Ash Seed Extract (Fraxinus excelsior)

Fraxinus excelsior L. (as reported) or Fraxinus angustifolia Vahl, seed and fruit
Evidence Level
Limited
6 Clinical Trials
5 Documented Benefits
2/5 Evidence Score

Ash seed extract is made from the seeds and fruits of ash trees in the olive family and is sold as Glucevia® (Ash Seed Extract) by Naturex, now part of Givaudan, and was studied earlier under the name FraxiPure. It is standardized to about 10% of two secoiridoid glycosides, nuzhenide and GI3. Early papers called the source European ash (Fraxinus excelsior), but the maker's raw material was later identified by DNA testing as narrow-leafed ash (Fraxinus angustifolia). In a single-dose study in healthy adults, 1 g taken with a glucose drink lowered the blood glucose curve compared with placebo. In a 3 week trial in older adults with overweight or obesity, fructosamine and fat mass differed from placebo, but only 17 people finished. All human studies had Naturex staff among the authors. A 90 day study found no blood test differences from placebo.

Studied Dose 1 g a day in all human studies: once with a 50 g glucose drink, daily for 3 weeks with a reduced-calorie diet (three 333 mg capsules), or daily for 90 days in a safety study. A single 1 g dose (three 334 mg capsules) was used in an absorption study.
Active Compound Seed and fruit extract made by a patented process and standardized to about 10% of the secoiridoid glycosides nuzhenide and GI3 (also written GL3); tested batches held 6.8% nuzhenide and 5.8% GI3, or 5.92% and 4.75%. Other compounds reported include the secoiridoids excelsides A and B, GI5 and ligstroside, and salidroside. The extract is about 72% carbohydrate, with about 6% each of protein and fiber.

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

1

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.

2

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.

3

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

1
FraxiPure 1 g With a 50 g Glucose Drink: Single-Dose Crossover
PubMed

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.

2
Glucevia 1 g Daily for 3 Weeks With a Reduced-Calorie Diet: Crossover Trial
PubMed

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.

3
FraxiPure 1,000 mg Daily for 90 Days: Safety Study
PubMed

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.

4
Single 1 g Dose: What Reaches the Blood and Urine
PubMed

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.

5
FraxiPure in High-Fat-Fed Mice for 16 Weeks (animal study)
PubMed

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.

6
Ash Seed Extract in Obese and Hypertensive Rats (animal study)
PubMed

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.

Side effects and drug interactions

Common Potential side effects

In a 90 day study in 100 healthy volunteers, 1,000 mg a day did not differ from placebo on blood chemistry or blood counts, and adverse events were similar in number and mild to moderate.
No adverse events were reported in a single-dose study of 1 g with a glucose drink.
Blood sugar: the extract lowered the glucose response in a small study, so people using glucose-lowering medication should check with their clinician and monitor glucose.
Pregnancy, breastfeeding and children: not studied in the trials cited here, so safety in these groups is not established.
Long-term use: the longest human study lasted 90 days, so effects of longer use are not known.

Important Drug interactions

Insulin, metformin, sulfonylureas and other glucose-lowering medications: the extract lowered the glucose response in a small study, so effects could add up; monitor glucose with your clinician.
Blood pressure medications: the extract lowered blood pressure in rats bred for high blood pressure; no human data exist, but tell your prescriber if you take one.
No drug interaction studies of ash seed extract have been published. Tell your doctor or pharmacist about any supplement you take.

Frequently asked questions about Ash Seed Extract (Fraxinus excelsior)

What is ash seed extract used for?

It is sold as Glucevia and marketed for blood sugar after meals. In one small study, a single 1 g dose lowered the glucose response to a glucose drink compared with placebo, and in one 3 week trial in older adults with overweight or obesity, fructosamine and fat mass differed from placebo. All human studies had authors from the maker, Naturex.

Is ash seed extract made from European ash or narrow-leafed ash?

Early studies and product names describe European ash (Fraxinus excelsior). A 2015 paper co-written with the maker reports that DNA testing by the maker and two outside laboratories identified its raw material, collected in Morocco, as narrow-leafed ash (Fraxinus angustifolia). Both are related trees in the olive family.

How much ash seed extract was used in studies?

Every human study used 1 g a day: once with a glucose drink, daily for 3 weeks alongside a reduced-calorie diet (as three 333 mg capsules), or daily for 90 days in a safety study. The extract is standardized to about 10% nuzhenide and GI3.

Is ash seed extract the same as ash leaf?

No. Ash seed extract comes from the seeds and fruits and is standardized to secoiridoids such as nuzhenide, and it has been studied for blood glucose responses. Ash leaf is used as a tea in Europe for traditional joint and urinary uses. Findings for one do not apply to the other.

What is Ash Seed Extract?

Ash seed extract is made from the seeds and fruits of ash trees in the olive family and is sold as Glucevia® (Ash Seed Extract) by Naturex, now part of Givaudan, and was studied earlier under the name FraxiPure. It is standardized to about 10% of two secoiridoid glycosides, nuzhenide and GI3.

Is Ash Seed Extract safe, and does it have side effects?

Side effects and cautions reported for Ash Seed Extract include: In a 90 day study in 100 healthy volunteers, 1,000 mg a day did not differ from placebo on blood chemistry or blood counts, and adverse events were similar in number and mild to moderate. No adverse events were reported in a single-dose study of 1 g with a glucose drink. It may also interact with some medications. Ash Seed Extract is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Ash Seed Extract interact with any medications?

Possible interactions include: Insulin, metformin, sulfonylureas and other glucose-lowering medications: the extract lowered the glucose response in a small study, so effects could add up; monitor glucose with your clinician. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Ash Seed Extract?

NutraSmarts rates the evidence for Ash Seed Extract as Limited (2 out of 5). It is backed by 6 study summaries and 10 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(10 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Visen P, Saraswat B, Visen A, Roller M, Bily A, Mermet C, He K, Bai N, Lemaire B, Lafay S, Ibarra A. Acute effects of Fraxinus excelsior L. seed extract on postprandial glycemia and insulin secretion on healthy volunteers. J Ethnopharmacol. 2009;126(2):226-32. doi: 10.1016/j.jep.2009.08.039.PubMedUsed to support: Double-blind, randomized, placebo-controlled crossover study in 16 healthy volunteers of a single 1.0 g dose of the ash seed extract FraxiPure (Naturex), containing 6.8% nuzhenide and 5.8% GI3, against a 50 g glucose load, with wheat bran as placebo. The extract reduced the glucose area under the curve versus placebo (P = 0.02); lower incremental glucose at 45 minutes (P = 0.06) and 120 minutes (P = 0.07) did not reach significance. Insulin was higher at 90 minutes (P = 0.002), but the insulin area under the curve did not differ from placebo. No adverse events were reported. The abstract names no primary outcome and no funder; co-authors Roller M, Bily A, Ibarra A and Bai N are listed with Naturex affiliations on other papers from 2010 to 2015, and He K, Roller M, Bily A, Bai N and Ibarra A are named inventors on the extract's patent (US 8293292).
  2. Zulet MA, Navas-Carretero S, Lara y Sánchez D, Abete I, Flanagan J, Issaly N, Fança-Berthon P, Bily A, Roller M, Martinez JA. A Fraxinus excelsior L. seeds/fruits extract benefits glucose homeostasis and adiposity related markers in elderly overweight/obese subjects: a longitudinal, randomized, crossover, double-blind, placebo-controlled nutritional intervention study. Phytomedicine. 2014;21(10):1162-9. doi: 10.1016/j.phymed.2014.04.027.PubMedUsed to support: Randomized, double-blind, placebo-controlled crossover trial in 22 non-diabetic adults aged 50 to 80 with overweight or obesity (mean BMI 31.0) on a 15% energy-restricted diet: three 333 mg capsules of Glucevia a day or placebo for 3 weeks each, with a 1 week washout. Compared with baseline, Glucevia lowered the incremental glucose area under the curve in a glucose tolerance test by 28.2% and 2 hour glucose by 14% (placebo: 7.9% and 1.6%, not significant); the abstract does not report a between-group test for these. Between-group differences were reported for serum fructosamine (p < 0.01), plasma glucagon (p < 0.05), the adiponectin to leptin ratio and fat mass. The abstract states no primary outcome. Five of the ten authors (Flanagan J, Issaly N, Fança-Berthon P, Bily A, Roller M) are listed at Naturex.
  3. Ughetto T. Glucevia Fraxinus excelsior Extract Effectively Controls Blood Glucose Levels in Randomized, Controlled Trial. Integr Med (Encinitas). 2014;13(4):30-2..PubMedUsed to support: Commentary written and sponsored by Naturex SA, by the deputy director of its nutrition and health business unit, describing the 3 week Glucevia crossover trial at the University of Navarra. It reports that 17 of the 22 enrolled volunteers completed the study, that fructosamine fell 1.8% on Glucevia and rose 3.3% on placebo, and that the trial was sponsored by Naturex and the Spanish Center for the Development of Industrial Technology. A promotional source, cited only for these trial details.
  4. Flanagan J, Meyer M, Pasamar MA, Ibarra A, Roller M, Alvarez i Genoher N, Leiva S, Gomez-García F, Alcaraz M, Martínez-Carrasco A, Vicente V. Safety evaluation and nutritional composition of a Fraxinus excelsior seed extract, FraxiPure™. Food Chem Toxicol. 2013;53:10-7. doi: 10.1016/j.fct.2012.11.030.PubMedUsed to support: Safety study of the ash seed extract FraxiPure led by Naturex Spain staff. The extract was high in carbohydrates, with minor protein, fiber, glucose and sucrose. Lab tests gave cell toxicity values (IC50 1.447 mg/mL at 72 hours) and protection against micronucleus formation in irradiated human lymphocytes; the oral LD50 in rats was above 2,500 mg/kg. In a double-blind, placebo-controlled parallel study of 100 healthy volunteers, 1,000 mg a day for 90 days did not differ from maltodextrin placebo on any blood chemistry or blood count measure, and adverse events were similar in number and mild to moderate.
  5. García-Villalba R, Tomás-Barberán FA, Fança-Berthon P, Roller M, Zafrilla P, Issaly N, García-Conesa MT. Targeted and Untargeted Metabolomics to Explore the Bioavailability of the Secoiridoids from a Seed/Fruit Extract (Fraxinus angustifolia Vahl) in Human Healthy Volunteers: A Preliminary Study. Molecules. 2015;20(12):22202-19. doi: 10.3390/molecules201219845.PubMedUsed to support: Pilot study in nine healthy young volunteers given a single 1 g dose (three 334 mg capsules) of the maker's seed and fruit extract, supplied by Naturex, whose staff co-authored it; funded by the Spanish Center for the Development of Industrial Technology (CDTI). The full text states that the raw material, earlier reported as Fraxinus excelsior, was re-identified by DNA testing as Fraxinus angustifolia (narrow-leaved ash) collected in Morocco, and that the extract is standardized to about 10% of the secoiridoids nuzhenide and GL3 (this batch 5.92% and 4.75%), made by a patented process (US 8293292), and is about 72% carbohydrate. Intact secoiridoids were not detected in plasma; tyrosol and ligstroside-aglycone glucuronides and sulfates appeared at low levels, peaking about 2 hours after intake, which the authors read as low uptake of the intact compounds.
  6. Bai N, He K, Ibarra A, Bily A, Roller M, Chen X, Rühl R. Iridoids from Fraxinus excelsior with adipocyte differentiation-inhibitory and PPARalpha activation activity. J Nat Prod. 2010;73(1):2-6. doi: 10.1021/np9003118.PubMedUsed to support: Lab study led by Naturex staff: two new secoiridoid glucosides (excelsides A and B) and eight known compounds, including nuzhenide, GI3, GI5, ligstroside and salidroside, were isolated from ash seeds. Nine compounds inhibited fat cell differentiation in 3T3-L1 cells, and a 1:10,000 dilution of the water extract and five of the compounds (including nuzhenide and GI3) activated a PPAR-alpha reporter system, the compounds at about 10^-4 M versus 10^-7 to 10^-8 M for the synthetic activator used for comparison. Not a human study.
  7. Ibarra A, Bai N, He K, Bily A, Cases J, Roller M, Sang S. Fraxinus excelsior seed extract FraxiPure™ limits weight gains and hyperglycemia in high-fat diet-induced obese mice. Phytomedicine. 2011;18(6):479-85. doi: 10.1016/j.phymed.2010.09.010.PubMedUsed to support: Animal study led by Naturex staff: in mice fed a high-fat diet for 16 weeks, FraxiPure at 0.5% of the diet reduced body weight gain by 32.30% and lowered fasting blood glucose by 76.52% and plasma insulin by 53.43% compared with high-fat controls, and reduced liver weight gain and the incidence of fatty livers. Not a human study.
  8. Montó F, Arce C, Noguera MA, Ivorra MD, Flanagan J, Roller M, Issaly N, D'Ocon P. Action of an extract from the seeds of Fraxinus excelsior L. on metabolic disorders in hypertensive and obese animal models. Food Funct. 2014;5(4):786-96. doi: 10.1039/c3fo60539f.PubMedUsed to support: Rat study with co-authors who appear with Naturex affiliations on other papers (Flanagan J, Roller M, Issaly N). In obese Zucker rats, chow with the seed extract at 100 mg/kg a day for 5 weeks lowered glycemia (16.3%), triglycerides (33.4%) and body weight (8.1%); in spontaneously hypertensive rats it lowered systolic blood pressure acutely at 200 mg/kg and by 6.7% with long-term feeding, with better endothelial function in both strains. Names nuzhenide and GI3 as the extract's principal secoiridoids. Not a human study.
  9. López-Carreras N, Fernández-Vallinas S, Miguel M, Aleixandre A. Long-Term Effect of an Aqueous Fraxinus excelsior L. Seed Extract in Spontaneously Hypertensive Rats. Int J Hypertens. 2014;2014:565212. doi: 10.1155/2014/565212.PubMedUsed to support: Rat study: in spontaneously hypertensive rats, a water-based ash seed extract at 20, 40 or 60 mg/kg a day attenuated the rise in blood pressure, less than captopril, with a smaller effect at the highest dose; body weight gain and food intake increased, and blood pressure returned to control values after the extract was stopped. Plasma antioxidant capacity rose and malondialdehyde fell. The abstract does not name the extract's source. Not a human study.
  10. Givaudan SA. Givaudan completes the acquisition and delisting of Naturex. Givaudan press release. 2018;Geneva, 18 September 2018. Accessed November 2026..SourceUsed to support: Not PubMed-indexed; company press release. States that Givaudan completed its acquisition of Naturex and that Naturex shares were removed from trading on Euronext Paris. Cited only to identify the current owner of the Naturex ingredient business.