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Ketogenic diet in the treatment of cancer - Where do we stand?
Weber, DD, Aminzadeh-Gohari, S, Tulipan, J, Catalano, L, Feichtinger, RG, Kofler, B
Molecular metabolism. 2020;33:102-121
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A literature review paper looking at complementary approaches to improve the efficacy of standard anticancer therapies – specifically the Ketogenic Diet (KD), characterised as a high-fat (90%), low-carbohydrate (2%) diet with adequate amounts of protein (8%). The KD is a low- cost adjuvant to cancer therapy and is considered promising due to its potential to target metabolic alterations in tumour cells. Research shows it potentially limits tumour growth, whilst protecting healthy cells from damage by chemotherapy or radiation and reducing inflammation. The ketones produced by the high ratio of fat in the diet are used to create ATP energy, which cancerous cells are unable to use. Preclinical studies show that in most cases the KD slowed tumour growth, prolonged survival rate, and delayed the initiation of tumours although this may be influenced by cancer type and genetic background. This implies it’s important to evaluate KD efficiency against each individual cancer rather than as a collective anticancer therapy. Gold standard therapy for some cancers is surgery, radiation, and chemotherapy. However aggressive cancer types with poor prognosis need new approaches where standard therapy is less successful. The authors recognise there is insufficient RCT evidence with large patient cohorts but smaller studies are emerging showing positive results for a KD with patients exceeding their expected lifespan, with reduced tumour growth and progression, reduced glucose up-take at the tumour site and overall improved quality of life. KD seemingly creates an environment in which cancer cells cannot thrive making it a promising adjuvant as a patient-specific multifactorial therapy.
Abstract
BACKGROUND Cancer is one of the greatest public health challenges worldwide, and we still lack complementary approaches to significantly enhance the efficacy of standard anticancer therapies. The ketogenic diet, a high-fat, low-carbohydrate diet with adequate amounts of protein, appears to sensitize most cancers to standard treatment by exploiting the reprogramed metabolism of cancer cells, making the diet a promising candidate as an adjuvant cancer therapy. SCOPE OF REVIEW To critically evaluate available preclinical and clinical evidence regarding the ketogenic diet in the context of cancer therapy. Furthermore, we highlight important mechanisms that could explain the potential antitumor effects of the ketogenic diet. MAJOR CONCLUSIONS The ketogenic diet probably creates an unfavorable metabolic environment for cancer cells and thus can be regarded as a promising adjuvant as a patient-specific multifactorial therapy. The majority of preclinical and several clinical studies argue for the use of the ketogenic diet in combination with standard therapies based on its potential to enhance the antitumor effects of classic chemo- and radiotherapy, its overall good safety and tolerability and increase in quality of life. However, to further elucidate the mechanisms of the ketogenic diet as a therapy and evaluate its application in clinical practice, more molecular studies as well as uniformly controlled clinical trials are needed.
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The Role of Diet and Nutrition in Migraine Triggers and Treatment: A Systematic Literature Review.
Hindiyeh, NA, Zhang, N, Farrar, M, Banerjee, P, Lombard, L, Aurora, SK
Headache. 2020;60(7):1300-1316
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Migraine is a disabling primary headache disorder with 2 major subtypes: migraine without aura and migraine with aura. Certain foods, such as chocolate, caffeine, milk, cheese and alcoholic beverages, have been identified as common triggers of migraine attacks. The aim of this study was to qualitatively summarize data from randomized controlled trials or observational studies on the role of diet patterns, diet-related triggers, and dietary interventions in adults with migraine. This study is a systematic review of forty-three articles. Of the studies included in the review, 11 outlined the evidence on diet patterns, 20 outlined the evidence on diet-related triggers, and 12 outlined evidence on diet as interventions in people with migraine. Results show that evidence regarding the effect of general diet patterns in people with migraine varied in the studies identified. Furthermore, limited high-quality evidence was found. Authors conclude that certain dietary interventions may help to improve clinical outcomes in some people with migraine, but these findings still need to be supported with robust evidence before being recommended for use in clinical practice.
Abstract
BACKGROUND Migraine is a disabling primary headache disorder often associated with triggers. Diet-related triggers are a common cause of migraine and certain diets have been reported to decrease the frequency of migraine attacks if dietary triggers or patterns are adjusted. OBJECTIVE The systematic literature review was conducted to qualitatively summarize evidence from the published literature regarding the role of diet patterns, diet-related triggers, and diet interventions in people with migraine. METHODS A literature search was carried out on diet patterns, diet-related triggers, and diet interventions used to treat and/or prevent migraine attacks, using an a priori protocol. MEDLINE and EMBASE databases were searched to identify studies assessing the effect of diet, food, and nutrition in people with migraine aged ≥18 years. Only primary literature sources (randomized controlled trials or observational studies) were included and searches were conducted from January 2000 to March 2019. The NICE checklist was used to assess the quality of the included studies of randomized controlled trials and the Downs and Black checklist was used for the assessment of observational studies. RESULTS A total of 43 studies were included in this review, of which 11 assessed diet patterns, 12 assessed diet interventions, and 20 assessed diet-related triggers. The overall quality of evidence was low, as most of the (68%) studies assessing diet patterns and diet-related triggers were cross-sectional studies or patient surveys. The studies regarding diet interventions assessed a variety of diets, such as ketogenic diet, elimination diets, and low-fat diets. Alcohol and caffeine uses were the most common diet patterns and diet-related triggers associated with increased frequency of migraine attacks. Most of the diet interventions, such as low-fat and elimination diets, were related to a decrease in the frequency of migraine attacks. CONCLUSIONS There is limited high-quality randomized controlled trial data on diet patterns or diet-related triggers. A few small randomized controlled trials have assessed diet interventions in preventing migraine attacks without strong results. Although many patients already reported avoiding personal diet-related triggers in their migraine management, high-quality research is needed to confirm the effect of diet in people with migraine.
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Dietary Patterns and Interventions to Alleviate Chronic Pain.
Dragan, S, Șerban, MC, Damian, G, Buleu, F, Valcovici, M, Christodorescu, R
Nutrients. 2020;12(9)
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A common symptom of many conditions is pain, with chronic pain being a significant cause of emotional distress and disability. Chronic pain is associated with a pro-inflammatory state. Diet interventions can be a helpful tool for the management of chronic pain and its associated inflammation. The increase of nutrient-dense, antioxidant-rich foods and the reduction of pro-inflammatory foods, as well as correcting nutrient deficiencies, all appear to have a positive effect on pain. Whilst previous research on the impact of diet therapy in chronic pain yielded varied results, the authors of this article sought to analyse the most important literature to gain more clarity and direction for future research. After a detailed introduction on the different types of pain, the article summarises the outcome of a range of dietary interventions for chronic pain management. These include calorie restriction and fasting, polyunsaturated fatty acids, low-fat plant-based diets, high protein diet, elimination diet, antioxidants and vitamins including vitamin D, fruits and fibres, prebiotics and probiotics. In the discussion, a helpful table presents the key results organised by type of pain (chronic musculoskeletal pain, chronic headache, neuropathic pain, chronic abdominal pain) and the clinical interventions that showed positive outcomes. In conclusion, diet interventions could be part of a multidisciplinary approach in the management of chronic pain. This article yields an oversight of the possible interventions to consider when supporting people with different types of chronic pain.
Abstract
Pain is one of the main problems for modern society and medicine, being the most common symptom described by almost all patients. When pain becomes chronic, the life of the patients is dramatically affected, being associated with significant emotional distress and/or functional disability. A complex biopsychosocial evaluation is necessary to better understand chronic pain, where good results can be obtained through interconnected biological, psychological, and social factors. The aim of this study was to find the most relevant articles existent in the PubMed database, one of the most comprehensive databases for medical literature, comprising dietary patterns to alleviate chronic pain. Through a combined search using the keywords "chronic pain" and "diet" limited to the last 10 years we obtained 272 results containing the types of diets used for chronic pain published in the PubMed database. Besides classical and alternative methods of treatment described in literature, it was observed that different diets are also a valid solution, due to many components with antioxidant and anti-inflammatory qualities capable to influence chronic pain and to improve the quality of life. Thirty-eight clinical studies and randomized controlled trials are analyzed, in an attempt to characterize present-day dietary patterns and interventions to alleviate chronic pain.
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Efficacy of ketogenic diet on body composition during resistance training in trained men: a randomized controlled trial.
Vargas, S, Romance, R, Petro, JL, Bonilla, DA, Galancho, I, Espinar, S, Kreider, RB, Benítez-Porres, J
Journal of the International Society of Sports Nutrition. 2018;15(1):31
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This randomised controlled trial investigated the effects of a ketogenic diet on body composition in bodybuilders. 24 healthy body-builders were randomised to either a ketogenic diet (KD), non-ketogenic diet (NKD) or to control group (CG). During the trial period, both the KD and the NKD group received a surplus of calories and the same amount of protein, 2g/kg body weight per day to promote anabolic activity. Macronutrient ratios were carbohydrate 55%, protein 20% and fat 25% in the NKD group versus <10% carbohydrate, 20% protein and 70% fat in the KD group. Participants could eat when and how often they wanted to and both groups carried out the same training programme. After eight weeks the KD group showed significantly lower total fat mass and visceral (abdominal) fat, but no gain in either total body weight or lean mass. The NKD group, on the other hand, gained lean mass and body weight, but saw no changes in total or visceral fat mass. No significant changes in body composition were observed in the CG.
Abstract
BACKGROUND Ketogenic diets (KD) have become a popular method of promoting weight loss. More recently, some have recommended that athletes adhere to ketogenic diets in order to optimize changes in body composition during training. This study evaluated the efficacy of an 8-week ketogenic diet (KD) during energy surplus and resistance training (RT) protocol on body composition in trained men. METHODS Twenty-four healthy men (age 30 ± 4.7 years; weight 76.7 ± 8.2 kg; height 174.3 ± 19.7 cm) performed an 8-week RT program. Participants were randomly assigned to a KD group (n = 9), non-KD group (n = 10, NKD), and control group (n = 5, CG) in hyperenergetic condition. Body composition changes were measured by dual energy X-ray absorptiometry (DXA). Compliance with the ketosis state was monitored by measuring urinary ketones weekly. Data were analyzed using a univariate, multivariate and repeated measures general linear model (GLM) statistics. RESULTS There was a significant reduction in fat mass (mean change, 95% CI; p-value; Cohen's d effect size [ES]; - 0.8 [- 1.6, - 0.1] kg; p < 0.05; ES = - 0.46) and visceral adipose tissue (- 96.5 [- 159.0, - 34.0] g; p < 0.05; ES = - 0.84), while no significant changes were observed in the NKD and CG in fat mass (- 0,5 [- 1.2, 0.3] kg; p > 0.05; ES = - 0.17 and - 0,5 [- 2.4, 1.3] kg; p > 0.05; ES = - 0.12, respectively) or visceral adipose tissue (- 33.8 [- 90.4, 22.8]; p > 0.5; ES = - 0.17 and 1.7 [- 133.3, 136.7]; p > 0.05; ES = 0.01, respectively). No significant increases were observed in total body weight (- 0.9 [- 2.3, 0.6]; p > 0.05; ES = [- 0.18]) and muscle mass (- 0.1 [- 1.1,1.0]; p > 0,05; ES = - 0.04) in the KD group, but the NKD group showed increases in these parameters (0.9 [0.3, 1.5] kg; p < 0.05; ES = 0.18 and (1.3[0.5, 2.2] kg; p < 0,05; ES = 0.31, respectively). There were no changes neither in total body weight nor lean body mass (0.3 [- 1.2, 1.9]; p > 0.05; ES = 0.05 and 0.8 [- 0.4, 2.1]; p > 0.05; ES = 0.26, respectively) in the CG. CONCLUSION Our results suggest that a KD might be an alternative dietary approach to decrease fat mass and visceral adipose tissue without decreasing lean body mass; however, it might not be useful to increase muscle mass during positive energy balance in men undergoing RT for 8 weeks.
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Calories, carbohydrates, and cancer therapy with radiation: exploiting the five R's through dietary manipulation.
Klement, RJ, Champ, CE
Cancer metastasis reviews. 2014;33(1):217-29
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Radiation therapy is standard care for cancer patients alongside surgery and chemotherapy. However, there are still some cancers which seem to withstand this treatment. This study looks at whether calorie reduction (CR) and carbohydrate restriction can have any impact on treatment outcomes. The reason for exploring this idea comes from data showing a high level of ‘glycolysis’ (a need for sugar) in cancer cells. Calorie reduction is defined as 30-50% less calories per day achieved either by intermittent fasting or a fixed calorie regime. Carbohydrate restriction is defined as a ketogenic diet (KD); a diet which removes carbohydrate foods and sugars and focuses on high fat foods and limited protein. Both nutritional protocols have been shown to have similar metabolic effects of reducing blood sugar levels and insulin activity, and thus reducing the ability of cancer cells to communicate. The 5R principle of radiotherapy tries to exploit the differences between cancer cells and healthy tissue. The 5Rs are Repair to DNA damage, Repopulation of the tumour, Redistribution of cells, Reoxygenation of the tumour area and Radio resistance in cells which do not respond to treatment. The concern with restricting calories and carbohydrates is triggering detrimental weight loss in cancer patients, although some fat loss may be beneficial in overweight patients with hormonal cancers. Intermittent fasting seems to fit well with typical radiation treatment schedules over 2-3-month periods. Trials of ketogenic diets on healthy volunteers have shown it encourages muscle mass which is a strong predictor of survival in cancer patients. Of the two, a carbohydrate-restricted, ketogenic diet appears the most viable adjunct to radiation therapy.
Abstract
Aggressive tumors typically demonstrate a high glycolytic rate, which results in resistance to radiation therapy and cancer progression via several molecular and physiologic mechanisms. Intriguingly, many of these mechanisms utilize the same molecular pathways that are altered through calorie and/or carbohydrate restriction. Furthermore, poorer prognosis in cancer patients who display a glycolytic phenotype characterized by metabolic alterations, such as obesity and diabetes, is now well established, providing another link between metabolic pathways and cancer progression. We review the possible roles for calorie restriction (CR) and very low carbohydrate ketogenic diets (KDs) in modulating the five R's of radiotherapy to improve the therapeutic window between tumor control and normal tissue complication probability. Important mechanisms we discuss include (1) improved DNA repair in normal, but not tumor cells; (2) inhibition of tumor cell repopulation through modulation of the PI3K-Akt-mTORC1 pathway downstream of insulin and IGF1; (3) redistribution of normal cells into more radioresistant phases of the cell cycle; (4) normalization of the tumor vasculature by targeting hypoxia-inducible factor-1α downstream of the PI3K-Akt-mTOR pathway; (5) increasing the intrinsic radioresistance of normal cells through ketone bodies but decreasing that of tumor cells by targeting glycolysis. These mechanisms are discussed in the framework of animal and human studies, taking into account the commonalities and differences between CR and KDs. We conclude that CR and KDs may act synergistically with radiation therapy for the treatment of cancer patients and provide some guidelines for implementing these dietary interventions into clinical practice.