Edulcorantes são seguros para gestantes, lactantes...

“Edulcorantes são seguros para gestantes, lactantes e crianças ?”

NORBERTO DAMIAN GIGLIO MSCDivisión Epidemiologia

Hospital de Niños Ricardo GutiérrezCiudad de Buenos Aires

Instituto Sabin Pfizer Sanofi PasteurMerckPAHO

“Cada avance en la ciencia nos aleja más de las uniformidades crudas que son

observadas al principio, y el círculo de factores causales es cada vez mayor”

Mysticism and Logic, London: Longmans, Green, 1918, pág. 188, citado en E.H. Carr, What is history,NY: Knopf, 1963, pág. 118.

Relación o asociaciones causales

Factor Enfermedad

Factor Enfermedad

Factor A Factor B Factor C+ Enfermedad

Factor A Factor B Factor Co o Enfermedad

Fact

or

A

Fact

or

B

Fact

or

C

Fact

or

D

Enfermedad…o

+

+ +

Epidemiología Clínica

Estimated Global, Regional, and NationalDisease Burdens Related to Sugar-SweetenedBeverage Consumption in 2010 Circulation. (2)

Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. (1)


Bases Moleculares

Modelización y el reporte de resultados subjetivos

Aspartame consumption in relation to childhood brain tumor risk: results from a case-control study. (3)

(1) Abou-Donia MB, El-Masry EM, Abdel-Rahman AA, McLendon RE, Schiffman SS.J Toxicol Environ Health A. 2008;71(21):1415-29. doi: 10.1080/15287390802328630(2) 2015;CIRCULATIONAHA.114.010636, published online before print June 29, 2015 http://dx.doi.org/10.1161/CIRCULATIONAHA.114.010636(3) J Natl Cancer Inst. 1997 Jul 16;89(14):1072-4. Gurney JG1, Pogoda JM, Holly EA, Hecht SS, Preston-Martin.

http://dx.doi.org/10.1161/CIRCULATIONAHA.114.010636


Huérfanos de Tratamiento(therapeutic orphan)1-2

• Neonatos

• Niños

• Mujeres durante el período de embarazo

• Adultos mayores

1.The Therapeutic Orphan- 30 years later. A Joint Conference of the Pediatric Pharmacology Research Unit Network; The European

Society of Developmental Pharmacology and the National Institute of Health and Human Development Held- Washington; DC. May 2,

1997. Pediatrics.Vol 104; 3. September 1999.

2. Wilson J. An update on the Therapeutic Orphan. Pediatrics;1999.104:585-590

Metabolismo CYP3A4 CYP2D6 (niños)

Kearns, G.L. N Engl J Med 2003;349:1157-1167Fig. 2

Epidemiología Clínica Significant Changes in the Expression of P-gp, CYP3A, and CYP2D Subsequent

to Sucralose Ingestion (Delivered in Splenda) Relative to Control (No Sucralose) in Rat

P-gp CYP3A CYP2D

Sucralosedosage(mg/kg/d)

Treatment 1.1 — — —3.3 ↑143.5% ↑43.5% ↑36.7% 5.5 ↑122.6% ↑70.0% ↑152.1% 11 ↓64% ↑151.3% ↑249.3%

Recovery 1.1 — — —3.3 ↑16% — —5.5 ↑56.8% — ↑32.9% 11 ↑82.2% ↑22.4% ↑22.1%

Note. Data from Abou-Donia et al. (2008).

J Toxicol Environ Health B Crit Rev. 2013 Sep; 16(7): 399–451.Fig. 1

BMJ. 2004 Jun19;328(7454):1490.Grading quality of evidence and strength of recommendations.

“Edulcorantes são seguros para gestantes, lactantes e crianças ?”

Modulación de receptores gustativos, neurotransmisores

cerebrales y compensación energética

Modificación de la microbiotaintestinal

Metabolitos intermedios

Neoplasias

partos prematuros

Exposure to non-nutritive sweeteners during pregnancy and lactation: Impact in programming of metabolic diseases in the progenylater in life Reproductive Toxicology 49 (2014) 196–201 Araujo et al

ObesidadS.Metabolico

ObesidadS.Metabolico

Aumento de Interleukinas

Corioamnionitis partos prematuros

Artificial sweeteners—do they bear a carcinogenic risk?

Annals of Oncology 15: 1460–1465, 2004

doi:10.1093/annonc/mdh256M. R. Weihrauch* & V. DiehlDepartment of Internal Medicine I of the University of Cologne, Cologne, Germany

.

Handbook of Basic Pharmacokinetics 5th EditionWolfgang A. Ritschel and Gregory L. Kearns

Dosis / respuesta

Sin efecto adverso observado (NOAEL)

Efecto adverso observado mas bajo (LOAEL)

0

500

1000

1500

2000

2500

3000

3500

4000

4500

Categoría 1

Consumo de Aspartamo comparado con IDA

NOAEL ( 4.000mg/kg/dia) IDA (40mg/kg/dia) consumo medio UE (4 mg/kg/dia)

Exposure to non-nutritive sweeteners during pregnancy and lactation: Impact in programming of metabolic diseases in the progeny later in life.Araújo JR, Martel F, Keating E.Reprod Toxicol. 2014 Nov;49:196-201. doi: 10.1016/j.reprotox.2014.09.007. Epub 2014 Sep 28

Fig. 11

*Includes only children born in 1981 or later. OR 4 odds ratio; CI 4 confidence interval. †Questions were asked about the child’s consumption of aspartame or NutraSweet, including age at first consumption, time period of consumption, and frequency of consumption, for any food, chewing gum, or diet drink. ‡The reference category is those with no reported consumption. ORs are adjusted for the study site, sex, age at diagnosis or reference date, and birth year.

J Natl Cancer Inst. 1997 Jul 16;89(14):1072-4.Aspartame consumption in relation to childhood braintumor risk: results from a case-control study.Gurney JG1, Pogoda JM, Holly EA, Hecht SS, Preston-Martin S.

Aspartame consumption in relation to brain tumor risk in children*Case patients (n = 56) Control subjects (n = 94) Unadjusted Adjusted†

Aspartame consumption No. % No. % OR 95% CI OR 95% CIAll sources‡ 17 30 26 28 1.1 0.6-2.4 1.1 0.5-2.6Age at first consumption, y <3 7 13 12 13 1.0 0.4-2.8 1.0 0.3-3.1 3-7 10 18 13 14 1.3 0.5-3.3 1.2 0.4-3.6 Years of consumption <2 9 16 14 15 1.1 0.4-2.8 1.2 0.4-3.3

≥2 8 14 11 12 1.3 0.5-3.4 1.1 0.3-3.4

Frequency of consumption (times/wk) <1 7 13 8 9 1.5 0.5-4.5 1.6 0.5-5.2 ≥ 1 10 18 18 19 1.0 0.4-2.3 0.9 0.3-2.4Diet drinks 9 16 19 20 0.8 0.3-1.8 0.9 0.3-2.4 Age at first consumption, y <3 4 7 8 9 0.8 0.2-2.8 0.8 0.2-3.13-8 5 9 10 11 0.8 0.3-2.5 1.0 0.3-3.4 Years of consumption <2 4 7 10 11 0.6 0.2-2.2 0.8 0.2-3.1 ≥ 2 5 9 8 9 1.0 0.3-3.2 0.9 0.3-3.4 Frequency of consumption (times/wk) <1 5 9 8 9 1.0 0.3-3.2 1.2 0.3-4.5 ≥ 1 4 7 11 12 0.6 0.2-1.9 0.6 0.2-2.3

VII

Fig. 12

*Includes only pregnancies in 1981 and later. OR 4 odds ratio; CI 4 confidence interval. †The reference category is those with no reported consumption. ORs are adjusted for study site, sex, age at diagnosis or reference date, and birth year. ‡Questions were asked about the mother’s consumption of aspartame or NutraSweet, including trimesters of consumption, time period of consumption, and frequency of consumption, for any food, chewing gum, or diet drink during pregnancy or while breast-feeding. §Categories are not mutually exclusive.

J Natl Cancer Inst. 1997 Jul 16;89(14):1072-4.Aspartame consumption in relation to childhood brain tumor risk: results from a case-control study.

Gurney JG1, Pogoda JM, Holly EA, Hecht SS, Preston-Martin S.

Maternal aspartame consumption during pregnancy* and breast-feeding in relation to brain tumor risk in childrenCase patients (n = 49) Control subjects (n = 90) Unadjusted Adjusted†

Aspartame consumption No. % No. % OR 95% CI OR 95% CIAll sources‡,§ 9 18 22 24 0.7 0.3-1.6 0.7 0.3-1.7Consumption during

pregnancy, trimester 7 14 19 21 0.6 0.2-1.6 0.6 0.2-1.71st 6 12 18 20 0.6 0.2-1.5 0.6 0.2-1.6 2nd 7 14 18 20 0.7 0.3-1.7 0.7 0.3-18 3rd 6 12 18 20 0.6 0.2-1.5 0.6 0.2-1.6 Consumption during

breast-feeding 5 10 14 16 0.6 0.2-1.8 0.7 0.2-2.0Diet drinks§ 5 10 11 12 0.8 0.3-2.5 0.9 0.3-2.8Consumption during

pregnancy, trimester 3 6 9 10 0.6 0.2-2.3 0.7 0.2-2.71st 3 6 9 10 0.6 0.2-2.3 0.7 0.2-2.7

2nd 3 6 6 7 0.9 0.2-3.9 1.1 0.3-5.13rd 2 4 7 8 0.5 0.1-2.6 0.6 0.1-3.2Consumption during

breast feeding 4 8 8 9 0.9 0.3-3.2 1.1 0.3-4.0

Fig. 13

The Use of Low-Calorie Sweeteners by Children:Implications for Weight ManagementJohn Foreyt, Ronald Kleinman, Rebecca J. Brown, and Rachel Lindstrom

American Society for Nutrition. 1155S

First published online May 9, 2012; doi:10.3945/jn.111.149609.

www.elsevier.com/locate/appetResearch report Metabolic and feeding behavior alterations provoked by prenatal exposure to aspartame☆E. von Poser Toigo*, A.P. Huffell, C.S. Mota, D. Bertolini, L.F. Pettenuzzo, C. Dalmaz - 169E.V.P. Toigo et al./Appetite 87 (2015) 168–174

(A) weight gain of males is represented on the left Y scale and of females is on the right Y scale; (B) Gonadal fat weight; (C) retroperitoneal fat weight; (D) total abdominal fat weight. # different from all other groups.

Effect of chronic consumption of sweeteners by mother on adult offspring weight gain and fat after 30 days of free access to chocolate

Fig. 23

http://www.elsevier.com/locate/appet

www.elsevier.com/locate/appetResearch report Metabolic and feeding behavior alterations provoked by prenatal exposure to aspartame☆E. von Poser Toigo*, A.P. Huffell, C.S. Mota, D. Bertolini, L.F. Pettenuzzo, C. Dalmaz - 169E.V.P. Toigo et al./Appetite 87 (2015) 168–174

(A) Total cholesterol;(B) LDL;(C) HDL;(D) triglycerides.*Different from control group; # different from all other groups.

Effect of chronic consumption of sweeteners by mother on adult offspring lipid profile

Fig. 24

http://www.elsevier.com/locate/appet

JAMA Pediatr. doi:10.1001/jamapediatrics.2016.0301 Published online May

9, 2016.

Maternal and Infant Characteristics According to Maternal Consumption of ASBs and SSBs During Pregnancy

Frequency of Beverage Consumption, Mean (SD) <1/mo ≤1/wk 2-6/wk ≥1/d P Value

Characteristic

Total,No. (%) 1702 (70.5) 404 (16.7) 185 (7.7) 122 (5.1) Maternalage,y 32.4 (4.6) 32.7 (4.7) 32.0 (4.3) 32.5 (4.7) .32 MaternalBMI 24.2 (5.0) 25.5 (5.5) 26.5 (6.6) 28.0 (6.5) <.001 Maternaldietquality,HEIscore/100 73.1 (8.6) 73.9 (7.7) 72.2 (9.0) 71.6 (7.7) .02 Maternalenergyintake,cal/d 2016 (706) 1969 (681) 1985 (699) 2050 (877) .57 Infantbirthweight,g 3461 (480) 3463 (468) 3395 (553) 3482 (409) .33 Infantgestationalage,wk 39.2 (1.4) 39.2 (1.4) 39.1 (1.5) 39.0 (1.3) .18 Breastfeedingdurationinfirstyear,mo 9.1 (4.0) 8.7 (4.0) 7.9 (4.2) 6.7 (4.6) <.001 Introductionofsolidfoods<4mo,No.(%) 305 (17.9) 79 (19.6) 39 (21.1) 34 (27.9) .04 Maternalsmokinginpregnancy,No. (%) 113 (6.6) 29 (7.2) 25 (13.5) 24 (19.7) <.001 Maternaldiabetesinpregnancy,No. (%)b 78 (4.6) 26 (6.4) 16 (8.6) 21 (17.2) <.001 Maternalpostsecondaryeducation,No.(%) 1335 (78.4) 326 (80.7) 136 (73.5) 89 (73.0) .10MaternalSSBconsumption,No. (%) 1337 (78.6) 324 (80.2) 134 (72.4) 68 (55.7) <.001

Total,No. (%) 550 (22.8) 629 (26.1) 670 (27.8) 564 (23.4) Maternalage,y 33.5 (4.3) 31.9 (4.6) 31.8 (4.7) 32.8 (4.7) <.001 MaternalBMI 24.3 (5.4) 24.4 (4.9) 25.1 (5.7) 25.2 (5.7) .003 Maternaldietquality,HEIscore/100 75.8 (7.5) 74.2 (7.5) 72.1 (8.9) 70.3 (8.9) <.001 Maternalenergyintake,cal/d 1906 (641) 1905 (626) 2030 (693) 2194 (837) <.001 Infantbirthweight,g 3439 (462) 3449 (472) 3479 (499) 3460 (487) .49 Infantgestationalage,wk 39.2 (1.3) 39.2 (1.4) 39.1 (1.4) 39.2 (1.3) .69 Breastfeedingdurationinfirstyear,mo 9.1 (3.9) 9.2 (3.9) 8.9 (4.1) 8.0 (4.3) <.001 Introductionofsolidfoods<4mo,No.(%) 91 (16.5) 114 (18.1) 136 (20.3) 116 (20.6) .25 Maternalsmokinginpregnancy,No. (%) 20 (3.6) 40 (6.4) 45 (6.7) 86 (15.2) <.001 Maternaldiabetesinpregnancy,No. (%)b 46 (8.4) 30 (4.8) 36 (5.4) 29 (5.1) .04Maternalpostsecondaryeducation,No.(%) 470 (85.5) 512 (76.4) 512 (76.4) 403 (71.5) <.001MaternalSSBconsumption,No. (%) 185 (33.6) 181 (28.8) 180 (26.9) 165 (29.3) .07

Abbreviations: ASB, artificially sweetenedbeverage; BMI, body massindex (calculated as weightin kilograms divided byheight in meters squared); HEI, Healthy Eating Index; SSB, sugar-sweetenedbeverage.aComparisons by χ2 test forbinary variables or byanalysis of variance forcontinuous variables.bMaternal diabetes includespreexisting and gestationaldiabetes.

ASB

sSS

Bs

Fig. 6

Maternal Consumption of ASBs and SSBs During Pregnancy and Infant BMI z Score at 1 Year

Infant BMI z Score (n = 2413)

Maternal BeverageConsumption

<1/mo 1702 0.17 (1.04) 0 [Reference] 0 [Reference] 0 [Reference] 0 [Reference]≤1/wk 404 0.13 (1.04) −0.04 (−0.15 to 0.08) −0.07 (−0.18 to 0.05) −0.08 (−0.19 to 0.03) −0.07 (−0.18 to 0.04) 2-6/wk 185 0.29 (1.06) 0.13 (−0.03 to 0.29) 0.07 (−0.09 to 0.23) 0.04 (−0.12 to 0.20) 0.02 (−0.13 to 0.17) ≥1/d 122 0.55 (1.01) 0.37 (0.18 to 0.57)c 0.28 (0.09 to 0.47)c 0.22 (0.02 to 0.41)c 0.20 (0.02 to 0.38)c

ASBs

SSBs

β(95%CI)

No. Mean(SD)

Crude(n = 2413)

Adjusted forMaternal BMI(n = 2413)

Adjusted forMaternal BMI and Covariates(n = 2413)

Adjusted for Maternal BMI and Covariates and Multiple Imputation(N = 3033)

<1/mo 550 0.21 (1.07) 0 [Reference] 0 [Reference] 0 [Reference] 0 [Reference] ≤1/wk 629 0.13 (1.03) −0.05 (−0.17 to 0.07) −0.06 (−0.17 to 0.06) −0.05 (−0.17 to 0.07) −0.05 (−0.16 to 0.07)2-6/wk 670 0.15 (1.05) −0.03 (−0.15 to 0.09) −0.06 (−0.17 to 0.06) −0.04 (−0.16 to 0.07 ) −0.04 (−0.16 to 0.07)

≥1/d 564 0.29 (1.02) 0.11 (−0.02 to 0.23) 0.08 (−0.04 to 0.20) 0.07 (−0.06 to 0.19) 0.05 (−0.07 to 0.17)

JAMA Pediatr. doi:10.1001/jamapediatrics.2016.0301 Published online May 9, 2016.

Abbreviations: ASBs, artificially sweetened beverages; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); SSBs, sugar-sweetened beverages. aCovariates include maternal total energy intake, Healthy Eating Index score, maternal post secondary education, maternal smoking and diabetes during pregnancy, breast feeding duration, infant sex, and introduction of solid foods before 4 months. All models are mutually adjusted for both beveragetypes. bMultiple imputation of missing out come and covariate data with fully conditional specification. c Significant confidence intervals.

Fig. 7

Maternal Consumption of ASBs and SSBs During Pregnancy and Infant Overweight at 1 Year

InfantOverweight(n = 2413)

Maternal BeverageConsumption

<1/mo 1702 77 (4.5) 1 [Reference] 1 [Reference] 1 [Reference] 1 [Reference] ≤1/wk 404 17 (4.2) 0.93 (0.55-1.60) 0.88 (0.52-1.52) 0.86 (0.50-1.49) 0.93 (0.58-1.50) 2-6/wk 185 15 (8.1) 1.85 (1.04-3.30)d 1.68 (0.93-3.01) 1.57 (0.87-2.83) 1.41 (0.82-2.40) ≥1/d 122 13 (10.7) 2.43 (1.30-4.55)d 2.08 (1.09-3.96)d 1.94 (1.00-3.76)d 2.19 (1.23-3.88)d

ASBs

SSBs

OddsRatio(95%CI)

Total No. No. %

Crude(n = 2413)

Adjusted forMaternal BMI(n = 2413)

Adjusted forMaternal BMI and Covariates(n = 2413)

Adjusted for Maternal BMI and Covariates and Multiple Imputation(N = 3033)

<1/mo 550 31 (5.6) 1 [Reference] 1 [Reference] 1 [Reference] 1 [Reference] ≤1/wk 629 27 (4.3) 0.84 (0.49-1.44) 0.83 (0.49-1.43) 0.85 (0.49-1.46) 1.03 (0.62-1.71) 2-6/wk 670 32 (4.8) 0.92 (0.55-1.53) 0.88 (0.53-1.48) 0.94 (0.56-1.61) 1.03 (0.62-1.71) ≥1/d 564 32 (5.7) 1.08 (0.65-1.80) 1.03 (0.62-1.73) 1.04 (0.60-1.80) 1.24 (0.76-2.01)

Abbreviations: ASBs, artificially sweetened beverages; BMI, body mass index (calculated asweight in kilograms divided by height in meters squared); SSBs, sugar-sweetened beverages. aOverweight in infants was defined as a BMI z score exceeding the 97th percentile forage and sex. B Covariates include maternal total energyintake, Healthy Eating Index score, maternal post secondary education, maternal smoking and diabetes during pregnancy, breast feeding duration, infant sex, andintroduction of solid foods before 4 months. All models are mutually adjusted for both beverage types. c Multiple imputation of missing out come and covariate data withfully conditional specification. D Significant confidence intervals.

JAMA Pediatr. doi:10.1001/jamapediatrics.2016.0301 Published online May 9, 2016. Fig. 8

III

de Ruyter JC et al. N Engl J Med 2012;367:1397-1406.

Fig. 14

Baseline Characteristics of the Study Participants.*Characteristic Sugar-free Group Sugar Group

(N = 319) (N = 322) Female sex (%) 46 47 Age (yr) 8.2±1.8 8.2±1.8 Ancestry (%)†

Dutch 80 76 Non-Western 19 22

Highest level of education attained by parent or guardian (%)‡ Elementary, vocational, or technical school 17 10 High-school diploma 33 28 College or university degree 49 61

Weight (kg) 30.04±8.93 30.33±8.82 Height

Measured (cm) 132.1±12.5 133.0±12.7 z score (SD units above or below mean in the Netherlands)§ –0.09±1.00 0.03±0.99

BMI Calculated BMI 16.9±2.6 16.8±2.6 BMI z score (SD units above or below mean in the Netherlands)§ 0.06±1.00 0.01±1.04 Low (%)¶ 1 1 Normal (%) 80 81Overweight (%) 16 15 Obese (%) 3 3

Sum of thicknesses of four skinfolds (mm)‖║ 36.4±17.7 35.6±17.9 Waist-to-height ratio (%) 44.6±4.0 44.2±4.0Fat mass on electrical impedance

Measured (kg)** 5.8±3.8 5.7±3.7 As % of body weight 18 18

* Plus–minus values are means ±SD. There were no significant between-group differences at baseline except for the educational level of the parent or guardian (P = 0.02). P values were based on chi-square tests and t-tests. † Data were available for 633 children; eight households did not provide this information. A child was classified as Dutch if both parents were born in the Netherlands and as non-Western if one or both parents were born in Suriname, Dutch Antilles, Turkey, Morocco, Russia, Egypt, or Vietnam. ‡ Data were available for 632 children; nine households did not provide this information. We based the educational level on that of the parent or guardian who had the higher level of education. § The z scores for BMI and height were calculated with the use of the data described by Schönbeck et al.23 ¶ We used international cutoff points for low and normal BMI24 and for overweight and obesity.25 ‖ Data were available for 640 children; 1 child declined to be measured. ** Data were available for 637 children; 4 children declined to be measured.


Fig. 15


Concentración urinaria de Sucralosa.

Fig. 16


Resultados

Fig. 17

Katan MB, de Ruyter JC, Kuijper LDJ, Chow CC, Hall KD, et al. (2016) Impact of Masked Replacement of Sugar-Sweetened with Sugar-Free Beverages on Body Weight Increases with Initial BMI: Secondary Analysis of Data from an 18 Month Double–Blind Trial in Children. PLoS ONE 11(7): e0159771. doi:10.1371/journal.pone.0159771http://journals.plos.org/plosone/article?id=info:doi/10.1371/journal.pone.0159771 Fig. 18

http://journals.plos.org/plosone/article?id=info:doi/10.1371/journal.pone.0159771

Association between intake of artificially sweetened andsugar-sweetened beverages and preterm deliveryAm J Clin Nutr 2012;96:552–9 and Am J Clin Nutr 2010;92:626–33. Printed in USA. 2010 American Society for

Nutrition

Intake of artificially sweetened soft drinks and risk of preterm delivery: a prospective cohort study in 59,334 Danish pregnant women1–3Thorhallur I Halldorsson, Marin Strøm, Sesilje B Petersen, and Sjurdur F OlsenJuly 7, 2016 ajcn.nutrition.org

1 OR, odds ratio. P values were determined by using the chi-square test.2 Adjusted for maternal age, height, prepregnancy BMI, total energy intake, cohabitant status, parity, smoking during pregnancy, and familial socio-occupational status.

Association between intake of carbonated soft drinks during pregnancy and preterm delivery (< 37 wk) in 59,334 women from the Danish National Birth Cohort1

Unadjusted OR Adjusted OR(95% CI) (95% CI)n Cases

n (%)

2

Fig. 30



Association between intake of noncarbonated soft drinks during pregnancy and preterm delivery(< 37 wk) in 59,281 women from the Danish National Birth Cohort1

Unadjusted OR Adjusted OR(95% CI) (95% CI)n Cases

n (%)

2

Fig. 31



Intake of artificially sweetened carbonated soft drinks in relation to preterm delivery (n = 59,334) stratified by prepregnancy BMI (in kg/m )

OR (95% CI)n Cases

n (%)

2

2 1

Fig. 33

Association between intake of artificially sweetened and sugar-sweetened beverages and preterm delivery: a large prospective cohort study1–Linda Englund-O ¨gge, Anne Lise Brantsæter, Margareta Haugen, Verena Sengpiel, Ali Khatibi, Ronny Myhre, Solveig Myking, Helle Margrete Meltzer, Marian Kacerovsky, Roy M Nilsen, and Bo JacobssonSeptember 5, 2012 ajcn.nutrition.

1AS, artificially sweetened; SS, sugar-sweetened.2Mean 6 SD (all such values).3Determined by using a test for linear trend.4Prepregnancy BMI.

Maternal characteristics in relation to intake of artificially and sugar-sweetened beverages in 60,761 women from the Norwegian Mother and Child Cohort study1

Servings Never < 1/wk 1–6/wk 1/d 2–3/d ≥ 4/d P

5Determined by chi-square test.6Daily or occasional smoking in pregnancy week 17 and/or week 30.7Education level refers to .12 y in school.8Percentage of women giving birth before 37 gestational weeks in previouspregnancies

Fig. 25


1ORs were calculated by using logistic regression models. AS, artificially sweetened; PTD, preterm delivery; SS, sugar-sweetened.2Adjusted for previous preterm delivery, maternal age, prepregnancy BMI, height, total energy intake, marital status, parity, smoking during pregnancy, and education.3Additional adjustments for the other type of beverage.4Percentage +SE (all such values).5 P values for linear trend were obtained by incorporating the variable as a linear term in logistic regression models.

Associations between intake of AS and SS beverages during pregnancy and PTD, < 37 completed gestational weeks, in 60,761 women from the Norwegian Mother and Child Cohort Study1

Unadjusted OR Adjusted OR Adjusted OR(95% CI) (95% CI) (95% CI)All PTD

n %

-

2 3

Fig. 26


1ORs were calculated by using logistic regression models. AS, artificially sweetened; PTD, preterm delivery; SS, sugar-sweetened.2Adjusted for previous preterm delivery, maternal age, prepregnancy BMI, height, total energy intake, marital status, parity, smoking during pregnancy,education, and the other type of beverage.3Percentage + SE (all such values).4 P values for linear trend were obtained by incorporating the variable as a linear term in logistic regression models.

Associations between intake of AS and SS beverages during pregnancy and PTD, < 37 completed gestational weeks, in 60,761 women from the Norwegian Mother and Child Cohort Study1

AS beverages SS beverages

All PTD Adjusted OR (95% CI) All PTD Adjusted OR (95% CI)

-

2 2

Fig. 27


1ORs were calculated by using logistic regression models. AS, artificially sweetened; PTD, preterm delivery; SS, sugar-sweetened.2Adjusted for previous preterm delivery, maternal age, prepregnancy BMI, total energy intake, height, marital status, parity, smoking duringpregnancy, education, and the other type of beverage.3Percentage + SE (all such values).4 P values for linear trend were obtained by incorporating the variable as a linear term in logistic regression models.

Intake of AS and SS beverages in relation to PTD, stratified by prepregnancy BMI (in kg/m2) in the Norwegian Mother and Child Cohort Study (n = 60,761)1

AS beverages SS beverages

All PTD Adjusted OR (95% CI) All PTD Adjusted OR (95% CI)

n % n %

-

2 2

Fig. 28

J Toxicol Environ Health A. 2002 Nov 22;65(22):1853-65.Selection of subjects for human milk surveillance and research studies.Wimberley Groer M1, Humenick S, Wilson J.

Potential Use of Variable Type by Goal of Breast-Milk Monitoring Study Possible study goals

MonitoringTrends exposure Influence

Representative of exposure of infants of lactation monitoring in overall in selected on chemical

Variables of human milk population situations body burden

Maternal demographics Age of mother Stratifying Stratifying Observed Stratifying Marital status Observed Observed Observed ObservedIncome (e.g., WIC Stratifying Stratifying Stratifying Observed

eligible, education) Ethnicity Stratifying Stratifying Stratifying Stratifying Geographic region Stratifying Stratifying Observed Observed

(census tract or ZIP codeand type, urban, suburban, rural, etc.)

Maternal perinatal history Parity Stratifying Stratifying Observed Stratifying Age of most recent infant Stratifying Stratifying Observed Observed General health/conditions/ Exclusionary Observed Observed Observed

lifestyle/health habits of mother

Health during most recent Exclusionary Observed Observed Observed pregnancy Amount/pattern of breast- Exclusionary Observed Observed Stratifying

feeding or observed Maternal body composition Observed Observed Observed ObservedInfant characteristics Health/conditions of infant Exclusionary Observed Stratifying Observed

or observed Gender NA Observed Stratifying Observed

or observed Weight/age NA Observed Stratifying Observed

or observed Exposure sources Occupation Observed Observed Observed Observed Hobbies Observed Observed Observed Observed Home chemical exposure Observed Observed Observed Observed

(cleaning agents, pesticides, lead paint)

Nutritional intake Observed Observed Observed Observed pattern

Regional mass exposure Stratifying Stratifying Stratifying Stratifying history or observed or observed or observed

Drinking water quality Observed Observed Observed ObservedAir quality Observed Observed Observed Observed Fig. 9

Acesulfame-K Saccharin Sucralose Asparteme

ID Reported µg/ml Reported µg/ml Reported µg/ml Reported µg/ml

Participants reporting no NNS intake

2 N 0 N <LOQ N 0 N <LOQ

4 N 0 N 0 N 0 N <LOQ

13 N 0.02 N <LOQ N 0 N <LOQ

15 N 0.04 N <LOQ N <LOQ N <LOQ



Participants reporting intake of ≥ 1 NNS

1 Y 2.22 N 0.02 Y 0.01 Y <LOQ

3 Y 1.22 N <LOQ N 0 Y <LOQ

5 Y 1.83 N 0 Y 0 N <LOQ

6 Y 0.13 N <LOQ Y 0.01 N <LOQ

7 Y 0.03 N 0 N 0 Y <LOQ

8 N 0.21 N 0.01 Y 0 N <LOQ

9 Y 1.00 N 0.01 Y 0.04 N <LOQ

10 N 0 N <LOQ Y <LOQ N 0

11 Y 0 N 0 N 0 Y 0

12 N 0.01 Y 1.42 N 0 Y 0

14 N 0 N 0 Y <LOQ N 0

17 N <LOQ N <LOQ Y <LOQ N <LOQ

18 Y <LOQ N <LOQ N <LOQ Y NF

20 Y 1.047 N <LOQ N <LOQ Y <LOQ

J Toxicol Environ Health A. 2015;78(16):1029-32. doi: 10.1080/15287394.2015.1053646. Epub 2015 Aug 12.Nonnutritive Sweeteners in Breast Milk.SylvetskyAC1,2, Gardner AL1, Bauman V1, BlauJE1, Garraffo HM3, Walter PJ3, RotherKI1.

Note. <LOQ, below limit of quantitation. N, no consumptionreported; Y, reported consumption.

VII

Fig. 10

The Journal of Nutrition Supplement: Low-Calorie Sweeteners and Weight Control—What the Science Tells UsThe Use of Low-Calorie Sweeteners by Children: Implications for Weight Management1–3 - John Foreyt, Ronald Kleinman, Rebecca J. Brown, and Rachel Lindstromjn.nutrition.org - June 5, 2012

Observational studies of LCS use in children1

1 LCS, low-calorie sweetener; LCSB, low-calorie sweetened beverage. 2 Ages área tstudy entry.

Fig. 20


Controlled trials of the acute effects of LCS on Food intake 1

1 LCS, low-calorie sweetener; 2 Ages are at study entry,3 Compensation after a preload is defined as the difference in subsequent ad libitum energy intake between 2 conditions, divided by the energy in the preload,

Reference n Participants2 Design Intervention randomization ResultsMethod of

Fig. 21


Short-term interventional studies on LCS use in children: RCT1

1 LCS, low-calorie sweetener; LCSB, low-calorie sweetener beverage; RCT, randomized controlled trial; SSB, sugar-sweetened beverage. 2 Ages are at study entry,

Reference n Participants2 Design Intervention Method of randomization Results

Fig. 22

Plausibilidad Biológica

Consistencia y Analogía

Principio dosis/respuesta

Evidencia experimental

Asociación temporal

Fuerza de asociación

Coherencia

Grado de Recomendación

Grado de recomendacion Claridad del riesgo beneficio Solidez metodologica de la evidencia Implicacias

1A clara RCTs sin limitaciones importantes Solidas, aplicables a todos los pacientes en la mayoria de las circustancias

1B clara RCTs con limitaciones importantes Solidas, aplicables probablemente a la mayoria de los pacientes

1C+ clara NO RCTs directos con una clara y valida extrapolacion

Solidas,que podrían aplicarse la mayoria de los pacientes y circusntancias

1C clara Estudios observacionales Recomendacion intermedia que podria variar con la aparicion de solidas nuevas evidencias

2A dudosa RCTs sin limitaciones importantes Recomendaciones intermedias que dependen de las circustancias y preferencias de los pacientes

2B dudosa RCTs con limitaciones importantes Debil, opciones alternativas probablemente seanmejores un algunos pacientes en algunascircustancias

2C dudosa Estudios observacionales Debil, otras alternativas probablemente seanmejores

Fig. 4

ConclusionesLa medicina basada en la evidencia implica un proceso de jerarquización de las investigaciones clínicaspara la toma de decisiones en salud.

La mayoría de los efectos adversos oncologicos observados con el uso de edulcorantes en embarazadas sehan observado en ensayos clínicos en animales que recibieron dosis por encima de la ingesta diariaadmisible. A la fecha no existe riesgo de enfermedad oncológica en los niños por el uso de edulcorantes

El uso de edulcorantes en niños no ha demostrado “per se” un impacto importante en la reducción deincremento de peso y debe acompañarse de una política “integral” de tratamiento

Los niveles de edulcorantes detectados en leche son extremadamente bajos o indetectables paraconsiderar efectos nocivos en niños que se alimentan con pecho.

Los resultados sobre riesgo de parto prematuro asociado al consumo de edulcorantes durante elembarazo son controversiales y se han observado con ingestas altas de consumo de bebidas

Se necesita continuar desarrollando ensayos clínicos ética y metodológicamente de jerarquía en niños y

muito obrigado

Edulcorantes são seguros para gestantes, lactantes...

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