Effects of a dietary load of acid or base on changes induced by lactose in rats

Groot, A. P. De; Lina, B.A.R.; Hagenaars, An; Hollanders, V.M.H.; Andringa, M.F.A.; Feron, V.J.

doi:10.1016/0278-6915(95)80241-x

Cited by 22 publications

(10 citation statements)

References 41 publications

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“…Casein is the major protein in skim milk powder and can display comparative anticancer activity (43,44). Lactose, a major component of milk and milk products and which is broken down during the fermentation process, has been suggested to promote the development of bladder cancer in animal studies (45,46). Fermented milk contains lactic acid bacteria, which have been shown to play a role in reducing bladder carcinogenesis (47).…”

Section: Discussionmentioning

confidence: 99%

Milk Consumption and Bladder Cancer Risk: A Meta-Analysis of Published Epidemiological Studies

Mao

Dai

Lin

et al. 2011

Nutrition and Cancer

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Studies investigating the association of milk consumption with bladder cancer risk have reported inconsistent findings. We conducted a meta-analysis of published cohort and case-control studies to pool the risk estimates of the association between milk intake and bladder cancer. We quantified associations with bladder cancer using meta-analysis of odds ratio (OR) associated with the highest vs. the lowest category of milk intake using fixed- or random-effect models depending on the heterogeneity of effects among studies. Nineteen cohort and case-control studies were eligible for inclusion. High milk intake was significantly associated with decreased risk of bladder cancer (OR, 0.84; 95% CI, 0.71-0.97) when comparing the highest with the lowest category of milk intake. The inverse association was stronger in Asia (OR, 0.60; 95% CI, 0.40-0.81) than North America (OR, 0.89; 95% CI, 0.76-1.03), and no association was observed in Europe (OR, 1.05; 95% CI, 0.85-1.26). This relationship also varied significantly by specific dairy products. Our results suggest that milk may be related to the reduction of bladder cancer risk. Further studies need to clarify the biological mechanisms.

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Section: Discussionmentioning

confidence: 99%

Milk Consumption and Bladder Cancer Risk: A Meta-Analysis of Published Epidemiological Studies

Mao

Dai

Lin

et al. 2011

Nutrition and Cancer

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“…These considerations indicate that the actual influence of intestinal fermentation on the acid-base equilibrium is difficult to evaluate. Furthermore, such an influence (if any) is probably quite different when colonic fermentation is poorly active, in practically neutral pH conditions, compared with when substrate availability allows the development of acidic fermentation (De Groot et al 1995), establishing an H + concentration gradient between the bulk colonic medium and extracellular fluid ranging from 10 to 50.…”

Section: Anions Produced In Situ In the Digestive Tractmentioning

confidence: 99%

Organic anions and potassium salts in nutrition and metabolism

et al. 2004

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The present review examines the importance of dietary organic anions in preventive nutrition. Organic anions are chiefly supplied by plant foods, as partially neutralised K salts such as potassium citrate, potassium malate and, to a lesser extent, oxalate or tartrate salts. Animal products may also supply K anions, essentially as phosphate, but also as lactate as a result of fermentative or maturation processes, but these K salts have little alkalinising significance. Citrate and malate anions are absorbed in the upper digestive tract, while a substantial proportion is probably metabolised in the splanchnic area. Whatever their site of metabolism, these anions finally yield KHCO 3 which is used by the kidneys to neutralise fixed acidity. This acidity essentially reflects the oxidation of excess S amino acids to sulfate ions, which is mainly related to the dietary protein level. Failure to neutralise acidity leads to low-grade metabolic acidosis, with possible long-term deleterious effects on bone Ca status and on protein status. Furthermore, low-grade acidosis is liable to affect other metabolic processes, such as peroxidation of biological structures. These metabolic disturbances could be connected with the relatively high incidence of osteoporosis and muscle-protein wasting problems observed in ageing individuals in Europe and Northern America. Providing a sufficient supply of K organic anions through fruit and vegetable intake should be recommended, fostering the actual motivational campaigns ('five (or ten) per d') already launched to promote the intake of plant foods rich in complex carbohydrates and various micronutrients.

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“…Treatments causing carbohydrate malabsorption in rats-such as lactose, sorbitol, xylitol, mannitol, and lactitol-are associated with abnormalities in calcium handling and in treatmentrelated adrenal medullary hyperplasia and pheochromocytomas (Roe and Bar 1985;Baer 1988;Sinkeldam et al 1992;de Groot et al 1995;Tischler et al 1996). Unlike in rats, lactose and xylitol do not induce pheochromocytomas in mice (Lynch et al 1996).…”

Section: Genotoxicity Assessment and Tumor Findings In 2-year Canaglimentioning

confidence: 88%

Successful Integration of Nonclinical and Clinical Findings in Interpreting the Clinical Relevance of Rodent Neoplasia with a New Chemical Entity

et al. 2014

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Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, has been developed for the treatment of adults with type 2 diabetes mellitus (T2DM). During the phase 3 program, treatment-related pheochromocytomas, renal tubular tumors, and testicular Leydig cell tumors were reported in the 2-year rat toxicology study. Treatment-related tumors were not seen in the 2-year mouse study. A cross-functional, mechanism-based approach was undertaken to determine whether the mechanisms responsible for tumorigenesis in the rat were of relevance to humans. Based on findings from nonclinical and clinical studies, the treatment-related tumors observed in rats were not deemed to be of clinical relevance. Here, we describe the scientific and regulatory journey from learning of the 2-year rat study findings to the approval of canagliflozin for the treatment of T2DM.

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Effects of a dietary load of acid or base on changes induced by lactose in rats

Cited by 22 publications

References 41 publications

Milk Consumption and Bladder Cancer Risk: A Meta-Analysis of Published Epidemiological Studies

Milk Consumption and Bladder Cancer Risk: A Meta-Analysis of Published Epidemiological Studies

Organic anions and potassium salts in nutrition and metabolism

Successful Integration of Nonclinical and Clinical Findings in Interpreting the Clinical Relevance of Rodent Neoplasia with a New Chemical Entity

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