Turmeric has been used as a food ingredient for millennia, and, for almost as long, has been recognized for its medicinal properties, promising health benefits for a wide range of conditions, such as metabolic syndrome, arthritis, anxiety and high cholesterol (1).
Turmeric’s bioactive compound, called curcumin, is a polyphenol found in the root of the Curcuma longa plant, which has traditionally been used as a medicinal herb in Asian countries (2). It has gained interest in both the health and scientific community for the countless therapeutic benefits it has in a multitude of health conditions. It’s curcumin’s role as an anti-inflammatory, antioxidant compound that provides these wide variety of benefits (3) as wide-spread inflammation and oxidation are paramount in the development and progression of disease.
Here’s how curcumin may improve the outcomes of disease and act as a preventative strategy to maintain health…
A focus on curcumin’s health benefits and mechanisms of action
Some of the most common diseases, such as cardiovascular disease, metabolic diseases, neurological disease and cancer have been shown to result from dysregulation of an array of various signalling pathways within the body. In fact, with the advancement in the development of molecular assessment tools, we now understand that there are over 500 different genes involved in the signalling pathways that control any given disease. While multiple pharmaceutical drugs have been developed and released in the past decade as a means to ameliorate these diseases, it has been found that they have influence on only one or two of the signalling pathways involved in the progression of the disease (4).
Curcumin, in contrast, has been found to exert its effects by directly or indirectly influencing multiple signalling pathways, including individual molecules involved in these processes. These molecular processes include the production and release of inflammatory molecules, distribution of cell survival proteins, and the modulation of a number of other proteins involved in cellular signalling, including DNA and RNA itself. It’s the interaction and binding to the building blocks of proteins, called amino acids, that is most fascinating about the mechanism by which curcumin exerts its therapeutic effects.
Because of curcumin’s molecular structure and functionality, it is able to bind to a diverse number of proteins with high affinity and adapt the nature of its bonds depending on the protein and the effects it is to exert.
In terms of health and the mitigation of disease, these effects can be summarized as follows (5,6):
- Directly binds to inflammatory molecules, such as TNF-a, COX-1 and COX-2, AGP and MD-2, to suppress inflammation, which promotes an anti-inflammatory effect.
- Directly binds to general enzymes associated with gene signalling and regulation, oxidation and free radical production, programmed cell death, as well as having the ability to disrupt enzymes responsible for the binding sites for viruses, for example.
- Binds directly to a variety of proteins and protein-controlling enzymes called kinases. These proteins and their enzymes control signalling pathways involved in a wide variety of physiological processes, where their dysfunction have been implicated in anything from the formation of tumours to the development of Alzheimer’s disease.
What does science say about these effects?
The effects of curcumin were first scientifically observed in 1949, where it was found that it has potent antibacterial effects (7). For the last 30 years, research into this compound has intensified, particularly when it comes to the effects it has on healthy ageing.
Now, one question that continues to circulate with regards to the effects of curcumin is in its bioavailability. How much do we absorb?
The answer: not much. When it’s in its natural form, that is.
You see, one of the major problems with ingesting curcumin by itself is that it is poorly absorbed by the human digestive system. The compound is rapidly metabolised by the liver and is just as rapidly eliminated from the body. This has posed a problem for many human trials, as the effects just aren’t able to be replicated using pure curcumin, like it is possible to do in many animal models.
Over the years, however, there have been several compounds tested to increase the bioavailability of curcumin to improve its therapeutic benefits. One of those compounds is the active ingredient in black pepper, called piperine. Studies show that it may increase the bioavailability of curcumin 2000%, which offers a resolution to the limitations on single ingredient curcumin supplements, and promotes a curcumin complex for enhanced absorption and activity (8).
With the ageing population growing so rapidly – particularly the diseased ageing population – there is a great need to find ways to live our lives out with our health intact, so that we may be able to enjoy the qualities that life has to offer.
Here are the most recent studies on the effects that curcumin may have on these goals.
In addition to its anti-inflammatory and antioxidant effects, curcumin has been well-researched in its ability to exert anti-apoptotic and antiproliferative effects. In this way, curcumin may be able to modulate tumour expression (9).
In a study conducted on breast cancer cells, researchers found curcumin to inhibit the specific proinflammatory compounds CXCL1 and CXCL2, which decreases the formation of breast cancer metastases. While CXCL1 and CXCL2 are expressed in very few types of breast cancer, it’s an important function of curcumin, as it’s the expression of these two inflammatory compounds that is found to increase the risk of aggressive types of breast cancer. Additionally, the study found that through regulation of specific parts of RNA, including miR181b, curcumin modulates metastatic breast cancer cells. It’s this downregulation that has a significant effect on CXCL1 and -2 (10).
Research has also been conducted into curcumin’s effects on other types of cancer, such as melanoma and glioblastoma.
Melanoma is not recognised as one of the most deadly forms of skin cancer. It is associated with very aggressive tumors that are difficult to treat. Presently, nearly 50% of patients do not respond well to treatment, which results in metastasis of the cancer (11).
Curcumin has so far shown promising results in the treatment of melanoma when used in skin cell lines. Curcumin appears to act on the inflammatory NF-kB pathway, which reduces proliferation of tumor cells and has been shown to increase programmed cell suicide (12). These results have been replicated in animal models of melanoma.
Glioblastoma is another highly invasive type of cancer that invades the central nervous system. Currently, there are limited available treatments, which is why alternative therapies have been studied. Curcumin is one of them. When researchers combined the use of nimustine hydrochloride, the pharmaceutical treatment currently being used to treat many patients with glioblastoma, and added curcmin to the regime, they found that the combination of the two resulted in significant inhibition of cell proliferation, colony formation, migration of cancerous cells, and reduced invasion of other tissues. Additionally, the combination of curcumin and the drug increased cancer cell suicide, which shows that the synergystic effect of these two therapies promoted far greater antitumour effects than either therapy on its own (13).
When it comes to colorectal cancer, which is one of the most common forms of cancer affecting our modern society, curcumin shows huge benefits. In one trial, which explored the effect of cucumin on malignancies and tumor markers, curcumin extracts, administered at doses ranging between 44o and 2,200mg a day, showed positive decreases in these markers in all participants (14). Multiple other studies in humans have reproduced these results.
In a later study, the use of either 2 or 4g of curcumin per day was assessed in its effects against aberrant crypt foci, which are known to cause polyps. These ACF are one of the first signs of colorectal cancer. Results from the study showed a 40% reduction in the ACF in those participants in the higher dose group; those taking only 2g of curcumin a day showed no difference in their ACF number (15).
Curcumin has also shown therapeutic benefit in other digestive tract disorders.
Inflammatory disorders of the digestive tract
One of the most common areas of the body known to be influenced by inflammatory conditions is the gut. Curcumin, which is well-known for its anti-inflammatory effects, has been studied in its effects against indigestion, flatulence, diarrhea, and gastric and duodenal ulcers. While studies in humans and these effects of curcumin have provided limited evidence due to small participant numbers in clinical trials, the outlook on its therapeutic benefits in inflammatory digestive disorders is promising.
As we know, curcumin is not a well absorbed compound. Its poor bioavailability has been one of the major restricting factors leading to poor study results, even when it comes to the effects it has on the digestive system itself, which is where it is absorbed.
Progress, however, has been made in terms of increasing the absorption rate of curcumin by adding other highly absorptive compounds to its formulation. We’ve mentioned piperine above, which has a significant effect on the availability of the ccurcumin compounds in the body. The trouble is, many people have been found to have low tolerance to piperine, particularly when they suffer from inflammatory bowel conditions. This makes a curcumin piperine combination difficult to use in treating bowel diseases.
Fortunately, this has led to even further investigation into how to make curcumin pass through into the bloodstream. Adding lecithin, a fatty substance, for example, has been shown to increase absorption by 29 times with greater tolerance than piperine.
With these advances, we have a far higher opportunity to use curcumin and its therapeutic benefits at much lower doses than would have been thought and which are well-tolerated by those with digestive disorders.
One of the most common forms of digestive diseases is inflammatory bowel disease, or IBD. Most of the time, there is no specific cause that can be found to result in the wide diversity of symptoms that are associated with the condition. It has, however, been confirmed that immune reactions as the subsequent release of inflammatory cytokines play a pivotal role in the severity of the disease. With curcumin acting on both the NF-kB inflammatory pathway and the release of other inflammatory chemicals, it offers a novel therapeutic agent for IBD (16).
One of the first studies in humans, while a small pilot study, showed positive responses when patients who suffered from Crohn’s disease (CD) and ulcerative colitis (UD) used curcumin. In addition to their regular medication, patients with UC were given 550mg curcumin twice daily for the first month and three times daily for the second month. Those with CD were given 360mg three times a day for the first month and then four times daily for another two months.
Results indicated that all of the patients in both groups self-reported significant improvements in their symptoms. Many of them were even able to lower their dose of their medication (17).
Another trial in UC patients evaluated the effects of 1,000mg of curcumin taken once at breakfast and once at dinner for six months, compared to a placebo for the same amount of time. Both groups continued to take their pharmaceutical medication as advised. The results showed a significant difference in symptoms between the treatment and placebo group improving both clinical scores and endoscopic scores, which are used as a measure of morbidity in UC (18). It is important to note that even in these high daily doses administered long-term, patients tolerated the curcumin well.
Liver health and protection
Non-alcoholic fatty liver disease (NAFLD) is an emerging disease that is associated with an accumulation of fats within and around the liver, most commonly as a result of high sugar, high fat diets. There is a limited course of treatment for the disease; along with vitamin E and anti-diabetic drugs, change in eating habits and increased physical activity are some of the only ways to reduce the consequences it has on the liver.
Curcumin, however, has been proposed as acting on the liver in four ways: as a biliary system regulator, decreasing the risk of fibrous tissue development, protecting the liver cells themselves and acting as an antioxidant.
In experimental studies, curcumin acts as a choleretic-cholagogue, which means it acts on the gallbladder and biliary system to produce and release bile acids. In fact, curcumin may increase bile production by around 62%. Along with ensuring the right composition of bile, curcumin also protects against gallbladder stones.
A common trait of NAFLD (an cirrhosis) is the formation of fibrous tissue within the liver. Fibrosis significantly hampers the liver’s ability to function. The process is under regulation by tissue growth factor TGF-B. Through regulation of NF-kB, curcumin targets TGF-B to protect from fibrosis (a process also involved in the development of kidney fibrosis). Curcumin also acts on the metalloproteinases, which give rise to the changes in the cellular structure of the liver cells. Suppressing their action, further protects from fibrosis development (19).
In a study conducted in participants with NAFLD, of which another typical trait is the enhanced levels of free radicals and oxidation of fatty acids, researchers concluded that no change in baseline oxidation levels was seen with the administration of 500mg of curcumin and 5mg piperine daily, for 8 weeks. The authors acknowledged that the dose may have been too low to produce an effect (20).
This is a significant conclusion, as there is evidence to suggest that high dose curcumin is not only effective, it has been shown to be safe for long term use.
This may be the reason another study, performed for a longer duration of 12 weeks with the same parameters of a daily dose of 500mg curcumin and 5mg piperine on the effects on NAFLD showed significant improvement in disease severity. In addition, multiple disease markers, including those associated with liver damage, were significantly improved when compared to participants taking a placebo for the same duration (21).
There is also mounting evidence to suggest that curcumin may protect the liver against the toxic effects of paracetamol and infections due to its potent antioxidant effects. It has already been shown that vitamin E is a powerful therapeutic agent in the treatment of liver disease, which is due to vitamin E’s free radical scavenging ability. Curcumin, however, has been suggested to be more than 10 times more potent in this regard than vitamin E (22).
Improving outcomes of heart disease
Using a mouse model, the effects of curcumin were studied on a common age-related disease, called atherosclerosis. Due to inflammation and oxidation, cholesterol plaques begin accumulating on the inside of the arterial walls, which may result in complete occlusion of the vessel as the disease progresses, typically resulting in heart attack or stroke. Curcumin-treated mice showed inhibition of formation of these cholesterol plaques, without influence on cholesterol levels themselves (23).
Newer research suggests this golden spice is key in treating cardiovascular disease. In a clinical trial in those with type 2 diabetes, a 12-week intervention with curcumin supplementation versus a placebo reduced the risk of developing acute heart events even when the diabetes was associated with irregular cholesterol levels (24). Further clinical trials have offered further support for its lipid lowering effects, its blood pressure modulatory benefits and even exercise induced ventricular load (25).
Living longer, living healthier
One of the most promising areas of research coming out of research conducted on curcumin’s therapeutic benefit is its role in longevity and aging.
Using various animals as a model of the pathways affected by curcumin, researchers have found great potential in curcumin and its role in delaying the effects of ageing.
A type of worm called Caenorhabditis elegans offers a great model to study genetic changes that may reflect what happens in humans. Having a very short lifespan in nature, it is also of great interest to see the effects of a potential longevity-boosting compound in C. elegans. In one study, when researchers investigated the effects of curcumin, they found there was an increase in their lifespan with particular impact attributed to its antioxidant properties where curcumin delayed the accumulation of age-related reactive oxygen species, which you’ll know as free radicals (26).
Despite bacteria having a serious influence on the lifespan of this species, and curcumin being found to have antibacterial properties, there was no influence of curcumin on this aspect of longevity found to be of relevance in this study.
Stress resistance was another area investigated in the activity of curcumin in promoting longevity in the worms in this study. Curcumin-treated insects showed increased resistance to both oxidative and heat stress, which contributed to their increased survival rate.
The common fruit fly, Drosophila melanogaster, is another animal model frequently used to study mechanisms and pathways of compounds that may be translated into mammals. Curcumin shows positive effects on life- and healthspan in two different D. melanogaster species, where curcumin offered overall benefits to the health of the flies, which included their ability to perform activities, resist carcinogenic (cancer-causing) chemicals, resist oxidative stress, and upregulate anti-ageing genes (27). Another study in this species offers the comments that curcumin slows the ageing rate such that it is comparable to that at which genetically selected long-lived animals age (28).
Human trials show similar results.
When administered to otherwise healthy middle-aged people, even at low doses, researchers found that a bioavailable form of curcumin produced statistically significant changes in various markers of ageing, including the promotion of free radical scavenging enzymes (29).
From the research above, it is clear that the beneficial effects of curcumin depends largely on a range of factors including the dose, time of treatment, bioavailability of the compound, and the mechanisms of the disease.
Human trials on the effectiveness of curcumin in humans and age-related disease (as well as other conditions of inflammation and oxidation) are ongoing. We believe strongly in continued evaluation of this content to provide you with a trusted source of information. We do, however, also believe that those who have used curcumin for its health benefits for thousands of years were definitely onto something…
Selection of studies used for this article:
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- Hewlings, S., & Kalman, D. Curcumin: A Review of Its Effects on Human Health. Foods. 2017 Oct; 6(10): 92.
- Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009 Jan; 41(1):40-59.
- Mencher SK, Wang LG. Promiscuous drugs compared to selective drugs (promiscuity can be a virtue). BMC Clin Pharmacol. 2005 Apr 26; 5():3.
- Gupta, S., et al. Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep. 2011 Nov; 28(12): 1937–1955.
- Pulido-Moran M, Moreno-Fernandez J, Ramirez-Tortosa C, Ramirez-Tortosa M. Curcumin and Health. Molecules. 2016 Feb 25; 21(3):264.
- SCHRAUFSTATTER E, BERNT H. Antibacterial action of curcumin and related compounds. Nature. 1949 Sep 10; 164(4167):456.
- Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998 May; 64(4):353-6.
- Kronski, E. et al. miR181b is induced by the chemopreventive polyphenol curcumin and inhibits breast cancer metastasis via down-regulation of the inflammatory cytokines CXCL1 and -2. Mol. Oncol. 2014, 8, 581–595.
- Bachmeier B, et al. The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice. Cell Physiol Biochem. 2007, 19: 137-152.
- Kesmodel SB, Spitz FR. Gene therapy for cancer and metastatic disease. Expert Rev Mol Med. 2003, 5: 1-18.
- Marin YE, et al. Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells. Melanoma Res. 2007, 17: 274-283.
- Zhao, J., et al. Curcumin potentiates the potent antitumor activity of ACNU against glioblastoma by suppressing the PI3K/AKT and NF-κB/COX-2 signaling pathways. Onco Targets Ther. 2017; 10: 5471–5482.
- Sharma R., et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res. 2004 Oct 15; 10(20):6847-54.
- Carroll R., et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila). 2011 Mar; 4(3):354-64.
- Hilsden R., et al. Use of complementary and alternative medicine by patients with inflammatory bowel disease. Inflamm Bowel Dis. 2011 Feb; 17(2):655-62.
- Holt P., et al. Curcumin therapy in inflammatory bowel disease: a pilot study. Dig Dis Sci. 2005 Nov; 50(11):2191-3.
- Hanai H., et al. Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol. 2006 Dec; 4(12):1502-6.
- Gaedeke J., et al. Curcumin blocks fibrosis in anti-Thy 1 glomerulonephritis through up-regulation of heme oxygenase 1. Kidney Int. 2005 Nov; 68(5):2042-9.
- Mirhafez S., et al. The effect of curcumin with piperine supplementation on pro-oxidant and antioxidant balance in patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial. Drug Metab Pers Ther. 2019;34(2)
- Panahi Y, Valizadegan G, Ahamdi N, Ganjali S, Majeed M, Sahebkar A. Curcuminoids plus piperine improve nonalcoholic fatty liver disease: A clinical trial. J Cell Biochem. 2019;120(9):15989‐15996.
- Motterlini R., et al. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic Biol Med. 2000 Apr 15; 28(8):1303-12.
- Olszanecki, R., et al. Effect of curcumin on atherosclerosis in apoE/LDLR-double knockout mice. J Physiol Pharmacol. 2005 Dec;56(4):627-35.
- Panahi, Y., et al. 2017. Curcuminoids modify lipid profile in type 2 diabetes mellitus: A randomized controlled trial. Complementary therapies in medicine 33, 1-5.
- Li, H., et al. (2019). Curcumin, the golden spice in treating cardiovascular diseases. Biotechnology Advances.
- Liao, V., et al. Curcumin-mediated lifespan extension in Caenorhabditis elegans. Mech Ageing Dev. 2011 Oct;132(10):480-7.
- Lee KS, Lee BS, Semnani S, Avanesian A, Um CY, Jeon HJ, Seong KM, Yu K, Min KJ, Jafari M. Curcumin extends life span, improves health span, and modulates the expression of age-associated aging genes in Drosophila melanogaster. Rejuvenation Res. 2010 Oct; 13(5):561-70.
- Soh JW, Marowsky N, Nichols TJ, Rahman AM, Miah T, Sarao P, Khasawneh R, Unnikrishnan A, Heydari AR, Silver RB, Arking R. Curcumin is an early-acting stage-specific inducer of extended functional longevity in Drosophila. Exp Gerontol. 2013 Feb; 48(2):229-39.
- DiSilvestro, R., et al. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J. 2012 Sep 26;11:79.