Curcumin Clinical Evidence

The Indian Journal of Medical Research
Deodhar SD, R Sethi, and RC Srimal. Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). 1980 Apr; 71:632–4.

Topic:
How does curcumin compare with phenylbutazone (an anti-inflammatory drug) in the treatment of rheumatoid arthritis?

Background:
Curcumin, the active constituent of the Indian spice turmeric, has been traditionally used to treat joint pain. Is it a good alternative to phenylbutazone, a drug with serious side effects?

Study Type:
Human clinical intervention trial

Study Design:
Double-blind, randomized, controlled trial. Patients with rheumatoid arthritis were treated with curcumin or phenylbutazone.

Dosage:
1,200 mg curcumin per day

Results:
Curcumin improved joint swelling, stiffness, and walking time.  Phenylbutazone was even more effective.

Phytotherapy Research
Pungcharoenkul K and P Thongnopnua. Effect of different curcuminoid supplement dosages on total in vivo antioxidant capacity and cholesterol levels of healthy human subjects.  2011 Nov; 25(11):1721–26.

Topic:
How do curcumin and vitamin E compare as antioxidants and in the treatment of elevated cholesterol and triglycerides?

Background:
Heart disease is one of the leading causes of death worldwide, with both free radical damage and high cholesterol considered significant cardiovascular risk factors.

Study Type:
Human clinical intervention trial

Study Design:
Subjects took curcumin or vitamin E. At base line and after 7 days, their ORAC scores (oxygen radical absorbance capacity, a measure of antioxidant power), cholesterol, and triglycerides were measured.

Dosage:
500 mg/day or 6 mg/day for 7 days{cke_protected_1}[MT2]{cke_protected_2} 

Results:
In the 500-mg dose group, ORAC rose from 13% at base line to 24%, while cholesterol and triglyceride levels decreased significantly. Vitamin E also raised ORAC scores, but it caused only small changes in cholesterol and triglycerides.

Conclusions:
“It is therefore suggested that curcumin supplementation would not be appropriate for healthy people except for reducing serum cholesterol or triglyceride levels.” [Emphasis added]

Surgical Endoscopy
Agarwal KA et al. Efficacy of turmeric (curcumin) in pain and postoperative fatigue after laparoscopic cholecystectomy: a double-blind, randomized, placebo-controlled study. 2011 Dec; 25(12):3805–10.

Topic:
How effective is curcumin at treating pain and fatigue in patients who have undergone a type of gallbladder surgery called laparoscopic cholecystectomy (LC)?

Background:
Turmeric has traditionally been used in India to treat pain and fatigue and for its anti-inflammatory, antioxidant, and healing properties.

Study Type:
Double-blind, randomized, placebo-controlled study

Study Design:
Patents took curcumin or placebo after surgery and kept diaries to record pain, fatigue, or other symptoms on a 100-point visual analog pain scale and a 10-point fatigue scale. Researchers followed up with patients after 3 days, 1 week, 2 weeks, and 3 weeks.

Dosage:
500 mg every 6 hours

Subjects:
50 LC patients

Results:
Subjects taking curcumin had significantly lower pain scores at 1 week and 2 weeks and significantly lower fatigue scores at 1 week, 2 weeks, and 3 weeks. In fact, after the first week, pain and fatigue scores among those taking curcumin were half those of subjects taking placebo (15 ± 5.204 versus 30 ± 13). Subjects in the treatment group also took fewer painkillers than those in the control group. After 3 weeks, everyone was pain-free.

Conclusions:
“Turmeric (curcumin) improves postoperative pain- and fatigue-related PROs [patient-reported outcomes] following LC.”

Drugs in R&D
Usharani P et al. Effect of NCB-02, atorvastatin and placebo on endothelial function, oxidative stress and inflammatory markers in patients with type 2 diabetes mellitus: a randomized, parallel group, placebo-controlled 8-week study. 2008; 9(4):243–50.

Topic:
How does curcumin compare with atorvastatin in the treatment of endothelial function, oxidative stress, and inflammation in diabetes patients?

Background:
Elevated blood sugar can cause oxidative stress and poor endothelial function (the endothelium is the interior lining of the blood vessels). Statin drugs can improve this condition but have side effects. How does curcumin compare with atorvastatin?

Study Type:
Human clinical intervention trial

Study Design:
Subjects took curcumin, atorvastatin, or placebo. Researchers measured endothelial function and collected blood samples to test for malondialdehyde (a marker of oxidative stress), enthothelin-1 (a protein that constricts blood vessels and raises blood pressure), interleukin-6 (a protein involved in inflammation), and tumor necrosis factor-alpha (TNF-alpha, an inflammatory cytokine).

Dosage:
72 patients with Type 2 diabetes, 67 completed

Subjects:
150 mg/2 times a day for 8 weeks

Results:
Subjects treated with curcumin or atorvastatin both showed significant improvement in endothelial function compared to placebo and had significant reductions in malondialdehyde, ET-A, IL-6, and TNF-alpha.

Conclusions:
“NCB-02 [a standardized preparation of curcuminoids] had a favorable effect, comparable to that of atorvastatin, on endothelial dysfunction in association with reductions in inflammatory cytokines and markers of oxidative stress.”

Phytotherapy Research
Lal B et al. Efficacy of curcumin in the management of chronic anterior uveitis. 1999 Jun; 13(4):318–22.

Topic:
Is curcumin an effective treatment for chronic anterior uveitis (an inflammation of the middle layer of the eye)?

Background:
Chronic anterior uveitis, which is sometimes caused by tuberculosis (TB), can be treated with corticosteroids; however, they have side effects. Is curcumin a good alternative?

Study Type:
Human clinical intervention study

Study Design:
Subjects without TB took curcumin alone, while those with TB also received antitubercular treatment.

Dosage:
375 mg/3 times a day for 12 weeks

Subjects:
53 patients with chronic anterior uveitis, 32 completed

Results:
All patients receiving curcumin alone improved, while 86% of those also receiving TB treatment did. Follow-up at 3 years showed a recurrence rate of 55% in the curcumin group and 36% in the curcumin plus TB treatment group. The response rate to treatment is similar to that of corticosteroids. There were no reported side effects.

Conclusions:
“The efficacy of curcumin and recurrences following treatment are comparable to corticosteroid therapy, which is presently the only available standard treatment for this disease. The lack of side effects with curcumin is its greatest advantage compared with corticosteroids.”

Phytotherapy Research

 Chandran B, A Goel. A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. 2012 Mar 9. doi: 10.1002/ptr.4639. [Epub ahead of print]

Topic:
How does curcumin compare with diclofenac sodium for the treatment of rheumatoid arthritis?

Background:
Diclofenac sodium is commonly used to treat inflammation and pain in arthritis patients, but it can have side effects. Is curcumin a better choice?

Study Type:
Human clinical intervention trial

Study Design:
Subjects took curcumin, diclofenac sodium, or both. Researchers measured their symptoms using the Disease Activity Score (DAS) and the American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joints.

Dosage:
500 mg curcumin, 50 mg diclofenac sodium, or both

Subjects:
45 rheumatoid arthritis patients

Results:
All 3 groups showed significant improvement in DAS scores. The curcumin group showed the most improvement in DAS and ACR scores. The difference between the curcumin and diclofenac groups was statistically significant. Curcumin treatment had no side effects.

Conclusions:
“Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions.”

BioActives LLC. MicroActive® Curcumin Powder (25%) In vitro and in vivo studies: Dissolution study. 2011 Jun 19. Unpublished paper.

Topic:
What is the bioavailability of MicroActive® curcumin powder?

Background:
Curcumin is a powerful antioxidant with anti-inflammatory action. However, because it does not dissolve well in water, it is difficult to absorb. Large doses may be therapeutic but can cause side effects such as gastric discomfort.

Study Type:
In vitro and human clinical intervention pilot study

Study Design:
In the in vitro phase of the study, researchers dissolved curcumin equivalent to 25 mg in hard gelatin capsules in 750 mL of hydrochloric acid, which is similar to gastric acid. After 2 hours, the pH of the acid was adjusted to resemble intestinal fluid. They did the same with 95% curcumin powder and 3 forms of commercially available curcumin supplements and compared the results.

In the human phase of the study, subjects took curcumin capsules after breakfast. Their blood was drawn and analyzed at base line and 1, 2, 4, 7, and 9 hours. The procedure was repeated with 95% curcumin powder.

Dosage:
250 mg/day for 2 days (1 day for each form of curcumin)

Subjects:
2 healthy subjects who were not consuming curcumin in food or taking any curcumin supplements

Results:
In the in vitro phase, researchers found that 10% of the dose was released into the simulated gastric fluid after 2 hours and that by 12 hours, approximately 88% had been released in a micronized form, meaning the particle size was less than 10 microns. Sustained release and smaller particle size may improve absorption. Other brands showed lower dissolution (0%–4% of the dose) in the simulated gastric acid and reached 13%–50% at 12 hours.

In the human phase of the study, the curcumin reached its peak levels in the subjects’ blood at 2 hours, with sustained release for 9 hours. The control curcumin peaked at 4 hours and had dropped to base line levels by 9 hours.

Conclusions:
“The results indicate the superior bioavailability of MicroActive® Curcumin with a reduction in time to reach maximum blood levels and sustained release for > 9 hours. The results warrant a larger clinical study for further validation.”

 Mechanism of Action

Curcumin works in myriad ways to combat inflammation. It down-regulates the activity of several pro-inflammatory enzymes (including COX-2, LOX, and iNOS) and cytokines (such as TNF-alpha) and suppresses the protein complex NF-kB. Curcumin also inhibits the metabolism of arachidonic acid, a fatty acid that plays a role in inflammation.

MicroActive Curcumin is more bioavailable than other forms of curcumin due to its:

1. Smaller particle size, which allows it to be incorporated into micelles (a structural unit composed of hydrophilic and hydrophobic parts), and

2. Sustained release, due to a special matrix of polymers that keeps the curcumin from precipitating out. Both of these factors lead to 10x better bioavailability than regular curcumin.