S-adenosylhomocysteine (SAH) is the end-product of methylation reactions in the body and the precursor to homocysteine. Elevated SAH in the blood is a reflection of the dysregulation of what is known as the S-adenosylmethionine (SAM) cycle and has been associated with poor health outcomes. The SAM cycle is a series of reversible reactions necessary for the regulation of many processes in the body. The goal of this clinical trial is to assess the ability of a dietary supplement to support healthy plasma SAH levels in individuals with high plasma SAH. Participants in the study will attend a total of 4 clinic visits and consume study product daily for 12 weeks.
Methionine, a dietary amino acid commonly found in meats, is processed by the body and yields the by-product S-adenosylhomocysteine (SAH), which then undergoes condensation with ATP to produce S-adenosylmethionine (SAM). SAM is the main methyl donor in many of the reactions that occur in the cell. These methyl reactions are well-known epigenetic mechanisms involved in DNA gene expression. When SAM donates its methyl group in a reaction, it becomes SAH which participates in a reversible reaction with homocysteine. Homocysteine is then removed through re-methylation to methionine using folate and vitamin B12. This decrease in homocysteine levels prevents the over-production of SAH, which can disrupt the methyl reactions throughout the body. Dysregulation of this pathway leads to elevated levels of SAH, which have been associated with various disease states. Therefore, an intervention which can lower SAH may ameliorate the outcomes associated with its elevation. This trial will evaluate the efficacy of a dietary supplement to lower SAH in individuals with elevated SAH and normal homocysteine. In addition, this study aims to explore the correlation between the MethylQ score (derived from 3 questionnaires) and measures of SAH level and the SAM:SAH ratio. The test product contains alpha-GPC, creatine, and ashwagandha. Individually, these ingredients have been shown to improve levels of either SAH or homocysteine in clinical trials. Participants will be assigned to either the test product or placebo at a 5:3 and consume study product orally for 12 weeks. Assessment measures will include methylation biomarkers, free cortisol index, mood states and MethylQ score in individuals with elevated SAH levels (≥ 20 nmol/L) and normal homocysteine (≤ 13 µmol/L). The study will include a screening visit followed by a screening period lasting up to 90 days in duration with a remote check-in via phone call occurring between Day -40 and Day -30 (inclusive) for participants screened more than 30 days prior to the baseline visit on (Visit 2). Following the screening period, participants will attend a baseline visit on Day 1, an interim visit on Day 43 ± 3, and an end of study visit on the day after the 12-week (± 3 days) study product use (Day 85 ± 3). The study will include a total of 4 in-person visit days: a screening visit (Visit 1), a baseline visit (Visit 2), an interim visit (Visit 3), and an EOS visit (Visit 4).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
40
Other Ingredients: Microcrystalline Cellulose, Rice Fiber, Maltodextrin, Silica, Vegetable Stearate
Microcrystalline Cellulose
Valiance Clinical Research
South Gate, California, United States
To determine the effect of the Test Product (TP) compared to placebo on plasma S-adenosylmethionine (SAM) concentration.
Change from baseline in plasma SAM (nmol/L).
Time frame: 12 weeks
To determine the effect of the TP compared to placebo on plasma S-adenosylhomocysteine (SAH) concentration.
Change from baseline in plasma SAH (nmol/L).
Time frame: 12 weeks
To determine the effect of the TP compared to placebo on plasma homocysteine concentration.
Change from baseline in plasma homocysteine (umol/L).
Time frame: 12 weeks
To determine the effect of the TP compared to placebo on plasma cystathionine concentration.
Change from baseline in plasma cystathionine (umol/dL).
Time frame: 12 weeks
To determine the effect of the TP compared to placebo on plasma cysteine concentration.
Change from baseline in plasma cysteine (umol/dL).
Time frame: 12 weeks
To determine the effect of the TP compared to placebo on plasma methionine concentration.
Change from baseline in plasma methionine (umol/dL).
Time frame: 12 weeks
To determine the effect of the TP compared to placebo on plasma SAM concentration.
Change from baseline in plasma SAM (nmol/L).
Time frame: 6 weeks
To determine the effect of the TP compared to placebo on plasma SAH concentration.
Change from baseline in plasma SAH (nmol/L).
Time frame: 6 weeks
To determine the effect of the TP compared to placebo on plasma homocysteine concentration.
Change from baseline in plasma homocysteine (umol/L).
Time frame: 6 weeks
To determine the effect of the TP compared to placebo on plasma cystathionine concentration.
Change from baseline in plasma cystathionine (umol/dL).
Time frame: 6 weeks
To determine the effect of the TP compared to placebo on plasma methionine concentration.
Change from baseline in plasma methionine (umol/dL).
Time frame: 6 weeks
To determine the effect of the TP compared to placebo on plasma cysteine concentration.
Change from baseline in plasma cysteine (umol/dL).
Time frame: 6 weeks
To determine the effect of the TP compared to placebo on overall mood state.
Change from baseline in total mood disturbance assessed by Profile of Mood States (POMS) questionnaire. A higher score indicates a worse outcome.
Time frame: 12 weeks
To determine the effect of the TP compared to placebo on anger-hostility.
Change from baseline in anger-hostility subscore from the POMS questionnaire. A higher score indicates a worse outcome.
Time frame: 12 weeks
To determine the effect of the TP compared to placebo on vigor-activity.
Change from baseline in vigor-activity subscore from the POMS questionnaire. A higher score indicates a better outcome.
Time frame: 12 weeks
To determine the effect of the TP compared to placebo on confusion-bewilderment.
Change from baseline in confusion-bewilderment subscore from the POMS questionnaire. A higher score indicates a worse outcome.
Time frame: 12 weeks
To determine the effect of the TP compared to placebo on depression-dejection.
Change from baseline in depression-dejection subscore from the POMS questionnaire. A higher score indicates a worse outcome.
Time frame: 12 weeks
To determine the effect of the TP compared to placebo on tension-anxiety.
Change from baseline in tension-anxiety subscore from the POMS questionnaire. A higher score indicates a worse outcome.
Time frame: 12 weeks
To determine the effect of the TP compared to placebo on friendliness.
Change from baseline in friendliness subscore from the POMS questionnaire. A higher score indicates a better outcome.
Time frame: 12 weeks
To determine the effect of the TP compared to placebo on fatigue-inertia.
Change from baseline in fatigue-interia subscore from the POMS questionnaire. A higher score indicates a worse outcome.
Time frame: 12 weeks
To determine the effect of the TP compared to placebo on free cortisol index.
Change from baseline in the ratio of total cortisol/cortisol-binding globulin (CBG).
Time frame: 12 weeks
To determine the effect of the TP compared to placebo on the MethylQ score.
Change from baseline in MethylQ score. A score greater than 30 indicates a worse outcome.
Time frame: 12 weeks
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