Curcumin Adds Spice to Brain Health

Numerous animal studies point to several mechanisms of action for curcumin’s neuroprotective properties. A study published in 2001 by Lim et al investigated the effects of low and high oral curcumin administration on a transgenic AD mouse model.² Investigators focused on inflammatory levels, degree of oxidative damage, and build-up of beta amyloid protein plaques, one of two key pathologic hallmarks of AD.

Oxidized proteins and an inflammatory chemical messenger, known as interleukin-1beta, were decreased by both low and high doses of curcumin when mouse brain slices were analyzed. Microglia numbers in the hippocampus, the brain’s memory center, were depressed by low doses of dietary curcumin. Microglia are inflammatory cells of the central nervous system (the brain and the spinal cord). Similarly, low but not high doses of curcumin were associated with diminished levels of both soluble (dissolvable in water) and insoluble (not dissolvable in water) beta amyloid protein and reduced beta amyloid plaque burden in both the hippocampus and the cortex, the outer layer of the brain.

Curcumin also directly boosts memory in rodent models. A study by Maher et al showed that a derivative of curcumin activates a specific kinase enzyme.³ A kinase’s function is to phosphorylate or add phosphate groups (phosphorus plus four oxygens) to proteins or other molecules, causing a change in the molecule’s shape, and thus its activity. Curcumin exerts its effects on a kinase called Ca2+/calmodulin-dependent protein kinase II (CaMKII).

CAMKII’s activity is necessary for long-term potentiation (LTP) to occur. LTP refers to the molecular processes by which a synapse, the little gap between neurons, or nerve cells, through which chemical messengers called neurotransmitters are sent and received, strengthens its communication force long-term.^a Study investigators demonstrated that the curcumin derivative was able to promote LTP in brain slices of rat hippocampus, the brain’s memory center. Furthermore, they showed that the rats performed better on an object recognition test after oral intake of the curcumin derivative.

Not only does curcumin reduce beta amyloid plaques in AD animal models, it also inhibits the other key pathologic process associated with AD dementia, the build-up of tau protein neurofibrillary tangles. A study by Frautschy et al published in 2011 studied the effects of oral curcumin on tau protein levels in a transgenic mouse model of AD.⁴ A formulation of curcumin with enhanced blood-brain barrier penetration (Longvida®) was used. The investigators found that Longvida curcumin treatment for five months enhanced memory performance on a water maze test and reduced soluble tau protein in the mouse hippocampus. Other studies demonstrate that curcumin stimulates neurogenesis, the creation of new neurons, in the hippocampus of rodents by altering gene expression.^5,6

To assess the impact of eating a turmeric-rich diet, an epidemiologic study published in 2006 examined the effects of curry consumption on performance on a standardized screening cognitive test, the mini-mental status exam (MMSE).⁷ A group of 1010 older Asian individuals from Singapore were administered a survey that included questions on their level of yellow curry consumption made from the turmeric spice. Subjects ranged from age 60 to 93 years old and were dementia-free. Study investigators found a correlation between higher levels of curry consumption and significantly higher scores on the MMSE. Occasional or frequent curry consumers outperformed rare consumers.

Several human studies also support a neuroprotective effect from curcumin consumption, although results are mixed. A study by Rainey-Smith et al published in 2016 investigated the effect of curcumin on cognitive performance in middle-aged and elderly adult subjects from the community.⁸ A total of 160 nondemented adults between the ages of 40 and 90 were given either a daily dose of 1500 mg of curcumin as Biocuromax (a curcumin formulation that has enhanced bioavailability) or placebo. They were followed over 12 months and tested at baseline, 6 months, and 12 months. Those receiving curcumin were protected from cognitive decline after 6 months, as assessed by the Montreal Cognitive Assessment exam.

A later study by Small et al published in 2018 followed 40 nondemented middle-aged and elderly subjects between the ages of 51 and 84 over 18 months.⁹ They received either 90 mg of curcumin twice daily as Theracumin (a bioavailable curcumin formulation) or placebo. Each participant received a battery of cognitive tests and underwent FDDNP-PET^b imaging, which uses a fluorescent imaging tracer to identify both beta-amyloid protein plaques and tau protein neurofibrillary tangles. Those given curcumin as Theracumin performed better than placebo on long-term retrieval, visual memory, and attention tests. Brain tau and amyloid buildup was also inhibited in the curcumin group compared to placebo in regions controlling mood and memory (the hypothalamus and amygdala).

In 2019, an Australian study was conducted by Scholey et al investigating the cognitive impact of the Longvida formulation of curcumin over a much shorter period of 12 weeks.¹⁰ The group had previously studied the effects of Longvida on a group of older adults over a period of only 4 weeks, which had led to significant improvements in working memory in conjunction with diminished fatigue and stress reactivity. For the 12-week study, 80 middle-aged and elderly subjects between the ages of 50 and 80 were enrolled, with cognitive assessments made at baseline, then at 4 and 12 weeks. Enrollees were given either 400 mg of Longvida containing 80 mg of curcumin or placebo. Study investigators found that curcumin treatment significantly improved tests of working memory and pattern separation at the end of 12 weeks. Both tasks rely on hippocampal function. The substance also improved fatigue scores at 4 and 12 weeks.

Side effects of curcumin are rare but reports of diarrhea, headache, and rash in doses higher than 500 mg have been reported.¹¹

Bioavailability is a concern, since curcumin is poorly absorbed and broken down and excreted very quickly. Versions of curcumin such as Longvida or Theracumin are preferred, with the former having the greatest penetration of the blood-brain barrier, since it is a lipid formulation.

Overall, there is growing evidence in the form of placebo-controlled studies on humans that curcumin can positively impact cognitive function and protect against cognitive decline. Animal studies point to multiple mechanisms of action.

Curcumin is readily available online and at health food stores. You can purchase a bottle of 50 pills of Now brand, containing Longvida curcumin at a dose of 400 mg (20% cucurminoids), at Walmart for about $22.

a. This may be due to an increase in neurotransmitters, an increase in neurotransmitter receptors, or eventually an increase in cellular projections resulting in a greater number of synapses between the cells and greater synapse surface area.

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

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2. Lim GP, et al. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001;21(21):8370-8377. doi: 10.1523/JNEUROSCI.21-21-08370.2001.

3. Maher P, et al. A pyrazole derivative of curcumin enhances memory. Neurobiol Aging. 2010;31(4):706-709. doi: 10.1016/j.neurobiolaging.2008.05.020.

4. Frautschy S, et al. Late-stage intervention with curcumin reduces soluble tau oligomers and corrects cognitive and synaptic deficits. Alzheimers Dement. 2011;7(4):S299-S300. https://doi.org/10.1016/j.jalz.2011.05.870.

5. Dong S, et al. Curcumin enhances neurogenesis and cognition in aged rats: implications for transcriptional interactions related to growth and synaptic plasticity. PloS One. 2012;7(2):e31211. doi: 10.1371/journal.pone.0031211.

6. Tiwari SK, et al. Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in Alzheimer’s disease model via canonical Wnt/β-catenin pathway. ACS Nano. 2014;8(1):76-103. doi: 10.1021/nn405077y.

7. Ng TP, et al. Curry consumption and cognitive function in the elderly. Am J Epidemiol. 2006;164(9):898-906. doi: 10.1093/aje/kwj267.

8. Rainey-Smith SR, et al. Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults. Br J Nutr. 2016;115(12):2106-2113. doi: 10.1017/S0007114516001203.

9. Small GW, 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;26(3): 266-277. doi: 10.1016/j.jagp.2017.10.010.

10. Scholey A, et al. A highly bioavailable curcumin extract improves neurocognitive function and mood in healthy older people: a 12-week randomised, double-blind, placebo-controlled trial (OR32-05-19). Curr Dev Nutr. 2019;Supplement_1: nzz052-OR32. https://doi.org/10.1093/cdn/nzz052.OR32-05-19.

11. Hewlings SJ, Kalman DS. Curcumin: a review of its’ effects on human health. Foods. 2017;6(10):92. doi: 10.3390/foods6100092.