Effect of altitude on brain intracellular pH and inorganic phosphate levels

Abstract

Normal brain activity is associated with task-related pH changes. Although central nervous system syndromes associated with significant acidosis and alkalosis are well understood, the effects of less dramatic and chronic changes in brain pH are uncertain. One environmental factor known to alter brain pH is the extreme, acute change in altitude encountered by mountaineers. However, the effect of long-term exposure to moderate altitude has not been studied. The aim of this two-site study was to measure brain intracellular pH and phosphate-bearing metabolite levels at two altitudes in healthy volunteers, using phosphorus-31 magnetic resonance spectroscopy (31P-MRS). Increased brain pH and reduced inorganic phosphate (Pi) levels were found in healthy subjects who were long-term residents of Salt Lake City, UT (4720 ft/1438 m), compared with residents of Belmont, MA (20 ft/6 m). Brain intracellular pH at the altitude of 4720 ft was more alkaline than that observed near sea level. In addition, the ratio of inorganic phosphate to total phosphate signal also shifted toward lower values in the Salt Lake City region compared with the Belmont area. These results suggest that long-term residence at moderate altitude is associated with brain chemical changes.

Cerebral bioenergetic differences measured by phosphorus‐31 magnetic resonance spectroscopy between bipolar disorder and healthy subjects living in two different regions suggesting possible effects of altitude

“…Another possible factor that affects intracellular pH may be mild hyperventilation under hypoxic condition. High‐altitude residents showed higher levels of pH in both arterial blood and brain than did sea‐level residents . This opposite directional drive in pH may dim the pH differences in the study population.…”

“…The comparability of spectral data across the two study sites has been validated using phantoms as reported in an earlier publication . Although the same type of scanner manufactured by Siemens and dual‐tuned RF coil were used at both sites, we also monitored the quality of MR spectroscopic imaging by performing repeated 31 P‐MRS scans at both sites.…”

“…This hypobaric hypoxia causes a compensatory hyperventilation, hypocapnia, and mild alkalosis; moreover the 15% decrease in atmospheric pressure between SLC and sea level is known to translate to a 20% decrease in the partial pressure of oxygen in arterial blood in healthy human volunteers . We have previously reported that healthy subjects living in SLC demonstrated a higher pH in the brain compared to subjects in the Boston area near sea level …”

An Open-Label Pilot Study of Combined Augmentation With Creatine Monohydrate and 5-Hydroxytryptophan for Selective Serotonin Reuptake Inhibitor– or Serotonin-Norepinephrine Reuptake Inhibitor–Resistant Depression in Adult Women

“…Healthy individuals residing at 1370m (Salt Lake City, UT) show reduced inorganic phosphate levels and increased brain pH compared to those residing near sea level (Belmont, MA or Charleston, SC). 56 In rodents, hypobaric hypoxia increases the ratios of cellular metabolites like inositol to total creatine in the frontal cortex, 57 which is compatible with reductions in total creatine level. Accordingly, the women participating in this study may have been more likely than women residing at sea level to respond to the intervention, and, because of reduced basal serotonin synthesis, less likely to develop serotonin syndrome.…”

Higher serum phosphorus is associated with catabolic/anabolic imbalance in heart failure

“…Tissue hypoxia and energy starvation might have resulted in the slowing of intracellular pumping of phosphorus, leaving part of the mineral outside. For example, hypobaric hypoxia is associated with reduction of phosphorus content within the brain . Shortage of bioavailable phosphorus within a cell may have impeded ATP production as was recently shown in case of chondrocytes and may have closed circulus vitiosus of detrimental events .…”