The benefits and effectiveness of the lowcalories sweeteners in beverages

Antonis Zampelas PhD

Professor in Human Nutrition

Department of Food Science and Human Nutrition

Agricultural University of Athens

Greece

The Problem

Two-thirds of adults in the United States are overweight orobese (1)

Americans are gaining an average of 1–2 lb (0.45–0.9 kg)/y

If the present trend is not halted, it is projected that by theyear 2030, 86.3% of adults in the United States will beoverweight or obese (2).

Flegal KM, et al JAMA 2010;303:235–41.Wang Y et al Obesity (Silver Spring) 2008;16:2323–30.

Farajian P et al Atherosclerosis 2011;217:525-30

Farajian P et al Atherosclerosis 2011;217:525-30

Overweight and Obesity rates in primary schoolchildren:

The GRECO Study

Prevalence of overweight and obesity according to the IOTF Criteria by gender

Boys Girls P

Normal weight (%) 58,0 61,7 0,01

Overweight (%) 29,6 28,3Obesity (%) 12,4 10,0

Farajian P et al Atherosclerosis 2011;217:525-30

Obesity statusCountry(city)

Sex Nonobese Overweight Obese P value*No. (%) No. (%) No. (%)

Algeria(Algiers city)

M 168 (86.6) 18 (9.3) 8 (4.1) <0.1372F 212 (80.0) 41 (15.5) 12 (4.5)

Jordan(Amman)

M 315 (68.2) 100 (21.6) 47 (10.2) <0.0005F 370 (77.9) 83 (17.5) 22 (4.6)

Kuwait(Kuwait city)

M 108 (39.6) 70 (25.6) 95 (34.8) <0.0000F 208 (58.6) 74 (20.8) 73 (20.6)

Libya(Tripoli)

M 207 (74.0) 46 (16.4) 27 (9.6) <0.007F 222 (63.4) 93 (26.6) 35 (10.0)

Palestine(Al-Khalil)

M 181 (82.3) 28 (12.7) 11 (5.0) <0.7095F 216 (84.0) 32 (12.5) 9 (3.5)

Syria(Damascus)

M 401 (73.0) 111 (20.3) 37 (6.7) <0.5898F 383 (74.7) 103 (20.1) 27 (5.3)

UAE(Sharjah city)

M 168 (64.1) 44 (16.8) 50 (19.1) <0.0000F 194 (79.8) 33 (13.6) 16 (6.6)

Prevalence of overweight and obesity among adolescents (15–18 years) inseven Arab countries based on IOTF reference

Musaiger AO et al. J Obes 2012; 2012: 981390

Alarjan JF et al J Educ Health Promot. 2015; 4: 17.

Health Professionals in Jordan

Variable Group Count Percentage

Gender

BMI

Male

Female

Underweight

Normal Weight

Overweight

Obese

285

463

5

385

276

82

38.1

61.9

0.70

51.5

36.9

11.0

It has been argued that drinks contribute significantly tothe increasing obesity rates worldwide mainly because of

their energy content

Joint WHO/FAO Expert Consultation.Diet, Nutrition and the Prevention ofChronic Diseases;

WHO: Geneva, Switzerland, 2003.

Human Evolution …

Systematic review and meta-analysis summarized the evidence in children

and adults

Search at PubMed, EMBASE, and Cochrane databases through March 2013

for prospective cohort studies and randomized controlled trials (RCTs) that

evaluated the SSB-weight relation

Separate meta-analyses were conducted in children and adults and for

cohorts and RCTs

Malik VS et al Am J Clin Nutr 2013;98:1084–102

One-year changes in BMI (95% CI) per 1-serving/dincrease in sugar-sweetened beverages from

prospective cohort studies in children

Weighted mean differences in BMI change (95%CI) between the intervention and control

regimens from randomized controlled trials inchildren

Malik VS et al Am J Clin Nutr 2013;98:1084–102

One-year changes (95% CI) in weight (kg) per 1-serving/d increase in sugar-sweetened beverages

from prospective cohort studies in adults

Weighted mean differences (95% CI) in weightchange (kg) between the intervention and control

regimens from randomized controlled trials inadults

Malik VS et al Am J Clin Nutr 2013;98:1084–102

Definitions

There are two types of sweeteners available:

Natural sweeteners (also called caloric sweeteners, sugars, nutritive

sweeteners) which provide calories (i.e., energy in the form of

carbohydrates) such as fructose and sucrose (e.g., table sugar, honey,

syrup; 3.75kcal·gram) and polyols (e.g., sorbitol, mannitol, xylitol;

2.4kcal·gram)

Artificial sweeteners (also called sugar substitutes, high-intensity

sweeteners, high-potency sweeteners, non-nutritive sweeteners) which

can be low-calorie or calorie-free

Name Sweetening powercompared to sucrose

Date discovered Used in the EU since

Acesulfame-K (E950)Aspartame (E951)Cyclamate (E952)Neotame (E961)Saccharin (E954)Steviol glycosides (E960)*Sucralose (E955)

150-200 times sweeter150-200 times sweeter

30-50 times sweeter7000-13000 times sweeter

300-400 times sweeter200-300 times sweeter400-600 times sweeter

1966196519371990187919011976

1983198319542010188720112000

*Steviol glycosides are the natural sweet components found in the leaves of the stevia plant

Examples of low calorie sweeteners

Systematically review and quantitatively evaluate randomized controlled trials (RCTs)

and prospective cohort studies, separately, that examined the relation between LCSs

and body weight and composition

A systematic literature search identified 15 RCTs and 9 prospective cohort studies

that examined LCSs from foods or beverages or LCSs consumed as tabletop

sweeteners

Meta-analyses generated weighted mean differences in body weight and

composition values between the LCS and control groups among RCTs and weighted

mean correlations for LCS intake and these parameters among prospective cohort

studiesMiller PE & Perez V Am J Clin Nutr 2014;100:765–77

Miller PE & Perez V Am J Clin Nutr 2014;100:765–77

Study selection process. http://www.ncbi.nlm.nih.gov/pubmed. LCS,low-calorie sweetener; RCT, randomized controlled trial

Forest plots derived from random effects modelssummarizing results from the meta-analysis ofprospective cohort studies that examined LCS

intake and change in BMI (A) or BW(B)

Forest plots derived from random-effects modelsdepicting the effects of LCS on BMI (A), fat mass

(B), and waist circumference (C) in RCTs

Miller PE & Perez V Am J Clin Nutr 2014;100:765–77

Conclusion

Findings from observational studies showed no association between

LCS intake and body weight or fat mass and a small positive association

with BMI

However, data from RCTs, which provide the highest quality of evidence

for examining the potentially causal effects of LCS intake, indicate that

substituting LCS options for their regular-calorie versions results in a

modest weight loss and may be a useful dietary tool to improve

compliance with weight loss or weight maintenance plans

Miller PE & Perez V Am J Clin Nutr 2014;100:765–77

Rogers PJ et al Int J Obesity 2016;40:381–94

Forest plot showing individual and combined effect sizes for prospective cohortstudies reporting the association between LES consumption and change in BMI

over the follow-up period. Effect sizes have been standardized to a 1 year follow-up period. Negative scores favor LES consumption (BMI decrease)

Rogers PJ et al Int J Obesity 2016;40:381–94

Summary of outcomes of meta-analyses of short-term intervention studies. EIdifference is the difference in cumulative EI (total of preload plus test meal EI) for

the LES condition minus the comparison condition

Rogers PJ et al Int J Obesity 2016;40:381–94

Forest plots showing individual and combined effect sizes for sustained interventionstudies comparing the effects on BW of LES versus sugar (upper panel) and LES

versus water (lower panel)

Rogers PJ et al Int J Obesity 2016;40:381–94

The possibility that low-calorie sweeteners (LCS) promote lower qualitydiets and, therefore, weight gain has been noted as a cause for concern.

Data from a representative sample of 22,231 adults were obtained fromfive cycles of the National Health and Nutrition Examination Survey (1999–2008 NHANES)

A single 24-hour recall was used to identify consumers of LCS beverages,foods and tabletop sweeteners

Diet quality was assessed using the Healthy Eating Index 2005 (HEI 2005)and its multiple subscores

Health behaviors of interest were physical activity, smoking and alcoholuse

Drewnowski A, & Rehm CD. Nutrients 2014;6:4389-4403; doi:10.3390/nu6104389

Drewnowski A, & Rehm CD. Nutrients 2014;6:4389-4403; doi:10.3390/nu6104389

Adjusted association between any low-calorie sweetener (LCS) consumption andmean Healthy Eating Index 2005 (HEI) subscores (maximum value indicated in

parentheses). Analysis adjusted for age group, race/ethnicity and gender

Drewnowski A, & Rehm CD. Nutrients 2014;6:4389-4403; doi:10.3390/nu6104389

Age-adjusted prevalence of health behaviors among consumers of any low-caloriesweetener (LCS) compared to non-consumers, NHANES 1999–2008

It is unclear whether consumption of low-calorie beverages (LCB) leads tocompensatory consumption of sweet foods, thus reducing benefits forweight control or diet quality.

This analysis investigated associations between beverage consumptionand energy intake and diet quality of adults in the UK National Diet andNutrition Survey (NDNS) (2008–2011; n = 1590), classified into: (a) non-consumers of soft drinks (NC); (b) LCB consumers; (c) sugar-sweetenedbeverage (SSB) consumers; or (d) consumers of both beverages (BB),based on 4-day dietary records.

Within-person data on beverage consumption on different days assessedthe impact on energy intake.

Gibson SA et al. Nutrients 2016;8:9; doi:10.3390/nu8010009

Energy intake from food and beverage sources according to beverageconsumer group

Gibson SA et al. Nutrients 2016;8:9; doi:10.3390/nu8010009

LCB consumers and NC consumed less energy and non-milk extrinsic sugars

than other groups.

Micronutrient intakes and food choices suggested higher dietary quality in

NC/LCB consumers compared with SSB/BB consumers.

Within individuals on different days, consumption of SSB, milk, juice, and

alcohol were all associated with increased energy intake, while LCB and tea,

coffee or water were associated with no change; or reduced energy intake

when substituted for caloric beverages.

Results indicate that NC and LCB consumers tend to have higher quality diets

compared with SSB or BB

Gibson SA et al. Nutrients 2016;8:9; doi:10.3390/nu8010009

Risk assessment issues

What can it do?

Hazzard identification

At what doses are adverse effects not seen? What can be a safe dose forhumans?

Hazard characterization

What is the intake by humans?

Intake assessment

Is there any risk associated with that issue?

Risk characterization

Hazard Characterization

Threshold effects

Analyze dose-response data to define most sensitive toxic effect – ie that

produced at the lowest doses in the most sensitive species

Define a daily intake that does not produce that effect

A health-based exposure limit is determined by dividing the experimental no-

observed-adverse-effect levels (NOAELs) in the most sensitive animal studies

(for long-term or short term intake) by an uncertainty factor to allow for

species differences and human variability

The Acceptable Daily Intake for ADI

ADI =NOAEL (mg/kg/day)

Safety Factor (usually 100)

ADI – Acceptable Daily IntakeAn estimate of the amount of a food additive, expressed on a body weight basis, that canbe ingested daily over a lifetime without appreciable health risk

WHO 1987

Aspartame intake (mg/kg/day) in the general population andvarious subpopulations in the US

(90th percentile, “eaters “ only, 14-day average)

Survey Dates Generalpopulation

2-5 years Diabetics Individuals ona reducing

diet

Women ofchildbearing

age

1984-19851985-19861986-19871987-19881988-19891989-19901990-19911991-1992

1.62.12.12.32.22.52.83.0

3.14.83.72.64.03.13.55.2

2.12.23.03.32.62.73.43.3

1.62.22.32.62.52.72.83.3

2.02.22.52.82.63.23.74.2

Butchko HH & Stargel WW Reg Toxicol Pharmacol 2001;34:221-33

ADI for aspartame: 40 mg/kg/day

10 cans of drink fully sweetened with aspartame

High level consumers rarely exceed 10 mg/day when using

combinations of sweeteners

Lean MEJ & Hankey CR BMJ 2004;329:755-6

PLoS ONE 2016;11(8): e0161264. doi:10.1371/journal.pone.0161264

PLoS ONE 2016;11(8): e0161264. doi:10.1371/journal.pone.0161264

Crude and adjusted associations between the consumption of artificially sweetenedbeverages and the development of metabolic diseases in observational prospective

studies

NHS: Nurses’ Health Study, ARIC: the Atherosclerosis Risk in Communities study, BWHS: the Blacks Women’s Health Study, MESA: the Multi-Ethnic Study of Atherosclerosis, HPFS: the Health Professionals Follow-Up Study, CARDIA: the Coronary Artery Risk Development in Young Adultsstudy, SAHS: the San Antonio Heart Study, EPIC: the European Prospective Investigation into Cancer and Nutrition study.Associations between the highest range of artificially sweetened beverages consumption and the incidence of the specific metabolic diseasestudied, expressed in relative risks, odds ratios or hazard ratios with 95% confidence intervals (95% CI). a The CARDIA study evaluates the risk ofthe non-consumers of diet beverages to develop metabolic syndrome compared to the consumers.

To quantify global, regional, and national levels of SSB, fruit juice, and milk intake

by age and sex in adults over age 20 in 2010

Data on intakes of these beverages in adults, by age and sex, from 193 nationally-

or subnationally-representative diet surveys worldwide, representing over half the

world’s population

Extraction of data relevant to milk, fruit juice, and SSB availability for 187 countries

from annual food balance information collected by the United Nations Food and

Agriculture Organization

Singh GM et al PLoS ONE 2015;10(8): e0124845. doi:10.1371/journal. pone.0124845

Consumption of non-alcoholic caloric beverages in 187 countries worldwide

Singh GM et al PLoS ONE 2015;10(8): e0124845. doi:10.1371/journal. pone.0124845

Data were obtained using the Water Balance Questionnaire(WBQ) from a sample of general population in Athens,Greece (n = 984)

473 individuals (42 ± 18 years) in summer

511 individuals (38 ± 20 years) in winter stratified by sex

and age

Contribution of Drinks to Total Energy Intake

Drinks contribute approximately 1/4 of the total energy intake of studypopulation; 23% of total energy intake in winter and 26.8% of total energy

intake in summer

Winter Summerkcal/day Men + Women

(n = 511)Men + Women

(n = 473)p

Energy Intake 2082 ± 892 1890 ± 894 0.001Energy from drinks 479 ± 286 492 ± 499 <0.001Energy from foods 1630 ± 750 1398 ± 663 <0.001Energy expenditure 1860 ± 390 1830 ± 491 0.19

Energy Balance 346 ± 897 63 ± 982 <0.001Water Intake (from all sources) 2891 ± 987 3943 ± 1603 <0.001

The main contributors to drink energy intake, both in winter and summer weremilk/chocolate milk, coffee/coffee drinks and alcoholic drinks. These add up to

approximately 75% of drink energy intake, 79.5% and 69.5% of drink energyintake in winter and in summer

Total SampleDrink Group Winter

(n = 511)Summer(n = 473) p

Fruit juice 100% 14 (0, 44) 14 (0, 68) 0.3Sugar-sweetened Drinks 34 (11, 94) 15 (0, 69) <0.001Low calorie soft drinks 0.5 (0, 1) 0 (0, 0.5) <0.001

Tea/herbal infusions 0 (0, 18) 0 (0, 18) <0.01Milk/chocolate milk 98 (32, 229) 41 (0, 134) <0.001Milkshakes/sherbets 0 (0, 0) 0 (0, 0) <0.001

Coffee 96 (32, 225) 48 (8, 151) <0.001Alcoholic drinks 22 (0, 62) 44 (6, 170) <0.001

To measure the effect of seasonality, on family diet & lifestyle habits in

Greece

To assess certain trends in drinking habits and understand the

consumption patterns of various age groups according to their diet habits

To measure how and whether these habits affect their body weight

To measure whether different levels of physical activity affect food &

drinks consumption or relevant lifestyle habits among the various age

groups

Volunteers aged 5 to 65 years old

n=1055

From Athens and Thessaloniki

Body weight height and waist circumference

Food (and Drinks) Frequency Questionnaire, Physical Activity

habits (IPAC), eating and drinking patterns and demographics

(kcal/day) Total sample

(n=854)

Males

(n=417)

Females

(n=437)

P

Energy Intake 3422 (2563, 4271) 3814 (3059, 4611) 2981 (2280, 3733) <0.001

Energy from beverages 379 (239, 595) 442 (292, 710) 314 (212, 503) <0.001

Energy from foods 3069±1240 3417±1307 2724±1070 <0.001

• Results are presented as mean±SD for the normally distributed variables and as P50 (P25-P75) for the skewed variables.• P-values derived through the independent t-test for the normally distributed variable and through the Mann-Whitney U-test for the skewed

variables.

(kcal/day) Total sample

(n=199)

Boys

(n=102)

Girls

(n=97)

P

Energy Intake 3392±1226 3742±1317 3025±1006 <0.001

Energy from beverages 428±201 464±211 390±183 <0.01

Energy from foods 2964±1155 3278±1262 2635±929 <0.001

• Results are presented as mean±SD• P-values derived through the independent t-test for the normally distributed variable.

Adults

Total

Water

Intake

(%)

Water

Intake from

liquids/fluids

(%)

Beverages

Water

Intake

(%)

Total

Energy

Intake

(%)

Beverages

Energy

Intake

(%)

Foods 18.10 86.25

Drinking water 59.45 72.59

Juice 2.53 3.09 11.25 1.44 10.45

Coffee 9.78 11.94 43.57 4.36 33.68

Alcoholic drinks 2.78 3.40 12.40 3.81 27.74

Soft drinks 2.01 2.46 8.95 0.59 4.95

Milk 2.92 3.45 12.58 2.18 15.86

Milkshakes/ chocolate drink 0.09 0.11 0.44 0.11 0.84

Tea/ herbal infusions 1.38 1.69 6.15 0.56 4.02

Energy drinks/isotonic drinks 1.04 1.28 4.66 0.06 3.08

Juice (natural squeezed, 100% natural packed, enriched 100%, nectar), Coffee (greek, espresso, freddo, capuccino, nes,filter, frapuccino, frappe) Softdrinks (regular, light, soda), Alcoholic drinks (wine, beer, coctails, other alcohol), Milk (full fat, reduced fat,chocolate)

KidsTotalWater

Intake

(%)

BeveragesWater

Intake

(%)

DrinksWater

Intake

(%)

TotalEnergy

Intake

(%)

BeveragesEnergy

Intake

(%)

Foods 18.8 87.36

Drinking water 61.35 75.55

Juice5.96

7.34 30.02 3.13 24.73

Coffee 0.69 0.85 3.47 0.42 3.29

Alcoholic drinks 0.14 0.17 0.68 0.12 0.95

Soft drinks 1.06 1.3 5.32 0.41 3.26

Milk 9.85 12.13 49.59 7.53 59.58

Milkshakes/ chocolate drink0.22 0.27 1.11 0.3 2.41

Tea/ herbal infusions0.63 0.78 3.18 0.24 1.84

Energy drinks/isotonic drinks1.32 1.62 6.63 0.49 3.87

Juice (natural squeezed, 100% natural packed, enriched 100%, nectar), Coffee (greek, espresso, freddo, capuccino, nes,filter, frapuccino, frappe) Softdrinks (regular, light, soda), Alcoholic drinks (wine, beer, coctails, other alcohol), Milk (full fat, reduced fat,chocolate)

Farajian P et al Public Health Nutr 2016

Food source Intake of freesugars (g/day)

Percentage of totalsugars coming

from free sugars

100% natural packaged andfreshly squeezed fruit juice

17.8 (16.9) 12.4 (9.7)

Sweets 11.5 (13.3) 8.3 (6.8)Nectar (sugared) fruit juices 9.2 (16.7) 5.7 (8.4)Chocolate milk 4.7 (7.6) 3.4 (4.6)Soft drinks 4.6 (11.0) 3.4 (5.9)Dairy desserts 3.5 (6.6) 2.3 (3.3)Biscuits 3.2 (5.8) 2.1 (2.8)Cereals 3.0 (3.2) 2.0 (2.5)Honey / Jam 2.7 (3.8) 2.0 (2.7)Breads 2.5 (2.5) 2.0 (2.2)Starchy pies 0.5 (0.9) 0.4 (0.5)Delicatessen 0.2 (0.3) 0.1 (0.4)

WHO definition:free sugars" (the

term preferred bythe WHO), are

defined as all mono-and disaccharidesadded to foods bythe manufacturer,

cook, and consumer,plus sugars naturally

present in honey,syrup, and fruit juice

should constitute<10% of energy

intake

Farajian P et al Public Health Nutr 2016

Model 1 Model 2

Gender

Females 1 1

Males 1.14 (0.91, 1.44) 1.12 (0.89, 1.42)

Age 0.77 (0.66, 0.91) 0.77 (0.66, 0.91)

PAQ-score 0.87 (0.72, 1.05) 0.87 (0.72, 1.05)

Added sugars intake (per 10 g) 0.98 (0.96, 1.01) 0.97 (0.94, 1.01)

Energy intake (per 100 kcal) - 1.10 (1.08, 1.13)

All odds ratios and their corresponding 95% confidence intervals werecalculated by performing multiple logistic regressions.

Farajian P et al Public Health Nutr 2016

Pattern analysis and added sugar intake

- After controlling for age, gender and energy intake,

• An “unhealthy” dietary pattern characterized by high intake ofSSBs, fast foods intake (i.e. pizza, burgers, souvlaki), fries, sweets,frequent eating/ordering outside from home, and having lunch infront of a screen was associated with added sugars intake (g / day).

• A “healthy” dietary pattern characterized by high intake of wholefruits, 100% fruit juices, vegetables, legumes and honey was alsoassociated with added sugars intake (g / day)

Farajian P et al Public Health Nutr 2016

Data on LCS use, from a single 24-h dietary recall, for a representative sampleof 22 231 adults were obtained from 5 cycles of the National Health andNutrition Examination Survey (1999–2008 NHANES).

Retrospective data on intent to lose or maintain weight during the prior 12-months and 10-year weight history were obtained from the weight historyquestionnaire.

Objectively measured heights and weights were obtained from theexamination.

Primary analyses evaluated the association between intent to lose/maintainweight and use of LCSs and specific LCS product types using survey-weightedgeneralized linear models.

We further evaluated whether body mass index (BMI) may mediate theassociation between weight loss intent and use of LCSs.

The association between 10-year weight history and current LCS use wasevaluated using restricted cubic splines.

Drewnowski A, & Rehm CD. Nutrition & Diabetes (2016) 6, e202; doi:10.1038/nutd.2016.9

Drewnowski A, & Rehm CD.Nutrition & Diabetes (2016)

Multivariable-adjusted prevalence ofobesity (a) and diabetes (b) by type ofLCS consumed. *** indicates P-value <

0.001 comparing LCS consumers to non-consumers

Drewnowski A, & Rehm CD.Nutrition & Diabetes (2016)

Multivariable-adjusted prevalence ratiobetween 10-year weight change and

consumption of any LCS (a) andLCS beverages (b)

• Obesity is a growing public health problem world wide and in

the Arab region

• Artificial sweeteners can contribute to negative energy

balance and healthier dietary habits

• Artificial sweeteners are considered safe within ADIs which

are very unlikely to be exceeded even from heavy consumers

• Each country has each own needs and interventions should be

designed according the needs of each country

The Balance of Soul, 1600 BC

Thank you very much foryour attention!