A recent study requires that we update an article we sent out a while back on curcumin and Alzheimer’s disease.  A while back turns out to be longer than guessed.  We sent out the article in June of 2010.

http://www.denvernaturopathic.com/Alzheimers2010update.htm

 

In it, we reviewed the research on curcumin and Alzheimer’s disease being done by Sally Frautschy and Greg Cole at UCLA.  Initially, curcumin looked very promising based on epidemiology and animal experiments.  People who eat significant amounts of turmeric in their diets had a significantly lower incidence of Alzheimer’s disease (Think India and Singapore).  Mice fed turmeric in their diets were resistant to developing Alzheimer-like symptoms.  It was exciting up until human trials were run and their results were dismal.  The problem seemed to be that humans, in contrast to rodents, have a hard time absorbing concentrated turmeric supplements that are known as curcumin.  In recent years several products have been developed that address this problem and greatly increase curcumin absorption.  There are three that we are comfortable using.  While the sales representatives of the companies that sell these products each claim that their version is superior, we remain skeptical and so far think they are all excellent products.  Those products are Meriva ™, Theracurmin ®, and Longvida ®.

 

We are prompted to send out this update because of a clinical trial published last spring.[1]

The study used a randomized, double-blind, two-group parallel design comparing placebo to Theracurmin, one of these newer proprietary absorbable forms of curcumin.  The researchers looked to see if taking curcumin was associated with cognitive performance.

 

The volunteers who took part in this study were required to have objective cognitive performance scores and clinical histories that were consistent with normal aging or MCI (i.e., mild neurocognitive disorder) and inconsistent with dementia (i.e., major neurocognitive disorder). All subjects were between 50 and 90 years old and went through a gauntlet of testing including,  neuropsychological testing, screening laboratory tests, and electrocardiograms.  A total of 46 volunteers were randomized to receive curcumin or placebo. A total of 21 subjects in the experimental group and 19 in the placebo group completed the trial and were included in the data analysis.

 

The experimental group took Theracurmin (containing 90 mg of curcumin) twice daily (i.e., 180 mg curcumin/day) for 18 months.

 

Cognitive performance was assessed through verbal[1] and visual[2] testing; attention[3] was assessed as a secondary outcome. FDDNP-PET [4] signals, a test that provides in vivo images of brain plaques and tangles was performed in 30 of the volunteers (15 curcumin, 15 placebo) in various brain regions.

 

Significant differences between the two groups were seen on a number of the tests.  Long-term memory retrieval improved in the curcumin group but not in the placebo group. Total long-term memory recall, visual memory, and attention also improved significantly in the curcumin group while not in the placebo group.  FDDNP binding decreased significantly in the amygdala with curcumin compared with placebo.  In the hypothalamus, FDDNP binding did not change with curcumin but increased with placebo.

 

This study is long overdue.  Researchers have thought that curcumin should, could and would improve cognitive function for years but been unable to prove it.

For further background please read our 2010 summary.

These early human trial failures led researchers to reevaluate curcumin absorption and led the way to the development of highly absorbable forms of curcumin.  Typically, we refrain from talking about specific products by names in newsletters but making an exception is appropriate in this situation.  At this point in time, we should pay attention to specific products by name.  Some work and some don’t.

Cole and Frautschy, the UCLA Alzheimer’s researchers, developed and patented an enhanced form of curcumin that is now sold under the brand name Longvida®. [2]

Other competing products also claiming enhanced absorption are now available and sold as ‘liposomal’ curcumin.   The two most often used in clinical research trials are Meriva ™ and Theracurmin®, the product used in this current trial.

While sales representatives of the vendors all claim greater effectiveness for their company’s product, this writer tends to consider all of them as nearly equivalent.

A trial of curcumin by Rainey-Smith et al published in 2016 gave either curcumin or placebo to 96 older adults for 12 months.  A battery of clinical and cognitive measures was administered at baseline and at the 6-month and 12-month follow-up assessments and revealed no significant changes in those who received the curcumin but a decline in those who received placebo. [3]  The curcumin product used in that trial was Biocurcumax ™, more commonly known as BCM-95.  PubMed lists only three clinical trials under a search for BCM-95 ®. It was considered state-of-the-art when it first came to market, but these days we are less enthused about it.  We occasionally still use it for cancers of the GI tract where absorption is not as important.  Eleven trials are listed for the competing product Meriva ™ and eight trials for Theracurmin ™ the product used in this current trial and two for Longvida ®, the UCLA product.  As a measure of how far behind PubMed often is, this current study does not come up in my PubMed search. They must be behind in their entry of new abstracts.  One might wonder if their budget has been cut in this era when scientific findings are held in lower regard.

In 2012, DiSivestro reported on blood changes measured in a group of 19 healthy middle-aged volunteers who took Longvida® for a month.  Those taking curcumin but not those taking placebo experienced  statistically significant changes: decreased plasma triglyceride values, decreased salivary amylase levels, increased salivary radical scavenging capacities, increased plasma catalase activities, decreased plasma beta amyloid protein concentrations, decreased plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. [4]

These new studies are exciting as they are reporting significant results in contrast to earlier disappointing trials using older less absorbable forms of curcumin. These new enhanced forms of curcumin appear to be both absorbed and capable of reaching the central nervous system.

 

Debate continues as to which, if any, of these enhanced curcumins might prove to be superior.  At this point, this practitioner will admit, in private, to preferring one particular product but has absolutely no evidence to support his preference.  It may be the result of one particular company’s representative taking him to dinner and not the result of either published or clinical observations.  In actual practice, we sometimes will switch patients between these various products to see if they have a personal preference and then have them use the one they like best.  As curcumin acts as an anti-inflammatory, people will choose the product that provides the best pain relief.  We cannot readily measure the impact on what’s happening inside their brains.

 

 

 

Footnotes:

[1] Buschke Selective Reminding Test [SRT]

[2] Brief Visual Memory Test-Revised [BVMT-R]

[3] Trail Making A

[4] 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2- naphthyl}ethylidene)malononitrile positron emission tomography

 

References:

[1] Small GW, Siddarth P, Li Z, Miller KJ, et al. Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial. Am J Geriatr Psychiatry. 2018 Mar;26(3):266-277.

[2] Begum AN, Jones MR, Lim GP, Morihara T, Kim P, Heath DD, Rock CL, Pruitt MA, Yang F, Hudspeth B, Hu S, Faull KF, Teter B, Cole GM, Frautschy SA. Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer’s disease. J Pharmacol Exp Ther. 2008 Jul;326(1):196-208. Epub 2008 Apr 16.

[3] Rainey-Smith SR, Brown BM, Sohrabi HR, et al. Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults. Br J Nutr. 2016 Jun;115(12):2106-13.

[4] DiSilvestro RA, Joseph E, Zhao S, Bomser J. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J. 2012 Sep 26;11:79.