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A review on betaine reports that higher dosages, for example 4 grams per day or more, can increase total cholesterol and LDL in some studies
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However, if the purpose of the drug is to be taken up by the liver, then first-pass metabolism may be irrelevant (the drug is still metabolized into hepatic glutathione, which is what matters)
Garduo-Jimnez AL, Carter LJ
Sex hormones modulate circulating antioxidant enzymes: impact of estrogen therapy
"Nonsteroidal Anti-inflammatory Drugs" in Principles of Medicinal Chemistry , Fourth Edition
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