Berries and their health benefits!

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Berries and their health benefits!

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♦ Many berries are prized for their health benefits while also being very delicious.
Modern science has identified an ‘active ingredient’ called Resveratrol, which scientific studies has shown to have highly therapeutic and prophylactic properties.

Thousands of scientific studies have documented the manifold prophylactic and therapeutic benefits of Resveratrol and include amongst others:
Cancer, Cardiovascular disease, lowering of Blood Pressure, LDL lowering, improvement of Cognitive Functions, prevention of Neurodegenerative disease, Diabetes, Arthritis, Longevity, etc.

♦ Sources of Resveratrol!

Table of various berries and their Resveratrol * content:
Berry, Fruit, Vegetable Resveratrol in mcg/g
Mulberry 50.61
Cranberries 19.2
Red Currants 15.7
Raisins 5.5 - 18.6
Red Wine ** 2.0 – 13.8
Red Grapes ** 1.5 – 12.5
Peanuts boiled *** 1.77 – 7.11
Blueberries 3.83
Strawberries 3.5
Red Cabbage 2.5
  • * Resveratrol is easily absorbed in the gut, but is also quickly metabolised leading to formation of conjugated sulfates and glucuronides so the bioavailability is limited.
    This is equally true for resveratrol from natural foods as for supplement concentrates.
However a study [α] concluded that the co-consumption of 10 mg/kg piperine, i.e. an amount of pepper providing the equivalent of piperine, will drastically increase the bioavailability, where an 1,544% increase of maximum serum concentration was recorded.
  • ** Content is very dependent upon type of grape, soil, growing condition, etc.
  • *** Boiled Peanuts are much healthier and contain more nutrients like resveratrol, etc.
♦ Diseases and conditions Resveratrol can benefit, cited by studies:
  • Alzheimer's Disease [1][3]
  • Anti-ageing, Longevity [13][21]
  • Bone Density [19]
  • Bowel Inflammation, Ulcerative Colitis [18]
  • Cancer [17]
  • Cardiovascular Disease [6]
  • Cholesterol LDL [6]
  • Cognitive Dysfunction, Sleep Deprivation-Induced [11]
  • Colon, Colorectal Cancer [7][9]
  • Diabetes [12][22]
  • Hypertension/High Blood Pressure [2][6]
  • Intestinal Inflammation [16]
  • Liver; Alcoholic Fatty Liver Disease [20]
  • Liver Cancer [10]
  • Lung Cancer [4]
  • Male Reproductive Health, Sperm production/motility [15]
  • Mental acuity, Cognition/Cerebrovascular function [8]
  • Neuro Degenerative Diseases [3]
  • Parkinson's Disease [3]
  • Prostate Cancer [14]
  • Rheumatoid Arthritis [5]
  • and many others
♦ Footnotes:
  • [α] Enhancing the bioavailability of resveratrol by combining it with piperine
    Methods and results:
    Mice were administered resveratrol (100 mg/kg; oral gavage)
    or resveratrol (100 mg/kg; oral gavage) + piperine (10 mg/kg; oral gavage),
    and the serum levels of resveratrol and resveratrol-3-O-β-D-glucuronide were analyzed at different times.
    We found that the degree of exposure (i.e. AUC) to resveratrol was enhanced to 229% and the maximum serum concentration (Cmax) was increased to 1544% with the addition of piperine.
    Our study demonstrated that piperine significantly improves the in vivo bioavailability of resveratrol.
    Jeremy J. Johnson,Minakshi Nihal,Imtiaz A. Siddiqui,Cameron O. Scarlett,Howard H. Bailey,Hasan Mukhtar,Nihal Ahmad
♦ References
  • [1] Resveratrol as a Potential Therapeutic Candidate for the Treatment and Management of Alzheimer's Disease
    Resveratrol (3,4',5-trihydroxystilbene) is a naturally occurring phytochemical present in red wine, grapes, berries, chocolate and peanuts.
    Clinically, resveratrol has exhibited significant antioxidant, anti-inflammatory, anti-viral, and anti-cancer properties.
    Resveratrol has demonstrated neuroprotective effects in several in vitro and in vivo models of AD (Alzheimer's Disease).
    Apart from its potent antioxidant and anti-inflammatory roles, evidence suggests that resveratrol also facilitates non-amyloidogenic breakdown of the amyloid precursor protein (APP), and promotes removal of neurotoxic amyloid beta (Aβ) peptides, a critical step in preventing and slowing down AD pathology.
    Resveratrol also reduces damage to neuronal cells via a variety of additional mechanisms, most notably is the activation of NAD(+)-dependent histone deacetylases enzymes, termed sirtuins.
    PMID: 26845555 DOI: 10.2174/1568026616666160204121431

  • [2] Effect of resveratrol on blood pressure: a meta-analysis of randomized controlled trials
    Six studies comprising a total of 247 subjects were included in our meta-analysis.
    The overall outcome of the meta-analysis indicates that resveratrol consumption can not significantly reduce SBP and DBP.
    Subgroup analyses indicated that higher-dose of resveratrol consumption (≥ 150 mg/d) significantly reduces SBP of -11.90 mmHg (95% CI: -20.99, -2.81 mmHg, P = 0.01), whereas lower dose of resveratrol did not show a significant lowering effect on SBP.
    The present meta-analysis indicates that resveratrol consumption significantly decreases the SBP level at the higher dose, while resveratrol has no significant effects on DBP levels.
    PMID: 24731650 DOI: 10.1016/j.clnu.2014.03.009

  • [3] Multiplicity of effects and health benefits of resveratrol
    Resveratrol is mainly found in grapes and red wine, also in some plants and fruits, such as peanuts, cranberries, pistachios, blueberries and bilberries.
    Moreover, nowadays this compound is available as purified preparation and dietary supplement.
    Resveratrol provides a wide range of benefits, including cardiovascular protective, antiplatelet, antioxidant, anti-inflammatory, blood glucose-lowering and anticancer activities, hence it exhibits a complex mode of action.
    It has been reported that this compound has low toxicity as it was well tolerated in the short-term experiments performed in humans.
    Recent clinical trials proved that resveratrol is well-tolerated and pharmacologically safe at doses up to 5 g/day.
    Concluding remarks
    Thousands of basic science experiments in vitro and in animal models suggest low toxicity and many positive effects of resveratrol.
    Resveratrol has also been entitled as a natural therapeutic agent with pharmacological potential in various neurodegenerative impairments including Alzheimer's, Huntington's, Parkinson's diseases, amyotrophic lateral sclerosis and alcohol-induced neurodegenerative disorder.

  • [b4] Resveratrol in lung cancer- a systematic review.
    Resveratrol, a phytochemical known for its anti- oxidative properties has been explored worldwide for anticancer potential.
    We performed this systematic review and meta-analysis in order to register the efficacy of resveratrol against lung carcinogenesis.
    In all of the above studies involving either animal models or in vitro cancer cell experiments a statistically significant reduction in tumor incidence emerged as compared with the control groups, yielding a relative risk reduction of 0.64 (p=0.002).
    It can be concluded that resveratrol holds a good potential for future use as a highly efficient therapeutic agent to deal with deadly lung carcinogenesis.
    J BUON. 2016 Jul-Aug;21(4):950-953. PMID: 27685918

  • [5] The pharmacological assessment of resveratrol on preclinical models of rheumatoid arthritis through a systematic review and meta-analysis.
    Resveratrol/RES (3,5,4'-trihydroxy-trans-stilbene) is a natural compound found in many food items and red wine, which exhibits pleiotropic biological effects.
    This meta-analysis suggests that RES can be a clinically effective therapy for RA (Rheumatoid Arthritis), pending clinical trials.
    Eur J Pharmacol. 2021 Nov 5 ;910:174504. Epub 2021 Sep 11. PMID: 34520733

  • [6] The effects of resveratrol intervention on risk markers of cardiovascular health in overweight and obese subjects: a pooled analysis of randomized controlled trials.
    Resveratrol intervention significantly lowered total cholesterol (WMD, -0.19 mmol/L; 95% CI, -0.32 to -0.06; P = 0.004),
    systolic blood pressure (WMD, -2.26 mmHg; 95% CI, -4.82 to -0.49; P = 0.02),
    and fasting glucose (WMD, -0.22 mmol/L; 95% CI, -0.42 to -0.03; P = 0.03).
    Our subgroup analysis showed significant reductions in total cholesterol, systolic blood pressure, diastolic blood pressure, glucose, and insulin in subjects ingesting higher dose of resveratrol (≥300 mg/day).
    Our finding provides evidence that daily resveratrol consumption might be a candidate as an adjunct to pharmacological management to better prevent and control cardiovascular disease in overweight/obese individuals.
    Obes Rev. 2016 Jul 26. Epub 2016 Jul 26. PMID: 27456934

  • [7] Effects of a grape-supplemented diet on proliferation and Wnt signaling in the colonic mucosa are greatest for those over age 50 and with high arginine consumption.
    A diet rich in fruits and vegetables, and a grape-derived compound, resveratrol, have been linked to a reduced incidence of colon cancer.
    Thirty participants were placed on a low resveratrol diet and subsequently allocated to one of three groups ingesting 1/3-to-1 lb (0.15-0.45 kg) of grapes per day for 2 weeks.
    Dietary information was collected via 24-h recall.
    Colon biopsies for biomarker analysis were obtained pre- and post-grape and evaluated for the expression of Wnt pathway target genes and for markers of proliferation by RT-PCR and immunohistochemistry.
    The reduction in Wnt signaling and mucosal proliferation seen following short-term ingestion of 1/3-1 lb (0.15-0.45 kg) of grapes per day may reduce the risk of mutational events that can facilitate colon carcinogenesis.
    The potential benefit is most marked for high-risk older individuals and individuals whose diet is high in arginine intake.
    Dietary grape supplementation may play a role in colon cancer prevention for high-risk individuals.
    Nutr J. 2015 ;14(1):62. Epub 2015 Jun 19. PMID: 26085034

  • [8] Long-term effects of resveratrol on cognition, cerebrovascular function and cardio-metabolic markers in postmenopausal women: A 24-month randomised, double-blind, placebo-controlled, crossover study.
    Ageing and menopause contribute to endothelial dysfunction, causing impaired cerebral perfusion, which is in turn associated with accelerated cognitive decline.
    In a 14-week pilot study, we showed that supplementation with low-dose resveratrol, a phytoestrogen that can enhance endothelial function, improved cerebrovascular and cognitive functions in postmenopausal women.
    A 24-month randomized, placebo-controlled crossover trial was undertaken in 125 postmenopausal women, aged 45-85 years, who took 75 mg trans-resveratrol or placebo twice-daily for 12 months and then crossover to the alternative treatment for another 12 months.
    Compared to placebo, resveratrol supplementation resulted a significant 33% improvement in overall cognitive performance (Cohen's d = 0.170, P = 0.005).
    Women ≥65 years of age showed a relative improvement in verbal memory with resveratrol compared to those younger than 65 years.
    Regular supplementation with low-dose resveratrol can enhance cognition, cerebrovascular function and insulin sensitivity in postmenopausal women.
    This may translate into a slowing of the accelerated cognitive decline due to ageing and menopause, especially in late-life women.
    Clin Nutr. 2021 03 ;40(3):820-829. Epub 2020 Aug 27. PMID: 32900519

  • [9] Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients.
    Resveratrol is a phytochemical with chemo-preventive activity in preclinical rodent models of colorectal carcinogenesis.
    Consumption of resveratrol reduced tumor cell proliferation by 5% (P = 0.05).
    The results suggest that daily p.o. doses of resveratrol at 0.5 or 1.0 g produce levels in the human gastrointestinal tract of an order of magnitude sufficient to elicit anti-carcinogenic effects.
    Resveratrol merits further clinical evaluation as a potential colorectal cancer chemo-preventive agent.
    Antiviral Res. 2008 Feb;77(2):153-6. Epub 2007 Oct 8. PMID: 20841478

  • [10] Alteration of Hepatic Proinflammatory Cytokines is Involved in the Resveratrol-Mediated Chemoprevention of Chemically-Induced Hepatocarcinogenesis.
    Hepatocellular carcinoma (HCC)(Liver Cancer), one of the most common cancers in the world, is a leading cause of cancer-related mortality.
    HCC develops most frequently in the background of oxidative stress and chronic hepatic inflammation due to viral infections, alcohol abuse as well as exposure to environmental and dietary carcinogens.
    As the prognosis of HCC is extremely poor and mostly unresponsive to current chemotherapeutic treatment regimens, novel preventive approaches like chemoprevention are urgently needed.
    As cytokines are considered to be important mediators of inflammation, the objective of the present study was to investigate the effects of resveratrol on hepatic cytokines during DENA-initiated hepatocarcinogenesis in rats.
    Liver samples were harvested from our previous study in which resveratrol (50, 100 and 300 mg/kg) was found to exert a chemopreventive action against rat liver tumorigenesis induced by DENA.
    Resveratrol treatment reversed the DENA-induced alteration of the level and expression of hepatic TNF-α, IL-1β and IL-6.
    From the current results in conjunction with our previous findings, it can be concluded that resveratrol-mediated chemoprevention of rat liver carcinogenesis is related to alteration of proinflammatory cytokines.
    Curr Pharm Biotechnol. 2011 Apr 5. Epub 2011 Apr 5. PMID: 21466437

  • [11] Novel Application of Brain-Targeting Polyphenol Compounds in Sleep Deprivation-Induced Cognitive Dysfunction.
    Sleep deprivation produces deficits in hippocampal synaptic plasticity and hippocampal-dependent memory storage.
    We found that Bioactive Dietary Polyphenol Preparation BDPP significantly improves sleep deprivation-induced contextual memory deficits, possibly through the activation of CREB and mTOR signaling pathways.
    Our data suggests the feasibility of using select brain-targeting polyphenol compounds derived from BDPP as potential therapeutic agents in promoting resilience against sleep deprivation-induced cognitive dysfunction.
    Neurochem Int. 2015 Jul 30. Epub 2015 Jul 30. PMID: 26235983

  • [12] Mechanisms underlying vascular effect of chronic resveratrol in streptozotocin-diabetic rats.
    In this study, some underlying mechanisms responsible for the beneficial effect of chronic oral administration of resveratrol on aortic reactivity of streptozotocin (STZ)-diabetic rats were investigated.
    Male diabetic rats received resveratrol (10 mg/kg/day) for 8 weeks, 1 week after diabetes induction.
    Treatment of diabetic rats with resveratrol produced a hypoglycaemic effect and there were appropriate changes regarding serum lipids.
    Resveratrol also attenuated the increased malondialdehyde (MDA) content and reduced activity of superoxide dismutase (SOD) in liver and aortic tissues.
    Chronic treatment with resveratrol may prevent diabetes-related changes in vascular reactivity observed in diabetic rats directly and/or indirectly due to its hypoglycaemic and hypolipidaemic effects and attenuation of lipid peroxidation and through endothelial-derived factors.
    Phytother Res. 2009 Dec 9. PMID: 20013818

  • [13] Resveratrol and 1,25-dihydroxyvitamin D co-administration protects the heart against D-galactose-induced aging in rats: evaluation of serum and cardiac levels of klotho.
    The current study investigates the cooperative cardioprotective effect of calcitriol (active form of vitamin D) combined with resveratrol in a rat model of D-galactose ( aging.
    It could be concluded that co-administration of resveratrol and vitamin D protects the heart against aging-induced damage by the modulation of hemodynamic parameters and antioxidant status of the heart.
    Furthermore, increased serum level of klotho could be a novel mechanism for antiaging effects of resveratrol and vitamin D.
    Aging Clin Exp Res. 2018 Nov 27. Epub 2018 Nov 27. PMID: 30484255

  • [14] Liposome encapsulation of curcumin and resveratrol in combination reduces prostate cancer incidence in PTEN knockout mice.
    Increasing interest in the use of phytochemicals to reduce prostate cancer led us to investigate 2 potential agents, curcumin and resveratrol as preventive agents.
    Findings from this study for the first time provide evidence on phytochemicals in combination to enhance chemopreventive efficacy in prostate cancer. These findings clearly suggest that phytochemicals in combination may reduce prostate cancer incidence due to the loss of the tumor suppressor gene PTEN.
    Int J Cancer. 2009 Jul 1;125(1):1-8. PMID: 19326431

  • [15] Benzo(a)pyrene Induced p53 Mediated Male Germ Cell Apoptosis: Synergistic Protective Effects of Curcumin and Resveratrol.
    Curcumin and resveratrol are phytochemicals with cytoprotective and anti-oxidative properties.
    At the same time resveratrol is also a natural Aryl hydrocarbon Receptor (AhR) antagonist.
    Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted the synergistic protective effect of curcumin and resveratrol against B(a)P induced p53 mediated germ cell apoptosis.
    Curcumin-resveratrol significantly prevented B(a)P induced decrease in sperm cell count and motility, as well as increased serum testosterone level.
    Curcumin-resveratrol co-treatment actively protected B(a)P induced testicular germ cell apoptosis.
    The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.
    Front Pharmacol. 2016 ;7:245. Epub 2016 Aug 8. PMID: 27551266

  • [16] Curcumin and Resveratrol Regulate Intestinal Bacteria and Alleviate Intestinal Inflammation in Weaned Piglets.
    Human infants or piglets are vulnerable to intestinal microbe-caused disorders and inflammation due to their rapidly changing gut microbiota and immaturity of their immune systems at weaning.
    Resveratrol and curcumin have significant anti-inflammatory, bacteria-regulating and immune-promoting effects.
    Both curcumin and resveratrol down-regulated the level of Toll-like-receptor 4 mRNA and protein expression in the intestine to inhibit the release of critical inflammation molecules (interleukin-1β, tumor necrosis factor-α), and increase the secretion of immunoglobulin.
    Our results suggested that curcumin and resveratrol can regulate weaned piglet gut microbiota, down-regulate the TLR4 signaling pathway, alleviate intestinal inflammation, and ultimately increase intestinal immune function.
    Molecules. 2019 Mar 28 ;24(7). Epub 2019 Mar 28. PMID: 30925757

  • [17] TriCurin, a synergistic formulation of curcumin (Turmeric), resveratrol (Red Berries), and epicatechin gallate (Green Tea), repolarizes tumor-associated macrophages and triggers an immune response to cause suppression of HPV+ tumors.
    Our earlier studies reported a unique potentiated combination (TriCurin) of curcumin (C) with two other polyphenols.
    The TriCurin-associated C displays an IC50 in the low micromolar range for cultured HPV+ TC-1 cells.
    In contrast, because of rapid degradation in vivo, the TriCurin-associated C reaches only low nano-molar concentrations in the plasma, which are sub-lethal to tumor cells.
    Yet, injected TriCurin causes a dramatic suppression of tumors in TC-1 cell-implanted mice (TC-1 mice) and xenografts of Head and Neck Squamous Cell Carcinoma (HNSCC) cells in nude/nude mice.
    Cancer Immunol Immunother. 2018 Feb 16. Epub 2018 Feb 16. PMID: 29453519

  • [18] Dietary supplementation of resveratrol attenuates chronic colonic inflammation in mice.
    Ulcerative colitis is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration and upregulation of inflammatory mediators. Resveratrol is a polyphenolic compound found in grapes and wine, with multiple pharmacological actions, mainly anti-inflammatory, antioxidant, antitumour and immunomodulatory activities.
    Our results demonstrated that resveratrol group significantly attenuated the clinical signs such as loss of body weight, diarrhea and rectal bleeding improving results from disease activity index and inflammatory score.
    Moreover, the totality of resveratrol-fed animals survived and finished the treatment while animals fed with standard diet showed a mortality of 40%.
    We conclude that resveratrol diet represents a novel approach to the treatment of chronic intestinal inflammation.
    Asia Pac J Clin Nutr. 2010;19(1):142-50. PMID: 20132809

  • [19] Effect of prior treatment with resveratrol on density and structure of rat long bones under tail-suspension.
    Physical inactivity during space flight or prolonged bed rest causes rapid and marked loss of bone mass in humans.
    Resveratrol, a red wine polyphenol that is currently under study for its therapeutic antioxidant properties, has been shown to significantly modulate biomarkers of bone metabolism, i.e., to promote osteoblast differentiation and to prevent bone loss induced by estrogen deficiency.
    Rats were treated with 400 mg/kg/day of resveratrol for 45 days and half of them were suspended during the last 2 weeks of treatment.
    Suspension caused a decrease in tibial and femoral Bone Mass Density and deterioration of trabecular and cortical bone.
    Bone deterioration during suspension was paralleled by increased bone marrow area, which could be caused by an increase in stromal cells with osteoclastogenic potential or in adipocytes.
    Resveratrol had a preventive effect against bone loss induced by hindlimb immobilization.
    In particular, trabecular bone in the proximal tibial metaphysis was totally preserved in rats treated with resveratrol before tail-suspension.
    Neurology. 2007 Feb 20;68(8):563-8. PMID: 20458604

  • [20] Resveratrol alleviates alcoholic fatty liver in mice.
    Resveratrol, a dietary polyphenol, has been identified as a potent activator for both SIRT1 and AMPK.
    In conclusion, resveratrol treatment led to reduced lipid synthesis and increased rates of fatty acid oxidation and prevented alcoholic liver steatosis.
    Our study suggests that resveratrol may serve as a promising agent for preventing or treating human alcoholic fatty liver disease.
    Am J Physiol Gastrointest Liver Physiol. 2008 Oct;295(4):G833-42. Epub 2008 Aug 28. PMID: 18755807

  • [21] Differential effects of resveratrol and SRT1720 on lifespan of adult Caenorhabditis elegans.
    At a dose of 5 micromolar, which is pharmacologically relevant and 20 times lower than previously published concentrations, resveratrol significantly extends C. elegans lifespan by 3.6% (mean lifespan) and 3.4% (maximum lifespan).
    Thus, in the model organisms C. elegans, resveratrol is capable of promoting longevity at a concentration that pharmacologically relevant and 20 times lower than previously published doses.
    Horm Metab Res. 2010 Nov;42(12):837-9. Epub 2010 Oct 5. PMID: 20925017

  • [22] Antidiabetic activity of resveratrol, a known SIRT1 activator in a genetic model for type-2 diabetes.
    The results showed that resveratrol exhibited significant antihyperglycemic activity with an improvement in the insulin levels compared with the control mice. There was also a significant improvement observed in the glucose excursion in the oral glucose tolerance test performed for 120 min;
    The present findings suggest that resveratrol is an antihyperglycemic agent and drugs similar to resveratrol can be considered as an effective therapeutic adjuvant for the current treatment of diabetes mellitus.
    Phytother Res. 2011 Jan;25(1):67-73. PMID: 20623590
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