Benefits
Salivary cortisol and mood scores in stressed adults on a two-herb blend
In a maker-funded four-week trial in 56 moderately stressed adults, Relora 500 mg a day, a magnolia plus phellodendron bark blend, lowered salivary cortisol exposure by 18 percent versus placebo and improved mood-state scores, including stress, tension, fatigue and vigor. The six-week trial in women found no cortisol difference from placebo, so the two trials disagree on cortisol.
Short-term anxiety scores with a magnolia plus phellodendron blend
In a maker-funded six-week trial of Relora 250 mg three times a day, 40 overweight premenopausal women who eat more under stress enrolled and 26 finished. State (short-term) anxiety fell more than with placebo, while trait anxiety, salivary cortisol, sleep, appetite and body measures did not differ. Two herbs were tested together, so phellodendron alone cannot take the credit.
Body weight in women who eat more under stress (two-herb blend)
A separate report from the same six-week Relora pilot trial found an average 1.5 kg gain within the placebo group and none with Relora, and fewer Relora users gained 1 kg or more (37 versus 75 percent). The trial's main report found no difference in body measures or appetite versus placebo, and the four-week Relora trial saw no change in body weight.
Body weight with a phellodendron plus orange peel blend
In a maker-sponsored eight-week pilot trial of a phellodendron plus orange peel extract blend (1,480 mg a day) in 80 adults with knee osteoarthritis, of whom 45 finished, overweight users lost an average of 4.2 kg versus 1.15 kg on placebo, but the change in BMI did not differ between groups. Orange peel was part of the blend.
Mechanism of action
Magnolia and phellodendron in the studied blend
The stress trials tested Relora, a proprietary blend of Magnolia officinalis and Phellodendron amurense bark extracts standardized to at least 1.5 percent honokiol (from magnolia) and 0.1 percent berberine (from phellodendron). The weight trial tested a different blend of phellodendron bark extract (at least 50 percent berberine) with orange peel extract. Because only blends were tested for these outcomes, their effects cannot be credited to phellodendron alone.
Cortisol as the measured stress marker
Salivary cortisol exposure was 18 percent lower than placebo after 4 weeks in one Relora trial, while the six-week trial in women found no difference from placebo; a separate weight report from that same trial described only a nonsignificant trend toward lower evening cortisol. How the blend might act on the stress hormone system has not been shown in people.
Berberine and related bark alkaloids
Phellodendron bark contains berberine together with palmatine and jatrorrhizine, in amounts that differed markedly between Japanese and Chinese bark. In kidney transplant patients, berberine at 0.2 g three times a day raised blood levels of the drug cyclosporine, an effect the authors attribute to inhibition of CYP3A4. Relora is standardized only to a 0.1 percent berberine minimum, so its actual berberine content per dose is not reported.
Clinical trials
Randomized double-blind placebo-controlled trial of Relora, a magnolia plus phellodendron bark blend standardized to not less than 1.5 percent honokiol and 0.1 percent berberine, 250 mg at breakfast and dinner (500 mg a day) or a rice-flour placebo for 4 weeks; 60 randomized; funded by the maker Next Pharmaceuticals; body weight and body fat percentage did not change (Talbott et al. 2013, J Int Soc Sports Nutr)
56 adults (35 men, 21 women) screened for moderate stress who completed the study.
Salivary cortisol exposure was 18 percent lower than placebo (p<0.05), and mood-state scores were better, including overall stress (11 percent lower), tension (13 percent lower), depression (20 percent lower), fatigue (31 percent lower) and vigor (18 percent higher). No adverse events were reported. Two herbs were tested together, so phellodendron's own share is unknown.
Randomized double-blind placebo-controlled pilot of Relora 250 mg three times daily for 6 weeks, standardized to not less than 1.5 percent honokiol and 0.1 percent berberine, supported by a grant from the maker Next Pharmaceuticals; the trial's weight results were published first in a separate report (Garrison et al. 2006, Altern Ther Health Med) whose first author was from Next Pharmaceuticals and which counted 28 completers (Kalman et al. 2008, Nutr J)
40 overweight premenopausal women aged 20 to 50 who eat more under stress and scored above average for anxiety; 26 completed (16 on Relora, 10 on placebo).
Relora lowered state (short-term) anxiety versus placebo. Trait anxiety, salivary cortisol and amylase, appetite, body measures, sleep quality and time to fall asleep did not differ from placebo. Three people withdrew because of adverse events (two on Relora, one on placebo). The separate weight report found an average 1.5 kg gain within the placebo group and none with Relora, and fewer Relora users gained 1 kg or more (37 versus 75 percent).
Randomized double-blind placebo-controlled 8-week pilot of NP 06-1, phellodendron bark extract standardized to at least 50 percent berberine plus orange (Citrus sinensis) peel extract standardized to at least 30 percent polymethoxylated flavones, two 370 mg capsules twice daily (1,480 mg a day); sponsored by the maker Next Pharmaceuticals, whose president and an employee were coauthors; knee and inflammation results from the same trial appeared in a second report in 2009 (Oben et al. 2008, Nutr J)
80 adults aged 25 to 60 with knee osteoarthritis in Cameroon (40 overweight, 40 normal weight); 45 completed.
The overweight group on the blend lost an average of 4.2 kg (5.1 percent of body weight) over 8 weeks versus 1.15 kg on placebo (p<0.001), and normal-weight users also lost more weight than placebo, but the change in BMI did not differ between groups in either weight group. Triglycerides and LDL cholesterol fell and HDL cholesterol rose more than with placebo. No serious adverse events were reported; 35 of 80 dropped out, and only completers were reported.
Single-arm tolerance study with no placebo group: Nexrutine, a phellodendron bark extract trademarked by Next Pharmaceuticals (the Relora maker), 500 mg by mouth three times a day for 30 to 80 days before surgery, or for 30 to 60 days before and then during radiation (4 months in total), with side effects graded by standard criteria; supported by National Cancer Institute and Veterans Affairs grants (Swanson et al. 2015, Phytother Res)
21 men with prostate cancer scheduled for surgery (9) or radiation (12).
Two severe (grade 3) events were recorded, urinary incontinence after surgery and low potassium two months after stopping the extract; there were no grade 4 events, and all events were transient. Moderate (grade 2) events were more common but varied, most often anemia and bladder irritation in men also having radiation. One man stopped early because of mild digestive upset. With no control group, the study was not designed to show benefits.