Examining the relationship between diet-induced acidosis and cancer

Nutrition & Metabolism (Impact Factor: 3.26). 08/2012; 9(1):72. DOI: 10.1186/1743-7075-9-72
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Increased cancer risk is associated with select dietary factors. Dietary lifestyles can alter systemic acid-base balance over time. Acidogenic diets, which are typically high in animal protein and salt and low in fruits and vegetables, can lead to a sub-clinical or low grade state of metabolic acidosis. The relationship between diet and cancer risk prompts questions about the role of acidosis in the initiation and progression of cancer. Cancer is triggered by genetic and epigenetic perturbations in the normal cell, but it has become clear that microenvironmental and systemic factors exert modifying effects on cancer cell development. While there are no studies showing a direct link between diet-induced acidosis and cancer, acid-base disequilibrium has been shown to modulate molecular activity including adrenal glucocorticoid, insulin growth factor (IGF-1), and adipocyte cytokine signaling, dysregulated cellular metabolism, and osteoclast activation, which may serve as intermediary or downstream effectors of carcinogenesis or tumor promotion. In short, diet-induced acidosis may influence molecular activities at the cellular level that promote carcinogenesis or tumor progression. This review defines the relationship between dietary lifestyle and acid-base balance and discusses the potential consequences of diet-induced acidosis and cancer occurrence or progression.

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    • "A diet with a persistently high acid load can cause blood pH to decrease towards the lower end of the normal physiological range [3]. This disequilibrium in acid/base balance, if not compensated for by homeostatic mechanisms or dietary modification can lead to the development of chronic mild metabolic acidosis [4] [5]. "
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    ABSTRACT: Western diets rich in animal protein and poor in fruit and vegetables increase the body acid load, a predictor of type 2 diabetes risk. The relationships between dietary acid load, mild metabolic acidosis and insulin resistance remain unclear. The objective of this study was to assess the association between dietary acid load, body acid/base markers and peripheral insulin resistance at baseline and following a short-term overfeeding intervention in healthy individuals. In a cross-sectional study of 104 men and women, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Plasma lactate, a marker of metabolic acidosis, was assessed and acid load scores (potential renal acid load, PRAL and net endogenous acid production, NEAP) derived from diet diaries. The cohort was grouped into lean and overweight/obese and the latter further classified as insulin-sensitive (Obsen) and insulin-resistant (Obres) based on hyperinsulinemic-euglycemic clamp glucose infusion rate (GIR, top tertile vs. bottom 2 tertiles). A subset of 40 individuals participated in an overfeeding intervention (+1250 kcal/day) for 28 days and studies repeated. Obsen and Obres were matched for adiposity (BMI and fat mass, both P = 1). Fasting plasma lactate was higher in Obres (0.78 [0.63-1.14] mmol/L) compared with both lean (0.71 [0.44-0.90] mmol/L, P = 0.02) and Obsen (0.67 [0.56-0.79] mmol/L, P = 0.04) and not different between lean and Obsen (P = 0.9). Overfeeding was characterized by an increase in dietary acid load scores PRAL (P = 0.003) and NEAP (P = 0.05), a reduction in GIR necessary to maintain euglycemia (P = 0.03) and an increase in fasting plasma lactate (P = 0.02). The change in lactate was inversely associated with the change in GIR (r = -0.36, P = 0.03). Mild metabolic acidosis, measured by plasma lactate, aligns with insulin resistance independent of obesity and is induced by short-term increases in energy and dietary acid load in healthy humans. Further studies are required to determine whether buffering mild metabolic acidosis improves insulin resistance and reduces diabetes risk. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
    Clinical nutrition (Edinburgh, Scotland) 08/2015; DOI:10.1016/j.clnu.2015.08.002 · 4.48 Impact Factor
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    • "There is some reporting on the palliative role of alkalinization through sodium bicarbonate treatment in cancer patients [36] [37], but most studies examining alkalinization in cancer treatment focus on animal models for breast and prostate cancer [15–19, 35, 38]. Although diet-induced, endogenous acid production is a relevant factor in chronic diseases [39] [40] [41] and may have a potential role in cancer [39] [42], it is not yet clear if dietary alkaline loading helps to prevent cancer or diminishes tumor aggression. Acidity appears to be paradoxically stressful, yet an important driver of tumor progression and aggression [43]. "
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    ABSTRACT: The extracellular pH (pHe) of many solid tumors is acidic as a result of glycolytic metabolism and poor perfusion. Acidity promotes invasion and enhances metastatic potential. Tumor acidity can be buffered by systemic administration of an alkaline agent such as sodium bicarbonate. Tumor-bearing mice maintained on sodium bicarbonate drinking water exhibit fewer metastases and survive longer than untreated controls. We predict this effect is due to inhibition of tumor invasion. Reducing tumor invasion should result in fewer circulating tumor cells (CTCs). We report that bicarbonate-treated MDA-MB-231 tumor-bearing mice exhibited significantly lower numbers of CTCs than untreated mice (P < 0.01). Tumor pHe buffering may reduce optimal conditions for enzymes involved in tumor invasion such as cathepsins and matrix metalloproteases (MMPs). To address this, we tested the effect of transient alkalinization on cathepsin and MMP activity using enzyme activatable fluorescence agents in mice bearing MDA-MB-231 mammary xenografts. Transient alkalinization significantly reduced the fluorescent signal of protease-specific activatable agents in vivo (P ≤ 0.003). Alkalinization, however, did not affect expression of carbonic anhydrase IX (CAIX). The findings suggest a possible mechanism in a live model system for breast cancer where systemic alkalinization slows the rate of invasion.
    07/2013; 2013(4):485196. DOI:10.1155/2013/485196
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    ABSTRACT: In 21st-century public health, rapid urbanization and mental health disorders are a growing global concern. The relationship between diet, brain function and the risk of mental disorders has been the subject of intense research in recent years. In this review, we examine some of the potential socioeconomic and environmental challenges detracting from the traditional dietary patterns that might otherwise support positive mental health. In the context of urban expansion, climate change, cultural and technological changes and the global industrialization and ultraprocessing of food, findings related to nutrition and mental health are connected to some of the most pressing issues of our time. The research is also of relevance to matters of biophysiological anthropology. We explore some aspects of a potential evolutionary mismatch between our ancestral past (Paleolithic, Neolithic) and the contemporary nutritional environment. Changes related to dietary acid load, advanced glycation end products and microbiota (via dietary choices and cooking practices) may be of relevance to depression, anxiety and other mental disorders. In particular, the results of emerging studies demonstrate the importance of prenatal and early childhood dietary practices within the developmental origins of health and disease concept. There is still much work to be done before these population studies and their mirrored advances in bench research can provide translation to clinical medicine and public health policy. However, the clear message is that in the midst of a looming global epidemic, we ignore nutrition at our peril.
    Journal of PHYSIOLOGICAL ANTHROPOLOGY 07/2014; 33(1):22. DOI:10.1186/1880-6805-33-22 · 1.27 Impact Factor
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