ArticlePDF AvailableLiterature Review


Aspartame is one of the most popular artificial sweeteners over the world. Although its consumption is considered to be safe in acceptable daily intake ranges which were set by the United States Food and Drugs Administration and other regulatory agencies, there are lots of controversies regarding its safety nowadays. Some of the recent experimental and epidemiological studies showed that consumption of aspartame may causes some adverse health effects including obesity, metabolic syndrome, and alteration in gut microbiota. Moreover, studies on the nephrotoxic effect of aspartame have increased. A search of several literature databases for publications on adverse effects of aspartame on the kidney function from 1980 to 2016 showed that long-term consumption of aspartame led to a dose-dependent increased production of free radicals in renal tissues as well as kidney injury, based on several studies on animals However, given the lack of clinical data in this area, it is difficult to make a definitive conclusion regarding nephrotoxic effect of aspartame. Overall, consumers should be aware of the potential side effects of aspartame and other artificial sweeteners. At present it may be recommended that only a minimal amount of them would be consumed.
Iranian Journal of Kidney Diseases | Volume 11 | Number 5 | September 2017
Brief Review
Nephrotoxic Effect of Aspartame as an Artificial Sweetener
A Brief Review
Mohammad Reza Ardalan,1 Hadi Tabibi,2
Vahideh Ebrahimzadeh Attari,1 Aida Malek Mahdavi3
Aspartame is one of the most popular artificial sweeteners over
the world. Although its consumption is considered to be safe in
acceptable daily intake ranges which were set by the United States
Food and Drugs Administration and other regulatory agencies,
there are lots of controversies regarding its safety nowadays. Some
of the recent experimental and epidemiological studies showed
that consumption of aspartame may causes some adverse health
effects including obesity, metabolic syndrome, and alteration in
gut microbiota. Moreover, studies on the nephrotoxic effect of
aspartame have increased. A search of several literature databases
for publications on adverse effects of aspartame on the kidney
function from 1980 to 2016 showed that long-term consumption
of aspartame led to a dose-dependent increased production of free
radicals in renal tissues as well as kidney injury, based on several
studies on animals However, given the lack of clinical data in
this area, it is difficult to make a definitive conclusion regarding
nephrotoxic effect of aspartame. Overall, consumers should be
aware of the potential side effects of aspartame and other artificial
sweeteners. At present it may be recommended that only a minimal
amount of them would be consumed.
IJKD 2017;11:339-43
1Kidney Research Center,
Tabriz University of Medical
Sciences, Tabriz, Iran
2Department of Human
Nutrition, Faculty of Nutrition
Sciences and Food Technology,
National Nutrition and Food
Technology Research Institute,
Tehran, Iran
3Connective Tissue Diseases
Research Center, Tabriz
University of Medical Sciences,
Tabriz, Iran
Keywords. artificial
sweeteners, aspartame,
nephrotoxicity, kidney injury
Artificial sweeteners are a class of food additives
that provide sweet taste without increasing caloric
intake. They are also named as ‘nonnutritive
sweeteners,’ ‘high-intensity sweeteners,’ and ‘low
caloric sweeteners’.1-3 Aspartame (L-aspartyl-
L-phenylalanine methyl ester) also known as
‘NutraSweet,’ is one of the most popular synthetic
artificial sweeteners over the world (Figure). The
global production of aspartame is assumed to
be more than 16 000 tons per year.4 Aspartame
is a white, odorless powder, approximately 200
times sweeter than sucrose.5-7 It is unstable during
prolonged heating; therefore, it cannot be used
for cooking.7,8 It was discovered in 1965 and got
its initial approval from the US Food and Drugs
Administration in 1974.
The Food and Drugs Administration and other
advisory agencies have set an acceptable daily
intake for each nonnutritive sweetener.9 The
acceptable daily intake of aspartame is 50 mg/
kg and 40 mg/kg per day, respectively, based
on the United States and the European Union
recommendations.9,10 Although consumption of
artificial sweeteners is considered to be safe in
acceptable daily intake range, the results of some
experimental and epidemiological studies showed
that their consumption may cause some adverse
health effects including obesity,11-15 metabolic
syndrome,14-17 alteration in gut microbiota,18-21
cancer,22,23 and adverse neurobehavioral effects.24
As the kidney has an important role in excretion
of various waste metabolites from the body, studies
on nephrotoxic effect of artificial sweeteners,
Nephrotoxic Effect of Aspartame—Ardalan et al
340 Iranian Journal of Kidney Diseases | Volume 11 | Number 5 | September 2017
especially aspartame, have recently increased,25-31
The present article review summarizes the results
of most relevant studies concerning the nephrotoxic
effect of aspartame as the most popular artificial
According to some experimental studies,
consumption of aspartame has been linked to
kidney dysfunction.25-31 Saleh28 and Bahr and
Zaki32 showed that oral administration of drinking
water containing 0.25 g/L of aspartame for 60
days significantly increased blood urea nitrogen,
serum creatinine, and potassium levels in male
rats. Similar findings were also reported by Waggas
and coworkers in female rats fed with 50 mg/d
and 150 mg/d of aspartame for 6 months, along
with significant structural changes in their renal
tubules compared to a control group.30 Moreover,
Martins and Azoubel showed that orogastric
administration of 14 mg/kg of aspartame to female
rats on the 9th, 10th, and 11th days of pregnancy
led to some alterations in the development of
fatal renal structures.25 In addition, karyometry
and stereology analyses of fetal rats suggested
the toxicity of glomerulus, proximal and distal
convoluted tubules, and to a lesser degree, the
collecting ducts of their kidneys.25
To the best of our knowledge such adverse
effects by aspartame intake have not been assessed
in humans. There are just few conflicting results
on the association of artificially sweetened soda
with chronic kidney disease. However, it should
be considered that soda is generally acidified using
phosphoric acid, which seems to affect the risk of
chronic kidney disease.33,34 Moreover, Chamberlain
and colleagues demonstrated that a mixture of
aspartame versus sucrose-based liquid with oral
sodium phosphate solutions used in colonoscopy
had no significant effect on serum sodium, serum
potassium, blood urea nitrogen, serum creatinine,
and blood urea nitrogen-creatinine ratio. Whereas,
serum phosphorous significantly increased in the
aspartame-based group compared to the sucrose,
which may be due to increasing the phosphate
absorption by aspartame or its amino acids.35
In contrast to the abovementioned nephrotoxic
effects of aspartame, there are some evidence
from the in vitro and a few animal studies that
aspartame may protect against the cytotoxic and
genotoxic effects of mycotoxins such as ochratoxin
A in the kidney and other tissues.36-38 Ochratoxin
A inhibits protein synthesis by competition with
phenylalanine, which is its structural analogue, as
well as induces lipid peroxidation in the tissue.
It was reported that aspartame may be effective
in washing out the toxin and preventing the
morphological and histological damages of the
kidney induced by the ochratoxin A in vivo.36
The protective effects of aspartame on ochratoxin
A-induced nephrotoxicity could be mainly due
to the delivery of phenylalanine by its cleavage
and also the direct effect of the aspartame on the
bending capacity and transport of the toxin.37-38
However, future studies are needed to investigate
the direct effect of aspartame and other artificial
sweeteners on human’s kidney function.
Results of experimental studies showed that the
administration of aspartame induced oxidative
stress and significantly decreased the activity
of antioxidant enzymes including superoxide
dismutase, catalase, glutathione peroxidase, and
glutathione reductase in both hepatic and renal
tissues of rats.27-32 Interestingly, some of these
articles examined the effect of antioxidant agents
such as aqueous extract of Majoram leaves,30
flaxseed oil and coenzyme Q10,32 Pimpinella anisum
oil,39 and Zingiber officinale extract40 in combination
with the aspartame to decrease the observed pro-
oxidant and nephrotoxic effects of aspartame in
The structure of aspartame.
Nephrotoxic Effect of Aspartame—Ardalan et al
Iranian Journal of Kidney Diseases | Volume 11 | Number 5 | September 2017
Oxidative stress is characterized by increased
level of pro-oxidants such as reactive oxygen species
and reactive nitrogen species or decreased level
of antioxidants that could lead to cell dysfunction
and degradation.41 It seems that the decreased
activity of antioxidant enzymes in aspartame-fed
animals might be due to methanol production or
some other metabolites. Once ingested, aspartame
is metabolized to aspartic acid, phenylalanine, and
methanol in the ratio of 50:40:10, respectively, and
also a small amount of aspartyl phenylalanine
diketopiperazine, especially during its heating.25
Methanol further oxidized to formaldehyde, which
is accompanied by the formation of superoxide
anion and hydrogen peroxide in the kidney and
some other organs like liver and brain.2,10, 42-44 The
other metabolite, diketopiperazine, seems to be a
Iyyaswamy and Rathinasamy reported a
significant increase of plasma methanol level
and free radical production after aspartame
administration.46 Moreover, Szponar and colleagues
reported a 61-year-old man with suspected
methanol poisoning transferred to the Regional
Center of Clinical Toxicology, the laboratory tests
of whom showed metabolic respiratory acidosis,
and investigations revealed that a few days prior
to the hospitalization the patient was drinking
a great amount of fruit juices sweetened with
aspartame and milk (more than 12 liters per day).
They concluded that excessive consumption of
aspartame might lead to methanol poisoning in
this patient.47
It seems that humans are more sensitive to
the toxic effects of methanol because of the slow
methanol oxidation and low liver folate content
compared to the other animals, such as rodents.48
In a recent study, Saleh reported a significant
decrease in glutathione level and the activity of
glutathione peroxidase and catalase in the kidney
tissue of aspartame-fed rats, which was significantly
reversed during the administration of folic acid
and N-acetyl cysteine.28 Similarly, Finamor and
associates showed the protective effect of N-acetyl
cysteine against the oxidative damage of the brain
in long-term aspartame-fed rats.49
Overall, most of the current data on the
nephrotoxic effect of aspartame are based on
the results of experimental studies and such
adverse effects have not been assessed in humans.
Moreover, one limitation of those animal studies
was oral treatment with a high dose of aspartame,
consumption of which seems to be unusual by
humans. However, future epidemiological studies
and clinical trials are needed to investigate the
adverse effects of long-term consumption of
aspartame at the acceptable daily intake.
In conclusion, based on these observations
long-term or high-dose consumption of aspartame
may lead to a dose-dependent increase in free
radical production and some adverse health
effects, including kidney injury, especially in some
conditions such as diabetes mellitus, older ages,
and intense and prolonged exercise with innately
increased production of free radicals. Therefore,
consumers should be aware of the potential side
effects of aspartame, albeit there is not a conclusive
clinical data about those adverse effects.
This study was supported by the Kidney Research
Center, Tabriz University of Medical Sciences
(Tabriz, Iran).
None declared.
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Correspondence to:
Vahideh Ebrahimzadeh Attari, Assistant Professor in Nutrition,
Kidney Research Center, Tabriz University of Medical Sciences,
Tabriz, Iran.
Tel: +98 914 300 9074
Fax: +98 41 3336 9315
Received September 2016
Revised January 2017
Accepted January 2017
... Além disso, há evidências na literatura científica do potencial comprometimento do sistema digestório, pela inibição indireta da enzima fosfatase alcalina intestinal, por meio dos subprodutos da fenilalanina, obtida pelo aspartame (Gul et al., 2017). Uma revisão de literatura reforçou que a longo prazo ou em altas doses, o aspartame pode levar a efeitos adversos para a saúde, incluindo lesão renal, principalmente em indivíduos que possuem a diabetes mellitus, praticam exercícios intensos com alta produção de radicais livres ou que possuem idade avançada (Ardalan et al., 2017). ...
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Sweeteners provide a sweet taste to foods and are used to replace sucrose and reduce caloric value. Acesulfame potassium, aspartame, sodium cyclamate, saccharin, sucralose and neotame are the artificial sweeteners regulated in Brazil by the Brazilian Health Regulatory Agency (ANVISA). The consumption of these additives has become controversial due to recent scientific evidence questioning their safety and outcomes regarding weight loss, dysbiosis of the intestinal microbiota, insulin resistance, diabetes and cancer. Even today, little is known about the long-term consequences of their consumption. Therefore, this study aimed to carry out a review of artificial sweeteners regulated in Brazil, contextualizing their regulatory framework, the technological implications regarding their use and the effects on health. Considering the now controversial outcomes regarding the consumption of many artificial sweeteners, and the long period in which levels of acceptable daily intake have been in place, it is suggested their consumption should now not be encouraged, being restricted to population groups that have a risk-based physiological or metabolic need to replace sucrose. Also, for these cases, it would be important to differentiate between foods containing different sweeteners (or tabletop sweeteners), to alleviate possible chronic health effects. New studies with more robust and consistent methodologies are required to support the safety assessment reviews of each artificial sweetener.
... There is no evidence of a link between aspartame and pancreatic, gastric, or endometrial cancer. Aspartame's consumption has been linked to free radical generation and decrease in antioxidant enzyme activity (Mohammad et al. 2017;Ab Qayoom et al. 2018;Zafar et al. 2017;Czarnecka et al. 1957;Iman 2011). Table 7 shows effects of aspartame in various diseases. ...
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Background Energy drinks (EDs) are a type of beverage that mostly contains caffeine and other dietary supplements (if present) and does not contain any alcohol in the ingredients. The products in this category include Red Bull, Redline, Monster, Full Throttle, and others. They are claimed to help in boosting energy, stamina, sports performance, and concentration among individuals. This article focused on the review of the benefits and disadvantages of consumption of energy drinks to health and well-being. ED provides health benefits effects such as improved physical performance, mood and attitude, cognition, and weight loss. Some adverse negative health challenges have been linked to consumption of ED. Therefore, this review is a wholistic appraisal of benefits or detriments of consumption of energy drink to our health and suggestions to curtail the excesses of ED consumption. Main body Energy drink has been around since 1950, and it is marketed as energy booster and comes in different types, energy shots, fruit-based, non-fruit-based (regular), sugar-free, and plant-based. These products are marketed as a low-calorie “instant” energy drink that can be consumed in a single sip, or bottle to boost energy or to boost the nutritional value of conventional products. Many of them contain different ingredients such as caffeine, guarana, ginseng, yerba mate, acai berry, ginkgo biloba, methylxanthines, sugar, glucuronolactone, taurine, maltodextrin, B vitamins. Vitamin B2 (riboflavin), B3 (niacin), B6 (pyridoxine, pyridoxal, and pyridoxamine), Inositol B8 and B12, vitamin C and vitamin D; calcium, Iron, chromium, zinc, manganese, molybdenum; artificial sweeteners, aspartame, and sucralose. Health benefits such as improved physical performance, improved mood and attitude, improved concentration, and memory, good source of vitamin B and weight loss have been reported. Negative impact on health such as adverse cardiovascular effect, headaches, epileptic seizures, ischemic stroke, hallucinations, muscular twitching, restlessness, sleeplessness, anxiety, depression, gastrointestinal effect, renal effects, dental effects, obesity and type II diabetes, cancer, and caffeine toxicity has been reported. Conclusions Most of the health detriments caused because of consumption of energy drink is mostly due to the presence of excess quantity of caffeine and sugar. If the quantities of caffeine and sugar content in energy drink are kept at FDA- and WHO-recommended daily consumption amount, then it will not be present any problem to health. Consumption of energy drink that contains natural ingredients such as yerba mate, acai berry, ginkgo biloba, methylxanthines, amino acid, guarana, and ginseng with moderate FDA- and WHO-approved daily consumption of caffeine and sugar is not detrimental to health.
... Specifically, chronic APM intake might have the capability to induce hepatic damage 14 and nephrotoxicity. 15 In addition, APM, together with its metabolites, has either direct or indirect cellular effects via damaging the integrity of the cell membrane and inducing cellular dysfunction. 2,16 Furthermore, phenylalanine could influence the homeostasis of the neurotransmitters in the brain, 2 while aspartic acid itself is an excitatory neurotransmitter. ...
... Although the global sugar demand has generally declined due to the rising concerns around the potential health effects caused by elevated sugar intakes, the Food and Agriculture Organization (FAO) data suggest generates concerns among health representatives and the general consumers since it is widely used by big F&B companies such as Coca-Cola in many of its products (FDA, 2019). The consumption has been associated with different health effects, including oxidative stress in blood cells (even at the recommended dose of 40 mg/kg per day), interference of neuronal cell function, hepatotoxicity and kidney disfunction (Ardalan, Tabibi, Attari, & Mahdavi, 2017;Choudhary & Pretorius, 2017). Moreover, its consumption is not recommended for people suffering from phenylketonuria since they cannot metabolize phenylalanine (a chemical component used in the aspartame synthesis). ...
Food producers have leaned towards alternative natural and synthetic sweeteners in food formulations to satisfy market demands. Even so, several synthetic sweeteners (e.g., aspartame, saccharin, sucralose) are becoming less popular due to health-related concerns, lower nutritional values, and controversies around their safety. Conversely, natural sweeteners confer favourable customer perceptions due to their association to a healthier lifestyle and higher nutritional values. This article discusses the evidence of natural sweeteners in the available commercial products. A comprehensive review of natural sweeteners is presented, which includes their resources, properties and extraction methods, as well as a discussion on several emerging technologies that offer improvements to the traditional extraction methods. Finally, the progress of natural sweeteners in the food industry is assessed, and the commercial food products containing these natural sweeteners are mentioned.
... To maintain the pleasure of sweet food and simultaneously avoid the negative sequelae of sugar consumption, artificial sweeteners without calories have become popular substitutes. Although initially denoted as safe, recent studies have shown that daily intake of artificial sweeteners can lead to metabolic syndrome, type II diabetes or cancer (Nettleton et al. 2009;Ardalan et al. 2017). ...
Canonically, sweet perception is mediated by specific T1R2/T1R3 sweet taste G-protein coupled receptors expressed in taste cells of the tongue. However, mice lacking these receptors or their downstream signaling components are still able to recognize natural sugars. Conversely, they do not perceive artificial sweeteners, which are mostly canonical sweet taste receptor agonists, suggesting the existence of a parallel “alternative pathway” for sweet perception. To address the molecular pathways, complexity and physiological relevance of sweet taste sensation, this study combines a deep literature survey on sweet taste biology with experimental work using 3D cell cultures of immortalized human tongue cells (HTC-8). The literature research revealed that sweet-sensitive taste cells may take up monosaccharides via Glucose transporters (GLUT/SGLT1) to induce depolarization-dependent Ca2+ signals upon oxidative metabolism and KATP channel inactivation. Disaccharides can activate this signal path upon digestion from taste cell-expressed Brush Boarder enzymes. Alternatively, disaccharides may be taken up with elusive transporters, induce osmotic swelling and activate volume regulated anion channels. Via unidentified neuronal and/or endocrine mechanisms, sweet taste receptor-independent pathways may contribute to behavioral attraction but may also induce cephalic phase Insulin release upon GLP 1 secretion from taste cells. This would suggest that the alternative pathway may prepare the body for digestion, while the canonical pathway might be rather responsible for the hedonic value of sugars. Since taste differs among species and human samples are limited, most hypotheses of the alternative pathway remain rather vague and are often based on cells of other organs that express extraoral sweet taste receptors and canonical downstream molecules like gastro-intestinal or pancreatic cells. Since perfused live imaging experiments conducted in this study revealed that individual HTC 8 cells responded to KCl, sweet and bitter stimulation, they might belong to the newly described broadly-sensitive taste cells, which is in contrast with the assumption that diverse taste modalities use different signaling pathways in distinct cell types. A preliminary transcriptome analysis of HTC 8 spheroids corroborated the finding that taste is not exclusively transduced by the canonical pathway. Accordingly, bitter responses of HTC-8 spheroids might have been mediated by family members of the canonical signaling pathway, while sugars may have used the alternative pathway, since spheroids were not sensitive to the artificial sweetener Acesulfame K and related signal molecules of the alternative signal pathway were expressed upon 3D culture of HTC-8 cells. Although the here established model contains several limitations and needs further adjustment it might serve as a first testing platform to obtain human-derived data on taste physiology in a higher throughput than in human subjects. Thereby, it may support the search for new sugar alternatives and to combat the current sugar overconsumption which goes along with a sickening society.
... Aspartam 200 kali lebih manis dari pada sukrosa. 1 Aspartam dapat ditemukan pada lebih dari 6000 produk, seperti minuman bersoda, permen ataupun beberapa obat-obatan seperti vitamin dan sirup bebas gula. 2 The katalis yang menyebabkan kerusakan oksidatif pada membran sel ginjal. 6 Penggunaan tumbuhan sebagai obat telah digunakan sejak lama di seluruh bagian dunia baik untuk tujuan terapi maupun pencegahan. ...
... 16 In contrast to SSBs, artificially sweetened beverages (ASBs) refer to all types of low-calorie or diet beverages using artificial sweetener, such as aspartame, saccharin and xylitol, which provides a sweet taste but with lower caloric intake. 17 ASBs are thought to potentially reduce excess energy intake 18 and may be an ideal alternative for sweet-tasting beverage lovers. Several prospective studies have suggested that ASB consumption is not associated with several kinds of cancer. ...
Background Conclusions remain controversial between the consumption of sugar and artificially sweetened beverages (SSBs and ASBs) and mortality. Methods We systematically searched the PubMed, Embase, Cochrane Library and Web of Science databases from their inception date to 1st January 2020, prospective cohort studies researching the mortality risk and SSBs or ASBs consumption were included. Random effects meta-analyses and dose–response analyses were performed to measure the association. Subgroup analyses and sensitivity analyses were further performed to explore the source of heterogeneity. Publication bias was assessed by Funnel plots and Egger’s regression test. Results Across all 15 cohorts, 1211 470 participants were included. High SSB consumption was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.06–1.19, P < 0.001; and cardiovascular disease [CVD] mortality [HR 1.20, 95% CI, 1.05–1.38, P < 0.001]), and high ASBs consumption showed similar result (HR 1.12, 95% CI, 1.04–1.21, P = 0.001 for all-cause mortality and HR 1.23, 95% CI, 1.00–1.50, P = 0.049 for CVD mortality), both showed a linear dose–response relationship. Conclusions High consumption of both ASBs and SSBs showed significant associations with a higher risk of CVD mortality and all-cause mortality. This information may provide ideas for decreasing the global burden of diseases by reducing sweetened beverage intake.
... Food Research International 137 (2020) 109414 patients with phenylketonuria patients; when aspartame is processed by chymotrypsin, present in the intestines, methanol, a toxic substance that causes neurological disorders, nausea, headache, mood disorders of balance, blurred vision, and blindness, is released; additionally, children are especially at risk. Aspartame degrades very easily when subjected to heat and therefore is not used in baked goods; moreover, the preservation of foods at any unsuitable temperature causes its decomposition with harmful effects (Ardalan, Tabibi, Attari, & Mahdavi, 2017;Lebda, Tohamy, & El-Sayed, 2017). Being 200 times sweeter than sucrose, it causes the early onset of metabolic diseases related to obesity, such as hyperlipidaemia, insulin resistance, cardiovascular problems and even some cancers. ...
In recent years, the concept of food has undergone a radical transformation to the point of attributing to foods, in addition to their nutritional and sensorial properties, an important role in maintaining health and psycho-physical well-being and in the prevention of certain diseases. However, foods can hide many pitfalls for human health. There are many critical points in food production processes and they can represent real risks of contamination or of unsafe food production for consumers. Proper conservation, physico-chemical and microbiological stability, cooking methods are fundamental control parameters to ensure the safety of food products. Generally, the development of a food-borne disease is due to specific conditions, such as the virulence of the microorganism present, the microbial load present in the food and the conditions of the host's immune system. Furthermore, the possible presence of other types of contaminants, in addition to microbial ones, can have implications for the health of consumers. Consequently, the rigorous compliance of personnel who work in contact with food during the phases of production, processing, transport and storage with hygienic rules is essential to guarantee food safety and prevent foodborne disease. So, in this review, major issues are addressed such as reviewing the major food-related causes of disease. From this point of view, the relevant microorganisms involved in food contamination (bacteria, viruses, parasites, fungi and mycotoxins), are taken into account. In addition, potentially allergenic foods or foods most commonly associated with food intolerance, are also considered. Many adverse reactions of the body towards foods are caused by the treatments to which they are subjected in order to maintain unchanged organoleptic characteristics as long as possible over time. This is also a critical point for food contamination that is considered in this review. A section is reserved to food additives potentially capable of causing disorders to the human body. In addition to biological contamination, the important issues represented by chemical contamination caused by pesticides, heavy metals, contaminants produced involuntarily are also considered. In conclusion, this review highlights that to protect consumers from food-borne diseases, an integrated approach to food safety must be adopted which affects the entire food chain, from farm to fork.
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Introduction and purpose: Even though sweeteners’ popularity is increasing as they are approved by the Food and Drug Administration (FDA) and generally considered to be safe, their whole impact on the human body is still confusing. Polyols are among one of the most used sweeteners, therefore in this review we will focus on their impact on the gut microbiome as this community of various bacteria influences many aspects of overall health. Brief description of the state of knowledge: The current conclusions mostly present prebiotic benefits of polyols and their ability to increase the number of Bifidobacteria, there is research supporting the evidence of it conducted on isomalt, maltitol, lactitol and xylitol. It is possible, as most of them are able to reach the colon. We also investigate other ways sweeteners are shaping the gut microbiome such as multiplication of short chain fatty acids (SCFAs) or decreasing the numbers of Clostridium difficile. Conclusions: The impact of polyols on the gut microbiome has many knowledge gaps. More long-term studies are needed in order to consider the individual diversity of the participants’ gut microbiota. In order to conduct more valuable conclusions dietary and lifestyle habits should be taken into consideration. All things considered, there is not enough data to clearly determine polyols' role in modifying the gut microbiota.
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Mikrobiyota, mikroorganizmaların oluşturduğu topluluk olarak ifade edilmektedir ve bağırsak mikrobiyotası doğum ile birlikte değişmeye ve gelişmeye başlamaktadır. Beslenme, bakteriler için gerekli besinleri sağlayarak, mikro çevrelerini değiştirerek ve kompozisyonları ile fonksiyonlarını modüle ederek mikrobiyota üzerine etkiler gösterebilmektedir. 20. yüzyılın başlarından beri insanların diyetlerinde önemli değişiklikler görülmeye başlanmış olup özellikle işlenmiş gıdalara yönelmeleri sonucu tüm bu vb. gıdalara eklenen katkı maddelerinin tüketimleri artış göstermiştir. Karbonhidratlar, yağlar, proteinler ve fitokimyasallar gibi bazı diyet bileşenlerinin mikrobiyota üzerine etkisi değerlendirilmiştir fakat gıda katkı maddelerinin mikrobiyota üzerine etkisi belirsizliğini korumaktadır. Günümüzde birçok gıda katkı maddesi için belirlenmiş üst limitler olsa da sağlığı olumsuz yönde etkileyebileceğini düşündüren çalışmalar mevcuttur. Bu nedenle mikrobiyota üzerine etkisini kapsamlı bir şekilde değerlendirerek toplumu bilinçlendirmek önem arz etmektedir. Bu derlemenin amacı gıda katkı maddelerinin bağırsak mikrobiyotası üzerine etkilerini inceleyen literatürde bulunan çalışmaları 3 grup halinde (tatlandırıcılar, emülsifiyerler ve diğer katkı maddeleri olarak) bir araya toplayıp güncel yaklaşımlar ile kapsamlı bir şekilde değerlendirmektir. ABSTRACT Microbiota is expressed as the community of microorganisms and intestinal microbiota begins to change and develop with birth. Nutrition can affect the microbiota by providing the necessary nutrients for bacteria, changing the microenvironment and modulating the composition and functions of bacteria. Since the early 20th century, important changes have been seen in the diets, especially consumption of processed foods began popular hence consumptions of food additives, added to almost all these foods, have increased. The effects of some dietary components such as carbohydrates, fats, proteins and phytochemicals on microbiota have been evaluated but the effect of food additives on microbiota is still uncertain. Today, although there are upper limits for many food additives, studies suggesting that they may affect health negatively. Therefore, it is important to raise awareness of the society by comprehensively evaluating their effect on microbiota. The aim of this review is to collect the studies, determining the effects of food additives on gut microbiota in 3 groups (as sweeteners, emulsifiers and other additives) and to evaluate them comprehensively with current approaches.
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Mycotoxins are secondary metabolites produced by various toxigenic fungi mainly belonging to three genera Aspergillus, Fusarium and Penicillium .Ubiquitous occurrence, heat stability and lipophilic nature pose serious threats in terms of toxic syndromes i.e. mycotoxicoses in animals and poultry. Toxicological spectrum of various mycotoxins is very wide encompassing different kind of toxicities viz. acute and chronic toxicities, carcinogenicity, genotoxicity, immunotoxicity, mutagenicity, and teratogenicity in animals and poultry. Feeds are frequently contaminated simultaneously by several moulds each of which is able to produce several mycotoxins. The synergism occurs naturally between different mycotoxins. The various in vivo and in vitro strategies have been tried to ameliorate/ detoxify/remove the toxic effects of mycotoxins/mycotoxicosis. The physical and chemical methods are impracticable in terms of safeguarding the nutritive quality of food and feed, while the biological methods like use of additives, antioxidant substances and food components; and toxin binding agents are showing promising results in amelioration/ detoxification of mycotoxins/mycotoxicosis in poultry.
This study examined whether sucrose, fructose, aspartame, and saccharin influences the association between obesity and glucose tolerance in 2856 adults from the NHANES III survey. Aspartame intake significantly influenced the association between body mass index (BMI) and glucose tolerance (interaction: P = 0.004), wherein only those reporting aspartame intake had a steeper positive association between BMI and glucose tolerance than those reporting no aspartame intake. Therefore, consumption of aspartame is associated with greater obesity-related impairments in glucose tolerance.
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.
Disruption in the gut microbiota is now recognized as an active contributor towards the development of obesity and insulin resistance. This review considers one class of dietary additives known to influence the gut microbiota that may predispose susceptible individuals to insulin resistance - the regular, long-term consumption of low-dose, low calorie sweeteners. While the data are controversial, mounting evidence suggests that low calorie sweeteners should not be dismissed as inert in the gut environment. Sucralose, aspartame and saccharin, all widely used to reduce energy content in foods and beverages to promote satiety and encourage weight loss, have been shown to disrupt the balance and diversity of gut microbiota. Fecal transplant experiments, wherein microbiota from low calorie sweetener consuming hosts are transferred into germ-free mice, show that this disruption is transferable and results in impaired glucose tolerance, a well-known risk factor towards the development of a number of metabolic disease states. As our understanding of the importance of the gut microbiota in metabolic health continues to grow, it will be increasingly important to consider the impact of all dietary components, including low calorie sweeteners, on gut microbiota and metabolic health.
The present study was carried out to investigate the acute effect of aspartame on oxidative stress in the Wistar albino rat brain. We sought to investigate whether acute administration of aspartame (75 mg/kg) could release methanol and induce oxidative stress in the rat brain 24 hours after administration. To mimic human methanol metabolism, methotrexate treated rats were used to study aspartame effects. Wistar strain male albino rats were administered with aspartame orally as a single dose and studied along with controls and methotrexate treated controls. Blood methanol and formate level were estimated after 24 hours and rats were sacrificed and free radical changes were observed in discrete regions by assessing the scavenging enzymes, reduce dglutathione (GSH), lipid peroxidation and protein thiol levels. There was a significant increase in lipid peroxidation levels, superoxide dismutase activity (SOD), glutathione peroxidase levels (GPx), and catalase activity (CAT) with a significant decrease in GSH and protein thiol. Aspartame exposure resulted in detectable methanol even after 24 hours. Methanol and its metabolites may be responsible for the generation of oxidative stress in brain regions. The observed alteration in aspartame fed animals may be due to its metabolite methanol and elevated formate. The elevated free radicals due to methanol induced oxidative stress.
Long-term intake of aspartame at the acceptable daily ingestion dose causes oxidative stress in the rat kidney through the dysregulation of glutathione homeostasis. N-acetylcysteine (NAC) provides the cystein required for the production of GSH, being effective in treating disorders associated with oxidative stress. The aim of this research was to investigate the effects of NAC on the aspartame-induced oxidative stress in the rat kidney. The animals received aspartame by gavage for six weeks (40 mg/kg). From the 5th week, NAC (1 mmol/kg, via intraperitoneal) was injected for two weeks. Then, they were anaesthetized for blood sample and euthanized for the kidney collection. The blood was centrifuged at 1800 g for 15 min and the serum was separated for creatinine measurement. The tissue was homogenized in 1.15% KCl buffer and centrifuged at 700 g for 10 min at 4 °C. The supernatant fraction obtained was used to the measurements of oxidative stress biomarkers. The creatinine levels were enhanced in the serum of aspartame-treated rats. NAC caused a reduction in the thiobarbituric acid reactive substances, lipid hydroperoxides, carbonyl protein and hydrogen peroxide levels, which were increased in the kidney of aspartame-treated animals. Additionally, NAC caused an elevation in the glutathione peroxidase and glutathione reductase activities, total glutathione, ascorbic acid, and total reactive antioxidant potential levels, which were decreased in the kidney of aspartame-treated rats. In conclusion, NAC may be useful for the protection of the rat kidney against aspartame-induced oxidative stress.
Purpose To evaluate gut microbiome in relation to recent high-intensity sweetener consumption in healthy adults. Methods Thirty-one adults completed a four-day food record and provided a fecal sample on the fifth day. Bacterial community in the samples was analyzed using Multitag Pyrosequencing. Across consumers and non-consumers of aspartame and acesulfame-K, bacterial abundance was compared using non-parametric statistics and bacterial diversity was compared using UniFrac analysis. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict mean relative abundance of gene function. Results There were seven aspartame consumers and seven acesulfame-K consumers. Three individuals overlapped groups, consuming both sweeteners. There were no differences in median bacterial abundance (class or order) across consumers and non-consumers of either sweetener. Overall bacterial diversity was different across non-consumers and consumers of aspartame (p<0.01) and acesulfame-K (p=0.03). Mean predicted gene abundance did not differ across consumers and non-consumers of aspartame or acesulfame-K. Conclusions Bacterial abundance profiles and predicted gene function were not associated with recent dietary high-intensity sweetener consumption. However, bacterial diversity differed across consumers and non-consumers. Given the increasing consumption of sweeteners and the role that the microbiome may have in chronic disease outcomes, work in further studies is warranted.
The effect of artificial sweetener consumption on cancer risk has been debated in animal models for over four decades. To further investigate this relationship, this study aims to synthesise results from several of the most recent studies in humans. An online literature search was performed in MEDLINE from 2003 to 2014 using Ovid, PubMed, Web of Science, and Scopus using keywords 'artificial', 'sweetener' and 'cancer'. Ninety-two results were then manually assessed for eligibility. Studies were included if the relationship between artificial sweeteners and cancer was their central hypothesis, and if they adjusted for age, gender, smoking status and body mass index. Extracted data included study design, patient characteristics, outcome measure and results. In the five publications that satisfied the inclusion criteria, significant direct associations with artificial consumption were found for laryngeal (odds ratio, OR 2.34, 95% CI: 1.20-4.55), urinary tract tumours (OR 2.12, 95% CI: 1.22-3.89), non-Hodgkin lymphoma in men (RR 1.31, 95% CI: 1.01-1.72), multiple myeloma in men (RR 2.02, 95% CI: 1.20-3.40) and leukaemia (RR 1.42, 95% CI: 1.00-2.02). Inverse relationships were found in breast (OR 0.70, 95% CI: 0.54-0.91, p trend = 0.015) and ovarian (OR 0.56, 95% CI: 0.38-0.81, p trend < 0.001) cancers. The statistical value of this review is limited by the heterogeneity and observational designs of the included studies. Although there is limited evidence to suggest that heavy consumption may increase the risk of certain cancers, overall the data presented are inconclusive as to any relationship between artificial sweeteners and cancer. © 2015 John Wiley & Sons Ltd.
To examine the relationship between diet soda (DS) intake (DSI) and long-term waist circumference (WC) change (ΔWC) in the biethnic San Antonio Longitudinal Study of Aging (SALSA). Prospective cohort study. San Antonio, Texas, neighborhoods. SALSA examined 749 Mexican-American and European-American individuals aged 65 and older at baseline (baseline, 1992-96); 474 (79.1%) survivors completed follow-up 1 (FU1, 2000-01), 413 (73.4%) completed FU2 (2001-03), and 375 (71.0%) completed FU3 (2003-04). Participants completed a mean of 2.64 follow-up intervals, for 9.4 total follow-up years. DSI, WC, height, and weight were measured at outset and at the conclusion of each interval: baseline, FU1, FU2, and FU3. Adjusted for initial WC, demographic characteristics, physical activity, diabetes mellitus, and smoking, mean interval ΔWC of DS users (2.11 cm, 95% confidence interval (CI) = 1.45-2.76 cm) was almost triple that of nonusers (0.77 cm, 95% CI = 0.29-1.23 cm) (P < .001). Adjusted interval ΔWCs were 0.77 cm (95% CI = 0.29-1.23 cm) for nonusers, 1.76 cm (95% CI = 0.96-2.57 cm) for occasional users, and 3.04 cm (95% CI = 1.82-4.26 cm) for daily users (P = .002 for trend). This translates to ΔWCs of 0.80 inches for nonusers, 1.83 inches for occasional users, and 3.16 for daily users over the total SALSA follow-up. In subanalyses stratified for selected covariates, ΔWC point estimates were consistently higher in DS users. In a striking dose-response relationship, increasing DSI was associated with escalating abdominal obesity, a potential pathway for cardiometabolic risk in this aging population. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.