Curcumin for Autoimmunity

Curcumin, the major anti-inflammatory compound found in turmeric, is a popular supplement for those with arthritis and many other autoimmune conditions. Unfortunately,  many of the clinical trials of curcumin in psoriasis and arthritis have produced disappointing results, likely because the compound is poorly absorbed and metabolized. The good news is that some newer formulations of turmeric appear to be better absorbed and may therefore be more effective.

The 2018 edition of The Keystone Approach goes into further detail on these newer formulation and describes the promising results of trials with the phytosome form known as Meriva. Meriva is the active ingredient in a range of good quality supplements, including:

Recommended dose: Clinical trials showing beneficial effect in autoimmune disease and joint pain use either 1 or 2 grams per day, which is typically two to four capsules.

— Excerpt from The Keystone Approach (2018) — 

Turmeric is a spice from the ginger family that has been used for thousands of years in Indian cuisine and traditional medicine. Curcumin is one of the many compounds found in turmeric and is widely regarded as having powerful anti-inflammatory effects, based on thousands of laboratory studies.

Yet the ability of curcumin to calm inflammation is limited by its poor absorption and stability.[i] As a result, the real-world effects of curcumin are less impressive than lab studies would suggest. Many human clinical studies of standard curcumin supplements have produced underwhelming results, particularly in the context of autoimmune disease.[ii]

There are, however, some new formulations of turmeric that are better absorbed and much more effective.[iii] Among these new formulations, Meriva® is supported by the most clinical research, particularly in the context of joint pain and psoriasis.

Meriva contains all three curcuminoids found in turmeric, rather than just curcumin. These curcuminoids are combined with phosphatidylcholine (a component of our cell membranes) to make the curcuminoids more soluble and stable. Meriva is sold by various good-quality supplement brands, including Doctor’s Best, Thorne, Jarrow, and Pure Encapsulations.

There is convincing evidence that Meriva can improve joint inflammation and pain, at least in the context of nonautoimmune arthritis. In a placebo-controlled clinical study of osteoarthritis, patients taking Meriva saw a significant improvement in pain, swelling, and stiffness, along with a drop in all measured inflammatory markers.[iv] The patients taking Meriva were also able to reduce their NSAIDs usage by 63 percent and as a result had fewer gastrointestinal complaints.

Although this study was done in the context of osteoarthritis, not autoimmune arthritis, it does support the view that the Meriva form of curcumin can reduce joint pain and inflammation. By contrast, similar studies using other formulations of curcumin, such as BCM-95 (in CuraMed) produced very little reduction in joint pain and no improvement in inflammatory markers.[v]

In addition to reducing some aspects of inflammation, Meriva also reduces perception of pain in the short term, in a similar way to acetaminophen. (Acetaminophen is the active ingredient in Tylenol, also known as paracetamol.) A dose of 2 grams of Meriva was found to produce a short-term reduction in pain equivalent to a full dose of acetaminophen.[vi] In this study, the pain-relieving effects started about two hours after it was taken and lasted about four hours. Note that pain relief was barely noticeable at a lower dose. A relatively large dose of 2 grams is required, which is typically four capsules.

Although the main value of Meriva is likely pain reduction, it does also show promise in directly controlling some autoimmune diseases. For example, one study found that Meriva can reduce the relapse rate in chronic anterior uveitis.[vii] This is an autoimmune eye condition that is closely linked to psoriatic arthritis and ankylosing spondylitis. Another clinical study found that Meriva is helpful for maintenance of remission in ulcerative colitis.[viii] Finally, in the context of psoriasis, Meriva significantly reduced the severity of psoriasis after 12 weeks, along with a reduction in one of the main inflammatory mediators that drives psoriasis (IL-22).[ix] This lies in sharp contrast to the disappointing results seen with other versions of curcumin, which produced no benefit in psoriasis.[x]

It may be that Meriva is so much more effective than standard curcumin supplements because this formulation specifically improves the absorption of other related compounds found in turmeric, not just curcumin. In fact, the major curcuminoid present in plasma after taking Meriva is not actually curcumin, but demethoxycurcumin, a related compound that may have even more potent anti-inflammatory effects.[xi]

An area of research to watch when it comes to curcumin is the effect on the microbiome. Initial studies published in 2017 and 2018 suggest that curcumin may have beneficial effects on the microbiome, such as increasing the abundance of beneficial butyrate-producing microbes and thereby boosting regulatory T cells.[xii]

New studies also hint at a possible role for curcumin in improving the gut barrier.[xiii] This is at odds with the old idea that the gut barrier was an obstacle that needed to be overcome in order for curcumin to work. Older formulations of curcumin actually used an ingredient called piperine to improve the absorption of curcumin by increasing intestinal permeability.[xiv] This is counterproductive because it also helps other molecules cross the gut barrier too, including bacterial toxins that may increase immune activation.

If you decide to add curcumin to your supplement regime, the best option is to choose one of the many Meriva supplements available, such as Thorne Meriva 500-SF, Jarrow Curcumin Phytosome, or Pure Encapsulations Curcumasorb. Clinical trials showing beneficial effect in autoimmune disease and joint pain use either 1 or 2 grams per day, which is typically two to four capsules.

References

[i] Kurd, S. K., Smith, N., VanVoorhees, A., Troxel, A. B., Badmaev, V., Seykora, J. T., & Gelfand, J. M. (2008). Oral curcumin in the treatment of moderate to severe psoriasis vulgaris: A prospective clinical trial. Journal of the American Academy of Dermatology, 58(4), 625-631.

[ii] Dcodhar, S. D., Sethi, R., & Srimal, R. C. (2013). Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Indian journal of medical research, 138(1).

Kurd, S. K., Smith, N., VanVoorhees, A., Troxel, A. B., Badmaev, V., Seykora, J. T., & Gelfand, J. M. (2008). Oral curcumin in the treatment of moderate to severe psoriasis vulgaris: A prospective clinical trial. Journal of the American Academy of Dermatology, 58(4), 625-631

[iii] Stohs, S. J., Ji, J., Bucci, L. R., & Preuss, H. G. (2018). A Comparative Pharmacokinetic Assessment of a Novel Highly Bioavailable Curcumin Formulation with 95% Curcumin: A Randomized, Double-Blind, Crossover Study. Journal of the American College of Nutrition37(1), 51-59.

[iv] Belcaro, G., Cesarone, M. R., Dugall, M., Pellegrini, L., Ledda, A., Grossi, M. G., … & Appendino, G. (2010). Efficacy and safety of Meriva (R), a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients. Altern Med Rev15(4), 337-44.

[v] Haroyan, A., Mukuchyan, V., Mkrtchyan, N., Minasyan, N., Gasparyan, S., Sargsyan, A., … & Hovhannisyan, A. (2018). Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC complementary and alternative medicine18(1), 7.

[vi] Di Pierro Francesco, R. G., Eleonora, A. D. M., Giovanni, A., Federico, F., & Stefano, T. (2013). Comparative evaluation of the pain-relieving properties of a lecithinized formulation of curcumin (Meriva®), nimesulide, and acetaminophen. Journal of pain research6, 201.

[vii] Allegri, P., Mastromarino, A., & Neri, P. (2010). Management of chronic anterior uveitis relapses: efficacy of oral phospholipidic curcumin treatment. Long-term follow-up. Clinical Ophthalmology (Auckland, NZ)4, 1201.

[viii] Kumar, S., Ahuja, V., Sankar, M. J., Kumar, A., & Moss, A. C. (2010). Curcumin for maintenance of remission in ulcerative colitis. Cochrane Database of Systematic Reviews10.

[ix] Antiga, E., Bonciolini, V., Volpi, W., Del Bianco, E., & Caproni, M. (2015). Oral curcumin (Meriva) is effective as an adjuvant treatment and is able to reduce IL-22 serum levels in patients with psoriasis vulgaris. BioMed research international2015.

[x] Kurd, S. K., Smith, N., VanVoorhees, A., Troxel, A. B., Badmaev, V., Seykora, J. T., & Gelfand, J. M. (2008). Oral curcumin in the treatment of moderate to severe psoriasis vulgaris: A prospective clinical trial. Journal of the American Academy of Dermatology, 58(4), 625-631.

[xi] Cuomo, J., Appendino, G., Dern, A. S., Schneider, E., McKinnon, T. P., Brown, M. J., … & Dixon, B. M. (2011). Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation. Journal of natural products74(4), 664-669.

[xii] Ohno, M., Nishida, A., Sugitani, Y., Nishino, K., Inatomi, O., Sugimoto, M., … & Andoh, A. (2017). Nanoparticle curcumin ameliorates experimental colitis via modulation of gut microbiota and induction of regulatory T cells. PloS one12(10), e0185999.

Feng, W., Wang, H., Zhang, P., Gao, C., Tao, J., Ge, Z., … & Bi, Y. (2017). Modulation of gut microbiota contributes to curcumin-mediated attenuation of hepatic steatosis in rats. Biochimica et Biophysica Acta (BBA)-General Subjects1861(7), 1801-1812.

McFadden, R. M. T., Larmonier, C. B., Shehab, K. W., Midura-Kiela, M., Ramalingam, R., Harrison, C. A., … & Ghishan, F. K. (2015). The role of curcumin in modulating colonic microbiota during colitis and colon cancer prevention. Inflammatory bowel diseases21(11), 2483-2494.

Shen, L., Liu, L., & Ji, H. F. (2017). Regulative effects of curcumin spice administration on gut microbiota and its pharmacological implications. Food & nutrition research61(1), 1361780.

[xiii] Wang, J., Ghosh, S. S., & Ghosh, S. (2017). Curcumin improves intestinal barrier function: modulation of intracellular signaling, and organization of tight junctions. American Journal of Physiology-Cell Physiology312(4), C438-C445.

[xiv] Khajuria, A., Zutshi, U., & Bedi, K. L. (1998). Permeability characteristics of piperine on oral absorption-An active alkaloid from peppers and a bioavailability enhancer. Indian journal of experimental biology, 36, 46-50.

Kaushal, N., Jain, S., Kondaiah, P., & Tiwary, A. K. (2009). Influence of piperine on transcutaneous permeation of repaglinide in rats and on tight junction proteins in HaCaT cells: unveiling the mechanisms for enhanced permeation. Sci Pharm, 77, 877-897.

Feng, X., Liu, Y., Wang, X., & Di, X. (2014). Effects of piperine on the intestinal permeability and pharmacokinetics of linarin in rats. Molecules, 19(5), 5624-5633.

Jin, M. J., & Han, H. K. (2010). Effect of piperine, a major component of black pepper, on the intestinal absorption of fexofenadine and its implication on food–drug interaction. Journal of food science, 75(3), H93-H96.