Ok, it’s not a simple as the headline, but it’s close.

Population studies in India showing a lower incidence of Alzheimer’s and better cognitive performance in older adults who regularly eat yellow curry have long intrigued researchers.  The effort to prove that curcumin is neuroprotective has been active for more than a decade, but previous curcumin research has had mixed results.  A new study from UCLA may change all that.

Curcumin vs Curry.  Curry starts with the underground stems of Curcuma longa (other famous members of the family are ginger and cardamom) that are dried and ground into turmeric.  Turmeric gives the yellow color to Indian curry and American mustard. Curcumin makes up only 2-6% of turmeric’s volume, but it is the most active ingredient and is a powerful antioxidant and anti-inflammatory.  So when we talk about the effects of eating curry we are really talking about the curcumin that it contains.

To better understand why recent research has had better luck finding positive results from the use of curcumin I looked at two of the trials from 2008 and 2012 and found them to be a bit of a dog’s breakfast.  Both studies used subjects who already had Alzheimer’s (at least one had to use caregiver consent when subjects were not able to understand their role in the study) and both used a bio-unavailable source of curcumin.  I’ll explain why both of those conditions are problematic (and yes this qualifies as hindsight bias).

When considering the previous disappointing results of research into curcumin and Alzheimer’s it’s important to understand that the neuropathology of Alzheimer’s (amyloid-β plaques and tau tangles) begins decades before people develop symptoms of dementia.  The studies showing no efficacy for curcumin were really showing that there was no efficacy for biounavailable curcumin in a demented population.  The older studies did not investigate the role of curcumin as a preventative measure (a neuroprotective).

The other critical difference, as you shall see, between the older studies and more recent research is the use of a bioavailable form of curcumin.  Bioavailable means that the body can move the desired compound from the gut into the bloodstream.  How important is a  bioavailabe form of curcumin to this research?   “In healthy subjects, the mean peak concentration of curcumin achieved from dosing 650 mg of a solid lipid curcumin particle was 22.43 ng/mL, whereas plasma curcumin from dosing an equal quantity of unformulated 95% curcuminoids extract was not detected.” (Gota et al. 2010)  In other words, taking the standard supplement form of curcumin was so biounavailable as to not even register in the blood.

When researchers began using bioavailable sources of curcumin and non-demented adult subjects, the results became much more interesting.  A randomized, double-blind, placebo-controlled trial examined the effects of solid lipid curcumin formulation (400 mg as Longvida®) on cognitive function, mood and blood biomarkers in 60 healthy adults aged 60-85.  Again, using a bioavailable form of curcumin, they were able to show significant improvement in attention and working memory only one hour after administering curcumin.  Working memory and mood were significantly better following four weeks of treatment.  Finally, curcumin was associated with significantly reduced cholesterol.

Australian researchers in 2016 in a randomized, double-blind, placebo-controlled study  conducted for 12 months, found that the bioavailable curcumin group (500 mg BiocurcumaxTM capsule three times a day) maintained general cognitive function over six months.  The placebo group declined in its performance on the MMSE.

All of this leads to a new UCLA study published in late 2017 looking at the possible neuroprotective benefits of curcumin entitled 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.  They used a bioavailable form of curcumin and adults who were not demented, but had mild cognitive impairment (MCI).  The results are exciting.

Simple Summary

Curcumin protected the brains of participants and improved their memory and attention.

More Detail

Compared to placebo, the curcumin group showed significant improvement for primary verbal memory, primary visual memory and measure of attention.  PET scans showed strong evidence that amyloid beta deposits and tau tangles in the amygdala declined significantly in the curcumin group.  Furthermore, deposits and tangles in the hypothalmus of the placebo group showed a significant increase after 18 months, but the curcumin group was spared this unfortunate result.

This was the first in vivo human study to look at curcumin’s effect on amyloid plaques and tau tangles.   Previously, the UCLA group had developed a method to view amyloid plaques and tau tangles in vivo, which they used here for measures at baseline and again at 18 months.

Into The Weeds

This was a randomized, double-blind, placebo-controlled study with a duration of 18-months.  Participants were middle-aged and older (between 50 and 90 years) non-demented adults.  The bioavailable form of curcumin was Theracurmin dispersed with colloidal nanoparticles.  The study sought to determine the effects of curcumin on memory performance and to explore its potential impact on neurodegeneration.

All subjects were screened to ensure they met inclusion criteria and given MRI scans to rule out any reversible causes of cognitive impairment.  During baseline assessments, participants received electrocardiograms, complete blood counts, and testing for vital signs, serum electrolytes, and thyroid function.

Mood and cognitive function were assessed using the Montreal Cognitive Assessment, and the Beck Depression Inventory.  To further exclude subjects with dementia, as opposed to MCI or normal aging, the researchers used a battery of tests including:

  • attention and psychomotor speed (Trail Making Test A, WAIS-III Digit Symbol Substitution);
  • visuospatial functioning (WAIS-III Block Design Test, Rey-Osterrieth Complex Figure Test [copy]);
  • executive functioning (Trail Making Test B, Stroop Interference [Kaplan version], F.A.S. Letter Fluency Test);
  • learning (Buschke-Fuld Selective Reminding Test [SRT][total recall], Wechsler Memory Scale-3rd Edition [WMS-III] Verbal Paired Associations I, Benton Visual Retention Test);
  • delayed recall (Buschke-Fuld SRT [Delayed Recall], Rey-Osterrieth Complex Figure Test [recall], WMS-III Verbal Paired Associations II);
  •        language or semantic memory (Boston Naming Test, Animal Naming Test);
  •        and finally subjects received a memory functioning questionnaire.

Participants also received a PET scan at baseline.  The PET scan technique used is called FDDNP-PET, which stands for 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile positron emission tomography.  I think we can all be grateful they decided to shorted the name.  The FDDNP is injected into the bloodstream, crosses the bbb, binds with amyloid plaques and tau tangles in the brain and “lights up” in the PET scanner.  The resulting images provide a detailed map of brain plaques and tangles.

Areas of interest in the brain included: “the parietal, medial temporal (limbic regions, including hippocampus, parahippocampal areas, and entorhinal cortex), lateral temporal, posterior cingulate, anterior cingulate, amygdalahypothalamusoccipital, motor, and frontal regions.”

The curcumin group received Theracurmin (containing 90 mg of curcumin) twice daily (i.e., 180 mg curcumin/day).  The placebo group received an identical looking pill.

To test the memory effects of curcumin, they used the Consistent Long Term Retrieval score and the Total Recall score from the Buschke SRT as primary outcome measures after 6, 12, and 18 months of treatment.  The Brief Visual Memory Test-Revised (BVMT-R) was the primary outcome measure for visual memory.  They used the Trail Making Test Part A, as a secondary outcome measure for attention.  For mood they repeated the Beck Depression Inventory.

For the primary verbal memory outcome the curcumin group showed significant improvement from baseline after 18 months of treatment and the placebo group did not.  For the SRT Total score the curcumin group showed significant improvement from baseline to 18 months and the placebo group did not.

For the primary visual memory outcome the curcumin group showed significant improvement from baseline to 18 months and the placebo group did not.  For the BVMT-R Delay score, the curcumin group showed significant improvement from baseline to 18 months and the placebo group did not.

For the secondary outcome measure of attention the curcumin group improved significantly from baseline to 18 months and the placebo group did not.

The curcumin group also showed significant improvements in Beck Depression Inventory scores and the placebo group did not.

At baseline, regional FDDNP binding values did not differ significantly between the curcumin and placebo treatment groups, but after 18 months of treatment there were significant changes in two regions of interest. In the amygdala (important to memory processing, decision-making, and emotional responses) FDDNP binding levels declined significantly in the curcumin group and not in the placebo group.  The amygdala binding values were significantly correlated with changes in Beck Depression Inventory scores in the curcumin group.  Binding values in the hypothalamus (links the CNS to the endocrine system, processes emotion response, and effects other cortical regions involved in Alzheimer’s) were inversely significant.  The curcumin group had no change, but the placebo group continued to accumulate amyloid plaque and tau tangles.

Final Thoughts

Curcumin is not particularly well absorbed by the intestine, and is rapidly metabolized and eliminated.  That the daily oral ingestion of a bioavailable form of curcumin had such dramatic results may also rest with the fact that dosing occurred 2x per day.

Curcumin does not cross the blood–brain barrier well, indicating that it’s beneficial effects start on the luminal (blood) side of the BBB.Exactly how curcumin pulls off these results isn’t certain, but its anti-inflammatory effects are a strong possibility, as brain inflammation has been linked to both Alzheimer disease and major depression. As an antioxidant, curcumin would help to counter oxidative stress which has also been linked to Alzheimer’s.Separately or together, curcumin’s ability to:

certainly doesn’t hurt.