Is there a role for carbohydrate restriction in the treatment and prevention of cancer
TL;DR: The possible beneficial effects of low CHO diets on cancer prevention and treatment are addressed, with emphasis on the role of insulin and IGF1 signaling in tumorigenesis as well as altered dietary needs of cancer patients.
Abstract: Over the last years, evidence has accumulated suggesting that by systematically reducing the amount of dietary carbohydrates (CHOs) one could suppress, or at least delay, the emergence of cancer, and that proliferation of already existing tumor cells could be slowed down. This hypothesis is supported by the association between modern chronic diseases like the metabolic syndrome and the risk of developing or dying from cancer. CHOs or glucose, to which more complex carbohydrates are ultimately digested, can have direct and indirect effects on tumor cell proliferation: first, contrary to normal cells, most malignant cells depend on steady glucose availability in the blood for their energy and biomass generating demands and are not able to metabolize significant amounts of fatty acids or ketone bodies due to mitochondrial dysfunction. Second, high insulin and insulin-like growth factor (IGF)-1 levels resulting from chronic ingestion of CHO-rich Western diet meals, can directly promote tumor cell proliferation via the insulin/IGF1 signaling pathway. Third, ketone bodies that are elevated when insulin and blood glucose levels are low, have been found to negatively affect proliferation of different malignant cells in vitro or not to be usable by tumor cells for metabolic demands, and a multitude of mouse models have shown antitumorigenic properties of very low CHO ketogenic diets. In addition, many cancer patients exhibit an altered glucose metabolism characterized by insulin resistance and may profit from an increased protein and fat intake. In this review, we address the possible beneficial effects of low CHO diets on cancer prevention and treatment. Emphasis will be placed on the role of insulin and IGF1 signaling in tumorigenesis as well as altered dietary needs of cancer patients.
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TL;DR: It is found that adherence to LCD was protectively associated with reduced odds of glioma among Iranian adults and further adjustment for dietary nutrient intakes strengthened the association.
5 citations
TL;DR: First results of the ongoing KETOCOMP study concerning body composition changes among rectal, breast and head & neck cancer patients who underwent concurrent KT during standard-of-care radiotherapy (RT) indicate some significant favorable effects of KT on body composition.
Abstract: Background: Ketogenic therapy (KT) in the form of ketogenic diets (KDs) and/or supplements that induce nutritional ketosis have gained interest as a complementary treatment for cancer patients. Besides putative anti-tumor effects, preclinical and preliminary clinical data indicate that KT could induce favorable changes in body composition of the tumor bearing host. Here we present first results of our ongoing KETOCOMP study (NCT02516501) concerning body composition changes among rectal, breast and head & neck cancer (HNC) patients who underwent concurrent KT during standard-of-care radiotherapy (RT).
Methods: Eligible patients were assigned to one of three groups: (i) a standard diet group; (ii) a ketogenic breakfast group taking 50-250 ml of a medium-chain triglyceride (MCT) drink plus 10 g essential amino acids in the morning of RT days; (iii) a complete KD group supplemented with 10 g essential amino acids on RT days. Body composition was to be measured prior to and weekly during RT using 8-electrode bioimpedance analysis. Longitudinal data were analyzed using mixed effects linear regression.
Results: A total of 17 patients underwent KT during RT thus far (rectal cancer: n=6; HNC: n=6; breast cancer: n=5). All patients consuming a KD (n=14) reached nutritional ketosis and finished the study protocol with only minor problems reported. Compared to control subjects, the ketogenic intervention in rectal and breast cancer patients was significantly associated with a decline in fat mass over time (−0.3 and −0.5 kg/week, respectively), with no significant changes in skeletal muscle mass. In HNC patients, concurrent chemotherapy was the strongest predictor of body weight, fat free and skeletal muscle mass decline during radiotherapy, while KT showed significant opposite associations. Rectal cancer patients who underwent KT during neoadjuvant RT had significantly better tumor response at the time of surgery as assessed by the Dworak regression grade (median 3 versus 2, p=0.04483).
Conclusions: While sample sizes are still small our results already indicate some significant favorable effects of KT on body composition. These as well as a putative radiosensitizing effect on rectal tumor cells need to be confirmed once the final analysis of our study becomes possible.
Clinical trial registration ID #NCT02516501.
5 citations
16 Dec 2016
TL;DR: In this paper, a discussion of the role of Palaoernahrung in modern evolutionaren medicine is presented, e.g., as an intervention gegen koronare and evtl. autoimmunologische Erkrankungen.
Abstract: Hintergrund: Der derzeit beobachtete Anstieg chronischer nicht ubertragbarer Krankheiten wird mithilfe vieler existierender Modelle versuchsweise erklart. Innerhalb der evolutionaren Medizin ergibt sich ein Erklarungsmodell aus der unvollstandigen Anpassung des Menschen an die moderne Lebensweise, was sich auch in dem Ausdruck „Zivilisationskrankheiten“ widerspiegelt. Der Ernahrung wird in diesem Kontext eine kritische Rolle eingeraumt. Diesem Ansatz folgend wurde der Begriff der „Palaoernahrung“ bzw. „Steinzeiternahrung“ als eine Ernahrungsweise eingefuhrt, welche sich an dem Nahrungsverhalten des Menschen wahrend der Altsteinzeit ausrichtet, die chronologisch den Grosteil der menschlichen Existenz ausmacht. Da sich die Palaoernahrung derzeit einer steigenden Beliebtheit nicht nur unter Konsumenten erfreut, sondern sich auch zunehmend im internationalen wissenschaftlichen Fokus wiederfindet, ist das Ziel dieser Arbeit, innerhalb des deutschsprachigen Raumes umfassend uber die Hintergrunde, Prinzipien und wissenschaftlichen Ergebnisse zur Palaoernahrung zu berichten. Material und Methodik: Aus anthropologischen und ethnografischen Daten, erganzt durch physiologische Hintergrunde, wird ein kurzer Abriss der menschlichen Ernahrung wahrend der Altsteinzeit skizziert. Aus diesen Einsichten werden die Prinzipien einer modernen Steinzeiternahrung abgeleitet. Alle bisher erschienenen klinischen Studien, mit einer Palaoernahrung als Intervention, wurden knapp beschrieben und ausgewertet. Schlieslich erfolgt eine Diskussion der Palaoernahrung als wichtiges Hilfsmittel einer modernen evolutionaren Medizin mit dem ubergeordneten Ziel der Pravention chronischer nicht ubertragbarer Krankheiten. Ergebnisse: Bisher existieren nur Studien mit kleinen Fallzahlen und methodischen Schwachen, die aber ein konsistentes Bild einer Uberlegenheit der Palaoernahrung gegenuber anderen, auch vollwertigen Ernahrungsformen ergeben. Die groste Evidenz besteht fur einen gunstigen Einfluss auf koronare Risikofaktoren; eine gunstige Wirkung auf autoimmune Erkrankungen erscheint wahrscheinlich. Schlussfolgerung: Eine Palaoernahrung eignet sich als Intervention gegen koronare und evtl. auch autoimmunologische Erkrankungen. Ihre Umsetzung wird durch den intuitiven Ansatz einer „artgerechten“ Ernahrung erleichtert.
5 citations
TL;DR: The complementary use of dietary ST with a taxol-based chemotherapy which work through separate mechanisms to reduce breast cancer metastasis support combining diet with chemotherapy in both treatment and prevention settings.
Abstract: A significant percentage of breast cancer victims will suffer from metastases indicating that new approaches to preventing breast cancer metastasis are thus needed. Dietary stearate (ST) and chemotherapy have been shown to reduce breast cancer metastasis. We tested the complementary use of dietary ST with a taxol-based chemotherapy which work through separate mechanisms to reduce breast cancer metastasis. We therefore carried out a prevention study in which diets were initiated prior to human MDA-MB-435 cancer cells being injected into the host and a treatment study in which diets were combined with paclitaxel (PTX). Using an orthotopic athymic nude mouse model and three diets [corn oil (CO) control diet, low fat (LF) or ST] the prevention study demonstrated that the ST diet decreased the incidence of lung metastasis by 50 % compared to both the LF and CO diets. The ST diet also reduced the number and size of metastatic lung nodules compared to the LF diet. Results of the treatment study indicated that both the CO and ST diets decreased the number of mice with lung metastasis compared to the LF diet. Both CO and ST also decreased the number of lung metastases per mouse compared to the LF diet however only the ST diet cohort was significant. Histomorphometric analysis of the lung tumor tissue indicated that the ST diet plus PTX decreased angiogenesis compared to the LF diet plus PTX. In conclusion these results support combining diet with chemotherapy in both treatment and prevention settings.
5 citations
Cites background from "Is there a role for carbohydrate re..."
...The idea of carbohydrate restriction for the treatment and prevention of cancer has been discussed in the literature [28] and may account for the beneficial effects of CO as well as ST in our studies....
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TL;DR: In this paper, a chemometrics-assisted second-order kinetic-spectrophotometric method has been developed for determining reducing sugars, glucose, fructose and lactose, in food samples, based on the reaction with hexacyanoferrate, HCF, at 70 °C in alkaline medium.
Abstract: In the present report, a chemometrics-assisted second-order kinetic-spectrophotometric method has been developed for determining reducing sugars, glucose, fructose and lactose, in food samples, based on the reaction with hexacyanoferrate, HCF, at 70 °C in alkaline medium. A suitable experimental design helped us to establish the conditions (pH, temperature, and HCF concentration) for optimal sensitivity and selectivity among analytes. Second order data were recorded by measuring the absorbance of unreacted HCF in the spectral range of 370 to 470 nm for five minutes using a diode array. A calibration set of samples was prepared according to a central composite design containing the three sugars for training the algorithms. Validation samples containing only the analytes were prepared for checking the reliability of the algorithms. In this particular system, identical profiles for sample components are obtained in the spectral dimension corresponding to unreacted HCF. Moreover, two kinds of interferents may be present: sample components active in the spectral region at which HCF absorbs as well as potential reducing interferents, causing linear dependence, since they provide identical profiles in spectral dimension to those of the analytes of interest. In the present work, MCR-ALS in the spectral augmentation mode was the only algorithm that could successfully resolve linear dependence. Satisfactory results were obtained by applying MCR-ALS in the spectral augmentation mode in order to achieve a second order advantage for the determination of fructose and glucose in validation samples, in test samples containing the two kinds of interferents and in real food samples, providing LODs of 4.0 and 5.0 mg L−1, respectively. However, bad results were obtained for lactose which may be due to its low sensitivity in the augmented dimension. Good results were also obtained by applying U-PLS/RBL and N-PLS/RBL for determining simultaneously the three sugars in validation samples and in test samples containing only active spectral interferents. Finally, lactose and also, glucose and fructose, were successfully quantified in real milk samples, with LODmin = 1.0 mg L−1, 1.0 mg L−1 and 0.1 mg L−1 and LODmax = 3.5, 3.8 and 4.4 mg L−1, respectively, using UPLS/RBL, and LODmin of 1.3, 1.1 and 0.1 mg L−1 and LODmax of 4.0, 4.3 and 4.9 mg L−1 for lactose, glucose and fructose, respectively, for NPLS/RBL. Results for real samples in all cases were statistically comparable to those obtained by applying a reference method based on HPLC (High Performance Liquid Chromatography).
4 citations
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TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
51,099 citations
"Is there a role for carbohydrate re..." refers background in this paper
..., a pathological capability common to most, if not all, cancer cells [39]....
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TL;DR: The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.
Abstract: The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.
9,282 citations
"Is there a role for carbohydrate re..." refers background in this paper
...Inflammation is a wellestablished driver of early tumorigenesis and accompanies most, if not all cancers [148]....
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TL;DR: In this article, the authors propose that persistent metabolism of glucose to lactate even in aerobic conditions is an adaptation to intermittent hypoxia in pre-malignant lesions, which leads to microenvironmental acidosis requiring evolution to phenotypes resistant to acid-induced cell toxicity.
Abstract: If carcinogenesis occurs by somatic evolution, then common components of the cancer phenotype result from active selection and must, therefore, confer a significant growth advantage. A near-universal property of primary and metastatic cancers is upregulation of glycolysis, resulting in increased glucose consumption, which can be observed with clinical tumour imaging. We propose that persistent metabolism of glucose to lactate even in aerobic conditions is an adaptation to intermittent hypoxia in pre-malignant lesions. However, upregulation of glycolysis leads to microenvironmental acidosis requiring evolution to phenotypes resistant to acid-induced cell toxicity. Subsequent cell populations with upregulated glycolysis and acid resistance have a powerful growth advantage, which promotes unconstrained proliferation and invasion.
4,361 citations
2,524 citations
TL;DR: Dietary restriction and reduced activity of nutrient-sensing pathways may slow aging by similar mechanisms, which have been conserved during evolution, and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible negative side effects.
Abstract: When the food intake of organisms such as yeast and rodents is reduced (dietary restriction), they live longer than organisms fed a normal diet. A similar effect is seen when the activity of nutrient-sensing pathways is reduced by mutations or chemical inhibitors. In rodents, both dietary restriction and decreased nutrient-sensing pathway activity can lower the incidence of age-related loss of function and disease, including tumors and neurodegeneration. Dietary restriction also increases life span and protects against diabetes, cancer, and cardiovascular disease in rhesus monkeys, and in humans it causes changes that protect against these age-related pathologies. Tumors and diabetes are also uncommon in humans with mutations in the growth hormone receptor, and natural genetic variants in nutrient-sensing pathways are associated with increased human life span. Dietary restriction and reduced activity of nutrient-sensing pathways may thus slow aging by similar mechanisms, which have been conserved during evolution. We discuss these findings and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible negative side effects.
2,522 citations
"Is there a role for carbohydrate re..." refers background in this paper
...As indicated in Figure 2, restriction of dietary CHOs would counteract this signalling cascade by normalizing glucose and insulin levels in subjects with metabolic syndrome, in this way acting similar to calorie restriction/fasting [61,62]....
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