Dr. Weil: The Anti-Inflammatory Diet

This week’s topic is anti-inflammatories. Many of you may have heard of Dr. Andrew Weil. He is a Harvard Medical school graduate who has been at the forefront of popularizing Integrative Medicine. He is the program director of the Arizona Center for Integrative Medicine here at the University of Arizona which he founded in 1994. Since his undergraduate career he has been interested in botany and the role plants can play in health. Interestingly, he wrote his thesis on the narcotic properties of nutmeg. However, in recent years he has concentrated his focus on different lifestyle interventions that may assist in medical treatment. One of these is the Anti-Inflammatory Diet.

Dr. Weil credits the Anti-Inflammatory diet as more of a lifestyle than an actual diet. However, he claims that “it is the blueprint for optimum nutrition”. He continues to say that simple changes in eating habits can counteract inflammation which is at the root of diseases such as: heart disease, Alzheimer Disease, Parkinson Disease, age related disorders including cancer and autoimmune diseases such as rheumatoid arthritis and lupus. At the heart of his diet plan is variety and a balance. The diet strives to balance omega-6 fatty acids (said to promote inflammation) and omega-3 fatty acids (anti-inflammatory). It recommends that we eat less meat and poultry which contain omega-6 fatty acids and eat more fish with have omega-3 fatty acids. It also aims to decrease refined and processed foods which often contain pro-inflammatory compounds called AGEs (advanced glycation end products) and have a high glycemic index. Dr. Weil’s modified version of the food pyramid depicts the Anti-Inflammatory diet’s key points very well.

I can definitely see the benefit in eating a healthy diet in order to maintain balance in our body and optimum functioning. I would say that the Anti-Inflammatory diet is a wonderful lifestyle to promote. However, I as being “anti-inflammatory”, I am still on the fence. But, it is all comparative: it is anti-inflammatory compared to the fast food nation we have become with diets high in saturated fat. Looking over the pyramid, the way of eating appears to be much more similar to our hunter/gatherer past with a greater emphasis on fruits, vegetables and fish and sparse consumption of poultry, red meat and sweets. Take a look for yourself and let me know what you think: http://www.drweil.com/drw/u/ART02012/anti-inflammatory-diet

Medications Used in the Treatment of Alzheimer’s Disease

I had discussed in the class the research that is being conducted regarding the relationship between fibrin and Alzheimer’s Disease. I was interested in finding the current medications that are used in the treatment of AD, and came across an article from a PhD student, Carrie Hill. We know that there is no current cure for AD, which is why studies like I discussed in class are being performed. There are, however, medications that improve symptom management of the disease. When developing treatment plans, the cognitive and behavioral symptoms are considered.
I wanted to focus on cognitive symptoms, which include problems with thought processes like memory, language, and judgment. Cholinesterase inhibitors and Namenda are two kinds of medications that have been approved by the FDA for treating these symptoms. Cholinesterase inhibitors increase the levels of acetylcholine in the brain, which plays a key role in memory and learning. Surprisingly, this alone can postpone the worsening of symptoms for 6 to 12 months in about half of the people who take it. Cholinesterase inhibitors are most commonly prescribed for mild to moderate Alzheimer’s disease. Namenda, known as memantine, regulates glutamate in the brain, which plays a key role in processing information. This drug is used to treat moderate to severe Alzheimer’s disease and may delay the worsening of symptoms in some people.
Cholinesterase inhibitors can be started as soon as Alzheimer’s symptoms appear, and are most effective in the early stages of disease. When a physician determines that the cholinesterase inhibitor is no longer effective, memantine is usually introduced. Sometimes, memantine and a cholinesterase inhibitor are taken simultaneously during the moderate stage of the disease. I wonder if this combination with the addition of anti-inflammatory drugs would show a decrease in the progression of Alzheimer’s Disease?

http://alzheimers.about.com/od/treatmentofalzheimers/a/treatments.htm

Multiple Sclerosis: A Causative Analysis

As we've already read in class, many researchers are looking at what they believe is/are the cause/s for the development and full expression of multiple sclerosis. We read a paper on microglia changing its phenotype to a cell somewhat identical to a phagocyte, and past research focuses have been on T cells. This condition is commonly referred to as an autoimmune response to some protein of the myelin sheaths, though this is still debatable. Current treatment can attenuate the response and lesson the symptoms, but there is no way to target any chemical treatment to the nervous tissue without effecting the entire immune system and its cells--so attenuating the cells of the immune system pharmacologically if a patient with MS also attenuates any immune response (depending on the compound used). The research of MS is further confounded by research models. Currently, rate or mice are generally used; however, since the cause of the disease is unknown, we cannot accurately say that the animal models are expressing the disease to the same or similar extent.

The affected tissue lies deep within the brain, forbidding any manual intervention that would not cause unknown irreversible consequences. Recent research has been done on the assumption that MS spontaneously begins with auto-reactive T cells, and this is supported by the mice models which much be injected with nervous tissue to develop the disease. Countering this idea is a group of scientists who have developed a murine which spontaneously develops MS. All murine models of MS have not been able to show B cell involvement, except this new model. The group found that yes, T cells are active in the model, but they are not actually inducing disease...B cells induce MS (shown by general good health in these models when B cells are removed). This is not to say that B cells are the prime player. T cells can do plenty of damage in the brain, but antibodies may be needed to sustain and develop the disease.

I just found this research interesting, and linked the paper's title above. I still feel it's important to take this with a grain of salt, simply because this is one study, published recently, in a species other than our own with a disease that is still not understood fully and may not completely represent how we express the disease. There's obviously a lot of research to do, but it's so very interesting to read about these finds which go against what the topic's body of research says.

The role of glial cells in Parkinson's Disease

The glial reaction is generally considered to be a consequence of neuronal death in neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. In Parkinson's disease, postmortem examination reveals a loss of dopaminergic neurons in the substantia nigra associated with a massive astrogliosis and the presence of activated microglial cells. Recent evidence suggests that the disease may progress even when the initial cause of neuronal degeneration has disappeared, suggesting that toxic substances released by the glial cells may be involved in the propagation and perpetuation of neuronal degeneration. Glial cells can release deleterious compounds such as proinflammatory cytokines (TNF-α, Il-1β, IFN-γ), which may act by stimulating nitric oxide production in glial cells, or which may exert a more direct deleterious effect on dopaminergic neurons by activating receptors that contain intracytoplasmic death domains involved in apoptosis. In line with this possibility, an activation of proteases such as caspase-3 and caspase-8, which are known effectors of apoptosis, has been reported in Parkinson's disease. Yet, caspase inhibitors or invalidation of TNF-α receptors does not protect dopaminergic neurons against degeneration in experimental models of the disease, suggesting that manipulation of a single signaling pathway may not be sufficient to protect dopaminergic neurons. In contrast, the antiinflammatory drugs pioglitazone, a PPAR-γ agonist, and the tetracycline derivative minocycline have been shown to reduce glial activation and protect the substantia nigra in an animal model of the disease. Inhibition of the glial reaction and the inflammatory processes may thus represent a therapeutic target to reduce neuronal degeneration in Parkinson's disease.

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AD-Cholesterol Connection

As I had mentioned in class, there has been an establishment of cholesterol as a risk factor in the pathogenesis of Alzheimer’s disease (AD). This is a major focus of current research for AD. I came across a review article from PubMed titled, Alzheimer’s disease: the cholesterol connection, and found that in the past few years, this link has been supported through genetic, epidemiological and biochemical data. The review was from Harvard Medical School’s Neurobiology of Disease Laboratory and Genetics and Aging Research Unit.

In all forms of Alzheimer’s disease (AD) there is an abnormal accumulation of the beta-amyloid protein in specific brain regions, which is regulation by cholesterol. It was found that elevated levels of cholesterol increase the beta-amyloid protein in cellular and most animal models of AD, and that drugs that inhibit cholesterol synthesis lower the beta-amyloid levels. Recent studies have shown that the total amount and distribution of cholesterol within neurons impact the beta-amyloid biogenesis. I mentioned in class the role of the apolipoprotien E gene, the identification of a variant of this gene as a major genetic risk factor for AD is consistent with a role for cholesterol in the pathogenesis of AD.

The review describes its recent findings concerning the molecular mechanisms underlying the cholesterol-AD connection. Drugs that lower cholesterol levels are currently being considered and tested as potential therapies for the treatment of AD. Statins, which are relatively safe and have been used for a long time against high cholesterol levels, are now being directly tested in clinical trials for efficacy against AD. Some of the potentially beneficial effects of statins might also represent improved cardiovascular health, resulting in a reduction in ischemic events that are also considered risk factors for AD. An effective therapy for patients whose cognitive function does not benefit from statin treatment may ultimately consist of a combination of lipid regulating products, perhaps in combination with statins. Alternative products for cholesterol management so far include extended-release niacin, cholesterol absorption inhibitiors, ACAT inhibitors and cholesteryl ester transfer protein (CETP) inhibitors. Results from in vitro studies suggest that ACAT inhibitors are good candidates for regulating beta-amyloid biogenesis, but more research is needed to understand the exact molecular mechanisms underlying the AD-cholesterol connection. Also, it is necessary to gain an in-depth understanding of brain cholesterol metabolism. With new technology that is developing, we may be able clarify how plasma and brain cholesterol contribute to AD.

Full PDF text found at EBSCHOhost:
Title: Alzheimer's disease: the cholesterol connection.
Author: Puglielli, Luigi; Tanzi, Rudolph E.; Kovacs, Dora M.;http://web.ebscohost.com/ehost/pdfviewer/pdfviewer?vid=2&hid=106&sid=86523406-21ed-4ee6-8f03-87d50b8af3df%40sessionmgr110

Sunlight (UV) and Multiple Sclerosis?

As I mentioned in class, the 2010 CDC study found a correlation between areas of highest MS prevalence and greater UV exposure. I've chosen to explore this idea and I've found an article which I've referenced below which discusses an exploration of this trend:

For some time now, the observation that MS prevalence increases with latitude, meaning the further from the equator one gets, the higher likelihood of MS in the environment. Researchers in this article therefore look at Vitamin D and how its levels may in these different latitudes may help explain the differences in prevalence.

The article notes that 400,000 people in the U.S. have MS, of nearly 309, 055, 803 people in the U.S. (U.S. Census Bureau). UV exposure, as well as vitamin D levels can effect immune responses, but the question which arises is whether immunoregulation is done via UV exposure, or indirectly via vitamin D levels, or the two? As referenced in the article, research somewhere (not cited) has shown that increased levels of the active form of vitamin D can "block" the disease in animals.

The experiment uses mice which are genetically predisposed to an MS-like disease state, and the mice are injected with nerve antigen to initiate the disease. After initiation, one group of animals were exposed to "moderate" UV strength (equal to 2 hours of direct summer sun) for one week and the other group was irradiated every 2nd or 3rd day. They found that the exposure reduced the expression of symptoms for MS, but not the prevalence, especially in those mice irradiated every other day. The researchers also deduced that although vitamin D levels were increased with UV exposure, that factor alone could not explain the results.

The groups next area of study is to see what role skin may play with UV exposure to the production and expression of compounds involved in inflammation and the inflammatory response. The article identifies two possibilities of usefulness:

1. In the short term, if they can identify the specific active wavelength at which these same results can be obtained, this can be used as a therapy for those people suffering from MS.

2. In a more long term goal, if the group can discover the compound or compounds that the skin may be producing, the may be able to isolate or synthesize the compound and market a drug treatment.

The group does caution that this information is in the early experimental stages of development, and that results of a similar treatment may not lead to intentions.

Article

Food Allergies linked to RA???

In class we discussed the possibility (mentioned in one of our lay articles) that RA may be linked to an "allergic" type of response to certain foods.

I did a little bit of research on the subject and found an article that suggests that RA symptoms may be caused by an "allergic" immune response to foods such as milk and other dairy products. The basic premise of the study the article mentions is that your body may produce antibodies to certain foods. These antibodies form immune complexes in your intestines and from there, these complexes can travel throughout your body and become inflammatory mediators.

This article mentions a study done by an individual doctor who noticed that up to a third of his RA patients felt improvement in their symptoms when they eliminated most allergy-causing foods and reverted to a basic "Stone Age" diet of fruits, vegetables, fish, and plain meat.

Here is a link to the article :http://www.arthritistoday.org/conditions/rheumatoid-arthritis/healthy-living/ra-food-allergies-2.php