Chemically, curcumin is a
diarylheptanoid, belonging to the group of curcuminoids, which are
phenolicpigments responsible for the yellow color of turmeric.[2]
Laboratory and clinical research have not confirmed any medical use for curcumin. It is difficult to study because it is both unstable and poorly
bioavailable. It is unlikely to produce useful leads for
drug development.[3]
History
Curcumin was named in 1815 when Henri Auguste Vogel and
Pierre Joseph Pelletier reported the first isolation of a "yellow coloring-matter" from the
rhizomes of turmeric.[4] Later, it was found to be a mixture of
resin and turmeric oil. In 1910, Milobedzka and Lampe reported the chemical structure of curcumin to be as diferuloylmethane.[5] Later in 1913, the same group accomplished the synthesis of the compound.
Although used in
traditional medicine, the possible therapeutic properties of turmeric or curcumin remain undetermined.[3][6][7]
Curcumin incorporates a seven carbon linker and three major functional groups: an α,β-unsaturated β-diketone moiety and an aromatic O-methoxy-phenolic group.[2][5] The aromatic ring systems, which are
phenols, are connected by two α,β-unsaturated
carbonyl groups.[2][12] It is a
diketonetautomer, existing in
enolic form in
organic solvents and in
keto form in water.[13] The diketones form stable enols and are readily deprotonated to form
enolates; the α,β-unsaturated carbonyl group is a good
Michael acceptor and undergoes
nucleophilic addition.[citation needed] Because of its hydrophobic nature, curcumin is poorly soluble in water[2] but is easily soluble in organic solvents.[5]
Biosynthesis
The biosynthetic route of curcumin is uncertain. In 1973, Peter J. Roughley and Donald A. Whiting proposed two mechanisms for curcumin biosynthesis. The first mechanism involves a chain extension reaction by
cinnamic acid and 5
malonyl-CoA molecules that eventually arylize into a curcuminoid. The second mechanism involves two cinnamate units coupled together by malonyl-CoA. Both use cinnamic acid as their starting point, which is derived from the amino acid
phenylalanine.[14]
Plant biosynthesis starting with cinnamic acid is rare compared to the more common
p-coumaric acid.[14] Only a few identified compounds, such as
anigorufone and
pinosylvin, build from cinnamic acid.[15][16]
Curcumin, which shows positive results in most
drug discovery assays, is regarded as a false lead that
medicinal chemists include among "
pan-assay interference compounds". This attracts undue experimental attention while failing to advance as viable therapeutic or drug leads,[3][6][17] although some derivatives of curcumin such as
EF-24 have seen a significant amount of research.[18]
Factors that limit the bioactivity of curcumin or its analogs include chemical instability, water insolubility, absence of potent and selective target activity, low bioavailability, limited tissue distribution, and extensive metabolism.[3] Very little curcumin escapes the
GI tract and most is excreted in feces unchanged.[19] If curcumin enters plasma in reasonable amounts, there is a high risk of toxicity since it is promiscuous, and interacts with several proteins known to increase the risk of adverse effects, including
hERG,
cytochrome P450s, and
glutathione S-transferase.[3]
Safety
As a component of turmeric, curcumin may interact with
prescription drugs and dietary supplements.[20] In high amounts, it may be unsafe for women during pregnancy.[20] It may cause side effects, such as
nausea,
diarrhea,
hives, or dizziness.[20] Between 2004 and 2022 there were ten cases of liver injury caused by curcumin herbal and dietary supplements.[21] Curcumin is a contact allergen.[22]
Although curcumin has been assessed in numerous laboratory and
clinical studies, it has no medical uses established by well-designed clinical research.[24] According to a 2017 review of more than 120 studies, curcumin has not been successful in any
clinical trial, leading the authors to conclude that "curcumin is an unstable, reactive, non-bioavailable compound and, therefore, a highly improbable lead".[3] Curcumin exhibits numerous interference properties which may lead to misinterpretation of results.[3][6][25]
Aggarwal cofounded a company in 2004 called Curry Pharmaceuticals based in
Research Triangle Park,
North Carolina, which planned to develop drugs based on synthetic analogs of curcumin.[31][33] SignPath Pharma, a company seeking to develop
liposomal formulations of curcumin, licensed three patents by Aggarwal related to that approach from MD Anderson in 2013.[34]
FDA warnings about dietary supplements
Between 2018 and 2023, the FDA issued 29
warning letters to American manufacturers of
dietary supplements for making false claims of anti-disease effects from using products containing curcumin.[35] In each letter, the FDA stated that the supplement product was not an
approved new drug because the "product is not generally recognized as safe and effective" for the advertised uses, that "new drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from FDA", and that the "FDA approves a new drug on the basis of scientific data and information demonstrating that the drug is safe and effective".[35]
Decontamination of food by ionizing radiation, or
food irradiation, is considered a safe and efficient process for elimination of
pathogenic bacteria.[39][40] Ionizing radiation treatment can be applied to either raw materials or ready to eat foods, with some countries, like the United States, imposing limitations on its use.[39][41] In 2016, laboratory research established and compared the
radiosensitivity of three organic food colorants including curcumin,
carmine, and
annatto to create data to be used for application whenever food products containing these food colors were to undergo the radiation process.[39] The researchers used
spectrophotometry and
capillary electrophoresis to establish radiosensitivity of the three organic food colorants. Carmine samples were quite stable against radiation treatment, annatto showed limited stability, and curcumin was found to be stable at high temperatures and in acids, but unstable in alkaline conditions and in the presence of light.[39]
^"Curcumin, E 100, page 9". Specifications for food additives listed in Annexes II and III to Regulation (EC) No 1333/2008 of the European Parliament. March 9, 2012. Retrieved July 24, 2019.
^Schmitt B, Hölscher D, Schneider B (February 2000). "Variability of phenylpropanoid precursors in the biosynthesis of phenylphenalenones in Anigozanthos preissii". Phytochemistry. 53 (3): 331–337.
doi:
10.1016/S0031-9422(99)00544-0.
PMID10703053.
^"Curcumin". Micronutrient Information Center; Phytochemicals. Linus Pauling Institute, Oregon State University, Corvallis. 2016. Retrieved June 18, 2016.