The Focus on Yellow Inspires Nefarious Adulteration Practices. Another major complicating factor in the CDS supply chain is the occurrence of adulteration. The addition of undeclared lower-cost ingredients to powdered turmeric root/rhizome and turmeric extracts is a major concern among regulators, healthcare professionals, and responsible members of the DS and herbal medicine industry. Reports of turmeric adulteration include substitution with other Curcuma species (e.g., C. zedoaria, C. xanthorrhiza, or C. aromatica), or the undeclared admixture of starches or yellow/orange dyes. Pigments such as Metanil Yellow, lead chromate, or Sudan Red have been added even to crude turmeric to produce a visually more appealing product. These practices appear to be more frequent in rural areas of India and Bangladesh. Particularly disturbing is a recent publication documenting elevated blood levels of lead in pregnant women living in rural Bangladesh due to the ingestion of turmeric adulterated with the lead chromate. The Consequences of Using a Single Compound to Represent a Whole Plant. In contemporary literature, the compound curcumin (1) is widely used as a sole "representative" of the plant, C. longa. This error has escalated to a point where products are sold in the marketplace that contains synthetic 1 rather than naturally derived 1, which are sometimes even labeled as C. longa extracts, allegedly standardized to a certain content of 1 and its congeneric curcuminoids 2 and 3. The discovery of this form of fraud has previously led to the investigation of its adverse effects in humans. Liver toxicity has been associated with products labeled as preparations that contain turmeric in a number of case reports. Moreover, between May and June of 2019, at least 21 cases of acute non-viral cholestatic hepatitis were reported in Italy and associated by authorities with over 20 different turmeric products. In a subset of products for which information was available, daily dosage recommendations ranged between 50 and 1200 mg of "turmeric extract", labeled as being standardized to 95% curcuminoids, and containing 5 to 160 mg of pepper (Piper nigrum, Piperaceae) extract, labeled as containing 95% piperine. To prevent further cases, in July 2019, the Italian Ministry of Health eventually requested manufacturers of turmeric food supplements to include a warning about avoiding turmeric in patients with pre-existing liver conditions, in line with a recommendation by the European Medicines Agency (EMA) in 2018. Moreover, in cases of concomitant use of API-based medicines, the Italian Ministry of Health, through testing, had excluded contaminants, reaction by-products, solvent residues, and substitution with other plants as possible causes of the observed hepatotoxicities. However, the authorities also stated that there was no correlation between turmeric(!) itself and liver injury. Synthetic curcumin can be made for about one-third of the cost of natural curcumin, providing a financial incentive to unethical suppliers for diluting or replacing turmeric extracts or refined products with synthetic materials. A 2019 study using 1 H NMR and HPTLC to investigate the quality of 56 turmeric food supplements sold in Europe and the United States found that at least three of these supplements contained synthetic curcumin or synthetic curcuminoids based on the absence of the typically co-occurring turmeric compounds. In addition, a number of products claiming to contain piperine did not show the characteristic signals of the aromatic hydrogens in the 1 H NMR spectrum or the yellow band for the alkaloid in the HPTLC traces. In order to develop a more untargeted approach for recognizing "curcumin fraud", the present study considered known targeted analytical methods that have employed NMR, MS, and countercurrent separation methodologies. The only currently accepted proof that "curcumin" is synthetic utilizes isotope ratio mass spectrometry (IRMS). For the detection of synthetic 1, the determination of C concentrations has proven useful as the synthesis of 1 uses petroleumbased starting materials, which are devoid of 14 C. Contrarily, an equilibrium exists between C intake via photosynthesis and its decay in living plants. Therefore, natural 1 and other natural turmeric compounds contain measurable amounts of C. The use of HPLC or HPTLC in the assessment of turmeric extract quality usually infers the presence of synthetic curcumin(oids) by the absence of the natural congeners or other compounds typical for turmeric extracts, e.g., arturmerone. The frequently observed admixture of other constituents such as (multi) vitamins and other plant extracts (e.g. those containing 4, or 4 itself) can produce HPLC peak overlap and, thereby, challenge even validated QC methods and provide additional rationale for the need to consider orthogonal analytical methods, such as NMR. Regardless of the analytical challenges associated with the untargeted detection of adulteration, economic calculations clearly show the (misguided) incentive of chemical synthesis over the purification of these compounds from a natural source.