Benefits
Blood glucose response to a glucose drink after one dose
In a crossover study in 16 healthy adults, 1 g of the extract taken with a 50 g glucose drink lowered the area under the blood glucose curve compared with wheat bran placebo. Insulin was higher at 90 minutes, but total insulin over 2 hours did not differ. This is a single-meal marker from one small study with maker-affiliated authors.
Glucose tolerance test results after 3 weeks of daily use
In older adults with overweight or obesity on a reduced-calorie diet, 1 g a day for 3 weeks lowered the glucose curve in a glucose tolerance test by 28% and 2 hour glucose by 14% from baseline, while placebo changes were not significant. The published summary gives no direct comparison with placebo for these results, and 17 of 22 people finished.
Fructosamine and glucagon over 3 weeks
In the same 3 week crossover trial, serum fructosamine, a marker of average blood glucose over recent weeks, and plasma glucagon differed significantly from placebo. Fructosamine fell slightly on the extract and rose on placebo. These are blood markers from one small maker-affiliated trial with no stated primary outcome.
Fat mass and adiponectin to leptin ratio over 3 weeks
In the same trial, fat mass fell and the ratio of adiponectin to leptin, two hormones made by fat tissue, rose compared with placebo while everyone followed a reduced-calorie diet. The summary does not name a primary outcome, and these results have not been repeated in another trial.
Weight gain, blood glucose and blood pressure in rodents (animal studies)
Animal work only. In mice on a high-fat diet, the extract at 0.5% of food reduced weight gain and fasting glucose and insulin. In obese rats it lowered glucose, triglycerides and body weight, and in rats bred for high blood pressure it lowered systolic pressure. Most of these studies had maker-affiliated authors.
Mechanism of action
Secoiridoid glycosides nuzhenide and GI3
Nuzhenide and GI3 are the main compounds of the extract and the ones it is standardized to. In lab tests they and related secoiridoids blocked fat cell maturation and activated PPAR-alpha, a receptor involved in fat burning, but only at concentrations about a thousand to ten thousand times higher than a synthetic activator. These effects have not been shown in people.
Low absorption of the intact compounds
After a single 1 g dose in nine healthy volunteers, intact nuzhenide and GI3 were not found in blood. Small amounts of broken-down forms, tyrosol and ligstroside-aglycone linked to sulfate or glucuronic acid, peaked about 2 hours later. The authors suggest the compounds mostly stay in the gut, so how the extract might act is unclear.
Chemistry shared with olive secoiridoids
Ash seed secoiridoids are built from tyrosol and elenolic acid, and their breakdown releases ligstroside aglycone, a compound also known from olives. Oleuropein, the main studied compound of olive leaf, is not among the compounds reported in the extract, so olive leaf findings do not transfer to it.
Clinical trials
Double-blind, randomized, placebo-controlled crossover study; 1.0 g of FraxiPure (6.8% nuzhenide, 5.8% GI3) or wheat bran placebo taken with 50 g glucose. No primary outcome or funder named in the abstract; no registry number found. Several co-authors are listed at Naturex on other papers (Visen et al. 2009, J Ethnopharmacol)
16 healthy volunteers.
The glucose area under the curve was lower than with placebo (P = 0.02); point differences at 45 and 120 minutes were not significant (P = 0.06 and 0.07). Insulin was higher at 90 minutes (P = 0.002), but the insulin area under the curve did not differ. No adverse events were reported.
Randomized, double-blind, placebo-controlled crossover trial at the University of Navarra; three 333 mg Glucevia capsules a day or placebo for 3 weeks each, 1 week washout, 15% energy-restricted diet. No primary outcome stated in the abstract; no ClinicalTrials.gov entry found. Five of ten authors at Naturex; sponsored by Naturex and a Spanish technology agency per a Naturex commentary (Zulet et al. 2014, Phytomedicine)
22 non-diabetic adults aged 50 to 80 with overweight or obesity enrolled; 17 completed.
Versus baseline, Glucevia lowered the glucose tolerance test curve by 28.2% and 2 hour glucose by 14%, while placebo changes were not significant; the abstract gives no between-group test for these. Fructosamine, glucagon, the adiponectin to leptin ratio and fat mass differed significantly from placebo.
Double-blind, placebo-controlled parallel study with maltodextrin placebo, alongside lab tests and an acute rat toxicity test; led by Naturex Spain staff (Flanagan et al. 2013, Food Chem Toxicol)
100 healthy volunteers.
No significant differences from placebo in any blood chemistry or blood count measure. Adverse events were similar in number in both groups and mild to moderate. The rat oral LD50 was above 2,500 mg/kg.
Uncontrolled pilot metabolism study; three 334 mg capsules of the maker's seed and fruit extract, which the paper reports was re-identified by DNA testing as Fraxinus angustifolia; extract supplied by Naturex, three Naturex co-authors (García-Villalba et al. 2015, Molecules)
Nine healthy volunteers aged 20 to 25.
Intact nuzhenide and GL3 were not detected in plasma. Tyrosol and ligstroside-aglycone conjugates appeared at low levels, peaking about 2 hours after intake, with large differences between people, suggesting low uptake of the intact compounds.
Animal study comparing FraxiPure at 0.5% of a high-fat diet with high-fat and low-fat controls; led by Naturex staff (Ibarra et al. 2011, Phytomedicine)
Mice fed a high-fat diet; no people.
Body weight gain was 32.30% lower and fasting glucose 76.52% and insulin 53.43% lower than in high-fat controls, with less liver weight gain and fewer fatty livers. Animal results only.
Animal study of acute and long-term oral dosing in two rat models, with three co-authors listed at Naturex on other papers (Montó et al. 2014, Food Funct)
Obese Zucker rats and spontaneously hypertensive rats; no people.
At 100 mg/kg a day, glucose fell 16.3%, triglycerides 33.4% and body weight 8.1% in Zucker rats, and systolic pressure fell 6.7% in hypertensive rats, with better blood vessel lining function. Animal results only.