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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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Association of Frequency of Organic Food Consumption With Cancer Risk: Findings From the NutriNet-Santé Prospective Cohort Study.
Baudry, J, Assmann, KE, Touvier, M, Allès, B, Seconda, L, Latino-Martel, P, Ezzedine, K, Galan, P, Hercberg, S, Lairon, D, et al
JAMA internal medicine. 2018;178(12):1597-1606
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Cancer has several risk factors for its development including the presence of pesticides in the environment. Organic foods arguably have less pesticides than conventionally grown produce and the consumption of these should therefore lower an individuals chance of developing cancer. However, very few studies exist looking at this association. This observational study of 68946 individuals aimed to determine the association between organic food intake and cancer risk. The results showed that the most prevalent cancers were breast, prostate and skin cancer and an increased consumption of organic food, lowered the risk for the development of cancer. It was concluded that a higher intake of organic foods could reduce the risk of developing cancer, however further studies are warranted to investigate initial findings. This study could be used by healthcare professionals to understand that a diet rich in organic food could be of benefit for the prevention of cancer, however further studies are required before firm recommendations can be made.
Abstract
Importance: Although organic foods are less likely to contain pesticide residues than conventional foods, few studies have examined the association of organic food consumption with cancer risk. Objective: To prospectively investigate the association between organic food consumption and the risk of cancer in a large cohort of French adults. Design, Setting, and Participants: In this population-based prospective cohort study among French adult volunteers, data were included from participants with available information on organic food consumption frequency and dietary intake. For 16 products, participants reported their consumption frequency of labeled organic foods (never, occasionally, or most of the time). An organic food score was then computed (range, 0-32 points). The follow-up dates were May 10, 2009, to November 30, 2016. Main Outcomes and Measures: This study estimated the risk of cancer in association with the organic food score (modeled as quartiles) using Cox proportional hazards regression models adjusted for potential cancer risk factors. Results: Among 68 946 participants (78.0% female; mean [SD] age at baseline, 44.2 [14.5] years), 1340 first incident cancer cases were identified during follow-up, with the most prevalent being 459 breast cancers, 180 prostate cancers, 135 skin cancers, 99 colorectal cancers, 47 non-Hodgkin lymphomas, and 15 other lymphomas. High organic food scores were inversely associated with the overall risk of cancer (hazard ratio for quartile 4 vs quartile 1, 0.75; 95% CI, 0.63-0.88; P for trend = .001; absolute risk reduction, 0.6%; hazard ratio for a 5-point increase, 0.92; 95% CI, 0.88-0.96). Conclusions and Relevance: A higher frequency of organic food consumption was associated with a reduced risk of cancer. If these findings are confirmed, further research is necessary to determine the underlying factors involved in this association.
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Consumption of ultra-processed foods and cancer risk: results from NutriNet-Santé prospective cohort.
Fiolet, T, Srour, B, Sellem, L, Kesse-Guyot, E, Allès, B, Méjean, C, Deschasaux, M, Fassier, P, Latino-Martel, P, Beslay, M, et al
BMJ (Clinical research ed.). 2018;360:k322
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Foods that are heavily processed tend to have high levels of total fat, sugar and salt and low levels of fibre and vitamins. They also tend to have high levels of contaminants (caused for example by high heat treatment), food additives and plastic packaging exposure. This large prospective population-based cohort study assessed the association between ultra-processed food consumption and the incidence of cancer. The study found that ultra-processed food intake was associated with a higher overall cancer risk and a higher breast cancer risk. A 10% increase in the consumption of ultra-processed foods was associated with an increase of more than 10% greater risk of overall and breast cancer risk. The authors call for further studies to better understand the different elements of food processing and their association to cancer risk.
Abstract
OBJECTIVE To assess the prospective associations between consumption of ultra-processed food and risk of cancer. DESIGN Population based cohort study. SETTING AND PARTICIPANTS 104 980 participants aged at least 18 years (median age 42.8 years) from the French NutriNet-Santé cohort (2009-17). Dietary intakes were collected using repeated 24 hour dietary records, designed to register participants' usual consumption for 3300 different food items. These were categorised according to their degree of processing by the NOVA classification. MAIN OUTCOME MEASURES Associations between ultra-processed food intake and risk of overall, breast, prostate, and colorectal cancer assessed by multivariable Cox proportional hazard models adjusted for known risk factors. RESULTS Ultra-processed food intake was associated with higher overall cancer risk (n=2228 cases; hazard ratio for a 10% increment in the proportion of ultra-processed food in the diet 1.12 (95% confidence interval 1.06 to 1.18); P for trend<0.001) and breast cancer risk (n=739 cases; hazard ratio 1.11 (1.02 to 1.22); P for trend=0.02). These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet (lipid, sodium, and carbohydrate intakes and/or a Western pattern derived by principal component analysis). CONCLUSIONS In this large prospective study, a 10% increase in the proportion of ultra-processed foods in the diet was associated with a significant increase of greater than 10% in risks of overall and breast cancer. Further studies are needed to better understand the relative effect of the various dimensions of processing (nutritional composition, food additives, contact materials, and neoformed contaminants) in these associations. STUDY REGISTRATION Clinicaltrials.gov NCT03335644.
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Weight Status and Alcohol Intake Modify the Association between Vitamin D and Breast Cancer Risk.
Deschasaux, M, Souberbielle, JC, Latino-Martel, P, Sutton, A, Charnaux, N, Druesne-Pecollo, N, Galan, P, Hercberg, S, Le Clerc, S, Kesse-Guyot, E, et al
The Journal of nutrition. 2016;146(3):576-85
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Experimental studies suggest that vitamin D may contribute to the prevention of breast cancer. However, population studies have been inconclusive, and it is possible that any relationship is dependent on other factors such as genetics or lifestyle. The objective of this study was to explore associations between blood vitamin D levels and breast cancer risk, along with 2 potential modifiers: body mass index (BMI; in kg/m(2)) and alcohol intake. The nested case-control study involved 233 women with breast cancer and 466 healthy controls. Overall, no association was found between vitamin D levels and breast cancer risk. However, a higher blood vitamin D concentration was associated with a decreased risk of breast cancer for women with a BMI under 22.4, whereas it was associated with an increased risk for women with a BMI 22.4 or over. A blood vitamin D concentration ≥ 10 ng/mL was associated with a decreased risk of breast cancer for women with alcohol intakes ≥ 7.1 g/day, whereas no association was observed for women with alcohol intakes < 7.1g/day. The authors concluded that BMI and alcohol intake modified the association between vitamin D and breast cancer risk. These lifestyle factors could explain the inconclusive results of previous studies.
Abstract
BACKGROUND Mechanistic hypotheses suggest that vitamin D may contribute to the prevention of breast cancer. However, epidemiologic evidence is inconsistent, suggesting a potential effect modification by individual factors. OBJECTIVE Our objective was to perform exploratory analyses on the prospective associations between the plasma 25-hydroxyvitamin D [25(OH)D] concentration, polymorphisms of genes encoding for the vitamin D receptor (VDR) and vitamin D-binding protein (also known as gc-globulin or group-specific component, GC), and breast cancer risk, along with 2 potential modifiers: body mass index (BMI; in kg/m(2)) and alcohol intake. METHODS A nested case-control study was set up in the SUpplémentation en VItamines et Minéraux Anti-oXydants (SU.VI.MAX) cohort (1994-2007), involving 233 women with breast cancer and 466 matched controls (mean ± SD age: 49 ± 6 y). The plasma total 25(OH)D concentration and gene polymorphisms were assessed on samples obtained at baseline. Conditional logistic regression models were computed. RESULTS A higher plasma 25(OH)D concentration was associated with a decreased risk of breast cancer for women with a BMI < the median of 22.4 [OR quartile (Q)4 compared with Q1: 0.46; 95% CI: 0.23, 0.89; P-trend = 0.01, P-interaction = 0.002], whereas it was associated with an increased risk for women with a BMI ≥ the median (OR Q4 compared with Q1: 2.45; 95% CI: 1.13, 5.28; P-trend = 0.02, P-interaction = 0.002). A plasma 25(OH)D concentration ≥ 10 ng/mL was associated with a decreased risk of breast cancer for women with alcohol intakes ≥ the median of 7.1 g/d (OR ≥10 compared with <10 ng/mL: 0.50; 95% CI: 0.26, 0.95; P = 0.03, P-interaction = 0.03). The genetic analyses were consistent with the results observed with plasma 25(OH)D. CONCLUSION In this prospective study, BMI and alcohol intake modified the association between vitamin D [plasma 25(OH)D and vitamin D-related gene polymorphisms] and breast cancer risk. These effect modifications suggest explanations for discrepancies in results of previous studies. This trial was registered at clinicaltrials.gov as NCT00272428.
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Randomised controlled trial of effect of fruit and vegetable consumption on plasma concentrations of lipids and antioxidants.
Zino, S, Skeaff, M, Williams, S, Mann, J
BMJ (Clinical research ed.). 1997;314(7097):1787-91
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Previous studies have suggested that people with high intake of fruit and vegetables or plasma antioxidant levels have a reduced risk of cancer and cardiovascular disease. There is limited data concerning the extent to which increased intake of fruit and vegetables, opposed to antioxidant supplementation, correlate with antioxidant plasma concentration levels. he aim of this trial was to examine whether advice to increase fruit and vegetable consumption affect the plasma concentrations of antioxidants, total and low-density lipoprotein (LDL). Eighty-seven subjects with normal lipid profiles who ate three of fewer servings of fruit and vegetables a day were included and the intervention group was asked to consume eight servings of fruit and vegetables a day for eight weeks. he findings of this study showed that plasma concentrations of vitamin C, alpha-carotene and beta-carotene, factors associated with reduced cancer risk, increased in parallel with increased fruit and vegetable intake in the intervention group. More specific dietary advice may be required to modify the levels of lipoprotein and vitamin E.
Abstract
OBJECTIVES To determine the extent to which plasma antioxidant concentrations in people with habitual low intake of fruit and vegetables respond to increased intakes of these foods. To examine whether advice to increase fruit and vegetables will result in reduction of concentrations of total and low density lipoprotein cholesterol. DESIGN Randomised controlled trial in which intervention and control groups were followed up for eight weeks. The intervention group was asked to consume eight servings of fruit and vegetables a day. SETTING Dunedin, New Zealand. SUBJECTS Eighty seven subjects with normal lipid concentrations who ate three or fewer servings of fruit and vegetables daily. MAIN OUTCOME MEASURES Plasma concentrations of vitamin C, retinol, alpha and beta carotene, alpha tocopherol, lipids, and lipoproteins. Dietary intake assessed with diet records over four days. RESULTS The mean plasma vitamin C, alpha carotene, and beta carotene concentrations increased in parallel with increased dietary intake of fruit and vegetables in the intervention group. Concentrations of retinol, alpha tocopherol, lipids, and lipoproteins remained unchanged despite some increase in dietary vitamin E and a small reduction in saturated fat intake. CONCLUSIONS Following a recommendation to increase fruit and vegetable consumption produces change in plasma concentrations of vitamin C, alpha carotene, and beta carotene likely to reduce incidence of cancer. More specific dietary advice to modify fat intake may be necessary to reduce the risk of cardiovascular disease mediated by lipoprotein and vitamin E.