Beyond Brain Health by Chris D. Meletis, ND

Turmeric (Curcuma longa) is a popular spice that has been used for centuries in Southeastern Asia and India; curcumin, the main constituent of turmeric, is the main flavoring agent in curry dishes. Turmeric and curcumin have been studied extensively for their antioxidant and anti-inflammatory effects in a variety of health concerns.

It is important for any natural health-promoting substance to have the ability to transit through the digestive process and arrive intact in clinically meaningful levels in the blood, where the substance carries out its effects in the body. Researchers from UCLA have been able to resolve this challenge by increasing the bioavailability of curcumin in a unique form known as Longvida®. As was mentioned in the November issue of Vitamin Research News, in clinical studies, Longvida shows demonstrably increased levels achieved in the blood stream, and perhaps even more important is the ability of this breakthrough form of curcumin to cross the blood-brain barrier.1 (The blood-brain barrier is composed of a specialized layer of cells that restricts the passage of many substances from the general circulation into the brain. It presents a challenge in the treatment of brain conditions as it limits the ability of many therapeutic agents to enter the brain.)

This ability to optimize the absorption of curcumin is important in that curcumin’s benefits are multifactorial, and it may perhaps be one of the most scientifically researched natural compounds as literally thousands of studies investigating its effects have been carried out. This article will serve as a review of some of curcumin’s most promising qualities,2 several of which will be highlighted below.

Neurological Health

Curcumin’s influence on the brain is mainly attributed to its anti-inflammatory and antioxidative effects; however, other mechanisms are apparent as well.3 In animal models of cognitive dysfunction, curcumin administration lowered amyloid beta (Abeta) (the principle component of senile plaques that are the driving pathology in brain disorders) by slowing the production of amyloid-beta precursor protein (APP).4 Curcumin will also bind to the Abeta fibrils and aggregates5 where it may have a direct effect on decreasing amyloid pathology.6 The anti-inflammatory, antioxidant and anti-amyloid activity of curcumin in cognitive health makes it a promising area of research.7

In mood balancing, curcumin is thought to have potential clinical usefulness because of its ability to 1) Inhibit monoamine oxidase and thereby enhance the release of serotonin and dopamine and 2) Enhance neurogenesis, namely in the frontal cortex and hippocampus.8-9 Several animal studies highlight the benefits of curcumin in improving mood; curcumin boosted monoamine oxidase inhibition, enhanced serotonin and dopamine levels and reversed stress-related behaviors.10-12 Additional animal studies show a protective effect of curcumin against seizures as well; the neuroprotective and antioxidative effects are thought to be responsible.13-15

Anti-Inflammatory Effects

Inflammation is widely used as a term to loosely define pathological immunologic effects. Overexpression of inflammatory pathways is undoubtedly associated with many disease processes. Curcumin exhibits a number of anti-inflammatory effects, and it has been studied in lung health and immune challenges. Controlling inflammation occurs at numerous levels; a number of studies have elucidated key areas where curcumin has an effective role in thwarting specific inflammatory processes thereby resulting in positive clinical outcomes.

Lung Health

In asthmatic mouse models, curcumin decreased the total number of leukocytes (white blood cells, a component of inflammation) and eosinophils (additional allergy-mediating cells) in lung fluid. Additionally, other inflammatory cells and mucus occlusion in lung tissues were decreased as well as IgE (a primary immunological mediator of allergy) in the lung fluid. Investigators of this study conclude that curcumin produced these positive effects through inhibition of NF-kappaB.16

Curcumin’s potent anti-inflammatory effects stem from its ability to modulate T and B cells, macrophages, neutrophils, dendritic and natural killer cells. It also down regulates the expression of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukins 1, 2, 6, 7 and 12, and NF-kappaB as previously mentioned.17

Curcumin is a direct free radical scavenger in the lung tissue (and elsewhere), and can down regulate other pro-inflammatory mediators including matrix metalloproteinase, adhesion molecules and growth factor receptor genes, thereby exerting antioxidative and anti-inflammatory effects in the lungs.18

As an adjunctive therapy to standard corticosteroid treatment in asthma and chronic obstructive pulmonary disease (COPD), curcumin shows promise as well. Histone deacetylase 2 (HDAC-2) is an enzyme that plays a major role in how corticosteroids work; its function is decreased in circumstances of steroid insensitivity, and oxidative stress further compromises its function. Curcumin improves HDAC activity and thereby restores corticosteroid function.19

Joint Function

Curcumin also shows benefit in joint health. Animals with arthritis who were given curcumin experienced a dose-related suppression in arthritic signs and symptoms; markers such as infiltration of immune cells, synovial hyperplasia (thickening of inner joint tissue), destruction of cartilage and bone erosion were all halted by curcumin.20 Additionally, matrix metalloproteinases 1 and 3 (MMP-1, MMP-3) and tumor necrosis factor-alpha (TNF-alpha)-stimulated chondrocytes and fibroblasts (diseased joint cells) were also inhibited by curcumin in a dose dependent manner.

Furthermore, in an animal model of osteoarthritis, curcumin significantly decreased interleukin-1beta stimulated release of glycosaminoglycans (GAGS) with increasing doses to pre-experimental levels.21 In a similarly designed study using human chondrocytes (cartilage cells found in joints), curcumin inhibited several inflammatory markers including nitric oxide, prostaglandin E2, interleukins 6 and 8 and MMP-3 all in direct relationship to the dose used.22 Curcumin’s potent anti-inflammatory effects on chondrocytes support its use in joint health.

Specific Organ Health

Curcumin and its metabolites offer protection for a variety of conditions and organ systems. At the root of curcumin’s efficacy in these areas are its anti-inflammatory and antioxidative effects, as previously discussed. The following are a few brief areas where curcumin research has provided some valuable insight into its protective effects.

Kidney and Liver

Tetrahydrocurcumin (THU1) is one of curcumin’s major metabolites and shows some of the highest antioxidative activity. THU1 has been shown to improve 2 major kidney functions, creatinine and urea clearance; it is also supportive in kidney health after kidney transplants. In the liver, previous studies have shown reduced liver damage from iron, aflatoxin- and benzo[a]pyrene- induced mutagenicity.23

Cardiovascular System

The effects of curcumin have been widely researched in the cardiovascular system. Benefits of curcumin here include diminished cardiotoxicity from Adriamycin (a chemotherapeutic drug) and supporting a healthy heart in diabetic patients. Curcumin’s anti-thrombotic (anti-clotting), anti-inflammatory and anti-proliferative effects may also protect the health of the arteries and heart. Other effects include lessening the development of cardiac hypertrophy (enlargement) and heart failure in animals, and supporting healthy atrial and ventricular heart rhythm.24

Through other avenues of effect, curcumin may preserve heart muscle function after ischemic (lack of oxygen) or biochemical damage to the heart. Also, curcumin decreases the extent of cardiovascular remodeling in experimental models of pressure overload (when the pressure from the circulation is excessive on the heart it damages the muscle).25

Conclusion

The medical literature contains thousands of studies investigating the role of curcumin in health. Curcumin’s health benefits are wide ranging, and this brief review only provides a fraction of the data concerning curcumin.

References

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2. Srivastava RM, Singh S, Dubey SK, et al. Immunomodulatory and therapeutic activity of curcumin. Int Immunopharmacol. 2010 Sep 8. [Epub ahead of print]

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5. Yanagisawa D, Shirai N, Amatsubo T, et al. Relationship between the tautomeric structures of curcumin derivatives and their Abeta-binding activities in the context of therapies for Alzheimer’s disease. Biomaterials. 2010 May;31(14):4179-85.

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11. Wang R, Xu Y, Wu HL, et al. The antidepressant effects of curcumin in the forced swimming test involve 5-HT1 and 5-HT2 receptors. Eur J Pharmacol. 2008 Jan 6;578(1):43-50. Epub 2007 Sep 19.

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13. Bharal N, Sahaya K, Jain S, et al. Curcumin has anticonvulsant activity on increasing current electroshock seizures in mice. Phytother Res. 2008 Dec;22(12):1660-4.

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15. Sumanont Y, Murakami Y, Tohda M, et al. Prevention of kainic acid-induced changes in nitric oxide level and neuronal cell damage in the rat hippocampus by manganese complexes of curcumin and diacetylcurcumin. Life Sci. 2006 Mar 13;78(16):1884-91. Epub 2005 Nov 2.

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18. Biswas S, Rahman I. Modulation of steroid activity in chronic inflammation: a novel anti-inflammatory role for curcumin. Mol Nutr Food Res. 2008 Sep;52(9):987-94.

19. Marwick JA, Ito K, Adcock IM, Kirkham PA. Oxidative stress and steroid resistance in asthma and COPD: pharmacological manipulation of HDAC-2 as a therapeutic strategy. Expert Opin Ther Targets. 2007 Jun;11(6):745-55.

20. Mun SH, Kim HS, Kim JW, et al. Oral administration of curcumin suppresses production of matrix metalloproteinase (MMP)-1 and MMP-3 to ameliorate collagen-induced arthritis: inhibition of the PKCdelta/JNK/c-Jun pathway. J Pharmacol Sci. 2009 Sep;111(1):13-21.

21. Clutterbuck AL, Mobasheri A, Shakibaei M, et al. Interleukin-1beta-induced extracellular matrix degradation and glycosaminoglycan release is inhibited by curcumin in an explant model of cartilage inflammation. Ann N Y Acad Sci. 2009 Aug;1171:428-35.

22. Mathy-Hartert M, Jacquemond-Collet I, Priem F, et al. Curcumin inhibits pro-inflammatory mediators and metalloproteinase-3 production by chondrocytes. Inflamm Res. 2009 Dec;58(12):899-908. Epub 2009 Jul 5.

23. Osawa T. Nephroprotective and hepatoprotective effects of curcuminoids. Adv Exp Med Biol. 2007;595:407-23.

24. Wongcharoen W, Phrommintikul A. The protective role of curcumin in cardiovascular diseases. Int J Cardiol. 2009 Apr 3;133(2):145-51. Epub 2009 Feb 23.

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