-
1.
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
-
-
-
Free full text
Plain language summary
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.
-
2.
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
-
-
-
Free full text
Plain language summary
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.
-
3.
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)
-
-
-
Free full text
Plain language summary
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.
-
4.
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
-
-
-
Free full text
-
Plain language summary
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.
-
5.
Vitamin C: should we supplement?
Spoelstra-de Man, AME, Elbers, PWG, Oudemans-Van Straaten, HM
Current opinion in critical care. 2018;24(4):248-255
-
-
-
Free full text
-
Plain language summary
Vitamin C deficiency is frequently encountered in critically ill patients due to their increased needs and diminished intake. The aim of this review was to summarise the current role of Vitamin C in critically ill patients. The review discussed clinical and preclinical studies published in the past 5 years investigating repletion and pharmacological dosing of intravenous vitamin C as adjuvant therapy in trauma, ischemia/reperfusion injury (tissue damage caused when blood supply returns to tissue) and sepsis (the body's response to an infection). Results indicate that during critical illness, vitamin C has antioxidant, anti-inflammatory and immune-supporting effects. It also acts as a cofactor for certain enzymes. Authors conclude that vitamin C supplementation (repletion and/or pharmacological dose) is a promising potential adjuvant therapy for critical illnesses with increased oxidative stress.
Abstract
PURPOSE OF REVIEW Hypovitaminosis C and vitamin C deficiency are very common in critically ill patients due to increased needs and decreased intake. Because vitamin C has pleiotropic functions, deficiency can aggravate the severity of illness and hamper recovery. RECENT FINDINGS Vitamin C is a key circulating antioxidant with anti-inflammatory and immune-supporting effects, and a cofactor for important mono and dioxygenase enzymes. An increasing number of preclinical studies in trauma, ischemia/reperfusion, and sepsis models show that vitamin C administered at pharmacological doses attenuates oxidative stress and inflammation, and restores endothelial and organ function. Older studies showed less organ dysfunction when vitamin C was administered in repletion dose (2-3 g intravenous vitamin C/day). Recent small controlled studies using pharmacological doses (6-16 g/day) suggest that vitamin C reduces vasopressor support and organ dysfunction, and may even decrease mortality. SUMMARY A short course of intravenous vitamin C in pharmacological dose seems a promising, well tolerated, and cheap adjuvant therapy to modulate the overwhelming oxidative stress in severe sepsis, trauma, and reperfusion after ischemia. Large randomized controlled trials are necessary to provide more evidence before wide-scale implementation can be recommended.
-
6.
Vitamin D: Nutrient, Hormone, and Immunomodulator.
Sassi, F, Tamone, C, D'Amelio, P
Nutrients. 2018;10(11)
-
-
-
Free full text
Plain language summary
Vitamin D is well known for its role in controlling bone metabolism. However, Vitamin D deficiency has been reported in conditions associated with inflammation and disordered immunity, such as diabetes and asthma. This review article summarises the evidence on the potential of Vitamin D in modulating the immune system. The authors present evidence of Vitamin D as a regulator of the innate immune system (first line, rapid defence against infection); discuss the relationship between Vitamin D and the gut microbiota; and examine evidence on Vitamin D and the adaptive or acquired immune system (second line, delayed defence against infection). The authors conclude that the evidence is strong in relation to Vitamin D and the innate immune system and more controversial in relation to the acquired immune system. There is no general consensus as yet on the desired level of 25(OH)D3 to modulate the immune system and further studies are needed to provide clarity. Nutrition Practitioners wishing to optimise Vitamin D levels could follow expert agreement of Vitamin D levels of 75-125nmol/l, which has been shown to provide skeletal effects without toxicity.
Abstract
The classical functions of vitamin D are to regulate calcium-phosphorus homeostasis and control bone metabolism. However, vitamin D deficiency has been reported in several chronic conditions associated with increased inflammation and deregulation of the immune system, such as diabetes, asthma, and rheumatoid arthritis. These observations, together with experimental studies, suggest a critical role for vitamin D in the modulation of immune function. This leads to the hypothesis of a disease-specific alteration of vitamin D metabolism and reinforces the role of vitamin D in maintaining a healthy immune system. Two key observations validate this important non-classical action of vitamin D: first, vitamin D receptor (VDR) is expressed by the majority of immune cells, including B and T lymphocytes, monocytes, macrophages, and dendritic cells; second, there is an active vitamin D metabolism by immune cells that is able to locally convert 25(OH)D₃ into 1,25(OH)₂D₃, its active form. Vitamin D and VDR signaling together have a suppressive role on autoimmunity and an anti-inflammatory effect, promoting dendritic cell and regulatory T-cell differentiation and reducing T helper Th 17 cell response and inflammatory cytokines secretion. This review summarizes experimental data and clinical observations on the potential immunomodulating properties of vitamin D.
-
7.
Reversing the immune ageing clock: lifestyle modifications and pharmacological interventions.
Duggal, NA
Biogerontology. 2018;19(6):481-496
-
-
-
Free full text
-
Plain language summary
Advancing age is accompanied by a compromised ability of older adults to combat bacterial and viral infections, increased risk of autoimmunity, poor vaccination responses and the re-emergence of latent infections. This review discusses current understanding of immunesenescence [the gradual deterioration of our immune system as we get older] and also focuses on lifestyle interventions and therapeutic strategies that have been shown to restore immune functioning in aged individuals. Findings show that: - changes in nutrition and lifestyle can be an effective approach towards improving immune outcome in older adults but may be hard to achieve at a population level. - improving immune responses, such as the developments of vaccines, may be used as an early biomarker for anti-ageing effects. Authors conclude that immunomodulation represents a promising therapeutic approach to improve the health of older adults.
Abstract
It is widely accepted that ageing is accompanied by remodelling of the immune system, including reduced numbers of naïve T cells, increased senescent or exhausted T cells, compromise to monocyte, neutrophil and natural killer cell function and an increase in systemic inflammation. In combination these changes result in increased risk of infection, reduced immune memory, reduced immune tolerance and immune surveillance, with significant impacts upon health in old age. More recently it has become clear that the rate of decline in the immune system is malleable and can be influenced by environmental factors such as physical activity as well as pharmacological interventions. This review discusses briefly our current understanding of immunesenescence and then focuses on lifestyle interventions and therapeutic strategies that have been shown to restore immune functioning in aged individuals.
-
8.
Gut dysbiosis: a potential link between increased cancer risk in ageing and inflammaging.
Biragyn, A, Ferrucci, L
The Lancet. Oncology. 2018;19(6):e295-e304
-
-
-
Free full text
-
Plain language summary
This study looks at the important role our gut bacterial and commensal microbes play in supporting immunity and potentially reducing the risk of cancer from aging. Cancer risk increases as we age and is one of the main causes of reduced life expectancy. Our gut microbiome changes continually in response to diet, lifestyle, infection, and activation of immune responses. Gut dysbiosis is characterised by a shift towards proinflammatory commensals and a reduction of beneficial microbes, which can cause impairment and leakiness of the intestinal barrier. This is thought to trigger inflammaging or rather aging in a state of continual inflammation, where the immune system is in a heightened state of activation, and the body essentially creates an environment conducive to cancer. The gut is populated by trillions of species of bacteria which work together with our immune cells. As we age the diversity and density of these beneficial bacteria reduce. Therapies which support the balance of our commensal bacteria may prove effective at reducing rates of cancer in the elderly.
Abstract
Cancer incidence substantially increases with ageing in both men and women, although the reason for this increase is unknown. In this Series paper, we propose that age-associated changes in gut commensal microbes, otherwise known as the microbiota, facilitate cancer development and growth by compromising immune fitness. Ageing is associated with a reduction in the beneficial commensal microbes, which control the expansion of pathogenic commensals and maintain the integrity of the intestinal barrier through the production of mucus and lipid metabolites, such as short-chain fatty acids. Expansion of gut dysbiosis and leakage of microbial products contributes to the chronic proinflammatory state (inflammaging), which negatively affects the immune system and impairs the removal of mutant and senescent cells, thereby enabling tumour outgrowth. Studies in animal models and the importance of commensals in cancer immunotherapy suggest that this status can be reversible. Thus, interventions that alter the composition of the gut microbiota might reduce inflammaging and rejuvenate immune functions to provide anticancer benefits in frail elderly people.
-
9.
Hemostasis, endothelial stress, inflammation, and the metabolic syndrome.
Grandl, G, Wolfrum, C
Seminars in immunopathology. 2018;40(2):215-224
-
-
-
Free full text
-
Plain language summary
The metabolic syndrome consists of several factors that significantly increase the risk of developing type 2 diabetes, cardiovascular disease and all-cause mortality. Underlying these conditions is a complex interaction between the immune response, blood glucose levels, blood lipid levels and both local and systemic inflammation. The purpose of this review is to provide an overview of various aspects of pathophysiology in metabolic syndrome and obesity through the lens of the western diet. According to the existing research, the authors conclude that both type 2 diabetes and cardiovascular disease should be viewed as an inflammatory disease and further suggest inflammation and insulin resistance are linked to chronic consumption of a western diet.
Abstract
Obesity and the metabolic syndrome (MS) are two of the pressing healthcare problems of our time. The MS is defined as increased abdominal obesity in concert with elevated fasting glucose levels, insulin resistance, elevated blood pressure, and plasma lipids. It is a key risk factor for type 2 diabetes mellitus (T2DM) and for cardiovascular complications and mortality. Here, we review work demonstrating that various aspects of coagulation and hemostasis, as well as vascular reactivity and function, become impaired progressively during chronic ingestion of a western diet, but also acutely after meals. We outline that both T2DM and cardiovascular disease should be viewed as inflammatory diseases and describe that chronic overload of free fatty acids and glucose can trigger inflammatory pathways directly or via increased production of ROS. We propose that since endothelial stress and increases in platelet activity precede inflammation and overt symptoms of the MS, they are likely the first hit. This suggests that endothelial activation and insulin resistance are probably causative in the observed chronic low-level metabolic inflammation, and thus both metabolic and cardiovascular complications linked to consumption of a western diet.
-
10.
Nutritional Ketosis for Weight Management and Reversal of Metabolic Syndrome.
Gershuni, VM, Yan, SL, Medici, V
Current nutrition reports. 2018;7(3):97-106
-
-
-
Free full text
Plain language summary
The five main components of Metabolic Syndrome — obesity, fasting blood sugar, high triglycerides (TGs), low HDL cholesterol, and hypertension — are all improved by carbohydrate restriction which reduces insulin secretion. Ketones are water-soluble molecules produced by the liver from fatty acids when blood glucose and liver glycogen stores are depleted, for example through fasting, low carbohydrate intake or intense exercise. Nutritional ketosis through a very low carbohydrate ketogenic diet (VLCKD) results in lower insulin levels which can lead to a shift in metabolism towards the use of fat stores for energy. A “well-formulated” ketogenic diet is described as composed of 5–10% carbohydrates (<20–50g/day), adequate protein (1–1.5g/kg/day), and fat until satiated, with blood ketone levels of 0.5 to 3 mg/dL. Nutritional ketosis is different from diabetic ketoacidosis which can affect type 1 diabetics and which is a medical emergency. A number of meta-analyses of randomised controlled trials have shown that VLCKD are better than low fat diets with respects to weight loss, lipid profiles, glucose metabolism, blood pressure and inflammatory markers. The authors review the literature and mechanisms of action.
Abstract
PURPOSE OF REVIEW The goal of this paper is to review current literature on nutritional ketosis within the context of weight management and metabolic syndrome, namely, insulin resistance, lipid profile, cardiovascular disease risk, and development of non-alcoholic fatty liver disease. We provide background on the mechanism of ketogenesis and describe nutritional ketosis. RECENT FINDINGS Nutritional ketosis has been found to improve metabolic and inflammatory markers, including lipids, HbA1c, high-sensitivity CRP, fasting insulin and glucose levels, and aid in weight management. We discuss these findings and elaborate on potential mechanisms of ketones for promoting weight loss, decreasing hunger, and increasing satiety. Humans have evolved with the capacity for metabolic flexibility and the ability to use ketones for fuel. During states of low dietary carbohydrate intake, insulin levels remain low and ketogenesis takes place. These conditions promote breakdown of excess fat stores, sparing of lean muscle, and improvement in insulin sensitivity.