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Exploring the Therapeutic Potential of Phytochemicals in Alzheimer's Disease: Focus on Polyphenols and Monoterpenes.
Piccialli, I, Tedeschi, V, Caputo, L, D'Errico, S, Ciccone, R, De Feo, V, Secondo, A, Pannaccione, A
Frontiers in pharmacology. 2022;13:876614
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Alzheimer’s disease (AD) is a complex chronic neurodegenerative disorder characterized by the irreversible loss of memory and brain functions. Many different hypotheses are circulating to explain the underlying cause of the disease, yet therapeutic strategies to treat the degenerative processes have been unsuccessful to date. In recent years research has broadened its focus, viewing the pathology of AD more as an interplay of many factors whilst also taking into account other comorbidities associated with AD, such as insulin resistance and low energy production in the brain. One of the big challenges for clinical treatment is that by the time symptoms present and the diagnosis is made, irreversible brain loss has already occurred. Many lifestyle interventions can influence the modifiable risk factors of ageing and hence present a promising preventative strategy for AD. Plant-derived compounds found in foods and medicinal herbs have received much interest due to their versatile action potential. This review specifically looked at compounds in the polyphenols and monoterpenes category and summarized the current evidence, possible mechanisms of action and how this could aid AD management. An overview of the various hypothesis believed to contribute to the development of AD is presented. These include Aβ aggregation and toxicity, Tau hyperphosphorylation and toxicity, oxidative stress and mitochondrial dysfunction, neuroinflammation and brain insulin resistance. A synopsis of the current state of treatments and treatment development is provided, before exploring the potential of plant-derived compounds, in particular polyphenols and monoterpenes and their potential from various sources. Concluding remarks discuss the challenges that come with turning plant-derived compounds into drug treatments. Many studies on mechanisms of action show therapeutic potential, clinical trials in humans have not yet managed to mirror those effects sufficiently. There is a need to advance the field further and assess more thoroughly the clinical relevance of these findings. This review yields a comprehensive and detailed summary of aspects of AD, the proposed mechanisms and the potential of some nutrition related management options.
Abstract
Alzheimer's disease (AD) is a chronic, complex neurodegenerative disorder mainly characterized by the irreversible loss of memory and cognitive functions. Different hypotheses have been proposed thus far to explain the etiology of this devastating disorder, including those centered on the Amyloid-β (Aβ) peptide aggregation, Tau hyperphosphorylation, neuroinflammation and oxidative stress. Nonetheless, the therapeutic strategies conceived thus far to treat AD neurodegeneration have proven unsuccessful, probably due to the use of single-target drugs unable to arrest the progressive deterioration of brain functions. For this reason, the theoretical description of the AD etiology has recently switched from over-emphasizing a single deleterious process to considering AD neurodegeneration as the result of different pathogenic mechanisms and their interplay. Moreover, much relevance has recently been conferred to several comorbidities inducing insulin resistance and brain energy hypometabolism, including diabetes and obesity. As consequence, much interest is currently accorded in AD treatment to a multi-target approach interfering with different pathways at the same time, and to life-style interventions aimed at preventing the modifiable risk-factors strictly associated with aging. In this context, phytochemical compounds are emerging as an enormous source to draw on in the search for multi-target agents completing or assisting the traditional pharmacological medicine. Intriguingly, many plant-derived compounds have proven their efficacy in counteracting several pathogenic processes such as the Aβ aggregation, neuroinflammation, oxidative stress and insulin resistance. Many strategies have also been conceived to overcome the limitations of some promising phytochemicals related to their poor pharmacokinetic profiles, including nanotechnology and synthetic routes. Considering the emerging therapeutic potential of natural medicine, the aim of the present review is therefore to highlight the most promising phytochemical compounds belonging to two major classes, polyphenols and monoterpenes, and to report the main findings about their mechanisms of action relating to the AD pathogenesis.
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Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.
Yang, K, Chen, J, Zhang, T, Yuan, X, Ge, A, Wang, S, Xu, H, Zeng, L, Ge, J
Frontiers in immunology. 2022;13:949746
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Non-alcoholic fatty liver disease (NAFLD) is characterised by fat accumulation in the liver that can result in liver damage. NAFLD affects approximately 25% of the global population. There is evidence that dietary polyphenols can improve metabolism and insulin resistance and reduce inflammation and oxidative stress, which are the mechanisms that lead to liver damage in NAFLD. This systematic review and meta-analysis aimed to assess the effectiveness of dietary polyphenols in the treatment of non-alcoholic fatty liver disease (NAFLD). Eight dietary polyphenols, such as curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein, were evaluated for their efficacy and safety. The administration of 80-3,000 mg of Curcumin for an 8-12 week duration is effective and safe for reducing body mass index, aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TG), total cholesterol (TC), and insulin resistance (HOMA-IR). Compared with the placebo, Naringenin reduced the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol. Hesperidin may potentially decrease body mass index (BMI), AST, ALT, TG, TC, and HOMA-IR. Catechin is safe, and 500-1000 mg supplementation for 12 weeks may reduce BMI, HOMA-IR, and TG. NAFLD patients who received silymarin showed improvements in ALT and AST, as well as reductions in hepatic fat accumulation and liver stiffness. 94–2100 mg of Silymarin supplementation for 8–48 weeks may reduce liver enzyme levels. Researchers can use the results of this study to understand the clinical utility of different polyphenol supplements in the treatment of NAFLD. Because the current evidence is highly heterogeneous in nature and limited in scope, further robust research is required on various classes of polyphenols and their effectiveness in reducing the severity of NAFLD.
Abstract
Background: Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD. Methods: The literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis. Results: The RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from Cornus mas L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients. Conclusion: Based on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.
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Curcumin Supplementation (Meriva®) Modulates Inflammation, Lipid Peroxidation and Gut Microbiota Composition in Chronic Kidney Disease.
Pivari, F, Mingione, A, Piazzini, G, Ceccarani, C, Ottaviano, E, Brasacchio, C, Dei Cas, M, Vischi, M, Cozzolino, MG, Fogagnolo, P, et al
Nutrients. 2022;14(1)
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Chronic kidney disease (CKD) is a disease associated with the body experiencing inflammation. Curcumin is a traditional herbal remedy found in turmeric, which is known to have anti-inflammatory properties. Curcumin is poorly absorbed and so formulations which increase absorption have been developed including one marketed as Meriva, which has an optimised formulation using lipids for absorption. This study of 24 individuals with CKD and 20 healthy individuals aimed to determine if supplementation was safe and its effects on inflammation and other clinical markers of disease. The study showed that after 6 months of curcumin supplementation inflammation was reduced, there was a change in gut microbiome composition and supplementation was safe. It was concluded that gut microbiome composition and inflammation associated with CKD were improved following curcumin supplementation and that stabilisation of disease was observed. This study could be used by health care professionals to understand that the supplementation of curcumin may be of benefit to individuals with CKD.
Abstract
Chronic kidney disease (CKD) subjects suffer from high risk of cardiovascular mortality, and any intervention preventing the progression of CKD may have an enormous impact on public health. In the last decade, there has been growing awareness that the gut microbiota (GM) can play a pivotal role in controlling the pathogenesis of systemic inflammatory state and CKD progression. To ameliorate the quality of life in CKD subjects, the use of dietary supplements has increased over time. Among those, curcumin has demonstrated significant in vitro anti-inflammatory properties. In this pilot study, 24 CKD patients and 20 healthy volunteers were recruited. CKD patients followed nutritional counselling and were supplemented with curcumin (Meriva®) for six months. Different parameters were evaluated at baseline and after 3-6 months: uremic toxins, metagenomic of GM, and nutritional, inflammatory, and oxidative status. Curcumin significantly reduced plasma pro-inflammatory mediators (CCL-2, IFN-γ, and IL-4) and lipid peroxidation. Regarding GM, after 6 months of curcumin supplementation, Escherichia-Shigella was significantly lower, while Lachnoclostridium was significant higher. Notably, at family level, Lactobacillaceae spp. were found significantly higher in the last 3 months of supplementation. No adverse events were observed in the supplemented group, confirming the good safety profile of curcumin phytosome after long-term administration.
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The Effect of Curcumin on Lipid Profile and Glycemic Status of Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.
Tian, J, Feng, B, Tian, Z
Evidence-based complementary and alternative medicine : eCAM. 2022;2022:8278744
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Dyslipidaemia is a common comorbidity of type 2 diabetes mellitus (T2DM), which is characterised by elevated triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) level, and/or decreased high-density lipoprotein cholesterol (HDL-c) concentrate serum. Dyslipidaemia and dysglycemia interact with each other, and they are the main risk factors of macro- and microvascular diseases in T2DM. The aim of this study was to outline curcumin’s efficacy and possible uses in clinical practice. This study is a meta-analysis of nine randomised controlled trials (RCTs). A total of 604 participants (284 in the curcumin group and 281 in the control group) were included in the selected studies. The design of all trials was parallel; seven of them were double-blind RCTs, and the other two were open label RCTs. Results show that curcumin significantly decreased TG, TC, fasting blood glucose, and haemoglobin A1C levels and also led to a reduction in LDL-c and an elevation in HDL-c concentration, although with no statistical difference. Authors conclude that curcumin has promising effects on the lipid profile and glycaemic status in patients with T2DM. It indicated that curcumin might be a favourable therapeutic option for T2DM patients with mixed dyslipidaemia.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Dyslipidemia and dysglycemia interact with each other, and are risk factors of macro- and microvascular diseases in T2DM.
Although effective intervention strategies exist for improving glycemic status of T2DM patients, they often need lipid-lowering drugs simultaneously to prevent CVD.
- Novel therapeutic interventions are needed to manage dyslipidemia and dysglycemia in diabetic patients, when statin therapy to treat dyslipidemia, may increase the risk of new-onset diabetes and myopathy.
- Other clinical studies have highlighted the benefits of curcumin supplementation on lipid profile and glycemic status. Clarifying its effects is important for assessing its potential as an alternative and complementary medicine on improving the metabolic status of T2DM patients.
- Overall there is limited evidence and further research is required.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This meta-analysis aimed to evaluate the effects of curcumin on lipid profile in patients with type 2 diabetes mellitus (T2DM), including: serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-c), and/or high-density lipoprotein cholesterol (HDL-c). Fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) were also assessed.
Methods
A search was performed on Pubmed, Embase, Web of Sciences, and the Cochrane Library up to March 2022. Quality assessment of all included studies was performed.
Results
9 studies were included in the review, with a total of 604 participants (284 in the curcumin group and 281 in the control group) of mean age from 41 to 60.95 years. Curcumin forms varied among the studies including, turmeric, curcuminoids, and curcumin. The dosage of curcumin in the intervention group ranged from 80 to 2100 mg/day. The duration of intervention was between 4 weeks and 3 months in different studies.
- Effect of Curcumin on TG: A difference was observed between curcumin supplementation and control (p = 0.03), indicating curcumin could reduce serum TG.
- Effect of Curcumin on TC: The mean difference in net changes of TC between intervention and control groups was −8.91mg/dL (p = 0.001), suggesting that curcumin could decrease serum TC.
- Effect of Curcumin on LDL-C: No difference in the net change of LDL-c between intervention and control groups (p = 0.26).
- Effect of Curcumin on HDL-C: No difference in HDL-c between intervention and control groups (p = 0.56).
- Effect of Curcumin on FBG: Curcumin reduced blood glucose levels compared with control treatment (p = 0.002). The effect was greater in trials with the treatment duration >8w (p = 0.037), curcumin dose >100mg/day (p = 0.004), and with the participants receiving the other therapy (p = 0.002).
- Effect of Curcumin on HbA1c: HbA1c (%) decreased in the intervention group compared with the control group (p ≤ 0.001).
Conclusion
Curcumin has promising effects on the lipid profile and glycemic status of T2DM patients and might be a therapeutic option for T2DM patients with mixed dyslipidemia.
Clinical practice applications:
- Limitations were the small number of included studies, mostly with small sample sizes. In some studies, treatment duration was short (<2 months) and may be insufficient to see a difference in some metabolic parameters.
- The reduction of FBG and HbA1c after treatment with curcumin suggested that it improved the glycemic metabolism in the T2DM patients studied.
- Studies have shown that curcumin could promote insulin release through inducing β-cell electrical activity and lower serum glucose level via decreasing the production of hepatic glucose and increasing glucose uptake. While changes of LDL-c and HDL-c was not statistically significant, the authors note the effect of curcumin on LDL-c/HDL-c and its potential clinical significance could not be neglected.
- The reduction of dyslipidemia by curcumin supplementation could improve the glucose metabolic status of T2DM patients, and multiple molecular targets including PPAR-c, cholesteryl ester transfer protein, and lipoprotein lipase contribute to the beneficial effects of curcumin.
Considerations for future research:
- While significant heterogeneity was found in pooled analyses of TG, LDL-c, FBG, and Hb1Ac, a random-effects model revealed that trial duration, curcumin dosage, and other therapy may contribute to the variation in pooled effects, and these aspects could be discussed in future studies.
- The study found that a higher dose of curcumin was more powerful in reducing plasma TG and FBG concentrations, but further large-scale multicenter RCTs are required to confirm the clinical improvement of curcumin.
Abstract
Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder, some natural compounds are thought to be beneficial in improving the metabolic status of patients with T2DM. Curcumin is the main bioactive agent of turmeric, the impact of curcumin on T2DM is still controversial. This meta-analysis aimed to evaluate the effects of curcumin on lipids profile and glucose status in patients with T2DM. Randomized controlled trials (RCTs) examining the effects of curcumin on lipids profile and glycemic control of T2DM patients were searched in PubMed, Embase, Web of Science and Cochrane Library. Pooled estimates of weighted mean difference (WMD) were calculated between intervention and control groups using random-effects or fixed-effects model. Subgroup and sensitivity analyses were conducted to assess the effects. Nine eligible RCT with 604 subjects were included. The estimated pooled mean changes with curcumin were -18.97 mg/dL (95% CI: -36.47 to -1.47; P=0.03) for triglyceride (TG), -8.91 mg/dL (95% CI: -14.18 to -3.63, P=0.001) for total cholesterol (TC), -4.01 mg/dL (95% CI: -10.96 to 2.95, P=0.259) for low density lipoprotein cholesterol (LDL-c), 0.32 mg/dL (95% CI: -0.74 to 1.37, P=0.557) for high density lipoprotein cholesterol (HDL-c), -8.85 mg/dL (95% CI: -14.4 to -3.29, P=0.002) for fasting blood glucose (FBG), -0.54 (95% CI: -0.81 to -0.27, P ≤ 0.001) for glycated hemoglobin (HbA1c) (%) compared with controls. There was a significant heterogeneity for the influence of curcumin on TG, LDL-c, FBG and HbA1c. Subgroup analysis revealed that the heterogeneity mainly attributed to trial period, curcumin dosage and other therapy. The results of this study showed that curcumin supplementation had beneficial effects on glycemic status and some lipid parameters in patients with T2DM. Further studies with large-scale are still needed to confirm the results.
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Effects of curcumin and/or coenzyme Q10 supplementation on metabolic control in subjects with metabolic syndrome: a randomized clinical trial.
Sangouni, AA, Taghdir, M, Mirahmadi, J, Sepandi, M, Parastouei, K
Nutrition journal. 2022;21(1):62
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Metabolic syndrome (MetS) is a cluster of metabolic disorders such as hyperlipidaemia, hypertension, hyperglycaemia, insulin resistance, and abdominal obesity. MetS is associated with cardiovascular disease (CVD), type 2 diabetes mellitus and non-alcoholic fatty liver disease. The aim of this study was to investigate the effects of curcumin and/or coenzyme Q10 supplementation on metabolic syndrome components in subjects with MetS. This study is a 2×2 factorial, randomised, double-blinded, placebo-controlled study which was conducted for 12 weeks. Eighty-eight subjects were randomly assigned into four groups. All subjects completed the trial. Results show that curcumin supplementation improves lipid profile, but it does not have any effect on body composition, hypertension and fasting plasma glucose. However, supplementation with coenzyme Q10 as well as curcumin plus coenzyme Q10 did not show any significant effects on lipid profile, body composition, hypertension and fasting plasma glucose. Authors conclude that curcumin supplementation (especially by its effects on dyslipidaemia) is more effective than coenzyme Q10 as well as the combination of curcumin and coenzyme Q10 in the management of MetS. However, curcumin, coenzyme Q10 and their combination have no effect on body composition, hypertension and glycaemic control.
Abstract
BACKGROUND Metabolic syndrome (MetS) as a cluster of conditions including hyperlipidemia, hypertension, hyperglycemia, insulin resistance, and abdominal obesity is linked to cardiovascular diseases and type 2 diabetes. Evidence suggested that intake of curcumin and coenzyme Q10 may have therapeutic effects in the management of MetS. AIMS We investigated the effects of curcumin and/or coenzyme Q10 supplementation on metabolic syndrome components including systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference (WC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-c) and fasting plasma glucose (FPG) as primary outcomes, and total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c) and body mass index (BMI) as secondary outcomes in subjects with MetS. METHODS In this 2 × 2 factorial, randomized, double-blinded, placebo-controlled study, 88 subjects with MetS were randomly assigned into four groups including curcumin plus placebo (CP), or coenzyme Q10 plus placebo (QP), or curcumin plus coenzyme Q10 (CQ), or double placebo (DP) for 12 weeks. RESULTS The CP group compared with the three other groups showed a significant reduction in HDL-c (P = 0.001), TG (P < 0.001), TC (P < 0.001), and LDL-c (P < 0.001). No significant differences were seen between the four groups in terms of SBP, DBP, FPG, WC, BMI and weight. CONCLUSION Curcumin improved dyslipidemia, but had no effect on body composition, hypertension and glycemic control. Furthermore, coenzyme Q10 as well as the combination of curcumin and coenzyme Q10 showed no therapeutic effects in subjects with MetS. The trial was registered on 09/21/2018 at the Iranian clinical trials website (IRCT20180201038585N2), URL: https://www.irct.ir/trial/32518 .
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Precision Nutrition and Cancer Relapse Prevention: A Systematic Literature Review.
Reglero, C, Reglero, G
Nutrients. 2019;11(11)
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This article looks at the role food plays in precision medicine and nutrition therapies targeting cancers, specifically the mechanistic role of bioactive phytochemicals and their interaction with tumour progression, metastasis, and chemo-resistance. The term precision medicine represents the advances in genomics, metabolomics, and proteomics which have made cancer treatments more targeted and ‘precise’. Lung, breast, prostate and colon cancers account for a 49.2% mortality rate amongst cancers. Relapses worsen the prognosis of patients. This review aims to provide a better understanding of metabolic variation between nutrients, metabolism, microbiota, and related genes, which may help to develop adjuvant cancer therapies for the above cancers. 35 studies from 2017-2019 were selected: 20 on polyphenols, 3 on lipids (omega 3) and 12 on bioactive plant extracts. Epigallocatechin-gallate (EGCG), a flavonoid present in green tea, is shown to inhibit tumour cell growth. Curcumin modulates gene expression and critical anti-apoptotic effectors and enhances the effect of some targeted drugs used in cancer treatment. Bioactive lipid docosahexaenoic acid (DHA) induces apoptosis and has inhibitory effects on breast cancer cells growth. Ginger is shown to have an antiproliferative impact on cancer cell growth. Grape seed extract was associated with antitumor effect in colon cancer in combination with curcumin. Bioavailability of these extracts is discussed as a barrier to clinical use. Precision nutritional therapies are seen as a new era in the treatment of cancer and precision medicine but the review concludes that more research is necessary.
Abstract
Cancer mortality rates are undergoing a global downward trend; however, metastasis and relapse after surgery and adjuvant treatments still correlate with poor prognosis and represent the most significant challenges in the treatment of this disease. Advances in genomics, metabolomics, and proteomics are improving our understanding regarding cancer metabolic diversity, resulting in detailed classifications of tumors and raising the effectiveness of precision medicine. Likewise, the growing knowledge of interactions between nutrients and the expression of certain genes could lead to cancer therapies based on precision nutrition strategies. This review aims to identify the recent advances in the knowledge of the mechanistic role of bioactive phytochemicals in foodstuffs in tumor progression, metastasis, and chemo-resistance in order to assess their potential use in precision nutrition therapies targeting relapse in lung, breast, colon, and prostate cancer, and leukemia. A considerable number of bioactive phytochemicals in foodstuffs were identified in the literature with proven effects modulating tumor growth, progression, and metastasis. In addition, the use of foodstuffs in cancer, and specifically in relapse therapies, is being reinforced by the development of different formulations that significantly increase the therapeutic efficiency of these products. This can open the possibility for testing combinations of bioactive phytochemicals with cancer relapse treatments as a potential prevention strategy.
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Dietary phytochemicals in breast cancer research: anticancer effects and potential utility for effective chemoprevention.
Kapinova, A, Kubatka, P, Golubnitschaja, O, Kello, M, Zubor, P, Solar, P, Pec, M
Environmental health and preventive medicine. 2018;23(1):36
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Bioactive phytochemicals are continually being studied for their role in cancer prevention with increasing evidence for flavonoids, carotenoids, phenolic acids, and organosulfur compounds (found in cruciferous vegetables). This 2018 review explores the protective effects of a broad spectrum of plant-derived substances. In total, more than 5000 individual phytochemicals have been identified in plant-derived foods, such as fruits, vegetables, and grains. These bioactive compounds have been shown to have antitumor activity, reduce inflammation, induce apoptosis (cell death), inhibit the proliferation of aggressive tumour cells, and impact on metastasis (migration of cancer cells). Specifically, in breast cancer, a few studies have examined phytochemicals on cancer stem cells (the originating tumour cells) and found that curcumin, genistein, indol-3-carbinol, c-phycocyanin, resveratrol, and quercetin downregulated their activity. Systematic reviews of dietary patterns and breast cancer show vegetables, and especially fibre, to be consistently protective against reduced risk of mammary carcinogenesis. Dietary polyphenols are considered a cost-effective approach to cancer care however there is still a lack of evidence due to the complex nature of combined phytochemicals versus isolated agents. Wholefood consumption is considered to improve bioavailability compared to supplementation however phytochemicals are a low-dose component of foods. There is also concern that some phytochemicals may act as carcinogens or tumour promoters (for example, beta-carotene). More clinical trials are required to fully understand phytochemicals and breast cancer care.
Abstract
Cancerous tissue transformation developing usually over years or even decades of life is a highly complex process involving strong stressors damaging DNA, chronic inflammation, comprehensive interaction between relevant molecular pathways, and cellular cross-talk within the neighboring tissues. Only the minor part of all cancer cases are caused by inborn predisposition; the absolute majority carry a sporadic character based on modifiable risk factors which play a central role in cancer prevention. Amongst most promising candidates for dietary supplements are bioactive phytochemicals demonstrating strong anticancer effects. Abundant evidence has been collected for beneficial effects of flavonoids, carotenoids, phenolic acids, and organosulfur compounds affecting a number of cancer-related pathways. Phytochemicals may positively affect processes of cell signaling, cell cycle regulation, oxidative stress response, and inflammation. They can modulate non-coding RNAs, upregulate tumor suppressive miRNAs, and downregulate oncogenic miRNAs that synergically inhibits cancer cell growth and cancer stem cell self-renewal. Potential clinical utility of the phytochemicals is discussed providing examples for chemoprevention against and therapy for human breast cancer. Expert recommendations are provided in the context of preventive medicine.
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Phytochemicals in Skin Cancer Prevention and Treatment: An Updated Review.
Ng, CY, Yen, H, Hsiao, HY, Su, SC
International journal of molecular sciences. 2018;19(4)
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This 2018 review discusses the anti-oxidative, anti-inflammatory, anti-proliferative, and anti-angiogenic effects of phytochemicals for the management of skin cancer. Melanoma and non-melanoma skin cancers are caused by cellular DNA damage, and as the skin is the body’s largest organ, it is most exposed to environmental stimulus. There are several promising phytochemicals in cancer chemoprevention including Epigallocatechin-3-gallate, resveratrol, curcumin, proanthocyanidins, silymarin, apigenin, capsaicin, genistein, indole-3-carbinol, and luteolin. Additionally, Gingerol has been applied topically to improve chemical stability in the skin. Caffeic Acid Phenethyl Ester (CAPE) is derived from bee propolis was shown to inhibit skin papilloma in animal studies. Capsaicin from red chillies induced apoptosis (cell death) in melanoma cells. Curcumin has been shown to modify numerous inflammatory markers including C-reactive protein and COX-2 whilst topically can promote remarkable symptomatic relief and reduce external cancer lesion size. Caffeic Acid exerts a protective effect towards skin cancer migration and invasion. EGCG has been shown to sensitize melanoma cells to inhibit growth, promote cell death and decrease cell proliferation. Genistein from soy has been shown to exert anti-angiogenesis properties, reduce tumour proliferation and metastasis. Resveratrol has a synergistic effect with other phytochemicals to suppress tumours. What all the studies reviewed show is the potential for phytochemicals in cancer treatment. They are widely available, cost effective and highly tolerated. They appear to have anti-carcinogenic effects through regulation of multiple different signalling pathways which help alter the typical progression of skin cancer.
Abstract
Skin is the largest human organ, our protection against various environmental assaults and noxious agents. Accumulation of these stress events may lead to the formation of skin cancers, including both melanoma and non-melanoma skin cancers. Although modern targeted therapies have ameliorated the management of cutaneous malignancies, a safer, more affordable, and more effective strategy for chemoprevention and treatment is clearly needed for the improvement of skin cancer care. Phytochemicals are biologically active compounds derived from plants and herbal products. These agents appear to be beneficial in the battle against cancer as they exert anti-carcinogenic effects and are widely available, highly tolerated, and cost-effective. Evidence has indicated that the anti-carcinogenic properties of phytochemicals are due to their anti-oxidative, anti-inflammatory, anti-proliferative, and anti-angiogenic effects. In this review, we discuss the preventive potential, therapeutic effects, bioavailability, and structure-activity relationship of these selected phytochemicals for the management of skin cancers. The knowledge compiled here will provide clues for future investigations on novel oncostatic phytochemicals and additional anti-skin cancer mechanisms.
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Spices and Atherosclerosis.
Tsui, PF, Lin, CS, Ho, LJ, Lai, JH
Nutrients. 2018;10(11)
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Cardiovascular disease (CVD) is one of the leading causes of death and disability in the world. Atherosclerosis, characterised by the accumulation of fat and inflammation in blood vessels, is the main feature of CVD. Common spices such as pepper, ginger, garlic, onion, cinnamon and chilli may have effects on the initiation and development of atherosclerosis. In this review, the authors focused on the potential protective effects of spices, in atherosclerosis and CVD. Most studies to date have been carried out either in cell culture or in animals. These have revealed various potential mechanisms by which spices exert their beneficial effects, including anti-oxidant, anti-atherogenic, anti-coagulant, anti-inflammatory and cholesterol-lowering properties. There are some human studies evaluating the effects of spices on high blood pressure. Although saffron, turmeric, and chilli pepper had no effect on blood pressure, cinnamon demonstrated significant blood pressure lowering effects in patients with diabetes. Garlic has been shown to have the potential to reduce blood pressure in patients with high blood pressure. These studies provide information on the beneficial roles of spices in reducing cardiovascular risk factors. The types of spices consumed vary across cultures, and currently there are no available population studies showing that consumption of spices is associated with reduction of CVD nor any recommendations for the amounts of spices to be consumed. The authors conclude that the consumption of spices should be encouraged across countries to promote good health.
Abstract
Cardiovascular disease is one of the leading causes of death and disability in the world. Atherosclerosis, characterized by lipid accumulation and chronic inflammation in the vessel wall, is the main feature of cardiovascular disease. Although the amounts of fruits and vegetables present in the diets vary by country, diets, worldwide, contain large amounts of spices; this may have positive or negative effects on the initiation and development of atherosclerosis. In this review, we focused on the potential protective effects of specific nutrients from spices, such as pepper, ginger, garlic, onion, cinnamon and chili, in atherosclerosis and atherosclerotic cardiovascular disease. The mechanisms, epidemiological analysis, and clinical studies focusing on a variety of spices are covered in this review. Based on the integrated information, we aimed to raise specific recommendations for people with different dietary styles for the prevention of atherosclerotic cardiovascular disease through dietary habit adjustments.
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Oral Curcumin (Meriva) Is Effective as an Adjuvant Treatment and Is Able to Reduce IL-22 Serum Levels in Patients with Psoriasis Vulgaris.
Antiga, E, Bonciolini, V, Volpi, W, Del Bianco, E, Caproni, M
BioMed research international. 2015;2015:283634
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Psoriasis is an immune-mediated inflammatory condition affecting the skin, nails, and joints. Turmeric contains curcumin, a yellow-pigmented polyphenol with anti-inflammatory properties. Several diseases, including psoriasis, have been treated with turmeric in Asian countries since ancient times as a topical application and dietary supplement. This phase 3, single-dose, randomised, double-blind, placebo-controlled clinical trial evaluated the efficacy of curcumin as a complementary therapy for the treatment of mild-to-moderate psoriasis. This study used Meriva, a curcumin supplement that contains lecithin to boost the bioavailability and absorption of curcumin. The study assessed the effect of curcumin supplementation on inflammatory cytokine secretion by the immune cells. For 12 weeks, sixty-three patients with mild-to-moderate psoriasis were randomly assigned to either receive 2 grams of oral curcumin supplement, Meriva, along with topical steroid cream (Methylprednisolone aceponate 0.1%), or topical steroid cream alone. Treatment with 2 grams of oral curcumin supplementation and topical steroid cream application for 12 weeks significantly reduced the secretion of inflammatory cytokine, IL-22, in the serum of psoriatic patients. Additionally, the treatment reduced the proliferation of outer skin cells. Further robust studies are required to analyse the beneficial effects of curcumin on other pathogenic pathways of psoriasis. The study can help healthcare professionals learn more about the benefits of curcumin supplements for treating psoriasis in conjunction with conventional medicine.
Abstract
Curcumin is a complementary therapy that may be helpful for the treatment of psoriasis due to its anti-inflammatory, antiangiogenic, antioxidant, and antiproliferative effects. In the present study we performed a randomized, double-blind, placebo-controlled clinical trial to assess the effectiveness of a bioavailable oral curcumin in the treatment of psoriasis. Sixty-three patients with mild-to-moderate psoriasis vulgaris (PASI < 10) were randomly divided into two groups treated with topical steroids and Meriva, a commercially available lecithin based delivery system of curcumin, at 2 g per day (arm 1), or with topical steroids alone (arm 2), both for 12 weeks. At the beginning (T0) and at the end of the therapy (T12), clinical assessment and immunoenzymatic analysis of the serum levels of IL-17 and IL-22 were performed. At T12, both groups achieved a significant reduction of PASI values that, however, was higher in patients treated with both topical steroids and oral curcumin than in patients treated only with topical steroids. Moreover, IL-22 serum levels were significantly reduced in patients treated with oral curcumin. In conclusion, curcumin was demonstrated to be effective as an adjuvant therapy for the treatment of psoriasis vulgaris and to significantly reduce serum levels of IL-22.