Tag Archives: MS

Conflicting Evidence – A Statin Paradox

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We know that all cells (all tissues) cease their exocytosis and endocytosis  activity, if the membrane cholesterol content drops by
around 10%.  This is easily achieved on statin therapy. Everything slows down.

In the case of bone remodelling both osteoclasts (cutters) and osteoblasts (builders) will reduce their repair activity in bone remodelling.
Calcium loss from bones will be reduced but micro-fracture repairs will not be repaired on statin therapy. Bone density is maintained on statin therapy but the developing micro-fractures weaken the skeleton.

It’s all about what is measured and how long you follow through.
Statin trials can be designed to prove both benefit and detriment to bones.
This is why experimental osteoporosis treatment by statins  to maintain bone density ultimately gives way to increased fracture risk.
Two competing bone remodelling processes are failing and conflicting measures can be used to conflict statin safety.

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You will find this pattern repeats in damage and  repair of myelin in MS studies.

To summarise: Short-term gain- long-term pain on statins

Dr Luca Mascitelli and myself went into this in our review paper 2009 at http://bit.ly/Ob9wKM

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Link

It is incredible that medications that lower cholesterol have been proposed for the treatment of Multiple Sclerosis.  Myelin is 50% cholesterol and maintaining it requires huge amounts. No wonder statins  devastate the neural systems!

Here is a quote from our published paper on what you are not told cholesterol lowering treatments: (click text for full paper)

The process in which axons are protected by the myelin secretions of the oligodendrocyte requires a specialised cholesterol-rich membrane [42]. Klopfleisch et al. [43] describe experimental in vivo evidence that new myelin (re-myelination) secretion by oligodendrocytes is impaired by statins.  

Whilst they attribute much of this failure to signalling interference, they also prevented detrimental outcomes in vitro by re-incubating oligodendrocytes with cholesterol. How long are oligodendrocytes able to repair and maintain myelin in an environment where cholesterol is depleted?  

It has been argued that statins can prevent de-myelination [44] through a pleiotropic anti-inflammatory effect and this has led to research on its use as a multiple sclerosis therapy.  

This would appear to contradict Klopfleisch’s findings [43], until you consider that initially there may be multiple conflicting effects over different time scales: Possibly the initial inhibiting of an auto-immune action associated with a de-myelination and  subsequent inhibition of oligodendrocyte repairs by cholesterol depletion.

Research is needed to establish whether the apparent initial slowing of de-myelination in statin therapy would be followed by a catastrophic failure of the re-myelination work of oligodendrocyte exocytosis [45] as cholesterol synthesis fails. Furthermore, consideration should be given to the structural state of membranes involved in any auto-immune process where a complex interplay of essential membrane lipids, mediated by cholesterol, affects the immune response [46].

[42] Fitzner D, Schneider A, Kippert A, et al. Myelin basic protein-dependent plasma membrane reorganization in the formation of myelin EMBO J 2006; 25: 5037-48.

[43] Klopfleisch S, Merkler D, Schmitz M, et al. Negative impact of statins on oligodendrocytes and myelin formation in vitro and in vivo J Neurosci 2008; 28: 13609-14.

[44] Paintlia AS, Paintlia MK, Singh AK, Singh I. Inhibition of rho family functions by lovastatin promotes myelin repair in ameliorating experimental autoimmune encephalomyelitis Mol Pharmacol 2008; 73: 1381-93.

[45] Trajkovic K, Dhaunchak AS, Goncalves JT, et al. Neuron to glia signaling triggers myelin membrane exocytosis from endosomal storage sites J Cell Biol 2006; 172: 937-48.

[46] Harbige LS. Fatty acids, the immune response, and autoimmunity: a question of n-6 essentiality and the balance between n-6 and n-3. Lipids 2003; 38: 323-41.

Cholesterol and Multiple Sclerosis