Posts tagged Anti-inflammatory

Why Fish Oils Work Swimmingly Against Inflammation and Diabetes

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Researchers at the University of California, San Diego School of Medicine have identified the molecular mechanism that makes omega-3 fatty acids so effective in reducing chronic inflammation and insulin resistance.

The discovery could lead to development of a simple dietary remedy for many of the more than 23 million Americans suffering from diabetes and other conditions.

Writing in the advance online edition of the September 3 issue of the journal Cell, Jerrold Olefsky, MD, and colleagues identified a key receptor on macrophages abundantly found in obese body fat. Obesity and diabetes are closely correlated. The scientists say omega-3 fatty acids activate this macrophage receptor, resulting in broad anti-inflammatory effects and improved systemic insulin sensitivity.

Macrophages are specialized white blood cells that engulf and digest cellular debris and pathogens. Part of this immune system response involves the macrophages secreting cytokines and other proteins that cause inflammation, a method for destroying cells and objects perceived to be harmful. Obese fat tissue contains lots of these macrophages producing lots of cytokines. The result can be chronic inflammation and rising insulin resistance in neighboring cells over-exposed to cytokines. Insulin resistance is the physical condition in which the natural hormone insulin becomes less effective at regulating blood sugar levels in the body, leading to myriad and often severe health problems, most notably type 2 diabetes mellitus.

Olefsky and colleagues looked at cellular receptors known to respond to fatty acids. They eventually narrowed their focus to a G-protein receptor called GPR120, one of a family of signaling molecules involved in numerous cellular functions. The GPR120 receptor is found only on pro-inflammatory macrophages in mature fat cells. When the receptor is turned off, the macrophage produces inflammatory effects. But exposed to omega-3 fatty acids, specifically docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the GPR120 receptor is activated and generates a strong anti-inflammatory effect.

“It’s just an incredibly potent effect,” said Olefsky, a professor of medicine and associate dean of scientific affairs for the UC San Diego School of Medicine. “The omega-3 fatty acids switch on the receptor, killing the inflammatory response.”

The scientists conducted their research using cell cultures and mice, some of the latter genetically modified to lack the GPR120 receptor. All of the mice were fed a high-fat diet with or without omega-3 fatty acid supplementation. The supplementation treatment inhibited inflammation and enhanced insulin sensitivity in ordinary obese mice, but had no effect in GPR120 knockout mice. A chemical agonist of omega-3 fatty acids produced similar results.

“This is nature at work,” said Olefsky. “The receptor evolved to respond to a natural product — omega-3 fatty acids — so that the inflammatory process can be controlled. Our work shows how fish oils safely do this, and suggests a possible way to treating the serious problems of inflammation in obesity and in conditions like diabetes, cancer and cardiovascular disease through simple dietary supplementation.”

However, Olefsky said more research is required. For example, it remains unclear how much fish oil constitutes a safe, effective dose. High consumption of fish oil has been linked to increased risk of bleeding and stroke in some people.

Should fish oils prove impractical as a therapeutic agent, Olefsky said the identification of the GPR120 receptor means researchers can work toward developing an alternative drug that mimics the actions of DHA and EPA and provides the same anti-inflammatory effects.

Co-authors of the paper are Da Young Oh, Saswata Talukdar, Eun Ju Bae, Hidetaka Morinaga, WuQuiang Fan, Pingping Li and Wendell J. Lu, all in the Department of Medicine, Division of Endocrinology and Metabolism at the University of California, San Diego; Takeshi Imamura, Division of Pharmacology, Shiga University of Medical Science; and Steven M. Watkins, Lipomics Technologies, Inc.

ScienceDaily (Sep. 2, 2010)

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How Dietary Supplements Reduce Health Care Costs

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Spending just pennies a day on healthcare can reduce our expenditures by $24 billion over five years.

New research from the Lewin Group has shown that spending pennies a day on a few key nutritional supplements can dramatically reduce sickness and chronic disease — and greatly decrease healthcare expenditures as a result.(i) How did they come to this conclusion? And why haven’t we heard about it?

The Lewin Group looked only at rigorous scientific studies that documented the benefits of nutritional supplements. They used the Congressional Budget Office’s accounting methods to determine the economic impact of supplements. And they kept their analysis specifically to Medicare patients and women of childbearing age.

Today I will review the Lewin Group’s research, explain the remarkable conclusions they came to, and outline the supplements I recommend you take every day if you want to optimize your health and possible reduce health care costs in the process.

Reviewing the Research: Supplements Have Dramatic Health Benefits

Although nutritional therapies can help a broad range of illnesses, the group only looked at four supplements and disease combinations because of the rigor and validity of the scientific evidence available for these nutrients and diseases.

While there are many other beneficial nutritional therapies that have been proven helpful in studies, the ones in this particular study are only those that are unquestionable, beyond scientific doubt, well-accepted, and proven to help. Yet they are also under-used and not generally recommended by healthcare providers. The study looked at:

1. Calcium and vitamin D and their effect on osteoporosis
2. Folic acid and its ability to prevent birth defects
3. Omega-3 fatty acids and their benefits for heart disease
4. Lutein and zeaxanthin and their benefit in preventing major age-related blindness, or macular degeneration

In this study, the researchers were extremely strict and only looked at nutrient interventions that met three criteria.

1. The supplement had to produce a measurable physiological effect.
2. This physiological effect had to create a change in health status.
3. The researchers only looked at health problems where a change in health status is associated with a decrease in healthcare expenditures.

Now, most of us hear the refrain from our physicians that nutritional supplements just produce expensive urine, that you do not know what you are getting, or that there is no scientific proof to support their claims. Based on this study and many others like it, my advice to these doctors is to do their scientific homework. Let’s start by looking at the effects of calcium and vitamin D.

First, I want to point out the vitamin D research referred to in The Lewin Group study is older research. Newer research, as I discussed in my vitamin D blog, suggests that higher doses of vitamin D3, such as 1,000 to 2,000 IU a day, have even greater benefit.

Yet even by focusing only on the older research, this study’s authors determined that providing Medicare-age citizens with 1,200 mg of calcium and 400 IU of vitamin D would result in reduced bone loss and fewer hip fractures. The researchers estimated these supplements could prevent more than 776,000 hospitalizations for hip fractures over five years and save $16.1 billion.

Next let’s look at omega-3 fats. Omega-3 fatty acids help prevent cardiac arrhythmias, improve cell membrane function, reduce inflammation, lower cholesterol and blood pressure, and have many other benefits.

The Lewin Group found that giving the Medicare population about 1,800 mg of omega-3 fats a day would prevent 374,000 hospitalizations from heart disease over five years. The Medicare savings from reduced hospital and physician expenses would be $3.2 billion.

This is pretty convincing data, but it doesn’t stop there. The Lewin Group also analyzed the economic effects of lutein and zeaxanthin–carotenoids that are found in yellow and orange vegetables. I recommend taking them in combination with the hundreds of other carotenoids found in yellow and orange foods.

Taken as supplements, these have been shown to treat macular degeneration, which is the loss of central vision, a major reason people over age 65 require nursing home care. The study found that taking 6 to 10 mg of lutein and zeaxanthin daily would help 190,000 individuals avoid dependent care and would result in $3.6 billion in savings over five years.

Lastly the Lewin Group looked at the effects of taking folic acid. 44 million women of childbearing age are not taking folic acid. If only 11.3 million of them began taking just 400 mcg of folic acid on a daily basis before conception, we could prevent birth defects called neural tube defects in 600 babies and save $344,700,000 in lifetime healthcare costs for these children. Over 5 years, this would account for $1.4 billion in savings.

Taken together, these four simple interventions, which cost pennies a day, could produce a combined savings of $24 billion over five years. This does not even include benefits to people younger than 65 or any of the other benefits of nutritional supplementation, such as improved immunity, cognitive function, and mood.

The Lewin Group’s study is intriguing. The economic impact of investing a few pennies a day in nutritional supplements is compelling. But what’s downright frightening is that studies by the US Department of Health and Human Services prove that the typical American diet does not always provide a sufficient level of vitamins and minerals — meaning we are at greater risk for conditions like those outlined above.

Because of our consumption of low-nutrient, high-calorie foods that are highly processed, hybridized, genetically modified, shipped long distances, and grown in nutrient-depleted soils, many of us are nutritionally depleted.

In fact, a whopping 92 percent of us are deficient in one or more nutrients at the Recommended Daily Allowance (RDA) level, which is the minimum amount necessary to prevent deficiency diseases like rickets or scurvy — diseases that are the result of not getting enough vitamins and minerals. The RDA standards do not necessarily outline the amount needed for optimal health.

What’s more, our government’s nutrient guidelines ignore the fact that many Americans, because of genetic variations and unique needs, may need higher doses of vitamins and minerals than the RDA. Vitamin deficiency does not cause acute diseases such as scurvy or rickets, but they do cause what have been called “long-latency deficiency diseases.” These include conditions like blindness, osteoporosis, heart disease, cancer, diabetes, dementia, and more.

What all this adds up to is clear. Nutritional supplements do not just make expensive urine. Based on mounting evidence and confirmed by the Journal of the American Medical Association (ii) and The New England Journal of Medicine (iii), I strongly believe that we should all be taking certain basic supplements.

Supplements You Should Take Every Day

Here are the supplements I recommend for everyone:

1. A high-quality multivitamin and mineral. The multivitamin should contain mixed carotenoids, which include lutein and zeaxanthin as part of their mix, as well as at least 400 mcg of folate and a mixed B-complex vitamin.
2. Calcium-magnesium with at least 600 mg of calcium and 400 mg of magnesium. The calcium should be calcium citrate or chelated versions of minerals. Do not use calcium carbonate or magnesium oxide, which are cheap minerals that are poorly absorbed.
3. Vitamin D3, 1,000 to 2,000 IU a day (people who are deficient in vitamin D will need more).
4. Omega-3 fatty acids that contain the fats EPA and DHA, 1,000 to 2,000 mg a day.

The cost is low, the benefit is high, and the risk is non-existent for these nutritional supplements. Not only will you feel better, have better immune function, and improve your energy and brain function, but you will also prevent many problems down the road. So, eat a healthy diet — and take your nutritional supplements every day. It is essential for lifelong vibrant health.

by Mark Hyman, MD

http://www.lewin.com/content/publications/3393.pdf

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Uncovering lithium’s mode of action

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Though it has been prescribed for over 50 years to treat bipolar disorder, there are still many questions regarding exactly how lithium works. However, in a study appearing in this month’s Journal of Lipid Research, researchers have provided solid evidence that lithium reduces brain inflammation by adjusting the metabolism of the health-protective omega-3-fatty acid called DHA.

Inflammation in the brain, like other parts of the body, is an important process to help the brain combat infection or injury. However, excess or unwanted inflammation can damage sensitive brain cells, which can contribute to psychiatric conditions like bipolar disorder or degenerative diseases like Alzheimers.

It’s believed that lithium helps treat bipolar disorder by reducing brain inflammation during the manic phase, thus alleviating some of the symptoms. Exactly how lithium operates, though, has been debated.

Mireille Basselin and colleagues at the National Institute of Aging and University of Colorado, Denver, took a detailed approach to this question by using mass spectrometry analysis to analyze the chemical composition of brain samples of both control and lithium-treated rats stressed by brain inflammation.

They found that in agreement with some other studies, rats given a six-week lithium treatment had reduced levels of arachidonic acid and its products, which can contribute to inflammation.

In addition, they also demonstrated, for the first time, that lithium treatment increased levels of a metabolite called 17-OH-DHA in response to inflammation. 17-OH-DHA is formed from the omega-3 fatty acid DHA (docosahexaenoic acid) and is the precursor to a wide range of anti-inflammatory compounds known as docosanoids. Other anti-inflammatory drugs, like aspirin, are known to also enhance docosanoids in their mode of action.

Basselin and colleagues noted that the concentration of DHA did not increase, which suggests that lithium may increase 17-OH-DHA levels by affecting the enzyme that converts DHA to 17-OH-DHA.

By reducing both pro-inflammatory AA products, and increasing anti-inflammatory DHA products, lithium exerts a double-protective effect which may explain why it works well in bipolar treatment. Now that its mechanism is a little better understood, it may lead to additional uses for this chemical.

Science Centric | 22 May 2010 10:11 GMT

Source: American Society for Biochemistry and Molecular Biology (ASBMB)

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Purple periwinkles battle inflammatory diseases

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A widely and safely used plant extract acts as a novel anti-inflammatory agent that may one day be used for the treatment of chronic obstructive pulmonary disease, or COPD, as well as other inflammatory conditions. There is an urgent need for new therapies for the treatment of chronic inflammatory diseases, such as COPD, otitis media (ear infection), and atherosclerosis (chronic inflammation in the walls of arteries), because the most effective and commonly used agents — steroids — often cause serious side effects, such as liver damage, which prevent long-term use.

In a study published today in the Proceedings of the National Academy of Sciences, researchers at the University of Rochester Medical Center were the first to find that vinpocetine, a natural product derived from the periwinkle plant, acts as a potent anti-inflammatory agent when tested in a mouse model of lung inflammation, as well as several other types of human cells. Results of the study show that vinpocetine greatly reduces inflammation, and, unlike steroids, does not cause severe side effects.

“What is extremely exciting and promising about these findings is vinpocetine’s excellent safety profile,” said Chen Yan, Ph.D., associate professor within the Aab Cardiovascular Research Institute at the Medical Center and a senior author of the study. “Previously, most drugs tested in this area have failed, not because of a lack of efficacy, but because of safety issues. We’re very encouraged by these results and believe vinpocetine has great potential for the treatment of COPD and other inflammatory diseases.”

Vinpocetine is a well-known natural product that was originally discovered nearly 30 years ago and is currently used as a dietary supplement for the prevention and treatment of cognitive disorders, such as stroke and memory loss, in Europe, Japan and China. The therapy has no evidence of toxicity or noticeable side effects in human patients. Scientists at the University of Rochester hope to reposition this compound as an anti-inflammatory agent for the treatment of COPD, and potentially other inflammatory conditions, such as asthma, otitis media, rheumatoid arthritis, atherosclerosis and psoriasis in the future.

While steroids successfully combat inflammation, patients often pay a high price when it comes to side effects. Steroids can cause liver damage, and can also suppress the immune system, increasing the likelihood of infections. With such a high risk profile, steroids are usually only used for a short period of time, which is problematic when treating chronic diseases.

“In managing chronic conditions such as COPD, it is crucial to have a therapy that can be used safely over the long term,” said Jian-Dong Li, M.D., Ph.D., professor in the Department of Microbiology and Immunology at the University of Rochester Medical Center and a senior author of the study. “There is a great need for a drug like vinpocetine, because patients currently have no good options when it comes to long-term care.”

Vinpocetine decreases inflammation by targeting the activity of a specific enzyme, known as IKK. IKK is responsible for regulating inflammation, and does so through the activation of a key protein, nuclear-factor kappaB (NF-kappaB). By directly inhibiting IKK, vinpocetine is able to switch off NF-kappaB, which normally produces pro-inflammatory molecules that cause inflammation. Halting the activity of NF-?B ultimately reduces inflammation.

“Inflammation is a hallmark of a wide range of human diseases, so there is great potential for vinpocetine to be used for several indications,” said Bradford C. Berk, M.D., Ph.D., CEO of the University of Rochester Medical Center and co-author of the study. “Given vinpocetine’s efficacy and solid safety profile, we believe there is great potential to bring this drug to market.”

Repositioning a therapy — taking a known compound that has been used safely in humans and testing it for a new application can be an effective way to bring new therapies to market more quickly than starting the discovery process from scratch.

Inflammatory diseases are a major cause of illness worldwide. For example, chronic obstructive pulmonary disease is the fourth leading cause of death in the United States. In people with COPD, airflow is blocked due to chronic bronchitis or emphysema, making it increasingly difficult to breathe. Most COPD is caused by long-term smoking, although genetics may play a role as well. Approximately 13.5 million people in the United States are diagnosed with COPD each year, and in 2004 the annual cost of the disease was $37.2 billion.

The research was funded by the National Heart, Lung and Blood Institute, the National Institute of Allergy and Infectious Diseases, and the National Institute on Deafness and Other Communication Disorders at the National Institutes of Health, and the University of Rochester Medical Center. The University has applied for a patent for vinpocetine for use as an IKK-inhibitor for the treatment of COPD. Drs. Li, Yan and Berk have formed a start-up company, Rock Pharmaceuticals, with the hope of licensing the intellectual property rights from the University of Rochester and commercializing this technology.

In addition to Li, Yan and Berk, Kye-Im Jeon, Ph.D., Xiangbin Xu, Ph.D., Jae Hyang Lim, Ph.D., DVM, Hirofumi Jono, Ph.D., and Jun-ichi Abe, M.D., Ph.D., from the Aab Cardiovascular Research Institute and the Department of Microbiology and Immunology at the University of Rochester Medical Center participated in the study. Toru Aizawa, M.D., a former post-doctoral associate at the Aab Cardiovascular Research Institute, and Dong-Seok Kwon, Ph.D., a collaborator in Korea, also contributed to this study.

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The most cost-effective defense against oxygen radicals

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Alpha-lipoic acid (ALA) is a substance made by cells of many kinds – bacterial, plant, and animal. It serves as a cofactor in several biochemical processes in the body, including the process by which energy is extracted from carbohydrates. ALA is also nature’s best antioxidant for neutralizing oxygen radicals that damage and age biological tissues.

ALA has been of great interest to medical biologists since it was discovered in the 1950s. Nearly 2500 scientific articles that deal with this substance have appeared since then, and numerous clinical trials have been conducted to test its effects on various medical conditions. The list of conditions for which ALA has been successfully applied is a long one, and includes:

  • Aging
  • Insulin resistance
  • Metabolic syndrome
  • Neuropathy
  • Cardiovascular disease
  • AtherosclerosisNeurological disorders
  • Burning mouth syndrome
  • Cancer
  • Hypertension
  • Chronic fatigue syndrome
  • HIV
  • Exercise-induced damage
  • Altered taste perception
  • Retinopathy
  • Down’s Syndrome
  • Pigmentation, skin bleaching
  • Cataracts
  • Diabetes
  • Multiple sclerosis
  • Lead toxicity
  • DNA damage
  • Iron depletion
  • Liver damage

Aging may be slowed by ALA.

Evidence that ALA interferes with the aging process comes from experiments showing that ALA decreases build-up of age-related lipofuscin deposits and prevents oxidative damage to mitochondria (cells’ energy extractors). In aging experiments with lab animals, ALA improves brain function, extends the lifespan, and restores age-impaired vascular function.

Neuropathy.

Treatment for 5 weeks with ALA improved neuropathic symptoms in a study of diabetic patients who received once-daily oral doses of 600 mg or more.

Other neurological disorders.

Experiments in tissue culture, lab animals, and in humans have shown that ALA counteracts the promoters (and reverses the symptoms) of neurological ailments including:

  • Alzheimer’s
  • Parkinson’s
  • Huntington’s
  • ALS
  • cognitive aging
  • various other neurological and neuromuscular diseases.

Cardiovascular conditions.

Oxidative stress is implicated as a major causative factor in atherosclerosis and hypertension. ALA‘s antioxidant activity has been shown to reduce arterial plaques, decrease lipid concentrations in the blood, and to improve the function of heart arteries. In experiments with mice, “the development of hypertension could be either totally prevented or markedly attenuated by chronic treatment with potent antioxidative therapies such as alpha lipoic acid.”

» For a more detailed discussion of alpha-lipoic acid and R-alpha-lipoic acid the medical studies that support its use, see the article on our website at:

http://www.ilifelink.com/r-alpha-lipoic_acid_100_mg_x_120_capsules.html

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