Cholesterol / Lipids

LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature

Michel de Lorgeril, David M Diamond, Rokuro Hama, Tomohito Hamazaki, Björn Hammarskjöld, Niamh Hynes, Malcolm Kendrick, Peter H Langsjoen, Luca Mascitelli, Kilmer S McCully, Harumi Okuyama ORCID Icon, Paul J Rosch, Tore Schersten, Sherif Sultan & Ralf Sundberg

For half a century, a high level of total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C) has been considered to be the major cause of atherosclerosis and cardiovascular disease (CVD), and statin treatment has been widely promoted for cardiovascular prevention. However, there is an increasing understanding that the mechanisms are more complicated and that statin treatment, in particular when used as primary prevention, is of doubtful benefit.

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Fasting Lipoprotein and Postprandial Triacylglycerol Responses to a Lowcarbohydrate Diet Supplemented With n-3 Fatty Acids

Jeff S. Volek, PhD, RD; Ana L. Gómez , MS; William J. Kraemer , PhD

Single arm prospective with 10 Participants:  A hypocaloric low-carbohydrate diet rich in MUFA and supplemented with n-3 fatty acids significantly reduced postabsorptive and postprandial TG in men that were not hypertriglyceridemic as a group before the diet.  This may be viewed as a clinically significant positive adaptation in terms of cardiovascular risk status.

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Effect of 6-month Adherence to a Very Low Carbohydrate Diet Program

Eric C Westman, MD, MHS; William S Yancy, MD; Joel S Edman, DSc; Keith F Tomlin; Christine E Perkins, MSW

Single arm prospective with 51 participants:  In these subjects, the mean body weight decreased 10.3% +/- 5.9% from baseline to 6 months. The mean percentage of body weight that was fat decreased 2.9% +/- 3.2% from baseline to 6 months. Serum total cholesterol level decreased 11 +/- 26 mg/dL, low-density lipoprotein cholesterol level decreased 10 +/- 25 mg/dL, triglyceride level decreased 56 +/- 45 mg/dL, high-density lipoprotein (HDL) cholesterol level increased 10 +/- 8 mg/dL, and the cholesterol/HDL cholesterol ratio decreased 0.9 +/- 0.6 units. A very low carbohydrate diet program led to sustained weight loss during a 6-month period.

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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

Jeff S. Volek; Matthew J. Sharman; Ana L. Gómez; Timothy P. Scheett; William J. Kraemer

Ramdomized crossover with 10 participants:  In normal weight, normolipidemic women, a short-term very low carbohydrate diet modestly increased LDL-C, yet there were favorable effects on cardiovascular disease risk status by virtue of a relatively larger increase in HDL-C and a decrease in fasting and postprandial triaclyglycerols.

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Effects of a Lowcarbohydrate Diet on Weight Loss and Cardiovascular Risk Factor in Overweight Adolescents

Stephen B. Sondike, MD; Nancy Copperman, MS, RD; Marc S. Jacobson, MD

RCT with 30 participants:  To compare the effects of a low-carbohydrate (LC) diet with those of a low-fat (LF) diet on weight loss and serum lipids in overweight adolescents. The LC group lost more weight (mean, 9.9 +/- 9.3 kg vs 4.1 +/- 4.9 kg) and had improvement in non-HDL cholesterol levels. There were no adverse effects on the lipid profiles of participants in either group. The LC diet appears to be an effective method for short-term weight loss in overweight adolescents and does not harm the lipid profile.

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A Low-carbohydrate as Compared With a Lowfat Diet in Severe Obesity

Frederick F. Samaha, MD; Nayyar Iqbal, MD; Prakash Seshadri, MD; Kathryn L. Chicano, CRNP; Denise A. Daily, RD; Joyce McGrory, CRNP; Terrence Williams, BS; Monica Williams, BS; Edward J. Gracely, PhD; and Linda Stern, MD

RCT with 132 participants:  Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fatrestricted diet, with a relative improvement in insulin sensitivity and triglyceride levels, even after adjustment for the amount of weight lost.

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Effect of a High Saturated Fat and No-starch Diet on Serum Lipid Subfractions in Patients With Documented Atherosclerotic Cardiovascular Disease

James H. Hays, MD; Angela DiSabatino, RN, MS; Robert T. Gorman, PhD; Simi Vincent, PhD, MD; Michael E. Stillabower, MD

Prospective single arm:  To determine whether a diet of high saturated fat and avoidance of starch (HSF-SA) results in weight loss without adverse effects on serum lipids in obese nondiabetic patients.  HSF-SA diet results in weight loss after 6 weeks without adverse effects on serum lipid levels verified by nuclear magnetic resonance, and further weight loss with a lipidneutral effect may persist for up to 52 weeks.

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A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia: A Randomized, Controlled Trial

William S. Yancy Jr., MD, MHS; Maren K. Olsen, PhD; John R. Guyton, MD; Ronna P. Bakst, RD; Eric C. Westman, MD, MHS

RCT with 120 participants:  Compared with a low-fat diet, a low-carbohydrate diet program had better participant retention and greater weight loss. During active weight loss, serum triglyceride levels decreased more and high-density lipoprotein cholesterol level increased more with the low-carbohydrate diet than with the low-fat diet.

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Comparison of a Very Low-Carbohydrate and Low-Fat Diet on Fasting Lipids, LDL Subclasses, Insulin Resistance, and Postprandial Lipemic Responses in Overweight Women

Jeff S. Volek , PhD, RD, FACN; Matthew J. Sharman , MA; Ana L. Gómez , MS; Chris DiPasquale , MS; Melissa Roti , PhD; Amy Pumerantz , BS; William J. Kraemer , PhD

Ramdomized crossover with 13 participants:  Compared to a low-fat weight loss diet, a short-term very low-carbohydrate diet did not lower LDL-C but did prevent the decline in HDL-C and resulted in improved insulin sensitivity in overweight and obese, but otherwise healthy women. Small decreases in body mass improved postprandial lipemia, and therefore cardiovascular risk, independent of diet composition.

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Very Low-carbohydrate and Low-fat Diets Affect Fasting Lipids and Postprandial Lipemia Differently in Overweight Men

Matthew J. Sharman; Ana L. Gómez; William J. Kraemer; Jeff S. Volek

Ramdomized crossover:  The primary purpose of this study was to compare the effects of a very low-carbohydrate and a low-fat diet on fasting blood lipids and postprandial lipemia in overweight men. In a balanced, randomized, crossover design, overweight men consumed 2 experimental diets for 2 consecutive 6-wk periods. One was a very low-carbohydrate (<10% energy as carbohydrate) diet and the other a low-fat (<30% energy as fat) diet. Both diets had the same effect on serum total cholesterol, serum insulin, and homeostasis model analysisinsulin resistance (HOMA-IR). Neither diet affected serum HDL cholesterol (HDL-C) or oxidized LDL (oxLDL) concentrations. The very low-carbohydrate diet was more effective at improving characteristics of the metabolic syndrome as shown by a decrease in fasting serum TAG, the TAG/HDL-C ratio, postprandial lipemia, serum glucose, an increase in LDL particle size, and also greater weight loss.

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A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity

Prakash Seshadri, MD; Nayyar Iqbal, MD; Linda Stern, MD; Monica Williams; Kathryn L. Chicano, CRNP; Denise A. Daily, RD; Joyce McGrory, CRNP; Edward J. Gracely, PhD; Daniel J. Rader, MD; Frederick F. Samaha, MD

RCT with 78 participants:  In this 6-month study involving severely obese subjects, we found an overall favorable effect of a low-carbohydrate diet on lipoprotein subfractions, and on inflammation in high-risk subjects. Both diets had similar effects on LDL and HDL subfractions.

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Long Term Effects of a Ketogenic Diet in Obese Patients

Hussein M Dashti, MD PhD FICS FACS; Thazhumpal C Mathew, MSc PhD FRCPath; Talib Hussein, MB ChB; Sami K Asfar, MB ChB MD FRCSEd FACS; Abdulla Behbahani, MB ChB FRCS FACSI PhD FICS FACS; Mousa A Khoursheed, MB ChB FRCS FICS; Hilal M Al-Sayer, MD PhD FICS FACS; Yousef Y Bo-Abbas, MD FRCPC; Naji S Al-Zaid, BSc PhD

Single arm prospective with 83 participants:  The present study shows the beneficial effects of a long-term ketogenic diet. It significantly reduced the body weight and body mass index of the patients.  Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol.  Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.

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The National Cholesterol Education Program Diet vs a Diet Lower in Carbohydrates and Higher in Protein and Monounsaturated Fat

Y. Wady Aude, MD; Arthur S. Agatston, MD; Francisco Lopez-Jimenez, MD, MSc; Eric H. Lieberman, MD; Marie Almon, MS, RD; Melinda Hansen, ARNP; Gerardo Rojas, MD; Gervasio A. Lamas, MD; Charles H. Hennekens, MD, DrPH

RCT with 60 participants:  Compared with the NCEP diet, the MLC diet, which is lower in total carbohydrates but higher in complex carbohydrates, protein, and monounsaturated fat, caused significantly greater weight loss over 12 weeks. Weight loss was significantly greater in the Modified Low Carbohydrate (13.6 lb) than in the National Cholesterol Education Program group (7.5 lb), a difference of 6.1 lb. There were significantly favorable changes in all lipid levels within the MLC but not within the NCEP group. Waist-to-hip ratio was significantly decreased within the MLC group.

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Comparison of the Atkins, Ornish, Weight Watchers, and Zone Diets for Weight Loss and Heart Disease Risk Reduction

Michael L. Dansinger, MD; Joi Augustin Gleason, MS, RD; John L. Griffith, PhD; Harry P. Selker, MD, MSPH; Ernst J. Schaefer, MD

RCT with 160 participants:  Each popular diet modestly reduced body weight and several cardiac risk factors at 1 year. Overall dietary adherence rates were low, although increased adherence was associated with greater weight loss and cardiac risk factor reductions for each diet group.

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Effect of a Low- Carbohydrate Diet on Appetite, Blood Glucose Levels, and Insulin Resistance in Obese Patients with Type 2 Diabetes

Guenther Boden, MD; Karin Sargrad, MS, RD, CDE; Carol Homko, PhD, RN, CDE; Maria Mozzoli, BS; T. Peter Stein, PhD

Single arm – meabolic ward with 10 participants:  In a small group of obese patients with type 2 diabetes, a low-carbohydrate diet followed for 2 weeks resulted in spontaneous reduction in energy intake to a level appropriate to their height; weight loss that was completely accounted for by reduced caloric intake; much improved 24-hour blood glucose profiles, insulin sensitivity, and hemoglobin A1c; and decreased plasma triglyceride and cholesterol levels.

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Short-Term Effects of Severe Dietary Carbohydrate-Restriction Advice in Type 2 Diabetes – a Randomized Controlled Trial

M. E. Daly; R. Paisey; B. A. Millward; C. Eccles; K. Williams; S. Hammersley; K. M. MacLeod; T. J. Gale

RCT with 102 participants:  Weight loss and high-density lipoprotein (HDL) ratio improved was greater in the low-carbohydrate (LC) group over low fat group. Carbohydrate restriction was an effective method of achieving short-term weight loss compared with standard advice.

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Carbohydrate Restriction has a More Favorable Impact on the Metabolic Syndrome than a Low Fat Diet

Jeff S. Volek; Stephen D. Phinney; Cassandra E. Forsythe; Erin E. Quann; Richard J. Wood; Michael J. Puglisi; William J. Kraemer; Doug M. Bibus; Maria Luz Fernandez; Richard D. Feinman

RCT with 40 participants:  Both interventions led to improvements in several metabolic markers, but subjects following the CRD had consistently reduced glucose (-12%) and insulin (-50%) concentrations, insulin sensitivity (-55%), weight loss (-10%), decreased adiposity (-14%), and more favorable triacylglycerol (TAG) (-51%), HDL-C (13%) and total cholesterol/HDL-C ratio (-14%) responses. In addition to these markers for MetS, the CRD subjects showed more favorable responses to alternative indicators of cardiovascular risk: postprandial lipemia (-47%), the Apo B/Apo A-1 ratio (-16%), and LDL particle distribution. The results support the use of dietary carbohydrate restriction as an effective approach to improve features of MetS and cardiovascular risk.

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Weight Loss with a Low- Carbohydrate, Mediterranean, or Low- Fat Diet

Iris Shai, RD, PhD; Dan Schwarzfuchs, MD; Yaakov Henkin, MD; Danit R. Shahar, RD, PhD; Shula Witkow, RD, MPH; Ilana Greenberg, RD, MPH; Rachel Golan, RD, MPH; Drora Fraser, PhD; Arkady Bolotin, PhD; Hilel Vardi, MSc; Osnat Tangi-Rozental, BA; Rachel Zuk-Ramot, RN; Benjamin Sarusi, MSc; Dov Brickner, MD; Ziva Schwartz, MD; Einat Sheiner, MD; Rachel Marko, MSc; Esther Katorza, MSc; Joachim Thiery, MD; Georg Martin Fiedler, MD; Matthias Blüher, MD; Michael Stumvoll, MD; Meir J. Stampfer, MD; Dr.PH

RCT – 3 arm with 322 participants:  Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions.

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Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 months

Grant D Brinkworth; Manny Noakes; Jonathan D Buckley; Jennifer B Keogh; Peter M Clifton

RCT with 69 participants:  Low Carb group (over a isocaloric low fat diet) had greater decreases in triglycerides, increases in HDL cholesterol, and LDL cholesterol, and a greater but nonsignificant increase in apolipoprotein B. Both dietary patterns resulted in similar weight loss and changes in body composition. The LC diet may offer clinical benefits to obese persons with insulin resistance.

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Limited Effect of Dietary Saturated Fat on Plasma Saturated Fat in the Context of a Low Carbohydrate Diet

Cassandra E. ForsytheStephen; D. Phinney; Richard D. Feinman; Brittanie M. Volk; Daniel Freidenreich; Erin QuannKevin Ballard; Michael J. Puglisi; Carl M. Maresh; William J. Kraemer; Douglas M. Bibus; Maria Luz Fernandez; Jeff S. Volek

Randomized crossover with 8 participants:  Authors showed that a hypocaloric carbohydrate restricted diet (CRD) had two striking effects: (1) a reduction in plasma saturated fatty acids (SFA) despite higher intake than a low fat diet, and (2) a decrease in inflammation despite a significant increase in arachidonic acid (ARA). These findings are consistent with the concept that dietary saturated fat is efficiently metabolize in the presence of low carbohydrate, and that a CRD results in better preservation of plasma ARA.

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Dietary carbohydrate restriction improves insulin sensitivity, blood pressure, microvascular function, and cellular adhesion markers in individuals taking statins

Kevin D. Ballarda, Erin E. Quanna, Brian R. Kupchaka, Brittanie M. Volka, Diana M. Kawieckia, Maria Luz Fernandez, Richard L. Seip, Carl M. Maresha, William J. Kraemera, Jeff S.Volek

Single arm perspective with 21 participants.  The results of this study suggest that a CRD could be a sustainable lifestyle that complements statin treatment to improve overall cardio-metabolic risk, particularly for individuals with other risk factors indicative of metabolic syndrome, but future research is needed to determine the effects over a longer period of time.

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