Research Highlights

September 2010-- An overview of the potential health benefits of turmeric, funded by the McCormick Science Institute.  An evaluation of the research is presented. Read the entire study (PDF)

Turmeric_paper_image

MSI Funded Paper:
Potential Health Benefits of Turmeric

Singletary, K

The spice turmeric, derived from the rhizome of Curcuma longa L, has been used for centuries in food preparation and in traditional medicines to treat numerous diseases and conditions.

The primary biologically active constituent of turmeric is the polyphenol, curcumin, an orange-yellow powder that has potent anti-inflammatory and antioxidant properties, which, in part, may contribute to curcumin’s potential to prevent such conditions as cancer, Alzheimer disease, heart disease, and arthritis, to name a few. Clinical confirmation of these putative benefits is limited, however, and progress in establishing the in vivo efficacy in humans especially at typical dietary intakes is constrained by the poor bioavailability of this hydrophobic molecule.

Strategies to improve absorption and distribution of curcumin in foods and findings from ongoing clinical studies should improve our understanding of how curcumin can best be used to improve human health. A brief summary of potential health benefits, and suggestions for future research are presented in this study.

An evaluation of the quality of the scientific research is presented below: Rating[1]

Anticancer actions - clinical evidence
Curcumin has been evaluated in several clinical studies for its action toward precancer lesions and surrogate tumor biomarkers.(10,20,25) For example, patients with advanced colorectal cancer consuming 3.6 g curcumin per day for 4 mo evidenced in leukocytes a reduction in inducible prostaglandin E2 levels, an indicator of cyclooxygenase (COX) 2 activity.(25) Likewise, levels of the deoxyguanosine M1G adduct, an indicator of oxidative DNA damage, were decreased in malignant colorectal tissue of individuals consuming 3.6 g curcumin for 1 wk. However, the opposite response to curcumin was observed in normal liver tissue and colorectal liver metastases.(25) In a small pilot study, curcumin (1440 mg/d along with 60 mg quercetin) lowered the number and size of polyps in patients with familial adenomatous polyposis.(26) Recently, results of a phase 2 study of the chemotherapeutic drug gemcitabine in combination with curcumin (8 g/d) for up to 12 mo duration were reported. The preliminary findings point to this combination strategy for treatment of advanced pancreatic cancer as worthy of further study, although some abdominal distress in a subset of patients was encountered.(27,28) Additional clinical cancer trials are in progress targeting numerous tissue neoplasms.(24,29)

Anticancer actions - preclinical evidence
Preclinical experiments indicate that administration of curcumin or turmeric can suppress several stages of cancer development in multiple tumor models.(15,21,30-35) Modified delivery strategies (eg, pegylation of curcumin or incorporation into nanoemulsions) and novel structural analogs of curcumin have been shown to enhance its efficacy.(36-38) In contrast, there is a study using a transgenic mouse model of lung cancer expressing human Ki-ras in a lung-specific manner, in which dietary curcumin (4000 ppm) increased oxidative stress and lung tumorigenesis.(39) The authors warned that curcumin may exhibit lung-specific capacity to accelerate reactive oxygen species formation and damage lung tissue of smokers and ex-smokers. Other toxic and carcinogenic properties of curcumin have been described.(31) The mechanisms underlying curcumin’s anticancer actions include inhibiting carcinogen metabolism; suppressing tumor invasion and metastasis; disrupting regulation of transcription factors, growth factors, protein kinases, or mTOR; and modulating levels of inflammatory cytokines that control cell proliferation, angiogenesis, and apoptosis.(4,5,29,30,40-43) In this regard, 2 reports of in vitro studies indicate that curcumin may induce degradation of the tumor suppressor protein p53 and inhibit its activity,(44,45) results that raise concerns about safety, although these findings have not been confirmed in vivo. Of relevance to cancer treatment, administration of curcumin to mice (100-250 mg/kg) has been reported to have potential use in adjuvant therapy of proteolysis and muscle wasting accompanying cachexia and other catabolic conditions.(46,47)

P

Alleviation of gastrointestinal tract disorders - clinical evidence
There is clinical evidence that oral curcumin may help alleviate common symptoms of irritable bowel disease as well as those of patients with ulcerative colitis.(20,23,24,29,48-50) For example, curcumin improved clinical indices of disease, Crohn Disease Activity Index, and endoscopic indices. Doses of curcumin used in these studies ranged from 0.5 to 12 g/d over periods of 1 d to 6 mo.

Alleviation of gastrointestinal tract disorders - preclinical evidence
Preclinical studies have provided additional evidence that curcumin can suppress experimental colitis and intestinal inflammation. This anti-inflammatory action was mediated in part by diverse mechanisms including suppression of nuclear factor kB (NF-kB) activation, proinflammatory cytokine expression, and generation of reactive nitrogen and oxygen species in colonic mucosa or inflammatory cells.(4,23,24,51) Colonic delivery of solid lipid microparticles of curcumin in a rat colitis model substantially attenuated colonic inflammation.(52) Collectively, these results clearly support the need for larger, well-controlled clinical studies.

P

Diabetes and metabolic syndrome - preclinical evidence
There are several reports using experimental rodent models suggesting that curcumin administration (80 mg/kg, i.g., for 21 d) can alleviate hyperglycemia and other consequences of diabetes.(4,23) Besides decreasing blood glucose levels, curcumin has been observed in animals to increase plasma insulin levels, inhibit diabetic cataracts, counteract dyslipidemia and renal dysfunction, and attenuate diabetes-associated neuropathic pain.(4,23,53) Supplementing a high-fat diet of mice with curcumin (500-mg/kg diet) for 12 wk reduced body weight gain, adiposity, and microvessel density in adipose tissue, changes that coincided with decreased serum cholesterol, increased fatty acid oxidation, and decreased fatty acid esterification, compared with controls.(54) The mechanisms mediating these multiple effects in rodents are several. Curcumin may suppress inflammatory processes mediated by cytokines (eg, tumor necrosis factor) and transcription factors (such as NF-kB, and peroxisome proliferator-activated receptor y [PPAR-y]) as well as inhibit oxidative stress, suppress peroxidation, and scavenge free radicals.(4,23,26) Curcumin also has been shown to inhibit protein glycosylation. Curcumin’s actions in inhibiting adipogenesis and lipogenesis may be mediated by its inhibition of expression of the transcription factors PPAR-y and CCAAT/enhancer-binding protein and its suppression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 expression.(54) It has been reported also in an in vitro study that curcumin (40 µM) may enhance the survival of ß cells of human pancreatic islets and thus may potentially improve islet transplantation outcomes.(55)

Diabetes and metabolic syndrome - clinical evidence
In contrast to animal models and preclinical investigations, there is limited human evidence demonstrating similar efficacy of curcumin. An early study(56) reported that curcumin can alter blood glucose levels in a diabetic patient. More recently, a preparation of curcuminoids favorably affected blood levels of inflammatory stress biomarkers in patients with type 2 diabetes. This was accompanied by improvement in endothelial dysfunction.(57)

P

Cardioprotective properties - preclinical evidence
There is considerable preclinical evidence indicating that curcumin exhibits a variety of cardioprotective properties. First of all, curcumin may protect against cardiac injury, in large part because of its anti-inflammatory actions. Several animal studies have suggested that curcumin administration (eg, 70-100 µmol/kg, intravenously) protects the heart from damage following cardiac ischemia and reperfusion (I/R) and from cardiopulmonary bypass (CPB).(23,58,59) Curcumin acted in part to protect the myocardium against ischemic damage by suppressing pathways generating reactive oxygen species and lipid peroxidation and by upregulating other pathways that detoxify free radicals. I/R and CPB were ameliorated by curcumin’s ability to counteract the upregulation of cardiac proinflammatory genes and to suppress the production of proinflammatory cytokines following damage to the heart.(23,58) In mice, curcumin dosing (50-100 mg/kg per day, subcutaneously, for 1-2 wk) prevented experimentally induced cardiac hypertrophy, fibrosis, inflammation, and heart failure in part via its inhibition of p300 histone acetyltransferase.(19) Curcumin also inhibited chemically induced cardiac injury following administration of such agents as isoproterenol and adriamycin.(58,60)

Curcumin may be cardioprotective by suppressing atherosclerotic lesion development. It can act in a variety of ways to do so, including inhibiting low-density lipoprotein oxidation, suppressing proliferation of vascular smooth muscle cells, decreasing thrombosis, reducing aortic fatty streak formation, and blocking homocysteine-induced endothelial dysfunction.(23,26,58,60,61) Provision of curcuminoids (30-90 mg/kg per day, i.g., for 12 wk) also has a lipid-lowering effect in rats fed high-fat diet.(62) There is some speculation that curcumin’s anti-inflammatory actions may help in the prevention of atrial and ventricular arrythrmias.(60) Recent preliminary evidence suggests that curcumin has the potential to prevent stroke and lessen vascular inflammation and cerebral vasospasm following hemorrhagic stroke.(63-65) Again, these beneficial cardiovascular effects of curcumin are apparently a consequence of its multiple antioxidant and anti-inflammatory actions.(4,26,61) In contrast, there is one preclinical study in which curcumin exhibited deleterious effects toward heart tissue exposed to chronic hypoxia by inactivating p53, p38, and C-Jun kinase pathways.(26)

Cardioprotective properties - clinical evidence
Well-controlled clinical trials in humans that examine curcumin’s efficacy toward cardiovascular disease and its biomarkers are relatively few in number.(12) Clearly, additional clinical trials are warranted to confirm these animal and cell culture data.

P

Benefits for neurodegenerative disorders and cognition - preclinical evidence
There is experimental evidence that curcumin may lessen the development and progression of Alzheimer disease (AD). In vitro studies indicate that curcumin exhibits anti-inflammatory properties that could counteract neurodegeneration.(23,26,66,67) Curcumin also has been reported to block ß-amyloid aggregation and fibril formation as well as to stimulate ß-amyloid removal by mononuclear cells of AD patients.(23,66,68) In animal models of AD, dietary curcumin (160-5000 ppm) has been observed to suppress levels of ß-amyloid and plaque burden and other concomitant pathologies.(23,26,66) For example, in an in vivo study, curcumin injected into the blood (7.5 mg/kg per day, 7 d) disrupted existing amyloid plaques and partially reversed neurite distortions in an AD mouse model.(69) In a variety of animal models of AD, dementia, and aging, curcumin also has been noted to improve memory function and cognition.(66,70-76) Curcumin’s capacity to lower serum cholesterol and lipid peroxides as well as to inhibit platelet aggregation may additionally improve symptoms of dementia.(66) Of related interest, curcumin is reported to be effective in counteracting oxidative stress and impaired cognition associated with traumatic brain injury.(77,78)

Benefits for neurodegenerative disorders and cognition - human evidence
There are few human studies examining curcumin as an agent to ameliorate neurological disorders. An epidemiological study of elderly Singaporeans who ate curry with turmeric had better cognitive function than those not consuming curry.(79) A recently published 6-mo randomized, placebo-controlled, double-blind clinical trial reported, however, that AD patients who consumed 4 g curcumin per day exhibited no protective effect.(80) The authors attributed this lack of benefit in part to insufficient cognitive decline in the placebo group during the relatively short 6-mo period of this intervention. Of interest, however, was that an increase in serum "-amyloid 40 in curcumin-treated patients was observed, which possibly reflects curcumin-induced disaggregation of ß-amyloid deposits in the brain.(23,80) Data from additional clinical studies should be forthcoming.(4,23,66)

P

Alleviation of arthritic diseases - preclinical evidence
Curcumin’s potent anti-inflammatory properties have prompted examination of its potential for preventing and managing rheumatoid arthritis and other related conditions.(81) There is preclinical evidence that curcumin has the potential to improve arthritis symptoms. Administration of curcumin to rodents (eg, 4 mg/kg per day, intraperitoneally [IP]) using experimental models of arthritis resulted in reduced levels of tissue inflammation as well as decreased expression of inflammation-associated cytokines and other inflammatory mediators.(23,82) Notably, curcumin can decrease expression of COX-2 and, in combination with celecoxib, can synergistically inhibit the COX-2 activity and cell proliferation associated with osteoarthritis. Other natural products, such as the isothiocyanate sulforaphane, may synergize with curcumin in suppressing inflammation.(83) A randomized, double-blind, placebo-controlled study of the effect of a mixture of curcuminoids on canine osteoarthritis yielded mixed results, however.(84)

Alleviation of arthritic diseases - clinical evidence
There is limited clinical evidence supporting the antirheumatic actions of curcumin,(4,23,24,85,86) prompting the recommendation that turmeric should not be used to treat osteoarthritis until reliable clinical evidence is provided.(85) Studies are in progress evaluating the efficacy of curcumin and celecoxib in treating patients with osteoarthritic disease.(87)

P

Allergy
Data from several animal studies suggest that curcumin can ameliorate immune cell-associated bronchial inflammation.(88,89)

P

Actions against infections and parasitic diseases
There are very limited evidence and mixed results regarding curcumin’s efficacy in counteracting microbial and viral infections. It was ineffective in reducing viral loads or CD4 counts in patients with HIV, although it did resolve HIV-associated diarrhea.(12,90) Curcuminoids did show potential as antitubercular agents.(91) A recent report suggests that curcumin demonstrated antibacterial activity toward human clinical isolates of Helicobacter pylori and substantially reduced H pylori-induced gastric damage in infected mice.(92) Curcumin also has been reported recently to possess antimalarial and antiparasitic properties.(93-96) In one mouse study, for example, curcumin given IP (400 mg/kg per day) to Schistosoma mansoni-infected mice altered cellular and humoral immune responses that coincided with a decrease in parasitic burden and liver pathology.(93)

P

Miscellaneous effects
There are preliminary data suggesting that curcumin may be beneficial in the prevention or treatment of other diverse conditions. Topical use of curcumin has been noted to improve outcomes in patients with psoriasis,(12) and its use as a nontoxic agent for treating a variety of skin disorders has been advocated.(23,24,97,98) Curcuminoids have been recommended as a cosmeceutical ingredient for dermatologic applications.(99) Curcumin has been shown to ameliorate renal failure in rats, to protect the kidney from nonimmune injury and, as part of a bioflavonoid formulation, to improve early outcomes in cadaveric renal transplantation.(100-102) Curcumin was reported to arrest surgically developed endometriosis in mice(103) and to alleviate pathological symptoms of a mouse model of multiple sclerosis.(104) It also may prevent gallstone formation and a rare inflammatory disease called chronic anterior uveitis.(24) There is interest in curcumin for preventing loss of muscle mass and for enhancing muscle regeneration after trauma, as well as for stimulating wound healing.(46,47,105,106) A preliminary study in rats suggested that curcumin can protect against druginduced orofacial dyskinesia and associated brain abnormalities.(107) Curcumin has been reported in animal models to attenuate chronic fatigue syndrome.(108) In large part, these actions are associated with curcumin’s ability to alter physiological processes involved in inflammation, oxidative damage, immunomodulation, and cell proliferation.(4,6,23,24,26,82)

P

[1] Key to grades

S: Strong, convincing evidence
E: Emerging, suggestive evidence
P: Preliminary, inconclusive evidence
 

Reference

Singletary, K. Turmeric: Overview of Health Benefits. Nutrition Today. 2010 September/October: 45(5): 216-225.

Read the entire study (PDF)

 

 

 

 

 
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