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Curcumin: An Effective or Deceptive Dietary Factor? Challenges for Functional Food Scientists Takanori Tsuda* College of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi 487-8501, Japan the blood, with very little existing in free form. To overcome this problem, various formulations of curcumin are being designed and developed to enhance its bioavailability.3 These formulations will help effectively exploit the various biological activities of curcumin; however, over-enhancing its bioavailability may induce toxicity. The safe intake quantity of these various bioavailable formulations should therefore be determined. Second, the roles of degradation and oxidation products as well as metabolites in the bioactivity of curcumin need to be examined in vivo. Curcumin itself has low chemical stability, giving rise to various degradation products.3,4 It has therefore been hypothesized that degradation and oxidation products as well as metabolites are involved in the various biological activities of curcumin.3 Curcumin degrades in neutral to alkaline solvents, producing ferulic acid, feruloyl methane, and vanillin.3,4 However, according to a recent study, these are minor products, with the majority comprising autoxidation urcumin, a yellow pigment and one of the polyphenols products, notably bicyclopentadione.3,4 contained in turmeric (Curcuma longa), is used as a spice, Could the various biological activities of curcumin be food coloring, and traditional herbal medicine. In addition to its explained by its degradation products, oxidation products, antioxidant and anti-inflammatory properties, curcumin is also and/or metabolites? Similar to curcumin, anthocyanins are thought to offer various health benefits. However, a recent chemically unstable plant pigments with low bioavailability. It report by the medicinal chemists Nelson et al. expressed doubt was recently suggested that phenolic acids, which are 1 about the health benefits of curcumin. More recently, Bahadori degradation products and metabolites of anthocyanins, play and Demiray re-reviewed the data and, subsequently, refuted an important role in the biological activities of berries.3 that the health benefits of curcumin are in doubt in a letter to Anthocyanin studies may therefore provide useful insight into the editor.2 We therefore recently reviewed the absorption, the biological activities of curcumin.3 Although the role of metabolism, and bioactivity of curcumin, highlighting future degradation products in the biological activity of curcumin has challenges for functional food scientists.3 This Viewpoint been examined, the overall relationship remains inconclusive, provides a summary of our findings. while the biological activity of curcumin oxidation products in Where should functional food scientists stand on the health vivo has yet to be examined. Understanding the role of the main benefits of curcumin, and how should we advance our research? metabolite, curcumin glucuronide, is also important, with only a Many functional food scientists are interested in the health few reports thus far documenting its biological activity. benefits of curcumin and turmeric, not only in terms of the Whether curcumin glucuronide and other metabolites can molecular mechanisms, metabolic pathways, and relationships explain the biological activity of curcumin therefore remains to between biological activity, degradation products, and metabbe validated.3 Our research group recently demonstrated that olites but also with regard to how much curcumin should be an increase in the blood curcumin glucuronide concentration consumed and in what form.3 From a medical chemistry causes an increase in free curcumin, resulting in suppression of 1 perspective, Nelson et al. warned that curcumin may fluoresce human colon carcinoma implants in mice.3,5 This interesting naturally, hampering attempts to use fluorescence to detect result suggests that curcumin glucuronide is indeed indirectly disease-associated protein binding.1 However, in our functional involved in the biological activity of curcumin in vivo.3 food science study, we did not use high-throughput drug In summary, the following points require further clarification: screening assessing the fluorescence strength of bonds between (1) whether curcumin-derived degradation and oxidation curcumin and disease-associated proteins when we identified products are detected in the body after curcumin intake3 and curcumin as a bioactive food-derived factor.3 Overall, we noted (2) whether the health benefits of curcumin can be explained three important points that need to be considered in future 3 by degradation and oxidation products or metabolites alone.3 If studies of the health benefits of curcumin (Figure 1). First, as a result of its poor solubility in water, native Received: December 14, 2017 curcumin has low oral bioavailability. The small amount of curcumin absorbed by the body exists largely as a conjugate in
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DOI: 10.1021/acs.jafc.7b05878 J. Agric. Food Chem. XXXX, XXX, XXX−XXX
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Journal of Agricultural and Food Chemistry
Figure 1. Challenges and future perspectives of curcumin health benefit research.3 This figure was reprinted with permission from ref 3. Copyright 2018 Royal Society of Chemistry.
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both hold true, we then need to determine how much and which products or metabolites have the most significant impact. Moreover, understanding whether differences in intestinal microflora play a role in manifesting these health benefits is also important, as is, conversely, determining whether curcumin intake has an impact on gut microflora.3 Lastly, because the effect of curcumin on humans has yet to be examined in full and in light of the contradicting results, further randomized, double-blind, and placebo-controlled trials are essential. Furthermore, cross-sectional studies using identical samples and conditions are also required.3 Bioavailable formulations would be useful in such studies, provided that the same formulation is used under uniform conditions.3 Also important is considering the substances other than curcumin that are contained in the turmeric extracts used in human trials.3 In other words, it is necessary to determine whether curcumin itself is responsible for its effects or whether other components, such as curcumin analogues and compounds with a completely unrelated structure, also play a role.3 The possibility that curcumin manifests its effects in combination with other substance(s) should therefore be investigated.3 Many studies have investigated the health benefits of curcumin. Although the findings are contradictory, these studies provide data for further research. By addressing the above challenges, functional food research on curcumin will contribute greatly to studies on the overall health benefits. The Journal of Agricultural and Food Chemistry therefore strongly encourages the submission of manuscripts aimed at these issues.
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REFERENCES
(1) Nelson, K. M.; Dahlin, J. L.; Bisson, J.; Graham, J.; Pauli, G. F.; Walters, M. A. The essential medicinal chemistry of curcumin. J. Med. Chem. 2017, 60, 1620−1637. (2) Bahadori, F.; Demiray, M. A realistic view on “The Essential Medicinal Chemistry of Curcumin”. ACS Med. Chem. Lett. 2017, 8, 893−896. (3) Tsuda, T. Curcumin as a functional food-derived factor: Degradation products, metabolites, bioactivity, and future perspectives. Food Funct. 2018, DOI: 10.1039/C7FO01242J. (4) Zhu, J.; Sanidad, K. Z.; Sukamtoh, E.; Zhang, G. Potential roles of chemical degradation in the biological activities of curcumin. Food Funct. 2017, 8, 907−914. (5) Ozawa, H.; Imaizumi, A.; Sumi, Y.; Hashimoto, T.; Kanai, M.; Makino, Y.; Tsuda, T.; Takahashi, N.; Kakeya, H. Curcumin β-Dglucuronide plays an important role to keep high levels of free-form curcumin in the blood. Biol. Pharm. Bull. 2017, 40, 1515−1524.
AUTHOR INFORMATION
Corresponding Author
*Telephone/Fax: +81-568-51-9659. E-mail:
[email protected]. ac.jp. ORCID
Takanori Tsuda: 0000-0002-7761-8824 Notes
The author declares no competing financial interest. B
DOI: 10.1021/acs.jafc.7b05878 J. Agric. Food Chem. XXXX, XXX, XXX−XXX
