Low Calorie Sweeteners

Transcription

1 Low Calorie Sweeteners John D. Fernstrom, Ph.D. University of Pittsburgh School of Medicine

2 Discussion Points What are the LCS? How do they work to generate sweetness? Are they safe? How much do we eat? What are the current safety concerns?

3 Structures of some LCS SUCRALOSE (600X sugar sweetness) SACCHARIN (300X sugar sweetness) ACESULFAME-K (200X sugar sweetness) vanillin Aspartate ADVANTAME (20,000X sugar sweetness) CH 3 Methylester ASPARTAME (180X sugar sweetness) Phenylalanine REBAUDIOSIDE A ( X sugar sweetness) 54 amino acids BRAZZEIN ( X sugar sweetness)

4 Taste Receptors in the Mouth Bitter Sweet Umami Source: adapted from Yasumatsu K et al. Am J Clin Nutr 90 (suppl): 747S-752S, 2009.

5 Sweet Taste Receptor Glucose-Sucrose-Sucralose Brazzein Aspartame CRD VFT Cyclamate Lactisole TMD T 1 R 2 T 1 R 3 Adapted from: Vigues S et al. The receptor basis of sweet taste in mammals. Results Probl Cell Differ 47: , 2009.

6 LCS: Daily Intake & ADI Sweetener Daily Intake All Consumers (mg/kg/d) Daily Intake Highest Consumers (mg/kg/d) ADI* (mg/kg/d) Saccharin < 2 < 4 5 Sucralose < 1 < Acesulfame-K < 1 < 4 15 Aspartame < 5 < Sources: Magnuson BM et al. Crit Rev Toxicol 37: , 2009; Renwick AG. Food Chem Toxicol 46 (suppl 7): S61-S69, *ADI (Acceptable Daily Intake): the intake level in humans that may be safely consumed daily for a lifetime by virtually any member of the population without health or safety concerns.

7 Scientific data required by the FDA to support safety in a Food Additive Petition 1. Short-term tests for genetic toxicity 2. Metabolism and pharmacokinetic studies 3. Short-term toxicity tests in rodents 4. Sub-chronic toxicity tests with rodents (usually 90 days in duration) 5. Sub-chronic toxicity tests with non-rodents (usually 90 days in duration) 6. Reproduction studies with a teratology phase to determine the potential of the additive to induce reproductive toxic effects or adversely affect any of the reproductive organs or reproductive systems of an animal, or produce birth defects of any type 7. One-year toxicity tests with non-rodents 8. Chronic (lifetime duration, i.e., 24 months, typically) toxicity and carcinogenicity studies with rodents 9. Additional data as required following FDA review. Source: Rulis AM, Levitt JA (2009). Regul Toxicol Pharmacol 53:

8 CH 3 Aspartate Methylester Phenylalanine

9 COMPREHENSIVE REVIEWS IN FOOD SCIENCE & FOOD SAFETY 5: 35-47, 2006

10 Regulatory Toxicology & Pharmacology 53 (2009) 20-31

11 What s are safety issues now? LCS make you fat? LCS stimulate sweet taste receptors on gut EE cells causing incretin (e.g., GLP-1) release which can lead to overeating and obesity? LCS alter the bowel microbiome, which can lead to obesity/diabetes?

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13 LCS don t cause obesity Fig 2. Changes in body weight during the course of the study for Aspartame (closed symbols) and placebo (open symbols) groups. Adult males & females (18-62 yr; BMI 23-24) ingested for 6 monoths capsules containing aspartame (75 mg/kg/day, n=53) or placebo (n=55). Data are means ± SEM. Source: Leon AS et al., Safety of Long Term Large Doses of Aspartame. Arch Intern Med 149: , 1989.

14 Other well-designed Human Intervention Studies showing NO LCS Effects on Body Weight 1. Porikos KP & Pi-Sunyer FX. Clin.Endocrinol. Metab. 13: (1984). (12 days) 2. Tordoff MG, Alleva AM. Am.J.Clin.Nutr. 51: , (1990). (3 weeks) 3. Raben A et al. Am.J.Clin.Nutr. 76: , (2002). (10 weeks) 4. de Ruyter JC et al. N.Engl.J.Med. 367: (2012). (18 MONTHS)

15 School children who drink sugar-sweetened beverages (n = 641). Half given sugar-sweetened (104 kcal) & half NNS-sweetened beverage. Double-blind study. Beverage consumed daily with snack at morning break (snack 140 kcal), & over weekend. Teachers monitored beverage intake at school. Parents reminded frequently about weekend consumption. Anthropometric measures at 0, 6, 12 and 18 months.

16 Important Points Diversity of LCS structures all act via one receptor. LCS approved by FDA after extensive testing for safety. They are safe. We actually consume very little of the LCS in our diet. BUT, Public still believes LCS aren t safe. Latest concern: LCS make us fat, although the data show this is not true. A conundrum.