1Laboratório de Biologia Molecular, Centro Infantil Boldrini, Campinas, Sao Paulo, Brazil and 2Departments of Radiology and Integrative Mathematical Oncology, Moffitt Cancer Center, Tampa, Florida
Requests for reprints: Robert A. Gatenby, Department of Radiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612. Phone: 813-745-2843; Fax: 813-745-6070; E-mail:Robert.Gatenby@moffitt.org.
A number of studies have shown that the extracellular pH (pHe) in cancers is typically lower than that in normal tissue and that an acidic pHe promotes invasive tumor growth in primary and metastatic cancers. Here, we investigate the hypothesis that increased systemic concentrations of pH buffers reduce intratumoral and peritumoral acidosis and, as a result, inhibit malignant growth. Computer simulations are used to quantify the ability of systemic pH buffers to increase the acidic pHe of tumors in vivo and investigate the chemical specifications of an optimal buffer for such purpose. We show that increased serum concentrations of the sodium bicarbonate (NaHCO3) can be achieved by ingesting amounts that have been used in published clinical trials. Furthermore, we find that consequent reduction of tumor acid concentrations significantly reduces tumor growth and invasion without altering the pH of blood or normal tissues. The simulations also show that the critical parameter governing buffer effectiveness is its pKa. This indicates that NaHCO3, with a pKa of 6.1, is not an ideal intratumoral buffer and that greater intratumoral pHe changes could be obtained using a buffer with a pKa of ∼7. The simulations support the hypothesis that systemic pH buffers can be used to increase the tumor pHe and inhibit tumor invasion. [Cancer Res 2009;69(6):2677–84]
Movement Science/Human Performance Laboratory, Department of Health & Human Development, H&PE Complex, Hoseaus Rm 121, Montana State University, Bozeman, MT USA. firstname.lastname@example.org.
The present study sought to determine whether the consumption of a mineral-rich alkalizing (AK) bottled water could improve both acid-base balance and hydration status in young healthy adults under free-living conditions. The AK water contains a naturally high mineral content along with Alka-PlexLiquid™, a dissolved supplement that increases the mineral content and gives the water an alkalizing pH of 10.0.
Thirty-eight subjects were matched by gender and self-reported physical activity (SRPA, hrs/week) and then split into Control (12 women, 7 men; Mean +/- SD: 23 +/- 2 yrs; 7.2 +/- 3.6 hrs/week SRPA) and Experimental (13 women, 6 men; 22 +/- 2 yrs; 6.4 +/- 4.0 hrs/week SRPA) groups. The Control group consumed non-mineralized placebo bottled water over a 4-week period while the Experimental group consumed the placebo water during the 1st and 4th weeks and the AK water during the middle 2-week treatment period. Fingertip blood and 24-hour urine samples were collected three times each week for subsequent measures of blood and urine osmolality and pH, as well as total urine volume. Dependent variables were analyzed using multivariate repeated measures ANOVA with post-hoc focused on evaluating changes over time within Control and Experimental groups (alpha = 0.05).
There were no significant changes in any of the dependent variables for the Control group. The Experimental group, however, showed significant increases in both the blood and urine pH (6.23 to 7.07 and 7.52 to 7.69, respectively), a decreased blood and increased urine osmolality, and a decreased urine output (2.51 to 2.05 L/day), all during the second week of the treatment period (P < 0.05). Further, these changes reversed for the Experimental group once subjects switched to the placebo water during the 4th week.
Consumption of AK water was associated with improved acid-base balance (i.e., an alkalization of the blood and urine) and hydration status when consumed under free-living conditions. In contrast, subjects who consumed the placebo bottled water showed no changes over the same period of time. These results indicate that the habitual consumption of AK water may be a valuable nutritional vector for influencing both acid-base balance and hydration status in healthy adults.
Changes in fingertip blood osmolality across the three study periods. Blood osmolality values correspond each of twelve (i.e., M1-M12) fingertip collections. Values marked with an asterisk (*) differed significantly from the M1 reference values of 335 and 352 mOsm/kg for the Control and Experimental groups, respectively (P < 0.05). Short dashed lines represent one-side SE bars.
Changes in fingertip blood pH across the three study periods. Blood pH values correspond each of twelve (i.e., M1-M12) fingertip collections. Values marked with an asterisk (*) differed significantly from the M1 reference values of 7.53 and 7.52 for the Control and Experimental groups, respectively (P < 0.05). Short dashed lines represent one-side SE bars.
The purpose of this study was to compare the ability of two types of bottled water to rehydrate cyclists following a dehydrating bout of cycling exercise. It was hypothesized that rehydration would occur faster and/or more completely following the consumption of bottled glacier water supplemented with Alka-PlexLiquid™ (experimental condition) as compared to a filtered bottled water (placebo condition).
Ten male cyclists (Mean ± SD: 40 ± 5 years age, 51.3 ± 7.8 ml/kg/min maximal oxygen uptake) performed two trials (1-week apart) of stationary cycling in a warm room (27.5–28.5°C, ≥50% relative humidity) for 75–105 minutes at a power output that initially elicited 70–80% of maximal heart rate. Subjects exercised until dehydrating to -2.5% of pre-exercise nude body weight. Each cycling bout was followed immediately by the consumption of either the experimental (Akali; Glacier Water Company, LLC; Auburn, WA USA) or placebo (Aquafina; PepsiCo Inc., Purchase, NY USA) bottled waters (counterbalanced order, double-blind design) in a volume equivalent to body weight lost. Blood and urine samples, as well as nude body weight, were measured at fixed time points: Immediately pre- and post-exercise, and 30, 60, 90, 120, and 180 minutes post-exercise. Urine samples were analyzed for volume output and specific gravity, while changes in total serum protein were determined from the blood samples. Data were evaluated with paired t-tests and repeated measures ANOVA with planned contrasts at the 0.05 alpha level.
Neither absolute (Mean ± SE; -2.00 ± 0.05 and -1.95 ± 0.07 kg) nor relative (-2.6 ± 0.1 and -2.5 ± 0.1%) amounts of body mass lost differed between placebo and experimental dehydration (P > 0.05), respectively. Urine output was significantly higher at time points ≥60 minutes post ingestion: 103.5 ± 24.4 versus 58.4 ± 14.0 mls, 183.1 ± 33.1 versus 125.2 ± 33.4 mls, 198.7 ± 35.9 versus 97.7 ± 25.5 mls, 234.5 ± 53.0 versus 107.6 ± 21.6 mls, for 60, 90, 120, and 180-min post ingestion, respectively (P < 0.05). At the same time points, urine specific gravity tended to be higher for the experimental (1.014–1.012) than placebo water (1.005–1.008;P = 0.02–0.08). Lastly, serum protein tended to be less concentrated in the blood for the experimental water trial than for the placebo water trial at 120-minutes (7.7 ± 0.03 versus 6.7 ± 0.2 g/L; P = 0.08) and 180-minutes (7.8 ± 0.3 versus 6.7 ± 0.2 g/L; P = 0.08) post ingestion. Water retention at the end of the 3-hour recovery period, calculated as 1 minus the ratio of total urine volume (TUV) to ingested water volume (IWV) as a percentage ([1-(TUV/IWV)] × 100)), was significantly higher for the experimental water trial (79.2 ± 3.9%) than for the placebo water trial (62.5 ± 5.4%; P < 0.05).
Consumption of the experimental water resulted in significantly less urine output, a tendency for more water to be retained in the blood, and a higher overall water retention rate over the placebo water. Collectively, these results indicate that consumption of the experimental bottled water following a dehydrating bout of exercise provided faster and more complete rehydration to cyclists than the highly-filtered bottled water. It is likely that the Alka-PlexLiquid™ supplement, the high pH of 10.0, or some other unidentified component of the experimental water, was responsible for these observations.