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."

In an apologetic fit of better-late-than-never, the Disease Management Care Blog announces that the latest Cavalcade of Risk is up.  Its themed after the Mayan non-apocalypse and has a number of links that take you to bloggery on topics that range from restraint of trade to health insurance exchanges to genetic testing to workers comp.  There is something for everyone interested in business and insurance risk.

Enjoy!

Aggressive treatment with statins reduces the risk of subsequent cardiovascular events in patients with coronary artery disease even if they have very low LDL cholesterol levels, reveals research presented at ESC Congress 2013 today by Dr. Emi Nakano from Japan.

Dr Nakano said: "Many randomised clinical trials, such as Treating to New Targets (TNT) and PROVE IT-TIMI, have shown that aggressive cholesterol lowering with statins improves clinical outcomes in patients with CAD and high LDL-C levels.1,2 But until now it was not known whether aggressive lipid lowering with statins would also benefit CAD patients with very low LDL-C levels."

The current study used the Ibaraki Cardiovascular Assessment Study (ICAS), a registry of 2,238 patients from 12 hospitals in the Ibaraki region of Japan, who between 0 and 1 month underwent percutaneous coronary interventions. Based on serum LDL-C levels at initial presentation participants were classified into three groups: very low (<70 mg/dl, n=214); low (71-100 mg/dl, n=669); and high (>101 mg/dl, n= 1,355). Decisions of whether to prescribe statins or not, as well as the type and dose, were left to the discretion of treating physicians.

Patients were followed up for a maximum of 3 years. The efficacy of statin treatment was analysed on the composite outcome of Major Cardiovascular Events (MACE), defined as all cause mortality, non-fatal myocardial infarction and non-fatal stroke.

Statins were prescribed in 68% of patients (143) with very low LDL-C, 67% of patients (450) with low LDL-C and 67% of patients (913) with high LDL-C. A total of 204 patients experienced MACE during the median follow-up of 404 days.

The results of a Kaplan-Meier estimate show that three years of statin treatment produced significant reductions in the incidence of MACE in all three groups (p<0.001 for all groups). A Cox regression hazard analysis adjusted for age and gender showed that statins were the main determinant of better outcome regardless of the LDL-C level (p<0.01).

Dr Nakano said: "Our study shows that CAD patients with very low LDL-C levels at initial presentation also benefit from statin treatment. We speculate that statins prevent the enlargement of atherosclerotic plaques and plaque disruption in these patients."

She added: "Some doctors have been hesitant to prescribe statins in patients with very low LDL-C because of uncertain benefit and the risk of side effects with statins. But our findings suggest that all CAD patients should receive statins to reduce their risk of future cardiovascular events."

Dr Nakano concluded: "The next step should now be to initiate a randomised controlled trial of statin use in patients with CAD and very low LDL-C levels. This trial should be designed to confirm the benefits of statins for preventing future cardiovascular events in these patients, and to identify which type and dose of statins are most beneficial."

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Care management planning

Hot off the heels of this cinematic debut on how NOT to conduct care management comes this handy Alliance of Community Health Plans 29 page handbook review on how to do it right.  Some of the experienced members of the Alliance shared insights on successful population health approaches, data on the "return on investment" and how to deal with the physicians.

But, say the Hardball-inspired Disease Management Care Blog readers, "tell us something we dont already know." 

The DMCB found three useful nuggets of information:

1. There is no firm rule on the operational balance between central administration and peripheral distribution.  Some of the Plans hire and oversee the care management nurses while others pay their network primary care sites to hire their own nurses.  If the practices employ the nurses, they are free to let the managers see patients on an all-payer basis.

2. Care management caseloads vary from 35 to 150 persons and the enrollee to nurse ratio ranges from one full time nurse to 5000 to 14,000 commercial members. If less than 5000 Plan members are assigned to a primary care site, care managers split their time among multiple sites.  As Plan members are further diluted or distributed through a network, there is greater reliance on remote telephonic communication and coaching. 

3. Reduced costs?  Group Health, Fallon and Security Health plan say they saved over $2.5 million, $2.3 million, and $1 million, respectively. Tufts Health Plan says they saved $1.90 for every dollar spent.

Other points known but worth repeating:

Features of successful care management include appropriate patient selection, person-to-person outreach, credentialed professionals, teaming, coaching on self-management, family involvement and access to community-based programs.

Embedding care managers in the primary care sites is worthwhile not only because face-to-face patient care has more of an impact, but because the physicians will benefit from the consultations, participation in "huddles" and discussion of the treatment plans. That also leads to a greater level of trust between the docs and the nurses.

Theres better buy-in if the care managers are viewed by enrollees as an extension of the physicians, not the sponsoring insurers. 

Technology is important: effective care managers are made more effective by electronic records, telemonitoring, decision support, work-flow aids and video/mobile communication.

 The backbone of care management is made up of generalist nurses who are simultaneously comfortable with multiple conditions such as, for example COPD, mental illness and diabetes.  That being said, there is a role for focused nurse support for patients with special needs, such as hospice, transplant or bariatric surgery.

An abundance of data support is only the beginning because the reports will need to be tailored to the physicians clinical needs  and communication perences.  They also have to be paired with regular meetings that promote best practices and solicit feedback.

When care management is first rolled out, physicians will first suspect this is another managed care ruse, assume its a fast track to prior authorization or try to "downjob" clinical duties to the nurses that are outside of their scope of practice.  It will take many months and much collaboration to sort out turf issues, control, office space, and offering care management to some but not all patients.