Bile acid (BA) production in mice is regulated by hepatic farnesoid X receptors and by intestinal fibroblast growth factor (FGF) 15, (in humans FGF19) a suppressor of BA synthesis that also reduces serum triglycerides and glucose. Cholestyramine treatment reduces FGF19 and induces BA synthesis while plasma triglycerides may increase of unclear reasons. We explored if FGF19 may suppress BA synthesis and plasma triglycerides in humans by modulation of FGF19 levels through long-term cholestyramine at increasing doses. In a second acute experiment, metabolic responses from one day of cholestyramine treatment were monitored. Long-term treatment reduced serum FGF19 by >90% and BA synthesis increased up to 17-fold while serum BAs, triglycerides, glucose and insulin were stable. After long-term treatment, serum BAs and FGF19 displayed rebound increases above baseline levels, and BA and cholesterol syntheses normalized after one week without rebound reductions. Acute cholestyramine treatment decreased FGF19 by 95% overnight and serum BAs by 60%, while BA synthesis increased 4-fold and triglycerides doubled. The results support that FGF19 represses BA synthesis but not serum triglycerides. However, after cessation of both long-term and one day cholestyramine treatment, circulating FGF19 levels were normalized within 2 days while BA synthesis remained significantly induced in both situations indicating that also other mechanisms than the FGF19 pathway are responsible for stimulation of BA synthesis elicited by cholestyramine. Several of the responses during cholestyramine treatment persisted at least 6 days after treatment highlighting the importance to remove such treatment at least a week prior to sampling.