Benefits
Body weight and fat reduction in the women with obesity (one manufacturer-sponsored trial)
In a randomized, double-blind, placebo-controlled trial, 50 overweight and obese women (mean age 47.5) took 400 mg a day for 12 weeks and 49 completed. The registered primary endpoint, body weight across the whole group, missed significance (0.9 kg between groups, P = .086). The result the product is sold on comes from the 25 women with obesity, 12 on the extract and 13 on placebo: body weight differed from placebo by 2.1 kg (P = .042), the supplement group lost 0.37% body fat (P = .044), and leptin fell only by trend (P = .065). The trial was sponsored by the manufacturer and two of its five authors are manufacturer employees.
Caffeine-free, but no energy outcome measured in people
The extract contains no caffeine, which is a real difference from stimulant energy ingredients. The energizing claim rests on laboratory work in the same paper as the trial: the extract bound adenosine receptor A2A in a radioligand binding assay, and it raised motility in the nematode Caenorhabditis elegans by 7.5%. A binding assay shows the extract attaches to the receptor; it does not establish whether it blocks the receptor the way caffeine does. No energy, fatigue or alertness measure was taken in the human trial.
Flavonoid antioxidant activity in laboratory and animal models only
Yerba santa flavanones, chiefly homoeriodictyol and hesperetin, show antioxidant activity in test-tube assays, and the same branded extract lowered body weight, fat mass and liver weight in mice fed a high-fat diet. A separate rat study tested isolated eriodictyol, not this extract, in a chemically induced colon-cancer model, so it says nothing about energy or weight. All of this is proposed mechanism measured in cells and animals, not in people.
Mechanism of action
Body-composition change, not measured energy expenditure
The trial registered body weight, body fat, body cell mass, waist-hip ratio, sagittal abdominal diameter, blood lipids, the lipokine 12,13-diHOME and an appetite questionnaire as its outcomes. What has been published is body weight and body fat in the women with obesity, lower scores on two appetite traits (emotional overeating and food responsiveness), a leptin trend, and no noteworthy effect on the inflammation marker hsCRP. No lipid, 12,13-diHOME, waist-hip or body-cell-mass result has been reported. Energy expenditure itself was never measured, so the phrase energy metabolism in the study title describes a body-composition result, not a measured metabolic rate.
Yerba santa flavanone antioxidant signaling (cell and animal work)
The extract is standardized to homoeriodictyol, and a compositional analysis of cultivated E. californicum found eriolic acid C, rosmarinic acid, sterubin and homoeriodictyol to be its most prominent polyphenols, with eriodictyol lower down the list. Several of these flavanones have antioxidant and Nrf2-related activity in cell and animal models. Whether any of that happens at 400 mg a day in a person has not been tested.
Clinical trials
Randomized, double-blind, placebo-controlled; 400 mg a day for 12 weeks, taken as one capsule twice daily with meals per the registered protocol. Sponsored by Mibelle AG and registered as NCT03853603 (Journal of Medicinal Food, 2021). The same publication also contains in vitro receptor-binding, antioxidant-capacity and Caenorhabditis elegans experiments that are not part of the human trial.
49 women analyzed (24 overweight, 25 obese; mean age 47.5) of 50 randomized
The registered primary endpoint, body weight in the whole group, missed significance (0.9 kg between groups, P = .086). In the 25 women with obesity (12 on the extract, 13 on placebo), body weight differed from placebo by 2.1 kg (P = .042) and the supplement group lost 0.37% body fat (P = .044); leptin fell only by trend (P = .065) and hsCRP did not change. No human energy, fatigue or alertness outcome was measured. Mibelle AG sponsored the trial and two of the five authors are Mibelle employees.