Role of a Dietary Supplement in Lowering SAH in Healthy Adults With Elevated Plasma SAH and Normal Homocysteine Levels

NCT05994794 | Completed

• 1 other identifier: S01-21-01-T0023
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Elevated S-adenosylhomocysteine

Keywords

Methylation; Alpha-GPC; Creatine; Ashwagandha

Outcome Measures

Primary Outcomes (6)

• 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).

  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).

  12 weeks

• To determine the effect of the TP compared to placebo on plasma homocysteine concentration.

  Change from baseline in plasma homocysteine (umol/L).

  12 weeks

• To determine the effect of the TP compared to placebo on plasma cystathionine concentration.

  Change from baseline in plasma cystathionine (umol/dL).

  12 weeks

• To determine the effect of the TP compared to placebo on plasma cysteine concentration.

  Change from baseline in plasma cysteine (umol/dL).

  12 weeks

• To determine the effect of the TP compared to placebo on plasma methionine concentration.

  Change from baseline in plasma methionine (umol/dL).

  12 weeks

Secondary Outcomes (16)

• To determine the effect of the TP compared to placebo on plasma SAM concentration.

  6 weeks

• To determine the effect of the TP compared to placebo on plasma SAH concentration.

  6 weeks

• To determine the effect of the TP compared to placebo on plasma homocysteine concentration.

  6 weeks

• To determine the effect of the TP compared to placebo on plasma cystathionine concentration.

  6 weeks

• To determine the effect of the TP compared to placebo on plasma methionine concentration.

  6 weeks

Other Outcomes (38)

• MethylQ score and Plasma SAH Correlation

  Screening, Baseline and Week 12

• MethylQ score and SAM/SAH Ratio Correlation

  Screening, Baseline and Week 12

• Post-dose change in Plasma SAH and MethylQ score Correlation

  12 weeks

Study Arms (2)

Alpha-GPC, Creatine and Ashwagandha (Sensoril®)

EXPERIMENTAL

Two servings (12 capsules) of study products will be taken twice per day with meals, one serving in the morning and one serving the afternoon/evening. One serving consists of 6 capsules. The time difference between the two servings must be at least 6 hours. One serving: * One capsule of Alpha GPC supplement * Four capsules of Creatine monohydrate supplement * One capsule of Sensoril (ashwagandha) supplement

Dietary Supplement: Alpha-GPC, Creatine and Ashwagandha (Sensoril®)

Placebo

PLACEBO COMPARATOR

Participants will consume one serving (6 capsules), twice per day, with meals at least 6 hours apart.

Other: Placebo

Interventions

Alpha-GPC, Creatine and Ashwagandha (Sensoril®) DIETARY_SUPPLEMENT

Other Ingredients: Microcrystalline Cellulose, Rice Fiber, Maltodextrin, Silica, Vegetable Stearate

Alpha-GPC, Creatine and Ashwagandha (Sensoril®)

Placebo OTHER

Microcrystalline Cellulose

Placebo

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy adults who are 30 to 75 years of age (inclusive).
• Have a BMI between 18.5 to 34.9 kg/m\^2 (inclusive).
• In good general health (no uncontrolled diseases or conditions) as deemed by the investigator and is able to consume the study product.
• Have elevated plasma SAH levels of ≥ 20 nmol/L and normal plasma homocysteine levels of ≤ 13 µmol/L at the screening visit (Visit 1).
• Individuals with childbearing potential must agree to practice an acceptable form of birth control for a certain timeframe prior to the first dose of study product and throughout the study, including:
• use for at least 3 months prior to the first dose of study product: hormonal contraceptives including oral contraceptives, hormone birth control patch (e.g., Ortho Evra), vaginal contraceptive ring (e.g., NuvaRing), injectable contraceptives (e.g., Depo-Provera, Lunelle), or hormone implant (e.g., Norplant System), or intrauterine devices (e.g., Mirena); or
• use for at least 1 month prior to the first dose of study product: double-barrier method, non-hormonal intrauterine devices (i.e., copper), or complete abstinence from sexual intercourse that may result in pregnancy; or
• vasectomy of partner at least 6 months prior to the first dose of study product.
• Individuals with the potential to impregnate others must agree to use condoms or other acceptable methods to prevent pregnancy throughout the study. Complete abstinence from sexual intercourse that may result in pregnancy is also acceptable.
• Agree to comply with concomitant treatment restrictions, permitted time frames and/or conditions listed in Study Protocol (No. S01-21-01-T0023) Section 6.5 (Concomitant Treatments).
• Have maintained stable dietary habits (including supplement intake), exercise habits and lifestyle for the last 3 months prior to screening and agree to maintain dietary and exercise habits and lifestyle throughout the study.
• Willing and able to agree to the requirements and restrictions of this study, be willing to give voluntary consent, be able to understand and read the questionnaires, and carry out all study-related procedures.

You may not qualify if:

• Individuals who are lactating, pregnant or planning to become pregnant during the study as confirmed at the baseline visit (Visit 2).
• Have a known sensitivity, intolerability, or allergy to any of the study products or their excipients.
• Currently has COVID-19 or tests positive for COVID-19 within 28 days prior to baseline visit.
• Currently has any post Covid-19 condition(s) as defined by World Health Organization (WHO) (i.e., individuals with a history of a probable or confirmed SARS-CoV-2 infection, usually three months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis).
• Have a history of heart disease/cardiovascular disease, uncontrolled hypertension (140/90 or greater mmHg), kidney dysfunction or disease (dialysis or renal failure), hepatic impairment or disease, or Type I or Type II diabetes.
• Have a history of thyroid disease, major affective disorder, psychiatric disorder (e.g., bipolar disorder) that required hospitalization in the prior year, autoimmune diseases (e.g., multiple sclerosis, Parkinson's, systemic lupus erythematosus, rheumatoid arthritis, etc.), or immune disorder (i.e., HIV/AIDS).
• Have an abnormality or obstruction of the gastrointestinal tract precluding swallowing (e.g. dysphagia) and digestion (e.g., known intestinal malabsorption, celiac disease, inflammatory bowel disease, chronic pancreatitis, steatorrhea).
• Have an active malignant disease, except basal or squamous cell skin carcinoma or carcinoma in situ of the uterine cervix.
• Major surgery in 3 months prior to the screening visit (Visit 1) or planned major surgery during the course of the study.
• History of alcohol or substance abuse in the 12 months prior to screening (including having been hospitalized for such in an in-patient or out-patient intervention program).
• Receipt or use of test product(s) in another research study within 28 days prior to baseline or longer if the previous test product is deemed by the investigator to have lasting effects that might influence the eligibility criteria or outcomes of current study.
• Any other active or unstable medical conditions or use of medications/supplements/ therapies that, in the opinion of the investigator, may adversely affect the participant's ability to complete the study or its measures or pose a significant risk to the participant.

Sponsors & Collaborators

• Standard Process Inc.: lead
• Nutrasource Pharmaceutical and Nutraceutical Services, Inc.: collaborator

Study Sites (1)

Valiance Clinical Research

South Gate, California, 90280, United States

Location

Related Publications (11)

• Kennedy BP, Bottiglieri T, Arning E, Ziegler MG, Hansen LA, Masliah E. Elevated S-adenosylhomocysteine in Alzheimer brain: influence on methyltransferases and cognitive function. J Neural Transm (Vienna). 2004 Apr;111(4):547-67. doi: 10.1007/s00702-003-0096-5. Epub 2004 Feb 4.

  PMID: 15057524 BACKGROUND

• Xiao Y, Huang W, Zhang J, Peng C, Xia M, Ling W. Increased plasma S-adenosylhomocysteine-accelerated atherosclerosis is associated with epigenetic regulation of endoplasmic reticulum stress in apoE-/- mice. Arterioscler Thromb Vasc Biol. 2015 Jan;35(1):60-70. doi: 10.1161/ATVBAHA.114.303817. Epub 2014 Oct 30.

  PMID: 25359864 BACKGROUND

• Lawson BR, Eleftheriadis T, Tardif V, Gonzalez-Quintial R, Baccala R, Kono DH, Theofilopoulos AN. Transmethylation in immunity and autoimmunity. Clin Immunol. 2012 Apr;143(1):8-21. doi: 10.1016/j.clim.2011.10.007. Epub 2011 Dec 24.

  PMID: 22364920 BACKGROUND

• Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015 Jan 10;14:6. doi: 10.1186/1475-2891-14-6.

  PMID: 25577237 BACKGROUND

• Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013 Jan;38(1):23-38. doi: 10.1038/npp.2012.112. Epub 2012 Jul 11.

  PMID: 22781841 BACKGROUND

• Troen AM, Lutgens E, Smith DE, Rosenberg IH, Selhub J. The atherogenic effect of excess methionine intake. Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15089-94. doi: 10.1073/pnas.2436385100. Epub 2003 Dec 1.

  PMID: 14657334 BACKGROUND

• Olthof MR, Brink EJ, Katan MB, Verhoef P. Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am J Clin Nutr. 2005 Jul;82(1):111-7. doi: 10.1093/ajcn.82.1.111.

  PMID: 16002808 BACKGROUND

• Innis SM, Davidson AG, Melynk S, James SJ. Choline-related supplements improve abnormal plasma methionine-homocysteine metabolites and glutathione status in children with cystic fibrosis. Am J Clin Nutr. 2007 Mar;85(3):702-8. doi: 10.1093/ajcn/85.3.702.

  PMID: 17344490 BACKGROUND

• Korzun WJ. Oral creatine supplements lower plasma homocysteine concentrations in humans. Clin Lab Sci. 2004 Spring;17(2):102-6.

  PMID: 15168891 BACKGROUND

• Bonilla DA, Moreno Y, Gho C, Petro JL, Odriozola-Martinez A, Kreider RB. Effects of Ashwagandha (Withania somnifera) on Physical Performance: Systematic Review and Bayesian Meta-Analysis. J Funct Morphol Kinesiol. 2021 Feb 11;6(1):20. doi: 10.3390/jfmk6010020.

  PMID: 33670194 BACKGROUND

• Pohl F, Dominique A, Dufour J, Wang J, Lin XL, Sharif B, Wilson M, Gonzalez L, El-Khodor BF. Lowering plasma S-Adenosylhomocysteine (SAH) in healthy adults with elevated SAH and normal homocysteine using nutritional supplementation. Nutr Metab Cardiovasc Dis. 2025 Dec;35(12):104221. doi: 10.1016/j.numecd.2025.104221. Epub 2025 Jul 5.

  PMID: 40883125 DERIVED

MeSH Terms

Interventions

Creatine; Ashwagandha

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Bassem F. El-Khodor, PhD

  Nutrition Innovation Center, Standard Process Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: August 16, 2023
• Study Start: December 9, 2022
• Primary Completion: October 5, 2023
• Study Completion: October 5, 2023
• Last Updated: March 7, 2024

Record last verified: 2024-03

Locations

US (1)