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At least 19 recordsLinked to original sources

PubMed1994

Serum glucose and insulin levels and erythritol balance after oral administration of erythritol in healthy subjects.

OBJECTIVES: To investigate the effect of an oral administration of erythritol on serum glucose and insulin levels in healthy subjects and estimate available energy of erythritol in human. DESIGN: Ingestion of erythritol (0.3 g/kg body weight) or the same dose of glucose as a control. SETTING: Omiya Research Lab., Nikken Chemicals Co., Japan. SUBJECTS: 5 healthy male volunteers aged 45-58 years. MAIN OUTCOME MEASURES: Serum glucose, insulin and erythritol levels after erythritol ingestion. Urinary erythritol excretion. RESULTS: Erythritol did not increase serum levels of glucose or insulin, while the same dose of glucose increased rapidly glucose and insulin levels within 30 min. Erythritol did not induce any significant effects on serum levels of total cholesterol, triacylglycerol, free fatty acids, Na, K and Cl. Also, urinary Na, K and Cl were not affected by erythritol ingestion. Serum levels of erythritol reached the maximum concentration of 426.5 +/- 113.4 micrograms/ml at 30 min and declined to 13.5 +/- 3.2 micrograms/ml at 24 h. Total urinary excretion of erythritol was 85.8 +/- 4.6% for 24 h and 90.3 +/- 4.5% for 48 h, respectively. CONCLUSIONS: Erythritol did not affect serum levels of glucose, insulin or other serum constituents. More than 90% of ingested erythritol was readily absorbed and excreted in urine without degradation. This fact suggests that available energy of erythritol in human is less than 1.7 kJ/g (0.4 kcal/g). DESCRIPTORS: erythritol, glucose, insulin, low energy sweetener.

Administration, Oral↗

PubMed2000

Biosynthesis of terpenoids: YgbB protein converts 4-diphosphocytidyl-2C-methyl-D-erythritol 2-phosphate to 2C-methyl-D-erythritol 2,4-cyclodiphosphate.

In many microorganisms, the putative orthologs of the Escherichia coli ygbB gene are tightly linked or fused to putative orthologs of ygbP, which has been shown earlier to be involved in terpenoid biosynthesis. The ygbB gene of E. coli was expressed in a recombinant E. coli strain and was shown to direct the synthesis of a soluble, 17-kDa polypeptide. The recombinant protein was found to convert 4-diphosphocytidyl-2C-methyl-D-erythritol 2-phosphate into 2C-methyl-D-erythritol 2,4-cyclodiphosphate and CMP. The structure of the reaction product was established by NMR spectroscopy using (13)C-labeled substrate samples. The enzyme-catalyzed reaction requires Mn(2+) or Mg(2+) but no other cofactors. Radioactivity from [2-(14)C]2C-methyl-D-erythritol 2,4-cyclodiphosphate was diverted efficiently to carotenoids by isolated chromoplasts from Capsicum annuum and, thus, was established as an intermediate in the deoxyxylulose phosphate pathway of isoprenoid biosynthesis. YgbB protein also was found to convert 4-diphosphocytidyl-2C-methyl-D-erythritol into 2C-methyl-D-erythritol 3,4-cyclophosphate. This compound does not serve as substrate for the formation of carotenoids by isolated chromoplasts and is assumed to be an in vitro product without metabolic relevance.

Bacterial Proteins↗

PubMed2000

Deuterium-labelled isotopomers of 2-C-methyl-D-erythritol as tools for the elucidation of the 2-C-methyl-D-erythritol 4-phosphate pathway for isoprenoid biosynthesis.

Escherichia coli synthesizes its isoprenoids via the mevalonate-independent 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. The MC4100dxs::CAT strain, defective in deoxyxylulose-5-phosphate synthase, which is the first enzyme in this metabolic route, exclusively synthesizes its isoprenoids from exogenous 2-C-methyl-D-erythritol (ME) added to the culture medium. The fate of the hydrogen atoms in the MEP pathway was followed by the incorporation of [1,1-(2)H(2)]ME and [3,5,5,5-(2)H(4)]ME. The two C-1 hydrogen atoms of ME were found without any loss in the prenyl chain of menaquinone and/or ubiquinone on the carbon atoms derived from C-4 of isopentenyl diphosphate (IPP) and on the E-methyl group of dimethylallyl diphosphate (DMAPP), the C-5 hydrogen atoms on the methyl groups derived from IPP C-5 methyl group and the Z-methyl group of DMAPP. This showed that no changes in the oxidation state of these carbon atoms occurred in the reaction sequence between MEP and IPP. Furthermore, no deuterium scrambling was observed between the carbon atoms derived from C-4 and C-5 of IPP or DMAPP, suggesting a completely stereoselective IPP isomerase or no significant activity of this enzyme. The C-3 deuterium atom of [3,5,5,5-(2)H(4)]ME was preserved only in the DMAPP starter unit and was completely missing from all those derived from IPP. This finding, aided by the non-essential role of the IPP isomerase gene, suggests the presence in E. coli of two different routes towards IPP and DMAPP, starting from a common intermediate derived from MEP.

Base Sequence↗

PubMed1969

Erythritol metabolism in wild-type and mutant strains of Schizophyllum commune.

Erythritol uptake and metabolism were compared in wild-type mycelium and a dome morphological mutant of the wood-rotting mushroom Schizophyllum commune. Wild-type mycelium utilized glucose, certain hexitols, and pentitols including ribitol, as well as d-erythrose, erythritol, and glycerol as sole carbon sources for growth. The dome mutant utilized all of these compounds except d-erythrose and erythritol. Erythritol- or glycerol-grown wild-type mycelium incorporated erythritol into various cellular constituents, whereas glucose-grown cells lagged considerably before initiation of erythritol uptake. This acquisition was inhibited by cycloheximide. Dome mycelium showed behavior similar to wild-type in uptake of erythritol after growth on glucose or glycerol, except that erythritol was not further catabolized. Enzymes of carbohydrate metabolism were compared in cell extracts of glucose-cultured wild-type mycelium and dome. Enzymes of hexose monophosphate catabolism, nicotinamide adenine dinucleotide (NAD)-dependent sugar alcohol dehydrogenases, and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-coupled erythrose reductase were demonstrated in both. The occurrence of erythrose reductase was unaffected by the nature of the growth carbon source, showed optimal activity at pH 7, and generated NAD phosphate and erythritol as products of the reaction. Glycerol-, d-erythrose-, or erythritol-grown wild-type mycelium contained an NAD-dependent erythritol dehydrogenase absent in glucose cells. Erythritol dehydrogenase activity was optimal at pH 8.8 and produced erythrulose during NAD reduction. Glycerol-growth of dome mycelium induced the erythritol uptake system, but a functional erythritol dehydrogenase could not be demonstrated. Neither wild-type nor dome mycelium produced erythritol dehydrogenase during growth on ribitol. Erythritol metabolism in wild-type cells of S. commune, therefore, involves an NADPH-dependent reduction of d-erythrose to produce erythritol, followed by induction of an NAD-coupled erythritol dehydrogenase to form erythrulose. A deficiency in erythritol dehydrogenase rather than permeability barriers explains why dome cannot employ erythritol as sole carbon source for mycelial growth.

Alcohols↗

PubMed1996

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.

Acetylglucosaminidase↗

PubMed1996

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.

Administration, Oral↗

PubMed1998

The defect in the metabolism of erythritol of the Brucella abortus B19 vaccine strain is unrelated with its attenuated virulence in mice.

The role of the defect in erythritol catabolism in the attenuated virulence of Brucella abortus B19 vaccine strain in mice was investigated by means of five different strains: (i) the erythritol sensitive B19 vaccine strain; (ii) a natural erythritol tolerant (NET) mutant obtained spontaneously from B19; (iii) an erythritol resistant derivative from B19 (FJS19) obtained by gene replacement of the deleted ery region; (iv) the erythritol resistant B. abortus 2308 reference virulent strain; and (v) an erythritol sensitive mutant (227 strain) obtained from strain 2308 by transposon insertion in the chromosomal ery region. Besides virulence for mice, erythritol oxidation as well as other phenotypic markers were tested in all the strains. The 2308 and FJS19 strains grew in the presence of erythritol and oxidized the sugar, whereas the B19 and 227 strains did not. The NET strain grew in presence of erythritol but was unable to oxidize it. The B19 vaccine strain and its two erythritol resistant derivatives, NET and FJS19, showed similar residual virulence and splenic time courses in mice. Moreover, the virulent strain 2308 and its erythritol sensitive derivative (227 strain) exhibited similar levels of splenic infection. Altogether, these results demonstrate that the genetic region implicated in erythritol catabolism is not related to the low virulence exhibited by B19 in mice.

Animals↗

PubMed1998

Erythritol: an interpretive summary of biochemical, metabolic, toxicological and clinical data.

A critical and comprehensive review of the safety information on erythritol was undertaken. Numerous toxicity and metabolic studies have been conducted on erythritol in rats, mice and dogs. The toxicity studies consist of long-term feeding studies conducted to determine carcinogenic potential, intravenous and oral teratogenicity studies to determine the potential for effects on the foetus, oral studies in which erythritol was administered over one or two generations to determine the potential for reproductive effects, and studies in bacterial and mammalian systems to determine mutagenic potential. The majority of the safety studies conducted were feeding studies in which erythritol was mixed into the diet at concentrations as high as 20%. The metabolic studies in animals have shown that erythritol is almost completely absorbed, not metabolized systemically and is excreted unchanged in the urine. The safety studies have demonstrated that erythritol is well tolerated and elicits no toxicological effects. The clinical program for erythritol involved a series of single-dose and repeat-dose, short-duration studies which have been used to investigate the human correlates to the physiological responses seen in the preclinical studies. The clinical studies showed erythritol to be well tolerated and not to cause any toxicologically relevant effects, even following high-dose exposure. Erythritol administered orally to humans was rapidly absorbed from the gastrointestinal tract and quantitatively excreted in the urine without undergoing metabolic change. At high oral doses, urinary excretion accounted for approximately 90% of the administered dose with minimal amounts appearing in the faeces. A comparison of the human and animal data indicated a high degree of similarity in the metabolism of erythritol and this finding supports the use of the animal species used to evaluate the safety of erythritol for human consumption. It can be concluded, based on the available studies that erythritol did not produce evidence of toxicity.

Animals↗

PubMed1992

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.

Administration, Oral↗

PubMed1996

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.

Absorption↗

PubMed1996

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.

Administration, Oral↗

PubMed1996

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.

Administration, Oral↗

PubMed1971

Effects of hexoses and anions on the erythritol permeability of human red cells.

1. The effect of hexoses and of the anions chloride, thiocyanate, and salicylate on the permeability of human red cells to [(14)C]erythritol has been studied.2. It was confirmed that erythritol competes with glucose, mannose, and galactose for the hexose transfer system of the red cell membrane. Approximately 25% of the erythritol influx was insensitive to the presence of hexoses or phloretin. Identical maximum degrees of inhibition were obtained with 0.3 M glucose and with phloretin (0.5 x 10(-3)M). In the absence of competing inhibitors the erythritol permeability, P, was 1.2 x 10(-7) cm/sec at 38 degrees C. At maximum inhibition P was 0.3 x 10(-7) cm/sec.3. Erythritol is able to penetrate the membrane by two pathways, only one of which is sensitive to hexoses. Both hexose-sensitive and hexose-insensitive erythritol influx are well described by first-order diffusion kinetics. The affinity of erythritol for the hexose transfer system is very low, and the half saturation constants of hexoses can be determined from their ability to retard erythritol permeation. The following values were found for the half saturation of the transport system with hexoses at 38 degrees C: glucose 6 mM, mannose 11 mM, and galactose 40 mM.4. Thiocyanate and salicylate reduce the hexose-sensitive fraction of erythritol influx, but the hexose-insensitive erythritol permeability is not affected when chloride is replaced by the foreign anions. This applies to the whole temperature range between 0 and 38 degrees C, where the ionic permeabilities of red cells have been shown to be profoundly changed by thiocyanate and salicylate.

Alcohols↗

PubMed2000

The genes for erythritol catabolism are organized as an inducible operon in Brucella abortus.

Erythritol utilization is a characteristic of pathogenic Brucella abortus strains. The attenuated vaccine strain B19 is the only Brucella strain that is inhibited by erythritol, so a role for erythritol metabolism in virulence is suspected. A chromosomal fragment from the pathogenic strain B. abortus 2308 containing genes for the utilization of erythritol was cloned taking advantage of an erythritol-sensitive Tn5 insertion mutant. The nucleotide sequence of the complete 7714 bp fragment was determined. Four ORFs were identified in the sequence. The four genes were closely spaced, suggesting that they were organized as a single operon (the ery operon). The first gene (eryA) encoded a 519 aa putative erythritol kinase. The second gene (eryB) encoded an erythritol phosphate dehydrogenase. The function of the third gene (eryC) product was tentatively assigned as D-erythrulose-1-phosphate dehydrogenase and the fourth gene (eryD) encoded a regulator of ery operon expression. The operon promoter was located 5' to eryA, and contained an IHF (integration host factor) binding site. Transcription from this promoter was repressed by EryD, and stimulated by erythritol. Functional IHF was required for expression of the operon in Escherichia coli, suggesting a role for IHF in its regulation in B. abortus. The results obtained will be helpful in clarifying the role of erythritol metabolism in the virulence of Brucella spp.

Animals↗

PubMed1996

Two-generation reproduction study of erythritol in rats.

Erythritol was fed at dietary concentrations of 0, 2.5, 5, or 10% to Crl:(WI) WU BR rats of both sexes through two successive generations (F0 and F1). Twenty-four rats of each sex were mated in each group. For each generation one litter was reared until the pups were 21 days old. In the 10% erythritol group, food consumption among F0-males and -females was initially significantly reduced until the animals adapted to the erythritol diet during the first week of the study. Thereafter, food intake was higher than in controls. A consistently increased food intake also was seen in F1-males and-females of this dose group. This effect was considered to result from the caloric dilution of the food by erythritol, which has a low physiological energy value. The lower body weight and weight gain of the F0-animals of the 10% erythritol group were attributed to the initially reduced food consumption and occurrence of transient diarrhea until the animals had adapted to the erythritol intake. In the F1-animals of the 10% erythritol group, which were adapted to the treatment from weaning, the rate of body weight gain did not differ from controls. The F1-males and -females of this dose group did, however, have a reduced body weight from weaning, which was attributed to a reduced energy intake among the corresponding F0-dams during Weeks 2 and 3 of lactation. This effect was not seen in the F2-generation. It is concluded that under the conditions of this experiment, the intake of erythritol had no adverse effect on fertility and reproductive performance of parent rats or on the development of their progeny. Gross necropsy and microscopic examination of the parenteral reproductive organs also did not reveal treatment-related changes.

Animals↗

PubMed1996

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.

Administration, Oral↗

PubMed1993

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.

Adult↗

PubMed1975

Inhibition of growth by erythritol catabolism in Brucella abortus.

The growth of Brucella abortus (US-19) in a complex tryptose-yeast extract medium containing D-glucose is inhibited by 10 mM erythritol. The enzymes of the erythritol pathway, except for D-erythrulose 1-phosphate dehydrogenase (D-glycero-2-tetrulose 1-phosphate:nicotinamide adenine dinucleotide (NAD+) 4-oxidoreductase) were detected in the soluble and membrane fractions of cell extracts. Glucose catabolism by cell extracts was inhibited by erythritol, whereas, phosphorylated intermediates of the hexose monophosphate pathway were converted to pyruvic acid with oxygen consumption. Erythritol kinase (EC 2.7.1.27; adenosine 5'-triphosphate (ATP): erythritol 1-phosphotransferase) was found to be eightfold higher in activity than the hexokinase in cell extracts. In vivo, ATP is apparently consumed with the accumulation of D-erythrulose 1-phosphate (D-glycero-2-tetrulose 1-phosphate) and no substrate level phosphorylation. ATP levels dropped 10-fold in 30 min after addition of erythritol to log phase cells in tryptose-yeast extract medium with D-glucose as the carbon source. These data suggest bacteriostasis in the presence of erythritol results from the ATP drain caused by erythritol kinase.

Adenosine Triphosphate↗