LOW CALORY SWEETNERS AND WEIGHT Dra Pilar Riobó MD, PhD Associate Head Endocrinology and Nutrition Department Hospital Fundacion Jimenez Diaz-Capio. Madrid FENS Meeting 2011
Overweight andObesity are Epidemic
Obesity and overweight have been reported to beassociated with decreases in life expectancy. Non-smoking women Smoking women Non-smoking men Smoking men Framingham Heart Study 13.7 Non-smoking women lost 7 years, 5.82 Non-smoking men 5.8 years 13.3 7.08 0 5 10 15 Implications of obesity at age 40 on life expectancy. Peeters, A, et al. Ann Int Med 2003;138:24-32
Obesity and other risk factors Blood HDL-C PCRP pressure pro-thrombotic T-Cholesterol-t OBESITY factors Insulín Diabetes Resistance TG,Lp(a) sdLDL
Diabetes epidemic 300 millions 300 250 Millones de personas 200 154 millionsio 135 millions 150 100 50 0 1995 2000 2025 King H. Diabetes Care 1998
Obesity is associated with increased riskfor most cancers (ACS) 1.44 Multiple myeloma (>35) 1.46 Colon & Rectum (>40)Type of Cancer (Highest BMI category) 1.51 Ovary (>35) 1.68 Liver (>35) 1.88 All Cancers (>40) 1.95 Non-Hodgkin’s Lymphoma (>35) 2.12 Breast (>40) 2.13 Gallbladder (>30) 2.51* All Other Cancers (>40) 2.64* Oesophagus (>30) 2.76 Pancreas (>40) 3.20 Cervix (>35) 4.75 Kidney (>40) 6.25 Uterus (>40) 0 1 2 3 4 5 6 7 8 9 10 11 Relative Risk of Death (95% Confidence Interval) Calle E et al. N Engl J Med 2003;348:1625-1638 Mortality from Cancer According to BMI >30->40 for U.S. Women in the Cancer Prevention Study II, 1982 through 1998
The RisingRate ofChildhoodObesity isAlarming 30% of children are overweight or at risk for overweight
Obesity Today: Future Impact “Because of increasing rates of obesity…we may see the first generation that will be less healthy and have a shorter life expectancy than their parents.” Surgeon General Richard Carmona
The Biological Cause ofObesity is Simple An imbalance of calories IN and calories OUT! But…
…The Social Factors that leadto the Imbalance are Complex • Changing food habits due to busy lifestyles (no family meals…) • Declining physical activity during work and leisure time • Changing physical environment (urban, safety) • Decreased sleep duration • Hedonic and reward aspects of food • Psychological problems • Side effects of common drugs
Weight Issues It’s Much More than ENERGY BALANCE Social factors play a role
• Sweet taste permits the identification of energy-rich nutrients • Umami (savoury/meaty taste) allows recognition of protein • Salty taste ensures proper electrolyte balance • Sour and Bitter tastes warn against the intake of potentially poisonous chemicalsTaste has the additional value of contributing to the overall pleasure and enjoyment of a food
Taste results from the stimulation of specialised cells (TRCs), grouped in clusters or taste buds, mainly located on the tongue, but also in gut. Circumvallate papillae, contain thousands of taste buds. Foliate papillae, contain hundreds of taste buds. Fungiform papillae contain one or a few taste buds
Structure of sucrose and various artificial sweeteners
LCSSaccharin, discovered in 1878Cyclamate in Europe (in 1969, banned in the USdue to association with bladder cancer in rats.Subsequent review of the evidence raised questionsabout the trials, but remained unapproved in USAAspartame, approved for use in food 1981,Acesulfame-KSucraloseNeotameStevia, a herb with intense sweetness
AspartameUsed worldwide in over 6000 productsADI levels of 50 (FDA)and 40 mg/kg bw/day, (EFSA)The rise in plasma levels of Phen and aspartic followingadministration of aspartame at doses < 50 mg/kg do notexceed those observed postprandially.No credible evidence that aspartame is carcinogenic.No evidence that aspartame will affect nervous systemfunction, learning or behavior.
What are the Consumption levels of LCS ?Approved NNS are regarded as “GRAS” producers and manufacturers are not required to provide content data on food labelsData on the amounts of NNS in foods not readilyaccessible.
Use of Sweetners in USA(millions tons)
Artificial sweetener use andobesity trends in the United States
Safety standards for consumption of NNSEuropean Food Safety Agency (EFSA) havs establishedAcceptable Daily Intakes (ADI)20 cans of diet cola for aspartame 9 to 12 packets of sweetener for saccharin30 to 32 cans of diet lemon soda for acesulfame-K6 cans of diet cola for sucralose
Calorie savings available by choosing foods and drinks with LCS Calories (kcal) Product With sugar Low calorie sweetenersCarbonated soft drinks 330 ml 145 2Powdered soft drinks 240 ml 86 5Desserts 240 ml 150 75Milk shake mix 180 ml 110 50Fruit yoghurt 180 g 207 81Table top sweetener tablets 16 1Table top sweetener powder 16 2
Key questions Does the replacement of a high energy sweetener (such as sucrose) with an artificial sweetener (such as saccharine or aspartame) lead to weight loss? Substituting sugar with low calorie sweeteners may be an efficacious weight management strategy? Does sweetness (with or without energy) contribute to over-consumption?
2.. normal-weight subjects Weight 1 150 g /day soda sweetened with aspartame HFCS , for 3 wk 7% decrease in calorie intake when subjects drank APM- sweetened soda Am J Clin Nutr 90
Energy and macronutrient intakes from ad libitum diet at 0, 5, 10 weeks After 10 wk, thesucrose group hadincreases in total energy, sucrose, and carbohydrate intakes and decreases in fat and protein intakes Raben A et al. Am J Clin Nutr 2002 ;76:721
Body weight and fat mass increased in the sucrose group (1.6 and 1.3 kg) and decreased in the sweetener group (-1.0 and -0.3 kg)Raben A et al. Sucrose compared with artificial sweeteners: different effects on ad libitum food intakeand body weight after 10 wk of supplementation in overweight subjects. Am J Clin Nutr 2002 ;76:721
PRCT, 160 obese women randomly assigned to consume or to abstain from aspartame- sweetened foods and beverages during 16-wk weight-reduction program a 1-y maintenance program, and a 2-y follow-up periodno difference in weight loss between groups usingand avoiding aspartame, but the aspartame group regained significantly less weight during maintenance and follow-up ( 3 years) Blackburn et al. AJCN 1997
Do artificial sweeteners actuallyhelp reduce weight? Replacement of sucrose with aspartame could result in a decrease in calorie intake, enough to produce a health benefit. Even modest reductions in the intake of calories can reduce the risk factors associated with diabetes and cardiovascular disease
But… Epidemiologic data suggest the opposite. Several large scale prospective cohort studies found positive correlation between artificial sweetener use and weight gain.
Do LCS promote weight gain?ACS surveyconducted over one year with 78,694 women 50–69 yoAfter controlling for initial body weight, those whoused LCS were significantly more likely to gain weightthan non-users.However, mean weight changes differed by less than1Kg, so no conclusion was drawnDespite the conservative interpretation of the data, thehypothesis generated considerable debate.
6,814 adults, 45–84 years,Diet soda consumption was assessed by food frequency questionnaire at baseline (2000–2002). At least daily consumption of diet soda was associated with a 36% greater relative risk of incident metabolic syndrome and a 67% greater relative risk of incident type 2 diabetes compared with non consumption Diabetes Care 32:688–694, 2009
The San Antonio Heart Study OR of becoming overweight OR of becoming obeseFowler. SP. Et al. Fueling the Obesity Epidemic? Artificially SweetenedBeverage Use and Long-term Weight Gain . Obesity (2008) 16, 1894–1900.
Fueling the Obesity Epidemic? Artificially Sweetened Beverage Use and Long-term Weight Gain in the San Antonio Heart Study Δ BMIs were 47%greater among artificial sweetner users than nonusers (+1.48 kg/m2 vs. +1.01 kg/m2, P < 0.0001).Fowler. SP. Et al. Obesity (2008) 16, 1894–1900.
Critics•These are observational studies, notclinical trials•The potential confounding of LCS usefor weight control cannot be ruled out•Prevalence of obesity is higher amongMexican Americans but use of AS is lower
Potential mechanisms blamed Dissociating sweetness from calories, LCS could interfere with physiological responses that control homeostasis. Changing the intestinal environment, LCS could affect the microbiota and, in turn, trigger inflammatory processes associated with metabolic disorders. Interacting with sweet-taste receptors discovered in the gut, LCS could affect glucose absorptive capacity and activate gut sweet-taste pathways that control incretin release and upregulate glucose transporters.
LCS and AppetiteAcute exposure to LCS in vehicles providing noenergy, augments hunger relative to effects ofexposure to the vehicle alone.Similar effects in a study of comparable design,using NaCl . The phenomenon may be attributable to oralexposure to a palatable stimulus in the absenceof an energy load
Is there any compensation? It has been told that after ingestion of a sweetened, non-energy-yielding beverage one can “compensate” increasing energy intake •Estimated compensation rate of around one-third of energy substituted •Soft drinks around 15%. This is reasonable as it is likely that energy obtained from liquids is less satiating Nevertheless, these compensation values are derived from short-term studies
Effect of preloads containing stevia,aspartame, or sucrose on food intake, satiety,and postprandial glucose and insulin levels. 19 healthy lean and 12 obese hunger and satiety levels were similar in all three conditions. In terms of hedonic ratings, participants rated the preloads containing aspartame as having a more pleasant taste than the preloads containing stevia or sucrose.Anton et al. Effects of stevia, aspartame, and sucrose on food intake, satiety, andpostprandial glucose and insulin levels. Appetite 2010 ; 55(1):37-43
Participants did not compensate(food intake at subsequent lunch and dinner meals was not increased) when they consumed lower calorie preloads containing stevia or aspartame compared to sucrose. . Anton et al. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite 2010 ; 55(1):37-43
Consumption of stevia in preloads significantly lowered postprandial insulin levels compared to both aspartame and sucrose, as well as postprandial glucose levels compared to sucrose. Consumption of aspartame in preloads reduced postprandial glucose compared to sucroseAnton et al. Effects of stevia, aspartame, and sucrose on food intake, satiety, andpostprandial glucose and insulin levels. Appetite 2010 ; 55(1):37-43
Is there any compensation? The preponderance of evidence in long- term feeding trials indicates that LCS results in no change or a reduction in energy intake
Meta-analyses 16 studies Subjects in 3 trials were obese Significant reduction in energy intake with aspartame mean reduction of about 10% of energy intake.de La Hunty Br Nutr FoundBull. 2006: 31; 115-128
Meta-analyses: 16 studies Significant reduction in weight about a 3% reduction in body weightde La HuntyBr Nutr FoundNutr Bull. 2006
The meta-analyses demonstrate that using foods and drinks sweetened with aspartame instead of sucroseresults in a significant reduction in both energy intakes and body weight. Rate of weight loss of about 0.2 kg/week.This is a low but meaningful rate of weight loss and, more than sufficient to counteract the current average rate of weight gain of around 0.007 kg/week de La Hunty A, Gibson S, Ashwell M. A review of the effectiveness of aspartame in helping with weight control. Br Nutr Found Nutr Bull. 2006: 31; 115-128
Sweet taste receptorsa heterodimer of two transmembraneproteins (T1R2 , T1R3 and gustducin) has several different binding sites Present in lingual taste buds, and GLP-1 secreting L cells of the gut Respond to caloric sugars and to LCS Serve as mediators of GLP-1 secretion
Role of Incretins in Glucose Homeostasis Ingestion of food Pancreas Glucose-dependent Insulin from β cells Glucose uptake by muscles Release of gut (GLP-1 and GIP) hormones — Blood glucose in GI tract incretins* fasting and β cells postprandial states Active α cells GLP-1 & GIP Glucose production DPP-4 Glucose dependent by liver enzyme Glucagon from α cells (GLP-1) Inactive Inactive GLP-1 GIP *Incretins are also released throughout the day at basal levels. Adapted from Kieffer TJ, Habener JF. Endocr Rev. 1999;20:876–913; Ahrén B. Curr Diab Rep. 2003;2:365–372; Drucker DJ. Diabetes Care. 2003;26:2929–2940; Holst JJ. Diabetes Metab Res Rev. 2002;18:430–441. 16
Effects of the Incretin Hormones GLP-1 GIP Is released from L cells in ileum Is released from K cells in and colon duodenum Stimulates insulin response from Stimulates insulin response from β cells in a glucose-dependent β cells in a glucose-dependent manner manner Inhibits gastric emptying Has minimal effects on gastric Reduces food intake and emptying body weight Has no significant effects on Inhibits glucagon secretion from satiety or body weight α cells in a glucose-dependent Does not appear to inhibit manner glucagon secretion from α cells Effect on β-cell turnover in Effect on β-cell turnover in preclinical models preclinical modelsMeier JJ et al. Best Pract Res Clin Endocrinol Metab. 2004;18:587–606; Drucker DJ. Diabetes Care. 2003;26:2929–2940;Farilla L et al. Endocrinology. 2003;144:5149–5158. 14
GLP-1 secretion after diet soda ingestion in volunteersdue to stimulation of gut taste receptors by LCS synergizing with glucose-mediated stimulation of GLP-1 release.
.in volunteers, consumption of diet soda before an oralglucose challenge potentiates GLP-1 secretion, and insulinsecretionTranslating these results into the clinical setting,consumption of a LCS in conjunction with a sugarcontaining food or drink could lead to more rapid sugarabsorption, as well as increased GLP-1and potentially altering both gastric emptying and insulinsecretion
sucralose given by intragastric infusion does not stimulates GLP-1 or GIP release in humans or slow gastric emptying. This implies that it may have no therapeutic benefit in the dietary management of diabetes, other than as a substitute for carbohydrateBut no GLP-1 increase with sucralose
ConclusionsThe use of LCS instead of sucrose seems to maintainand lose weight and to promote long-term dietarycompliance without losing the palatability of the dietThe decrease in energy intakes and the rate of weightloss that can reasonably be achieved is low, butmeaningful.There is no clear evidence that LCS augment appetiteor compensationIndeed, there is emerging evidence that selected NNSmay stimulate the release of satiety hormones likeGLP-1
Conclusion IILCS can help to reduce energy intake, withoutcompromising tasteLCS give people the opportunity to enjoy a sweet tastewithout adding calories to their diet.LCS, either as ingredients in foods and drinks or as table-top products, can help people who are seeking to reducetheir energy and sugar intake as part of a healthy andbalanced diet.