Curcumin for Autoimmune and Rheumatic Diseases: What the Clinical Trials Show

Table of Contents

• Key Points
• Background: What Is Curcumin and Why Study It?
• How the Researchers Selected Studies
• Curcumin in Osteoarthritis
• Curcumin Compared with NSAIDs
• Effects on Inflammation and Oxidative Stress in Osteoarthritis
• Curcumin in Type 2 Diabetes
• Detailed Diabetes Trial Results
• Curcumin in Ulcerative Colitis, Rheumatoid Arthritis, Lupus Nephritis, and Multiple Sclerosis
• How Curcumin Works in the Body
• What These Findings Mean for Patients
• Limitations of the Research
• Recommendations and Next Steps
• Frequently Asked Questions
• Source Information

Key Points

• Curcumin, the active compound in turmeric, was studied in 32 randomized controlled trials across six autoimmune and rheumatic conditions.
• In osteoarthritis, 14 of 16 trials showed significant improvement; in type 2 diabetes, all 8 trials showed significant clinical or laboratory benefit.
• Four studies found curcumin as effective as NSAIDs like ibuprofen for knee osteoarthritis, with fewer gastrointestinal side effects.
• Evidence for ulcerative colitis is promising but limited; results for rheumatoid arthritis, lupus nephritis, and multiple sclerosis are inconclusive.
• Curcumin was consistently well tolerated with minimal side effects; reported issues were minor itching, constipation, or vertigo in a few patients.

Background: What Is Curcumin and Why Study It?

Curcumin is the main active component of turmeric, a spice that comes from the Curcuma longa plant. Turmeric belongs to the ginger family, Zingiberaceae. People in India and across Asia have used turmeric in cooking for its flavor and yellow color for centuries.

Beyond cooking, curcumin has been used for its medicinal properties for thousands of years. The most common traditional use in India was wound healing. Turmeric contains three curcuminoids (curcumin-related compounds): curcumin, desmethoxycurcumin, and bisdemethoxycurcumin. Curcumin is the main active component.

Scientists first isolated curcumin from turmeric in 1815. In 1937, the first published article on curcumin in human disease described its beneficial effects in biliary disease (a condition affecting the bile ducts). Since then, research has continued to explore curcumin's effects on many human diseases.

Animal studies have shown a direct relationship between higher curcumin concentrations inside cells and the ability to modulate (adjust) inflammatory mediators. Experiments on cell lines and in humans confirmed these findings. Curcumin plays a role in the anti-inflammatory response by inhibiting the COX-2 pathway and blocking NF-kB activation. Both of these are key switches in the body's inflammatory response.

In more recent years, many studies have shown that curcumin has potential anti-inflammatory, anti-oxidant, anti-diabetic, and anti-cancer properties. Curcumin acts on numerous targets through various mechanisms. It alters the activity of enzymes, receptors, and transcription factors (proteins that control which genes are turned on or off).

Importantly, curcumin supplementation has been reported to cause nearly no side effects. This makes it a potential alternative to NSAIDs (nonsteroidal anti-inflammatory drugs) and other medications that carry known severe adverse effects.

Previous systematic reviews of curcumin in rheumatic diseases focused on only one specific disease or covered fewer studies than this review. Examining all studies across different rheumatic diseases allows a better evaluation of how curcumin produces its therapeutic potential through various mechanisms in multiple disease processes. This article reviews studies on curcumin's efficacy in osteoarthritis (OA), type 2 diabetes mellitus (T2DM), ulcerative colitis (UC), rheumatoid arthritis (RA), lupus nephritis (LN), and multiple sclerosis (MS).

How the Researchers Selected Studies

The researchers conducted a literature search on PubMed, a major medical research database. They used search terms combining curcumin (or curcuminoid or curcuma) with each of the six diseases studied.

The search identified 473 articles in total. Of these, 139 were on osteoarthritis, 135 were on type 2 diabetes, 95 were on ulcerative colitis, 88 were on rheumatoid arthritis, 6 were on lupus nephritis, and 32 were on multiple sclerosis.

From this initial search, the researchers applied four criteria to decide which articles to include:

1. Original research articles written in English
2. Randomized trial design
3. Included a control group receiving at least a placebo or multiple curcumin dosage arms
4. Reported a quantifiable daily oral dosage of curcumin

Only full texts of relevant articles were included after screening titles and abstracts. From this process, a total of 32 articles were included in the review.

Curcumin in Osteoarthritis

A total of 16 published articles on curcumin supplementation in osteoarthritis met the inclusion criteria. All 16 studies were randomized, placebo-controlled trials. Trial length ranged from 6 to 40 weeks. The amount of curcumin ingested ranged from 100 to 2000 mg daily.

Among the clinically effective studies — those reporting significant improvement in clinical or laboratory outcomes — the mean curcumin dosage was 834.29 mg per day, with an interquartile range of 1300 mg.

Most commonly, the curcumin used in these trials came from curcuminoids isolated from the rhizome (root) of turmeric. One study specified the use of pure curcuminoid. Seven studies specified the formulation of curcuminoids used, consisting of a ratio of curcumin to desmethoxycurcumin to bisdemethoxycurcumin.

Two studies administered oral Boswellia serrata together with curcumin supplementation. Boswellia serrata is a gum resin extract that has anti-inflammatory and anti-arthritic effects. It works by decreasing glycosaminoglycan levels, which are necessary for cartilage repair.

The clinical outcomes measured in most studies included:

• The Western Ontario and McMaster Universities Arthritis Index (WOMAC) — a standard questionnaire measuring pain, stiffness, and physical function
• Walking distance
• Visual analogue scale (VAS) — a pain rating scale
• Karnofsky performance scale — a measure of daily functioning
• Lequesne's pain functional index (LPFI)
• Clinical Global Impression (CGI)
• Knee injury and Osteoarthritis Outcome Score (KOOS)

All but two studies measured clinical outcomes. Those two studies measured only inflammatory markers and oxidative stress indicators.

In 13 of the 16 studies, dietary curcumin intake resulted in improvement of at least two clinical measures. Furthermore, seven studies showed improvement of at least three clinical measures. Studies with positive clinical outcomes most commonly reported increased walking distance and decreased WOMAC scores.

One study reported no significant improvements in pain and function, although there was a tendency toward improved scores. A total of eight studies reported laboratory findings after curcumin supplementation. Five of those eight studies reported either significantly decreased inflammatory markers or oxidative stress markers. In three studies, patients continued NSAID use alongside the curcumin supplement.

Curcumin Compared with NSAIDs

Four studies directly compared the effectiveness of NSAID use versus curcumin supplementation in osteoarthritis. NSAIDs work by inhibiting prostaglandin-synthesizing enzymes. In particular, NSAIDs inhibit the COX-1 and COX-2 pathways, which can cause adverse effects such as gastrointestinal pain. NSAIDs are also documented to inhibit the lipoxygenase pathway and interfere with G protein signal transduction.

In 2014, Kuptniratsaikul and colleagues compared the effectiveness of curcumin with ibuprofen. A total of 367 patients with knee osteoarthritis were split into two groups. One group received 1200 mg daily ibuprofen. The other group received 1500 mg daily of curcumin for 4 weeks.

Both treatment groups showed significant improvement in clinical parameters of WOMAC pain and function scores. The number of patients with adverse events was the same in both groups. However, there was a significantly higher number of patients with abdominal pain in the ibuprofen group.

These findings indicate that curcumin supplementation for osteoarthritis is as effective as ibuprofen, with fewer gastrointestinal adverse effects. A 2014 study by Nakagawa and colleagues supported this conclusion. That study reported a decrease in use of NSAIDs and other painkillers in the curcumin treatment group, as well as decreased gastrointestinal complaints.

Kuptniratsaikul and colleagues conducted a similar study in 2009. In that study, patients received either 800 mg daily ibuprofen or 2 g daily curcumin extract for 6 weeks. There was no difference in improvement in main outcomes such as pain while walking and increased knee function, except for pain on stairs. No significant difference in adverse effects between the two groups was reported.

In 2013, Kizhakkedath and colleagues tested the effectiveness of a curcumin and boswellia combination supplement versus celecoxib, a selective COX-2 pathway inhibitor. The 500 mg curcumin and boswellia formulation contained 350 mg curcumin extract and 150 mg Boswellia serrata extract. Patients were split into two groups. One group took 1000 mg of the curcumin-boswellia mixture daily. The other group took 200 mg celecoxib daily for 12 weeks.

Both treatment groups experienced significant improvement in pain scores, walking distance, joint line tenderness, and crepitus (a crackling sound in the joint). There was no significant difference between the two groups. However, the curcumin and boswellia formulation showed greater improvement in pain scores, walking distance, and joint line tenderness compared with celecoxib. Treatment was well tolerated without toxicities or adverse effects.

Overall, these studies support the comparable efficacy of curcumin in treating osteoarthritis compared with NSAIDs, with decreased adverse effects.

Effects on Inflammation and Oxidative Stress in Osteoarthritis

A total of five studies measured inflammatory markers after curcumin supplementation in osteoarthritis. Of these studies, three reported a decrease in inflammatory markers and two reported no change.

Sterzi and colleagues in 2016 was one study that did not report changes in inflammatory markers. Patients received a combination of glucosamine hydrochloride, chondroitin sulfate, and bio-curcumin, which consisted of 100 mg curcumin daily for 12 weeks. Inflammatory markers CRP (C-reactive protein) and ESR (erythrocyte sedimentation rate) did not change in the treatment group.

One study suggests that glycosaminoglycans have only a short-term effect on pain relief compared with the long treatment duration. This may explain why there was no improvement in inflammatory markers or knee range of motion. In addition, the 100 mg curcumin dosage is considerably lower than other trials with positive outcomes included in this review.

However, in 2015, Rahimnia and colleagues conducted a study in which patients received 1500 mg curcumin daily for 40 weeks. That study also did not report significant improvement in inflammatory markers.

In 2016, Srivastava and colleagues conducted a 16-week study where patients consumed 500 mg curcumin daily. Inflammatory IL-1β values significantly decreased in the curcumin group. Similarly, in 2010, Belcaro and colleagues also reported a decrease in IL-1β in the treatment group.

Patients in the Belcaro study received 1000 mg Meriva, a curcumin-phosphatidylcholine complex with improved stability and oral absorption. This complex contains a dosage of 200 mg daily of curcumin, given for 32 weeks. The treatment group used Meriva with the "best available treatment" as defined by the patient's general practitioner. In addition to decreased IL-1β levels, all tested inflammatory markers decreased. These included ESR, IL-6, sCD40L, and sVCAM-1.

Belcaro and colleagues conducted another study in 2010 with the same curcumin dosing on 50 patients for 12 weeks. That study reported a decrease in CRP, an inflammatory marker. Together, these results show that curcumin remarkably decreases inflammatory players involved in osteoarthritis.

Three studies reported decreased oxidative stress markers in osteoarthritis patients treated with curcumin. Srivastava and colleagues reported decreased GSH, ROS, and MDA. These results are supported by a study by Panahi and colleagues in 2016. That study also reported decreased MDA levels, as well as increased GSH and SOD. GSH and SOD are antioxidants that increased after a 6-week treatment of 1500 mg daily curcumin. In addition, Badria and colleagues reported a decrease in oxidative stress markers after 12 weeks of treatment with 500 mg daily curcumin.

Curcumin in Type 2 Diabetes

At least 8 studies have been conducted on the efficacy of curcumin supplements in type 2 diabetes mellitus. All included studies were placebo-controlled and randomized clinical trials. The average duration of curcumin intake ranged from 4 to 36 weeks. The amount of curcumin intake ranged from 200 to 1500 mg daily.

In the studies where curcumin supplementation proved to be clinically effective, the mean dosage was 570.79 mg, and the interquartile range was 700 mg.

Six studies specified use of varying ratios of natural curcuminoid mixtures of curcuminoid to desmethoxycurcuminoid to bisdemethoxycurcumin. The remaining study used encapsulated turmeric rhizomes. Six of the seven studies used patients already diagnosed with type 2 diabetes. One study used a pre-diabetic patient population.

The laboratory outcomes measured in most studies included:

• Blood glucose
• TNF-α (tumor necrosis factor alpha, an inflammatory signal)
• IL-6 (interleukin-6, an inflammatory signal)
• HOMA-IR (a measure of insulin resistance)

A total of five studies reported significantly improved clinical outcomes in the curcumin group. Six studies reported three or more improved laboratory measures. Three included studies assessed the effect of curcumin supplementation on complications associated with type 2 diabetes, such as atherosclerosis (hardening of the arteries) and diabetic microangiopathy (damage to small blood vessels).

Overall, the studies showed that curcumin supplementation has anti-diabetic effects and improves type 2 diabetes parameters in patients.

Detailed Diabetes Trial Results

Two of the seven studies reported anti-diabetic outcomes of glucose lowering and improved beta-cell function. Beta cells are the pancreatic cells that produce insulin.

In 2012, Chuengsamarn and colleagues conducted a 36-week study with 240 pre-diabetic patients. Patients were split into two groups. The curcumin group consumed 1500 mg curcumin daily. The placebo group consumed placebo capsules.

At the end of the study, 16.4% of subjects in the placebo group were diagnosed with type 2 diabetes. No patients in the curcumin group were diagnosed with type 2 diabetes. Curcumin improved beta-cell function, indicated by a significant increase in HOMA-β and significant decreases in C-peptide and HOMA-IR.

Curcumin also reduced inflammation by significantly increasing adiponectin, an anti-inflammatory cytokine (a signaling molecule that reduces inflammation). Interestingly, there was a slight reduction in mean body weight and waist circumference in the curcumin group by the last follow-up visit. No serious adverse effects were noted. However, a few patients noted minor symptoms of itching, constipation, or vertigo.

In 2013, Na LX and colleagues conducted a study with 100 overweight or obese type 2 diabetes patients for 12 months. Curcumin supplementation was administered as 300 mg daily. By the end of treatment, patients in the curcumin group had significantly lower fasting blood glucose levels. Patients in the curcumin group also had significantly lower HbA1c (a marker of long-term blood sugar control), HOMA-IR, free fatty acids, and triglycerides. The curcumin group also had a significant increase in LPL activity, which promotes fatty acid oxidation and utilization. This suggests a glucose-lowering effect of curcumin due to decreased serum free fatty acids.

In 2014, Na LX and colleagues investigated the role of serum adipocyte fatty acid binding protein (A-FABP) in regulating fatty acid metabolism and metabolic syndrome in patients taking curcumin. A-FABP is a cytoplasmic protein implicated in intracellular fatty acid trafficking. Animal studies have shown that a deficiency in A-FABP can improve glucose and lipid metabolism in obese and ApoE-deficient mice.

Curcumin supplementation of 300 mg daily for 12 weeks led to significant decreases in inflammation markers. These included CRP, TNF-α, and IL-6. Additionally, there were significant decreases in serum A-FABP levels. A-FABP levels positively correlated with changes in serum free fatty acid levels. Thus, serum A-FABP reduction by curcumin is associated with improved free fatty acid metabolism and lipid profile. The curcumin group also showed improved insulin resistance compared with the placebo group.

Post treatment, patients receiving curcumin in another study showed significant reductions of inflammatory markers. These included CRP, TNF-α, and IL-6. Curcumin also reduced oxidative stress markers. In a separate study, patients with type 2 diabetes taking curcumin showed significant decreases in TNF-α and IL-6. Curcumin supplementation also lowered fasting blood glucose and HbA1c.

Curcumin in Ulcerative Colitis, Rheumatoid Arthritis, Lupus Nephritis, and Multiple Sclerosis

Beyond osteoarthritis and type 2 diabetes, the review examined trials in four other conditions. The results in these conditions were more mixed.

Ulcerative colitis (UC): Three trials were conducted in ulcerative colitis. Two of the three yielded significant improvement in at least one clinical outcome.

Rheumatoid arthritis (RA): Two clinical trials were conducted in rheumatoid arthritis. The results were inconclusive.

Lupus nephritis (LN): One clinical trial was conducted in lupus nephritis. The result was inconclusive.

Multiple sclerosis (MS): Two clinical trials were conducted in multiple sclerosis. The results were inconclusive.

The authors noted that longer duration, larger cohort size, and multiple dosage arm trials are warranted to establish the long-term benefits of curcumin supplementation in these conditions.

How Curcumin Works in the Body

Multiple mechanisms of action of curcumin in these diseases have been researched. Two key mechanisms stand out.

The first is the modulation of the eicosanoid pathway toward a more anti-inflammatory pathway. The eicosanoid pathway is a series of chemical reactions that produce signaling molecules involved in inflammation.

The second is the modulation of serum lipid levels toward a favorable profile. Serum lipid levels are the levels of fats such as cholesterol and triglycerides in the blood.

At the cellular level, curcumin acts on numerous targets with various mechanisms of action. It alters enzyme, receptor, and transcription factor activity. Curcumin inhibits the COX-2 pathway and NF-kB activation, both of which are central to the body's inflammatory response.

What These Findings Mean for Patients

Overall, curcumin supplementation emerges as an effective therapeutic agent with minimal to no side effects. It can be added alongside current standard of care.

The strongest evidence supports curcumin use in osteoarthritis and type 2 diabetes. In osteoarthritis, 14 of 16 trials yielded significant improvements in multiple disease parameters. In type 2 diabetes, all 8 trials yielded significant improvement in clinical or laboratory outcomes.

For patients with osteoarthritis, the evidence suggests curcumin may be as effective as common NSAIDs such as ibuprofen. Importantly, curcumin caused fewer gastrointestinal side effects than ibuprofen in the studies that compared them directly. This is a meaningful finding for patients who cannot tolerate NSAIDs due to stomach problems.

For patients with type 2 diabetes or pre-diabetes, curcumin showed benefits for blood sugar control, insulin resistance, and inflammation. In one study of 240 pre-diabetic patients, no patients in the curcumin group progressed to type 2 diabetes, compared with 16.4% in the placebo group.

For patients with ulcerative colitis, the evidence is promising but more limited. For rheumatoid arthritis, lupus nephritis, and multiple sclerosis, the current evidence is inconclusive. Patients with these conditions should discuss curcumin with their doctor before adding it to their treatment plan.

Limitations of the Research

The authors identified several limitations across the reviewed studies.

• Study durations varied widely, from 4 weeks to 40 weeks, making it difficult to compare results directly.
• Dosages varied widely, from 66.3 mg to 2000 mg daily, with no standardized dosing protocol.
• Curcumin formulations differed across studies, including pure curcuminoid, curcuminoid mixtures, and curcumin-phosphatidylcholine complexes.
• Some studies used curcumin alongside other supplements such as Boswellia serrata, making it hard to isolate curcumin's specific effects.
• Several studies allowed patients to continue NSAID use, which could confound the results.
• Some conditions, such as lupus nephritis, had only one trial, limiting the strength of conclusions.
• Longer duration, larger cohort size, and multiple dosage arm trials are needed to establish long-term benefits.

The authors also noted that curcumin has poor oral absorption on its own. This is why some studies used special formulations, such as curcumin-phosphatidylcholine complexes, to improve stability and absorption.

Recommendations and Next Steps

Based on this review, the authors recommend the following:

1. Patients with osteoarthritis may consider curcumin supplementation as an alternative or addition to NSAIDs, particularly if they experience gastrointestinal side effects from NSAIDs.
2. Patients with type 2 diabetes or pre-diabetes may discuss curcumin supplementation with their doctor as an add-on to standard care.
3. Larger, longer trials with multiple dosage arms are needed to confirm long-term benefits across all conditions studied.
4. Future research should standardize curcumin formulations and dosages to allow better comparison between studies.
5. Patients with rheumatoid arthritis, lupus nephritis, or multiple sclerosis should wait for more conclusive evidence before relying on curcumin as a treatment.

Curcumin was consistently well tolerated across all studies. Reported side effects were minor and included itching, constipation, and vertigo in a small number of patients. In one ulcerative colitis clinical trial, serious adverse events occurred in both the curcumin group and the placebo group, and one patient taking curcumin was hospitalized with abdominal pain due to a peptic ulcer, although the rate of severe adverse events did not differ between the two groups.

Frequently Asked Questions

What is curcumin and where does it come from?

Curcumin is the main active compound in turmeric, a spice from the Curcuma longa plant in the ginger family. It has been used in cooking and for medicinal purposes for centuries, especially in India. Scientists first isolated curcumin in 1815, and it has been studied for its anti-inflammatory, anti-oxidant, anti-diabetic, and anti-cancer properties.

Which conditions have the strongest evidence for curcumin?

The strongest evidence supports curcumin for osteoarthritis and type 2 diabetes. In osteoarthritis, 14 of 16 trials showed significant improvements in multiple disease parameters. In type 2 diabetes, all 8 trials showed significant improvement in clinical or laboratory outcomes. Evidence for ulcerative colitis is promising but more limited, and results for rheumatoid arthritis, lupus nephritis, and multiple sclerosis are inconclusive.

How does curcumin compare to NSAIDs like ibuprofen for osteoarthritis?

In four studies directly comparing curcumin with NSAIDs, curcumin was as effective as ibuprofen for knee osteoarthritis. For example, a 2014 study of 367 patients found both 1200 mg daily ibuprofen and 1500 mg daily curcumin improved pain and function, but the ibuprofen group had significantly more abdominal pain. Curcumin caused fewer gastrointestinal side effects.

What does the research show for curcumin in type 2 diabetes?

All 8 reviewed trials of curcumin in type 2 diabetes showed significant improvement in clinical or laboratory outcomes. Benefits included lower fasting blood glucose, HbA1c, insulin resistance, and inflammatory markers like TNF-α and IL-6. In one 36-week study of 240 pre-diabetic patients, none taking 1500 mg curcumin daily progressed to diabetes, compared with 16.4% on placebo.

Can curcumin help rheumatoid arthritis, lupus nephritis, or multiple sclerosis?

The evidence for these conditions is inconclusive. Two trials in rheumatoid arthritis, one in lupus nephritis, and two in multiple sclerosis did not provide clear results. The authors recommend that patients with these conditions wait for more conclusive evidence before relying on curcumin as a treatment, and discuss any use with their doctor.

What are the limitations of the curcumin research?

Study durations varied from 4 to 40 weeks, and dosages ranged from 66.3 mg to 2000 mg daily with no standard protocol. Curcumin formulations differed, some studies combined curcumin with other supplements like Boswellia serrata, and some allowed continued NSAID use. Some conditions had only one trial. Curcumin also has poor oral absorption on its own.

When should a patient with osteoarthritis or type 2 diabetes seek a second opinion before adding curcumin to their treatment?

Curcumin supplementation has the strongest supporting evidence in osteoarthritis, where 14 of 16 trials showed significant improvement, and in type 2 diabetes, where all 8 trials showed benefit in clinical or laboratory outcomes. In osteoarthritis, curcumin performed comparably to ibuprofen with fewer gastrointestinal side effects. Evidence in rheumatoid arthritis, lupus nephritis, and multiple sclerosis remains inconclusive, so patients with those conditions should discuss curcumin with their doctor before adding it. A second opinion can help clarify whether curcumin fits your treatment plan. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: Curcumin in Autoimmune and Rheumatic Diseases

Authors: Melissa Yang, Umair Akbar, and Chandra Mohan

Author affiliation: Department of Biomedical Engineering, University of Houston, Houston, Texas, USA

Journal: Nutrients, 2019, Volume 11, Issue 5, Article 1004

Publication date: Published May 2, 2019

DOI: 10.3390/nu11051004

This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and should not replace consultation with a qualified healthcare provider. Patients should discuss any changes to their treatment plan with their doctor.