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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Betaine supplement | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Betaine supplement | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in sperm motility from baseline | Assessed using Computer-Aided Sperm Analysis methodology | 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 | 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 | 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 | 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 | 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 | On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| Betaine intake | Assessed using 3-day food records | At screening and every 21 days during the study |
| Change in complete blood count from baseline | At 0, 10, 30, 50, and 75 days on treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Steven Zeisel, MD, PhD | University of North Carolina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UNC Nutrition Research Institute | Kannapolis | North Carolina | 28081 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22558321 | Background | 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. |
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| ID | Term |
|---|---|
| D007248 | Infertility, Male |
| ID | Term |
|---|---|
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007246 | Infertility |
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| Change in uric acid concentration from baseline | At 0, 10, 30, 50, and 75 days on treatment |
| Change in alkaline phosphatase concentration from baseline | At 0, 10, 30, 50, and 75 days on treatment |
| Change in aspartate transaminase concentration from baseline | At 0,10, 30, 50, and 75 days on treatment |
| Change in lactic dehydrogenase concentration from baseline | At 0, 10, 30, 50, and 75 days on treatment |
| Change in bilirubin concentration from baseline | At 0, 10, 30, 50, and 75 days on treatment |
| Change in blood urea nitrogen concentration from baseline | At 0, 10, 30, 50, and 75 days on treatment |
| Change in creatinine concentration from baseline | At 0, 10, 30, 50, and 75 days on treatment |
| Change in urinalysis parameters from baseline | At 0, 10, 30, 50, and 75 days on treatment |
| D052801 |
| Male Urogenital Diseases |