Nano-medicine study pinpoints the real, genetics-driven problem 11/25/2019
Growing evidence undermines long-standing, damaging myths about the effects of diet on blood cholesterol.
And companion myths about how blood cholesterol affects a person’s risk for cardiovascular problems have led to likely over-prescription of statin-type drugs.
Those myths regard the exaggerated links between levels of total LDL cholesterol and the risk for cardiovascular disease, heart attacks, stroke, and sudden cardiac death.
For decades, doctors have prescribed cholesterol-lowering drugs — usually statins but also niacin or fibrates — to anyone whose total or LDL cholesterol measured above certain levels, with those benchmarks being steadily lowered.
The findings of a “nano-medicine” study from Ohio University add to growing evidence that total LDL levels make unreliable guides to risk and to making the best diet, lifestyle, and (if necessary) drug prescriptions.
Importantly, the new nano-medicine study confirms that LDL subclass B — consisting of the three smallest-densest LDL particles — poses the primary threat.
And that finding supports growing evidence that doctors should change their advice concerning the best diet, lifestyle, and other prescriptions for each patient.
Before we get to the Ohio University study, let’s quickly review the different types of cholesterol and the growing new consensus on how they affect cardiovascular health.
We'll then turn to examining the latest evidence on how sugars and saturated fats affect our cholesterol profiles and its implications for diet.
Cholesterol isn’t all equal and has widely varying effects
Cholesterol travels your bloodstream in any one of three basic types of lipoprotein “envelope”, called LDL, IDL, and HDL, which come in different sizes and densities.
Higher total-HDL levels are linked to lower risks, and higher levels of IDL cholesterol appear to damage artery linings.
To oversimplify, higher total-LDL levels are linked to higher cardiovascular risks. This has led to LDL being called “bad” cholesterol, which distorts the more nuanced and accurate picture that’s emerged in recent years.
People’s blood contains all types of LDL, and what matters is the numbers of each type of particle and the resulting proportions of each type that constitutes all your LDL.
Particles of LDL cholesterol vary in character from large, fluffy particles to several smaller, denser types of particles collectively called sdLDL.
Cardiovascular risks are lower when most LDL particles are the large-fluffy kind, but rise along with proportions of the smaller-denser sdLDL-type particles in your blood.
Many doctors seem unaware of the new evidence
Sadly, a counterproductive focus on blood levels of total and LDL cholesterol persists.
That focus persists even though it’s long been clear that the mix of different LDL types matters much more.
Doctors place people into one of two cholesterol subclasses — A or B — which are defined by the proportions of the various types of LDL particles in their blood:
- Subclass A – More large-fluffy particles, lower cardiovascular risk
- Subclass B – More small-dense particles, higher cardiovascular risk
The proportions of different LDL types in your blood is determined partially by your genes and partially by the gene-influencing (epigenetic) effects of diet and lifestyle.
Scientists use the term “phenotype” to describe the combined effects of your genes, diet, lifestyle, and environment on your physical characteristics, including your cholesterol profile.
Accordingly, they classify people as having cholesterol phenotype A or B, depending on the proportions of the various types of LDL in their blood — which diet and lifestyle can affect for better or worse.
People classified as phenotype B (more small-dense LDL particles in their blood) are also likely to have high triglyceride levels, low HDL cholesterol levels, and diabetes-promoting insulin resistance: a package of risk factors that triples their risk for developing cardiovascular disease.
Ohio University study further clarifies the cholesterol picture
The new findings come from biochemistry professor Dr. Tadeusz Malinski and Dr. Jiangzhou Hua, who leads the school’s nanomedical lab.
Dr. Malinski and his co-author used nano-sensors to measure the levels of nitric oxide and peroxynitrite — chemicals the body uses to expand (dilate) blood vessels — in artery lining (endothelial) tissue, after they were exposed to large-fluffy LDL subclass A particles or to smaller-denser LDL subclass B particles (Hua J, Malinski T et al. 2019).
Levels of nitric oxide and peroxynitrite measured in endothelial (artery lining) tissue after exposure to different types of cholesterol help predict how those different types will affect artery health over the long term.
Explaining why they conducted their study, Malinski noted that three out of four patients who suffer a heart attack had total or LDL cholesterol levels that — judging by standard medical guidelines — didn’t indicate particularly high risks.
Confirming prior indications, the Ohio University study showed that LDL cholesterol subclass B (i.e., smaller, denser LDL particles) did the most damage to the endothelial cells that line our arteries — damage that promotes cardiovascular disease.
As Dr. Malinski said, “Our studies explain why a correlation of total “bad” [LDL] cholesterol with a risk of heart attack is poor and dangerously misleading — it’s wrong three quarters of the time … [official] national guidelines may seriously underestimate the noxious effects [of this erroneous picture] … in cases where the content of subclass B [smaller-denser LDL particles] in total LDL is 50 percent or higher.”
Dr. Malinski stressed the practical effect of their finding and related ones: “Understanding this [difference in the arterial effects of different cholesterol subclasses] could lead to improving the accuracy of diagnosis … [and] … estimating the risk of cardiovascular disease.”
Sugar and starch are bigger promoters of risky cholesterol profiles
Saturated fats come in different forms that have very different effects on blood cholesterol.
In fact, the effects of some — such as the stearic acid that predominates in some meats and in cocoa fat and chocolate — on blood cholesterol profiles appeared relatively benign.
Generally speaking, while saturated fats can raise total LDL levels, they mostly raise levels of the relatively benign large-fluffy LDL particles, while low-fat/high-carb diets promote higher levels of the smaller-denser, damaging particles.
And it's become clear that, compared with saturated fats, sugars and refined starches pose greater cardiovascular risks.
In line with that new evidence, the authors of a recent evidence review urged public health officials to urge reductions in dietary sugars — especially sucrose (cane/table sugar), high-fructose corn syrups — and to urge people to cut back on processed drinks and foods, which, for most Americans, are the biggest sources of both sugars.
As they wrote, “When saturated fats are replaced with refined carbohydrates, and specifically with added sugars (like sucrose or high fructose corn syrup), the end result is not favorable for heart health.” (DiNicolantonio JJ et al., 2016)
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- DiNicolantonio JJ, Lucan SC, O'Keefe JH. The Evidence for Saturated Fat and for Sugar Related to Coronary Heart Disease. Prog Cardiovasc Dis. 2016 Mar-Apr;58(5):464-72. doi: 10.1016/j.pcad.2015.11.006. Epub 2015 Nov 14. Review.
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- Hua J, Malinski T. Variable Effects Of LDL Subclasses Of Cholesterol On Endothelial Nitric Oxide/Peroxynitrite Balance – The Risks And Clinical Implications For Cardiovascular Disease. International Journal of Nanomedicine. Volume 2019:14 Pages 8973—8987. DOI https://doi.org/10.2147/IJN.S223524. Accessed at https://www.dovepress.com/variable-effects-of-ldl-subclasses-of-cholesterol-on-endothelial-nitri-peer-reviewed-fulltext-article-IJN
- Krauss RM. Atherogenic lipoprotein phenotype and diet-gene interactions. J Nutr. 2001 Feb;131(2):340S-3S. Review
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