Safety evaluation of high bioavailability curcumin in Healthy Japanese Adults: A Randomized, placebo-controlled, double-blind, parallel-group comparison study
Hyunjin Lee, Yoshitaka Kuwabara, Akiko Hirose, Toshihiro Kakinuma, Asami Baba, Tsuyoshi Takara
Functional Foods in Health and Disease, doi:10.31989/ffhd.v13i12.1207
Background: Curcumin is the principal component responsible for the pharmacological action of Curcuma longa. It has been proven to exhibit a diverse range of functions. It has been used in many fields as a spice, coloring agent, cosmetic, and food preservative. Objective: To evaluate the safety of the intake of highly bioavailable curcumin (CR-033P and TS-P1) in humans.
Methods: We conducted two trials. The participants were healthy Japanese adults. Participants of tria1 1 (Long-term intake trial) took CR-033P or TS-P1 for 12 weeks (as curcumin 150 mg/day). Participants of Trial 2 (Excessive intake trial) took TS-P1 for 4 weeks (as curcumin 750 mg/day). The safety assessment involved monitoring the occurrence of side effects or adverse events, along with the analysis of urinalysis and blood parameters.
Results: The safety analysis population of Trial 1 included 33 participants in the CR-033P group, 32 participants TS-P1, Functional Foods in Health and Disease 2023;13(12):702-716 FFHD Page 703 of 716 INTRODUCTION Curcuma longa has long garnered significant attention for its pharmacological effects. Not only used as a spice, coloring agent, cosmetic, and food preservative, it has also been utilized for medicinal purposes in India, China, and the rest of South-east Asia [1]. Curcumin, the principal component responsible for the pharmacological action of Curcuma longa, has been proven to exhibit a diverse range of functions. These manifest in hypothermic and hypotensive effects, while also performing roles such as being an anticoagulant, antivenom, antiprotozoal, antifungal, antibacterial, and 30 participants in the Placebo group. The safety analysis population of trial 2 included 22 participants in TS-P1 and 20 participants in the Placebo group. In both Trial 1 and Trial 2, few participants were observed to experience adverse events and however these were not adverse events related to the CR-033P or TS-P1. Results of urinalysis and blood analysis were confirmed to not exhibit medically problematic changes related to the CR-033P or TS-P1. Conclusions: These trials proved the safety of the long-term intake of CR-033P or TS-PI-(as curcumin 150mg/ day) and the safety of the excessive intake of TS-P1 for four weeks (as curcumin 750mg/ day). TS-P1 and CR-033P can be considered a safe curcumin supplement based on these results.
was significantly increased compared to baseline. However, those numbers were changes in the reference range [28] . In a previous study of 8-week intake, there was a significant difference in total bilirubin, Ibil, and triglyceride from placebo group, but the changes were showed to be within the reference range [9] . Based on the results of such previous studies, we further confirmed whether there were any items outside the reference range (Appendix 1, 2). As a result, the item that showed outside the standard value during the test period was the uric acid level of TS-P1 8 weeks after administration, as shown in Appendix 1. The uric acid levels were examined in each subject case and confirmed that no medically problematic changes occurred due to the intake of the test food. Drawing conclusions from Trial 1 and Trial 2 outcomes, it is substantiated that the safety of ingesting 150 mg/day curcumin equivalent of CR-033P or TS-P1 over a 12-week duration, alongside the ingestion of 750 mg/day curcumin equivalent of TS-P1 for 4 weeks, has been confirmed.
CONCLUSION: We investigated the safety of high bioavailability curcumin TS-P1 and CR-033P in healthy Japanese adults. These trials found that the safety of consuming 150 mg/day of curcumin is equivalent to TS-P1 or CR-033P for 12 weeks and 750 mg/day of curcumin equivalent of TS-P1 for 4 weeks. Therefore, the intake of TS-P1 and CR-033P to receive possible health benefits proves to be safe in healthy individuals.
List of..
References
Anand, Kunnumakkara, Newman, Aggarwal, Bioavailability of Curcumin: Problems and Promises, Mol Pharm,
doi:10.1021/mp700113rChung, Yoon, Cho, Yeo, Shin et al., Comparative pharmacokinetics of Theracurmin, a highly bioavailable curcumin, in healthy adult subjects, Int J Clin Pharmacol Ther,
doi:10.5414/CP204058Hirose, Kuwabara, Kanai, Kato, Makino et al., Comparative pharmacokinetics of new curcumin preparations and evidence for increased bioavailability in healthy adult participants, Int J Clin Pharmacol Ther,
doi:10.5414/CP204257Kuwabara, Hirose, Lee, Kakinuma, Baba et al., Effects of Highly Bioavailable Curcumin Supplementation on Common Cold Symptoms and Immune and Inflammatory Functions in Healthy Japanese Subjects: A Randomized Controlled Study, J Diet Suppl,
doi:10.1080/19390211.2023.2185723Lombardi, Crescioli, Maggini, Ippoliti, Ippolito et al., Acute liver injury following turmeric use in Tuscany: an analysis of the Italian Phytovigilance database and systematic review of case reports, Br. J. Clin. Pharmacol,
doi:10.1111/bcp.14460Luber, Rentsch, Lontos, Pope, Aung et al., Turmeric induced liver injury: a report of two cases, Case Reports Hepatol,
doi:10.1155/2019/6741213Martirosyan, Lampert, Ekblad, Classification and regulation of functional food proposed by the Functional Food Center, Functional Food Science,
doi:10.31989/ffs.v2i2.890Mega, Marzi, Kob, Piccin, Floreani, Food and Nutrition in the Pathogenesis of Liver Damage, Nutrients,
doi:10.3390/nu13041326Pancholi, Smina, Kunnumakkara, Maliakel, Krishnakumar, Safety assessment of a highly bioavailable curcumin-galactomannoside complex (CurQfen) in healthy volunteers, with a special reference to the recent hepatotoxic reports of curcumin supplements: A 90-days prospective study, Toxicology Reports,
doi:10.1016/j.toxrep.2021.06.008Polshettiwar, Sawant, Abhale, Chavan, Baheti et al., Review on Regulation of Herbal Products Used as a Medicine Across the Globe: A Case Study on Turmeric -Golden Medicine, Biomed Pharmacol J,
doi:10.13005/bpj/2458Shikishima, Moriyama, Takahashi, Takahashi, Maruyama et al., Novel ELISA technology in assessing undenatured type II collagen in functional foods and dietary supplements used for knee joint health care: its sensitivity, precision, and accuracy, Functional Foods in Health and Disease,
doi:10.31989/ffhd.v12i5.933Shikishima, Yoshinari, Shiojima, Moriyama, Bagchi et al., Safety and toxicological evaluation of a novel Citrus sudachi extract powder, Functional Foods in Health and Disease,
doi:10.31989/ffhd.v6i10.301Shiojima, Takahashi, Takahashi, Moriyama, Maruyama et al., Safety of dietary undenatured type II collagen: a pilot open-label overdose clinical investigation, Functional Foods in Health and Disease,
doi:10.31989/ffhd.v12i3.897Suhail, Masood, Sharma, John, Dhamoon, Turmeric supplement induced hepatotoxicity: a rare complication of a poorly regulated substance, Clin.Toxicol,
doi:10.1080/15563650.2019.1632882Sunagawa, Hirano, Katanasaka, Miyazaki, Funamoto et al., Colloidal Submicron-Particle Curcumin Exhibits High Absorption Efficiency—A Double-Blind, 3-Way Crossover Study&mdash, J Nutr Sci Vitaminol,
doi:10.3177/jnsv.61.37Suzuki, Baba, Kakinuma, Sano, Tanaka et al., A novel dietary questionnaire: The Calorie and Nutrition Diary (CAND), New Food Ind
Takahashi, Iio, Takara, Safety Evaluation of Theracurmin in Healthy Japanese Adults-A Randomized, Double-blind, Placebo-controlled Parallel-group Study, Jpn Pharmacol Ther
{ 'indexed': { 'date-parts': [[2023, 12, 21]],
'date-time': '2023-12-21T00:25:21Z',
'timestamp': 1703118321128},
'reference-count': 0,
'publisher': 'Functional Food Center',
'issue': '12',
'license': [ { 'start': { 'date-parts': [[2023, 12, 20]],
'date-time': '2023-12-20T00:00:00Z',
'timestamp': 1703030400000},
'content-version': 'unspecified',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by-nc/4.0'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'abstract': '<jats:p>Background: \xa0Curcumin is the principal component responsible for the '
'pharmacological action of Curcuma longa. It has been proven to exhibit a diverse range of '
'functions. It has been used in many fields as a spice, coloring agent, cosmetic, and food '
'preservative.Objective:\xa0To evaluate the safety of the intake of highly bioavailable '
'curcumin (CR-033P and TS-P1) in humans.\xa0Methods:\xa0We conducted two trials. The '
'participants were healthy Japanese adults.\xa0 Participants of tria1 1 (Long-term intake '
'trial) took CR-033P or TS-P1 for 12 weeks (as curcumin 150 mg/day). Participants of Trial 2 '
'(Excessive intake trial) took TS-P1 for 4 weeks (as curcumin 750 mg/day). \xa0The safety '
'assessment involved monitoring the occurrence of side effects or adverse events, along with '
'the analysis of urinalysis and blood parameters.Results:\xa0The safety analysis population of '
'Trial 1 included 33 participants in the CR-033P group, 32 participants TS-P1, and 30 '
'participants in the Placebo group. The safety analysis population of trial 2 included 22 '
'participants in TS-P1 and 20 participants in the Placebo group.\xa0In both Trial 1 and Trial '
'2, few participants were observed to experience adverse events and\xa0 however these were not '
'adverse events related to the CR-033P or TS-P1. Results of urinalysis and blood analysis were '
'confirmed to not exhibit medically problematic changes related to the CR-033P or '
'TS-P1.Conclusions:\xa0These trials proved the safety of the long-term intake of CR-033P or '
'TS-PI- (as curcumin 150mg/ day) and the safety of the excessive intake of TS- P1 for four '
'weeks (as curcumin 750mg/ day). TS-P1 and CR-033P can be considered a safe curcumin '
'supplement based on these results.\xa0 \xa0 \xa0Keywords: Curcumin, bioavailability, safety, '
'high dose, long term dose, Healthy Japanese Adults, BMI, Blood pressure\xa0Trial '
'registration: Trial 1: UMIN000046160, Trial 2: UMIN000048797.\xa0Foundation:Theravalues '
'Corporation</jats:p>',
'DOI': '10.31989/ffhd.v13i12.1207',
'type': 'journal-article',
'created': { 'date-parts': [[2023, 12, 20]],
'date-time': '2023-12-20T19:51:06Z',
'timestamp': 1703101866000},
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Safety evaluation of high bioavailability curcumin in Healthy Japanese Adults: A Randomized, '
'placebo-controlled, double-blind, parallel-group comparison study',
'prefix': '10.31989',
'volume': '13',
'author': [ {'given': 'Hyunjin', 'family': 'Lee', 'sequence': 'first', 'affiliation': []},
{'given': 'Yoshitaka', 'family': 'Kuwabara', 'sequence': 'additional', 'affiliation': []},
{'given': 'Akiko', 'family': 'Hirose', 'sequence': 'additional', 'affiliation': []},
{'given': 'Toshihiro', 'family': 'Kakinuma', 'sequence': 'additional', 'affiliation': []},
{'given': 'Asami', 'family': 'Baba', 'sequence': 'additional', 'affiliation': []},
{'given': 'Tsuyoshi', 'family': 'Takara', 'sequence': 'additional', 'affiliation': []}],
'member': '17268',
'published-online': {'date-parts': [[2023, 12, 20]]},
'container-title': 'Functional Foods in Health and Disease',
'original-title': [],
'link': [ { 'URL': 'https://www.ffhdj.com/index.php/ffhd/article/viewFile/1207/1991',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://www.ffhdj.com/index.php/ffhd/article/viewFile/1207/1992',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://www.ffhdj.com/index.php/ffhd/article/viewFile/1207/1992',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2023, 12, 20]],
'date-time': '2023-12-20T19:51:07Z',
'timestamp': 1703101867000},
'score': 1,
'resource': {'primary': {'URL': 'https://www.ffhdj.com/index.php/ffhd/article/view/1207'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2023, 12, 20]]},
'references-count': 0,
'journal-issue': {'issue': '12', 'published-online': {'date-parts': [[2023, 12, 7]]}},
'URL': 'http://dx.doi.org/10.31989/ffhd.v13i12.1207',
'relation': {},
'ISSN': ['2160-3855', '2378-7007'],
'subject': ['Nutrition and Dietetics', 'Biochemistry', 'Medicine (miscellaneous)', 'Food Science'],
'container-title-short': 'FFHD',
'published': {'date-parts': [[2023, 12, 20]]}}
