“Lipids” include waxes, sterols (including cholesterol). phospholipids, and fats (including saturated, monoglyceride, diglyceride, and triglycerides). Fatty acids are the small building blocks that come together to form lipids.
Mounting evidence exonerates DIETARY CHOLESTEROL (eggs, lobster, shrimp) and natural sources of SATURATED FATS:
February 2015 – Dietary Guidelines Advisory Committee Report (pdf) to the U.S. Departments of Health and Human Services and USDA. Based on this, the HHS and USDA will jointly release the 2015 Dietary Guidelines later this year. Select notes from the DGAC report:
- The report suggests removing the 300mg/day limit on dietary cholesterol from previous guidelines and states: “…available evidence shows no appreciable relationship between consumption of dietary cholesterol and serum cholesterol consistent with the conclusions of the AHA/ACC (page 2970). Cholesterol is not a nutrient of concern for overconsumption“. (page 90)
- “It is now well established that higher intake of TRANS fat from partially hydrogenated vegetable oils is associated with increased risk of CVD and thus, should be minimized in the diet.” (page 451)
- The report discusses conflicting data on saturated fat but does not remove restrictions. It does, however, site the following points from literature:
- “recent meta-analysis of prospective observational studies did not find a significant association between higher saturated fat intake and risk of CVD in large populations”. (page 451)
- “…top sources of foods contributing to saturated fat intake are mixed dishes, particularly burgers and sandwiches, and snacks and sweets.” (page 451)
- “…reducing total fat (replacing total fat with overall carbohydrates) does NOT lower CVD risk. Consistent evidence from prospective cohort studies shows that higher SFA intake as compared to total carbohydrates is NOT associated with CVD risk. DGAC Grade: Strong.” (page 452)
- “In low fat diets, fats are often replaced with refined carbohydrates and this is of particular concern becasue such diets are generally associated with dyslipidemia (hypertriglyceridemia and low HDL-C concentrations). Therefor, dietary advice should put the emphasis on optimizing types of dietary fat and not reducing total fat.” (page 453)
- “…results suggest that simply reducing SFA or total fate in the diet by replacing it with any type of carbohydrates is not effective in reducing risk of CVD.” (page 455)
May 2015 – In response to the DGAC Report, the Academy of Nutrition and Diatetics (AND) released comments re The DGAC Scientific Report. The AND is the education and regulatory board in the U.S. for all registered dietitians. Their comments are SUPPORTIVE for removing the dietary cholesterol restriction and suggest the future guidelines go even further!
- Confirming the cholesterol recommendation: “The Academy supports the decision by the 2015 DGAC NOT to carry forward previous recommendations that cholesterol intake be limited to no more than 300 mg/day, as ‘available evidence shows no appreciable relationship between consumption of dietary cholesterol and serum cholesterol.'” (Section I. B.)
Commentary: No restriction on cholesterol
- Pushing for a stronger stance in favor of saturated fat: “…the Academy suggests that HHS and USDA support a similar revision (as eliminating limits to dietary cholesterol) by deemphasizing saturated fat as a nutrient of concern.” (Section V. B.)
Commentary: Saturated fat no longer a villain
- A strong statement on what really contributes to cardiovascular disease: “Carbohydrate contributes a greater amount to the risk for cardiovascular disease than saturated fat, so the replacement of carbohydrate will…result in a greater improvement in risk.” (Section V. B.)
Commentary: High intake of carbohydrates is more detrimental to heart health than high intake of saturated fat Impact on CV Risk
- As an aside, they also make a comment on dietary sodium: “There is a distinct and growing lack of scientific consensus on making a single sodium consumption recommendation for all Americans, owing to a growing body of research suggesting that the low sodium intake levels recommended by the DGAC are actually associated with increased mortality for healthy individuals.” (Section V. A.)
Commentary: Restricting sodium can lead to negative health consequences
This seems like a complete about-face by a very influential, often slow-to-change, organization. Support like this will make it much easier to give patients information and options that can greatly improve metabolic syndrome – such as a lower carbohydrate, higher (natural) fat eating plan.
Question: Isn’t eating saturated fat and cholesterol bad for your heart?
Evidence points to the short answer being no (as seen by some of the scientific evidence above and below), so the bigger question is; what ultimately causes heart disease? Glycation and inflammation leading to damaged arterial walls which get infiltrated by large numbers of small dense LDL particles that are prone to oxidation. This is presumed to be the root cause of arterial plaques. Remember, LDL and cholesterol are essential for human life. The devil is in the inflammation and oxidation.
Here’s additional select evidence from the current scientific literature regarding dietary saturated fat consumption:
•Dietary Intake of Saturated Fat Is Not Associated with Risk of Coronary Events or Mortality in Patients with Established Coronary Artery Disease. Study of 2412 CVD patients over 4.8 years. “…no significant associations beween SFA intake and risk or coronory events. There was no association betrween dietary intake of SFA and incident cornoary events or mortality in patients with established CAD.” (American Society for Nutrition. Puaschitz, et al. Dec 2014)
• Association of Dietary Fatty Acids with Coronary Risk Analysis of studies involving 643,226 subjects. “Conclusion: Current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats.” (Annals of Internal Medicine. Chowdhury, et al. Mar 2014)
• Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, CV disease and Type 2 diabetes: systematic review and meta-analysis. With some limitations, here is the conclusion from a very large analysis: “Saturated fats are not associated with all cause mortality, CVD, CHD, ischemic stroke or type to diabetes……” (BMJ, de Souza, Aug 2015)
• Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Analysis of studies involving 347,747 subjects. “Conclusion: There is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD.” (American Journal of Clinical Nutrition. Siri-Tarino, et al. Mar 2010)
• Meta-Analysis: Evidence to Support Dietary Fat Restriction Recommendations. Analysis concludes the 1977 US Dietary Guidelines lacked evidence to recommend that Americans limit overall fat and saturated fat daily energy intake. (BMJ-Open Heart. Harcombe, et al. Dec 2014)
• Reduced or modified dietary fat for preventing cardiovascular disease. Systematic review. “…no evidence that trials of reduced or modified SFA reduced cardiovascular mortality…found no significant associations of total fat reduction with cardiovascular events or mortality”. (Cochrane Database. Hooper, et al. 2012 / DGAC Report 2015, page 455)
• Dietary fat and coronary heart disease: summary of evidence from prospective cohort and randomized controlled trials. Analysis of 28 cohorts among 280,000 participants “found no clear association between total fat or saturated fat intake and CHD events or deaths.” (Annals of Nutrition and Metabolism. Skeaff, et al. Sep 2009)
• Diets with high-fat cheese, high-fat meat, or carbohydrate on cardiovascular risk markers. This was a small, but well designed (crossover) study that showed diets with cheese or meat as the main saturated fat source appeared to be less atherogenic than low fat, high carb diets. (Am J Clin Nutr. Throning TK, et al. July 2015)
We should consider rethinking our fear of natural fats while placing an even stronger emphasis on avoiding “man-made” and industrial fats that are most prone to oxidation and subsequent inflammation.
• Use of dietary linoleic acid for secondary prevention of coronary heart disease and death. A study showing that replacing butter with vegetable oil increased mortality and heart disease. (BMJ. Ramsden, et al. Feb 2013)
• The cardiometabolic consequences of replacing saturated fats with carbohydrates or omega-6 polyunsaturated fats. (A 2014 BMJ editorial and review with 39 references.)
All of this is getting serious attention in the media: TIME Magazine FAT, June 2014
Specific Evidence in favor of EGGS (and dietary cholesterol):
Association of egg and cholesterol intake on risk of coronary artery disease. Egg or cholesterol intakes were not associated with increased heart attack risk even in highly susceptible individuals. (Am J Clinical Nutrition. Virtanen JK, et al. Feb 2016)
One egg per day improves inflammation when compared to an oatmeal-based breakfast without increasing other cardiometabolic risk factors in diabetic patients. Consumption of eggs versus oatmeal showed no deleterious effects on lipid results but showed reduction in factors associated with chronic low grad inflammation. (Nutrients. Ballesteros MN, et al. May 2015)
Egg consumption and risk of incident type 2 diabetes in med: the Kuopio Ischaemic Heart Disease Risk Factor Study. 423 men followed for 19 years, conclusion: “Higher Egg intake was associated with a lower risk of T2D in this cohort. (American Journal of Clinical Nutrition. Virtanen, et al. Apr 2015)
Egg consumption and risk of heart failure, myocardial infarction and stroke. “Egg consumption was not associated with any (negative) CVD outcome in individuals with diabetes.” (American Journal of Clinical Nutrition. Larsson, et al. Nov 2015)
One egg per day improves inflammation when compared to an oatmeal based breakfast with increased cardiometabolic risk factors in diabetic patients. (Nutrients. Ballesteros, et al. Sept 2015)
Whole eggs improve lipids and insulin sensitivity to a greater extent than yolk-free egg substitute in patients with metabolic syndrome. (Metabolism. Blessso, et al. Mar 2013)
Influence of resistance training combined with daily consumption of an egg-based or bagel-based breakfast on risk factors for chronic disease. A small, but interesting study concluding, “two eggs daily for 12 weeks did not adversely affect lipids…triglycerides decreased significantly in the egg group…insulin sensitivity was significantly decreased in the bagel group”. (Journal of American College of Nutrition. Clayton, et al. Mar 2015)
Effects of carbohydrate restriction and dietary cholesterol by eggs on risk factors in metabolic syndrome. “…inclusion of whole eggs (with a moderate carb background diet) improves inflammation to a greater extent than yolk-free egg substitute in those with MetS.” (Journal of Clinical Lipidology. Blesso, et al. Sep 2013)
Egg consumption as part of an energy restricted high protein diet improves blood lipid / glucose / blood pressure in individuals with type 2 diabetes. (British Journal of Nutrition. Pearce, et al. Feb 2011)
Revisiting dietary cholesterol recommendations: does the evidence support a limit of 300mg/d? “…data have clearly demonstrated that increasing concentrations of dietary cholesterol are NOT correlated with increased risk for CHD…if LDL rises (hyper-responders) it is offset by an increase in HDL so the LDL/HDL cholesterol ratio is maintained. More importantly, dietary cholesterol REDUCES circulating levels of small, dense LDL particles, a well-defined risk factor for CHD.” (Current Atherosclerosis, Fernandez, et al. Nov 2010)
Effects of eggs on plasma lipoproteins in healthy populations. “…eggs are a good source of numerous nutrients including lutein and zeaxanthin, potent antioxidants, which may exert a protective effect against lipoprotein oxidation. …Egg intake has been shown to promote the formation of large LDL and HDL subclasses in addition to shifting individuals from the LDL pattern B to pattern A, which is less athrogenic.” (Food and Function. Fernandez. Nov 2010)
Dietary cholesterol from eggs increases plasma HDL (and reduces MetS risk factors) in overweight men consuming a carbohydrate restricted diet. Randomized trial in 28 overweight men, 3 eggs per day vs egg substitute for 12 weeks. (Journal of Nutrition. Mutungi, et al. Feb 2008)
2008 Lipid profile after alpha-linolenic acid (ALA) enriched eggs diet. ALA enriched eggs lowered triglycerides and fibrinogen compared to no eggs with no deleterious effects on CRP or other lipids. (Archiva Zootechnica. Manda, D et al. 2008)
Short-term effect of eggs on satiety in overweight and obese subjects. “Compared to a bagel, an egg breakfast induced greater satiety and significantly reduced short-term food intake.” (J Am Coll Nutr. Vanderwals, et al. Dec 2005)
Other articles to read:
Consuming egg yolks with vegetables INCREASES nutritive value. Combining cooked eggs with vegetables increased carotenoid absorption 3-9 fold (beta-carotene, alpha-caroten, lycopene, lutein and zeaxanthin). Researches will further explore the effect on fat soluble vitamins A, D, E, and K.
Select Evidence in favor of DAIRY FAT:
Total and Full-Fat, but not Low-Fat dairy product intakes are inversely associated with metabolic syndrome in adults. Associations seem to be mediated by dairy saturated fat and dietary recommendations to avoid full-fat daily “are not supported by our findings.” (Journal of Nutrition. Drehmer M, et al. Jan 2016)
Dairy consumption and CVD: a systematic review and meta-analysis. Results show that dairy consumption may be associated with reducced risk of CVD. (British J Nutr. Alexander DD, et al. Feb 2016)
The association between dietary saturated fatty acids (including dairy) and ischemic heart disease. A Dutch study which showed higher saturated fat intake was not associated with higher heart disease risk. (Am J Clin Nutr. Praagman, J, et al. Feb 2016)
No benefits for children from reduced-fat dairy diet. Low fat versus high fat daily consumption in children showed no future change in cardiometabolic risk associations in adolescents. (Nutrients. O’Sullivan TA, et al. Jan 2016)
Food sources of fat may clarify the inconsistent role of dietary fat intake for incidence of type 2 diabetes. A cohort study of 26,930 people for 14 years. Conclusions: Higher intake of high-fat dairy reduced risk of T2DM, whereas low-fat dairy did not confer a protective effect. (American Journal of Clinical Nutrition. Ericson, et al. Apr 2014)
Yogurt and dairy product consumption to prevent cardiometabolic diseases, a review. “…dairy products such as cheese to not exert negative effects on blood lipids…the consumption of yogurt, and other dairy products is associated with reduced risk of weight gain, obesity and CVD.” (American Journal of Clinical Nutrition. Astrup. May 2014)
Effects of low-fat or full-fat fermented and on-fermented daily on select cardiovascular biomarkers in overweight adults. Suggests that full-fat fermented dairy products produce a more favorable cardiovascular risk factor profile. (British J Nutrition. Nestel PJ, et al. Dec 2013)
The relationship between high-fat dairy consumption and obesity, cardiovascular, and metabolic disease. “The observational evidence does not support the hypothesis that dairy far or high-fat dairy foods contribute to obesity or cardiometabolic risk, and suggests that high-fat dairy consumption within typical dietary patterns is inversely associated with obesity risk.” (European Journal of Nutrition. Kratz, et al. Feb 2013)
trans-Palmitoleic acid, other dairy fat markers, and incident diabetes (MESA study). …associated with higher LDL but also lower TG, fasting insulin, blood pressure and incident diabetes. (American Journal of Clinical Nutrition. Mozaffarian, et al. Apr 2013)
Adolescent dairy product consumption and risk of type 2 diabetes. “…data suggests higher diary product intake during adolescence is associated with lower risk of Type 2 diabetes.” (American Journal of Clinical Nutrition. Malik, et al. Sep 2011)
Stroke and plasma markers of milk fat intake. “…dairy fat intake may be inversely related to the risk of a first event of stroke…” (Nutrition Journal. Warensjo, et al. May 2009)
Select Evidence that LOW FAT doesn’t work:
(see Diabetes page appendix for more)
Effect of low-fat diet interventions versus other diet interventions on long-term weight changes in adults: a systematic review and meta-analysis. “Evidence form RCTs does not support low-fat diets over other dietary interventions (such as low-carb higher fat diets) for long-term weight loss. (Lancet Diabetes Endocrinol. Tobias DK, et al. Dec 2015)
Effects of low-carbohydrate and low-fat diets: a randomized trial. “Low carb improved cholesterol, triglycerides, and weight loss.” (Annals of Internal Medicine. Bazzano, et al. Sept 2014)
Low-fat dietary pattern and risk of cardiovascular disease: the Women’s Heart Initiative (WHI) Randomized Controlled Dietary Modification Trial. A randomized study of 48,835 women for 8.1 years…”a diet that reduced total fat intake and increased vegetables, fruits and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women, nor did it reduce colorectal or breast cancer“. (JAMA, Howard, et al. Feb 2006)
One thing everyone seems to agree on….artificial Trans Fats are very bad for human health. And unfortunately they’re often hidden in plain site.
Notice that Trans fats often go hand in hand with higher carbohydrate foods…if only there was a diet-pattern that would eliminate both?
Processed foods are often packed with hydrogenated, processed oils.
Common sources of TRANS FAT from the grocery store…interesting that most of these would be thought of as “low fat”:
Contrast the perception below…processed foods vs natural saturated fat sources:
Select Cholesterol/Lipids Science Appendix (there is overlap, so please see the extensive reference list at the bottom of the Diabetes page):
Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, CV disease and Type 2 diabetes: systematic review and meta-analysis. With limitations, here is the conclusion: “Saturated fats are not associated with all cause mortality, CVD, CHD, ischemic stroke or type 2 diabetes……” (BMJ, de Souza, Aug 2015)
2015 Annals of Nutrition and Metabolism Cholesterol Supplement. (Hazmazaki, et al.)
Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers and blood pressure, DIVAS study. Short term randomized trial of 195 patients with moderate CVD risk. Replacing SFA with MUFA or PUFA did not affect flow mediated dilation. (American Society for Nutrition. Vafeiadou, et al. May 2015)
Paleolithic nutrition improves lipids of hypercholesterolemic adults to a greater extent than traditional heart-healthy dietary recommendations. Small study. (Nutrition Research. Pastore, et al. June 2015)
Dietary intake of saturated fat is not associated with risk of coronary events or mortality in patients with established coronary artery disease. 2412 patients followed for 4.8 years; “there was no associated between dietary intake of SFA and incident of coronary events or mortality in patients with established CAD.” (The Journal of Nutrition, Puaschitz, Dec 2014)
Research: Effects of Step-Wise Increases in Dietary Carbs on Circulating Saturated Fatty Acids in Adults with Metabolic Syndrome. “The results show dietary and plasma saturated fat are not related and that increasing dietary carbohydrates across a range increased plasma palmitoleic acid.
Study: Association of Dietary, Circulating, and Supplement Fatty Acids with Coronary Risk: “Current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats.” (Annals of Internal Medicine, Chowdhury, Mar 2014)
Use of dietary linoleic acid for secondary prevention of coronary heart disease and death “Clinical benefit of omega 6 linoleic acid have not been established…an updated meta-analysis showed no evidence of cardiovascular benefit.” (BMJ, Ramsden, Feb 2013)
Study: Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Corrected for Age Confounding rise in total cholesterol and showed the increasing total cholesterol was associated with lower all cause mortality. (J Eval Clin Pract, Petursson, Feb 2012)
Study: Association Between Serum Cholesterol and Noncardiovascular Mortality in Older Age: “…(patients) in the lowest quartiles of total cholesterol, non-HDL cholesterol and LDL cholesterol were approximately twice as likely to die as those in the highest quartile.”
Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease: “A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.” (Am J Clin Nutr, Siri-Tarino, Mar 2010)
Saturated fat and cardiometabolic risk factors, coronary heart disease, stroke, and diabetes: a fresh look at the evidence. “Public health emphasis on reducing SFA consummption without considering the replacemnt nutrient is unlikely to produce substantial intended health benefits. (Lipids. Micha, et al. Oct 2010)
Lipid Levels in Patients Hospitalized with coronary artery disease “in patients presenting with their first heart attack….half had LDL-C cholesterol levels < 100.”
Low-fat dietary pattern and risk of CV disease (and Cancer): the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. “Intensive behavior modification to reduce total fat intake to <20% and increase veggies, fruits and grains in 48,835 women over 8.1 years did NOT reduce risk of CHD, stoke, or CVD……and did NOT reduce the risk of colorectal cancer.” (JAMA, Howard, et al. Feb 2006)
Study: Association of A1c with CV Disease and Mortality. Showed that going from an A1c of 5 to 7 increased risk of death 4x.
Dietary fats, carbohydrate, and progression of coronary atherosclerosis in post menopausal women. Analysis in 235 women with established coronary heart disease. Conclusion: “In postmenopausal women with relatively low total fat intake, a greater saturated fat intake is associated with LESS progression of coronary atherosclerosis, whereas carbohydrate intake is associated with a GREATER progression.” (American Journal of Clinical Nutrition. Mozaffarian, et al. Nov 2004). Commentary.
Prospective study of fat and protein intake and risk of intrparenchymal hemorrhage in women. “Low intake of saturated fat and animal protien was associated with an increased risk of hemorrhage. (Circulation. Iso, et al. Feb 2001)
General Lipid Pathophysiology:
Below is a borrowed summary of Peter Attia’s MD blog post called The Straight Dope On Cholesterol. The original is a series of post from Dr. Attia summarizing the current research and thoughtful approaches to managing cholesterol.
◾Cholesterol is “just” another fancy organic molecule in our body but with an interesting distinction: we eat it, we make it, we store it, and we excrete it – all in different amounts.
◾The pool of cholesterol in our body is essential for life. No cholesterol = no life.
◾Cholesterol exists in 2 forms – unesterified or “free” (UC) and esterified (CE) – and the form determines if we can absorb it or not, or store it or not (among other things).
◾Much of the cholesterol we eat is in the form of CE. It is not absorbed and is excreted by our gut (i.e., leaves our body in stool). The reason this occurs is that CE not only has to be de-esterified, but it competes for absorption with the vastly larger amounts of UC supplied by the biliary route.
◾Re-absorption of the cholesterol we synthesize in our body (i.e., endogenous produced cholesterol) is the dominant source of the cholesterol in our body. That is, most of the cholesterol in our body was made by our body.
◾The process of regulating cholesterol is very complex and multifaceted with multiple layers of control. I’ve only touched on the absorption side, but the synthesis side is also complex and highly regulated. You will discover that synthesis and absorption are very interrelated.
◾Eating cholesterol has very little impact on the cholesterol levels in your body. This is a fact, not my opinion. Anyone who tells you different is, at best, ignorant of this topic. At worst, they are a deliberate charlatan. Years ago the Canadian Guidelines removed the limitation of dietary cholesterol. The rest of the world, especially the United States, needs to catch up. To see an important reference on this topic, please look here.
◾Cholesterol and triglycerides are not soluble in plasma (i.e., they can’t dissolve in water) and are therefore said to be hydrophobic.
◾To be carried anywhere in our body, say from your liver to your coronary artery, they need to be carried by a special protein-wrapped transport vessel called a lipoprotein.
◾As these “ships” called lipoproteins leave the liver they undergo a process of maturation where they shed much of their triglyceride “cargo” in the form of free fatty acid, and doing so makes them smaller and richer in cholesterol.
◾Special proteins, apoproteins, play an important role in moving lipoproteins around the body and facilitating their interactions with other cells. The most important of these are the apoB class, residing on VLDL, IDL, and LDL particles, and the apoA-I class, residing for the most part on the HDL particles.
◾Cholesterol transport in plasma occurs in both directions, from the liver and small intestine towards the periphery and back to the liver and small intestine (the “gut”).
◾The major function of the apoB-containing particles is to traffic energy (triglycerides) to muscles and phospholipids to all cells. Their cholesterol is trafficked back to the liver. The apoA-I containing particles traffic cholesterol to steroidogenic tissues, adipocytes (a storage organ for cholesterol ester) and ultimately back to the liver, gut, or steroidogenic tissue.
◾All lipoproteins are part of the human lipid transportation system and work harmoniously together to efficiently traffic lipids. As you are probably starting to appreciate, the trafficking pattern is highly complex and the lipoproteins constantly exchange their core and surface lipids.
◾The measurement of cholesterol has undergone a dramatic evolution over the past 70 years with technology at the heart of the advance.
◾Currently, most people in the United States (and the world for that matter) undergo a “standard” lipid panel, which only directly measures TC, TG, and HDL-C. LDL-C is measured or most often estimated.
◾More advanced cholesterol measuring tests do exist to directly measure LDL-C (though none are standardized), along with the cholesterol content of other lipoproteins (e.g., VLDL, IDL) or lipoprotein subparticles.
◾The most frequently used and guideline-recommended test that can count the number of LDL particles is either apolipoprotein B or LDL-P NMR, which is part of the NMR LipoProfile. NMR can also measure the size of LDL and other lipoprotein particles, which is valuable for predicting insulin resistance in drug naïve patients, before changes are noted in glucose or insulin levels.
◾The progression from a completely normal artery to a “clogged” or atherosclerotic one follows a very clear path: an apoB containing particle gets past the endothelial layer into the subendothelial space, the particle and its cholesterol content is retained, immune cells arrive, an inflammatory response ensues “fixing” the apoB containing particles in place AND making more space for more of them.
◾While inflammation plays a key role in this process, it’s the penetration of the endothelium and retention within the endothelium that drive the process.
◾The most common apoB containing lipoprotein in this process is certainly the LDL particle. However, Lp(a) and apoB containing lipoproteins play a role also, especially in the insulin resistant person.
◾If you want to stop atherosclerosis, you must lower the LDL particle number. Period.
◾At first glance it would seem that patients with smaller LDL particles are at greater risk for atherosclerosis than patients with large LDL particles, all things equal.
◾“A particle is a particle is a particle.” If you don’t know the number, you don’t know the risk.
◾With respect to laboratory medicine, two markers that have a high correlation with a given outcome are concordant – they equally predict the same outcome. However, when the two tests do not correlate with each other they are said to be discordant.
◾LDL-P (or apoB) is the best predictor of adverse cardiac events, which has been documented repeatedly in every major cardiovascular risk study.
◾LDL-C is only a good predictor of adverse cardiac events when it is concordant with LDL-P; otherwise it is a poor predictor of risk.
◾There is no way of determining which individual patient may have discordant LDL-C and LDL-P without measuring both markers.
◾Discordance between LDL-C and LDL-P is even greater in populations with metabolic syndrome, including patients with diabetes. Given the ubiquity of these conditions in the U.S. population, and the special risk such patients carry for cardiovascular disease, it is difficult to justify use of LDL-C, HDL-C, and TG alone for risk stratification in all but the most select patients.
◾To address this question, however, one must look at changes in cardiovascular events or direct markers of atherosclerosis (e.g., IMT) while holding LDL-P constant and then again holding LDL size constant. Only when you do this can you see that the relationship between size and event vanishes. The only thing that matters is the number of LDL particles – large, small, or mixed.
◾HDL-C and HDL-P are not measuring the same thing, just as LDL-C and LDL-P are not.
◾Secondary to the total HDL-P, all things equal it seems smaller HDL particles are more protective than large ones.
◾As HDL-C levels rise, most often it is driven by a disproportionate rise in HDL size, not HDL-P.
◾In the trials which were designed to prove that a drug that raised HDL-C would provide a reduction in cardiovascular events, no benefit occurred: estrogen studies (HERS, WHI), fibrate studies (FIELD, ACCORD), niacin studies, and CETP inhibition studies (dalcetrapib and torcetrapib). But, this says nothing of what happens when you raise HDL-P.
◾Don’t believe the hype: HDL is important, and more HDL particles are better than few. But, raising HDL-C with a drug isn’t going to fix the problem. Making this even more complex is that HDL functionality is likely as important, or even more important, than HDL-P, but no such tests exist to “measure” this.
Understanding the REAL role of FAT in the diet:
Here are two short clips from the movie Fat Head
A brief history of present day nutrition.
An intro to how calories, processed foods and fat work in the body.