Gastrointestinal tolerance of erythritol-containing beverage in young children: a double-blind, randomised controlled trial.

BACKGROUND/OBJECTIVE: To determine gastrointestinal (GI) responses and maximum tolerated dose of erythritol in young children given as a single oral dose in a 250-ml non-carbonated fruit-flavoured beverage in between meals. This is a multicentre double-blind study with sequential design for multiple dose groups and randomised crossover for comparators of placebo vs dose. SUBJECTS/METHODS: A total of 185 healthy young children aged 4-6 years were recruited at three clinical investigation centres after informed consent of both parents; 184 children completed the study. Children were included in one of the four dose groups (5, 15, 20 or 25 g erythritol) and exposed randomly to only one single dose vs an isosweet sucrose placebo. After consumption in the clinic and an observation period, GI symptoms and stooling patterns were recorded during the next 48 h. RESULTS: Statistically significantly more episodes of diarrhoea and/or severe GI symptoms were observed in the 20 and 25 g groups compared with placebo, but not in the 5 and 15 g groups. Stool consistency, as measured by Bristol stool scale, was lower in the 15-, 20- and 25 g groups for the first 24 -h period, but not at later time points. Incidences of nausea, vomiting, borborygmi, excess flatus and abdominal pain were not significantly different from the placebo controls at all doses of erythritol. CONCLUSIONS: Rapid ingestion of up to and including 15 g (6% w/v) of erythritol in a beverage in between meals by young children aged 4-6 years was well tolerated. The no observed effect level for diarrhoea and/or severe GI symptoms was 15 g (0.73 g/kg body weight (bw)). Children appeared not to be more sensitive to the GI effects of erythritol than published for adults on a g/kg bw basis.

Small intestinal permeability is increased in diarrhoea predominant IBS, while alterations in gastroduodenal permeability in all IBS subtypes are largely attributable to confounders.

BACKGROUND: Intestinal permeability has been studied in small groups of IBS patients with contrasting findings. AIMS: To assess intestinal permeability at different sites of the GI tract in different subtypes of well-characterised IBS patients and healthy controls (HC), and to assess potential confounding factors. METHODS: IBS patients and HC underwent a multi-sugar test to assess site-specific intestinal permeability. Sucrose excretion and lactulose/rhamnose ratio in 0-5 h urine indicated gastroduodenal and small intestinal permeability, respectively. Sucralose/erythritol ratio in 0-24 h and 5-24 h urine indicated whole gut and colonic permeability, respectively. Linear regression analysis was used to assess the association between IBS groups and intestinal permeability and to adjust for age, sex, BMI, anxiety or depression, smoking, alcohol intake and use of medication. RESULTS: Ninety-one IBS patients, i.e. 37% IBS-D, 23% IBS-C, 33% IBS-M and 7% IBS-U and 94 HC were enrolled. Urinary sucrose excretion was significantly increased in the total IBS group [µmol, median (Q1;Q3): 5.26 (1.82;11.03) vs. 2.44 (0.91;5.85), P < 0.05], as well as in IBS-C and IBS-D vs. HC. However, differences attenuated when adjusting for confounders. The lactulose/rhamnose ratio was increased in IBS-D vs. HC [0.023 (0.013;0.038) vs. 0.014 (0.008;0.025), P < 0.05], which remained significant after adjustment for confounders. No difference was found in 0-24 and 5-24 h sucralose/erythritol ratio between groups. CONCLUSIONS: Small intestinal permeability is increased in patients with IBS-D compared to healthy controls, irrespective of confounding factors. Adjustment for confounders is necessary when studying intestinal permeability, especially in a heterogeneous disorder such as IBS.

Erythritol is a sweet antioxidant.

OBJECTIVE: Hyperglycemia, oxidative stress, and the onset and progression of diabetic complications are strongly linked. Reduction of oxidative stress could be of utmost importance in the long-term treatment of diabetic patients. The chronic nature of the disease calls for a mode of antioxidant intake that can be sustained easily, e.g., by the diet. Erythritol, a simple polyol, could be such a compound. It is orally available, well tolerated, and its chemical structure resembles that of mannitol, a well-known hydroxyl radical (HO*) scavenger. METHODS: We studied the antioxidant properties of erythritol in vitro and subsequently determined its antioxidant activity and its vasoprotective effect in the streptozotocin diabetic rat. RESULTS: Erythritol was shown to be an excellent HO* radical scavenger and an inhibitor of 2,2'-azobis-2-amidinopropane dihydrochloride-induced hemolysis but inert toward superoxide radicals. High-performance liquid chromatographic and electron spin resonance spectroscopy studies showed that the reaction of erythritol with hydroxyl radicals resulted in the formation of erythrose and erythrulose by abstraction of a carbon-bound hydrogen atom. In the streptozotocin diabetic rat, erythritol displayed an endothelium-protective effect and, in accordance with the in vitro experiments, erythrose was found in the urine of erythritol-consuming rats. CONCLUSION: Erythritol acts as an antioxidant in vivo and may help protect against hyperglycemia-induced vascular damage.

Sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis patients causes urinary accumulation of sedoheptulose: elucidation of the CARKL gene.

The most common mutation in the nephropathic cystinosis (CTNS) gene is a homozygous 57-kb deletion that also includes an adjacent gene carbohydrate kinase-like (CARKL). The latter gene encodes a protein that is predicted to function as a carbohydrate kinase. Cystinosis patients with the common 57-kb deletion had strongly elevated urinary concentrations of sedoheptulose (28-451 mmol/mol creatinine; controls and other cystinosis patients <9) and erythritol (234-1110 mmol/mol creatinine; controls and other cystinosis patients <148). Enzyme studies performed on fibroblast homogenates derived from patients carrying the 57-kb deletion revealed 80% reduction in their sedoheptulose phosphorylating activity compared to cystinosis patients with other mutations and controls. This indicates that the CARKL-encoded protein, sedoheptulokinase (SHK), is responsible for the reaction: sedoheptulose + ATP --> sedoheptulose-7-phosphate + ADP and that deletion of CARKL causes urinary accumulation of sedoheptulose and erythritol.

Transaldolase deficiency: a new cause of hydrops fetalis and neonatal multi-organ disease.

Transaldolase (TALDO) deficiency is a newly recognized metabolic disease, which has been reported so far in 2 patients presenting with liver failure and cirrhosis. We report a new sibship of 4 infants born to the same consanguineous parents; all presented at birth or in the antenatal period with dysmorphic features, cutis laxa and hypertrichosis, hepatomegaly, splenomegaly, liver failure, hemolytic anemia, thrombocytopenia, and genitourinary malformations. The clinical courses were variable: the first child died of liver failure at 4 months of age; the second pregnancy was medically terminated at 28 weeks gestation because of hydrops fetalis with oligohydramnios. The third child is doing well at age 7 with liver fibrosis and mild kidney failure. The fourth child is now 21 months old and has hepatosplenomegaly, mild anemia, and thrombocytopenia. Urine assessment of polyols showed elevations of erythritol, arabitol, and ribitol consistent with TALDO deficiency. TALDO activity was undetectable in the patients' tissues, and mutation in the TALDO1 gene was found in the 4 patients.

Analysis of polyols in urine by liquid chromatography-tandem mass spectrometry: a useful tool for recognition of inborn errors affecting polyol metabolism.

Several inborn errors of metabolism with abnormal polyol concentrations in body fluids are known to date. Most of these defects can be diagnosed by the assessment of urinary concentrations of polyols. We present two methods using tandem mass spectrometry for screening for inborn errors affecting polyol metabolism. Urine samples supplemented with internal standards ([13C4]erythritol, [13C2]arabitol and [2H3]sorbitol) were desalted by a mixed-bed ion-exchange resin. Separation was achieved by two different columns. Sugar isomers could not be separated using a Prevail Carbohydrate ES 54 column (method 1), whereas with the other column (Aminex HPX-87C) separation of the isomers was achieved (method 2). Multiple reaction monitoring polyol detection was achieved by tandem mass spectrometry with an electron ion-spray source operating in the negative mode. Age-related reference ranges of polyols (erythritol, treitol, arabitol, ribitol, xylitol, galactitol, mannitol, sorbitol, sedoheptitol and perseitol) in urine were established. The applicability of the method was demonstrated by the abnormal polyol concentrations observed in patients with transaldolase deficiency, ribose-5-phosphate isomerase deficiency and classical galactosaemia. This paper describes two methods for the analysis of urinary polyols by liquid chromatography-tandem mass spectrometry. Method 1 is a fast screening method with the quantification of total isomers and method 2 is a more selective method with the separate quantification of the polyols. Both methods can be used for diagnosing inborn errors of metabolism affecting polyol metabolism.

Disposition of 14C-erythritol in germfree and conventional rats.

The metabolism and disposition of U-14C-erythritol was examined in four groups of three male and three female, nonfasted rats each. The rats of groups A and D were germfree; the rats of groups B and C were kept under conventional conditions. The rats of group B received an erythritol-supplemented diet for 3 weeks prior to the experiment (adapted rats). The rats of groups A, C, and D were kept on an ordinary diet which was sterile for groups A and D (not adapted rats). On the day of the experiment, each rat was dosed with U-14C-erythritol by gavage (5 microCi/kg body wt; sp act 50 microCi/g erythritol). The radiochemical purity of the erythritol was 96.43% for groups A-C. Group D, which was attached to the study after evaluation of the results of groups A-C, received a more purified erythritol with a radiochemical purity of 99.46% because the data of group A pointed to a possible interference by a 14C-labeled impurity in the commercial 14C-erythritol. After dosing, respiratory CO2 and urine were collected from each rat at regular intervals for 24 hr. At termination, feces were also collected. The animals were killed and intestinal contents, organs, tissues, and the remaining carcass processed for determination of 14C-14C was excreted rapidly in the urine of all groups (range of groups A-D: 47.3-60.6% of the administered dose within the first 4 hr). Total 24-hr urinary excretion varied between 67.0% (group B) and 81.4% (group D). HPLC analysis of the urine showed that more than 96% of the eluted radiolabel represented erythritol. Conventional, adapted rats expired more 14CO2 than conventional, unadapted rats [10.9% (B) vs 6.7% (C)]. Germfree rats expired much less 14CO2 [0.8% (A) and 0.3% (D)]. In germfree rats, 14CO2 expiration started shortly after dosing, reaching half of the 24-hr excretion after about 2.5 hr. In conventional rats 14CO2 expiration started with a delay of about 2 hr reaching half the 24-hr excretion after 4-6 hr. The excretion of 14C with feces was similar in all groups (8.3% on average of all rats). Slightly more 14C was retained in the intestinal contents of germfree than conventional rats (1.9 vs 0.5%). The body retention was higher in conventional than in germfree rats (3.4 vs 2.0%). In group D, body retention was lowest (1.6%). The total recovery of 14C was similar in all groups (95.6%, average of all rats). It is concluded that ingested erythritol is efficiently absorbed mainly from the small intestine, is not metabolized to a relevant extent in the body, and is excreted unchanged in the urine. The fraction of erythritol not absorbed is fermented by the gut microflora to intermediate products which are largely absorbed and metabolized. The data support a proposed physiological energy value for erythritol of about 0.5 kcal/g.

Fate of erythritol after single oral administration to rats and dogs.

The absorption and distribution of radiolabeled erythritol were studied in Wistar rats and beagle dogs after a single oral administration in doses ranging from 0.125 to 2.0 g erythritol/kg body wt. Erythritol concentrations in blood and plasma of rats reached their maxima 1 hr after administration and then declined biexponentially. In the blood and plasma of dogs, the highest concentrations occurred after 1/2 hr followed by a similar decline. Blood plasma distribution ratios and plasma protein binding ratios increased as blood plasma levels declined. At 120 hr after administration, 95.68 +/- 2.25% of the radioactivity had been excreted in the urine of dogs and 92.70 +/- 0.44% in the urine of rats; 0.33 +/- 0.05% had been excreted in the feces of dogs and 1.19 +/- 0.09% in the feces of rats; 1.17 +/- 0.04% had been excreted in expired air from dogs and 4.80 +/- 0.32% in expired air from rats. The results demonstrate that erythritol is rapidly absorbed and excreted, principally through the urinary pathway.

Subchronic oral toxicity studies with erythritol in mice and rats.

Erythritol is a sugar alcohol (polyol) with potential applications as a low-calorie, bulk sweetener. Ingested erythritol is efficiently absorbed and excreted unchanged via the urine since it is not metabolized systemically by the animal or human body. Erythritol was administered to four groups of 10 male and 10 female Swiss CD-1 mice and four groups of 15 male Wistar Crl:(WI) WU BR rats at dietary levels of 0, 5, 10, or 20% for 90 days. A fifth group of rats received a diet containing 20% erythritol on a time-restricted basis (6 hr/day), and a sixth group received a diet containing 20% mannitol for comparison. There were no treatment-related mortalities in either mice or rats. Soft stools and occasional diarrhea were observed in rats fed diets with 20% erythritol or mannitol but not in mice. Body weights were slightly yet significantly reduced in rats fed 20% erythritol or mannitol and in male mice of the 20% dose group. Erythritol intake in the high-dose group was approximately 12 g/kg body wt in rats and 44 and 45 g/kg body wt in male and female mice, respectively. Hematological and clinicochemical examinations of blood and plasma did not reveal any treatment-related effects. Urine output increased with increasing erythritol dose. In male and female mice of the 20% erythritol group, the creatinine-normalized urinary excretion of protein, K-glutamyltransferase (GGT), and electrolytes (Na+, K+, Ca2+, Pi, citrate) was significantly increased while urinary N-acetylglucosaminidase (NAG) remained unchanged. At the 10% level, significantly increased urinary protein (both sexes) and GGT (males only) excretion were seen. In rats, the creatinine-normalized urinary excretion of GGT, NAG, and some electrolytes (Na+, K+, and Ca2+) was increased in some erythritol groups but a clear dose-response relationship was evident only for calcium. On termination of the study, cecal enlargement was seen in rats of the 10 and 20% dose groups and in mice of the 20% dose group. Increased relative and absolute kidney weights were observed in both sexes of mice in the 20% erythritol group, in male mice of the 5 and 10% groups, and in rats of the 10 and 20% erythritol groups. Histopathological examination did not reveal any treatment-related abnormalities in either mice or rats. In conclusion, the ingestion of erythritol for 90 days at dietary levels of up to 20% did not produce signs of toxicity in mice or rats. In particular, the morphological integrity of the kidneys was not adversely affected by the treatment in either species. The increases in urinary excretion of protein, GGT, NAG, and electrolytes were considered to result from extensive osmotic diuresis and a potential overload of the renal excretory system at the high dose levels employed.

Chronic (1-year) oral toxicity study of erythritol in dogs.

The chronic oral toxicity of erythritol was examined by feeding erythritol at dietary levels of 0 (controls), 2, 5, or 10% to groups of four male and four female dogs for 53 weeks. Erythritol was well tolerated at all dose levels without evidence of diarrhea. Water consumption was slightly higher in the high-dose group than in controls. Body weights and weight gains were not affected by treatment. There were no clinically relevant changes in hematological or clinicochemical parameters attributable to treatment. In particular, plasma electrolyte concentrations remained unaffected. Evaluation of a number of urinary parameters (including electrolytes and renal enzymes) was hampered by widely varying urine volumes among individual dogs; however, the available data did not indicate treatment-related effects on the urinary excretion of electrolytes (K+, Na+, Mg2+, and Pi) or enzymes (gamma-glutamyltranspeptidase, N-acetyl glucosaminidase, and lactate dehydrogenase). Quantitation of erythritol in the urine demonstrated that 50 to 80% of the ingested dose was absorbed and excreted in the urine. Analysis of terminal organ weights did not reveal treatment-related differences. No histopathological changes attributable to treatment were observed in the kidneys or in any other organ or tissue examined. It was concluded that daily erythritol consumption of up to 3.5 g/kg body wt was well tolerated by dogs.

Chronic toxicity and carcinogenicity study of erythritol in rats.

The potential toxicity and carcinogenicity of erythritol, a low-calorie sugar substitute, were examined in Wistar Crl:(WI) WU BR rats. Groups of 50 rats of each sex consumed diets with 0, 2, 5, or 10% erythritol, or 10% mannitol, for a period of 104-107 weeks. To each of these main groups, two satellite groups of 20 males each were attached for interim kills after 52 and 78 weeks of treatment. At start of the study, the rats were 5-6 weeks old. The average intakes of erythritol in the 2, 5, and 10% groups were 0.9, 2.2, and 4.6 g/kg body wt/day for males and 1.0, 2.6, and 5.4 g/kg body wt/day for females, respectively. Mannitol intakes were 4.4 and 5.2 g/kg body wt/day in males and females, respectively. All treatments were well tolerated without diarrhea or other side effects. Body weights were significantly below control levels during most of the study in males of the 5% erythritol group and in males and females of the 10% erythritol and 10% mannitol groups. Survival of the animals was not adversely affected by the treatments. Hematological and clinicochemical examinations did not reveal noticeable changes which could be attributed to treatment. Analysis of urine samples collected during five 48-hr periods, from rats of the satellite groups in Weeks 26, 42, 50, and 78 and from rats of the main groups in Week 102, showed that about 60% of ingested erythritol was excreted unchanged. The urine volumes increased with increasing dietary erythritol levels. In line with previous observations on other polyols, erythritol and mannitol ingestion led to an increased excretion of urinary calcium and citrate. The urinary excretions of sodium, potassium, phosphate, N-acetylglucosaminidase (NAG), gamma-glutamyltransferase (GGT), low-molecular-weight protein (LMP), and total protein (TP) were slightly elevated in the 10% erythritol group. Increased GGT and NAG excretions also were seen occasionally at the 5% dose. Significantly increased relative cecum weights were seen in rats of either sex in the 10% mannitol and, somewhat less pronounced, 10% erythritol groups. Some cecal enlargement also was seen in the 5% erythritol group. The relative weight of the kidneys was highest in the 10% erythritol group, the difference from controls reaching statistical significance at interim kills (males) and termination (females). Except for more frequent pelvic nephrocalcinosis in female rats of all erythritol dose groups, the histopathological examinations did not reveal any nonneoplastic, preneoplastic, or neoplastic changes that could be attributed to the ingestion of erythritol. In male and female rats of the 10% mannitol group, pelvic nephrocalcinosis, which in females was associated occasionally with pelvic hyperplasia, was the only remarkable finding. The incidence and progression of nephrosis, which is commonly seen in aging rats of this strain, were not influenced by the treatments. In the absence of morphological alterations in the kidneys or other signs of nephrotoxicity, the increased excretions of NAG, GGT, LMP, and TP are regarded as innocuous, functional sequelae of the renal elimination of erythritol. In conclusion, the toxicological profile of erythritol in rats resembles that of other polyols in several respects. Except for nephrocalcinosis, which is commonly seen in polyol-fed rats, no other treatment-related, morphological changes were observed in the kidneys. Evidence for a tumor-inducing or tumor-promoting effect of erythritol was not seen.

Plasma and urine kinetics of erythritol after oral ingestion by healthy humans.

The plasma and urine kinetics of erythritol and the effect of erythritol on plasma glucose and insulin levels were studied in human volunteers administered a single oral dose of 1 g erythritol/kg body wt. The plasma level of erythritol increased during the first 30 to 40 min, reaching a maximum value of approximately 2.2 mg/ml after 90 min. Plasma levels of erythritol then declined gradually to approximately 1.5 to 1.7 mg/ml at the end of the 3-hr sampling period. An average of 30% of the ingested amount of erythritol was excreted unchanged in the urine during the first 3 hr. Total urinary excretion increased to 78% after 24 hr. Renal clearance of erythritol was approximately half that of creatinine, indicating tubular reabsorption of erythritol by the kidney. Mean plasma glucose and insulin levels, measured for up to 3 hr after ingestion, were unaffected by erythritol. The results of this study indicate that erythritol was readily absorbed following oral administration and was excreted unchanged in the urine. Less than 20% of erythritol remained unabsorbed and was available for colonic fermentation and potential production of short-chain fatty acids. Its caloric value was estimated to be < or = 0.4 kcal/g.

Tolerance to subchronic, high-dose ingestion of erythritol in human volunteers.

Erythritol is a sugar alcohol (polyol) which is absorbed from the small intestine in substantial amounts, not metabolized in the human body, and therefore excreted in the urine. Erythritol holds promise as a low-calorie sugar substitute. Human tolerance to repeated oral doses of erythritol was examined in a double-blind, two-way crossover study in 12 healthy, male volunteers. The participants consumed erythritol and, for comparison, sucrose for a duration of 7 days each. The daily dose of the test compounds ingested was 0.3 g/kg on Day 1, 0.6 g/kg on Day 2, and 1.0 g/kg on subsequent days. The daily dose was consumed under supervision in five portions, i.e., with the three main meals, a midmorning snack, and during the afternoon. The test compounds were incorporated into yoghurt, cookies, soft drinks, and chocolate. On each treatment day, body weight and blood pressure were measured and the participants were interviewed about side effects and their perception of stool and urine production. During the last 96 hr of each treatment period, urine was collected at 3-hr intervals during the day and for a 9-hr interval overnight for analysis of erythritol and different urinary parameters. On Days 3 to 7 of each treatment period, the participants were institutionalized. Body weights and blood pressure remained stable during the entire study. Signs of gastrointestinal intolerance were not seen and stool frequency and appearance were not different between the two treatments. The intake of liquids, which were provided ad libitum, was generally rather high (32.8 g/kg body wt/day on average) but not different between erythritol and sucrose consumption. Urine output also was high during both treatment periods. About 78% of ingested erythritol was excreted in the urine which led to a higher urinary osmolality but did not influence the 24-hr output of creatinine, citrate, urea, or electrolytes (Na+, K+, Cl-, Pi). The excretion of calcium was slightly higher during the erythritol test period but in absolute terms this increase was small. The urinary excretions of albumin, beta 2-microglobulin, and N-acetyl-glucosaminidase were slightly elevated during the erythritol test period but they were still well within the physiological range. None of the observed urinary changes became more pronounced with increasing duration of the erythritol treatment. In conclusion, the results of the present study demonstrate that the repeated ingestion of erythritol at daily doses of 1 g/kg body wt was well tolerated by humans.

Gastrointestinal response and plasma and urine determinations in human subjects given erythritol.

This study was undertaken to examine the influence of erythritol on certain plasma and urinary parameters and to assess the gastrointestinal response of humans given erythritol at single oral doses of 0.4 or 0.8 g/kg body wt/day. Three groups of six healthy volunteers each received a midmorning snack containing the equivalent of 0.4 or 0.8 g erythritol/kg body wt or 0.8 g sucrose/kg body wt. A fourth group received no snack and served as a negative control group. Consumption of erythritol did not affect plasma osmolarity, water consumption, or diuresis, and no significant variations in plasma or urine electrolyte balance were observed. Plasma glucose and insulin concentrations also were not affected by erythritol. Gastrointestinal responses to erythritol were comparable to those of sucrose. Plasma and urine erythritol concentrations increased within 2 hr of ingestion in proportion to the amount ingested. Approximately 60% of the erythritol dose was eliminated in the urine within 22 hr. The results of this study demonstrate that ingestion of erythritol at doses of up to 0.8 g/kg body wt does not alter plasma or urine osmolarity or electrolyte balance and is well tolerated by the digestive tract.

Metabolism of erythritol in humans: comparison with glucose and lactitol.

The metabolism of erythritol was assessed in six normal volunteers by measuring the amount of 13CO2 excretion and H2 excretion in breath, and erythritol in urine after intake of 25 g 13C-labelled erythritol. The results were compared with the same variables obtained after intake of 25 g 13C-labelled glucose and 13C-labelled lactitol. In addition, the H2 production by faecal flora supplemented with small amounts of erythritol, glucose and lactitol was measured in vitro, as an index of bacterial metabolism of non-absorbed substrate. In contrast to the results obtained after intake of glucose and lactitol, no increase in breath 13CO2 and H2 was observed after intake of erythritol, and erythritol was nearly completely recovered in urine. The in vitro experiments showed that no H2 was formed by faecal flora from erythritol as compared with glucose and lactitol. It is concluded that erythritol is a substrate that is readily absorbed, and undergoes no metabolism by the host. If part of it escapes absorption, it is not metabolized by faecal flora.

Metabolism and disposition of erythritol after oral administration to rats.

The metabolism and disposition of erythritol was studied using [14C]erythritol in rats. When [14C]erythritol was administered orally at a dose of 0.1 g/kg body wt to male rats, only 6% of the total radioactivity was excreted as expired 14CO2 and 88% was excreted in the urine within 24 h. The excreted metabolite in the urine consisted of a single component identified as intact [14C]erythritol. The excretion of 14CO2 and the incorporation ratios of radioactivity into tissues increased with the oral dosage. After rats were given an intravenous injection of [14C]erythritol, approximately 1% was excreted as 14CO2 and greater than 94% was excreted in the urine as intact [14C]erythritol. The excretion of 14CO2 within 24 h was increased to approximately 10% when [14C]erythritol was administered to rats that had been adapted to erythritol by feeding a diet containing 10% erythritol for 2 wk. When [14C]erythritol was incubated in vitro with the cecal contents from rats adapted to erythritol, greater than 20% was fermented to 14CO2 and 60% to short-chain fatty acids in 6 h. These results indicate that most orally administered erythritol was excreted in the urine without any degradation and that the remainder was transferred to the lower intestine and fermented by microbes.