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The occurrence of resveratrol in foodstuffs and its potential for supporting cancer prevention and treatment. A review
Dybkowska, E, Sadowska, A, Świderski, F, Rakowska, R, Wysocka, K
Roczniki Panstwowego Zakladu Higieny. 2018;69(1):5-14
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There has been increasing interest in plant-based substances that show potential for preventing cancer development. Resveratrol is among these and is found in the skin of grapes, tomatoes and in red wine. Resveratrol displays anti-carcinogenic capacity by neutralising reactive oxygen species and modulating cell proliferation, differentiation and apoptosis. The purpose of this review was to present the characteristics of resveratrol as a bioactive compound and assess the mechanism of its anti-cancer properties. According to many in vitro and in vivo studies, resveratrol is able to inhibit all stages of carcinogenesis in several types of cancer. Based on these findings, the authors conclude there is a need to promote knowledge of the beneficial effects of resveratrol, and that conventional cancer treatment should be supported by an increase of this substance from both foodstuffs and supplements.
Abstract
Over recent years, there has been increasing interest noted in those active substances derived from plants that show potential for preventing cancer development. The most promising candidate is resveratrol which can be found in large amounts in the skin of grapes, tomatoes and in red wine. Its beneficial effects on the human body are seen both in prevention and therapy. The anti-carcinogenic action of resveratrol is linked with its ability to neutralise reactive oxygen species and to modulate cellular processes such as apoptosis, and both cancerous cell proliferation and differentiation. This article presents the characteristics of resveratrol as a bioactive compound derived from natural sources exhibiting anti-cancer properties, which, because of a wide spectrum of biological activities may be used in the prevention of cancer. Many in vitro and animal-based studies have demonstrated such preventative anti-cancer action in the colon, prostate, breast and lungs. The beneficial effects of resveratrol are also presented when adopted as a support to conventional treatments of cancer using chemo- and radio-therapy.
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Autophagy and intermittent fasting: the connection for cancer therapy?
Antunes, F, Erustes, AG, Costa, AJ, Nascimento, AC, Bincoletto, C, Ureshino, RP, Pereira, GJS, Smaili, SS
Clinics (Sao Paulo, Brazil). 2018;73(suppl 1):e814s
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Autophagy is a cellular mechanism that removes unnecessary or dysfunctional components and is being studied intensively with regards to chronic disease, including cancer. Dietary restriction, as in intermittent fasting, is thought to activate autophagy. The authors review the literature and possible mechanisms for autophagy in cancer, noting that autophagy can both suppress and support cancer development and growth. It appears that fasting in combination with cytotoxic drugs elicits differential responses in normal and cancer cells, whereby normal cells prioritise maintenance pathways and inactivate growth factor signalling when nutrients are absent, whilst cancer cells, do not inhibit stress resistance pathways, thus becoming vulnerable to cytotoxic treatment Preclinical studies on calorie restriction or intermittent fasting in combination with chemo- and/or radiotherapy have found beneficial effects in animal and in vitro studies. There are a number of clinical human trials underway, but only two completed pilot trials, which showed promising results with reducing side effects and increasing efficacy of the chemotherapeutic drugs through intermittent fasting.
Abstract
Cancer is a leading cause of death worldwide, and its incidence is continually increasing. Although anticancer therapy has improved significantly, it still has limited efficacy for tumor eradication and is highly toxic to healthy cells. Thus, novel therapeutic strategies to improve chemotherapy, radiotherapy and targeted therapy are an important goal in cancer research. Macroautophagy (herein referred to as autophagy) is a conserved lysosomal degradation pathway for the intracellular recycling of macromolecules and clearance of damaged organelles and misfolded proteins to ensure cellular homeostasis. Dysfunctional autophagy contributes to many diseases, including cancer. Autophagy can suppress or promote tumors depending on the developmental stage and tumor type, and modulating autophagy for cancer treatment is an interesting therapeutic approach currently under intense investigation. Nutritional restriction is a promising protocol to modulate autophagy and enhance the efficacy of anticancer therapies while protecting normal cells. Here, the description and role of autophagy in tumorigenesis will be summarized. Moreover, the possibility of using fasting as an adjuvant therapy for cancer treatment, as well as the molecular mechanisms underlying this approach, will be presented.
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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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Cruciferous Vegetables, Isothiocyanates, and Bladder Cancer Prevention.
Abbaoui, B, Lucas, CR, Riedl, KM, Clinton, SK, Mortazavi, A
Molecular nutrition & food research. 2018;62(18):e1800079
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Worldwide, almost 400,000 cases of bladder cancer are diagnosed each year, with 150,000 deaths, a high rate of recurrence and a high treatment cost. This review article evaluates the literature regarding the potential role of cruciferous vegetables (broccoli, cauliflower, cabbages, pak choi, watercress, wasabi are all examples of cruciferous vegetables) in bladder cancer prevention and as an adjunct to current treatment protocols. In vitro studies have shown inhibition of bladder cancer cell reproduction, stalled cancer cell cycles, and cancer cell death by compounds in cruciferous vegetables, in particular sulphoraphane (known to be high in broccoli and broccoli sprouts) and erucin (available in rocket for example). Studies show an inverse relationship between cruciferous vegetable intake and risk of bladder cancer, with those consuming 2 or more portions per week having a 39% lower risk of bladder cancer than those who consume less than 1 portion per week. The review also looks at cooking method, with steaming, stir-frying and sauteeing protecting the important nutrients when compared to boiling. The authors call for pre-clinical studies to be performed, examining multiple formulations of cruciferous vegetables in a variety of bladder cancer models, looking at prevention in high risk groups and adjuvant to standard treatment protocols. Nutrition Practitioners may want to consider including regular intake of cruciferous vegetables in their client protocols.
Abstract
Bladder cancer is a significant health burden due to its high prevalence, risk of mortality, morbidity, and high cost of medical care. Epidemiologic evidence suggests that diets rich in cruciferous vegetables, particularly broccoli, are associated with lower bladder cancer risk. Phytochemicals in cruciferous vegetables, such as glucosinolates, which are enzymatically hydrolyzed to bioactive isothiocyanates, are possible mediators of an anticancer effect. In vitro studies have shown inhibition of bladder cancer cell lines, cell cycle arrest, and induction of apoptosis by these isothiocyanates, in particular sulforaphane and erucin. Although not yet completely understood, many mechanisms of anticancer activity at the steps of cancer initiation, promotion, and progression have been attributed to these isothiocyanates. They target multiple pathways including the adaptive stress response, phase I/II enzyme modulation, pro-growth, pro-survival, pro-inflammatory signaling, angiogenesis, and even epigenetic modulation. Multiple in vivo studies have shown the bioavailability of isothiocyanates and their antitumoral effects. Although human studies are limited, they support oral bioavailability with reasonable plasma and urine concentrations achieved. Overall, both cell and animal studies support a potential role for isothiocyanates in bladder cancer prevention and treatment. Future studies are necessary to examine clinically relevant outcomes and define guidelines on ameliorating the bladder cancer burden.
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Nutritional issues in patients with obesity and cirrhosis.
Schiavo, L, Busetto, L, Cesaretti, M, Zelber-Sagi, S, Deutsch, L, Iannelli, A
World journal of gastroenterology. 2018;24(30):3330-3346
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Non-alcoholic fatty liver disease (NAFLD) occurs when fats accumulate in the liver in the absence of excess alcohol intake and if unmanaged can advance to severe liver disease known as cirrhosis. NAFLD and cirrhosis can be associated with obesity, muscle wastage and nutrient deficiencies. This review of 165 papers aimed to discuss muscle wastage and nutrient deficiencies in patients with obesity and cirrhosis with a view to making supplementation recommendations. The authors first discussed that the risk of muscle wastage in patients with obesity and cirrhosis is high and when combined with obesity may affect other chronic diseases and impact the progression of NAFLD to cirrhosis. The paper then discusses that vitamin and mineral deficiencies are common in patients with cirrhosis possibly due to reduced intake, poor absorption and the reduction of carrier protein production in the liver. Deficiencies in vitamins D and E and zinc and magnesium were extensively featured. Protein and calorie intake were also reviewed and although weight loss should be encouraged in patients with obesity and cirrhosis, over-restriction could exacerbate muscle breakdown. Any low-calorie diets should contain adequate protein content. Bariatric surgery, in patients with obesity and cirrhosis needs to be performed on a case-by-case basis involving many different medical disciplines. It was concluded that obesity and cirrhosis are commonly occurring simultaneously and poses a management challenge for medical professionals. This paper could be used by health care professionals to understand the possible nutritional deficiencies that need to be monitored in patients with obesity and cirrhosis and where bariatric surgery may be indicated.
Abstract
Obesity and metabolic syndrome are considered as responsible for a condition known as the non-alcoholic fatty liver disease that goes from simple accumulation of triglycerides to hepatic inflammation and may progress to cirrhosis. Patients with obesity also have an increased risk of primary liver malignancies and increased body mass index is a predictor of decompensation of liver cirrhosis. Sarcopenic obesity confers a risk of physical impairment and disability that is significantly higher than the risk induced by each of the two conditions alone as it has been shown to be an independent risk factor for chronic liver disease in patients with obesity and a prognostic negative marker for the evolution of liver cirrhosis and the results of liver transplantation. Cirrhotic patients with obesity are at high risk for depletion of various fat-soluble, water-soluble vitamins and trace elements and should be supplemented appropriately. Diet, physical activity and protein intake should be carefully monitored in these fragile patients according to recent recommendations. Bariatric surgery is sporadically used in patients with morbid obesity and cirrhosis also in the setting of liver transplantation. The risk of sarcopenia, micronutrient status, and the recommended supplementation in patients with obesity and cirrhosis are discussed in this review. Furthermore, the indications and contraindications of bariatric surgery-induced weight loss in the cirrhotic patient with obesity are discussed.
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Anti-Obesity Effects of Medicinal and Edible Mushrooms.
Ganesan, K, Xu, B
Molecules (Basel, Switzerland). 2018;23(11)
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Medicinal mushrooms have long been considered healthful due to of their anti-oxidant and anti-inflammatory properties, such as high-quality proteins, polyunsaturated fatty acids, polyphenols etc. More recently they have been analysed for their anti-obesity effects. The health implications of obesity are extensive, often affecting all bodily systems. The purpose of this review was to analyse previous animal studies to determine whether consuming edible mushrooms has a positive effect on obesity related illnesses, such as Type 2 diabetes and cardiovascular disease etc. The authors explore and summarise the different methods used to treat obesity including pharmacotherapy (weight loss drugs), natural products such as Ayurveda medicine and exercise. They present promising results that suggest the therapeutic properties of edible mushrooms have anti-obesity potentials and propose that the findings from animal studies could likely be mirrored in humans and recommend consuming mushrooms to aid weight loss and therefore improve health.
Abstract
Obesity is a group of metabolic disorders caused by multiple factors, including heredity, diet, lifestyle, societal determinants, environment, and infectious agents, which can all lead to the enhancement of storage body fat. Excess visceral fat mass in adipose tissue generate several metabolic disorders, including cardiovascular diseases with chronic inflammation based pathophysiology. The objective of the current review is to summarize the cellular mechanisms of obesity that attenuate by antioxidant potentials of medicinal and edible mushrooms. Studies have showed that mushrooms potentially have antioxidant capacities, which increase the antioxidant defense systems in cells. They boost anti-inflammatory actions and thereby protect against obesity-related hypertension and dyslipidemia. The practice of regular consumption of mushrooms is effective in the treatment of metabolic syndrome, including obesity, and thus could be a good candidate for use in future pharmaceutical or nutraceutical applications.
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Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review.
Campagnolo, N, Johnston, S, Collatz, A, Staines, D, Marshall-Gradisnik, S
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2017;30(3):247-259
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This systematic review evaluated the evidence available for dietary and nutritional interventions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). 17 studies met the inclusion criteria the authors used. Notably, studies that used multi-treatments were excluded from this review. The quality of the studies varied, but two thirds were considered to be of high quality. None of the trials reported a dietary intake method at start and end of the trial period, so dietary changes alongside the intervention may have influenced the results. A variety of scales were used to measure improvement of symptoms, making it difficult to compare studies, and study designs limited recruitment to those CFS/ME sufferers who were well enough to attend a clinic/hospital. Positive results were found for nicotinamide adenine dinucleotide hydride (NADH), with and without Co-enzyme Q10, polyphenol rich chocolate and probiotics, however, studies were either of short duration or had small samples sizes, and for most interventions there was only one study. The authors conclude that, whilst there is insufficient evidence for the general prescription of supplements or elimination diets for CFS/ME patients, such interventions may be considered on an individual basis.
Abstract
BACKGROUND Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is characterised by unexplained fatigue for at least 6 months accompanied by a diverse but consistent set of symptoms. Diet modification and nutritional supplements could be used to improve patient outcomes, such fatigue and quality of life. We reviewed and discussed the evidence for nutritional interventions that may assist in alleviating symptoms of CFS/ME. METHODS Medline, Cinahl and Scopus were systematically searched from 1994 to May 2016. All studies on nutrition intervention were included where CFS/ME patients modified their diet or supplemented their habitual diet on patient-centred outcomes (fatigue, quality of life, physical activity and/or psychological wellbeing). RESULTS Seventeen studies were included that meet the inclusion criteria. Of these, 14 different interventions were investigated on study outcomes. Many studies did not show therapeutic benefit on CFS/ME. Improvements in fatigue were observed for nicotinamide adenine dinucleotide hydride (NADH), probiotics, high cocoa polyphenol rich chocolate, and a combination of NADH and coenzyme Q10. CONCLUSIONS This review identified insufficient evidence for the use of nutritional supplements and elimination or modified diets to relieve CFS/ME symptoms. Studies were limited by the number of studies investigating the interventions, small sample sizes, study duration, variety of instruments used, and studies not reporting dietary intake method. Further research is warranted in homogeneous CFS/ME populations.
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Treatment of Obesity: Weight Loss and Bariatric Surgery.
Wolfe, BM, Kvach, E, Eckel, RH
Circulation research. 2016;118(11):1844-55
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Individuals with obesity who have been unable to lose weight through non-surgical means may be candidates for bariatric surgery. Criteria was established over 20 years ago and stated that individuals with a BMI >40 and individuals with a BMI >35-40 with other related conditions who have failed to achieve weight loss medically, are appropriate for surgery. However, individuals with less severe obesity who have type 2 diabetes have now been highlighted as possible candidates also, indicating that it is an evolving process. This review of 123 papers focused on the indications, safety and reasons for bariatric surgery and its role in the reduction of heart disease. The reason for bariatric surgery is to achieve weight loss and decrease an individual’s risk of death and conditions associated with obesity. Indications for surgery were discussed and the types of surgery that are available. Safety has improved due to a number of changes such as recognition of experience of surgeons and centres, the enactment of care protocols and a switch to minimally invasive procedures. However less invasive surgeries appear to accomplish considerably less weight loss. Benefits to body fat, blood fat levels, high blood pressure, diabetes, non-alcoholic fatty liver disease, inflammation, the ability of the blood vessels to dilate and sleep apnoea were all discussed. These were all used as evidence to support the argument that surgery improves an individual’s chances of survival compared to lifestyle interventions, as sufficiently designed trials to support this have not been performed. It was concluded that bariatric surgery has greater improved heart disease and death compared to lifestyle interventions due to the significantly higher weight loss that results.
Abstract
This review focuses on the mechanisms underlying, and indications for, bariatric surgery in the reduction of cardiovascular disease (CVD), as well as other expected benefits of this intervention. The fundamental basis for bariatric surgery for the purpose of accomplishing weight loss is the determination that severe obesity is a disease associated with multiple adverse effects on health, which can be reversed or improved by successful weight loss in patients who have been unable to sustain weight loss by nonsurgical means. An explanation of possible indications for weight loss surgery as well as specific bariatric surgical procedures is presented, along with review of the safety literature of such procedures. Procedures that are less invasive or those that involve less gastrointestinal rearrangement accomplish considerably less weight loss but have substantially lower perioperative and longer-term risk. The ultimate benefit of weight reduction relates to the reduction of the comorbidities, quality of life, and all-cause mortality. With weight loss being the underlying justification for bariatric surgery in ameliorating CVD risk, current evidence-based research is discussed concerning body fat distribution, dyslipidemia, hypertension, diabetes mellitus, inflammation, obstructive sleep apnea, and others. The rationale for bariatric surgery reducing CVD events is discussed and juxtaposed with impacts on all-cause mortalities. Given the improvement of established obesity-related CVD risk factors after weight loss, it is reasonable to expect a reduction of CVD events and related mortality after weight loss in populations with obesity. The quality of the current evidence is reviewed, and future research opportunities and summaries are stated.
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Current experience in testing mitochondrial nutrients in disorders featuring oxidative stress and mitochondrial dysfunction: rational design of chemoprevention trials.
Pagano, G, Aiello Talamanca, A, Castello, G, Cordero, MD, d'Ischia, M, Gadaleta, MN, Pallardó, FV, Petrović, S, Tiano, L, Zatterale, A
International journal of molecular sciences. 2014;15(11):20169-208
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Many conditions are associated with mitochondrial dysfunction (MDF) and oxidative stress (OS). For example; some genetic diseases, aging and age-associated disorders, neurologic and psychiatric diseases, malignancies and autoimmune diseases. This review looks at the clinical trials focused on the use of mitochondrial cofactors (mitochondrial nutrients - MN) such as alpha-lipoic acid (ALA), Coenzyme Q 10 (CoQ10) and L-carnitine (CARN) which are essential in the functioning of mitochondria. Of the trials that were used in the review, 81 tested ALA, 107 tested CoQ10, 74 reports tested CARN, only 7 reports were retrieved testing double MN associations, while no report was found testing a triple MN combination. A total of 28 reports tested MN associations with “classical” antioxidants, such as antioxidant nutrients or drugs. Combinations of MN showed better outcomes than individual MN. Further studies are therefore needed.
Abstract
An extensive number of pathologies are associated with mitochondrial dysfunction (MDF) and oxidative stress (OS). Thus, mitochondrial cofactors termed "mitochondrial nutrients" (MN), such as α-lipoic acid (ALA), Coenzyme Q10 (CoQ10), and l-carnitine (CARN) (or its derivatives) have been tested in a number of clinical trials, and this review is focused on the use of MN-based clinical trials. The papers reporting on MN-based clinical trials were retrieved in MedLine up to July 2014, and evaluated for the following endpoints: (a) treated diseases; (b) dosages, number of enrolled patients and duration of treatment; (c) trial success for each MN or MN combinations as reported by authors. The reports satisfying the above endpoints included total numbers of trials and frequencies of randomized, controlled studies, i.e., 81 trials testing ALA, 107 reports testing CoQ10, and 74 reports testing CARN, while only 7 reports were retrieved testing double MN associations, while no report was found testing a triple MN combination. A total of 28 reports tested MN associations with "classical" antioxidants, such as antioxidant nutrients or drugs. Combinations of MN showed better outcomes than individual MN, suggesting forthcoming clinical studies. The criteria in study design and monitoring MN-based clinical trials are discussed.