Comparison of the Atkins, Zone, Ornish, and LEARN Diets for Change in Weight and Related Risk Factors Among Overweight Premenopausal Women The A TO Z Weight Loss Study: A Randomized Trial Context Popular diets, particularly those low in carbohydrates, have challenged cur-
rent recommendations advising a low-fat, high-carbohydrate diet for weight loss. Po-
tential benefits and risks have not been tested adequately. Objective To compare 4 weight-loss diets representing a spectrum of low to high carbohydrate intake for effects on weight loss and related metabolic variables. Design, Setting, and Participants Twelve-month randomized trial conducted in
the United States from February 2003 to October 2005 among 311 free-living, over-
weight/obese (body mass index, 27-40) nondiabetic, premenopausal women. Intervention Participants were randomly assigned to follow the Atkins (n=77), Zone (n=79), LEARN (n=79), or Ornish (n=76) diets and received weekly instruction for 2
THEONGOINGOBESITYEPI- months,thenanadditional10-monthfollow-up. Main Outcome Measures Weight loss at 12 months was the primary outcome.
Secondary outcomes included lipid profile (low-density lipoprotein, high-density lipo-
protein, and non–high-density lipoprotein cholesterol, and triglyceride levels), per-
centage of body fat, waist-hip ratio, fasting insulin and glucose levels, and blood pres-sure. Outcomes were assessed at months 0, 2, 6, and 12. The Tukey studentized range
tional dietary weight loss guidelines (ie,
test was used to adjust for multiple testing.
energy-restricted, low in fat, high in car-bohydrate)7 have been challenged, par-
Results Weight loss was greater for women in the Atkins diet group compared with
the other diet groups at 12 months, and mean 12-month weight loss was significantlydifferent between the Atkins and Zone diets (PϽ.05). Mean 12-month weight loss
was as follows: Atkins, −4.7 kg (95% confidence interval [CI], −6.3 to −3.1 kg), Zone,
−1.6 kg (95% CI, −2.8 to −0.4 kg), LEARN, −2.6 kg (−3.8 to −1.3 kg), and Ornish,
−2.2 kg (−3.6 to −0.8 kg). Weight loss was not statistically different among the Zone,
LEARN, and Ornish groups. At 12 months, secondary outcomes for the Atkins group
were comparable with or more favorable than the other diet groups.
h i g h - c a r b o h y d r a t e w e i g h t - l o s s
Conclusions In this study, premenopausal overweight and obese women assigned
to follow the Atkins diet, which had the lowest carbohydrate intake, lost more weight
and experienced more favorable overall metabolic effects at 12 months than women
assigned to follow the Zone, Ornish, or LEARN diets. While questions remain about
long-term effects and mechanisms, a low-carbohydrate, high-protein, high-fat diet
may be considered a feasible alternative recommendation for weight loss. Trial Registration clinicaltrials.gov Identifier: NCT00079573
were limited by combinations of smallsample sizes, high rates of attrition,
Author Affiliations: Stanford Prevention Research Cen- ter and the Department of Medicine, Stanford Uni-
stantially different diets and 1 diet based
versity Medical School, Stanford, Calif. Corresponding Author: Christopher D. Gardner,
PhD, Hoover Pavilion, N229, 211 Quarry Rd,Stanford, CA 94305-5705 (cgardner@stanford
2007 American Medical Association. All rights reserved.
(Reprinted) JAMA, March 7, 2007—Vol 297, No. 9 969
diet books: Dr Atkins’ New Diet Revo-
cific goals for energy restriction, while
ships, and Nutrition; low in fat, high in
lution,8 Enter the Zone,9 The LEARNManual for Weight Management,18 or Eat
were no specific energy restriction goals.
classes led by a registered dietitian once
gest multiple strategies, such as relapse
Participants
Participants were recruited from the local
“strongly disagree” to “strongly agree,”
aged 25 to 50 years were invited to enroll
Process and Outcome Measures Diet and Physical Activity Data. Di-
etary intake data were collected by tele-
the other 3 diet groups. Efforts to maxi-
tions); type 1 or 2 diabetes mellitus; heart,
renal, or liver disease; cancer or active
apolis). Data collectors were trained and
month data collection, respectively.
expenditure; alcohol intake of at least 3
for 20 g/d or less of carbohydrate for “in-
within the next year. Race/ethnicity data
duction” (usually 2-3 months) and 50 g/d
quent “ongoing weight loss” phase. The
ancillary analyses of subgroups. All study
drate, protein, and fat, respectively. The
Anthropometric Data. Height was Intervention
10% energy from saturated fat, caloric re-
the nearest 0.1 kg on a calibrated clini-
striction, increased exercise, and behav-
diet book.8,9,18,19 The guidelines for the
970 JAMA, March 7, 2007—Vol 297, No. 9 (Reprinted)
2007 American Medical Association. All rights reserved. Metabolic Measures. Blood samples
fast. Plasma total cholesterol and triglyc-
established methods.22,23 High-density li-
mal distributions for testing; for ease of
coefficients of variation were all Յ3.1%).
Blood glucose was measured using amodification of the glucose oxidase/
Figure 1. Participant Flow Through the Trial
sured 3 times at 2-minute intervals asdescribed elsewhere30; the initial read-
Statistical Analyses
ing a spectrum of carbohydrate in-take, was more effective than any other
group difference in weight change was2.7 kg (6 lb, approximately 3% for a
to-treat methods with baseline valuescarried forward for missing values.
2007 American Medical Association. All rights reserved.
(Reprinted) JAMA, March 7, 2007—Vol 297, No. 9 971
(PϽ.001): −497 (SD, 496), −387 (SD,
were no significant interactions. All sta-
groups (P = .30). Participant ratings
tistical tests were 2-tailed using a sig-
tober 2005. FIGURE 1 shows partici-
pant flow; TABLE 1 shows baseline Dietary Intake and Energy Expenditure
LEARN (P = .05) (Table 2). At subse-
all) (TABLE 2). However, relative to
pattern, higher to lower intakes, wasstatistically significant for protein, fat,and saturated fat at all time points. Table 1. Baseline Participant Characteristics* All Diets Characteristics
significant mean increase (PϽ.05) in
energy expenditure at all time points for
Weight and Anthropometric Outcomes
−6.3 to −3.1 kg) for Atkins, −1.6 kg
(95% CI, −2.8 to −0.4 kg) for Zone, −2.2
(FIGURE 2). At the 2- and 6-month in-
Abbreviations: HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol. SI conversions: To convert LDL-C, HDL-C, and total cholesterol to mmol/L, multiply by 0.0259. To convert triglycerides to
mmol/L, multiply by 0.0113. To convert glucose to mmol/L, multiply by 0.0555.
*Data are expressed as mean (SD) unless otherwise indicated. †Calculated as weight in kilograms divided by height in meters squared.
groups (PϽ.05). Weight change among
972 JAMA, March 7, 2007—Vol 297, No. 9 (Reprinted)
2007 American Medical Association. All rights reserved. Ancillary Analyses of Diet Group Effects Independent of
mained statistically significant after in-
Changes in Weight
(P = .07) or waist-hip ratio (P = .10)
(TABLE 3).
using linear regression. Each of the sta-
signed to follow diets having higher car-
Lipid Outcomes Results generated by 84% of the study population (n = 262) with baseline Table 2. Mean Dietary Intake and Energy Expenditure by Diet Group and Time Point* P Value†
were not significant at any time point. Insulin, Glucose, and Blood Pressure Outcomes
month differences were significantly dif-
*Data presented are unadjusted raw data with no imputations for missing data. Standard deviations are presented in pa-
rentheses. Sample sizes for baseline and 2, 6, and 12 months, respectively, are: Atkins, n = 77, 73, 71, and 68; Zone,
n = 79, 73, 67, and 57; LEARN, n = 79, 73, 66, and 60; and Ornish, n = 76, 72, 67, and 56.
pressure was significantly greater for the
a,b,c,d When the analysis of variance (last column) was statistically significant (PϽ.05), all pairwise comparisons among diet
Atkins group than for any other group.
groups were tested for statistical significance using the Tukey studentized range test. Pairwise comparisons that weresignificantly different from one another are indicated by superscripts as follows: when the values for 2 diet groups within
For diastolic pressure, the only signifi-
a row do not share a common superscript, they are significantly different, whereas if the values do share a commonsuperscript, they are not significantly different.
2007 American Medical Association. All rights reserved.
(Reprinted) JAMA, March 7, 2007—Vol 297, No. 9 973 Figure 2. Weight Change Relative to
most consistent findings in recent trials
observed statistically significant differ-
able to at least 2 factors. One factor con-
these study conditions. The triglyceride-
Baseline values were carried forward for any missing
values. The overall diet groupϫtime interaction wassignificant (P
Ͻ.001). The analysis of variance test for
differences among diet groups in weight change from
baseline was significant at 2 and 6 months (PϽ.001),
and at 12 months (P=.01). Analyses of all pairwisedifferences by the Tukey standardized range test (Ͻ.05)
its inclusion criteria. A second likely fac-
indicate that the Atkins diet group was significantly
tor was differences in statistical power;
different than all other diet groups at 2 and 6 monthsand that the Atkins diet group was significantly dif-
ings are consistent with a beneficial in-
ferent than the Zone diet group at 12 months. There
were no significant differences among the Zone,LEARN, or Ornish diet groups at any time point. Er-
ror bars indicate standard error of the mean.
bolic risk factors at 2 and 6 months. The
finding of greater weight loss for the At-
tically adjusting for weight loss differ-
reaching statistical significance in com-
no significant differences in weight loss
level of significance was diminished.
not designed to specifically address this
fat, will adversely affect blood lipid lev-
in recent weight-loss diet trials. The re-
cent trials, like the current study, have
were greater for participants in the very-
974 JAMA, March 7, 2007—Vol 297, No. 9 (Reprinted)
2007 American Medical Association. All rights reserved. Table 3. Mean Changes in Secondary Outcomes Relative to Baseline, by Diet Group and Time* P Value Overall Diet Group ϫ Time† Months‡
SI conversions: To convert LDL-C, HDL-C, and total cholesterol to mmol/L, multiply by 0.0259. To convert triglycerides to mmol/L, multiply by 0.0113. To convert glucose to
*Intention-to-treat analysis, with baseline data carried forward for missing values. Standard deviations are presented in parentheses. For LDL-C, HDL-C, triglyceride,
non−HDL-C, insulin, and glucose data, results are presented for those with available blood sample data (84% of full sample): Atkins, n = 70; Zone, n = 65; LEARN, n = 63;and Ornish, n = 64.
†P value for diet group ϫ time interaction, determined using mixed-model and autoregressive covariance structure. ‡P values for 12-month change from baseline results, determined by analysis of variance. §Calculated as weight in kilograms divided by height in meters squared. a,bFor a given outcome measure at the 12-month time point, when the analysis of variance (last column) was statistically significant (PϽ.05), all pairwise comparisons among diet
groups were tested for statistical significance using the Tukey studentized range test. Pairwise comparisons that were significantly different from one another are indicated bysuperscripts as follows: when the values for 2 diet groups within a row do not share a common superscript, they are significantly different, whereas if the values do share acommon superscript, they are not significantly different.
2007 American Medical Association. All rights reserved.
(Reprinted) JAMA, March 7, 2007—Vol 297, No. 9 975
attrition rates, the contrast of 4 rather
differed significantly in composition be-
were attributable specifically to the low
weight-loss trials that substituted either
drate constant40,41 or protein for carbo-
stant,38,42,43 the higher-protein diets led
increase the external validity of the find-
at least as large as for any other dietary
pattern and that the lipid effects are un-
regardless of macronutrient content. Author Contributions: Drs Gardner and Balise had full
access to all of the data in the study and take respon-
sibility for the integrity of the data and the accuracyof the data analysis. Study concept and design: Gardner, Kraemer, King. Acquisition of data: Gardner. Analysis and interpretation of data: Gardner, Kiazand,
Alhassan, Kim, Stafford, Balise, Kraemer, King. Drafting of the manuscript: Gardner, Kiazand, Balise,Kraemer, King. Critical revision of the manuscript for important in-tellectual content: Gardner, Kiazand, Alhassan, Kim,Stafford, Kraemer, King. Statistical analysis: Gardner, Alhassan, Stafford, Balise,
Obtained funding: Gardner, King. Administrative, technical, or material support: Kiazand. Financial Disclosures: None reported. Funding/Support: This investigation was supported by
National Institutes of Health grant R21AT1098, by a
grant from the Community Foundation of Southeast-ern Michigan, and by Human Health Service grant
M01-RR00070, General Clinical Research Centers, Na-
tional Center for Research Resources, National Insti-
level.4-6,45,46 Greater success with long-
tutes of Health. Role of the Sponsor: None of the funding agencies
played any role in the design and conduct of the study;
collection, management, analysis, and interpretationof the data; or preparation, review, and approval of
Acknowledgment: We gratefully acknowledge the work of the study staff who worked with participants in re-
cruitment, intervention, and data collection, including
Rise Cherin, MS, RD, Kathryn Newell, MS, Suzanne Ol-son, MS, Jennifer Morris, PhD, Jane Borchers, MS, RD,
diture (ie, regular physical activity), and
CONCLUSIONS
Laurie Ausserer, MS, Ellen DiNucci, MA, Kelly Boying-
ton, Jana Stone, Andrea Vaccarella, RD, Noel Segali,
tal factors, such as portion sizes of res-
RD, and Gretchen George, MS, RD, all of Stanford Uni-versity, as well as the staff of the Stanford University
Hospital General Clinical Research Center. 976 JAMA, March 7, 2007—Vol 297, No. 9 (Reprinted)
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2007 American Medical Association. All rights reserved.
(Reprinted) JAMA, March 7, 2007—Vol 297, No. 9 977
Table 4, the Reynolds Risk Score correctly results in an ab-
Financial Disclosures: Dr Ridker reports that he currently or in the past 5 years has received research funding support from multiple not-for-profit entities includ-
solute increase in the number who would be recom-
ing the National Heart, Lung, and Blood Institute, the National Cancer Institute,
mended for treatment when thresholds are set at either 20%
the American Heart Association, the Doris Duke Charitable Foundation, the Leducq
10-year risk or at 10% 10-year risk, thus achieving a net clini-
Foundation, the Donald W. Reynolds Foundation, and the James and Polly An-nenberg La Vea Charitable Trusts. Dr Ridker also reports that currently or in the
cal benefit. As with any risk classification system, perfect
past 5 years he has received investigator-initiated research support from multiple
prediction will not be achieved, but an overall improve-
for-profit entities including AstraZeneca, Bayer, Bristol-Myers Squibb, Dade-Behring, Novartis, Pharmacia, Roche, Sanofi-Aventis, and Variagenics. Dr Ridker
ment in the targeting of prescription drugs to those women
reports being listed as a coinventor on patents held by the Brigham and Women’s
with the most appropriate levels of risk should help maxi-
Hospital that relate to the use of inflammatory biomarkers in cardiovascular dis-ease and has served as a consultant to Schering-Plough, Sanofi/Aventis, Astra-
mize benefits while minimizing cost and toxicity. Wang et
Zeneca, Isis Pharmaceutical, Dade-Behring, and Vascular-Biogenics. Dr Cook re-
al are also concerned about the use of self-reported blood
ports having received funding from the National Heart, Lung, and Blood Institute,the National Cancer Institute, and Roche Diagnostics, and has served as a con-
pressure, weight, diabetes, and smoking. However, these vari-
ables show a similar magnitude of prediction in our data as
1. Hosmer DW, Lemeshow S. Goodness of fit tests for the multiple logistic re-
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With regard to comments from Dr Stevens and Ms Cole-
2. D’Agostino RB, Griffith JL, Schmidt CH, Terrin N. Measures for evaluating model performance. In: American Statistical Association 1996 Proceedings of the Sec-
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tion on Biometrics, Chicago, IL, August 1996. Alexandria, VA: American Statisti-
ten used in clinical practice, Table 4 shows superiority of
cal Association; 1997:253-258. 3. Salomaa V, Harold K, Sundvill J, Jousilahti P. Brain natriuretic peptide as a pre-
the new models built using the same population and out-
dictor of coronary and cardiovascular events and all-cause deaths in general popu-
come definition. We acknowledge that external validation,
lation [abstract]. Circulation. 2007;115(8):e269.
using different cohorts, would be a useful next step. It istrue that the Hosmer-Lemeshow statistic can be consid-ered a general measure of goodness of fit.1 However, since
CORRECTIONS
it directly compares observed with expected events, it is more
Incorrect Wording and Data Error: In the Original Contribution entitled “Com-
sensitive to recalibration than most other measures, par-
parison of the Atkins, Zone, Ornish, and LEARN Diets for Change in Weight and
ticularly the c-statistic, and is often treated as a measure of
Related Risk Factors Among Overweight Premenopausal Women: The A TO ZWeight Loss Study: A Randomized Trial” published in the March 7, 2007, issue of
JAMA (2007;297(9):969-977), a sentence was incorrectly worded in the ab-
We do not concur with Dr Daniels and colleagues that
stract, and data were reported incorrectly in the text. On page 969, in the “Con-clusions” section of the abstract, the first sentence should have read “In this study,
epidemiologic data on natriuretic peptides support the
premenopausal overweight and obese women assigned to follow the Atkins diet,
use of this biomarker in healthy populations. Of the
which had the lowest carbohydrate intake, had lost more weight at 12 monthsthan those assigned to the Zone diet, and had experienced comparable or more
articles cited, most included prevalent myocardial infarc-
favorable metabolic effects than those assigned to follow the Zone, Ornish, or LEARN
tion at baseline or evaluated elderly cohorts without
diets.” On page 972, in the last paragraph, the mean 12-month weight changesfor the LEARN and Ornish diets were reversed: for LEARN it should have been
adequate exclusion of prior cardiovascular events. More
−2.6 kg (95% CI, −3.8 to −1.3 kg) and for Ornish it should have been −2.2 kg
recent data suggest that B-type natriuretic peptide does
not predict cardiovascular events among those free of dis-
Incorrect Prevalence: In the Editorial entitled “Mandatory HPV Vaccination: Pub-
lic Health vs Private Wealth” published in the May 2, 2007, issue of JAMA (2007;297(17):1921-1923), 2 sentences regarding HPV prevalence were inaccurate. On
Paul M Ridker, MD
page 1921, in the second paragraph, the second to last sentence should read: “Al-
[email protected]
though infection with high-risk HPV types . . . high-risk types 16 and 18 have a
Nancy R. Cook, ScD
relatively low prevalence (2.3% among screened females),4 and not all wom-en. . . . ” Also on page 1921, second column, the last paragraph on the page should
Brigham and Women’s Hospital
read: “Given that the overall prevalence of HPV vaccine types associated with cer-
Boston, Massachusetts
vical cancer is relatively low (2.3%). . . . ”
178 JAMA, July 11, 2007—Vol 298, No. 2 (Reprinted)
2007 American Medical Association. All rights reserved.
Table 4, the Reynolds Risk Score correctly results in an ab-
Financial Disclosures: Dr Ridker reports that he currently or in the past 5 years has received research funding support from multiple not-for-profit entities includ-
solute increase in the number who would be recom-
ing the National Heart, Lung, and Blood Institute, the National Cancer Institute,
mended for treatment when thresholds are set at either 20%
the American Heart Association, the Doris Duke Charitable Foundation, the Leducq
10-year risk or at 10% 10-year risk, thus achieving a net clini-
Foundation, the Donald W. Reynolds Foundation, and the James and Polly An-nenberg La Vea Charitable Trusts. Dr Ridker also reports that currently or in the
cal benefit. As with any risk classification system, perfect
past 5 years he has received investigator-initiated research support from multiple
prediction will not be achieved, but an overall improve-
for-profit entities including AstraZeneca, Bayer, Bristol-Myers Squibb, Dade-Behring, Novartis, Pharmacia, Roche, Sanofi-Aventis, and Variagenics. Dr Ridker
ment in the targeting of prescription drugs to those women
reports being listed as a coinventor on patents held by the Brigham and Women’s
with the most appropriate levels of risk should help maxi-
Hospital that relate to the use of inflammatory biomarkers in cardiovascular dis-ease and has served as a consultant to Schering-Plough, Sanofi/Aventis, Astra-
mize benefits while minimizing cost and toxicity. Wang et
Zeneca, Isis Pharmaceutical, Dade-Behring, and Vascular-Biogenics. Dr Cook re-
al are also concerned about the use of self-reported blood
ports having received funding from the National Heart, Lung, and Blood Institute,the National Cancer Institute, and Roche Diagnostics, and has served as a con-
pressure, weight, diabetes, and smoking. However, these vari-
ables show a similar magnitude of prediction in our data as
1. Hosmer DW, Lemeshow S. Goodness of fit tests for the multiple logistic re-
gression model. Commun Stat Theor Methods. 1980;A9:1043-1069.
With regard to comments from Dr Stevens and Ms Cole-
2. D’Agostino RB, Griffith JL, Schmidt CH, Terrin N. Measures for evaluating model performance. In: American Statistical Association 1996 Proceedings of the Sec-
man, while Table 5 compares fit using the model most of-
tion on Biometrics, Chicago, IL, August 1996. Alexandria, VA: American Statisti-
ten used in clinical practice, Table 4 shows superiority of
cal Association; 1997:253-258. 3. Salomaa V, Harold K, Sundvill J, Jousilahti P. Brain natriuretic peptide as a pre-
the new models built using the same population and out-
dictor of coronary and cardiovascular events and all-cause deaths in general popu-
come definition. We acknowledge that external validation,
lation [abstract]. Circulation. 2007;115(8):e269.
using different cohorts, would be a useful next step. It istrue that the Hosmer-Lemeshow statistic can be consid-ered a general measure of goodness of fit.1 However, since
CORRECTIONS
it directly compares observed with expected events, it is more
Incorrect Wording and Data Error: In the Original Contribution entitled “Com-
sensitive to recalibration than most other measures, par-
parison of the Atkins, Zone, Ornish, and LEARN Diets for Change in Weight and
ticularly the c-statistic, and is often treated as a measure of
Related Risk Factors Among Overweight Premenopausal Women: The A TO ZWeight Loss Study: A Randomized Trial” published in the March 7, 2007, issue of
JAMA (2007;297(9):969-977), a sentence was incorrectly worded in the ab-
We do not concur with Dr Daniels and colleagues that
stract, and data were reported incorrectly in the text. On page 969, in the “Con-clusions” section of the abstract, the first sentence should have read “In this study,
epidemiologic data on natriuretic peptides support the
premenopausal overweight and obese women assigned to follow the Atkins diet,
use of this biomarker in healthy populations. Of the
which had the lowest carbohydrate intake, had lost more weight at 12 monthsthan those assigned to the Zone diet, and had experienced comparable or more
articles cited, most included prevalent myocardial infarc-
favorable metabolic effects than those assigned to follow the Zone, Ornish, or LEARN
tion at baseline or evaluated elderly cohorts without
diets.” On page 972, in the last paragraph, the mean 12-month weight changesfor the LEARN and Ornish diets were reversed: for LEARN it should have been
adequate exclusion of prior cardiovascular events. More
−2.6 kg (95% CI, −3.8 to −1.3 kg) and for Ornish it should have been −2.2 kg
recent data suggest that B-type natriuretic peptide does
not predict cardiovascular events among those free of dis-
Incorrect Prevalence: In the Editorial entitled “Mandatory HPV Vaccination: Pub-
lic Health vs Private Wealth” published in the May 2, 2007, issue of JAMA (2007;297(17):1921-1923), 2 sentences regarding HPV prevalence were inaccurate. On
Paul M Ridker, MD
page 1921, in the second paragraph, the second to last sentence should read: “Al-
[email protected]
though infection with high-risk HPV types . . . high-risk types 16 and 18 have a
Nancy R. Cook, ScD
relatively low prevalence (2.3% among screened females),4 and not all wom-en. . . . ” Also on page 1921, second column, the last paragraph on the page should
Brigham and Women’s Hospital
read: “Given that the overall prevalence of HPV vaccine types associated with cer-
Boston, Massachusetts
vical cancer is relatively low (2.3%). . . . ”
178 JAMA, July 11, 2007—Vol 298, No. 2 (Reprinted)
2007 American Medical Association. All rights reserved.
M A SURI DE PROTEC T IE PERSONAL A ÎMPOTRIVA INFEST A RII CU C A PU S E 1 Purtarea unor haine dechise la culoare cu pantaloni lungi introdusi în sosete de culoare deschisa si textura mai deasa. 2 Purtarea unor pantofi sport deschisi la culoare fara orificii sau decupaje; papucii/ sandalele sunt excluse. 3 Utilizarea DEET (Dietil toluamida) drept repelent prin aplicare pe pielea ce va ven
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