CitrOlive® (Olive Leaf + Citrus Flavonoid Cardio Complex — Frutarom/IFF)

Evidence Level
Limited
3 Clinical Trials
5 Documented Benefits
2/5 Evidence Score

CitrOlive is a water-soluble blend of a bitter orange (Citrus aurantium) flavonoid extract and an olive (Olea europaea) leaf extract, made in Murcia, Spain, by Nutrafur for Frutarom Health, now IFF Health. IFF standardizes it to more than 18 percent oleuropeosides and more than 12 percent flavonoids. One small placebo-controlled trial has tested it by name: in 23 untreated adults with raised cholesterol, two 500 mg capsules a day for 3 months lowered oxidized LDL, a marker of oxidative damage to LDL, compared with placebo, while total, LDL and HDL cholesterol and triglycerides did not differ between the groups. A maker employee helped design that trial. A larger 8-week trial tested Citroven, a related IFF blend that adds grapefruit extract, so its results are not CitrOlive results.

Studied Dose 1000 mg per day, taken as two 500 mg capsules 12 hours apart for 90 days, per the trial methods; IFF's handout also gives 1000 mg/day as the recommended dose. The trial registration lists one 500 mg capsule a day, which does not match the published methods.
Active Compound Blend of two hydroethanolic extracts: bitter orange (Citrus aurantium) supplying flavanones (naringin, neohesperidin, neoeriocitrin, hesperidin) and flavones (luteolin, apigenin and diosmetin glycosides), and olive (Olea europaea) leaf supplying oleuropein-family secoiridoids and hydroxytyrosol. IFF specifies more than 18 percent oleuropeosides and more than 12 percent flavonoids; water-soluble powder.

Benefits

Less LDL oxidation in one small trial

In a 3-month randomized double-blind trial in 23 untreated adults with raised cholesterol, oxidized LDL fell from about 94 to 63 U/L on CitrOlive (two 500 mg capsules daily) and rose slightly on placebo, a significant difference between groups. The oxidized LDL to LDL ratio moved the same way. The trial was small and co-designed by a maker employee.

Cholesterol and triglycerides: no clear change versus placebo

In the same trial, total cholesterol fell within the CitrOlive group (236 to 228 mg/dL) but not significantly more than on placebo, and triglycerides, LDL and HDL cholesterol and apolipoproteins A1 and B did not differ between groups. Launch materials reported a triglyceride drop; the published trial did not find one.

Paraoxonase (PON1) activity rose within the CitrOlive group

PON1 is an HDL-linked enzyme that helps protect LDL from oxidation. In the 3-month trial it rose from 64.5 to 78.7 U/L on CitrOlive and was unchanged on placebo, but the paper reports this as a within-group change, not a significant difference between groups, and the placebo group started higher (81.6 U/L).

Vessel function and blood pressure with a related blend (Citroven)

In an 8-week randomized trial in 96 adults aged 40 to 75 with mildly raised cholesterol, Citroven, a sister IFF blend that adds grapefruit extract to bitter orange and olive leaf, improved flow-mediated dilation, diastolic pressure, total and LDL cholesterol and oxidized LDL (LDL-oxidase) versus placebo. Systolic pressure did not differ. It is not CitrOlive alone.

Olive leaf extract class evidence for blood pressure and lipids

In a 6-week crossover trial in 60 men with high-normal blood pressure, a different olive leaf extract supplying 136 mg oleuropein a day lowered daytime and 24-hour blood pressure by about 2 to 4 mmHg and reduced total and LDL cholesterol and triglycerides versus control. It was half-funded by its maker and did not test CitrOlive.

Mechanism of action

1

Protecting LDL from oxidation

Oxidized LDL is LDL whose fats and proteins have been damaged by oxidation, a change linked to fatty build-up in artery walls. Olive leaf and citrus polyphenols act as antioxidants in laboratory studies, which is the proposed reason oxidized LDL fell in the CitrOlive trial; this has not been measured directly in people.

2

Paraoxonase (PON1)

PON1 is an enzyme carried on HDL that breaks down oxidized lipids and helps protect LDL from oxidation. In the CitrOlive trial its activity rose only within the supplement group, so whether CitrOlive raises PON1 compared with placebo is not established.

3

Bitter orange flavonoids

The bitter orange extract supplies flavanones such as naringin, neohesperidin and hesperidin and flavones such as luteolin and diosmetin glycosides, as listed by the trial authors. These flavonoids are studied for effects on blood vessel lining cells and lipid handling, mostly in laboratory and animal work.

4

Olive leaf polyphenols

The olive leaf extract supplies oleuropein-family secoiridoids and hydroxytyrosol; IFF standardizes CitrOlive to more than 18 percent oleuropeosides. Separate trials of other olive leaf extracts have reported small blood pressure and lipid changes, but those products are not CitrOlive.

5

Vessel relaxation (animal tissue only)

In an ex vivo study, CitrOlive and separate citrus and olive leaf extracts relaxed aorta rings from spontaneously hypertensive rats in an endothelium-dependent way that relied on nitric oxide. This is animal tissue work; the CitrOlive human trial did not report blood pressure or vessel function results.

Clinical trials

1
CitrOlive and Oxidized LDL in Untreated Adults With Raised Cholesterol
PubMed

3-month randomized, double-blind, placebo-controlled trial at the Catholic University of Murcia (UCAM), Spain (NCT04330937, registered after enrolment began). Two capsules daily, 2 x 500 mg CitrOlive per the methods (the abstract says 500 mg, two capsules a day; the registry lists one 500 mg capsule), or maltodextrin placebo. Outcomes: oxidized LDL, lipids, apolipoproteins, PON1. The paper reports no external funding; an IFF employee co-authored it and helped design the protocol. Blood pressure, one of the registered primary outcomes, is not reported. (Victoria-Montesinos et al. 2021, Antioxidants (Basel))

30 adults randomized, 23 completed (14 CitrOlive, 9 placebo); mean age 41.9, 70 percent men, total cholesterol above 200 mg/dL and LDL above 130 mg/dL, not on cholesterol, blood pressure or diabetes medicines.

Oxidized LDL fell from 93.8 to 62.8 U/L on CitrOlive and rose from 98.2 to 105.7 U/L on placebo, a significant difference between groups; the oxidized LDL to LDL and HDL to LDL ratios also differed. Total cholesterol fell significantly only within the CitrOlive group (236 to 228 mg/dL; placebo 246 to 241 mg/dL), and triglycerides, LDL and HDL cholesterol and apolipoproteins A1 and B did not differ between groups. PON1 rose from 64.5 to 78.7 U/L within the CitrOlive group, not reported as a between-group difference. Weight and body fat did not change. The authors call the small sample and 3-month length the main limitations.

2
Related Blend Citroven (Not CitrOlive Alone) and Vessel Function, 8-Week RCT
PubMed

Single-centre randomized, double-blind, placebo-controlled trial at UCAM, Spain (NCT04114916). Citroven, an IFF blend of grapefruit and bitter orange extracts plus olive leaf extract (the registry lists it as apigenin, luteolin, grapefruit extract and CitrOlive), 2 x 500 mg daily for 8 weeks, or maltodextrin placebo. Primary outcome: flow-mediated dilation (FMD). Two authors were affiliated with the maker, Nutrafur iff-Health, although the paper declares no conflict. (Sánchez Macarro et al. 2020, Nutrients)

110 healthy adults aged 40 to 75 with total cholesterol of at least 180 mg/dL and LDL of at least 110 mg/dL randomized; 96 analysed per protocol (51 active, 45 placebo).

FMD rose from 6.7 to 9.8 percent on the blend versus 6.9 to 7.4 percent on placebo (between-group p = 0.039). Diastolic pressure, total and LDL cholesterol, oxidized LDL, the glutathione ratio, protein carbonyls and IL-6 also improved versus placebo. Systolic pressure fell within the active group, but the between-group difference was not significant (p = 0.168), although the abstract groups it with the significant results; HDL, triglycerides, CRP and TNF-alpha did not differ. No adverse events were reported. This tested a different product and is not CitrOlive evidence.

3
Olive Leaf Extract (Class Evidence) and Blood Pressure and Lipids, Crossover RCT
PubMed

Randomized, double-blind, controlled crossover trial at the University of Reading, UK: an olive leaf extract supplying 136 mg oleuropein and 6 mg hydroxytyrosol daily, or a polyphenol-free control, for 6 weeks each with a 4-week washout. Half the funding came from Comvita, maker of the extract. This is not CitrOlive. (Lockyer et al. 2017, European Journal of Nutrition)

60 men with high-normal blood pressure (systolic 121 to 140, diastolic 81 to 90 mmHg), mean age 45.

Compared with control, daytime and 24-hour systolic pressure were lower by about 4 and 3 mmHg and diastolic by about 3 and 2 mmHg, and total cholesterol, LDL and triglycerides were lower. Interleukin-8 fell, but other inflammation markers, vascular function and glucose measures did not change.

Side effects and drug interactions

Common Potential side effects

In the 3-month CitrOlive trial, blood counts, creatinine and liver enzymes showed no significant changes; the paper does not describe adverse events separately.
In the 8-week trial of the related Citroven blend, no adverse events were reported.
Safety beyond 3 months, and in pregnancy or breastfeeding, has not been studied.
The trial paper reports that CitrOlive was classified as GHS category 5 (very low acute toxicity); IFF's acute toxicity studies themselves are not published.
The citrus part is a bitter orange flavonoid extract; IFF does not state its synephrine content. Some studies of bitter orange products have reported raised heart rate and blood pressure and others have not, so people sensitive to stimulants should check the finished product label.
People allergic to citrus or olive should avoid it.

Important Drug interactions

Blood pressure medicines: olive leaf extracts have lowered blood pressure slightly in trials; monitor if combining.
Cholesterol-lowering medicines: the CitrOlive trial enrolled only people not taking them, so combined use is unstudied; tell your prescriber.
Medicines that interact with grapefruit or Seville (bitter) orange juice: whether this flavonoid extract has a similar effect is unknown; ask a pharmacist.
Anticoagulant and diabetes medicines: no interaction data exist for CitrOlive; tell your prescriber before combining.

Frequently asked questions about CitrOlive® (Olive Leaf + Citrus Flavonoid Cardio Complex — Frutarom/IFF)

What is CitrOlive?

CitrOlive is a water-soluble blend of a bitter orange (Citrus aurantium) flavonoid extract and an olive (Olea europaea) leaf extract, made in Murcia, Spain, by Nutrafur for Frutarom Health, now IFF Health. IFF standardizes it to more than 18 percent oleuropeosides and more than 12 percent flavonoids.

What is CitrOlive used for?

CitrOlive is researched primarily for Cardiovascular and Antioxidant. In a 3-month randomized double-blind trial in 23 untreated adults with raised cholesterol, oxidized LDL fell from about 94 to 63 U/L on CitrOlive (two 500 mg capsules daily) and rose slightly on placebo, a significant difference between gro…

What is the recommended dosage of CitrOlive?

The clinically studied dose is 1000 mg per day, taken as two 500 mg capsules 12 hours apart for 90 days, per the trial methods; IFF's handout also gives 1000 mg/day as the recommended dose. The trial registration lists one 500 mg capsule a day, which does not match the published methods. Always follow the product label and check with a healthcare provider for personal advice.

Is CitrOlive safe, and does it have side effects?

Side effects and cautions reported for CitrOlive include: In the 3-month CitrOlive trial, blood counts, creatinine and liver enzymes showed no significant changes; the paper does not describe adverse events separately. In the 8-week trial of the related Citroven blend, no adverse events were reported. It may also interact with some medications. CitrOlive 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 CitrOlive interact with any medications?

Possible interactions include: Blood pressure medicines: olive leaf extracts have lowered blood pressure slightly in trials; monitor if combining. Cholesterol-lowering medicines: the CitrOlive trial enrolled only people not taking them, so combined use is unstudied; tell your prescriber. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for CitrOlive?

NutraSmarts rates the evidence for CitrOlive as Limited (2 out of 5). It is backed by 3 study summaries and 3 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(3 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. Victoria-Montesinos D, Abellán Ruiz MS, Luque Rubia AJ, Guillén Martínez D, Pérez-Piñero S, Sánchez Macarro M, García-Muñoz AM, Cánovas García F, Castillo Sánchez J, López-Román FJ. Effectiveness of Consumption of a Combination of Citrus Fruit Flavonoids and Olive Leaf Polyphenols to Reduce Oxidation of Low-Density Lipoprotein in Treatment-Naïve Cardiovascular Risk Subjects: A Randomized Double-Blind Controlled Study. Antioxidants (Basel). 2021;10(4):589. doi: 10.3390/antiox10040589.PubMedUsed to support: The only trial of CitrOlive by name (Citrolive, iff-Murcia Natural Ingredients): 3-month double-blind RCT, 2 x 500 mg/day per methods (abstract: 500 mg, two capsules/day), 30 randomized, 23 analysed (14 vs 9). Oxidized LDL and the ox-LDL/LDL-C and HDL-C/LDL-C ratios differed between groups; total cholesterol fell within-group only; triglycerides, LDL-C, HDL-C, apo A1 and apo B did not differ; PON1 rose within the CitrOlive group only. NCT04330937 (blood pressure, a registered primary outcome, not reported). No external funding; IFF employee co-author helped design the protocol.
  2. Lockyer S, Rowland I, Spencer JPE, Yaqoob P, Stonehouse W. Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: a randomised controlled trial. Eur J Nutr. 2017;56(4):1421-1432. doi: 10.1007/s00394-016-1188-y.PubMedUsed to support: Class evidence, not CitrOlive: double-blind controlled crossover RCT in 60 pre-hypertensive men; an olive leaf extract (136 mg oleuropein, 6 mg hydroxytyrosol daily) for 6 weeks lowered daytime and 24-h systolic and diastolic BP and total cholesterol, LDL and triglycerides versus control; IL-8 fell, other inflammatory, vascular and glucose markers unchanged. 50 percent funded by Comvita, the extract maker.
  3. Sánchez Macarro M, Martínez Rodríguez JP, Bernal Morell E, Pérez-Piñero S, Victoria-Montesinos D, García-Muñoz AM, Cánovas García F, Castillo Sánchez J, López-Román FJ. Effect of a Combination of Citrus Flavones and Flavanones and Olive Polyphenols for the Reduction of Cardiovascular Disease Risk: An Exploratory Randomized, Double-Blind, Placebo-Controlled Study in Healthy Subjects. Nutrients. 2020;12(5):1475. doi: 10.3390/nu12051475.PubMedUsed to support: Sister product, not CitrOlive alone: Citroven (grapefruit + bitter orange + olive leaf, Nutrafur iff-Health), 2 x 500 mg/day for 8 weeks, 110 randomized, 96 per protocol. Primary FMD improved vs placebo (p = 0.039); diastolic BP, total and LDL cholesterol, LDL-oxidase, GSH/GSSG ratio, protein carbonyl and IL-6 differed between groups; systolic BP between-group p = 0.168 despite the abstract; HDL, triglycerides, CRP, TNF-alpha n.s. NCT04114916. Two Nutrafur-affiliated authors; paper declares no conflict.