The theme for AOR this month is Arthritis and Joint Health, so I thought this was a topic worth discussing. Ankylosing spondylitis (AS) is a progressive inflammatory bone disease that usually begins in the sacroiliac joints of the pelvis and then migrates up the spine through the lumbar, thoracic and cervical areas. Deterioration of the bone and cartilage can lead to fibrous tissue deposits and eventual fusion of the spinal segments, commonly referred to as “bamboo spine”. AS affects approximately 1% of Canadians with prevalence being three times more likely in males than females. While the direct cause is unknown,
Several years ago, it was observed that patients with advanced cardiovascular disease were far more likely to have amyloid plaques in their brains than individuals without cardiovascular disease33. High blood cholesterol was also linked to the development of Alzheimer’s earlier in life34. Similarly, people who effectively managed their cholesterol with statin treatment were less likely to develop Alzheimer’s and similar dementias than individuals with high and unmanaged cholesterol35. Taken together, the data suggests a strong connection between cholesterol and Alzheimer’s disease.
There are several possible reasons for the connection. Cardiovascular disease due to high blood cholesterol also affects blood vessels in the brain.
Cholesterol plaques in blood vessels reduce the efficiency with which amyloid beta and similar toxins are removed from the brain; thus, increasing the likelihood that amyloid plaques will form. A key characteristic of cardiovascular disease is inflammation, which is also associated with Alzheimer’s disease.
People who use anti-inflammatory drugs over a long time period are less likely to develop Alzheimer’s disease36. Inflammation increases both the formation of amyloid beta and its deposition into amyloid plaques; thus, promoting both the development and progression of Alzheimer’s disease37,38. This means that natural health products which lower cholesterol and reduce inflammation may protect the brain from Alzheimer’s disease.
ANKASCIN AND ALZHEIMER’S DISEASE
Dr. Pan made the surprising and welcome discovery that red yeast rice supplements containing monascin and ankaflavin effectively reduced the signs and symptoms of Alzheimer’s disease.
Researchers in Dr. Pan’s laboratory used several methods to verify this finding. It is possible to mimic the early stages of Alzheimer’s disease in rats by injecting amyloid beta aggregates into their brains. The researchers used this approach with rats that were also fed high-fat diets, to simulate the high-cholesterol risk conditions associated with early onset Alzheimer’s disease. They treated some of these rats daily with either monascin or ankaflavin for 4 weeks, and then tested their ability to learn and remember how to escape from maze. The amyloid beta-injected rats had difficulties in both learning and remembering the escape task. In contrast, the performance of rats supplemented with monascin or ankaflavin performed just as well as normal, healthy rats39. This suggested that monascin and ankaflavin could reverse the cognitive decline seen in Alzheimer’s disease.
Dr. Pan’s group used another method to evaluate the use of Ankascin in this context. High levels of aluminum in the brain can induce Alzheimer’s disease by making amyloid beta more likely to form plaques40,41. In this experiment, rats with aluminum-induced Alzheimer’s disease were treated with Ankascin, or with donepezil (a drug used to treat Alzheimer’s) for 1 month, after which their symptoms were evaluated. As expected, the aluminum caused several symptoms of Alzheimer’s disease, including memory problems, higher amyloid beta production, and amyloid plaques.
However, rats supplemented with Ankascin had none of these symptoms42. Remarkably, the only effect of donepezil was to improve short-term memory, and had no benefit against the plaques themselves.
These exciting results showed that Ankascin was actually more effective at treating Alzheimer’s disease than a prescription drug.
33. Sparks, D. L., Hunsaker, J. C., Scheff, S. W., Kryscio, R. J., Henson, J. L. and Markesbery, W. R. (1990). Cortical senile plaques in coronary artery disease, aging and Alzheimer’s disease. Neurobiology of Aging 11: 601–7
34. Pappolla, M. A., Bryant-Thomas, T. K., Herbert, D., Pacheco, J., Fabra Garcia, M., Manjon, M., Girones, X., Henry, T. L., Matsubara, E., Zambon, D., et al. (2003). Mild hypercholesterolemia is an early risk factor for the development of Alzheimer amyloid pathology. Neurology 61: 199–205.
35. Jick, H., Zornberg, G., Jick, S., Seshadri, S. and Drachman, D. (2000). Statins and the risk of dementia. The Lancet 356: 1627–1631
36. Etminan, M., Gill, S. and Samii, A. (2003). Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer’s disease: systematic review and meta-analysis of observational studies. BMJ 327: 128. ed0 Grid
37. Harris-White, M. E., Chu, T., Balverde, Z., Sigel, J. J., Flanders, K. C., Frautschy, S. A., Tran, T., Ubeda, O., Ashe, K. H., Frautschy, S. A., et al. (1998). Effects of transforming growth factor-beta (isoforms 1-3) on amyloid- beta deposition, inflammation, and cell targeting in organotypic hippocampal slice cultures. The Journal of Neuroscience 18: 10366–74.
38. Weggen, S., Eriksen, J. L., Das, P., Sagi, S. A., Wang, R., Pietrzik, C. U., Findlay, K. A., Smith, T. E., Murphy, M. P., Bulter, T., et al. (2001). A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity. Nature 414: 212–216.
39. Lee, C. L., Lin, P. Y., Hsu, Y. W. and Pan, T. M. (2015). Monascus-fermented monascin and ankaflavin improve the memory and learning ability in amyloid β-protein intracerebroventricular-infused rat via the suppression of Alzheimer’s disease risk factors. Journal of Functional Foods 18: 387–399
40. Kawahara, M. (2005). Effects of aluminum on the nervous system and its possible link with neurodegenerative diseases. Journal of Alzheimer’s Disease 8: 171–82
41. Rondeau, V., Jacqmin-Gadda, H., Commenges, D., Helmer, C. and Dartigues, J.-F. (2008). Aluminum and Silica in Drinking Water and the Risk of Alzheimer’s Disease or Cognitive Decline: Findings From 15-Year Follow-up of the PAQUID Cohort. American Journal of Epidemiology 169: 489–496
42. Chen, C.-L. L., Chang, K.-Y. Y. and Pan, T.-M. M. (2016). Monascus purpureus NTU 568 fermented product improves memory and learning ability in rats with aluminium-induced Alzheimer’s disease. Journal of Functional Foods 21: 167–177