Crocin Improves Sleep Quality and Removes Amyloid, Quality Sleep Washes Out Alzheimer’s Toxins and Amyloid.

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In the November 1, 2019 issue of Science, two studies were published: "Deep sleep drives brain fluid oscillations” by Grubb & Lauritzen of University of Copenhagen in Denmark and "Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep" by Fultz N, et al. of Boston University and Harvard Medical School. Through these two articles as well as previous studies, we now know how enough deep sleep or non-rapid eye movement sleep (NREM) helps the brain clear toxins, amyloid, and metabolic wastes that are associated with Alzheimer’s disease and other neurodegenerative diseases. By simultaneously measuring electrophysiological, hemodynamic, and cerebrospinal fluid (CSF) flow signals in the human brain with fMRI and EEG, researchers observed a coherent pattern of oscillating brain electric waves, blood flow, and CSF flow during deep sleep. In layman’s words, deep sleep or quality sleep in the night triggers a mechanism like a washing machine to generate waves of CSF into and out of the brain to clear toxins, amyloid and metabolic wastes. A sequential of events kick start in cycles in the brain when a person enters deep sleep. Neural slow waves first appear. Then blood flow into the brain reduces 25%, which leads to larger space in ventricles and fluid-filled cavities in the central brain. Subsequently, large amount of CSF flows into and out of the brain. Duration of deep sleep with this cyclic washing is believed to contribute to the clearance of toxins, amyloid and metabolic wastes from the brain.

It is known that sleep problems are common in people who have symptomatic Alzheimer's disease. In recent years, scientists have begun to learn that sleep problems also may be an indicator of early disease. Previous studies at Washington University, conducted in people and in animals, have found that levels of amyloid fluctuate in predictable ways during the day and night. Amyloid levels decrease during sleep, and several studies have shown that levels increase when sleep is disrupted or when people don't get enough deep sleep. In a study published in Nature Neuroscience on June 1, 2015, UC Berkeley researchers also found evidence in human subjects that poor sleep is linked to the buildup of toxic Alzheimer’s protein, amyloid. Without enough deep sleep washing away this toxic protein at night, amyloid would build up and harm brain cells. These researchers also looked at how the quantity of amyloid in the brain’s medial frontal lobe impairs deep sleep. Deep sleep is believed to help retain and consolidate fact-based memories. Powerful brain waves generated during deep sleep were observed to play a key role in transferring memories from the hippocampus - which forms and supports short-term storage for information - to longer-term storage in the frontal cortex. Amyloid PET scan study found subjects who had the highest levels of amyloid in the medial frontal cortex had the poorest quality of sleep and performed worst on the memory tests. Similarly, in study published in Science on July 5, 2017, researchers from University of Wisconsin-Madison found that people with worse sleep quality, more sleep problems and daytime sleepiness had more amyloid and other markers for Alzheimer's disease in CSF than people who did not have sleep problems. Therefore, the more amyloid we have in certain parts of our brain, the less deep sleep we get and the less deep sleep we have, the less effective we are at clearing out this protein. This vicious cycle could lead to worse memory and Alzheimer’s.

As Alzheimer’s is a multi-factorial caused disease, having enough quality sleep in the night helps reduce the risk of developing Alzheimer's. 

Crocin Improves Sleep Quality and Removes Amyloid

Saffron is traditionally used for the treatment of insomnia, anxiety and other diseases of the nervous systems. Crocin, identified as the main active constituent of saffron, has been extensively studied in recent years, revealing its multi-targeting and multi-functional effects. Scientists in Japan investigated both crocin and its metabolite crocetin. They found crocin markedly increased sleep quality measured by the total time of deep sleep in experimental animals and was more effective than crocetin. In a human study, 21 healthy adult men with a mild sleep complaint from Kansai University of Welfare Sciences in Japan were given crocetin and evaluated. Crocetin improved quality of sleep in the subjects assessed by actigraph and St Mary’s Hospital Sleep Questionnaire. More recently, crocin was found significantly improved sleep quality, depression, anxiety, and general health in patients of an 8-week study who were under Methadone maintenance treatment. Effects of crocin on amyloid were also reported in several studies. Crocin was found to prevent generation of toxic amyloid peptides through inhibiting two key enzymes in Alzheimer Disease Neuronal Cell Culture Models (Chalatsa et al 2019). In animal study, crocin was demonstrated to clear amyloid from brain through increasing expression of an amyloid clearance enzyme (Batarseh, 2017). In additional to above effects on improving sleep quality and removing amyloid from brain, crocin has been shown in at least 20 animal studies to improve memory deficits induced by amyloid and other drugs or toxins (Finley 2017, Hadipour, et al. 2018). Therefore, Crocin is considered as an effective option for better sleep quality and against Alzheimer’s.

 

Reference:

  1. Fultz N, et al "Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep" Science 2019; DOI: 10.1126/science.aax5440.
  2. Grubb S, Lauritzen M "Deep sleep drives brain fluid oscillations" Science 2019; DOI: 10.1126/science.aaz5191.
  3. Khalatbari-mohseni, A, et al. The effects of crocin on psychological parameters in patients under methadone maintenance treatment: a randomized clinical trial. Subst Abuse Treat Prev Policy 2019, 14, 9. doi:10.1186/s13011-019-0198-1
  4. Masaki M, et al. Crocin promotes non-rapid eye movement sleep in mice. Mol Nutr Food Res. 2012, 56(2): 304-8.
  5. Chalatsa et al. Crocin and Crocetin Modulate the Amyloidogenic Pathway and Tau Misprocessing in Alzheimer Disease Neuronal Cell Culture Models. Front Neurosci. 2019 Mar 26;13:249. doi: 10.3389/fnins.2019.00249.
  6. Finley JW & Gao S. Perspective on Crocus sativus L. (Saffron) Constituent Crocin: A Potent Water-Soluble Antioxidant and Potential Therapy for Alzheimer’s Disease. J. Agric. Food Chem. 2017, 65, 1005−1020.
  7. Hadipour M, et a. Crocin improved amyloid beta induced long‐term potentiation and memory deficits in the hippocampal CA1 neurons in freely moving rats. Synapse. 2018, 72(5):e22026. doi: 10.1002/syn.22026.

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