Bioavailability of the Microconstituents of Natural Chios Mastiha in Healthy Adults.

Biological Availability Clinical Trial

Official title:

A Bioavailability Study of the Natural Chios Mastiha in Blood and Urine Samples of Healthy Adults.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02847117
• Other study ID #: Mastiha BIO-GR (304)
• Status: Completed
• Phase: N/A
• Start date: July 2016
• Est. completion date: March 10, 2021

Study information

• Verified date: June 2021
• Source: Harokopio University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Mastiha is a natural product from the tree Pistacia lentiscus var. Chia (Anacardiaceae) growing exclusively in the Southern part of Chios Island. It is the natural resinous exudate produced after longitudinal incisions made at close intervals from the base of the trunk up to the thicker branches of the tree. U.S. Food and Drug Administration has classified Mastiha as GRAS. Previous research demonstrates Mastiha's safety, as well as anti-inflammatory, antimicrobial and antioxidant properties. In addition, the European Medicine Agency has recently recognized Mastiha as a natural medicine and classified it to the category of traditional herbal medicines in diarrhea problems, mild dyspeptic disorders, skin inflammation and healing (EMA/HMPC/46758/2015).

However, the bioavailability of its microconstituents in human biological samples is still undetermined. To this end, the current study aims to investigate the whether Mastiha's compounds are bioavailable in healthy adults. Twenty apparently healthy men, aged 20-40 years old, will be enrolled based on certain inclusion and exclusion criteria. The staff of the study will provide detailed information regarding the aims, the methods, anticipated benefits and potential hazards of the study and all patients will receive the Patient Information Leaflet (PIL). Ample time (48 hours) will be provided in order to decide whether they want to participate in the protocol. Each patient agreeing to participate will sign an Informed Consent document and the staff will explain to patients that they are under no obligation to enter the trial and that they can withdraw at any time during the trial, without having to give a reason. A copy of the signed Informed Consent will be given to the participant.

After enrollment, the volunteers will undergo a medical and dietary assessment and their health status will be evaluated through a complete blood count. Then, they will follow a low-phytochemical diet for five days, meaning that they will exclude fruits, vegetables, legumes, coffee, tea, alcoholic beverages and chocolate. On the day of the experiment and after overnight fasting, the volunteers will consume 10g of natural Mastiha and blood samples will be obtained on timepoints 0h, 30min, 1h, 2h, 4h, 6h and 24h after Mastiha intake. Until timepoint 6h, they will be allowed to consume only water. Urine samples will also be collected on timepoints 0h, 4h, 8h and 24h.

After collection, the phenolic and terpenoid content or metabolites of Mastiha will be identified in plasma samples applying LC-HRMS. Additionally, the metabolomic profile will be assessed in plasma samples with LC-HRMS and in urine samples with NMR-based metabolomics. Oxidative stress will be evaluated through the CuSO4 technique and oxidised LDL levels in serum samples, as well as F-2 isoprostanes in urine samples.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 10, 2021
• Est. primary completion date: February 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 40 Years

Eligibility

Inclusion Criteria:

• Age: 20-40 years old

• BMI: 18.5-24.9 kg/m2

Exclusion Criteria:

• BMI > 25 kg/m2

• Alcohol or drug abuse

• Medication, vitamin or inorganic supplements

• Vegan or macrobiotic diet before and during the study

• Gastrointestinal diseases, such as IBD, peptic ulcer or GI cancer

Related Conditions & MeSH terms

• Biological Availability

Intervention

Other:
• Mastiha
The volunteers will follow a low-phytochemical diet for five days, meaning that they will exclude fruits, vegetables, legumes, coffee, tea, alcoholic beverages and chocolate. On the day of the experiment and after overnight fasting, the volunteers will consume 10g of natural Mastiha and blood samples will be obtained on timepoints 0h, 30min, 1h, 2h, 4h, 6h and 24h after Mastiha intake. Until timepoint 6h, will be allowed to consume only water. Urine samples will also be collected on timepoints 0h, 4h, 8h and 24h.

Locations

Country	Name	City	State
Greece	Harokopio University	Athens

Sponsors (1)

Lead Sponsor	Collaborator
Harokopio University

Country where clinical trial is conducted

Greece, 

References & Publications (16)

Andrikopoulos NK, Kaliora AC, Assimopoulou AN, Papapeorgiou VP. Biological activity of some naturally occurring resins, gums and pigments against in vitro LDL oxidation. Phytother Res. 2003 May;17(5):501-7. — View Citation

Crowell PL. Prevention and therapy of cancer by dietary monoterpenes. J Nutr. 1999 Mar;129(3):775S-778S. Review. — View Citation

Ding Y, Nguyen HT, Kim SI, Kim HW, Kim YH. The regulation of inflammatory cytokine secretion in macrophage cell line by the chemical constituents of Rhus sylvestris. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3607-10. doi: 10.1016/j.bmcl.2009.04.129. Epub 2009 May 3. — View Citation

Gioxari A, Kaliora AC, Papalois A, Agrogiannis G, Triantafillidis JK, Andrikopoulos NK. Pistacia lentiscus resin regulates intestinal damage and inflammation in trinitrobenzene sulfonic acid-induced colitis. J Med Food. 2011 Nov;14(11):1403-11. doi: 10.1089/jmf.2010.0240. Epub 2011 May 25. — View Citation

González-Burgos E, Gómez-Serranillos MP. Terpene compounds in nature: a review of their potential antioxidant activity. Curr Med Chem. 2012;19(31):5319-41. Review. — View Citation

Inouye S, Takizawa T, Yamaguchi H. Antibacterial activity of essential oils and their major constituents against respiratory tract pathogens by gaseous contact. J Antimicrob Chemother. 2001 May;47(5):565-73. — View Citation

Inouye S, Yamaguchi H, Takizawa T. Screening of the antibacterial effects of a variety of essential oils on respiratory tract pathogens, using a modified dilution assay method. J Infect Chemother. 2001 Dec;7(4):251-4. — View Citation

Kaliora AC, Dedoussis GV, Schmidt H. Dietary antioxidants in preventing atherogenesis. Atherosclerosis. 2006 Jul;187(1):1-17. Epub 2005 Nov 28. Review. — View Citation

Kanellos PT, Kaliora AC, Liaskos C, Tentolouris NK, Perrea D, Karathanos VT. A study of glycemic response to Corinthian raisins in healthy subjects and in type 2 diabetes mellitus patients. Plant Foods Hum Nutr. 2013 Jun;68(2):145-8. doi: 10.1007/s11130-013-0348-y. — View Citation

Kountouri AM, Mylona A, Kaliora AC, Andrikopoulos NK. Bioavailability of the phenolic compounds of the fruits (drupes) of Olea europaea (olives): impact on plasma antioxidant status in humans. Phytomedicine. 2007 Oct;14(10):659-67. Epub 2007 Sep 17. — View Citation

Lemonakis N, Magiatis P, Kostomitsopoulos N, Skaltsounis AL, Tamvakopoulos C. Oral administration of chios mastic gum or extracts in mice: quantification of triterpenic acids by liquid chromatography-tandem mass spectrometry. Planta Med. 2011 Nov;77(17):1916-23. doi: 10.1055/s-0031-1279996. Epub 2011 Aug 25. — View Citation

Ohno T, Kita M, Yamaoka Y, Imamura S, Yamamoto T, Mitsufuji S, Kodama T, Kashima K, Imanishi J. Antimicrobial activity of essential oils against Helicobacter pylori. Helicobacter. 2003 Jun;8(3):207-15. — View Citation

Papalois A, Gioxari A, Kaliora AC, Lymperopoulou A, Agrogiannis G, Papada E, Andrikopoulos NK. Chios mastic fractions in experimental colitis: implication of the nuclear factor ?B pathway in cultured HT29 cells. J Med Food. 2012 Nov;15(11):974-83. doi: 10.1089/jmf.2012.0018. Epub 2012 Aug 14. — View Citation

Rodrigues TG, Fernandes A Jr, Sousa JP, Bastos JK, Sforcin JM. In vitro and in vivo effects of clove on pro-inflammatory cytokines production by macrophages. Nat Prod Res. 2009;23(4):319-26. doi: 10.1080/14786410802242679. — View Citation

Romani A, Pinelli P, Galardi C, Mulinacci N, Tattini M. Identification and quantification of galloyl derivatives, flavonoid glycosides and anthocyanins in leaves of Pistacia lentiscus L. Phytochem Anal. 2002 Mar-Apr;13(2):79-86. — View Citation

Williamson G, Manach C. Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. Am J Clin Nutr. 2005 Jan;81(1 Suppl):243S-255S. doi: 10.1093/ajcn/81.1.243S. Review. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phenolic and terpenoid content or metabolites of Mastiha identification		The phenolic and terpenoid content or metabolites of Mastiha will be identified in plasma samples applying LC-HRMS. Data will be presented through study completion, an average of 1 year.
Primary	Targeted and untargeted metabolic profile assessment		Plasma metabolites assessment with GC-MS, LC-HRMS and urine metabolites assessment with NMR will take place . Data will be presented through study completion, an average of 1 year.
Secondary	Oxidative stress assessment		Serum resistance to oxidation will be assessed through the CuSO4 technique, oxidised LDL levels and uric acid levels. F-2 isoprostanes determination will take place in urine samples. Data will be presented through study completion, an average of 1 year.