Consumption of nutraceuticals is a major and potent dietary intervention for delaying aging. As the timing of administration is critical for the efficacy of bioactive compounds in medicine, the effectiveness of nutraceuticals may also be dramatically affected by the timing of supplementation. Cranberry exact (CBE), rich in polyphenols, is consumed as a nutraceutical, and possesses anti-aging properties. Here, we examined the influence of timing on the beneficial effects of CBE supplementation in C. elegans. The prolongevity effect of CBE in different aged worms, young adults, middle-age adults, and aged adults, was determined. Early-start intervention with CBE prolonged the remaining lifespan of worms of different ages more robustly than late-start intervention. The effectiveness of CBE on stress responses and physiological behaviors in different aged worms was also investigated. The early-start intervention prominently promoted motility and resistance to heat shocks and V. cholera infection, especially in aged worms. Together, these findings suggest that the timing of CBE supplementation critically influences its beneficial effects on C. elegans lifespan and healthspan. It is of interest to further investigate whether the similar results would occur in humans.

Dietary polyphenolics can be converted into smaller phenolic acids (PA) by microorganisms in the colon and may contribute to health benefits associated with the parent polyphenolics. Urinary excretion of 18 PA and their conjugates was studied, using HPLC-MS/MS, in rats fed AIN93 G-based diets containing 5% (dry weight basis) of either cranberry (CB), blueberry (BB), or black raspberry (BRB). Hippuric, 4-hydroxyphenylacetic, 3-methoxy-4-hydroxyphenylacetic, and 4-hydroxybenzoic acids were excreted in greatest quantity in the urine over a 24 h period in all diets. Primary PA excreted in the berry diets were 4-hydroxycinnamic acid for CB; chlorogenic, ferulic, and 3,4-dihydroxycinnamic acids for BB; and 3-hydroxyphenylpropionic, 3-hydroxybenzoic, and 3-hydroxycinnamic acids for BRB. PA were present in conjugated form with cinnamic acid derivatives being 50-70% and phenylacetic acid derivatives conjugated 10%. Conjugated, and not just the free, PA are significant contributors to total urinary excretion.

Flavonoids, present in high levels in cranberries, are potent bioactives known for their health-promoting benefits, but cranberry beverages (CB) are not typically recommended as part of a healthy diet. We examine the association between CB consumption with macronutrient intake and weight status. Data for US adults (>19 years, n = 10,891) were taken from the National Health and Nutrition Examination Survey (NHANES) Survey 2005-2008. Total CB consumption was measured over two non-consecutive 24-h dietary recalls. Linear and logistic regression models adjusting for important covariates were used to examine predicted differences between CB consumers and non-consumers on macronutrient and anthropometric outcomes. Results are weighted to be nationally representative. CB consumers (n = 581) were older (>50 year) non-Hispanic black females. They consumed an average 221 mL (7.5 oz) CB per day. In fully adjusted models CB consumers (vs. non-consumers) had higher carbohydrates and total sugars and lower percent energy from protein and total fat (all p 0.001), but no difference in total energy. A significantly higher proportion of CB consumers were predicted to be normal weight (BMI 25 kg/m2; p = 0.001) and had to have lower waist circumferences (p = 0.001). Although there was not a significant trend across level of CB intake, low and middle level CB consumers compared to non-consumers were more likely to be normal weight (p 0.001) and less likely to be overweight/obese (BMI > 25 kg/m2, p 0.001). Despite having slightly higher daily macronutrient intakes, CB consumers have more desirable anthropometric measures compared to non-consumers.

Background: Our main objective was to evaluate the ability of cranberry phytochemicals to modify immunity, specifically gamma delta -T cell proliferation, after daily consumption of a cranberry beverage, and its effect on health outcomes related to cold and influenza symptoms. Methods: The study was a randomized, double-blind, placebo-controlled, parallel intervention. Subjects drank a low calorie cranberry beverage (450 ml) made with a juice-derived, powdered cranberry fraction (n=22) or a placebo beverage (n=23), daily, for 10 wk. PBMC were cultured for six days with autologous serum and PHA-L stimulation. Cold and influenza symptoms were self-reported. Results: The proliferation index of gamma delta -T cells in culture was almost five times higher after 10 wk of cranberry beverage consumption (p0.001). In the cranberry beverage group, the incidence of illness was not reduced, however significantly fewer symptoms of illness were reported (p=0.031). Conclusions: Consumption of the cranberry beverage modified the ex vivo proliferation of gamma delta -T cells. As these cells are located in the epithelium and serve as a first line of defense, improving their function may be related to reducing the number of symptoms associated with a cold and flu.

Botanicals possess numerous bioactivities, and some promote healthy aging. Dietary macronutrients are major determinants of life span. The interaction between botanicals and macronutrients that modulates life span is not well understood. Here, we investigated the effect of a cranberry-containing botanical on life span and the influence of macronutrients on the longevity-related effect of cranberry in Drosophila. Flies were supplemented with cranberry on three dietary conditions: standard, high sugar-low protein, and low sugar-high protein diets. We found that cranberry slightly extended life span in males fed with the low sugar-high protein diet but not with other diets. Cranberry extended life span in females fed with the standard diet and more prominently the high sugar-low protein diet but not with the low sugar-high protein diet. Life-span extension was associated with increased reproduction and higher expression of oxidative stress and heat shock response genes. Moreover, cranberry improved survival of sod1 knockdown and dfoxo mutant flies but did not increase wild-type fly's resistance to acute oxidative stress. Cranberry slightly extended life span in flies fed with a high-fat diet. These findings suggest that cranberry promotes healthy aging by increasing stress responsiveness. Our study reveals an interaction of cranberry with dietary macronutrients and stresses the importance of considering diet composition in designing interventions for promoting healthy aging.

Vaccinium macrocarpon (cranberry) products have been used to prevent uropathogenic Escherichia (E.) coli adherence to uroepithelial cells (UEC) and may help reduce risk of urinary tract infection. Reported herein are the development and validation of an assay to assess antiadhesion activity of V. macrocarpon extracts and human urine. P-fimbriated E. coli (CFT073) was labeled with H-uridine, then co-incubated with HTB-4 UEC at a 400:1 ratio. V. macrocarpon extracts (0-17 mg proanthocyanidins/mL) were added to H-labeled E. coli before co-incubating with UEC. The assay yielded a sensitive inhibition curve: the lower limit of detection and half-maximal inhibitory concentration were 0.43 and 1.59 mg proanthocyanidins/mL for V. macrocarpon extract CEP 55; intra- and interassay coefficients of variance were 10% and 15%, respectively. V. macrocarpon extract CEP 3283 showed identical adhesion inhibition. Serial dilutions of urine from human participants who consumed V. macrocarpon beverages showed a linear decrease in antiadhesion activity. Antiadhesion assays conducted with urine from a human intervention study also showed good agreement with results obtained using the hemagglutination assay. Therefore, a sensitive, high-throughput, biologically relevant antiadhesion assay using H-E. coli co-incubated with UEC is reported, which can be used for studying the action of V. macrocarpon bioactives.

BACKGROUND: Cranberry is one of the most commonly used herbs during pregnancy. The herb has been used traditionally against urinary tract infections. No studies are found that specifically address the risk of malformations after use of cranberry during pregnancy. The aim of the study was to investigate the safety of cranberry use during pregnancy, including any effects on congenital malformations and selected pregnancy outcomes.

METHODS: The study is based on data from The Norwegian Mother and Child Cohort Study including more than 100,000 pregnancies from 1999 to 2008. Information on use of cranberry and socio-demographic factors was retrieved from three self-administered questionnaires completed by the women in pregnancy weeks 17 and 30, and 6 months after birth. Information on pregnancy outcomes was retrieved from the Medical Birth Registry of Norway.

RESULTS: Among the 68,522 women in the study, 919 (1.3%) women had used cranberry while pregnant. We did not detect any increased risk of congenital malformations after use of cranberry. Furthermore, the use of cranberry was also not associated with increased risk for stillbirth/neonatal death, low birth weight, small for gestational age, preterm birth, low Apgar score (7), neonatal infections or maternal vaginal bleeding in early pregnancy. Although an association was found between use of cranberry in late pregnancy and vaginal bleeding after pregnancy week 17, further sub-analyses of more severe bleeding outcomes did not support a significant risk.

CONCLUSIONS: The findings of this study, revealing no increased risk of malformations nor any of the following pregnancy outcomes; stillbirth/neonatal death, preterm delivery, low birth weight, small for gestational age, low Apgar score and neonatal infections are reassuring. However, maternal vaginal bleeding should be investigated further before any firm conclusion can be drawn. Treatment guidelines on asymptomatic bacteriuria in pregnancy recommend antimicrobial therapy as the first line treatment. According to our data and the outcomes studied, cranberry does not appear to be a harmful adjunctive self-treatment.

In this study, five common proanthocyanidin purification techniques were evaluated prior to phloroglucinolysis, followed by HPLC analysis. An optimized purification method was then used to identify and quantify the proanthocyanidins (extension and terminal units of epigallocatechin, catechin, epicatechin, A type trimer, and A type dimer) of commercially available cranberry products (juices, concentrates, tablets, and capsules; n=17). Two size exclusion beads (Toyopearl 4 TSK HW-40C and Sephadex LH-20) were found suitable for proanthocyanidin purification, though proanthocyanidin extension and terminal unit composition was contingent upon the cleanup procedure utilized. These data illustrate that purification methods require consideration prior to conducting any cranberry proanthocyanidin analyses, and have to be accounted for when comparing values between studies. Total proanthocyanidin levels ranged from 11.7 (juice) to 436.4 (tablet) mg/100 mL or 100 g values obtained from Sephadex LH-20 purification, while total anthocyanin levels ranged from 0.54 (juice) to 98.00 (tablet) mg/100 mL or 100 g.

The present work proposes a new UHPLC-PDA-fluorescence method able to identify and quantify the main polyphenols present in commercial fruit juices in a 28-min chromatogram. The proposed method improve the IFU method No. 71 used to evaluate anthocyanins profiles of fruit juices. Fruit juices of strawberry, American cranberry, bilberry, sour cherry, black grape, orange, and apple, were analysed identifying 70 of their main polyphenols (23 anthocyanins, 15 flavonols, 6 hydroxybenzoic acids, 14 hydroxycinnamic acids, 4 flavanones, 2 dihydrochalcones, 4 flavan-3-ols and 2 stilbenes). One standard polyphenol of each group was used to calculate individual polyphenol concentration presents in a juice. Total amount of polyphenols in a fruit juice was estimated as total individual polyphenols (TIP). A good correlation (r(2)=0.966) was observed between calculated TIP, and total polyphenols (TP) determined by the well-known colorimetric Folin-Ciocalteu method. In this work, the higher TIP value corresponded to bilberry juice (607.324 mg/100mL fruit juice) and the lower to orange juice (32.638 mg/100mL fruit juice). This method is useful for authentication analyses and for labelling total polyphenols contents of commercial fruit juices. Copyright 2012 Elsevier Ltd. All rights reserved.

Nutraceuticals are known to have numerous health and disease preventing properties. Recent studies suggest that extracts containing cranberry may have anti-aging benefits. However, little is known about whether and how cranberry by itself promotes longevity and healthspan in any organism. Here we examined the effect of a cranberry only extract on lifespan and healthspan in Caenorhabditis elegans. Supplementation of the diet with cranberry extract (CBE) increased the lifespan in C. elegans in a concentration-dependent manner. Cranberry also increased tolerance of C. elegans to heat shock, but not to oxidative stress or ultraviolet irradiation. In addition, we tested the effect of cranberry on brood size and motility and found that cranberry did not influence these behaviors. Our mechanistic studies indicated that lifespan extension induced by CBE requires the insulin/IGF signaling pathway and DAF-16. We also found that cranberry promotes longevity through osmotic stress resistant-1 (OSR-1) and one of its downstream effectors, UNC-43, but not through SEK-1, a component of the p38 MAP kinase pathway. However, SIR-2.1 and JNK signaling pathways are not required for cranberry to promote longevity. Our findings suggest that cranberry supplementation confers increased longevity and stress resistance in C. elegans through pathways modulated by daf-16 and osr-1. This study reveals the anti-aging property of widely consumed cranberry and elucidates the underpinning mechanisms.