Obstet Gynecol Sci.  2020 Mar;63(2):195-204. 10.5468/ogs.2020.63.2.195.

Oxaloacetate reduces emotional symptoms in premenstrual syndrome (PMS): results of a placebo-controlled, cross-over clinical trial

Affiliations
  • 1Nutritional Supplements Division, Energy Medicine Research Institute, Boulder, CO, USA.
  • 2The Center for Health and Wellbeing, San Diego, CA, USA.
  • 3Terra Biological LLC, San Diego, CA, USA. acash@TerraBiological.com

Abstract


OBJECTIVE
Premenstrual syndrome (PMS) affects millions of women. While over-the-counter products have helped with the physical symptoms of PMS, emotional symptoms have been less well supported. The objective of this trial was to measure the effect of an oxaloacetate/vitamin C combination on the major emotional symptoms of PMS, including depression, anxiety, perceived stress, aggression, and suicidal ideation.
METHODS
Forty-eight women experiencing PMS completed a baseline survey comprising the Beck's Depression Inventory, Cohen Perceived Stress Scale, Generalized Anxiety Disorder Test, and Buss-Perry Aggression Questionnaire. After baseline measurements, participants were randomly assigned to take either 2 capsules of 100 mg oxaloacetate/150 mg ascorbic acid, or 2 capsules of rice flour (placebo) for their entire menstrual cycle. At menstruation, the women completed the 4 surveys again. The women then switched capsules in a cross-over design and continued the study for an additional menstrual cycle. The final assessment was repeated at menstruation. Statistical analysis of the 4 surveys was performed to examine efficacy.
RESULTS
Oxaloacetate/vitamin C supplementation during PMS significantly improved depression, perceived stress, anxiety, aggression, and suicidal ideation. The mean improvement in depression was 54.1%, 35.8% for perceived stress, 51.43% for generalized anxiety, and 17.8% for aggression. Suicidal ideation was reduced by 47.9%. All results were highly significant.
CONCLUSION
A combination of oxaloacetate and vitamin C supplementation helped to alleviate depression, anxiety, perceived stress, aggression, and suicidal ideation symptoms associated with PMS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03509714

Keyword

Oxaloacetate; Premenstrual syndrome; Depression; Anxiety; Suicidal ideation

MeSH Terms

Aggression
Anxiety
Anxiety Disorders
Ascorbic Acid
Capsules
Cross-Over Studies
Depression
Female
Flour
Humans
Menstrual Cycle
Menstruation
Oxaloacetic Acid*
Premenstrual Syndrome*
Suicidal Ideation
Surveys and Questionnaires
Ascorbic Acid
Capsules
Oxaloacetic Acid

Figure

  • Fig. 1 Single dose oral pharmacokinetics study of oxaloacetate in male BALB/c mice.PK, pharmacokinetics.

  • Fig. 2 An analysis of changes from baseline measurements of 4 emotional symptoms surveys versus treatment with an oxaloacetate/vitamin C mix or placebo in 48 participants with premenstrual syndrome.


Reference

1. Zendehdel M, Elyasi F. Biopsychosocial etiology of premenstrual syndrome: a narrative review. J Family Med Prim Care. 2018; 7:346–356. PMID: 30090776.
Article
2. Hoyer J, Burmann I, Kieseler ML, Vollrath F, Hellrung L, Arelin K, et al. Menstrual cycle phase modulates emotional conflict processing in women with and without premenstrual syndrome (PMS)--a pilot study. PLoS One. 2013; 8:e59780. PMID: 23637739.
3. Beck AT, Beamesderfer A. Assessment of depression: the depression inventory. Mod Probl Pharmacopsychiatry. 1974; 7:151–169. PMID: 4412100.
Article
4. Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol. 1988; 56:893–897. PMID: 3204199.
Article
5. Löwe B, Decker O, Müller S, Brähler E, Schellberg D, Herzog W, et al. Validation and standardization of the Generalized Anxiety Disorder Screener (GAD-7) in the general population. Med Care. 2008; 46:266–274. PMID: 18388841.
Article
6. Andreou E, Alexopoulos EC, Lionis C, Varvogli L, Gnardellis C, Chrousos GP, et al. Perceived Stress Scale: reliability and validity study in Greece. Int J Environ Res Public Health. 2011; 8:3287–3298. PMID: 21909307.
Article
7. Lee EH. Review of the psychometric evidence of the perceived stress scale. Asian Nurs Res. 2012; 6:121–127.
Article
8. Diamond PM, Magaletta PR. The short-form Buss-Perry Aggression Questionnaire (BPAQ-SF): a validation study with federal offenders. Assessment. 2006; 13:227–240. PMID: 16880276.
9. Rapkin AJ, Berman SM, Mandelkern MA, Silverman DH, Morgan M, London ED. Neuroimaging evidence of cerebellar involvement in premenstrual dysphoric disorder. Biol Psychiatry. 2011; 69:374–380. PMID: 21092938.
Article
10. Wolf U, Rapoport MJ, Schweizer TA. Evaluating the affective component of the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci. 2009; 21:245–253. PMID: 19776302.
Article
11. Kimbrell TA, Ketter TA, George MS, Little JT, Benson BE, Willis MW, et al. Regional cerebral glucose utilization in patients with a range of severities of unipolar depression. Biol Psychiatry. 2002; 51:237–252. PMID: 11839367.
Article
12. Schmahmann JD, Weilburg JB, Sherman JC. The neuropsychiatry of the cerebellum - insights from the clinic. Cerebellum. 2007; 6:254–267. PMID: 17786822.
Article
13. Schmahmann JD, Caplan D. Cognition, emotion and the cerebellum. Brain. 2006; 129:290–292. PMID: 16434422.
Article
14. Schmahmann JD. The role of the cerebellum in cognition and emotion: personal reflections since 1982 on the dysmetria of thought hypothesis, and its historical evolution from theory to therapy. Neuropsychol Rev. 2010; 20:236–260. PMID: 20821056.
Article
15. Trout KK, Basel-Brown L, Rickels MR, Schutta MH, Petrova M, Freeman EW, et al. Insulin sensitivity, food intake, and cravings with premenstrual syndrome: a pilot study. J Womens Health (Larchmt). 2008; 17:657–665. PMID: 18447765.
Article
16. Michener W, Rozin P, Freeman E, Gale L. The role of low progesterone and tension as triggers of perimenstrual chocolate and sweets craving: some negative experimental evidence. Physiol Behav. 1999; 67:417–420. PMID: 10497961.
17. Møller SE. Serotonin, carbohydrates, and atypical depression. Pharmacol Toxicol. 1992; 71(Suppl 1):61–71. PMID: 1480561.
Article
18. Yoshikawa K. Studies on the anti-diabetic effect of sodium oxaloacetate. Tohoku J Exp Med. 1968; 96:127–141. PMID: 4884771.
19. Cash A. Oxaloacetic acid supplementation as a mimetic of calorie restriction. Open Longev Sci. 2009; 3:22–27.
20. Marco R, Pestaña A, Sebastian J, Sols A. Oxaloacetate metabolic crossroads in liver. Enzyme compartmentation and regulation of gluconeogenesis. Mol Cell Biochem. 1974; 3:53–70. PMID: 4363722.
Article
21. Ford TC, Nibbs R, Crewther DP. Glutamate/GABA+ ratio is associated with the psychosocial domain of autistic and schizotypal traits. PLoS One. 2017; 12:e0181961. PMID: 28759626.
Article
22. Stan AD, Schirda CV, Bertocci MA, Bebko GM, Kronhaus DM, Aslam HA, et al. Glutamate and GABA contributions to medial prefrontal cortical activity to emotion: implications for mood disorders. Psychiatry Res. 2014; 223:253–260. PMID: 24973815.
Article
23. Zlotnik A, Sinelnikov I, Gruenbaum BF, Gruenbaum SE, Dubilet M, Dubilet E, et al. Effect of glutamate and blood glutamate scavengers oxaloacetate and pyruvate on neurological outcome and pathohistology of the hippocampus after traumatic brain injury in rats. Anesthesiology. 2012; 116:73–83. PMID: 22129535.
Article
24. Zlotnik A, Gurevich B, Tkachov S, Maoz I, Shapira Y, Teichberg VI. Brain neuroprotection by scavenging blood glutamate. Exp Neurol. 2007; 203:213–220. PMID: 17014847.
Article
25. Wilkins HM, Harris JL, Carl SM, e L, Lu J, Eva Selfridge J, et al. Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis. Hum Mol Genet. 2014; 23:6528–6541. PMID: 25027327.
Article
26. A Cash. Method for extending lifespan and delaying the onset of age-related disease. European Patent Office EP1824470B1. 2005.
27. von Glischinski M, von Brachel R, Hirschfeld G. How depressed is “depressed”? A systematic review and diagnostic meta-analysis of optimal cut points for the Beck Depression Inventory revised (BDI-II). Qual Life Res. 2019; 28:1111–1118. PMID: 30456716.
28. Cohen S. Perceived stress in a probability sample of the United States. In : Spacapan S, Oskamp S, editors. The social psychology of health: the Claremont symposium on applied social psychology. Newbury Park, CA: Sage Publications, Inc.;1988. p. 31–67.
29. Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006; 166:1092–1097. PMID: 16717171.
30. Buss AH, Perry M. The aggression questionnaire. J Pers Soc Psychol. 1992; 63:452–459. PMID: 1403624.
Article
31. Ducasse D, Jaussent I, Olié E, Guillaume S, Lopez-Castroman J, Courtet P. Personality traits of suicidality are associated with premenstrual syndrome and premenstrual dysphoric disorder in a suicidal women sample. PLoS One. 2016; 11:e0148653. PMID: 26863007.
Article
32. Dhahbi JM, Mote PL, Wingo J, Tillman JB, Walford RL, Spindler SR. Calories and aging alter gene expression for gluconeogenic, glycolytic, and nitrogen-metabolizing enzymes. Am J Physiol. 1999; 277:E352–60. PMID: 10444432.
Article
33. Gangwisch JE, Hale L, Garcia L, Malaspina D, Opler MG, Payne ME, et al. High glycemic index diet as a risk factor for depression: analyses from the Women's Health Initiative. Am J Clin Nutr. 2015; 102:454–463. PMID: 26109579.
Article
34. Cui T, Qiu HM, Huang D, Zhou QX, Fu XY, Li HY, et al. Abnormal levels of seven amino neurotransmitters in depressed rat brain and determination by HPLC-FLD. Biomed Chromatogr. 2017; 31:e3937.
Article
35. Li CT, Lu CF, Lin HC, Huang YZ, Juan CH, Su TP, et al. Cortical inhibitory and excitatory function in drug-naive generalized anxiety disorder. Brain Stimulat. 2017; 10:604–608.
Article
36. Zlotnik A, Gruenbaum SE, Artru AA, Rozet I, Dubilet M, Tkachov S, et al. The neuroprotective effects of oxaloacetate in closed head injury in rats is mediated by its blood glutamate scavenging activity: evidence from the use of maleate. J Neurosurg Anesthesiol. 2009; 21:235–241. PMID: 19543002.
37. Courtet P, Lopez-Castroman J. Antidepressants and suicide risk in depression. World Psychiatry. 2017; 16:317–318. PMID: 28941085.
Article
38. Friedman RA, Leon AC. Expanding the black box - depression, antidepressants, and the risk of suicide. N Engl J Med. 2007; 356:2343–2346. PMID: 17485726.
Article
Full Text Links
  • OGS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr