Clinical effects of Emblica officinalis fruit consumption in CVD CVDon cardiovascular disease risk factors: a systematic review and meta-analysi s

 

Background

                     Embelia officinale (Amala or Awala)

Cardiovascular disease (CVD) is the leading cause of death globally, accounting for ~ 17.8 million deaths annually [1]. Mortality associated with CVD is expected to increase to > 22.2 million per year by 2030 [2]. Due to increasing prevalence, further efforts are required for both primary and secondary prevention of CVD. Aging demographics combined with improved survival post-cardiovascular event contribute to the growing pool of individuals living with established CVD [3]. Secondary prevention of subsequent events via improvement in modifiable CVD risk factors can help reduce morbidity and mortality in this growing population [3].

Modifiable risk factors associated with CVD are 

both behavioural and physiological. 

 Research indicates a linear progression of risk factors leading to CVD, beginning with unhealthy lifestyle behaviours (e.g., physical inactivity, poor nutritional intake), leading to uncontrolled physiological risk factors,

 ultimately translating to CVD. Dyslipidemia,

 inflammation, and hypertension are common physiological risk factors for developing CVD via the progression

 of atherosclerosis [1]. Evidence-based dietary 

patterns have been developed to improve

 CVD physiological risk factors, including the Dietary Approaches to Stop Hypertension (DASH) diet [4]

 and the Portfolio diet [5, 6]. Although these dietary interventions have been associated with improvement in physiological CVD risk factors, 

CVD remains a significant global health concern.

 Therefore, the identification of efficacious, safe, affordable, and convenient options for primary or secondary prevention of CVD as either monotherapy or adjunct to evidence-based dietary patterns and/or standard pharmacotherapy is essential [7]. Furthermore, metabolic syndrome is a multicomponent risk factor for CVD and type 2 diabetes mellitus (T2DM) [1]. Metabolic syndrome is diagnosed when any three or more of the following five cardiometabolic risk factors are present: 1) hypertriglyceridemia, 2) decreased high-density lipoprotein cholesterol (HDL-C), 3) hypertension, 4) hyperglycemia, or 5) central adiposity [1]. Metabolic syndrome increases the risk of CVD mortality and all-cause mortality even for those with metabolic syndrome without T2DM [8]. Therefore, a single agent with the ability to produce beneficial changes in multiple cardiometabolic risk factors would be ideal when treating patients living with metabolic syndrome.

Emblica officinalis (EO)—also known as Phyllanthus emblica, Indian gooseberry in English, Amla in Hindi, and Amalaki in Sanskrit [9]—is a 5-25 m tall deciduous tree, native to tropical and subtropical regions of India, Nepal, Sri Lanka, and throughout South-East Asia to southern China [10]. Although many components of the EO plant (e.g., root bark, stem bark, leaves) are traditionally used in Ayurveda, an Indian indigenous system of medicine, the edible fruit is typically used the most for health reasons [7]. EO berries are spherical and smooth, growing to 2-5 cm in diameter [11]. EO berries are initially pale green in colour, changing to yellow when mature [10]. EO fruit, and formulations incorporating EO fruit, have traditionally been used as dietary supplements to treat an abundance of health ailments, including fever, jaundice, anemia, cough, asthma, headache, dyspepsia, ophthalmic disorders, vomiting, leprosy, diabetes, and menorrhagia [9].

The phytoconstituents of EO fruit include many bioactive compounds including hydrolysable tannins (e.g., chebulinic acid, chebulagic acid, corilagin, punigluconin, pedunculagin, emblicanin A and B), alkaloids, phenols (e.g., gallic acid, ellagic acid, pyrogallol), amino acids, carbohydrates (e.g., pectin), vitamins (e.g., ascorbic acid), flavonoids (e.g., quercetin, kaempferol, rutin), and organic acids (e.g., citric acid) [12]. EO fruit is a rich source of ascorbic acid (vitamin C), with 470-680 mg per 100 g [9]. Vitamin C accounts for ~ 45–70% of the total antioxidant activity of the EO fruit, along with tannins (particularly punigluconin, pedunculagin, emblicanin A and B), flavonoids, and ellagic acid [11]. Furthermore, experimental research indicates the EO fruit to have antibacterial [13], antidiabetic [14], antidiarrheal [15], antihyperlipidemic [16, 17], antioxidant [18], antipyretic [19], anti-hyperthyroid [20], antitussive [21], antiulcer [22], chemopreventive [23], cognitive enhancing [24], gastroprotective [25], hepatoprotective [26], nephroprotective [27], skin antiaging [28], and wound healing [29] properties, among many others.

Preliminary clinical interventional trials have also shown promising results of EO fruit consumption on a variety of health conditions, including cardiovascular disease [9, 12, 30, 31]. Specifically, significant improvements in participant blood lipids and/or biomarkers of inflammation following consumption of EO fruit in various forms [32–49]. These initial studies have subsequently led to randomized controlled trials (RCTs) investigating the effects of EO on CVD physiological risk factors [50–58]. Thus, a body of evidence now exists on the effects of EO on physiological risk, however, these effects have not been systematically reviewed or meta-analyzed. The purpose of this systematic review and meta-analysis is to: 1) systematically describe the clinical research examining EO; and 2) quantitatively assess the effects of EO on CVD physiological risk factors, including blood lipids, blood pressure, and biomarkers of inflammation.

Ref

. 2023 Jun 9;23:190. doi: 10.1186/s12906-023-03997-8

Clinical effects of Emblica officinalis fruit consumption on cardiovascular disease risk factors: a systematic review and meta-analysis

Paul D S Brown ¹, Nicole Ketter ^2,3, Mathew Vis-Dunbar ¹, Brodie M Sakakibara 

 

5.3. Artificial Sweeteners, Gut Microbiota, and Obesity

 The GI tract is inhabited by many microbial species,

 including bacteria, viruses, and fungi, which have

 been shown to affect the host’s growth,

 metabolic, and immunological status [125]. NNSs are metabolized by the gut microbiota and have significant effects on biological mechanisms.

A study in mice has shown that the use of acesulfame-k reduced the levels of Akkermansia muciniphilia, leading to glucose intolerance [75]. Also, the same study showed that the use of aspartame induced glucose intolerance by altering the abundance of gut microbiota [75]. Another study in mice showed that the administration of neotame reduced the abundance of Firmicutes and increased the abundance of Bacteroidetes [126]. In actuality, it has been shown that in children with obesity, the levels of Firmicutes are increased and those of Bacteroidetes are reduced [127]. There are three hypotheses on the pathophysiological mechanisms that are possibly associated with the use of NNSs and obesity development: 1. Uncoupling sweet taste with calories by using NNSs may negatively affect energy balance, leading to obesity. 2. Increased NNSs consumption leads to changes in the gut microbiota, to a more obesogenic one. 3. It is possible that NNSs act directly on gut microbiota, thus affecting host defense mechanisms and triggering inflammatory processes, leading to metabolic dysregulation [119,128].

Ref

Nutrients. 2024 Sep 19;16(18):3162. doi: 10.3390/nu16183162

Chronic Use of Artificial Sweeteners: Pros and Cons

Lydia Kossiva 1, Kostas Kakleas 2, Foteini Christodouli 1, Alexandra Soldatou 1, Spyridon Karanasios 1, Kyriaki Karavanaki 1,*

Editor: Xiaohua Pan

Artificial sweetnerers and cancer

 

5.4. Artificial Sweeteners and Cancer

The relationship between the consumption of artificial sweeteners and the occurrence of cancer according to meta-analyses is inconsistent. A possible link between NNSs use and carcinogenesis was initially investigated in animal models. In the 1970s, the FDA banned cyclamate based on scientific data indicating that high doses of cyclamate and saccharin given to rodents increased the risk of developing bladder cancer [129]. The Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JECFA) conducted an independent risk assessment of aspartame consumption and cancer in June 2023. The JECFA concluded that the ingestion of aspartame is not associated with adverse effects based on existing animal and human studies; therefore, the committee reaffirmed their recommendations on acceptable daily intake [130]. No other artificial sweeteners were identified as potential cancerous triggers in animal studies.

Another cohort study conducted in France, called the NutriNet-Santé Study, found that the consumption of great amounts of artificial sweeteners may result in carcinogenesis more often compared to controls [80]. They also reported that adults who consumed acesulfame-k had a slightly higher risk of cancer overall than those who did not consume acesulfame-k [80]. Because different studies have implied that artificial sweeteners are associated with obesity, and obesity is subsequently associated with cancer, the NutriNet-Santé investigators also assessed the risk of associations between artificial sweetener intake and obesity-related cancers as a group. A slightly higher risk of obesity-related cancers was found in consumers of higher amounts of all artificial sweeteners compared to the risk of nonconsumers. Nevertheless, another study from Australia found no association between artificially sweetened beverage intake and the risk of obesity-related cancers [131].

Studies in specific population groups have also been inconsistent. A study found that the intake of artificially sweetened beverages was associated with an increased risk of kidney cancer in a US cohort of postmenopausal women [132], but no association was found in a European cohort of healthy adults [133]. An “umbrella review” (i.e., a review of systematic reviews or meta-analyses) found a weak association between intake of artificially sweetened beverages and any type of cancer, and especially with colorectal cancer, pancreatic cancer, gastrointestinal cancer, and cancer mortality [134,135].

No studies have associated the consumption of sucralose, neotame, and advantame with the future development of cancer [136].

The inconsistency in the studies searching for causality in the association between artificial sweeteners and cancer is mainly due to the study design limitations. For example, individuals examined in various studies differ in significant parameters, including the quality and quantity of artificial sweeteners’ consumption. Therefore, seeking evidence for a causal relationship necessitates the evaluation of evidence from multiple harmoniously designed studies and the description of a plausible underlying pathophysiological mechanism to account for the connection [137].

Inversely, there is a possibility that natural sweeteners may be used as therapeutic agents for cancer. Thus, Khaybullin et al. [138] reported in 2014 that isosteviol triazole conjugates could be used for cancer therapy. The authors reported that the conjugates reduced the proliferation of cancer cell lines. The above finding is interesting and needs to be evaluated by further studies.

Ref

Nutrients. 2024 Sep 19;16(18):3162. doi: 10.3390/nu16183162

Chronic Use of Artificial Sweeteners: Pros and Cons

Lydia Kossiva 1, Kostas Kakleas 2, Foteini Christodouli 1, Alexandra Soldatou 1, Spyridon Karanasios 1, Kyriaki Karavanaki 1,*

Editor: Xiaohua Pan

Artificial Sweeteners &Nonalcoholic Fatty Liver Disease

5.1. Artificial Sweeteners and Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a severe complication of obesity, which may present even in childhood. NAFLD is a condition where

 fat accumulates in the liver, due to the

 disruption of de novo lipogenesis (DNL), fatty acid β-oxidation, fatty acid uptake, and 

very-low-density lipoprotein (VLDL) synthesis and secretion mechanisms in the liver [91]. 

Experimental studies in mice have revealed the association between consumption of 

artificially sweetened beverages and

 the development of NAFLD [92]. Also, a recent study that included adults from the U.S. identified a relationship between the consumption of

 AS beverages and the risk of NAFLD development [93]. Furthermore, another paper that included four European studies showed that the consumption

 of low/no-calorie beverages is associated with NAFLD [94]. Inversely, a systematic review and meta-analysis of seven observational studies reported that there is no clear connection between the consumption of artificially sweetened beverages (ASBs) and NAFLD due to insufficient studies in human subjects [95].

Sucralose is the most studied NNS for possible deleterious effects on the liver. Sucralose exerts its effect through various mechanisms, such as the stimulation of hepatic proinflammatory cytokines, the promotion of hepatic lymphocytic infiltration, and the increased hepatic lipogenesis [96,97]. Additionally, sucralose activates the T1R3-ROS-ER stress-dependent pathway [98]. The activation of T1R3 generates reactive oxygen species and triggers lipolysis and endoplasmic reticulum (ER) stress in the liver. ER stress stimulates the production of lipid droplets and interferes with very-low-density lipoprotein (VLDL) metabolism, both enhancing VLDL delivery to hepatocytes and inhibiting VLDL synthesis and export from these cells, which in turn triggers intracellular triglyceride accumulation, which favors the development of NAFLD [99,100]. ER stress also promotes apoptosis and reduces autophagy in the liver, which is connected to the development of NAFLD in mice [101]. In addition, sucralose alters the composition of gut microbiota, thus promoting the production of bile acids that have a proinflammatory effect on hepatocytes [102]. Hence, in order to elucidate any possible association between NNSs and NFALD, longer-term prospective studies in children and adults with objective methods measuring the intake of sweeteners are needed.

Regarding natural sweeteners’ effects on adipogenesis, there are very limited previous studies. Kakleas et al. [21] reported that stevia and trehalose may have a protective effect on NAFLD. An experimental study in db/db mice hepatocytes showed that stevia and stevioside attenuated liver steatosis through the mechanism of PPARa-mediated lipophagy [103].

Thus, most previous studies showed that AS consumption is associated with the development of NAFLD, whereas natural sweeteners, such as stevia, may have a protective effect on NAFLD. Further studies are necessary 

to elucidate these findings

Ref

Nutrients. 2024 Sep 19;16(18):3162. doi: 10.3390/nu16183162

Chronic Use of Artificial Sweeteners: Pros and Cons

Lydia Kossiva 1, Kostas Kakleas 2, Foteini Christodouli 1, Alexandra Soldatou 1, Spyridon Karanasios 1, Kyriaki Karavanaki 1,*

Editor: Xiaohua Pan

Artificial Sweeteners and Insulin Resistance

 5.3 Artificial Sweeteners &,

Insulin Resistance 

Prolonged use of artificial sweeteners by healthy

 individuals may be associated with the development of insulin resistance and T2DM [104,105] or 

the deterioration of glycemic control in patients with diabetes [64]. This seemingly paradoxical association between artificial sweeteners consumption and metabolic disorders has been epidemiologically 

observed and explained by the following hypotheses.

One hypothesis is based on the suppression 

of the cephalic phase of digestion by the sweet taste

 artificial sweeteners [106]. Consumption of artificial sweeteners by mice led to hyperglycemic responses to oral glucose load combined with decreased levels of circulating GLP-1. This was not observed when glucose was infused directly into the stomach, suggesting that altered glucose homeostasis is related to the response to the sweet taste [107].

A second hypothesis supports that consuming artificial sweetener affects the gut microbiota. Artificial sweeteners, such as saccharin, sucralose, aspartame and stevia, resist fermentation by oral bacteria and have bacteriostatic activity [108,109]. They have similar effects on the gut microbiota in both animals and humans [75], impairing digestion and glucose homeostasis.

The third hypothesis supports that sweet taste receptors, including T1R (taste receptor one) and a-gustducin, respond to both caloric sugars, such as sucrose and glucose, and to artificial sweeteners, such as sucralose and acesulfame-k [110,111]. These receptors are also found in the intestinal mucosal secretory L cells, which secrete the peptide GLP-1 [112] and promote insulin excretion. The effect of NNSs on insulin sensitivity can be explained by activation of taste receptor type 1 member 3 (T1R3) and extracellular signal-regulated kinase (ERK1/2) signaling pathway [113]. Studies in mice have revealed that sucralose, through the activation of T1R3, generates reactive oxygen species and triggers lipolysis and endoplasmic reticulum stress in the liver [114]. Endoplasmic reticulum stress results in increased production of proinflammatory cytokines, such as TNF-α and interleukin 6, which further exacerbate inflammation, increase cortisol levels, and promote insulin resistance via the disruption of the insulin signaling pathway [115,116]. Furthermore, studies in trophoblasts treated with aspartame have exhibited cessation of cell proliferation due to increased oxidative stress [117]. Activation of the ERK1/2 pathway in hepatic cells results in decreased expression of adiponectin and increased lipolysis [113]. Consequently, the released free fatty acids from lipolysis can promote the expression of inflammatory cytokines and provoke an inflammatory response, contributing to the development of insulin resistance [118].

Studies in mice also suggest that AS consumption affects the absorption of glucose from the intestinal lumen cells by increasing the expression of the glucose transporter SGLT1 (sodium-dependent glucose transporter isoform 1) and GLUT2 (apical glucose transporter 2) [119,120].

On the other hand, a possible favorable effect of natural sweeteners on glucose metabolism has been reported in animal studies [121]. Specifically, moderate intake of hoodia decreased insulin resistance and inflammatory markers levels [122]. Although the underlying mechanism is still unclear, studies suggest an antidiabetic effect of stevia [123]. In particular, the phenols contained in the leaves of stevia—about 91 mg/g—are the main contributors to the antihyperglycemic activity. Indeed, the leaves of stevia have an antioxidative action, with the highest benefit being found in rats with diabetes [124].

Since only the last two mechanisms have been evaluated in humans, and existing studies’ methodologies vary, further research is needed to determine underlying pathophysiological mechanisms.

Thus, from the above studies, it is concluded that artificial sweeteners use is associated with the development of insulin resistance and T2DM, while, oppositely, natural sweeteners seem to decrease insulin resistance and may be beneficial for chronic use by patients with diabetes

Ref

Nutrients. 2024 Sep 19;16(18):3162. doi: 10.3390/nu16183162

Chronic Use of Artificial Sweeteners: Pros and Cons

Lydia Kossiva 1, Kostas Kakleas 2, Foteini Christodouli 1, Alexandra Soldatou 1, Spyridon Karanasios 1, Kyriaki Karavanaki 1,*

Editor: Xiaohua Pan

कृत्रिम गोड पदार्थ (artificial sweetener)आणि कर्क रोगाचा (कॅन्सर ) धोका

 

कृत्रिम गोड पदार्थ आणि

कर्करोगाचा धोका

पार्श्वभूमी

अन्न उद्योग कृत्रिम गोड पदार्थांचा वापर करतो

विविध प्रकारच्या अन्न आणि पेयांमध्ये साखरेला पर्याय म्हणून वापरला जातो, ज्याचे अनेक जुनाट आजारांवर हानिकारक परिणाम आता चांगलेच स्थापित झाले आहेत.

या अन्न पूरक पदार्थांच्या सुरक्षिततेवर वाद आहे,

विविध रोगांच्या कारणांमध्ये त्यांच्या भूमिकेबद्दल परस्परविरोधी निष्कर्षांसह. विशेषतः, त्यांची कर्करोगजन्यता

अनेक प्रायोगिक अभ्यासांनी सुचवली आहे, परंतु मजबूत साथीच्या पुराव्यांचा अभाव आहे.  अशाप्रकारे, आमचे उद्दिष्ट होते

 कृत्रिम गोड पदार्थांचे सेवन (सर्व आहारातील स्रोतांमधून आणि 

सर्वाधिक सेवन केले जाणारे: एस्पार्टम [E951], एसेसल्फेम-के [E950], आणि सुक्रॅलोज [E955]) आणि कर्करोगाचा धोका (एकूण आणि साइटनुसार)

 यांच्यातील संबंधांची तपासणी करणे.

पद्धती आणि निष्कर्ष

एकूणच, फ्रेंच लोकसंख्या-आधारित गट NutriNet-Santé (2009-2021) 

मधील 102,865 प्रौढांचा समावेश करण्यात 

आला (मध्यम फॉलो-अप वेळ = 7.8 वर्षे). औद्योगिक उत्पादनांच्या ब्रँड नावांसह 24-तासांच्या आहारातील नोंदींद्वारे आहारातील सेवन आणि गोड पदार्थांचे सेवन प्राप्त केले गेले.  वय, लिंग, शिक्षण, शारीरिक क्रियाकलाप, धूम्रपान, बॉडी मास इंडेक्स, उंची, फॉलो-अप दरम्यान वजन वाढणे, मधुमेह, कर्करोगाचा कौटुंबिक इतिहास, २४-तासांच्या आहारातील नोंदींची संख्या आणि उर्जेचे मूलभूत सेवन, अल्कोहोल, सोडियम, संतृप्त फॅटी अॅसिड, फायबर, साखर, फळे आणि भाज्या, संपूर्ण धान्ययुक्त पदार्थ आणि दुग्धजन्य पदार्थांसाठी समायोजित केलेल्या स्वीटनर्स आणि कर्करोगाच्या घटनांमधील संबंधांचे मूल्यांकन कॉक्स प्रोपोर्शनल हॅझर्ड्स मॉडेल्सद्वारे केले गेले. गैर-ग्राहकांच्या तुलनेत, एकूण

 कृत्रिम स्वीटनर्सचे जास्त ग्राहक (म्हणजे, ग्राहकांमध्ये सरासरी एक्सपोजरपेक्षा जास्त) एकूण कर्करोगाचा धोका जास्त होता (n = 3,358 प्रकरणे, धोका प्रमाण [HR] = 1.13 [95% CI 1.03 ते 1.25], P-ट्रेंड = 0.002).  विशेषतः, एस्पार्टम (HR = 1.15 [95% CI 1.03 ते 1.28], P = 0.002) आणि एसेसल्फेम-K (HR = 1.13 [95% CI 1.01 ते 1.26], P = 0.007) कर्करोगाच्या वाढीव जोखमीशी संबंधित होते. 

 स्तनाच्या कर्करोगासाठी उच्च जोखीम देखील आढळून आली (n = 979 प्रकरणे, HR = 1.22 [95% CI 1.01 ते 1.48], P = 0.036, aspartame साठी) आणि लठ्ठपणाशी संबंधित कर्करोगांसाठी (n = 2,023 प्रकरणे, HR = 1.13 [95% CI 1.00 ते 1.28], P = 0.036, एकूण कृत्रिम गोड पदार्थांसाठी, आणि HR = 1.15 [95% CI 1.01 ते 1.32], P = 0.026, aspartame साठी). 

या अभ्यासाच्या मर्यादांमध्ये संभाव्य निवड पूर्वाग्रह, अवशिष्ट गोंधळ आणि उलट कार्यकारणभाव यांचा समावेश आहे, जरी या चिंता दूर करण्यासाठी संवेदनशीलता विश्लेषण केले गेले.

निष्कर्ष

या मोठ्या गट अभ्यासात, कृत्रिम गोड पदार्थ (विशेषतः aspartame आणि acesulfame-K), जे

जगभरातील अनेक अन्न आणि पेय ब्रँडमध्ये वापरले जातात,

वाढत्या कर्करोगाच्या जोखमीशी संबंधित होते.  हे निष्कर्ष

युरोपियन फूड सेफ्टी अथॉरिटी आणि जागतिक स्तरावर इतर 

आरोग्य संस्थांकडून अन्न मिश्रित गोड पदार्थांच्या चालू 

पुनर्मूल्यांकनासाठी महत्त्वाचे आणि नवीन अंतर्दृष्टी प्रदान करतात.

संदर्भ

PLoS मेड. २०२२ मार्च २४;१९(३):e१००३९५०.  doi: 10.1371/journal.pmed.1003950

कृत्रिम गोड करणारे आणि कर्करोगाचा धोका: NutriNet-Santé लोकसंख्या-आधारित समूह अभ्यासाचे परिणाम

शार्लोट डेब्रास 1,2,*, एलोई चझेलास 1,2, बर्नार्ड स्रॉर 1,2, नॅथली ड्रुस्ने-पेकोलो 1,2, युनेस एस्सेडिक 1, फॅबियन स्झाबो डी एडेलेनी 1, सेड्रिक अगासे 1, अलेक्झांड्रे डे सा 1, सेंट्रिए 1, रेबेग्ने, सेंट 1, 1, 2  ह्युब्रेक्ट्स 2,4, चँटल ज्युलिया 1,5, इमॅन्युएल केसे-ग्युयोट 1,2, बेंजामिन ऍलस 1, व्हॅलेंटीना ए अँड्रीवा 1, पिलर गॅलन 1,2, सर्ज हर्कबर्ग 1,2,5, मेलानिया  Deschasaux-Tanguy 1,2, Mathilde Touvier 1,2

संपादक: वेई झेंग6

Ref

 PLoS Med. 2022 Mar 24;19(3):e1003950. doi: 10.1371/journal.pmed.1003950

Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study

Charlotte Debras 1,2,*, Eloi Chazelas 1,2, Bernard Srour 1,2, Nathalie Druesne-Pecollo 1,2, Younes Esseddik 1, Fabien Szabo de Edelenyi 1, Cédric Agaësse 1, Alexandre De Sa 1, Rebecca Lutchia 1, Stéphane Gigandet 3, Inge Huybrechts 2,4, Chantal Julia 1,5, Emmanuelle Kesse-Guyot 1,2, Benjamin Allès 1, Valentina A Andreeva 1, Pilar Galan 1,2, Serge Hercberg 1,2,5, Mélanie Deschasaux-Tanguy 1,2, Mathilde Touvier 1,2

Editor: Wei Zheng6

Artificial sweetners and cancer risk

Artificial Sweetners & 

Cancer Risk

Abstract

Background

The food industry uses artificial sweeteners

 in a wide range of foods and beverages as alternatives to added sugars, for which deleterious effects on several chronic diseases are now well established. 

The safety of these food additives is debated, 

with conflicting findings regarding their role in 

the aetiology of various diseases. In particular, their carcinogenicity has been suggested by

 several experimental studies, but robust epidemiological evidence is lacking. Thus, our objective was to

 investigate the associations between artificial sweetener intakes (total from all dietary sources, and most frequently consumed ones: aspartame [E951], acesulfame-K [E950], and sucralose [E955]) and cancer risk (overall and by site)

Methods and findings

Overall, 102,865 adults from the French population-based cohort NutriNet-Santé (2009–2021) were included (median follow-up time = 7.8 years). Dietary intakes and consumption of sweeteners were obtained by repeated 24-hour dietary records including brand names of industrial products. Associations between sweeteners and cancer incidence were assessed by Cox proportional hazards models, adjusted for age, sex, education, physical activity, smoking, body mass index, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, and baseline intakes of energy, alcohol, sodium, saturated fatty acids, fibre, sugar, fruit and vegetables, whole-grain foods, and dairy products. Compared to non-consumers, higher consumers of total artificial sweeteners (i.e., above the median exposure in consumers) had higher risk of overall cancer (n = 3,358 cases, hazard ratio [HR] = 1.13 [95% CI 1.03 to 1.25], P-trend = 0.002). In particular, aspartame (HR = 1.15 [95% CI 1.03 to 1.28], P = 0.002) and acesulfame-K (HR = 1.13 [95% CI 1.01 to 1.26], P = 0.007) were associated with increased cancer risk. Higher risks were also observed for breast cancer (n = 979 cases, HR = 1.22 [95% CI 1.01 to 1.48], P = 0.036, for aspartame) and obesity-related cancers (n = 2,023 cases, HR = 1.13 [95% CI 1.00 to 1.28], P = 0.036, for total artificial sweeteners, and HR = 1.15 [95% CI 1.01 to 1.32], P = 0.026, for aspartame). Limitations of this study include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

Conclusions

In this large cohort study, artificial sweeteners (especially aspartame and acesulfame-K), which are used in

 many food and beverage brands worldwide, 

were associated with increased cancer risk. These findings provide

 important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally.

Ref

 PLoS Med. 2022 Mar 24;19(3):e1003950. doi: 10.1371/journal.pmed.1003950

Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study

Charlotte Debras 1,2,*, Eloi Chazelas 1,2, Bernard Srour 1,2, Nathalie Druesne-Pecollo 1,2, Younes Esseddik 1, Fabien Szabo de Edelenyi 1, Cédric Agaësse 1, Alexandre De Sa 1, Rebecca Lutchia 1, Stéphane Gigandet 3, Inge Huybrechts 2,4, Chantal Julia 1,5, Emmanuelle Kesse-Guyot 1,2, Benjamin Allès 1, Valentina A Andreeva 1, Pilar Galan 1,2, Serge Hercberg 1,2,5, Mélanie Deschasaux-Tanguy 1,2, Mathilde Touvier 1,2

Editor: Wei Zheng6