If you have any interest in your health you should be aware that too much sugar is not good for you. The consumption of excess refined sugars has been shown to cause weight gain, dyslipidemia (elevation of cholesterol, triglycerides, or both, in the blood), glucose intolerance and insulin resistance (1, 2). Unfortunately, we humans have evolved to enjoy sweet tasting things and unless you have amazingly strong will power, there are going to be times that you will want to satisfy your sweet tooth. So which sweetener should you choose and which low calorie sweeteners are the healthiest? Mainstream media has vilified many ‘artificial sweeteners’ so here is a review of the most common sweeteners that are available based on factual, peer-reviewed science.
Nutritive sweeteners (sugars and sugar alcohols)
Sweeteners can be grouped as nutritive and nonnutritive. Nutritive sweeteners contain carbohydrates and therefore calories, while nonnutritive sweeteners (NNS) provide very little to no calories. Nutritive sweeteners are often referred to as sugars, caloric sweeteners and added sugars and include:
- Glucose – the primary energy source used by our bodies (monosaccharide)
- Fructose – found in fruit, honey and some vegetables
- Galactose – found in diary products and some plants
- Sucrose – occurs naturally in fruits and vegetables and is a combination of glucose and fructose (known as a disaccharide), typical table sugar
- Maltose – made up of two glucose molecules and is found in molasses
- Corn based sweeteners – refers to products made from corn, an example is high-fructose corn syrup which is a combination of glucose and fructose
- Honey – can contain up to 200 substances and is mainly made up of sugars (mostly fructose), water, proteins and amino acids (0.1% – 3.3%) with proline being the most abundant amino acid, organic acids (0.57%), small amounts of vitamins, especially the vitamin B complex (the vitamin content may be reduced due to commercial filtering), minerals (0.04% – 0.2%) including potassium, magnesium, calcium, iron and zinc and phenolic compounds, which act as antioxidants. These compounds can change due to processing and storage of honey. The composition, colour, aroma and flavour of honey depends on the flowers, location and climate, and honeybee species involved in the production (3).
- Agave nectar – liquid sweetener derived from the sap of either the Agave tequilana or Agave slamina plant containing xylose, fructose, glucose and sucrose (4, 5)
- Maple syrup – obtained by concentrating the sap collected from certain species of maple trees, contains mostly sucrose, also contains minerals, oligosaccharides, amino acids and phenolic compounds (6)
Sugar alcohols, or polyols, are another form of nutritive sweetener. The energy provided by polyols can vary due to differences in digestibility, metabolism and because polyols are slowly or incompletely absorbed.
Many sugar alcohols exist in nature, but are typically manufactured from sugars to be used as food ingredients. They can be produced chemically (this is not a bad thing just because of the word ‘chemical’ – essentially everything is made of chemicals) or through fermentation by certain species of yeast and bacteria.
Sugar alcohols are incompletely metabolized in humans, meaning they are not completely by broken down to provide energy. For example, 10 – 20% of ingested sorbitol and xylitol and 30 – 40% of ingested mannitol is excreted in the urine (7).
Examples of polyols include:
- Erythritol (discussed in detail later)
Following ingestion, polyols are absorbed in varying amounts by the human small intestine. Polyols that are not absorbed from the small intestine reach the colon. In the colon, polyols are fermented by gut bacteria to produce short-chain fatty acids and gases, such as hydrogen and methane (8, 9). Short-chain fatty acids are absorbed and provide energy to the body, so this is why polyols that are not absorbed can still provide calories.
The gases produced from the fermentation of polyols can result in gastrointestinal (GI) symptoms, such as flatulence, cramping, bloating and diarrhea. GI symptoms are likely to occur when more than 10 – 20 grams of polyols are consumed at once. This could be from 1 no-added sugar chocolate bar or 2 no-added-sugar cookies.
Polyols may cause problems for people with Irritable Bowel Syndrome (IBS). Studies have shown that low-FODMAP diets can improve the symptoms of IBS. FODMAPs are fermentable oligo-, di- and monosaccharides and polyols. It is thought that the increase in osmotic load in the colon, meaning an increase in un-absorbable, water-soluble solutes in the bowel that cause an influx of water, and the gas generated during fermentation of polyols could contribute to the symptoms of IBS (10).
Most polyols do not raise blood glucose or insulin levels after consumption, which is why they are a suitable choice for people with diabetes. Mannitol, however, which is broken down into sorbitol and glucose after absorption, can cause a small increase in glucose and insulin levels (11).
Polyols cannot be used as an energy source for bacteria that cause tooth decay, also known as dental caries. Dental caries are the destruction of dental hard tissue by acidic material produced by the fermentation of carbohydrates from the diet by oral bacteria.
Xylitol may actually stop the growth of decay-causing bacteria (12). The evidence shows that chewing sugar-free gum sweetened with polyols immediately after meals can prevent tooth decay because of the production of saliva from the chewing action and because oral bacteria cannot metabolise the polyols into acids (13). This, of course, must be combined with tooth brushing to be effective. It should be noted that there is only a small amount of sugar alcohols present in chewing gum.
Nonnutritive sweeteners (NNS)
NNS provide little energy and have been used since the late 1800’s when saccharine was discovered (14). Prior to the 1970’s NNS were used to sweeten medicines and as a sugar substitute in foods for diabetic patients. Since then, a huge industry has developed for NNS to provide sweetness to food without the calories (15).
NNS can be referred to as artificial, alternative, synthetic, low calorie, non-caloric, sugar-substitute, hyper-intense, high-intensity and high-potency sweeteners. NNS are referred to as high-intensity sweeteners because they are many times ‘sweeter’ than sugar. This term high-intensity sweeteners can be misleading and implies that NNS are some sort of ‘super-normal’ stimuli that over stimulate sweet receptors. NNS are actually high-potency sweeteners, meaning that it takes a very small amount of these compounds to activate the sensation of sweetness. Therefore, NNS are able to provide sweetness without contributing a lot of calories to the diet. NNS are ‘sweeter’ than sugar on a weight-to-weight comparison (16).
- Stevia (steviol glycosides – rebaudioside A and stevioside)
- Acesulfame K
- Luo han guo extract
My research revealed that aspartame is quite a controversial item. It was approved by the US Food and Drug Administration (FDA) in 1981 for use in a small number of food products. In 1983 it was approved for use in soft drinks, then in all foods in 1996. It is the most commonly used artificial sweetener in the world found in soft drinks, desserts, yoghurts, chewable multi-vitamins, breakfast cereals and tabletop sweeteners. G. D Searle & Company discovered aspartame in the 1970s and conducted 3 studies on rats looking at the potential of aspartame to cause cancer prior to its approval by the FDA (17). The results from these studies were not published in peer-reviewed scientific literature and did not meet the current standards for conducting these types of studies, referred to as carcinogenic bioassays (18). The final reports from these studies were finally made available at the end of 2011 on the website of the European Food Safety Authority (EFSA).
The results from the studies conducted in the 1970s are somewhat dubious. One of the studies showed that female rats feed aspartame daily from 4 to 104 weeks consumed less food, weighed less and had higher death rates than control rats and had an increased incidence of mammary cancers. The other two studies showed no increase in tumors in rats feed aspartame which survived to the end of the study, but again death rates were higher among the rats feed aspartame.
In 2006 the Cesare Maltoni Cancer Research Center of the Ramazzini Institute (RI) conducted studies feeding male and female rats aspartame for their entire life span starting from 8 weeks of age. Results from these studies showed increased incidences of lymphomas/leukemias and tumors of the renal pelvis in male and female rats and of peripheral nerves in males (18, 21). These results were repeated in 2007 (22). In 2010, the same research center conducted studies on mice and showed that aspartame increases cancers of the liver and lung in males (23). These studies have been criticized by experts in the area, including the FDA and the European Food Safety Authority (EFSA), for a number of reasons such as: the large number of animals used in the studies meant that animals from treatment and control groups were housed under different environmental conditions, there was apparently a high level of infection among the animals used in these studies leading to low survival rates in treated and control groups, specific details of the diets were not provided, there was uncertainty in the diagnosis of some tumor types and a lack of relevance to human cancer risks (24). In defense of the Cesare Maltoni Cancer Research Center of the Ramazzini Institute, they were first to demonstrate carcinogenicity in animals of vinyl chloride and benzene, which are recognized as human cancer causing agents (15).
A recent review by Professor Marina Marinovich, from the Laboratory of Toxicology at the University of Milan concluded that there is no evidence to support an association between aspartame consumption and leukemia, haematopoietic neoplasms, brain cancers, pancreatic cancer, breast cancer or cancers of the digestive tract, endometrium, ovary, prostate and kidneys in humans (25).
Another area of concern regarding aspartame is one of its breakdown products, methanol. However, Professor Marina Marinovich states that a glass of tomato juice provides about 6 times as much methanol as an equivalent amount of diet beverage sweetened with aspartame (25).
So should you be worried about consuming aspartame? I find the animal studies from the Cesare Maltoni Cancer Research Center of the Ramazzini Institute somewhat concerning. However, in the USA the estimated intake of aspartame is 1/10 of the Acceptable Daily Intake (ADI) (26). To reach the ADI an adult would have to drink 12 cans of soft drink per day for their whole life (25). Also bear in mind that the mass media loves a good fear-mongering story and often misinterpret or over interpret scientific publications. The issue, I believe, is that food and drinks containing aspartame, such as diet soft drinks and processed sugar-free desserts, really have little nutritional value. If you use small amounts of aspartame now and then as a low calorie sweetener then the risk to your health is most likely negligible.
The sweet tasting components of stevia are actually the steviol glycosides (rebaudioside A and stevoside) extracted from the leaves of the plant Stevia rebaudiana (Bertoni). The steviol glycosides are not digested or absorbed in the upper gastrointestinal tract meaning these compounds enter the colon intact. The steviol glycosides are then degraded by microbes in the colon to the compound steviol, some of which is excreted in the fecaes while the remainder is absorbed into the circulation. Steviol is then converted to steviol glucuronide, where it is excreted in the urine (27, 28)
The safety of steviol glycosides for use in foods has been extensively evaluated by national and international food safety agencies including the Joint Expert Committee on Food Additives (JECFA), a scientific advisory body of Food and Agriculture Organisation (FAO) of the United Nations, and the World Health Organisation (WHO) (29), as well as in the scientific literature.
As far as I can tell there is no evidence for any potential negative health impacts from consuming the steviol glycosides in the scientific literature for animals or humans. The only study I came across was a recent publication in the journal Molecular and Cellular Endocrinology looking at the effects of the steviol glycosides and the metabolite of these glycosides, steviol, on hormone production by human mammary gland cells and human sperm cells (30). This study was undertaken because the steviol glycosides and steviol have a steroid-like structure. The sex hormones, estradiol and testosterone are examples of steroids. This study found that steviol had an impact on progesterone production in these human cells, however, the cells in these studies were literally bathed in this compound.
Are the results of these studies concerning? In my opinion, probably not, as studies conducted on laboratory animals have failed to show any effect on fertility or reproductive organs. However, as there are studies on the long-term use of stevia in humans, it advisable not to use stevia in excessive quantities on a regular basis. I myself have used liquid steviol glycosides and use an erythritol/steviol glycoside blend as a sweetener in dessert recipes. I also use a plant-based protein powder that is sweetened with steviol glycosides. It is not technically a whole food so I try to use only small amounts (which is easy to do as it is far sweeter than sucrose) and I try not to consume it every day.
Sucralose is a modified version of sucrose. The majority of sucralose (approximately 85%) is not absorbed after it is ingested, and is passed through the body unchanged in the feces (31).
Sucralose is found in the low-calorie sweetener SPLENDA®. Actually, granulated SPLENDA® contains only 1% sucralose and 99% maltodextrin, a starch based carbohydrate. Sucralose is 385 – 650 times sweeter than sugar. Studies have identified a number of potential health issues with sucralose. These issues are:
- Sucralose may affect the absorption of glucose in laboratory animals, This has not been proven in humans.
- High-intensity sweeteners, such as sucralose, may disrupt the brains association between sweet-tasting foods and calories. It is proposed that this disruption can lead to weight gain.
- A study using male rats showed that SPLENDA® can increase the levels of a protein that acts as a pump to remove harmful chemicals from the body, known as P-glycoprotein, and of an enzyme, intestinal cytochrome P-450, responsible for the metabolism of drugs and foreign chemicals. This could cause problems if medications are taken with sucralose as these medications may be metabolized more rapidly and unable to have their intended affect (32).
- This same study found that SPLENDA® decreased and changed the gut microbiota of male rats after 12 weeks. Bacterial species considered to be beneficial were impacted the greatest (32). The effect of sucralose on the bacteria in the human gastrointestinal tract has not been looked at.
- The long-term effects of regular sucralose consumption in humans are unknown and build up of sucralose and/or its breakdown products in the body may occur.
- Sucralose may break down into potentially harmful compounds when heated and the presence of other ingredients can impact on this break down (33).
Due to the number of potential negative health issues associated with sucralose, it is probably best to avoid using this sweetener on a regular basis.
Acesulfame K is a combination of an organic acid and potassium (for the chemists) and was approved for use by the US FDA in 1988 as a tabletop sweetener. In 1998 it was approved for use in beverages and in 2003 it was approved as a general use sweetener (34). 95% of this NNS is excreted in the urine unchanged so it does not provide energy and does not have an effect on potassium intake (35).
Neotame was approved by the FDA as a sweetener in 2002. It is partially absorbed in the small intestine and rapidly broken down in the body and excreted in urine and feces (36).
Saccharin appears to be another controversial NNS. It was the first chemical sugar substitute to be approved and its use was increased during World War I and II because of its low production costs and because sugar was less available. More than 50 studies have been published about saccharin and laboratory rats. From these studies it was shown that high doses of saccharin cause bladder cancer in rats, especially males, when both the parent and the offspring are feed saccharin (37). The National Institute for Environmental Health Sciences found that the mechanism by which saccharin causes cancer in rats is not applicable to humans because rats have a different urine composition and react differently to certain compounds (38). Epidemiological studies in humans have failed to find a direct association between saccharin and cancer risk (38, 39).
Luo Han Guo
Luo Han Guo is a concentrate from the Chinese monk fruit, also known as Siraitia grosvenori, or Swingle fruit extract. It has been recently approved as a sweetener by the FDA and is considered generally recognized as safe (GRAS) (40). A powdered concentrate of Luo Han Guo called PureLo is sold as a sweetener or food ingredient and is estimated to be up to 200 times sweeter than sugar. The sweetness of Luo Han Guo is due to the mogrosides, which are members of the family of triterpene glycosides (41). Interestingly, Luo Han Guo has been shown to have antidiabetic properties in rats by suppressing rises in blood glucose levels (42, 43).
How does a sweetener become approved for use?
Now that I have given you some information of the nutritive and nonnutritive sweeteners that are available, let me tell you about the process involved to bring these products to the market. In order for a food additive, such as sweetener, to be approved, the manufacturer or company must compile and present all the safety data for the proposed use of the additive to the Food and Drug Administration in the US or other regulatory agencies. The FDA requires extensive toxicology studies to be carried out. Toxicology studies look at the absorption, tissue distribution, metabolism and the excretion of the sweetener in the short-term and long-term in animals. If potential issues with a food additive, such as allergic reactions or interactions with medications, are identified, the FDA may require clinical studies in humans to be performed (44).
Three safety aspects are crucial to the FDA approving a food additive: 1. The highest no effect level, meaning the FDA must be able to figure out the highest level of intake at which no adverse effects occur; 2. The Acceptable Daily Intake (ADI), meaning the amount considered safe to consume every day over the course of a lifetime without adverse effects (this amount is determined by the No Observed Adverse Effect Level then multiplying it by 100 so that the ADI is 100 times less than the amount found to have no harmful effects); and 3. The estimated daily intake, meaning the amount of the additive to be added to foods, assuming 100% replacement of sugars and other NNS and the typical consumption of those foods by people of different ages and health status (45).
An FDA ruling may be challenged after approval if new evidence becomes available. The FDA will examine the post-market evidence with the same strictness that pre-market studies received and will consider new data in the context of the entire body of evidence to ensure appropriate risk analysis to protect the health of the public (46).
In Australia, Food Standards Australia and New Zealand (FSANZ) carry out very similar safety assessments before a food additive, such as a sweetener, can be used by consumers (47).
Is erythritol safe?
My sweetener of choice is a blend of the sugar alcohol erythritol with a small percentage of stevia (I typically use Natvia brand). So is erythritol safe to consume?
Firstly, what is erythritol and how is erythritol made? Erythritol is a 4-carbon sugar alcohol and is found naturally in several foods including wine, sake, beer, watermelon, pear, grapes and soy sauce. It is also present in our tissues and body fluids. Erythritol is produced from breaking down corn or wheat starch into glucose which is fermented by safe, food-grade yeast (48).
After ingestion, the majority of erythritol (about 90%) is absorbed from the small intestines. It is not metabolised by our body’s cells, therefore all absorbed erythritol is excreted unchanged in the urine, with only small amounts excreted in the feces. Any unabsorbed erythritol is transported to the large intestine.
Erythritol results in less gas production than other polyols. This is because it seems that erythritol is resistant to fermentation by bacteria found in the human colon (49). This lack of fermentation of erythritol means that it is not converted to short-chain fatty acids and provides virtually no calories.
Erythritol does not raise blood glucose levels or insulin levels in healthy or diabetic individuals (50).
Extensive short-term (28 days) and long-term (up to 2 years) studies on the potential toxicology of erythritol have been conducted in laboratory animals and on human subjects. The results from these studies show that erythritol shows no signs of toxicity, has no effects on reproductive performance or fertility, is well tolerated, and has no cancer-causing potential (48).
The safety of erythritol for use in foods and beverages was confirmed by the Joint WHO/FAO Expert Committee on Food Additives in 1999 (51), the EU Scientific Committee on Food in 2003 (52) and by many other Regulatory Authorities around the world. In the EU, erythritol is authorised for the same uses as other polyols (53).
There is some evidence that consumption of erythritol may reduce dental caries. One study showed that three-year consumption of erythritol-containing candies by 7- to 8-year old children was associated with reduced plaque growth, lower levels of plaque acetic acid and propionic acid, and reduced oral counts of mutans streptococci compared with the consumption of xylitol or sorbitol candies (54). I did notice, however, that this study was funded by the company that made the candies, and I felt that this study was lacking appropriate controls.
The only adverse events that I was able to find related to the consumption of erythritol are diarrhea in adults and children following single high doses; 42 grams for adults and 25 grams in solution for children. This is due to the high osmotic activity of unabsorbed erythritol in the gut, which draws in fluid (55, 56).
I did find one other study that suggested long-term consumption of fructose, acesulfame K, rebaudioside, and erythritol in mice might aggravate the cerebral ischemic injury (stroke). This may partly result from the impairment of endothelial progenitor cells (EPCs) and the reduction of angiogenesis in the ischemic brain (57), meaning that there may be impairment in the development of new blood vessels to the brain.
Conclusions – which sweetener should you use?
Like anything in life, too much of one thing is not good for you. This is especially true for refined sugars and carbohydrates. The occasional ice cream or piece of chocolate cake is not going to be too harmful to your health, but it is advisable to avoid refined carbohydrates as much as possible and focus on nutrient dense food. If you are going to use a sweetener in a recipe then which should you choose?
Out of the nutritive sweeteners, raw honey seems to be the best option. It contains a number of nutritional components, such as amino acids, vitamins and minerals. Maple syrup also has nutritional properties. However, both of these sweeteners provide calories in the form of carbohydrates.
If you are trying to avoid the calories and prefer to use a nonnutritive or low calorie sweetener, then I would go for the sugar alcohol erythritol. Many of the other nonnutritive sweeteners seem to have potential side effects and it is probably best to try to avoid them as much as possible.
- Johnson RJ, et al. (2007) Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. The American journal of clinical nutrition 86(4):899-906.
- Tappy L, Le KA, Tran C, & Paquot N (2010) Fructose and metabolic diseases: new findings, new questions. Nutrition 26(11-12):1044-1049.
- da Silva PM, Gauche C, Gonzaga LV, Costa AC, & Fett R (2016) Honey: Chemical composition, stability and authenticity. Food Chem 196:309-323.
- Willems JL & Low NH (2012) Major carbohydrate, polyol, and oligosaccharide profiles of agave syrup. Application of this data to authenticity analysis. Journal of agricultural and food chemistry 60(35):8745-8754.
- Michel-Cuello C, Juarez-Flores BI, Aguirre-Rivera JR, & Pinos-Rodriguez JM (2008) Quantitative characterization of nonstructural carbohydrates of mezcal Agave (Agave salmiana Otto ex Salm-Dick). Journal of agricultural and food chemistry 56(14):5753-5757.
- Perkins TD & van den Berg AK (2009) Maple syrup-production, composition, chemistry, and sensory characteristics. Advances in food and nutrition research 56:101-143.
- Livesey G (1992) The energy values of dietary fibre and sugar alcohols for man. Nutrition research reviews 5(1):61-84.
- Ballongue J, Schumann C, & Quignon P (1997) Effects of Lactulose and Lactitol on Colonic Microflora and Enzymatic Activity. Scandinavian journal of gastroenterology 32 Suppl 222:41-44.
- Lee A, Zumbe A, & Storey D (1994) Breath hydrogen after ingestion of the bulk sweeteners sorbitol, isomalt and sucrose in chocolate. The British journal of nutrition 71(5):731-737.
- Khan MA, Nusrat S, Khan MI, Nawras A, & Bielefeldt K (2015) Low-FODMAP Diet for Irritable Bowel Syndrome: Is It Ready for Prime Time? Digestive diseases and sciences 60(5):1169-1177.
- Wolever T, Piekarz A, Hollands M, & Younker K (2002) Sugar Alcohols and Diabetes: A review. Canadian Journal of Diabetes 26(4):356-362.
- Vadeboncoeur C, Trahan L, Mouton C, & Mayrand D (1983) Effect of xylitol on the growth and glycolysis of acidogenic oral bacteria. Journal of dental research 62(8):882-884.
- Mickenautsch S, Leal SC, Yengopal V, Bezerra AC, & Cruvinel V (2007) Sugar-free chewing gum and dental caries: a systematic review. Journal of applied oral science : revista FOB 15(2):83-88.
- (U.S) NRC (1955) The safety of artificial sweetners for use in foods, a report. (Food Protection Committee, Washington).
- Soffritti M, et al. (2014) The carcinogenic effects of aspartame: The urgent need for regulatory re-evaluation. American journal of industrial medicine 57(4):383-397.
- Antenucci RG & Hayes JE (2015) Nonnutritive sweeteners are not supernormal stimuli. International journal of obesity 39(2):254-259.
- Administration FaD (1981) Aspartame: commissioner’s final decision. in Federal Register), pp 38285-38308.
- 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):379-385.
- Ishii H (1981) Incidence of brain tumors in rats fed aspartame. Toxicology letters 7(6):433-437.
- Ishii H, Koshimizu T, Usami S, & Fujimoto T (1981) Toxicity of aspartame and its diketopiperazine for Wistar rats by dietary administration for 104 weeks. Toxicology 21(2):91-94.
- Belpoggi F, et al. (2006) Results of long-term carcinogenicity bioassay on Sprague-Dawley rats exposed to aspartame administered in feed. Annals of the New York Academy of Sciences 1076:559-577.
- Soffritti M, Belpoggi F, Tibaldi E, Esposti DD, & Lauriola M (2007) Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats. Environmental health perspectives 115(9):1293-1297.
- Soffritti M, et al. (2010) Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice. American journal of industrial medicine 53(12):1197-1206.
- Magnuson BA, et al. (2007) Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies. Critical reviews in toxicology 37(8):629-727.
- Marinovich M, Galli CL, Bosetti C, Gallus S, & La Vecchia C (2013) Aspartame, low-calorie sweeteners and disease: regulatory safety and epidemiological issues. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 60:109-115.
- Butchko HH, et al. (2002) Aspartame: review of safety. Regulatory toxicology and pharmacology : RTP 35(2 Pt 2):S1-93.
- Roberts A & Renwick AG (2008) Comparative toxicokinetics and metabolism of rebaudioside A, stevioside, and steviol in rats. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 46 Suppl 7:S31-39.
- Wheeler A, et al. (2008) Pharmacokinetics of rebaudioside A and stevioside after single oral doses in healthy men. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 46 Suppl 7:S54-60.
- FAO (2010) JECFA Additives. Steviol Glycosides.).
- Shannon M, et al. (2016) In vitro bioassay investigations of the endocrine disrupting potential of steviol glycosides and their metabolite steviol, components of the natural sweetener Stevia. Molecular and cellular endocrinology.
- Grice HC & Goldsmith LA (2000) Sucralose–an overview of the toxicity data. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 38 Suppl 2:S1-6.
- Abou-Donia MB, El-Masry EM, Abdel-Rahman AA, McLendon RE, & Schiffman SS (2008) Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. Journal of toxicology and environmental health. Part A 71(21):1415-1429.
- Schiffman SS & Rother KI (2013) Sucralose, a synthetic organochlorine sweetener: overview of biological issues. Journal of toxicology and environmental health. Part B, Critical reviews 16(7):399-451.
- Administration FaD (2003) Food additives permitted for direct addition to food for human consumption; acesulfame potassium.).
- Renwick AG (1986) The metabolism of intense sweeteners. Xenobiotica; the fate of foreign compounds in biological systems 16(10-11):1057-1071.
- Nofri C & Tinti JM (2000) Neotame: Discovery, properties, utility. Food Chemistry 69(3):245-257.
- Taylor JM, Weinberger MA, & Friedman L (1980) Chronic toxicity and carcinogenicity to the urinary bladder of sodium saccharin in the in utero-exposed rat. Toxicology and applied pharmacology 54(1):57-75.
- Weihrauch MR & Diehl V (2004) Artificial sweeteners–do they bear a carcinogenic risk? Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 15(10):1460-1465.
- Gallus S, et al. (2007) Artificial sweeteners and cancer risk in a network of case-control studies. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 18(1):40-44.
- Administration FaD (2009) Agency response letter GRAS notice no. GRN 000301.).
- Marone PA, Borzelleca JF, Merkel D, Heimbach JT, & Kennepohl E (2008) Twenty eight-day dietary toxicity study of Luo Han fruit concentrate in Hsd:SD rats. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 46(3):910-919.
- Suzuki YA, Murata Y, Inui H, Sugiura M, & Nakano Y (2005) Triterpene glycosides of Siraitia grosvenori inhibit rat intestinal maltase and suppress the rise in blood glucose level after a single oral administration of maltose in rats. Journal of agricultural and food chemistry 53(8):2941-2946.
- Suzuki YA, et al. (2007) Antidiabetic effect of long-term supplementation with Siraitia grosvenori on the spontaneously diabetic Goto-Kakizaki rat. The British journal of nutrition 97(4):770-775.
- Rulis AM & Levitt JA (2009) FDA’S food ingredient approval process: Safety assurance based on scientific assessment. Regulatory toxicology and pharmacology : RTP 53(1):20-31.
- Renwick AG (1990) Acceptable daily intake and the regulation of intense sweeteners. Food additives and contaminants 7(4):463-475.
- Fitch C, Keim KS, Academy of N, & Dietetics (2012) Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners. Journal of the Academy of Nutrition and Dietetics 112(5):739-758.
- Zealand FSAaN (2013) How FSANZ ensures the safety of food additives. in Additives).
- Munro IC, et al. (1998) Erythritol: an interpretive summary of biochemical, metabolic, toxicological and clinical data. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 36(12):1139-1174.
- Arrigoni E, Brouns F, & Amado R (2005) Human gut microbiota does not ferment erythritol. The British journal of nutrition 94(5):643-646.
- Noda K, Nakayama K, & Oku T (1994) Serum glucose and insulin levels and erythritol balance after oral administration of erythritol in healthy subjects. European journal of clinical nutrition 48(4):286-292.
- WHO (2000) Evaluation of certain food additives and contaminants. World Health Organ Tech Rep Ser 896:1-128.
- Food SCo (2003) Opinion of the Scientific Committee on Food on Erythritol. in SCF/CS/ADD/EDUL/215, ed European Commission HaCPD-GBrussel-Belgium).
- Union E (2006) European Union Commission Directive 2006/52/EC of 26 July 2006amending Directive 95/2/EC on food additives other than colours and sweeteners and Directive 94/35/EC on sweeteners for use in foodstuffs. in Official J Eur Union), pp 10-22.
- Runnel R, et al. (2013) Effect of three-year consumption of erythritol, xylitol and sorbitol candies on various plaque and salivary caries-related variables. Journal of dentistry 41(12):1236-1244.
- Jacqz-Aigrain E, et al. (2015) Gastrointestinal tolerance of erythritol-containing beverage in young children: a double-blind, randomised controlled trial. European journal of clinical nutrition 69(6):746-751.
- Oku T & Okazaki M (1996) Laxative threshold of sugar alcohol erythritol in human subjects. Nutrition Research 16(4):577-589.
- Dong XH, Sun X, Jiang GJ, Chen AF, & Xie HH (2015) Dietary intake of sugar substitutes aggravates cerebral ischemic injury and impairs endothelial progenitor cells in mice. Stroke; a journal of cerebral circulation 46(6):1714-1718.