potassium-bicarbonate and Neoplasms

The effects of diet-induced acid-base disturbances were examined in 4-week, 13-week and 18-month toxicity studies, and in a 30-month carcinogenicity study. Rats were fed a natural ingredient diet (controls), supplemented with 2% or 4% KHCO(3) (base-forming diets), or with 1% or 2.1% NH(4)Cl (acid-forming diets). Additional controls were fed 3% KCl (neutral diet providing K(+) and Cl(-) in amounts equimolar to those in the 4% KHCO(3) diet and the 2.1% NH(4)Cl diet, respectively). NH(4)Cl induced the expected metabolic acidosis, as shown by decreased base excess in blood, decreased urinary pH and increased urinary net acid excretion. KHCO(3) induced the opposite effects. KCl did not affect the acid-base balance. Clinical condition and death rate were not affected. The feeding of high levels of each salt resulted in growth retardation and increased water intake and urinary volume. Plasma potassium and urinary potassium excretion were increased with KHCO(3) and KCl. Plasma chloride was increased with NH(4)Cl, but not with KCl. Urinary calcium and phosphate excretion were increased with NH(4)Cl, but there were no indications that bone minerals were involved (weight, calcium content and fat free solid of the femur were not affected). Standard haematological and clinical chemistry parameters were not affected. Kidney weights were increased with 2.1% NH(4)Cl. Hypertrophy of the adrenal zona glomerulosa occurred with KHCO(3), KCl and NH(4)Cl, due to chronic stimulation of the adrenal cortex by either K(+) or by NH(4)Cl-induced acidosis. An early onset (from week 13) of oncocytic tubules was noted in the kidneys of rats fed KHCO(3) and, after 30 months, the incidence of this lesion was much higher than the background incidence in ageing controls. No progression to oncocytomas was noted. KCl showed only slight effects on the early onset of oncocytic tubules (from 18 months). In contrast, the severity of nephrosis and the incidence of oncocytic tubules were decreased with 2.1% NH(4)Cl, suggesting a protective effect of acidosis. The feeding of KHCO(3) resulted in hyperplasia, papillomas and carcinomas of the urinary bladder. With KCl only a slight increase in proliferative urothelial lesions was noted. Apart from these (pre-)neoplastic lesions in the urinary bladder there were no treatment-related differences in tumour response among the groups. We concluded that most of the observed changes represent physiological adaptations to the feeding of acid- or base-forming

Topics: Acid-Base Equilibrium; Ammonium Chloride; Animals; Bicarbonates; Blood Gas Analysis; Bone and Bones; Calcium; Carcinogenicity Tests; Carcinogens; Diet; Drinking; Eating; Feces; Growth; Hydrogen-Ion Concentration; Male; Neoplasms; Organ Size; Phosphorus; Potassium Chloride; Potassium Compounds; Quaternary Ammonium Compounds; Rats; Rats, Wistar; Sex Characteristics

Feeding lactose or other slowly digestible carbohydrates to adult mammals may induce a variety of effects including hyperplasia and neoplasia. The most fundamental effect probably is the increased production in the large intestine of short-chain fatty acids (SCFA) resulting from increased fermentation of carbohydrate residues. To find out whether the increased production of these acidic compounds is involved in the induction of certain alterations caused by low-digestibility carbohydrates, the modifying effects of an acidifying (NH4Cl) or an alkalizing (KHCO3) diet supplement on lactose-induced changes in rats were studied. Three groups of 50 rats per sex were fed a 20% lactose diet unsupplemented or supplemented with 1% NH4Cl or 2% KHCO3, for at most 2.5 yr. One control group was fed the basal diet which contained wheat starch instead of lactose. Feeding lactose resulted in wet faecal pellets, reduced pH of the faeces, higher intake of food and water, lower body weights, increased caecal weights and fewer deaths. These effects were not significantly modified by NH4Cl or KHCO3. Feeding lactose increased urinary calcium levels, the effect being enhanced by NH4Cl and reduced by KHCO3. Lactose also tended to increase blood values of alkaline phosphatase and to decrease those for bicarbonate and base excess. These tendencies were generally more marked with NH4Cl, and less marked or absent with KHCO3. In addition, rats fed lactose showed decreased severity of nephrosis, increased mineralization and hyperplasia of the renal pelvic epithelium, and relatively high incidences of Leydig cell hyperplasia and neoplasia. NH4Cl supplementation was associated with a relatively small number of single and multiple tumours, with decreased incidences of hyperplasia and mineralization of the renal pelvis epithelium and with a markedly reduced incidence of proliferative changes in the adrenal medulla. With the KHCO3 supplement the incidences of Leydig cell proliferation and of bladder tumours were relatively high. These findings, in particular the differences between the diet groups in urinary calcium levels and possibly also the variations in blood levels of alkaline phosphatase, bicarbonate and base excess, suggest that the acidic end products of carbohydrate fermentation (SCFA) act as an acid load on the body.

Topics: Acid-Base Equilibrium; Alkaline Phosphatase; Ammonium Chloride; Animal Feed; Animals; Bicarbonates; Body Weight; Calcium; Cecum; Diarrhea; Diet; Drug Interactions; Female; Hydrogen-Ion Concentration; Kidney; Lactose; Male; Neoplasms; Organ Size; Potassium Compounds; Random Allocation; Rats; Rats, Wistar; Starch; Testis