Curcumin, a natural bioactive compound derived from turmeric, has been recognized for its wide-ranging health benefits in scientific research for a long time. However, the poor gut absorption, rapid metabolism, and systemic elimination of curcumin significantly restrict its bioavailability. This challenge has driven researchers to explore more efficient alternatives — leading to growing interest in tetrahydrocurcumin (THC).

Tetrahydrocurcumin (THC), a major color-free metabolite of curcumin formed by reducing its central double bonds, displays better bioavailability and different biological activity and molecular mechanisms than curcumin.

Figure 1. Source of Tetrahydrocurcumin [2]

Biological Activities and Health Applications of Tetrahydrocurcumin (THC)

Protective Effects of THC in Neurodegenerative Diseases

THC has shown promising neuroprotective effects in models of Alzheimer’s disease, Parkinson’s disease, and ischemic brain injury. It reduces the toxic accumulation of amyloid-beta (Aβ) and alpha-synuclein (α-synuclein) proteins while alleviating neuroinflammation.

Emerging data also suggest THC may help stabilize mood and cognitive function by mitigating inflammation-driven neuronal damage, pointing to potential benefits in depression and cognitive decline related to neuroinflammation.

THC in Cardiovascular and Metabolic Diseases

THC also demonstrates protective effects in experimental models of cardiovascular and metabolic diseases. It can inhibit LDL oxidation and reduce atherosclerotic plaque formation, while its antithrombotic effect involves inhibition of the MAPK/PLA2 and PI3K/Akt pathways—key regulators of platelet activation.

In myocardial ischemia models, THC improves mitochondrial efficiency and prevents cardiomyocyte apoptosis, supporting overall heart health.

In metabolic disorders such as type 2 diabetes, THC improves glucose metabolism, lowers fasting blood glucose, and enhances insulin sensitivity by protecting pancreatic β-cells. In non-alcoholic fatty liver disease (NAFLD), THC supplementation reduces hepatic fat accumulation and improves lipid metabolism, potentially through modulation of gut microbiota composition.

Potential of THC in Cancer Prevention and Therapy

Extensive research supports THC’s anticancer potential across various tumor models, including lung, breast, prostate, colorectal, cervical, and brain cancers, as well as leukemia.

Key mechanisms include:

• ● Inhibiting tumor proliferation: THC interferes with cancer cell growth signaling and induces cell cycle arrest. In esophageal squamous carcinoma (TE-1) cells, THC combined with 5-fluorouracil significantly enhances antiproliferative activity.

• ● Inducing apoptosis: THC activates pro-apoptotic proteins (Bax, caspase-3) and suppresses anti-apoptotic Bcl-2, triggering programmed cancer cell death.

• ● Suppressing metastasis and angiogenesis: THC reduces tumor cell invasion and new blood vessel formation, partly by regulating matrix metalloproteinases.

• ● Multi-pathway synergy: It inhibits oncogenic pathways such as NF-κB, STAT3, and Wnt/β-catenin, while activating tumor suppressors like p53, enhancing the therapeutic effects of agents such as paclitaxel or docetaxel.

Combination studies highlight THC’s synergistic potential with standard chemotherapies—enhancing efficacy, overcoming drug resistance, and reducing required dosages.

THC in Other Chronic Conditions

Arthritis: THC reduces pro-inflammatory mediators (IL-1β, TNF-α) in cartilage and synovial tissues, protecting against joint degradation in osteoarthritis models.

Skin Health: THC inhibits tyrosinase, a key enzyme in melanin synthesis, providing a stable skin-brightening effect superior to traditional antioxidants like vitamin C. It also protects against UV-induced photoaging, preventing collagen breakdown and wrinkle formation. Furthermore, THC accelerates wound healing and minimizes scarring, making it an attractive ingredient in post-procedure repair creams and soothing skincare formulations.

Allergy and Inflammation: In allergic asthma models, THC reduces airway inflammation and hyperresponsiveness by lowering cytokine levels and oxidative stress. In vitro studies confirm that THC inhibits histamine release from mast cells, suggesting its potential as a natural anti-allergic compound.

Future Applications and Market Potential

1. Skincare and Cosmetics

THC’s colorless nature, antioxidant strength, and formulation stability make it an exceptional ingredient for skin-brightening, anti-aging, and sensitive-skin care products. It can also be combined with probiotics or plant extracts to develop innovative, multifunctional cosmetic formulations.

2. Nutritional Supplements

As a high-value nutraceutical, THC offers superior bioavailability and sustained systemic presence compared with curcumin. Its efficient absorption allows lower effective doses, reducing both material costs and potential gastrointestinal irritation. It is well suited for use in standalone antioxidant supplements or multi-ingredient formulas that support skin health and oxidative balance.

3. Drug Development

THC shows strong potential for combination drug therapies, particularly with chemotherapeutic, antidiabetic, or anti-inflammatory agents. By enhancing drug activity and mitigating side effects, THC could become a valuable component in next-generation treatment regimens.

Conclusion and Outlook

As the primary metabolite of curcumin, tetrahydrocurcumin combines the biological richness of its parent compound with substantial improvements in bioavailability, stability, and safety. Preclinical evidence supports its therapeutic potential across neurological, cardiometabolic, oncological, and dermatological domains.

With its robust pharmacokinetic profile and multi-target biological activity, THC offers a solid scientific foundation for the development of advanced nutraceuticals, functional foods, and pharmaceutical innovations. Ongoing and future clinical research will be crucial to fully realize its role in disease prevention and therapy — marking a new chapter in the application of turmeric-derived bioactives.

Hunan Huateng Pharmaceutical Co., Ltd. is a world-leading supplier of high-quality PEG derivatives and pharmaceutical intermediates, providing comprehensive support for the biopharmaceutical industry from R&D to commercial production. Backed by advanced technology platforms and GMP-compliant facilities, Huateng Pharma is capable of large-scale production of Tetrahydrocurcumin (THC) with consistent quality, high purity, and reliable global supply. To learn more or request samples, please visit us.huatengsci.com or contact us at sales@huatengusa.com  .

References:
[1] Zhou M, Li R, Hua H, Dai Y, Yin Z, Li L, Zeng J, Yang M, Zhao J, Tan R. The role of tetrahydrocurcumin in disease prevention and treatment. Food Funct. 2024 Jul 1;15(13):6798-6824. doi: 10.1039/d3fo05739a. PMID: 38836693
[2] Zeng, A., Quan, Y., Tao, H., Dai, Y., Song, L., & Zhao, J. (2025). The Role of Tetrahydrocurcumin in Tumor and Neurodegenerative Diseases Through Anti-Inflammatory Effects. International journal of molecular sciences, 26(8), 3561. https://doi.org/10.3390/ijms26083561