Oxaloacetate Supplementation for Emotional PMS

Premenstrual Syndrome (PMS) Clinical Trial

— OAA4PMS  

Official title:

Oxaloacetate Supplementation for Emotional PMS; Measuring Improvements in Depression, Anxiety, Perceived Stress, and Aggression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03509714
• Other study ID #: EmotionalPMS1
• Secondary ID: TV-OX-108
• Status: Completed
• Phase: N/A
• First received: April 6, 2018
• Last updated: April 20, 2018
• Start date: October 17, 2016
• Est. completion date: September 1, 2017

Study information

• Verified date: April 2018
• Source: Terra Biological LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Emotional Premenstrual Syndrome (PMS) affects millions of women worldwide. For Emotional PMS, including depression, anxiety, perceived stress and aggression, there are very few options. Recent observational data suggest that nutritional supplementation with oxaloacetate, a human energy metabolite, greatly reduced the symptoms of Emotional PMS. The aim of this study was to confirm these observations on the effects of oxaloacetate on Emotional PMS symptom severity within a controlled clinical trial setting.

Description:

Oxaloacetate is an energy metabolite found in every cell of the human body. It holds a key place in the Krebs Cycle within the mitochondria, providing energy to the cells. It is also a critical early metabolite in gluconeogenesis, which provides glucose for the heart and brain during times of low glucose. It is critical to human metabolism, proper cellular function and it is central to energy production and use in the body.

Oxaloacetate may affect Emotional PMS through multiple mechanisms. During PMS, there is a large increase in glucose utilization in the cerebellum of the brain in women who are affected with emotional mood swings. Oxaloacetate supplementation has been shown to support proper glucose levels in the body. Having an excess of oxaloacetate allows gluconeogenesis take place upon demand, thereby fueling the brain, and perhaps meeting cerebellum glucose need.

In addition to oxaloacetate's ability to support proper glucose regulation, oxaloacetate affects two chemicals in the brain, GABA and glutamate. Altering the GABA/Glutamate ratio can affect mood. Oxaloacetate supplementation can reduce glutamate levels in the brain via a process called "Glutamate Scavenging". In addition, oxaloacetate supplementation was shown to increase GABA levels in animal models. By both lowering glutamate and increasing GABA, the GABA/Glutamate ratio is affected, which may also help women with Emotional PMS.

This study will investigate oxaloacetate's effect on Emotional PMS using patient completed surveys to measure depression, anxiety, perceived stress, and aggression, and statistically compare these results against placebo (rice flour) and baseline measurements.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: September 1, 2017
• Est. primary completion date: September 1, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Women with Emotional Premenstrual Syndrome (PMS),

• Women who speak English as their primary language

• Women who understand the Human Consent Form

• Ability to swallow capsules

Exclusion Criteria:

• Formal diagnosis of clinical depression

• Formal diagnosis of premenstrual dysphoric disorder (PMDD).

Related Conditions & MeSH terms

• Premenstrual Syndrome
• Premenstrual Syndrome (PMS)

Intervention

Dietary Supplement:
• Jubilance (100 mg Oxaloacetate/150 mg Ascorbic Acid)
2 Pills to be taken orally per day during their entire menstrual cycle
• rice flour (Placebo)
250 mg rice flour (Placebo)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Terra Biological LLC

References & Publications (5)

Rapkin AJ, Berman SM, Mandelkern MA, Silverman DH, Morgan M, London ED. Neuroimaging evidence of cerebellar involvement in premenstrual dysphoric disorder. Biol Psychiatry. 2011 Feb 15;69(4):374-80. doi: 10.1016/j.biopsych.2010.09.029. Epub 2010 Nov 18. — View Citation

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 Sep;20(3):236-60. doi: 10.1007/s11065-010-9142-x. Epub 2010 Sep 7. Review. — View Citation

Wilkins HM, Harris JL, Carl SM, E L, Lu J, Eva Selfridge J, Roy N, Hutfles L, Koppel S, Morris J, Burns JM, Michaelis ML, Michaelis EK, Brooks WM, Swerdlow RH. Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis. Hum Mol Genet. 2014 Dec 15;23(24):6528-41. doi: 10.1093/hmg/ddu371. Epub 2014 Jul 15. — View Citation

Williams DS, Cash A, Hamadani L, Diemer T. Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathway. Aging Cell. 2009 Dec;8(6):765-8. doi: 10.1111/j.1474-9726.2009.00527.x. Epub 2009 Sep 30. — View Citation

Yoshikawa K. Studies on the anti-diabetic effect of sodium oxaloacetate. Tohoku J Exp Med. 1968 Oct;96(2):127-41. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Depression associated with Emotional PMS	Depression as measured during Emotional PMS with Beck's Depression Inventory Survey, which scores depression with 26 questions rated 0 to 3. Total score ranges from 0 to 78. Higher values indicate worse depression.	Change from baseline value to value after supplementation for entire menstrual cycle (about 28 days) for each study arm in cross-over design (3 data points compared 1 at baseline 1 after menstrual cycle 1 and 1 after menstrual cycle 2).
Primary	Anxiety associated with Emotional PMS	Anxiety as measured during Emotional PMS with Generalized Anxiety Disorder Survey, which scores anxiety with 7 questions rated 0 to 3. Total score ranges from 0 to 21. Higher values indicate worse anxiety.	Change from baseline value to value after supplementation for one entire menstrual cycle (about 28 days) for each study arm in cross-over design (3 data points compared 1 at baseline 1 after menstrual cycle 1 and 1 after menstrual cycle 2).
Primary	Perceived Stress with Emotional PMS	Perceived Stress as measured during Emotional PMS with Cohen's Perceived Stress Survey, which scores perceived stress with 9 questions rated 0 to 4. Total score ranges from 0 to 36. Higher values indicate worse perceived stress.	Change from baseline value to value after supplementation for one entire menstrual cycle (about 28 days) for each study arm in cross-over design (3 data points compared 1 at baseline 1 after menstrual cycle 1 and 1 after menstrual cycle 2).
Primary	Aggression with Emotional PMS	Aggression as measured during Emotional PMS with Buss-Perry Aggression Scale, which scores depression with 29 questions rated 1 to 5. Total score ranges from 29 to 145. Higher values indicate worse aggression.	Change from baseline value to value after supplementation for one entire menstrual cycle (about 28 days) for each study arm in cross-over design (3 data points compared 1 at baseline 1 after menstrual cycle 1 and 1 after menstrual cycle 2).
Primary	Adverse Event Reporting	Safety of oxaloacetate supplementation in Emotional PMS patients	Through study completion, an average of 60 days (2 menstrual cycles)
Secondary	Suicidal Ideation with Emotional PMS	Suicidal Ideation as measured with a subscale of Beck's Depression Inventory, with a scale ranging from 0 to 3 in women who initially record suicidal ideation of greater than 0.	Change from baseline value to value after supplementation for one entire menstrual cycle (about 28 days) for each study arm in cross-over design (3 data points compared 1 at baseline 1 after menstrual cycle 1 and 1 after menstrual cycle 2).