A Pharmacokinetic Study of Different Quercetin Formulations in Healthy Participants: A Diet-Controlled, Crossover, Single- and Multiple-Dose Pilot Study.

This study aimed to evaluate the blood concentrations of quercetin in healthy participants after the administration of different formulations in single- and multiple-dose phases. Ten healthy adults (males, 5; females, 5; age 37 ± 11 years) participated in a diet-controlled, crossover pilot study. Participants received three different doses (250 mg, 500 mg, or 1000 mg) of quercetin aglycone orally. In the single-dose study, blood concentrations (AUC0-24 and Cmax) of standard quercetin were compared with those of LipoMicel®-a food-grade delivery form of quercetin. In the multiple-dose study, blood concentrations of formulated quercetin were observed over 72 h, after repeated doses of LipoMicel (LM) treatments. The AUC0-24 ranged from 77.3 to 1128.9 ng·h/ml: LM significantly increased blood concentrations of quercetin by 7-fold (LM 500) compared to standard quercetin, when tested at the same dose, over 24 h (p < 0.001); LM administered at a higher dose (LM 1000) achieved 15-fold higher absorption (p < 0.001); LM tested at half a dose of standard quercetin increased concentration by approx. 3-fold (LM 250). Quercetin blood concentrations were attained over 72 h. The major metabolites measured in the blood were methylated, sulfate, and glutathione (GSH) conjugates of quercetin. Significant differences in concentrations between quercetin conjugates (sulfate vs. methyl vs. GSH) were observed (p < 0.001). Data obtained from this study suggest that supplementation with LipoMicel® is a promising strategy to increase the absorption of quercetin and its health-promoting effects in humans. However, due to the low sample size in this pilot study, further research is still warranted to confirm the observations in larger populations. This trial is registered with NCT05611827.

Prenatal iodine supplementation and early childhood neurodevelopment: the PoppiE trial - study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Observational studies suggest both low and high iodine intakes in pregnancy are associated with poorer neurodevelopmental outcomes in children. This raises concern that current universal iodine supplement recommendations for pregnant women in populations considered to be iodine sufficient may negatively impact child neurodevelopment. We aim to determine the effect of reducing iodine intake from supplements for women who have adequate iodine intake from food on the cognitive development of children at 24 months of age. METHODS AND ANALYSIS: A multicentre, randomised, controlled, clinician, researcher and participant blinded trial with two parallel groups. Using a hybrid decentralised clinical trial model, 754 women (377 per group) less than 13 weeks' gestation with an iodine intake of ≥165 µg/day from food will be randomised to receive either a low iodine (20 µg/day) multivitamin and mineral supplement or an identical supplement containing 200) µg/day (amount commonly used in prenatal supplements in Australia), from enrolment until delivery. The primary outcome is the developmental quotient of infants at 24 months of age assessed with the Cognitive Scale of the Bayley Scales of Infant Development, fourth edition. Secondary outcomes include infant language and motor development; behavioural and emotional development; maternal and infant clinical outcomes and health service utilisation of children. Cognitive scores will be compared between groups using linear regression, with adjustment for location of enrolment and the treatment effect described as a mean difference with 95% CI. ETHICS AND DISSEMINATION: Ethical approval has been granted from the Women's and Children's Health Network Research Ethics Committee (HREC/17/WCHN/187). The results of this trial will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04586348.

A randomized, double-blind, placebo-controlled, cross-over trial to evaluate the effect of EstroSense® on 2-hydroxyestrone:16α-hydroxyestrone ratio in premenopausal women.

OBJECTIVES: Some estrogen metabolites are associated with increased breast cancer risk, while others are protective. Research efforts have focused on modifiable factors, including bioactive compounds found in food or supplements, promoting estrogen profiles with anti-cancer properties. EstroSense® is a nutraceutical product with bioactive compounds, including Indole-3-carbinol and green-tea catechins, which may favourably affect estrogen profiles. This study was conducted to determine if EstroSense use, compared to placebo, promotes a higher urinary 2-hydroxyestrone:16α-hydroxyestrone ratio (2-OHE1:16α-OHE1), a biomarker associated with a lowered risk of breast cancer. METHODS: A total of 148 premenopausal women were recruited from British Columbia, Canada to participate in a randomized, double-blind, cross-over, multicentre, placebo-controlled study in which women were randomized to a treatment sequence that consisted of either EstroSense®, followed by placebo or vice-versa. The women were instructed to consume three capsules per day of EstroSense® or the placebo for three menstrual cycles (∼12 weeks). The primary outcome was the measurement of 2-OHE1:16α-OHE1 in casual samples at baseline and after each treatment phase. RESULTS: After 12 weeks of intervention, the mean (95% CI) urinary 2-OHE1:16α-OHE1 was 4.55 (2.69, 6.42) (p<0.001) higher following EstroSense than placebo adjusted for baseline values. CONCLUSIONS: EstroSense use led to markedly higher urinary 2-OHE1:16α-OHE1 than the placebo, a biomarker associated with a lower risk of breast cancer. REGISTRATION: http://clinicaltrials.gov (NCT02385916).

Micronutrient status of individuals with overweight and obesity following 3 months' supplementation with PolyGlycopleX (PGX®) or psyllium: a randomized controlled trial.

BACKGROUND: Safe and effective weight control strategies are needed to curtail the current obesity epidemic worldwide. Increasing dietary fibre has shown positive results with weight loss as well as in the reduction of metabolic syndrome risk factors. However, fibre can act as an inhibitor to the bioavailability of micronutrients in the gastrointestinal tract. While there is a substantial amount of scientific research into psyllium fibre, PolyGlycopleX (PGX®) is a novel fibre and as yet the effects of PGX® on micronutrient status is not well researched. AIM: To determine whether 3-months' supplementation with 15 g of psyllium or PGX® fibre daily affects micronutrient status of overweight and obese adults. METHODS: Overweight and obese individuals with a BMI between 25-40 kg/m2 and aged between 18 and 65 years, but otherwise healthy, were instructed to consume a 5 g sachet of psyllium, PGX® fibre or a rice flour placebo three times a day for 52 weeks as part of a larger long-term study. Blood sample data for the first 3 months were analysed for associations between serum micronutrient levels and psyllium fibre and/or PGX® supplements. RESULTS: No significant differences between fibre supplement groups and micronutrient status were found after 3 months at p > 0.05. Dietary intake of vitamin C was significantly lower for PGX® at 3 months compared to baseline and compared to control (p < 0.05). Folate was significantly lower in the control group after 3 months (p < 0.05). In the psyllium group, folate, sodium, zinc and magnesium intake decreased after 3 months (p < 0.05). A limitation of dietary intake data (tertiary measure) is the potential for inaccurate self-reporting, although reduced nutrient intake could be due to the satiating effect of dietary fibre. CONCLUSIONS: There were no significant between group differences in serum micronutrient concentrations after a 3-month psyllium fibre or PGX® supplementation intervention of 15 g per day. Fibre supplementation is unlikely to compromise the nutritional status of overweight and obese individuals in the short term. Further research is recommended to monitor micronutrient status over a longer period or with a higher fibre dosage.

Study protocol for a randomised controlled trial evaluating the effect of folic acid supplementation beyond the first trimester on maternal plasma unmetabolised folic acid in late gestation.

INTRODUCTION: Taking folic acid containing supplements prior to and during early pregnancy reduces the risk of neural tube defects. Neural tube defects occur prior to 28 days postconception, after which, there is no proven benefit of continuing to take folic acid. However, many women continue to take folic acid containing supplements throughout the pregnancy. At higher intakes, folic acid is not converted to its active form and accumulates in circulation as unmetabolised folic acid (UMFA). Recently, concerns have been raised about possible links between late gestation folic acid supplementation and childhood allergy, metabolic disease and autism spectrum disorders. We aim to determine if removing folic acid from prenatal micronutrient supplements after 12 weeks gestation reduces circulating levels of maternal UMFA at 36 weeks gestation. METHODS AND ANALYSIS: This is a parallel-design, double-blinded randomised controlled trial. Women ≥12 and <16 weeks' gestation with a singleton pregnancy and able to give informed consent are eligible to participate. Women (n=100; 50 per group) will be randomised to receive either a micronutrient supplement containing 0.8 mg of folic acid or a micronutrient supplement without folic acid daily from enrolment until delivery. The primary outcome is plasma UMFA concentration at 36 weeks gestation. Secondary outcomes include red blood cell folate and total plasma folate concentration. We will assess whether there is a difference in mean UMFA levels at 36 weeks gestation between groups using linear regression with adjustment for baseline UMFA levels and gestational age at trial entry. The treatment effect will be described as a mean difference with 95% CI. ETHICS AND DISSEMINATION: Ethical approval has been granted from the Women's and Children's Health Network Research Ethics Committee (HREC/19/WCHN/018). The results of this trial will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12619001511123.

Effect of PolyGlycopleX (PGX) Consumption on Blood Lipid Profiles in Healthy, Low CVD Risk Overweight Adults.

Raised blood lipid levels are associated with a risk of a cardiovascular disease (CVD). Moderate reductions in several CVD factors such as total, low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (non-HDL) cholesterol concentrations may be more effective in reducing overall risk than a major reduction in just one. A blind, randomised controlled trial was conducted with 120 healthy overweight (BMI 25⁻30) adults aged 25⁻70 years who were non-smokers, not diabetic and of low risk of cardiovascular disease, as assessed by the Framingham risk equation. Participants consumed 4.5 g PolyGlycopleX (PGX) as softgel capsules (PGXS) or 5 g PGX granules (PGXG) or 5 g rice flour (RF) with meals three times a day for 12 weeks. Total, LDL and non-HDL cholesterol were all significantly reduced (-6%, -5% and -3.5%, respectively) post the PGX granule treatment; however, PGX in softgel capsule form did not affect blood lipid profiles. Daily consumption of PGX granules in overweight low CVD risk adults produced lipid changes indicating a CVD preventative benefit.

Effect of Fibre Supplementation on Body Weight and Composition, Frequency of Eating and Dietary Choice in Overweight Individuals.

Fibre supplementation can potentially reduce energy intake and contribute to weight loss. The mechanism may be reduced frequency of eating, resulting in reduced food consumption. The objective of this research was to determine the effectiveness of fibre supplementation with PolyGlycopleX® (PGX®), on body weight and composition, frequency of eating and dietary intake in 118 overweight adults. In a three-arm, parallel, blind, randomised controlled trial participants were randomised to one of three groups; 4.5 g PGX as softgels (PGXS), 5 g PGX granules (PGXG) or 5 g rice flour (RF) control. Prior to supplementation and at 12 weeks, participants captured before and after images of all food and beverages consumed within 4 days using a mobile food record app (mFR). The mFR images were analysed for food group serving sizes and number of eating occasions. In the PGXG group, per-protocol analysis [corrected] analysis showed there was a significant reduction in waist circumference (2.5 cm; p = 0.003). Subgroup analysis showed that PGXG supplementation at the recommended dose resulted in a reduction in body weight (-1.4 ± 0.10 kg, p < 0.01), body mass index (BMI) reduction (-0.5 ± 0.10, p < 0.01), reduced number of eating occasions (-1.4 ± 1.2, p < 0.01) and a reduced intake of grain food (-1.52 ± 1.84 serves, p = 0.019). PGXG at the recommended dose resulted in a reduction in weight and BMI which was significantly greater than that for RF (p = 0.001). These results demonstrate the potential benefits of PGX fibre in controlling frequency of eating and in weight loss.

Effect on Insulin, Glucose and Lipids in Overweight/Obese Australian Adults of 12 Months Consumption of Two Different Fibre Supplements in a Randomised Trial.

Higher fibre intakes are associated with risk reduction for chronic diseases. This study investigated the effects of supplementation with PolyGlycopleX® (PGX), a complexed polysaccharide, on insulin, glucose and lipids in overweight and obese individuals. In this double-blind 12 months study, participants were randomised into three groups: control (rice flour); PGX or psyllium (PSY). Participants followed their usual lifestyle and diet but consumed 5 g of their supplement before meals. Insulin was significantly lower in the PGX and PSY groups compared to control at 3 and 6 months and in the PSY group compared to control at 12 months. Serum glucose was significantly lower in the PGX group at 3 months compared to control. Total cholesterol was significantly lower in the PGX and PSY groups compared to control at 3 and 6 months. High density lipoprotein (HDL) cholesterol was significantly increased in the PGX group compared to control at 12 months. low density lipoprotein (LDL) cholesterol was significantly lower in the PGX group at 3 and 6 months compared to control and in the PSY group at 3 months compared to control. A simple strategy of fibre supplementation may offer an effective solution to glucose, insulin and lipid management without the need for other nutrient modification.

Consumption of the Soluble Dietary Fibre Complex PolyGlycopleX(®) Reduces Glycaemia and Increases Satiety of a Standard Meal Postprandially.

The effect of consumption of PolyGlycopleX(®) (PGX(®)) was compared to wheat dextrin (WD) in combination with a standard meal, on postprandial satiety and glycaemia in a double-blind, randomised crossover trial, of 14 healthy subjects trained as a satiety panel. At each of six two-hour satiety sessions, subjects consumed one of three different test meals on two separate occasions. The test meals were: a standard meal plus 5 g PGX; a standard meal plus 4.5 g of PGX as softgels; and a standard meal plus 5 g of WD. Subjects recorded fullness using a labelled magnitude scale at 0, 15, 30, 45, 60, 90, and 120 min and the total area under the curve (AUC), mean fullness vs. time was calculated. The meals with PGX (in granular and softgel form) gave higher satiety (AUC) (477 ± 121 and 454 ± 242 cm·min), than the meal with WD (215 ± 261 cm·min) (p < 0.001). Subjects had blood glucose levels measured after the meals with PGX (granules) and WD. Glucose response (AUC) was significantly lower (p < 0.001) after the PGX meal than for the WD meal.  The high viscosity reported for PGX is a likely mechanism behind the significant satiety and blood glucose modulating effects observed in this study.

A clinical trial to investigate the effect of Cynatine HNS on hair and nail parameters.

OBJECTIVE: A new, novel product, Cynatine HNS, was evaluated for its effects as a supplement for improving various aspects of hair and nails in a randomized, double-blind, placebo-controlled clinical trial. METHODS: A total of 50 females were included and randomized into two groups. The active group (n = 25) received 2 capsules containing Cynatine HNS, comprised of Cynatine brand keratin (500 mg) plus vitamins and minerals, per day, and the placebo group (n = 25) received 2 identical capsules of maltodextrin per day for 90 days. End points for hair loss, hair growth, hair strength, amino acid composition, and hair luster were measured. End points were also measured for nail strength and the appearance of nails. RESULTS: The results show that subjects taking Cynatine HNS showed statistically significant improvements in their hair and nails when compared to placebo. CONCLUSION: Cynatine HNS is an effective supplement for improving hair and nails in 90 days or less. EudraCT number is 2014-002645-22.

Decreasing cardiovascular risk factors in obese individuals using a combination of PGX® meal replacements and PGX® granules in a 12-week clinical weight modification program.

In this open, clinically based, weight modification program, we determined in six sedentary obese adults (five women; one male; age range 30-62 years) that the combination of a modified calorie diet plus PGX® meal replacement and PGX® supplementation resulted in a significant reduction in several cardiovascular risk factors over a 12-week time period. This included a significant improvement in lipids (-0.98 mmol/l LDL-C), reduction in average weight (-9.2 kg), mean reduction in fat (-4.1%) and an increase in fat-free mass (2.8%).

Meal replacements and fibre supplement as a strategy for weight loss. Proprietary PGX® meal replacement and PGX® fibre supplement in addition to a calorie-restricted diet to achieve weight loss in a clinical setting.

Meal replacements and viscous soluble fibre represent safe and sustainable aids for weight loss. Our purpose was to determine if PGX® meal replacements and PGX(®) fibre complex in combination with a calorie-restricted diet would aid in weight loss in a clinical setting. Fifty-two overweight and obese participants (49 women, 3 men; average age 47.1 years) with a mean body mass index (BMI) of 33.8 ± 6.4 kg/m(2) consumed 57 g of proprietary PGX® meal replacement product at breakfast and another 57 g at lunch for 12 weeks. In addition to the meal replacements, they were also asked to consume 5 g/day of PGX® fibre in the form of granules, powder or capsules together with 250 mlwater. A registered dietician recommended low-fat, low-glycaemic-index foods for snacks and the dinner menus such that each volunteer was consuming a total of 1200 kcal/day. All participants (n = 52) lost a significant amount of weight from baseline (-4.69 ± 3.73 kg), which was further reflected in the reductions in their waist (-7.11 ± 6.35 cm) and hip circumference (-5.59 ± 3.58 cm) over the 12-week study (p < 0.0001). BMI scores (n = 51) were reduced by 1.6 ± 1.4 kg/m(2). The use of PGX® meal replacements and PGX(®) fibre along with a controlled dietary caloric intake is of benefit for short-term weight loss.

Effects of added PGX®, a novel functional fibre, on the glycaemic index of starchy foods.

The development of lower-glycaemic index (GI) foods requires simple, palatable and healthy strategies. The objective of the present study was to determine the most effective dose of a novel viscous fibre supplement (PGX®) to be added to starchy foods to reduce their GI. Healthy subjects (n 10) consumed glucose sugar (50 g in water × 3) and six starchy foods with a range of GI values (52-72) along with 0 (inert fibre), 2.5 or 5 g granular PGX® dissolved in 250 ml water. GI testing according to ISO Standard 26,642-2010 was used to determine the reduction in GI. PGX® significantly reduced the GI of all six foods (P < 0.001), with an average reduction of 19 % for the 2.5 g dose and 30 % for the 5 g dose, equivalent to a reducing the GI by 7 and 15 units, respectively. Consuming small quantities of the novel functional fibre PGX®, mixed with water at the start of a meal, is an effective strategy to reduce the GI of common foods.

The soluble fiber complex PolyGlycopleX lowers serum triglycerides and reduces hepatic steatosis in high-sucrose-fed rats.

Viscous soluble fibers have been shown to reduce risk factors associated with type 2 diabetes and cardiovascular disease. The novel functional fiber, PolyGlycopleX (PGX) (InovoBiologic Inc, Calgary, Alberta, Canada) displays greater viscosity than other currently identified soluble fibers. The objective of this study was to determine if PGX lowers serum and hepatic triglycerides (TGs) in a high-sucrose-fed rat model. In this rodent model, feeding a high-sucrose diet consistently increases serum TGs. We hypothesized that consumption of PGX would attenuate hypertriglyceridemia and reduce hepatic steatosis compared with cellulose in rats fed a high-sucrose background diet. Male Sprague-Dawley rats were fed diets containing 65% sucrose and supplemented with either 5% cellulose (control) or 5% PGX (wt/wt) for 43 weeks. At study termination, serum insulin and TGs, hepatic steatosis, and hepatocellular injury were assessed. Body weight increased over time in both groups, but weight gain was attenuated in rats fed PGX vs cellulose in weeks 2 through 22 (P < .05). Serum TGs did not differ from baseline for the first half of the study but consistently increased in the cellulose group thereafter. PolyGlycopleX significantly reduced serum TG to near-baseline levels. At study termination, rats fed PGX had significantly lower hepatic steatosis scores (measured by Sudan black staining) compared with rats fed cellulose. Hepatocellular injury scores did not differ between the groups. In conclusion, PGX reduced serum TG and lipid accumulation in the liver of sucrose-fed rats. Further examination of its potential as a fiber supplement aimed at lessening the burden of hepatic steatosis is warranted.

Effects of the soluble fiber complex PolyGlycopleX® (PGX®) on glycemic control, insulin secretion, and GLP-1 levels in Zucker diabetic rats.

AIMS: The effects of the novel water soluble, viscous fiber complex PolyGlycopleX® [(α-D-glucurono-α-D-manno-ß-D-manno-ß-D-gluco), (α-L-gulurono-ß-D mannurono), ß-D-gluco-ß-D-mannan (PGX®)] on body weight, food consumption, glucose, insulin, and glucagon-like peptide (GLP-1) levels were determined in Zucker diabetic rats (ZDFs). Such fibers are thought to improve glycemic control through increased GLP-1 induced insulin secretion. MAIN METHODS: ZDFs were treated 12 weeks with normal rodent chow supplemented with cellulose (control, inert fiber), inulin or PGX® at 5% wt/wt and effects on body weight, glycemic control, and GLP-1 determined. KEY FINDINGS: In the fed state, PGX® reduced blood glucose compared to the other groups from week 5 until study termination while insulin was significantly elevated when measured at week 9, suggesting an insulin secretagogue effect. Fasting blood glucose was similar among groups until 7-8 weeks when levels began to climb with a modest reduction caused by PGX®. An oral glucose tolerance test in fasted animals (week 11) showed no change in insulin sensitivity scores among diets, suggesting an insulinotropic effect for PGX® rather than increased insulin sensitivity. PGX® increased plasma levels of GLP-1, while HbA(1c) was markedly reduced by PGX®. Body weights were not changed despite a significant reduction in food consumption induced by PGX® up to week 8 when the PGX®-treated group showed an increase in body weight despite a continued reduction in food consumption. SIGNIFICANCE: PGX® improved glycemic control and reduced protein glycation, most likely due to the insulin secretagogue effects of increased GLP-1.

Genotoxicity studies of PolyGlycopleX (PGX): a novel dietary fiber.

PolyGlycopleX (PGX), a novel dietary fiber, produces no mutagenic effects in bacterial tester strains Salmonella typhimurium TA 98, TA 100, TA 1535, and TA 1537 and Escherichia coli WP2 uvrA at concentrations of 0.316, 1.00, 3.16, 10.0, 31.6, and 100 microg/plate. No biologically relevant increases in revertant colonies of any of the 5 strains are observed at any concentration; however, a reduction at 100 microg/plate in TA 1537 is noted. PGX, analyzed for polychromatic erythrocyte micronuclei induction in mice following a single 1x, 0.5x, and 0.2x maximum tolerable dose intraperitoneal treatment, produces no biologically relevant increase in any dose group. Males at 1x maximum tolerable dose show a reduction of micronuclei-containing cells. High-dose animals show signs of systemic toxicity, including a reduction of spontaneous activity, rough fur, palpebral closure, prone position, and constricted abdomen. These genotoxicity studies show PGX to be nonmutagenic in both the Ames bacterial reverse mutation assay and the mammalian erythrocyte micronucleus test.

Supplementation of the diet with the functional fiber PolyGlycoplex is well tolerated by healthy subjects in a clinical trial.

BACKGROUND: The relationship of dietary fiber to overall health is of great importance, as beneficial effects have been demonstrated with the use of fiber from diverse sources, some traditional, other novel. PolyGlycopleX (PGX) is a unique proprietary product composed of three water-soluble polysaccharides, that when processed using novel technology give rise to a final product - a soluble, highly viscous functional fiber. METHODS: Because of its potential use in food and dietary supplements, a randomized, double-blind, placebo controlled clinical study was conducted to evaluate the tolerance to PGX ingestion for 21 days, to a maximum dose level of 10 g per day, in healthy male and female volunteers. The main objective of the study was to evaluate the overall gastrointestinal (GI) tolerance, while secondary objectives were to evaluate possible changes in hematological, biochemical, urinary and fecal parameters. RESULTS: Results show that PGX is well tolerated as part of a regular diet with only mild to moderate adverse effects, similar to those seen with a moderate intake of dietary fiber in general, and fruits and vegetables. Because PGX is a highly viscous, functional fiber, it also demonstrates several physiological responses including, but not limited to maintaining healthy total and LDL cholesterol and uric acid levels.

The safety of PolyGlycopleX (PGX) as shown in a 90-day rodent feeding study.

BACKGROUND: This study was designed to evaluate the safety of PolyGlycopleX (PGX), a novel viscous dietary polysaccharide (fiber), when administered to Sprague Dawley(R) rats in the diet for 90 days. METHODS: Groups of ten male and ten female rats each consumed PGX mixed in the diet at levels of 0, 1.25, 2.5 or 5.0% for 90 days, then evaluated for toxicological effects on parameters that included neuromotor activity, body weight, clinical chemistry, urinalysis, hematology, and histopathology. RESULTS: Mean body weight, mean feed consumption and food efficiency in the treated groups were generally comparable to controls for both male and female rats. No changes were noted in neuromotor behavior, and histopathological analysis revealed no significant changes between treated and control animals. There were no differences in mean organ weight, organ-to-body weight or organ-to-brain weight values between controls and treated animals. Decreased red blood cell count occurred in the high dose males and increases in aspartate and alanine aminotransferase enzyme levels and triglycerides, while significant decreases in serum sodium, potassium and chloride concentrations were observed in the females fed 5.0% PGX. However, the decreased mineral concentrations may be the result of significantly increased urinary volume in both males and females at the high dose, with a concomitant decrease in urinary specific gravity (males and females) and protein concentration (females). These results were within historical control values, did not correlate with any histopathological changes, and were not considered adverse. CONCLUSION: The results indicate a no observed adverse effect level (NOAEL) for PGX at 5.0% of the diet, corresponding to an average daily intake of 3219 and 3799 mg/kg bw/day in male and female rats, respectively.