oligofructose (1990).

Intestinal acceptability.

    Principles. Intestinal acceptability of nondigestible components is determined mainly by two phenomena. First is the osmotic effect, which leads to an increased presence of water in the colon. Smaller molecules exert a higher osmotic pressure and bring more water into the colon. This is probably the reason why sorbitol, for example, has a higher laxative potential than oligofructose (Hata and Nakajima 1984 ). Second is the fermentation effect, which is caused by the fermentation products, mainly short-chain fatty acids and gases. Slowly fermenting compounds appear to be easier to tolerate than their fast fermenting analogs. This can explain why inulin is easier to tolerate than oligofructose.

It is difficult to distinguish between an acceptable and a nonacceptable side effect of fermentation. Flatulence, for instance, is a well-known and often accepted side effect of the intake of vegetables. Dietary fibers, in general, are known and rewarded for their properties of stool softening; the step to a laxative effect is thus small.

The intestinal acceptability of a food can be judged only by the person who eats it. Diarrhea is certainly a symptom of nonacceptability, but soft stools may be an acceptable or even desired phenomenon. A dose of indigestible compounds that does not cause diarrhea can create other unwanted side effects such as flatulence and intestinal pressure. These parameters are much more difficult to measure objectively. Moreover, the same amount of flatulence can be acceptable to one person while being too much for another person.

For all of these reasons, the traditional concept of no-effect level (NOEL) for diarrhea is not very meaningful in the case of substances such as inulin and oligofructose. The 50% effective dose values for fructo-oligosaccharides have been proposed to be ~30g/d (Briet et al. 1995 ). A new approach, based on a personal judgement of discomfort, was developed by Orafti.

For this purpose, a food is considered unacceptable if it causes one of the following symptoms: too much flatulence, too much intestinal pressure, too much intestinal noise, too many intestinal cramps or diarrhea, as observed and evaluated by the test person himself.

Meaningful tests can be done only if the volunteers are unadapted to the product because only this reflects the reality in the consumer market. The test doses should be taken in a predetermined amount of time. The resulting "levels causing discomfort" appear at doses that are considerably lower than the traditionally calculated NOEL. This approach is therefore much more severe than the "laxative dose" approach found in much of the literature; in that approach, often only diarrhea is considered and the volunteers have passed an adaptation period.

Test results.

Orafti's tests and experience show that, regarding the sensitivity to (totally) fermentable carbohydrates, three categories of people can be distinguished: 1) nonsensitive persons can consume 30 g/d or more of the compound almost without undesirable reactions as defined above; 2) sensitive persons can consume 10 g/d of the compound without undesirable reactions but might experience undesirable reactions with doses of 20 g/d; 3) very sensitive persons can already experience undesirable reactions at doses of 10 g/d.

The distribution of the sensitivity of the adult population is given in Table 4 (Absolonne et al. 1995 ). The values in this table were calculated from the average reactions of a panel of nearly 100 adult volunteers to ingestion of three nondigestible or poorly digestible but totally fermentable compounds of the type disaccharide sugar alcohols or low-molecular-weight oligosaccharides. Indeed, it was found that the intestinal acceptability of these indigestible carbohydrates is quite comparable, and that it is reasonable to calculate averages that are valid for the whole group.

Experiences.

Several hundred different food products containing added inulin or oligofructose are on the market today. The most successful applications occur in dairy products, such as fermented milks, milk, milk drinks, cheeses, and desserts, bakery products, spreadable products, chocolate, meal replacers, bars, cereals and ice creams. This provides a solid base of experience. Most foods contain doses of 2–4 g of inulin or oligofructose per portion. Many others contain higher amounts. In all of these cases as far as we know, acceptability problems with consumers have never caused the manufacturers to reconsider the formulation or labeling of the products.

Conclusions and recommendations.

It can be concluded that intestinal acceptability of nondigestible fermentable carbohydrates differs from person to person. Many people can consume 10 g without noticeable side effects, whereas some people experience intestinal discomfort that they consider too much after ingestion of even small amounts of nondigestible fermentable carbohydrates. Moreover, the reactions are influenced by the type of food (differing mainly between solid foods and liquid foods). It is therefore neither possible nor relevant to define no-effect levels for these substances.

Inulin, in general, performs slightly better than oligofructose, which in turn performs slightly better than most sugar alcohols. Inulin rarely causes diarrhea. The values that can be recommended as formulation doses, based on both the tests with volunteers and the experience in the food industry, range from 5–8 g per portion for oligofructose and 10 g for inulin. These doses are not to be taken as NOEL values, which are significantly higher.

Other nutritional side effects.

Dietary fibers can have other unwanted side effects, such as a negative influence on vitamin or mineral absorption, allergic reactions, and an undesirable influence on the gut flora and their metabolism. No such negative effects have been found for inulin and oligofructose. On the contrary, recent research suggests that the effects on mineral absorption and gut flora might well be positive.

	Legal status

TOP ABSTRACT INTRODUCTION Safe intakes Legal status Labeling: ingredients list Analytical determination Nutrition labeling Health claims Future labeling REFERENCES

 
Legal classification and acceptance.

Inulin and oligofructose are legally classified as food or food ingredients, and not as additives, in all countries in which they are used. Although this seems evident if one considers the nutritional properties and the use of both substances, it has not been easy to obtain confirmation of this legal status from many of the legal authorities in the world. As a consequence, neither inulin nor oligofructose are listed as accepted food additives in the standard positive lists from the European Union or from Codex Alimentarius. EU Directive EC 95/2 explicitly lists inulin as a substance that is not an additive. The EU Standing Committee meeting of June 1995 confirmed that oligofructose is a food ingredient.

In Europe, both inulin and oligofructose were brought to market long before the Novel Foods Regulation (EC 258/97) came into force. Since 1987, Orafti has applied for authorization as a food ingredient for both substances in all European countries separately. In most countries, the files were submitted to the Superior Health Council (or the corresponding government body) for advice. None of the European countries has ever expressed reservations with regard to the safety of inulin or oligofructose. In all countries, both substances are accepted for food use without limitations. No ADI were fixed.

In the U.S., a committee of experts convened by Orafti declared both inulin and oligofructose as Generally Recognized As Safe in 1992 (Kolbye et al. 1992 ). The committee was composed of Albert C. Kolbye, Herbert Blumenthal, Barbara A. Bowman, John H. Byrne, C. Jelleff Carr, John C. Kirschman, Marcel B. Roberfroid and Morris A. Weinberger. The evaluation took all of the elements of Table 5 into account. The conclusion was as follows: Our opinion regarding the safety of inulin and oligofructose is based on reasoned judgement, primarily on the fact that inulin and oligofructose are natural components of many of our present foods that have been safely consumed by humans over millennia.

In addition, available scientific evidence clearly indicates that inulin and oligofructose are not hydrolysed in the stomach or small intestine, but are fermented completely into harmless metabolites in the colon, where they are specific substrates for the growth of Bifidobacteria. We now know that Bifidobacteria are desirable organisms in the human colon. Most convincing are the findings in patients with disease states and normal subjects of different ages fed oligofructose.

Inulin and oligofructose intake is self-limiting because of a gaseous response in the colon that prevents over-usage. Available animal toxicity studies are consistently free of any suggestions of adverse effects to be expected from such proposed levels of use in foods.

The exact chemical structures and compositions of inulin and oligofructose have been established and fall into the non-toxic classification. This represents an advantage of direct knowledge as compared to many other naturally occurring food components with unknown chemical composition and structure.

Inulin and oligofructose are dietary fibers by definition and by their nutritional properties. These substrates have not always been classified as `dietary fiber', and classical analytical methods for dietary fiber analysis do not measure them. However, we conclude that the most appropriate classification and labelling for inulin and oligofructose is that of `dietary fiber.'

Accordingly, we find there is no scientific evidence in the available data and literature on the food uses of these substances that demonstrates or suggests reasonable grounds to suspect a hazard to the public when used at levels that are current or that might reasonably be expected to be used in the future.

Our position regarding the safety of inulin and oligofructose is based on the long human experience of consuming inulin containing foods as well as evaluation of available scientific evidence relating to inulin and its hydrolysis products. Since inulin and oligofructose have been natural components of many foods consumed safely by humans over millennia, there is no reason to suspect a significant risk to the public health when used in foods.

Therefore, we conclude that these food substances are generally recognized as safe, both by long-established history of use in foods and by the opinion of experts qualified by scientific training and experience in food safety after a thorough review of the available scientific evidence.

	Labeling: ingredients list

TOP ABSTRACT INTRODUCTION Safe intakes Legal status Labeling: ingredients list Analytical determination Nutrition labeling Health claims Future labeling REFERENCES

 
The labeling laws of most countries require that a specific name be used for the ingredients list. For chicory inulin, the name inulin is a logical and legally accepted choice. For oligofructose, either fructo-oligosaccharides or oligofructose can be used, the latter being a more consumer friendly choice. About 70% of chicory inulin molecules have a degree of polymerization (DP) >10. Oligosaccharides are defined as having a DP between 2 and 10 (IUB-IUPAC 1982 ). Oligofructose was defined by AOAC as having a DP between 2 and 10 (Hoebregs 1997 ). Therefore, it is not acceptable to label inulin as "oligofructose."

The commercial products contain fractions of mono- and disaccharides (Table 1 and Table 2 ). These sugars may need separate labeling. Native inulin and standard oligofructose products always contain some sugars, which can be considered as a normal part of the inulin or oligofructose. Therefore, it has been legally accepted that these sugars do not have to be labeled specifically in most practical cases. Of course, those sugars do have to be labeled separately in the nutrition labeling.

	Analytical determination

TOP ABSTRACT INTRODUCTION Safe intakes Legal status Labeling: ingredients list Analytical determination Nutrition labeling Health claims Future labeling REFERENCES

 
Inulin and oligofructose can be analyzed using the AOAC Fructan Method nr. 997.08 (Hoebregs 1997 ). This method measures the total of inulin plus oligofructose in any food product. The method is very specific for both substances and has proven to be accurate and reliable. Oligofructose can be measured separately using HPLC or gas chromatography techniques (Van Loo et al. 1995 ).

	Nutrition labeling

TOP ABSTRACT INTRODUCTION Safe intakes Legal status Labeling: ingredients list Analytical determination Nutrition labeling Health claims Future labeling REFERENCES

 
Inulin and oligofructose behave as dietary fibers in the human body; therefore, it is logical to classify these substances as dietary fiber. This principle has already been accepted by almost all European countries and is now being evaluated in most other countries. Both substances comply with the Codex Alimentarius definition of dietary fiber which is "edible plant and animal material not hydrolyzed by the endogenous enzymes of the human digestive tract as determined by the agreed upon method" [Codex Guidelines on Nutrition Labelling CAC/GL 2–1985 (Rev. 1 - 1993)]. They also meet the AOAC definition as "remnants of plant cells resistant to hydrolysis by the alimentary enzymes of man" (Trowell 1975 ).

In many countries, dietary fiber is defined for labeling purposes as the substances measured by a specifically prescribed analytical method. Most often, the AOAC methods are the standard. These methods do not measure inulin or oligofructose, and neither do the Englyst methods (Van Loo et al. 1995 ). Therefore, the specific AOAC Fructan method must be used. This method can be combined with the AOAC Total Dietary Fiber methods (Fig. 1 ). It seems most logical to include inulin and oligofructose in the "soluble dietary fiber" group.

View larger version (22K): [in this window] [in a new window]   Figure 1. Schematic presentation of AOAC methods for dietary fiber determination including inulin and oligofructose.

	Health claims

TOP ABSTRACT INTRODUCTION Safe intakes Legal status Labeling: ingredients list Analytical determination Nutrition labeling Health claims Future labeling REFERENCES

 
In Europe, Japan and several other countries, the nutritional properties of inulin and oligofructose are used to formulate health claims on food products and food supplements. An overview of these is given by Coussement (1997) . In most countries including the United States and the European countries, such claims should not suggest the cure or prevention of disease, should not be misleading and should be based on sound science.

At the moment, claims regarding the dietary fiber effects and the stimulation of Bifidobacteria, all based on inulin or oligofructose, are legally being made in many countries. In some countries, a specific authorization from the legal authorities has been obtained for specific claims. Such claims are also called "nutrient-function" claims or "positive" claims.

In the United States, the DSHEA (Dietary Supplement Health and Education Act) allows four "statements of nutritional support" under certain conditions. The stimulation of Bifidobacteria by inulin or oligofructose can be classified among such claims.

	Future labeling

TOP ABSTRACT INTRODUCTION Safe intakes Legal status Labeling: ingredients list Analytical determination Nutrition labeling Health claims Future labeling REFERENCES

 
Inulin and oligofructose as novel dietary fibers might have significant consequences for nutrition labeling systems. In most countries, these substances have pushed the experts to reconsider the definitions of a.o. carbohydrates, complex carbohydrates and dietary fiber (Lee and Prosky 1995 ). Furthermore, the standard nutrition labeling might not accommodate the appearance of these nondigestible oligosaccharides. Suggestions have been made that the classification of carbohydrates be reconsidered (Cummings et al. 1997 ).

In the United States, the NLEA (Nutrition Labeling and Education Act) in principle allows "disease-related" claims on the condition that an official authorization from the FDA or a confirmation from a National Institute of Health has been obtained. This situation might allow more claims for inulin and oligofructose, in particular relating to osteoporosis, heart disease or colon cancer, on the condition that the present research indications are confirmed by further research. In Europe, such claims on food products would require a fundamental change in the labeling directives; however, the first suggestions have been made.

	FOOTNOTES

² Abbreviations used: ADI, acceptable daily intake; a.o., xxxx; DP, degree of polymerization; GRAS, generally recognized as safe; JECFA, Joint FAO/WHO Expert Committee on Food Additives; NOEL, no-effect level.

	REFERENCES

TOP ABSTRACT INTRODUCTION Safe intakes Legal status Labeling: ingredients list Analytical determination Nutrition labeling Health claims Future labeling REFERENCES

 

1. Absolonne J., Jossart M., Coussement P. & Roberfroid M. (1995) Digestive acceptability of oligofructose. In: Proc. First Orafti Research Conference, pp. 151–161. Orafti, Tienen, Belgium.

2. Briet F., Achour L., Flourié B., Beaugerie L., Pellier P., Franchisseur C., Bornet F., Rambaud J.-C. Symptomatic response to varying levels of fructo-oligosaccharides consumed occasionally or regularly. Eur. J. Clin. Nutr. 1995;49:501-507[Medline]

3. Cadranel, S. & Coussement, P. (1995) Tolerance study with oligofructose for school children. In: Proc. First Orafti Research Conference, p. 217. Orafti, Tienen, Belgium.

4. Clevenger M. A., Turnbull D., Inoue H., Enomoto M., Allen J. A., Henderson L. M., Jones E. Toxicological evaluation of neosugar: genotoxicity, carcinogenicity and chronic toxicity. J. Am. Coll. Toxicol. 1988;7:643-662

5. Coussement P. Powerful products. The World of Ingredients 1997;August 1997:12-17

6. Cummings J. H., Roberfroid M. B., Members of the Paris Carbohydrate Group Review—a new look at dietary carbohydrate: chemistry, physiology and health. Eur. J. Clin. Nutr. 1997;51:417-423[Medline]

7. De Leenheer L., Hoebregs H. Progress in the elucidation of the composition of chicory inulin. Starch 1994;46:193-196

8. Hata, H. & Nakajima, K. (1984) Fructo-oligosaccharides intake and effect on digestive tract. In: Proc. 2nd Neosugar Research Conference, Tokyo, Japan.

9. Hoebregs H. Fructans in foods and food products, ion-exchange chromatographic method: collaborative study. J. Assoc. Off. Anal. Chem. Int. 1997;80:1029-1039

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13. Lee S. C., Prosky L. International survey on dietary fiber: definition, analysis and reference materials. J. Assoc. Off. Anal. Chem. Int. 1995;78:22-36

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15. Norman B. E., Hojer-Pedersen B. The production of fructo-oligosaccharides from inulin or sucrose using inulinase or fructosyltransferase from Aspergillus ficuum. Denpun Kagaku 1989;36:103-111

16. Price M., Schwartz R., Hoyt H. Evaluation and characteristics of currently available inulin. Investig. Urol. 1978;16:13-14[Medline]

17. Roberfroid M. Dietary fiber, inulin and oligofructose: a review comparing their physiological effects. Crit. Rev. Food Sci. Nutr. 1993;33:103-148[Medline]

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20. Strauss (1911) Therapie der Gegenwart III, p. 337.

21. Takeda, U. & Niizato, T. (1982) Acute and subacute safety tests. In: Proc. 1st Neosugar Research Conference, Incorporated Foundation Academic Journal Publication Center, Tokyo, Japan.

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