http://www.medscape.com/viewarticle/531007_print (I couldnt format the tables so you may want to have a look at the link)
Clinical Nutrition & Obesity
Conference Coverage: Nutrition and Metabolic Aspects of Carbohydrate Restriction -- 2006 Nutrition and Metabolism Scientific Sessions
Heather Hutchins, MS, RD
Medscape General Medicine. 2006;8(2):80. ©2006 Medscape
Posted 06/21/2006
Introduction
Carbohydrate-restricted diets remain very controversial in both the medical community and the general public. Much of this confusion stems from inconsistencies in defining "carbohydrate-restricted diet." Many nutrition experts present at this conference believe that the current epidemic of metabolic disorders results from insulin overproduction and that this could be partially due to chronic excessive carbohydrate intake. Thus, a major goal of the conference was to provide a forum for discussion of the implications of carbohydrate restriction. In addition, evidence for implementation of carbohydrate-restricted diets and mechanisms to support carbohydrate restriction were summarized. A complete list of the presenters is outlined in Table 1 .
Diet Definitions
A very low-carbohydrate, moderate-protein, high-fat diet is commonly referred to as the Atkins diet with a carbohydrate
rotein:fat ratio of approximately 10:25:65. A moderate-carbohydrate restriction that adds protein to replace carbohydrate while maintaining a low-fat content of approximately 30% of total calories is commonly referred to as the Zone diet (40:30:30); this would be considered a moderate-carbohydrate, high-protein, low-fat diet. These 2 carbohydrate-restricted diets, and other similar carbohydrate-restricted diets, can be compared with a standard recommended diet with a percentage ratio of 55:15:30, which would be considered a high-carbohydrate, low-protein, low-fat diet.
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Dietary Studies
There is significant, new clinical data related to a variety of carbohydrate-restricted diets. This research will be organized into 2 categories for review: very low-carbohydrate diets (very low-carbohydrate, moderate-protein, and high-fat) and moderate-carbohydrate diets (moderate-carbohydrate, high-protein, low-fat). A number of carbohydrate-restricted diets were discussed at the conference and are outlined in Table 2 .
Very Low-Carbohydrate Diets
A recent study of very low-carbohydrate diets suggests that a low-carbohydrate, high-fat diet leads to spontaneous calorie restriction due to decreased appetite.[1] Although long-term studies (1 year) have failed to find superiority in low-carbohydrate, high-fat diets that gradually reintroduce carbohydrate into the diet compared with high-carbohydrate, low-fat diets in regard to weight loss,[2,3] improvements in triglycerides (TGs)[2,3] and high-density lipoprotein-cholesterol (HDL-C)[2] were observed at the 12-month point in patients who followed the low-carbohydrate, high-fat diet.
Similar very low-carbohydrate, high-fat diets were studied by Volek and colleagues[4] in hyperlipidemic, overweight, and obese participants. Volek and colleagues found that overweight men and women with elevated TG and low HDL-C levels (features of the metabolic syndrome) who followed a very low-carbohydrate, high-fat diet with approximately 10% carbohydrate, 30% protein, and 60% fat had greater weight and fat mass loss, improved fasting, and postprandial TG (-39%), HDL-C (+12%), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL) and HDL size, apoB (-8%), apoC-I (-14%), apoC-III (-21%), apoE (-13%), lecithin cholesterol acyltransferase, lipoprotein(a), and inflammatory markers (C-reactive protein [CRP] -19%, tumor necrosis factor [TNF] alpha -7%, Lp(a) -12%) compared with patients on a high-carbohydrate, low-fat diet with approximately 30% total fat and less than 10% saturated fat. The high-carbohydrate, low-fat diet showed no improvements in dyslipidemia.[4] Volek's group also found that the number of large LDL particles increased while there was a decrease in the small LDL particles (pattern B genotype) from 95% of participants to 20% of the participants with the pattern B genotype.[4]
Research conducted by Vernon and colleagues[5] involved diabetic patients who were placed on either a very low-carbohydrate, high-fat diet or a high-carbohydrate, low-fat diet with an anorectic agent. The high-carbohydrate, low-fat diet plus anorectic agent produced more weight loss (14.1 kg vs 9.5 kg, P < .01) in 3 months while the very low-carbohydrate, high-fat group had more favorable changes in TG (P = .02), HDL-C (P < .001), and correspondingly the TG/HDL-C ratio (P = .01).[5] Multiple case studies of type 2 diabetics on the very low-carbohydrate, high-fat diet who were followed up for an average of 8 months showed significant changes in HgA1c from 10.0% to 5.9%, with half of the participants within normal limits (< 5.5%). There were also significant improvements in total cholesterol (TC), TG, TG/HDL-C ratio, and TC/HDL-C ratio after following a very low-carbohydrate, high-fat diet. Furthermore, diabetic patients following a very low-carbohydrate, high-fat diet required close medication monitoring during the 8 months of follow-up, and 13/14 diabetic patients were able to discontinue all medications for glycemic control.[5] Yancy[6] described a 4-month, 1-arm study of diabetics who followed an 11% carbohydrate, 30% protein, and 59% fat diet that resulted in 6% weight loss, a 16% decrease in HgA1c from 7.4 to 6.3, and a decreased need for diabetic medications.
Fernandez and colleagues[7] used guinea pigs to study the effect of diet on lipoprotein metabolism and atherosclerosis development. Guinea pigs are a favored animal model because their lipoprotein characteristics are similar to those of humans. In a recent study composed of 3 diet groups (low-cholesterol, high-carbohydrate; high-cholesterol, high-carbohydrate; and high-cholesterol, low-carbohydrate); the dietary cholesterol intake increased atherogenicity of both VLDL and HDL, while a carbohydrate restriction (~10%) increased the number of large LDL and decreased the concentrations of the more atherogenic smaller LDL particles. The less atherogenic (larger) LDL was found to be associated with lower concentrations of cholesterol esters and inflammatory cytokines measured in the aorta of the guinea pigs.[7]
Moderate Carbohydrate Diets
Noakes and colleagues[8] observed the benefits of moderate-carbohydrate, high-protein, low-fat diets in healthy overweight, obese, hyperlipidemic, and also diabetic patients. Increased protein in the diet seems to have a satiating effect that is unrelated to ghrelin secretion, but the effects do seem to be a hormonal response of appetite.[8] In a study that used liquid meals,[9] those with higher protein content resulted in greater satiety and were associated with glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), and peptide YY (PYY) over 3 hours with a diminished energy intake at the following meal. In diet studies, the dropout rates for high-protein, low-fat groups are lower compared with those for high-carbohydrate, low-fat groups. Although weight loss is similar when comparing these diets, the loss of fat mass was twice as great in higher protein groups.[9] Noakes' group[10] also found improvements in fat and abdominal mass and LDL (5.7% in the high-protein group vs 2.7% in the low-protein group, P < .01) in type 2 diabetics patients following a moderate-carbohydrate, high-protein, low-fat diet compared with a high-carbohydrate, low-protein, low-fat diet. There were sex by diet interactions for the fat and abdominal mass changes in that women lost more fat (5.3 vs 2.8 kg) and abdominal mass (1.3 vs 0.7 kg) on the high-protein diet compared with the low-protein diet, respectively.
Type 2 diabetics can have metabolic improvements while following a 30% protein, 40% carbohydrate, and 30% fat diet; this diet regime resulted in improved 24-hour glucose area under the concentration curve (AUC), increased insulin AUC, and decreased total glycosylated hemoglobin (%tGHb) compared with high-carbohydrate, low-fat diet regimens.[11] Total glycosylated hemoglobin or %tGHb is the total of all glycosylated hemoglobins in the blood, whereas HgA1c is one specific glycosylated hemoglobin. While maintaining protein at 30% with a drop in carbohydrate to 20% and rise in fat to 50% of energy, the fasting glucose dropped to near-normal levels with reductions in %tGHb and 24-hour glucose AUC as well.[12] Nuttall and Gannon[13] suggest that this 20:30:50 (carbohydrate
rotein:fat) diet lacks negative side effects. Data from Nuttall and Gannon's work[14] also show that the 20:30:50 diets are comparable to a 40:30:30 diets (carbohydrate
rotein:fat) with similar declines in 24-hour glucose AUC and %tGHb. Therefore, the fat content need not be high to observe metabolic improvements in diabetics. In studies comparing diabetics to healthy subjects, the latter had a negative glucose AUC when ingesting a starch with fat; however, the type 2 diabetics had no difference in glucose AUC, indicating that data may not be easily translated between healthy subjects and type 2 diabetics.[14]
Leucine is an essential amino acid, and humans need at least 7 g per day for regulation of protein synthesis and insulin signaling pathways. Sources of leucine are whey protein (14% leucine), milk proteins (10% leucine), and wheat proteins (7% leucine). In an animal model, it appears that leucine increases protein synthesis via the modulation of biomarkers for mRNA translation.[15] Leucine may provide protein-sparing benefits during caloric restriction and weight loss via glucose recycling and glucose use by skeletal muscle.[16] The benefits of increased leucine in high-protein diets may explain their superiority in appetite control, weight loss, and compliance compared with high-carbohydrate, low-protein, low-fat diets.
The Basic Science of Carbohydrate Restriction
There are 2 key molecular pathways to explain the potential benefits of carbohydrate-restricted diets: the generation of necessary glucose for brain function via gluconeogenesis and the loss of stored body fat via lipolysis.
Gluconeogenesis
Gluconeogenesis is a means to produce energy in fasting states when glucose is not available. Because very low-carbohydrate diets mimic fasting states, gluconeogenesis is considered the means of producing sufficient glucose from the Krebs cycle.
Phosphoenolpyruvate carboxykinase (PEPCK) is the enzyme responsible for the conversion of pyruvate to phosphoenolpyruvate (PEP) during gluconeogenesis. Insulin-sensitizing drugs commonly used in the treatment of type 2 diabetes increase PEPCK, gluconeogenesis, and free fatty acid levels.[17] In rats fed a high-protein, low-carbohydrate diet, PEPCK and gluconeogenesis are unregulated and de novo fatty acid synthesis pathways are decreased.[18] Lowering the ratio of carbohydrate to fat can decrease the de novo fatty acid synthesis and enhance adipose tissue lipolysis.[19]
Pyruvate dehydrogenase complex (PDC) is an enzyme that is a catalyst for oxidative decarboxylation of pyruvate to form acetyl CoA during gluconeogenesis. One of the 4 isoforms, pyruvate dehydrogenase kinase-4 (PDK-4) is increased 30-fold in starved mice muscle and also elevated in the heart, kidney, and liver of starved mice. PDK-4 is essential for the glucose/fatty acid cycle when glucose oxidation inhibits fatty acid oxidation.[20] The isoforms of PDK are responsible for the regulation of the PDC, which is involved in the regulation of oxidative disposal of carbohydrate.[21] In a 3-day study of humans consuming a high-fat diet (75% fat, 5% carbohydrate, 20% protein) in which 15% of the fat content was from omega-3 fatty acids, the PDK activity decreased with a corresponding decrease of approximately 50% in PDC activity compared with a high-fat diet without added omega-3 fatty acids. This finding is consistent with results from animal studies[22] that omega-3 fatty acid supplementation in a high-fat diet doesn't completely reverse the suppression of PDC activity, even though PDK activity was able to return to control levels and suggests that it is important to determine the source of fat in high-fat diets.
Lipolysis
Lipolysis is the process of cleaving inert TG from the adipose tissue to produce active free fatty acids. Hormone-sensitive lipase (HSL) is thought to be the enzyme responsible for initiating the lipolysis of fat from the adipose tissue. Studies with HSL knockout mice have demonstrated that the knockouts are resistant to high-fat, diet-induced, and genetic obesity with a reduction in white and increase in brown adipose tissue. The knockout mice also exhibit increased adipose macrophages, alterations in markers for adipose differentiation and enzymes for fatty acid and TG synthesis with a reduction in lipogenesis and altered adipose metabolism as a result.[23] Type 2 diabetics show decreased levels of HSL possibly because of elevated plasma insulin levels, which inhibit this enzyme.[24] In the mouse model,[25] a high-protein (70%), carbohydrate-free diet, seems to cause a reduction in HSL activity and decreased rate of lipolysis. There may also be an interaction between fatty acid binding proteins (FABP) at the adipocyte and HSL.[26]
Free fatty acid (FFA) metabolism represents a very flexible metabolic pathway. Insulin indirectly regulates FFA levels because insulin inhibits HSL and the release of FFA from the adipocyte. Average basal FFA release is strongly related to resting energy expenditure (REE), but not free fat mass.[27] Interestingly, women release approximately 40% more FFA than men relative to their REE, but this increase is not associated with higher plasma FFA concentrations or fat oxidation by indirect calorimetry. The increased release of FFA in women may be due to increased nonoxidative FFA clearance.[27] There is no sex difference in glucose release related to REE or fat mass.[28] Parks and colleagues[29] also found that there is no difference in FFA from low-fat or high-fat, low-carbohydrate diets.
Excess plasma FFA can lead to the adverse health consequences of obesity. Glucose-stimulated insulin secretion (GSIS) is related to FFAs.[30] FFAs can alter GSIS in animals and humans. Fasting rats that consume lipid emulsions require an elevated plasma FFA concentration to trigger GSIS; this effect is influenced by both chain length and degree of saturation of the lipid,[30] highlighting the importance for the type of fat ingested and insulin secretion.
The response to typical levels of surplus carbohydrate intake does not seem to be a significant conversion of excess carbohydrate in the liver for eventual storage as fat; therefore, suggesting the surplus carbohydrate does not go through de novo lipogenesis.[31] With surplus carbohydrate, the pathway of last resort (the massive overfeeding pathway) can be used to oxidize the glucose to rid the body of the excess carbohydrate. However, in a study that overfed isocaloric amounts of fat or carbohydrate there were similar increases of fat storage for both diet groups with difference in the increase in body weight, fat-free mass, and fat mass (1.5, 0.6, and 0.9 kg, respectively). The excess carbohydrate seems to be converted to fat via both hepatic and extrahepatic de novo lipogenesis.[31]
Disease States
Insulin Resistance and Diabetes
Insulin resistance (IR) is a precursor to type 2 diabetes. Increased levels of FFA in the blood are associated with both IR and type 2 diabetes, while fat in the muscle is an even more accurate predictor of IR.[32] An alternative mechanism for IR in the skeletal muscle suggests that FFAs interfere with an earlier stage of GLUT4 transporter activity.[33]
In mice models a novel transcription factor, FOXa2, is a promising intervention for IR and type 2 diabetes because it controls hepatic lipid metabolism in fasting states and in type 2 diabetes. FOXa2 controls the expression of key genes in fatty acid oxidation; ketogenesis and glycolysis in fasting states.[34] In hyperinsulimic states FOXa2 is inactive, and lipid accumulation ensues as does IR in the liver.[34]
Uncoupling proteins (UCP2) influence type 2 diabetes, body mass index, and cardiovascular disease (CVD). UCP2 is expressed in pancreatic cells and alleles of UCP influence type 2 diabetes. In a mouse model where UCP2 is overexpressed, there is less fat accumulation and longer life span.[35] In mice fed a ketogenic diet compared with a standard diet, those fed the ketogenic diet had an increase in UCP2, with corresponding reductions in reactive oxygen species (ROS) and ATP production.[36]
Inflammation
Inflammation is strongly associated with obesity and type 2 diabetes as well as heart disease. In 1992, elevated white blood cell counts (WBC) were first associated with increased risk of CVD.[37] This association sparked a different way to look at the etiology of CVD, as a disease of an inflammatory nature. Biomarkers for inflammation include total WBC, CRP, interleukin-6 (IL-6), fibrinogen, and serum amyloid A. Elevated CRP is related to heart disease,[38] obesity,[39] and type 2 diabetes.[40] Dietary modifications may prove to be a suitable means of modifying inflammation without medicinal side effects. Diet studies have found gamma tocopherols[41]; omega-3 fatty acids[42]; moderate alcohol intake[43]; and antioxidants including flavonoids, curcumin, and anthrocyannis to decrease inflammatory biomarkers[44]; while omega-6 fatty acids, trans fat and iron have pro-inflammatory properties.[45] Weight loss via either high-carbohydrate, low-fat, or very low-carbohydrate, high-fat diets accentuates positive changes in both the inflammatory biomarkers of CRP, and serum amyloid A, proportional to the amount of weight loss and independent on macronutrient composition.[46] This was confirmed by the work of Sharman and Volek,[47] who found that a low-fat and very low-carbohydrate diets in overweight men resulted in significant decreases in TNF alpha, IL-6, and CRP with similar changes in weight loss. Thus weight loss, regardless of the macronutrient composition, seems to improve inflammatory biomarkers.
Conclusions
The presentations at the Nutritional and Metabolic Aspects of Carbohydrate Restriction Conference support the metabolic benefits of a lower carbohydrate content of the diet. Although not discussed at the conference, recent data indicates carbohydrate-restricted diets work significantly better in those individuals with existing IR and indicate that the metabolic state of the individual may determine which diet is appropriate for maximum weight loss.[48] Identifying genetic markers to target these individuals, and those who may best respond to carbohydrate restricted diets, is emerging from the work of Ruano and colleagues.[49]
Research suggests that favorable metabolic changes can occur with very low-carbohydrate and/or moderate-carbohydrate restricted diets. Diets involving moderate protein intake can improve glycemic control and blood lipid levels. This suggests that weight loss and metabolic enhancements might be due to the combination of an increased protein intake and restriction of carbohydrate. A diet consisting of 150 g or less of carbohydrate, with 120 g or greater of protein per day is recommended by Layman.[50] This moderate diet approach reduces hepatic glucose production and minimizes the excessive secretion of insulin giving rise to improved glycemic control.[50] The Women's Health Initiative[51] demonstrated that long-term, low-fat diet adherence is difficult for many people. Long-term compliance might improve with higher protein diets that promote satiety, and carbohydrate-restricted diets that improve insulin control. Further research is needed to assess long-term carbohydrate-restricted diet compliance rates as well as long-term alterations in metabolism and enzymatic reactions that occur with carbohydrate-restricted diets.
Table 1. Presenters at the Nutritional and Metabolic Aspects of Carbohydrate Restriction Conference
Presenter Title
Richard D. Feinman, PhD Metabolic consequences of carbohydrate restriction and defining low carbohydrate diets as a research protocol
Eric C. Westman, MD Weight reduction and clinical aspects of a low carbohydrate diet program
Manny Noakes, PhD Recent results in high protein weight loss diets
Daniel Tome, PhD Effect of macronutrient composition of diet in rats
Gary J. Schwartz, PhD Roles for central and peripheral nutrient sensing in the control of food intake and energy balance
Anthony Sclafani, PhD Nutrient reinforcement and satiety
R.H. Migliorini MD, PhD Lipid metabolism in the rats adapted to high-protein, carbohydrate- free diet
Robert H. Harris, PhD Importance of control of the mitochondrial alpha-ketoacid dehydrogenase complexes
Donald K. Layman, PhD Impact of dietary protein on glycemic control and weight loss
Richard W. Hanson, PhD PEPCK and control of gluconeogenesis
Douglas Eagles, PhD Control of ketosis
Asker E. Jeukendrup, PhD Carbohydrate intake and exercise
Sandra Peters, PhD Control of metabolism by diet and exercise
Richard D. Feinman, PhD and Eugine J. Fine, PhD The metabolic regime and nonequilibrium thermodynamics. Theory and practice
K.R. Westerterp, PhD Energy expenditure during overfeeding
Craig Warden, PhD Uncoupling and thermogenesis
Mary Vernon, MD Carbohydrate restriction in practice
Mary C. Gannon, PhD and Frank Q. Nuttall, MD, PhD Metabolic response to a high protein, low carbohydrate diet in people with type 2 diabetes
William S. Yancy Jr., MD Clinical trials in type 2 diabetes mellitus
Gualberto Ruano, MD, PhD Genetic markers for dietary treatment of obesity and metabolic syndrome
Michael Raab, PhD and Gregory Stephanopoulos, PhD Differentially expressed genes during periods of high and low glucose production
Fredric B. Kraemer, MD Hormone-sensitive lipase knockouts
Hubert Chen, PhD Inhibition of lipid synthesis enzymes as a therapeutic strategy for obesity and type 2 diabetes: Lessons from knockout models
Gerald I. Shulman, MD, PhD Insulin resistance and inflammation
Markus Stoffel, MD, PhD Insulin signaling and insulin resistance
Stephen Phinney, MD, PhD Dietary bioactives that modulate inflammation
Jeff S. Volek, PhD, RD Very low carbohydrate diets: Effects on lipids, inflammatory markers and endothelial function in metabolic syndrome
Daniel T. Stein, MD Lipid-carbohydrate interaction in insulin secretion
Michael D. Jensen, MD Free fatty acid turnover
Marc Hellerstein, MD, PhD In vivo responses of multiple metabolic systems to altered intake of carbohydrate or fats
Maria Luz-Fernandez, PhD Carbohydrate restriction reduces atherosclerosis and alters the distribution of lipoprotein subfractions in guinea pigs
Table 2. Variations and Outcomes of Carbohydrate-Restricted Diets
Author Year Population N (complete) Diet Description Duration Outcome
Boden et al.[1] 2005 Type 2 diabetics 10 (10) Carbohydrate < 21 g/d, protein and fat adlib vs participant's normal diet 14 d Low-carbohydrate diet: ↑ ketone bodies, blood urea nitrogen (BUN), and ↓ fasting plasma glucose, HgA1C, insulin, leptin, triglycerides (TG), total cholesterol (TC) compared with normal diets.
Foster et al.[2] 2003 Obese 63 (37) Carbohydrate < 20 g/d, then gradual increase in carbohydrate until weight stabilization; protein and fat adlib vs low-fat diet 12 mo At 3 months: ↓ weight, TG, TC, low-density lipoprotein-cholesterol (LDL-C), ↑ high-density lipoprotein-cholesterol (HDL-C). At 6 mo: ↓ weight, TC, ↑ HDL-C. At 12 mo: ↓ weight, TG, ↑ HDL-C compared with low-fat group.
Brehm et al.[52] 2003 Obese women 53 (42) At 3 months: carbohydrate 15%, protein 28%, fat 57%. At 6 months: 31% carbohydrate, 23% protein, 46% fat vs low-fat, calorie-restricted diet 6 mo Low-carbohydrate diet greater ↓ weight, fat and fat-free mass loss compared with low-fat diet.
Samaha et al.[53] 2003 Severely obese, high % with diabetes mellitus (DM) and metabolic syndrome 132 (79) Low-carbohydrate group: carbohydrate 37%, protein 22%, fat 41% vs low-fat group: carbohydrate 51%, protein 16%, fat 33% 6 mo Low-carbohydrate diet: ↓ weight, TG compared with low-fat diet. ↓ fasting glucose in diabetic patients.
Stern et al.[3] 2004 Severely obese, high % with DM and metabolic syndrome 132 (87) Low-carbohydrate group: carbohydrate 30% (120 g), protein 18% (73 g), fat 52% (93 g). Low-fat group: carbohydrate 50% (230 g), protein 16% (74 g), fat 34% (69 g) 12 mo No significant weight loss differences between groups at 12 mo, low-carbohydrate group stable mo 6-12, continued to decline in low-fat group. In low fat group ê TG, HDL. In low-carbohydrate group diabetics ↓ HgA1c.
Yancy et al.[54] 2004 Overweight hyperlipidemic 120 (79) Low-carbohydrate group: carbohydrate 8%, protein 26%, fat 68%. Low-fat group: carbohydrate 52%, protein 19%, fat 29% 6 mo Low-carbohydrate group: ↓ weight, TG, TG/HDL ratio, ↑ HDL-C, and BUN compared with low-fat group. More study finishers in low-carbohydrate group.
Meckling et al.[55] 2004 Overweight and obese 40 (31) Low-carbohydrate group: carbohydrate 15% (59 g), protein 26% (101 g), fat 56% (95 g) vs low-fat group: carbohydrate 62% (225 g), protein 20% (71 g), fat 18% (29 g) 10 wk Low-carbohydrate group greater ↓ lean mass, fasting insulin, ↑ HDL-C. In low-fat group, ↓ TC, HDL-C.
Moran et al.[8] 2005 Overweight hyperinsulinemic 73 (57) Carbohydrate 30%, protein 40% (136 g), 30% fat (46 g) vs carbohydrate 30%, protein 20% (67 g), fat 50% (76 g) 12 wk weight loss, 4 wk maintenance Improvements in weight, fat mass, lean mass, glucose, insulin, Homeostasis Model Assessment (HOMA), fasting ghrelin, postprandial respiratory quotient were independent of diet. Desire to eat decreased after consuming a higher protein test meal.
Sondike et al.[56] 2003 Overweight adolescents 39 (30) Carbohydrate 8% (37 g), protein 32% (na g), fat 60% (121 g) vs carbohydrate 56% (154 g), protein 32%, fat 12% (15 g) 12 wk Low carbohydrate greater ↑ body mass index (BMI), TG. Low fat greater ↓ LDL-C.
Parker et al (10) 2002 Obese type 2 diabetics 66 (54) Higher protein (HP): carbohydrate 42%, protein 28%, fat 28%. Standard protein (SP): carbohydrate 55%, protein 16%, fat 27% 12 wk, 8 wk weight loss, 4 wk maintenance Women lost more weight on HP, men on SP. LDL-C decreased more on HP diet. No other diet or gender differences.
Luscombe et al.[57] 2002 Obese type 2 diabetics 32 (26) HP: carbohydrate 42%, protein 28%, fat 28%. SP: carbohydrate 55%, protein 16%, fat 26%. 12 wk, 8 wk weight loss, 4 wk maintenance Thermic Effect of Food (TEF) 28% greater after HP test meal compared with SP meal. No other diet or gender differences.
Farnsworth et al.[58] 2003 Overweight hyperlipidemic 66 (57) HP: carbohydrate 44%, protein 27%, fat 27%. SP: carbohydrate 57%, protein 16%, fat 27% 16 wk, 12 wk weight loss, 4 wk maintenance Women lost more lean mass on SP diet. Area under the curve glucose smaller for HP diet. Greater ↓ TG with HP diet.
Layman et al.[59] 2005 Overweight, obese women 48 (48) 4 groups, 2 different diets with and without exercise. Protein group: carbohydrate 38% (141 g), protein 30% (110 g), fat 32% (52 g) 4 mo Protein groups greater ↓ weight, fat mass, TG, TG/HDL-C ratio. High protein plus exercise even greater ↓ weight. carbohydrate groups greater ↓ lean mass, TC, LDL-C.
Layman et al.[60] 2003 Overweight, obese women 24 (24) HP: carbohydrate 40% (171 g), protein 30% (125 g), fat 30% (54 g). carbohydrate group: carbohydrate 56% (239 g), protein 16% (68), fat 26% (48 g) 10 wk Carbohydrate group: ↑ insulin response over time, ↓ fasting glucose compared with HP group.
Gannon and Nuttall[12] 2004 Type 2 diabetic males 8 (8) Low-carbohydrate group: carbohydrate 20% (142 g), protein 30% (210 g), fat 50% (158 g). Low fat group: carbohydrate 55% (388 g), protein 15% (106 g), fat 30% (94 g) 5 wk, crossover with 5-wk washout between Low-carbohydrate group ↓ fasting glucose, mean glucose concentration, 24-hr total integrated insulin response, C-peptide, %tGHb, and TG compared with low-fat group.
Yancy et al.[6] 2005 Overweight type 2 diabetics 28 (21) Week 16: carbohydrate 10% (34 g), protein 29% (99 g), fat 61% (842 g) 16 wk Significant ↓ weight, BMI, waist circumference, % fat, heart rate, fasting glucose, TG, HgA1c and uric acid.
Dansigner et al.[61] 2005 Overweight, obese adults with dyslipidemia, hypertension, or hyperglycemia 160 (160 ITT, 93 completers) All diets are at 12 mo. Atkins: carbohydrate 42% (190 g), protein 19% (86 g), fat 40% (80.5 g). Zone: carbohydrate 41% (73 g), protein 21% (90.4 g), fat 38% (71.5 g). Weight Watchers: carbohydrate 48% (208 g), protein 19% (82.5 g), fat 33% (64 g). Ornish: carbohydrate 39% (218 g), protein 17% (82.5 g), fat 33% (64 g). 12 mo At 12 mo all diets except Atkins significantly ↓ LDL-C; ↑ HDL-C in all but Ornish; significant ↓ C-reactive protein (CRP) in all but Zone. Similar weight loss occurred in all groups.
Volek et al.[62] 2004 Overweight women 13 (13) Low-carbohydrate group: carbohydrate 9% (29 g), protein 28% (88 g), fat 63% (88 g). Low-fat group: carbohydrate 59% (186 g), protein 19% (59 g), fat 21% (29 g) 4-wk crossover, 4-wk washout between Low-carbohydrate group greater ↓ weight, TG/HDL ratio, fasting glucose, insulin, HOMA, VLDL compared with low-fat group.
Sharman et al.[63] 2004 Overweight men 15 (15) Low-carbohydrate group: carbohydrate 8% (36 g), protein 28% (130 g), fat 63% (130 g). Low-fat group: carbohydrate 56% (224 g), protein 20% (79 g), fat 23% (39 g). 4-wk crossover, 4-wk washout between Low-carbohydrate group greater ↓ TG/HDL ratio, fasting glucose, more large LDL-1, less LDL-3 and LDL-4. Low-fat group greater ↓ TC.
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Tome D. Effect of macronutrient composition of diet in rats. Program and abstracts of the Nutritional & Metabolic Aspects of Carbohydrate Restriction; January 20-22, 2006; Brooklyn, New York.
Harris R. Importance of control of the mitocarbohydratendrial a-keto-acid dehydrogenase complexes. Program and abstracts of the Nutritional & Metabolic Aspects of Carbohydrate Restriction; January 20-22, 2006; Brooklyn, New York.
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Phinney S. Dietary bioactives that modulate inflammation. Program and abstracts of the Nutritional & Metabolic Aspects of Carbohydrate Restriction; January 20-22, 2006; Brooklyn, New York.
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Ruano G. Genetic markers for dietary treatment of obesity and metabolic syndrome. Program and abstracts of the Nutritional & Metabolic Aspects of Carbohydrate Restriction; January 20-22, 2006; Brooklyn, New York.
Layman D. Impact of dietary protein on glycemic control and weight loss. Program and abstracts of the Nutritional & Metabolic Aspects of Carbohydrate Restriction; January 20-22, 2006; Brooklyn, New York.
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Brehm BJ, Seeley RJ, Daniels SR, D'Alessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab. 2003;88:1617-1623. Abstract
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Volek JS, Sharman MJ, Gomez AL, et al. 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;23:177-184. Abstract
Sharman MJ, Gomez AL, Kraemer WJ, Volek JS. Very low-carbohydrate and low-fat diets affect fasting lipids and postprandial lipemia differently in overweight men. J Nutr. 2004;134:880-885. Abstract
Heather Hutchins, MS, RD, Registered Dietitian, Zone Labs, Inc., Marblehead, Massachusetts. Email: hhutchins~eicosresearch.org
Disclosure: Heather Hutchins, MS, RD, has disclosed that she is employed by Zone Labs, Inc.
Conference Coverage: Nutrition and Metabolic Aspects of Carbohydrate Restriction
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