Aspartame: Decades of Science Point to Serious Health Risks

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Long History of Concerns
Key Scientific Studies on Aspartame
Industry PR Efforts
Scientific References

Key Facts About Diet Soda Chemical 

What is Aspartame?

  • Aspartame is the world’s most widely used artificial sweetener. It is also marketed as NutraSweet, Equal, Sugar Twin and AminoSweet.
  • Aspartame is present in more than 6,000 products, including Diet Coke and Diet Pepsi, Kool Aid, Crystal Light, Tango and other artificially sweetened drinks; sugar-free Jell-O products; Trident, Dentyne and most other brands of sugar-free gum; sugar-free hard candies; low- or no-sugar sweet condiments such as ketchups and dressings; children’s medicines, vitamins and cough drops.
  • Aspartame is a synthetic chemical composed of the amino acids phenylalanine and aspartic acid, with a methyl ester. When consumed, the methyl ester breaks down into methanol, which may be converted into formaldehyde.

Decades of Studies Raise Concerns about Aspartame

Since aspartame was first approved in 1974, both FDA scientists and independent scientists have raised concerns about possible health effects and shortcomings in the science submitted to the FDA by the manufacturer, G.D. Searle. (Monsanto bought Searle in 1984).

In 1987, UPI published a series of investigative articles by Gregory Gordon reporting on these concerns, including early studies linking aspartame to health problems, the poor quality of industry-funded research that led to its approval, and the revolving-door relationships between FDA officials and the food industry. Gordon’s series is an invaluable resource for anyone seeking to understand the history of aspartame/NutraSweet:

Health Effects and Key Studies on Aspartame 

While many studies, some of them industry sponsored, have reported no problems with aspartame, dozens of independent studies conducted over decades have linked aspartame to a long list of health problems, including:

Cancer

In the most comprehensive cancer research to date on aspartame, three lifespan studies conducted by the Cesare Maltoni Cancer Research Center of the Ramazzini Institute, provide consistent evidence of carcinogenicity in rodents exposed to the substance.

  • Aspartame “is a multipotential carcinogenic agent, even at a daily dose of … much less than the current acceptable daily intake,” according to a 2006 lifespan rat study in Environmental Health Perspectives.1
  • A follow-up study in 2007 found significant dose-related increases in malignant tumors in some of the rats. “The results … confirm and reinforce the first experimental demonstration of [aspartame’s] multipotential carcinogenicity at a dose level close to the acceptable daily intake for humans … when life-span exposure begins during fetal life, its carcinogenic effects are increased,” the researchers wrote in Environmental Health Perspectives.2
  • The results of a 2010 lifespan study “confirm that [aspartame] is a carcinogenic agent in multiple sites in rodents, and that this effect is induced in two species, rats (males and females) and mice (males),” the researchers reported in American Journal of Industrial Medicine.3

Harvard researchers in 2012 reported a positive association between aspartame intake and increased risk of non-Hodgkin lymphoma and multiple myeloma in men, and for leukemia in men and women. The findings “preserve the possibility of a detrimental effect … on select cancers” but “do not permit the ruling out of chance as an explanation,” the researchers wrote in the American Journal of Clinical Nutrition.4

In a 2014 commentary in American Journal of Industrial Medicine, the Maltoni Center researchers wrote that the studies submitted by G. D. Searle for market approval “do not provide adequate scientific support for [aspartame’s] safety. In contrast, recent results of life-span carcinogenicity bioassays on rats and mice published in peer-reviewed journals, and a prospective epidemiological study, provide consistent evidence of [aspartame’s] carcinogenic potential. On the basis of the evidence of the potential carcinogenic effects … a re-evaluation of the current position of international regulatory agencies must be considered an urgent matter of public health.”5

Brain Tumors

In 1996, researchers reported in the Journal of Neuropathology & Experimental Neurology on epidemiological evidence connecting the introduction of aspartame to an increase in an aggressive type of malignant brain tumors. “Compared to other environmental factors putatively linked to brain tumors, the artificial sweetener aspartame is a promising candidate to explain the recent increase in incidence and degree of malignancy of brain tumors … We conclude that there is need for reassessing the carcinogenic potential of aspartame.”6

  • Neuroscientist Dr. John Olney, lead author of the study, told 60 minutes in 1996: “there has been a striking increase in the incidence of malignant brain tumors (in the three to five years following the approval of aspartame) … there is enough basis to suspect aspartame that it needs to be reassessed. FDA needs to reassess it, and this time around, FDA should do it right.”

Early studies on aspartame in the 1970s found evidence of brain tumors in laboratory animals, but those studies were not followed up.

Cardiovascular Disease 

A 2017 meta-analysis of research on artificial sweeteners, published in the Canadian Medical Association Journal, found no clear evidence of weight loss benefits for artificial sweeteners in randomized clinical trials, and reported that cohort studies associate artificial sweeteners with “increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events.”7 See also:

  • “Artificial sweeteners don’t help with weight loss and may lead to gained pounds,” by Catherine Caruso, STAT (7.17.2017)
  • “Why one cardiologist has drunk his last diet soda,” by Harlan Krumholz, Wall Street Journal (9.14.2017)
  • “This cardiologist wants his family to cut back on diet soda. Should yours, too?” by David Becker, M.D., Philly Inquirer (9.12.2017)

 A 2016 paper in Physiology & Behavior reported, “there is a striking congruence between results from animal research and a number of large-scale, long-term observational studies in humans, in finding significantly increased weight gain, adiposity, incidence of obesity, cardiometabolic risk, and even total mortality among individuals with chronic, daily exposure to low-calorie sweeteners – and these results are troubling.”8

Women who consumed more than two diet drinks per day “had a higher risk of [cardiovascular disease] events … [cardiovascular disease] mortality … and overall mortality,” according to a 2014 study from the Women’s Health Initiative published in the Journal of General Internal Medicine.9

Stroke, Dementia and Alzheimer’s Disease

People drinking diet soda daily were almost three times as likely to develop stroke and dementia as those who consumed it weekly or less. This included a higher risk of ischemic stroke, where blood vessels in the brain become obstructed, and Alzheimer’s disease dementia, the most common form of dementia, reported a 2017 study in Stroke.10

In the body, the methyl ester in aspartame metabolizes into methanol and then it may be converted to formaldehyde, which has been linked to Alzheimer’s disease. A two-part study published in 2014 in the Journal of Alzheimer’s Disease linked chronic methanol exposure to memory loss and Alzheimer’s Disease symptoms in mice and monkeys.

  • “[M]ethanol-fed mice presented with partial AD-like symptoms … These findings add to a growing body of evidence that links formaldehyde to [Alzheimer’s disease] pathology.” (Part 1)11
  • “[M]ethanol feeding caused long-lasting and persistent pathological changes that were related to [Alzheimer’s disease] … these findings support a growing body of evidence that links methanol and its metabolite formaldehyde to [Alzheimer’s disease] pathology.” (Part 2)12

Seizures

“Aspartame appears to exacerbate the amount of EEG spike wave in children with absence seizures. Further studies are needed to establish if this effect occurs at lower doses and in other seizure types,” according to a 1992 study in Neurology.13

Aspartame “has seizure-promoting activity in animal models that are widely used to identify compounds affecting … seizure incidence,” according to a 1987 study in Environmental Health Perspectives.14

Very high aspartame doses “might also affect the likelihood of seizures in symptomless but susceptible people,” according to a 1985 study in The Lancet. The study describes three previously healthy adults who had grand mal seizures during periods when they were consuming high doses of aspartame.15

Neurotoxicity, Brain Damage and Mood Disorders

Aspartame has been linked to behavioral and cognitive problems including learning problems, headache, seizure, migraines, irritable moods, anxiety, depression, and insomnia, wrote the researchers of a 2017 study in Nutritional Neuroscience. “Aspartame consumption needs to be approached with caution due to the possible effects on neurobehavioral health.”16

“Oral aspartame significantly altered behavior, anti-oxidant status and morphology of the hippocampus in mice; also, it may probably trigger hippocampal adult neurogenesis,” reported a 2016 study in Neurobiology of Learning and Memory.17 

“Previously, it has been reported that consumption of aspartame could cause neurological and behavioural disturbances in sensitive individuals. Headaches, insomnia and seizures are also some of the neurological effects that have been encountered,” according to a 2008 study in the European Journal of Clinical Nutrition. “[W]e propose that excessive aspartame ingestion might be involved in the pathogenesis of certain mental disorders … and also in compromised learning and emotional functioning.”18 

“(N)eurological symptoms, including learning and memory processes, may be related to the high or toxic concentrations of the sweetener [aspartame] metabolites,” states a 2006 study in Pharmacological Research.19

Aspartame “could impair memory retention and damage hypothalamic neurons in adult mice,” according to a 2000 mice study published in Toxicology Letters.20

“(I)ndividuals with mood disorders are particularly sensitive to this artificial sweetener and its use in this population should be discouraged,” according to a 1993 study in the Journal of Biological Psychiatry.21

High doses of aspartame “can generate major neurochemical changes in rats,” reported a 1984 study in American Journal of Clinical Nutrition.22

Experiments indicated brain damage in infant mice following oral intake of aspartate, and showing that “aspartate [is] toxic to the infant mouse at relatively low levels of oral intake,” reported a 1970 study in Nature.23

Headaches and Migraines

“Aspartame, a popular dietetic sweetener, may provoke headache in some susceptible individuals. Herein, we describe three cases of young women with migraine who reported their headaches could be provoked by chewing sugarless gum containing aspartame,” according to a 1997 paper in Headache Journal.24

A crossover trial comparing aspartame and a placebo published in 1994 in Neurology, “provides evidence that, among individuals with self-reported headaches after ingestion of aspartame, a subset of this group report more headaches when tested under controlled conditions. It appears that some people are particularly susceptible to headaches caused by aspartame and may want to limit their consumption.”25

A survey of 171 patients at the Montefiore Medical Center Headache Unit found that patients with migraine “reported aspartame as a precipitant three times more often than those having other types of headache … We conclude aspartame may be an important dietary trigger of headache in some people,” 1989 study in Headache Journal.26

A crossover trial comparing aspartame and a placebo on the frequency and intensity of migraines “indicated that the ingestion of aspartame by migraineurs caused a significant increase in headache frequency for some subjects,” reported a 1988 study in Headache Journal.27

Kidney Function Decline

Consumption of more than two servings a day of artificially sweetened soda “is associated with a 2-fold increased odds for kidney function decline in women,” according to a 2011 study in the Clinical Journal of American Society of Nephrology.28

Weight Gain, Increased Appetite and Obesity Related Problems

Several studies link aspartame to weight gain, increased appetite, diabetes, metabolic derangement and obesity-related diseases. See our fact sheet: Diet Soda Chemical Tied to Weight Gain.

This science linking aspartame to weight gain and obesity-related diseases raises questions about the legality of marketing aspartame-containing products as “diet” or weight loss aids. In 2015, USRTK petitioned the Federal Trade Commission and FDA to investigate the marketing and advertising practices of “diet” products that contain a chemical linked to weight gain. See related news coverage, response from FTC, and response from FDA.

Diabetes and Metabolic Derangement

Aspartame breaks down in part into phenylalanine, which interferes with the action of an enzyme intestinal alkaline phosphatase (IAP) previously shown to prevent metabolic syndrome (a group of symptoms associated with type 2 diabetes and cardiovascular disease) according to a 2017 study in Applied Physiology, Nutrition and Metabolism. In this study, mice receiving aspartame in their drinking water gained more weight and developed other symptoms of metabolic syndrome than animals fed similar diets lacking aspartame. The study concludes, “IAP’s protective effects in regard to the metabolic syndrome may be inhibited by phenylalanine, a metabolite of aspartame, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks.”29

People who regularly consume artificial sweeteners are at increased risk of “excessive weight gain, metabolic syndrome, type 2 diabetes, and cardiovascular disease,” according to a 2013 Purdue review over 40 years published in Trends in Endocrinology & Metabolism.30

In a study that followed 66,118 women over 14 years, both sugar-sweetened beverages and artificially sweetened beverages were associated with risk of Type 2 diabetes. “Strong positive trends in T2D risk were also observed across quartiles of consumption for both types of beverage … No association was observed for 100% fruit juice consumption,” reported the 2013 study published in American Journal of Clinical Nutrition.31

Intestinal Dysbiosis, Metabolic Derangement and Obesity

Artificial sweeteners can induce glucose intolerance by altering the gut microbiota, according to a 2014 study in Nature. The researchers wrote, “our results link NAS [non-caloric artificial sweetener] consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage … Our findings suggest that NAS may have directly contributed to enhancing the exact epidemic [obesity] that they themselves were intended to fight.”32

A 2016 study in Applied Physiology Nutrition and Metabolism reported, “Aspartame intake significantly influenced the association between body mass index (BMI) and glucose tolerance… consumption of aspartame is associated with greater obesity-related impairments in glucose tolerance.”33

According to a 2014 rat study in PLOS ONE, “aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal … Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria…”34

 Pregnancy Abnormalities: Pre Term Birth 

According to a 2010 cohort study of 59,334 Danish pregnant women published in the American Journal of Clinical Nutrition, “There was an association between intake of artificially sweetened carbonated and noncarbonated soft drinks and an increased risk of preterm delivery.” The study concluded, “Daily intake of artificially sweetened soft drinks may increase the risk of preterm delivery.”35

  • See also: “Downing Diet Soda Tied to Premature Birth,” by Anne Harding, Reuters (7.23.2010)

Overweight Babies

Artificially sweetened beverage consumption during pregnancy is linked to higher body mass index for babies, according to a 2016 study in JAMA Pediatrics. “To our knowledge, we provide the first human evidence that maternal consumption of artificial sweeteners during pregnancy may influence infant BMI,” the researchers wrote.36

Early Menarche

The National Heart, Lung, and Blood Institute Growth and Health Study followed 1988 girls for 10 years to examine prospective associations between consumption of caffeinated and noncaffeinated sugar- and artificially sweetened soft drinks and early menarche. “Consumption of caffeinated and artificially sweetened soft drinks was positively associated with risk of early menarche in a US cohort of African American and Caucasian girls,” concluded the study published in 2015 in Journal of American Clinical Nutrition.37

Sperm Damage

“A significant decrease in sperm function of aspartame treated animals was observed when compared with the control and MTX control,” according to a 2017 study in the International Journal of Impotence Research. “… These findings demonstrate that aspartame metabolites could be a contributing factor for development of oxidative stress in the epididymal sperm.”38

Liver Damage and Glutathione Depletion

A mouse study published in 2017 in Redox Biology reported, “Chronic administration of aspartame … caused liver injury as well as marked decreased hepatic levels of reduced glutathione, oxidized glutathione, γ-glutamylcysteine, and most metabolites of the trans-sulphuration pathway…”39

A rat study published in 2017 in Nutrition Research found that, “Subchronic intake of soft drink or aspartame substantially induced hyperglycemia and hypertriacylglycerolemia… Several cytoarchitecture alterations were detected in the liver, including degeneration, infiltration, necrosis, and fibrosis, predominantly with aspartame. These data suggest that long-term intake of soft drink or aspartame-induced hepatic damage may be mediated by the induction of hyperglycemia, lipid accumulation, and oxidative stress with the involvement of adipocytokines.”40

Caution for Vulnerable Populations

A 2016 literature review on artificial sweeteners in the Indian Journal of Pharmacology reported, “there is inconclusive evidence to support most of their uses and some recent studies even hint that these earlier established benefits … might not be true.” Susceptible populations such as pregnant and lactating women, children, diabetics, migraine, and epilepsy patients “should use these products with utmost caution.”41

Industry PR Efforts and Front Groups 

From the start, G.D. Searle (later Monsanto and the NutraSweet Company) deployed aggressive PR tactics to market aspartame as a safe product. In October 1987, Gregory Gordon reported in UPI:

“The NutraSweet Co. also has paid up to $3 million a year for a 100-person public relations effort by the Chicago offices of Burson Marsteller, a former employee of the New York PR firm said. The employee said Burson Marsteller has hired numerous scientists and physicians, often at $1,000 a day, to defend the sweetener in media interviews and other public forums. Burson Marsteller declines to discuss such matters.”

Recent reporting based on internal industry documents reveals how beverage companies such as Coca-Cola also pay third party messengers, including doctors and scientists, to promote their products and shift the blame when science ties their products to serious health problems.

See reporting by Anahad O’Connor in the New York Times, Candice Choi in the Associated Press, and findings from the USRTK investigation about sugar industry propaganda and lobbying campaigns.

News articles about soda industry PR campaigns:

Overview news stories about aspartame:

USRTK Fact Sheets

Reports on Front Groups and PR Campaigns

Scientific References

[1] Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L, Tibaldi E, Rigano A. “First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats.” Environ Health Perspect. 2006 Mar;114(3):379-85. PMID: 16507461. (article)

[2] Soffritti M, Belpoggi F, Tibaldi E, Esposti DD, Lauriola M. “Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats.” Environ Health Perspect. 2007 Sep;115(9):1293-7. PMID: 17805418. (article)

[3] Soffritti M et al. “Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice.” Am J Ind Med. 2010 Dec; 53(12):1197-206. PMID: 20886530. (abstract / article)

[4] Schernhammer ES, Bertrand KA, Birmann BM, Sampson L, Willett WC, Feskanich D., “Consumption of artificial sweetener– and sugar-containing soda and risk of lymphoma and leukemia in men and women.” Am J Clin Nutr. 2012 Dec;96(6):1419-28. PMID: 23097267. (abstract / article)

[5] Soffritti M1, Padovani M, Tibaldi E, Falcioni L, Manservisi F, Belpoggi F., “The carcinogenic effects of aspartame: The urgent need for regulatory re-evaluation.” Am J Ind Med. 2014 Apr;57(4):383-97. doi: 10.1002/ajim.22296. Epub 2014 Jan 16. (abstract / article)

[6] Olney JW, Farber NB, Spitznagel E, Robins LN. “Increasing brain tumor rates: is there a link to aspartame?” J Neuropathol Exp Neurol. 1996 Nov;55(11):1115-23. PMID: 8939194. (abstract)

[7] Azad, Meghan B., et al. Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. CMAJ July 17, 2017 vol. 189 no. 28 doi: 10.1503/cmaj.161390 (abstract / article)

[8] Fowler SP. Low-calorie sweetener use and energy balance: Results from experimental studies in animals, and large-scale prospective studies in humans. Physiol Behav. 2016 Oct 1;164(Pt B):517-23. doi: 10.1016/j.physbeh.2016.04.047. Epub 2016 Apr 26. (abstract)

[9] Vyas A et al. “Diet Drink Consumption And The Risk of Cardiovascular Events: A Report from The Women’s Health Initiative.” J Gen Intern Med. 2015 Apr;30(4):462-8. doi: 10.1007/s11606-014-3098-0. Epub 2014 Dec 17. (abstract / article)

[10] Matthew P. Pase, PhD; Jayandra J. Himali, PhD; Alexa S. Beiser, PhD; Hugo J. Aparicio, MD; Claudia L. Satizabal, PhD; Ramachandran S. Vasan, MD; Sudha Seshadri, MD; Paul F. Jacques, DSc. “Sugar and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia. A Prospective Cohort Study.” Stroke. 2017 April; STROKEAHA.116.016027 (abstract / article)

[11] Yang M et al. “Alzheimer’s Disease and Methanol Toxicity (Part 1): Chronic Methanol Feeding Led to Memory Impairments and Tau Hyperphosphorylation in Mice.” J Alzheimers Dis. 2014 Apr 30. (abstract)

[12] Yang M et al. “Alzheimer’s Disease and Methanol Toxicity (Part 2): Lessons from Four Rhesus Macaques (Macaca mulatta) Chronically Fed Methanol.” J Alzheimers Dis. 2014 Apr 30. (abstract)

[13] Camfield PR, Camfield CS, Dooley JM, Gordon K, Jollymore S, Weaver DF. “Aspartame exacerbates EEG spike-wave discharge in children with generalized absence epilepsy: a double-blind controlled study.” Neurology. 1992 May;42(5):1000-3. PMID: 1579221. (abstract)

[14] Maher TJ, Wurtman RJ. “Possible neurologic effects of aspartame, a widely used food additive.” Environ Health Perspect. 1987 Nov; 75:53-7. PMID: 3319565. (abstract / article)

[15] Wurtman RJ. “Aspartame: possible effect on seizure susceptibility.” Lancet. 1985 Nov 9;2(8463):1060. PMID: 2865529. (abstract)

[16] Choudhary AK, Lee YY. “Neurophysiological symptoms and aspartame: What is the connection?” Nutr Neurosci. 2017 Feb 15:1-11. doi: 10.1080/1028415X.2017.1288340. (abstract)

[17] Onaolapo AY, Onaolapo OJ, Nwoha PU. “Aspartame and the hippocampus: Revealing a bi-directional, dose/time-dependent behavioural and morphological shift in mice.” Neurobiol Learn Mem. 2017 Mar;139:76-88. doi: 10.1016/j.nlm.2016.12.021. Epub 2016 Dec 31. (abstract)

[18] Humphries P, Pretorius E, Naudé H. “Direct and indirect cellular effects of aspartame on the brain.” Eur J Clin Nutr. 2008 Apr;62(4):451-62. (abstract / article)

[19] Tsakiris S, Giannoulia-Karantana A, Simintzi I, Schulpis KH. “The effect of aspartame metabolites on human erythrocyte membrane acetylcholinesterase activity.” Pharmacol Res. 2006 Jan;53(1):1-5. PMID: 16129618. (abstract)

[20] Park CH et al. “Glutamate and aspartate impair memory retention and damage hypothalamic neurons in adult mice.” Toxicol Lett. 2000 May 19;115(2):117-25. PMID: 10802387. (abstract)

[21] Walton RG, Hudak R, Green-Waite R. “Adverse reactions to aspartame: double-blind challenge in patients from a vulnerable population.” J. Biol Psychiatry. 1993 Jul 1-15;34(1-2):13-7. PMID: 8373935. (abstract / article)

[22] Yokogoshi H, Roberts CH, Caballero B, Wurtman RJ. “Effects of aspartame and glucose administration on brain and plasma levels of large neutral amino acids and brain 5-hydroxyindoles.” Am J Clin Nutr. 1984 Jul;40(1):1-7. PMID: 6204522. (abstract)

[23] Olney JW, Ho OL. “Brain Damage in Infant Mice Following Oral Intake of Glutamate, Aspartate or Cysteine.” Nature. 1970 Aug 8;227(5258):609-11. PMID: 5464249. (abstract)

[24] Blumenthal HJ, Vance DA. “Chewing gum headaches.” Headache. 1997 Nov-Dec; 37(10):665-6. PMID: 9439090. (abstract/article)

[25] Van den Eeden SK, Koepsell TD, Longstreth WT Jr, van Belle G, Daling JR, McKnight B. “Aspartame ingestion and headaches: a randomized crossover trial.” Neurology. 1994 Oct;44(10):1787-93. PMID: 7936222. (abstract)

[26] Lipton RB, Newman LC, Cohen JS, Solomon S. “Aspartame as a dietary trigger of headache.” Headache. 1989 Feb;29(2):90-2. PMID: 2708042. (abstract)

[27] Koehler SM, Glaros A. “The effect of aspartame on migraine headache.” Headache. 1988 Feb;28(1):10-4. PMID: 3277925. (abstract)

[28] Julie Lin and Gary C. Curhan. “Associations of Sugar and Artificially Sweetened Soda with Albuminuria and Kidney Function Decline in Women.” Clin J Am Soc Nephrol. 2011 Jan; 6(1): 160–166. (abstract / article)

[29] Gul SS, Hamilton AR, Munoz AR, Phupitakphol T, Liu W, Hyoju SK, Economopoulos KP, Morrison S, Hu D, Zhang W, Gharedaghi MH, Huo H, Hamarneh SR, Hodin RA. “Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice.” Appl Physiol Nutr Metab. 2017 Jan;42(1):77-83. doi: 10.1139/apnm-2016-0346. Epub 2016 Nov 18. (abstract / article)

[30] Susan E. Swithers, “Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements.” Trends Endocrinol Metab. 2013 Sep; 24(9): 431–441. (article)

[31] Guy Fagherazzi, A Vilier, D Saes Sartorelli, M Lajous, B Balkau, F Clavel-Chapelon. “Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes in the Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l’Education Nationale–European Prospective Investigation into Cancer and Nutrition cohort.” Am J Clin Nutr. 2013, Jan 30; doi: 10.3945/ ajcn.112.050997 ajcn.050997. (abstract/article)

[32] Suez J et al. “Artificial sweeteners induce glucose intolerance by altering the gut microbiota.” Nature. 2014 Oct 9;514(7521). PMID: 25231862. (abstract / article)

[33] Kuk JL, Brown RE. “Aspartame intake is associated with greater glucose intolerance in individuals with obesity.” Appl Physiol Nutr Metab. 2016 Jul;41(7):795-8. doi: 10.1139/apnm-2015-0675. Epub 2016 May 24. (abstract)

[34] Palmnäs MSA, Cowan TE, Bomhof MR, Su J, Reimer RA, Vogel HJ, et al. (2014) Low-Dose Aspartame Consumption Differentially Affects Gut Microbiota-Host Metabolic Interactions in the Diet-Induced Obese Rat. PLoS ONE 9(10): e109841. (article)

[35] Halldorsson TI, Strøm M, Petersen SB, Olsen SF. “Intake of artificially sweetened soft drinks and risk of preterm delivery: a prospective cohort study in 59,334 Danish pregnant women.” Am J Clin Nutr. 2010 Sep;92(3):626-33. PMID: 20592133. (abstract / article)

[36] Meghan B. Azad, PhD; Atul K. Sharma, MSc, MD; Russell J. de Souza, RD, ScD; et al. “Association Between Artificially Sweetened Beverage Consumption During Pregnancy and Infant Body Mass Index.” JAMA Pediatr. 2016;170(7):662-670. (abstract)

[37] Mueller NT, Jacobs DR Jr, MacLehose RF, Demerath EW, Kelly SP, Dreyfus JG, Pereira MA. “Consumption of caffeinated and artificially sweetened soft drinks is associated with risk of early menarche.” Am J Clin Nutr. 2015 Sep;102(3):648-54. doi: 10.3945/ajcn.114.100958. Epub 2015 Jul 15. (abstract)

[38] Ashok I, Poornima PS, Wankhar D, Ravindran R, Sheeladevi R. “Oxidative stress evoked damages on rat sperm and attenuated antioxidant status on consumption of aspartame.” Int J Impot Res. 2017 Apr 27. doi: 10.1038/ijir.2017.17. (abstract / article)

[39] Finamor I, Pérez S, Bressan CA, Brenner CE, Rius-Pérez S, Brittes PC, Cheiran G, Rocha MI, da Veiga M, Sastre J, Pavanato MA., “Chronic aspartame intake causes changes in the trans-sulphuration pathway, glutathione depletion and liver damage in mice.” Redox Biol. 2017 Apr;11:701-707. doi: 10.1016/j.redox.2017.01.019. Epub 2017 Feb 1. (abstract/article)

[40] Lebda MA, Tohamy HG, El-Sayed YS. “Long-term soft drink and aspartame intake induces hepatic damage via dysregulation of adipocytokines and alteration of the lipid profile and antioxidant status.” Nutr Res. 2017 Apr 19. pii: S0271-5317(17)30096-9. doi: 10.1016/j.nutres.2017.04.002. [Epub ahead of print] (abstract)

[41] Sharma A, Amarnath S, Thulasimani M, Ramaswamy S. “Artificial sweeteners as a sugar substitute: Are they really safe?” Indian J Pharmacol 2016;48:237-40 (article)

Chemicals on Our Food: When “Safe” May Not Really Be Safe

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Scientific scrutiny of pesticide residue in food grows; regulatory protections questioned

This article was originally published in Environmental Health News.

By Carey Gillam

Weed killers in wheat crackers and cereals, insecticides in apple juice and a mix of multiple pesticides in spinach, string beans and other veggies – all are part of the daily diets of many Americans. For decades, federal officials have declared tiny traces of these contaminants to be safe. But a new wave of scientific scrutiny is challenging those assertions.

Though many consumers might not be aware of it, every year, government scientists document how hundreds of chemicals used by farmers on their fields and crops leave residues in widely consumed foods. More than 75 percent of fruits and more than 50 percent of vegetables sampled carried pesticides residues in the latest sampling reported by the Food and Drug Administration. Even residues of the tightly restricted bug-killing chemical DDT are found in food, along with a range of other pesticides known by scientists to be linked to a range of illnesses and disease. The pesticide endosulfan, banned worldwide because of evidence that it can cause neurological and reproductive problems, was also found in food samples, the FDA report said.

U.S. regulators and the companies that sell the chemicals to farmers insist that the pesticide residues pose no threat to human health. Most residue levels found in food fall within legal “tolerance” levels set by the Environmental Protection Agency (EPA), regulators say.

“Americans depend on the FDA to ensure the safety of their families and the foods they eat,” FDA Commissioner Scott Gottlieb said in a press release accompanying the agency’s Oct. 1 release of its residue report. “Like other recent reports, the results show that overall levels of pesticide chemical residues are below the Environmental Protection Agency’s tolerances, and therefore don’t pose a risk to consumers.”

The EPA is so confident that traces of pesticides in food are safe that the agency has granted multiple chemical company requests for increases in the allowed tolerances, effectively providing a legal basis for higher levels of pesticide residues to be allowed in American food.

But recent scientific studies have prompted many scientists to warn that years of promises of safety may be wrong. While no one is expected to drop dead from eating a bowl of cereal containing pesticide residues, repeated low level exposures to trace amounts of pesticides in the diet could be contributing to a range of health problems, particularly for children, scientists say.

“There are probably many other health effects; we just haven’t studied them”

A team of Harvard scientists published a commentary in October stating that more research about potential links between disease and consumption of pesticide residues is “urgently needed” as more than 90 percent of the U.S. population has pesticide residues in their urine and blood. The primary route of exposure to these pesticides is through the food people eat, the Harvard research team said.

Several additional Harvard-affiliated scientists published a study earlier this year of women who were trying to get pregnant. The findings suggested that dietary pesticide exposure within a “typical” range was associated both with problems women had getting pregnant and delivering live babies, the scientists said.

“Clearly the current tolerance levels protect us from acute toxicity. The problem is that it is not clear to what extent long-term low-level exposure to pesticide residues through food may or may not be health hazards,” said Dr. Jorge Chavarro, associate professor of the Departments of Nutrition and Epidemiology at the Harvard T.H. Chan School of Public Health, and one of the study authors.

“Exposure to pesticide residues through diet is associated [with] some reproductive outcomes including semen quality and greater risk of pregnancy loss among women undergoing infertility treatments. There are probably many other health effects; we just haven’t studied them sufficiently to make an adequate risk assessment,” Chavarro said.

Toxicologist Linda Birnbaum, who directs the U.S. National Institute of Environmental Health Sciences (NIEHS), has also raised concerns about pesticide dangers through exposures once assumed to be safe. Last year she called for “an overall reduction in the use of agricultural pesticides” due to multiple concerns for human health, stating that “existing US regulations have not kept pace with scientific advances showing that widely used chemicals cause serious health problems at levels previously assumed to be safe.”

In an interview Birnbaum said that pesticide residues in food and water are among the types of exposures that need greater regulatory scrutiny.

“Do I think that levels that are currently set are safe? Probably not,” said Birnbaum. “We have people of different susceptibility, whether because of their own genetics, or their age, whatever may make them more susceptible to these things,” she said.

“While we look at chemicals one at a time, there is a lot of evidence for things acting in a synergistic fashion. A lot of our standard testing protocols, many that were developed 40 to 50 years ago, are not asking the questions we should be asking,” she added.

Legal doesn’t mean safe

Other recent scientific papers also point to troubling findings. One by a group of international scientists published in May found glyphosate herbicide at doses currently considered “safe” are capable of causing health problems before the onset of puberty. More research is needed to understand potential risks to children, the study authors said.

And in a paper published Oct. 22 in JAMA Internal Medicine, French researchers said that when looking at pesticide residue links to cancer in a study of the diets of more than 68,000 people, they found indications that consumption of organic foods, which are less likely to carry synthetic pesticide residues than foods made with conventionally grown crops, was associated with a reduced risk of cancer.

A 2009 paper published by a Harvard researcher and two FDA scientists found 19 out of 100 food samples that children commonly consumed contained at least one insecticide known to be a neurotoxin. The foods the researchers looked at were fresh vegetables, fruits and juices. Since then, evidence has grown about the harmful human health impacts of insecticides, in particular.

Unacceptable levels

“A number of current legal standards for pesticides in food and water do not fully protect public health, and do not reflect the latest science,” said Olga Naidenko, senior science advisor to the non-profit Environmental Working Group, which has issued several reports looking at potential dangers of pesticides in food and water. “Legal does not necessarily reflect ‘safe,'” she said.

One example of how regulatory assurances of safety have been found lacking when it comes to pesticide residues is the case of an insecticide known as chlorpyrifos. Marketed by Dow Chemical, which became the DowDuPont company in 2017, chlorpyrifos is applied to more than 30 percent of apples, asparagus, walnuts, onions, grapes, broccoli, cherries and cauliflower grown in the U.S. and is commonly found on foods consumed by children. The EPA has said for years that exposures below the legal tolerances it set were nothing to worry about.

Yet scientific research in recent years has demonstrated an association between chlorpyrifos exposure and cognitive deficits in children. The evidence of harm to young developing brains is so strong that the EPA in 2015 said that it “cannot find that any current tolerances are safe.”

The EPA said that because of unacceptable levels of the insecticide in food and drinking water it planned to ban the pesticide from agricultural use. But pressure from Dow and chemical industry lobbyists have kept the chemical in wide use on American farms. The FDA’s recent report found it the 11th most prevalent pesticides in U.S. foods out of hundreds included in the testing.

A federal court in August said that the Trump Administration was endangering public health by keeping chlorpyrifos in use for agricultural food production. The court cited “scientific evidence that its residue on food causes neurodevelopmental damage to children” and ordered the EPA to revoke all tolerances and ban the chemical from the market. The EPA has yet to act on that order, and is seeking a rehearing before the full 9th Circuit Court of Appeals.

When asked how to explain its changing positions on chlorpyrifos, an agency spokesman said that the EPA “plans to continue to review the science addressing neurodevelopmental effects” of the chemical.

The fact that it is still in wide use frustrates and angers physicians who specialize in child health and leaves them wondering what other pesticide exposures in food might be doing to people.

“The bottom line is that the biggest public health concerns for chlorpyrifos are from its presence in foods,” said Dr. Bradley Peterson director of the Institute for the Developing Mind at the Children’s Hospital of Los Angeles. “Even small exposures can potentially have harmful effects.”

The EPA decision to continue to allow chlorpyrifos into American diets is “emblematic of a broader dismissal of scientific evidence” that challenges human health as well as scientific integrity, according to Dr. Leonardo Trasande, who directs the Division of Environmental Pediatrics within the Department of Pediatrics at New York University’s Langone Health.

Epidemiologist Philip Landrigan, director of Boston College’s Global Public Health initiative, and a former scientist with the U.S. Centers for Disease Control, is advocating for a ban on all organophosphates, a class of insecticides that includes chlorpyrifos, because of the danger they pose to children.

“Children are exquisitely vulnerable to these chemicals,” said Landrigan. “This is about protecting kids.”

Increased tolerances at industry request

The Federal Food, Drug, and Cosmetic Act authorizes the EPA to regulate the use of pesticides on foods according to specific statutory standards and grants the EPA a limited authority to establish tolerances for pesticides meeting statutory qualifications.

Tolerances vary from food to food and pesticide to pesticide, so an apple might legally carry more of a certain type of insecticide residue than a plum, for instance. The tolerances also vary from country to country, so what the U.S. sets as a legal tolerance for residues of a pesticide on a particular food can – and often is – much different than limits set in other countries. As part of the setting of those tolerances, regulators examine data showing how much residue persists after a pesticide is used as intended on a crop, and they undertake the dietary risk assessments to confirm that the levels of pesticide residues don’t pose human health concerns.

The agency says that it accounts for the fact that the diets of infants and children may be quite different from those of adults and that they consume more food for their size than adults. The EPA also says it combines information about routes of pesticide exposure – food, drinking water residential uses – with information about the toxicity of each pesticide to determine the potential risks posed by the pesticide residues. The agency says if the risks are “unacceptable,” it will not approve the tolerances.

The EPA also says that when it makes tolerance decisions, it “seeks to harmonize U.S. tolerances with international standards whenever possible, consistent with U.S. food safety standards and agricultural practices.”

Monsanto, which became of unit of Bayer AG earlier this year, has successfully asked the EPA to expand the levels of glyphosate residues allowed in several foods, including in wheat and oats.

In 1993, for example, the EPA had a tolerance for glyphosate in oats at 0.1 parts per million (ppm) but in 1996 Monsanto asked EPA to raise the tolerance to 20 ppm and the EPA did as asked. In 2008, at Monsanto’s suggestion, the EPA again looked to raise the tolerance for glyphosate in oats, this time to 30 ppm.

At that time, it also said it would raise the tolerance for glyphosate in barley from 20 ppm to 30 ppm, raise the tolerance in field corn from 1 to 5 ppm and raise the tolerance of glyphosate residue in wheat from 5 ppm to 30 ppm, a 500 percent increase. The 30 ppm for wheat is matched by more than 60 other countries, but is well above the tolerances allowed in more than 50 countries, according to an international tolerance database established with EPA funding and maintained now by a private government affairs consulting group.

“The Agency has determined that the increased tolerances are safe, i.e, there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue,” the EPA stated in the May 21, 2008 Federal Register.

“All these statements from EPA – trust us it’s safe. But the truth is we have no idea if it actually is safe,” said Dr. Bruce Lanphear, a clinician scientist at the Child & Family Research Institute, BC Children’s Hospital, and a professor in the faculty of health sciences at Simon Fraser University in Vancouver, British Columbia. Lanphear said that while regulators assume toxic effects increase with dose, scientific evidence shows that some chemicals are most toxic at the lowest levels of exposure. Protecting public health will require rethinking basic assumptions about how agencies regulate chemicals, he argued in a paper published last year.

In recent years both Monsanto and Dow have received new tolerance levels for the pesticides dicamba and 2,4-D on food as well.

Raising tolerances allows farmers to use pesticides in various ways that may leave more residues, but that doesn’t threaten human health, according to Monsanto. In a blog posted last year, Monsanto scientist Dan Goldstein asserted the safety of pesticide residues in food generally and of glyphosate in particular. Even when they exceed the regulatory legal limits, pesticide residues are so minuscule they pose no danger, according to Goldstein, who posted the blog before he retired from Monsanto this year.

About half of foods sampled contained traces of pesticides

Amid the scientific concerns, the most recent FDA data on pesticide residues in food found that roughly half of the foods the agency sampled contained traces of insecticides, herbicides, fungicides and other toxic chemicals used by farmers in growing hundreds of different foods.

More than 90 percent of apple juices sampled were found to contain pesticides. The FDA also reported that more than 60 percent of cantaloupe carried residues. Overall, 79 percent of American fruits and 52 percent of vegetables contained residues of various pesticides – many known by scientists to be linked to a range of illnesses and disease. Pesticides were also found in soy, corn, oat and wheat products, and finished foods like cereals, crackers and macaroni.

The FDA analysis “almost exclusively” is focused on products that are not labeled as organic, according to FDA spokesman Peter Cassell.

The FDA downplays the percentage of foods containing pesticide residues and focuses on the percentage of samples for which there is no violation of the tolerance levels. In its most recent report, the FDA said that more than “99% of domestic and 90% of import human foods were compliant with federal standards.”

The report marked the agency’s launch of testing for the weed killer glyphosate in foods. The Government Accountability Office said in 2014 that both the FDA and the U.S. Department of Agriculture should start regularly testing foods for glyphosate. The FDA did only limited tests looking for glyphosate residues, however, sampling corn and soy and milk and eggs for the weed killer, the agency said. No residues of glyphosate were found in milk or eggs, but residues were found in 63.1 percent of the corn samples and 67 percent of the soybean samples, according to FDA data.

The agency did not disclose findings by one of its chemists of glyphosate in oatmeal and honey products, even though the FDA chemist made his findings known to supervisors and other scientists outside the agency.

Cassell said the honey and oatmeal findings were not part of the agency’s assignment.

Overall, the new FDA report covered sampling done from Oct. 1, 2015, through Sept. 30, 2016, and included analysis of 7,413 samples of food examined as part of the FDA’s “pesticide monitoring program.” Most of the samples were of food to be eaten by people, but 467 samples were of animal food. The agency said that pesticide residues were found in 47.1 percent of the samples of food for people produced domestically and 49.3 percent of food imported from other countries destined for consumer meals. Animal food products were similar, with pesticide residues found in 57 percent of the domestic samples and 45.3 percent of imported foods for animals.

Many imported food samples showed residues of pesticides high enough to break the legal limits, the FDA said. Nearly 20 percent of imported grain and grain product samples showed illegally high levels of pesticides, for example.