Freeze-dried Grape Powder Research Articles

Effect of Grape and its Derivatives on Cognitive Function: A Systematic Review of Clinical Trials

Background: According to the world health organization (WHO), in 2019, around 50 million people suffer from dementia, worldwide; and approximately 60% live in low- and middle-income countries. Dementia has physical, psychological, social, and economic effects on dementia sufferers, their caregivers, families, and the community.
 Objectives: This systematic review investigated the effect of short-term and long-term interventions with grapes and their derivatives on different cognitive functions, such as executive function, memory, attention and language in all people.
 Methods: Pubmed, Scopus, and Proquest were searched until June 12, 2020 for English studies. Clinical trials in which grapes and its derivatives were considered as an intervention and changes of cognition and its components as an outcome, were selected. Two independent individuals assessed the quality of the articles according to Jadad checklist and extracted the information of the articles with inclusion criteria based on a specific table. The differences were resolved with the discussion and opinion of a third person.
 Results: Nine Studies (211 individuals) were included in the content analysis, of which 3 studies had short-term intervention and 6 studies had long-term intervention with grape juice, freeze-dried grape powder, and a syrup made from grapes (Enoant Syrup). It can be said that the consumption of grapes and its derivatives improved various cognitive components (such as attention, executive function, immediate spatial memory, learning, and driving skill) between groups.
 Conclusion: In general, long-term intervention with grapes and their derivatives has led to the improvement of some cognitive functions, but its short-term intervention is not very effective and only 2 studies showed improvement in attention speed. However, the included studies were highly heterogeneous and more research is needed using similar cognitive assessment tools.

Effects of Freeze-Dried Grape Powder on High-Density Lipoprotein Function in Adults with Metabolic Syndrome: A Randomized Controlled Pilot Study.

High-density lipoprotein (HDL) particles are protective against atherosclerosis. However, HDL function is impaired in metabolic syndrome (MetS) due to low-grade inflammation and dyslipidemia. Foods containing polyphenols, such as grapes, may prevent HDL dysfunction via antioxidant or anti-inflammatory effects. We evaluated the effects of grape powder ingestion on measures of HDL function in adults with MetS. Twenty adults (age: 32-70 years; body mass index: 25.3-45.4 kg/m2) consumed either 60 grams/day of freeze-dried grape powder (GRAPE) or a placebo for 4 weeks, separated by a 3-week washout period, in a randomized, double-blind crossover study. The primary outcome was serum paraoxonase-1 (PON1) arylesterase activity, a measure of HDL antioxidant function. Secondary outcomes included PON1 lactonase activity, plasma lipids, metabolic markers, cholesterol efflux capacity, and other HDL functional markers. After 4 weeks, GRAPE did not alter the serum PON1 activity or other markers of HDL function compared with placebo. Measures of HDL function were positively correlated with each other and inversely with measures of insulin resistance and inflammation. GRAPE intake led to a significant reduction in fasting plasma triglycerides compared with placebo (P = 0.032). No other significant effects of GRAPE were observed for other plasma lipids, anthropometrics, or metabolic measures. Grape powder consumption did not impact HDL function in this cohort of adults with MetS. However, it was shown to improve fasting triglycerides, a risk factor for cardiovascular disease.

Protective effects of a grape-supplemented diet in a mouse model of retinal degeneration

ObjectiveRetinal degenerations are a class of devastating blinding diseases that are characterized by photoreceptor dysfunction and death. In this study, we tested whether grape consumption, in the form of freeze-dried grape powder (FDGP), improves photoreceptor survival in a mouse model of retinal degeneration. MethodsRetinal degeneration was induced in mice by acute oxidative stress using subretinal injection of paraquat. The grape-supplemented diet was made by formulating base mouse chow with FDGP, corresponding to three daily human servings of grapes, and a control diet was formulated with equivalent sugar composition as FDGP (0.68% glucose–0.68% fructose mixture). Mice were placed on the diets at weaning for 5 wk before oxidative stress injury until analysis at 2 wk post-injection. Retinal function was measured using electroretinography, thickness of the photoreceptor layer was measured using optical coherence tomography, and rows of photoreceptor nuclei were counted on histologic sections. ResultsIn mice fed the control diet, oxidative stress significantly reduced photoreceptor layer thickness and photoreceptor numbers. In contrast, retinal thickness and photoreceptor numbers were not reduced by oxidative stress in mice on the grape-supplemented diet, indicating significantly higher photoreceptor survival after injury than mice on the control diet. Furthermore, mice on the grape diet showed preservation of retinal function after oxidative stress injury compared with mice on the control diet. ConclusionsA diet supplemented with grapes rescued retinal structure and function in an oxidative stress–induced mouse model of retinal degeneration, which demonstrates the beneficial effect of grapes on photoreceptors.

A Grape-Enriched Diet Increases Bone Calcium Retention and Cortical Bone Properties in Ovariectomized Rats1–3

Grapes and their associated phytochemicals have been investigated for beneficial effects on cardiovascular health, cancer prevention, and other chronic diseases, but the effect of grape consumption on bone health has not been fully determined. We previously found short-term benefits of grape products on reducing bone turnover in ovariectomized rats. The objective of this study was to determine the long-term benefits of a grape-enriched diet on bone in ovariectomized rats. Rats were ovariectomized at 3 mo of age and were administered a single dose of (45)Ca to prelabel bones at 4 mo of age. After a 1-mo equilibration period, baseline urinary (45)Ca excretion was determined. Rats (n = 22/group) were then randomly assigned to a modified AIN93M diet containing 25% freeze-dried grape powder or to a control diet for 8 wk. Urinary (45)Ca excretion was monitored throughout the study to determine changes in bone (45)Ca retention. Calcium balance was assessed after 1 and 8 wk of consuming the experimental diets, and a calcium kinetic study was performed at 8 wk. After 8 wk, femurs were collected for micro-computed tomographic imaging, 3-point bending, and reference point indentation. Rats fed the grape-enriched diet had 44% greater net bone calcium retention than did rats fed the control diet. There were no differences in calcium balance due to diet at either week 1 or week 8, but there was a significant increase in net calcium absorption (10.6%) and retention (5.7%) from week 1 to week 8 in the grape-enriched diet group only. Grape-enriched diet-fed rats had 3% greater cortical thickness and 11% greater breaking strength. There were no differences in femur bone mineral density, trabecular microarchitecture, or reference point indentation variables due to diet. This study of ovariectomized rats indicates that the consumption of grape products may improve calcium utilization and suppress bone turnover, resulting in improvements in bone quality.

Evaluation of the Aromatase Inhibition Potential of Freeze-Dried Grape Powder

ABSTRACTObjective: To determine the role of freeze-dried grapes as a potential aromatase inhibitor by testing of plasma hormone levels. Methods: A six-week study was conducted involving postmenopausal women during which 94 g of freeze-dried grape powder was consumed in addition to their usual diet. Plasma hormones were measured before and after the treatment. Results: Of the 18 women involved in the study, average age and body mass index were 61.4 years and 24.4 respectively. For the hormone levels studied, the following median (interquartile range) percentage changes from baseline to six-week values were found: estradiol +11.8% (−34.4%, +44.2%), p = .42; estrone +3.4% (−15.7%, +12.9%), p = .64; estrone sulfate +5.3% (−19.9%, +56.3%), p = .35; testosterone −1.5% (−14.7%, +10.7%), p = .97; and androstenedione +12.6% (−17.1%, +49.1%), p = .15. The hormone levels did not significantly change between baseline and six weeks. Further, the changes that were observed did not tend to go in the hypothesized direction (estrogens and conjugates increased slightly, and testosterone decreased slightly). Only androstenedione showed a trend toward change in the hypothesized direction. Conclusions: In this study, there was no evidence that plasma hormone levels are altered by six weeks of daily consumption of 94 g of freeze-dried grape powder.

Freeze-Dried Grape Powder Reduces Joint Pain and Influences Serum Cartilage and Inflammatory Biomarkers in Older Adults with Self-Reported Knee Osteoarthritis

Freeze-Dried Grape Powder Reduces Joint Pain and Influences Serum Cartilage and Inflammatory Biomarkers in Older Adults with Self-Reported Knee Osteoarthritis

Consumption of whole grape powder reduces joint pain and influences serum biomarkers in individuals with self‐reported knee osteoarthritis (1025.10)

Osteoarthritis (OA) is clinically associated with joint pain and stiffness leading to loss of mobility. There is growing interest in use of natural as opposed to invasive therapies in joint pain management. Consumption of grapes, a rich source of polyphenols may reduce inflammation and influence OA outcomes. We have examined the effect of grape consumption on self‐reported pain, joint range‐of‐motion (ROM) and biochemical markers of inflammation (CRP) and cartilage metabolism (IGF‐1, YKL‐40). Using convenience sampling, 72 men and women with knee OA were recruited and assigned to one of two groups. The treatment group (n =28, 21 female) consumed 47 g of freeze‐dried grape powder (FDGP) daily for 4 months. The placebo group (n=28, 21 female) consumed a comparable placebo. For pain related to activity, the FDGP group had a significant decrease from baseline compared to placebo (‐5.3 vs. ‐2.1, p < .05). At midpoint, both groups had a significant reduction in total knee symptoms, evident in the FDGP group only at the end of study. Further, this effect was greater in females. There was no significant change in overall ROM for either group. FDGP intake led to gender specific changes in IGF‐1 compared to placebo group: male (19.9 vs. 2.0 ng/mL, p <.05) and female (3.2 vs. 8.9 ng/mL, p >.05). Whole grape consumption with its bioactive constituents can be a natural alternative to improving symptoms associated with OA.Grant Funding Source: Supported by California Table Grape Commission

Age‐associated effect of freeze‐dried grape powder on inflammatory markers and physical activity in adults with knee osteoarthritis (1025.8)

Osteoarthritis (OA) is the most common joint disease among US adults, leading to pain and disability. Treatment ranges from symptom management to joint replacement, leading many to seek natural dietary approaches. Grapes, rich in anti‐inflammatory polyphenols may aid in management of OA symptoms. The purpose of this study was to assess the effect of grape consumption on physical activity, biochemical markers of inflammation (IL1‐β) and cartilage metabolism (COMP). A total of 72 men and women with knee OA were recruited and randomized. Group 1 (n=28, 21 female) consumed 47 grams of freeze‐dried grape powder (FDGP) daily for four months. Group 2 (n=28, 21 female) consumed 47 grams of a comparable placebo. Self‐reported physical activity and serum specimens were obtained at baseline and at four months. There was a significant decrease in very hard activity in the placebo group. However, a 70 % increase was seen in very hard activity for those <64 yr. in the FDGP group. Participants >65 yr. reported a significant decline in moderate and hard activities (P<.05) in both groups. A statistically significant increase in IL1‐β was observed in both groups, males > females. A greater increase occurred in the placebo group (637.33%) vs. FDGP (194.64%). Levels of IL‐1β and COMP increased more in those >65 yr. Both groups had a statistically significant increase in COMP (154.2% FDGP vs. 172.27% placebo). Longer treatment duration with FDGP may be necessary to see benefits on physical activity levels in this population.Grant Funding Source: Supported by California Table Grape Commission

Vascular and Cardiac Effects of Grape Powder in the Spontaneously Hypertensive Rat

We previously reported that resveratrol, a polyphenol found in red grapes, attenuated changes in small artery geometry and stiffness, as well as cardiac hypertrophy and cardiac function in the spontaneously hypertensive rat (SHR). However, in addition to resveratrol, grapes contain a variety of bioactive polyphenols such as catechins, anthocyanins, and flavonoids. Therefore, we investigated the effects of grape consumption in SHR. Wistar-Kyoto (WKY) rats and SHR were treated with freeze-dried grape powder for 10 weeks. Dilatory, geometry, and stiffness properties of mesenteric small arteries were assessed by pressurized myography. Left ventricular mass index and cardiac function were assessed by two-dimensional guided M-mode and pulse-wave Doppler echocardiography. Elevated blood pressure in SHR was associated with remodeling and impaired endothelium-dependent relaxation of small arteries. Augmented left ventricular mass index (reflecting hypertrophy) and diminished cardiac function were also evident in SHR. Although grape treatment failed to affect cardiac dysfunction, it elicited a significant reduction in blood pressure, improved arterial relaxation, increased vascular compliance, and attenuated cardiac hypertrophy. Treatment with whole grape powder conferred mild vascular and cardiac benefits in SHR. Therefore, dietary grape consumption may be a feasible and salutary adjunct to pharmacological treatment of human hypertension.

Characterization of critical physical and mechanical properties of freeze-dried grape powder for development of a clinical patient delivery system

Grapes are hypothesized to be a “food medicine.” Freeze-dried grape powder (FDGP) is being used to test clinical activity for a variety of applications and a reproducible and reliable delivery system was required. The FDGP was characterized using traditional physico-chemical methods to generate the data needed to identify its primary liability, i.e. moisture sorption. Above a threshold level of moisture content (~25% w/w, at RT), the material becomes both difficult to handle and exhibits significant degradation of several potentially clinically important chemical components (catechin, epicatechin, resveratrol). A moisture sorption isotherm was then used to tie the threshold to the exposure relative humidity above which this occurs. Kinetic uptake studies were used to estimate the maximum safe exposure time at a given humidity (a square root time dependence of moisture uptake was observed). Armed with this knowledge, a FDGP compact coated with a compression coat [100% bees wax or combinations of carnauba wax (70%) with HPC (30%) or Avicel® PH 102 (30%) or lactose monohydrate (30%)] was developed that will insure the shelf life of the material without the need for special handling for approximately more than 3 months.

Identification of components of grape powder with anti-apoptotic effects

This study is to investigate the mechanism underlying the anti-apoptotic effects of freeze-dried grape powder (FDGP) and identify the polyphenolic compounds involved. We examined apoptotic signaling pathways affected by FDGP and by its active components, including epicatechin, cyanidin, quercetin, and resveratrol, in human Huh7 hepatoma cells by assaying cell viability assays, the activities of caspase 3 and caspase 7, and the expression of endoplasmic reticulum stress-associated proteins. FDGP dramatically decreased taurodeoxycholic acid (TDCA)-induced production of reactive oxygen species (ROS). Assessment of individual active components revealed that at concentrations corresponding to 300 μg/mL FDGP, only quercetin demonstrated cytoprotective effects against mitochondrial-mediated apoptosis. In contrast, increased concentrations of other individual polyphenolic compounds were required to produce measurable cytoprotective effect. Only combinations of all four polyphenolic compounds (epicatechin, cyanidin, quercetin, and resveratrol) restored a degree of the anti-apoptotic effects seen with FDGP. The pretreatment of FDGP at 30 μg/mL concentration could reverse the thapsigargin-induced effects on the expression of endoplasmic reticulum stress-associated proteins. In conclusion, FDGP reduced oxidative stress, endoplasmic reticulum stress, and apoptosis. The mechanisms involved in the anti-apoptotic effects of FDGP included reduced generation of ROS, and reduced processing of certain caspases. We demonstrated that quercetin, epicatechin, and cyanidin are active compounds within FDGP that attenuate apoptosis. These findings contribute to our understanding of the molecular mechanisms of anti-apoptotic and anti-oxidant effects of grape and are expected to assist in developing clinical protocols to treat a variety of stress-mediated conditions.

Inhibition of Murine Skin Carcinogenesis by Freeze-Dried Grape Powder and Other Grape-Derived Major Antioxidants

Overexposure of the skin to carcinogenic insults causes a variety of adverse effects, among them the development of skin carcinomas. Since there is a need to develop efficient chemopreventive agents based on nutrition, our goal was to determine antioxidant and anti-carcinogenic properties of grapes by evaluating grape powder developed by the California Table Grape Commission. In order to elucidate the mechanism(s) of action of grape powder, three of the major antioxidant components found in grapes—resveratrol, catechin, quercetin, and grape seed extract, containing a proanthocyanidin B-2-gallate—were evaluated for their abilities to inhibit oxidative stress and to protect the immune system. Tested antioxidants given topically and/or systemically strongly inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced epidermal hyperplasia, proliferation, and inflammation. The hydroxylation of 2′-deoxyguanosine was markedly inhibited by topical and dietary administration of test variables, i.e., by approximately 40–70%. Simultaneous dietary and topical treatment with antioxidants reduced these biomarkers, showing strong additive and in some combinations synergistic effects. DMBA-mediated Ha-ras mutations in codon 61 were reduced by up to 50% with topical applications, but much higher inhibition was observed in mice treated with different combinations. The results of the present study clearly show impressive effects of combined topical and dietary treatments with above grape-derived antioxidants.

Freeze-Dried Grape Powder Attenuates Mitochondria- and Oxidative Stress-Mediated Apoptosis in Liver Cells

The beneficial effects of grape consumption have been attributed to the antioxidant activity of its polyphenols. This study was conducted to investigate the cytoprotective effects of a freeze-dried grape powder (FDGP) on liver cells. FDGP treatment of primary hepatocytes and hepatoma cells revealed increased metabolic activity of cells and phosphorylation of Akt and IkappaBalpha, as well as up-regulation of proliferating cell nuclear antigen (PCNA) level. To study the molecular mechanisms of FDGP effects, cells were treated with TNF-related apoptosis-inducing ligand (TRAIL); taurodeoxycholic acid (TDCA); thapsigargin (TG), to induce cell apoptosis through death receptor-, mitochondria-, or ER-mediated pathway; and H(2)O(2), to induce oxidative stress, respectively. TDCA-induced activation of caspase-3, caspase-7, caspase-9, and Bax was dramatically decreased with cotreatment of FDGP. Furthermore, FDGP reduced levels of annexin V positive cells by 4-fold. Also, FDGP pretreatment restored cellular glutathione content by 71% in cells treated with H(2)O(2). However, FDGP did not inhibit ER-mediated apoptosis. In conclusion, FDGP increased the viability and metabolic activity of liver cells and attenuated oxidative stress- and mitochondria-mediated apoptosis. These data may contribute to the understanding of the mechanisms involved in protective effects of grape in a variety of liver conditions associated with cellular stress.

Diets Rich in Polyphenols and Vitamin A Inhibit the Development of Type I Autoimmune Diabetes in Nonobese Diabetic Mice ,3

Type I juvenile diabetes mellitus is characterized by the infiltration of activated T lymphocytes and monocytes into the islets of Langerhans of the pancreas, resulting in inflammation and progressive destruction of the insulin-producing β cells. We hypothesized that feeding nonobese diabetic (NOD) mice diets rich in polyphenols or vitamin A, both known modulators of immune function, would decrease the autoimmune inflammatory process associated with type I diabetes. NOD mice were fed a control diet (C) and diets containing either 1% freeze-dried grape powder (GP) or 250 IU vitamin A/g (VA; 0.262 μmol retinyl acetate/g) of food. Mice were considered diabetic and killed when blood glucose reached 13.9 mmol/L or greater. By ∼7 mo of age, 71% of C mice progressed to diabetes. Incidence of diabetes was reduced to 33% (P < 0.05) and 25% (P < 0.05) in mice receiving 1% dietary grape powder and VA, respectively. Splenocytes from mice receiving both GP and VA had lower TNF-α production after LPS stimulation than C mice (P < 0.05). Histological analysis of pancreatic tissue showed a significant reduction in the severity of insulitis in the mice receiving GP and VA compared with C mice. These data suggest that diets rich in polyphenols or vitamin A have protective effects against autoimmune inflammatory attack of the islet β cells and have the potential to reduce the onset and pathogenesis of autoimmune diabetes.

Diets rich in polyphenols and vitamin A inhibit type I autoimmune diabetes in non‐obese diabetic mice

Type I juvenile diabetes is characterized by infiltration of activated T lymphocytes and monocytes into the islets of Langerhans of the pancreas (insulitis), resulting in the inflammation and progressive destruction of the insulin-producing beta cells. We hypothesized that feeding non-obese diabetic (NOD) mice diets rich in polyphenols or vitamin A, both known modulators of immune function, would decrease the inflammatory process associated with type I diabetes. NOD mice were fed control diet, diet containing 1% freeze-dried grape powder rich in polyphenols, or diet with 250 IU vitamin A/gram of food. Mice were euthanized when the blood glucose levels reached 250 mg/dl or greater. By approximately seven months of age, 71% of control mice progressed to diabetes. However, the incidence of diabetes was 33% in mice receiving 1% dietary grape powder and 25% in mice receiving vitamin A enriched diet. Splenocytes from mice were stimulated with mitogens and assayed for cytokine production. A statistically significant decrease in TNF-alpha production by the monocytic population in mice that received grape powder was observed. Mice receiving vitamin A showed a significant reduction of TNF-alpha production by both the T lymphocytic and monocytic populations. Histological analyses of pancreatic tissue showed a reduction in the severity of insulitis in the mice receiving the grape powder and vitamin A enriched diets compared to control mice. These data suggest that diets rich in polyphenols or vitamin A may have potential for reducing the onset and pathogenesis of autoimmune diabetes. Supported by NIH RO1AI50863 and USDA CRIS 5306-51530-013-00D.