Oxaloacetate Supplementation for Emotional PMS

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Premenstrual Syndrome (PMS)

Intervention / Treatment
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* Dietary Supplement: Jubilance (100 mg Oxaloacetate/150 mg Ascorbic Acid)
* Dietary Supplement: rice flour (Placebo)


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Baseline measurement of all participants. Randomized double-blinded placebo controlled crossover study for Phase 1. Due to carry-over effects, Phase 2 of the study started each participant with placebo.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Experimental: Part 1 Oxaloacetate Random<br>Participants take 2 capsules Jubilance 100 mg Oxaloacetate/150 mg Ascorbic Acid blend per day during their entire menstrual cycle (approximately 28 days) or 2 capsules of 250 mg rice flour (Placebo). After one menstrual cycle, they cross-over to the other option. | Dietary Supplement: Jubilance (100 mg Oxaloacetate/150 mg Ascorbic Acid)<br>* 2 Pills to be taken orally per day during their entire menstrual cycle<br>* Other names: Jubilance for Emotional PMS;Dietary Supplement: rice flour (Placebo)<br>* 250 mg rice flour (Placebo)<br>|
| Active Comparator: Experimental: Part 2 Oxaloacetate Second<br>Participants take 2 capsules of 250 mg rice flour (Placebo) per day during their entire menstrual cycle (approximately 28 days). After one menstrual cycle, they cross-over to 2 capsules of Jubilance 100 mg Oxaloacetate/150 mg Ascorbic Acid blend. | Dietary Supplement: Jubilance (100 mg Oxaloacetate/150 mg Ascorbic Acid)<br>* 2 Pills to be taken orally per day during their entire menstrual cycle<br>* Other names: Jubilance for Emotional PMS;Dietary Supplement: rice flour (Placebo)<br>* 250 mg rice flour (Placebo)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 
| 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). | 
| 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). | 
| 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). | 
| Adverse Event Reporting | Safety of oxaloacetate supplementation in Emotional PMS patients | Through study completion, an average of 60 days (2 menstrual cycles) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). |