OLIVIE PHARMA,
a department of Atlas Olive Oils sarl

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DESERT OLIVE TREES
ANTIOXIDANTS

POLYPHENOLS WITH ANTIOXIDANT, ANTI-INFLAMMATORY, ANTICANCER, ANTI-AGING AND HEART PROTECTIVE ACTIONS.

We made several clinical studies on the desert olive trees organic powder: OLIVIE. More than 1’000’000 US$ invested on science for your benefit. Just the Joints anti-inflammation study costed 140.000 US$. In the next pages you will find all the clinical studies about the OLIVIE products.
As matter of fact, OLIVIE products are backed to deep sciences as we have realized 10 clinical studies on:
– lowering diabetes (2 studies realized)
– lowering arthritis and arthrosis pain and inflammation for patient suffering from joints inflammation (2 studies realized in this).
– lowering cancer tumor growth-anti-microbial effect.
– lowering Alzheimer incidence and improving brain cognition.
Last but not least, the story behind this powder is unique:
We produce OLIVIE powder from suffering olive trees in a rocky desert. Because of high temperatures (up to 127°F during summer), a lot of rocks in the soil making the trees not able to grow their roots to look for nutrients, nearly no rain throughout the year, our olive trees stress and think they will die. So, they trigger a self-defense mechanism through which they produce abnormally high quantity of antioxidants to defend themselves. These polyphenols, born because of this harsh environment, are more active, more potent and this is the main reason why we obtained excellent results.

CLINICAL STUDY N° 10

Effects of Desert Olive Tree Pearls Containing High Hydroxytyrosol Concentrations on the Cognitive Functions of Middle-Aged and Older Adults

Jieun Yoon1, Kazunori Sasaki 2,3, Iku Nishimura 4, Haruna Hashimoto 2, Tomohiro Okura 1,2, and Hiroko Isoda 2,3,5

ABSTRACT

Japanese population has the world’s longest life expectancy but faces the challenge of extending the healthy life expectancy without developing chronic diseases. Therefore, the effectiveness of products derived from olives used in the Mediterranean diet as a potential dietary solution has attracted attention. This study examined the effects of desert olive tree pearls (DOTPs), which contain 162 times more polyphenol hydroxytyrosol than olive oil, on the cognitive function of middle-aged and older adults using the Cognitrax test. Participants (aged 51–82 years) were assigned to the DOTP intake (n = 36) or placebo group (n = 36) in a randomized, double-blind, placebo-controlled, parallel-group study. The participants received 3 g of DOTP or placebo in olive oil twice daily for 12 weeks. Among cognitive domains, complex attention had a significant time × group interaction effect (P = 0.049) between the DOTP and placebo groups. The simple main effect for this item was significantly different (P < 0.001 and P = 0.572, respectively). Time effects were significant (P < 0.05) for the psychomotor speed, reaction time, cognitive flexibility, processing speed, and executive function domains. Therefore, DOTP has the potential to alleviate cognitive problems faced by middle-aged and older adults in Japan.

Keywords: olive oil; desert olive tree pearls; polyphenols; hydroxytyrosol; cognitive function; brain activity

CLINICAL STUDY N° 9

High Tyrosol and Hydroxytyrosol Intake Reduces Arterial Inflammation and Atherosclerotic Lesion Microcalcification in Healthy Older Populations

Nada Zoubdane 1, Redha-Alla Abdo 1, Michel Nguyen 2, M’hamed Bentourkia 3, Eric E. Turcotte 4, Hicham Berrougui 1, Tamas Fulop 1 and Abdelouahed Khalil 1,*

ABSTRACT

Aging is an important risk factor for cardiovascular diseases and convincing data have shown that chronic low-grade inflammation, which develops with advanced age, contributes significantly to cardiovascular risk. The present study aimed to use 18F-FDG/18F-NaF-PET/CT imaging to, respectively, gauge arterial inflammation and microcalcification in a healthy elderly population and to assess the potential benefits of a tyrosol- and hydroxytyrosol-rich diet on these two markers of atherosclerotic plaque fragility. Eleven healthy participants (mean age 75 ± 5.67 years) were supplemented for 6 months with high polyphenol-rich extra virgin olive oil (HP-EVOO), extra virgin olive oil (EVOO), or refined olive oil (ROO). The participants underwent PET/CT imaging with 18F-FDG and 18F-NaF radiotracers at baseline and after 6 months. 18F-FDG and 18F-NaF uptakes were quantified using standardized uptake values (SUV) and were categorized based on artery calcification and olive oil type. A total of 324 slices of the aortas of the imaged participants were analyzed for arterial inflammation and 327 slices were analyzed for microcalcification. 18F-FDG uptake was significantly higher in the non-calcified segments than in the calcified segments (SUVmax = 2.70 ± 0.62 and SUVmax = 2.54 ± 0.44, respectively, p < 0.042). Conversely, the non-calcified segments displayed significantly lower 18F-NaF uptake than the calcified segments (SUVmax = 1.90 ± 0.37 and 2.09 ± 0.24, respectively, p < 0.0001). The 6-month supplementation with HP-EVOO induced a significant reduction in 18F-FDG uptake in both the non-calcified (2.93 ± 0.23 to 2.75 ± 0.38, p < 0.004) and calcified segments of the aortas (2.25 ± 0.29 to 2.15 ± 0.19, p < 0.02). 18F-NaF uptake was also significantly lower in patients supplemented with HP-EVOO (SUVmax = 1.98 ± 0.33 at baseline compared to 1.85 ± 0.28, after the 6-month supplementation, p < 0.004), whereas no significant effect was observed
with EVOO.
Conversely, participants supplemented with ROO displayed a significant increase in 18F-NaF uptake (SUVmax = 1.78 ± 0.34 to 1.95 ± 0.34, p < 0.0001). The present study confirmed that a phenolic-compound-rich diet reduces both arterial inflammation and atherosclerotic lesion microcalcification and demonstrated that 18F-FDG/18F-NaF-PET/CT imaging is a valuable approach for assessing age-related arterial damage.

Keywords: atherosclerosis; positron emission tomography; 18F-FDG/18F-NaF; vascular inflammation; aging; tyrosol; hydroxytyrosol

CLINICAL STUDY N° 8

Dietary consumption of desert olive tree pearls reduces brain Aβ content and improves learning and memory ability in aged mice

Kazunori Sasakia,b, Hiroko Isodaa,b,c
a Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan
b Open Innovation Laboratory for Food and Medicinal Resource Engineering, National Institute of Advanced Industrial Science and Technology (AIST) and University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan
c Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan

ABSTRACT

Recently, the number of patients with neurodegenerative diseases, such as Alzheimer’s disease (AD), has increased with aging of the population. Desert Olive Tree Pearls (DOTP), one of the olive oil products rich in functional compounds such as polyphenols is considered to have beneficial effect on neuronal activities. In this study, our study showed that pre-treatment of SH-SY5Y cells with DOTP ameliorated Aβ-induced cytotoxicity. Moreover, the Morris water maze test indicated that DOTP improves learning and memory in aged mice. Also, DOTP induced a decrease in Aβ42 and inflammatory cytokine levels and increase in neurotransmitter levels in limbic system and serum of aged mice. These results suggest that DOTP may have anti-oxidative effects and decreased oxidative stress associated with overproduction of pro-inflammatory cytokines in Aβ accumulations by aging, thus protecting neurons. Generally, the results of the present study suggest that DOTP is a promising dietary ingredient for improvement of cognitive function.

CLINICAL STUDY N° 7

Supplementation with a rich-polyphenols olive tree powder reduces circulating inflammatory markers, disease activity, and pain intensity in patients with rheumatoid arthritis: a 9-weeks randomized, doubleblind, placebo-controlled clinical trial

Ghanam Jamal, Laaboudi W and Benlemlih M*
Biotechnology Laboratory, Faculty of Science Dhar El Mahraz, P.O. Box 1796, Atlas-Fez, University Sidi Mohammed Ben Abdellah, Fez, Morocco.

ABSTRACT

Background- Notwithstanding the way that olive fruits polyphenols and olive leafs polyphenols have been known for their natural anti-inflammatory effect in the Mediterranean countries, there is little deep scientific study to confirm these benefits.

Objective- To assess the effect of rich-polyphenols olive tree powder (made of leafs, baby leafs, olive fruit and olive oil) on inflammatory process and pain intensity, a randomized, double-blinded, placebo-controlled trial was conducted on human subjects with rheumatoid arthritis (RA).

Methods- Seventy-nine RA patients were randomized to get either 1 g per day of olive tree powder or 1 g of placebo powder during 9 weeks. Laboratory analysis, questionnaires administration, pain intensity, disease activity score, and inflammatory biomarkers were determined at the baseline and at the end of the trial. Specialists have monitored eventual side effects and antagonistic impacts of taking the olive tree powder through the period of the study.

Results- Good compliance (over 95%) with the treatment was observed, without any side effect or study-intervention adverse. Significant decrease in disease activity score has shown at the end of intervention within the treated group, and between groups (P<0.0001). Compared with the placebo group, inflammatory biomarkers decreased significantly in treated participants (P<0.0001). Here are the changes noticed from baseline in treated group were -1.25 mg/L (CI, -1.75 to -0.75), -2.09 pg/mL (CI, -2.63 to -1.54), -0.82 pg/mL (CI, -1.14 to -0.49) and -1769 pg/mL (CI, -2254 to -1283) for hs- CRP, IL-6, TNF-α and PGE2 respectively. Additionally, it is important to note that pain relief and global participants satisfaction increased significantly (P<0.0001) after 9 weeks of olive tree powder supplementation.

Conclusion- A net improvement in circulating inflammatory markers, disease activity, and pain intensity was observed in RA patients allocated to rich-polyphenols olive tree powder food supplement.

CLINICAL STUDY N° 6

Supplementation with Rich-Polyphenols Olive Tree Powder Improves Fasting Blood Glucose and Insulin Resistance in Patients with Type 2 Diabetes Mellitus: A 14-Weeks Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Jamal Ghanam1, Mohammed Benlemlih2
Biotechnology Laboratory, Faculty of Science Dhar El Mahraz, P.O. Box 1796, Atlas-Fez, University Sidi Mohammed Ben Abdellah, Fez, Morocco.

ABSTRACT

Despite the fact that olive tree extracts have been used for long time as antidiabetics in Mediterranean folk medicine, there are few studies providing support to this view. To assess the effect of rich-polyphenols olive extract on glucose metabolism and insulin resistance, a randomized, double-blinded, placebo-controlled trial was conducted on human subjects with type 2 diabetes. 80 T2DM patients were randomized to receive 3 g of olive tree powder or placebo during 14 weeks. changes from baseline in glucose metabolism, insulin resistance, and lipid profile were determined and compared between groups. The lipid profile levels of treated group have been decreased significantly (p< 0.0001 vs. placebo group), while the value of HDL-cholesterol raises to 51.5 ± 9.4 mg/dL (p= 0.007 vs. placebo). The administration of rich-polyphenols olive tree powder resulted in a significant reduction (vs. placebo) in HbA1c (p<
0.0001), fasting glucose (p< 0.0001), and insulin resistance (p= 0.0002). The average value of fasting glucose of the treated group was under the normal level defined by the American Diabetic Association (114.2 ± 15.2 mg/dL) by the end of the 14 weeks. Supplementation with olive tree extract was associated to a net improvement in fasting plasma glucose, insulin resistance, and lipid profile in subjects with T2DM, suggesting its potential therapeutic effect as an antidiabetic.

Keywords: Olive tree extract-Type 2 diabetes mellitus-Insulin resistance -Glucose control- Randomized clinical trial.

CLINICAL STUDY N° 5

Eco-Extraction of Phenolic Compounds from Moroccan Olive Fruits and Leaves and their Potential use as Antimicrobial Agents

Wafa Laaboudi
Corresponding Author, Biotechnology Laboratory, Faculty of Science Dhar El Mahraz University Sidi Mohamed Ben Abdellah – Fez – Morocco
Jamal Ghanam
Biotechnology Laboratory, Faculty of Science Dhar El Mahraz University Sidi Mohamed Ben Abdellah – Fez – Morocco
Mohammed Merzouki
Biotechnology Laboratory, Faculty of Science Dhar El Mahraz University Sidi Mohamed Ben Abdellah – Fez – Morocco
Mohamed Benlemlih
Biotechnology Laboratory, Faculty of Science Dhar El Mahraz University Sidi Mohamed Ben Abdellah – Fez – Morocco

ABSTRACT

In Morocco, the olive harvest generates regenerates a lot of waste such as leaves and olive fruits. Valuation by the extraction of polyphenols from this
waste could be a promising source. In our work, we have prepared an olive tree extract from this waste, our extract contains 148 g/l of polyphenols, 8.4 g/l of flavonoids and 39.11 g/l of o-diphenols. Polyphenols, major natural antioxidants play a key role in hundreds biological reactions. The antioxidant activity test revealed great antioxidant potential of our extract with high ORAC value 3 848 100 μmol Te/kg. The present work has as objective to evaluate the antimicrobial activity. The olive tree extract showed broad- spectrum antibacterial activity against Escherichia coli, Escherichia coli TG1, Escherichia
coli DH5α, Staphylococcus aureus, Bacillus cereus, Bacillus cereus MED5 and Streptococcus agalactiae. While pure phenolic compounds (caffeic acid, ascorbic
acid and quercetin) showed more limited activity. The antifungal effect of the olive tree extract exceed the antibiotics at a concentration of 3 mg/disc (p<0.05). Industrial technology can therefore exploit this extract, rich in polyphenols, in order to use instead of a synthetic antioxidants and antibiotics that could be dangerous. This would lead Morocco to enhance the olive harvest waste as an important economic source.

Keywords: Olive leaves; Olive fruit; Polyphenols; Antioxidants; Antibacterial; Antifungal.

CLINICAL STUDY N° 4

Anti-inflammatory and analgesic activities of olive tree extract

Wafa Laaboudi*, Jamal Ghanam1, Hala Aissam1, Mohammed Merzouki1, Mohamed Benlemlih1
1Biotechnology Laboratory, Faculty of Science Dhar El Mahraz, University Sidi Mohamed Ben Abdellah – Fez – Morocco

ABSTRACT

Objectif- The aim of this study was the in vivo evaluation of analgesic and anti-inflammatory effect of an olive tree extract with high polyphenols content.

Methods- This olive tree extract was obtained from Moroccan olive fruits and leaves using an eco-extraction free of chemical solvents and toxic additives. Antiinflammatory activity was evaluated using carrageenan and histamine-induced paw edema methods. Analgesic activity of the olive tree extract was estimated against a hot plate, acetic acid induced writhing and formalin tests.

Results- The extracts showed significant antiinflammatory and analgesic activities with a dosedependent manner. Anti-inflammatory activity of olive tree extract at 250 and 500 mg/kg doses was more important compared to the used standard drugs (p<0.05), in both carrageenan and histamine-induced paw edema tests. In analgesic assays, results showed that 500 mg/kg dose of olive tree extract has a significant analgesic effect through both peripheral and central mechanisms.

Conclusion- Our findings suggest that olive tree extract is safe and has potential anti-inflammatory and analgesic activities, which promote this use as a food supplement against pain and inflammation related to inflammatory diseases.

Keywords: Olive leaves, Olive fruit, Polyphenols, Anti-inflammatory, and Analgesic, In vivo.

CLINICAL STUDY N° 3

Hypoglycemic and hypolipidemic effects of phenolic olive tree extract in streptozotocin diabetic rats

Wafa Laaboudi*, Jamal Ghanam1, Oumaima Ghoumari1, Fatiha Sounni1, Mohammed Merzouki1, Mohamed Benlemlih1
1Biotechnology, Laboratory, Faculty of Science, Dhar, El Mahraz, University Sidi Mohamed, Ben Abdellah – Fez – Morocco

ABSTRACT

Objective- The aim of the present study was to determine the effects of an olive tree extract with high polyphenols content on blood glucose level and other related parameters in streptozotocin-induced diabetic rats.

Methods- Diabetes was induced in rats by intraperitoneal injection of streptozotocin (55 mg/kg bw). 72h after injection, rats with fasting blood glucose higher than 2 g/l were used for the experiments. Olive tree extract was administered for 28 d and blood glucose level was measured every 4 d. Total cholesterol, triglycerides, HDL-cholesterol, creatinine, urea, total protein, uric acid, aspartate aminotransferase and alanine aminotransferase
levels, were determined at the end of the experiment.

Results- The oral administration of olive tree extract contributes to blood glucose level decreasing in diabetic rats group, which was significantly lower at 4th week compared to the diabetic control rats. Moreover, supplementation by olive tree extract decreased significantly (p<0.05) the values of total cholesterol, triglycerides, HDL-cholesterol, creatinine, urea, total protein, uric acid, aspartate aminotransferase and alanine aminotransferase resulting from damage caused by streptozotocin treatment. Beside this, significant reduce (p<0.05) in heart disease risk ratio was observed for treated group (4.1±0.14) compared to untreated group (7.64±0.36), which was quite similar to normal rats (4.50±0.36). Studied olive tree extract effects were similar to those of glibenclamide, a well-known antidiabetic drug.

Conclusion- Results herein obtained reveal the hypoglycemic effect of this olive tree extract, suggesting his potential use as a natural antidiabetic agent.

Keywords: Olive leaves, Olive fruit, Polyphenols, Antidiabetic, Streptozotocin, In vivo.

CLINICAL STUDY N° 2

Anticancer effect of an olive tree extract through his cytotoxic, antioxidant and antiangiogenic activities

Laure Eloy2, Thierry CRESTEIL2,3, Jamal GHANAM1, Wafa LAABOUDI1, and Mohammed BENLEMLIH1
3 IPSIT, Faculté de Pharmacie, Université Paris Sud, 92290 Chatenay-Malabry, France.
2 ICSN-CNRS UPR 2301, Avenue de la terrasse, 91190 Gif sur Yvette, France.
1 Biotechnology Laboratory, Faculty of Science Dhar El Mahraz University Sidi Mohamed Ben Abdellah, P.O. Box 1796 Atlas, Fez-Morocco.

ABSTRACT

The aim of the current study was to evaluate the anticancerous potential of a phenolic olive tree extract through his cytotoxic, antioxidant and antiangiogenic activities. The in vitro cytotoxic activity of a crude olive tree extract and his major constitutive components has been evaluated against human KB, HL60 cancer cell lines using MTS and flow cytometry. ROS production was estimated with the DCFHDA assay. Antiangiogenic activity was evaluated in vitro on endothelial cells tube formation and the pro-angiogenic factor expression was quantified using qRT-PCR. In vitro cellular assays have demonstrated the cytotoxic effect of the crude olive tree extract. This extract reduces significantly (p<0.05) ROS produced in cells exposed to oxidative stress. Beside this, olive tree extract has demonstrated a strong antiangiogenic activity, which was correlated with a significant decrease (p<0.05) in VEGF, angiopoietin and HIF1α expression. Basically, the evaluation of antiproliferative, antioxidant and anti-angiogenic activities could be the first step to formulate an efficient pharmaceutical product with preventive and/or curative properties against cancer.

Key words: Olive tree extract; Anticancerous; Cytotoxic; Antioxidant; Antiangiogenic.

CLINICAL STUDY N° 1

Effects of Rich Polyphenols Olive Tree Extract on Inflammation and Pain in Patients with Rheumatoid Arthritis: A 8-weeks Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Ghanam Jamal, Laaboudi W and Benlemlih M*
Biotechnology Laboratory, Faculty of Science Dhar El Mahraz, P.O. Box 1796, Atlas-Fez, University Sidi Mohammed Ben Abdellah, Fez, Morocco.

ABSTRACT

Olive tree polyphenols have been known as natural anti-inflammatory agents. The aim of the current clinical trial was to assess the therapeutic effect of an olive tree extract with high polyphenols content on inflammatory process and pain intensity in rheumatoid arthritis (RA) patients. This is a randomized, double-blind, placebo-controlled clinical trial. Ninety RA patients were randomized into two groups; treated group received a daily dose of 3 g of olive extract (6 capsules, 500 mg each) during 8 weeks, while patients in placebo group received capsules with maltodextrin. Laboratory analysis, questionnaires administration, pain intensity, and inflammatory biomarkers were determined at the baseline and the end of the trial. Doctors assessed potential adverse effects of olive tree extract through the period of study. Significant decrease in disease activity score has shown at the end of intervention in the treated group and between groups (P<0.0001). Compared to the placebo group, inflammatory biomarkers decreased significantly in treated participants (P<0.0001). The changes from baseline in treated group were -1.37 mg/L (CI, – 2.71 to -1.57 mg/L), -2.14 pg/mL (CI, -2.71 to -1.57), -1.046 pg/mL (CI, -1.50 to -0.59) and -1795 pg/mL (CI, -2283 to -1308) for hs-CRP, IL-6, TNF-α and PGE2 respectively. Pain relief and global participants satisfaction increased significantly (P<0.0001) after 8 weeks of olive tree extract supplementation. Results obtained after 2 months of supplementation demonstrate for the first time the potential therapeutic effect of olive tree extract with high polyphenols content against inflammation and associated pain in RA.

Clinical Studies made on OLIVIE Polyphenols.