Statin Adverse Effects: Evidence for a Mitochondrial Mechanism

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849981/?tool=pmcentrez




Statin Adverse Effects: A Review of the Literature and Evidence for a Mitochondrial Mechanism
 
In the case of statins, a potential basis for opposing effects occurring in muscle and in other organs can be identified. Evidence supports the proposition that antioxidant effects of statins underlie (or contribute to) many fundamental statin benefits – including benefits to flow and oxygen delivery46-48 and inflammation.49, 50 These effects may participate in improved walking distance in patients on statins, including benefits to muscle/walking in persons with and without peripheral artery disease.29 Yet a subset of people reproducibly exhibit increases in markers of oxidation on statins,51 and the occurrence of this increase has been tied to muscle pain on statins.52, 53
...
A range of cases have now been reported in which statin use has “uncovered” previously clinically silent or clinically tolerated conditions, ranging from McArdle disease159, 160 to myotonic dystrophy159 to acid maltase deficiency161 to possible Kennedy disease.159 Statins have also exacerbated known muscle conditions, such as myasthenia gravis.78 In the case of mitochondrial myopathies, the relative degree to which statins have unmasked vs induced disease may not always be clear.159, 162
...

Several widely used statins – atorvastatin, simvastatin, and lovastatin (and previously cerivastatin, now off the market) – are metabolized by the cytochrome P450 (CYP)3A4 pathway.^318
...
While a medley of potential mechanisms may cause or contribute to statin AEs (and these merit more full review in another venue), mitochondrial mechanisms have been repeatedly implicated in muscle AEs. Mitochondrial defects predispose to problems on statins (as shown in the second to last entry of Table IV, ‘Genetic mutations associated with mitochondrial dysfunction’). Additionally, statins predispose to mitochondrial defects (Table V,^{22 31, 32, 112, 155, 158, 162, 397, 406-414}) – in all users and, to a greater degree, in vulnerable individuals. Dose-dependent reductions in coenzyme Q10^20-22 can reduce cell energy, promote oxidation,^{362, 415} promote apoptosis, and unmask silent mitochondrial defects.^{23-25, 362, 415-418} The mevalonate pathway, which statins inhibit, also produces heme-A, which has it own central involvement in mitochondrial electron transport.^419
...
 For instance, mitochondrial encephalomyopathy resulting from heritable coenzyme Q10 deficiency classically produces fatigue, muscle symptoms, and cognitive problems,⁴⁴⁰ although the cases referred for analysis are often relatively severe.^{429, 441} Gastrointestinal²⁶ and neurological symptoms,^{432, 442} psychiatric symptoms,^443-446 sleep problems,^{444, 447} glucose elevations,¹⁸² and a range of other symptoms reported on statins also arise in mitochondrial dysfunction.^{379, 448-457
...}
Thus, in an analysis of data, presented in the Australian Adverse Drug Reaction Bulletin, it was noted that “Statin-associated peripheral neuropathy may persist for months or years after withdrawal of the statin… In two ADRAC (Adverse Drug Reactions Advisory Committee) cases of persistent peripheral neuropathy, motor and sensory conduction tests showed minimal recovery 4 and 12 months, respectively, after discontinuation of simvastatin, despite clinical improvement.”561


As reviewed here, AEs on statins may signal a mitochondrial vulnerability, which may alter or perhaps even reverse an otherwise favorable impact of statins on cell energetics. And AEs may signal occurrence of a net prooxidant rather than antioxidant effect of statins53 with possible unfavorable implications for a range of statins' proposed pleiotropic effects.892


Full report here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849981/?tool=pmcentrez

Dr. Klinghardt's Treatment of Lyme Disease

http://articles.mercola.com/sites/articles/archive/2009/08/04/Dr-Klinghardts-Treatment-of-Lyme-Disease.aspx

Extract:

Regular lab parameters affected by Lyme:


•Abnormal lipid profile (moderate cholesterol elevation with significant LDL elevation)

•Insulin resistance

•Borderline low white blood cells, normal SED rate and CRP

•Normal thyroid hormone tests but positive Barnes test and excellent response to giving T3

•Type 2 (high cortisol, low DHEA) or type 3 adrenal failure (low cortisol and DHEA)

•Low testosterone and DHEA

•Decreased urine concentration (low specific gravity)

•Complex changes in cytokines, interferones, NK cells, white blood cell indicators, etc.
 
...

Symptomen van een dopaminestoornis

Symptomen van een dopaminestoornis

• besluiteloosheid
• arm aan initiatieven
• depressie
• angst
• uitputting
• chronisch vermoeid, de hele dag kunnen slapen
• tremor

Supplement: Tyrosine: 1 à 2 x 500 mg per dag (nooit 's avonds)

zit in pompoenzaden, amandelen, avocado's, bananen, haring, kaas, sesamzaad

Niet geschikt bij migraine, hoge bloeddruk of tegelijkertijd met antidepressiva


Extra:
Vit B = nodig voor aanmaak neurotransmitters
Vit C minimaal 2g
magnesium
Visolie EPA DHA 1 g


Goed supplement bij depressie algemeen:
Nutramin Emotio Balans, 1 x ochtend en 1 x avond
Niet bij zwangerschap of borstvoeding

CBT doesn't cure and here's the proof



click on the picture



Symptomen van een serotoninestoornis

Symptomen van een serotoninestoornis

• slaapproblemen
• spijsverteringsproblemen
• te weinig serotonine geeft obstipatie
• teveel serotonine geeft diarrhee
• angst met diepe triestheid
• depressie
• verhoogde pijngevoeligheid
• hoofdpijn
• niet lekker in je vel zitten
• uitputting

Supplement: Tryptofaan
= essentieel aminozuur, zit in melk, vlees en chocolade

• L-tryptofaan: lichaam kan het omzetten naar believen en wat het nodig heeft  
• 5 hydroxitryptofaan: kan alleen omgezet worden in serotonine en geeft soms bijwerkingen

 Supplement: SAMe butaandisulfonaat

 = lichaamseigen stof
 = even effectief als antidepressivum (SSRI)
 verbetert membraanfluiditeit

Vooraleer je aan de slag gaat met SAMe, lees deze link eerst:

http://www.alternativementalhealth.com/articles/walshQZ.htm

A quick way to test for need for methylation therapy is to carry out a cautious trial of SAMe. Within a week or two you should have your answer. If she clearly is improving on the SAMs (which is frightfully expensive)..... you can get usually the same benefits (albeit more slowly) using methionine plus calcium, magnesium, and B-6. This should be side-effect free unless (a) the methylation is begun too abruptly or (b) the patient has a rare genetic enzyme disorder which disrupts the SAM cycle. We've found that direct methylation is usually more successful than tinkering with the SAM cycle. The primary way humans receive most of their methyl groups is from dietary methionine. It's often hard to improve on Mother Nature. (Jan 20, 2003)


SAMe is likely to cause great worsening of symptoms, including mania, if given to an OVER-methylated person. The incidence of overmethylation in our patient database of 1,500 bipolar cases is about 18%. Bipolar disorder is not a single condition, but a collection of very different biochemical disorders under the same umbrella diagnosis. SAMe works great for truly undermethylated patients, but all hell breaks out if given to someone who is overloaded (genetically) with methyl groups. The right way to do this is to (a) first determine the person's innate methylation tendency & then (b) act accordingly. (Jan 31, 2003)

Multiple food & chemical sensitivities are also associated with histapenia (low histamine, overmethylation), the largest of all SZ groups, amounting to about 48% of all cases. For this group, SZ symptoms often worsen if exposed to the offending substances, & nice improvements often occur if they are identified & avoided. However, the food sensitivities usually disappear after about 1 year of aggressive Folate/B-12/B-3 treatment, which is the primary route to a normal life for these patients.

...

Histamine assays for depression were introduced by Dr. Carl Pfeiffer of Princeton, NJ in the 1970' and 1980's. My clinic has found whole blood histamine to be very useful & has used this assay more than 30,000 times.

First of all, the analysis must be done for whole blood (not plasma, serum, etc), strictly adhering to the sampling protocol. We presently use LabCorp but in the past Quest also had proficiency for this assay.

The reference "normal" range for mental health is 40 to 70 ng/dL. Levels above 70 indicate undermethylation, whereas levels below 40 suggest overmethylation.

Undermethylated depressives thrive on l-methionine, calcium, magnesium, B-6, Zinc, and Vitamin C. In severe cases, up to 3,000 mg/day of methionine and 2,000 mg/day of Ca may be needed. However, we also like to routinely run a homocysteine test to assure the safety of the methylation protocol. This population is believed to result in low serotonin activity. This methylation therapy is quite slow in taking effect.... and often 6-8 weeks pass before progress is obvious.

Overmethylated (low-histamine) depressives thrive on folic acid, B-12, niacin (or niacinamide), B-6, Zinc, Manganese, DMAE, and Vitamins, C and E. In severe cases, up to 5,000 mcg/day of FA may be needed. Response is more rapid with this phenotype, with clear progress usually by week 4. This population is believed to have an innate tendency for elevated serotonin, dopamine, and norepinephrine levels.



This test can also help guide psychiatrists in selection of psychiatric medications. For example high histamine persons may do quite well on SSRI's, but low-histamine persons usually reactly very badly to SSRI's and are better candidates for benzodiazapines.



We like to augment the histamine blood test with an "absolute basophil" test offered by Direct Healthcare, Inc. The histamine assay can be affected by antihistamines and other medications with AH properties. The reference range for ABC's is 30-50.

Herprogrammeer uw hond

http://www.gva.be/nieuws/wetenschap/aid1120069/hond-aan-de-rilatine.aspx

Honden zijn het volgende slachtoffer van de farma-industrie. Ze worden nu ook aan de Rilatine en antidepressiva gezet. De farma-industrie heeft reeds alle koeien, varkens en kippen volgepropt met antibiotica. Dat volstond blijkbaar niet.

Dierengedragstherapeut Dany Grosemans zegt in een artikel spijtige trend". "In mijn praktijk zie ik iets helemaal anders. Ik heb de indruk dat de farmaceutische firma's de dierenartsen het hoofd gek maken. Het is zelfs zo ver gekomen dat ik in een krant een advertentie zag verschijnen van een farmaceutisch bedrijf met de slogan "Herprogrammeer uw hond".

Tiens, dat zei die biopsychosociale arts in het CVS-centrum ook tegen mij tijdens mijn eerste gesprek: "U moet geherprogrammeerd worden."

Het zal wel toeval zijn zeker ...

Bron: http://www.gva.be/nieuws/wetenschap/aid1120069/hond-aan-de-rilatine.aspx

Panax Ginseng

I wanted to try a new supplement to stimulate the bloodcirculation as well as my brain. A therapist in plants and herbs had recommended me asian panax ginseng. The siberian ginseng was a no go.
Two days later I was blessed with an acute attack of rheumatoid arthritis in my hand. First, a miserable night in which every cell of my body ached as if I was lying in barbed wire. The next morning my fingers were swollen with thick veins, a few hours later I was bedridden with a flu attack. Then my fingers were very painful and stiff for some days. It feels better now. .

So, for those who want to stimulate their immune system, go for panax ginseng.

But if you're sure that you suffer from Crohn's disease or lupus, stay away from it!

Panax ginseng

Ik dacht eens een nieuw supplement uit te proberen om de bloedsomloop te stimuleren en mijn brein wat aan de praat te houden. Het plantje dat een fytotherapeut had aangeraden was panax ginseng, de aziatische. De siberische, die mocht ik zeker niet nemen. Zo gezegd, zo gedaan.


Twee dagen later ben ik gezegend met een acute aanval van reumatoide artritis aan mijn hand blijkt nu. Eerst een mega-ellendige nacht waarbij elke cel van mijn lijf pijn deed alsof ik in de prikkeldraad lag. De volgende ochtend dikke vingers met gezwollen aders, enkele uren laten een griepaanval van jewelste. Dan een paar dagen zeer pijnlijke en stijve vingers. Vandaag is het voor het eerst weer wat beter.

Zo, voor diegenen die hun immuunsystem willen stimuleren: neem panax ginseng

En als je zeker bent dat je aan Crohn of lupus lijdt, a.f.b.l.i.j.v.e.n.

Neuron memory key to taming chronic pain

http://www.mcgill.ca/newsroom/news/item/?item_id=214078

Neuron memory key to taming chronic pain


Feb. 13, 2012

Study suggests erasing neuronal memories may help control persistent pain

For some, the pain is so great that they can’t even bear to have clothes touch their skin. For others, it means that every step is a deliberate and agonizing choice. Whether the pain is caused by arthritic joints, an injury to a nerve or a disease like fibromyalgia, research now suggests there are new solutions for those who suffer from chronic pain.

A team of researchers led by McGill neuroscientist Terence Coderre, who is also affiliated with the Research Institute of the McGill University Health Centre, has found the key to understanding how memories of pain are stored in the brain. More importantly, the researchers are also able to suggest how these memories can be erased, making it possible to ease chronic pain.

It has long been known that the central nervous system “remembers” painful experiences, that they leave a memory trace of pain. And when there is new sensory input, the pain memory trace in the brain magnifies the feeling so that even a gentle touch can be excruciating.

“Perhaps the best example of a pain memory trace is found with phantom limb pain,” suggests Coderre. “Patients may have a limb amputated because of gangrene, and because the limb was painful before it was amputated, even though the limb is gone, the patients continue to feel they are suffering from pain in the absent limb. That’s because the brain remembers the pain. In fact, there’s evidence that any pain that lasts more than a few minutes will leave a trace in the nervous system.” It’s this memory of pain, which exists at the neuronal level, that is critical to the development of chronic pain. But until now, it was not known how these pain memories were stored at the level of the neurons.

Recent work has shown that the protein kinase PKMzeta plays a crucial role in building and maintaining memory by strengthening the connections between neurons. Now Coderre and his colleagues have discovered that PKMzeta is also the key to understanding how the memory of pain is stored in the neurons. They were able to show that after painful stimulation, the level of PKMzeta increases persistently in the central nervous system (CNS).

Even more importantly, the researchers found that by blocking the activity of PKMzeta at the neuronal level, they could reverse the hypersensitivity to pain that neurons developed after irritating the skin by applying capsaicin – the active ingredient in hot peppers. Moreover, erasing this pain memory trace was found to reduce both persistent pain and heightened sensitivity to touch.

Coderre and his colleagues believe that building on this study to devise ways to target PKMzeta in pain pathways could have a significant effect for patients with chronic pain. “Many pain medications target pain at the peripheral level, by reducing inflammation, or by activating analgesia systems in the brain to reduce the feeling of pain,” says Coderre. “This is the first time that we can foresee medications that will target an established pain memory trace as a way of reducing pain hypersensitivity. We believe it’s an avenue that may offer new hope to those suffering from chronic pain.”

The full article can be found at: http://www.molecularpain.com/content/7/1/99

Other contributing researchers on this study include Andre Laferrière, Mark H Pitcher, Anne Haldane, Yue Huang, Virginia Cornea, Naresh Kumar, Fernando Cervero (all from the Alan Edwards Centre for Research on Pain at McGill) and co-author Todd C Sacktor (State University of New York Downstate Medical Center).

This research was supported by grants from Canadian Institutes of Health Research (CIHR), the Louise and Alan Edwards Foundation, National Institutes of Health (NIH) and an Astra-Zeneca/AECRP fellowship.

Source : http://www.mcgill.ca/newsroom/news/item/?item_id=214078

This is ME

http://www.youtube.com/watch?v=ab9FGaoEMlk&feature=youtu.be