Curcumin – a natural therapeutic agent

Curcumin, an active constituent of the root of the perennial herb turmeric (also known as Curcuma longa) and a member of the ginger (Zingiberaceae) family, has been used in India and the Far East for thousands of years as a culinary spice and a medicinal herb.

In the last couple of decades, there has been an explosion in scientific interest and research around curcumin’s potential as a natural therapeutic agent for a wide range of chronic inflammatory health conditions. A search on PubMed for curcumin in the title/abstract gives nearly 12,000 search results – much of this research is in vitro or using animal models to demonstrate mechanisms and pathways.

The US website www.clinicaltrials.gov lists 183 clinical trials using curcumin; of which 64 are still underway.

In this article we review the properties and molecular targets of curcumin, recent improvements to the technology available to address the problem of curcumin’s poor bioavailability and absorption, and noteworthy clinical trials.

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Traditional use of curcumin

Curcumin was first isolated in 1815¹ and its chemical structure and synthesis were confirmed in 1910 and 1913.² Turmeric is used as a culinary spice and provides curry with its distinctive orange-yellow colour. It is also commonly used as a colouring agent in cheese, butter and cosmetics.

In Ayurvedic medicine (the Indian system of holistic medicine) and traditional Chinese medicine it has been used for gynaecological problems, gastric problems, hepatic disorders, skin conditions, stress, depression, infectious diseases, and blood disorders.^3,4 In ancient Hindu medicine it was used to treat sprains and swelling. Topically, turmeric is used for analgesia, ringworm, bruising, eye infections, inflammatory skin conditions, inflammation of the oral mucosa and infected wounds. 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.

Properties of Curcumin

Curcumin has antimicrobial, antioxidant, anti-inflammatory and liver detoxification properties.  Goel et al (2008)⁵ list a number of molecular targets for curcumin including gene transcription factors, inflammatory cytokines, enzymes, growth factors, receptors and others.

• Antimicrobial properties: curcumin has broad-spectrum antimicrobial activity including antibacterial, antiviral and antifungal activities.⁶
• Antioxidant properties: Oxidative stress is an imbalance between the production of free radicals (e.g. reactive oxidative species and reactive nitrogen species) and antioxidant defences. Curcumin possesses antioxidant and free radical scavenging activities,⁷ it increases levels of some of the body’s own antioxidant systems – glutathione, catalase and superoxide dismutase.⁸
• 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 (NF-κB) pathway, which is the major initiator for the amplification of the inflammatory process. 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; “curcumin…shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases”.⁹
• 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. Ideally, phase I and phase II pathways work in balance. When they are not in balance phase I may be upregulated and 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 pathways. Curcumin has also been shown to have hepatoprotective effects.¹⁰

Bioavailability and absorption 

Many studies have shown that curcumin is safe even at high doses and  turmeric is generally well tolerated orally with few side effects reported in clinical trials. However, it is also considered to have a low systemic bioavailability¹ resulting in low plasma and tissue levels. This is due to its low aqueous solubility and rapid hepatic and intestinal metabolism. 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%.¹¹ However, piperine may be a problem for some individuals as it may alter drug metabolism and influence intestinal permeability.

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. Based on this knowledge, other delivery platforms to improve absorption have now been developed e.g. liposomal, phospholipid or optimised formulations.

Longvida® Optimised Curcumin is an innovative, more bioavailable form of curcumin. The patented SLCP™ (Solid Lipid Curcumin Particle) technology behind Longvida® renders the curcumin highly permeable, soluble, and stable. It was developed by neuroscientists in the U.S. and is one of the only curcumin supplement ingredients to undergo systematic “gold-standard” randomised controlled trials for both efficacy and safety; scientifically proven to be 67-285 times more bioavailable than standard 95% curcumin depending on cMAX, AUC, and AUC normalised calculations.¹² Longvida® provides therapeutic levels of free, active (not deactivated/metabolised or glucuronidated) curcumin and delivers free curcumin into the bloodstream and target tissues (including across the blood-brain barrier and blood-retinal barrier) for a full 24 hours of circulation and hence biological action. The SLCP™ encapsulation technology protects the curcumin from the harsh environment of the stomach and from being quickly broken down and excreted from the body. Longvida® is free of piperine, harsh solvents and volatile oils.

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. 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.

Rheumatoid arthritis:  A clinical trial compared the effects of curcumin with the 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.¹³

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.¹⁴

Osteoarthritis: In a clinical trial 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.¹⁵

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.¹⁶

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 ulcerative colitis.”¹⁷

In another pilot study of 5 patients with Crohn’s and 5 with ulcerative proctitis, all the proctitis patients improved and 4 reduced their medication. Of the Crohn’s disease patients, 4 of 5 had lowered Crohn’s Disease Activity Index scores.¹⁸

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.¹⁹

Currently, there are more than a dozen published independent clinical studies behind Longvida^® curcumin’s anti-inflammatory and anti-oxidant properties which have been studied for various health applications including:

Cognitive health and neurogenesis 

In a recent randomised, double-blind, placebo-controlled trial people from a healthy older population reported improved cognitive function and mood improvement using 400mg Longvida^®.²⁰

Exercise-induced muscle damage and inflammation

A 2016 study conducted at the University of North Texas was published on Longvida^®’s ability to reduce inflammatory and muscle damage biomarkers following oral supplementation. After exercise-induced muscle damage, subjects showed significantly smaller increases in key inflammatory biomarkers (such as inflammatory cytokines) with administration of 400mg/day versus placebo.²² 

Vascular endothelial function

Longvida^® improved endothelial-dependent dilation (EDD) of blood vessels after 12 weeks in middle-aged and older adults mediated, in part, by an increase in nitric oxide bioavailability, reduction in oxidative stress and inflammatory signalling.²¹ 

Promotion of longevity

A 2012 study published in Nutrition Journal demonstrated that one small, single daily dose of Longvida^® offered significant health benefits (including lowered plasma triglyceride values and increased plasma nitric oxide) in healthy middle-aged people in just 30 days.²³

Areas of ongoing research include muscle repair, cardiovascular health, joint health, sports nutrition, eye health, cancer prevention, cognition/mood and brain health.

Conclusion

Curcumin has multiple molecular targets and many mechanisms of its action are now understood thanks to in vitro and animal models. Clinical trials were initially hampered by its low bioavailability. This has now been improved by liposomal or optimised formulations such as Longvida^® Optimised Curcumin. Curcumin continues to be an exciting area of on-going clinical research.

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

madelinet@cytoplan.co.uk, 01684 310099

Madeline Taylor and the Cytoplan Editorial Team

New & Improved Cell-Active Curcumin Plus

Cell-Active Curcumin Plus contains curcumin from turmeric root and gingerols from ginger root.

Cell-Active Curcumin Plus now includes Longvida^® Optimised Curcumin which is scientifically proven to be up to 285 times more bioavailable than standard 95% curcumin.

Longvida^® was developed by neuroscientists in the US and is one of the only curcumin supplement ingredients to undergo systematic “gold-standard” randomised controlled trials for both efficacy and safety.

Find out more

References

1. Kunnumakkara, A. B. et al (2017) ‘Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases’, Br J Pharmacol, 174(11), pp.1325-1348.
2. Zhou, H et al (2011) ‘Targets of curcumin’, Curr Drug Targets, 12(3), pp. 332-347.
3. Gupta, S., C., et al (2013) ‘Multitargeting by turmeric, the golden spice: From kitchen to clinic, Mol Nutr Food Res, 59(9), pp.1510-28. Abstract only.
4. Kocaadam, B. et al (2017) ‘Curcumin, an active component of turmeric (Curcuma longa), and its effects on health’. Crit Rev Food Sci Nutr, 57(13), pp. 2889-2895. Abstract only.
5. Goel, A. et al (2008) ‘Curcumin as “Curecumin”: From kitchen to clinic’, Biochemical Pharmacology, 75(4), pp. 787-809. Abstract only.
6. Arutselvi, R. et al (2012) ‘Phytochemical screening and comparative study of anti microbial activity of leaves and rhizomes of turmeric varieties’, Asian Journal of Plant Science and Research, 2(2), pp. 212-219.
7. Borra, S. K. et al (2013) ‘Antioxidant and free radical scavenging activity of curcumin determined by using different in vitro and ex vivo models’, Journal of Medicinal Plants Research, 7(36), pp. 2680-2690
8. Trujillo, J. et al (2013) ‘Renoprotective effect of the antioxidant curcumin: Recent findings’, Redox Biology, 1(1), pp. 448-456
9. Yan, H. et al (2015) ‘Curcumin, Inflammation, and Chronic Diseases: How Are They Linked?’, Molecules, 20(5), pp. 9183-9213
10. Pari, L. et al (2008) ‘Role of curcumin in health and disease’, Arch Physiol Biochem, 114(2), pp.127-49. Abstract only.
11. Shoba, G. et al (1998), ‘Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers’, Planta Med, 64(4), pp. 353-6. Abstract only
12. Gota, V. S. et al. (2010) ‘Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers’, J Ag Food Chem, 58(4), pp. 2095-2099. Abstract only.
13. Satoskar, R. et al (1986), ‘Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation’, Int J Clin Pharmacol Ther Toxicol, 24(12), pp. 651-4. Abstract only.
14. Chandran, B. & Goel, A. (2012) ‘A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis’, Phytother Res, 26(11): 1719-25. Abstract only.
15. Henrotin, Y. et al (2014) ‘Decrease of a specific biomarker of collagen degradation in osteoarthritis, Coll2-1, by treatment with highly bioavailable curcumin during an exploratory clinical trial’, 14(159)
16. Kuptniratsaikaul, V. et al (2014) ‘Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study’, 20(9), pp. 451-8
17. Hanai, H. et al (2006) ‘Curcumin Maintenance Therapy for Ulcerative Colitis: Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial’, Clinical Gastroenterology and Hepatology, 4(12), pp. 1502-1506
18. Holt, P. et al (2005) ‘Curcumin Therapy in Inflammatory Bowel Disease: A Pilot Study’, Digestive Diseases and Sciences, 50(11), pp.        2191-2193. Abstract only.
19. Akazawa, N. et al (2012) ‘Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women’, 32(10), pp. 795-6. Abstract only.
20. Cox, K. et al (2015) ‘Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population’, Centre for Human Psychopharmacology’, J Psychopharmacol. 29(5), pp. 642-651.
21. Santos-Parker, J. et al (2015), ‘Curcumin supplement improves vascular endothelial function in middle-aged and older adults’, Geront, 55(2), pp.195.
22. McFarlin, B. et al (2016) ‘Reduced inflammatory and muscle damage biomarkers following oral supplementation with bioavailable curcumin’, BBA Clinical, 18(5), pp. 72-78.
23. Disilvestro, R. et al (2012) ‘Diverse effects of a low-dose supplement of lipidated curcumin (as Longvida®) in healthy middle-aged people’, Nutr. J., 26(11), pp. 79

Last updated on 20th November 2020 by cytoffice