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Journal ArticleDOI

Is there a role for carbohydrate restriction in the treatment and prevention of cancer

26 Oct 2011-Nutrition & Metabolism (BioMed Central)-Vol. 8, Iss: 1, pp 75-75
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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Journal ArticleDOI
TL;DR: It is suggested that SSB accounts for a leading risk factor of stroke, depression, cancer, and mortality, and that the risk rises in parallel with the increment of SSB intake (and is affected by participant characteristics).
Abstract: The associations between sugar-sweetened beverage (SSB) consumption and the risk of stroke, depression, cancer, and cause-specific mortality have not been determined, and the quantitative aspects of this link remain unclear. This meta-analysis therefore conducted a systematic review and dose-response analysis to determine their causal links. The database searches were conducted in PubMed, Cochrane library, Embase, Web of Science up to 10 November 2021. The intervention effects were evaluated by relative risk (RR) with 95% confidences (CI). Thirty-two articles met the inclusion criteria. Higher levels of SSB consumption significantly increased the risk of stroke (RR 1.12, 95% CI 1.03–1.23), depression (1.25, 1.11–1.41), cancer (1.10, 1.03–1.17), and all-cause mortality (1.08, 1.05–1.11) compared with none or lower SSB intake. The associations were dose-dependent, with per 250 mL increment of SSB intake daily increasing the risk of stroke, depression, cancer, and all-cause mortality by RR 1.09 (1.03–1.15), 1.08 (1.06–1.10), 1.17 (1.04–1.32), and 1.07 (1.03–1.11), respectively. The link was curved for depression and cancer risk (pnon-linear < 0.05). Subgroup analysis suggested that higher SSB intake increased ischemic stroke by 10%, CVD-caused mortality by 13%, and cancer-caused mortality by 6.0% than none or lower SSB consumption. It is suggested that SSB accounts for a leading risk factor of stroke, depression, cancer, and mortality, and that the risk rises in parallel with the increment of SSB intake (and is affected by participant characteristics).

10 citations

Journal ArticleDOI
TL;DR: Appropriateness of this therapy still needs to be improved, especially in addressing the issues of non-evidence-based combined use of multiple enteral nutrition formulas, the relatively high rate of concomitant use of enteral and parenteral nutrition, off-label use of diabetes-specific Fresubin Diabetes, insufficient use ofsupportan in cancer patients, and unnecessary use of Supportan in intensive care patients not suffering from cancer.
Abstract: Background A retrospective utilization study was performed to evaluate utilization patterns for enteral nutrition in a university teaching hospital.

10 citations


Cites background from "Is there a role for carbohydrate re..."

  • ...(ie, a high glucose demand compared with benign cells of the same tissue) and is thus specific for cancer patients with malnutrition.(9) It is also indicated for patients with an increased demand for omega-3 fatty acids....

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Journal ArticleDOI
TL;DR: The proteomic profile change between CSO and CSR is analyzed and a new biomarker ALCAM is identified in recurrent chordomas, shedding light on unraveling the pathophysiology of chordoma recurrence and on exploring more effective prognostic biomarkers and targeted therapies against this devastating disease.
Abstract: Chordomas are locally destructive tumors with high rates of recurrence and a poor prognosis. The mechanisms involved in chordoma recurrence remain largely unknown. In the present study, we examined the proteomic profile of a chordoma primary tumor (CSO) and a recurrent tumor (CSR) through mass spectrum in a chordoma patient who underwent surgery. Bioinformatic analysis of the profile showed that 359 proteins had a significant expression difference and 21 pathways had a striking alteration between the CSO and the CSR. The CSR showed a significant increase in carbohydrate metabolism. Immunohistochemistry (IHC) confirmed that the cancer stem cell marker activated leukocyte cell adhesion molecule (ALCAM or CD166) expression level was higher in the recurrent than that in the primary tumor. The present study analyzed the proteomic profile change between CSO and CSR and identified a new biomarker ALCAM in recurrent chordomas. This finding sheds light on unraveling the pathophysiology of chordoma recurrence and on exploring more effective prognostic biomarkers and targeted therapies against this devastating disease.

10 citations

Journal ArticleDOI
TL;DR: NEDD4L elicits tumor-suppressive functions via inhibition of OSCC cell proliferation, cell cycle transition, and glycolysis by stimulating ENO1 ubiquitination and degradation, which unraveled a signaling axis important forOSCC cell survival and metabolism, which can serve as a potential therapeutic target.
Abstract: ABSTRACT Glycolysis contributes to cell metabolism and facilitates cell proliferation of oral squamous cell carcinoma (OSCC), the most common type of oral cancer. Understanding the regulatory mechanisms involved in the glycolysis of OSCC cells may provide important therapeutic inspirations. Immunohistochemistry was used to examine protein localization patterns in human OSCC tissues and Western blot was conducted to gauge protein level. Lentivirus transduction was used to overexpress or silence genes of interest. Cell proliferation was assessed by Cell Counting Kit (CCK)-8 assay while glycolysis was examined via measurement of extracellular acidification rate, oxygen consumption rate, and lactate and ATP production. In vivo cancer development was evaluated with a mouse tumor growth model. OSCC tissues displayed reduced expression of NEDD4L compared with normal tissues. NEDD4L expression positively correlated with 5-year patient survival rate, indicating that NEDD4L may be a prognosis marker for OSCC. NEDD4L overexpression suppressed proliferation, cell cycle transition, and glycolysis in OSCC cells, and inhibited in vivo tumor growth. UbiBrowser identified ENO1, an enzyme that catalyzes glycolysis, as a substrate of NEDD4L. Overexpression of NEDD4L resulted in the ubiquitination and subsequent degradation of ENO1 whereas overexpression of ENO1 reversed the functional effects of NEDD4L overexpression, restoring proliferation, cell cycle transition, and glycolysis in OSCC cells. NEDD4L elicits tumor-suppressive functions via inhibition of OSCC cell proliferation, cell cycle transition, and glycolysis by stimulating ENO1 ubiquitination and degradation. Our results unraveled a signaling axis important for OSCC cell survival and metabolism, which can serve as a potential therapeutic target.

10 citations

Journal ArticleDOI
TL;DR: In this article, the authors evaluated associations between consumption of sugar-sweetened beverages and ASBs and risks of total and subtype-specific breast cancer and found no substantial increase in the risk of breast cancer with consumption of ASBs.
Abstract: BACKGROUND Whether consumption of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) is associated with the risk of breast cancer is of public health interest. OBJECTIVES We sought to evaluate associations between consumption of SSBs and ASBs and risks of total and subtype-specific breast cancer. METHODS We followed 82,713 women from the Nurses' Health Study (1980 to 2016) and 93,085 women from the Nurses' Health Study II (1991 to 2017). Cumulatively averaged intakes of SSBs and ASBs from FFQs were tested for associations with incident breast cancer cases and subtypes using Cox regression models. We also evaluated the associations stratified by menopausal status, physical activity, BMI, and alcohol intake. RESULTS We documented 11,379 breast cancer cases during 4,655,153 person-years of follow-up. Consumption of SSBs or ASBs was not associated with total breast cancer risk: pooled HRs comparing extreme categories (≥1/day compared with <1/month) were 1.03 (95% CI, 0.95-1.12) and 0.96 (95% CI, 0.91-1.02), respectively. We observed a suggestive interaction by BMI using pooled data (P-interaction = 0.08), where a modestly higher risk of breast cancer with each serving per day increment of SSBs was found in lean women (HR, 1.06; 95% CI, 1.01-1.11) but not among overweight or obese women (HR, 1.00; 95% CI, 0.95-1.06). Moreover, in the pooled, fully adjusted analysis, compared to infrequent consumers (<1/month), those who consumed ≥1 serving of ASBs per day had a lower risk of luminal A breast tumors (HR, 0.90; 95% CI, 0.80-1.01; P-trend = 0.02). CONCLUSIONS Although no significant associations were observed overall, consumption of SSBs was associated with a slightly higher risk of breast cancer among lean women. This finding could have occurred by chance and needs confirmation. Our findings also suggest no substantial increase in the risk of breast cancer with consumption of ASBs.

9 citations

References
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Journal ArticleDOI
04 Mar 2011-Cell
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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Journal ArticleDOI
24 Jul 2008-Nature
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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Journal ArticleDOI
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

Journal ArticleDOI
10 Aug 1956-Science

2,524 citations

Journal ArticleDOI
16 Apr 2010-Science
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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