Best Curcumin Supplements

Introduction

Introduction

Hundreds of studies have been published in peer-reviewed journals on the potential health benefits of curcumin. Curcumin is a vibrant yellow compound found in the spice turmeric. It is a small molecule that is the archetypal 'curcuminoid', and has effects similar to other polyphenols (e.g., blueberry-derived flavonoids).

When I first became interested in supplementing curcumin, I succumbed to paralysis by analysis. There are too many curcumin formulations on the market and it's difficult to evaluate how they stack up.

Many proprietary curcumin brands fund the research on their own product. This makes it hard to trust some of the comparative studies on curcumin bioavailability. The most helpful and unbiased study may very well be Munjal's study compares 7 different curcumin formulations. The curcumin-hydroxypropyl-β-cyclodextrin inclusion complex (HIC) performed the best in terms of overall bioavailability. To my knowledge, HIC is not available to the consumer.

Part of the appeal of curcumin is that it's:

  • benign, even at high doses
  • plant-derived - it comes from the spice turmeric used in Indian curries
  • may prevent Alzheimer's, a disease that's notoriously intractable. As yet, there's no medicine that alters the progression of the disease - currently available drugs only temporarily control the symptoms.

Most evidence for the beneficial effects of curcumin are from studies in animal models (like rodents) and in the petri dish. It remains to be seen whether putative health benefits will translate to humans. But at the very least, curcumin is not harmful. Curcumin was safe even when consumed at a daily doses as high as 12g for 3 months [1].

BioPerine

BioPerine

BioPerine curcumin is a combination of piperine (derived from black pepper) and curcumin. Adding piperine to curcumin is the original approach used to enhance the bioavailability of curcumin.

Piperine inhibits the enzyme that metabolizes curcumin, CYP3A4. If you co-ingest curcumin with piperine (or pepper), you prolong the effect of curcumin and increase its absorption.

The BioPerine patent (US5536506) was filed February 24, 1995 by Sabinsa Corporation. The patent expired in 2015, resulting in many copycat products.

Nevertheless, BioPerine is preferred because Sabinsa has an established history of manufacturing the product. Many lesser known brands use BioPerine in their product.

Further reading: Influence of Piperine on the Pharmacokinetics of Curcumin in Animals and Human Volunteers (1997)

Note: Sabinsa is listed as a conflict of interest in the paper because they funded the study.

Longvida

Longvida

There's some compelling evidence that Longvida's formulation tangibly boosts absorption of curcumin. According to Longvida, their product is 65x more bioavailable than curcumin alone.

This claim is based on results from a 2010 paper, Safety and Pharmacokinetics of a Solid Lipid Curcumin Particle Formulation in Osteosarcoma Patients and Healthy Volunteers.

Longvida uses SLCP technology to deliver free curcumin. SLCP is solid-lipid curcumin particle technology.

Notable facts:

  • Longvida delivers free (not glucuronidated or inactive) curcumin.
  • Longvida's been the subject of both placebo-controlled efficacy as well as published safety trials.
  • SLCP entails dissolving curcumin into a lipid particle. When this particle enters the small intestine, it dissolves into bile acids where it is absorbed into the bloodstream. The idea is to "protect" the curcumin from inactivation by liver enzymes.
  • This approach to curcumin delivery hinges on the fact that curcumin is lipid soluble (or hydrophobic). Because curcumin won't dissolve in water, it makes sense to dissolve it in lipids. Indian curries are often oily and contain other fats that naturally enhance curcumin absorption.

Meriva

Meriva

Complexing curcumin with phospholipids (a phosphatidylcholine-curcumin complex referred to as Meriva) can increase its incorporation into lipophilic membranes, raising Cmax and AUC fivefold in rats.

This makes 450mg Meriva as powerful as 4g curcumin in individuals (unpublished research). Other trials reported a 29-fold higher absorption, although the increased absorption favors the inactive demethoxycurcumin metabolite rather than curcumin

Further reading: Colloidal Submicron-Particle Curcumin Exhibits High Absorption Efficiency: A Double-Blind, 3-Way Crossover Study (2015)

Theracumin

Theracumin

Theracumin is curcumin dispersed with colloidal sub-micron particles.

Researchers compared the absorption efficiency in human voluneteers of three curcumin formulations: Theracumin, Meriva (curcumin-phospholipid), and BCM-95. Read the paper here: Colloidal Submicron-Particle Curcumin Exhibits High Absorption Efficiency (2015)

Here's some quick-and-dirty background info on the study

  • BCM-95 is produced by micronizing curcumin and complexing it with essential oils of the tumeric rhizome. The bioavailability of BCM-95 is 6.9x higher than typical curcumin [1].
  • Meriva is a lecithinized formulation of curcumin. Cuomo et al found it increased curcumin absorption by 29x compared with controls [2].
  • Theracumin is curcumin dispersed with colloidal submicron-particles. Theracurmin contains dextrin, maltose, Curcuma longa extract, gum ghatti, citric acid, cornstarch, silicon dioxide, calcium stearate, hydroxypropyl methylcellulose (capsule)

The maximal plasma curcumin concentration (0–24 h) of Theracur-min was 10.7 to 5.6 times higher than those of BCM-95 and Meriva, respectively.

Moreover, the area under the blood concentration-time curve at 0–24 h was found to be 11.0- and 4.6-fold higher with Theracurmin than BCM-95 and Meriva, respectively. These data indicate that Theracurmin exhibits a higher absorption efficiency than other curcumin formulations.

So what's the catch?

The problem is that the researchers had a conflict of interest, because this study was partly funded by Theracumin:'This work was supported by a grant from .. joint research funding from the Theravalues Corporation'.

1. Antony B, Merina B, Iyer VS, Judy N, Lennertz K, Joyal S. 2008. A pilot cross-over study to evaluate human oral bioavailability of BCM-95CG (BiocurcumaxTM), a novel bioenhanced preparation of curcumin. Indian J Pharm Sci 70: 445–449

2. Cuomo J, Appendino G, Dern AS, Schneider E, McKin- non TP, Brown MJ, Togni S, Dixon BM. 2011. Compara- tive absorption of a standardized curcuminoid mixture and its lecithin formulation. J Nat Prod 74: 664–669.

Bioavailability Woes of Curcumin

Curcumin suffers from notoriously poor oral bioavailability. In pharmacology, bioavailability is:

The fraction of a drug that enters the bloodstream when introduced into the body.

This is the fraction of drug that is able to have an active, biological effect. When a drug is consumed it can be transformed into an inactive compound or excreted unchanged too quickly to have an effect.

In practice, poor bioavailability means that you can ingest a lot of curcumin, but little of it makes it into circulation without being degraded by the liver and excreted.

What happens if you take a large dose of curcumin? You’ll see a spike in curcumin blood levels that lasts maybe 15 minutes - but then it will drop off to zero. The top of this spike is the Cmax, the maximum drug concentration observed.

In order to realize the health benefits of curcumin, you need a sustained increase in circulating curcumin.

Curcumin metabolism

The major biliary metabolites of curcumin are glucuronides of tetrahydrocurcumin (THC) and hexahydrocurcumin (HHC). The minor metabolites are dihydroferulic acid and ferulic acid.

Orally administered curcumin is absorbed from the alimentary tract and present in the bloodstream after being metabolized to glucuronide/sulphate conjugates.

Bioavailability != Absorption

Dr. Easton says it best:

There is a lot of confusion about curcumin bioavailability versus absorption. Curcumin is absorbed, but not necessarily bioavailable. Further GI and liver glucuronidation or sulfation "tagged curcumin" which interfere with bioavailability it some tissues also leadds to its rapid removal by the kidneys. Unliked tagged curcumin, free curcumin readily crossed the blood brain barrier and is relatively stable.

Enhancing Curcumin’s Bioavailability

Curcumin is rapidly glucuronidated and sulphonated in the liver (called hepatic first-pass effect). The glucuronidated curcumin is an inactive metabolite so it doesn't contribute to curcumin's beneficial effects.

Nutraceutical companies have tried to tackle curcumin’s bioavailability issues through a few strategies. The original approach is adding piperine (derived from pepper) to curcumin. If you look on Amazon, the vast majority of the curcumin products will be a simple combination of piperine (often as bioperine) with curcumin.

How Does Piperine Improve Bioavailability?

Piperine inhibits the enzyme that metabolizes curcumin, CYP3A4. If you co-ingest curcumin with piperine (or pepper), you prolong the effect of curcumin and enhance its bioavailability.

Which Curcumin Supplement Should You Get?

In many cases, brand doesn't really matter. You can pay a lot of money for a fancy bottled water, but it’s probably no better than tap water.

But with curcumin, brand matters! That's because how curcumin is formulated markedly affects bioavailability and absorption. Curcumin brands adopt different drug delivery technologies to enhance the bioavailability (and therefore potential health benefits) of curcumin.

Comparing Curcumin Supplements

There's a great 2011 study by Munjal et. al. that compares seven different curcumin formulations. You can read it here: Comparative oral bioavailability advantage from curcumin formulations (2011).

Specifically, the authors evaluate these formulations:

  • Aqueous suspension (AS). This is like the control group - it's curcumin mixed with water. Curcumin isn't water soluble which is why this strategy is ineffective.
  • Micronized suspension (MS).
  • Nanosuspension (NS), e.g., Theracumin.
  • Amorphous solid dispersion (ASD).
  • Hydroxypropyl-β-cyclodextrin inclusion complex (HIC).
  • Combination with piperine (WP).
  • Curcumin–milk composite (MC).

All of these approaches work by protecting curcumin from degradation so that it has time to diffuse into tissues throughout the body. To my knowledge, no company has combined these strategies. It is only natural for people to want to hedge their bets, so it would be an interesting to add piperine to liposomal curcumin, for example.

Munjal's Comparative Study of Curcumin Oral Bioavailability

AS = aqueous suspension, MS = micronized suspension, NS = nanosuspension, ASD = amorphous solid dispersion, HIC = hydroxypropyl-β-cyclodextrin inclusion complex, WP = combination with piperine, MC = curcumin–milk composite.

Munjal's paper concludes:

The aim of the present study was to study the oral bioavailability of seven different formulations of curcumin (CRM)…

Aqueous suspension provided a Cmax and AUC(0−t) of 28.9 ng/ml and 26.9 ng h/ml, respectively.

In comparison, statistically significant increase in the oral bioavailability was obtained with the nanosuspension, HP-β-CD inclusion complex, and amorphous solid dispersion with 251%, 567%, and 446% increase in terms of AUC(0−t) and 405%, 415%, and 270% in terms of Cmax.

However, no significant increase in AUC(0−t) and Cmax was observed with piperine and micronized suspension. The milk composite reduced the oral bioavailability of CRM (10% and 37% in terms of AUC(0−t) and Cmax).

A statistically significant increase in the Tmax was observed with piperine and in HP-β-CD complex, while the Tmax was reduced for nanosuspension. The results provide interesting insights into the role of solubility enhancement and metabolism inhibition, for improving the oral bioavailability of CRM.

Formulations

Curcumin inherently is poorly absorbed when ingested alone 1. 8 grams of curcumin fails to increase serum levels.2 Thus, biomedical science has attempted to invent methods to enhance the amount of curcumin that reaches circulation.

Curcumin plus piperidine from black pepper extract (inhibitor of glucuronidation) increases the bioavailability of curcumin 20-fold when 20mg piperidine is used alongside 2,000mg curcumin.3

Theracumin emulsions (nanoparticles) possesses a 40-fold higher AUC (area under the curve) when compared with basic curcumin power in rats, and a 27-fold higher AUC in individuals.4

Although another study found just a 10-fold increase in AUC and a 40-fold increase in Cmax in rodents.5 This increased bioavailability is, in part, due to increased water-solubility.6 Nanoparticles can be used up to 210mg without any ceiling effects. Nanoparticles increase Cmax to 275 /-67ng/mL, an AUC of 3,649 /-430 ng/ml/h, and a half-life of 13 /-3.3 hours.6

Benefits of Curcumin Supplementation

Curcumin boasts beneficial effects on the nervous and cardiovascular systems. It has anti-inflammatory, anti-cancer, and neuroprotective properties, to name a few 7. The curcumin in curries may even explain the lower incidence of neurodegenerative disease in India 8. Here’s a laundry list of the documented health benefits of curcumin (with citations):

  • Pronounced anti-inflammatory effects
  • Antioxidative, anti-lipofusinogenesic, and anti-aging effects in the brain of animals 9
  • Increased expression or activity of antioxidant enzymes like superoxide dismutase (SOD) 10
  • Decreased beta-amyloid, the protein implicated in the pathogenesis of Alzheimer’s disease 11
  • Neuroprotective effects mediated by decreased microglial activation, metal chelation, and suppression of inflammatory mediators
  • Enhanced hippocampal neurogenesis 12(the process by which new neurons are integrated into the adult mammalian CNS)
  • Decreased risk of neurodegenerative disease 13

References

Further reading: Comparative oral bioavailability advantage from curcumin formulations (2011).

  1. Sharma RA, Mclelland HR, Hill KA, et al. Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res. 2001;7(7):1894-900.

  2. Lao CD, Ruffin MT, Normolle D, et al. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med. 2006;6:10.

  3. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998;64(4):353-6.

  4. Sasaki H, et al. Innovative preparation of curcumin for improved oral bioavailability . Biol Pharm Bull. (2011)

  5. Zhongfa L, et al Enhancement of curcumin oral absorption and pharmacokinetics of curcuminoids and curcumin metabolites in mice . Cancer Chemother Pharmacol. (2012)

  6. Kanai M, et al Dose-escalation and pharmacokinetic study of nanoparticle curcumin, a potential anticancer agent with improved bioavailability, in healthy human volunteers. Cancer Chemother Pharmacol. (2012) 2

  7. "Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis."

  8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2781139/

  9. Bala K, Tripathy BC, Sharma D. Neuroprotective and anti­ageing effects of curcumin in aged rat brain regions . Biogerontology. 2006;7(2):81­9.

  10. Kalpravidh RW, Siritanaratkul N, Insain P, et al. Improvement in oxidative stress and antioxidant parameters in beta­thalassemia/Hb E patients treated with curcuminoids . Clin Biochem. 2010;43(4­5):424­9. [ref30] Mishra S, Palanivelu K. The effect of curcumin (turmeric) on Alzheimer's disease: An overview. Ann Indian Acad Neurol . 2008;11(1):13­9.

  11. Mishra S, Palanivelu K. The effect of curcumin (turmeric) on Alzheimer's disease: An overview. Ann Indian Acad Neurol . 2008;11(1):13­9.

  12. Kim SJ, Son TG, Park HR, et al. Curcumin stimulates proliferation of embryonic neural progenitor cells and neurogenesis in the adult hippocampus . J Biol Chem. 2008;283(21):14497­505.

  13. http://alzheimer.neurology.ucla.edu/Curcumin.html