NFL – Prevent &Treat Chronic Traumatic Encephalopathy, CTE – Opioids Blamed Wrongly


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Crowdfunding Needed

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Prevent and Treat

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Chronic Traumatic Encephalopathy

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C.T.E.

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Opioids Wrongly Blamed

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Leagues may have known about this technology since 2002 publications

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Football players have demonstrated ability to influence others

and raise money for important medical causes.

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This is not about class action law suits.

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This can be imaged early and likely treated.

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It’s about science and bringing medicine into the 21st century.

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A paradigm shift began with the discovery

of the innate immune system by internationally recognized scientists in 1991.

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The clock has been turned off.

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We can change this now.

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Funding is needed for internationally recognized leaders to continue this work.

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The tragic deaths of former NFL football players from repeated concussions has led to brain damage and death from Chronic Traumatic Encephalopathy (CTE). Suicide profoundly shocks us when many players like Junior Seau at age 43 and now Tyler Sash, die at age 27. He is the youngest found to have such extensive brain damage, as bad as that seen in Junior Seau. So much can be done with state of the art science now that has been ignored.

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Disclosure: I was asked by a research institute if I would evaluate retired NFL players. I chose not to do that so that I might be free to post unbiased information that is not subject to being manipulated by either side in the ongoing appeals for compensation that must be going on with the NFL for $70 million. Tragic that this is such a fight. Even more tragic, this may be diagnosed early and treated.

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Pearls

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Fear of compensation claims after concussion injury prevents imaging of football players and veterans early, while still treatable, before severe changes and death.

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Fear of compensation claims has prevented decades of research funding by internationally recognized scientists. Could politics at NIH & the VA have turned off funding for veterans with pain and with concussion blast injuries? Does cancer and heart disease forever lock up all the research money and now it shifts to stem cells?

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It is inaccurate to say that CTE cannot be diagnosed except after death at autopsy.

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PET scan imaging of glia can show changes early, while alive.

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The ligand PK1195 must be used for PET scan to image glia, available for years in Australia, not yet in America.

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FDA approval must be obtained for the ligand PK1195 before it is used to  image glia in the United States.

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CTE can be diagnosed early.

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CTE is likely to be treatable.

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Internationally distinguished scientists have shown reversal of complete paralysis in rat models of multiple sclerosis in 2010, a so called “degenerative” neurological disease.

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Intractable pain and treatment resistant depression can be put into remission with glial modulators. Surely CTE and other neurological diseases can be approached with scientifically recognized mechanisms and treatments – even if doctors are not aware of the paradigm shift and how to modulate neuro-inflammation. See years of posting on this site since 2009 based on the most important finds in the field of neuroscience for more than 100 years: the innate immune system, glia, neuro-inflammation, and ability to use glial modulators, to modulate intractable conditions that are known to lead to suicide and/or death.

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Paradigm shifts in all fields including medicine, fail to be recognized.

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CTE gives opioids a bad name and misled Taylor Sash and likely others from the diagnosis of CTE that caused years of severe forgetfulness and behavior changes. He may have chosen suicide by opioid.

 

 

 

FACT:

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Trauma such as concussion or infection or stroke triggers inflammation in the brain:  “cytokine storm”

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Inflammation kills brain cells

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Inflammatory cytokines (inflammation) are produced by glia that has been activated by trauma or other causes such as infection, stroke, etc.

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Activated glia produce neuroinflammation and cell death.

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Inflammatory cytokines produce pain and “degenerative” neurological and psychiatric disorders including dementia, depression, anxiety, delirium and death.

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Neuro-inflammation in brain has been found in teens with early signs of schizophrenia, in rats made depressed, and rodents with chronic pain.

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Glia have been detected in life, in vivo, with PET scan imaging, by internationally-recognised radiologist working at Imperial College London, now based in Australia.

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PET scans require a ligand, PK1195, approved for years in Australia – must be approved by FDA in the United States before it can be used here.

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There is good clinical data and publications in animal models to show that damage in brain and spinal cord produced by activated glia can be reversed.

E.g., In 2010, total paralysis has been completely reversed in a rat model of multiple sclerosis by internationally-recognised glial researcher who, in 1991, transformed the understanding of glia that comprise 85% of the brain, since then known to be the innate immune system.

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Publications have shown that patients with major depressive disorder and patients with chronic low back pain have memory loss and brain atrophy.

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Opioids cause pain by stimulating production of inflammatory cytokines that are known to damage neurons in brain and spinal cord – and must be tapered off. We have better treatment for pain.

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Insurance carriers routinely deny payment for recognized medications and procedures to relieve pain.

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CDC is planning a nationwide experiment to radically limit opioids.

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Treatment with glial modulators that reduce neuroinflammation has been shown clinically to relieve treatment resistant major depressive disorder, PTSD, bipolar depression and intractable pain. They are neuroprotective.

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We need to be able to flag players off the field early and intervene with treatment such as glial modulators either before, during or after repeated injury.

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GOALS

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1.  PK1195, a ligand for PET scans, must be tested and approved by FDA. Approval is mandatory for all medications or substances injected into vein or body.

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It simply “tags” the PET scanner to image glia, the cells of the innate immune system that are activated by trauma, infection, stroke, etc.

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2. Do serial PET scans using PK1195 to image glia in NFL players and veterans after blast injury.

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Trauma from concussion is causing cytokine storm, killing brain cells –> ultimately end stage dementia, anxiety, depression, suicide

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3. Flag that player off the field. Follow glial changes during treatment to determine if able to return or if permanent, but prior to end stage damage.

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4.  Treat with glial modulators preventively, early, middle, and/or late

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This subject will be continued. My apologies for lack of time to delete and edit. Days pass by quickly to post brief comments. Time is limited. Please send comments, below.

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The material on this site is for informational purposes only.

It is not a substitute for medical advice,

diagnosis or treatment provided by a qualified health care provider.

Relevant comments are welcome.

If any questions, please call the office to schedule an appointment.

This site is not email for personal questions.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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NOT advocated by me and NOT approved by me.

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Dementia, Memory Loss, Brain Atrophy – not always Alzheimer’s Disease. We are all at risk.


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Dementia

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Alzheimer’s Disease

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Sustained Reversal Published by UCLA

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If you have a medical problem that involves the brain, this may apply to you.

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In a major breakthrough, Dale E. Bredesen reported that 9 of 10 patients with Alzheimer’s Disease were able to return to full time work. His report appeared in the journal Aging, September 2014. A PDF can be downloaded. He is UCLA Augustus Rose Professor of Neurology, director of the UCLA Easton Center Center for Alzheimer’s Disease Research.

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He used a 36 point holistic approach based on published neuroscience research. There is no drug. .

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There is No Magic Bullet – Highly Individualized

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Dementia is the third leading cause of death in the U.S. behind cardiovascular disease and cancer. It affects roughly 25 to 30 percent of the population over 80, with 70 percent of those having Alzheimer’s Disease.

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The number of cases doubles every 5 years in people over 65. By age 85, almost half of all people are afflicted. A family history of Alzheimer’s increases risk. Five percent have onset early in age.

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In other words, once we pass 60, we are all at risk for this disease, but may occur as young as 30 in rare cases.

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What to do?

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1. See a good neurologist for a proper diagnosis. If  dementia, there are at least 9 causes, Alzheimer’s is 40% of those [N.B. source, verify].

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Some are treatable, such as deficiency of vitamin B12 or thyroid. Remember, do not take folic acid unless you are taking adequate B12 as folate will mask B12 deficiency and lead to neurological problems that may be severe.

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2. Read the Alzheimer’s Disease In-Depth Report in the New York Times. It gives clear and comprehensive advice for the patient and the caregiver. It is not a diagnosis.

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3. Memory loss can be reversed and sustained. Dr. Bredeson reports, “Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement.”

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He points out the failure of the so called Alzheimer’s drugs, that help little or not at all. Instead, he uses a 36 point metabolic approach, discussed in more detail below. He said the findings are “very encouraging,” but he added that the results are anecdotal, and a more extensive, controlled clinical trial is needed.

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Alzheimers has the potential to devastate the economy worldwide in the near future. The Bredesen report is a first. Ideally it may revolutionize medical research, fiscal budgets, dietary guidelines, policy changes, school lunches, advertizing and foods that promote all the wrong changes in brain. But it involves changing behavior and even simple school lunch programs that improve cognitive function and health have been mercilessly attacked.

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Alzheimer’s Disease is relentless. The causes are not known and there is no cure. Changing behavior is dificult.

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There are three hallmarks of the diagnosis of Alzheimer’s Disease:

  • amyloid plaques

  • neurofibrillary tau tangles, the primary marker

  • loss of connections in the brain

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Plaques and tangles may be present for years and may appear quite early in life, without ever developing Alzheimer’s. We do not have a specific marker for diagnosis, but we can exclude treatable conditions. More importantly, doctors and families need a better tool to monitor cognitive decline so that we may intervene early before the devastating and costly disease captures the lives and finances of patients, caregivers and families alike.

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Risk Factors For Alzheimers Are The Same As For Heart Disease

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Obesity, inactivity, smoking, diabetes, hypertension, hyperlipidemia, low Vitamin D – serum level of 50 ng/mL is ideal.

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Benzodiazepines increase risk of Alzheimers 50%, reported in 2014, particularly with long acting forms (Valium, clonazepam) or long term use. They are widely prescribed for insomnia or anxiety, yet almost 50% of older adults continue to use these drugs. It is unrealistic to think they can be eliminated – they are habit forming after all, but a Quebec study showed that a brochure alone helped 27 percent of elderly users taper down and discontinue their drug in six months. Another 11 percent reduced dosage. Do taper off slowly with proper guidance. Informed consent can help each person to choose the risk or the taper. If the brochure doesn’t scare you, I don’t know what will.

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Systems Approach – No Silver Bullet

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The small trial published by Dr. Bredesen showed reversal of cognitive decline using an individualized 36 point ‘systems approach’ to memory disorders. Results started to be seen after 3 to 6 months.

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In the UCLA Newsroom interview, he says: “The existing Alzheimers drugs affect a single target, but Alzheimers disease is more complex. Imagine having a roof with 36 holes in it, and your drug patched one hole very well, he said. The drug may have worked, and a single hole may have been fixed, but you still have 35 other leaks, and so the underlying process may not be affected much.”

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It “involves comprehensive diet changes, brain stimulation, exercise, sleep optimization, specific pharmaceuticals and vitamins, and multiple additional steps that affect brain chemistry.” Though each target may be affected in a modest way, the overall effect may be additive or even synergistic.

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The downside is its complexity. No one was able to stick to the entire protocol. The side effect was improved health and improved body mass index. Successful candidates did lose weight. He emphasizes that this small study needs to be individualized and replicated on a large scale. The program for one patient included:

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  • eliminating all simple carbohydrates, gluten and processed food from her diet, and eating more vegetables, fruits and non-farmed fish

  • meditating twice a day and beginning yoga to reduce stress

  • sleeping seven to eight hours per night, up from four to five

  • taking melatonin, methylcobalamin, vitamin D3, fish oil and coenzyme Q10 each day

  • optimizing oral hygiene using an electric flosser and electric toothbrush

  • reinstating hormone replacement therapy, which had previously been discontinued.

  • fasting for a minimum of 12 hours between dinner and breakfast, and for a minimum of three hours between dinner and bedtime

  • exercising for a minimum of 30 minutes, four to six days per week

 

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Diet

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We have known that calorie restriction reverses amyloid deposition.

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One diet was developed by nutritional epidemiologist Martha Clare Morris, Ph.D., of Rush University in Chicago, and her colleagues.

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According to the findings, the MIND diet was able to lower the risk of AD by as much as 53 percent in participants who strictly adhered to the diet, and by about 35 percent in those who followed it fairly well. It was compared to the DASH diet and Mediterranean diet.

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“To follow the MIND diet, a person should eat at least three servings of whole grains, a salad and one other vegetable every day —  along with a glass of wine —  snack most days on nuts, eat beans every other day or so, eat poultry and berries at least twice a week, and eat fish at least once a week.

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However, a person should limit consumption of the designated unhealthy foods, especially butter (less than one tablespoon a day), cheese, and fried or fast food (less than a serving a week for any of the three), to have a real shot at avoiding the devastating effects of AD, according to the study.

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Berries are the only fruit included in the MIND diet. “Blueberries are one of the more potent foods in terms of protecting the brain,” Morris said, and strawberries have also performed well in past studies of the effect of food on cognitive function.”

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I recommend that my patients Google pro and anti-inflammatory foods and move their diet in the direction of lowering the burden of inflammation.

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Supplements

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CurcuViva or Longvida is a special formulation of curcumin, the active ingredient in turmeric spice that is able to cross through the blood brain barrier and reach the brain. I posted on it here and it is reviewed in more detail here. Turmeric does not enter the brain. It was developed by researchers at UCLA Alzheimer’s Research Center showing the relationship between pre-tangle tau, brain cell death, and cognitive function. Full memory was restored in mice that had dysfunction caused by tau tangles. It has been shown to help Alzheimers and joint pain.

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WARNING: Do not take CurcuViva if ulcers or gallbladder disease.

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Supplements Can Harm – Caution Toxic

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Supplements can cause great harm. Many are toxic and deplete the brain of essential nutrients or cause irreparable harm.

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Always research the value and harm of every supplement put into your body. The best site on herbs and botanical I have found is updated regularly by the expert in integrative medicine and alternative therapies at Memorial Sloan Kettering Cancer Center. They research supplements and herbs to show efficacy and how they interact with prescription medications to verify if they may help or harm. Ask, does this drug – yes, vitamins and supplements are drugs but unregulated and untested – cause toxic increase in medication or rapid loss (speeded metabolism) of prescription medications resulting in less effective serum levels and no benefit.

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Metabolism of drugs and drug-drug interactions is critical to know.We do not have enough data on supplements. We ignore behavioral changes such as diet, exercise, stress reduction at our peril in favor of unregulated, unproven, costly silver bullets.

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Reflecting the importance of my interest in supplements since the majority of Americans take so many, one of the first things I did in starting this website is to post on benefit and harms of vitamins and supplements.

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In addition to that detailed list, use the search box just above my photo top left to find other posts on frequently used supplements mentioned below.

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The Good, The Bad and The Ugly

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  • Vitamin B6 in excess can cause irreversible neurological disease – know the safe dose because it is now overdosed in many things.

  • Heavy NSAID use increases risk of Alzheimers.

  • Zinc blocks copper that is essential for every cell in the body.

  • Vitamins A and E have no proven benefit and serious risks.

  • CoQ-10 is essential for every cell. Statins deplete CoQ-10. It is essential in the electron transport chain to make ATP, the energy used by every cell. Research has shown it helpful for mitochondrial diseases such as migraine and Parkinsons Disease though very high doses for the latter. I do not know of any publications for its use in Alzheimers.

  • Fish oil can reduce triglycerides 45%. Adjust dose based upon level of triglycerides – elevated levels increase risk of Alzheimers.

  • Hormones affect function of many organs including brain. If low, then restore at least to low normal. If high, rule out tumor.

  • Low vitamin D doubles the risk of dementia and Alzheimers.

Low Vitamin D Doubles Risk of Dementia & Alzheimers Disease

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That was published in the journal Neurology, August 2014. Vitamin D is a special category and I have posted on its anti-inflammatory and analgesic benefit many times, its effect on the immune system, on pain relief, and on depression. It is important for five cancers, heart disease. Again, use the search function top left by my photo for details.

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WARNING: Make sure before taking any Vitamin D that your MD checks PTH and then if normal, recommend a dose of D3 based upon serum levels of 25(OH)D. I maintain my patients on a serum level of ~50 ng/mL, not more, not less, in accord with the most recent research.

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B Vitamins

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Brain atrophy occurs in those with aging as well as with Major Depression or Chronic Pain and with aging. They were able to prevent 90% atrophy of the hippocampus and areas targeted by Alzheimers Disease with specific doses of B vitamins, below. The OPTIMA (Oxford Project to Investigate Memory and Ageing) at Oxford University, March 2013. I disagree with their dose of Vitamin B6 as I have seen tragic toxicity in patients that takes at least one year to reverse, if ever.

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These are the doses I suggest:

  • .B12 500 mcg/day

  • Folic Acid 800 mcg/day

  • B Complex —-B6 not to exceed 2 mg ! B6 is one of the vitamins in B Complex and it

    can be toxic to nerve. It is being overdosed in many supplements and energy drinks.

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Inflammation

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If you haven’t gathered by now, the focus is on inflammation. The brain and spinal cord has an innate immune system different than the immune system in the rest of your body. The cells of the innate immune system are called glia, and they produce many chemicals, in particular, microglia and astrocytes produce cytokines. Anti-inflammatory and pro-inflammatory cytokines. They must be in balance.

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Inflammatory cytokines are shown to be involved in almost every known disease including Alzheimers, Parkinsons, ALS, MS, autoimmune disease, chronic pain, major depression, cancer, atherosclerosis.

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Pro-inflammatory drugs: opioids and alcohol for example.

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Anti-inflammatory drugs: low dose naltrexone, dextromethorphan, ketamine, amitriptyline, Vitamin D, melatonin. Again, use the search function above photo for the many posts including case studies. It would be helpful to see more medications studied to show if they are pro- or anti-inflammatory, and to see studies on these medications in persons with memory difficulty. That will not happen since they are generic, low cost.

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Living Wills & Healthcare Power of Attorney

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Be aware of the changing laws in your state. In the event dementia prevents you from choosing your care, if you have asked that no food or water be given, medical staff are not legally permitted to follow that directive. Legal precedent directs that if you reach for food or water, that indicates your intent to be fed, regardless of written requests made when you were of sound mind. It behoves us all to change behavior now.

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Summary

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  • Use an Alzheimers self test for early detection. This is not a diagnosis.

  • Obtain a neurological evaluation.

  • Be aware of the importance of the 36 step metabolic approach.

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The material on this site is for informational purposes only.
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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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This site is not for email and not for appointments.

If you wish an appointment, please telephone the office to schedule.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please ignore the ads below. They are not from me.

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PeaPure – Palmitoylethanolamide for Nerve Pain or Migraine


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PeaPure is a glial modulator. It is available in Italy and the Netherlands as a food supplement and has been studied in multicenter clinical trials in Europe for several years. It is well tolerated with no side effects and is very helpful for neuropathic pain, headache, and osteoarthritis. It is anti-inflammatory and neuroprotective.

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Because it inhibits astrocyte activation and the over-expression of pro-inflammatory molecules and signals, it is being investigated in Alzheimer’s Disease.

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The mechanism of action of PEA was discovered in 1993 by Nobel laureate Rita Levi-Montalcini in her work on nerve growth factors. She found it is involved in metabolism of mast cells and published a series of papers on its self-healing effect of the body in response to inflammation and pain. Two recent publications from Jan M Keppel Hesselink, MD, PhD, and his colleagues at the Institute for Neuropathic Pain, Amsterdam, The Netherlands, describe case reports, one of which is the case of a woman with CRPS.

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The purpose of this post is to clarify dosing of PeaPure and how to take it for a sudden flare of pain. My apologies for failing to recall the source of these instructions which I believe was from the manufacturer and from here and here. The latter includes an excellent review of its mechanism.

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Description of PeaPure® 400 mg capsules
PeaPure® is a food supplement based on a natural and fatty-acid like compound.
The substance palmitoylethanolamide (PEA) is a physiologically active molecule that the body produces naturally.
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What the user should know prior to ingestion:
•    There are no known significant side effects.
•    PeaPure® can be taken simultaneously with other medicine. In case of doubt, it is recommended to first consult your doctor or a pharmacist.
•    Use during pregnancy is NOT recommended.
•    PeaPure® does not contain sugar, yeast, allergens, sorbitol, magnesium stearate, povidone or other ingredients.

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Dosage and administration – please refer to the manufacturer.

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UPDATE SEPTEMBER 2014

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It is with a heavy heart that I report this news:

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Palmitoylethanolamide is

now available only from the Netherlands,

sold as PeaPure, a food supplement.

  It is no longer able to be imported by a pharmacy, but we are hoping

that may change if we can interest a supplement manufacturer to make it available for the US.

Patent rights, attorneys are far beyond the resources of my local pharmacy.

 

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I have published this year, 2014, on the treatment of

vulvodynia and proctodynia with PeaPure and a topical cream.

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There are no studies to show us how often it may relieve nerve pain, but it is astonishing when it works. No toxicity, no side effects. Your brain makes it, plants make it. There is a growing literature on it and I have posted on some of its mechanisms. And in particular, its Anti-inflammatory, Analgesic, Neuroprotective Mechanisms.

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The material on this site is for informational purposes only, and is not a substitute for

medical advice, diagnosis or treatment provided by a qualified health care provider.

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Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office or contact your local psychiatrist.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Spine Fusions: No Better Than Cognitive Behavioral Therapy & Exercise


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Spine Fusions: no better than Cognitive Behavioral Therapy and Exercise

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This reportfrom the Academy of Neurology may help guide you in decision making: 

Deaths, Complications, Higher Costs Accompany Increase in Complex Spine Fusions Among Elderly.

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“Fusion is usually performed for degenerative disc disease for chronic low back pain, but a number of studies have shown that their outcomes are no better than a combination of graded exercise and cognitive behavioral therapy.”

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Tragically, dementia can result from extensive spine surgery. Many factors can contribute to that. If I were having spine surgery, I would look at the data of dementia following open heart surgery and the protective benefits of ketamine given prior to surgery. Ketamine can spare neuronal function. It is neuroprotective. I link to a publication on that in this post. The problem may be that so few physicians are willing to provide ketamine as they may lack information on its use, yet it is one of the safest medications we have, nontoxic and neuroprotective.

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The material on this site is for informational purposes only,

and is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here: 

Welcome to my Weblog on Pain Management!

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“Heavy NSAID Use Linked to Higher Dementia Risk” – Exercise, Antidepressants Both Help Neurogenesis


NSAIDs are anti-inflammatory drugs used to treat pain, inflammation, or fever.  The only NSAIDs that are NOT associated with increased risk of heart attack or arrhythmia are naproxen (Aleve) or aspirin.  Taking high doses of aspirin has a greater risk of GI bleed than naproxen, which is why I usually recommend naproxen.

Background:

Several past studies have shown NSAIDs delay or prevent dementia, but there have been contradictory results.  Last year Neurology published a study of 49,349 patients’ usage ranging from ≤1 year to ≥7 years done at Boston University and Bedford VA. They showed long term use of NSAIDs protects against Alzheimers:

Compared with no NSAID use, the relative risk of Alzheimer’s disease decreased from 0.98 for ≤1 year of use (95% CI 0.95 to 1.00) to 0.76 for >5 years of use (95% CI 0.68 to 0.85).

Among patients who specifically cited use of ibuprofen, the risk of Alzheimer’s disease declined from 1.03 (95% CI 1.00 to 1.06) to 0.56 (95% CI 0.42 to 0.75).

Ibuprofen came out ahead in that study perhaps because it is the most commonly used.

They also sought to answer whether NSAIDs known to suppress Aβ1-42 amyloid would more likely protect .  Aβ1-42 amyloid is a major component of plaques found in Alzheimer’s Disease.

Aβ1-42 amyloid suppressors include ibuprofen, diclofenac, flurbiprofen — but as for suppressing Alzheimer’s, these were found to be no different than other NSAIDs, putting that theory to rest.


methusala-tree

Risk of dementia and Alzheimer’s Disease with prior exposure to NSAIDs in an elderly community-based cohort:

This new study by Breitner  et al, from the University of Washington School of Medicine was published online April 22, 2009, before the print edition in Neurology.  

Their outcome contradicts earlier protective studies possibly because they started with an older cohort, healthy adults 65 and older, which “could be enriched for cases [of Alzheimer’s] that would otherwise have appeared earlier.”

They prospectively followed 2,736 persons in a Seattle health plan.  Before starting the study, they reviewed pharmacy records as much as 17 years earlier.

Findings:

12.8% of the study participants [were] heavy NSAID users at baseline. Heavy use was defined as taking 500 or more standard daily doses over a two-year period.

Another 3.9% of participants became heavy users during follow-up.

Ibuprofen, naproxen, indomethacin, and sulindac accounted for about 80% of all NSAIDs used.

Through follow-up, 476 participants developed dementia; for 356 of them, it was Alzheimer’s disease.

After controlling for age, gender, education, APOE status, hypertension, diabetes, obesity, osteoarthritis, and physical activity, the risk of developing all-cause dementia was 66% higher among heavy users than among those with little or no NSAID use (HR 1.66, 95% CI 1.24 to 2.24).

The risk of developing Alzheimer’s disease was 57% higher (HR 1.57, 95% CI 1.10 to 2.23).

Strengths of the study: the community-based sample, biennial assessment of dementia, rigorous exposure classification, and large numbers of dementia cases, outweigh the limitations.

Limitations:  lack of generalizability to a younger patient population, the lack of exact dosing information, and the possibility of bias from unmeasured confounders.

Can we draw conclusions on one study alone? We know that exercise is protective against Alzheimer’s Disease and pain may have prevented this older age group from being active. Though they did control for that, this research needs to be supported by further studies. What is helpful is to remain as active as you can.  Keep and maintain every bit of function you can and get help for depression and anxiety as they may profoundly affect memory, morbidity and mortality.  For a review of the literature on the morbidity and mortality of stress and mood, refer to my post on Cognitive Behavioral Therapy and the importance of a positive outlook.

The brain makes new neurons – neurogenesis.  I will write more in the future on exercise, mood, stress, brain atrophy and memory loss.   Exercise improves depression and anxiety, and exercise stimulates neurogenesis.  It appears that the action of antidepressants also may be to stimulate neurogenesis.  Chronic low back pain has been reported to cause brain atrophy.  Chronic depression leads to brain atrophy and memory loss with atrophy occurring in the hippocampus, the area essential for memory.  This important publication from Vancouver reviews the topic in great detail and proposes a hypothesis:  Antidepressant effects of exercise: Evidence for an adult-neurogenesis hypothesis?

Further medication is being tested to reduce neuronal cell death that leads to Alzheimer’s Disease, using a very simple compound that blocks free radicals and inflammation.  More on this later.

The material on this site is for informational purposes only, and

is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

Vitamin D – A Steroid Hormone, Anti-inflammatory


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The Sunshine Vitamin Controversy

What should normal values  be for calcium homeostasis?

My attention was drawn to Vitamin D several years ago when a review appeared in the journal Neurology, published by the Academy of Neurology, that linked low levels of Vitamin D to Multiple Sclerosis.  The article was unusual for its length and the breadth of research cited over several decades.  More recently, a Johns Hopkins article published “the most conclusive evidence to date” that Low Vitamin D Levels Pose Large Threat to Health.

New publications on Vitamin D seem to appear every week with the focus on levels of 25-hydroxyvitamin D, also written as 25(OH)D. Its half life in serum is ~ 10 days to 3 weeks.

The biologically active form 1,25-dihydroxyvitamin D, written as 1,25(OH)D²,  is made in the kidneys and has a much shorter serum half-life of ~ 4-6 hours, thus making it less useful as a serum marker for measuring.

Sources & Metabolism: Vitamin D is a fat soluble vitamin that’s absorbed in the small intestine from  foods such as egg yolks, fatty fish, fish liver oils, fortified milk, margarine, and cereals.  Bile salts are required for absorption.  Sunlight stimulates the skin to synthesize vitamin D, but exposure of hands and face as little as 15 minutes may not be sufficient and it is not as effective for everyone.  It won’t work in winter months, it won’t work for the aged, for those who have pigmented skin, and it won’t work for those who cover their skin.

Vitamin D Metabolism - click to enlarge

Vitamin D Metabolism

The Controversy –  How Do We Determine Normal Values?

Surprisingly, in a well designed multicenter study of healthy young Hawaiians in their 20’s who were exposed to at least 29 hours of sun per week, 51% were found to have vitamin D deficiency using the usual cut off of 30 ng/ml for normal.  This study from 2007 found the mean concentration of 31.6 ng/ml, and the highest of 62 ng/ml.  It raises the question whether

“it seems prudent to use this value [60 ng/ml] as an upper limit when prescribing vitamin D supplementation,”

rather than the generally published normal range of 30 to 80 ng/ml or even 100 ng/ml quoted in some labs.  This study is important in discussing the controversial question of what normal values should be for calcium homeostasis and reviews several possible explanations for inadequate production of D3 including genetic differences.

They note the highest reported values in “Nebraska outdoor workers… were between 81 and 84 ng/ml” but the assay system differed compared to theirs and results in a higher value.   Reviewing this study that was published in the Journal of Clinical Endocrinology & Metabolism has allowed me just now to readjust my own patient practice.

Laboratory Testing:  results can differ from one laboratory to another.  My hospital sends specimens to ARUP for testing, whereas Quest has acknowledged errors in laboratory testing and problems with standardization as reported by the New York Times here.

Function:  It is important for absorption of calcium and phosphorous from the small intestine, for bone health, osteoporosis, risk of falls, certain cancers(colon, breast, prostate), and possibly 6 to 7 years of longevity.  Deficiency of vitamin D is associated with suboptimal health and possibly increased pain; it is linked to infections, gum disease, hypertension, diabetes, coronary disease, neurological diseases such as Multiple Sclerosis, Parkinson’s Disease, dementia and Alzheimer’s Disease though it may not be causal. Its receptor is found all over the body including the brain.

I recommend this review by one of the best web resources at Memorial Sloan Kettering Cancer Center Herbs & Botanicals.

They quote a reference showing it reduces postmenopausal weight gain and “In adults with impaired fasting blood glucose, giving calcium and vitamin D reduced increases in plasma glucose and insulin resistance….”

It is the only vitamin that is a steroid hormone, and my interest increased on learning that it functions as an anti-inflammatory.  But as I tested blood levels for 25(OH) vitamin D and parathyroid hormone (PTH), I discovered more than 90% of my patients had vitamin D deficiency and a few had hyperparathyroidism.  There are four parathyroid glands next to the thyroid, and for some reason doctors have rarely tested their hormone levels.

***Persons with hyperparathyroidism should NOT take calcium or vitamin D.

It may lead to kidney stones and bone pain:  stones, bones and groans.***

Evidence for Optimizing Vitamin D Concentrations

On the other hand, if vitamin D is low, there is some evidence that replacement with vitamin D3 so that blood levels are in the high normal range, may help pain.  That is, it may raise the pain threshold and possibly have other benefits for health and longevity. It is desirable to avoid toxic levels of D as it causes hypercalcemia with depression, drowsiness, weakness, headache, polydipsia,  bone loss, and metastatic calcifications of many organs, soft tissues and blood vessels.  The generally quoted range of normal for 25(OH) vitamin D is 30 to 80, that varies with the lab.

great-western-divide-wp1

Doesn’t that photo of the Great Western Divide make you want to get outside into the sun?

Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes was reviewed by Heike Bischoff-Ferrari et al, in 2006,  though it has been superseded by much additional work since then.

To quote from their article:

This review summarizes the evidence for optimal serum  25(OH)D concentrations. The endpoint selection for this review was based the strongest evidence to date—ie, that from RCTs [randomized controlled trials], consistent evidence from prospective and cross-sectional epidemiologic studies, and strong mechanistic evidence or dose response relations.  BMD [bone mineral density], fracture prevention, lower-extremity function, falls, oral health, and colorectal cancer met these criteria. Weaker evidence exists of a beneficial effect of vitamin D on other diseases, including multiple sclerosis (15), tuberculosis (16), insulin resistance (17, 18), cancers other than colorectal (19 –22), osteoarthritis (23, 24), and hypertension (25–27), but these diseases are not considered here.

They did not review pain studies.  I would add that “weaker” evidence merely means that it must be confirmed by more studies, not that it excludes those conditions.  There is an epidemic of vitamin D deficiency in the country, and the incidence is very high in pain clinics as reported in several studies.

A new multi-center epidemiology study  “Demographic Differences and Trends of Vitamin D Insufficiency in the US Population, 1988-2004”  by Ginde, et al, in 2006,  “demonstrate a marked decrease in serum 25(OH)D levels from the 1988-1994 to the 2001-2004 NHANES data collections.”  And like others before them, they point out:

“Current recommendations for vitamin D supplementation are inadequate to address the growing epidemic of vitamin D insufficiency.”

Summary:

Make sure your doctor checks both your 25(OH)Vitamin D and parathyroid hormone level (PTH) – not thyroid – to determine if you have hyperparathyroidism or if you have normal or low vitamin D.  That will determine if you need replacement or if you should stop using calcium and D as it will cause kidney stones and calcium deposits on your bones leading to pain.

If vitamin D levels are low it may result in increased physical pain and may cause or aggravate many medical conditions.

If PTH levels are high indicating hyperparathyroidism it will cause new painful conditions.

Intake does vary with the patient, the season, the age, but the recommended daily allowance may perhaps be double what it is now.  It is unclear when the federal government will adjust that dosage.   As always, your physician’s recommendation will be based upon blood levels of 25(OH)D and PTH.

Do not make changes in your dosage without careful evaluation.

Could this possibly be one of the most important areas of research this century?

The material on this site is for informational purposes only, and

is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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