Vitamin B6 toxicity mimicked ALS, lost vocal cords, food backed up through nose


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I saw a patient recently whose B6 toxicity was misdiagnosed for months as ALS, including on EMG. Vocal cords stopped working. He lost the gag reflex and ability to swallow, therefore food backed up through his nose. The type of ALS that affects ability to swallow usually leads to  death in months.

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This man was an executive in a major city at the time. He lost a lot of weight and had the more typical burning pain from scalp to toes that I have seen with B6 toxicity.

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Once discontinued, he says it took 2 weeks for the burning to go away,  and he feels 95% better now 4 years later.

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Other patients took one year for burning to go away after discontinuing the vitamin —energy drinks are loaded with them. B6 sales are pushed hard. Beware.

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RDS of B6 is 2 mg = 100%

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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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Vitamin B6 toxic effects – sensory & motor neuropathies, some not reversible


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HIGH DOSES GONE WILD

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TOXICITY OF B6

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So many of us fail to study the supplements that we take, and trust our bodies to inadequately trained people trying to sell vitamins. It’s a multi-billion dollar business.

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In my first posts on this site April 2009, I warned about several vitamins that can be toxic. Yet I see so many people who are taking harmful doses. Many have harmful cardiovascular effects, as I posted later after publication by a colleague at Mayo Clinic.

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Vitamin B6 is almost always found in high doses in “energy” drinks and in higher and higher doses in vitamins. I have seen patients taking 11,000 times higher dose than the recommended daily allowance, the RDA.

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Eleven thousand times higher dose.

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Eleven thousand.

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No wonder they are barely able to move due to nerve pain from scalp to toe. So severe they cannot tolerate anyone touching the skin. And they are seeking opioids? to relieve pain?

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Vitamin B6 can cause severe nerve pain and much worse. Damage may not be reversible, but if it is, it may take more than one year.

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Less is more.

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The information on Vitamin B6 toxicity below is directly quoted from Memorial Sloan Kettering Cancer Center Herbs and Botanicals website. Refer to their page for references and much longer discussion of benefits that I have omitted.

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From Memorial Sloan Kettering Cancer Center

Herbs and Botanicals website

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High B6 intakes can have toxic effects including sensory and motor neuropathies, and some case reports of neurotoxicity have not been reversible (29). B6 levels can also be elevated due to environmental exposures or genetic defects (1).

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At the same time, because PLP is the metabolically active form of B6, it is thought to be responsible in instances of vitamin B6 toxicity (29). High circulating pyridoxine levels may have direct toxic effects on peripheral sensory ganglia neurons in the lower blood–nerve barrier, whereas the blood–brain barrier protects neurons in those regions from higher levels (35). The negative impact of B6 upon levels of other B vitamins appears to be dose-dependent and occur with chronic exposure (29).

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Warnings

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Long-term intake of high doses vitamin B6 can lead to nerve problems (29).

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Adverse Reactions
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High concentrations of vitamin B6 may result in severe peripheral sensory neuropathies and ataxia. Toxicities have reversed following discontinuation in some instances (37), but some case reports of neurotoxicity have not been reversible (29).

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Case reports

Irreversible sensory ataxia in octogenarians: Three elderly patients in their eighties presented with sensory ataxia (lack of voluntary coordination of muscle movements) and signs of polyneuropathy (damage or disease affecting peripheral nerves) for 3–8 months. Pyridoxine 600 mg daily was consumed for 3–10 years in a B1-6-12-combination tablet. B6 blood levels were markedly elevated at 66–104x ULN. After 2 years of vitamin discontinuation, the patients showed no significant improvement in either neuropathy or gait, and no other likely cause for neuropathy in these patients could be identified (29).

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Severe sensorimotor neuropathy: Due to B6 hypervitaminosis in a 75-year-old white man, accompanied by yellowish-brown skin pigmentation. Discontinuation of B6 led to improvement 1 year later, when he no longer used a wheelchair and could walk without a cane. Skin color also resolved, but ataxic signs were still present (38).

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Herb-Drug Interactions
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Altretamine: Pyridoxine may diminish its therapeutic effect (39).
Oral contraceptives: May moderately increase pyridoxine requirements (40).
Levodopa: Enhances levodopa metabolism, thereby reducing its effects (41) (42).
Penicillamine: May increase the requirements for pyridoxine (32).
Seizure medications (phenytoin, phenobarbital): High-dose pyridoxine may decrease serum concentrations (43).

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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.

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Metformin Targets Aging – no lactic acidosis, no significant hypoglycemia in 18,000 patients-years of follow-up


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Metformin targets multiple pathways affected by aging (pdf)

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Authors Nir Barzilai, Jill P. Crandall, Stephen B. Kritchevsky, and Mark A. Espeland from aging research centers at Albert Einstein Medical School and Wake Forest Medical School, Cell Metabolism June 2016

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….in 2012, when over 18,000 patients-years of follow-up had accrued, and by which time 20% of the cohort was age 70 or older (mean age 64). There were no cases of lactic acidosis or significant hypoglycemia (Diabetes Prevention Pro- gram Research Group, 2012). Mild anemia occurred in 12% of metformin-treated participants versus 8% in the placebo group (p = 0.04). Vitamin B12 deficiency occurred in 7% of metformin group versus 5% in placebo group after 13 years; risk of B12 deficiency increases with duration of use but was not greater in older compared with younger subjects in DPPOS (Lalau et al., 1990). Further, the risk of lactic acidosis appears to be related to renal function, not age per se, and is currently considered to be very low (Aroda et al., 2016).

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B12 deficiency is related to MTHFR. I prescribe the doses of B vitamins to take daily, as published by University of Oxford for seniors. Their work shows it prevents 90% of brain atrophy in those areas that are known to involve Alzheimers Disease [avoid toxic B6 doses that damage brain].

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When time permits, I will be adding more on metformin.

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If low blood sugar (hypoglycemia) occurs, juice works quickly but rapidly disappears and then blood sugar is low again in minutes. Use good diet practices, and use plenty of small protein snacks if needed. Protein lasts longer and does not trigger sugar spikes like juice.

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Common side effects, if present at all, are mostly GI such as diarrhea, nausea, gas, distension of the belly with discomfort, indigestion, anorexia, headache, asthenia. If present, stop the drug, wait till all resolve, and very slowly, increase only as tolerated. This is not a speed test.

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Lactic Acidosis potential rare side effect

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The potentially serious side effect of concern is lactic acidosis. I advise patients to review its list of potential side effects.

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http://www.medsafe.govt.nz/profs/PUarticles/5.htm

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https://www.healthgrades.com/conditions/lactic-acidosis–symptoms

Introduction

Symptoms

Causes

Treatments

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What are the symptoms of lactic acidosis?

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Symptoms of lactic acidosis may include nausea and vomiting, abdominal pain, weakness, rapid breathing, rapid heart rate or irregular heart rhythm, and mental status changes.

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Common symptoms of lactic acidosis

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If you experience lactic acidosis, it may be accompanied by symptoms that include:

Abdominal pain

Anxiety

Fatigue

Irregular heart rate (arrhythmia)

Lethargy

Nausea with or without vomiting

Rapid breathing (tachypnea)

Rapid heart rate (tachycardia)

Shortness of breath

Weakness

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Serious symptoms that might indicate a life-threatening condition

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In some cases, lactic acidosis can be life threatening.

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Seek immediate medical care (call 911) if you, or someone you are with, have any of these life-threatening symptoms including:

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Bluish coloration of the lips or fingernails

Change in level of consciousness or alertness, such as passing out or unresponsiveness

Chest pain, chest tightness, chest pressure, palpitations

High fever (higher than 101 degrees Fahrenheit)

Not producing any urine, or an infant who does not produce the usual amount of wet diapers

Rapid heart rate (tachycardia)

Respiratory or breathing problems, such as shortness of breath, difficulty breathing, labored breathing, rapid breathing, or not breathing

Severe abdominal pain

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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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Medication Summary for Intractable Pain, CRPS/RSD


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  Medication Summary for

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Intractable Pain, CRPS/RSD

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I spoke only briefly this morning at the RSDSA conference but there is so much to add. Most importantly, thanks to RSDSA for helping so many people with CRPS. They fund pain research, they are starting a free children’s camp, and now offer physicians one hour free CME teaching about CRPS.

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Holistic view, 36 points – that’s how I view caring for brain and nerves, very similar to the details used by UCLA Alzheimers Research Unit. In June 2015, I posted on their work on memory loss, dementia. We know chronic pain means inflammation in the brain, excess of proinflammatory cytokines. CT scans show memory loss and brain atrophy in those with chronic low back pain.  Can this inflammation lead to Alzheimers? Even if it doesn’t, why not maximize what we know we can do to help brain. As I view it, simply be meticulously detailed in giving the central nervous system (CNS) the best chance to relieve or prevent pain or disease.

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Below is a brief list.

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To find detail and sometimes depth, check the alphabetical lists on either side column until you see the category or tag when I first posted on that. Or simply plow through 7.5 years of detail with references. You do the work to check the side columns as I have no time to embed links below, taken from throughout this site.

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For now just a list of medication players that may be strikingly important in trying to bring intractable pain into remission even after 20 years. Yes, even chronic for decades.

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The list applies to intractable pain of all causes. I omitted listing standard interdisciplinary approaches commonly used by every pain specialist around the world. My patients have failed all those.

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Some patients with CRPS combine my medications with ketamine infusions.

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For those who remain on opioids, ultra low dose naltrexone (10 to 60 mcg three times daily) can significantly reduce pain, reduce opioid induced hyperalgesia, reduce windup, and thus reduce the dose of opioid needed to give improved relief.

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Opioids cause pain and trigger pro-inflammatory cytokines that create more pain.

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I strongly recommend slowly, gently tapering off opioid, and remaining off for 3 weeks before the following is trialed:

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 1. Vitamin D is anti-inflammatory. Important. Helps pain, depression. If bone loss is an issue, you will not absorb calcium from food if D is low. Mayo Clinic’s publication in 2012 showed more morphine is needed for pain if D is low. Huge literature of its benefit for depression. First topic I posted on – it is that important.

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2. Vitamin B6 can cause burning pain from scalp to toe, a toxic neuropathy. It can be toxic to brain. It is loaded in tons of soft drinks, “energy” drinks, supplements.

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3. MTHFR mutation may be present. Body cannot process  the B12 and folic acid you are eating or taking in supplement. A simple blood test, costly. Treatment is as simple as buying methyl folate and methyl B12 – no prescription needed. Folic acid in particular is profoundly important for one of the major energy cycles in the body. Can cause multiple conditions, some fatal, all from one single cause.

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4. Minocycline 100 mg/day is the dose I use but higher doses could be given. It is used daily for decades for acne. I may prevent spread of CRPS if given before surgery, dental work, even minor procedures. I start 24 hrs before, and continue for days after full recovery from surgery.

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5. Testosterone  in either male or female is depleted by opioids, it may be depleted by stress. Low T is a risk for depression, weakness and osteoporosis.

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6. Naltrexone low dose (LDN) – profoundly important. A glial modulator. Lifelong use.

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7. Dextromethorphan – reduces hyperexcitable glutamate

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8. Oxytocin

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9. Memantine – double the Alzheimers dose for CRPS. Like ketamine, it blocks the NMDA receptor.

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10. Lamotrigine

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11. Palmitoylethanolamide (PEA, PeaPure) a glial modulator, also acts on mast cells. A food supplement. No Rx. Your body makes it. Plants make it. Capsules & cream

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12. Ketamine via nasal spray, under tongue combined with IV or not, works on glutamate-NMDA receptor. Not an essential drug. Where ketamine has stopped working, patients have become pain free after years of CRPS.

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13. Creams combinations, so many

most of my CRPS pts very much like   Mg++/guai  10% each.

You may or may not trial various combinations lido/keto/keta, etc. Numerous. DMSO 50%.

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14. Medical Marijuana (CBD, THC, terpenes) Marijuana saves lives. Entire issue of Science, November 4, 2016, devoted to pain.

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NAC and alpha lipoic acid are noted by research from the Netherlands.

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Appendicitis

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If it has not burst, treat it like the infection that it is. Surgery may never be needed. I posted details of publications early 2016 with a case report. That young man was being rolled into the OR, instead was discharged 100% better without surgery 2 days later.
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Medications target 3 main systems

as discussed at the conference

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The opioid receptor – opioids create pain. They trigger glia to produce pro-inflammatory cytokines. Opioid induced hyperalgesia may occur. Cannot be used with low dose naltrexone.

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The glutamate NMDA receptor – ketamine, memantine

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Glia, the innate immune system – glial modulators

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Before they see me, my patients have failed all prior therapies even ketamine coma. I view it like football. You have one guy running down the field with one ball. Do you want to win the game? You’ve dealt with this for years. Let’s not prolong it. Hit it with my main choice of meds all at once. Jump on it. What if you get 10% relief – will you even notice 10% after many years of severe pain? But if you get 10% from each of 5 meds, then you are talking 50% relief as a start. Address those 3 main pain systems – even without ketamine – and I have posted a case report after 20 years and 3 suicide attempts before seeing me, she has been pain free for about 4 years as I recall. A surgeon nicked her sciatic nerve when she was 27. Two years ago, pain free, running on her treadmill, she twisted her ankle. She has permanent foot drop from the sciatic nerve injury, but even spraining her ankle did not flare her CRPS. Twenty years of CRPS, pain free for about 4 years. And ultimately, years ago, she was tapered off all the drugs with one exception: LDN lifelong.

 

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Most importantly, I did not have time to relay a very special message from my patient in Brooklyn:

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.Surround yourself with friends and family who love you.

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.Never give up hope.

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She had her first 2 or 3 pain free days this week, as she slowly increases doses of medication. She’s not yet at maximal effect and even then there can be increases. Sending love and courage.

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MOVEMENT

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Watch this on the RSDSA video, afternoon speakers, the parents of young ones who had RSD discussed today all the toys and games they had to devise to slowly force yourself to move through the pain, every single day, several times a day, all day, begin to move the body as much as you can. Set goals and slowly, at a pace you set, do the work. Make progress. Go forward. Keep moving. Do whatever you can to keep moving.

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RSD support groups are essential and I am glad to see the RSDSA list of so many throughout the country.

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There is so much more. Indeed, at least 36 points discussed on June 2015.

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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.

~~
This site is not for email and not for appointments.

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

~~~~~

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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Magnesium Deficient? – Add 3 or 4 Daily for Pain or Depression


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Here’s a keen publication from 1988:

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Magnesium and immune function:

an overview.

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*****Add Magnesium 3 or 4 per day for months.*****

*****Let me know if it helped your pain or depression.*****

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It’s got to be anti-inflammatory – possibly in CNS, and may influence pain, depression, other conditions. Since it is inside the cell, we cannot measure true deficiency. It may be subtle. Only in retrospect 5 months later, during some of the most intense work stress months of one patient’s life, did she realize not one single infection over fall/winter months when there would always be 3 or 4. You may not realize what it has done unless you think about it.

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If it does nothing but stop infections, that alone may prevent Alzheimer’s, years later. Or save your life from the flu that killed a healthy 20 year old. 

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Mg participates in immune responses in numerous ways: as a cofactor for immunoglobulin synthesis, C’3 convertase, immune cell adherence, antibody-dependent cytolysis, IgM lymphocyte binding, macrophage response to lymphokines, T helper-B cell adherence, binding of substance P to lymphoblasts and antigen binding to macrophage RNA. Mg deficiency in rodents impairs IgG synthesis and cell-mediated immunity; complications include thymus atrophy, elevated IgE, hypereosinophilia, histaminosis and lymphoma. Immunologic sequelae of Mg deficiency in humans are subtle and may be affected by genetic control of blood cell Mg concentration. Abnormal C’ activation, excess antibody production and susceptibility to allergy and to chronic fungal and viral infections have been reported. Mg appears to play a protective role in acute allergic reactions.

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From 2001, we learn how crucial magnesium is in many diseases:

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The multifaceted and widespread

pathology of magnesium deficiency

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Abstract

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…extremely important for the metabolism of Ca, K, P, Zn, Cu, Fe, Na, Pb, Cd, HCl, acetylcholine, and nitric oxide (NO), for many enzymes, for the intracellular homeostasis and for activation of thiamine and therefore, for a very wide gamut of crucial body functions. Unfortunately, Mg absorption and elimination depend on a very large number of variables, at least one of which often goes awry, leading to a Mg deficiency that can present with many signs and symptoms. Mg absorption requires plenty of Mg in the diet, Se, parathyroid hormone (PTH) and vitamins B6 and D. Furthermore, it is hindered by excess fat. On the other hand, Mg levels are decreased by excess ethanol, salt, phosphoric acid (sodas) and coffee intake, by profuse sweating, by intense, prolonged stress, by excessive menstruation and vaginal flux, by diuretics and other drugs and by certain parasites (pinworms). The very small probability that all the variables affecting Mg levels will behave favorably, results in a high probability of a gradually intensifying Mg deficiency. It is highly regrettable that the deficiency of such an inexpensive, low-toxicity nutrient result in diseases that cause incalculable suffering and expense throughout the world. The range of pathologies associated with Mg deficiency is staggering: hypertension (cardiovascular disease, kidney and liver damage, etc.), peroxynitrite damage (migraine, multiple sclerosis, glaucoma, Alzheimers disease, etc.), recurrent bacterial infection due to low levels of nitric oxide in the cavities (sinuses, vagina, middle ear, lungs, throat, etc.), fungal infections due to a depressed immune system, thiamine deactivation (low gastric acid, behavioral disorders, etc.), premenstrual syndrome, Ca deficiency (osteoporosis, hypertension, mood swings, etc.), tooth cavities, hearing loss, diabetes type II, cramps, muscle weakness, impotence (lack of NO), aggression (lack of NO), fibromas, K deficiency (arrhythmia, hypertension, some forms of cancer), Fe accumulation, etc. Finally, because there are so many variables involved in the Mg metabolism, evaluating the effect of Mg in many diseases has frustrated many researchers who have simply tried supplementation with Mg, without undertaking the task of ensuring its absorption and preventing excessive elimination, rendering the study of Mg deficiency much more difficult than for most other nutrients.

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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.

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If any questions, please schedule an appointment with my office.

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Help now: Spread awareness of Complex Regional Pain Syndrome, also known as Reflex Sympathetic Dystrophy


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This alert has been just received from RSDSA – Reflex Sympathetic Dystrophy Association.

I am not affiliated with them, but they fund research into treatment of intractable pain of all causes.

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The RSDSA is very special. Unique among philanthropic organizations. The best of the best.

RSDSA with Mission

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Dear Nancy
Color The World Orange is an annual event held the first Monday of November each year to spread awareness of Complex Regional Pain Syndrome, also known as Reflex Sympathetic Dystrophy. This year’s event is Monday, November 2, 2015.
The easiest way to Color The World Orange on November 2nd is to wear orange and post pictures to social media with the hashtag: #CRPSORANGEDAY.
Across the globe CRPS/RSD patients and supporters will be wearing orange, as well as planning events to spread awareness of CRPS, and raising funds to support research of this debilitating condition. All donations to this page will go to RSDSA for research.
Color The World Orange is a day for the whole community to join together and show that even though we are in pain, we are strong! For more ideas on how to Color The World Orange, visit the Color The World Orange Website or Facebook page. Please see the links below.
 
Best of health,
JWbroatchnew    
Jim Broatch, MSW
executive Vice President, Director  

RSDSA-New

Be sure to visit the RSDSA website for the latest CRPS/RSD information including new treatment options, valuable resources, upcoming, events, and Support Group in your area.

Click Here to Visit Now!

  • SUICIDE CRISIS INFORMATION
    If you or a loved one are in crisis
    • Please call 1.800.SUICIDE (800.784.2433)
    • Hope Line or The National Suicide Prevention Lifeline
    • 800.273-TALK (8255) – (888-628-9454 en Espanol)

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      I know some of you ignore this, but I must repeat:

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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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      This material 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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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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Vitamin Drinks Risk Serious Harm


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Are Vitamin Drinks a Bad Idea?

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from New York Times

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Free full report below

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I need time to write about so many exciting things I am seeing in my practice, but this is always lurking. Children and athletes are at most risk for growing toxicity from overdosing on supplements. This has yet to be studied. Not just from vitamin drinks but daily vitamins pills too.

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IV Infusion clinics are the rage now popping up all over London. The very luxurious price alone would convince most people that the more they pay, the better it feels. Did it begin in Hollywood? Surely La Jolla will be soon.

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I see so much of the excess. My thoughts are often on the harm of vitamins and supplements and I’ve posted here, here, here, here, here, here, here, here, here, here about their risk to brain, peripheral nerves, heart, hypertension, cancer, interference with chemotherapy and cardiovascular medications, and in some cases risk to every cell of the entire body.

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$18 Billion a year business in the U.S

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This is an $18 billion a year business in the U.S. which explains why, since the 1970’s, Congress shot down the FDA’s authority to regulate dietary supplements and nutrients that could be fortified. Of course, congress restricts and excludes trade of European supplements that have proven scientific value. Usually this would be called unfair trade, but ….

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Forgive me for being superfluous to point out that those who bring in one bottle with 30 ingredients astonishes me. Centrum Silver I’m thinking of you. How much titanium, molybdenum, chromium and zinc do we need every day to go with its toxic doses of B6 and the proven harmful Vitamins A and E? What is so completely lacking in the diet? How easy is this on seniors with reduced capacity to metabolize medications? No studies, thanks.

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I favor several important vitamins for key reasons based on blood work, but known essential supplements seem to lost on many. Zinc is everywhere. This is rarely tested in a patient. Who has ever once tested most things in Centrum Silver? Could the popularity be due to bombardment or with unproven labeling or endless aisles of bottles?

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This is a rich person’s game.Typically female, unless guys are hiding or avoiding them.

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There are those who drag behind them truck loads of large suitcases bursting with expensive supplements. They need to stop the cause of their problems that is in those bags. They may link bags together with cabling like a train or walk back several times to pull in more and more.

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Stop all of them. That is the treatment. That and a long, long drug holiday to wash them out of the system. Eat a basic healthy diet in moderation and always exercise. There is then hope to re-establish equilibrium. Who could swallow that many pills every day and have any room left for food?

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But I digress.

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The Report – free full text.

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An examination of the nutrient content and

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on-package marketing of novel beverages.

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Risks

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46 novel beverages tested

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“there is little evidence that consumers stand to benefit

from the micronutrients most commonly found in these products.”

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But aiyee!!! the problems.

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At long last, after billions spent on vitamin drinks, the risks are addressed by Valerie Tarasuk, lead author of the study. She is nutrition science professor at the University of Toronto faculty of medicine. I quote extensively from the New York Times but recommend the entire article.

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“A nationwide study carried out by the National Institutes of Health in 2012 found that Americans who take vitamins and supplements were already getting large amounts of nutrients from their food, and on top of that they had the lowest prevalence of vitamin deficiencies to begin with. The study found that supplement use put these people at increased risk of potentially excessive consumption of folic acid, calcium, iron, zinc, magnesium and vitamins A, C and B6.”

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 “…for much of the general population today, there is no scientific justification for a high intake of vitamins and minerals, said Mara Z. Vitolins, a registered dietitian and professor of epidemiology and prevention at Wake Forest Baptist Medical Center.”

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“When consumed in excess, some water-soluble vitamins like B and C are excreted in the urine [unless toxic to nerves and kidneys, those of you who develop nerve pain and kidney stones from them]. But fat soluble-vitamins – including A, D, E and K – accumulate in tissues, posing potential risks.”

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“These fat soluble vitamins are very stable,” she said. “They’re not released in the urine. If you are over-consuming them, you can raise your levels gradually over time and get into trouble with liver function. You have to be very careful with them.”

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Authors should warn be even more cautious when you lose weight, the fat and that giant stash must somehow get out or what harm will they all cause next?

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“Data from clinical trials have highlighted clear risks from excess. A large study published in JAMA in 2009, for example, looked at clinical trial data on more than 6,000 heart disease patients who were treated daily with either B vitamins or placebo over a seven year period. The study found that those who were given folic acid and B12 had higher mortality and cancer rates.”

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“In 2012, a review of 78 clinical trials involving 300,000 people that was published in the Cochrane Database found that antioxidant supplements like beta carotene, vitamin A and vitamin E actually increased mortality. A year later, the United States Preventive Services Task Force concluded that there was “limited evidence” that taking vitamins and minerals could prevent cancer and cardiovascular disease.”

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“The task force noted that two clinical trials had found “small, borderline” reductions in cancer incidence in men who took multivitamins. But the group also said there was good evidence that high doses of antioxidants could cause harm.”

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No one could ever be funded to study the untold combinations of a single bottle that contains 30 ingredients. Studies require placing humans at risk long term, not a quick look at test tubes or a few mice.

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The majority who have finances for these products are often among the best fed in the world if not the the most prosperous.

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If you have read this far, you are not the person lumbering to push these truckloads of supplements ahead like Sisyphus.

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Know hope.

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That readers will read.

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Is there any hope with congress?

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Do not overlook the A, B, C’s

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Balancing the harms, the staggering 90% less atrophy has been shown in areas typically harmed by Alzheimers in the OPTIMA study (Oxford Project to Investigate Memory and Ageing) at Oxford University, March 2013, when they looked at persons with mild cognitive impairment (MCI).

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They looked at brain MRI changes in 156 volunteers before and after two years after placebo vs certain doses of B vitamins. No one has tested these doses long term for toxicity. I would never recommend their dose of B6 that has known toxicity to brain and peripheral nerves, see my post here. And they hold a patent on this vitamin regimen, making the protocol potentially suspect.

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It has been shown a few years before, that size of the hippocampus tends to predict Alzheimers to some extent.

 

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We know that those with Major Depressive Disorder and those with chronic low back pain have been shown to develop brain atrophy and memory loss. It would seem essential to test these vitamins again on those groups and replicate the study on mild cognitive impairment, with placebo controlled double blind testing. Again, caution, B6 can be toxic.

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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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Depression PTSD – Ketamine Rapid Relief


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  • PTSD has a more direct link to suicide than previously thought, a current Texas A&M University study concludes – references below.

  • A high lifetime risk of suicide occurs in women who have been sexually and physically abused as young girls.

  • More than 300,000 veterans have been diagnosed with PTSD or major depression – many not yet diagnosed.

  • Risk of suicide is the highest during the first month of standard antidepressant therapy, and a significant number of patients do not have adequate improvement even after months, resulting in harm to personal and professional lives.

  • Patients are at suicide risk upon discharge from psychiatric hospitals.

  • Significant predictors of both suicide attempts and preoccupation with suicide are guilt and anger and impulsive behaviors.

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  • Ketamine is the most important breakthrough in treatment of major depression with rapid and lasting effects.

  • Ketmine can help immediately, unlike all other antidepressants that may require weeks or months to work, if they help at all. See NPR report here – that appeared soon after I posted this (skip to their last section). It is FDA approved and legal. NPR again reports ketamine’s rapid relief of depression. A 28 year old man whose refractory depression began at age 15, after ketamine, says:

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    ‘I Wanted To Live Life’

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    Stephens himself has vivid memories of the day he got ketamine. It was a Monday morning and he woke up feeling really bad, he says. His mood was still dark when doctors put in an IV and delivered the drug.”Monday afternoon I felt like a completely different person,” he says. “I woke up Tuesday morning and I said, ‘Wow, there’s stuff I want to do today.’ And I woke up Wednesday morning and Thursday morning and I actually wanted to do things. I wanted to live life.”.
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    Since then, they treated him with Riluzole that is FDA approved for ALS and has one of the dirtiest side effect profiles I have ever seen in medicine with serious organ toxicity. Ketamine rarely causes mild transient side effects, usually none. It appears the concern is how ketamine is used on the street with potential for abuse. I do not see ketamine abuse in my patients, some of whom are on opioids for pain or Valium family medicines from their psychiatrist. All of those have a greater potential for abuse, also not occurring in my patients. Pain and/or depression can lead to suicide.
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    About 18 months ago, researchers at Yale found a possible explanation for ketamine’s effectiveness. It seems to affect the glutamate system in a way that causes brain cells to form new connections.
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    Researchers have long suspected that stress and depression weaken some connections among brain cells. Ketamine appears to reverse the process.

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    It would be of interest to see a case report of the bladder problems they mention. Is this in a single drug addict who used many unknown medications on the street? Several physicians have infused IV ketamine for persons with pain for many years, in far higher doses than I prescribe, with no report of any but transient minor symptoms.

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    Memory loss and brain atrophy occur with chronic depression, reported by the National Institute of Mental Health ~2001. The mechanism is described by Barsook referenced here.

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  • You do not need to be hospitalized.

  • A single low dose ketamine treatment, given nasally, may reduce core symptoms of PTSD and depression. It can save your life.

  • Relief of depression may occur in 2 minutes to 2 hours and may last 1 to 2 weeks.

  • National Institute of Mental Health published 100% relief in a group with depression refractory to all treatment that failed as long as 43 years.

  • You cannot anticipate when suicidal thoughts occur, but you can carry ketamine with you for instant relief.

  • Ketamine is not toxic, not expensive, side effects if any are transient – usually none. It is compounded by pharmacy.

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  • I can help. I’ve prescribed this medication for 11 years, spoken with some of the world’s foremost psychiatrists. Some of my patients with profound pain/depression travel to Germany for high dose ketamine coma treatment of RSD/CRPS and tolerate those doses. Ketamine is safe even in babies and children. Very few MD’s prescribe ketamine, and even fewer have much experience with it.

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  • I need to examine you in person.

  • I can meet with you at my office and it is essential that you meet with my colleagues, a psychologist and psychiatrist.

  • Time is of the essence because we may need to adjust the concentration of ketamine. We need to determine your comfort level with its use.

  •  This must be a team approach.

  •  Please ask your psychiatrist to call me with your diagnoses and speak with me in person.

  • If you live long distance, this team should include your local psychiatrist, or one nearby, who will prescribe ketamine for depression.

  • Alternately, I will need to see you in my office every few months to renew the medication.

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  • The medical literature on ketamine use is profoundly important. There are over 6,800 medical publications. Ketamine has potent healing powers. Karl Jansen, psychiatrist in London, believes that “ketamine has potent healing powers when used as an adjunct to psychotherapy.” There is nothing like it; however, treatment for serious depression still requires team support, not medication only.

  •  The World Health Organization reports that disability to due depression is second only to heart disease.

  • Suicide is a catastrophic medical emergency. I cannot stress this enough. Depression is treatable.

  • Your death is unnecessary. It would be a terrible loss to all who love you.

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    References
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    http://emedicine.medscape.com/article/2013085-clinical#aw2aab6b3b3
    Suicide Clinical Presentation

http://www.ptsd.va.gov/professional/pages/ptsd-suicide.asp The Relationship Between PTSD and Suicide  

PTSD alone out of six anxiety diagnoses was significantly associated with suicidal ideation or attempts. Anger and impulsivity have also been shown to predict suicide risk in those with PTSD.

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Articles, below, support use of ketamine for rapid relief of depression, even for resistant bipolar depression. The lead author of the first three studies is Carlos Zarate, M.D., Chief of the Mood and Anxiety Disorders Research Unit of the National Institute of Mental Health, NIMH:

http://www.ncbi.nlm.nih.gov/pubmed/20673547   Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder

100% response in persons with refractory depression: 29% went into remission, another 71% were responders.

http://archpsyc.ama-assn.org/cgi/content/full/67/8/793  A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression It even works for resistant bipolar depression

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726824/figure/F1/  Ketamine and the next generation of antidepressants with a rapid onset of action

Potential targets for ketamine and similar agents induce rapid and sustained antidepressant effects. A diagram scientists and physicians will find useful for mechanisms. “Notably, ketamine’s rapid antidepressant effects have been shown to be modulated by AMPA relative to NMDA throughput. Excessive glutamate also stimulates the extrasynaptic NMDA receptors, which antagonizes the activation of neurotrophic cascades. The potential sustained (sub-acute) antidepressant effects of ketamine are hypothesized to be mediated by increases in CREB and BDNF expression, as well as the anti-apoptotic protein Bcl-2.”

https://www.sciencemag.org/content/329/5994/959.abstract mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists

“The rapid antidepressant response after ketamine administration in treatment-resistant depressed patients suggests a possible new approach for treating mood disorders compared to the weeks or months required for standard medications….Our results demonstrate that these effects of ketamine are opposite to the synaptic deficits that result from exposure to stress and could contribute to the fast antidepressant actions of ketamine.”

http://psychiatry.jwatch.org/cgi/content/full/2010/1008/5 Ketamine’s quick antidepressant actions

“The resulting protein synthesis and neuronal alterations in the medial prefrontal cortex are the opposite of those produced by chronic stress….”

 

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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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Medications Physician Training


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Doctors can call to schedule a 3 hour appointment for training in these medications. I do not train patients in prescribing. If you are a physician needing these treatments, please discuss with your treating physician and ask her/him to schedule a time.

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Patients with pain need to slowly taper off opioids and remain off for three weeks before starting. This is assuming good manual physical therapy and cognitive behavioral therapy is also prescribed.

 

Relevant medications can be started in one week for major depression or bipolar depression.

If for treatment resistant pain, these can be started in two or three weeks.

Medications may or may not include the following:

ketamine nasal spray – this may not be the most important medication. It takes a team.

naltrexone low dose  or  ultra low dose*****  one of the most valuable medications I have ever prescribed

dextromethorphan sustained release

oxytocin – a hormone. Your brain makes it, your heart makes it. It is NOT oxycontin.

memantine high dose – research in France has shown it may work for pain, exceeds the FDA approved 28 mg/day dose

lamotrigine an epilepsy drug

B complex – do not take more than 2 mg B6 as it is neurotoxic, creates burning pain and ataxia that may be irreversible

Vitamin D

Boswellia (migraine)

Others

They are not magic bullets, not cures. Experience comes in how and when to time the use of these medications to minimize risk of side effects and “clamp” pain and/or major depression. Thankfully, I do have patients whose “intractable” pain is in remission. Intractable means there has been no response to opioids or other medications or combinations tried so far.

Medications that I use are based on my focus on neuropharmacology, not on injections and spinal cord stimulators or ECT or rTMS which often have already been tried and failed to help.

Bear in mind, some physicians who do not use these medications may be unwilling to prescribe them. Some specialists limit their practice to procedures, others do not specialize in neuropharmacology. Most of my patients are complex and have usually been tried on a long list of medications and interventions that failed to help.

Use the search function on my website to read about some of the medications I prescribe or case studies, particularly note the articles posted May 26, 2009, for some of these medications and January 2011 to read some of the science of glia and inflammation that is present in chronic pain or in depression.

There is not a doctor on the planet who can predict what anyone’s response to treatment will be. If they do, you should avoid them for dishonest practices.

I cannot speculate what percentage of patients would be helped by my approach. To do that, you would need large numbers and placebo group to compare one person’s pain with another – no such standardized comparison exists. Research dollars are very limited and only one medication is tested at one time. However, if you get 10% result with 4 or 5 medications, you are noticing some change when one alone may do nothing noticeable.

Treatment and outcomes are individualized for every person with pain or Major Depression. Each person has a different pain threshold. Some lack a chromosome and/or have difficulty metabolizing medications.

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I do not recommend spinal cord stimulators because:

1. Most important, there are no long term studies showing lasting benefit;

2. they may cause complications, for example infection, paralysis, migration of the device or the leads, or new pain and scarring at the site of the external box, tethering to the cord itself;

3. for the rest of your life, you will never be able to have an MRI scan once the leads are in place, regardless of whether you have cancer or stroke;

4. there may be other ways to relieve intractable pain. Consider trying them first.

 

Patients who have had issues with substance abuse including alcoholism are not candidates for outpatient use of ketamine.

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Compounding Pharmacy

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LaVita Compounding Pharmacy 800-866-507-1990 open Monday – Friday until 5:00 P.M., has information and instructions on these medications if not used by your local compounder. LaVita ships to 11 or 12 states.

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Physical Therapy

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Bruce Inniss, P.T. at Inniss Physical Therapy, 1-619-287-4678, F 1-619-287-0350, 6475 Alvarado Rd, San Diego CA 92120. Bruce is an orthopedic physical therapist, a rare degree for therapists to achieve. Many of my treatment refractory patients who had no benefit from decades of physical therapy have found relief with Bruce and return two or three times a year even from London to see him. His office is 30 minutes from mine in good traffic. Besides the invaluable assessment and treatment, they are one of the first clinics west of Texas to introduce Unloaded Ambulation, partial Body Weight treadmill training and the first physical therapy clinic in San Diego to introduce isoinertial training and Norsk Sequence Training.

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Return to home page: Welcome to my Weblog on Pain Management!

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Posted in . 33 Comments »

Health supplements – a brilliant graphic. Are they interfering with YOUR medication?



Some supplements can be extremely helpful for conditions I follow in my practice, while others may harm. Go to this constantly updating link to enlarge a brilliant and very useful bubble graph “like painting with data.”

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Their image is a “balloon race”. The higher a bubble, the greater the evidence for its effectiveness. But the supplements are only effective for the conditions listed inside the bubble.” Try it!

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When you click to the right of their active link to select a medical condition, it will suggest a supplement that has been shown to help. Then return back, below the graphic to check on cautions and toxicity that importantly is not mentioned in their work.

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As explained for the graph, “This visualisation generates itself from this Google Doc. So when new research comes out, we can quickly update the data and regenerate the image.” The Google Doc is a spreadsheet of references from large human, blind, placebo-controlled trials only, sourced from PubMed and Cochrane that publishes leading medical research.

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CAUTION: Toxicity is still important. For example, even though licorice is helpful for coughs, it may seriously increase blood pressure. Valerian may help sleep but may be toxic to liver and may have a withdrawal syndrome.

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Make sure you check here to review the benefits and toxicity to see how supplements may alter your chemotherapy or medication for heart and blood pressure. Another review here: Use of Herbal Products and Potential Interactions in Patients With Cardiovascular Diseases.

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The paper lists several common common drug-herb interactions: Grapefruit juice can be especially risky, increasing your dose of statins and calcium-channel blockers by slowing the metabolism of those prescriptions. St. John’s Wort raises blood pressure and heart rate;  garlic and ginger increase the risk of bleeding in patients on blood thinners. Soy milk and green tea can decrease the effectiveness of warfarin. Ginkgo biloba, ginseng, echinacea, aloe vera and licorice are also discussed.~

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A recent multi-center, double blind, randomized trial of Ginkgo Biloba involving 3,019 subjects over a median of 6.1 years showed that it fails to help memory. Further, a new report in the Journal of Natural Products summarizes beneficial uses but also discusses toxic effects on heart and brain due to the ginkgotoxin. The authors recommend that sales should be restricted. Toxicity to the heart may occur from heart block, ventricular fibrillation and death. And it may lower the seizure threshold in persons with epilepsy. The toxin depletes vitamin B6 in the brain, impairs glutamate metabolism, and triggers seizures via an imbalance in neurotransmitters: high glutamate and low GABA. It has been shown to induce metabolism of epilepsy medication, thus dropping blood serum levels below therapeutic range further increasing risk of seizure.

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Remember to ask your doctor how these may interact with your medication.

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Check here on Vitamin D, a steroid hormone that is anti-inflammatory. Vitamin D is one of the hottest topics in kidney research and hypertension today, as discussed here. And hypertension is important. The latest research on Alzheimers Disease in the last two years from Columbia University Medical School in NYC tells us that risk factors for Alzheimers Disease are the same as for coronary heart disease: exercise, hypertension, cholesterol, obesity, diabetes, smoking. And research suggests that low vitamin D increases risk of cancer of breast, colon, prostate among many other functions. “Vitamin D insufficiency is associated with suboptimal health.

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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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Vitamin D status and arterial hypertension: a systematic review


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This is an excellent article from Nature Reviews Cardiology, 18 August 2009, and offers doctors CME 0.75 AMA PRA Category 1 Credits. Click blue link below for complete article.

Vitamin D status and arterial hypertension: a systematic review

Stefan Pilz1, Andreas Tomaschitz1, Eberhard Ritz2 & Thomas R. Pieber1

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A short excerpt is included here:

Vitamin D deficiency is common and is primarily caused by a lack of ultraviolet-B (UVB) radiation from reduced sun exposure, and the consequent limiting of vitamin D production in the skin. The vitamin D endocrine system regulates about 3% of the human genome. Observational data support the concept that vitamin D is involved in the pathogenesis of cardiovascular diseases and arterial hypertension. The antihypertensive properties of vitamin D include renoprotective effects, suppression of the renin–angiotensin–aldosterone system, direct effects on vascular cells, and effects on calcium metabolism, including prevention of secondary hyperparathyroidism. The results of clinical studies largely, but not consistently, favor the hypothesis that vitamin D sufficiency promotes lowering of arterial blood pressure. Randomized, placebo-controlled trials are greatly needed to clarify and definitively prove the effect of vitamin D on blood pressure. In general, the antihypertensive effects of vitamin D seem to be particularly prominent in vitamin-D-deficient patients with elevated blood pressure. Thus, in view of the relatively safe and inexpensive way in which vitamin D can be supplemented, we believe that vitamin D supplementation should be prescribed to patients with hypertension and 25-hydroxyvitamin D levels below target values.

Key points
  • Vitamin D deficiency is common and can be attributed to reduced sun exposure, which limits ultraviolet-B (UVB)-induced vitamin D production in the skin
  • Most cells express the vitamin D receptor (VDR) as well as 1alpha-hydroxylase, which underlies several regulatory mechanisms and converts 25-hydroxyvitamin D (25[OH]D; used to classify vitamin D status) to 1,25-dihydroxyvitamin D (1,25[OH]2D)
  • 1,25(OH)2D has high affinity for the VDR, but circulates in lower concentrations than 25(OH)D and is more an indicator of calcium homeostasis and kidney function than vitamin D status
  • About 3% of the human genome is directly or indirectly regulated by the vitamin D endocrine system
  • The antihypertensive effects of vitamin D include renoprotective effects, suppression of the renin–angiotensin–aldosterone system, effects on calcium homeostasis including the prevention of secondary hyperparathyroidism, and vasculoprotection
  • Accumulating evidence—from insights into molecular mechanisms to the outcome of randomized trials—favors the hypothesis that vitamin D deficiency contributes to arterial hypertension, but further data are needed
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Introduction

Vitamin D insufficiency affects almost 50% of the population worldwide.1 This pandemic of hypovitaminosis D can mainly be attributed to lifestyle (for example, reduced outdoor activities) and environmental (for example, air pollution) factors that reduce exposure to sunlight, which is required for ultraviolet-B (UVB)-induced vitamin D production in the skin. Levels of UVB radiation diminish with increasing distance from the earth’s equator, during the winter months, and as a result of air pollution. Black people absorb more UVB in the melanin of their skin than do white people and, therefore, require more sun exposure to produce same amounts of vitamin D.2 Importantly, conditions associated with reduced UVB-induced vitamin D production, such as high latitude, industrialization, and dark skin, have all been associated with increased blood pressure values.2 The logical hypothesis that high UVB-induced vitamin D production is associated with low blood pressure was confirmed by a small trial of 18 patients with untreated essential hypertension.3 The researchers found that systolic and diastolic blood pressure values were reduced by 6 mmHg after 6 weeks of UVB irradiation three times per week. UVB irradiation was also associated with a 162% rise in plasma 25-hydroxyvitamin D (25[OH]D) concentrations, but in hypertensive patients who received UVA irradiation, no significant change in 25(OH)D levels or blood pressure occurred.3

The high prevalence of vitamin D insufficiency is a particularly important public health issue because hypovitaminosis D is an independent risk factor for total mortality in the general population.4 A meta-analysis published in 2007 showed that vitamin D supplementation was associated with significantly reduced mortality.5 Furthermore, vitamin D insufficiency is associated with an increased risk of cardiovascular events, but whether this association reflects a causal relationship remains unclear.6, 7, 8 The effect of vitamin D on blood pressure could be one of the potential mechanisms underlying the link between vitamin D and cardiovascular disease. In this Review, we will summarize the mechanisms that are presumed to underlie the relationship between vitamin D and arterial hypertension, and examine the clinical data for this association.

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Vitamin D metabolism

In humans, the primary source of vitamin D is UVB-induced conversion of 7-dehydrocholesterol to vitamin D in the skin.1 Just 10–20% of our vitamin D comes from dietary sources, such as fish, eggs, or vitamin-D-fortified milk (Figure 1).1 Vitamin D is hydroxylated in the liver to 25(OH)D—the main circulating vitamin D metabolite, which is largely bound to vitamin D binding protein in serum, and is used to classify vitamin D status: vitamin D sufficient (25[OH]D greater than or equal to30 ng/ml [or greater than or equal to75 nmol/l]), vitamin D insufficient (25[OH]D 20–30 ng/ml [or 50–75 nmol/l]), and vitamin D deficient (25[OH]D <20 ng/ml [or <50 nmol/l]).1 These cut-points are currently the most commonly used classification of vitamin D status, but some debate about exact threshold values still exists. Some researchers consider 25(OH)D levels of 10–20 ng/ml (25–50 nmol/l) as vitamin D insufficient and levels below 10 ng/ml (25 nmol/l) as vitamin D deficient, whereas others use a cut-off level of 40 ng/ml (100 nmol/l) to define sufficient vitamin D status.9, 10 25(OH)D is transformed by renal or extrarenal 1alpha-hydroxylase into 1,25-dihydroxyvitamin D (1,25[OH]2D), which circulates at much lower serum concentrations than 25(OH)D, but has a much higher affinity to the vitamin D receptor (VDR).11 Serum levels of 1,25(OH)2D are mainly determined by renal 1,25(OH)2D production, which is closely related to calcium homeostasis, and is upregulated by parathyroid hormone, the concentration of which increases when calcium levels are low.1, 12 In addition, other factors such as fibroblast growth factor 23 and Klotho, which suppress 1alpha-hydroxylase expression, have also been shown to regulate the renal conversion of 25(OH)D to 1,25(OH)2D.13 Studies have, however, shown that many other cell types, including those of the vascular wall, express 1alpha-hydroxylase with subsequent intracellular conversion of 25(OH)D to 1,25(OH)2D, which exerts its effects at the level of the individual cell or tissue before being catabolized to biologically inactive calcitroic acid.1, 12, 14 These intracellular tissue levels of 1,25(OH)2D are determined by the concentration of circulating 25(OH)D, which is, therefore considered the best indicator of whole-body vitamin D status. Importantly, extrarenal 1alpha-hydroxylase expression also underlies various regulatory mechanisms. In this context, extrarenal 1,25(OH)2D production in macrophages is stimulated by Toll-like receptor as part of the innate immune response against intracellular bacteria.15 Another example of extrarenal regulation of 1alpha-hydroxylase is the increased production of 1,25(OH)2D by keratinocytes in wounds, which could be induced by transforming growth factor beta1.16 25(OH)D serum levels, therefore, provide a good estimate of vitamin D status, but regulation of 1alpha-hydroxylase activity should also be considered.

1,25(OH)2D binds to the VDR and, after forming a heterodimer with the retinoid X receptor (RXR), binds to specific DNA sequences—the so called ‘vitamin D responsive elements’. These sequences are located in the promoter regions of various vitamin-D-dependent genes that are either upregulated or downregulated by the RXR–VDR complex.1, 12, 14 Approximately 3% of the human genome is directly or indirectly regulated by the vitamin D endocrine system, which supports the idea that vitamin D insufficiency has widespread adverse consequences for human health.14 In addition to cardiovascular pathology, vitamin D insufficiency can cause musculoskeletal, malignant, metabolic, or immunological diseases.1, 12, 14

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Vitamin D Anti-hypertensive effects

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Vitamin D toxicity

When discussing the beneficial effects of vitamin D on blood pressure, one must consider that pharmacological doses of vitamin D have been shown to cause arterial hypertension, vascular stiffness, and atherosclerosis in rodents; whether this finding has any relevance for humans is unclear.129 In humans, vitamin D toxicity and associated hypercalcemia—which can cause reversible hypertension—is observed when 25(OH)D levels are higher than 150 ng/ml (374.4 nmol/l).1 In clinical trials, vitamin D toxicity was not observed with doses of up to 10,000 IU vitamin D per day, which is approximately the level of vitamin D production that can be achieved by endogenous UVB-induced vitamin D synthesis in the skin.130, 131 Consequently, at 10,000 IU vitamin D per day, and in the absence of increased vitamin D sensitivity (for example, sarcoidosis or tuberculosis), vitamin D supplementation is safe. Presumably there is a wide margin between the level of 25(OH)D needed for vitamin D sufficiency (greater than or equal to30 ng/ml [or 75 nmol/l]) and the level of toxicity (>150 ng/ml [or >374.4 nmol/l]).

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Vitamin D supplementation

An intake of 1,000 IU (25 microg) of vitamin D per day can be generally assumed to result in an increase in 25(OH)D levels of approximately 10 ng/ml (25 nmol/l).132, 133 Evidence indicates that daily, weekly, and monthly vitamin D dosing frequencies can equally increase serum 25(OH)D levels, which have a half-life of about 1 month. In this context, an oral vitamin D intake of 1,500 IU daily, 10,500 IU once weekly, or 45,000 IU once every 28 days has been demonstrated to result in similar increases of 15–16 ng/ml (37.4–40.0 nmol/l) in 25(OH)D levels.134 The dose to correct vitamin D deficiency should be sufficiently high to achieve 25(OH)D levels of at least 30 ng/ml (75 nmol/l). For example, a patient with 25(OH)D levels of 10 ng/ml (25 nmol/l) should receive at least 2,000 IU daily, which corresponds to weekly doses of at least 14,000 IU or monthly doses of at least 56,000 IU. Several authors recommend loading doses in the initial phase of treatment (that is, 50,000 IU weekly for 8 weeks or 50,000 IU daily for 1 week) before starting maintenance therapy (that is, at least 1,000 IU vitamin D for a person with initial 25[OH]D levels of 20 ng/ml [50 nmol/l]).1, 10 Individual response to vitamin D doses does, however, vary widely and certain patients, such as those who are obese or suffer from malabsorption, might require much higher vitamin D doses than individuals without comorbidities.1, 133 Measurements of 25(OH)D levels are, therefore, useful to monitor 25(OH)D levels and to allow for adequate correction of the vitamin D dose. 25(OH)D levels should be reassessed 3–6 months after initiation of vitamin D supplementation. In patients with increased vitamin D sensitivity, such as those with sarcoidosis or tuberculosis, calcium should be measured in the initial phase of treatment. One problem with vitamin D treatment is that, although maintaining 25(OH)D levels above 30 ng/ml (75 nmol/l) is generally recommended, no consensus exists about optimal 25(OH)D levels. At present, many researchers recommend maintaining 25(OH)D levels between 30 and 60 ng/ml (75.0–149.8 nmol/l).1, 10 We do not know whether higher levels than this are beneficial or detrimental. Data from NHANES-III indicate a ‘J-shaped’ association between 25(OH)D levels and mortality, with the highest mortality in persons with the lowest 25(OH)D levels, but with slightly increasing mortality in those with supraphysiological 25(OH)D levels. However, other data indicate that particularly high levels of vitamin D are optimal for cancer prevention.4, 10

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Conclusions

Accumulating evidence, ranging from insights into molecular mechanisms to the outcome of randomized controlled trials, favors the hypothesis that vitamin D deficiency contributes to arterial hypertension. The antihypertensive effects of vitamin D are mediated by renoprotective effects, suppression of the RAAS, by beneficial effects on calcium homeostasis, including the prevention of secondary hyperparathyroidism, and by vasculoprotection. However, definitive evidence from appropriately powered, controlled, intervention trials is lacking. Some inconsistent results from studies of the relationship between vitamin D status and arterial hypertension have been reported, possibly because the effects of 25(OH)D on blood pressure are not apparent in normotensive individuals with 25(OH)D levels within the normal range. In general, evidence for the antihypertensive effects of vitamin D is strongest in patients with elevated blood pressure and vitamin D deficiency; these patients would, in our opinion, benefit from vitamin D supplementation. In addition to cardiovascular sequelae, vitamin D deficiency has been associated with autoimmune, malignant, neurological, metabolic, and infectious diseases, as well as with bone fractures.1, 12, 14, 117, 130, 131 In view of the multiple health benefits of vitamin D and the high prevalence of vitamin D deficiency, as well as the easy, safe, and inexpensive ways in which vitamin D can be supplemented, we believe that the implementation of public health strategies for maintaining a sufficient vitamin D status of the general population is warranted.1, 12, 117, 130, 131

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