Curcumin – An Ancient Remedy

Natural plant products have been used throughout the history of mankind for a variety of different purposes. Many of these plants have evolved alongside us and are billions of years old.

Around 61% of the drugs introduced worldwide between 1981 and 2002 can trace back their origins to natural products. This is hardly a surprising statistic considering that around 80% of individuals in developing countries rely entirely on natural products for their healthcare.

In today’s article we are going to look at one of these natural products, curcumin, an active component of the perennial herb Turmeric (also known as Curcuma longa), a member of the Zingiberaceae family.

Traditional use of Curcumin

Curcumin was first isolated in 1815 and was sourced in a crystalline form in 1870 – it is frequently used as a spice and provides curry with its distinctive yellow colour. It is also commonly used as a colouring agent in cheese and butter.

In Ayurvedic medicine, the Indian system of holistic medicine, it has been traditionally used for various respiratory conditions as well as liver disorders, anorexia, rheumatism and diabetic wounds. In traditional Chinese medicine it is used to treat diseases associated with abdominal pain. In ancient Hindu medicine it was used to treat sprains and swelling. Throughout the Orient it has traditionally been used as an anti-inflammatory and many of its therapeutic effects are being researched and confirmed by modern scientific research.

Topically, turmeric is used for analgesia, ringworm, bruising, eye infections, inflammatory skin conditions, inflammation of the oral mucosa and infected wounds.

Benefits of Curcumin

Curcumin has antimicrobial, antioxidant, anti-inflammatory and liver detoxification properties.  Goel et al (2008) list over 90 molecular targets for curcumin including gene transcription factors, inflammatory cytokines, enzymes, growth factors, receptors and others.

Antimicrobial properties – Several studies have reported broad-spectrum antimicrobial activity for curcumin including antibacterial, antiviral and antifungal activities.

Antioxidant properties: Oxidative stress is an imbalance between the production of free radicals (eg reactive oxidative species and reactive nitrogen species) and antioxidant defences. Free radicals are atoms or molecules with one or more unpaired electrons. They can be endogenous or exogenous and are highly reactive causing damage to lipids, proteins and DNA. Persistent oxidative stress can lead to chronic inflammation. Antioxidants are molecules that in low concentrations can prevent or delay oxidation reactions. They scavenge free radicals by donating electrons, thus reducing their reactivity. Curcumin’s antioxidant properties include increasing levels of some of the body’s own antioxidant systems – glutathione, catalase and superoxide dismutase.

Anti-Inflammatory properties: Acute and chronic inflammation is a major factor in the progression of many diseases including obesity, type II diabetes, arthritis, pancreatitis, cardiovascular and neurodegenerative diseases, as well as some types of cancer.

The process of inflammation begins with an environmental trigger leading to the activation of the Nuclear Factor kappa B (NFkB) pathway, which is the major initiator for the amplification of the inflammatory process. NFK-kB is a nuclear transcription factor that promotes the activation of genes that encode for inflammatory mediators and enzymes. It increases the production of direct mediators of inflammation such as cytokines, prostaglandins, leukotrienes, nitric oxides and reactive oxidative species (ROS). NFk-B is kept in an inactive state in the cytoplasm of cells by Inhibitor kappa B (IkB). When triggered by inflammatory triggers IkB is destroyed and this allows NFk-B to move into the nucleus of the cell, where it binds with DNA and activates genes encoding inflammatory responses. These genes then produce their inflammatory products including IL-6, TNF-α, iNOS and COX-2:

• IL-6 stimulates the production of C-reactive protein (CRP), a serum marker of inflammation which is associated with increased risk of cardiovascular disease
• TNF-α stimulates the production of inflammatory cytokines
• iNOS increases production of the free radical nitric oxide
• COX-2 is responsible for converting arachidonic acid to prostaglandins which recruit leukocytes to the area of inflammation.

These mediators of inflammation cause tissue damage and contribute to the development of many inflammatory disorders.

It is now widely documented that curcumin has the ability to inhibit inflammation through multiple molecular targets and mechanisms of action, including by preventing the initiation of inflammation via the NFk-B pathway.

He et al (2015) state “Curcumin has been demonstrated to have therapeutic potential for various chronic inflammatory diseases especially due to its anti-inflammatory and anti-oxidative properties against a vast array of molecular targets”.

Liver detoxification: One of the functions of the liver is detoxification of toxins and hormones. The detoxification process is undertaken by two sequential steps referred to as Phase I and Phase II. Within each of these steps are multiple enzymes and pathways to deal with different substances. Phase I enzyme systems (P450 enzymes) generally convert fat soluble toxins and hormones to a more water soluble form. They use oxidation, reduction or hydrolysis reactions to form a reactive site on the toxic molecule. The products from Phase I are often highly reactive and so more dangerous than their precursors. It is important they quickly enter Phase II where another compound is ‘conjugated’ to the reactive site, enabling the toxin to be safely excreted either via the bile or urine. Ideally Phase I and Phase II systems work in balance.

Sometimes the Phase I / Phase II systems are out of balance. For example, if Phase I is upregulated it may produce toxic intermediate metabolites at a level that exceeds Phase II capacity. Curcumin has been shown to downregulate Phase I and upregulate Phase II, thus supporting balance between these two systems.

Clinical trials

In vitro and in vivo studies indicate curcumin may be a therapeutic agent in many chronic diseases such as autoimmune, cardiovascular, inflammatory bowel, neurological and psychological diseases. There is also interest in the use of curcumin in cancer prevention and alongside chemotherapy. A search on PubMed for curcumin gives over 8000 search results – much of this research is in vitro or using animal models to demonstrate mechanisms and pathways. However, the US website www.clinicaltrials.gov lists 124 clinical trials using curcumin; of which 51 are still underway. Success in some of the reported clinical trials to-date has been limited due to issues with bioavailability and absorption when administered as an extract (see Bioavailability and Absorption below).

Rheumatoid arthritis:  A clinical trial compared the effects of curcumin with a well known anti-rheumatic drug, phenylbutazone. The 18 patients in the trial received a daily dose of either curcumin or phenylbutazone for 2 weeks. Curcumin was well tolerated, had no side effects, and exerted an anti-rheumatic activity comparable to that of phenylbutazone (Satoskar et al 1986).

In another study of 45 patients, curcumin (500 mg) and diclofenac sodium (50 mg) were administered alone or together to 3 groups of patients with RA. The curcumin group showed the highest percentage of improvement in Disease Activity Score (DAS) and American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joints and these scores were significantly better than the patients in the diclofenac sodium group (Chandran & Goel 2012).

Osteoarthritis: In a clinical trial by Henrotin et al (2014) with 22 patients, curcumin significantly reduced cartilage matrix degradation markers, reduced CRP, and there was an improvement in the ‘global assessment of disease activity’ in the patients.

In a larger trial of 367 patients, curcumin was as effective as ibuprofen in relieving pain and stiffness and improving function after 4 weeks of treatment (Kuptniratsaikaul et al 2014).

Inflammatory bowel disease: Hanai et al (2006) investigated curcumin in patients with quiescent ulcerative colitis. The trial involved 89 patients and concluded that curcumin “seems to be a promising and safe medication for maintaining remission in patients with quiescent UC”.

In another study of 5 patients with Crohn’s and 5 with Ulcerative proctitis, all the proctitis patients improved and four reduced their medication. Of the Crohn’s disease patients, four of five had lowered Crohn’s Disease Activity Index scores (Holt et al 2005).

Cardiovascular disease: An 8 week trial with 32 postmenopausal women compared the effectiveness of curcumin and exercise in improving vascular function. The researchers concluded “Curcumin is as effective in improving vascular function in postmenopausal women as a moderate aerobic exercise training programme” (Akazawa et al 2012).

Cancer: A number of mechanisms whereby curcumin may prevent the initiation and development of cancer have been demonstrated in vitro and in animal models. Clinical trials are looking at using curcumin alongside conventional treatment eg to reduce some of the side effects of chemotherapy and radiotherapy. There is also interest in whether curcumin may  inhibit the rate of progression of certain cancers. This is an exciting area of research to watch in the future.

Bioavailability and Absorption

Many studies have shown that curcumin is safe even at high doses. However it is also considered to have a low systemic bioavailability and this has made clinical trials difficult to date. This is due to its low aqueous solubility and extensive hepatic and intestinal metabolism. Curcumin undergoes extensive Phase I and Phase II hepatic metabolism. When metabolized in the liver, the major metabolic products of curcumin are glucuronides of Tetrahydrocurcumin (THC) and Hexahydrocurcumin (HHC), which are less active than curcumin itself. Thus, to improve the oral bioavailability of curcumin, both low solubility and high metabolic clearance must be overcome.

When curcumin is co-administered with piperine, which increases intestinal absorption and reduces enterohepatic metabolism, bioavailability is increased; in one study serum levels of curcumin increased by 2000% (Shoba et al 1998).

When turmeric/curcumin is heated gently and dissolved in oil (as in traditional Indian cooking) it bypasses intestinal enzymes and can be directly absorbed into chylomicrons and then the lymphatic system, thus bypassing the liver. So other delivery platforms are also being investigated and used eg liposomal or phospholipid formulations to improve absorption.

Conclusion

Curcumin is believed to have over 90 molecular targets and many mechanisms of its action are understood thanks to in vitro and animal models. Clinical trials were initially hampered by its low bioavailability. This has now been improved by concomitantly administering curcumin with piperine or liposomal formulations. It is an exciting area of research to watch.

Cautionary Note:

Because of its effects on liver detoxification pathways, curcumin has the potential to alter the metabolism of some prescription medications. Therefore we recommend drug-nutrient interactions are checked if taking prescription medications. In addition we recommend patients with cancer consult with their oncologist about any proposed supplements. Some studies have shown curcumin interfering with the absorption and efficacy of certain chemotherapy drugs.

References:
Available on request.

If you have any questions regarding the health topics that have been raised, or any other health matters please do contact me (Clare) by phone or email at any time.

clare@cytoplan.co.uk, 01684 310099

Amanda Williams and the Cytoplan Editorial Team: Joseph Forsyth, Simon Holdcroft and Clare Daley

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Last updated on 5th March 2020 by cytoffice