Sunday, November 25, 2012

Should I Take a Statin?

This blog post is for informational purposes only and is not meant to diagnose or treat any medical condition.
 
If you haven't already see Troubleshooting High Cholesterol Part 1 and Part 2
 
What Are Statins? 

HMG-CoA reductase is part of the mevalonate pathway, which ultimately synthesises cholesterol, but also some other molecules like coenzyme Q10, squalene and Rho.  Statins inhibit HMG-CoA reductase and so are also referred to as HMG-CoA reductase inhibitors.  By inhibiting HMG-CoA reductase statins reduce cholesterol synthesis, but they also reduce the synthesis of other products of the mevalonate pathway.  To compensate the liver increases activity of the LDL receptor, which lowers LDL-C and LDL-P levels. 

Statins are thought to have other cardio-protective independent of lowering cholesterol such as increasing nitric oxide and (which supports endothelial function), having an anti-inflammatory effect [1].  However, statins have adverse side effects which may be related to it decreasing cholesterol and consequently steroid hormone levels like testosterone [2] and decreasing coenzyme Q10 [3] [4], squalene [5] and isoprenes [6

The Benefits vs. the Costs 

Drugs (and other interventions) should improve quality of life (lower morbidity/symptoms) and/or improve longevity (lower total mortality).  However, many drugs have adverse side effects so a drug should either:

  • Improve quality of life and improve longevity (ideal)
  • Improve quality of life greater than it decreases longevity 
  • Improve longevity greater than it decreases quality of life 

The nature of statins and CVD means you’re likely trading an increase in longevity for a decrease in quality of life (although non-fatal heart attacks and strokes decrease quality of life), but to what degree depends on the context. 

The Number Needed to Treat (meta-analysis of statin trials)
Benefits in Percentage
Harms in Percentage
Statin Drugs Given for 5 Years for Heart Disease Prevention (Without Known Heart Disease) [7]
60 for non-fatal heart attack
·         98% saw no benefit
·         0% were helped by being saved from death
·         1.6% were helped by preventing a heart attack
·         0.4% were helped by preventing a stroke
·         2% were harmed by developing diabetes
·         10% were harmed by muscle damage
Statins Given for 5 Years for Heart Disease Prevention (With Known Heart Disease) [8]
83 for mortality
·         96% saw no benefit
·         1.2% were helped by being saved from death
·         2.6% were helped by preventing a repeat heart attack
·         0.8% were helped by preventing a stroke
·         2% were harmed by developing diabetes
·         10% were harmed by muscle damage

However, statins are ineffective at reducing mortality in all women and men aged 80 or over, regardless of whether it’s for primary or secondary preventions.  Also, most of the RCTs for statins were funded by drug companies.  RCTs funded by drug companies are more likely to report better outcomes and fewer side effects, so the benefits are likely exaggerated while the harms are underreported [9].  Something you can’t tell from the NNT data is the minor quality of life issues (muscle pain, memory loss, loss of libido, etc) that can occur from statins and are more common but less severe than muscle damage and type 2 diabetes 

That being said statins are probably more therapeutic for people with FH or ApoE4 genotypes. 

Also, consider your individual risk.  How likely are you to have a heart attack or stroke?  How much atherosclerosis do you currently have?  How much of my list on Part 1 applies to you?  The lower your risk, the less benefit statins are to you 

Remember that diet and lifestyle are far more powerful than most drugs.  Statins come nowhere near close to the 72% reduction in cardiac events, 65% reduction in cardiac deaths and 56% reduction in total mortality observed in the experimental group of the Lyon Diet Heart Study [10

Dealing with the Adverse Side Effects 

Should you decide to take statins it’s in your interests to prevent and deal with the side effects: 

CoQ10.  I mentioned before that statins lower CoQ10, which is a suspected cause of several of the side effects.  However, there have been conflicting results as to whether CoQ10 supplementation is effective at reducing the adverse side effects of statins [3], though probably on balance the evidence is in favour of benefit [11].  That being said, I would err on the side of supplementing the CoQ10 because statins lower CoQ10 levels, the proposed mechanisms are pretty sound, several studies do find a benefit, CoQ10 supplementation is safe and well tolerated and the side effects of CoQ10 are generally only going to be positive.  The only real negative would be the cost as they are more expensive than your average supplement 

Vitamin D.  One of the potential symptoms of vitamin D deficiency (< 20 ng/dl) is myalgia (muscle pain).  There seems to be a relationship between low vitamin D levels (< 30 ng/dl) and statin-induced myalgia, as vitamin D activates enzymes that metabolise some, but not all classes of statins.  Vitamin D supplementation appears to be very therapeutic in these contexts.  (Interestingly some statins appear to increase vitamin D) [12

There seems to be less research on sides effects resulting from a lack of steroid hormones, squalene and isoprenes and on supplementing any of them to prevent some of the adverse side effects.  (I suppose funding research to investigate and minimise the adverse side effects legitimises them, whereas it’s probably in the drug companies interests to sweep them under the rug).  Squalene seems to have anti-cancer effects and protects the skin from UV and singlet oxygen [13].  Squalene is mainly found in olive oil, a fairly health promoting food anyway (squalene may inhibit the cholesterol lowering effect of statins, not sure).

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