Tuesday, May 2, 2023

The Problematic Paradigm of LDL-C, Part 11

Part 11 - The Effects of Diet on Markers of Cardiovascular and Metabolic Health


Previous - Part 10 - Other Factors in the Development of Atherosclerosis


Now that we’ve thoroughly examined the manner by which poor metabolic health can lead to small, damaged LDL particles and compromised blood vessels, lets finish our exploration of the LDL disease paradigm by examining common health markers and the effects of dietary choices on each.  

 

Impaired Metabolic Health

As has been made extremely clear by now, an individual with poor lipid metabolism will have several characteristic features. They will take up triglycerides slowly and inefficiently, which increases both the lifespan and the triglyceride count of the VLDL particles that transport them. This will lead to increased trading with HDL and LDL particles in order to share the excess triglyceride burden that must return to the liver. As a result, HDL-C will do down, while triglyceride-rich LDL particles will be acted on at the liver and reduced in size. This leads to a preponderance of small, dense LDL particles that are prime targets for modification, damage, and an immune response instrumental in atherosclerotic development.

Let’s walk through several of these and other markers one at a time, highlighting dozens of controlled trials that have sought to examine how dietary choices affect each of them.

 

Triglycerides

High triglycerides levels, as we have explored, are not primarily indicative of high triglyceride production but instead of poor triglyceride uptake by the cells of the body. This is effectively where metabolic dyslipidemia begins; Many other markers of poor metabolic health – low HDL-C, high VLDL-C, etc. – stem directly from the surplus of triglycerides in the blood of a person who cannot effectively utilize them.

Conventional advice on triglyceride lowering is mixed, but improving. Some authoritative sources, such as the Mayo Clinic, correctly blame high carbohydrate consumption above all else as a cause of elevated triglycerides (“If you regularly eat more calories than you burn, particularly from high-carbohydrate foods, you may have high triglycerides”).1 However, this position is hardly unanimous. Recent guidelines on triglyceride management from the American College of Cardiology include the advice that “clinicians are advised to further reduce TGs with a very low-fat diet.”2

The scientific literature on this topic, however, is extremely clear. To my knowledge (and believe me, I’ve looked), there does not yet exist a controlled trial in which the replacement of fat with carbohydrates has demonstrated a reduction in triglycerides. On the contrary, it is a fairly trivial task to find dozens that demonstrate the opposite.3–55 The reasons for this are multiple:

  • Elevated blood sugar causes glucose to be preferentially burned in an effort to return blood sugar levels to normal, inhibiting fat-utilization and essentially leaving triglycerides to accumulate as they wait to be taken up.
  • Long-term exposure to excess carbohydrates can lead to chronically elevated insulin and potential insulin resistance, making it more difficult for some cells to take in triglycerides.  
  • Some carbohydrates (fructose, most specifically) are directly converted to triglycerides in the liver. Thus it is common to heavily utilize carbs for energy while also creating new triglycerides that can’t presently be taken up.

In short – in order to lower triglycerides, one must eat fewer carbohydrates and “teach” the body to begin utilizing fat at a more efficient rate.

 

HDL-C

The largest factor in HDL-C levels is of course the degree to which HDL particles must trade away cholesterol in order to take on triglycerides from heavily-burdened VLDL particles. It should be no surprise whatsoever, then, that the science on HDL-C is just as consistently clear and overwhelming as is the science of triglycerides. When one eats too many carbohydrates, HDL-C goes down.6,15,21,23,27,30–34,41–43,47,48,54,56–71

This is not the only way diet can affect HDL however. A high HDL particle count is also associated with decreased risk for cardiovascular disease, and tends to increase alongside HDL-C. High fat consumption drives further production of apoA1, the main structural component of HDL particles.71–75 Unsurprisingly, then, greater fat consumption is associated with increased HDL particle count.66,76–79

Again we see that in order to improve HDL-C levels, one absolutely must replace some dietary carbohydrates with fat. 

 

VLDL-C

This one should be fairly clear as well. Because poor triglyceride utilization both increases the risk for cardiovascular disease and increases the lifespan of a triglyceride-rich VLDL particle, it meets all expectations that studies show a strong connection between elevated VLDL-C and cardiovascular disease.80–84

Equally as expected, trials routinely indicate that reducing carbohydrate intake improves VLDL-C levels.8,37,85–88

 

LDL particle size and sdLDL  

The reasons for the strong association between decreased LDL particle size and increased cardiovascular risk have been detailed at length – poor triglyceride utilization and increased return of triglycerides to the liver drives these changes. Again, as was the case with the previous markers, numerous trials have demonstrated that increased carbohydrate consumption at the expense of fat drives an increase in sdLDL and a decrease in average LDL particle size.4,36,37,76,77,89–94

 

Other factors

The markers outlined above are common health markers and major players in lipid metabolism that have been extensively demonstrated to improve with reduced carbohydrate consumption. Many other factors are affected by carbohydrate consumption as well, including:

  • Oxidized LDL – Decreasing the glycemic load, decreasing fructose consumption, and increasing fat consumption have all been demonstrated to reduce levels of oxidized LDL particles.95–101
  • lipoprotein(a) – lp(a), an LDL-like particle considered to be particularly atherogenic, serves as a primary carrier of oxidized lipoproteins. While many incorrectly assume lp(a) levels to be genetically fixed, they can in fact be lowered through increased saturated fat consumption.101–104
    • The primary reason the above points are true is because highly unsaturated fatty acids (such as those found in seed oils like corn, soybean, canola, etc.) are more reactive than saturated fatty acids and those more susceptible to modification. This may be exacerbated by the inflammatory conditions consistent with long-term elevated blood sugar.
  • Hyperglycemia decreases the availability of nitric oxide, contributing to increases in oxidized LDL and impairing vascular integrity.105–109
  • Hyperglycemia increases the expression of the free radical-generating NADPH oxidase and the immune-modulating protein NF-kB, instrumental in the inflammatory immune response that binds LDL particles at the walls of the blood vessel.110–117
  • Hyperglycemia both damages and impairs rebuilding of the protective glycocalyx that lines the walls of the blood vessels. 118–122

 

Hundreds of studies demonstrate that these and other risk factors for cardiovascular disease are made worse by increasing adherence to a carbohydrate-heavy diet. The reasons for this are readily apparent with an understanding of lipid mechanics, and the ways in which poor triglyceride utilization and excess blood sugar lead to a variety of atherogenic conditions. There is one metric left to examine though – LDL-C – which we’ll cover in the next, and final, section.

 

**Key Takeaways

  • Every common cardiometabolic marker (leaving aside LDL-C) reliably and consistently improves with a decrease in carbohydrate consumption and an increase in fat
  • Modification and damage to both LDL particles and the overall vascular environment is increased by the presence of excess carbohydrate in the bloodstream

 


Part 12 - The Effects of Diet of LDL-C, As Told By Energy Delivery




1.               Triglycerides: Why do they matter? - Mayo Clinic. Accessed April 22, 2023. https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/triglycerides/art-20048186

2.               Hypertriglyceridemia Management According to the 2018 AHA/ACC Guideline. American College of Cardiology. Accessed August 12, 2022. https://www.acc.org/latest-in-cardiology/articles/2019/01/11/07/39/http%3a%2f%2fwww.acc.org%2flatest-in-cardiology%2farticles%2f2019%2f01%2f11%2f07%2f39%2fhypertriglyceridemia-management-according-to-the-2018-aha-acc-guideline

3.               Volek JS, Sharman MJ, Gómez AL, Scheett TP, Kraemer WJ. An Isoenergetic Very Low Carbohydrate Diet Improves Serum HDL Cholesterol and Triacylglycerol Concentrations, the Total Cholesterol to HDL Cholesterol Ratio and Postprandial Lipemic Responses Compared with a Low Fat Diet in Normal Weight, Normolipidemic Women. The Journal of Nutrition. 2003;133(9):2756-2761. doi:10.1093/jn/133.9.2756

4.               Forsythe CE, Phinney SD, Feinman RD, et al. Limited Effect of Dietary Saturated Fat on Plasma Saturated Fat in the Context of a Low Carbohydrate Diet. Lipids. 2010;45(10):947-962. doi:10.1007/s11745-010-3467-3

5.               Mousavi SM, Ejtahed HS, Marvasti FE, et al. The Effect of a Moderately Restricted Carbohydrate Diet on Cardiometabolic Risk Factors in Overweight and Obese Women With Metabolic Syndrome: A Randomized Controlled Trial. Clinical Therapeutics. Published online March 4, 2023. doi:10.1016/j.clinthera.2023.02.002

6.               Foster GD, Wyatt HR, Hill JO, et al. A Randomized Trial of a Low-Carbohydrate Diet for Obesity. New England Journal of Medicine. 2003;348(21):2082-2090. doi:10.1056/NEJMoa022207

7.               Yamada Y, Uchida J, Izumi H, et al. A Non-calorie-restricted Low-carbohydrate Diet is Effective as an Alternative Therapy for Patients with Type 2 Diabetes. Internal Medicine. 2014;53(1):13-19. doi:10.2169/internalmedicine.53.0861

8.               Parks EJ, Krauss RM, Christiansen MP, Neese RA, Hellerstein MK. Effects of a low-fat, high-carbohydrate diet on VLDL-triglyceride assembly, production, and clearance. J Clin Invest. 1999;104(8):1087-1096. doi:10.1172/JCI6572

9.               Chiu S, Bergeron N, Williams PT, Bray GA, Sutherland B, Krauss RM. Comparison of the DASH (Dietary Approaches to Stop Hypertension) diet and a higher-fat DASH diet on blood pressure and lipids and lipoproteins: a randomized controlled trial1–3. The American Journal of Clinical Nutrition. 2016;103(2):341-347. doi:10.3945/ajcn.115.123281

10.             Properzi C, O’Sullivan TA, Sherriff JL, et al. Ad Libitum Mediterranean and Low-Fat Diets Both Significantly Reduce Hepatic Steatosis: A Randomized Controlled Trial. Hepatology. 2018;68(5):1741-1754. doi:10.1002/hep.30076

11.             Bradley U, Spence M, Courtney CH, et al. Low-Fat Versus Low-Carbohydrate Weight Reduction Diets: Effects on Weight Loss, Insulin Resistance, and Cardiovascular Risk: A Randomized Control Trial. Diabetes. 2009;58(12):2741-2748. doi:10.2337/db09-0098

12.             Marckmann P, Sandström B, Jespersen J. Low-fat, high-fiber diet favorably affects several independent risk markers of ischemic heart disease: observations on blood lipids, coagulation, and fibrinolysis from a trial of middle-aged Danes. The American Journal of Clinical Nutrition. 1994;59(4):935-939. doi:10.1093/ajcn/59.4.935

13.             Bazzano LA, Hu T, Reynolds K, et al. Effects of Low-Carbohydrate and Low-Fat Diets. Ann Intern Med. 2014;161(5):309-318. doi:10.7326/M14-0180

14.             Ebbeling CB, Leidig MM, Feldman HA, Lovesky MM, Ludwig DS. Effects of a Low–Glycemic Load vs Low-Fat Diet in Obese Young AdultsA Randomized Trial. JAMA. 2007;297(19):2092-2102. doi:10.1001/jama.297.19.2092

15.             Dashti HM, Mathew TC, Hussein T, et al. Long-term effects of a ketogenic diet in obese patients. Exp Clin Cardiol. 2004;9(3):200-205.

16.             Abbasi F, McLaughlin T, Lamendola C, et al. High carbohydrate diets, triglyceride-rich lipoproteins, and coronary heart disease risk. The American Journal of Cardiology. 2000;85(1):45-48. doi:10.1016/S0002-9149(99)00604-9

17.             Shai I, Schwarzfuchs D, Henkin Y, et al. Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet. New England Journal of Medicine. 2008;359(3):229-241. doi:10.1056/NEJMoa0708681

18.             Brinkworth GD, Noakes M, Buckley JD, Keogh JB, Clifton PM. Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo. The American Journal of Clinical Nutrition. 2009;90(1):23-32. doi:10.3945/ajcn.2008.27326

19.             Hudgins LC, Hellerstein M, Seidman C, Neese R, Diakun J, Hirsch J. Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet. J Clin Invest. 1996;97(9):2081-2091. doi:10.1172/JCI118645

20.             Nordmann AJ, Nordmann A, Briel M, et al. Effects of Low-Carbohydrate vs Low-Fat Diets on Weight Loss and Cardiovascular Risk Factors: A Meta-analysis of Randomized Controlled Trials. Archives of Internal Medicine. 2006;166(3):285-293. doi:10.1001/archinte.166.3.285

21.             Ruth MR, Port AM, Shah M, et al. Consuming a hypocaloric high fat low carbohydrate diet for 12weeks lowers C-reactive protein, and raises serum adiponectin and high density lipoprotein-cholesterol in obese subjects. Metabolism. 2013;62(12):1779-1787. doi:10.1016/j.metabol.2013.07.006

22.             Parillo M, Rivellese AA, Ciardullo AV, et al. A high-monounsaturated-fat/low-carbohydrate diet improves peripheral insulin sensitivity in non-insulin-dependent diabetic patients. Metabolism. 1992;41(12):1373-1378. doi:10.1016/0026-0495(92)90111-M

23.             Huntriss R, Campbell M, Bedwell C. The interpretation and effect of a low-carbohydrate diet in the management of type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. Eur J Clin Nutr. 2018;72(3):311-325. doi:10.1038/s41430-017-0019-4

24.             Martens EA, Gatta-Cherifi B, Gonnissen HK, Westerterp-Plantenga MS. The Potential of a High Protein-Low Carbohydrate Diet to Preserve Intrahepatic Triglyceride Content in Healthy Humans. PLOS ONE. 2014;9(10):e109617. doi:10.1371/journal.pone.0109617

25.             Sanfelippo ML, Swenson RS, Reaven GM. Reduction of plasma triglycerides by diet in subjects with chronic renal failure. Kidney International. 1977;11(1):54-61. doi:10.1038/ki.1977.7

26.             Stern L, Iqbal N, Seshadri P, et al. The Effects of Low-Carbohydrate versus Conventional Weight Loss Diets in Severely Obese Adults: One-Year Follow-up of a Randomized Trial. Ann Intern Med. 2004;140(10):778-785. doi:10.7326/0003-4819-140-10-200405180-00007

27.             Volek JS, Sharman MJ. Cardiovascular and Hormonal Aspects of Very-Low-Carbohydrate Ketogenic Diets. Obesity Research. 2004;12(S11):115S-123S. doi:10.1038/oby.2004.276

28.             Hays JH, DiSabatino A, Gorman RT, Vincent S, Stillabower ME. Effect of a high saturated fat and no-starch diet on serum lipid subfractions in patients with documented atherosclerotic cardiovascular disease. Mayo Clin Proc. 2003;78(11):1331-1336. doi:10.4065/78.11.1331

29.             Kirkpatrick CF, Bolick JP, Kris-Etherton PM, et al. Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: A scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force. Journal of Clinical Lipidology. 2019;13(5):689-711.e1. doi:10.1016/j.jacl.2019.08.003

30.             Schwingshackl L, Hoffmann G. Comparison of Effects of Long-Term Low-Fat vs High-Fat Diets on Blood Lipid Levels in Overweight or Obese Patients: A Systematic Review and Meta-Analysis. Journal of the Academy of Nutrition and Dietetics. 2013;113(12):1640-1661. doi:10.1016/j.jand.2013.07.010

31.             Chawla S, Tessarolo Silva F, Amaral Medeiros S, Mekary RA, Radenkovic D. The Effect of Low-Fat and Low-Carbohydrate Diets on Weight Loss and Lipid Levels: A Systematic Review and Meta-Analysis. Nutrients. 2020;12(12):3774. doi:10.3390/nu12123774

32.             Dashti H, Bo-Abbas Y, Asfar S, et al. Ketogenic diet modifies the risk factors of heart disease in obese patients. Nutrition (Burbank, Los Angeles County, Calif). 2003;19:901-902. doi:10.1016/S0899-9007(03)00161-8

33.             Dashti HM, Mathew TC, Khadada M, et al. Beneficial effects of ketogenic diet in obese diabetic subjects. Mol Cell Biochem. 2007;302(1):249-256. doi:10.1007/s11010-007-9448-z

34.             Yancy WS, Olsen MK, Guyton JR, Bakst RP, Westman EC. A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia. Ann Intern Med. 2004;140(10):769-777. doi:10.7326/0003-4819-140-10-200405180-00006

35.             Dashti HM, Al-Zaid NS, Mathew TC, et al. Long Term Effects of Ketogenic Diet in Obese Subjects with High Cholesterol Level. Mol Cell Biochem. 2006;286(1):1. doi:10.1007/s11010-005-9001-x

36.             Guay V, Lamarche B, Charest A, Tremblay AJ, Couture P. Effect of short-term low- and high-fat diets on low-density lipoprotein particle size in normolipidemic subjects. Metabolism. 2012;61(1):76-83. doi:10.1016/j.metabol.2011.06.002

37.             Sharman MJ, Kraemer WJ, Love DM, et al. A Ketogenic Diet Favorably Affects Serum Biomarkers for Cardiovascular Disease in Normal-Weight Men. The Journal of Nutrition. 2002;132(7):1879-1885. doi:10.1093/jn/132.7.1879

38.             Samaha FF, Iqbal N, Seshadri P, et al. A Low-Carbohydrate as Compared with a Low-Fat Diet in Severe Obesity. New England Journal of Medicine. 2003;348(21):2074-2081. doi:10.1056/NEJMoa022637

39.             Harvey CJ d C, Schofield GM, Zinn C, Thornley SJ, Crofts C, Merien FLR. Low-carbohydrate diets differing in carbohydrate restriction improve cardiometabolic and anthropometric markers in healthy adults: A randomised clinical trial. PeerJ. 2019;7:e6273. doi:10.7717/peerj.6273

40.             Wolfe BMJ, Piche LA. Replacement of carbohydrate by protein in conventional-fat diet reduces cholesterol and triglyceride concentrations in healthy normolipidemic subjects. Clinical and Investigative Medicine. 1999;22(4):140-148.

41.             Buga A, Welton GL, Scott KE, et al. The Effects of Carbohydrate versus Fat Restriction on Lipid Profiles in Highly Trained, Recreational Distance Runners: A Randomized, Cross-Over Trial. Nutrients. 2022;14(6):1135. doi:10.3390/nu14061135

42.             Tay J, Thompson CH, Luscombe-Marsh ND, et al. Effects of an energy-restricted low-carbohydrate, high unsaturated fat/low saturated fat diet versus a high-carbohydrate, low-fat diet in type 2 diabetes: A 2-year randomized clinical trial. Diabetes, Obesity and Metabolism. 2018;20(4):858-871. doi:10.1111/dom.13164

43.             Li S, Ding L, Xiao X. Comparing the Efficacy and Safety of Low-Carbohydrate Diets with Low-Fat Diets for Type 2 Diabetes Mellitus Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. International Journal of Endocrinology. 2021;2021:e8521756. doi:10.1155/2021/8521756

44.             Barnard ND, Scialli AR, Bertron P, Hurlock D, Edmonds K, Talev L. Effectiveness of a low-fat vegetarian diet in altering serum lipids in healthy premenopausal women. The American Journal of Cardiology. 2000;85(8):969-972. doi:10.1016/S0002-9149(99)00911-X

45.             Coulston AM, Liu GC, Reaven GM. Plasma glucose, insulin and lipid responses to high-carbohydrate low-fat diets in normal humans. Metabolism. 1983;32(1):52-56. doi:10.1016/0026-0495(83)90155-5

46.             Pelkman CL, Fishell VK, Maddox DH, Pearson TA, Mauger DT, Kris-Etherton PM. Effects of moderate-fat (from monounsaturated fat) and low-fat weight-loss diets on the serum lipid profile in overweight and obese men and women. The American Journal of Clinical Nutrition. 2004;79(2):204-212. doi:10.1093/ajcn/79.2.204

47.             Roche HM. Low-fat diets, triglycerides and coronary heart disease risk. Nutrition Bulletin. 2000;25(1):49-53. doi:10.1046/j.1467-3010.2000.00020.x

48.             Garg A, Bonanome A, Grundy SM, Zhang ZJ, Unger RH. Comparison of a High-Carbohydrate Diet with a High-Monounsaturated-Fat Diet in Patients with Non-Insulin-Dependent Diabetes Mellitus. New England Journal of Medicine. 1988;319(13):829-834. doi:10.1056/NEJM198809293191304

49.             Turley ML, Skeaff CM, Mann JI, Cox B. The effect of a low-fat, high-carbohydrate diet on serum high density lipoprotein cholesterol and triglyceride. Eur J Clin Nutr. 1998;52(10):728-732. doi:10.1038/sj.ejcn.1600634

50.             Brussaard JH, Katan MB, Groot PHE, Havekes LM, Hautvast JGAJ. Serum lipoproteins of healthy persons fed a low-fat diet or a polyunsaturated fat diet for three months: A comparison of two cholesterol-lowering diets. Atherosclerosis. 1982;42(2):205-219. doi:10.1016/0021-9150(82)90151-4

51.             Grundy SM. Comparison of Monounsaturated Fatty Acids and Carbohydrates for Lowering Plasma Cholesterol. New England Journal of Medicine. 1986;314(12):745-748. doi:10.1056/NEJM198603203141204

52.             Volk BM, Kunces LJ, Freidenreich DJ, et al. Effects of Step-Wise Increases in Dietary Carbohydrate on Circulating Saturated Fatty Acids and Palmitoleic Acid in Adults with Metabolic Syndrome. PLOS ONE. 2014;9(11):e113605. doi:10.1371/journal.pone.0113605

53.             Sacks FM, Katan M. Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease. The American Journal of Medicine. 2002;113(9, Supplement 2):13-24. doi:10.1016/S0002-9343(01)00987-1

54.             Knopp RH, Retzlaff B, Walden C, Fish B, Buck B, Mccann B. One-Year Effects of Increasingly Fat-Restricted, Carbohydrate-Enriched Diets on Lipoprotein Levels in Free-Living Subjects (44564E). Proceedings of the Society for Experimental Biology and Medicine. 2000;225(3):191-199. doi:10.1177/153537020022500305

55.             Wachsmuth NB, Aberer F, Haupt S, et al. The Impact of a High-Carbohydrate/Low Fat vs. Low-Carbohydrate Diet on Performance and Body Composition in Physically Active Adults: A Cross-Over Controlled Trial. Nutrients. 2022;14(3):423. doi:10.3390/nu14030423

56.             Gan CF, Gong RR, Lin J, et al. [Effects of high-carbohydrate/low-fat diet on serum lipid ratios in healthy young subjects]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2008;39(2):267-271, 275.

57.             Meng Y, Bai H, Wang S, Li Z, Wang Q, Chen L. Efficacy of low carbohydrate diet for type 2 diabetes mellitus management: A systematic review and meta-analysis of randomized controlled trials. Diabetes Research and Clinical Practice. 2017;131:124-131. doi:10.1016/j.diabres.2017.07.006

58.             Mutungi G, Ratliff J, Puglisi M, et al. Dietary Cholesterol from Eggs Increases Plasma HDL Cholesterol in Overweight Men Consuming a Carbohydrate-Restricted Diet. The Journal of Nutrition. 2008;138(2):272-276. doi:10.1093/jn/138.2.272

59.             MEYER N, DIEKMANN LM, KABISCH S, DAMBECK U, PFEIFFER AF. 784-P: Effects of Low-Carb and Low-Fat Dietary Strategies on Lipid Profile in Subjects with Prediabetes—DiNA-P. Diabetes. 2019;68(Supplement_1):784-P. doi:10.2337/db19-784-P

60.             Asztalos B, Lefevre M, Wong L, et al. Differential response to low-fat diet between low and normal HDL-cholesterol subjects. Journal of Lipid Research. 2000;41(3):321-328. doi:10.1016/S0022-2275(20)34470-9

61.             Vélez-Carrasco W, Lichtenstein AH, Welty FK, et al. Dietary Restriction of Saturated Fat and Cholesterol Decreases HDL ApoA-I Secretion. Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19(4):918-924. doi:10.1161/01.ATV.19.4.918

62.             DELTA Investigators. HDL-subpopulation patterns in response to reductions in dietary total and saturated fat intakes in healthy subjects. The American Journal of Clinical Nutrition. 1999;70(6):992-1000. doi:10.1093/ajcn/70.6.992

63.             Siri-Tarino PW, Sun Q, Hu FB, Krauss RM. Saturated fat, carbohydrate, and cardiovascular disease. The American Journal of Clinical Nutrition. 2010;91(3):502-509. doi:10.3945/ajcn.2008.26285

64.             Ehnholm C, Huttunen JK, Pietinen P, et al. Effect of a diet low in saturated fatty acids on plasma lipids, lipoproteins, and HDL subfractions. Arteriosclerosis: An Official Journal of the American Heart Association, Inc. 1984;4(3):265-269. doi:10.1161/01.ATV.4.3.265

65.             Jackson RL, Yates MT, McNerney CA, Kashyap ML. Diet and HDL Metabolism: High Carbohydrate vs. High Fat Diets. In: Malmendier CL, Alaupovic P, eds. Lipoproteins and Atherosclerosis. Advances in Experimental Medicine and Biology. Springer US; 1987:165-172. doi:10.1007/978-1-4684-1268-0_24

66.             Wood RJ, Volek JS, Liu Y, Shachter NS, Contois JH, Fernandez ML. Carbohydrate Restriction Alters Lipoprotein Metabolism by Modifying VLDL, LDL, and HDL Subfraction Distribution and Size in Overweight Men. The Journal of Nutrition. 2006;136(2):384-389. doi:10.1093/jn/136.2.384

67.             Andersen CJ, Blesso CN, Park Y, et al. Carbohydrate restriction favorably affects HDL metabolism in men and women with Metabolic Syndrome. Addition of egg yolk further increases large HDL particles. The FASEB Journal. 2012;26(S1):254.5-254.5. doi:10.1096/fasebj.26.1_supplement.254.5

68.             Morgan SA, O’dea K, Sinclair AJ. A Low-Fat Diet Supplemented With Monounsaturated Fat Results in Less HDL-C Lowering Than a Very-Low-Fat Diet. Journal of the American Dietetic Association. 1997;97(2):151-156. doi:10.1016/S0002-8223(97)00770-0

69.             Wu L, Ma D, Walton-Moss B, He Z. Effects of low-fat diet on serum lipids in premenopausal and postmenopausal women: a meta-analysis of randomized controlled trials. Menopause. 2014;21(1):89-99. doi:10.1097/GME.0b013e318291f5c2

70.             Seim HC, Holtmeier KB. Effects of a six-week, low-fat diet on serum cholesterol, body weight, and body measurements. Fam Pract Res J. 1992;12(4):411-419.

71.             Brinton EA, Eisenberg S, Breslow JL. A low-fat diet decreases high density lipoprotein (HDL) cholesterol levels by decreasing HDL apolipoprotein transport rates. J Clin Invest. 1990;85(1):144-151. doi:10.1172/JCI114405

72.             Hayek T, Ito Y, Azrolan N, et al. Dietary fat increases high density lipoprotein (HDL) levels both by increasing the transport rates and decreasing the fractional catabolic rates of HDL cholesterol ester and apolipoprotein (Apo) A-I. Presentation of a new animal model and mechanistic studies in human Apo A-I transgenic and control mice. J Clin Invest. 1993;91(4):1665-1671. doi:10.1172/JCI116375

73.             Bhanpuri NH, Hallberg SJ, Williams PT, et al. Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study. Cardiovasc Diabetol. 2018;17(1):56. doi:10.1186/s12933-018-0698-8

74.             Mooradian AD, Haas MJ, Wong NCW. The Effect of Select Nutrients on Serum High-Density Lipoprotein Cholesterol and Apolipoprotein A-I Levels. Endocrine Reviews. 2006;27(1):2-16. doi:10.1210/er.2005-0013

75.             Wolf G. High-Fat, High-Cholesterol Diet Raises Plasma Hdl Cholesterol: Studies on the Mechanism of This Effect. Nutrition Reviews. 1996;54(1):34-35. doi:10.1111/j.1753-4887.1996.tb03772.x

76.             Falkenhain K, Roach LA, McCreary S, et al. Effect of carbohydrate-restricted dietary interventions on LDL particle size and number in adults in the context of weight loss or weight maintenance: a systematic review and meta-analysis. The American Journal of Clinical Nutrition. 2021;114(4):1455-1466. doi:10.1093/ajcn/nqab212

77.             Ebbeling C, Knapp A, Johnson A, et al. Effects of a Low-Carbohydrate Diet on Cardiometabolic Risk Factors During Weight-Loss Maintenance: A Randomized Controlled Feeding Trial. Current Developments in Nutrition. 2020;4(Supplement_2):625. doi:10.1093/cdn/nzaa049_018

78.             Siri PW, Krauss RM. Influence of dietary carbohydrate and fat on LDL and HDL particle distributions. Curr Atheroscler Rep. 2005;7(6):455-459. doi:10.1007/s11883-005-0062-9

79.             Alzahrani AH, Skytte MJ, Samkani A, et al. Effects of a Self-Prepared Carbohydrate-Reduced High-Protein Diet on Cardiovascular Disease Risk Markers in Patients with Type 2 Diabetes. Nutrients. 2021;13(5):1694. doi:10.3390/nu13051694

80.             Duran EK, Aday AW, Cook NR, Buring JE, Ridker PM, Pradhan AD. Triglyceride-Rich Lipoprotein Cholesterol, Small Dense LDL Cholesterol, and Incident Cardiovascular Disease. J Am Coll Cardiol. 2020;75(17):2122-2135. doi:10.1016/j.jacc.2020.02.059

81.             Sanders FWB, Griffin JL. De novo lipogenesis in the liver in health and disease: more than just a shunting yard for glucose. Biol Rev Camb Philos Soc. 2016;91(2):452-468. doi:10.1111/brv.12178

82.             Gentile M, Iannuzzi A, Giallauria F, et al. Association between Very Low-Density Lipoprotein Cholesterol (VLDL-C) and Carotid Intima-Media Thickness in Postmenopausal Women Without Overt Cardiovascular Disease and on LDL-C Target Levels. Journal of Clinical Medicine. 2020;9(5):1422. doi:10.3390/jcm9051422

83.             Liaquat A, Javed Q. Current Trends of Cardiovascular Risk Determinants in Pakistan. Cureus. 2018;10(10). doi:10.7759/cureus.3409

84.             Balling M, Afzal S, Varbo A, Langsted A, Davey SG, Nordestgaard BG. VLDL Cholesterol Accounts for One-Half of the Risk of Myocardial Infarction Associated With apoB-Containing Lipoproteins. Journal of the American College of Cardiology. 2020;76(23):2725-2735. doi:10.1016/j.jacc.2020.09.610

85.             Freedland SJ, Howard LE, Ngo A, et al. Low Carbohydrate Diets and Estimated Cardiovascular and Metabolic Syndrome Risk in Prostate Cancer. Journal of Urology. 2021;206(6):1411-1419. doi:10.1097/JU.0000000000002112

86.             Garg A, Grundy SM, Unger RH. Comparison of Effects of High and Low Carbohydrate Diets on Plasma Lipoproteins and Insulin Sensitivity in Patients With Mild NIDDM. Diabetes. 1992;41(10):1278-1285. doi:10.2337/diab.41.10.1278

87.             Koutsari C, Karpe F, Humphreys SM, Frayn KN, Hardman AE. Exercise prevents the accumulation of triglyceride-rich lipoproteins and their remnants seen when changing to a high-carbohydrate diet. Arterioscler Thromb Vasc Biol. 2001;21(9):1520-1525. doi:10.1161/hq0901.095553

88.             Liu Y, Bharmal SH, Kimita W, Petrov MS. Effect of acute ketosis on lipid profile in prediabetes: findings from a cross-over randomized controlled trial. Cardiovascular Diabetology. 2022;21(1):138. doi:10.1186/s12933-022-01571-z

89.             Maruyama C, Imamura K, Teramoto T. Assessment of LDL Particle Size by Triglyceride/HDL-Cholesterol Ratio in Non-diabetic, Healthy Subjects without Prominent Hyperlipidemia. Journal of Atherosclerosis and Thrombosis. 2003;10(3):186-191. doi:10.5551/jat.10.186

90.             Julius U, Dittrich M, Pietzsch J. Factors influencing the formation of small dense low-density lipoprotein particles in dependence on the presence of the metabolic syndrome and on the degree of glucose intolerance. International Journal of Clinical Practice. 2007;61(11):1798-1804. doi:10.1111/j.1742-1241.2007.01507.x

91.             Westman EC, Yancy WS, Olsen MK, Dudley T, Guyton JR. Effect of a low-carbohydrate, ketogenic diet program compared to a low-fat diet on fasting lipoprotein subclasses. International Journal of Cardiology. 2006;110(2):212-216. doi:10.1016/j.ijcard.2005.08.034

92.             McNamara JR, Jenner JL, Li Z, Wilson PW, Schaefer EJ. Change in LDL particle size is associated with change in plasma triglyceride concentration. Arteriosclerosis and Thrombosis: A Journal of Vascular Biology. 1992;12(11):1284-1290. doi:10.1161/01.ATV.12.11.1284

93.             Stan S, Levy E, Delvin EE, et al. Distribution of LDL Particle Size in a Population-Based Sample of Children and Adolescents and Relationship with Other Cardiovascular Risk Factors. Clinical Chemistry. 2005;51(7):1192-1200. doi:10.1373/clinchem.2004.046771

94.             Dreon DM, Fernstrom HA, Williams PT, Krauss RM. Reduced LDL particle size in children consuming a very-low-fat diet is related to parental LDL-subclass patterns. The American Journal of Clinical Nutrition. 2000;71(6):1611-1616. doi:10.1093/ajcn/71.6.1611

95.             Tanaka J, Qiang L, Banks AS, et al. Foxo1 Links Hyperglycemia to LDL Oxidation and Endothelial Nitric Oxide Synthase Dysfunction in Vascular Endothelial Cells. Diabetes. 2009;58(10):2344-2354. doi:10.2337/db09-0167

96.             Wang L, Tao L, Hao L, et al. A Moderate-Fat Diet with One Avocado per Day Increases Plasma Antioxidants and Decreases the Oxidation of Small, Dense LDL in Adults with Overweight and Obesity: A Randomized Controlled Trial. J Nutr. 2020;150(2):276-284. doi:10.1093/jn/nxz231

97.             Fitó M, Guxens M, Corella D, et al. Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial. Arch Intern Med. 2007;167(11):1195-1203. doi:10.1001/archinte.167.11.1195

98.             Vos MB, Weber MB, Welsh J, et al. Fructose and Oxidized LDL in Pediatric Nonalcoholic Fatty Liver Disease: A Pilot Study. Arch Pediatr Adolesc Med. 2009;163(7):674-675. doi:10.1001/archpediatrics.2009.93

99.             Jones JL, Comperatore M, Barona J, et al. A Mediterranean-style, low–glycemic-load diet decreases atherogenic lipoproteins and reduces lipoprotein (a) and oxidized low-density lipoprotein in women with metabolic syndrome. Metabolism - Clinical and Experimental. 2012;61(3):366-372. doi:10.1016/j.metabol.2011.07.013

100.           Barona J, Jones JJ, Kopec RE, et al. A Mediterranean-style low-glycemic-load diet increases plasma carotenoids and decreases LDL oxidation in women with metabolic syndrome. The Journal of Nutritional Biochemistry. 2012;23(6):609-615. doi:10.1016/j.jnutbio.2011.02.016

101.           Silaste ML, Rantala M, Alfthan G, et al. Changes in dietary fat intake alter plasma levels of oxidized low-density lipoprotein and lipoprotein(a). Arterioscler Thromb Vasc Biol. 2004;24(3):498-503. doi:10.1161/01.ATV.0000118012.64932.f4

102.           Faghihnia N, Tsimikas S, Miller ER, Witztum JL, Krauss RM. Changes in lipoprotein(a), oxidized phospholipids, and LDL subclasses with a low-fat high-carbohydrate diet. J Lipid Res. 2010;51(11):3324-3330. doi:10.1194/jlr.M005769

103.           Ginsberg HN, Kris-Etherton P, Dennis B, et al. Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: the DELTA Study, protocol 1. Arterioscler Thromb Vasc Biol. 1998;18(3):441-449. doi:10.1161/01.atv.18.3.441

104.           Healthy Dietary Interventions and Lipoprotein (a) Plasma Levels: Results from the Omni Heart Trial | PLOS ONE. Accessed April 21, 2023. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114859

105.           Williams IL, Wheatcroft SB, Shah AM, Kearney MT. Obesity, atherosclerosis and the vascular endothelium: mechanisms of reduced nitric oxide bioavailability in obese humans. Int J Obes. 2002;26(6):754-764. doi:10.1038/sj.ijo.0801995

106.           Du XL, Edelstein D, Dimmeler S, Ju Q, Sui C, Brownlee M. Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. J Clin Invest. 2001;108(9):1341-1348. doi:10.1172/JCI11235

107.           Klein AV, Kiat H. The mechanisms underlying fructose-induced hypertension: a review. J Hypertens. 2015;33(5):912-920. doi:10.1097/HJH.0000000000000551

108.           Kersten JR, Toller WG, Tessmer JP, Pagel PS, Warltier DC. Hyperglycemia reduces coronary collateral blood flow through a nitric oxide-mediated mechanism. American Journal of Physiology-Heart and Circulatory Physiology. 2001;281(5):H2097-H2104. doi:10.1152/ajpheart.2001.281.5.H2097

109.           Cominacini L, Rigoni A, Pasini AF, et al. The Binding of Oxidized Low Density Lipoprotein (ox-LDL) to ox-LDL Receptor-1 Reduces the Intracellular Concentration of Nitric Oxide in Endothelial Cells through an Increased Production of Superoxide *. Journal of Biological Chemistry. 2001;276(17):13750-13755. doi:10.1074/jbc.M010612200

110.           Prasad K, Dhar I. Oxidative stress as a mechanism of added sugar-induced cardiovascular disease. Int J Angiol. 2014;23(4):217-226. doi:10.1055/s-0034-1387169

111.           Jansen H, Verhoeven AJM, Sijbrands EJG. Hepatic lipase. Journal of Lipid Research. 2002;43(9):1352-1362. doi:10.1194/jlr.R200008-JLR200

112.           Balteau M, Tajeddine N, de Meester C, et al. NADPH oxidase activation by hyperglycaemia in cardiomyocytes is independent of glucose metabolism but requires SGLT1. Cardiovascular research. 2011;92:237-246. doi:10.1093/cvr/cvr230

113.           Lee Y, Fluckey JD, Chakraborty S, Muthuchamy M. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle. The FASEB Journal. 2017;31(7):2744-2759. doi:10.1096/fj.201600887R

114.           Stefano GB, Challenger S, Kream RM. Hyperglycemia-associated alterations in cellular signaling and dysregulated mitochondrial bioenergetics in human metabolic disorders. Eur J Nutr. 2016;55(8):2339-2345. doi:10.1007/s00394-016-1212-2

115.           Pahwa R, Jialal I. Hyperglycemia Induces Toll-Like Receptor Activity Through Increased Oxidative Stress. Metabolic Syndrome and Related Disorders. 2016;14(5):239-241. doi:10.1089/met.2016.29006.pah

116.           Khodami B, Hatami B, Yari Z, et al. Effects of a low free sugar diet on the management of nonalcoholic fatty liver disease: a randomized clinical trial. Eur J Clin Nutr. 2022;76(7):987-994. doi:10.1038/s41430-022-01081-x

117.           Morigi M, Angioletti S, Imberti B, et al. Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-kB-dependent fashion. J Clin Invest. 1998;101(9):1905-1915. doi:10.1172/JCI656

118.           Nieuwdorp M, van Haeften TW, Gouverneur MCLG, et al. Loss of Endothelial Glycocalyx During Acute Hyperglycemia Coincides With Endothelial Dysfunction and Coagulation Activation In Vivo. Diabetes. 2006;55(2):480-486. doi:10.2337/diabetes.55.02.06.db05-1103

119.           Aldecoa C, Llau JV, Nuvials X, Artigas A. Role of albumin in the preservation of endothelial glycocalyx integrity and the microcirculation: a review. Annals of Intensive Care. 2020;10(1):85. doi:10.1186/s13613-020-00697-1

120.           Singh A, Fridén V, Dasgupta I, et al. High glucose causes dysfunction of the human glomerular endothelial glycocalyx. American Journal of Physiology-Renal Physiology. 2011;300(1):F40-F48. doi:10.1152/ajprenal.00103.2010

121.           Lopez-Quintero SV, Cancel LM, Pierides A, Antonetti D, Spray DC, Tarbell JM. High Glucose Attenuates Shear-Induced Changes in Endothelial Hydraulic Conductivity by Degrading the Glycocalyx. PLOS ONE. 2013;8(11):e78954. doi:10.1371/journal.pone.0078954

122.           Zuurbier CJ, Demirci C, Koeman A, Vink H, Ince C. Short-term hyperglycemia increases endothelial glycocalyx permeability and acutely decreases lineal density of capillaries with flowing red blood cells. Journal of Applied Physiology. 2005;99(4):1471-1476. doi:10.1152/japplphysiol.00436.2005






at
Labels: , , , , ,

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)