Cholesterol and Inflammation

Last week, I cited evidence that statins work to lower risk of heart disease, but their benefit is probably independent of their design function, which is to deprive the body of cholesterol. I believe the benefits of statin drugs come from anti-inflammatory action. Their effect on cholesterol is at best a subsidiary benefit, at worst a cause of multiple systemic problems. Reviewing a handful of studies over 30 years, I didn’t find any consistent relationship between heart risk and blood levels of cholesterol (HDL, LDL or TC). The only exceptions were at the very extremes. Both the top ½% and the bottom ½% had elevated risk of heart attack.

This 1994 study was titled Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years.But if you read past the abstract to the data tables, you’ll find that people with low cholesterol had twice as many fatal heart attacks as people with high cholesterol [sic]. Deaths from other causes than heart disease were higher in subjects with high cholesterol, and this added up to a negligible difference in overall mortality rates for high or low cholesterol. (This was pointed out to me by Uffe Ravnskoff, a Danish doctor and researcher, author of The Cholesterol Myths.)

Statins tamper with body chemistry that doesn’t need tampering. This line of thinking suggests that alternative anti-inflammatory strategies might avoid the side effects while lowering risk of heart attacks as much or more than with statins.

CV mortality rates are falling

If our NIH had declared “war on heart disease” in 1965, they would be well-justified in crowing today. Since a peak in the 1960s, cardiovascular mortality in the Western world has been declining steadily.

Age-adjusted CV mortality, 1950 – 2006

The decline is the more impressive in that it has fought twin headwinds in the form of an epidemic of obesity and an aging population. The rise of statin prescriptions may be part of the story, but statins only came into widespread use beginning 1995-2000. The prevalence of smoking started declining steeply in 1965, and this is surely a contributing factor. Other than that, experts can’t seem to agree on the cause of our good fortune.

Side effects of statins

Statins don’t just affect blood chemistry, but interfere with the manufacture of cholesterol. But cholesterol is an important ingredient in cell membranes and nerve sheaths; it is also a substrate from which other essential molecules are manufactured, including vitamin D. It is no surprise that statins carry powerful complications. All the side-effects come from the cholesterol metabolism, and not the anti-inflammatory action, so they may be completely unnecessary.

• Lowering inflammation ought to improve insulin sensitivity. But most statins are associated with elevated risk of diabetes. Since loss of insulin sensitivity is a primary driver of aging, even marginal effects on insulin resistance could be important. Diabetes is an independent risk factor for heart disease [ref]. Simvastatin seems to have the worst effect on insulin sensitivity, and pravastatin may actually improve insulin sensitivity [ref].
• Cognitive impairment is of great concern for most of us, but it is difficult to measure reproducibly. There are enough subjective reports of cognitive impairment from statins to be worrisome [ref, ref] but there may be a slightly lowered risk of dementia (as you would expect from an anti-inflammatory) [ref].
• Muscle cramping (myalgia) is reported in some industry-sponsored studies to be 18% or 5% or even as low as 3%. But in my small sample, everyone I know who takes statins notices muscle cramps. This rises from being a nuisance to a clinical risk when it interferes with patients’ ability to exercise, which is potentially a more powerful heart protector than statins.
• Probably related, people on statin drugs report fatigue and intolerance to exercise. Statins interfere with the energy metabolism, and in particular reduce the concentration of CoQ10=ubiquinone, which already declines with age and is essential for mitochondrial function. Everyone who chooses to take statins should be supplementing with CoQ10.

Alternatives for lowering CV risk without statins

• Exercise. The #1 most cardioprotective form of exercise is interval training. The #1 most difficult discipline to maintain is: interval training. Establish an exercise program you can live with, and then live with it.  Intense exercise makes a world of difference, but even taking a walk a few times a week has significant benefit.
• Lose weight.
• Less meat, more Mediterranean in your diet. Vegan seems to help. If you can tolerate it, a raw foods vegan diet is all-purpose for weight loss, heart health, anti-inflammation, and anti-cancer.
• Daily aspirin or ibuprofen after age 50. (A reader has recently made me aware of a link between macular degeneration and daily aspirin. No such link seems to be documented for ibuprofen. If you have AMD in the family, you may want to substitute ibuprofen for aspirin, or lower the dosage. There is no evidence that a full aspirin daily is better for your hear than ¼ aspirin, but it does seem that the full pill is worse for AMD.)
• Other anti-inflammatories include turmeric, fish oil, boswellia, cat’s claw. A reader has alerted me to the potential of anatabine citrate. This is an alkaloid compound found in small quantities in nightshade vegetables and tobacco. Some people who have taken it say it is the best anti-inflammatory ever, but it was taken off the market 2 years ago based on a scandal that was purely political and had nothing to do with the biological merits of anatabine.
• Supplement with CoQ10 [Ref1, Ref2, Ref3, Ref4] or ubiquinol, which is offers enhanced absorption for a closely-related molecule.
• Both kinds of dietary fiber decrease heart risk. (The reasons for this are still debated, and may include intestinal flora, appetite control, and speed of food absorption.) Wheat bran and leafy greens are the best sources of insoluble fibre (“roughage”). Oat bran, beans and nuts are the best sources of soluble fibre.
• 8 cardioprotective foods (garlic and ginger should be on this list, but were not as I found it)
  • avocado
  • lentils
  • edamame
  • nuts
  • olive oil
  • pears
  • tea (black is good, green is better)
  • tomatoes
• Get your vitamin D blood levels up to 70 (In people like me, this can require 10,000 to 30,000 iu daily. Whole body sun exposure can help, too, but it ages the skin.)
• Supplement with niacin (vit B3). Niacin raises HDL and cut risk of heart attacks by 30% in people not taking statins in a meta-analysis. Mechanism of niacin explained here.
  Am I being inconsistent in saying that cholesterol has nothing to do with heart risk and then recommending a vitamin that raises HDL (good cholesterol) levels?  Perhaps so, or perhaps I’m hedging my bets.  In include this recommendation because there is independent evidence linking niacin not just to HDL but also to a lower rate of CV events.
• Hawthorn(e) berry seems promising, and some naturopaths have had good results prescribing it for congestive heart failure.
• Don’t worry about salt.
• Trans fats (or partially hydrogenated vegetable oils) do not exist in nature, but are created in food processing because they retard spoilage. Trans fat consumption is associated with heart risk as well as all-cause mortality, and should be avoided. (I’ll bet you already knew that.)
• Cut sugar and grains to keep up your insulin sensitivity. Diabetes is a heart risk factor.
• Avoid foods high in iron. Don’t supplement iron, unless you have been diagnosed with a deficiency. [Ref1, Ref2] Donate blood.

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