Simvastatin and the ApoE4 Allele

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KatieS
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Re: Simvastatin and the ApoE4 Allele

Postby KatieS » Thu May 31, 2018 7:55 am

cwicker wrote:For me, I think the benefits outweigh the risks too. But, I just can't tolerate the muscle pain. I do get some benefit with micro doses. I take 5 mg Atorvastatin twice a week but need to take about every 4th week off as the muscle pain becomes intolerable enough that I am reluctant to exercise. But, I think those side-effects are genetically determined.

The dose sounds too low to be therapeutic. I found that the muscle pain varied not just with the low dose, but also a different statin. Currently, I'm on simvastatin 10mg. Rousuvastatin 10mg decreased my lipids significantly, without muscle pain, but my liver enzyme (ALT) increased (a chronic problem for me, not that likely ). Pravastatin 20mg seem to be associated with mild cognitive effects even though it is hydrophilic like rousuvastatin.Yes, I realize it seems like a lot of experimenting, that I could have circumvented if I just took what my 3/4 100 y/o mother is on successfully for decades. Have you tried other statins?

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Re: Simvastatin and the ApoE4 Allele

Postby Verax » Thu May 31, 2018 8:48 am

cwicker wrote:For me, I think the benefits outweigh the risks too. But, I just can't tolerate the muscle pain.


Have you taken Coenzyme Q-10? My doc was prescribing a lot of it some years ago because a lot of his patients had similar complaints about statins, but I didn't consider it because I thought the rhabdomyolysis had been found soon after starting on a high dose, and I never experienced it on a low dose. However, he did urge me to drink more fluids, as rhabdo can cause kidney problems; I never had protein in my urine. Bredesen suggests other reasons to take CoQ10, to support mitochondrial function, maybe it is a good idea. I'd be interested in experience of others.

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Re: Simvastatin and the ApoE4 Allele

Postby cwicker » Thu May 31, 2018 9:37 am

KatieS wrote:The dose sounds too low to be therapeutic. I found that the muscle pain varied not just with the low dose, but also a different statin. ..Have you tried other statins?

But it is therapeutic, or at least it reduces my LDL by 30%. Yes, I have tried many other statins.

And yes, I have tried CoQ10. It doesn't work for me. Plus, the research says it doesn't reduce muscle pain.

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KatieS
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Re: Simvastatin and the ApoE4 Allele

Postby KatieS » Thu May 31, 2018 12:29 pm

cwicker wrote:
KatieS wrote:The dose sounds too low to be therapeutic. I found that the muscle pain varied not just with the low dose, but also a different statin. ..Have you tried other statins?

But it is therapeutic, or at least it reduces my LDL by 30%. Yes, I have tried many other statins.

And yes, I have tried CoQ10. It doesn't work for me. Plus, the research says it doesn't reduce muscle pain.

That's great that you're so stain responsive. Even though I do not have muscle pain with SV, I take the CoQ10 since stains reportedly lower these levels and CoQ10 benefits mitochondrial function related to AD prevention.

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Re: Simvastatin and the ApoE4 Allele

Postby Verax » Thu May 31, 2018 4:24 pm

KatieS wrote:
cwicker wrote:my liver enzyme (ALT) increased (a chronic problem for me, ?


Do you drink coffee or tea or caffeinated beverages? "Coffee and caffeine consumption reduce the risk of elevated serum alanine aminotransferase activity in the United States." --CONCLUSIONS: In this large, national, population-based study, among persons at high risk for liver injury, consumption of coffee and especially caffeine was associated with lower risk of elevated ALT activity. https://www.ncbi.nlm.nih.gov/pubmed/15633120 Does this depend on whether or not you are a fast or slow metabolizer? I'm a fast one so I drink lots of coffee, but drip now instead of French press. https://www.thepaleomom.com/genes-know-caffeine-metabolism/

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Re: Simvastatin and the ApoE4 Allele

Postby cwicker » Fri Jun 01, 2018 2:19 am

I'm a fast metabolizer and yes, I do drink coffee. But I don't think that was my quote as elevated ALT is not a problem for me. It's the muscle pain and my genetics say I am at a 17x's increased risk for statin myopathy.

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Julie G
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Re: Simvastatin and the ApoE4 Allele

Postby Julie G » Fri Jun 01, 2018 9:57 am

cwicker, I applaud your caution given such a high risk of myopathy. While rare, we did have a member who permanently developed the same after taking his full prescribed dosage. The medical literature seems mixed on whether or not coenzyme Q10 helps with statin myopathy, but given the minimal side effects (and other benefits) it's likely worth it. Here's a very recent paper suggesting that the failures to date have been due to reduced bioavailability and ubiquinol may be the better choice. I can't access full-text, but got the gist from the first few paragraphs. You're in a tricky spot- sorry :(.

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Re: Simvastatin and the ApoE4 Allele

Postby cwicker » Fri Jun 01, 2018 11:04 am

Julie G wrote:cwicker, I applaud your caution given such a high risk of myopathy. :(.


It's not really caution, I just can't take them and walk across the parking lot. When I tried one for example (Crestor 5 mg/day) I remember sitting in my car and wondering how I was going to walk to the store, much less exercise. The genetics thing was nice as it helped let me know I am not imagining the symptoms. Thanks for the tip of Ubiquinol. I will try it and see if I can at least tolerate my micro doses without taking a week off every month.

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Re: Simvastatin and the ApoE4 Allele

Postby Verax » Fri Jun 01, 2018 3:23 pm

JulieG has several times wisely pointed out the role of immunity in AD, whether it be statins or otherwise. She noted that LDL seems to be part of the normal immune system. The recent Li-Huei Tsai group paper about ApoE effect on brain cells found many genes involved both with AD and immune reactions, and I see an earlier MIT paper on the epigenomics of AD at https://www.nature.com/articles/nature14252 explained at https://news.mit.edu/2015/epigenomics-alzheimers-disease-0218 that "They also found that the regions with increased activity in the mouse model of Alzheimer’s disease had immune functions in humans, and the regions that showed decreased activity had neural functions in humans."

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Re: Simvastatin and the ApoE4 Allele

Postby Harrison » Fri Jun 01, 2018 11:41 pm

Very interesting topic.

Some of the comments suggest why it may be so difficult to see a consistent effect of statin use on AD:
1. Statins vary in their ability to cross the blood brain barrier among other properties (synthetic vs. fungus-derived; effects on lowering apoE levels!)
2. People may change statins quite a bit until they settle on one with an acceptable side effect profile
3. Statins likely need to be taken for years to prevent AD; some people might start taking them too late for this effect

I believe that in order to detect a preventative effect of statins, a study would need to have a substantial number of people taking the same statin with optimal properties for 10-20 years beginning before or around the onset of brain amyloid accumulation (age 45-55). Mechanisms of statins effects on AD could be increased LDL receptor activity, decreased inflammation, apoE lowering, or a combination of those or something else entirely.


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