Sugar substitute

Packets of Assugrin, a brand of cyclamate.

A sugar substitute is a food additive that provides a sweet taste like that of sugar while containing significantly less food energy. Some sugar substitutes are produced by nature, and others produced synthetically. Those that are not produced by nature are, in general, called artificial sweeteners.

Types

An important class of sugar substitutes is known as high-intensity sweeteners. These are compounds with many times the sweetness of sucrose, common table sugar. As a result, much less sweetener is required and energy contribution is often negligible. The sensation of sweetness caused by these compounds (the "sweetness profile") is sometimes notably different from sucrose, so they are often used in complex mixtures that achieve the most natural sweet sensation.

If the sucrose (or other sugar) that is replaced has contributed to the texture of the product, then a bulking agent is often also needed. This may be seen in soft drinks or sweet teas that are labeled as "diet" or "light" that contain artificial sweeteners and often have notably different mouthfeel, or in table sugar replacements that mix maltodextrins with an intense sweetener to achieve satisfactory texture sensation.

In the United States, seven intensely sweet sugar substitutes have been approved for use. They are stevia, aspartame, sucralose, neotame, acesulfame potassium (Ace-K), saccharin, and advantame. Cyclamates are used outside the U.S., but have been prohibited in the U.S. since 1969. Others, which may or may not be approved depending on jurisdiction, include allulose (psicose) and monk fruit. The U.S. Food and Drug Administration regulates artificial sweeteners as food additives.[1] Food additives must be approved by the FDA, which publishes a generally recognized as safe (GRAS) list of additives.[2] Stevia is exempt under the FDA's GRAS policy due to its being a natural substance in wide use well before 1958, and the FDA has approved it on these grounds. The conclusions about safety are based on a detailed review of a large body of information, including hundreds of toxicological and clinical studies.[3]

The majority of sugar substitutes approved for food use are artificially synthesized compounds. However, some bulk natural sugar substitutes are known, including sorbitol and xylitol, which are found in berries, fruit, vegetables, and mushrooms. It is not commercially viable to extract these products from fruits and vegetables, so they are produced by catalytic hydrogenation of the appropriate reducing sugar. For example, xylose is converted to xylitol, lactose to lactitol, and glucose to sorbitol. Other natural substitutes are known, but these have yet to gain official approval for food use.

Sorbitol and xylitol are examples of sugar alcohols (also known as polyols). These are, in general, less sweet than sucrose but have similar bulk properties and can be used in a wide range of food products. Sometimes the sweetness profile is fine-tuned by mixing these with high-intensity sweeteners. As with all food products, the development of a formulation to replace sucrose is a complex proprietary process.

Use

Sugar substitutes are used instead of sugar for a number of reasons, including:

Common practice

The three primary compounds used as sugar substitutes in the United States are saccharin (e.g., Sweet'N Low), aspartame (e.g., Equal, NutraSweet) and sucralose (e.g., Splenda, Altern). Maltitol and sorbitol are often used, frequently in toothpaste, mouth wash, and in foods such as "no sugar added" ice cream. Erythritol is gaining momentum as a replacement for these other sugar alcohols in foods as it is much less likely to produce gastrointestinal distress when consumed in large amounts. In many other countries, xylitol, cyclamate, and the herbal sweetener stevia are used extensively.

When sweeteners are provided for restaurant customers to add to beverages such as tea and coffee themselves, they are often available in paper packets which can be torn and emptied. In North America, the colors are typically white for sucrose, blue for aspartame, pink for saccharin,[note 1] yellow for sucralose (United States) or cyclamate (Canada), tan for turbinado, orange for monk fruit extract, and green for stevia.[7]

Food industry use

The food and beverage industry is increasingly replacing sugar or corn syrup with artificial sweeteners in a range of products traditionally containing sugar.

According to market analysts Mintel, a total of 3,920 products containing artificial sweeteners were launched in the U.S. between 2000 and 2005. In 2004 alone, 1,649 artificially sweetened products were launched. According to market analysts Freedonia in 2012, the United States artificial sweetener market is set to grow at around 8% per year.[8]

Aspartame is currently the most popular artificial sweetener in the U.S. food industry, as the price has dropped significantly since its patent registered by Monsanto Company expired in 1992. However, sucralose may soon replace it, as alternative processes to Tate & Lyle's patent seem to be emerging. According to Morgan Stanley, this can mean that the price of sucralose will drop by thirty percent.[9]

Sugar substitutes are highly consumed in America. In 2003–2004, Americans two years of age and older consumed 585 grams (21 oz) per day of beverages and 375 grams (13 oz) per day of foods with caloric sweeteners. More than 66% of Americans consumed these beverages with sugar substitutes and 82.3% of Americans consumed foods with added caloric sweeteners. On the other hand, 10.8% of Americans in 2003–2004 consumed non-caloric sweetener flavored beverages and 5.8% consumed non-caloric sweetener flavored foods.[10]

Some commonly consumed foods with sugar substitutes are diet sodas, cereals, and sugar-free desserts such as ice cream. Sugar substitutes are found in many products today due to their low or non-caloric characteristics. This can be used to market a product to dieters or those conscious of their sugar intake, such as consumers with diabetes. Sugar substitutes such as xylitol and saccharin have many positive research results that show qualities of dental decay prevention,[11] which causes them to be popular for use in chewing gums and toothpaste.

One packet of sugar substitute is equal to 1 dessertspoon (2 teaspoons)

Sugar substitutes

Aspartame

Aspartame was discovered in 1965 by James M. Schlatter at the G.D. Searle company. He was working on an anti-ulcer drug and accidentally spilled some aspartame on his hand. When he licked his finger, he noticed that it had a sweet taste. Torunn Atteraas Garin oversaw the development of aspartame as an artificial sweetener. It is an odorless, white crystalline powder that is derived from the two amino acids aspartic acid and phenylalanine. It is about 200 times as sweet as sugar and can be used as a tabletop sweetener or in frozen desserts, gelatins, beverages, and chewing gum. When cooked or stored at high temperatures, aspartame breaks down into its constituent amino acids. This makes aspartame undesirable as a baking sweetener. It is more stable in somewhat acidic conditions, such as in soft drinks. Though it does not have a bitter aftertaste like saccharin, it may not taste exactly like sugar. When eaten, aspartame is metabolized into its original amino acids. Because it is so intensely sweet, relatively little of it is needed to sweeten a food product, and is thus useful for reducing the number of calories in a product.

The safety of aspartame has been studied extensively since its discovery with research that includes animal studies, clinical and epidemiological research, and postmarketing surveillance,[12] with aspartame being one of the most rigorously tested food ingredients to date.[13] Aspartame has been subject to multiple claims against its safety, including supposed links to cancer as well as complaints of neurological or psychiatric side effects.[14] Multiple peer-reviewed comprehensive review articles and independent reviews by governmental regulatory bodies have analyzed the published research on the safety of aspartame and have found aspartame is safe for consumption at current levels.[12][14][15][16] Aspartame has been deemed safe for human consumption by over 100 regulatory agencies in their respective countries,[16] including the UK Food Standards Agency,[17] the European Food Safety Authority (EFSA)[18] and Canada's Health Canada.[19]

Cyclamate

Cyclamate-based sugar substitute sold in Canada.

In the United States, the Food and Drug Administration (FDA) banned the sale of cyclamate in 1969 after lab tests in rats involving a 10:1 mixture of cyclamate and saccharin that at levels comparable to humans ingesting 550 cans of diet soda per day, caused bladder cancer, a disease to which rats are particularly susceptible.[20] Cyclamates are still used as sweeteners in many parts of the world, including Europe (e.g. UK and Russia).

Saccharin

Saccharin, historical wrapping; Sugar Museum (Berlin)

Apart from sugar of lead (used as a sweetener in ancient through medieval times before the toxicity of lead was known), saccharin was the first artificial sweetener and was originally synthesized in 1879 by Remsen and Fahlberg. Its sweet taste was discovered by accident. It had been created in an experiment with toluene derivatives. A process for the creation of saccharin from phthalic anhydride was developed in 1950, and, currently, saccharin is created by this process as well as the original process by which it was discovered. It is 300 to 500 times as sweet as sugar (sucrose) and is often used to improve the taste of toothpastes, dietary foods, and dietary beverages. The bitter aftertaste of saccharin is often minimized by blending it with other sweeteners.

Fear about saccharin increased when a 1960 study showed that high levels of saccharin may cause bladder cancer in laboratory rats. In 1977, Canada banned saccharin due to the animal research. In the United States, the FDA considered banning saccharin in 1977, but Congress stepped in and placed a moratorium on such a ban. The moratorium required a warning label and also mandated further study of saccharin safety.

Subsequent to this, it was discovered that saccharin causes cancer in male rats by a mechanism not found in humans. At high doses, saccharin causes a precipitate to form in rat urine. This precipitate damages the cells lining the bladder (urinary bladder urothelial cytotoxicity) and a tumor forms when the cells regenerate (regenerative hyperplasia). According to the International Agency for Research on Cancer, part of the World Health Organization, "Saccharin and its salts was [sic] downgraded from Group 2B, possibly carcinogenic to humans, to Group 3, not classifiable as to carcinogenicity to humans, despite sufficient evidence of carcinogenicity to animals, because it is carcinogenic by a non-DNA-reactive mechanism that is not relevant to humans because of critical interspecies differences in urine composition."

In 2001, the United States repealed the warning label requirement, while the threat of an FDA ban had already been lifted in 1991. Most other countries also permit saccharin, but restrict the levels of use, while other countries have outright banned it.

The EPA has officially removed saccharin and its salts from their list of hazardous constituents and commercial chemical products. In a 14 December 2010 release, the EPA stated that saccharin is no longer considered a potential hazard to human health.

Stevia

Stevia has been widely used as a natural sweetener in South America for centuries and in Japan since 1970. Due to its unique characteristics of zero glycemic index and zero calories,[21] it is fast becoming popular in many other countries. In 1987, the FDA issued a ban on stevia because it had not been approved as a food additive, although it continued to be available as a dietary supplement.[22] After being provided with a significant amount of scientific data proving that there was no side-effect of using stevia as a sweetener from companies such as Cargill and Coca-Cola, the FDA gave a "no objection" approval for GRAS status in December 2008 to Truvia, a blend of rebiana and erythritol[23] (developed by Cargill and The Coca-Cola Company), as well as PureVia (developed by PepsiCo and the Whole Earth Sweetener Company, a subsidiary of Merisant),[24] both of which using rebaudioside A derived from the stevia plant. In Australia, the brand Vitarium have used Natvia, a natural stevia sweetener, to do a range on sugar-free children's milk mixes.[25]

Sucralose

Sucralose is a chlorinated sugar that is about 600 times as sweet as sugar. It is produced from sucrose when three chlorine atoms replace three hydroxyl groups. It is used in beverages, frozen desserts, chewing gum, baked goods, and other foods. Unlike other artificial sweeteners, it is stable when heated and can therefore be used in baked and fried goods. The FDA approved sucralose in 1998.[26]

Most of the controversy surrounding Splenda, a sucralose sweetener, is focused not on safety but on its marketing. It has been marketed with the slogan, "Splenda is made from sugar, so it tastes like sugar." Sucralose is prepared from either of two sugars, sucrose or raffinose. With either base sugar, processing replaces three oxygen-hydrogen groups in the sugar molecule with three chlorine atoms.[27]

The "Truth About Splenda" website was created in 2005 by The Sugar Association, an organization representing sugar beet and sugar cane farmers in the United States,[28] to provide its view of sucralose. In December 2004, five separate false-advertising claims were filed by the Sugar Association against Splenda manufacturers Merisant and McNeil Nutritionals for claims made about Splenda related to the slogan, "Made from sugar, so it tastes like sugar". French courts ordered the slogan to no longer be used in France, while in the U.S. the case came to an undisclosed settlement during the trial.[27]

There are few safety concerns pertaining to sucralose[29] and the way sucralose is metabolized suggests a reduced risk of toxicity. For example, sucralose is extremely insoluble in fat and, thus, does not accumulate in fatty tissues; sucralose also does not break down and will dechlorinate only under conditions that are not found during regular digestion (i.e., high heat applied to the powder form of the molecule).[30] Only about 15% of sucralose is absorbed by the body and most of it passes out of the body unchanged.[30]

Acesulfame potassium

Acesulfame potassium (Ace-K) is 200 times sweeter than sucrose (common sugar), as sweet as aspartame, about two thirds as sweet as saccharin, and one third as sweet as sucralose. Like saccharin, it has a slightly bitter aftertaste, especially at high concentrations. Kraft Foods has patented the use of sodium ferulate to mask acesulfame's aftertaste. Acesulfame potassium is often blended with other sweeteners (usually aspartame or sucralose), which give a more sucrose-like taste, whereby each sweetener masks the other's aftertaste and also exhibits a synergistic effect in which the blend is sweeter than its components.

Unlike aspartame, acesulfame potassium is stable under heat, even under moderately acidic or basic conditions, allowing it to be used as a food additive in baking or in products that require a long shelf life. In carbonated drinks, it is almost always used in conjunction with another sweetener, such as aspartame or sucralose. It is also used as a sweetener in protein shakes and pharmaceutical products, especially chewable and liquid medications, where it can make the active ingredients more palatable.

Lead acetate (historic)

Lead acetate (sometimes called sugar of lead) is an artificial sugar substitute made from lead that is of historical interest because of its widespread use in the past, such as by ancient Romans.[31] The use of lead acetate as a sweetener eventually produced lead poisoning in any individual ingesting it habitually. Lead acetate was abandoned as a food additive throughout most of the world after the high toxicity of lead compounds became apparent.

Mogrosides

More recently, mogrosides (typically extracted from monk fruit) have been used in commercial products after the FDA granted some of the compounds GRAS status in 2010.[32][33] As of 2011, it is not (yet) a permitted sweetener in the EU, although it is allowed as a natural flavor at concentrations where it does not function as a sweetener.[33][34] Some of the products incorporating it are Nestlé's Milo in Asia and certain Kellogg cereals in the U.S.[35] It is also the basis of McNeil Nutritionals's tabletop sweetener Nectresse in the U.S. and Norbu Sweetener in Australia.[35] As of 2012, the New Zealand company BioVittoria provides more than 90 percent of the global supply of monk fruit extract; its main manufacturing facility for the product is in Guilin, China.[35]

Sweetness

Natural sugar substitutes

The sweetnesses and energy densities are in comparison to those of sucrose.

Name Sweetness by weight Sweetness by food energy Energy density Notes
Brazzein 800 Protein
Curculin 550 Protein; also changes the taste of water and sour solutions to sweet
Erythritol 0.7 14 0.05
Fructooligosaccharide 0.5
Glycyrrhizin 50
Glycerol 0.6 0.55 1.075 E422
Hydrogenated starch hydrolysates 0.4–0.9 0.5×–1.2 0.75
Inulin 0.1
Isomalt 0.45–0.65 0.9–1.3 0.5 E953
Isomaltooligosaccharide 0.5
Isomaltulose 0.5
Lactitol 0.4 0.8 0.5 E966
Mogroside mix 300
Mabinlin 100 Protein
Maltitol 0.9 1.7 0.525 E965
Maltodextrin 0.15
Mannitol 0.5 1.2 0.4 E421
Miraculin A protein that does not taste sweet by itself but modifies taste receptors to make sour things taste sweet temporarily
Monatin 3,000 Naturally occurring sweetener isolated from the plant Sclerochiton ilicifolius
Monellin 3,000 Protein; the sweetening ingredient in serendipity berries
Osladin 500
Pentadin 500 Protein
Polydextrose 0.1
Psicose 0.7
Sorbitol 0.6 0.9 0.65 sugar alcohol, E420
Stevia 250 Extracts known as rebiana, Sweet and Fit Stevia, Enliten Truvia, PureVia; mainly containing rebaudioside A, a steviol glycoside
Tagatose 0.92 2.4 0.38 monosaccharide
Thaumatin 2,000 Protein; E957
Xylitol 1.0 1.7 0.6 E967

Artificial sugar substitutes

Artificial sweeteners contain little or no food energy, making a comparison of sweetness based on energy content not meaningful.

Name Sweetness (by weight) Trade name Approval Notes
Acesulfame potassium 200 Nutrinova FDA 1988 E950 Hyet Sweet
Advantame 20,000 FDA 2014
Alitame 2,000 approved in Mexico, Australia, New Zealand and China. Pfizer
Aspartame 160–200 NutraSweet, Equal FDA 1981, EU-wide 1994 E951 Hyet Sweet
Salt of aspartame-acesulfame 350 Twinsweet E962
Sodium cyclamate 30 FDA Banned 1969, approved in EU and Canada E952, Abbott
Dulcin 250 FDA Banned 1950
Glucin 300
Neohesperidin dihydrochalcone 1,500 E959
Neotame 8,000 NutraSweet FDA 2002 E961
P-4000 4,000 FDA banned 1950
Saccharin 300 Sweet'N Low FDA 1958, Canada 2014 E954
Sucralose 600 Kaltame, Splenda Canada 1991, FDA 1998, EU 2004 E955, Tate & Lyle

Health effects

Weight gain

A 2017 review did not find evidence supporting the use of non-nutritive sweeteners for weight loss, with a possible association of routine consumption with weight gain and risk of heart disease.[36] A 2010 review concluded there is a correlation between consumption of artificially sweetened beverages and weight gain in children, but that no clear causal link has been determined.[37] Research has shown that the consumption of artificial sweeteners weakens the association of sweet taste as a food cue with post-ingestive caloric sensory. In turn, this can lead to the over-consumption of high-calorie sweet tasting foods when eaten in a diet alongside artificial sweeteners, which may cause weight gain.[38]

Metabolic disorder

A 2015 review found that there is no evidence that non-caloric sweeteners cause metabolic disorders in humans.[39]

Cancer

A 2015 review of the literature found that there was no clear evidence for a link between the use of artificial sweeteners and an increased risk of cancer.[40]

https://en.wikipedia.org/wiki/Hazard_ratio

Stroke and Dementia

Intake of artificially sweetened soft drinks were associated with an increased risk of ischemic stroke, all-cause dementia, and Alzheimer’s disease dementia. When comparing daily cumulative intake to 0 per week (reference), the hazard ratios were 2.96 (95% confidence interval, 1.26–6.97) for ischemic stroke and 2.89 (95% confidence interval, 1.18–7.07) for Alzheimer’s disease.[41]

Concerns with sugar alcohols

Sugar alcohols may cause bloating and diarrhea when consumed in excessive amounts, usually more than 50 grams but sometimes as little as 10 grams.[42]

Consumption of sugar alcohols effects blood sugar levels, although less than of sucrose.[43][44]

Comparison to sugar

Eating natural sugars like glucose and sucrose instead of a sugar substitute can have negative health effects. The consumption of added sugars has been positively associated with multiple measures known to increase cardiovascular disease risk amongst adolescents as well as adults.[45] The calories contained in sugar-sweetened beverages contribute to increases in body weight and body fat, and replacement of sugar by artificial sweeteners reduces weight.[46] Obesity contributes to diabetes and cardiovascular disease. Glucose has a high glycemic index, sucrose medium, and fructose low. There is evidence that sugar-sweetened beverages "may increase the risk of metabolic syndrome and type 2 diabetes not only through obesity but also by increasing dietary glycemic load, leading to insulin resistance, β-cell dysfunction, and inflammation," according to a 2010 meta-analysis.[47]

There is "convincing evidence from human intervention studies, epidemiological studies, animal studies and experimental studies, for an association between the amount and frequency of free sugars intake and dental caries" while other sugar (complex carbohydrate) consumption is normally associated with a lower rate of dental caries, according to the World Health Organization.[48]

A 2013 review found that there is insufficient evidence to suggest that replacing dietary sugar with non-caloric sweeteners alone is beneficial for energy balance, weight loss, or diabetes risk factors. The review found that restricting calories is more important than avoidance of sugar for weight management. However, the review concluded that replacing dietary sugar with non-caloric sweeteners is useful for managing blood sugar in diabetes patients. The review recommends that all sweeteners be consumed in moderation.[49]

See also

Notes

  1. ↑ One U.S. brand of saccharin uses yellow packets.

References

  1. ↑ "High-Intensity Sweeteners". U.S. Food and Drug Administration. 19 May 2014. Retrieved 17 September 2014.
  2. ↑ "Generally Recognized as Safe (GRAS)". U.S. Food and Drug Administration. 14 July 2014. Retrieved 17 September 2014.
  3. ↑ "Generally Recognized as Safe (GRAS)". fda.gov.
  4. ↑ C (2010). "Unique Sweetener Supports Oral health". vrp.com.
  5. ↑ Mela, D. (ed.). (2005). Food, diet and obesity. Cambridge, England: Woodhead Publishing Limited.
  6. ↑ Coultate, T. (2009). Food: The chemistry of its components. Cambridge, UK: The Royal Society of chemistry
  7. ↑ "Artificial sweeteners. What's the difference?". tribunedigital-chicagotribune.
  8. ↑ Sugar demand rising at expense of sweeteners, claims sugar industry
  9. ↑ "Sucralose breakthrough could smash Tate & Lyle monopoly". FoodNavigator-USA.com.
  10. ↑ Mattes RD, Popkin BM (2009). "Nonnutritive sweetener consumption in humans: effects on appetite and food intake and their putative mechanisms". The American Journal of Clinical Nutrition. 89 (1): 1–14. PMC 2650084 Freely accessible. PMID 19056571. doi:10.3945/ajcn.2008.26792.
  11. ↑ Coultate, T. (2009). Food: The chemistry of its components. Cambridge, UK: The Royal Society of Chemistry.
  12. 1 2 EFSA National Experts (May 2010). "Report of the meetings on aspartame with national experts" (PDF). EFSA. Retrieved 22 September 2010.
  13. ↑ Mitchell, Helen (2006). Sweeteners and sugar alternatives in food technology. Oxford, UK: Wiley-Blackwell. p. 94. ISBN 1-4051-3434-8
  14. 1 2 Magnuson BA, Burdock GA, Doull J, Kroes RM, Marsh GM, Pariza MW, Spencer PS, Waddell WJ, Walker R, Williams GM (2007). "Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies". Crit. Rev. Toxicol. 37 (8): 629–727. PMID 17828671. doi:10.1080/10408440701516184.
  15. ↑ "Food Standards Australia New Zealand: Aspartame – what it is and why it's used in our food". Archived from the original on 14 October 2008. Retrieved 2008-12-09.
  16. 1 2 Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger C, Blackburn GL, de Sonneville LM, Geha RS, Hertelendy Z, Koestner A, Leon AS, Liepa GU, McMartin KE, Mendenhall CL, Munro IC, Novotny EJ, Renwick AG, Schiffman SS, Schomer DL, Shaywitz BA, Spiers PA, Tephly TR, Thomas JA, Trefz FK (April 2002). "Aspartame: review of safety". Regul. Toxicol. Pharmacol. 35 (2 Pt 2): S1–93. PMID 12180494. doi:10.1006/rtph.2002.1542.
  17. ↑ "Aspartame". UK FSA. 17 June 2008. Retrieved 23 September 2010.
  18. ↑ "Aspartame". EFSA. Retrieved 23 September 2010.
  19. ↑ "Aspartame". Health Canada. Retrieved 23 September 2010.
  20. ↑ Taubes, Gary (2017). The Case against Sugar. London, England: Portobello books. pp. 143–144. ISBN 9781846276378.
  21. ↑ "All About Stevia Rebaudiana - Nature's Zero-Calorie Sweetener". steviainfo.com.
  22. ↑ Sweet on Stevia: Sugar Substitute Gains Fans, Columbia Daily Tribune, 23 March 2008
  23. ↑ New Artificial Sweetener
  24. ↑ Newmarker, Chris (18 December 2008). "Federal regulators give OK for Cargill's Truvia sweetener". Minneapolis / St. Paul Business Journal. Retrieved 18 December 2008.
  25. ↑ "du Chocolat -". vitarium.com.au.
  26. ↑ FDA approves new high-intensity sweetener sucralose
  27. 1 2 "Bitter Battle over Truth in Sweeteners". LiveScience.com.
  28. ↑ Truth About Splenda, Sugar Association website
  29. ↑ Grotz VL, Munro IC (2009). "An overview of the safety of sucralose". Regulatory toxicology and pharmacology : RTP. 55 (1): 1–5. PMID 19464334. doi:10.1016/j.yrtph.2009.05.011.
  30. 1 2 Daniel JW, Renwick AG, Roberts A, Sims J (2000). "The metabolic fate of sucralose in rats". Food Chem Toxicol. 38 (S2): S115–S121. doi:10.1016/S0278-6915(00)00034-X.
  31. ↑ Lead Poisoning and Rome
  32. ↑ Lyn O'Brien-Nabors (2011). Alternative Sweeteners. CRC Press. pp. 226–227. ISBN 978-1-4398-4614-8.
  33. 1 2 Rachel Wilson (26 July 2011), "New and Emerging Opportunities for Plant-Derived Sweeteners", Natural Products Insider
  34. ↑ Chinese monk fruit latest all-natural sweetener to make waves, The Independent, 12 April 2011
  35. 1 2 3 Christopher Adams (28 August 2012), US launch sweet news for kiwi supplier, The New Zealand Herald
  36. ↑ Azad, Meghan B.; Abou-Setta, Ahmed M.; Chauhan, Bhupendrasinh F.; Rabbani, Rasheda; Lys, Justin; Copstein, Leslie; Mann, Amrinder; Jeyaraman, Maya M.; Reid, Ashleigh E.; Fiander, Michelle; MacKay, Dylan S.; McGavock, Jon; Wicklow, Brandy; Zarychanski, Ryan (16 July 2017). "Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies". Canadian Medical Association Journal. 189 (28): E929–E939. doi:10.1503/cmaj.161390.
  37. ↑ Brown, R. J.; de Banate, M. A.; Rother, K. I. (August 2010). "Artificial sweeteners: a systematic review of metabolic effects in youth". International Journal of Pediatric Obesity. 5 (4): 305–312. PMC 2951976 Freely accessible. PMID 20078374. doi:10.3109/17477160903497027.
  38. ↑ Davidson T. L., Sample C. H., Swithers S. E. (2014). "An Application of Pavlovian Principles to the Problems of Obesity and Cognitive Decline". Neurobiology of Learning and Memory. 108: 172–184. doi:10.1016/j.nlm.2013.07.014.
  39. ↑ Pepino, M. Yanina (2015-12-01). "Metabolic effects of non-nutritive sweeteners". Physiology & Behavior. 152 (Pt B): 450–455. ISSN 1873-507X. PMC 4661066 Freely accessible. PMID 26095119. doi:10.1016/j.physbeh.2015.06.024. Taken as a whole, despite several epidemiological studies showing an association between NNS consumption and metabolic disorders [9– 14], and strong data supporting causality between NNS exposure and metabolic disorders in animal models [18–24,43–45], there is no clear evidence that NNSs cause metabolic disorders in human subjects. However, data from at least five different mammalian species (rats, mice, pigs, cows, human) show that NNSs can be metabolically active [49, 63,65,76,66–69]. Therefore, the old concept that NNSs are invariably metabolically inert no longer holds true. More research is needed to elucidate the mechanisms by which NNSs may drive metabolic effects and better understand potential effects of these commonly used food additives.
  40. ↑ Mishra, A; Ahmed, K; Froghi, S; Dasgupta, P (December 2015). "Systematic review of the relationship between artificial sweetener consumption and cancer in humans: analysis of 599,741 participants.". International journal of clinical practice. 69 (12): 1418–26. PMID 26202345. doi:10.1111/ijcp.12703.
  41. ↑ "Sugar- and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia?". American Health Association. 2017-04-20. Retrieved 2017-07-20.
  42. ↑ "Eat any sugar alcohol lately?". Yale-New Haven Hospital. 2005-03-10. Retrieved 2012-06-25.
  43. ↑ Sue Milchovich, Barbara Dunn-Long: Diabetes Mellitus: A Practical Handbook, p. 79, 10th ed., Bull Publishing Company, 2011
  44. ↑ Paula Ford-Martin, Ian Blumer: The Everything Diabetes Book, p. 124, 1st ed., Everything Books, 2004
  45. ↑ Welsh JA, Sharma A, Cunningham SA, Vos MB (2011). "Consumption of Added Sugars and Indicators of Cardiovascular Disease Risk Among US Adolescents". Circulation. 123 (3): 249–57. PMID 21220734. doi:10.1161/CIRCULATIONAHA.110.972166.
  46. ↑ Ebbeling CB, Feldman HA, Chomitz VR, Antonelli TA, Gortmaker SL, Osganian SK, Ludwig DS (2012). "A randomized trial of sugar-sweetened beverages and adolescent body weight". N. Engl. J. Med. 367 (15): 1407–16. PMC 3494993 Freely accessible. PMID 22998339. doi:10.1056/NEJMoa1203388.
  47. ↑ Malik, V. S.; Popkin, B. M.; Bray, G. A.; Despres, J.-P.; Willett, W. C.; Hu, F. B. (2010). "Sugar-Sweetened Beverages and Risk of Metabolic Syndrome and Type 2 Diabetes: A meta-analysis". Diabetes Care. 33 (11): 2477–2483. PMC 2963518 Freely accessible. PMID 20693348. doi:10.2337/dc10-1079.
  48. ↑ Moynihan P, Petersen PE (2004). "Diet, nutrition and the prevention of dental diseases" (PDF). Public health nutrition. 7 (1A): 201–226. PMID 14972061. doi:10.1079/PHN2003589.
  49. ↑ Shankar, Padmini; Ahuja, Suman; Sriram, Krishnan (2013-12-01). "Non-nutritive sweeteners: review and update". Nutrition (Burbank, Los Angeles County, Calif.). 29 (11–12): 1293–1299. ISSN 1873-1244. PMID 23845273. doi:10.1016/j.nut.2013.03.024.

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