Scientific Opinion on the substantiation of health claims related to fructooligosaccharides (FOS) from sucrose and decreasing potentially pathogenic gastro-intestinal microorganisms (ID 774), changes in short chain fatty acid (SCFA) production and pH in the gastro-intestinal tract
(ID 775), changes in bowel function (ID 775, 778), reduction of gastro-intestinal discomfort (ID 775, 778), increase in calcium and/or
magnesium absorption leading to an increase in magnesium and/or calcium retention (ID 776, 777), maintenance of normal blood LDL-cholesterol
concentrations (ID 805) and maintenance of normal (fasting) blood concentrations of triglycerides (ID 805) pursuant to Article 13(1) of
Regulation (EC) No 1924/2006[sup]1[/sup]
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)2, 3
European Food Safety Authority (EFSA), Parma, Italy
Słowa kluczowe:
Fructooligosaccharides
LDL-cholesterol
bowel function
calcium absorption
gastro-intestinal comfort
health claims
magnesium absorption
pathogenic microorganisms
triglycerides
2. Znaczenie oświadczenia dla zdrowia człowieka
2.1. Zmniejszenie ilości potencjalnie patogennych mikroorganizmów przewodu pokarmowego (ID 774)
The claimed effect is “prebiotic/bifidogenic”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings, the Panel assumes that the claimed effect refers to increasing numbers of bacteria which are considered to be “beneficial”.
The numbers/proportions of bacterial groups that would constitute a “beneficial” colon/gastro-intestinal flora have not been established. Increasing the number of any group of microorganisms, including lactobacilli and/or bifidobacteria, is not in itself considered to be a beneficial physiological effect.
The Panel considers that the evidence provided does not establish that increasing numbers of gastro-intestinal microorganisms is a beneficial physiological effect.
The Panel considers that the claimed effect, in the context of decreasing potentially pathogenic gastro-intestinal microorganisms, might be a beneficial physiological effect.
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2.2. Zmienia produkcję krótkołańcuchowych kwasów tłuszczowych (SCFA) i odczyn pH w przewodzie pokarmowym (ID 775)
The claimed effect is “improved intestinal conditions (pH, SCFA production) and intestinal functions”. The Panel assumes that the target population is the general population.
The Panel notes that the claimed effect refers to changes in short chain fatty acid (SCFA) production and pH in the gastro-intestinal tract.
The Panel considers that changes in SCFA production and pH in the gastro-intestinal tract are not per se beneficial physiological effects, but need to be linked to a beneficial physiological or clinical outcome. No evidence has been provided to indicate the context in which the claimed effect could be considered as a beneficial physiological effect.
The Panel concludes that a cause and effect relationship has not been established between the consumption of fructooligosaccharides from sucrose and a beneficial physiological effect related to changes in SCFA production and pH in the gastro-intestinal tract.
2.3. Zmiany w funkcjach jelita (ID 775, 778)
The claimed effects are “improved intestinal conditions (pH, SCFA production) and intestinal functions”, and “gastrointestinal conditions and functions”. The Panel assumes that the target population is the general population.
In the context of the proposed wording, the Panel assumes that the claimed effects refer to changes in bowel function.
The Panel considers that changes in bowel function such as reduced transit time, more frequent bowel movements, increased faecal bulk, or softer stools may be a beneficial physiological effect, provided these changes do not result in diarrhoea.
2.4. Zmniejszenie dolegliwości ze strony przewodu pokarmowego (ID 775, 778)
The claimed effects are “improved intestinal conditions (pH, SCFA production) and intestinal functions”, and “gastrointestinal conditions and functions”. The Panel assumes that the target population is the general population.
In the context of the proposed wording, the Panel assumes that the claimed effects refer to reducing gastro-intestinal discomfort.
The Panel considers that reduction of gastro-intestinal discomfort is a beneficial physiological effect.
2.5. Wzrost wchłaniania wapnia i/lub magnezu prowadzący do zwiększenia ilości wapnia i/lub magnezu w organizmie (ID 776, 777)
The claimed effects are “increase mineral (Ca/Mg) absorption” and “mineral absorption”. The Panel assumes that the target population is the general population.
The Panel notes that the claimed effect (improved nutrient absorption) is only considered beneficial where absorption is a limiting factor for the maintenance of adequate status of the nutrient, and where increased absorption leads to increased retention.
The Panel considers that an increase in magnesium and/or calcium absorption leading to an increase in magnesium and/or calcium retention may be a beneficial physiological effect.
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2.6. Utrzymanie prawidłowego stężenia cholesterolu LDL we krwi (ID 805)
The claimed effect is “blood lipids”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings, the Panel assumes that the claimed effect refers to the maintenance of normal blood LDL-cholesterol concentrations.
Low-density lipoproteins (LDL) carry cholesterol from the liver to peripheral tissues, including the arteries. Elevated LDL-cholesterol, by convention >160 mg/dL (>4.1 mmol/L), may compromise the normal structure and function of the arteries.
The Panel considers that maintenance of normal blood LDL-cholesterol concentrations is a beneficial physiological effect.
2.7. Utrzymanie prawidłowego stężenia cholesterolu we krwi na czczo (ID 805)
The claimed effect is “blood lipids”. The Panel assumes that the target population is the general population.
In the context of the references provided, the Panel assumes that the claimed effect refers to the maintenance of normal (fasting) blood concentrations of triglycerides.
Triglycerides in plasma are either derived from dietary fats or synthesised in the body from other energy sources like carbohydrates. In fasting conditions, serum triglycerides are mainly transported in very-low-density lipoproteins (VLDL) synthesised in the liver. Hormones regulate the release of triglycerides from adipose tissue in order to meet energy needs between meals. Normal values for blood concentrations of triglycerides have been defined.
The Panel considers that maintenance of normal (fasting) blood concentrations of triglycerides may be a beneficial physiological effect.
3. Naukowe uzasadnienia wpływu na zdrowie człowieka
3.1. Zmniejszenie ilości potencjalnie patogennych mikroorganizmów przewodu pokarmowego (ID 774)
Among the references provided were reviews, textbooks and opinions/guidelines from authoritative bodies which either did not address the claimed effect or did not contain any original data which could be used for the scientific substantiation of the claimed effect. Some human studies were not related to the food constituent that is the subject of the claim, or examined the effect of FOS in combination with other substances, and several human and animal studies addressed outcomes unrelated to the claimed effect. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect. One conference report related to the effect of FOS on intestinal microbiota was not accessible to the Panel after having made every reasonable effort to retrieve it (Rochat et al., 1994).
Several human studies focused on the effects of FOS on faecal bifidobacteria (Bouhnik et al., 2004; Gibson and Wang, 1994a; Gibson and Wang, 1994b), or on bifidobacteria together with other bacterial groups (e.g. total aerobes, total anaerobes, staphylococci, enterococci, Bacteroides, enterobacteria, clostridia, fusobacteria, coliforms) (Bouhnik et al., 1996; Bouhnik et al., 1999; Bouhnik et al., 2006; Buddington et al., 1996; Gibson et al., 1995; Rao, 2001; Waligora-Dupriet et al., 2007). The Panel notes that the bacterial groups analysed in these studies are part of the commensal intestinal microbiota, and that the studies did not provide evidence for the characterisation of any of these groups as pathogens. In three human studies the effect of FOS on Clostridium perfringens was analysed (Mitsuoka et al., 1986; Mitsuoka et al., 1987; Tokunaga et al., 1993), but no information was given about the pathogenicity of the bacterial strains studied. The Panel considers that no conclusions can be drawn from these studies for the scientific substantiation of the claimed effect.
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The Panel notes that no human studies have been provided from which conclusions can be drawn for the scientific substantiation of the claimed effect. The Panel considers that human studies are required for the substantiation of a claim, and that evidence provided in animal and in vitro studies is not sufficient to predict the occurrence of an effect of FOS consumption on decreasing potentially pathogenic intestinal microorganisms in humans.
The Panel concludes that a cause and effect relationship has not been established between the consumption of fructooligosaccharides from sucrose and decreasing potentially pathogenic intestinal microorganisms.
3.2. Zmiany w funkcjach jelita (ID 775, 778)
Among the references provided were reviews, textbooks and opinions from authoritative bodies which either did not address the claimed effect or did not contain any original data which could be used for the scientific substantiation of the claimed effect. A number of human studies addressed the effects of substances other than FOS or of a mixture of FOS with other substances, or addressed outcomes not related to the claimed effect (e.g. abdominal comfort). The provided animal and in vitro studies assessed endpoints not related to the claimed effect (e.g. butyrate content in faeces, SCFA content, number of selected microbiota, β-galactosidase, α-glucosidase, β-glucosidase and β-glucuronidase activity, colon crypts depth, numbers of epithelial and mitotic cells in the crypt columns, caecal wall weight, proliferation index and indices of artificially provoked colitis). The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
Bouhnik et al. (1996) found, in a randomised, placebo-controlled study in a group of healthy volunteers (n=20) with saccharose as placebo, that FOS consumption of 12.5 g/day did not significantly affect stool weight (FOS group: 134±22 g/day, placebo group: 121±19 g/day, p>0.05).
In a randomised, single-blind, parallel trial FOS (mean dose 0.74±0.39 g/day) was added to cereal formula intended for feeding infants and given for 28 days to a group of healthy term infants (n=27) aged 4–12 months (mean 8.3 months) (Moore et al., 2003). The effect of FOS addition to cereals was compared to the same cereals with the addition of the equivalent amount of maltodextrin (n=29). Stool frequency was recorded by parents. The Panel notes that the tool used for assessing bowel function (parent's assessment) was not validated, that the main aim of the study was to assess tolerance of FOS given to infants, and that the sample size was relatively small. The Panel considers that no conclusions can be drawn from this reference for the scientific substantiation of the claimed effect.
In a single-blind study, Tokunaga et al. (1993) studied the effect of FOS (daily dose 1.3 or 5 g) on intestinal microbiota and bowel function in 27 healthy volunteers. The Panel notes that the study was not placebo-controlled, that no information about randomisation was given, and that multiple comparison testing was not included in the statistical analysis. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claimed effect.
In weighing the evidence, the Panel took into account that the only relevant human study showed no effect of FOS consumption on bowel function.
The Panel concludes that a cause and effect relationship has not been established between the consumption of fructooligosaccharides from sucrose and changes in bowel function.
3.3. Zmniejszenie dolegliwości ze strony przewodu pokarmowego (ID 775, 778)
All references considered in section 3.2. were also provided for the substantiation of this claim.
A number of human studies addressed the effects of substances other than FOS or of a mixture of FOS with other substances, or addressed outcomes not related to the claimed effect (e.g. stool frequency and intestinal microbiota). The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
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Only one human study addressed the effect of FOS from sucrose on abdominal comfort.
Paineau et al. (2008) evaluated in a randomised, multicentre, double-blind, placebo-controlled study the effect of FOS from sucrose (5 g/day) vs. placebo (sucrose and maltodextrins) on the digestive comfort of subjects with minor functional bowel disorders (n=105, mean age 38 years, 85 % women). The prevalence and general frequency of digestive symptoms based on Rome II criteria were recorded in a questionnaire including questions about the presence and intensity of five abdominal symptoms (discomfort or pain; fullness, bloating or swelling; feeling of incomplete bowel movement; urgency; straining at stool). This questionnaire (called the initial questionnaire) was used for inclusion, and at the end of the study to determine changes in intensity of symptoms. The participants were also asked to complete a questionnaire (called the consultation questionnaire) designed to assess the frequency of digestive symptoms and stool quality before the intervention period and at the end of the study. Quality of life was assessed using the French language functional digestive disorders quality of life questionnaire (FDDQL). Baseline intensity of symptoms at the beginning of the study was similar in both studied groups. The participants took two packets daily containing 2.5 g FOS or placebo for six weeks. Eight subjects dropped out during the study (four in each group) and compliance was estimated as good for 50 subjects (24 in FOS and 26 in placebo group). Final results were presented only for these 50 subjects. The Panel notes that except for the quality of life questionnaire no information was provided on the validation of the other questionnaires, that the validated quality of life questionnaire alone is insufficient as an outcome measure, that a power calculation was not presented, that only the data obtained from 48 % of the participants included in the study were used for statistical analysis of the results, that no intention-to-treat analysis of the data was reported, and that in the statistical analysis correction for multiple testing was not performed. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between the consumption of fructooligosaccharides from sucrose and reduction of gastro-intestinal discomfort.
3.4. Wzrost wchłaniania wapnia i/lub magnezu prowadzący do zwiększenia ilości wapnia i/lub magnezu w organizmie (ID 776, 777)
Among the references cited in relation to this claim were narrative reviews that either did not contain original data that could be used for the scientific substantiation of the claimed effect, or did not address the food constituent which is the subject of the claim. A number of references addressed outcomes not related to the claimed effect, or used different inulin-type fructans or a mixture of short- chain fructooligosaccharides and inulin. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
Five human studies explicitly used FOS from sucrose (Fukushima et al., 2002; Hosono et al., 1997; Ohta et al., 1999; Tahiri et al., 2001; 2003), which is the subject of the claim.
Three of the human intervention studies addressed the effects of FOS from sucrose on urinary excretion of calcium as a surrogate measure of calcium absorption after a single oral dose of calcium administered in different chemical forms (Fukushima et al., 2002; Hosono et al., 1997; Ohta et al., 1999). None of the studies provided measures of calcium retention. The Panel considers that no conclusions can be drawn from these acute and small-scale studies for the scientific substantiation of the claimed effect.
A first study by Tahiri et al. (2001) was conducted in 11 healthy postmenopausal women not receiving hormone replacement therapy who consumed 10 g/day of FOS for five weeks, and placebo for another five weeks, with a three-week wash-out period in between, following a cross-over, double-blind, randomised design. Magnesium absorption from the diet (providing around 250 mg Mg/day) was determined by ingestion of a stable isotope (25Mg) and a faecal marker. The absorption of magnesium was significantly increased from 30.2±5 % to 33.9±7.2 % (i.e. a 12 % increase) in the FOS group. This increase was accompanied by an increase in 25Mg plasma concentrations and by an increase in
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magnesium urinary excretion. Isotope-labelled 25Mg retention was reported to be significantly higher with FOS (27.5±5.6 mg) than without FOS (24.7±4.0 mg), however the increase in urinary excretion of magnesium was similar to the increase in magnesium absorption (10 mg/day). No significant increase in apparent magnesium retention was observed.
A second study by Tahiri et al. (2003) was a double-blind, cross-over, randomised control trial (RCT) conducted in 12 healthy post-menopausal women not receiving hormonal therapy who consumed 10 g FOS and placebo for five weeks each with a three-week wash-out period in between. Calcium absorption from the diet (providing about 900 mg Ca/day) was determined using oral isotope-labelled 44Ca and a faecal marker. Changes in intestinal absorption of calcium were not different between groups. Calcium retention was not measured in this study.
Two studies in rats investigated the effects of FOS from sucrose of different chain length on calcium and magnesium absorption and excretion (Ohta et al., 1995; 1998). The Panel considers that evidence provided in rat studies is not sufficient to predict the occurrence of an effect of the consumption of FOS on mineral absorption in humans, especially when considering anatomical differences in the caecum and large intestine between rats and humans.
In weighing the evidence, the Panel took into account that only two chronic studies in a low number of human subjects were provided, and that these studies, though suggesting an effect on magnesium (but not calcium) absorption, do not show an effect of FOS from sucrose on mineral retention.
The Panel concludes that a cause and effect relationship has not been established between the consumption of fructooligosaccharides from sucrose and an increase in magnesium and/or calcium absorption leading to an increase in magnesium and/or calcium retention.
3.5. Utrzymanie prawidłowego stężenia cholesterolu LDL we krwi (ID 805)
Among the references cited in relation to this claim were general reviews on “prebiotic” substances, references addressing outcomes either not related to the claimed effect or using different oligosaccharides or polysaccharides than FOS from sucrose, which is the subject of the claim, and a meta-analysis on the effects of fructans on triglyceride concentrations in humans. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
A total of eight human studies addressed the effects of FOS from sucrose on blood cholesterol concentrations (Alles et al., 1999; Daubioul et al., 2005; Giacco et al., 2004; Hidaka et al., 1991; Luo et al., 1996; 2000; van Dokkum et al., 1999; Yamashita et al., 1984).
In the 2-week study by Yamashita et al. (1984), no direct comparison between the intervention (18 diabetic subjects consuming 8 g/day of FOS from sucrose) and control (10 subjects consuming 5 g/day of sucrose) groups with respect to changes in total and LDL-cholesterol concentrations was reported. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claimed effect.
In the randomised, controlled intervention by Hidaka et al. (1991), 46 hyperlipidaemic patients (20 men, 26 women) received either 8 g/day of FOS from sucrose or the same amount of sucrose (control) for five weeks. Total cholesterol concentrations were significantly decreased in the intervention group compared to placebo. In a second experiment reported in the same publication, seven hypercholesterolaemic subjects with type II hyperlipoproteinaemia received 8 g/day of FOS from sucrose for one month. This intervention was not controlled (one arm). The Panel considers that no conclusions can be drawn from the second experiment for the scientific substantiation of the claimed effect.
In the remaining six studies, 8-20 g/day of FOS from sucrose were consumed by 7-30 subjects (healthy or with type 2 diabetes) during two to eight weeks, using either a double-blind, randomised
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controlled design or a cross-over design. These studies (91 subjects in total, including 24 healthy, 30 mildly hypercholesterolaemic, 30 with type 2 diabetes, and seven with non alcoholic liver steatosis) reported no significant differences on total blood cholesterol concentrations or cholesterol sub- fractions between the FOS and the control groups (Alles et al., 1999; Daubioul et al., 2005; Giacco et al., 2004; Luo et al., 1996; 2000; van Dokkum et al., 1999).
In weighing the evidence, the Panel took into account that six out of the seven small intervention studies from which conclusions could be drawn for the scientific substantiation of the claim did not observe a significant effect of FOS from sucrose on blood cholesterol concentrations.
The Panel concludes that a cause and effect relationship has not been established between the consumption of fructooligosaccharides from sucrose and maintenance of normal blood LDL-cholesterol concentrations.
3.6. Utrzymanie prawidłowego stężenia cholesterolu we krwi na czczo (ID 805)
All references considered in section 3.5. were also provided for the substantiation of this claim.
A meta-analysis of randomised clinical trials on the effects of inulin-type fructans and FOS from sucrose on plasma concentrations of triglycerides (Brighenti, 2007) was provided. No separate conclusions on the effects of inulin-type fructans and FOS from sucrose were presented, and hence no conclusions can be drawn from this meta-analysis for the scientific substantiation of the claimed effect.
In addition, eight human intervention studies which addressed the effects of FOS from sucrose on blood concentrations of triglycerides were provided (Alles et al., 1999; Daubioul et al., 2005; Giacco et al., 2004; Hidaka et al., 1991; Luo et al., 1996; 2000; van Dokkum et al., 1999; Yamashita et al., 1984).
In the two-week study by Yamashita et al. (1984), no direct comparison between the intervention (18 diabetic subjects consuming 8 g/day of FOS from sucrose) and control (10 subjects consuming 5 g/day of sucrose as placebo) groups with respect to changes in blood concentrations of triglycerides was reported. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claimed effect.
The remaining seven publications reported on randomised, controlled trials with either parallel or cross-over designs, in which 8-20 g/day of FOS from sucrose were consumed by 7-30 subjects during two to eight weeks. None of these studies (181 subjects in total, including 24 healthy, 120 mildly hypercholesterolaemic, 30 with type 2 diabetes, and seven with non alcoholic liver steatosis) reported statistically significant differences on blood concentrations of triglycerides between the FOS and the control group (Alles et al., 1999; Daubioul et al., 2005; Giacco et al., 2004; Hidaka et al., 1991; Luo et al., 1996; 2000; van Dokkum et al., 1999).
In weighing the evidence, the Panel took into account that none of the seven intervention studies from which conclusions could be drawn for the scientific substantiation of the claim observed a significant effect of FOS from sucrose on blood concentrations of triglycerides.
The Panel concludes that a cause and effect relationship has not been established between the consumption of fructooligosaccharides from sucrose and the maintenance of normal (fasting) blood concentrations of triglycerides.
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