Choline Dehydrogenase and Sperm Function: Effects of Betaine
Choline Dehydrogenase and Sperm Function: Effects of Betaine
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.
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.
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