Cognition Supplement of the Year: 2021
CURCUMIN
An Often-Overlooked Supplement that May Assist Cognition
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Introduction

Curcumin, the primary bioactive substance found in the spice turmeric, has been selected as “Cognition Supplement of the Year: 2021″ by MCI911.com. Nicknamed “Indian Saffron” because of its brilliant yellow color, its purported benefits include anti-oxidant, anti-inflammatory, anticancer, antimicrobial, neuroprotective, and cardioprotective effects. It is generally safe, and is available over-the-counter without a prescription.

FACT:

“Americans spend over 35 billion dollars a year on dietary supplements.”

Background

Curcumin intake dates back nearly 4000 years to the Ayurvedic culture in India1 and has been utilized in many ways over the centuries for its pigment, flavor, and healing properties. It makes up about 8% of the turmeric root,2 is insoluble in water, and is often modified to increase its absorption, making it the best option for harnessing the medicinal qualities of turmeric. India is the world’s leading supplier.

Effects of Curcumin on the Brain

As we get older, our brain begins to shrink in volume; this is associated with the loss of neurons or their reduction in size and primarily affects the prefrontal cortex, cerebellum, and hippocampus. The number of synapses in the brain can also decrease and the formation of new neurons may decline. Scientists have observed age-related reductions in neurotransmitter levels.3

Inflammation, often referred to as “inflammaging,” is thought to increase with age; mounting evidence suggests that it can negatively impact the brain and cognitive health.4 Inflammation induction in rodents led to cognitive decline;4,5 other studies indicated that elevated pro-inflammatory cytokine levels are associated with decreased cognitive function.6 Curcumin has been shown to defend against neurodegeneration while promoting the growth of new neurons,7-10 which help combat the loss of brain volume. It can affect the levels of various brain neurotransmitters and, perhaps, aid in restoring their balance, which is lost as people grow older.9,11 Turmeric and curcumin have long been used for their anti-inflammatory properties.12-14

What is Cognitive Health?

Cognitive health defines how well we learn, think, and remember things. Most people think of age as an issue when it comes to declining cognitive function, but high blood pressure, depression, lack of exercise, smoking, brain injuries, alcohol consumption, social isolation, and a poor diet are also contributors.

Curcumin Aids Cognition

Several key trials using bioavailable forms of curcumin demonstrate that it can have positive effects on cognition over time. Cox et al administered curcumin to 60 elderly individuals for four weeks, assessing immediate word recall, reaction time, and visual information processing. They found that the substance improved the participants’ working memory and sustained attention.15 After repeating this study for 12 weeks in a larger cohort (85 elderly subjects), they found similar results.16
Small et al studied curcumin in a group of 40 older subjects for 18 months. The positive cognitive effects were detected by 6 months of administration and maintained throughout the duration of the trial.17 Fifteen people each from the treated and placebo groups were evaluated using a brain PET scan. The curcumin cohort displayed significantly less amyloid-beta plaque and neurofibrillary tangle deposition,17 which are associated with cell death and cognitive disorders.

Lifestyle Can Aid Cognition

A healthy lifestyle can help support optimal cognition and wellbeing. Some of the things you can do to support your cognition include:

• Staying physically active
• Maintaining a healthy diet
• Getting adequate sleep
• Remaining socially connected

Curcumin and Alzheimer’s Disease

Alzheimer’s disease (AD), a neurodegenerative disease, is the sixth leading cause of death in the United States.18 Loss of memory and cognitive function are two of its main clinical symptoms. As it progresses, people with AD can have difficulties completing normal daily tasks, getting lost, and repeating questions, while also experiencing behavior and personality changes.

AD is characterized by the buildup of amyloid-beta protein plaques and tau protein-containing neurofibrillary tangles in the brain, which form lesions and interrupt cognitive functioning.

Curcumin has been used experimentally as a diagnostic tool for AD because of how well it binds to these plaques,19 providing more evidence that the supplement can cross, and interact with, the blood-brain barrier. It can also help break down or prevent plaque formation, shown in studies using a curcumin-treated AD mouse model.20

Evidence suggests that curcumin lowers amyloid-plaque levels by suppressing beta-secretase 1 (BACE1) expression,21 an enzyme that catalyzes the first step in their formation. It also accelerated the plaque clearance by increasing the expression of proteins necessary for the phagocytosis of those proteins.22 Macrophages taken from curcumin-treated patients with AD displayed an increase in the protein uptake.23

Antimicrobial Properties of Curcumin

Although there are likely many genetic and environmental factors that contribute to the development of AD, one area of interest for scientists has been the role of infection. Curcumin has been evaluated against a number of microorganisms suspected of causing or facilitating AD, including Herpes simplex virus type 1 (HSV-1), Chlamydia pneumoniae, Borrelia burgdorferi, and Porphyromonas gingivalis,24 and has displayed antibacterial, antiviral, antifungal, and antimicrobial activities.25,26

Curcumin may also benefit cognition by modulating the balance of the bacterial species in the microbiome. The human body coexists with about 100 trillion bacteria, mostly located in the gut. This population is made up of many species that are both good and bad for the body but must live in harmony with its organ systems, cells, and immune cells.

Microbiome dysbiosis occurs when this balance is disturbed (due to diet, illness, infection, antibiotic usage, and inflammation). This can agitate the “microbiota-gut-brain-axis,” an important system that involves the bidirectional communication between gut bacteria and the brain. Data show that this occurs in individuals with AD.27 Several studies have evaluated how curcumin affects the diversity of the microbiome in rodents. Overall, the supplement significantly increased the levels of beneficial Bifidobacteria and Lactobacilli, while decreasing the pathogenic Prevotellaceae, Coriobacterales, Enterobacteria, and Enterococci bacteria.28

Poor Absorption a Drawback

Some of the criticism of curcumin stems from its suboptimal absorption.29 But a new formulation, Longvida,® composed of solid lipid curcumin particles, has increased its bioavailability30 and has been evaluated for its anti-inflammatory, cardioprotective, neuroprotective, and antioxidant properties,15,31,32while also improving cognitive function15,16 and more readily crossing the blood-brain barrier.33

Conclusions

Curcumin and its beneficial effects on inflammation, neuroprotection, neurotransmitter levels, and antimicrobial activity may improve cognition in some cases. Safe and inexpensive, compared to many prescription medicines, curcumin deserves its recognition as Cognition Supplement of the Year: 2021.

References

1. Prasad S, Aggarwal BB. Turmeric, the golden spice: from traditional medicine to modern medicine. In: Benzie IFF, Wachtel-Galor S, eds. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd ed. Boca Raton, FL: CRC Press/Taylor & Francis; 2011. Chapter 13. Available from: https://www.ncbi.nlm.nih.gov/books/NBK92752/.

2. Ruby AJ, et al. Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett. 1995;94(1):79-83. doi: 10.1016/0304-3835(95)03827-j.

3. Peters R. Ageing and the brain. Postgrad Med J. 2006;82(964):84-88. doi:10.1136/pgmj.2005.036665.

4. Simen AA, et al. Cognitive dysfunction with aging and the role of inflammation. Ther Adv Chronic Dis. 2011;2(3):175-195. doi: 10.1177/2040622311399145.

5. Murray C, et al. Systemic inflammation induces acute working memory deficits in the primed brain: relevance for delirium. Neurobiol Aging. 2012;33(3):603-616.e3. doi: 10.1016/j.neurobiolaging.2010.04.002.

6. Marsland AL, et al. Interleukin-6 covaries inversely with cognitive performance among middle-aged community volunteers. Psychosom Med. 2006;68(6):895-903. doi: 10.1097/01.psy.0000238451.22174.92.

7. 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.

8. Wu A, et al. Dietary curcumin counteracts the outcome of traumatic brain injury on oxidative stress, synaptic plasticity, and cognition. Exp Neurol. 2006;197(2):309-317. doi: 10.1016/j.expneurol.2005.09.004.

9. Xu Y, et al. Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats. Brain Res. 2007;1162:9-18. doi: 10.1016/j.brainres.2007.05.071.

10. Xu Y, et al. Curcumin reverses impaired cognition and neuronal plasticity induced by chronic stress. Neuropharmacology. 2009;57(4):463-471. doi: 10.1016/j.neuropharm.2009.06.010.

11. Pyrzanowska J, et al. The influence of the long-term administration of Curcuma longa extract on learning and spatial memory as well as the concentration of brain neurotransmitters and level of plasma corticosterone in aged rats. Pharmacol Biochem Behav. 2010;95(3):351-358. doi: 10.1016/j.pbb.2010.02.013.

12. Davis JM, et al. Curcumin effects on inflammation and performance recovery following eccentric exercise-induced muscle damage. Am J Physiol Regul Integr Comp Physiol. 2007;292(6):R2168-73. doi: 10.1152/ajpregu.00858.2006.

13. Tiwari V, Chopra K. Attenuation of oxidative stress, neuroinflammation, and apoptosis by curcumin prevents cognitive deficits in rats postnatally exposed to ethanol. Psychopharmacology (Berl). 2012;224(4):519-535. doi: 10.1007/s00213-012-2779-9.

14. Yin H, et al. Curcumin suppresses IL-1β secretion and prevents inflammation through inhibition of the NLRP3 inflammasome. J Immunol. 2018;200(8):2835-2846. doi: 10.4049/jimmunol.1701495.

15. Cox KHM, Pipingas A, Scholey AB. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. J Psychopharmacol. 2015;29(5):642-651. doi: 10.1177/0269881114552744.

16. Cox KHM, et al. Further evidence of benefits to mood and working memory from lipidated curcumin in healthy older people: a 12-week, double-blind, placebo-controlled, partial replication study. Nutrients. 2020;12(6):1678. doi: 10.3390/nu12061678.

17. 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.

18. Alzheimer’s Association. 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 2016;12(4):459-509. doi: 10.1016/j.jalz.2016.03.001.

19. Chen M, et al. Use of curcumin in diagnosis, prevention, and treatment of Alzheimer’s disease. Neural Regen Res. 2018;13(4):742-752. doi: 10.4103/1673-5374.230303.

20. Yang F, et al. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005;280(7):5892-5901. doi: 10.1074/jbc.M404751200.

21. Liu H, et al. The inhibitory effects of different curcuminoids on β-amyloid protein, β-amyloid precursor protein and β-site amyloid precursor protein cleaving enzyme 1 in swAPP HEK293 cells. Neurosci Lett. 2010;485(2):83-88. doi: 10.1016/j.neulet.2010.08.035.

22. Maiti P, et al. Curcumin modulates molecular chaperones and autophagy-lysosomal pathways in vitro after exposure to Aβ42. J Alzheimer Dis Parkinsonism. 2017;7:299.

23. Zhang L, et al. Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer’s disease patients. J Alzheimers Dis. 2006;10(1):1-7. doi: 10.3233/jad-2006-10101.

24. Abbott A. Are infections seeding some cases of Alzheimer’s disease? [Internet]. Nature News. Nature Publishing Group; 2020. Available from: https://www.nature.com/articles/d41586-020-03084-9.
Accessed January 19, 2021.

25. Moghadamtousi SZ, et al. A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed Res Int. 2014;2014:186864. doi: doi.org/10.1155/2014/186864.

26. Izui S, et al. Antibacterial activity of curcumin against periodontopathic bacteria. J Periodontol. 2016;87(1):83-90. doi: 10.1902/jop.2015.150260.

27. Kowalski K, Mulak A. Brain-gut-microbiota axis in Alzheimer’s disease. J Neurogastroenterol Motil. 2019;25(1):48-60. doi: 10.5056/jnm18087.

28. Zam W. Gut microbiota as a prospective therapeutic target for curcumin: a review of mutual influence. J Nutr Metab. 2018;2018:1367984. doi: 10.1155/2018/1367984.

29. Nelson KM, et al. The essential medicinal chemistry of curcumin. J Med Chem. 2017;60(5):1620-1637. doi: 10.1021/acs.jmedchem.6b00975.

30. Gota VS, et al. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J Agric Food Chem. 2010;58(4):2095-2099. doi: 10.1021/jf9024807.

31. Nahar PP, et al. Anti-inflammatory effects of novel standardized solid lipid curcumin formulations. J Med Food. 2015;18(7):786-792. doi: 101089/jmf.2014.0053.

32. Santos-Parker JR, et al. Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress. Aging (Albany NY). 2017;9(1):187-208. doi: 10.18632/aging.101149.

33. Begum AN, et al. Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer’s disease. J Pharmacol Exp Ther. 2008;326(1):196-208. doi: 10.1124/jpet.108.137455.

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