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"Quality of HDL differs in diabetics but improves with niacin therapy December 22, 2009 | Michael O'Riordan Hannover, Germany - A small study published this week hints that the effects of HDL cholesterol differ in healthy patients from those with diabetes mellitus [1]. HDL cholesterol in individuals with diabetes has impaired endothelial protective functions compared with the HDL from healthy subjects, although treatment with extended-release niacin can improve these endothelial protective effects, according to researchers. Publishing their findings online December 21, 2009 in Circulation, lead investigator Dr Sajoscha Sorrentino (Hannover Medical School, Germany) and colleagues write that because recent HDL-raising intervention studies have yielded mixed results, "circulating HDL-cholesterol levels alone likely do not represent an adequate measure of therapeutic efficacy, and indexes of HDL functionality are urgently needed for assessment of the potential of HDL-targeted therapies to exert vasoprotective effects." Speaking with heartwire, senior investigator Dr Ulf Landmesser (University of Zürich, Switzerland), said the results have implications for clinical research. "We have to understand that we can't look only at the HDL levels in the plasma, but we need to look at the quality," he said. "The quality of the HDL is not the same in different patients. This is very important for targeting HDL as a treatment. Second, niacin therapy is a promising way not only to raise HDL but also to improve the quality; it is a good treatment option, especially if the larger outcomes data are positive.""

Fish consumption shifts lipoprotein subfractions to a less atherogenic pattern in humans. Li Z, Lamon-Fava S, Otvos J, Lichtenstein AH, Velez-Carrasco W, McNamara JR, Ordovas JM, Schaefer EJ. J Nutr. 2004 Jul;134(7):1724-8. PMID: 15226460 The effect of fish consumption on plasma lipoprotein subfraction concentrations was studied in 22 men and women (age > 40 y). Subjects were provided an average American diet (AAD, 35% of energy as fat, 14% as saturated fat, and 35 mg cholesterol/MJ) for 6 wk before being assigned to a National Cholesterol Education Program (NCEP) Step 2 high-fish diet (n = 11, 26% of energy as fat, 4.5% as saturated fat, and 15 mg cholesterol/MJ) or a NCEP Step 2 low-fish diet (n = 11, 26% of energy as fat, 4.0% as saturated fat, and 11 mg cholesterol/MJ) for 24 wk. All food and drink were provided to study participants. Consumption of the high-fish NCEP Step 2 diet was associated with a significant reduction in medium and small VLDL, compared with the AAD diet, whereas the low-fish diet did not affect VLDL subfractions. Both diets significantly reduced LDL cholesterol concentrations, without modifying LDL subfractions. Both diets also lowered HDL cholesterol concentrations. However, the high-fish diet significantly lowered only the HDL fraction containing both apolipoprotein (apo) AI and AII (LpAI:AII) and did not change HDL subfractions assessed by NMR, whereas the low-fish diet significantly lowered the HDL fraction containing only apo AI (LpAI) and the large NMR HDL fractions, resulting in a significant reduction in HDL particle size. Neither diet affected VLDL and LDL particle size. Our data indicate that within the context of a diet restricted in fat and cholesterol, a higher fish content favorably affects VLDL and HDL subspecies

The serum LDL/HDL cholesterol ratio is influenced more favorably by exchanging saturated with unsaturated fat than by reducing saturated fat in the diet of women. Müller H, Lindman AS, Brantsaeter AL, Pedersen JI. J Nutr. 2003 Jan;133(1):78-83. PMID: 12514271 We conclude that, to influence the LDL/HDL cholesterol ratio, changing the proportions of dietary fatty acids may be more important than restricting the percentage of total or saturated fat energy, at least when derived mainly from lauric and myristic acids, both of which increase HDL cholesterol.

The effect of select nutrients on serum high-density lipoprotein cholesterol and apolipoprotein A-I levels. Mooradian AD, Haas MJ, Wong NC. Endocr Rev. 2006 Feb;27(1):2-16. Epub 2005 Oct 21. Review. PMID: 16243964 One of the factors contributing to the increased risk of developing premature atherosclerosis is low plasma concentrations of high-density lipoprotein (HDL) cholesterol (HDLc). Multiple potential mechanisms account for the cardioprotective effects of HDL and its main protein apolipoprotein A-I (apo A-I). The low plasma concentrations of HDL could be the result of increased fractional clearance and reduced expression of apo A-I. To this end, nutrients play an important role in modulating the fractional clearance rate, as well as the rate of apo A-I gene expression. Because medical nutrition therapy constitutes the cornerstone of management of dyslipidemias, it is essential to understand the mechanisms underlying the changes in HDL level in response to alterations in dietary intake. In this review, we will discuss the effect of select nutrients on serum HDLc and apo A-I levels. Specifically, we will review the literature on the effect of carbohydrates, fatty acids, and ketones, as well as some of the nutrient-related metabolites, such as glucosamine and the prostanoids, on apo A-I gene expression. Because there are multiple mechanisms involved in the regulation of serum HDLc levels, changes in gene transcription do not necessarily correlate with clinical observations on serum levels of HDLc.

Dietary cholesterol from eggs increases plasma HDL cholesterol in overweight men consuming a carbohydrate-restricted diet. Mutungi G, Ratliff J, Puglisi M, Torres-Gonzalez M, Vaishnav U, Leite JO, Quann E, Volek JS, Fernandez ML. J Nutr. 2008 Feb;138(2):272-6. PMID: 18203890 Carbohydrate-restricted diets (CRD) significantly decrease body weight and independently improve plasma triglycerides (TG) and HDL cholesterol (HDL-C) . [..] Eighteen subjects were classified as having the metabolic syndrome (MetS) at the beginning of the study, whereas 3 subjects had that classification at the end. These results suggest that including eggs in a CRD results in increased HDL-C while decreasing the risk factors associated with MetS.

Endothelial-Vasoprotective Effects of High-Density Lipoprotein Are Impaired in Patients With Type 2 Diabetes Mellitus but Are Improved After Extended-Release Niacin Therapy. Sorrentino SA, Besler C, Rohrer L, Meyer M, Heinrich K, Bahlmann FH, Mueller M, Horváth T, Doerries C, Heinemann M, Flemmer S, Markowski A, Manes C, Bahr MJ, Haller H, von Eckardstein A, Drexler H, Landmesser U. Circulation. 2009 Dec 21. [Epub ahead of print] PMID: 20026785 doi: 10.1161/CIRCULATIONAHA.108.836346 Conclusions-HDL from patients with type 2 diabetes mellitus and metabolic syndrome has substantially impaired endothelial-protective effects compared with HDL from healthy subjects. ER niacin therapy not only increases HDL plasma levels but markedly improves endothelial-protective functions of HDL in these patients, which is potentially more important.

The Diet-Heart Hypothesis: Subdividing Lipoproteins Two posts ago, we made the rounds of the commonly measured blood lipids (total cholesterol, LDL, HDL, triglycerides) and how they associate with cardiac risk. It's important to keep in mind that many things associate with cardiac risk, not just blood lipids. For example, men with low serum vitamin D are at a 2.4-fold greater risk of heart attack than men with higher D levels. That alone is roughly equivalent to the predictive power of the blood lipids you get measured at the doctor's office. Coronary calcium scans (a measure of blood vessel calcification) also associate with cardiac risk better than the most commonly measured blood lipids. Lipoproteins Can be Subdivided into Several Subcategories In the continual search for better measures of cardiac risk, researchers in the 1980s decided to break down lipoprotein particles into sub-categories. One of these researchers is Dr. Ronald M. Krauss. Krauss published extensively on the association between lipoprotein size and cardiac risk, eventually concluding (source): The plasma lipoprotein profile accompanying a preponderance of small, dense LDL particles (specifically LDL-III) is associated with up to a threefold increase in the susceptibility of developing [coronary artery disease]. This has been demonstrated in case-control studies of myocardial infarction and angiographically documented coronary disease. Krauss found that small, dense LDL (sdLDL) doesn't travel alone: it typically comes along with low HDL and high triglycerides*. He called this combination of factors "lipoprotein pattern B"; its opposite is "lipoprotein pattern A": large, buoyant LDL, high HDL and low triglycerides. Incidentally, low HDL and high triglycerides are hallmarks of the metabolic syndrome, the quintessential modern metabolic disorder. Krauss and his colleagues went on to hypothesize that sdLDL promotes atherosclerosis because of its ability to penetrate the artery wall more easily

Eggs modulate the inflammatory response to carbohydrate restricted diets in overweight men. Ratliff JC, Mutungi G, Puglisi MJ, Volek JS, Fernandez ML. Nutr Metab (Lond). 2008 Feb 20;5:6. PMID: 18289377 Carbohydrate restricted diets (CRD) consistently lower glucose and insulin levels and improve atherogenic dyslipidemia [decreasing triglycerides and increasing HDL cholesterol (HDL-C)]. We have previously shown that male subjects following a CRD experienced significant increases in HDL-C only if they were consuming a higher intake of cholesterol provided by eggs compared to those individuals who were taking lower concentrations of dietary cholesterol. Here, as a follow up of our previous study, we examined the effects of eggs (a source of both dietary cholesterol and lutein) on adiponectin, a marker of insulin sensitivity, and on inflammatory markers in the context of a CRD. Conclusion A CRD with daily intake of eggs decreased plasma CRP and increased plasma adiponectin compared to a CRD without eggs. These findings indicate that eggs make a significant contribution to the anti-inflammatory effects of CRD, possibly due to the presence of cholesterol, which increases HDL-C and to the antioxidant lutein which modulates certain inflammatory responses.

"MedWire News: Zinc supplements could increase the risk for coronary heart disease (CHD) in healthy people by decreasing high-density lipoprotein (HDL) cholesterol levels, researchers claim. Initial findings from a meta-analysis in 14,238 participants from 20 trials suggested no impact of zinc supplements on plasma lipoprotein levels. But a secondary analysis in healthy individuals showed that zinc was associated with a significant decrease in plasma HDL concentrations. Furthermore, zinc was linked with a significant decrease in HDL cholesterol levels among participants with Type 2 diabetes or those undergoing hemodialysis. The researchers suggest the result in patients with diabetes may relate to the action of zinc in determining insulin levels. The meta-analysis included 33 interventions investigating the impact of zinc on lipid levels. The mean dose of elemental zinc used was 58 mg per day, which the researchers note is beyond the recommended upper level of intake of 40 mg."

An isoenergetic very low carbohydrate diet improves serum HDL cholesterol and triacylglycerol concentrations, the total cholesterol to HDL cholesterol ratio and postprandial pipemic responses compared with a low fat diet in normal weight, normolipidemic women. Volek JS, Sharman MJ, Gómez AL, Scheett TP, Kraemer WJ. J Nutr. 2003 Sep;133(9):2756-61. PMID: 12949361

Add vitamin D to achieve our target serum level . . . HDL jumps to 50, 60, 70, even 90 mg/dl. The first few times this occurred, I thought it was an error or fluke. But now that I've witnessed this effect many dozens of time, I am convinced that it is real. Just today, I saw a 40-year old man whose starting HDL was 25 mg/dl increase to 87 mg/dl. Responses like this are supposed to be impossible. Before vitamin D, I had never witnessed increases of this magnitude.

Dark chocolate consumption increases HDL cholesterol concentration and chocolate fatty acids may inhibit lipid peroxidation in healthy humans. Mursu J, Voutilainen S, Nurmi T, Rissanen TH, Virtanen JK, Kaikkonen J, Nyyssönen K, Salonen JT. Free Radic Biol Med. 2004 Nov 1;37(9):1351-9. PMID: 15454274 doi:10.1016/j.freeradbiomed.2004.06.002 Cocoa polyphenols may increase the concentration of HDL cholesterol, whereas chocolate fatty acids may modify the fatty acid composition of LDL and make it more resistant to oxidative damage.

The joint effects of apolipoprotein B, apolipoprotein A1, LDL cholesterol, and HDL cholesterol on risk: 3510 cases of acute myocardial infarction and 9805 controls. Parish S, Peto R, Palmer A, Clarke R, Lewington S, Offer A, Whitlock G, Clark S, Youngman L, Sleight P, Collins R; International Studies of Infarct Survival Collaborators. Eur Heart J. 2009 Sep;30(17):2137-46. Epub 2009 Jun 11. PMID: 19520708 doi:10.1093/eurheartj/ehp221 Conclusion: Apolipoprotein ratios are more informative about risk than lipid fractions are. This suggests that, among lipoprotein particles of a particular type (LDL or HDL), some smaller and larger subtypes differ in their effects on risk. Direct measurements of even more specific subtypes of lipoprotein particles may be even more informative about risk.

This week sees the publication of yet another study showing the superiority of the low-carbohydrate diet as compared to the low-fat diet. This study, published in the prestigious American Journal of Clinical Nutrition, demonstrates that subjects following the low-carb diet experience a decrease in triglyceride levels and an increase in HDL-cholesterol (HDL) levels; and that these changes are accompanied by a minor increase in LDL-cholesterol (LDL), which prompts the authors to issue a caveat. Yes, although just about all the parameters that lipophobes worry about improved with the low-carb diet, the small increase in LDL has caused great concern and has prompted the authors to gravely announce that this small increase is troublesome and should be monitored closely in anyone who may be at risk for heart disease. Since most people who go on low-carb diets do so to deal with obesity issues, and since obesity is a risk factor for heart disease, it would appear that this small increase in LDL often seen in those following a low-carb diet could put these dieters at risk. Does it? We'll see.

In response to the Heart Scan Blog post, Post-Traumatic Grain Disorder, Anne commented: While on the American Heart Association diet my lipids peaked in 2003. I even tried the Ornish diet for a short time, but found it impossible. Total Cholesterol: 201 Triglycerides: 263 HDL: 62 LDL: 86 After I stopped eating gluten (I am very sensitive), my lipid panel improved slightly. This past year I started eating to keep my blood sugar under control by eliminating sugars and other grains. Now this is my most recent lab: Total Cholesterol: 162 Triglycerides: 80 HDL: 71 LDL: 75

Eggs distinctly modulate plasma carotenoid and lipoprotein subclasses in adult men following a carbohydrate-restricted diet. Mutungi G, Waters D, Ratliff J, Puglisi M, Clark RM, Volek JS, Fernandez ML. J Nutr Biochem. 2009 Apr 13. [Epub ahead of print] PMID: 19369056 We previously reported that carbohydrate restriction (CR) (10-15% en) during a weight loss intervention lowered plasma triglycerides (TG) by 45% in male subjects (P<.05). However, only those subjects from the EGG group presented higher concentrations of these two carotenoids in plasma, which were correlated with the higher concentra

It is not difficult to raise HDLs. This is observed at TYP and in clinical practice ALL THE TIME. Eliminating wheat/d*mn-dirty-GRAINS/carbs, adding some vitamin D, omega-3s, Taurine, and Slo-Niacin 1-2 grams/day. Throwing away the Mazola and any packaged food items. Oh yeah, and add some fat. Individuals may continue their EVO (but not too much b/c it cranks up hepatic lipase, see HERE) but they increase eggs 2-6 daily, add some (organic nitrate-free preferably) bacon and some coconut oil.

"Want more of that good HDL cholesterol? Try a timed-release niacin, and be skeptical if your doctor gives the sales pitch for Zetia or Vytorin. The authority for this is a study dubbed ARBITER-6, which was stopped suddenly this summer, with the study's authors insisting safety had nothing to do with it. It was a question of efficacy. The results, described in the New England Journal of Medicine, make clear that niacin does better at the main job, keeping arteries open"

High-density lipoprotein cholesterol changes after continuous egg consumption in healthy adults. Mayurasakorn K, Srisura W, Sitphahul P, Hongto PO. J Med Assoc Thai. 2008 Mar;91(3):400-7. PMID: 18575296 CONCLUSION: In the majority of healthy adults, an addition of one egg per day to a normal fat diet could raise HDL-c levels and decreased the ratio of TC toHDL-c. Therefore, egg consumption might benefit blood cholesterol.

Relationships between 25-Hydroxyvitamin D Levels and Plasma Glucose and Lipid Levels in Pediatric Outpatients. Johnson MD, Nader NS, Weaver AL, Singh R, Kumar S. J Pediatr. 2009 Nov 17. [Epub ahead of print] PMID: 19926097 Conclusions Low 25(OH) D levels in children and adolescents are associated with higher plasma glucose and lower HDL concentrations.