A Phase I, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety and Tolerance of Oil Palm Phenolics (OPP) in Healthy Volunteers

Nur Balqis Muhammad Ismail Tadj, Nurul 'Izzah Ibrahim, Qodriyah Haji Mohd Saad, Tg Mohd Ikhwan Tg Abu Bakar Sidik, Soon-Sen Leow, Syed Fairus, Isa Naina Mohamed, Nur Balqis Muhammad Ismail Tadj, Nurul 'Izzah Ibrahim, Qodriyah Haji Mohd Saad, Tg Mohd Ikhwan Tg Abu Bakar Sidik, Soon-Sen Leow, Syed Fairus, Isa Naina Mohamed

Abstract

Background and aim: Oil palm aqueous by-products rich in phenolic content are known as oil palm phenolics (OPP), and pre-clinical research has shown that OPP has great potential to be further developed as an anti-hyperlipidemic agent. Hence, in order to introduce OPP into market, its safety profile needs to be established by undergoing a phase I clinical trial on healthy humans. Methods: A parallel, placebo-controlled, randomized, and double-blinded clinical trial was conducted for 2 months on 100 healthy subjects aged 20-40 years old. This trial was registered at clinicaltrials.gov (NCT04164446). The subjects were randomly allocated to four treatment arms with 25 participants each: placebo, 250, 1,000, and 1,500 mg of OPP. During the trial, subjects were required to consume four capsules simultaneously per day. Withdrawal of fasting blood for hematology, liver and renal function analysis, and medical examination were conducted at baseline (day 1), day 30, and day 60. For monitoring, vital signs (blood pressure and pulse rate) and weight measurements were taken during each visit. Results: Minor adverse events (AEs) were reported in all groups especially at high dose (1,500 mg) but none were serious adverse events (SAEs). Fasting blood parameters between control and all OPP-treated groups demonstrated no statistically significant difference from baseline to day 60. Conclusion: With no major AEs and SAEs reported and no abnormal findings in biochemistry and hematology results, OPP supplementation in capsule form is safe to be taken up to 1,500 mg a day.

Keywords: antihyperlipidemia; antioxidant; clinical trial (CT); natural products; oil palm phenolics; safety and toxicology.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Muhammad Ismail Tadj, Ibrahim, Haji Mohd Saad, Tg Abu Bakar Sidik, Leow, Fairus and Naina Mohamed.

Figures

FIGURE 1
FIGURE 1
Flow diagram of an OPP supplementation clinical trial vs. placebo.

References

    1. Amaya-Cruz D., Peréz-Ramírez I. F., Pérez-Jiménez J., Nava G. M., Reynoso-Camacho R. (2019). Comparison of the Bioactive Potential of Roselle (Hibiscus sabdariffa L.) Calyx and its By-Product: Phenolic Characterization by UPLC-QTOF MSE and Their Anti-obesity Effect In Vivo . Food Res. Int. 126, 108589. 10.1016/j.foodres.2019.108589
    1. Bolsinger J., Pronczuk A., Sambanthamurthi R., Hayes K. C. (2014). Anti-diabetic Effects of Palm Fruit Juice in the Nile Rat (Arvicanthis Niloticus). J. Nutr. Sci. 3, e5. 10.1017/jns.2014.3
    1. Burris K. P., Harte F. M., Michael Davidson P., Neal Stewart Jr C., Jr, Zivanovic S. (2012). Composition and Bioactive Properties of Yerba Mate (Llex Paraguariensis A. St.-Hil.): A Review. Chil. J. Agric. Res. 72 (2), 268–275. 10.4067/s0718-58392012000200016
    1. Chan J. Y., Kwong M., Lu R., Chang J., Wang B., Yen T. S., et al. (1998). Targeted Disruption of the Ubiquitous CNC-bZIP Transcription Factor, Nrf-1, Results in Anemia and Embryonic Lethality in Mice. EMBO J. 17 (6), 1779–1787. 10.1093/emboj/17.6.1779
    1. Che Idris C. A., Karupaiah T., Sundram K., Tan Y. A., Balasundram N., Leow S.-S., et al. (2014). Oil Palm Phenolics and Vitamin E Reduce Atherosclerosis in Rabbits. J. Funct. foods 7, 541–550. 10.1016/j.jff.2014.01.002
    1. Conlon M. A., Sambanthamurthi R., Tan Y. A., Sundram K., Fairus S., Abeywardena M. Y. (2020). Consumption of an Oil Palm Fruit Extract Promotes Large Bowel Health in Rats. Nutrients 12 (3), 644. 10.3390/nu12030644
    1. Diez-Echave P., Vezza T., Rodríguez-Nogales A., Ruiz-Malagón A. J., Hidalgo-García L., Garrido-Mesa J., et al. (2020). The Prebiotic Properties of Hibiscus sabdariffa Extract Contribute to the Beneficial Effects in Diet-Induced Obesity in Mice. Food Res. Int. 127, 108722. 10.1016/j.foodres.2019.108722
    1. Dzierzak E., Philipsen S. (2013). Erythropoiesis: Development and Differentiation. Cold Spring Harb. Perspect. Med. 3 (4), a011601. 10.1101/cshperspect.a011601
    1. Ebbert J. O., Elrashidi M. Y., Jensen M. D. (2014). Managing Overweight and Obesity in Adults to Reduce Cardiovascular Disease Risk. Curr. Atheroscler. Rep. 16 (10), 445–447. 10.1007/s11883-014-0445-x
    1. El-shiekh R. A., Al-Mahdy D. A., Hifnawy M. S., Abdel-Sattar E. A. (2019). In-vitro Screening of Selected Traditional Medicinal Plants for Their Anti-obesity and Anti-oxidant Activities. South Afr. J. Bot. 123, 43–50. 10.1016/j.sajb.2019.01.022
    1. Essien N. M., Bassey S. C., Nna V. U., Ofem O. E. (2014). Comparative Effect of Chronic Consumption of Some Edible Vegetable Oils on Lipid Profile and Some Haematological Parameters in Rats. Ann. Biol. Res. 5 (7), 16–21.
    1. Fairus S., Leow S. S., Mohamed I. N., Tan Y. A., Sundram K., Sambanthamurthi R. (2018). A Phase I Single-Blind Clinical Trial to Evaluate the Safety of Oil Palm Phenolics (OPP) Supplementation in Healthy Volunteers. Sci. Rep. 8 (1). 10.1038/s41598-018-26384-7
    1. Goorden S. M., Buffart T. E., Bakker A., Buijs M. M. (2013). Liver Disorders in Adults: ALT and AST. Ned. Tijdschr. Geneeskd. 157 (43), A6443.
    1. Hsu C. L., Yen G. C. (2008). Phenolic Compounds: Evidence for Inhibitory Effects against Obesity and Their Underlying Molecular Signaling Mechanisms. Mol. Nutr. Food Res. 52 (5), 53–61. 10.1002/mnfr.200700393
    1. Kamarudin K. F., Tao D. G., Yaakob Z., Takriff M. S., Rahaman M., Salihon J. (2015). A Review on Wastewater Treatment and Microalgal By-Product Production with a Prospect of Palm Oil Mill Effluent (POME) Utilization for Algae. Der Pharma Chem. 7 (7), 73–89.
    1. Leow S. S., Sekaran S. D., Sundram K., Tan Y., Sambanthamurthi R. (2011). Differential Transcriptomic Profiles Effected by Oil Palm Phenolics Indicate Novel Health Outcomes. BMC Genomics 12 (1), 432. 10.1186/1471-2164-12-432
    1. Leow S. S., Fairus S., Sambanthamurthi R. (2021). Water-soluble Palm Fruit Extract: Composition, Biological Properties, and Molecular Mechanisms for Health and Non-health Applications. Crit. Rev. Food Sci. Nutr. 10.1080/10408398.2021.1939648
    1. Lynch B. S., West S., Roberts A. (2017). Safety Evaluation of Water-Soluble Palm Fruit Bioactives. Regul. Toxicol. Pharmacol. 88, 96–105. 10.1016/j.yrtph.2017.05.021
    1. Malaysian Palm Oil Board M. (2020). Production of Oil Palm Products 2019. Retrieved from: .
    1. Mokhele M. S., Tswaledi D., Aboyade O., Shai J., Katerere D. (2020). Investigation of Aloe Ferox Leaf Powder on Anti-diabesity Activity. South Afr. J. Bot. 128, 174–181. 10.1016/j.sajb.2019.10.012
    1. Monplaisir K. M. (2016). Effect of Oil Palm Phenolics on Beta Amyloid Deposition in Cholesterol Induced Rat Model of Alzheimer's Disease: Histological Evidence. Detroit, MI: Wayne State University.
    1. Nair A. B., Jacob S. (2016). A Simple Practice Guide for Dose Conversion between Animals and Human. J. Basic Clin. Pharm. 7 (2), 27–31. 10.4103/0976-0105.177703
    1. Naranjo C. A., Busto U., Sellers E. M., Sandor P., Ruiz I., Roberts E. A., et al. (1981). A Method for Estimating the Probability of Adverse Drug Reactions. Clin. Pharmacol. Ther. 30, 239–245. 10.1038/clpt.1981.154
    1. Olaokun O. O., McGaw L. J., Eloff J. N., Naidoo V. (2013). Evaluation of the Inhibition of Carbohydrate Hydrolysing Enzymes, Antioxidant Activity and Polyphenolic Content of Extracts of Ten African Ficus Species (Moraceae) Used Traditionally to Treat Diabetes. BMC Complement. Altern. Med. 13 (1), 94–10. 10.1186/1472-6882-13-94
    1. Patten G. S., Abeywardena M. Y., Sundram K., Tan Y. A., Sambanthamurthi R. (2015). Effect of Oil Palm Phenolics on Gastrointestinal Transit, Contractility and Motility in the Rat. J. Funct. Foods 17, 928–937. 10.1016/j.jff.2015.06.008
    1. Rice-Evans C. A., Miller N. J., Paganga G. (1996). Structure-antioxidant Activity Relationships of Flavonoids and Phenolic Acids. Free Radic. Biol. Med. 20 (7), 933–956. 10.1016/0891-5849(95)02227-9
    1. Rodgers R. J., Tschöp M. H., Wilding J. P. (2012). Anti-obesity Drugs: Past, Present and Future. Dis. Model Mech. 5 (5), 621–626. 10.1242/dmm.009621
    1. Sakpal T. V. (2010). Sample Size Estimation in Clinical Trial. Perspect. Clin. Res. 1 (2), 67–69.
    1. Salazar J. H. (2014). Overview of Urea and Creatinine. Lab. Med. 45 (1), e19–e20. 10.1309/lm920sbnzpjrjgut
    1. Sambanthamurthi R., Tan Y., Sundram K., Abeywardena M., Sambandan T. G., Rha C., et al. (2011). Oil Palm Vegetation Liquor: a New Source of Phenolic Bioactives. Br. J. Nutr. 106 (11), 1655–1663. 10.1017/S0007114511002121
    1. Sambanthamurthi R., Tan Y. A., Sundram K. (2008). Treatment of Vegetation Liquors Derived from Oil-Bearing Fruit: Google Patents.
    1. Sekaran S. D., Leow S.-S., Abobaker N., Tee K. K., Sundram K., Sambanthamurthi R., et al. (2010). Effects of Oil Palm Phenolics on Tumor Cells In Vitro and In Vivo . Afr. J. Food Sci. 4 (8), 495–502.
    1. Sergent T., Vanderstraeten J., Winand J., Beguin P., Schneider Y.-J. (2012). Phenolic Compounds and Plant Extracts as Potential Natural Anti-obesity Substances. Food Chem. 135 (1), 68–73. 10.1016/j.foodchem.2012.04.074
    1. Syarifah-Noratiqah S.-B. (2021). The Effects of Water-Soluble Palm Fruit Extract (WSPFE) on Lipid Metabolism, Liver Injury and Oxidative Stress Bi-omarkers on Hyperlipidemic Golden Syrian Hamsters. Universiti Kebangsaan Malaysia. Manuscript to be submitted.
    1. Wang S., Moustaid-Moussa N., Chen L., Mo H., Shastri A., Su R., et al. (2014). Novel Insights of Dietary Polyphenols and Obesity. J. Nutr. Biochem. 25 (1), 1–18. 10.1016/j.jnutbio.2013.09.001
    1. Yen G.-C., Cheng H.-L., Lin L.-Y., Chen S.-C., Hsu C.-L. (2020). The Potential Role of Phenolic Compounds on Modulating Gut Microbiota in Obesity. J. Food Drug Analysis 28 (2), 195–205. 10.38212/2224-6614.1054
    1. Zhang Y., Xiang Y. (2016). Molecular and Cellular Basis for the Unique Functioning of Nrf1, an Indispensable Transcription Factor for Maintaining Cell Homoeostasis and Organ Integrity. Biochem. J. 473 (8), 961–1000. 10.1042/BJ20151182

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться