Metabolic and feeding behavior alterations provoked by prenatal exposure to aspartame

Toigo, Eduardo von Poser; Huffell, Ana Paula; Mota, Carina de Souza; Bertolini, Diego; Pettenuzzo, Letícia Ferreira; Dalmaz, Carla

doi:10.1016/j.appet.2014.12.213

Cited by 37 publications

(32 citation statements)

References 43 publications

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“…On the other hand, aspartame did not worsen nor improve fertility or reproductive outcomes compared with the Obese group. Nevertheless, metabolic and feeding behavior disturbances have been shown previously in offspring of rats that consumed aspartame during gestation (17).…”

Section: Discussionmentioning

confidence: 92%

Impact of Food Ingredients (Aspartame, Stevia, Prebiotic Oligofructose) on Fertility and Reproductive Outcomes in Obese Rats

Cho

Klančič

Nettleton

et al. 2018

Obesity

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Objective This study aimed to investigate the interaction between obesity, low‐calorie sweeteners, and prebiotic oligofructose on reproductive parameters in rats. Methods Data were derived from two separate studies of female Sprague‐Dawley rats with (1) Lean (n = 24), (2) Obese (n = 27), (3) Obese+Aspartame (n = 14), (4) Obese+Stevia (n = 15), and (5) Obese+Prebiotic (n = 15) groups. Obesity was induced with a high‐fat/high‐sucrose diet prior to pregnancy. In one study, human‐approved doses of aspartame (5‐7 mg/kg/d) and stevia (2‐3 mg/kg/d) in drinking water were examined, and in the second, 10% prebiotics (oligofructose) in the diet was examined. Reproductive parameters, including fertility, pregnancy, and delivery indexes, were analyzed. Results Obesity significantly reduced pregnancy index in Obese dams (60.7% successful pregnancies) compared with lean (100%). Obesity also reduced the number of pups born alive and pup survival percentage compared with those of Lean dams (P < 0.001). Only 53.3% of rats were able to conceive in the Obese+Stevia group, but if rats did become pregnant, they had 100% pregnancy and delivery index. While prebiotic administration rescued the pregnancy index, it could not remediate pup survival percentage (P = 0.025) in Obese dams. Conclusions Both obesity status and dietary ingredients affect the ability to conceive. Future rigorously controlled studies designed to examine reproductive outcomes in depth are needed to confirm these findings.

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Section: Discussionmentioning

confidence: 92%

Impact of Food Ingredients (Aspartame, Stevia, Prebiotic Oligofructose) on Fertility and Reproductive Outcomes in Obese Rats

Cho

Klančič

Nettleton

et al. 2018

Obesity

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“…The dosages of specific LCSs, and whether they have been administered in isolation or in combination with other compounds, have also varied dramatically, and have ranged from a 5% LCS + 95% glucose solution reported in one study [29], for example, to the maximum acceptable daily intake (ADI) of specific individual LCSs in another [24], to a 0.006% LCS solution reported in yet another study [30]. Although the initiation of LCS administration has generally begun in adulthood, some studies have initiated it prenatally or neonatally [25,31,32]. These multiple factors – combined with the overall variety of animal strains included in the experiments, their environments of origin, and resultant differences in their gut microbiota [33], even prior to the initiation of LCS – have undoubtedly contributed to the range of outcomes reported in these studies, and would be expected to influence variation in the outcomes of human studies, as well.…”

Section: Results From Animal Studiesmentioning

confidence: 99%

Low-calorie sweetener use and energy balance: Results from experimental studies in animals, and large-scale prospective studies in humans

Fowler

2016

Physiology & Behavior

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For more than a decade, pioneering animal studies conducted by investigators at Purdue University have provided evidence to support a central thesis: that the uncoupling of sweet taste and caloric intake by low-calorie sweeteners (LCS) can disrupt an animal's ability to predict the metabolic consequences of sweet taste, and thereby impair the animal's ability to respond appropriately to sweet-tasting foods. These investigators’ work has been replicated and extended internationally. There now exists a body of evidence, from a number of investigators, that animals chronically exposed to any of a range of LCSs – including saccharin, sucralose, acesulfame potassium, aspartame, or the combination of erythritol + aspartame – have exhibited one or more of the following conditions: increased food consumption, lower post-prandial thermogenesis, increased weight gain, greater percent body fat, decreased GLP-1 release during glucose tolerance testing, and significantly greater fasting glucose, glucose area under the curve during glucose tolerance testing, and hyperinsulinemia, compared with animals exposed to plain water or – in many cases – even to calorically-sweetened foods or liquids. Adverse impacts of LCS have appeared diminished in animals on dietary restriction, but were pronounced among males, animals genetically predisposed to obesity, and animals with diet-induced obesity. Impacts have been especially striking in animals on high-energy diets: diets high in fats and sugars, and diets which resemble a highly-processed ‘Western’ diet, including trans-fatty acids and monosodium glutamate. These studies have offered both support for, and biologically plausible mechanisms to explain, the results from a series of large-scale, long-term prospective observational studies conducted in humans, in which longitudinal increases in weight, abdominal adiposity, and incidence of overweight and obesity have been observed among study participants who reported using diet sodas and other LCS-sweetened beverages daily or more often at baseline. Furthermore, frequent use of diet beverages has been associated prospectively with increased long-term risk and/or hazard of a number of cardiometabolic conditions usually considered to be among the sequelae of obesity: hypertension, metabolic syndrome, diabetes, depression, kidney dysfunction, heart attack, stroke, and even cardiovascular and total mortality. Reverse causality does not appear to explain fully the increased risk observed across all of these studies, the majority of which have included key potential confounders as covariates. These have included body mass index or waist circumference at baseline; total caloric intake and specific macronutrient intake; physical activity; smoking; demographic and other relevant risk factors; and/or family history of disease. Whether non-LCS ingredients in diet beverages might have independently increased the weight gain and/or cardiometabolic risk observed among frequent consumers of LCS-sweetened beverages deserves further exploration. In the me...

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“…Rodent studies demonstrated that animals exhibited heightened preferences for both caloric sweeteners (sucrose) and NNS (acesulfame-potassium) in adulthood, when they were exposed to acesulfame-potassium either in utero or through breastfeeding (Zhang et al, 2011). Other investigators reported that NNS exposure during lactation may promote development of metabolic abnormalities (von Poser Toigo et al, 2015) and obesity (Araujo et al, 2014), yet similar studies do not exist in humans.…”

Section: Discussionmentioning

confidence: 97%

Nonnutritive Sweeteners in Breast Milk

Sylvetsky

Gardner

Bauman

et al. 2015

Journal of Toxicology and Environmental Health, Part A

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Nonnutritive sweeteners (NNS), including saccharin, sucralose, aspartame, and acesulfame-potassium, are commonly consumed in the general population, and all except for saccharin are considered safe for use during pregnancy and lactation. Sucralose (Splenda) currently holds the majority of the NNS market share and is often combined with acesulfame-potassium in a wide variety of foods and beverages. To date, saccharin is the only NNS reported to be found in human breast milk after maternal consumption, while there is no apparent information on the other NNS. Breast milk samples were collected from 20 lactating volunteers, irrespective of their habitual NNS intake. Saccharin, sucralose, and acesulfame-potassium were present in 65% of participants’ milk samples, whereas aspartame was not detected. These data indicate that NNS are frequently ingested by nursing infants, and thus prospective clinical studies are necessary to determine whether early NNS exposure via breast milk may have clinical implications.

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Metabolic and feeding behavior alterations provoked by prenatal exposure to aspartame

Cited by 37 publications

References 43 publications

Impact of Food Ingredients (Aspartame, Stevia, Prebiotic Oligofructose) on Fertility and Reproductive Outcomes in Obese Rats

Impact of Food Ingredients (Aspartame, Stevia, Prebiotic Oligofructose) on Fertility and Reproductive Outcomes in Obese Rats

Low-calorie sweetener use and energy balance: Results from experimental studies in animals, and large-scale prospective studies in humans

Nonnutritive Sweeteners in Breast Milk

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