Curcuma and Alzheimer’s

Turmeric (Curcuma longa) has been used in many ancient systems of medicine including Ayuveda, Siddha, and Unani. It also has special religious significance in Hinduism. It is widely consumed in Asia as a cooking spice, either as turmeric directly or as part of curry powder. In 1815, Vogel and Pelletier made the remarkable scientific discovery of curcumin by isolating the yellow colored pigment from the rhizomes of turmeric: Curcumin is a polyphenolic compound of turmeric that is poorly soluble in water and comprises 3–5% of turmeric extract. All over the world it is used as cosmetic agent and dying agent. Several years of research confirmed that curcumin has many protective and therapeutic properties, including anti-inflammatory, antioxidant, antiproliferative, anti-atherosclerotic, and anti-arthritic.

Some properties of curcumin (according to in vitro and animal models studies):

  • prevention of oxidative stress (by inhibiting lipid peroxidation)
  • anti-oxidative effect: Curcumin has more potent oxidants than alpha-tocopherol (vitamin E)
  • anti- inflammatory effect: Inhibition of inflammatory enzymes (lipoxygenase and cyclooxygenase 2)
  • increase in the levels of natural antioxidants (like glutathione, superoxide dismutase and catalase) in the brains of lead-poisoned rats leading to a reduction of lead-induced damage
  • regulation of multiple cellular signaling pathways (anticancer function)
    modulatory function on oncogenes

Once the association between inflammation and oxidative stress in the development of Alzheimer’s disease (AD) has became more and more clear (in addition to the results of epidemiological observative reports – see below), the use of curcumin in the treatment and prevention of AD has been recently studied.

Observative studies indicate a lower incidence and prevalence of AD in India. The prevalence of AD among adults aged 70-90 years in India is 4.4 times less than among adults in the same age group in different other parts of the world. This fact was easily associated with the extensive use of turmeric in Indian food. It was showed that even an occasional consumption of curry (less than once a month) can lead to better performance on standard cognitive function tests (MMSE).

Effects of curcumin in AD (in vitro and animal models studies):

  • inhibition of amyloid-β aggregation, the protein involved in the pathology of AD (formation of amyloid plaques)
  • disaggregation of existing amyloid deposits
  • prevention of aggregation of new amyloid deposits
  • reduction in the size of existing deposits
  • promotion of beneficial effects against amyloid-β-induced cognitive impairment
  • enhancement in synaptic activities

Even though human clinical trials have confirmed the high safety index of curcumin, its fundamental limitation is its poor bioavailability. Curcumin has been reported to have a low absorption rate, high biotransformation rate in intestines, and fast elimination rate from the systemic circulation. Such features significantly affect its therapeutic application and make the development of a curcumin-based drug a major challenge for the pharmaceutical industry.

In order to enhance the bioavailability of curcumin different formulations have been made:

Piperine, a major component of black pepper, known as inhibitor of hepatic and intestinal glucuronidation could be administered concomitantly with curcumin to increase bioavailability. This effect of piperine on the pharmacokinetics of curcumin has been shown to be even greater in humans than in rats. In humans, curcumin bioavailability was increased by 2,000% at 45 minutes after co-administering curcumin orally with piperine, whereas in rats, it has been found that concomitant administration of piperine 20 mg/kg with curcumin 2 g/kg increased the serum concentration of curcumin by 154% for a short period of 1-2 hours post drug. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.

Also, nanotechnology has been used to prepare nanoformulations of curcumin which have higher solubility profiles and slower biotransformation rates, like:

  • Phospholipid complexes
  • Emulsion-based delivery systems
  • Liposomes
  • Polymeric micelles
  • Curcumin nanoparticles

These represent a potential solution, enabling the use of curcumin as an effective therapeutic agent.

Side effects of curcumin:

Curcumin has been recognized to be safe by US-FDA with no toxic effects. However, some studies reported that curcumin induces dose-dependent chromosomal aberrations and DNA alterations in mammalian cell lines at a very high concentration. Gastric ulceration, hyperplasia, and inflammation of stomach, colon, and cecum were observed in rodents. Curcumin affects the metabolism of various drugs (by inhibiting cytochrome P450, glutathione-S-transferase, and UDP-glucuronosyl transferase) thereby leading to an increase in plasma concentration of drugs and toxicity. To the best of our knowledge, as of today (july 2019), there are no reports on long term toxicity of curcumin in humans.

What we can clearly note is that most of the studies are conducted using a formulation containing only curcumin or an artificial association between curcumin and other curcuminoids. Some very recent studies have demonstrated that other components of turmeric (bisdemethoxycurcumin and demethoxycurcumin), but not curcumin, have an acetylcholinesterase (AChE) inhibitory effect – the same effect of some of the actual drugs used for the treatment of AD. In the same way as observed for the other drugs used in the treatment of AD, the majority of the studies are aimed at individuals who already present clinical symptoms in a moderate or severe phase of the disease. Studies aimed for prevention, in earlier stages of cognitive impairment, could bring more consistent evidence on the benefits of Curcumin.

Maybe the “secret” would be to use the whole turmeric root, instead of one or two compounds. Another point is that the use should be constant throughout the years or at least for a long period of time, so the benefits can be noted. If used together with black pepper (piperina) the effects can certainly be enhanced.

Conclusion:

Evidence suggests that turmeric consumption has diverse potential health benefits to the elderly. Apart from its role in the treatment and prevention, curcumin acts in AD therapies as an antioxidant, anti-inflammatory agent, inhibitor of Aβ aggregation, and chelator of metal ions. Those effects are, independent of clinical studies results, a good reason to incorporate curcuminoids into our alimentary habits.

References:

  1. Rainey-Smith, S., Brown, B., Sohrabi, H., Shah, T., Goozee, K., Gupta, V., & Martins, R. (2016). Curcumin and cognition: A randomised, placebo-controlled, double-blind study of community-dwelling older adults. British Journal of Nutrition, 115(12), 2106-2113. https://www.ncbi.nlm.nih.gov/pubmed/27102361
  2. Goozee, K., Shah, T., Sohrabi, H., Rainey-Smith, S., Brown, B., Verdile, G., & Martins, R. (2016). Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer’s disease. British Journal of Nutrition, 115(3), 449-465. https://www.ncbi.nlm.nih.gov/pubmed/26652155
  3. Serafini, M.M., Catanzaro, M., Rosini, M., Racchi, M. & Lanni, C. (2017). Curcumin in Alzheimer’s disease: Can we think to new strategies and perspectives for this molecule? Pharmacological research, 124, 146-155. https://www.ncbi.nlm.nih.gov/pubmed/28811228
  4. Reddy, P. H., Manczak, M., Yin, X., Grady, M. C., Mitchell, A., Tonk, S., … Reddy, A. P. (2018). Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer’s Disease. Journal of Alzheimer’s disease: JAD61(3), 843–866. https://www.ncbi.nlm.nih.gov/pubmed/29332042
  5. Sudaram, J.R., Poore, C.P., Sulaimee, N.H.B., Pareek, T., Cheong, W.F., Wenk, M.R., Pant, H.C., Frautschy, S. A., Low, C.M. & Kesavapany, S. (2017). Curcumin Ameliorates Neuroinflammation, Neurodegeneration, and Memory Deficits in p25 Transgenic Mouse Model that Bears Hallmarks of Alzheimer’s Disease. Journal of Alzheimer’s Disease, 60(4), 1429-1442. https://www.ncbi.nlm.nih.gov/pubmed/29036814
  6. Armed, T., Enam, A., Gilani, A.H. (2010). Curcuminoids enhance memory in an amyloid-infused rat model of Alzheimer’s disease. Neuroscience, 169 (3), 1296-1306. https://www.ncbi.nlm.nih.gov/pubmed/20538041
  7. Ahmed, T., Gilani, A.H. (2009). Inhibitory effect of curcuminoids on acetylcholinesterase activity and attenuation of scopolamine-induced amnesia may explain medicinal use of turmeric in Alzhiemer’s disease. Pharmacology, Biochemistry and Behavior, 91 (4), 554-559. https://www.ncbi.nlm.nih.gov/pubmed/18930076
  8. Hishikawa, N., Takahashi, Y., Amakusa, Y., Tanno, Y., Tuji, Y., Niwa, H., … Krishna, U. K. (2012). Effects of turmeric on Alzheimer’s disease with behavioral and psychological symptoms of dementia. Ayu33(4), 499–504 https://www.ncbi.nlm.nih.gov/pubmed/23723666
  9. Bhat, A., Mahalakshmi, A. M., Ray, B., Tuladhar, S., Hediyal, T. A., Manthiannem, E., … Sakharkar, M. K. (2019). Benefits of curcumin in brain disorders. BioFactors, biof.1533. https://www.ncbi.nlm.nih.gov/pubmed/31185140

 

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