Abstract
Oral administration of pH buffers can reduce the development of spontaneous and experimental metastases in mice, and has been proposed in clinical trials. Effectiveness of buffer therapy is likely to be affected by diet, which could contribute or interfere with the therapeutic alkalinizing effect. Little data on food pH buffering capacity was available. This study evaluated the pH and buffering capacity of different foods to guide prospective trials and test the effect of the same buffer (lysine) at two different ionization states. Food groups were derived from the Harvard Food Frequency Questionnaire. Foods were blended and pH titrated with acid from initial pH values until 4.0 to determine "buffering score", in mmol H+/pH unit. A "buffering score" was derived as the mEq H+ consumed per serving size to lower from initial to a pH 4.0, the postprandial pH of the distal duodenum. To differentiate buffering effect from any metabolic byproduct effects, we compared the effects of oral lysine buffers prepared at either pH 10.0 or 8.4, which contain 2 and 1 free base amines, respectively. The effect of these on experimental metastases formation in mice following tail vein injection of PC-3M prostate cancer cells were monitored with in vivo bioluminescence. Carbohydrates and dairy products' buffering score varied between 0.5 and 19. Fruits and vegetables showed a low to zero buffering score. The score of meats varied between 6 and 22. Wine and juices had negative scores. Among supplements, sodium bicarbonate and Tums® had the highest buffering capacities, with scores of 11 and 20 per serving size, respectively. The "de-buffered" lysine had a less pronounced effect of prevention of metastases compared to lysine at pH 10. This study has demonstrated the anti-cancer effects of buffer therapy and suggests foods that can contribute to or compete with this approach to manage cancer.
Highlights
Solid tumors exhibit a higher rate of glucose uptake and metabolism compared to normal surrounding tissues, which is a strong negative prognostic factor for disease outcome [1]
Gastric juices are kept at low pH (~2) by the secretion of hydrochloric acid (HCl) by parietal cells, which are part of a control mechanism to keep the gastric pH at this optimum level, which maximizes the activation of pepsin and absorption of nutrients [35,36,37]
Measurements of duodenal pH have been accomplished via insertion of electrodes in different regions, and measurements have been performed for several hours to account for periods of fasting, feeding and digestion
Summary
Solid tumors exhibit a higher rate of glucose uptake and metabolism compared to normal surrounding tissues, which is a strong negative prognostic factor for disease outcome [1]. It is notable that cancer cells maintain a high level of glucose metabolism even in the presence of oxygen, which was first documented by Warburg more than 80 years ago [2,3]. Prior mathematical models and empirical studies have shown that solid tumors export acid to the surrounding parenchyma [6,7]. This is consistent with measurements of tumor pH in mouse models, which have shown that the extracellular pH of solid tumors is acidic [8,9]. The acid produced by hyperglycolytic cancer cells selects for increased acid resistance in the tumor population, while the normal stromal cells are relatively more sensitive to acid-induced cell death [10,11,12]
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