1. Saurabh Patel 12/07/2011 Product safety and Risk management Instructor: Dr. Anthony Schatz Nutrasweet/Equal (Aspartame)

2. What is Aspartame?? An artificial, non-saccharide low calorie sweetener used as sugar substitute in some food and beverages. 200 times sweeter than sugar Chemically it is L-aspartyl-L-phenylalanine methyl ester Molecular formula: C14H18N2O5 Mol. Wt 294 3. History at a glance Aspartame was discovered serendipitously by Dr. James Schlatter (G.D. Searle pharmaceutical) in 1965 while he was working on antiulcer drug. Regulated by US-FDA Approved by FDA in 1974 for restricted use in dry foods. Petition filed by Searle pharmaceuticals for use in carbonated beverages in 1982 First carbonated beverages containing Aspartame sold in Fall 1983. Eventually approved as general sweetener in 1996 4. In the market Widely marketed and available as: Nutrasweet - Chemically pure aspartame Equal: Packets of 33 mg Tablets of 19 mg Equal consist of dextrose with maltodextrin and aspartame 5. Recommended uses and limits Suggested to be used for Various foods and beverages Chewable multi-vitamins Pharmaceuticals ADI for aspartame is 50 mg/kg of body weight (3500 mg/day for 70 kg individual), it falls under OEB category 1 (OEL being >1 mg/ m3) and it is considered safe for human consumption Accordingly an individual will have to consume 97 packets of tabletop sweetener to reach these ADI value. 6. Anticipated toxicity As a whole considered safe at recommended levels, however the primary concerns are centered upon its chronic usage or ingestion of very large single dose >10 g especially in Phenylketonurics (PKU) Phenylketonuria is a rare congenital condition in which a baby is born without the ability to properly metabolize an amino acid called phenylalanine, due to lack of hepatic enzyme phenylalanine hydroxylase Lactating women should avoid aspartame in diet if child is PKU 7. Benefits Sugar substitutes with low calorie No contribution to obesity and thus may help in losing weight Helps to prevent high blood pressure Diabetic can satisfy his craving for sweet using such artificial sweeteners 8. Associated Risks Most of the adverse conditions are due to its metabolic products: methanol, formaldehyde, phenylalanine etc. Formaldehyde has been shown to be very toxic at very small concentrations and is considered as occupational carcinogen by NIOSH. Independent studies carried out over a decade from 1998-2007 links aspartame to various adverse conditions like painful fibromyalgia, brain tumors, memory loss, Lymphomas, leukemias and many other complication. 9. Toxicity studies There is no acute toxicity. Aspartame is safely consumed in single dose < 10 gm except in case of phenylketonurics. There have been some case reports of adverse effects upon chronic use of aspartame, especially the metabolic fate of aspartame has been a concern due to formation of methanol and formaldehyde both of which are known to be toxic. Also carcinogenic potential have been evaluated in numerous studies with positive as well as negative results but FDA has always concluded that Aspartame is safe for general use as sweetener and there is no need to review the previously established ADI value. But the safety of aspartame still remains questionable since it appears that food industry has a profound influence on these safety studies on aspartame 10. Animal Toxicity Studies A studies performed by Soffritti et al. in 2005 and sequel studies in 2007/2008 which support the previous studies and reinstated the consclusions. Aspartame was administered to 8 week old male and female rats in groups of 100-150/sex/group at 100,000; 50,000; 10,000; 2000; 400; 80; and 0 ppm till their natural death. With increased incidence of malignant tumor bearing animals with significant positive trend, aspartame was shown to be a multipotential carcinogen even at daily dose of 20 mg/kg body weight. However in a review by Magnuson B, et al. they pointed out various flaws in studies performed by Soffritti, et al The reviewers Magnuson B and Williams GM worked for Burdock group which managed independent review and was financially supported by Ajinomoto company Inc. a producer of aspartame. 11. Exposure assessment It has been shown in one of the study that 1 liter diet soda consist of about 600mg of aspartame as studied using HPLC analytical method. Each molecule of aspartame gives a molecule of phenylalanine and methanol. This corresponds to 10 mg/kg of aspartame for a 60 kg individual 600 mg of aspartame (Mol. Wt 294) converts to 65.4 mg methanol (Mol. Wt. 32) which further gets converted to 61.3 mg of formaldehyde (Mol. Wt. 30) 12. Exposure assessment. cont This is based upon simple correlations of their molar weight as follows: Similarly 65.4 mg of methanol converts to 61.3 mg of formaldehyde However only 70-75% of methanol is absorbed from aspartame and of which 90% converts to formaldehyde Thus 61.3 x 72.5% x 90% = 39.99 mg of formaldehyde exposure from 1 liter diet soda (approximately three 12 oz cans of soda) Amount of formaldehyde causing irreversible genetic damage to human is shown to be 3.375 mg/ m3 or 33.75 mg/day Thus a person consuming 3 cans of diet soda per day may be exposed to significant amount of formaldehyde which may accumulate in the body 13. Risk/Benefit analysis As per FDAs conclusion for various studies Aspartame still remains safe for human consumption at recommended ADI. However since aspartame is a widely used consumer product an unbiased review by independent panel of scientist is also necessary to answer the unsettled controversies especially those related to metabolic fate of aspartame and thereby exposure to formaldehyde (recognized as carcinogen by NIOSH)