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Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical… Accurso, Anthony; Bernstein, Richard K; Dahlqvist, Annika; Draznin, Boris; Feinman, Richard D; Fine, Eugene J; Gleed, Amy; Jacobs, David B; Larson, Gabriel; Lustig, Robert H; Manninen, Anssi H; McFarlane, Samy I; Morrison, Katharine; Nielsen, Jørgen V; Ravnskov, Uffe; Roth, Karl S; Silvestre, Ricardo; Sowers, James R; Sundberg, Ralf; Volek, Jeff S; Westman, Eric C; Wood, Richard J; Wortman, Jay; Vernon, Mary C Apr 8, 2008

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ralssBioMed CentNutrition & MetabolismOpen AcceReviewDietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisalAnthony Accurso1, Richard K Bernstein2, Annika Dahlqvist3, Boris Draznin4, Richard D Feinman*1, Eugene J Fine5, Amy Gleed1, David B Jacobs1, Gabriel Larson1, Robert H Lustig6, Anssi H Manninen7, Samy I McFarlane1, Katharine Morrison8, Jørgen Vesti Nielsen9, Uffe Ravnskov10, Karl S Roth11, Ricardo Silvestre12, James R Sowers13, Ralf Sundberg14, Jeff S Volek15, Eric C Westman16, Richard J Wood17, Jay Wortman18 and Mary C Vernon19Address: 1State University of New York Downstate Medical Center, Brooklyn, New York, USA, 2New York Diabetes Center, Mamaroneck, New York, USA, 3Private Practice, Njurunda, Sweden, 4University of Colorado Health Sciences Center, Denver, Colorado, USA, 5Albert Einstein College of Medicine, Bronx, New York, USA, 6Division of Pediatric Endocrinology, University of California Medical Center, San Francisco, California, USA, 7Manninen Nutraceuticals Oy, Oulu, Finland, 8Ballochmyle Medical Group, Mauchline Ayrshire, UK, 9County Hospital, Karlshamn, Sweden, 10Independent Researcher, Lund, Sweden, 11Department of Pediatrics, Creighton University, Omaha, Nebraska, USA, 12Portuguese Sports Institute, Cruz Quebrada, Portugal, 13Cosmopolitan International Diabetes Center, University of Missouri, Columbia, Missouri, USA, 14Slottsstadens Läkarhus, Malmö, Sweden, 15Department of Kinesiology, University of Connecticut, Storrs, Connecticut, USA, 16Lifestyle Medicine Clinic, Duke University Medical Center, Durham, North Carolina, USA, 17Springfield College, Springfield, Massachusetts, USA, 18Health Canada, First Nations Division, Vancouver, British Columbia, Canada and 19Private Practice, Lawrence, Kansas, USAEmail: Anthony Accurso - anthony.accurso@downstate.edu   ; Richard K Bernstein - md@diabetesscientist.com; Annika Dahlqvist - annika.dahlqvist@telia.com; Boris Draznin - Boris.Draznin@va.gov; Richard D Feinman* - rfeinman@downstate.edu; Eugene J Fine - efine@downstate.edu; Amy Gleed - amy.gleed@downstate.edu; David B Jacobs - david.jacobs@downstate.edu; Gabriel Larson - gabriel.larson@downstate.edu; Robert H Lustig - rlustig@peds.ucsf.edu; Anssi H Manninen - anssi.manninen@gmail.com; Samy I McFarlane - sammy.mcfarlane@downstate.ed; Katharine Morrison - morrisons@ballochmyle.wanadoo.co.uk; Jørgen Vesti Nielsen - jvesti_nielsen@hotmail.com; Uffe Ravnskov - ravnskov@tele2.se; Karl S Roth - KarlRoth@creighton.edu; Ricardo Silvestre - blue_ricardo@yahoo.com; James R Sowers - sowersj@health.missouri.edu; Ralf Sundberg - ralfsundberg@telia.com; Jeff S Volek - Jeff.volek@uconn.edu; Eric C Westman - westm001@mc.duke.edu; Richard J Wood - rwood@spfldcol.edu; Jay Wortman - jwortman@interchange.ubc.ca; Mary C Vernon - mvernonmd@yahoo.com* Corresponding author    AbstractCurrent nutritional approaches to metabolic syndrome and type 2 diabetes generally rely on reductionsin dietary fat. The success of such approaches has been limited and therapy more generally relies onpharmacology. The argument is made that a re-evaluation of the role of carbohydrate restriction, thehistorical and intuitive approach to the problem, may provide an alternative and possibly superior dietarystrategy. The rationale is that carbohydrate restriction improves glycemic control and reduces insulinfluctuations which are primary targets. Experiments are summarized showing that carbohydrate-restricteddiets are at least as effective for weight loss as low-fat diets and that substitution of fat for carbohydrateis generally beneficial for risk of cardiovascular disease. These beneficial effects of carbohydrate restrictiondo not require weight loss. Finally, the point is reiterated that carbohydrate restriction improves all of thePublished: 8 April 2008Nutrition & Metabolism 2008, 5:9 doi:10.1186/1743-7075-5-9Received: 17 March 2008Accepted: 8 April 2008This article is available from: http://www.nutritionandmetabolism.com/content/5/1/9© 2008 Accurso et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 8(page number not for citation purposes)features of metabolic syndrome.Nutrition & Metabolism 2008, 5:9 http://www.nutritionandmetabolism.com/content/5/1/9BackgroundThe epidemic of diabetes continues unabated, and impas-sioned calls for better treatment and prevention strategiesare common features of scientific conferences. While it isgenerally acknowledged that total dietary carbohydrate isthe major factor in glycemic control, strategies based onreduction of dietary carbohydrate have received little sup-port. The American Diabetes Association, for example, hastraditionally recommend against low carbohydrate diets(less than 130 g/day[1]; while the most recent guidelines[2] admit such diets as an alternative approach to weightloss, they continue to emphasize concerns and downplaybenefits. Similarly, the Diabetes and Nutrition StudyGroup of the European Association for the Study of Dia-betes [3] reported "no justification for the recommenda-tion of very low carbohydrate diets in persons withdiabetes." We feel, however, that there is ample evidenceto warrant an alternative perspective and that diets basedon carbohydrate restriction should be re-evaluated in lightof current understanding of the underlying biochemistryand available clinical data.Whatever success low fat dietary approaches have had inimproving diabetes is to be applauded but it is reasonablefor patients to be aware of the potential benefits of analternative approach which we present here. The key fea-ture is that low carbohydrate diets are based on mecha-nism. That is, glucose directly or indirectly throughinsulin, is a major control element in gluconeogenesis,glycogen metabolism, lipolysis and lipogenesis. Thedownstream stimulus-response processes are a currentresearch interest (see e.g. [4,5]) but, according to the viewconsidered here, dietary fat has a generally passive roleand deleterious effects of fat are almost always seen in thepresence of high carbohydrate.While low carbohydrate diets may not be appropriate foreveryone, choices should be left to individual physiciansand patients. Key points that bear on the assessment ofbenefit vs. risk of carbohydrate restriction are presentedbelow. The discussion focuses on type 2 diabetes butmany of the principles will apply to metabolic syndromeand possibly to type 1 as well[6,7].1. Carbohydrate restriction improves glycemic control,the primary target of nutritional therapy and reducesinsulin fluctuations.2. Carbohydrate-restricted diets are at least as effectivefor weight loss as low-fat diets.3. Substitution of fat for carbohydrate is generally ben-eficial for markers for and incidence of CVD.4. Carbohydrate restriction improves the features ofmetabolic syndrome.5. Beneficial effects of carbohydrate restriction do notrequire weight loss.Carbohydrate restriction is an intuitive and rationalapproach to improvement of glycemic and metabolic con-trol. Data demonstrating that weight loss and cardiovas-cular risk are also improved remove these barriers to theacceptance of carbohydrate restriction as a reasonable ifnot the preferred treatment for type 2 diabetes. Finally,carbohydrate restriction is a potentially favorable diet forimproving components of the metabolic syndrome andthereby for the prevention of diabetes.1. Carbohydrate restriction improves glycemic control, the primary target of nutritional therapy and reduces insulin fluctuationsFigure 1 shows glycemic and insulin responses in a care-fully controlled inpatient comparison of 10 obese patientswith type 2 diabetes[8]. Fourteen days of a low-carbohy-drate diet led to a mean decrease in energy intake ofapproximately 1000 kcal/d, a reduction in plasma glucoselevels and average hemoglobin A1c (HbA1c) from 7.3% to6.8%. Insulin sensitivity improved by approximately75%. No adverse effects were reported, and the carbohy-drate that was removed was not replaced by substantialprotein or fat.Dashti, et al. showed dramatic and sustained reduction inblood glucose in 31 obese diabetic patients on a ketogenicdiet over 56 weeks. Normal levels were reached by week48 [9]. Similarly, Nielsen, et al.[10] reported that a 20%carbohydrate diet was superior to a 55–60% carbohydratediet with regard to bodyweight, glycemic control andreduction in HbA1c. At follow-up, after 22 months, HbA1cremained improved. In a 16-week pilot study of Yancy, etal., 21 overweight participants with type 2 diabetesshowed a mean decrease in HbA1c from 7.4% to 6.3%.These results are not isolated. Many studies have demon-strated the benefits of carbohydrate reduction [11-16] onglycemic control. Reaven, Garg, Grundy and coworkershave shown benefits of even moderate carbohydratereduction, from 55% to 40%[17,18].Reduction or elimination of medicationA striking effect of carbohydrate restriction is reduction orelimination of medication. Table 1 shows results fromYancy, et al. [19] in which 17 of 21 patients with type 2diabetes reduced or discontinued diabetes medicationupon carbohydrate restriction. Similar results were foundPage 2 of 8(page number not for citation purposes)by Boden [8] and Nielsen [10,20]. Practitioners havepointed out the need to reduce medication in advance ofNutrition & Metabolism 2008, 5:9 http://www.nutritionandmetabolism.com/content/5/1/9undertaking a low carbohydrate diet [6,10,20,21] high-lighting the power of carbohydrate restriction to bringabout the same therapeutic effect as drugs.2. Carbohydrate-restricted diets are at least as effective for weight loss as low-fat dietsLow-carbohydrate diets generally perform better thanlow-fat diets for weight loss in normal subjects, andpatients with metabolic syndrome or diabetes [22-25].Studies by Foster, et al. [26] and Samaha, et al. [27] areoften cited as examples where low carbohydrate diets aremore effective at 6 months but no better than low-fat dietsat 1 year. The experimental design, however, allowed re-introduction of carbohydrate in the low carbohydrategroup as the study proceeded. Even if there were equalweight loss at one year, other physiologic markers, partic-ularly TG and HDL, were greatly improved on the low-car-3. Substitution of fat for carbohydrate is generally beneficial for markers for and incidence of CVDThe diet-heart hypothesis states that dietary fat, or at leastsaturated fat, promotes CVD. There are, however, numer-ous counter-examples and the popular and scientific liter-ature has seriously challenged many of the underlyingassumptions of the hypothesis [28-33]. In fact, total fat inthe diet is not associated with an increase in CVD, asshown by experiments going back to Ancel Keys's SevenCountry Study [34]and, most recently and dramatically,the Women's Health Initiative [35].Lipid markers for CVDClinically significant elevation of LDL-cholesterol is gen-erally considered a primary indicator of CVD risk butinterpretation must be tempered by the effect of particlesize: small dense LDL particles are significantly moreatherogenic than large, buoyant LDL particles [36,37].Krauss, et al. identified a genetically influenced pattern (B)in people with higher levels of the smaller particles andfound a strong linear relation between carbohydrateintake and prevalence of the atherogenic pattern B pheno-type. Thus, replacing dietary fat with carbohydrate tendsto worsen LDL size distribution for most of the popula-tion[36,37].Other factors, such as high triglyceride (TG) and low HDL,are independent markers of insulin resistance and CVDrisk. Indeed, the triglyceride:HDL ratio has been positedto be a surrogate measure of insulin resistance [38]. Thisratio is frequently exacerbated under conditions thatlower LDL [24]. An increase in apolipoprotein B (apoB)may be a preferred marker since each atherogenic lipopro-tein particle contains one molecule of apoB; total LDLwould bias results towards lower risk [39]. There is alsostrong evidence that the apoB/apoA-I ratio is superior toconventional cholesterol ratios [39] as a predictor of CVDrisk. Of particular importance is circulating TG because ofits mechanistic link to the formation of atherogenic parti-cles [40,41], and its responsiveness to dietary manipula-tion. There is probably no dietary outcome as reliable asthe reduction in TG due to carbohydrate restriction[41].The role of saturated fatA primary goal of current recommendations is to put lim-its on dietary saturated fat but published results are incon-sistent (see e.g. [42]). Several critical reviews have pointedup the general failure to meet the kind of unambiguousoutcomes that would justify blanket condemnation of sat-urated fat, per se [29,30,41,43,44]. Notably, during theobesity and diabetes epidemic, the proportion of dietarysaturated fat decreased. In men, the absolute amountdecreased by 14%. Similarly, the WHI revealed no differ-Glucose and Insulin response for patients with type 2 diabe-tes on low carbohydrate diet vs. controlFigure 1Glucose and Insulin response for patients with type 2 diabetes on low carbohydrate diet vs. control. Data (means ± SE) are for 9 patients with type 2 diabetes after seven days on their usual high-carbohydrate diet (control) and after 2 weeks) on a low-carbohydrate diet. Medication was reduced in 4 patients and discontinued in one during the low-carbohydrate diet. Figure redrawn from Boden, et al. [8].Page 3 of 8(page number not for citation purposes)bohydrate diet compared with the high carbohydrate dietas shown in Figure 2.ence in CVD incidence for people who consumed < 10%saturated fat or those whose consumption was > 14%[35].Nutrition & Metabolism 2008, 5:9 http://www.nutritionandmetabolism.com/content/5/1/9Dreon, et al. [44] showed that increased saturated fat leadto a decrease in small, dense LDL. Perhaps most remarka-ble was a study by Mozaffarian [45] which showed thatgreater intake of saturated fat was associated with reducedprogression of coronary atherosclerosis; greater carbohy-drate intake was linked to increased progression.In our view, inconsistencies in the experimental resultswith dietary saturated fat arise from a failure to distin-guish between replacement by unsaturated fat or by car-bohydrate [3]. In the former case, there is usuallyimprovement in CVD risk or outcome (although it is notexcluded that this is due to the effect of the unsaturated fatis almost always deleterious [46,47]. Again, the idea thatcarbohydrate is a control element determining the fate ofingested lipid is overriding.The assumption that the dietary fatty acid profile isreflected in plasma distribution is not always true, espe-cially for saturated fatty acids which seems to be subject tomuch metabolic processing [42]. It was also expected thatan increase in total fat might show changes in lipid pat-tern but Raatz, et al. showed that such differences wereextremely small between a low fat and high fat diet [48].A recent report comparing two low-CHO groups that dif-fered in dietary SFA showed little difference in plasma lev-Table 1: Changes in diabetes medication of 19 overweight participants with type 2 diabetes who underwent a 16-week diet intervention trial. Patients were provided with VLCKD counseling with an initial goal of <20 g carbohydrate/day. Medication was reduced at diet initiation. Data from Yancy, et al. [62].Patient number Daily Dose – Week 0 Daily Dose – Week 16Medications discontinued (n = 7 of 19 originally on medication)5 glipizide 10 mg nonemetformin 1000 mg6 metformin 1500 mg none7 none9 metformin 1000 mg none15 metformin 1000 mg none22 metformin 1000 mg none24 metformin 1000 mg noneMedications reduced (n = 10 of 19)3 70/30 insulin 50 units metformin 1000 mgmetformin 1000 mg11 metformin 2000 mg metformin 2000 mgglyburide 20 mg16 metformin 2000 mg metformin 2000 mgpioglitazone 45 mgglypizide 20 mg21 metformin 1500 mg metformin 1000 mgpioglitazone 30 mg8 NPH 145 units NPH 25 unitsmetformin 1000 mg metformin 1000 mg13 70/30 insulin 70 units 70/30 insulin 35 unitsmetformin 2550 mg metformin 2550 mg23 70/30 insulin 110 units 70/30 insulin 80 unitspioglitazone 45 mg pioglitazone 45 mgmetformin 1000 mg25 NPH 70 units, r 30 units NPH 8 unitsmetformin 2000 mg metformin 2000 mgpioglitazone 45 mg pioglitazone 45 mg27 70/30 insulin 86 units 70/30 insulin 18 unitsmetformin 2000 mg metformin 2000 mg28 NPH insulin 90 units NPH insulin 30 unitslispro insulin 90 units glypizide 20 mgglypizide 20 mgPage 4 of 8(page number not for citation purposes)rather than reduction in the risk from the saturated fat).Replacement of saturated fat with carbohydrate, however,els of stearic or palmitic acid [49]. Most telling, Volek'sgroup compared a VLCK diet (% CHO:fat 12:59) with aNutrition & Metabolism 2008, 5:9 http://www.nutritionandmetabolism.com/content/5/1/9low-fat (LF) diet (56:24) and found that after 12 weeks,SFA in TG and cholesteryl ester were lower in the VLCKgroup than the LF group even thought the low carbohy-drate group had a 3-fold higher intake of dietary SFA [50].4. Carbohydrate restriction improves the features of metabolic syndromeAn important idea guiding current medical thinking isthat clustering of seemingly disparate physiologic states,obesity, atherogenic dyslipidemia, hyperglycemia andhypertension, termed metabolic syndrome (MetS) sug-gests a common underlying cause. Inherent in this con-cept lies the possibility that treating one risk factor ordisease state might confer benefit for risk of other dis-eases. A recent review showed that carbohydrate restric-tion improves all of these markers[24]. Indeed, metabolicsyndrome might be consistently defined as those physio-logic markers that respond to reduction in dietary carbo-hydrate. Metabolic syndrome might be seen as ageneralization of the carbohydrate intolerance that char-acterizes frank diabetes[24].In a prospective study testing the hypothesis linking car-bohydrate restriction to MetS, the carbohydrate-restrictedgroup showed greater improvements in weight loss andapo A1 ratio) compared to a low fat arm. Unexpectedly,the carbohydrate-restricted arm, with three times greaterdietary saturated fat, showed a reduction in plasma satu-rated fat, while plasma saturated fat in the low-fat armremained unchanged [50].Similarly, Petersen, et al. [51] showed that ingestion of ahigh carbohydrate meal led to a greater increase in de novofatty acid synthesis and hepatic triglyceride formation ininsulin-resistant men compared to a similar group ofinsulin-sensitive controls. Carbohydrate-induced athero-genic dyslipidemia is thus enhanced by insulin resistance.Carbohydrate restriction will generally reduce the con-sumption of fructose, which makes up half the mass ofcommon sweeteners (high-fructose corn syrup orsucrose). Fructose consumption has been implicated inthe epidemics of obesity, MetS, and type 2 diabetes and isknown to induce hypertension, de novo lipogenesis,hepatic insulin resistance and adiposity [52-54].In summary, carbohydrate restriction is one of the fewcommon interventions that targets all of the features ofMetS. If such a straight-forward approach can alleviate acondition for which there is no known effective drug, itspotential should be vigorously explored.5. Beneficial effects of carbohydrate restriction do not require weight lossObesity is commonly considered a cause of insulin resist-ance. Obesity, however, does not occur spontaneously.Obesity is a response. The effects of obesity that lead toinsulin resistance in peripheral tissues, largely increasedfatty acids, are downstream from the primary impact ofdiet. This argues for an emphasis of treatment on glycemiccontrol and improved hepatic metabolism rather thanweight loss. A simpler alternative hypothesis considersthat insulin resistance represents a down-regulation ofhormonal response as a result of persistent high levels ofinsulin, a feature common to other hormonal systems[55]. In this view, diabetes, obesity and the componentsof MetS are parallel effects of hyperinsulinemia and/orhyperglycemia.The finding that lipid improvements seen in carbohy-drate-restricted diets persist even after no further weightloss (Figure 2) suggests that the benefit of carbohydraterestriction is independent of weight loss. Two additionallines of evidence support this idea:1) In experiments in which body mass is kept constant innormal-weight men[56]or patients with type 2 diabe-tes[11,13], a very low carbohydrate diet resulted in dra-Comparison of low and high carbohydrate diets at 6 and 12 m nthsFigure 2Comparison of low and high carbohydrate diets at 6 and 12 months. Results from a multi-center trial in which 63 obese men and women were randomly assigned to either diet. Data from Foster, et al. [26]. Figure from Volek & Fein-man [24], used with permission.  DBP, diastolic blood pres-sure; TAG, triglycerides.Page 5 of 8(page number not for citation purposes)multiple markers of atherogenic dyslipidemia (increasedHDL and LDL diameter and reductions in TG and apo B/matic improvements in triglycerides and HDL cholesterolwith minimal change in body mass.Nutrition & Metabolism 2008, 5:9 http://www.nutritionandmetabolism.com/content/5/1/92) Experiments in which change in macronutrients andweight loss are separated in time show that eucaloric car-bohydrate reduction leads to greater improvement inatherogenic lipid markers (TG, HDL, apoB/apoA1 andmean LDL particle size) even in the presence of higher sat-urated fat[57,58]. A low fat diet, however, required weightloss to achieve effective improvement in the lipid profile(Figure 3). Notably, the sum of the two effects showedthat eucaloric carbohydrate restriction plus weight losswas more effective than eucaloric low fat plus weight loss.Practical considerations and recommendationsDefinitions and recommendationsResponse to carbohydrate restriction shows both continu-ous, graded outcomes [17,18] as well as a thresholdeffects. LDL particle size, e.g. appears to depend linearlycarbohydrate intake; the early phases of popular low car-bohydrate diets target such very low levels[6,15,21,59,60]. The principle rests on the concept of acatalytic or threshold effect for insulin in shifting the bodyfrom an anabolic state to fat oxidation. The tipping pointis empirically taken as the onset of ketonuria, also used asan indicator of compliance with a very low carbohydrateketogenic diet (VLCKD). The threshold carbohydratereduction for ketonuria varies among individuals, but arough estimate is 50 g of carbohydrate per day or, approx-imately 10% of energy on a nominal 2000 kcal diet, (a tar-get of 30 g/d is common in the early phases of popularVLCKD diets)[15,21,60].We suggest the following definitions:The ADA designates low carbohydrate diets as less than130 g/d or 26% of a nominal 2000 kcal diet and we con-sider this a reasonable cutoff for the definition of a low-carbohydrate diet. Carbohydrate consumption before theepidemic of obesity averaged 43%, and we suggest 26% to45% as the range for moderate-carbohydrate diets. Theintake of less than 30 g/d, as noted above should bereferred to as a very low carbohydrate ketogenic diet(VLCKD). The term Ketogenic Diet should be reserved forthe therapeutic approach to epilepsy. These diets do notindependently specify the level of carbohydrate, butrather the sum of carbohydrate and protein.In practice, many low carbohydrate dieters do not addadditional fat. First shown by LaRosa, [61] it has nowbeen observed by many other investigators. [8,62,63] Areduced carbohydrate diet may show significant per centincrease in fat, but there may be no change in the absoluteamount consumed. Not everybody on a low carbohydratediet follows this pattern, but a recommendation based onthis behavior would seem more appropriate than unqual-ified rejection of low-carbohydrate diets.While some proponents of carbohydrate restriction forthe management of diabetes favor sustained adherence tovery low levels of carbohydrate intake [6], all options maybe considered and therapeutic choices can be determinedby individual physicians and their patientsThe term low-carbohydrate diet is frequently taken as syn-onymous with the popular Atkins diet[60] which remainshighly controversial. Carbohydrate control, however, hasmany implementations and the severity of the epidemicof diabetes makes it appropriate to go beyond historicalcontroversy and analyze dietary interventions as they areactually implemented.Effect of dietary interventions on reduction in triglyceridesFigure 3Effect of dietary interventions on reduction in triglyc-erides. Eucaloric diets of indicated carbohydrate content were begun at time 0. At week 3, a 1000 kcal reduction in energy was implemented and at week 9, dieters were put on maintenance diet. Combined effect of calorie reduction and maintenance are reported at week 12. Solid Lines: data from Krauss, et al. [58] were converted from reported log values in their Table 2 and per cent of baseline was calcu-lated. Dashed line: data from Sharman, et al [56]: A euca-loric ketogenic diet was instituted for six weeks (no weight loss phase). Points were recorded at week 3 and 6. Figure modified from Feinman & Volek [57]. Similar results were found for HDL, apoB/apoA1 and other markers of CVD [57, 58]Page 6 of 8(page number not for citation purposes)on the level of dietary carbohydrate[36,37]. On the otherhand, many studies show maximum benefit for very lowThere is reluctance to make recommendations for low car-bohydrate diets on the grounds that people will not fol-Nutrition & Metabolism 2008, 5:9 http://www.nutritionandmetabolism.com/content/5/1/9low them but compliance and efficacy of dietaryrecommendations are separate phenomena. In fact, allrecommendations are specifically intended to be differentfrom average consumption[1] and it is sensibly the pur-pose of health agencies to encourage conformance to thebest therapies.It is time to re-appraise the role of carbohydrate restric-tion. Although pessimism exists in the medical commu-nity on the efficacy of any diet in the treatment of diabetes2 and MetS, the success of carbohydrate restriction formany practitioners and individual patients[64] mandatesthat we should determine how this approach can be con-sistently and effectively employed.Finally, while no systematic study of clinical practice hasbeen done, anecdotal evidence suggests that carbohydraterestriction is a common clinical recommendation for dia-betes. We believe that there is a need to codify these rec-ommendations in light of current evidence.Basic biochemistry, clinical experience and an evolvingunderstanding of metabolic syndrome support the needfor evaluation of the efficacy and safety of carbohydrate-restricted diets for the treatment of type 2 diabetes. Thefact that carbohydrate restriction improves markers of car-diovascular health, even in the absence of weight loss,sensibly removes historical objections to the dangers ofthis approach. A critical re-appraisal could form the basisfor an alternative for those patients for whom current rec-ommendations are not successful.Competing interestsMCV has been a consultant for Atkins Nutritionals, Inc.All other authors declare that they have nothing todeclare.Authors' contributionsRDF wrote the first version of this article based on pub-lished material and correspondence with the otherauthors who modified and approved the final version.Abbreviationsapo B, apolipoprotein B; apo A1, apolipoprotein A1:CVD, cardiovascular disease; HbA1c, hemoglobin A1c;HDL, high density lipoprotein; LDL, low density lipopro-tein; MetS, metabolic syndrome; SFA, saturated fattyacids; TG, triglycerides (triacylglycerol); VLCKD (VLCKdiet), very low carbohydrate ketogenic diet.   References1. American Diabetes Association: Nutrition Recommendationsand Interventions for Diabetes-2007.  Diabetes Care 2007,30(Suppl 1):S48-S65.3. 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