![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
* Department of Nutritional Sciences and Department of Kinesiology, University of Connecticut, Storrs, CT 06269; ** Department of Medicine, Columbia University, New York, NY 10032; and Liposcience, Incorporated, Raleigh, NC 27616
2 To whom correspondence should be addressed. Email: maria-luz.fernandez{at}uconn.edu.
 |
ABSTRACT |
|---|
 TOP ABSTRACT SUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
10% carbohydrate, 65% fat, and 25% protein. Because the groups did not differ in any of the variables measured, all data were pooled and comparisons were made between baseline and 12 wk. After 12 wk, subjects had a mean weight loss of 7.5 kg (P < 0.001), and abdominal fat was reduced by 20% (P < 0.001). Plasma LDL cholesterol and triglycerides (TG) were significantly reduced by 8.9 and 38.6%, respectively. Similarly, apolipoproteins C-I (–13.8%), C-III (–21.2%) and E (–12.5%) were significantly lower after the intervention. In contrast plasma HDL-cholesterol concentrations were increased by 12% (P < 0.05). Changes in plasma TG were positively correlated with reductions in large (r = 0.615, P < 0.01) and medium VLDL particles (r = 0.432, P < 0.05) and negatively correlated with LDL diameter (r = –0.489, P < 0.01). Changes in trunk fat were positively correlated with medium VLDL (r = 0.474, P < 0.0) and small LDL (r = 0.405, P < 0.05) and negatively correlated with large HDL (r = –0.556, P < 0.01). We conclude that weight loss induced by CR favorably alters the secretion and processing of plasma lipoproteins, rendering VLDL, LDL, and HDL particles associated with decreased risk for atherosclerosis and coronary heart disease.
KEY WORDS: • carbohydrate restriction • weight loss • lipoprotein metabolism • LDL size • HDL subclasses
As research about carbohydrate-restricted diets (CRD)3 continues to emerge, evidence is mounting to support carbohydrate restriction (CR) as an effective means for weight loss and cardiovascular disease (CVD) risk improvement. CRD have been shown to outperform low-fat diets in body weight and body fat reduction, fasting and postprandial triglyceride (TG) reduction, and in HDL cholesterol (HDL-C) response (1). These findings are particularly important when considering dietary treatment for the estimated 47 million Americans (2) with metabolic syndrome, a condition characterized by android obesity, elevated fasting and postprandial TG, and low plasma HDL-C (3).
The complications from this atherogenic dyslipidemia stem from alterations in lipoprotein metabolism and lipoprotein particle morphology. Abnormalities in VLDL particle size are considered a major contributing factor to dysfunctional lipoprotein metabolism (4). Elevated hepatic TG levels lead to the secretion of large VLDL particles, which are most susceptible to modification by hepatic lipase (HL). Through the delipidation cascade, TG-rich VLDL are precursors for the formation of small, dense LDL particles (5). The phenotype characterized by a predominance of small LDL particles is termed "pattern B" and is characteristic of the metabolic syndrome (6,7). Small, dense LDL particles are considered more atherogenic because of a decreased binding to the LDL receptor, leading to increased plasma residence time (8) and an increased susceptibility to oxidation (9).
Elevated plasma TG also affects HDL-C levels and HDL particle size. Through the actions of cholesterol ester transfer protein (CETP), intravascular exchange of neutral lipids and apolipoproteins occurs between TG-rich lipoproteins (TRL) and HDL. CETP activity is regulated by TG content (10). Thus, elevated TG leads to the generation of TG-rich HDL particles, which are more susceptible to modification by HL (7). This modification leads to the formation of smaller HDL particles, which have a reduced plasma residence time, creating an environment of diminished reverse cholesterol transport (11).
Although several clinical trials showed that CRD consistently improve TG and HDL-C levels (1), little work has examined the intravascular processing of lipoproteins associated with these changes. A better understanding of these mechanisms would provide important insight into the biological adaptations to CR, and may address concerns about the long-term safety and efficacy of a CRD. We hypothesized that reductions in trunk fat and plasma TG resulting from CR would be associated with a less atherogenic lipoprotein profile.
|
SUBJECTS AND METHODS |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Subjects. A total of 30 men with a BMI between 25 and 35 kg/m2, aged 20–69 y, volunteered to participate in the study. One subject from the fiber group left the study due to military obligations. Subjects completed a detailed medical history questionnaire during subject recruitment. Exclusion criteria included consumption of a CRD or weight loss >2.5 kg in the past 6 mo, presence of cardiovascular or thyroid disease or diabetes mellitus, consumption of lipid-lowering prescriptions or supplements, or blood pressure >160/90 mm Hg. All procedures were approved by the Institutional Review Board at the University of Connecticut, and all subjects provided written informed consent to participate.
Study Design. The study was designed to investigate the effects of adding a soluble fiber supplement to a CRD on clinical markers of cardiovascular risk. The 12-wk study followed a placebo-controlled, double-blind, parallel-arm design. Subjects were carefully matched according to BMI and age, then randomly assigned to supplement a CRD with 3 g/d of either Konjac-mannan (n = 14) or a placebo (n = 15) containing maltodextrin and no Konjac-mannan. Plasma lipoprotein levels or body composition variables did not differ between the groups (data not shown); thus, subjects were pooled to determine the effects of the CRD on the intravascular processing of lipoproteins.
Diet. This was a free-living study and no food was provided to subjects. Registered dietitians held group meetings and instructed subjects how to follow a CRD and how to accurately complete a weighed food record; they also provided instructions regarding supplement consumption. Each subject received written materials to reinforce the principles covered during the meeting. A 5-d weighed food record was completed before the intervention and 7-d weighed food records were completed at wk 1, 6, and 12.
The diet was designed to provide >60% of energy from fat, 25–30% from protein, and 10% from carbohydrate. No guidelines were given regarding energy consumption. Subjects were instructed to consume the diet ad libitum. However, specific guidelines were given regarding the types of food to be consumed. Food choices included unlimited amounts of beef, poultry, fish, and eggs, moderate amounts of cheese, low-carbohydrate vegetables, low-carbohydrate salad dressing, and small amounts of nuts and seeds. No restrictions were given regarding the type of fat from saturated or unsaturated sources or amount of dietary cholesterol.
Due to the recent increase in popularity of CRD, a large number of low-carbohydrate foods are commercially available, many replacing simple sugars with sugar alcohols or fiber. Subjects were limited to 2 sugar alcohol–containing snacks/d, and were instructed to avoid low-carbohydrate breads and cereals.
Data collection. At baseline and wk 6 and 12, subjects reported to the laboratory after an overnight fast. Whole blood was obtained from an antecubital vein into EDTA tubes, and plasma was obtained via centrifugation at 1500 x g at 4°C for 20 min. After plasma was isolated, a preservation cocktail was added to the samples (5 mL/L aprotinin, 1 mL/L PMSF and 1 mL/L sodium azide). Plasma was stored in individual aliquots at –80°C for later analysis. Body composition and abdominal fat were determined using dual-energy X-ray absorptiometery equipment from ProdigyTM (Lunar Corporation). Abdominal fat was determined by placing a box between the 1st and 4th lumbar vertebrae using commercial software (encore version 6.00.270). All measurements were completed by trained technicians.
Plasma lipids. Our laboratory has participated in the CDC/National Heart, Lung, and Blood Institute Lipid Standardization Program since 1989 for quality control and standardization for plasma total cholesterol (TC), HDL-C, and TG assays. The CV assessed by the standardization program during the study were 0.76–1.42% for total cholesterol, 1.71–2.72% for HDL-C, and 1.64–2.47% for TG. Plasma lipids were determined by averaging values obtained from blood drawn on 2 separate days of the same week. TC was measured by enzymatic methods (12). TG was measured by enzymatic methods after adjusting for free glycerol (13). HDL-C was determined in the supernatant following precipitation of apo-B containing lipoproteins using magnesium chloride and dextran sulfate (14). LDL cholesterol (LDL-C) was calculated according to Friedewald et al. (15).
Plasma apolipoproteins. Apo B was measured using an immunoturbidimetric method with turbidity determined at 340 nm (16). Apo C-I was determined using an ELISA (17). Apo C-III (18) and apo E (19) were measured on a Hitachi Autoanalyzer 740 with Wako kits used according to the manufacturer's instructions.
Plasma lecithin cholesteryl acyltransferase (LCAT) and CETP activity determinations. LCAT and CETP activities were determined using previously described methods (20) in which the mass transfer of cholesterol ester between HDL and apo B–containing lipoproteins is calculated. Some of the plasma aliquots for LCAT and CETP were incubated in a shaking water bath for 6 h at 37°C. After incubation, total and free cholesterol were measured using enzymatic methods. The change in cholesterol ester mass from 0 to 6 h determined CETP activity without LCAT inhibition. LCAT activity was determined by analysis of the decrease in free cholesterol between 0 and 6 h (21).
LDL particle size pattern. The Lipoprint LDL system (22) was used to determine LDL particle size pattern via nongradient, high-resolution PAGE. According to this method, pattern A is a peak particle size >25.5 nm, whereas pattern B is a peak particle size <25.5 nm (6).
HDL, LDL, and VLDL particle size and number. H NMR analysis was performed on a 400-MHz NMR analyzer (Bruker BioSpin) as previously described (23,24). Briefly, lipoprotein subclasses of different sizes produce a distinct lipid methyl signal whose amplitude is directly proportional to lipoprotein particle concentration. NMR simultaneously quantifies >30 lipoprotein subclasses that are empirically grouped into 9 smaller subclasses based on particle diameters: large VLDL (36–60 nm), medium VLDL (27–35 nm), small VLDL (23–27nm), large LDL (21.2–23 nm), medium LDL (19.8–21.2), small LDL (18–19.8 nm), large HDL (8.8–13 nm), medium HDL (8.2–8.8 nm), and small HDL (7.3–8.2 nm). Weighted average lipoprotein particle sizes in diameters were calculated based on the diameter of each lipoprotein subclass multiplied by its respective relative concentration.
Statistical analysis. To determine differences between groups before data pooling, a repeated-measures ANOVA was used with supplement assignment as the between-group factor and time as the within-subject factor. A repeated-measures ANOVA was used to determine pooled data for changes in macronutrient composition over time. A paired t test was used to determine differences in dependent variables from baseline to wk 12. Pearson correlation coefficients were used to determine the relation between changes in dependent variables. Differences with a P < 0.05 were considered significant. Data are presented as means ± SD. Statistical analyses were completed using SPSS version 12.0 for Windows.
|
RESULTS |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Anthropometrics, plasma lipids and apolipoproteins, and LCAT and CETP activity. Body weight was reduced by 8.0% from baseline to 12 wk (P < 0.001) (Table 1). Abdominal fat was also reduced over time by 19.6% (P < 0.001). Total cholesterol (–8.1%), LDL-C (–9.2%), and TG (–38.7%) were all significantly reduced over time, and HDL-C (+12.0%) was significantly increased (Table 1). Subjects who had LDL pattern B decreased from 55% at baseline to 45% after the intervention. Plasma apo B concentrations decreased 5.5% (P < 0.05) after 12 wk.
|
LCAT activity was increased from 18.3 ± 6.8 to 28.3 ± 16.6 nmol/(mg·h) after 12 wk (P < 0.01), whereas CETP activity at wk 12 did not differ from baseline (Fig. 1).
|
|
|
|
|
|
|
DISCUSSION |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Carbohydrate restriction and metabolism of apo B-containing lipoproteins
One of the most consistent results of CR is a significant reduction in fasting and postprandial TG (25). Many of the changes in lipoprotein metabolism in the current intervention appear to have resulted from the 38.7% reduction in TG. Apos C-I and C-III are components of TRL, which impede their uptake (26). Significant reductions occurred in both apo C-I and apo C-III, which likely allowed for increased TG uptake and subsequent reduction in plasma TG levels. This is consistent with several of our earlier studies showing decreased postprandial lipemia after a CRD (27–30). Further, because of the reductions in TG, it was not surprising to find a significant reduction in apo E. Apo E was shown to displace apo C-II, the activator of lipoprotein lipase (LPL), and there is a positive relation between humans with hypertriglyceridemia and plasma levels of apo E. In addition, transgenic mice expressing high plasma levels of apo E3 display hypertriglyceridemia (17). LPL may also have increased in skeletal muscle during CR as a means of fuel provision (31).
The reductions in plasma TG likely led to numerous downstream effects as reflected by the strong positive relations between change in TG and change in large and medium VLDL particles and small LDL particles, and the negative relation between change in TG and changes in the number of large LDL particles.
The reductions in plasma TG were accompanied by altered VLDL metabolism. VLDL are created through the combination of apo B and TG via the actions of microsomal transfer protein (32). Because mean VLDL particle size was unchanged, reductions in TG were due primarily to the 19% reduction in the quantity of VLDL particles and the reduction of TG in the particles. The most substantial changes in VLDL particle size were a 47.7% reduction in large particles and a 40% reduction in medium VLDL particles. The reduction in large VLDL particles is clinically relevant because these particles are closely related to atherosclerosis (33). It is believed that there are 3 main sources for the TG incorporated into VLDL, i.e., fatty acids (FA) from peripheral tissue (particularly adipose tissue), chylomicron and VLDL remnants, and de novo hepatic lipogenesis (34). It is thought that hepatic oxidation of FA is favored during CR, as evidenced by significant ketone production (1), which leads to reduced FA esterification and TG availability for incorporation into VLDL. Reduced TG availability can affect apo B viability through either proteosomal degradation or post-translational degradation (34). In agreement with the decreases in VLDL and LDL particles, we also observed reductions in apo B.
The reduction in large VLDL particles affected LDL particle size. Large VLDL particles are the precursors for the development of small-dense LDL particles (33) primarily due to the actions of HL (7). The quantities of very small and small LDL particles were reduced by 24.7 and 30.0%, respectively. Further, the 35.4% increase in large LDL particles and significant increase in mean LDL particle diameter led to the reduction in subjects classified as "pattern B." These results are similar to our previous findings that CR increases mean LDL particle size and shifts particle pattern (28). The change in LDL particle diameter and small and large LDL particle quantity were significantly related to the change in TG. Thus, we contend that changes in plasma TG concentrations, resulting from decreased VLDL secretion, reduced remodeling of VLDL particles via HL, leading to the formation of a less atherogenic LDL particle.
Carbohydrate restriction and HDL metabolism
Reverse cholesterol transport was affected by the intervention. Mean HDL particle size was significantly increased by wk 12. The total number of HDL particles remained unchanged, although the distribution of differently sized HDL particles was altered. Large and medium HDL particle quantity was significantly increased, whereas small HDL particles were unchanged. Because of reduced TG concentrations, it is likely that decreased neutral lipid exchange occurred, resulting in the formation of fewer TG-rich HDL particles. Although CETP activity was not significantly reduced, the number of TG-rich particles was reduced, decreasing the potential for intravascular lipid exchange. Thus, HDL particles would be relatively TG poor, reducing susceptibility to remodeling by HL and yielding fewer small HDL particles. In combination with the observed increase in LCAT activity, mean HDL particle size was increased, causing the reduced uptake of HDL particles and subsequent increased plasma HDL-C concentrations.
Consumption of the CRD significant reduced body weight and abdominal fat. Intra-abdominal fat is associated with all 5 of the National Cholesterol Education Programs Adult Treatment Panel III diagnostic criteria for the metabolic syndrome, and has been hypothesized to have a pathophysiologic role (35). The contribution of abdominal fat to total body fat was reduced postintervention (11.9% at baseline vs. 11.3% at wk 12, P < 0.05), supporting our previous reports that CR preferentially targets abdominal fat (36). Our results support an association between the reduction in abdominal fat and improvement in cardiovascular risk through altered lipoprotein metabolism. The change in abdominal fat was significantly related to the change in the quantity of medium VLDL, small LDL, and large HDL particles as well as mean LDL particle diameter. However, it is unlikely that weight loss alone caused the significant changes in lipoprotein metabolism. Changes in TG and HDL-C were not related to weight loss, consistent with our previous findings (1,29).
This study provided novel information about the alterations in lipoprotein metabolism resulting from CR. A 12-wk CRD significantly reduced TG and apolipoproteins involved in TG metabolism, leading to a decreased number of VLDL particles. This reduction in TRL was reflected by an increase in mean LDL particle size and a decrease in small and very small LDL particle quantity. Further, the changes in plasma TG led to an increased mean HDL particle diameter, which was also contributed to by increased LCAT activity. These results provide important information about the beneficial effects of a CRD on cardiovascular risk. The results are limited to overweight and slightly obese men who are otherwise healthy and not taking lipid-lowering medication. The duration of the intervention was relatively short but tightly controlled, thus clearly representing the true biological adaptations to a CRD. Future research is warranted to confirm our hypotheses regarding LPL and HL activity. We conclude that the alterations in lipoprotein metabolism resulting from CR are achieved through changes in VLDL, LDL, and HDL particle morphology and apolipoprotein concentrations.
|
FOOTNOTES |
|---|
3 Abbreviations used: apo, apolipoprotein; CETP, cholesterol ester transfer protein; CR, carbohydrate restriction; CRD, carbohydrate restricted diet; CVD, cardiovascular disease; FA, fatty acids; HDL-C, HDL cholesterol; HL, hepatic lipase; LCAT, lecithin cholesteryl acyltransferase; LDL-C, LDL cholesterol; LPL, lipoprotein lipase; PMSF, phenylmethylsulfonyl fluoride; TC, total cholesterol; TG, triglyceride; TRL, triglyceride-rich lipoprotein.
Manuscript received 30 September 2005. Initial review completed 26 October 2005. Revision accepted 1 November 2005.
|
LITERATURE CITED |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
1. Volek JS, Sharman MJ, Forsythe CE. Modification of lipoproteins by very low-carbohydrate diets. J Nutr. 2005;135:1339–42.
2. Saylor J. Risk factor clusters for metabolic syndrome in coronary heart disease: state of the science. Dimens Crit Care Nurs. 2005;24:64–9.[Medline]
3. Shaw DI, Hall WL, Williams CM. Metabolic syndrome: what is it and what are the implications? Proc Nutr Soc. 2005;64:349–57.[Medline]
4. Millar JS, Packard CJ. Heterogeneity of apolipoprotein B-100-containing lipoproteins: what we have learnt from kinetic studies. Curr Opin Lipidol. 1998;9:197–202.[Medline]
5. Zambon A, Bertocco S, Vitturi N, Polentarutti V, Vianello D, Crepaldi G. Relevance of hepatic lipase to the metabolism of triacylglycerol-rich lipoproteins. Biochem Soc Trans. 2003;31:1070–4.[Medline]
6. Austin MA, King MC, Vranizan KM, Krauss RM. Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk. Circulation. 1990;82:495–506.
7. Packard CJ. Triacylglycerol-rich lipoproteins and the generation of small, dense low-density lipoprotein. Biochem Soc Trans. 2003;31:1066–9.[Medline]
8. Nigon F, Lesnik P, Rouis M, Chapman MJ. Discrete subspecies of human low density lipoproteins are heterogeneous in their interaction with the cellular LDL receptor. J Lipid Res. 1991;32:1741–53.[Abstract]
9. Tribble DL, Holl LG, Wood PD, Krauss RM. Variations in oxidative susceptibility among six low density lipoprotein subfractions of differing density and particle size. Atherosclerosis. 1992;93:189–99.[Medline]
10. Fielding CJ, Fielding PE. Molecular physiology of reverse cholesterol transport. J Lipid Res. 1995;36:211–28.[Abstract]
11. Xu Y, Fu M. Alterations of HDL subclasses in hyperlipidemia. Clin Chim Acta. 2003;332:95–102.[Medline]
12. Allain CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic determination of total serum cholesterol. Clin Chem. 1974;20:470–5.[Abstract]
13. Carr TP, Andressen CJ, Rudel LL. Enzymatic determination of triglyceride, free cholesterol, and total cholesterol in tissue lipid extracts. Clin Biochem. 1993;26:39–42.[Medline]
14. Warnick GR, Benderson J, Albers JJ. Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol. Clin Chem. 1982;28:1379–88.
15. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.[Abstract]
16. Rifai N, King ME. Immunoturbidimetric assays of apolipoproteins A, AI, AII, and B in serum. Clin Chem. 1986;32:957–61.
17. Conde-Knape K, Bensadoun A, Sobel JH, Cohn JS, Shachter NS. Overexpression of apoC-I in apoE-null mice: severe hypertriglyceridemia due to inhibition of hepatic lipase. J Lipid Res. 2002;43:2136–45.
18. Fredenrich A, Giroux LM, Tremblay M, Krimbou L, Davignon J, Cohn JS. Plasma lipoprotein distribution of apoC-III in normolipidemic and hypertriglyceridemic subjects: comparison of the apoC-III to apoE ratio in different lipoprotein fractions. J Lipid Res. 1997;38:1421–32.[Abstract]
19. Cohn JS, Tremblay M, Amiot M, Bouthillier D, Roy M, Genest J Jr, Davignon J. Plasma concentration of apolipoprotein E in intermediate-sized remnant-like lipoproteins in normolipidemic and hyperlipidemic subjects. Arterioscler Thromb Vasc Biol. 1996;16:149–59.
20. Ogawa Y, Fielding CJ. Assay of cholesteryl ester transfer activity and purification of a cholesteryl ester transfer protein. Methods Enzymol. 1985;111:274–85.[Medline]
21. Herron KL, Vega-Lopez S, Conde K, Ramjiganesh T, Roy S, Shachter NS, Fernandez ML. Pre-menopausal women, classified as hypo- or hyperresponders, do not alter their LDL/HDL ratio following a high dietary cholesterol challenge. J Am Coll Nutr. 2002;21:250–8.
22. Rajman I, Kendall MJ, Cramb R, Holder RL, Salih M, Gammage MD. Investigation of low density lipoprotein subfractions as a coronary risk factor in normotriglyceridaemic men. Atherosclerosis. 1996;125:231–42.[Medline]
23. Otvos JD. Measurement of lipoprotein subclass profiles by nuclear magnetic resonance spectroscopy. Clin Lab. 2002;48:171–80.[Medline]
24. Freedman DS, Otvos JD, Jeyarajah EJ, Shalaurova I, Cupples LA, Parise H, D'Agostino RB, Wilson PW, Schaefer EJ. Sex and age differences in lipoprotein subclasses measured by nuclear magnetic resonance spectroscopy: the Framingham Study. Clin Chem. 2004;50:1189–200.
25. Volek JS, Westman EC. Very-low-carbohydrate weight-loss diets revisited. Cleve Clin J Med. 2002;69:849, 853, 856–848 passim.
26. Shachter NS. Apolipoproteins C–I and C–III as important modulators of lipoprotein metabolism. Curr Opin Lipidol. 2001;12:297–304.[Medline]
27. Volek JS, Gomez AL, Love DM, Avery NG, Sharman MJ, Kraemer WJ. Effects of a high-fat diet on postabsorptive and postprandial testosterone responses to a fat-rich meal. Metabolism. 2001;50:1351–5.[Medline]
28. Sharman MJ, Kraemer WJ, Love DM, Avery NG, Gomez AL, Scheett TP, Volek JS. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. J Nutr. 2002;132:1879–85.
29. Volek JS, Sharman MJ, Gomez 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. J Nutr. 2003;133:2756–61.
30. Volek JS, Sharman MJ, Gomez AL, DiPasquale C, Roti M, Pumerantz A, Kraemer WJ. Comparison of a very low-carbohydrate and low-fat diet on fasting lipids, LDL subclasses, insulin resistance, and postprandial lipemic responses in overweight women. J Am Coll Nutr. 2004;23:177–84.
31. Kiens B, Essen-Gustavsson B, Gad P, Lithell H. Lipoprotein lipase activity and intramuscular triglyceride stores after long-term high-fat and high-carbohydrate diets in physically trained men. Clin Physiol. 1987;7:1–9.[Medline]
32. Gibbons GF, Wiggins D, Brown AM, Hebbachi AM. Synthesis and function of hepatic very-low-density lipoprotein. Biochem Soc Trans. 2004;32:59–64.[Medline]
33. Krauss RM. Lipids and lipoproteins in patients with type 2 diabetes. Diabetes Care. 2004;27:1496–504.
34. Ginsberg HN, Zhang YL, Hernandez-Ono A. Regulation of plasma triglycerides in insulin resistance and diabetes. Arch Med Res. 2005;36:232–40.[Medline]
35. Carr DB, Utzschneider KM, Hull RL, Kodama K, Retzlaff BM, Brunzell JD, Shofer JB, Fish BE, Knopp RH. Kahn SE. Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome. Diabetes. 2004;53:2087–94.
36. Volek JS, Sharman MJ, Love DM, Avery NG, Gomez AL, Scheett TP, Kraemer WJ. Body composition and hormonal responses to a carbohydrate-restricted diet. Metabolism. 2002;51:864–70.[Medline]
This article has been cited by other articles:
|
|
 |
|
  T. Al-Sarraj, H. Saadi, M. C. Calle, J. S. Volek, and M. L. Fernandez Carbohydrate Restriction, as a First-Line Dietary Intervention, Effectively Reduces Biomarkers of Metabolic Syndrome in Emirati Adults J. Nutr., September 1, 2009; 139(9): 1667 - 1676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Mutungi, J. Ratliff, M. Puglisi, M. Torres-Gonzalez, U. Vaishnav, J. O. Leite, E. Quann, J. S. Volek, and M. L. Fernandez Dietary Cholesterol from Eggs Increases Plasma HDL Cholesterol in Overweight Men Consuming a Carbohydrate-Restricted Diet J. Nutr., February 1, 2008; 138(2): 272 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C Westman, R. D Feinman, J. C Mavropoulos, M. C Vernon, J. S Volek, J. A Wortman, W. S Yancy, and S. D Phinney Low-carbohydrate nutrition and metabolism Am. J. Clinical Nutrition, August 1, 2007; 86(2): 276 - 284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ardoin, C. Sandborg, and L. Schanberg Review: Management of dyslipidemia in children and adolescents with systemic lupus erythematosus Lupus, August 1, 2007; 16(8): 618 - 626. [Abstract] [PDF]
|
|
|
|
|
|
E. C Westman, J. S Volek, and R. D Feinman Carbohydrate restriction is effective in improving atherogenic dyslipidemia even in the absence of weight loss Am. J. Clinical Nutrition, December 1, 2006; 84(6): 1549 - 1549. [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
