Artificial Sweeteners

Why Avoid?

• MOST IMPORTANTLY, maltitol in humans is largely absorbed by the small intestine and it breaks down into SORBITOL (which breaks down to fructose + glucose) + GLUCOSE, the very monosaccharides that comprise SUCROSE (iv, v, vi). Sugar-free on the label, SUGAR INSIDE the body. What is not absorbed by the small intestine is fermented by colonic bacteria and there is insufficient research yet on whether or not it has a detrimental effect therein.
• Maltitol is HIGHLY LAXATIVE. Even a dose of 20g in an adult causes flatulence, bloating, stomach pain and diarrhoea (ii). Most maltitol-sweetened sugar-free chocolate bars contain > 40g/100g. The sweetest maltitol chocolates usually are 50% maltitol by weight, so this amount is easily edible by any unsuspecting consumer.
• There is NO RELEVANT CALORIE ‘SAVING’ when switching from SUGAR to MALTITOL (iii, iv).
• During pregnancy, maltitol may cause HYPERGLYCAEMIA and can be EMBRYOTOXIC, causing low embryonic weight at doses of even just 1g/kg body weight (a physiologic amount one might consume) (vii).

(i) Nabors, L.O. (2001) ‘Alternative Sweeteners, Third Edition, Revised and Expanded’, Marcel Dekker, Inc., p. 250

(ii) Koizumi, N. et al. (1982) ‘Studies on transitory laxative effects of sorbitol and maltitol: II: Differences in laxative effects among various foods containing the sweetening agents’, Chemosphere, 12(1), pp. 105-116

(iii) Kruger, D. et al. (1992) ‘Gastrointestinal transit and digestibility of maltitol, sucrose and sorbitol in rats: A multicompartmental model and recovery study’, Experientia, 48

(iv) Beaugerie, L. et al. (1990) ‘Digestion and Absorption in the Human Intestine of Three Sugar Alcohols’, Gastroenterology, 99(3), pp. 717-723

(v) Wursch, P. et al. (1990) ‘Metabolism of maltitol by conventional rats and mice and germfree mice, and comparative digestibility between maltitol and sorbitol in germ-free mice’, British Journal of Nutrition, 63, pp. 7-15

(vi) Lian-Loh, R. et al. (1982), ’The metabolism of maltitol in the rat’, British Journal of Nutrition, 48, p. 477

(vii) Canimoglu, S. and Rencuzogullari, E. (2012) ‘The genotoxic and teratogenic effects of maltitol in rats’, Toxicology and Industrial Health, 29(10), pp. 935-943

Why Avoid?

• Isomalt breaks down partly into sorbitol and mannitol, both of which turn into FRUCTOSE. If you want to avoid fructose, this artificial sweetener does not help you to.
• Isomalt is LAXATIVE and causes borborygmi, colic, stomach-ache, bloating and flatulence at doses of 25g- 40g (ii, iii, iv).
• Isomalt promotes gas (400% more than sucrose) (iv).

(i) Goldstein, D. (2015) ‘The Oxford Companion to Sugar and Sweets’, Oxford University Press

(ii) Lee, A. et al. (2002) ‘The comparative gastrointestinal responses of children and adults following consumption of sweets formulated with sucrose, isomalt and lycasin HBC’, Eur J Clin Nutr., 56(8), pp. 755-64

(iii) Kotsou, G.A. et al. (1996), ‘Dose-related gastrointestinal response to the ingestion of either isomalt, lactitol or maltitol in milk chocolate’, Eur J Clin Nutr., 50(1), pp. 17-21

(iv) Lee, A. et al. (1994) ‘Breath hydrogen after ingestion of the bulk sweeteners sorbitol, isomalt and sucrose in chocolate’, British Journal of Nutrition 71(5), pp. 731-737

Why Avoid?

• Sorbitol’s conversion to fructose in the polyol pathway leads to MITOCHONDRIAL DYSFUNCTION (i).
• Sorbitol is HIGHLY LAXATIVE. Even a dose of 10g in an adult causes flatulence, bloating, stomach pain and diarrhoea (ii). Most sorbitol-sweetened sugar-free chocolate bars contain > 40g/100g.
• There is NO CALORIE ‘SAVING’ when switching from SUGAR to SORBITOL (iii, iv).
• Sorbitol’s conversion to fructose in the polyol pathway leads to INFLAMMATION, AGEing and DIABETIC COMPLICATIONS from retinopathy to nephropathy (i, v, vi, vii, viii)
• Sorbitol is metabolised by: E. coli, Salmonella and Shigella, bacterial species that are associated with pathology (ix, x).

(i) Tang, W.H. et al. (2012) ‘Aldose reductase, oxidative stress, and diabetic mellitus’, Frontiers in Pharmacology, 3(87)

(ii) Koizumi, N. et al. (1982) ‘Studies on transitory laxative effects of sorbitol and maltitol: II: Differences in laxative effects among various foods containing the sweetening agents’, Chemosphere, 12(1), pp. 105-116

(iii) Kruger, D. et al. (1992) ‘Gastrointestinal transit and digestibility of maltitol, sucrose and sorbitol in rats: A multicompartmental model and recovery study’, Experientia, 48

(iv) Beaugerie, L. et al. (1990) ‘Digestion and Absorption in the Human Intestine of Three Sugar Alcohols’, Gastroenterology, 99(3), pp. 717-723

(v) Friedman, E.A. (1999) ‘Advanced glycosylated end products and hyperglycemia in the pathogenesis of diabetic complications’, Diabetes Care, 22(2), pp. B65-71

(vi) Lorenzi, M. and Oates, P.J. (2008) ‘The Polyol Pathway and Diabetic Retinopathy’, Contemporary Diabetes: Diabetic Retinopathy, Humanah Press, Totowa, NJ.

(vii) Bjornstad, P. et al. (2015) ’Fructose and uric acid in diabetic nephropathy’, Diabetologia, 58(9), pp. 1993-2002.

(viii) Julius U. et al. (2008) ‘Sorbitol Pathway of Glucose Metabolisn and Dyslipidemia’, 77th Congress of the European Atherosclerosis Society, PO6-40

(ix) Lee, A. et al. (1994) ‘Breath hydrogen after ingestion of the bulk sweeteners sorbitol, isomalt and sucrose in chocolate’, British Journal of Nutrition 71(5), pp. 731-737

(x) Payne, A.N. et al. (2012) ‘Gut microbial adaptation to dietary consumption of fructose, artificial sweeteners and sugar alcohols: implications for host–microbe interactions contributing to obesity’, Obesity Reviews, 13, pp. 799-809

Why Avoid?

• Ace-K consumption CHANGES the GUT MICROBIOME composition (i).
• Ace-K has been shown to cause WEIGHT GAIN in animal studies, albeit at >double the dose one might expect to consume in one day. These same studies also observed epigenetic changes in energy metabolism genes which provide a possible explanation for the weight gain (i, vi).
• Ace-K increased INFLAMMATORY endotoxin lipolysaccharide (LPS) synthesis genes significantly and the synthesis gene for a bacterial toxin that is a VIRULENCE factor that stimulates inflammatory mediators including CYTOKINES (i).
• Toxicity testing on Ace-K has been insufficient, so its toxicity (incl. carcinogenicity) to human health is still UNCLEAR (ii, iii, iv).
• Ace-K INCREASES GLUCOSE RESPONSES and STIMULATES INCRETIN (e.g. GLP-1) secretion, which RAISES INSULIN. In those with insulin resistance or metabolic syndrome, GLP-1 increases cardiovascular risk (v, vi).
• Ace-K may directly stimulate ADIPOGENESIS and suppress LIPOLYSIS, leading to FAT GAIN (vii).
• Chronic Ace-K intake may cause cognitive impairment (viii).

(i) Bian, X. et al. (2017) ‘The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice’, PLOS ONE, 12(6)

(ii) Karstadt, M.L. (2009) ‘Regulation of carcinogenic food additives in the United States’, Eur. J. Oncol., 14(2), pp. 79-92

(iii) Bloomgarden, Z.T. (2010 ‘Nonnutritive Sweeteners, Fructose, and Other Aspects of Diet’, Diabetes Care, 34

(iv) Karstadt, M.L. (2009) ‘Testing Needed for Acesulfame Potassium, an Artificial Sweetener’, Environ Health Perspect. 114(9)

(v) Chan, C. et al. (2017) ‘The impact of low and no-caloric sweeteners on glucose absorption, incretin secretion and glucose tolerance’, Applied Physiology, Nutrition and Metabolism

(vi) Yamaoka-Tojo, M. (2010) ‘Elevated circulating levels of an incretin hormone, glucagon-like peptide-1, are associated with metabolic components in high-risk patients with cardiovascular disease’, Cardiovascular Diabetology, 9(17)

(vii) Simon, B.R. (2013) ‘Artificial Sweeteners Stimulate Adipogenesis and Suppress Lipolysis Independently of Sweet Taste Receptors’, The Journal of Biological Chemistry, 288, pp. 32475-32489

(viii) Cong, W-n. (2013) ‘Long-Term Artificial Sweetener Acesulfame Potassium Treatment Alters Neurometabolic Functions in C57BL/6J Mice’, PLOS ONE, 8(8)

Why Avoid?

• KEY: most aspartame studies have been performed on rats, which hydroxylate (transform) aspartame 5x faster than humans, so studies on rats using the acceptable daily intake (ADI) of 40mg/kg body weight for humans, might show benign results, yet might show adverse impacts at 200mg/kg body weight, which might be the relevant-to-human dose (i).
• Even at lower than the ADI for humans, aspartame consumption appears to generate CARCINOGENIC effects and may be directly cytotoxic (ii, iii).
• Aspartame causes CARDIAC OXIDATIVE STRESS, even at levels deemed safe by regulators (iv).
• Aspartame causes NEUROBEHAVIOURAL changes and negatively impacts mood, increasing IRRITABILITY and DEPRESSION (v). The mechanisms by which aspartame causes this are quite clear and include: disturbed amino acid (protein) metabolism, neuronal dysfunction, hormonal imbalances and neurotransmitter changes that impact serotonin regulation (vi).
• Aspartame’s breakdown products may cause DNA damage and abnormal brain development so should be AVOIDED during PREGNANCY (vii).
• Aspartame and its breakdown products cause MITOCHONDRIAL DAMAGE, which leads to impaired FAT METABOLISM and impaired GABA production, which directly disrupts mood (viii).
• Aspartame creates permeability and compromises the blood-brain barrier, leading to NEURODEGENERATION (viii).
• Aspartame causes adverse MICROBIOME CHANGES, with increases in bacteria associated with pathology, and increases in propionate, a bacterial end-product that is highly GLUCONEOGENIC (increases GLUCOSE) (ix).
• Aspartame causes HIGHER FASTING GLUCOSE and INSULIN RESISTANCE, possibly due to the MICROBIOME changes it produces (x).

(i) Fernstrom, J.D. (1989) ‘Oral aspartame and plasma phenylalanine: pharmacokinetic difference between rodents and man, and relevance to CNS effects of phenylalanine’, Journal of Neural Transmission, 75, pp. 159-164

(ii) Soffritti, M. et al. (2006) ’ First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats’, Environmental Health Perspectives, 114(3), pp. 379-385

(iii) Maghiari, A. L. et al. (2020) ‘High Concentrations of Aspartame Induce Pro-Angiogenic Effects in Ovo and Cytotoxic Effects
in HT-29 Human Colorectal Carcinoma Cells’, Nutrients, 2020, 12, p. 3600

(iv) Choudhary, A.K. et al. (2015) ‘Aspartame induced cardiac oxidative stress in Wistar albino rats’, Nutrition clinique et metabolisme, 30, pp. 29-37

(v) Lindseth, G.N. et al. (2014) ‘Neurobehavioral Effects of Aspartame Consumption’, Res Nurs Health, 37(3), pp. 185-193

(vi) Choudhary, A.K. (2018) ‘The debate over neurotransmitter interaction in aspartame usage’, Journal of Clinical Neuroscience, 56, pp. 7-15

(vii) Manabe, S. et al. (1993), ‘Effect of excess phenylalanine diet during pregnancy on fetal brain growth in rats. Tokushima J Exp Med., 40(3-4), pp. 125-35

(viii) Humphries, P. et al. (2008), ‘Direct and indirect cellular effects of aspartame on the brain’, 62, pp. 451-62

(ix) Palmnäs, M.S.A. et al. (2014), ‘Low-Dose Aspartame Consumption Differentially Affects Gut Microbiota-Host Metabolic Interactions in the Diet-Induced Obese Rat’, PLOS ONE, 9(10)

(x) Kuk, J.L. and Brown, R.E. (2016) ‘Aspartame intake is associated with greater glucose intolerance in individuals with obesity’ Appl Physiol Nutr Metab., 41(7), pp. 795-8

Why Avoid?

• Saccharin reduces plasma antioxidants significantly and generates OXIDATIVE STRESS and excess reactive-oxygen species (ROS). It increases lipid peroxidation, secondary oxidants and DNA-reactive aldehydes that may lead to DNA DAMAGE (i, ii).
• Saccharin causes changes that indicate LIVER DYSFUNCTION, including (but not only) significantly increased alkaline phosphatase, a biomarker associated with LIVER DISEASE (i, ii).
• Saccharin causes OVEREXPRESSION of a key ONCOGENE (CANCER) gene and DOWNREGULATION of a TUMOUR SUPPRESSOR gene (i).
• Saccharin appears to cause CANCEROUS changes in LIVER TISSUE within 8 weeks in animal studies, at the ADI levels (25mg/kg body weight) (i).
• Chronic saccharin consumption increases creatinine significantly and may cause KIDNEY INJURY (iii).
• Saccharin INCREASES URIC ACID, one of the key pathological mechanisms by which fructose metabolism HARMS our cardiometabolic health (iii).
• Saccharin INCREASES BLOOD GLUCOSE over time, in a dose-dependent manner.
• Saccharin can cross the placenta, be transferred via breastmilk and should be AVOIDED during pregnancy and while breastfeeding.

(i) El-Sayed Alkafafy, M. et al. (2015) ‘Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach’, International Journal of Immunopathology and Pharmacology, 28(2), pp. 247-255

(ii) Amin, K.A. et al. (2016) ‘Effect of sweetener and flavoring agent on oxidative indices, liver and kidney function levels in rats’, Indian J Exp Biol. 54(1), pp. 56-63

(iii) Azeez, O.A. et al. (2019) ‘Long-Term Saccharin Consumption and Increased Risk of Obesity, Diabetes, Hepatic Dysfunction, and
Renal Impairment in Rats’, Medicina, 55, p. 681

(iv) Labrecque, M.T. et al. (2015) ‘Impact of ethanol and saccharin on fecal microbiome in pregnant and non-pregnant mice’, J Pregnancy Child Health, 2

(v) Bian, X. et al. (2017) ‘Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions’, Food Chem Toxicol, 107, pp. 530-539

(vi) Suez, J. et al. (2014) ‘Artificial sweeteners induce glucose intolerance by altering the gut microbiota’, Nature, 514(7521)

Why Avoid?

• Tagatose INCREASES URIC ACID levels, potentially to even greater degrees than fructose itself (i)! Elevated uric acid leads to many pathological impacts, as discussed in the sugar section of this website. In fact it is one of the main ways in which excess fructose consumption leads to disease.
• Tagatose INCREASES glucagon-like-peptide-1 (GLP-1), increasing the risk of HYPERINSULINEMIA.
• Tagatose in animal research causes SIGNIFICANT INCREASES in LIVER SIZE, similar to that seen during high-sucrose and high-fructose diets (ii).

(i) Buemann, B. et al. (2000) ‘D-Tagatose, a stereoisomer of D-fructose, increases blood uric acid concentration’, Metabolism, 49(8)
(ii) Bär, A. et al. (1999) ‘Characteristics and significance of D-tagatose-induced liver enlargement in rats: An interpretative review’, Regul Toxicol Pharmacol. 29(2)

Why Avoid?

• Sucralose causes a REDUCTION in beneficial GUT MICROBIOTA, leading to DYSBIOSIS (i).
• Sucralose LOWERS INSULIN SENSITIVITY and can cause HYPERINSULINAEMIA and SIGNIFICANTLY INCREASED LIPOGENESIS (FAT CREATION) (ii, iii).
• Sucralose increases ADIPOCYTE (FAT CELL) size significantly (via SREBP-1-induced hyperinsulinemia), and appears to cause whitening of adipocytes (FAT CELLS). Generally, it is a move away from health to have a lower % of brown adipose tissue (brown fat) and a higher % of white adipose tissue (iii).
• Persistent (even low) sucralose consumption leads to increased sweet taste receptors in the intestinal epithelium and GLUT2 (glucose transporter) in enterocytes, INCREASING GLUCOSE ABSORPTION and BLOOD GLUCOSE LEVELS. These phenomena are seen in obese subjects and are associated with INSULIN RESISTANCE, the very pathology that is meant to be averted by avoiding sugar (iii, iv).
• Sucralose increases INFLAMMATION via activating the toll-like-receptor (TLR)-4 signalling pathway (iii).
• Long-term sucralose consumption significantly increases incretins, resulting in WEIGHT GAIN, HYPERINSULINEMIA and HYPERGLYCAEMIA. Sucralose increased phosphorylation of cJun-N-terminal-kinase (JNK), which is associated with insulin resistance (iii). Similar results have been observed in normal-weight as well as obese humans. Even one sucralose dose caused elevated glycaemic and insulin responses to an oral glucose test in obese individuals (v).
• Sucralose causes gut MICROBIOME changes towards that seen in humans with Type 2 diabetes, indicating that replacing sugar consumption with sucralose may lead to the same/similar pathology (vi).
• Sucralose may lead to INFLAMMATORY BOWEL DISEASE (IBD), exacerbate CROHN’S DISEASE and INTESTINAL PERMEABILITY (vii, viii, ix).
• Sucralose withstands heat, acidification, pH and temperature changes, and is NOT DEGRADED by WASTEWATER TREATMENT. It is ACCUMULATING in the ENVIRONMENT (it has been found in wastewater, rivers, estuaries and the Gulf Stream) and it is BACTERIOSTATIC (prevents bacteria from growing), in a concentration-dependent manner. It is contaminating micro-environments and we do not know the long-term consequences of this accumulating synthetic compound on environmental or human health (x).
• Sucralose in the presence of glycerol generates toxic chloropropanols, as found in research on using sucralose in baked goods (xi).

(i) Abou-Donia, M.B. et al. (2008) ‘Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats’, J Toxicol Environ Health A., 71, pp. 1415-1429

(ii) Romo-Romo, A. et al. (2018) ‘Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial’, Am J Clin Nutr. (108), pp. 485–491

(iii) Sánchez-Tapia, M. et al. (2019) ‘Natural and Artificial Sweeteners and High Fat Diet Modify Differential Taste Receptors, Insulin, and TLR4-Mediated Inflammatory Pathways in Adipose Tissues of Rats’, Nutrients, 11(880)

(iv) Swithers, S.E. (2013) ‘Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements’, Trends in Endocrinology and Metabolism, 24(9)

(v) Pepino, M.Y. et al. (2013) ‘Sucralose Affects Glycemic and Hormonal Responses to an Oral Glucose Load’, Diabetes Care, 36

(vi) Suez, J. et al. (2014) ‘Artificial sweeteners induce glucose intolerance by altering the gut microbiota’, Nature, 514(7521)

(vii) Qin, X. (2011) ‘What made Canada become a country with the highest incidence of inflammatory bowel disease: Could sucralose be the culprit?’, Can J Gastroenterol, 25(9)

(viii) Abou-Donia, M.B. et al. (2008) ‘Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats’, J Toxicol Environ Health A., 71(21), pp. 1415-29

(ix) Rodriguez-Palacios, A. et al. (2018) ’ The Artificial Sweetener Splenda Promotes Gut Proteobacteria, Dysbiosis, and Myeloperoxidase Reactivity in Crohn’s Disease-Like Ileitis’, Inflamm Bowel Dis., 24(5), 1005-1020

(x) Omran, A. et al. (2013) ‘Metabolic Effects of Sucralose on Environmental Bacteria’, Journal of Toxicology, 2013

(xi) Rahn, A. and Yaylayan, V.A. (2010) ‘Thermal degradation of sucralose and its potential in generating chloropropanols
in the presence of glycerol’, Food Chemistry, 118, pp. 56-61