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D-Lactate and the False Suffocation Alarm

D-Lactate and the False Suffocation Alarm The false suffocation alarm hypothesis was proposed by Klein1 in light of his and his colleagues' earlier finding that D-lactate infusion was almost as effective as L-lactate in inducing panic attacks.2 This hypothesis has now become widely accepted, but in our view, it is fundamentally flawed. Klein's assumption was that D-lactate could not be metabolized by humans, and he drew the conclusion from his findings that theories of lactate-induced panic requiring metabolism of the lactate were invalid. There was at the time a considerable literature demonstrating that D-lactate is metabolized by humans,3-5 and this has grown6 with the confirmation that enzymes required for this are present in humans.7 Additionally, the data presented by the Columbia Group2 are indicative that D-lactate was being metabolized by their subjects. Specifically, changes in venous bicarbonate, pH, PCO2, and plasma phosphate induced by infusions of D-lactate and DL-lactate, were statistically indistinguishable, indicating that both were undergoing similar metabolic fates and producing similar physiological effects in blood chemistry. In attempting to explain the nonstereospecificity of the lactate-panic effect, Klein proposed the existence of lactate receptors unable to distinguish between the stereoisomeric forms, and he justified their existence by (what he believed to be) the absence of naturally occurring D-lactate, and therefore, the lack of evolutionary pressure to develop stereospecific receptors. This belief is erroneous. D-lactate is naturally present in humans, taken in through diet, and formed by bacteria in the colon and by blood-level increase during exercise.8 This aside, however, Klein's teleology has a further flaw. To distinguish between the various carboxylic acids involved in glycolysis, enzymes require 3-point attachment specificity.9 Stereospecificity is, therefore, a by-product of this primary evolutionary requirement rather than the result of direct selection pressure or, in the case of the suffocation alarm receptor, lack of it. Klein's receptor could only function if lactate were bound by a 2-point attachment. If this is indeed the case, then propionate should also bind to it and induce panic when infused. In light of the above, we would suggest that Klein's false suffocation alarm hypothesis requires reconsideration, and in particular, that theories of lactate panic induction requiring metabolism of lactate may deserve a new lease of life. References 1. Klein DF False suffocation alarms, spontaneous panics, and related conditions. Arch Gen Psychiatry. 1993;50306- 317Google ScholarCrossref 2. Gorman JMGoetz RRDillon DLiebowitz MRFyer AJDavies SKlein DF Sodium D-lactate infusion of panic disorder patients. Neuropsychopharmacology. 1990;3181- 190Google Scholar 3. Conor MWoods HFLeddingham JGG Comparison of the kinetics and utilization of D- and L-sodium lactate in normal man. Ann Nutr Metab. 1983;27481- 487Google ScholarCrossref 4. Oh MSUrbarri LAlverauga D Metabolic utilization and renal handling of D-lactate in man. Metab Clin Exp. 1985;34621- 625Google ScholarCrossref 5. Sacks W The cerebral metabolism of L- and D-lactate in humans. Ann N Y Acad Sci. 1965;1191091- 1108Google ScholarCrossref 6. Kuze SNaruse IYamazaki MHirota KIto YMiyahara T Effects of L-lactate and sodium racemic lactate on intraopemtive acid-base stares. Anesth Analg. 1992;75702- 707Google ScholarCrossref 7. Yasuda TOzawa SShiba CMaeba TKanazawa TSugiyama MOwada SIshida M D-lactate metabolism in patients with chronic renal failure undergoing CAPD. Nephron. 1993;63416- 422Google ScholarCrossref 8. Kondoh YKawase MOhmoh S D-lactate concentration in blood, urine, and sweat before and after exercise. Eur J Appl Physiol Occup Physiol. 1992;6588- 93Google ScholarCrossref 9. Ogston AG Interpretation of experiments on metabolic processes using trace elements. Nature. 1948;162963Google ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

D-Lactate and the False Suffocation Alarm

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Publisher
American Medical Association
Copyright
Copyright © 2002 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.59.3.287
Publisher site
See Article on Publisher Site

Abstract

The false suffocation alarm hypothesis was proposed by Klein1 in light of his and his colleagues' earlier finding that D-lactate infusion was almost as effective as L-lactate in inducing panic attacks.2 This hypothesis has now become widely accepted, but in our view, it is fundamentally flawed. Klein's assumption was that D-lactate could not be metabolized by humans, and he drew the conclusion from his findings that theories of lactate-induced panic requiring metabolism of the lactate were invalid. There was at the time a considerable literature demonstrating that D-lactate is metabolized by humans,3-5 and this has grown6 with the confirmation that enzymes required for this are present in humans.7 Additionally, the data presented by the Columbia Group2 are indicative that D-lactate was being metabolized by their subjects. Specifically, changes in venous bicarbonate, pH, PCO2, and plasma phosphate induced by infusions of D-lactate and DL-lactate, were statistically indistinguishable, indicating that both were undergoing similar metabolic fates and producing similar physiological effects in blood chemistry. In attempting to explain the nonstereospecificity of the lactate-panic effect, Klein proposed the existence of lactate receptors unable to distinguish between the stereoisomeric forms, and he justified their existence by (what he believed to be) the absence of naturally occurring D-lactate, and therefore, the lack of evolutionary pressure to develop stereospecific receptors. This belief is erroneous. D-lactate is naturally present in humans, taken in through diet, and formed by bacteria in the colon and by blood-level increase during exercise.8 This aside, however, Klein's teleology has a further flaw. To distinguish between the various carboxylic acids involved in glycolysis, enzymes require 3-point attachment specificity.9 Stereospecificity is, therefore, a by-product of this primary evolutionary requirement rather than the result of direct selection pressure or, in the case of the suffocation alarm receptor, lack of it. Klein's receptor could only function if lactate were bound by a 2-point attachment. If this is indeed the case, then propionate should also bind to it and induce panic when infused. In light of the above, we would suggest that Klein's false suffocation alarm hypothesis requires reconsideration, and in particular, that theories of lactate panic induction requiring metabolism of lactate may deserve a new lease of life. References 1. Klein DF False suffocation alarms, spontaneous panics, and related conditions. Arch Gen Psychiatry. 1993;50306- 317Google ScholarCrossref 2. Gorman JMGoetz RRDillon DLiebowitz MRFyer AJDavies SKlein DF Sodium D-lactate infusion of panic disorder patients. Neuropsychopharmacology. 1990;3181- 190Google Scholar 3. Conor MWoods HFLeddingham JGG Comparison of the kinetics and utilization of D- and L-sodium lactate in normal man. Ann Nutr Metab. 1983;27481- 487Google ScholarCrossref 4. Oh MSUrbarri LAlverauga D Metabolic utilization and renal handling of D-lactate in man. Metab Clin Exp. 1985;34621- 625Google ScholarCrossref 5. Sacks W The cerebral metabolism of L- and D-lactate in humans. Ann N Y Acad Sci. 1965;1191091- 1108Google ScholarCrossref 6. Kuze SNaruse IYamazaki MHirota KIto YMiyahara T Effects of L-lactate and sodium racemic lactate on intraopemtive acid-base stares. Anesth Analg. 1992;75702- 707Google ScholarCrossref 7. Yasuda TOzawa SShiba CMaeba TKanazawa TSugiyama MOwada SIshida M D-lactate metabolism in patients with chronic renal failure undergoing CAPD. Nephron. 1993;63416- 422Google ScholarCrossref 8. Kondoh YKawase MOhmoh S D-lactate concentration in blood, urine, and sweat before and after exercise. Eur J Appl Physiol Occup Physiol. 1992;6588- 93Google ScholarCrossref 9. Ogston AG Interpretation of experiments on metabolic processes using trace elements. Nature. 1948;162963Google ScholarCrossref

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Mar 1, 2002

References