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Glycemic Response and Type II Diabetes

A Polyphenol-Rich Cranberry Extract Reverses Insulin Resistance and Hepatic Steatosis Independently of Body Weight Loss.

Posted: April 4, 2018
Authors: Anhe FF; Nachbar RT; Varin TV; Vilela V; Dudonne S; Pilon G; Fournier M; Lecours MA; Desjardins Y; Roy D; Levy E; Marette A.
Journal: Molecular Metabolism. 6(12):1563-1573

Abstract: OBJECTIVE: Previous studies have reported that polyphenol-rich extracts from various sources can prevent obesity and associated gastro-hepatic and metabolic disorders in diet-induced obese (DIO) mice. However, whether such extracts can reverse obesity-linked metabolic alterations remains unknown. In the present study, we aimed to investigate the potential of a polyphenol-rich extract from cranberry (CE) to reverse obesity and associated metabolic disorders in DIO-mice. METHODS: Mice were pre-fed either a Chow or a High Fat-High Sucrose (HFHS) diet for 13 weeks to induce obesity and then treated either with CE (200mg/kg, Chow+CE, HFHS+CE) or vehicle (Chow, HFHS) for 8 additional weeks. RESULTS: CE did not reverse weight gain or fat mass accretion in Chow- or HFHS-fed mice. However, HFHS+CE fully reversed hepatic steatosis and this was linked to upregulation of genes involved in lipid catabolism (e.g., PPARalpha) and downregulation of several pro-inflammatory genes (eg, COX2, TNFalpha) in the liver. These findings were associated with improved glucose tolerance and normalization of insulin sensitivity in HFHS+CE mice. The gut microbiota of HFHS+CE mice was characterized by lower Firmicutes to Bacteroidetes ratio and a drastic expansion of Akkermansia muciniphila and, to a lesser extent, of Barnesiella spp, as compared to HFHS controls. CONCLUSIONS: Taken together, our findings demonstrate that CE, without impacting body weight or adiposity, can fully reverse HFHS diet-induced insulin resistance and hepatic steatosis while triggering A. muciniphila blooming in the gut microbiota, thus underscoring the gut-liver axis as a primary target of cranberry polyphenols.

Evaluation of Phenolic Phytochemical Enriched Commercial Plant Extracts on the In Vitro Inhibition of alpha-Glucosidase.

Posted: April 4, 2018
Authors: Brown A; Anderson D; Racicot K; Pilkenton SJ; Apostolidis E.
Journal: Frontiers in Nutrition. 4:56

Abstract: Green tea (GT), cranberry (CR), and tart cherry extracts were evaluated for their ability to inhibit yeast alpha-glucosidase, relevant to glucose uptake. The total phenolic content (TPC), antioxidant activity, and in vitro inhibitory activity of yeast alpha-glucosidase were examined for the extracts in the present study. GT had higher TPC and antioxidant activity, but CR demonstrated a greater alpha-glucosidase inhibitory activity, on phenolic basis. CR was fractionated using LH-20 column chromatography into two fractions: 30% methanol (CME) and 70% acetone (CAE). TPC, antioxidant activity, and yeast alpha-glucosidase inhibitory activity were determined for the fractions. CAE had a greater TPC and antioxidant activity than CME, but the two fractions had a synergistic effect when inhibiting yeast alpha-glucosidase. Our findings suggest that CR has the greatest potential to possibly manage post-prandial blood glucose levels via the inhibition of alpha-glucosidase, and that the effect is through synergistic activity of the extract's phenolic compounds.

Cranberries Improve Postprandial Glucose Excursions in type 2 Diabetes

Posted: August 15, 2017
Authors: Schell J; Betts NM; Foster M; Scofield RH; Basu A.
Journal: Food & Function, DOI:10.1039/C7FO00900C

Abstract: Recent research supports a favorable role of cranberries on cardiometabolic health. Postprandial metabolism, especially hyperglycemia, has been shown to be an independent cardiovascular risk and few clinical studies have reported the role of berries in improving postprandial dysmetabolism. We investigated the postprandial effects of dried cranberries following a high-fat breakfast challenge in obese participants with type 2 diabetes (T2DM), in a randomized crossover trial. Blood draw and vascular measurements were conducted at fasting, 1, 2 and 4 hours (h), following the consumption of a fast-food style high-fat breakfast (70 g fat, 974 kcal) with or without cranberries (40 g). Analyses of our data (n = 25; BMI (kg m-2) (mean +/- s.d.) = 39.5 +/- 6.5; age (years) = 56 +/- 6) revealed that postprandial increases in glucose were significantly lower in the cranberry vs. control at 2 & 4 h (p < 0.05). No significant differences were noted in insulin, insulin resistance evaluated by homeostasis model assessment, lipid profiles and blood pressure between the cranberry and control groups. Among the biomarkers of inflammation and oxidation, postprandial serum interleukin-18 and malondialdehyde were significantly lower at 4 h, and serum total nitrite was higher at 2 h in the cranberry vs. control group (all p < 0.05). No effects were noted on C-reactive protein or interlukin-6. Overall, dietary cranberries had notable effects in improving high-fat breakfast induced postprandial glucose and selected biomarkers of inflammation and oxidation in participants with T2DM. These findings provide evidence that adding whole cranberries to a high-fat meal may improve postprandial blood glucose management and warrant further investigation.

Strawberry and Cranberry Polyphenols Improve Insulin Sensitivity in Insulin-Resistant, Non-Diabetic Adults: a Parallel, Double-Blind, Controlled and Randomised Clinical Trial.

Posted: August 15, 2017
Authors: Paquette M, Medina Larqué AS, Weisnagel SJ, Desjardins Y, Marois J, Pilon G, Dudonné S, Marette A, Jacques H.
Journal: Br J Nutr.117(4):519-531

Abstract: Plant-derived foods rich in polyphenols are associated with several cardiometabolic health benefits, such as reduced postprandial hyperglycaemia. However, their impact on whole-body insulin sensitivity using the hyperinsulinaemic-euglycaemic clamp technique remains under-studied. We aimed to determine the effects of strawberry and cranberry polyphenols (SCP) on insulin sensitivity, glucose tolerance, insulin secretion, lipid profile, inflammation and oxidative stress markers in free-living insulin-resistant overweight or obese human subjects (n 41) in a parallel, double-blind, controlled and randomised clinical trial. The experimental group consumed an SCP beverage (333 mg SCP) daily for 6 weeks, whereas the Control group received a flavour-matched Control beverage that contained 0 mg SCP. At the beginning and at the end of the experimental period, insulin sensitivity was assessed by a hyperinsulinaemic-euglycaemic clamp, and glucose tolerance and insulin secretion by a 2-h oral glucose tolerance test (OGTT). Insulin sensitivity increased in the SCP group as compared with the Control group (+0·9 (sem 0·5)×10-3 v. -0·5 (sem 0·5)×10-3 mg/kg per min per pmol, respectively, P=0·03). Compared with the Control group, the SCP group had a lower first-phase insulin secretion response as measured by C-peptide levels during the first 30 min of the OGTT (P=0·002). No differences were detected between the two groups for lipids and markers of inflammation and oxidative stress. A 6-week dietary intervention with 333 mg of polyphenols from strawberries and cranberries improved insulin sensitivity in overweight and obese non-diabetic, insulin-resistant human subjects but was not effective in improving other cardiometabolic risk factors.

Cranberry Supplement and Metabolic Risk Factors in Obese and Overweight Females

Posted: March 1, 2017
Authors: Eftekhari MH, Allaei M, Khosropanah S, Rajaeifard A, Sohrabi Z
Journal: Jentashapir Journal of Health Research. 2016 Apr;7(3):e37255

Abstract: Background: Due to the higher susceptibility of metabolic syndrome (MS)-afflicted patients to different metabolic abnormalities, treatment programs are vital parts of MS management. One of the possible adjunctive therapies is taking cranberry supplements as important sources of polyphenols that bear antioxidative and health-promoting properties.Objectives: The aim of this study was to evaluate the effect of cranberry extract on some components of metabolic syndrome.Patients and Methods: In a randomized, double-blind placebo-controlled clinical trial, 48 obese and overweight females diagnosed with MS were assigned into two groups to receive cranberry supplement or placebo for an eight-week period. Serum glucose, lipoproteins, inflammatory markers and blood pressure were evaluated at the baseline and at the end of the treatment phase.Results: Cranberry supplements had no effect on any of the variables including glucose, insulin, malondialdehyde (MDA), high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), and blood pressure, except for high-density lipoprotein cholesterol (HDL-c), which significantly increased (P < 0.05) at the eighth-week period compared with the placebo samples.Conclusions: The results of the present study revealed that cranberry supplement might only ameliorate low HDL-c as a component of metabolic syndrome, and not the other risk factors of MS.

Triggering Akkermansia with dietary polyphenols: A new weapon to combat the metabolic syndrome?

Posted: August 22, 2016
Authors: Anhe FF; Pilon G; Roy D; Desjardins Y; Levy E; Marette A
Journal: Gut Microbes. 7(2):146-53

Abstract: The gut and its bacterial colonizers are now well characterized as key players in whole-body metabolism, opening new avenues of research and generating great expectation for new treatments against obesity and its cardiometabolic complications. As diet is the main environmental factor affecting the gut microbiota, it has been suggested that fruits and vegetables, whose consumption is strongly associated with a healthy lifestyle, may carry phytochemicals that could help maintain intestinal homeostasis and metabolic health. We recently demonstrated that oral administration of a cranberry extract rich in polyphenols prevented diet-induced obesity and several detrimental features of the metabolic syndrome in association with a remarkable increase in the abundance of the mucin-degrading bacterium Akkermansia in the gut microbiota of mice. This addendum provides an extended discussion in light of recent discoveries suggesting a mechanistic link between polyphenols and Akkermansia, also contemplating how this unique microorganism may be exploited to fight the metabolic syndrome.

Glycemic Responses to Sweetened Dried and Raw Cranberries in Humans with Type 2 Diabetes

Posted: March 23, 2016
Authors: Wilson T, Luebke JL, Morcomb EF, Carrell EJ, Leveranz MC, Kobs L, Schmidt TP, Limburg PJ, Vorsa N, Singh AP
Journal: J Food Sci 75(8):H218-23

Abstract: This study assessed the metabolic response to sweetened dried cranberries (SDC), raw cranberries (RC), and white bread (WB) in humans with type 2 diabetes. Development of palatable cranberry preparations associated with lower glycemic responses may be useful for improving fruit consumption and glycemic control among those with diabetes. In this trial, type 2 diabetics (n= 13) received WB (57 g, 160 cal, 1 g fiber), RC (55 g, 21 cal, 1 g fiber), SDC (40 g, 138 cal, 2.1 g fiber), and SDC containing less sugar (SDC-LS, 40 g, 113 cal, 1.8 g fiber + 10 g polydextrose). Plasma glucose (mmol/L) peaked significantly at 60 min for WB, and at 30 min for RC, SDC, and SDC-LS at 9.6 ± 0.4, 7.0 ± 0.4, 9.6 ± 0.5, and 8.7 ± 0.5, respectively, WB remained significantly elevated from the other treatments at 120 min. Plasma insulin (pmol/mL) peaked at 60 min for WB and SDC and at 30 min for RC and SDC-LS at 157 ± 15, 142 ± 27, 61 ± 8, and 97 ± 11, respectively. Plasma insulin for SDC-LS was significantly lower at 60 min than either WB or SDC. Insulin area under the curve (AUC) values for RC and SDC-LS were both significantly lower than WB or SDC. Phenolic content of SDC and SDC-LS was determined following extraction with 80% acetone prior to high-performance liquid chromatography (HPLC) and electronspray ionization-mass spectrometry (ESI-MS) and found to be rich in 5-caffeoylquinic cid, quercetin-3-galactoside, and quercetin-3-galactoside, and the proanthocyanidin dimer epicatechin. In conclusion, SDC-LS was associated with a favorable glycemic and insulinemic response in type 2 diabetics. Practical Application: This study compares phenolic content and glycemic responses among different cranberry products. The study seeks to expand the palatable and portable healthy food choices for persons with type 2 diabetes. The novel use of polydextrose as a bulking agent making possible a reduction in caloric content and potential glycemic response is also characterized in this study.

Influence of Polyphenols from Lingonberry, Cranberry, and Red Grape on In Vitro Digestibility of Rice.

Posted: March 23, 2016
Authors: Quek R, Henry CJ
Journal: Int J Food Sci Nutr 66(4):378-82

Abstract: Dietary polyphenols are abundant antioxidants in the human diet and are associated with lower rates of diabetes and cardiovascular disease. This study aims to determine the effects of cooking white rice (WR) added with lingonberry (WRLB), cranberry (WRCB), and red grape (WRRG) on in vitro digestibility. There was significantly lower level of glucose release for WRRG compared with WR (p<0.05). WRLB and WRCB showed no effect on glucose release compared with WR (p>0.05). Increasing concentrations of red grape polyphenol decreased digestibility of white rice (p<0.05). A positive correlation between the red grape phenolic content and the resistant starch was observed (R=0.9854). Red grape polyphenol had the greatest impact on reducing in vitro digestibility of white rice. The addition of polyphenols in carbohydrate-rich foods may be a practical means to reduce the high glycemic response of rice eaten around the world.

A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice

Posted: September 28, 2015
Authors: Anhe FF, Roy D, Pilon G, Dudonne S, Matamoros S, Varin TV, Garofalo C, Moine Q, Desjardins Y, Levy E, Marette A
Journal: Gut 64(6):872-883.

Abstract: Objective: The increasing prevalence of obesity and type 2 diabetes (T2D) demonstrates the failure of conventional treatments to curb these diseases. The gut microbiota has been put forward as a key player in the pathophysiology of diet-induced T2D. Importantly, cranberry (Vaccinium macrocarpon Aiton) is associated with a number of beneficial health effects. We aimed to investigate the metabolic impact of a cranberry extract (CE) on high fat/high sucrose (HFHS)-fed mice and to determine whether its consequent antidiabetic effects are related to modulations in the gut microbiota. Design C57BL/6J mice were fed either a chow or a HFHS diet. HFHS-fed mice were gavaged daily either with vehicle (water) or CE (200 mg/kg) for 8 weeks. The composition of the gut microbiota was assessed by analysing 16S rRNA gene sequences with 454 pyrosequencing. Results: CE treatment was found to reduce HFHS-induced weight gain and visceral obesity. CE treatment also decreased liver weight and triglyceride accumulation in association with blunted hepatic oxidative stress and inflammation. CE administration improved insulin sensitivity, as revealed by improved insulin tolerance, lower homeostasis model assessment of insulin resistance and decreased glucose-induced hyperinsulinaemia during an oral glucose tolerance test. CE treatment was found to lower intestinal triglyceride content and to alleviate intestinal inflammation and oxidative stress. Interestingly, CE treatment markedly increased the proportion of the mucin-degrading bacterium Akkermansia in our metagenomic samples. Conclusions: CE exerts beneficial metabolic effects through improving HFHS diet-induced features of the metabolic syndrome, which is associated with a proportional increase in Akkermansia spp. population.

A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice.

Posted: April 1, 2015
Authors: Anhê FF, Roy D, Pilon G, Dudonné S, Matamoros S, Varin TV, Garofalo C, Moine Q, Desjardins Y, Levy E, Marette A
Journal: Gut pii: gutjnl-2014-307142

Abstract: OBJECTIVE: The increasing prevalence of obesity and type 2 diabetes (T2D) demonstrates the failure of conventional treatments to curb these diseases. The gut microbiota has been put forward as a key player in the pathophysiology of
diet-induced T2D. Importantly, cranberry (Vaccinium macrocarpon Aiton) is associated with a number of beneficial health effects. We aimed to investigate the metabolic impact of a cranberry extract (CE) on high fat/high sucrose (HFHS)-fed mice and to determine whether its consequent antidiabetic effects are related to modulations in the gut microbiota.
DESIGN: C57BL/6J mice were fed either a chow or a HFHS diet. HFHS-fed mice were gavaged daily either with vehicle (water) or CE (200&#8197;mg/kg) for 8&#8197;weeks. The composition of the gut microbiota was assessed by analysing 16S rRNA gene
sequences with 454 pyrosequencing.
RESULTS: CE treatment was found to reduce HFHS-induced weight gain and visceral obesity. CE treatment also decreased liver weight and triglyceride accumulation in association with blunted hepatic oxidative stress and inflammation. CE
administration improved insulin sensitivity, as revealed by improved insulin tolerance, lower homeostasis model assessment of insulin resistance and decreased glucose-induced hyperinsulinaemia during an oral glucose tolerance test. CE treatment was found to lower intestinal triglyceride content and to alleviate intestinal inflammation and oxidative stress. Interestingly, CE treatment markedly increased the proportion of the mucin-degrading bacterium Akkermansia in
our metagenomic samples.
CONCLUSIONS: CE exerts beneficial metabolic effects through improving HFHS
diet-induced features of the metabolic syndrome, which is associated with a
proportional increase in Akkermansia spp. population.

Effects of cranberry powder on biomarkers of oxidative stress and glucose control in db/db mice.

Posted: February 15, 2014
Authors: Kim MJ, Chung JY, Kim JH, Kwak HK
Journal: Nutr Res Pract 7(6):430-8

Abstract: Increased oxidative stress in obese diabetes may have causal effects on diabetic complications, including dyslipidemia. Lipopolysccharides (LPS) along with an atherogenic diet have been found to increase oxidative stress and insulin resistance. Cranberry has been recognized as having beneficial effects on diseases related to oxidative stress. Therefore, we employed obese diabetic animals treated with an atherogenic diet and LPS, with the aim of examining the effects of cranberry powder (CP) on diabetic related metabolic conditions, including lipid profiles, serum insulin and glucose, and biomarkers of oxidative stress. Forty C57BL/KsJ-db/db mice were divided into the following five groups: normal diet + saline, atherogenic diet + saline, atherogenic diet + LPS, atherogenic diet + 5% CP + LPS, and atherogenic diet + 10% CP + LPS. Consumption of an atherogenic diet resulted in elevation of serum total cholesterol and atherogenic index (AI) and reduction of high density lipoprotein (HDL)-cholesterol. However, with 10% CP, the increase in mean HDL-cholesterol level was close to that of the group with a normal diet, whereas AI was maintained at a higher level than that of the group with a normal diet. LPS induced elevated serum insulin level was lowered by greater than 60% with CP (P < 0.05), and mean serum glucose level was reduced by approximately 19% with 5% CP (P > 0.05). Mean activity of liver cytosolic glutathione peroxidase was significantly increased by LPS injection, however it was reduced back to the value without LPS when the diet was fortified with 10% CP (P < 0.05). In groups with CP, a reduction in mean levels of serum protein carbonyl tended to occur in a dose dependent manner. Particularly with 10% CP, a reduction of approximately 89% was observed (P > 0.05). Overall results suggest that fortification of the atherogenic diet with CP may have potential health benefits for obese diabetes with high oxidative stress, by modulation of physical conditions, including some biomarkers of oxidative stress.

Berries reduce postprandial insulin responses to wheat and rye breads in healthy women

Posted: September 15, 2013
Authors: Torronen R. Kolehmainen M. Sarkkinen E. Poutanen K. Mykkanen H. Niskanen L.
Journal: J Nutr 143(4):430-6

Abstract: Starch in white wheat bread (WB) induces high postprandial glucose and insulin responses. For rye bread (RB), the glucose response is similar, whereas the insulin response is lower. In vitro studies suggest that polyphenol-rich berries may reduce digestion and absorption of starch and thereby suppress postprandial glycemia, but the evidence in humans is limited. We investigated the effects of berries consumed with WB or RB on postprandial glucose and insulin responses. Healthy females (n = 13-20) participated in 3 randomized, controlled, crossover, 2-h meal studies. They consumed WB or RB, both equal to 50 g available starch, with 150 g whole-berry puree or the same amount of bread without berries as reference. In study 1, WB was served with strawberries, bilberries, or lingonberries and in study 2 with raspberries, cloudberries, or chokeberries. In study 3, WB or RB was served with a mixture of berries consisting of equal amounts of strawberries, bilberries, cranberries, and blackcurrants. Strawberries, bilberries, lingonberries, and chokeberries consumed with WB and the berry mixture consumed with WB or RB significantly reduced the postprandial insulin response. Only strawberries (36%) and the berry mixture (with WB, 38%; with RB, 19%) significantly improved the glycemic profile of the breads. These results suggest than when WB is consumed with berries, less insulin is needed for maintenance of normal or slightly improved postprandial glucose metabolism. The lower insulin response to RB compared with WB can also be further reduced by berries.

Inhibition of -amylase and glucoamylase by tannins extracted from cocoa, pomegranates, cranberries, and grapes

Posted: September 15, 2013
Authors: Barrett A, Ndou T, Hughey CA, Straut C, Howell A, Dai Z, Kaletunc G
Journal: J Agric Food Chem 61(7):1477-86

Abstract: Proanthocyanidins and ellagitannins, referred to as "tannins", exist in many plant sources. These compounds interact with proteins due to their numerous hydroxyl groups, which are suitable for hydrophobic associations. It was hypothesized that tannins could bind to the digestive enzymes -amylase and glucoamylase, thereby inhibiting starch hydrolysis. Slowed starch digestion can theoretically increase satiety by modulating glucose "spiking" and depletion that occurs after carbohydrate-rich meals. Tannins were isolated from extracts of pomegranate, cranberry, grape, and cocoa and these isolates tested for effectiveness to inhibit the activity of -amylase and glucoamylase in vitro. The compositions of the isolates were confirmed by NMR and LC/MS analysis, and tannin-protein interactions were investigated using relevant enzyme assays and differential scanning calorimetry (DSC). The results demonstrated inhibition of each enzyme by each tannin, but with variation in magnitude. In general, larger and more complex tannins, such as those in pomegranate and cranberry, more effectively inhibited the enzymes than did less polymerized cocoa tannins. Interaction of the tannins with the enzymes was confirmed through calorimetric measurements of changes in enzyme thermal stability.

Reduced-energy cranberry juice increases folic acid and adiponectin and reduces homocysteine and oxidative stress in patients with the metabolic syndrome.

Posted: September 15, 2013
Authors: Simão TN, Lozovoy MA, Simão AN, Oliveira SR, Venturini D, Morimoto HK, Miglioranza LH, Dichi I
Journal: Br J Nutr DOI: 10.1017/S0007114513001207

Abstract: The metabolic syndrome (MetS) comprises pathological conditions that include insulin resistance, arterial hypertension, visceral adiposity and dyslipidaemia, which favour the development of CVD. Some reports have shown that cranberry ingestion reduces cardiovascular risk factors. However, few studies have evaluated the effect of this fruit in subjects with the MetS. The objective of the present study was to assess the effect of reduced-energy cranberry juice consumption on metabolic and inflammatory biomarkers in patients with the MetS, and to verify the effects of cranberry juice concomitantly on homocysteine and adiponectin levels in patients with the MetS. For this purpose, fifty-six individuals with the MetS were selected and divided into two groups: control group (n 36) and cranberry-treated group (n 20). After consuming reduced-energy cranberry juice (0·7 litres/d) containing 0·4 mg folic acid for 60 d, the cranberry-treated group showed an increase in adiponectin (P= 0·010) and folic acid (P= 0·033) and a decrease in homocysteine (P< 0·001) in relation to baseline values and also in comparison with the controls (P< 0·05). There was no significant change in the pro-inflammatory cytokines TNF-&#945;, IL-1 and IL-6. In relation to oxidative stress measurements, decreased (P< 0·05) lipoperoxidation and protein oxidation levels assessed by advanced oxidation protein products were found in the cranberry-treated group when compared with the control group. In conclusion, the consumption of cranberry juice for 60 d was able to improve some cardiovascular risk factors. The present data reinforce the importance of the inverse association between homocysteine and adiponectin and the need for more specifically designed studies on MetS patients.

Postprandial glucose, insulin and glucagon-like peptide 1 responses to sucrose ingested with berries in healthy subjects

Posted: July 31, 2012
Authors: Torronen R, Sarkkinen E, Niskanen T, Tapola N, Kilpi K, Niskanen L

Abstract: Berries are often consumed with sucrose. They are also rich sources of polyphenols which may modulate glycaemia after carbohydrate ingestion. The present study investigated the postprandial glucose, insulin and glucagon-like peptide 1 (GLP-1) responses to sucrose ingested with berries, in comparison with a similar sucrose load without berries. A total of twelve healthy subjects were recruited to a randomised, single-blind, placebo-controlled crossover study. They participated in two meal tests on separate days. The berry meal was a puree (150 g) made of bilberries, blackcurrants, cranberries and strawberries with 35 g sucrose. The control meal included the same amount of sucrose and available carbohydrates in water. Fingertip capillary and venous blood samples were taken at baseline and at 15, 30, 45, 60, 90 and 120 min after starting to eat the meal. Glucose, insulin and GLP-1 concentrations were determined from the venous samples, and glucose also from the capillary samples. Compared to the control meal, ingestion of the berry meal resulted in lower capillary and venous plasma glucose and serum insulin concentrations at 15 min (P = 0.021, P < 0.007 and P = 0.028, respectively), in higher concentrations at 90 min (P = 0.028, P = 0.021 and P = 0.042, respectively), and in a modest effect on the GLP-1 response (P = 0.05). It also reduced the maximum increases of capillary and venous glucose and insulin concentrations (P = 0.009, P = 0.011 and P = 0.005, respectively), and improved the glycaemic profile (P < 0.001 and P = 0.003 for capillary and venous samples, respectively). These results suggest that the glycaemic control after ingestion of sucrose can be improved by simultaneous consumption of berries.

The effects of cranberry juice on serum glucose, apoB, apoA-I, Lp (a), and Paraoxonase-1 activity in type 2 diabetic male patients

Posted: April 30, 2012
Authors: Shidfar F,Heydari I, Hajimiresmaiel SJ, Hosseini S, Shidfar S, Amiri F
Journal: J Res Med Sci 17(6):Epub

Abstract: Background: Type 2 diabetic patients are faced with a higher risk of dyslipidemia and cardiovascular disorders. This study was undertaken to assess the effect of consumption of 1 cup cranberry juice by type 2 diabetic patients on serum paraoxonase-1 (PON-1) activity, apoA-1, apoB, glucose, and Lp(a).
Materials and Methods: In a double-blind randomized clinical trial, 58 type 2 diabetic male patients were randomly divided to receive 1 cup cranberry juice (CJ) or placebo drink daily for 12 weeks. Fasting blood were obtained at beginning and at the end of study (12th week). Serum glucose and PON-1 activity were measured by enzymatic and colorimetric methods, respectively. ApoB, apoA-I, and Lp(a) were determined immunoturbidimetrically. The data were analyzed by SPSS version 16.
Results: There were significant decrease in serum glucose and apoB (P>0.05 and P>0.01, respectively) and significant increase in serum apoA-1 and PON-1 activity (P>0.05 and P<0.01, respectively) at the end of study in CJ group compared with control group. In CJ group at the end of study, there were significant decrease in serum glucose and apoB (P<0.01 and P<0.01, respectively) and significant increase in serum apo A-1 and PON-1 activity (P<0.01 and P<0.01, respectively) compared with initial values. In CJ group, there was no significant change in Lp(a) at the end of study compared with initial values and also compared with control group.
Conclusion: 1 cup CJ for 12 weeks is effective in reducing serum glucose and apoB and increasing apoA-1 and PON-1 activity, so may have favorite effects on reducing CVD risk factors in type 2 diabetic male patients.

Effects of long-term cranberry supplementation on endocrine pancreas in aging rats

Posted: January 22, 2012
Authors: Zhu M, Hu J, Perez E, Phillips D, Kim W, Ghaedian R, Napora JK, Zou S
Journal: J Gerontol A Biol Sci Med Sci 66(11):1139-51

Abstract: The effects of long-term cranberry consumption on age-related changes in endocrine pancreas are not fully understood. Here we treated male Fischer 344 rats with either 2% whole cranberry powder supplemented or normal rodent chow from 6 to 22 month old. Both groups displayed an age-related decline in basal plasma insulin concentrations, but this age-related decline was delayed by cranberry. Cranberry supplementation led to increased &#946;-cell glucose responsiveness during the oral glucose tolerance test. Portal insulin concentration was 7.6-fold higher in rats fed cranberry, coupled with improved &#946;-cell function. However, insulin resistance values were similar in both groups. Total &#946;-cell mass and expression of pancreatic and duodenal homeobox 1 and insulin within islets were significantly enhanced in rats fed cranberry relative to controls. Furthermore, cranberry increased insulin release of an insulin-producing &#946;-cell line, revealing its insulinotropic effect. These findings suggest that cranberry is of particular benefit to &#946;-cell function in normal aging rats.

Cranberry phytochemicals inhibit glycation of human hemoglobin and serum albumin by scavenging reactive carbonyls

Posted: January 17, 2012
Authors: Liu H, Liu H, Wang W, Khoo C, Taylor J, Gu L
Journal: Food Funct 2:475-482

Abstract: Protein glycation caused by sugars and reactive carbonyls is a contributing factor to diabetic complications, aging, and other chronic diseases. The objective of this study was to investigate the inhibitory effects of cranberry phytochemicals on protein glycation. Cranberries, purified to yield sugar-free phytochemical powder, were fractionated into ethyl acetate and water fractions. Water fraction was further separated into water fraction I, II, and III on a Sephadex LH-20 column. Cranberry phytochemical powder and its fractions significantly inhibited the formation of glycated hemoglobin. The concentrations of cranberry phytochemicals required to inhibit 50% of albumin glycation (EC(50)) in albumin-glucose assay were lower than that of aminoguanidine except for water fraction I. Cranberry phytochemicals inhibited glycation of human serum albumin mediated by methylglyoxal, but the EC(50) were higher than that of aminoguanidine. Carbonyl scavenging assay showed that water fraction II scavenged 89.3% of methylglyoxal at 6 h of reaction. Fractions enriched with procyanidins showed higher antiglycation activities, suggesting procyanidins were the major active components. The hypothesis whether cranberry procyanidins scavenged reactive carbonyls by forming adducts was tested. Epicatechin was used as a model compound to react with methylglyoxal and glyoxal at pH 7.4. Five adducts were detected and their structures were tentatively identified using HPLC-ESI-MS/MS.

Berries modify the postprandial plasma glucose response to sucrose in healthy subjects

Posted: January 11, 2011
Authors: Torronen R, Sarkkinen E, Tapola N, Hautaniemi E, Kilpi K and Niskanen L
Journal: Br J Nutr 103(8):1094-7

Abstract: Sucrose increases postprandial blood glucose concentrations, and diets with a high glycaemic response may be associated with increased risk of obesity, type 2 diabetes and CVD. Previous studies have suggested that polyphenols may influence carbohydrate digestion and absorption and thereby postprandial glycaemia. Berries are rich sources of various polyphenols and berry products are typically consumed with sucrose. We investigated the glycaemic effect of a berry puree made of bilberries, blackcurrants, cranberries and strawberries, and sweetened with sucrose, in comparison to sucrose with adjustment of available carbohydrates. A total of twelve healthy subjects (eleven women and one man, aged 25–69 years) with normal fasting plasma glucose ingested 150 g of the berry pure´e with 35 g sucrose or a control sucrose load in a randomised, controlled cross-over design. After consumption of the berry meal, the plasma glucose concentrations were significantly lower at 15 and 30 min (P<0·05, P<0·01, respectively) and significantly higher at 150 min (P<0·05) compared with the control meal. The peak glucose concentration was reached at 45 min after the berry meal and at 30 min after the control meal. The peak increase from the baseline was 1·0 mmol/l smaller (P=0·002) after ingestion of the berry meal. There was no statistically significant difference in the 3 h area under the glucose response curve. These results show that berries rich in polyphenols decrease the postprandial glucose response of sucrose in healthy subjects. The delayed and attenuated glycaemic response indicates reduced digestion and/or absorption of sucrose from the berry meal.

Can cranberry supplementation benefit adults with type 2 diabetes?

Posted: November 22, 2010
Authors: Chambers BK, Camire ME
Journal: Diabetes Care 26(9):2695-6

Abstract: "Adults controlling their type 2 diabetes through diet alone were recruited from the Bangor, Maine, community. Fourteen subjects (aged 57.9 [+ or -] 10.6 years, 6 women, 8 men, duration of diabetes 6.0 [+ or -] 8.5 years) were randomized to the cranberry group; 13 subjects (aged 52.6 [+ or -] 13.7 years, 6 women, 7 men, duration of diabetes 4.1 [+ or -] 4.9 years) were assigned to the placebo group. Subjects consumed six capsules filled with either cranberry juice concentrate powder or a placebo daily for 12 weeks. Six capsules were equivalent to a 240-ml serving of cranberry juice cocktail. The artificially colored placebo mimicked the cranberry powder in all respects but flavonoid content. Subjects were asked to discontinue use of dietary supplements, but no other diet and lifestyle changes were made during the study.

More than one-half of the subjects had good control of blood glucose levels (<7.0 mmol/l) at the beginning of the study. No differences were found between the treatment groups in fasting serum glucose, Hb[A.sub.1c], fructosamine, triglyceride, or HDL or LDL levels after 6 and 12 weeks. Placebo subjects had higher insulin values throughout the study (160 [+ or -] 167 vs. 86 [+ or -] 51 pmol/l at week 12, P < 0.05). Different effects might be seen in subjects with poor glucose control, individuals with type 1 diabetes, or people who use medications to control their type 2 diabetes. "

Potential of cranberry powder for management of hyperglycemia using in vitro models

Posted: November 15, 2010
Authors: Pinto Mda S, Ghaedian R, Shinde R, Shetty K
Journal: J Med Food 13(5):1036-44

Abstract: Aqueous solutions of two different cranberry powders (CP and CP-SAB) were evaluated for organic acids, sugars, total phenolics, antioxidant activity based on the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay, and functionality such as in vitro inhibition of -amylase, -glucosidase, and angiotensin I-converting enzyme (ACE) relevant for potential management of hyperglycemia and hypertension linked to type 2 diabetes. The total phenolics content was 11 and 51 mg/g of sample dry weight for CP and CP-SAB, respectively. p-Coumaric acid and quercetin derivatives were the main phenolic compounds identified in the cranberry powders. CP-SAB had -glucosidase inhibitory activity that increased with increased dose (1-5 mg/mL) from 60% to 100% inhibition. There was limited amount of -amylase inhibitory activity that reached a maximum of 40% inhibition at 5 mg/mL treatment. Significant ACE inhibitory activity was detected for CP-SAB at 100 and 200 mg/mL sample concentrations. These in vitro results indicate the potential of cranberry powders as dietary supplement and food-based strategies for potential hyperglycemia management. This biochemical rationale provides the basis for further design of animal and clinical studies using standardized extracts.

Effect of cranberry extracts on lipid profiles in subjects with Type 2 diabetes

Posted: November 4, 2010
Authors: Lee IT, Chan YC, Lin CW, Lee WJ, Sheu WH
Journal: Diabet Med 25(12):1473-7

Abstract: AIM: To examine the effect of cranberry ingestion on lipid profiles in Type 2 diabetic patients taking oral glucose-lowering drugs.

METHODS: Thirty Type 2 diabetic subjects (16 males and 14 females; mean age 65 +/- 1 years) who were taking oral glucose-lowering medication regularly were enrolled in this randomized, placebo-controlled, double-blind study. Changes in lipid profiles, oxidized low-density lipoprotein (ox-LDL), glycaemic control, components of the metabolic syndrome, C-reactive protein (CRP) and urinary albumin excretion (UAE) were assessed after cranberry or placebo treatment for 12 weeks.

RESULTS: Low-density lipoprotein (LDL) cholesterol decreased significantly in the cranberry group (from 3.3 +/- 0.2 to 2.9 +/- 0.2 mmol/l, P = 0.005) and the decrease was significantly greater than that in the placebo group (-0.4 +/- 0.1 vs. 0.2 +/- 0.1 mmol/l, P < 0.001). Total cholesterol and total : high-density lipoprotein (HDL) cholesterol ratio also decreased significantly (P = 0.020 and 0.044, respectively) in the cranberry group and the reductions were significantly different from those in the placebo group (P < 0.001 and P = 0.032, respectively). However, ox-LDL levels did not change significantly in response to cranberry consumption. Neither fasting glucose nor glycated haemoglobin improved in either group. Changes in components of the metabolic syndrome, UAE and CRP were not significantly different between groups.

CONCLUSIONS: Cranberry supplements are effective in reducing atherosclerotic cholesterol profiles, including LDL cholesterol and total cholesterol levels, as well as total : HDL cholesterol ratio, and have a neutral effect on glycaemic control in Type 2 diabetic subjects taking oral glucose-lowering agents.

Favorable glycemic response of type 2 diabetics to low-calorie cranberry juice

Posted: October 30, 2010
Authors: Wilson T, Meyers SL, Singh AP, Limburg PJ and Vorsa N
Journal: J Food Sci 73(9):H241-5

Abstract: Fruit and vegetable intake is typically low for type 2 diabetics, possibly due to a perceived adverse effect on glycemic control. Cranberry juice (CBJ) may represent an attractive means for increasing fruit intake and simultaneously affording positive health benefits. This single cross-over design compared metabolic responses of type 2 diabetics (n= 12) to unsweetened low-calorie CBJ (LCCBJ; 19 Cal/240 mL), carbohydrate sweetened normal calorie CBJ (NCCBJ; 120 Cal/240 mL), isocaloric low-calorie sugar water control (LCC), and isocaloric normal calorie sugar water control (NCC) interventions. CBJ flavonols and anthocyanins, and proanthocyanidins were quantified with HPLC, LC-MS, and MALDI-TOF that includes an original characterization of several large oligomeric proanthocyanidins. Blood glucose peaked 30 min postingestion after NCCBJ and NCC at 13.3 +/- 0.5 and 12.8 +/- 0.9 (mmol/L), and these responses were significantly greater than the LCCBJ and LCC peaks of 8.1 +/- 0.5 and 8.7 +/- 0.5, respectively. Differences in glycemic response remained significant 60 min, but not 120 min postingestion. Plasma insulin values 60 min postingestion for NCCBJ and NCC interventions were 140 +/- 19 and 151 +/- 18 (pmol/L), respectively, and significantly greater than the LCCBJ and LCC values of 56 +/- 10 and 54 +/- 10; differences were not significant 120 min postingestion. Metabolic responses within the 2 high and 2 low-calorie beverages were virtually identical; however, exposure to potentially beneficial nutrients was greater with CBJ. Relative to conventionally sweetened preparation, LCCBJ provides a favorable metabolic response and should be useful for promoting increased fruit consumption among type 2 diabetics or others wishing to limit carbohydrate intake.

Human glycemic response and phenolic content of unsweetened cranberry juice

Posted: October 31, 2008
Authors: Wilson T, Singh AP, Vorsa N, Goettl CD, Kittleson KM, Roe CM, Kastello GM and Ragsdale FR
Journal: J Med Food 11(1):46-54

Abstract: This cross-sectional study determined the phenolic composition of an over-the-counter cranberry juice (CBJ) with high-performance liquid chromatography and examined the effects of low- and normal-calorie CBJ formulations on the postprandial glycemic response in healthy humans. The CBJ used in this study contained seven phenolic acids, with 3- and 5-caffeoylquinic acid being the primary components, and 15 flavonol glycosides, with myricetin-3-galactoside and quercetin-3-galactoside being the most prevalent. CBJ proanthocyanidins consisted of three different tetramers and a heptamer, which were confirmed with matrix-assisted laser desorption ionization-time of flight-mass spectrometry analysis. Participants received one of the following six treatments: nothing (no water/beverage), water (480 mL), unsweetened low-calorie CBJ (38 Cal/480 mL), normal-calorie CBJ (280 Cal/480 mL), isocaloric normal calorie (high fructose corn syrup [HFCS]), or isocaloric low-calorie beverages. No significant differences in postprandial blood glucose or insulin were observed in the groups receiving nothing, water, or low-calorie treatments. In contrast, the ingestion of normal-calorie CBJ and normal-calorie control beverage resulted in significantly higher blood glucose concentrations 30 minutes postprandially, although the differences were no longer significant after 180 minutes. Plasma insulin of normal-calorie CBJ and control (HFCS) recipients was significantly higher 60 minutes postprandially, but not significantly different 120 minutes postprandially. CBJ ingestion did not affect heart rate or blood pressure. This study suggests that the consumption of a low-calorie CBJ rich in previously uncharacterized trimer and heptamer proanthocyanidins is associated with a favorable glycemic response and may be beneficial for persons with impaired glucose tolerance.