by Aliza Becker, BA, MPS
Sugar, together with fruits, vegetables, fibers, and legumes, falls under the umbrella term of carbohydrates, which is one of the three macronutrients— alongside protein and fat—present in the human diet.1 Sugar may be categorized in several different ways. First, there are simple sugars, known as monosaccharides, which are considered the most basic, fundamental units of a carbohydrate. Examples of simple sugars include glucose, galactose, and fructose.1 In addition, there are compound sugars, called disaccharides, which contain two monosaccharides. Examples of compound sugars include sucrose and lactose.1
An oligosaccharide is any carbohydrate formed using 3 to 10 monosaccharide units, examples of which include raffinose and stachyose (found in legumes). A polysaccharide contains more than 10 monosaccharide units, and includes starches, glycogen, and fiber, such as pectin and cellulose.1,2 Monosaccharides and disaccharides are known as simple carbohydrates, whereas oligosaccharides and polysaccharides are considered complex carbohydrates.1 All carbohydrates, including sugars, contain carbon, hydrogen, and oxygen atoms in varying numbers arranged in different ways.1
Sugar in the Body
Healthy sugar processing in a healthy body. Carbohydrate digestion begins in the mouth, where an enzyme in saliva, salivary amylase, breaks the bonds between the monomeric sugar units of more complex carbohydrates. Digestion of carbohydrates continues by mechanical means in the stomach; however, carbohydrate digestion is most extensive in the small intestine, where pancreatic amylase from the pancreas and enzymes secreted by intestinal cells that line the villi initiate further breakdown of any remaining larger carbohydrate chains; the resulting monosaccharides are subsequently absorbed into the bloodstream and transported to the liver.1,3
Upon the arrival of monosaccharides, the liver then works to convert galactose to glucose and to break fructose into smaller carbon-containing units, either storing glucose as glycogen or returning it back to the blood.3 In the latter case, the resultant increase in blood glucose prompts cells in the pancreas to secrete insulin, which triggers other cells throughout the body to transport glucose from the blood into different organ cells to use as fuel.1,3 As this process occurs and blood glucose levels are reduced, other pancreatic cells release glucagon, which signals the liver to break down stored glycogen and release it into the blood as glucose, thus ensuring that blood glucose levels remain within the target range.1,3
Dysfunctional sugar processing in the body. Lactose intolerance. In individuals with lactose intolerance, an inadequate amount of the enzyme lactase leads to subpar breakdown of lactose in the small intestine. This results in undigested lactose continuing to the large intestine, where bacteria digest it, generating gases that cause diarrhea, bloating, and abdominal cramps.3
Hypoglycemia and hyperglycemia. Hypoglycemia occurs when the blood glucose level is too low, often defined by a plasma glucose concentration of less than 70mg/dL,4 and is most commonly the result of medications taken to control diabetes, although other medications, critical illness or organ failure, a reaction to carbohydrates, an insulin-producing tumor in the pancreas, and some types of bariatric surgery can also trigger this state. In contrast, hyperglycemia may be diagnosed when the blood glucose is too high (i.e., greater than 125mg/dL while fasting or greater than 180mg/dL 2 hours after a meal). Hyperglycemia may result from damage to the pancreas, endocrine disorders that cause peripheral insulin resistance, the use of certain medications, total parental nutrition and dextrose infusion, or following surgery or trauma.6 Although hyperglycemia can be a symptom of diabetes, it does not necessarily warrant a diagnosis of diabetes when presenting alone.6
Prediabetes and diabetes. A diagnosis of prediabetes is typically based on the individual having a fasting (i.e., having nothing to eat or drink for at least 8 hours other than water) plasma glucose level of 100 to 125mg/dL, a hemoglobin A1c concentration (i.e., the amount of glucose attached to hemoglobin) of 5.7 to 6.4 percent, or a two-hour postload glucose level of 140 to 199mg/dL. A diagnosis of diabetes is typically based on having a fasting plasma glucose level of at least 126mg/dL, a two-hour plasma glucose level of at least 200mg/dL during a 75g oral glucose tolerance test, or a hemoglobin A1c concentration of 6.5 percent or higher.7
Three primary types of diabetes exist—namely, Type 1, Type 2, and gestational diabetes. Type 1 diabetes, also known as insulin-dependent diabetes, immune-mediated diabetes, or juvenile-onset diabetes (although it can occur at any age), results from cellular-mediated autoimmune destruction of β-cells in the pancreas, leading to limited or no secretion of insulin.8 Type 2 diabetes, also known as noninsulin-dependent diabetes or adult-onset diabetes, in contrast, occurs in individuals with insulin resistance or a relative (rather than absolute) insulin deficiency.8 Type 2 diabetes may be clearly differentiated from Type 1 diabetes by its lack of autoimmune destruction of β-cells in the latter.8 Given the autoimmune component, patients with Type 1 diabetes are also not generally overweight/obese, while those with or at risk for Type 2 diabetes typically are overweight or obese. Excess carbohydrate intake contributes both to weight gain and higher levels of sugar in the blood, and obesity increases the amounts of substances involved in the development of insulin resistance.9 Gestational diabetes, on the other hand, occurs or is first identified during pregnancy,8 although the International Association of Diabetes and Pregnancy Study Groups recommended in 2009 that high-risk women found to have diabetes at their initial prenatal visit should receive a diagnosis of overt (i.e., pre-pregnancy) diabetes rather than gestational diabetes.10 Women at higher risk for developing gestational diabetes during pregnancy include those with marked obesity, a personal history of gestational diabetes, glycosuria (too much sugar in the urine), or a strong family history of diabetes.8 As a general rule, therefore, diabetes can be either a result of dysfunction in the body’s ability to process sugar or due to taking in more sugar than the body can properly process.
It has been recommended by the American Association of Clinical Endocrinologists and American College of Endocrinology that all adults aged 45 years and older be screened for prediabetes and diabetes regardless of their perceived risk,11 while the United States Preventative Service Task Force (USPSTF) has suggested screening individuals with overweight or obesity who are 40 to 70 years of age.12 According to the USPSTF, asymptomatic pregnant individuals should be screened for gestational diabetes no earlier than 24 weeks of pregnancy.13
Health Effects of Sugar Consumption
Natural vs. refined. Sugars as a group may be divided into two main types: natural and processed (or refined) sugars. While some sugar, such as glucose, fructose, and lactose, can be found in plants, fruits, and milk, others (e.g., high-fructose corn syrup) are created by way of heavy processing of certain natural sources such as sugar cane, sugar beets, and corn and are known as processed or refined sugars.14 Certain sugars, such as sucrose, may also be defined as natural or processed depending on their source.14
Although natural and processed sugars are essentially metabolized in the body the same way, different effects can be observed among the different types of sugars.15 Natural sugars are typically consumed in more limited quantities along with other nutrients, such as fiber and protein; as a result, natural sugars tend to be digested more slowly than added/refined sugars, ensuring the metabolism remains more stable over time.15 In contrast, refined/processed sugars are typically added to foods in variable, sometimes significant, quantities,15 resulting in variable processes of breakdown and variable amounts released into the bloodstream.
In a study that compared of the effects of different amounts of glucose, sucrose, or fructose added to tea to differing portions of carbohydrates in white bread (containing sucrose) on plasma glucose and insulin responses, Lee et al16 found that the mean postconsumption glycemic and insulinemic index values of glucose were greater and those of fructose were smaller, respectively, in tea than those of the bread.
Evans et al17 reported following a systematic review and meta-analysis that substituting fructose for glucose or sucrose in food or beverages lowers both peak postprandial blood glucose and insulin concentrations.
Yunker et al18 concluded from their study that sucrose is less efficient at signaling postprandial satiation than glucose.
Finally, Teff et al19 contended that, because fructose does not stimulate insulin secretion as glucose does, meals high in fructose likely result in lower concentrations of the hormone leptin, which is regulated by insulin-mediated glucose metabolism and is responsible, along with insulin, for long-term regulation of energy balance.As such, chronic consumption of diets high in fructose could facilitate persistent reductions in both insulin and leptin, leading to increased caloric intake and weight gain.
Cardiovascular disease (CVD). Persistently increased amounts of sugar intake, which can raise the blood sugar level, have been linked to a number of adverse health effects. Malik et al20 reported that the consumption of sugar-sweetened beverages, collectively considered to be one of the most significant contributors to added sugar intake in the United States,21 was positively associated with CVD in a dose-response manner.
In a meta-analysis and systematic review of 5,301 articles, Yin et al22 narrowed the effect further, observing that a one serving-per-day increment of sugar-sweetened beverages was associated with an eight-percent higher risk of both CVD and mortality.
According to the results of a study by Kim et al,23 a one serving-per-day increment of sugar-sweetened beverages was also associated with a similarly heightened risk of hypertension.
In a Swedish population-based prospective cohort study, Janzi et al24 found that more than eight servings a week of sugar-sweetened beverages was associated with an increased risk (19%) of stroke.
Swaminathan et al25 reported that systolic and diastolic blood pressure values were higher in study participants with a greater intake of refined grains, which include fewer nutrients and may be processed more rapidly in the body, leading to a greater increase in postprandial blood glucose concentrations as a result of the refinement process. Along these lines, Musa-Veloso et al26 also documented an association between the consumption of intact oat kernels and a significant reduction in postprandial blood glucose levels compared to the consumption of refined grain.
In a meta-analysis, Meng et al27 reported that increased intake of both sugar-sweetened and artificially sweetened beverages was associated with increased risk of Type 2 diabetes, CVD, and all-cause mortality.
Kidney and liver disease. The kidneys are also adversely affected by excess sugar in the blood. While the kidneys normally help to filter most glucose out from the blood for reabsorption, when the blood glucose level reaches at least 180mg/dL, such as in those individuals with uncontrolled diabetes, the kidneys begin excreting sugar into the urine in larger amounts (≥25mg/dL)—a condition known as glycosuria.28 In patients with diabetes, diabetic nephropathy may emerge as a result of hyperglycemia,29 leading to chronic kidney disease and end-stage renal failure.30 Excess consumption of fructose may also be associated with gout as a result of the former’s propensity to increase uric acid levels.32 Fructose consumption has also been reported as a risk factor for nonalcoholic fatty liver disease.31
Compromised immunity. High blood sugar levels may also render individuals more susceptible to frequent and/or serious infections.33 Both Type 1 and Type 2 diabetes have been found to significantly increase the risk of experiencing more severe complications from COVID-19 infection.34
Oral disesase. Research suggests sugar consumption also has a direct relationship with oral health, specifically pertaining to the formation of dental caries, as the presence of sugars—especially sucrose,35,36 which is fermentable—disrupts the pH in the mouth, resulting in an oral environment more favorable to those bacteria that produce dental biofilm.
Mood and cognitive dysfunction. Knüppel et al37 documented an adverse effect of sugar intake on mental health, particularly noting an increase in incident mood disorders in men.
Seetharaman et al,38 using data from the Swedish Adoption/Twin Study of Aging, found that high blood glucose levels correlated with poorer overall performance in perceptual speed as well as greater rates of cognitive decline in general, perceptual mental speed, verbal ability, and spatial ability scores. The same study reported that diet-based glycemic load was correlated with poorer overall performance in both perceptual speed and spatial ability.
Francis et al39 found that a diet high in fat and refined sugar (HFS) was associated with poorer performance on hippocampal-sensitive memory tasks; a second experiment clarified that this effect is specific to hippocampal functioning and does not extend to measures of prefrontal cortex function. Also, in a laboratory-based test of food intake, the HFS-rich diet groups were less accurate when attempting to recall what they had previously eaten and demonstrated reduced sensitivity to internal signals of hunger and satiety.39
Cancer. Some research has attempted to discern sugar’s role in cancer formation. In a French study, Debras et al40 noted that consumption of diets with a higher glycemic load (e.g., those containing bread), which is a measure of how rapidly a specific carbohydrate food raises blood sugar, was associated with a higher overall risk for cancer, specifically postmenopausal breast cancer.
Sieri et al41 reported similar results, finding that diets with a higher glycemic load appeared to inflate the risk of breast cancer, especially in premenopausal women and those with body mass index values of less than 25mg/m2.
Laguna et al42 linked simple sugar intake in drinks and fruit juice with an increased risk of both overall cancer incidence and mortality and all-cause mortality.
Finally, a 2017 report based on internal documents from a research project funded by the Sugar Research Foundation in the 1960s revealed that sucrose consumption was associated with elevated levels of beta-glucuronidase, an enzyme previously associated with bladder cancer in humans.43
Artificial and sugar alcohol sweeteners. Of note, the aforementioned studies focused on natural and processed sugars and did not include artificial (also known as no- or low-calorie) sweeteners (e.g., aspartame, sucralose) or sugar alcohols, (e.g., xylitol, maltitol, erythritol), which have their own health effects. Artificial sweeteners, which impart sweetness without the calories, could initially facilitate a modest amount of weight loss,44 but over time may lead to weight gain by disrupting the brain’s association between sweetness and caloric intake.45 Artificial sweeteners have also been linked to shifts in the gut microbiota, which may promote antibiotic resistance47 or even render certain bacteria pathogenic.47
Sugar alcohols are a kind of carbohydrate that raises the blood sugar less significantly than traditional sugars, potentially making them a good alternative; Mohsenpour et al48 reported that a mixture of sugars and a sugar alcohol (lactose, fructose, sucrose, and erythritol) led to improved blood glucose levels compared to the same amount of glucose or sucrose, without any significant adverse effects. However, sugar alcohols have been linked to irritable bowel syndrome.49
Guidelines and Moving Forward
Both the 2020 to 2025 Dietary Guidelines for Americans50 and the World Health Organization51 recommend that consumption of added sugar should compose no more than 10 percent of an adult’s daily calorie count. The American Heart Association52 recommends limiting the amount of added sugars to not more than half of one’s daily discretionary calorie allowance(i.e., no more than 100 calories per day for women and no more than 150 calories per day for men [or ~6 and ~9 teaspoons per day, respectively]). However, although Powell et al53 documented a notable decline in calories from added sugars between 2003 and 2012 following a significant increase between 1977 and 2003, no further decline occurred from 2003 to 2012, and added sugar intake levels remained above the recommended level of 10 percent of the total energy intake as of 2016. Indeed, the 2020 to 2025 Dietary Guidelines for Americans50 suggest that 80 percent of men and 77 percent of women in the United States still exceed the recommended 10 percent limitation for added sugar intake.
Key Takeaways
• Sugar, as a type of carbohydrate, provides energy to the body, and it may be found in both simple or complex and natural or processed (added) forms.
• Dysfunction in the body’s processing of sugars as a result of disease, genetics, medication, or injury leads to blood sugar levels that are too low or too high, which may lead to further complications.
• Excess sugar intake, which can overwhelm the body’s processing efforts, can also lead to disease.
• It is recommended that added sugars compose no more than 6% to 10% of an adult’s daily calorie count.
• Sugar consumption in the United States remains too high, although it has decreased from decades ago.
• Artificial sweeteners and sugar alcohols are alternatives to traditional sugars and carry their own risks and benefits.
Editor’s note: Please consult with your physician or nutritionist regarding sugar intake and what kind of diet is best for you.
About the Author
Ms. Becker is the managing editor of The Journal of Innovations in Cardiac Rhythm Management. She also works as a freelance editor and as a teaching assistant for the George Washington University’s Master of Professional Studies in Publishing program.
Sources
1. Holesh JE, Aslam S, Martin A. Physiology, carbohydrates. [Updated 2021 Jul 26]. In: StatPearls [Internet]. Treasure Island, Florida: StatPearls Publishing; 2021.
2. Morris AL, Mohiuddin SS. Biochemistry, Nutrients. [Updated 2021 May 12]. In: StatPearls [Internet]. Treasure Island, Florida: StatPearls Publishing; 2021.
3. Digestion and absorption of carbohydrates. In: University of Hawaii at Mānoa Food Science and Human Nutrition Program. Human Nutrition [Depreciated]. Honolulu, Hawaii: University of Hawaii at Mānoa. http://pressbooks-dev.oer.hawaii.edu/humannutrition/chapter/digestion-and-absorption-of-carbohydrates/. Accessed 28 Oct 2021.
4. Mathew P, Thoppil D. Hypoglycemia. [Updated 2021 Jan 13]. In: StatPearls [Internet]. Treasure Island, Florida. StatPearls Publishing; 2021.
5. Brutsaert EF. Hypoglycemia. https://www.merckmanuals.com/home/hormonal-and-metabolic-disorders/diabetes-mellitus-dm-and-disorders-of-blood-sugar-metabolism/hypoglycemia. Accessed 3 Nov 2021.
6. Mouri MI, Badireddy M. Hyperglycemia. [Updated 2021 May 10]. In: StatPearls [Internet]. Treasure Island, Florida: StatPearls Publishing; 2021.
7. American Diabetes Association. Classification and diagnosis of diabetes: standards of medical care in diabetes—2020. Diabetes Care. 2020;43(Suppl 1):S14–S31.
8. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33(Suppl 1):S62–S69.
9. Al-Goblan AS, Al-Alfi MA, Khan MZ. Mechanism linking diabetes mellitus and obesity. Diabetes Metab Syndr Obes. 2014;7:587–591.
10. International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010;33(3):676–682.
11. Handelsman Y, Bloomgarden ZT, Grunberger G, et al. American Association of Clinical Endocrinologists and American College of Endocrinology—clinical practice guidelines for developing a diabetes mellitus comprehensive care plan—2015. Endocr Pract. 2015;21 Suppl 1(Suppl 1):1–87.
12. US Preventive Services Task Force, Davidson KW, Barry MJ, et al. Screening for prediabetes and type 2 diabetes: US Preventive Services Task Force recommendation statement. JAMA. 2021;326(8):
736–743.
13. US Preventive Services Task Force; Davidson KW, Barry MJ. Screening for Gestational Diabetes: US Preventive Services Task Force Recommendation Statement. JAMA. 2021;326(6):531–538.
14. Institute of Food Technologists. Sugars: a scientific overview. https://www.ift.org/career-development/learn-about-food-science/food-facts/food-facts-food-ingredients-and-additives/sugars-a-scientific-overview. Accessed 3 Nov 2021.
15. Malik V. Are certain types of sugars healthier than others?. https://www.health.harvard.edu/blog/are-certain-types-of-sugars-healthier-than-others-2019052916699. Accessed 3 Nov 2021.
16. Lee BM. Wolever TM. Effect of glucose, sucrose and fructose on plasma glucose and insulin responses in normal humans: comparison with white bread. Eur J Clin Nutr. 1998;52(12):924–928.
17. Evans RA, Frese M, Romero J, et al. Fructose replacement of glucose or sucrose in food or beverages lowers postprandial glucose and insulin without raising triglycerides: a systematic review and meta-analysis. Am J Clin Nutr. 2017;106(2):506–518.
18. Yunker AG, Luo S, Jones S, et al. Appetite-regulating hormones are reduced after oral sucrose vs glucose: influence of obesity, insulin resistance, and sex. J Clin Endocrinol Metab. 2021;106(3):654–664.
19. Teff LK, Elliott SS, Tschöp M, et al. Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J Clin Endocrinol Metab. 2004;89(6):2963–2972.
20. Malik VS, Li Y, Pan A, et sal. Long-term consumption of sugar-sweetened and artificially sweetened beverages and risk of mortality in US adults. Circulation. 2019;139(18):2113–2125.
21. Hu FB, Malik VS. Sugar-sweetened beverages and risk of obesity and type 2 diabetes: epidemiologic evidence. Physiol Behav. 2010;100(1):47–54.
22. Yin J, Zhu Y, Malik V, et al. Intake of sugar-sweetened and low-calorie sweetened beverages and risk of cardiovascular disease: a meta-analysis and systematic review. Adv Nutr. 2021;12(1):89–101.
23. Kim Y, Je Y. Prospective association of sugar-sweetened and artificially sweetened beverage intake with risk of hypertension. Review Arch Cardiovasc Dis. 2016;109(4):
242–253.
24. Janzi S, Ramne S, González-Padilla E, et al. Associations between added sugar intake and risk of four different cardiovascular diseases in a Swedish population-based prospective cohort study. Front Nutr. 2020;7:603653.
25. Swaminathan S, Dehghan M, Raj JM. Associations of cereal grains intake with cardiovascular disease and mortality across 21 countries in Prospective Urban and Rural Epidemiology study: prospective cohort study. BMJ. 2021;372:m4948.
26. Musa-Veloso K, Noori D, Venditti C, et al. A systematic review and meta-analysis of randomized controlled trials on the effects of oats and oat processing on postprandial blood glucose and insulin responses. J Nutr. 2021;151(2):341–351.
27. Meng Y, Li S, Khan J, et al. Sugar- and artificially sweetened beverages consumption linked to type 2 diabetes, cardiovascular diseases, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective cohort studies. Nutrients. 2021;13(8):2636.
28. Liman MNP, Jialal I. Physiology, Glycosuria. [Updated 2021 Mar 24]. In: StatPearls [Internet]. Treasure Island, Florida: StatPearls Publishing; 2021.
29. Tavafi M. Complexity of diabetic nephropathy pathogenesis and design of investigations. J Renal Inj Prev. 2013;2(2):59–62.
30. Nasri H, Rafieian-Kopaei M. Diabetes mellitus and renal failure: prevention and management. J Res Med Sci. 2015;20(11):1112–1120.
31. Ouyang X, Cirillo P, Sautin Y, et al. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol. 2008;48(6):993–999.
32. Rho YH, Zhu Y, Choi HK. The epidemiology of uric acid and fructose. Semin Nephrol. 2011;31(5):410–419.
33. Casqueiro J, Casqueiro J, Alves C. Infections in patients with diabetes mellitus: a review of pathogenesis. Indian J Endocrinol Metab. 2012;16(Suppl1):S27–S36.
34. Holman N, Knighton P, Kar P, et al. Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study. Lancet Diabetes Endocrinol. 2020;8(10):823–833.
35. Du Q, Fu M, Zhou Y, et al. Sucrose promotes caries progression by disrupting the microecological balance in oral biofilms: an in vitro study. Sci Rep. 2020;10(1):2961.
36. Paes Leme AF. Koo H, Bellato CM, Bedi G, Cury JA. The role of sucrose in cariogenic dental biofilm formation—new insight. J Dent Res. 2006;85(10):878–887.
37. Knüppel A, Shipley MJ, Llewellyn CH, Brunner EJ. Sugar intake from sweet food and beverages, common mental disorder and depression: prospective findings from the Whitehall II study. Sci Rep. 2017;7:6287.
38. Seetharaman S, Andel R, McEvoy C, et al. Blood glucose, diet-based glycemic load and cognitive aging among dementia-free older adults. J Gerontol A Biol Sci Med Sci. 2015;70(4):471–479.
39. Francis HM, Stevenson RJ. Higher reported saturated fat and refined sugar intake is associated with reduced hippocampal-dependent memory and sensitivity to interoceptive signals. Behav Neurosci. 2011;125(6):943–955.
40. Debras C, Chazelas E, Srour B, et al. Glycaemic index, glycaemic load and cancer risk: results from the prospective NutriNet-Santé cohort [published online ahead of print . Int J Epidemiol. September 7, 2021].
41. Sieri S, Pala V, Brighenti F, et al. Dietary glycemic index, glycemic load, and the risk of breast cancer in an Italian prospective cohort study. Am J Clin Nutr. 2007;86(4):
1160–1166.
42. Laguna JC, Alegret M, Cofán M, et al. Simple sugar intake and cancer incidence, cancer mortality and all-cause mortality: a cohort study from the PREDIMED trial. Clin Nutr. 2021;40(10):5269–5277.
43. Kearns CE, Apollonio D, Glantz SA. Sugar industry sponsorship of germ-free rodent studies linking sucrose to hyperlipidemia and cancer: An historical analysis of internal documents. PLoS Biol. 2017;15(11):e2003460.
44. Miller PE, Perez V. Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies. Am J Clin Nutr. 2014;100(3):765–777.
45. Davidson TL, Martin AA, Clark K, Swithers SE. Intake of high-intensity sweeteners alters the ability of sweet taste to signal caloric consequences: implications for the learned control of energy and body weight regulation. Q J Exp Psychol (Hove). 2011;64(7):1430–1441.
46. Yu Z, Wang Y, Lu Ji, et al. Nonnutritive sweeteners can promote the dissemination of antibiotic resistance through conjugative gene transfer. ISME J. 2021;15(7):2117–2130.
47. Shil A, Chichger H. Artificial sweeteners negatively regulate pathogenic characteristics of two model gut bacteria, E. coli and E. faecalis. Int J Mol Sci. 2021;22(10):5228.
48. Mohsenpour MA, Kaseb F, Nazemian R, et al. The effect of a new mixture of sugar and sugar-alcohols compared to sucrose and glucose on blood glucose increase and the possible adverse reactions: a phase I double-blind, three-way randomized cross-over clinical trial. Endocrinol Diabetes Nutr (Engl Ed). 2019;66(10):647–653.
49. Yao CK, Tan H-L, van Langenberg DR. Dietary sorbitol and mannitol: food content and distinct absorption patterns between healthy individuals and patients with irritable bowel syndrome. J Hum Nutr Diet. 2014;27 Suppl 2:263–275.
50. United States Department of Agriculture. 2020–2025 dietary guidelines for Americans. https://www.dietaryguidelines.gov/sites/default/files/2020-12/Dietary_Guidelines_for_Americans_2020-2025.pdf. Accessed 4 Nov 2021.
51. The World Health Organization. WHO calls on countries to reduce sugars intake among adults and children. https://www.who.int/news/item/04-03-2015-who-calls-on-countries-to-reduce-sugars-intake-among-adults-and-children. Accessed 4 Nov 2021.
52. American Heart Association. Added sugars. https://www.heart.org/en/healthy-living/healthy-eating/eat-smart/sugar/added-sugars. Accessed 4 Nov 2021.
53. Powell ES, Smith-Taillie LP, Popkin BM. Added sugars intake across the distribution of US children and adult consumers: 1977–2012. J Acad Nutr Diet. 2016;116(10):
1543–1550.e1.
54. Taddio A, Shah V, Hancock R, et al. Effectiveness of sucrose analgesia in newborns undergoing painful medical procedures. CMAJ. 2008;179(1):37–43.
55. Chirife J, Herszage L, Joseph A, Kohn ES. In vitro study of bacterial growth inhibition in concentrated sugar solutions: microbiological basis for the use of sugar in treating infected wounds. Antimicrob Agents Chemother. 1983;23(5):766–773.
56. Hossain A, Yamaguchi F, Matsuo T, et al. Rare sugar D-allulose: Potential role and therapeutic monitoring in maintaining obesity and type 2 diabetes mellitus. Pharmacol Ther. 2015;155:49–59.
57. Hayashi N, Iida T, Yamada T, et al. Study on the postprandial blood glucose suppression effect of D-psicose in borderline diabetes and the safety of long-term ingestion by normal human subjects. Study on the postprandial blood glucose suppression effect of D-psicose in borderline diabetes and the safety of long-term ingestion by normal human subjects. Biosci Biotechnol Biochem. 2010;74(3):510–519.
58. Soterakis J, Iber FL. Increased rate of alcohol removal from blood with oral fructose and sucrose. Am J Clin Nutr. 1975;28(3):254–257.
