Curcumin

What Is It?

Curcumin is an orange-yellow powder found in the root of turmeric, a type of ginger plant that grows in South Asia. Turmeric containing curcumin is most widely used in Indian curries, however it is also added to some Japanese teas and Korean drinks$^{1}$. While curcumin is a traditional medicine in many Asian cultures due to its anti-inflammatory and antimicrobial properties, it has more recently been studied for its anticancer activity$^{1}$. Curcumin’s potential to prevent and treat cancer arises from its ability to block the formation of harmful free radicals, as well as induce apoptosis (programmed cell death) in abnormal cells$^{2}$.

What Are Its Other Names?

Curcumin is also known as diferuloylmethane$^{3}$, Natural Yellow 3$^{4}$, and Turmeric Yellow$^{4}$. The IUPAC name for curcumin is (1E,6E)-1,7-bis (4-hydroxy- 3-methoxyphenyl) -1,6- heptadiene-3,5-dione$^{3}$. Turmeric, the source of curcumin, is also known as Haldi, Curcuma, Huang jiang, Yellow Root, and Kurkum$^{5}$.

What Foods Have It?

*It is important to note that curcumin content varies in many products depending on the manufacturer. Turmeric powder can be added to meat and vegetable curries, lentils, soups, milks, teas, and rice. However, the amount of curcumin in these foods varies significantly with the amount and type of turmeric that is used.

What Are Its Main Benefits?

Improvement of Precancerous Conditions

Curcumin has been shown to cause improvements in precancerous conditions, such as oral leukoplakia (a white lesion inside the mouth), submucous fibrosis (scarring of oral submucosal tissue), and lichen-planus (purple, itchy flat bumps that may occur on the skin, hair, nails, mouth, or genitals)$^{8-10}$.  While these abnormal growths are benign, they may progress to become cancerous tumors$^{2}$. However, curcumin has demonstrated promise in reducing the pain and size of these growths either by increasing antioxidant activity, or by inducing apoptosis in abnormal cells$^{2}$.

Benefits for Cancer Treatment

Curcumin can also benefit patients who have already been diagnosed with cancer. One study found that curcumin increased the rate of cancer cell apoptosis in colorectal cancer patients and improved their general health$^{11}$. Another study concluded that curcumin supplementation helped sensitize cervical cancer cells to radiotherapy, potentially leading to more effective treatment of these patients$^{12}$. 

Benefits for the Side-Effects of Cancer Treatment

Clinical trials have shown that curcumin can ameliorate symptoms of oral mucositis (a side effect of some chemotherapies and radiotherapies), and delay the onset of radiation-induced oral mucositis$^{13,14}$. As well, curcumin can potentially reduce the severity of radiation dermatitis in breast cancer patients undergoing radiotherapy$^{15}$.

Benefits for Inflammatory Conditions

Finally, curcumin possesses anti-inflammatory properties through a variety of cell signaling pathways. This suggests curcumin could aid in the treatment of diseases where chronic inflammation is an underlying problem, such as cardiovascular disease, neurological disorders, rheumatoid arthritis, and gastrointestinal disease$^{16,17}$.

It is essential to note that all of the above claimed benefits stem from preclinical and/or clinical studies, and there are currently no curcumin-based drugs approved by the FDA$^{18}$. A further benefit of curcumin is that it is not toxic at high doses of up to 8,000 mg daily, indicating a wide therapeutic range$^{19}$.

What Are Its Main Drawbacks?

The main drawback of curcumin is its low bioavailability in humans, meaning that after oral administration of curcumin, a very limited amount of the original dosage ever reaches its intended targets$^{20}$. Curcumin’s low bioavailability is due to its poor intestinal absorption, rapid metabolism in the liver, and elimination via the gallbladder$^{21}$. While curcumin has shown cytotoxicity and genotoxicity in cell cultures, this is at concentrations that are unattainable in humans, and curcumin has a wide range of safe doses$^{22}$.

Preclinical/Potential Drawbacks

Another potential drawback of curcumin is that its effects may vary at different concentrations. In essence, while at low concentrations curcumin may act as an antioxidant, at high concentrations it may have pro-oxidant effects. This could have implications on how curcumin interacts with chemotherapy drugs$^{23}$.

It has been suggested that as an antioxidant, curcumin can potentially reduce levels of reactive oxygen species (ROS), which are molecules that can cause cancer if allowed to accumulate$^{23}$. Thus, curcumin’s antioxidant properties may be valuable as a chemopreventative (cancer preventing) agent$^{23}$. However, some chemotherapy drugs and radiation therapies work by increasing the ROS levels in cancer cells to a point at which they die$^{23}$. If curcumin is reducing ROS levels in these cells at the same time these therapies are being used, it may potentially reduce the effectiveness of some chemotherapies and/or radiation therapies$^{23}$. It is essential to note that these findings have only been made in preclinical cell line and animal studies (such as in mice with human breast cancer cells transplanted onto them$^{24}$), and these effects have not been demonstrated in humans. On the other hand, human studies have shown the potential for curcumin to reduce the side effects of chemotherapies, as well as potentially speed up apoptosis in cancer cells$^{11,13-15}$. Another human study demonstrated that curcumin may possibly sensitize cervical cancer cells to radiotherapy, potentially making the treatment more successful$^{12}$.

Curcumin has also been hypothesized to enhance the effectiveness of chemotherapy and/or radiotherapy due to its possible pro-oxidant properties$^{23}$. Curcumin at high concentrations can increase the ROS levels in cells and exhibit chemotherapeutic effects by helping induce apoptosis$^{23}$. Overall, this highlights the importance of consulting your doctor to determine what dosage of curcumin is beneficial for your needs while undergoing chemotherapy and/or radiotherapy.

How Does It Work?

Curcumin has been shown to exert its anti-cancer effects through the following mechanisms: blocking free radical formation to protect cells from damage$^{2}$, inducing apoptosis in abnormal cells$^{2,25,26}$, and increasing the expression of proteins controlling the cell cycle and cell death$^{11}$.

What Are Its Mechanisms of Action?

1. Blocking Free Radical Formation: Curcumin increases the local and systemic levels of antioxidants, particularly Vitamins C and E, which are responsible for neutralizing harmful free radicals$^{2}$. Free radicals are unstable molecules that are a normal byproduct of cellular processes$^{27}$. However, if allowed to accumulate, free radicals can cause both DNA damage and lipid peroxidation (a type of lipid degradation), which could lead to cancer$^{17}$. Thus, by increasing antioxidant levels to limit quantities of free radicals, curcumin could play an important role in cancer prevention$^{2}$. One study found that curcumin administration was associated with an increase in levels of Vitamins C and E in patients with oral leukoplakia, submucosal fibrosis, and lichen-planus$^{2}$. This increase in antioxidants was accompanied by a decrease in markers of DNA damage and lipid peroxidation, as well as a decrease in the size of these precancerous lesions$^{2}$.
2. Induction of Apoptosis: Conversely, curcumin also has pro-oxidant effects where it can induce apoptosis (programmed cell death) in abnormal cells$^{2}$. Although the exact mechanism by which this occurs remains unclear, it is suggested that curcumin activates enzymes in a cell’s mitochondria that produce reactive oxygen species (ROS), which are a subset of free radicals that can cause damage within cells$^{2,25,26}$.
3. Increased p53 Expression: Clinical trials in humans have found that curcumin increases the expression of the p53 protein in colorectal cancer cells$^{11}$. Since p53 is essential in modulating the cell cycle and cell death, increasing its levels led to a faster rate of tumor cell death and improved quality of life in patients supplemented with curcumin$^{11}$. It is important to note that this is just one of many clinical trials of curcumin in colorectal cancer patients, and others have found no change in quality of life following curcumin supplementation.

Preclinical/Potential Mechanisms of Action Curcumin has also demonstrated a variety of anti-cancer properties in cell line studies that have yet to be confirmed in humans. For instance, cell line data has shown that curcumin can inhibit tumor invasion as well as suppress angiogenesis (the recruitment of blood vessels to help a tumor grow)$^{28}$. Also, curcumin exhibits broad anticancer effects by suppressing the function of NFκB$^{29,30}$. NFκB is a pro-inflammatory transcription factor that is implicated in cancer growth as it blocks apoptosis, induces cell proliferation, and promotes angiogenesis$^{29,30}$. Similarly, curcumin also inhibits the activity of Activation Protein 1, a transcription factor that is associated with genes that block apoptosis, stimulate mitosis (cell division) and angiogenesis, all of which can lead to tumor growth$^{29,31}$.

What Are Typical Doses and Durations?

Dosage Clinical studies examining curcumin’s anticancer effects have utilized dosages ranging from 180 mg/day$^{32,33}$ to 15,000 mg/day$^{34}$. It is crucial to note that curcumin is only considered tolerable at doses up to 8,000 mg/day, and that the very few select studies which exceeded this threshold did so under controlled conditions$^{19}$. Due to the potential applications of curcumin for a variety of cancers and cancer side effects, there is a wide range of doses used in studies, with the majority using between approximately 500 to 6,000 mg/day of curcumin$^{15,35-37}$. This was typically administered as multiple capsules taken at regular intervals throughout a day. Due to the nature of some conditions being investigated, a few studies have used specially prepared curcumin mouthwashes or curcumin ointments which can have very different curcumin concentrations than what is taken orally$^{14,38}$. Studies utilizing nanomicelle curcumin capsules used much lower doses that were between 80 to 160 mg/day$^{39,40}$. Duration Most clinical studies examine the effects of curcumin usage for 3 weeks to 6 months$^{37,38,41,42}$. However, there have been longer studies up to 12 months long$^{43}$, as well as shorter ones that involve just one course of curcumin over the span of a few hours$^{44}$. Some studies operate on a basis where curcumin is administered for the entire duration of a patient’s chemotherapy/radiotherapy$^{15}$. It is important to note that these findings are based on preliminary data, and there is no conclusive evidence as to the beneficial effects of curcumin. You should always consult your healthcare provider before starting any new dietary regimen to determine whether it is suitable for your needs.

Summary of Data

Curcumin for Cancer A total of 30 human clinical studies or randomized controlled trials were identified from PubMed that investigated curcumin as a means of preventing or treating cancer. A summary of the results for each cancer type is as follows:

Curcumin for the Side Effects of Cancer Treatment A further 10 human clinical studies or randomized control trials were identified from PubMed that considered curcumin as a means of ameliorating various side effects of cancer treatments. A summary of the results for each type of side effect is as follows:

📄 Detailed Curcumin human clinical trial study notes analyzed by Anticancer.ca

References

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25. Uddin S, Hussain AR, Manogaran PS, Al-Hussein K, Platanias LC, Gutierrez MI, et al. Curcumin suppresses growth and induces apoptosis in primary effusion lymphoma. Oncogene. 2005;24:7022–30.
26. Atsumi T, Fujisawa S, Tonosaki K. Relationship between intracellular ROS production and membrane mobility in curcumin- and tetrahydrocurcumin-treated human gingival fibroblasts and human submandibular gland carcinoma cells. Oral Diseases. 2005;11:236–42.
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35. Panahi Y, Saberi-Karimian M, Valizadeh O, Behnam B, Saadat A, Jamialahmadi T, et al. Effects of curcuminoids on systemic inflammation and quality of life in patients with colorectal cancer undergoing chemotherapy: A randomized controlled trial. Natural Products and Human Diseases. 2021;1–9.
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• Curcumin
• What Is It?
• What Are Its Other Names?
• What Foods Have It?
• What Are Its Main Benefits?
• What Are Its Main Drawbacks?
• How Does It Work?
• What Are Its Mechanisms of Action?
• What Are Typical Doses and Durations?
• Summary of Data
• References
• About This Article
• Disclaimer