Turmeric - A curry spice with surprising clinical therapeutic and disease prevention potentials
Curcuma longa, aka turmeric, is a curry spice and a traditional Chinese medicinal herb with a long history of use as a treatment for inflammatory conditions. Lately, curcumin - an active substance found in turmeric - has peaked researchers’ interest, leading to the development of an extensive literature on this topic. That is because many recent findings suggest that curcumin has a surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activities.
To date, many clinical trials suggested that curcumin may be a potential remedy for the prevention and treatment of chronic diseases including inflammatory bowel disease, arthritis, pancreatitis, allergies, asthma, and cancer. Its effectiveness is currently under investigation in human clinical trials for a variety of conditions, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis and Alzheimer's disease.
What is inflammation?
Inflammation is triggered by the body’s immune system and is an adaptive physiological response to various circumstances including infections and tissue injuries. Inflammation has been shown to increase the levels of inflammatory markers, lipid peroxides and free radicals in the blood, leading to a wide range of physiological and pathological morbidities. Inflammation that lasts only for a short amount of time is usually beneficial for the organism. However if inflammation persists for a long time (chronic inflammation), it may initialize various chronic diseases such as obesity, diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Given the anti-inflammatory properties of curcumin, a broad range of clinical trials are currently investigating the effectiveness of curcumin on the prevention and treatment of such inflammatory conditions.
Activities of curcumin
Anti-inflammatory and anti-oxidant activities
As it is currently suggested by both in-vivo and in-vitro studies, many of the activities associated with curcumin relate to its ability to suppress acute and chronic inflammation. In-vitro studies (studies taking place in a test tube or elsewhere outside a living organism) suggest that, one way that curcumin can suppress inflammation, is by inhibiting the production of pro-inflammatory cytokines such as interleukin-8 (IL-8) and tumor necrosis factor-a (TNF- a). A recent in-vitro study revealed that curcumin can also suppress oxidative stimulation of G-proteins in human brain membranes by substances such as metabolic prooxidants, homocysteine and hydrogen peroxide. In in-vivo (studies taking place in living organisms) animal studies, curcumin had comparable activity to phenylbutazone, a commonly used anti-inflammatory agent. It is worth noting that even topical application of curcumin markedly inhibited epidermal inflammation (ear edema) in mice.
Chemopreventive, chemotherapeutic, and chemosensitizing activities
Curcumin was found to inhibit cancer development and progression, targeting multiple steps in the pathway to malignancy. It is suggested that curcumin acts as both a blocking agent, inhibiting the initiation of cancer by preventing carcinogen activation, and as a suppressing agent, inhibiting malignant cell proliferation during promotion and progression of carcinogenesis. To date, several animal studies have shown that curcumin has a dose-dependent chemopreventive effect in colon, duodenal, stomach, esophageal and oral cancers. Curcumin may also function as a chemosensitizer, enhancing the activity of other anti-neoplastic agents, in part by inhibiting pathways that lead to cancer treatment resistance.
Inhibition of angiogenesis and metastasis
Angiogenesis - a fundamental process by which new blood vessels are formed from existing vessels - is essential in reproduction, development, and wound repair. Tumor growth and metastasis are dependent upon the formation of new blood vessels to sustain growth and to allow tumor cells to enter the blood circulation and metastasize to distant sites. Curcumin has been shown to interfere with many of the processes involved in angiogenesis, thus preventing tumor cells from metastasizing to other tissues.
What is wrong with this rosy picture?
Although it is clear that curcumin appears to have a wide variety of beneficial activities, not all studies are consistent with these data. Specifically, several studies have suggested that in selected settings, curcumin may not only be ineffective, but may have adverse activities. For example, findings of curcumin-induced DNA damage were reported by both in-vivo and in-vitro studies. Curcumin has also been reported to inhibit p53 function in colon cancer cells. P53 is a critical protein in the protection against genotoxic stress, and as such, curcumin-mediated inhibition of p53 function may also contribute to the accumulation of tumor-inducing DNA damage. As reported by another trial, curcumin may also inhibit the activity of chemotherapeutic agents.
Curcumin in human clinical trials
Curcumin is under active investigation for its clinical benefit, although clinical trials in humans are still in relatively early phases. Promising initial results were reported in limited subsets of patients treated with curcumin for chronic anterior uveitis (eye inflammation), idiopathic inflammatory orbital pseudo tumors, post-operative inflammation, external cancerous lesions, and pancreatic cancer. While continuing to assess safety and pharmacokinetics of curcumin, current trials are also exploring its efficacy. Consonant with demonstrations of curcumin's anti-inflammatory and anti-cancer properties, disease targets include neoplastic and pre-neoplastic diseases such as multiple myeloma, pancreatic cancer, myelodysplastic syndromes, and colon cancer, as well as conditions associated with inflammation including psoriasis, and Alzheimer's disease.
Are there sufficient data to support effectiveness in human subjects?
To date, there are scientific data to support possible effectiveness of curcumin in the following conditions:
- Osteoarthirits (OA): One disease associated with inflammation is OA and several studies have shown the anti-arthritic effects of curcumin in humans with OA. In 2016, a systematic review and meta-analyses study concluded that curcumin does appear to be beneficial to several aspects of OA. Specifically the study provided scientific evidence that 8–12 weeks of standardized turmeric extracts (typically 1000 mg/day of curcumin) treatment can reduce arthritis symptoms (mainly pain and inflammation-related symptoms) and result in similar improvements in the symptoms as ibuprofen.
- Elevated cholesterol: The fact that curcumin can attenuate inflammation has implications beyond arthritis, as systemic inflammation has been associated with many conditions including Metabolic syndrome (MetS). MetS includes insulin resistance, hyperglycemia, hypertension, low HDL cholesterol, elevated LDL cholesterol, elevated triglyceride levels, and obesity. Early research has shown that curcumin may attenuate several aspects of MetS by improving insulin sensitivity, suppressing adipogenesis, and reducing elevated blood pressure, inflammation, and oxidative stress. However, to date there are sufficient data to support the effectiveness of curcumin only in reducing total and LDL cholesterols and triglycerides in overweight people with high cholesterol.
- Itching (pruritus) - Research suggests that taking turmeric by mouth 3 times daily for 8 weeks reduces itching in people with chronic kidney disease. Also, early research suggests that taking a specific combination product containing curcumin plus black pepper daily for 4 weeks reduces itching severity and improves quality of life in people with chronic itching caused by mustard gas.
Although results are promising, there are currently insufficient data to support the efficacy of curcumin in conditions other than hypercholesterolemia, osteoarthritis and itching (pruritus), since research is currently in the early stages.
Safety, side effects and and pharmacology
Curcumin is well tolerated, and non-toxic for animals or humans; however its bioavailability appears to be poor. Despite curcumin’s highly promising features for treatment and prevention of various diseases, clinical uses have been hindered by poor absorption, rapid metabolism in the liver and intestinal wall, short biological half-life, and low oral bioavailability. It was suggested that very high doses (>3.6 g/day in humans) are required to produce any medicinal effect. Thus, a number of clinical trials cited that curcumin's bioavailability needs to be improved to exert significant medical effects.
Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural substance to the forefront of therapeutic agents for treatment of human diseases. Adding a bio-enhancer such as piperine (found in black pepper) was found to enhance the cellular uptake of curcumin by up to 2000%. Pharmaceutical development of natural compounds like curcumin and synthetic derivatives, as well as improved delivery technologies including nanodisks, have strong scientific rationale, but will require overcoming various hurdles including high cost of trials, concern about profitability and misconceptions about drug specificity, stability, and bioavailability.
Turmeric usually does not cause significant side effects; however, some people have reported symptoms including upset stomach, nausea, dizziness, or diarrhoea.
Take home message: Curcumin indeed presents surprising antioxidant, anti-inflammatory, chemopreventive and chemotherapeutic properties. However, further research is needed for well established conclusions to be made on its effectiveness on a variety of chronic conditions/diseases. The many desirable medicinal effects of curcumin should not obscure the need for caution until all the data have been fully assessed. Given the explosive enthusiasm for this natural compound and the number of ongoing clinical trials, such data should be available in the nearest future.
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