Beauty Health for Life

Cinnamon: Can the red-brown spice with the unmistakable fragrance and variety of uses offer an important benefit? The common baking spice might hold the key to delaying the onset of –– or warding off –– the effects of Alzheimers disease.

That is, according to Roshni George and Donald Graves, scientists at UC Santa Barbara. The results of their study, "Interaction of Cinnamaldehyde and Epicatechin with Tau: Implications of Beneficial Effects in Modulating Alzheimers Disease Pathogenesis," appears in the online early edition of the Journal of Alzheimers Disease, and in the upcoming Volume 36, issue 1 print edition.

Alzheimers disease is the most common form of dementia, a neurodegenerative disease that progressively worsens over time as it kills brain cells. No cure has yet been found, nor has the major cause of Alzheimers been identified.

However, two compounds found in cinnamon –– cinnamaldehyde and epicatechin –– are showing some promise in the effort to fight the disease. According to George and Graves, the compounds have been shown to prevent the development of the filamentous "tangles" found in the brain cells that characterize Alzheimers.

Responsible for the assembly of microtubules in a cell, a protein called tau plays a large role in the structure of the neurons, as well as their function.

"The problem with tau in Alzheimers is that it starts aggregating," said George, a graduate student researcher. When for the protein does not bind properly to the microtubules that form the cells structure, it has a tendency to clump together, she explained, forming insoluble fibers in the neuron. The older we get the more susceptible we are to these twists and tangles, Alzheimers patients develop them more often and in larger amounts.

The use of cinnamaldehyde, the compound responsible for the bright, sweet smell of cinnamon, has proven effective in preventing the tau knots. By protecting tau from oxidative stress, the compound, an oil, could inhibit the proteins aggregation. To do this, cinnamaldehyde binds to two residues of an amino acid called cysteine on the tau protein. The cysteine residues are vulnerable to modifications, a factor that contributes to the development of Alzheimers.

"Take, for example, sunburn, a form of oxidative damage," said Graves, adjunct professor in UCSBs Department of Molecular, Cellular, and Developmental Biology. "If you wore a hat, you could protect your face and head from the oxidation. In a sense this cinnamaldehyde is like a cap." While it can protect the tau protein by binding to its vulnerable cysteine residues, it can also come off, Graves added, which can ensure the proper functioning of the protein.

Oxidative stress is a major factor to consider in the health of cells in general. Through normal cellular processes, free radical-generating substances like peroxides are formed, but antioxidants in the cell work to neutralize them and prevent oxidation. Under some conditions however, the scales are tipped, with increased production of peroxides and free radicals, and decreased amounts of antioxidants, leading to oxidative stress.

Epicatechin, which is also present in other foods, such as blueberries, chocolate, and red wine, has proven to be a powerful antioxidant. Not only does it quench the burn of oxidation, it is actually activated by oxidation so the compound can interact with the cysteines on the tau protein in a way similar to the protective action of cinnamaldehyde.

"Cell membranes that are oxidized also produce reactive derivatives, such as Acrolein, that can damage the cysteines," said George. "Epicatechin also sequesters those byproducts."

Studies indicate that there is a high correlation between Type 2 diabetes and the incidence of Alzheimers disease. The elevated glucose levels typical of diabetes lead to the overproduction of reactive oxygen species, resulting in oxidative stress, which is a common factor in both diabetes and Alzheimers disease. Other research has shown cinnamons beneficial effects in managing blood glucose and other problems associated with diabetes.

"Since tau is vulnerable to oxidative stress, this study then asks whether Alzheimers disease could benefit from cinnamon, especially looking at the potential of small compounds," said George.

Although this research shows promise, Graves said, they are "still a long way from knowing whether this will work in human beings." The researchers caution against ingesting more than the typical amounts of cinnamon already used in cooking.

If cinnamon and its compounds do live up to their promise, it could be a significant step in the ongoing battle against Alzheimers. A major risk factor for the disease –– age –– is uncontrollable. In the United States, Alzheimers presents a particular problem as the population lives longer and the Baby Boom generation turns gray, leading to a steep rise in the prevalance of the disease. It is a phenomenon that threatens to overwhelm the U.S. health care system. According to the Alzheimers Association, in 2013, Alzheimers disease will cost the nation $203 billion.

"Wouldnt it be interesting if a small molecule from a spice could help?" commented Graves, "perhaps prevent it, or slow down the progression."

Earlier this year, researchers reported finding insulin being produced in an organ other than the pancreas:

"Researchers at Rhode Island Hospital and Brown Medical School have discovered that insulin and its related proteins are produced in the brain, and that reduced levels of both are linked to Alzheimers disease."

The amounts were low. But the idea that Alzheimers Disease (AD) could be a form of diabetes specific to the central nervous system prompted additional study. Subsequently, a supportive follow-up report was published in November that described a link between the progressive nature of AD and the availability of insulin and insulin-like growth factors - the lower the quantity of insulin and functioning insulin receptors in the brain, the more advanced was the stage of AD.

The type of diabetes described here as associated with Alzheimers Disease (coined "type 3 diabetes" by researchers) is not the same as type 2 diabetes, which affects approximately 18 million Americans. Type 2 diabetes is characterized by higher than normal levels of blood glucose (throughout the body) which result from malfunctions in the production or utilization of insulin made in the pancreas.

A connection between the two disorders may exist, but has yet to be clarified. If a relationship can be shown, the possibilities for therapies that could target both type 2 diabetes and Alzheimers Disease are promising.

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For press release on "brain insulin" finding:
Researchers discover link between insulin and Alzheimers

For some summaries of the recent study:
Evidence Grows That Alzheimers Is A Type Of Diabetes
and
Alzheimers Disease May Be Type 3 Diabetes

For the abstract and review article:
Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: Relevance to Alzheimers disease

Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimers disease - is this type 3 diabetes?