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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
6
UNC Nutrition Research Institute
Kannapolis, North Carolina, United States
Change in sperm motility from baseline
Assessed using Computer-Aided Sperm Analysis methodology
Time frame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Change in sperm count from baseline
Time frame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Change in sperm mitochondrial function from baseline
Using Seahorse biochemical function assessment
Time frame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Change in sperm ultrastructure from baseline
Using light and transmission electron microscopy
Time frame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Change in sperm choline dehydrogenase concentration from baseline
Assessed by Western Blot analysis
Time frame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Change in sperm betaine concentration from baseline
Time frame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Betaine intake
Assessed using 3-day food records
Time frame: At screening and every 21 days during the study
Change in complete blood count from baseline
Time frame: At 0, 10, 30, 50, and 75 days on treatment
Change in uric acid concentration from baseline
Time frame: At 0, 10, 30, 50, and 75 days on treatment
Change in alkaline phosphatase concentration from baseline
Time frame: At 0, 10, 30, 50, and 75 days on treatment
Change in aspartate transaminase concentration from baseline
Time frame: At 0,10, 30, 50, and 75 days on treatment
Change in lactic dehydrogenase concentration from baseline
Time frame: At 0, 10, 30, 50, and 75 days on treatment
Change in bilirubin concentration from baseline
Time frame: At 0, 10, 30, 50, and 75 days on treatment
Change in blood urea nitrogen concentration from baseline
Time frame: At 0, 10, 30, 50, and 75 days on treatment
Change in creatinine concentration from baseline
Time frame: At 0, 10, 30, 50, and 75 days on treatment
Change in urinalysis parameters from baseline
Time frame: At 0, 10, 30, 50, and 75 days on treatment
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