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Low-Carbohydrate Diets: Assessing the Science andKnowledge Gaps, Summary of an ILSI North America

Workshop

Marci J. Levine, PhD; Julie M. Jones, PhD; David R. Lineback, PhD

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n April 12 and 13, 2005, theInternational Life Sciences In-stitute (ILSI) North America

echnical Committee on Carbohy-rates sponsored a workshop onow-carbohydrate diets at the ILSIffices in Washington, DC. Over 50articipants from academia, govern-ent, industry, and scientific asso-

iations assembled to discuss andeview the current science, regula-ory, and health impacts of low-car-ohydrate diets.The goals of the workshop were to

ssess the state of the science, to ad-ress and clarify definitions and be-avioral questions regarding low-

M. J. Levine was an ILSI NorthAmerica Postdoctoral Fellow,North American Branch of theInternational Life Sciences Insti-tute, Washington, DC; J. M.Jones is a professor of Nutritionand Food Science, Department ofFamily, Consumer, and Nutri-tional Sciences, College of St.Catherine, St Paul, MN, and Sci-ence Advisor to the ILSI NA Tech-nical Committee on Carbohy-drates; and D. R. Lineback isdirector (retired), Joint Institutefor Food Safety and Applied Nu-trition (JIFSAN), University ofMaryland, College Park, and Sci-ence Advisor to the ILSI NA Tech-nical Committee on Carbohy-drates.

Address correspondence to:Marci J. Levine, PhD, Staff Scien-tist, International Life Sciences In-stitute, One Thomas Circle, NW,Ninth Floor, Washington, DC20005. E-mail: mlevine@ilsi.org0002-8223/06/10612-0018$32.00/0

doi: 10.1016/j.jada.2006.09.033

086 Journal of the AMERICAN DIETETIC ASSOCIATI

arbohydrate diets, and to identify re-earch gaps relative to improvingublic health. The workshop con-isted of presentations and discus-ions organized into three majorhemes: Perspectives, Mechanisms,nd Gap Analysis. Perspectives pro-ided information on efficacy and def-nitions regarding “low-carbohydrate”iets from the perspective of the re-earcher/clinician, the consumer, andhe regulator. The Mechanisms ses-ion addressed hypotheses of the effi-acy and other possible effects of low-arbohydrate diets. The third andnal session, Gap Analysis, enabledttendees to consider scientific andonsumer perspectives to determinereas of agreement, identify dataaps, and identify ways to improveommunication of this information.he purpose of this article is to relatehe key points of the workshop to di-tetics professionals.

ERSPECTIVES ON EFFICACYdult Populationsew published studies have ade-uately assessed the efficacy of low-arbohydrate diets, particularly foronger than 6 months. It is difficult toompare studies because the level ofarbohydrates can fluctuate from 1%o 25% of total energy intake (1), thentervention diet is not always wellefined, subject characteristics vary,nd the degree of subject compliances often unclear. However, despiteheir shortcomings, six recent ran-omized controlled trials provide dataegarding possible health effects ofow-carbohydrate diets (Table 1) (2-7)ompared with more conventionalow-calorie, low-fat diets in obesebody mass index [BMI]�30) subjects.

As shown in Table 1, subjects on w

ON © 2006

he low-carbohydrate diets lost be-ween 3% and 13% of their bodyeight at 5 months, whereas those on

he low-calorie, low-fat (control) dietost between 1.4% and 7% . However,y 1 year, the differences in weightoss did not persist (2,4). For example,oster and colleagues observedeight regain in both groups by 1ear, with a greater regain in the low-arbohydrate group (4). In the studyy Stern and colleagues, the low-fatroup continued to lose weight after 6onths, resulting in similar weight

osses by 1 year (6). Only three stud-es assessed dietary intake (2,6,7), sot is difficult to assess study protocolompliance to link dietary factors tohe apparent success. These limitedndings suggest that a low-carbohy-rate approach may be more effica-ious than conventional (eg, low-calo-ie, low-fat) approaches for short-erm weight loss. Beyond 6 months,ore data are needed.

ediatric Populationsf there are few studies rigorously de-igned to test the long-term effects ofow-carbohydrate interventions inbese adults, there exist even feweruch studies in overweight or obesehildren. One recent trial compared aow-carbohydrate, high-protein dietsimilar to those discussed for adults)ith a low-fat diet for weight loss in0 overweight adolescents (mean age4 years; BMI 35.5) (8). After 12eeks, those on the low-carbohydrateiet lost more weight than those onhe low-fat diet (9.9�9.3 kg vs.1�4.9 kg, P�0.05) (8), even thoughheir caloric intake was greater (ac-ording to self report). Other investi-ations of low-carbohydrate diets for

eight loss in children tested extreme

by the American Dietetic Association

Table 1. Weight loss reported by randomized trials comparing low-carbohydrate diets with conventional low-calorie, low-fat diets at 6 months and 1 year in adultsa

Author(reference) n

Age�SDb

(y) BMIc�SDHealth statusof subjects

Control diet(low-calorie, low-fat)carbohydrate:protein:fat, %

Low-carb dietcarbohydrate:protein:fat, %

Interventionprotocol

Mean Weight Loss (% Change)

6 mo 1 y

ControlLow-carbohydrate Control

Low-carbohydrate

Brehm andcolleagues (2)

53 44�7 34�2 Healthy Goal: 55:15:30Report: 53:18:29

Goal: carbohydrate �20 g/dfor initial 2 weeks,increase to 40-60 g/d

Report: 30:23:46

3 months counseling,individual andgroup, weekly 3-dfood records

4.2 9.3 Not tested Not tested

Dansinger andcolleagues (3)

80 49�11 35�3.9 Hypertension,dyslipidemia,or fastinghyperglycemia

Weight Watchers Atkins Group counseling,cookbook

3.6 3.2 3.1 2.1

Foster andcolleagues (4)

63 44�8 34�4 Healthy Goal: 55:15:30 Goal: carbohydrate �20 g/dfor initial 2 weeks, thenincrease until weightstable

Self-help based onprovided books

3.2 7.0 2.5 4.4

Samaha andcolleagues (5),Stern andcolleagues (6)d

132 54�9 43�7 39% DM,e 43%metabolicsyndrome

Goal: 55:15:30Report: 50:16:34

Goal: carbohydrate �30 g/dReport: 30:18:52

Some guidance 1.4 4.5 2.3 3.9

Yancy andcolleagues (7)

120 45�10 34�5 High totalcholesterol,LDL,f

triglycerides

Goal: 55:15:30Report: 52:19:29

Goal: carbohydrate �20 g/dfor initial 2 weeks, thenincrease until weightstable

Report: 8:26:68

Group meetings,exerciserecommended

6.7 12.9 Not tested Not tested

aResults reported were those presented to workshop attendees (intent-to-treat analysis by primary authors). When available, the goal and reported dietary composition are included. See reference for thorough protocol details.bSD�standard deviation.cBMI�body mass index; calculated as kg/m2.dThe 6-month and 1-year time points from same weight loss trial reported in two publications.eDM�diabetes mellitus.fLDL�low-density lipoprotein.

OFPROFESSIONAL

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ersions of low-carbohydrate diets suchs protein-sparing modified fasts (9-11)r severely energy restricted (600 to00 kcal) plans (9-11). Although weightoss was reported, it is unclear how tonterpret these findings.

In summary, the data available areot yet generalizable to adult or pedi-tric populations and do not warrantodification of the current clinical

ecommendations for weight loss withreduced-calorie, moderately low-fat

�30%) diet. The evidence does sug-est, however, that low-carbohydrateiets should be studied as a poten-ially viable alternative for weightoss in obese adults. Additional stud-es evaluating low-carbohydrate dietsith less severe energy restriction inouth and adolescents are needed.

onsumer Perspectivesonsumer attention to carbohydrates

s reflected in consumer attitudes, in-ustry actions, and media coverage.s concern about carbohydrates in-

reased through 2003 (12), the foodndustry responded by developing aariety of new no-carbohydrate, low-arbohydrate, or reduced-carbohydrateroducts (13). Concurrently, sales flat-ened or declined for traditional “high-arb” foods. Concern about sugar andarbohydrates and the number of ad-erents to a low-carbohydrate lifestyleeclined by 2005 (14,15). As a result,low-carb” product introductions de-reased sharply in the fourth quarter of004 and early 2005 (13). Similarly, theontent of media stories shifted fromrticles touting the popularity of low-arbohydrate diets throughout 2004 tohose proclaiming “low-carbohydrate”o be a fad and the increasing favor ofgood” carbohydrates by the end of005 (14).There is also confusion regarding

arbohydrates. Consumers associatearbohydrates with positive attributesthey give you energy; they provide fi-er and nutrients; and they are foundn nutritious whole grains, fruits, andegetables), and with negative quali-ies (they make you fat, raise insulinevels, and slow down your metabo-ism) (14). However, most consumersannot articulate why they think cer-ain carbohydrates are healthful or not.lthough some consumers recognized

arbohydrate restriction as an easyay to lose weight (14), the degree of

arbohydrate restriction and which a

088 December 2006 Volume 106 Number 12

arbohydrates were eliminated variedreatly. For some, cutting out seem-ngly healthful foods was counterintui-ive; many consumers believe that re-tricting foods does not provide a long-erm path to a more healthful weight or

healthful diet. Although others ac-nowledged that low-carbohydrate di-ts may not be healthful, the desire foreight loss compelled many to try low-

arbohydrate diets. Unfortunately forany consumers, eating for health and

ating for weight control are two sepa-ate practices (14).

The low-carbohydrate fad increasedwareness of carbohydrates, and theew/reformulated products enabledonsumers to personalize their defini-ion and approach for low-carbohydrateieting. Research is needed to identifyhe extent to which low-carbohydrateifestyles were adopted and what foodsre included in such approaches. Nutri-ion communicators need the tools andesources to convey the facts aboutarbohydrate foods and the messagehat eating for health and eatingor weight loss are one and the same.s these gaps are narrowed, con-umers will likely select nutrient-richarbohydrate-containing foods suchs whole grains, fruits, and vegeta-les, as recommended by the Dietaryuidelines for Americans (16).

ERSPECTIVES ON REGULATIONS,EFINITIONS, AND ANALYSIS OF “LOWARBOHYDRATE”egulationsn 2004 and early 2005, terms such asow carb, net carb, available carb, im-act carb, carb lite, and carb simpleere found throughout the globalarketplace to describe the level of

arbohydrate content of a food. Forhe manufacturer, the plethora oferms to describe the level of carbo-ydrates in foods has no regulatory

abeling status in many countries.lthough US regulations have quan-

itatively defined “no” or “low” for aumber of nutrients [eg, fat and cho-

esterol (16), sodium (17), and calories18)], presently, “low-carbohydrateood” and “low-carbohydrate diet” areot terms defined by the US Food andrug Administration (FDA). The FDAoes not have a guidance on theseerms, thus they cannot be placed onackaging. However, the lack of objec-ion to the use of the terms net carb or

vailable carbs does not constitute an t

pinion that their use is appropriate.he USDA Food Safety and Inspectionervice guidance related to meat andoultry products states that such labelerms must be accompanied by specificnformation telling the consumer the

eaning and usage of such terms androviding the calculation necessary toetermine the number of carbohy-rates included by the term (19). In thenited States, these terms may besed in ad copy or labeling only in con-

unction with terms to describe a diet orifestyle (not a level of carbohydrate in

particular food or product), providedhey are truthful and not misleading.

It became common practice by mostanufacturers to measure the total

onglycemic or nondigestible carbo-ydrates (typically dietary fiber, re-istant starch, and sugar alcohols)nd subtract this quantity from thealculated quantity of total carbohy-rates (Figure 1). Because of warningetters and position papers, Americanood producers generally gravitatedoward the use of the terms net car-ohydrates, available carbohydrates,r net available carbohydrates to in-icate the levels of carbohydrateresent in a product, but each manu-acturer has created its own schemeor applying the designations.

Several petitions for proposedutrient content claims such asarbohydrate-free, low-carbohydrate,educed-carbohydrate, good source ofarbohydrates, and excellent sourcef carbohydrates have been receivedy the FDA. These are under review,s are comments regarding guide-ines for the use of the term net car-ohydrate on food labels. The FDAs presently gathering informationbout the science surrounding low-arbohydrate labeling so that appro-riate actions are taken.

efinitionsn an effort to harmonize terms de-cribing foods of relatively low-carbo-ydrate content, the Board of Direc-ors of AACC International (formerlyhe American Association of Cerealhemists) formed an ad hoc commit-

ee charged with developing a sci-nce-based, measurable definition(s)or glycemic carbohydrates (20),hich would contribute to the low-

arbohydrate dialogue. Accepted def-nitions would enable manufacturers

o communicate how the carbohy-

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rate content of a certain amount of aiven food will affect blood glucoseevels and possible risk of chronic dis-ase, thus standardizing calculationso unify label claims across productsnd manufacturers. The AACC Inter-ational Committee is presently re-iewing three interconnected defini-ions (Figure 2) developed with theid of a flow chart (Figure 1), publicomments, and revisions.

nalysishere are two related philosophies foruantifying the glycemic effect of car-ohydrates. The first is to measurend report the portion of carbohy-rate known to elicit a glycemic effectthe available/net carbohydrate). Asong as the meaning of net carbohy-rate is agreed on, analytical meth-ds currently exist to determine thisuantity in foods (21), although alter-ative approaches are being investi-ated (22). The second philosophy iso indicate the physiological glycemic

igure 1. Carbohydrate (CHO) classification scy metabolic fate. It was presented at the Intercheme the AACC International Committee refeealth Canada, Ottawa, Ontario, and Stuart Cr

Available carbohydrate in a food can be absothe body. Net carbohydrate is equivalent t

Glycemic response is the change in blood gl

Glycemic impact is the blood glucose responequivalent weight of glucose.

igure 2. Proposed AACC International definition current as of submission. See www.aaccnf arriving at definitions.)

ffect that the food produces. To mea- r

ure the glycemic effect of carbohy-rates currently requires in vivoethods, although in vitro methodol-

gy is being researched. The mostidely used in vivo measurement is

he glycemic index (GI). Comparedith other routine analytical proce-ures, GI measurements are ex-remely variable (Table 2), not onlyith regard to the calculated ratios to

he standard food, and among indi-iduals, but with regard to the indi-idual’s blood glucose response whenhe individual consumes replicateamples of the same food (23). Theffects of processing and mixtures ofoods on the overall glycemic impactlso remains a methodological chal-enge. Derivative methods of the GI,uch as glycemic load and glycemiclucose equivalents, will all show theame shortcomings because of the dif-culties with the basic measurement.Because of these limitations, it is

ifficult to apply GI values in a mean-ngful manner to aid individuals inood selection. For example, oat por-

e. This flow chart shows the relationships beonal Life Sciences Institute North America Wored as it proposed definitions of carbohydratesDanisco USA, Inc, Ardsley, NY.

d as monosaccharides and metabolized byailable carbohydrate.

se concentration induced by ingested food.

of a serving of food relative to that of an

related to glycemic carbohydrates. (Informa-rg for more information related to the process

idge has a GI of 58, carrots a GI of i

December 2006 ● Journal

2, and chocolate cake with chocolaterosting a GI of 38. If GI were on theabel, a consumer who might selectoods purely on the basis of GI mightelieve that frosted cake is a betterhoice than oatmeal or carrots. Fu-ure research is needed to improveethods of measuring the glycemic

ffect of carbohydrates, which may beranslated to consumers through pos-ible labeling designations.

ECHANISMS FOR EFFICACY OF LOW-ARBOHYDRATE DIETShere are several hypotheses re-

ated to how reduced-carbohydratetrategies may promote weight loss.hese involve behavior and ease ofompliance, changing macronutri-nt distribution and use, and induc-ng satiety. Factors influencing sati-ty include the level or type ofarbohydrate, effects of hormones,he level or type of protein, or theverall dietary energy density.hese elements, each having com-lex regulatory pathways, may alsonteract with one another.

ieting Behaviorlthough reducing caloric intake de-reases weight, it is challenging forndividuals to achieve weight loss byrying to control calories on their own.here is general agreement that aomprehensive weight-loss treatmenthould focus on health and self-steem and incorporate self-monitor-

en different types of carbohydrates organizedop on Low-Carbohydrate Diets to illustrate theure 2). Developed from work by Steve Brooks,

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ivity, nutrition education (includingortion control), stress management,nd social support (24-26).Research shows that subjects in-

tructed to follow a low-carbohydrateiet (without guidance on calorie reduc-ion) spontaneously decrease their ca-oric intake (2,6,7). Decreasing intakef high-carbohydrate foods may offern easy-to-follow, prescriptive strategyor decreasing total caloric intake (4).here is enough variety in most low-arbohydrate plans, particularly withhe new and reformulated products,hat an individual is unlikely to feeleprived. In addition, low-carbohy-rate dietary patterns that emphasizeruits and vegetables may actually im-rove an individual’s dietary nutrientrofile. Because the pounds drop fasterhan with a “low-fat” diet in the shorterm, there is increased incentive, andhis may lead to enhanced compliancend efficacy.

etosis vs Caloriest was theorized that low-carbohy-rate diets put the body into a state ofetosis, thereby conferring a meta-olic advantage that permits moreapid weight loss. This implies thatalories do not count, but rather thathe source of the calories does, andhat greater weight loss can be gainedrom a low-carbohydrate diet thanrom a high-fiber diet with availablearbohydrates at traditional levels�55% kcal). If ketosis were contrib-ting to weight loss, one would expectn increase in ketone production to bessociated with weight loss of individ-als on a low-carbohydrate diet, buthis was not the case in two studies2,4) in which ketone levels were as-

Table 2. Variability of the glycemic index (G

Food sampleGI result(mean�SD)b

White bread 72.5�35.8Instant mashed potatoes 84.5�32.7Long-grain rice 71.1�38.2White spaghetti 46.9�26.7Pot barley 34.7�24.7

aResults of a multicenter trial in which 68 participantstriplicate and the remaining foods in singlet. As can readilindividual results for each food significantly overlap acrosconfidence intervals in every case. Table presented durinbSD�standard deviation.

essed. On closer inspection, low- b

090 December 2006 Volume 106 Number 12

arbohydrate diets are almost alwaysypocaloric in comparison to the con-rol diet. This concept was tested inubjects consuming isocaloric 1,000-cal low-carbohydrate or normal-arbohydrate diets (low-fat) over 6eeks, and results showed thateight loss did not differ between the

wo groups (27,28). Therefore, calo-ies apparently are the more relevantactor.

I and Insulinhe theory that weight loss can bechieved by selecting foods that min-mize postprandial insulin secretions predicated on the belief that carbo-ydrates, through insulin, increaseunger. Proponents of such diets of-en do not distinguish between nor-al insulin responses to meals and

isordered adaptive responses exist-ng in insulin resistance states. Foodsith a low GI value, in theory, could

educe the insulin response. How-ver, studies of the effect of GI onnsulin response and satiety are few,ften are not rigorous, and taken to-ether are inconclusive (29). Epidemi-logic studies show no effect of GI orlycemic load on insulin response ineople with BMIs below 23 (30-33).entral adiposity is associated with

ncreased circulating insulin, and in-ulin sensitivity is inversely relatedo BMI (34,35). Further, during nor-al insulin signaling, reduced glu-

ose-stimulated insulin secretion pre-icts greater future weight gain (36);herefore, increased insulin secretionn response to meals is unlikely toontribute to weight gain and obesity.Furthermore, considerable evidence

upports that insulin signaling in the

95% confidenceinterval

99% confidenceinterval

1.1-143.9 �22.3-167.319.3-149.7 �2.09-171.1

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ale, 40 female) consumed the white bread sample inseen the variability of the measurements is so great thatGI range and include zero and negative numbers in the

e workshop was adapted from reference 24.

rain actually decreases food intake, t

cting as a negative feedback signal ofecent energy intake and body adipos-ty (37). Reduced insulin delivery intohe central nervous system or disrup-ion of insulin signaling pathways re-ults in weight gain and developmentf obesity in animals. Insulin also facil-tates leptin secretion; thus, mealsigher in carbohydrate tend to increaseot only insulin levels, but also leptin

evels to signal satiety. Research iseeded to clarify how dietary carbohy-rates and GI affect satiety and eatingehaviors through a myriad of hor-ones including insulin.

roteineveral lines of evidence suggest thathe higher protein level consumed onow-carbohydrate diets is key in reg-lating food intake and body weight.t is generally accepted that proteinsuppress food intake and are moreatiating than fats or carbohydratesnd by a greater percentage than cane accounted for by energy contentlone (38,39). Compared with fat andarbohydrate, protein delays the re-urn of hunger (40) and reduces themount of calories consumed at a sec-nd meal (41). There is also limitedata that indicate that the proteinource, not just the quantity, impactsatiety (42,43). For example, subjectseported higher feelings of satiety af-er consuming 50 g protein as leansh compared with beef or chicken,lthough this study did not investi-ate the impact of this protein mealn subsequent meal intake (44).hort-term studies with 1.5 g pro-ein/kg and moderate-low carbohy-rate (up to 200 g per day) increasedatiety, increased thermogenesis,pared loss of muscle protein, and en-anced glycemic control comparedith low-protein, high-carbohydrateiets. The effects of moderate proteinnd lower carbohydrate intake mayontribute to decreasing postprandialncreases in blood glucose and insulinesponse, while increasing substratesor gluconeogenesis (45). Protein inhe diet helps maintain lean bodyass and, therefore, increases resting

nergy expenditure.Several mechanisms may explain

ow protein affects satiety and over-ll intake (46,47). Bioactive peptidesctivated during protein digestion actn centers within the digestive tract

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mino acids activate neurochemicalystems within the brain to terminateating as well as to impact macronutri-nt choice. Also, the end products ofrotein metabolism (amino acids, am-onia, and urea) signal excess intake

nd probably play a role in determin-ng meal intervals. Although the rolesf cholecystokinin, insulin, glucagon,eptin, ghrelin, peptide YY (PYY), andlucagon-like peptide-1 (GLP-1) in ap-etite regulation are becoming eluci-ated, how proteins, especially as mix-ures in the diet, impact satiety viahese hormone signaling pathways toegulate food intake and weight is notompletely understood. The evidenceuggests that increasing protein to 26%f energy (from the average of 15% to8%) is enough to reduce appetite. Theigher-protein (lower-carbohydrate),nergy-restricted diets seem to be moreatiating and result in better weightoss, contributing to adherence.

nergy Densitygrowing body of laboratory-based,

linical-based, and epidemiology-basedata suggest that low-energy-densityiets can reduce body weight in thehort term (48). Energy density (mea-ured in kcal/g) is primarily impactedy water, which adds weight and vol-

Low-carbohydrate diets result in weight lossno difference in weight loss after 1 year btraditional approaches.

Calories are calories, and calories do count.

Low-carbohydrate diets lower blood triglycershort-term and long-term studies.

Low-carbohydrate diets increase low-densityand during weight maintenance.

To fully compare and evaluate dietary effectsdiet protocol, subjects, and dietary compo

igure 3. Scientific points of agreement idenorth America Workshop on Low-Carbohydrate

Atkins-type diets are easy to comprehend an

Calories are too hard to count.

The low-carbohydrate diet has enthusiastic s

There are carbohydrates with different effect

igure 4. Consumer points of agreement ideorth America Workshop on Low-Carbohydrate

me with no calories; thus, it lowers o

he energy density of foods, even high-at foods. Fruits and vegetables tend toave low energy densities because ofoth their high water and their highber contents. It has been postulatedhat satiety is increased when energyensity decreases because foods high inater and fiber are associated with en-anced satiety, reduced energy intakesnd body weight, and better diet qual-ty. Hence, consumption of high vol-mes of low-energy-density foods is as-ociated with lower total caloric intakend enhanced satiety (49). Consumingood preloads with high water contentnd low energy density, such as soupsr salads, enhances satiety and reducesverall energy intake at the meal. In atudy in which the energy density of aeal was reduced by 30% and the sub-

ects consumed the same weight ofood, caloric intake was reduced by 30%50). Perhaps some low-carbohydrateiet regimens are satiating due to thenclusion of foods with lower energyensities.

ardiovascular Disease Risk and Otheronsiderationsprincipal concern regarding low-car-

ohydrate diets is that the (relatively)igh fat content of the diet may ad-ersely affect serum lipids and the risk

the short term (6 months), but there waseen low-carbohydrate and other more

and raise high-density lipoprotein in both

protein in short-term weight loss studies

various studies, details surrounding then need to be accurate and complete.

d at the International Life Sciences Instituteets.

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orters and is palatable for many.

health (like fats).

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f cardiovascular disease. Paradoxi- o

December 2006 ● Journal

ally, preliminary findings challengehis argument. If the dietary fatty acidomposition is known, mathematicalquations predict that large increasesn low-density lipoprotein cholesterolLDL) with low-carbohydrate dietshould only be realized in extremeases in which carbohydrates are re-laced almost exclusively with satu-ated fatty acids (51). Furthermore, vir-ually any implementation of a low-arbohydrate diet should produceeneficial changes in high density li-oprotein (HDL) and triglyceride levelsnd the ratio of total cholesterol toDL cholesterol. Clinical research gen-

rally supports these models. Thereere no differences in total cholesterolr LDL concentrations between groupscross four studies at 6 or 12 months.ow-carbohydrate diets consistentlyecreased triglycerides (2,4,5,7) andended to increase HDL, and no studieshowed an increase in LDL. One studyeported decreases in HDL in partici-ants following a low-carbohydrateiet, but the decrease was less than theecrease in the low-calorie group (6).o adverse effects on the lipid profileere observed in the sole pediatric

tudy (8). Furthermore, no significantifferences in blood pressure were ob-erved between groups in these stud-es. Alhough results should be inter-reted cautiously, because means maybscure important individual differ-nces, low-carbohydrate diets seem toe less harmful than might be antici-ated in terms of traditional measuresf cardiovascular disease risk.At 6 months, any improvement in

riglyceride or HDL levels may beonfounded by weight loss, becauseosing weight decreases triglycerideevels. However, decreasing carbohy-rate intake reduced triglyceride lev-ls more than diets with the sameevel of fat and higher levels of pro-ein (52). When carbohydrates are ex-hanged for protein, there is no effectn LDL and the effects on HDL arenconsistent, but all studies show aecrease in triglycerides because ofhe independent effect of carbohy-rates on very-low-density lipopro-ein synthesis and, therefore, triglyc-rides (52-55). Although there may bedditional beneficial effects of low-arbohydrate diets, such as decreasedostprandial lipemia and prevalencef low LDL levels, not all of the effects

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ascular disease risk are necessarilyediated through changes in macro-utrient composition.Not all low-carbohydrate diet stud-

es investigated possible side effects.inor side effects including constipa-

ion, halitosis, and muscle cramps oc-urred more frequently in subjectsonsuming the low-carbohydrate dietompared with the low-calorie diet ac-ording to Yancy and colleagues (4).ome less desirable immediate ef-

ects, such as enhanced lean bodyass loss, increased urinary calcium

oss, increased plasma homocysteineevels, and increased LDL levels,ave been reported (45). Results ofhese and other studies should be in-erpreted with caution given the rel-tive small sample sizes, varied sub-ect characteristics, high attritionate, and short duration of treatment.

Research is needed to evaluate thehort-term and long-term safety andffectiveness of dietary managementf carbohydrates for weight loss. Fu-ure studies, some of which are un-

Develop definition of “low carbohydrate.”

Document composition and determine nutritiomultiple low-carbohydrate dietary patternschanges in energy and macronutrient intasettings.

Compare varying degrees of carbohydrate repotential threshold/dose effects on weight

Determine what risk factors should be includefficacy and safety of low-carbohydrate di

Investigate short-term and long-term use ofdiets in more population subgroups (healthas well as those with chronic diseases anfactors) to obtain data on multiple safety eidentify weight-loss responders.

igure 5. Scientific research gaps identified a

Explore what “low-carbohydrate food” and “mean to consumers. What are individualslow-carbohydrate diet?

Assess composition and quality of personalizdietary approaches of consumers.

Determine what consumers understand “ene

igure 6. Consumer gaps identified at the Int

erway, should assess the effects of t

092 December 2006 Volume 106 Number 12

he diet on other clinical endpointsie, renal function, bone health, exer-ise endurance, and cognitive func-ion) and in larger study populations,nd should distinguish between thempact of weight loss and dietary fac-ors on metabolic outcomes in bothdults and children. Additional efforts needed to translate the findings tohe general population.

APS ANALYSISfter the data were presented, work-hop participants were challenged toonsider what information is agreedn from both a scientific and a con-umer perspective (Figures 3 and 4)nd to identify questions that remaino be answered (Figures 5 and 6). Re-earch to bridge the gaps in knowl-dge between scientists and consum-rs will enable effective translation ofhe science of low-carbohydrate dietso the public so that dietary choicesan be made to optimize the health of

l quality ofunderstandn research

tion to understandother endpoints.

in analysis of the

-carbohydratedults and childrenrange of riskpoints and to

Elucidate mechanismscarbohydrate diets.fat, fiber, energy dpalatability), role of

Determine why low-cthe longer term.

Explore possible healtweight loss, of follo

Understand how the sglucose absorption.

Research glycemic indimprove applicabilit

Determine the degreelow-carbohydrate ddelineate their rese

e International Life Sciences Institute North A

-carbohydrate diet”ually eating on a

low-carbohydrate

density” to mean.

Clarify role of label mproduct claims fowhether and howperceptions, beha

Investigate strategiesnegative impactscarbohydrates.

tional Life Sciences Institute North America W

he individual. t

LSI North America Statement of Purposehe North American branch of the In-

ernational Life Sciences InstituteILSI NA) is a public, nonprofit scien-ific foundation. ILSI NA advances thenderstanding and application of sci-ntific issues related to the nutritionaluality and safety of the food supply asell as health issues related to con-

umer self-care products. The organi-ation carries out its mission by spon-oring relevant research programs,rofessional education programs andorkshops, seminars, and publica-

ions, as well as providing a neutralorum for government, academic, andndustry scientists to discuss and re-olve scientific issues of common con-ern for the well-being of the generalublic. ILSI NA also strives to fosterhe career development of outstandingew scientists. ILSI NA’s programs areupported primarily by its industryembership.

his workshop and preparation of

short-term weight loss success of low-nsider factors related to satiety (protein,ty), behavior (structure, perceptions,tones, and glucose, among others.

hydrate diets seem to lose efficacy over

enefits, beyond benefits attributed tog a low-carbohydrate diet.

ce(s) of carbohydrate(s) impacts the rate of

methodology(ies) to reduce variability and

comfort clinicians have in recommendingin the short term and long term and

tions, if any.

ica Workshop on Low-Carbohydrate Diets.

sages and images, advertising copy, and-carbohydrate foods and determine

h designations impact consumer, and health.

at will enable consumers to understand thexcess calories instead of a focus on

shop on Low-Carbohydrate Diets.

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OF PROFESSIONAL INTEREST

he ILSI North America Technicalommittee on Carbohydrates.The authors thank the members of

he Technical Committee on Carbohy-rates and its Low-Carbohydrate Di-ts Working Group for their supportf this workshop and publication. Welso thank the speakers for theirtimulating presentations, the inter-ctive participation of the guests, andhe assistance of Richard Carson, Se-ior Project Manager, and the staff ofLSI NA, who contributed to the suc-essful workshop.Workshop Speakers and Panel-

sts: Dr G. Harvey Anderson, Univer-ity of Toronto; Sue Borra, Interna-ional Food Information CouncilIFIC); Dr Stuart Craig, DaniscoSA, Inc; Dr Jon DeVries, Generalills; Dr Gary Foster, University ofennsylvania; Dr Julie Jones, Collegef St Catherine; Dr Michael Lefevre,ennington Biomedical Researchenter; Dr David Lineback, Joint In-titute for Food Safety and Appliedutrition, (JIFSAN), University ofaryland; Dr Xavier Pi-Sunyer, Co-

umbia University; Dr Barbara Rolls,enn State University; Dr Barbarachneeman, Center for Food Safetynd Applied Nutrition (CFSAN), USood and Drug Administration (FDA);r Christine Williams, Columbianiversity.

eferences1. Freedman MR, King J, Kennedy E.

Popular diets: A scientific review.Obes Res. 2001;9(suppl 1):1S-40S.

2. Brehm BJ, Seeley RJ, Daniels SR,D’Alessio DA. A randomized trialcomparing a very low carbohydratediet and a calorie-restricted low fatdiet on body weight and cardiovas-cular risk factors in healthywomen. J Clin Endocrinol Metab.2003;88:1617-1623.

3. Dansinger ML, Gleason JA, Grif-fith JL, Selker HP, Schaefer EJ.Comparison of the Atkins, Or-nish, Weight Watchers, and Zonediets for weight loss and heartdisease risk reduction: A random-ized trial. JAMA. 2005;293:43-53.

4. Foster GD, Wyatt HR, Hill JO,McGurkin BG, Bill C, Moham-med BS, Szapary PO, Rader DJ,Edman JS, Kliein S. A random-ized trial of a low-carbohydratediet for obesity. N Engl J Med.

2003;348:2082-2090.

5. Samaha FF, Iqbal N, Seshadri P,Chicano KL, Daily DA, McGroryJ, Williams T, Williams M,Gracely EJ, Stern L. A low-carbo-hydrate as compared with a low-fat diet in severe obesity. N EnglJ Med. 2003;348:2074-2081.

6. Stern L, Iqbal N, Seshadri P, Chi-cano KL, Daily DA, McGrory J,Williams M, Gracely EJ, SamahaFF. The effects of low-carbohy-drate versus conventional weightloss diets in severely obeseadults: One-year follow-up of arandomized trial. Ann InternMed. 2004;140:778-785.

7. Yancy WS Jr, Olsen MK, CurtisLH, Schulman KA, Cuffe MS, Odd-one EZ. A low-carbohydrate, keto-genic diet versus a low-fat diet totreat obesity and hyperlipidemia:A randomized, controlled trial. AnnIntern Med. 2004;140:769-777.

8. Sondike SB, Copperman N, Ja-cobson MS. Effects of a low-carbo-hydrate diet on weight loss andcardiovascular risk factor in over-weight adolescents. J Pediatr.2003;142:253-258.

9. Willi SM, Oexmann MJ, WrightNM, Collop NA, Key LL Jr. Theeffects of a high protein, low fat,ketogenic diet on adolescentswith morbid obesity: Body compo-sition, blood chemistries, andsleep abnormalities. Pediatrics.1998;101:61-66.

0. Stallings VA, Archibald EH, Pen-charz PB, Harrison JE, Bell LE.One year follow-up of weight, to-tal body potassium, and totalbody nitrogen in obese adoles-cents treated with the protein-sparing modified fast. Am J ClinNutr. 1998;48:91-94.

1. Archibald EH, Harrison JE, Pen-charz PB. Effect of a weight-re-ducing high-protein diet on thebody composition of obese adoles-cents. Am J Dis Child. 1983;137:657-662.

2. Food Marketing Institute. Trendsin the United States: ConsumerAttitudes and the Supermarket.Washington, DC: Food MarketingInstitute; 2004.

3. Global New Products Database.Available at: www.gnpd.com. Ac-cessed March 27, 2005.

4. International Food InformationCouncil Foundation. Fitting di-etary carbohydrates into a

healthful diet—A consumer point

December 2006 ● Journal

of view. 2004. Available at: http://www.ific.org/research/upload/Fitting_Carbohydrates_into aHealthful_Diet.pdf. AccessedMarch 27, 2005.

5. NPD Group. Report on Carbohy-drate Consumption Patterns. PortWashington, NY: NPD Group;2005.

6. Department of Health and HumanServices, US Department of Agri-culture. Dietary Guidelines forAmericans 2005. Available at: http://www.health.gov/dietaryguidelines/dga2005/document/pdf/dga2005.pdf.Accessed April 2, 2005.

7. Federal Register 2002, Depart-ment of Health and Human Ser-vices, Food and Drug Administra-tion, 21 CFR Parts 101, Section101.62. Food labeling: Nutrientcontent claims for fat, fatty acid,and cholesterol content of foods.April 1, 2002, pp 104-113.

8. Federal Register 2002, Depart-ment of Health and Human Ser-vices, Food and Drug Administra-tion, 21 CFR Parts 101, Section101.61. Food labeling: Nutrientcontent claims for the sodiumcontent of foods. April 1, 2002, pp101-104.

9. Federal Register 1993, Depart-ment of Health and Human Ser-vices, Food and Drug Administra-tion, 21 CFR Parts 101 and 104.Food labeling: Reference Daily In-takes and Daily Reference Values.January 6, 1993, pp 2206-2228.

0. Labeling and consumer protec-tion: FSIS statement of interimpolicy on carbohydrate labelingstatements. Available at: http://www.fsis.usda.gov/OPPDE/larc/Policies/CarbLabel.htm. AccessedApril 2, 2005.

1. AACC International. AACC Inter-national Task Force holds open fo-rum on proposed definitions re-lated to glycemic carbohydrates,April 6, 2005 press release. Avail-able at: http://www.aaccnet.org/news/GlycemicDefinitions.asp. Ac-cessed April 2, 2005.

2. AOAC official methods. Availableat: http://eoma.aoac.org/. AccessedApril 2, 2005.

3. Lilla Z, Sullivan D, Ellefson W,Welton K, Crowley R. Determina-tion of “net carbohydrates” usinghigh-performance anion exchangechromatography. J AOAC Int.

2005;88:714-719.

of the AMERICAN DIETETIC ASSOCIATION 2093

2

2

2

2

2

2

3

3

3

3

3

3

3

3

3

3

4

4

4

4

4

4

4

4

4

4

5

5

5

5

5

5

OF PROFESSIONAL INTEREST

2

4. Wolever TM, Vorster HH, Bjorck I,Brand-Miller J, Brighenti F, MannJI, Ramdath DD, Granfeldt Y, HoltS, Perry TL, Venter C, Xiaomei W.Determination of the glycaemic in-dex of foods: Interlaboratory study.Eur J Clin Nutr. 2003;57:475-482.

5. Foreyt JP, Goodrick GK. LivingWithout Dieting. New York:Warner Books; 1994.

6. Landers PS, Landers TL. Sur-vival analysis of dropout patternsin dieting clinical trials. JADA.2004;104:1586-1588.

7. Hill JO, Wing RR. Long-termmaintenance of weight loss. In:Medeiros-Neto G, Halpern A, Bou-chard C, eds. Progress in ObesityResearch. Montrouge, France: JohnLibby Eurotext; 2003:1026-1029.

8. Golay A, Allaz AF, Morel Y,deTonnac N, Tankova S, ReavenGM. Similar weight loss withlow- or high-carbohydrate diets.Am J Clin Nutr. 1996;63:174-178.

9. Rabast U, Kasper H, SchonbornJ. Comparative studies in obesesubjects fed carbohydrate-re-stricted and high carbohydrate1,000-calorie formula diets. NutrMetab. 1978;22:269-277.

0. Pi-Sunyer FX. Glycemic indexand disease. Am J Clin Nutr.2002;76(suppl):290S-298S.

1. Liese AD, Schulz M, Fang F,Wolever TMS, D’Agostino RB Jr.,Sparks KC, Mayer-Davis EJ. Di-etary glycemic index and glyce-mic load, carbohydrate and fiberintake, and measures of insulinsensitivity, secretion, and adipos-ity in the Insulin Resistance Ath-erosclerosis Study. Diabetes Care.2005;28:2832-2838.

2. Lau C, Faerch K, Glumer C,Tetens I, Pedersen O, CarstensenB, Jorgensen T, Borch-JohnsenK. Dietary glycemic index, glyce-mic load, fiber, simple sugars,and insulin resistance: The In-ter99 Study. Diabetes Care. 2005;28:1397-1403.

3. Salmeron J, Ascherio A, RimmEB, Colditz GA, Spiegelman D,Jenkins DJ, Stampfer MJ, WingAL, Willett WC. Dietary fiber,glycemic load, and risk of NIDDMin men. Diabetes Care. 1997;20:545-550.

4. Salmeron J, Manson JE, StampferMJ, Colditz GA, Wing AL, WillettWC. Dietary fiber, glycemic load,

and risk of non-insulin-dependent

094 December 2006 Volume 106 Number 12

diabetes mellitus in women.JAMA. 1997;277:472-477.

5. Campbell PJ, Carlson MG. Im-pact of obesity on insulin actionin NIDDM. Diabetes. 1993;42:405-410.

6. Pouliot MC, Despres JP, NadeauA, Moorjani S, Prud’Homme D, Lu-pien PJ, Tremblay A, Bouchard C.Visceral obesity in men. Associa-tions with glucose tolerance,plasma insulin, and lipoproteinlevels. Diabetes. 1992;41:826-834.

7. Sigal RJ, El-Hashimy M, MartinBC, Soeldner JS, Krolewski AS,Warram JH. Acute postchallengehyperinsulinemia predicts weightgain: A prospective study. Diabe-tes. 1997;46:1025-1029.

8. Gerozissis K. Brain insulin andfeeding: A bi-directional commu-nication. Eur J Pharmacol. 2004;490:59-70.

9. Fryer JH, Moore NS, WilliamsHH, Young CM. A study of the in-terrelationship of the energy-yield-ing nutrients, blood glucose levels,and subjective appetite in man.J Lab Clin Med. 1955;45:684-696.

0. Peters CT, Choi YH, BrubakerPL, Anderson GH. A glucagon-like peptide-1 receptor agonistand an antagonist modify macro-nutrient selection by rats. J Nutr.2001;131:2164-2170.

1. Booth DA, Chase A, CampbellAT. Relative effectiveness of pro-tein in the late stages of appetitesuppression in man. Physiol Be-hav. 1970;5:1299-1302.

2. Marmonier C, Chapelot D, Louis-Sylvestre J. Effects of macronu-trient content and energy densityof snacks consumed in a satietystate on the onset of the nextmeal. Appetite. 2000;34:161-168.

3. Hall WL, Millward DJ, Long SJ,Morgan LM. Casein and whey ex-ert different effects on plasmaamino acid profiles, gastrointesti-nal hormone secretion and appe-tite. Br J Nutr. 2003;89:239-248.

4. Anderson GH, Moore SE. Dietaryproteins in the regulation of foodintake and body weight in hu-mans. J Nutr. 2004;134:974S-979S.

5. Uhe AM, Collier GR, O’Dea K. Acomparison of the effects of beef,chicken and fish protein on sati-ety and amino acid profiles inlean male subjects. J Nutr. 1992;

122:467-472.

6. Layman DK, Baum JI. Dietaryprotein impact on glycemic con-trol during weight loss. J Nutr.2004;134:968S-973S.

7. Anderson GH, Li ET. Protein andamino acids in the regulation ofquantitative and qualitative as-pects of food intake. Int J Obes.1987;11(suppl 3):97-108.

8. Anderson GH, Moore SE. Dietaryproteins in the regulation of foodintake and body weight in hu-mans. J Nutr. 2004;134:974S-979S.

9. Stubbs RJ, Johnstone AM,O’Reilly LM, Barton K, Reid C.The effect of covertly manipulat-ing the energy density of mixeddiets on ad libitum food intake in‘pseudo free-living’ humans. Int JObes Relat Metab Disord. 1998;22:980-987.

0. Kral TV, Rolls BJ. Energy den-sity and portion size: Their inde-pendent and combined effects onenergy intake. Physiol Behav.2004;82:131-138.

1. Rolls BJ, Bell EA. Dietary ap-proaches to the treatment of obe-sity. Med Clin North Am. 2000;84:401-418, vi.

2. Mensink RP, Zock PL, Kester AD,Katan MB. Effects of dietaryfatty acids and carbohydrates onthe ratio of serum total to HDLcholesterol and on serum lipidsand apolipoproteins: A meta-analysis of 60 controlled trials.Am J Clin Nutr. 2003;77:1146-1155.

3. Brinkworth GD, Noakes M, Ke-ogh JB, Luscombe ND, WittertGA, Clifton PM. Long-term ef-fects of a high-protein, low-carbo-hydrate diet on weight controland cardiovascular risk markersin obese hyperinsulinemic sub-jects. Int J Obes Relat Metab Dis-ord. 2004;28:661-670. Erratumin: Int J Obes Relat Metab Disord.2004;28:1187.

4. Skov AR, Toubro S, Ronn B,Holm L, Astrup A. Randomizedtrial on protein vs carbohydratein ad libitum fat reduced diet forthe treatment of obesity. Int JObes Relat Metab Disord. 1999;23:528-536.

5. Adam-Perrot A, Clifton P, BrounsF. Low-carbohydrate diets: Nutri-tional and physiological aspects.

Obes Rev. 2006;7:49-58.