Studies

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STUDIES: Chronic Pain

Curcumin Protects Against Inflammation from Fat

Excess fat causes inflammation and throws metabolism, hormone levels, and gut bacteria out of balance. This, in turn, makes the resulting organ damage and increased likelihood of other associated conditions – heart disease, diabetes, and high cholesterol levels – much more likely. Fortunately, curcumin from turmeric may help put a stop to this cycle.

Researchers at Texas Tech University found that curcumin not only reduced inflammatory markers from adipose (fat) tissue, it also preserved and promoted short-chain fatty acid (SCFA) in the gut.

Short-chain fatty acids are produced in the gut during fermentation of polysaccharides from food, and assist in the way our bodies resist disease inflammation. They are key to homeostasis – the natural balance of optimal health.

As research on curcumin continues, it appears that this compound really does enhance our well-being in virtually every way imaginable, and in some ways that we are just discovering.

Abstract:

Islam T, Koboziev I, Scoggin S, Ramalingam L, Moustaid-Moussa N. Protective Effects of Curcumin in High Fat Diet (HFD)-Induced Obesity Include Anti-Inflammatory Effects in Adipose Tissue and Changes in Gut Microbiome (P06-075-19). Curr Dev Nutr. 2019;3(Suppl 1):nzz031.P06-075-19. Published 2019 Jun 13.

OBJECTIVES: Curcumin, a traditionally used spice in Asia has several health-protecting effects. However, its role on gut microbiota and obesity-associated inflammation is still poorly understood. The objective of this study was to determine whether the protective effects of curcumin in high fat diet (HFD)-induced obesity are mediated by reduced white adipose tissue (WAT) inflammation and changes in gut bacteria.

METHODS: Male B6 mice were fed a HFD (45% kcal fat) or HFD supplemented with 0.4% (w/w) curcumin (HFC) for thirteen weeks. Body weight, adiposity, glucose and, insulin tolerances, and serum triglycerides, insulin, leptin, resistin levels were measured. Gut microbiome composition was determined by 16S RNA metagenomics sequencing. Expression of inflammation-related genes in WAT was measured by qRT-PCR. Macrophage contents in WAT were evaluated by galectin-3 immunohistochemical staining.

RESULTS: Pro-inflammatory transcription factor nuclear factor NF-kappa-B p65 subunit (p65) and toll-like receptor-4 (TLR-4) gene expression was downregulated in HFC group compared to HFD mice. Furthermore, curcumin reduced total macrophage infiltration in WAT in HFC mice compared to HFD group. Expression of both M1 (CD80, CD38) and M2 (Arginase-1) associated genes was decreased. The relative abundance of bacteria representing the Clostridium genus, which contains numerous short-chain fatty acid (SCFA) producing species, was increased by the curcumin supplement.

CONCLUSIONS: Curcumin exerts protective effects in dietary obesity, in part through downregulation of adipose tissue inflammation which may be due to the production of SCFA and, possibly other curcumin metabolites by gut microflora.

FUNDING SOURCES: Startup funds and Come N Go award from the College of Human Sciences at Texas Tech University.

Move Over, Arthritis Prescriptions – Curcumin Works Better!

According to the Centers for Disease Control, 30 million American adults suffer from osteoarthritis. And even though the side effects of many prescription drugs have become well known, many people will still assume that overall, they are the only choice. But research with curcumin casts that old mind set in doubt.

This clinical study compared a commonly used prescription drug, diclofenac (Voltaren is one brand name) to a curcumin, a compound extracted from turmeric (Curcuma longa) blended with turmeric essential oil, a source of ar-turmerone, which enhances the botanical’s absorption and blood retention.

While diclofenac is widely used, it can also cause stomach ulcers, acid reflux, GI bleeding, headaches, dizziness, and even kidney damage. The gastrointestinal side effects of diclofenac alone are enough to turn most people off: gas, bloating, and flatulence are just some of the problems – issues that curcumin also relieves, aside from pain.

The researchers found that curcumin provided just as much pain relief as the prescription drug, but with a much higher level of safety. In fact, 28 percent of the people taking diclofenac in this study had such severe gastrointestinal issues, they had to take a second drug to alleviate stomach pain and acidity caused by the first drug.

Curcumin is an excellent choice for everyone, especially those who can’t tolerate the side effects of over-the-counter or prescription drugs or have noticed the onset of serious side effects of those drugs.

This is excellent news for anyone who has felt steered to prescription or over-the-counter choices that do, in fact, dull arthritis pain but come with a steep price of unwanted effects. Curcumin does relieve pain – it is a powerful COX-2 inhibitor – but it also works through multiple inflammatory pathways, helping the body heal, not just masking underlying symptoms and taking a single-track approach.

The amount of curcumin – three, 500 mg doses a day – is easy to incorporate into a daily regimen. The type of curcumin used in the study, which provide a family of beneficial compounds called curcuminoids and include curcumin, demethoxycurcumin, bisdemethoxycurcumin is readily available as BCM-95/Curcugreen Curcumin and has been used in over 50 published studies. Unlike prescription or over-the-counter pain killers, it is safe, effective, and does not cause side effects or organ damage.

Abstract:

Shep D, Khanwelkar C, Gade P, Karad S. Safety and efficacy of curcumin versus diclofenac in knee osteoarthritis: a randomized open-label parallel-arm study. Trials. 2019;20(1):214.

Background: The purpose of this study was to compare the efficacy and safety of curcumin with those of diclofenac in the treatment of knee osteoarthritis (OA).

Methods: In this randomized, open-label, parallel, active controlled clinical study, 139 patients with knee OA were randomly assigned to receive either a curcumin 500-mg (BCM-95®) capsule three times daily or a diclofenac 50-mg tablet two times daily for 28 days. Patients underwent assessment at baseline and days 7, 14, and 28. The main outcome measure was severity of pain using visual analogue scale score at days 14 and 28. Knee Injury and Osteoarthritis Outcome Score (KOOS) (at days 14 and 28), anti-flatulent effect (at day 7), anti-ulcer effect, weight-lowering effect, and patient’s and physician’s global assessment of therapy at day 28 were included as secondary outcome measures. Safety after treatment was evaluated by recording adverse events and laboratory investigation.

Results: At days 14 and 28, patients receiving curcumin showed similar improvement in severity of pain and KOOS scale when compared with diclofenac, and the difference was not statistically significant. At day 7, the patients who received curcumin experienced a significantly greater reduction in the number of episodes of flatulence compared with diclofenac (P <0.01). At day 28, a weight-lowering effect (P <0.01) and anti-ulcer effect (P <0.01) of curcumin were observed. None of the patients required H2 blockers in the curcumin group, and 19 patients required H2 blockers in the diclofenac group (0% versus 28%, respectively; P <0.01). Adverse effects were significantly less in the curcumin group (13% versus 38% in the diclofenac group; P <0.01). Patient’s and physician’s global assessment of therapy was similar in the two treatment groups.

Conclusion: Curcumin has similar efficacy to diclofenac but demonstrated better tolerance among patients with knee OA. Curcumin can be an alternative treatment option in the patients with knee OA who are intolerant to the side effects of non-steroidal anti-inflammatory drugs.

Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research.

Curcuma longa (turmeric) has a long history of use in Ayurvedic medicine as a treatment for inflammatory conditions. Turmeric constituents include the three curcuminoids: curcumin (diferuloylmethane; the primary constituent and the one responsible for its vibrant yellow color), demethoxycurcumin, and bisdemethoxycurcumin, as well as volatile oils (tumerone, atlantone, and zingiberone), sugars, proteins, and resins. While numerous pharmacological activities, including antioxidant and antimicrobial properties, have been attributed to curcumin, this article focuses on curcumin's anti-inflammatory properties and its use for inflammatory conditions. Curcumin's effect on cancer (from an anti-inflammatory perspective) will also be discussed; however, an exhaustive review of its many anticancer mechanisms is outside the scope of this article. Research has shown curcumin to be a highly pleiotropic molecule capable of interacting with numerous molecular targets involved in inflammation. Based on early cell culture and animal research, clinical trials indicate curcumin may have potential as a therapeutic agent in diseases such as inflammatory bowel disease, pancreatitis, arthritis, and chronic anterior uveitis, as well as certain types of cancer. Because of curcumin's rapid plasma clearance and conjugation, its therapeutic usefulness has been somewhat limited, leading researchers to investigate the benefits of complexing curcumin with other substances to increase systemic bioavailability. Numerous in-progress clinical trials should provide an even deeper understanding of the mechanisms and therapeutic potential of curcumin.

Source: Jurenka JS. Altern Med Rev. 2009;14(2):141-53.

 

Mechanism of the Anti-inflammatory Effect of Curcumin: PPAR-gamma Activation.

Curcumin, the phytochemical component in turmeric, is used as a dietary spice and a topical ointment for the treatment of inflammation in India for centuries. Curcumin (diferuloylmethane) is relatively insoluble in water, but dissolves in acetone, dimethylsulphoxide, and ethanol. Commercial grade curcumin contains 10-20% curcuminoids, desmethoxycurcumin, and bisdesmethoxycurcumin and they are as effective as pure curcumin. Based on a number of clinical studies in carcinogenesis, a daily oral dose of 3.6 g curcumin has been efficacious for colorectal cancer and advocates its advancement into Phase II clinical studies. In addition to the anticancer effects, curcumin has been effective against a variety of disease conditions in both in vitro and in vivo preclinical studies. The present review highlights the importance of curcumin as an anti-inflammatory agent and suggests that the beneficial effect of curcumin is mediated by the upregulation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation.

Source: Jacob A, Wu R, Zhou M, Wang P. PPAR Res. 2007;89369.

 

Curcumin as "Curecumin": from kitchen to clinic.

Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be "Curecumin".

Source: Goel A, Kunnumakkara AB, Aggarwal BB. Biochem Pharmacol. 2008 Feb 15;75(4):787-809.

 

A Randomized, Pilot Study to Assess the Efficacy and Safety of Curcumin in Patients with Active Rheumatoid Arthritis.

In this study, 45 patients with rheumatoid arthritis were randomized into 3 groups, with patients receiving either BCM-95 curcumin 500 mg twice daily, the prescription drug diclofenac sodium (one brand name is Voltaren®) 50 mg twice daily, or a combination of the two. The results were judged using the clinically validated Disease Activity Score (DAS) 28 and also with the American College of Rheumatology (ACR) criteria and scores for pain and swelling in joints. Patients in all 3 groups improved. The curcumin group showed the greatest improvement, and the endpoint scores were significantly better than the patients in the drug group. Using both interventions concurrently did not show any additional benefit with regards to disease scores. Curcumin was found to be safe with no adverse effects in this study. In the drug group. 14% of the patients withdrew because of adverse effects

Source: Chandran B, Goel A. Phytother Res. 2012 Mar 9. doi: 10.1002/ptr.4639.

 

Clinical Evaluation of a herbal product in the management of knee osteoarthritis.

Originally presented at the Osteoarthritis Research Symposium Internationale (OARSI) Annual World Congress on Osteoarthritis, September 15-18, 2011. San Diego, CA. 28 subjects with diagnosed osteoarthritis of the knee were randomized to a 500 mg blend BCM-95 curcumin and Bospure® Boswellia twice a day or to the prescription drug celecoxib (one brand name is Celebrex®) 100 mg twice a day. Symptom scoring and clinical evaluation yielded superior results on pain relief and distance walked for the BCM-95 and Bospure blend compared to celecoxib. BCM-95 and Bospure equaled celecoxib on joint flexibility. No serious adverse effects noted.

Source: Antony B, Kizhakedath R, Benny M, Kuruvilla BT. Abstract 316. Osteoarthritis Cartilage. 2011;19(S1):S145-S146.

 

Human Clinical Study to evaluate the bioavailability of a high-absorption curcumin.  

15 healthy men and women ages 24-45; 8 assigned to plain curcumin and 7 assigned to BCM-95 curcumin. Results: overall, 7-fold increase over course of 12 hours. BCM-95 peak at 1600 ng/g; plain curcumin peak at ~230 ng/g. BCM-95 curcumin remained above 200 ng/g for 12 hours. Plain curcumin remained above 200 ng/g for less than 2 hours. Two hours after ingestion, BCM-95 levels are 10-fold over plain curcumin.

Source: Benny B, Antony B. Spice India. September, 2006:11-15.

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