Choline Dehydrogenase and Sperm Function: Effects of Betaine

NCT ID: NCT02122211

Last Updated: 2016-09-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2016-07-31

Brief Summary

The ability of sperm to swim is important for normal fertility. Men with a genetic variation in the gene coding for Choline Dehydrogenase (CHDH) have decreased energy production by sperm, and their sperm do not swim normally. The metabolic product of this gene is a nutrient called betaine (found normally in the diet as a part of many foods such as spinach, beets and grain products). This study tests whether treatment with betaine is safe and whether it can normalize energy production in sperm of these men and restore normal swimming ability.

Detailed Description

Unidentified genetic aberrations such as single nucleotide polymorphisms (SNPs) may be the underlying cause of many cases of idiopathic infertility in men. Choline dehydrogenase (encoded by CHDH) converts choline to betaine in the mitochondria. 5-9% of men have 2 alleles for a functional SNP in CHDH (rs12676), and they have low sperm adenosine triphosphate (ATP) concentrations with impaired sperm motility (asthenospermia) that should decrease fertility. Male mice in which CHDH is deleted also have very low sperm ATP, asthenospermia and are infertile. Supplementation of these mice with dietary betaine increases sperm motility and ATP concentrations.

This purpose of this study is to conduct a phase I study of betaine treatment in men with 2 minor alleles for CHDH rs12676 to determine whether betaine supplementation is safe and to obtain preliminary data on the effects of betaine on sperm mitochondrial ATP concentrations and sperm motility in these men.

Conditions

Men Carrying 2 Minor Alleles for Choline Dehydrogenase rs12676; Male Infertility

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Betaine supplement

Will use powdered betaine (BetaPower, Dupont Nutrition) that is commercially available for food uses. This powder will be delivered as capsules containing 0.5 gram of powdered betaine which will be administered as eleven capsules twice per day (6 in the morning, 5 in the evening) for a daily total of 6 grams of betaine.

Group Type: EXPERIMENTAL

Betaine supplement

Intervention Type: DRUG

Interventions

Betaine supplement

Intervention Type: DRUG

Other Intervention Names

BetaPower (Dupont Nutrition)

Eligibility Criteria

Inclusion Criteria

• 18 - 60 year old men of multiple races and ethnicities
• Estimated dietary intake of betaine of <150 mg/day
• Carrying two alleles of the rs 12676 single nucleotide polymorphism

Exclusion Criteria

• Cystathionine-beta-synthase (CBS) deficiency
• Currently taking betaine supplements
• Currently receiving chemotherapy, radiation or any gonadotoxic drug
• Female gender

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven Zeisel, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina

Locations

UNC Nutrition Research Institute

Kannapolis, North Carolina, United States

Countries

United States

References

Johnson AR, Lao S, Wang T, Galanko JA, Zeisel SH. Choline dehydrogenase polymorphism rs12676 is a functional variation and is associated with changes in human sperm cell function. PLoS One. 2012;7(4):e36047. doi: 10.1371/journal.pone.0036047. Epub 2012 Apr 27.

Reference Type: BACKGROUND

PMID: 22558321 (View on PubMed)

Other Identifiers

13-2424

Identifier Type: -

Identifier Source: org_study_id