Choline Dehydrogenase and Sperm Function: Effects of Betaine

University of North Carolina (UNC)

Status and phase: Completed; Phase 1

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

Treatments: Drug: Betaine supplement

Study type: Interventional

Funder types: Other

Identifiers

NCT02122211

13-2424

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6 patients

Sex: Male

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

Betaine supplement

Experimental group

Description:

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.

Treatment:

Drug: Betaine supplement