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Curcumin is a bright yellow chemical produced by plants of the ''Curcuma longa'' species. It is the principal curcuminoid of turmeric (''Curcuma longa''), a member of the
ginger Ginger (''Zingiber officinale'') is a flowering plant whose rhizome, ginger root or ginger, is widely used as a spice A spice is a seed, fruit, root, bark, or other plant substance primarily used for flavoring or coloring food. Spices ...
family, Zingiberaceae. It is sold as a herbal supplement, cosmetics ingredient, food flavoring, and food coloring. Chemically, curcumin is a diarylheptanoid, belonging to the group of curcuminoids, which are phenolic pigments responsible for the yellow color of turmeric. 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.


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
rhizome In botany and dendrology, a rhizome (; , ) is a modified subterranean plant stem that sends out roots and shoots from its nodes. Rhizomes are also called creeping rootstalks or just rootstalks. Rhizomes develop from axillary buds and grow hori ...
s of turmeric. 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. Later in 1913, the same group accomplished the synthesis of the compound. Although curcumin has been used historically in Ayurvedic medicine, its potential for medicinal properties remains unproven as a therapy when used orally.


Uses

The most common applications are as an ingredient in
dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
, in cosmetics, as flavoring for foods, such as turmeric-flavored beverages in
South South is one of the cardinal directions or Points of the compass, compass points. The direction is the opposite of north and is perpendicular to both east and west. Etymology The word ''south'' comes from Old English ''sūþ'', from earlier Pro ...
and Southeast Asia, and as coloring for foods, such as curry powders, mustards, butters,
cheese Cheese is a dairy product produced in wide ranges of flavors, textures, and forms by coagulation of the milk protein casein. It comprises proteins and fat from milk, usually the milk of cows, buffalo, goats, or sheep. During production, ...
s. As a
food additive Food additives are substances added to food to preserve flavor or enhance taste, appearance, or other sensory qualities. Some additives have been used for centuries as part of an effort to preserve food, for example vinegar (pickling), salt (salt ...
for orange-yellow coloring in prepared foods, its
E number E numbers ("E" stands for "Europe") are codes for substances used as food additives, including those found naturally in many foods such as vitamin C, for use within the European Union (EU) and European Free Trade Association (EFTA). Commonly ...
is E 100 in the European Union. It is also approved by the U.S. FDA to be used as a food coloring in US.


Chemistry

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. The aromatic ring systems, which are
phenols In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of one or more hydroxyl groups (— O H) bonded directly to an aromatic hydrocarbon group. The simplest is phenol, . Phenolic compounds ...
, are connected by two α,β-unsaturated
carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containin ...
groups. It is a diketone
tautomer Tautomers () are structural isomers (constitutional isomers) of chemical compounds that readily interconvert. The chemical reaction interconverting the two is called tautomerization. This conversion commonly results from the relocation of a hyd ...
, existing in enolic form in organic solvents and in keto form in water. 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 In organic chemistry, a nucleophilic addition reaction is an addition reaction where a chemical compound with an electrophilic double or triple bond reacts with a nucleophile, such that the double or triple bond is broken. Nucleophilic additions ...
. Because of its hydrophobic nature, curcumin is poorly soluble in water. However, it is easily soluble in organic solvents. Curcumin is used as a complexometric indicator for boron. It reacts with boric acid to form a red-colored compound, rosocyanine.


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 Cinnamic acid is an organic compound with the formula C6H5-CH=CH- COOH. It is a white crystalline compound that is slightly soluble in water, and freely soluble in many organic solvents. Classified as an unsaturated carboxylic acid, it occurs n ...
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 Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...
. Plant biosynthesis starting with cinnamic acid is rare compared to the more common ''p''-coumaric acid. Only a few identified compounds, such as anigorufone and
pinosylvin Pinosylvin is an organic compound with the formula C6H5CH=CHC6H3(OH)2. A white solid, it is related to trans-stilbene, but with two hydroxy groups on one of the phenyl substituents. It is very soluble in many organic solvents, such as acetone. O ...
, build from cinnamic acid.


Pharmacology

Curcumin, which shows positive results in most
drug discovery In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered. Historically, drugs were discovered by identifying the active ingredient from traditional remedies or by ...
assays, is regarded as a false
lead Lead is a chemical element with the Symbol (chemistry), symbol Pb (from the Latin ) and atomic number 82. It is a heavy metals, heavy metal that is density, denser than most common materials. Lead is Mohs scale of mineral hardness#Intermediate ...
that medicinal chemists include among "
pan-assay interference compounds Pan-assay interference compounds (PAINS) are chemical compounds that often give false positive results in high-throughput screens. PAINS tend to react nonspecifically with numerous biological targets rather than specifically affecting one desired ...
". This attracts undue experimental attention while failing to advance as viable therapeutic or drug leads,
See also:
although some derivatives of curcumin such as EF-24 have seen a significant amount of research. 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. Very little curcumin escapes the
GI tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans an ...
and most is excreted in feces unchanged. 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 P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...
s, and glutathione S-transferase.


Safety

As a component of turmeric, curcumin may interact with prescription drugs and dietary supplements. In high amounts, it may be unsafe for women during pregnancy. It may cause side effects, such as
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
,
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin ...
,
hives Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...
, or dizziness. Two preliminary clinical studies in cancer patients consuming high doses of curcumin (up to 8 grams per day for 3–4 months) showed no toxicity, though some subjects reported mild nausea or diarrhea. Curcumin is a contact allergen. The intended use of curcumin as a food additive is generally recognized as safe by the U.S. Food and Drug Administration.


Medical research

Although curcumin has been assessed in numerous laboratory and clinical studies, it has no medical uses established by well-designed clinical research. According to a 2017 review of more than 120 studies, curcumin has not been successful in any
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
, leading the authors to conclude that "curcumin is an unstable, reactive, non-bioavailable compound and, therefore, a highly improbable lead". Curcumin exhibits numerous interference properties which may lead to misinterpretation of results. The US government has supported US$150 million in research into curcumin through the
National Center for Complementary and Integrative Health The National Center for Complementary and Integrative Health (NCCIH) is a United States government agency which explores complementary and alternative medicine (CAM). It was initially created in 1991 as the Office of Alternative Medicine (OAM) ...
, and no support has been found for curcumin as a medical treatment. Curcumin has been identified by the U.S. Food and Drug Administration as a "fake cancer 'cure'".


Research fraud

Bharat Aggarwal was a cancer researcher at the University of Texas MD Anderson Cancer Center, who had 29 papers retracted for research fraud. Aggarwal's research had focused on potential anti-cancer properties of herbs and spices, particularly curcumin, and according to a March 2016 article in the ''
Houston Chronicle The ''Houston Chronicle'' is the largest daily newspaper in Houston, Texas, United States. , it is the third-largest newspaper by Sunday circulation in the United States, behind only ''The New York Times'' and the ''Los Angeles Times''. With i ...
'', "attracted national media interest and laid the groundwork for ongoing clinical trials". Aggarwal co-founded a company in 2004 called Curry Pharmaceuticals, based in
Research Triangle Park Research Triangle Park (RTP) is the largest research park in the United States, occupying in North Carolina and hosting more than 300 companies and 65,000 workers. The facility is named for its location relative to the three surrounding citie ...
,
North Carolina North Carolina () is a state in the Southeastern region of the United States. The state is the 28th largest and 9th-most populous of the United States. It is bordered by Virginia to the north, the Atlantic Ocean to the east, Georgia a ...
, which was seeking to develop drugs based on synthetic analogs of curcumin. SignPath Pharma, a company seeking to develop liposomal formulations of curcumin, licensed three patents invented by Aggarwal related to that approach from MD Anderson in 2013.


Alternative medicine

Though there is no evidence for the safety or efficacy of using curcumin as a therapy, some
alternative medicine Alternative medicine is any practice that aims to achieve the healing effects of medicine despite lacking biological plausibility, testability, repeatability, or evidence from clinical trials. Complementary medicine (CM), complementary and ...
practitioners give it intravenously, supposedly as a treatment for numerous diseases. In 2017, two serious cases of adverse events were reported from curcumin or turmeric products—one severe
allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...
and one death—that were caused by administration of a curcumin-
polyethylene glycol Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular w ...
(PEG40)
emulsion An emulsion is a mixture of two or more liquids that are normally immiscible (unmixable or unblendable) owing to liquid-liquid phase separation. Emulsions are part of a more general class of two-phase systems of matter called colloids. Althou ...
product by a naturopath. One treatment caused
anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follo ...
leading to death.


Stability

Decontamination of food by ionizing radiation, or food irradiation, is considered a safe and efficient process for elimination of pathogenic bacteria. 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. 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. The researchers used
spectrophotometry Spectrophotometry is a branch of electromagnetic spectroscopy concerned with the quantitative measurement of the reflection or transmission properties of a material as a function of wavelength. Spectrophotometry uses photometers, known as sp ...
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.


References

{{Transient receptor potential channel modulators Curcuminoids CYP2D6 inhibitors E-number additives Experimental medical treatments Food colorings Histone deacetylase inhibitors Natural dyes Vinylogous carboxylic acids