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Age-related macular degeneration (AMD) is one of the most prevalent eye diseases among the ageing population worldwide. It is a leading cause of blindness in individuals over 55, particularly in industrialised Western countries. The prevalence of AMD increases with age, and genetic factors and environmental influences are believed to contribute to its development. Among the environmental factors, diet plays a significant role in AMD. This review explores the association between dietary components, dietary patterns and AMD. Various nutrients, non-nutrient substances and dietary models that have the potential to counteract oxidative stress and inflammation, which are underlying mechanisms of AMD, are discussed. Consuming fruits, vegetables, fish and seafood, whole grains, olive oil, nuts and low-glycaemic-index foods has been highlighted as beneficial for reducing the risk of AMD. Adhering to the Mediterranean diet, which encompasses these elements, can be recommended as a dietary pattern for AMD. Furthermore, the modulation of the gut microbiota through dietary interventions and probiotics has shown promise in managing AMD.
Ulcerative Colitis (UC), a type of Inflammatory Bowel Disease (IBD), is a chronic, relapsing gastrointestinal condition with increasing global prevalence. The gut microbiome profile of people living with UC differs from healthy controls and this may play a role in the pathogenesis and clinical management of UC. Probiotics have been shown to induce remission in UC; however, their impact on the gut microbiome and inflammation is less clear. Anthocyanins, a flavonoid subclass, have shown anti-inflammatory and microbiota-modulating properties; however, this evidence is largely preclinical. To explore the combined effect and clinical significance of anthocyanins and a multi-strain probiotic, a 3-month randomised controlled trial will be conducted in 100 adults with UC. Participants will be randomly assigned to one of four groups: anthocyanins (blackcurrant powder) + placebo probiotic, probiotic + placebo fruit powder, anthocyanin + probiotic, or double placebo. The primary outcome is a clinically significant change in the health-related quality-of-life measured with the Inflammatory Bowel Disease Questionnaire-32. Secondary outcomes include shotgun metagenomic sequencing of the faecal microbiota, faecal calprotectin, symptom severity, and mood and cognitive tests. This research will identify the role of adjuvant anti-inflammatory dietary treatments in adults with UC and elucidate the relationship between the gut microbiome and inflammatory biomarkers in this disease, to help identify targeted individualised microbial therapies. ANZCTR registration ACTRN12623000630617.
Tea (Camellia sinensis (L.) Kuntze) leaves are an important beverage crop due to their high caffeine content. Although the north of Iran is the main region for high-quality tea plants, there is no document on variations of phenotypic traits of different accessions. The present study was to assess the biodiversity of 12 tea accessions originating from four tea main sites in Iran (Langroud, Siahkal, Kobijar and Bazkiaguorab) using multivariate analysis. Two-year-old tea plants were cultivated in a completely randomized design with five replicates in a greenhouse. One year after plant establishment, phenotypic characteristics were studied. The tea accessions showed different responses in chlorophyll and total ash contents. The highest and lowest amount of caffeine in tea accessions was found in Kobijar A7 and Langroud A2, respectively. Epicatechin was obtained in a 6.48–15.44 mg g−1 range, and the maximum variability was found in epigallocatechin gallate (EGCG), differing from 0.94 to 21.03 mg g−1. Langroud A2 and Bazkiaguorab A11 contained the maximum EGCG and the total polyphenolic content in Bazkiaguorab was greater than other accessions. Heat map analysis showed the maximum variability of EGCG, catechin, and GA among the accessions. The main essential oil compounds were 2-pentyl furan followed by hexanal, gamma-terpinene, octane, ortho-cymene, terpinen-4-ol, alpha-copaene and E-caryophyllene. In conclusion, changes in phytochemical traits caused by genetics and origin can significantly alter the quality of tea compounds. The results of this study can be utilized as raw materials in future breeding projects to improve new cultivars with superior characteristics.
This chapter concerns neuroprotective diets, and the use of particular diets and dietary components as an intervention. The first section examines the Mediterranean diet, with its beneficial effects – as prevention and intervention – on cognitive performance, mental health and neurodegeneration. The second section explores the DASH (dietary approaches to stop hypertension) diet, which has shown promise across the same set of conditions as the Mediterranean diet, and with probably a similar set of common mechanisms (e.g., reductions in inflammation and oxidative stress, plus benefits to the cardiovascular system). The third section looks at the ketogenic diet and its variants, with its high fat to carbohydrate ratio, originally and successfully developed for paediatric epilepsy, and its more recent use in other conditions (e.g., multiple sclerosis, brain tumours). The final part of the chapter reviews single nutrients, these being either examples of polyphenols or omega-3 fatty acids, with research focussing on mental health, aging and neurodegeneration.
Olive oil (OO) polyphenols have been shown to improve HDL anti-atherogenic function, thus demonstrating beneficial effects against cardiovascular risk factors. The aim of the present study was to investigate the effect of extra virgin high polyphenol olive oil (HPOO) v. low polyphenol olive oil (LPOO) on the capacity of HDL to promote cholesterol efflux in healthy adults. In a double-blind, randomised cross-over trial, fifty participants (aged 38·5 (sd 13·9) years, 66 % females) were supplemented with a daily dose (60 ml) of HPOO (320 mg/kg polyphenols) or LPOO (86 mg/kg polyphenols) for 3 weeks. Following a 2-week washout period, participants crossed over to the alternate treatment. Serum HDL-cholesterol efflux capacity, circulating lipids (i.e. total cholesterol, TAG, HDL, LDL) and anthropometrics were measured at baseline and follow-up. No significant between-group differences were observed. Furthermore, no significant changes in HDL-cholesterol efflux were found within either the LPOO and HPOO treatment arms; mean changes were 0·54 % (95 % CI (0·29, 1·37)) and 0·10 % (95 % CI (0·74, 0·94)), respectively. Serum HDL increased significantly after LPOO and HPOO intake by 0·13 mmol/l (95 % CI (0·04, 0·22)) and 0·10 mmol/l (95 % CI (0·02, 0·19)), respectively. A small but significant increase in LDL of 0·14 mmol/l (95 % CI (0·001, 0·28)) was observed following the HPOO intervention. Our results suggest that additional research is warranted to further understand the effect of OO with different phenolic content on mechanisms of cholesterol efflux via different pathways in multi-ethnic populations with diverse diets.
It is often stated that organic rice has a higher content of healthy phytochemicals than ordinary rice, and the facts on this claim obtained experimentally are rare. Riceberry is a new rice variety in Thailand. This study aimed to evaluate the effects of organic practice and conventional practice on the content of chemical composition and bioactive compounds in Riceberry rice. The results showed that agricultural practices were not significantly different for grain yield in the first year, but they were different in the second year. Rice produced by organic practice had a higher content of iron, gamma-aminobutyric acid, total phenolic and anthocyanin (4.15, 1.67, 41.3 and 20.1 mg/100 g dry weight in the first year, and 4.06, 3.37, 89.7 and 14.7 mg/100 g dry weight in the second year) than that produced by conventional practice (2.25, 1.11, 38.8 and 6.89 mg/100 g dry in the first year, and 1.96, 2.77, 54.1 and 5.71 mg/100 g dry in the second year). Rice produced by organic practice also had lower sugar content (2.92 g/100 g dry weight in the first year, and 1.99 g/100 g dry weight in the second year) than that produced by conventional practice (3.46 g/100 g dry weight in the first year, and 2.81 g/100 g dry weight in the second year). Gamma oryzanol and antioxidant capacity were also lower in organic rice compared to conventional rice. This study indicated that organic Riceberry rice had a higher quality compared to non-organic rice.
Assessing the dietary intake of polyphenols and their major food sources is the first step towards documenting the associations with health outcomes. Considering recent changes in dietary patterns of the Brazilian population, continuous monitoring of polyphenol intake is important. Thus, the present study was conducted to estimate the polyphenol intake and major food sources in the diet of the Brazilian population using data from the most recent National Dietary Survey (NDS, 2017–2018), to characterise the intake changes according to demographic characteristics and to compare the intake over the past decade in Brazil. Data from two cross-sectional population-based surveys were analyzed in the study. Trends in polyphenol intake and major food sources were estimated using food consumption data from NDS 2008–2009 (n 34 003) and 2017–2018 (n 46 164). The median (25–75th percentiles) of energy-adjusted polyphenol intake in 2017–2018 was 216·3 mg (125·3–495·2 mg) per 1000 kcal/d (4184 kJ/d), representing an increase of 12·3 mg/d from 2008–2009. However, unadjusted polyphenol intakes were similar between the surveys (medians: 364·3 mg/d in 2008–2009 and 366·9 mg/d in 2017–2018). The main food sources of total and polyphenol intake classes presented some variations between 2008–2009 and 2017–2018, with greater contribution of beans preparations, salads and tea to polyphenol intake, and decrease of orange contribution. Our study provided an updated information on polyphenol intake and its major food sources. The median intake remains lower than the reported by other populations. Furthermore, the results may contribute to future studies investigating temporal trends in polyphenol intake and disease risk.
Resveratrol supplementation during pregnancy and lactation has been associated with a reduced risk of maternal obesity, gestational diabetes mellitus , and preeclampsia. In addition, emerging evidence has shown that maternal resveratrol supplementation diminishes cardio-metabolic disorders in offspring, highlighting its role in modulating adaptative responses involving phenotypical plasticity. Therefore, it is reasonable to infer that administration of resveratrol during pregnancy and lactation periods could be considered an important nutritional intervention to decrease the risk of maternal and offspring cardio-metabolic disorders. To highlight these new insights, this literature review will summarize the understanding emerging from experimental and clinical studies about resveratrol supplementation and its capacity to prevent or minimize maternal and offspring cardio-metabolic disorders.
Olive oil and wine are consumed daily worldwide, and they constitute the fundamental pillars of the healthy Mediterranean diet. Polyphenolic compounds, naturally present in both olive oil and wine, are responsible for their beneficial properties. Current studies have shown the neuroprotective effects of polyphenols independently of their well-known antioxidant action. In this work, we have focused on reviewing the protective effect of polyphenols from extra virgin olive oil and wine in Alzheimer´s disease (AD), to emphasise that both foods could be a possible therapeutic tool. Beneficial effects have been described in β-aggregation, neurofibrillary tangles, autophagy and mitochondrial function, as well as in cerebral insulin resistance. Furthermore, to date, a harmful dose has not been described. Both pre-clinical and clinical works demonstrate that polyphenols act on neuropathological and cognitive disorders of AD, preventing or stopping the onset of this devastating disease. However, there are certain limitations in these studies, since it is very difficult to research diseases that lead to cognitive impairment. Although all the findings obtained are very encouraging, more studies should be carried out investigating the use of the polyphenols from olive oil and wine as therapeutic agents in the progression of AD. Therefore, more longitudinal studies in humans with a homogeneous cohort of patients are necessary to corroborate the efficacy of these nutraceuticals, as well as determine the most appropriate dose for this purpose.
Tea contains polyphenols such as flavonoids, anthocyanidins, flavanols and phenolic acids which in laboratory studies have reported to promote antioxidant enzyme formation, reduces excess inflammation, slow cancer cell proliferation and promote apoptosis. Evidence from epidemiological studies on the effect of tea consumption on prostate cancer (CaP) incidence has been conflicting. We analysed data from 25 097 men within the intervention arm of the 155 000 participant Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Histologically confirmed cases of prostate cancer were reported in 3088 men (12·3 %) during the median 11·5 year follow-up. Tea consumption was assessed with a FFQ. Baseline characteristics were compared between groups using χ2 and Kruskal–Wallis tests. Cox regression models were used to assess associations between tea intake and CaP incidence. There was no statistical difference between the risk of CaP between men who never drank tea to those who drank tea at any quantity. Amongst tea drinkers, those in the highest third of consumption group had a small but significantly lower risk compared with those in the lowest third (11·2 % v. 13·2 % hazard ratio 1·16; (95 % CI 1·05, 1·29), P = 0·004). This pattern persisted with adjustments for demographics and lifestyle. In conclusion, among tea drinkers, there was a small positive association between drinking tea and a reduced risk of prostate cancer. It does not support starting to drink tea, if men previously did not, to reduce the risk. Further research is needed to establish whether tea is justified for future prospective nutritional intervention studies investigating CaP prevention.
Flavonoids are natural polyphenol secondary metabolites that are widely produced in planta. Flavonoids are ubiquities in human dietary intake and exhibit a myriad of health benefits. Flavonoids-induced biological activities are strongly influenced by their in situ availability in the human GI tract, as well as the levels of which are modulated by interaction with the gut bacteria. As such, assessing flavonoids–microbiome interactions is considered a key to understand their physiological activities. Here, we review the interaction between the various classes of dietary flavonoids (flavonols, flavones, flavanones, isoflavones, flavan-3-ols and anthocyanins) and gut microbiota. We aim to provide a holistic overview of the nature and identity of flavonoids on diet and highlight how flavonoids chemical structure, metabolism and impact on humans and their microbiomes are interconnected. Emphasis is placed on how flavonoids and their biotransformation products affect gut microbiota population, influence gut homoeostasis and induce measurable physiological changes and biological benefits.
There is an inverse association between bioactive compounds intake and disease risk. The knowledge of its consumption according to socio-economic strata is important, which allows identification of potential intervention targets. Thus, we aimed to investigate bioactive compounds intake according to income level in Brazilian population. Data were obtained from the Brazilian Household Budget Survey, a cross-sectional survey which included data on individual food intake of 34,003 subjects aged 10 years and over collected using two 24-h dietary records. Polyphenol and carotenoid content of foods was identified using published databases. Total polyphenol and carotenoid intake were determined according to per capita income, as well as main food sources. Total polyphenols and flavonoids intake increased with income level, and subjects with lower income showed higher phenolic acids intake than individuals in highest income (p = 0.0001). Total carotenoids and classes intake (with exception to β-cryptoxanthin and zeaxanthin) were higher among subjects in highest income quartile, compared to the lowest quartile (p = 0.0001). Coffee was major source to total polyphenols and phenolic acids intake, and orange juice was main flavonoid provider in individuals from all income levels. In the upper income quartile, total carotenoid was supplied mainly by tomato and kale, and fruits had important contribution to carotenoid intake in the lowest income quartile. There is important influence of income level on diet quality regarding intake of foods with bioactive compounds, and individuals with lower income may experience lower quality diets due to less availability of foods with bioactive compounds.
We examine the validity and reproducibility of a food frequency questionnaire (FFQ) in a subsample of participants in the Japan Public Health Center-based Prospective Cohort Study using a database of polyphenol-containing foods commonly consumed in the Japanese population. Participants of the validation study were recruited from two different cohorts. In Cohort I, 215 participants completed a 28-d dietary record (DR) and the FFQ, and in Cohort II, 350 participants completed DRs and the FFQ. The total polyphenol intake estimated from the 28-d DR and FFQ were log-transformed and adjusted for energy intake by the residual method. Spearman correlation coefficients (CCs) between estimates from the FFQ and 28-d DR as well as two FFQs administered at a 1-year interval were computed. Median intakes of dietary polyphenols calculated from the DRs were 1172 mg/d for men and 1024 mg/d for women in Cohort I, and 1061 mg/d for men and 942 mg/d for women in Cohort II. The de-attenuated CCs for polyphenol intake between the DR and FFQ were 0⋅47 for men and 0⋅37 for women in Cohort I and 0⋅44 for men and 0⋅50 for women in Cohort II. Non-alcoholic beverages were the main contributor to total polyphenol intake in both men and women, accounting for 50 % of total polyphenol intake regardless of cohort and gender, followed by alcoholic beverages and seasoning and spices in men, and seasoning and spices, fruits and other vegetables in women. The present study showed that this FFQ had moderate validity and reproducibility and is suitable for use in future epidemiological studies.
Beneficial effects of probiotic, prebiotic and polyphenol-rich interventions on fasting lipid profiles have been reported, with changes in the gut microbiota composition believed to play an important role in lipid regulation. Primary bile acids, which are involved in the digestion of fats and cholesterol metabolism, can be converted by the gut microbiota to secondary bile acids, some species of which are less well reabsorbed and consequently may be excreted in the stool. This can lead to increased hepatic bile acid neo-synthesis, resulting in a net loss of circulating low-density lipoprotein. Bile acids may therefore provide a link between the gut microbiota and cardiovascular health. This narrative review presents an overview of bile acid metabolism and the role of probiotics, prebiotics and polyphenol-rich foods in modulating circulating cardiovascular disease (CVD) risk markers and bile acids. Although findings from human studies are inconsistent, there is growing evidence for associations between these dietary components and improved lipid CVD risk markers, attributed to modulation of the gut microbiota and bile acid metabolism. These include increased bile acid neo-synthesis, due to bile sequestering action, bile salt metabolising activity and effects of short-chain fatty acids generated through bacterial fermentation of fibres. Animal studies have demonstrated effects on the FXR/FGF-15 axis and hepatic genes involved in bile acid synthesis (CYP7A1) and cholesterol synthesis (SREBP and HMGR). Further human studies are needed to determine the relationship between diet and bile acid metabolism and whether circulating bile acids can be utilised as a potential CVD risk biomarker.
Spot urinary polyphenols have potential as a biomarker of polyphenol-rich food intakes. The aim of this study is to explore the relationship between spot urinary polyphenols and polyphenol intakes from polyphenol-rich food sources. Young adults (18–24 years old) were recruited into a sub-study of an online intervention aimed at improving diet quality. Participants’ intake of polyphenols and polyphenol-rich foods was assessed at baseline and 3 months using repeated 24-h recalls. A spot urine sample was collected at each session, with samples analysed for polyphenol metabolites using LC-MS. To assess the strength of the relationship between urinary polyphenols and dietary polyphenols, Spearman correlations were used. Linear mixed models further evaluated the relationship between polyphenol intakes and urinary excretion. Total urinary polyphenols and hippuric acid (HA) demonstrated moderate correlation with total polyphenol intakes (rs = 0·29–0·47). HA and caffeic acid were moderately correlated with polyphenols from tea/coffee (rs = 0·26–0·46). Using linear mixed models, increases in intakes of total polyphenols or polyphenols from tea/coffee or oil resulted in a greater excretion of HA, whereas a negative relationship was observed between soya polyphenols and HA, suggesting that participants with higher intakes of soya polyphenols had a lower excretion of HA. Findings suggest that total urinary polyphenols may be a promising biomarker of total polyphenol intakes foods and drinks and that HA may be a biomarker of total polyphenol intakes and polyphenols from tea/coffee. Caffeic acid warrants further investigation as a potential biomarker of polyphenols from tea/coffee.
Accumulating evidence indicates that dietary phenolic compounds can prevent obesity-related disorders. We investigated whether the consumption of polyphenol-rich jabuticaba peel and seed powder (JPSP) could ameliorate the progression of diet-induced obesity in mice. Male mice were fed a control diet or a high-fat (HF) diet for 9 weeks. After this period, mice were fed control, HF or HF diets supplemented with 5 % (HF-J5), 10 % (HF-J10) or 15 % (HF-J15) of JPSP, for 4 additional weeks. Supplementation with JPSP not only attenuated HF-induced weight gain and fat accumulation but also ameliorated the pro-inflammatory response associated with obesity, as evidenced by the absence of mast cells in the visceral depot accompanied by lower IL-6 and TNF-α at the tissue and circulating levels. JPSP-supplemented mice also exhibited smaller-sized adipocytes, reduced levels of leptin and higher levels of adiponectin, concomitant with improved glucose metabolism and insulin sensitivity. The magnitude of the observed effects was dependent on JPSP concentration with HF-J10- and HF-J15-fed mice showing metabolic profiles similar to control. This study reveals that the consumption of JPSP protects against the dysfunction of the adipose tissue and metabolic disturbances in obese mice. Thus, these findings indicate the therapeutic potential of the phenolic-rich JPSP in preventing obesity-related disorders.
Gallic acid (GA) is widely used as a dietary supplement due to several health-promoting effects, although its effects on intestinal-epithelial-cell integrity and transport remain mostly unknown. The present study aims to clarify the effects of GA on tight junctions and intestinal nutrient uptake through in vitro and ex vivo models. Both intestinal porcine enterocyte cell line-J2 cells and porcine middle-jejunum segments were treated with 5 (T5), 25 (T25) and 50 (T50) µm GA and mounted in Ussing chambers to determine transepithelial resistance (TEER), claudin-1 (CLDN1), occludin (OCLN), zonula occludens-1 (ZO-1) protein (in tissues and cells) and mRNA (in cells) expression. In addition, uptake of l-glutamate (l-Glut), l-arginine (l-Arg), l-lysine (l-Lys) and l-methionine (l-Meth) together with cationic-amino-acid transporter-1 (CAT-1) and excitatory-amino-acid transporter-3 (EAAT3) expression was evaluated. No apoptosis was observed in GA-treated cells, but TEER and CLDN1 protein abundance was lower with T50 compared with untreated cells. l-Arg and l-Lys uptake was greater with T5 than with T25 and T50. Ex vivo, T50 decreased the TEER values and the protein levels of CLDN1, OCLN and ZO-1, whereas T5 and T25 only decreased CLDN1 protein expression compared with untreated tissues. Moreover, T25 increased l-Glut and l-Arg uptake, the latter confirmed by an increased protein expression of CAT-1. GA influences intestinal uptake of the tested cationic amino acids at low concentrations and decreases the intestinal-cell barrier function at high concentrations. Similarities were observed between in vitro and ex vivo, but different treatment times and structures must be considered.
Epidemiological studies have suggested an inverse association between polyphenol intake and the risk of chronic diseases. However, the lack of comprehensive data on population-level intakes, especially in Latin American countries, has limited research on this topic. We aimed to estimate total and individual polyphenol intakes and determine the major dietary contributors in a representative sample of the Brazilian population. Data were obtained from the Brazilian Household Budget Survey, a cross-sectional survey which included data on individual food intake of 34 003 subjects aged 10 years and over collected using two 24-h dietary records. Polyphenol content of foods was identified using the Phenol-Explorer database and Brazilian Food Composition Database. Total and individual polyphenol intake was calculated, as well as the intake distribution by socio-demographic factors. The median and 25–75th percentiles of polyphenol intake were 364·3 and 200·9–1008 mg/d, respectively. After energy adjustment, the median and 25–75th percentiles of polyphenol intake were 204 and 111·4–542·1 mg/1000 kcal/d (4184 kJ/d), respectively. Non-alcoholic beverages and fruits were the major polyphenol suppliers, and coffee and orange juice the main individual food contributors to polyphenol intake. The individual compounds most consumed were isomers of chlorogenic acid (5-caffeoylquinic acid, 4-caffeoylquinic acid, 3-caffeoylquinic acid), naringenin and hesperetin. The present study provides, for the first time, data on dietary intake of total and individual polyphenols by the Brazilian population and illustrates the low quality of their diet. These results will facilitate the study of associations between polyphenol class intake and health outcomes, and will also be useful for future dietary intake recommendations.
The global growing rates of cognitive decline and dementia, together with the absence of curative therapies for these conditions, support the interest in researching potential primary prevention interventions, with particular focus on dietary habits. The aim was to assess the association between polyphenol intake and 6-year change in cognitive function in the ‘Seguimiento Universidad de Navarra’ (SUN) Project, a Spanish prospective cohort study. Changes (final – initial) in cognitive function were evaluated in a subsample of 806 participants (mean age 66 (sd 5) years, 69·7 % male) of the SUN Project using the validated Spanish Telephone Interview for Cognitive Status-modified score. Polyphenol intake was derived from a validated semi-quantitative FFQ and matching food composition data from the Phenol-Explorer database. Multivariable linear regression models were used to evaluate the association between total polyphenol intake, polyphenol subclasses and cognitive changes. No significant association between total polyphenol intake and changes in cognitive function was found. However, a higher intake of lignans (βQuintile (Q) 5 v. Q1 0·81; 95 % CI 0·12, 1·51; Ptrend = 0·020) and stilbenes (βQ5 v. Q1 0·82; 95 % CI 0·15, 1·49; Ptrend = 0·028) was associated with more favourable changes in cognitive function over time, particularly with respect to immediate memory and language domains. Olive oil and nuts were the major sources of variability in lignan intake, and wine in stilbene intake. The results suggest that lignan and stilbene intake was associated with improvements in cognitive function.
Although grape polyphenols can decrease chronic inflammations, their effect on C-reactive protein (CRP) levels is still controversial. So, this meta-analysis was conducted to investigate the effect of grape products containing polyphenols on CRP concentrations. In order to collect the relevant randomised controlled trials (RCT), the databases of PubMed, Scopus, Web of Science and Google Scholar were searched up to 30 March 2020. The random effects model, standardised mean difference (SMD) and 95 % CI were applied in data analysis. Meta-analysis was conducted over seventeen eligible RCT containing a total of 668 participants. The study registration number is CRD42018110169. Based on the results, grape products containing polyphenols decreased CRP levels significantly (SMD = −0·229; 95 % CI −0·41, −0·05; P = 0·013). Sensitivity analysis was performed by removing each individual study and the results did not change. According to the subgroup analysis, higher doses of grape polyphenols (>500 mg/d) and longer intervention periods (≥12 weeks) had significant effects on CRP levels. Furthermore, grape polyphenols significantly reduced the CRP levels in patients with a clinical condition. In the same vein, grape seed extract and other grape products, such as grape extract, juice and raisins, decreased CRP levels significantly. According to the meta-regression results, the CRP level depends on the dose and duration of the grape polyphenol supplementation. Based on the findings, grape products containing polyphenols had a significant effect on CRP levels. Further well-designed and long-term clinical trials are highly recommended to achieve more comprehensive and accurate results.