Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Psicose: Difference between pages

{{Short description|Chemical compound}}

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| Name = Psicose

| verifiedrevid = 464375941

| ImageFile = Psicose.png

| ImageSize = 200px

| IUPACName = Psicose

| OtherNames = <small>D</small>-Allulose; <small>D</small>-Psicose; <small>D</small>-Ribo-2-hexulose; Pseudofructose

| SystematicName = (3''R'',4''R'',5''R'')-1,3,4,5,6-Pentahydroxyhexan-2-one

| Section1 = {{Chembox Identifiers

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| CASNo_Ref = {{cascite|correct|CAS}}

| CASNo= 551-68-8

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = QCC18LNG3E

| PubChem=90008

| ChEBI_Ref = {{ebicite|correct|EBI}}

| MeSHName=psicose

| Section2 = {{Chembox Properties

| C=6 | H=12 | O=6

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| MeltingPtC= 58

| MeltingPt_ref = <ref>{{cite book |title= CRC Handbook of Data on Organic Compounds |editor-first1= David R. |editor-last1= Lide |editor-first2= G.W.A. |editor-last2= Milne |page= 4596 |edition= 3rd |publisher= CRC Press |date= 30 Dec 1993 }}</ref>

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| Section3 = {{Chembox Hazards

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'''<small>D</small>-Psicose''' (C₆H₁₂O₆), also known as '''<small>D</small>-allulose''', or simply '''allulose''', is a low-calorie [[epimer]] of the [[monosaccharide]] [[sugar]] [[fructose]], used by some major commercial food and beverage manufacturers as a low-calorie sweetener.<ref name="HossainYamaguchi2015">{{cite journal |last1=Hossain |first1=Akram |last2=Yamaguchi |first2=Fuminori |last3=Matsuo |first3=Tatsuhiro |last4=Tsukamoto |first4=Ikuko |last5=Toyoda |first5=Yukiyasu |last6=Ogawa |first6=Masahiro |last7=Nagata |first7=Yasuo |last8=Tokuda |first8=Masaaki |title=Rare sugar d-allulose: Potential role and therapeutic monitoring in maintaining obesity and type 2 diabetes mellitus |journal=Pharmacology & Therapeutics |date=November 2015 |volume=155 |pages=49–59 |doi=10.1016/j.pharmthera.2015.08.004 |pmid=26297965 }}</ref> First identified in wheat in the 1940s, allulose is naturally present in small quantities in certain foods.

The U.S. [[Food and Drug Administration]] (FDA) has accepted a petition for [[generally recognized as safe]] (GRAS) for allulose as a sugar substitute in various specified food categories.<ref name=GRN400>{{cite web|title=GRN No. 400|url=https://www.accessdata.fda.gov/scripts/fdcc/index.cfm?set=GRASNotices&id=400|website=fda.gov|publisher=FDA|access-date=26 December 2019}}</ref><ref name=GRN498>{{cite news|title=GRN No. 498|url=https://www.accessdata.fda.gov/scripts/fdcc/?set=GRASNotices&id=498|access-date=19 December 2019|publisher=FDA}}</ref> Because it is absorbed and metabolized differently from other sugars, the FDA has exempted allulose from the listing of total and added sugars on the [[Nutrition facts label|Nutrition and Supplement Facts]] labels, but requires its weight listing as a carbohydrate, with 0.4{{nbsp}}kcal/g (about 1/10 the calories of ordinary carbohydrates).<ref name=NutrFactsRuling>{{Cite web|date=2020-10-19|title=The Declaration of Allulose and Calories From Allulose on Nutrition and Supplement Facts Labels; Availability|url=https://www.federalregister.gov/documents/2020/10/19/2020-22901/the-declaration-of-allulose-and-calories-from-allulose-on-nutrition-and-supplement-facts-labels|access-date=2020-11-16|website=Federal Register}}</ref>

Studies have shown the commercial product is not absorbed in the human body the way common sugars are and does not raise [[insulin]] levels, but more testing may be needed to evaluate any other potential side effects.<ref>{{Cite news |url=https://www.chicagotribune.com/business/ct-biz-allulose-sugar-substitute-20190822-ayfcmkmol5a33jziuoguubrt7i-story.html |title=A natural sweetener with a tenth of sugar's calories. Allulose, developed in Hoffman Estates, could be 'breakthrough ingredient.' |last=Elejalde-Ruiz |first=Alexia |date=August 22, 2019 |work=Chicago Tribune |access-date=2019-08-25}}</ref> In 2020, the U.S. FDA accepted the conclusion by Samyang that the maximum tolerable consumption for a 60&nbsp;kg adult was 33 to 36 grams per day.<ref name=GRAS828/>

==Biochemistry==

The [[sweetness]] of allulose is estimated to be 70% of the sweetness of [[sucrose]].<ref name="Hypo">{{cite journal |last1=Chung |first1=Min-Yu |last2=Oh |first2=Deok-Kun |last3=Lee |first3=Ki Won |title=Hypoglycemic Health Benefits of d -Psicose |journal=Journal of Agricultural and Food Chemistry |date=February 2012 |volume=60 |issue=4 |pages=863–869 |doi=10.1021/jf204050w |pmid=22224918 }}</ref><ref name="Tiefenbacher2017">{{cite book|author=Karl F. Tiefenbacher|title=The Technology of Wafers and Waffles I: Operational Aspects|url=https://books.google.com/books?id=jysUDgAAQBAJ&pg=PA182|date=16 May 2017|publisher=Elsevier Science|isbn=978-0-12-811452-0|pages=182–}}</ref> It has some cooling sensation and no [[Bitter (taste)|bitterness]].<ref name="HossainYamaguchi2015" /> Its taste is said to be sugar-like, in contrast to certain other sweeteners, like the high-intensity [[artificial sweetener]]s [[aspartame]] and [[saccharin]].<ref name="HossainYamaguchi2015" /> The caloric value of allulose in humans is about 0.2 to 0.4&nbsp;kcal/g, relative to about 4&nbsp;kcal/g for typical carbohydrates.<ref name="Tiefenbacher2017" /><ref name="LêRobin2016" /> In rats, the relative energy value of allulose was found to be 0.007&nbsp;kcal/g, or approximately 0.3% of that of sucrose.<ref name="MuZhang2012" /> Similar to the [[sugar alcohol]] [[erythritol]], allulose is minimally [[metabolism|metabolized]] and is [[excretion|excreted]] largely unchanged.<ref name="Tiefenbacher2017" /> The [[glycemic index]] of allulose is very low or negligible.<ref name="HossainYamaguchi2015" /><ref name="Tiefenbacher2017" />

Allulose is a weak [[enzyme inhibitor|inhibitor]] of the [[enzyme]]s [[α-glucosidase]], [[α-amylase]], [[maltase]], and [[sucrase]].<ref name="HossainYamaguchi2015" /> Because of this, it can inhibit the [[metabolism]] of [[starch]] and [[disaccharide]]s into [[monosaccharide]]s in the [[gastrointestinal tract]].<ref name="HossainYamaguchi2015" /> Additionally, allulose inhibits the absorption of [[glucose]] via [[Membrane transport protein|transporters]] in the [[intestine]]s.<ref name="HossainYamaguchi2015" /> For these reasons, allulose has potential [[antihyperglycemic]] effects, and has been found to reduce [[postprandial]] [[hyperglycemia]] in humans.<ref name="HossainYamaguchi2015" /><ref name="LêRobin2016">{{cite journal |last1=Lê |first1=Kim-Anne |last2=Robin |first2=Frédéric |last3=Roger |first3=Olivier |title=Sugar replacers: from technological challenges to consequences on health |journal=Current Opinion in Clinical Nutrition & Metabolic Care |date=July 2016 |volume=19 |issue=4 |pages=310–315 |doi=10.1097/MCO.0000000000000288 |pmid=27168355 |s2cid=5300107 }}</ref> Through modulation of [[lipogenesis|lipogenic]] [[enzyme]]s in the [[liver]], allulose may also have [[antihyperlipidemic]] effects.<ref name="HossainYamaguchi2015" /><ref name="LêRobin2016" />

Due to its effect of causing incomplete absorption of carbohydrates from the [[gastrointestinal tract]], and subsequent [[fermentation]] of these carbohydrates by intestinal bacteria, allulose can result in unpleasant symptoms such as [[flatulence]], [[abdominal discomfort]], and [[diarrhea]].<ref name="HossainYamaguchi2015" /> The maximum non-effect dose of allulose in causing diarrhea in humans has been found to be 0.55&nbsp;g/kg of body weight.<ref name="HossainYamaguchi2015" /> This is higher than that of most sugar alcohols (0.17–0.42&nbsp;g/kg), but is less than that of erythritol (0.66–1.0+&nbsp;g/kg).<ref name="Mäkinen2016">{{cite journal |last1=Mäkinen |first1=Kauko K. |title=Gastrointestinal Disturbances Associated with the Consumption of Sugar Alcohols with Special Consideration of Xylitol: Scientific Review and Instructions for Dentists and Other Health-Care Professionals |journal=International Journal of Dentistry |date=2016 |volume=2016 |pages=1–16 |doi=10.1155/2016/5967907 |pmid=27840639 |pmc=5093271 |doi-access=free }}</ref><ref name="O'DonnellKearsley2012">{{cite book|author1=Kay O'Donnell|author2=Malcolm Kearsley|title=Sweeteners and Sugar Alternatives in Food Technology|url=https://books.google.com/books?id=3Mnwdwx2xDgC&pg=PT322|date=13 July 2012|publisher=John Wiley & Sons|isbn=978-1-118-37397-2|pages=322–}}</ref><ref name="MeisterDoyle2009">{{cite book|author1=Kathleen A. Meister|author2=Marjorie E. Doyle|title=Obesity and Food Technology|url=https://books.google.com/books?id=8zdeA2QZjJQC&pg=PA14|year=2009|publisher=Am Cncl on Science, Health|pages=14–|id=GGKEY:2Q64ACGKWRT}}</ref>

D-allulose was found to be more reactive than fructose and glucose in glycation reactions.<ref>{{cite journal |last1=Namli |first1=Serap |last2=Sumnu |first2=S. Gulum |last3=Oztop |first3=Mecit H. |title=Microwave glycation of soy protein isolate with rare sugar (D-allulose), fructose and glucose |journal=Food Bioscience |date=April 2021 |volume=40 |page=100897 |doi=10.1016/j.fbio.2021.100897 }}</ref>

=== Effect on carbohydrate absorption ===

A [[meta-analysis]] was conducted of the effect on [[postprandial glucose]] and insulin responses of adding a median of 5 grams of allulose (range, 2.5-10 g) to a fixed carbohydrate-containing drink or meal, versus the same meal alone. Overall, compared to the carbohydrate-containing meal alone, the same meal with a small dose of added allulose resulted in a 10% lower integrated [[area under the curve]] (iAUC) of postprandial glucose.<ref name="BraunsteinMeta">{{cite journal |vauthors=Braunstein CR, Noronha JC, Khan TA, Mejia SB, Wolever TM, Josse RG, Kendall CW, Sievenpiper JL |title=Effect of fructose and its epimers on postprandial carbohydrate metabolism: A systematic review and meta-analysis |journal=[[Clinical Nutrition (journal)|Clinical Nutrition]] |date=November 2020 |volume=39 |issue=11 |pages=3308–3318 |doi=10.1016/j.clnu.2020.03.002 |pmid=32220498 |doi-access=free }}</ref> The quality of the evidence was rated as moderate.<ref name="BraunsteinMeta"/>

==Chemistry==

[[File:D-Psicose Haworth.svg|alt= Haworth projection of D-psicose|thumb|[[Haworth projection]] of <small>D</small>-psicose]]

Allulose, also known by its [[systematic name]] <small>D</small>-ribo-2-hexulose as well as by the name <small>D</small>-psicose, is a [[monosaccharide]] and a [[ketohexose]].<ref name="HossainYamaguchi2015" /><ref name="MuZhang2012">{{cite journal |last1=Mu |first1=Wanmeng |last2=Zhang |first2=Wenli |last3=Feng |first3=Yinghui |last4=Jiang |first4=Bo |last5=Zhou |first5=Leon |title=Recent advances on applications and biotechnological production of d-psicose |journal=Applied Microbiology and Biotechnology |date=June 2012 |volume=94 |issue=6 |pages=1461–1467 |doi=10.1007/s00253-012-4093-1 |pmid=22569636 |s2cid=15940502 }}</ref> It is a C3 [[epimer]] of [[fructose]].<ref name="HossainYamaguchi2015" /> Fructose can be converted to allulose by the [[enzyme]]s [[D-tagatose 3-epimerase|<small>D</small>-tagatose 3-epimerase]] ({{EC number|5.1.3.31}}) and/or [[D-psicose 3-epimerase|<small>D</small>-psicose 3-epimerase]] ({{EC number|5.1.3.30}}), which has allowed for [[mass production]] of allulose.<ref name="HossainYamaguchi2015" /> The compound is found naturally in trace amounts in [[wheat]], [[Common fig|fig]]s, [[raisin]]s, [[maple syrup]], and [[molasses]].<ref name="HossainYamaguchi2015" /><ref name="MuZhang2012" /><ref name="ChicagoTribune2019" /> Allulose has similar physical properties to those of regular sugar, such as bulk, mouthfeel, browning capability, and freeze point depression.<ref name="ChicagoTribune2019" /> This makes it favorable for use as a sugar replacement in food products, including ice cream.<ref name="ChicagoTribune2019" />

In a paper produced for the [[European Food Safety Authority]], the enzyme d-psicose 3-epimerase, manufactured by Matsutani Chemical Industry Co., Ltd, was investigated for safety and allergenicity.<ref name=EFSA>{{cite journal |doi-access=free |doi=10.2903/j.efsa.2021.6565 |journal=EFSA Journal |volume=19 |issue=4 |date=30 April 2021 |title=Safety evaluation of the food enzyme d-psicose 3-epimerase from the genetically modified Escherichia coli strain K-12 W3110 (pWKLP) |author=Claude Lambré |author2=José Manuel Barat Baviera |display-authors=etal|hdl=10251/185436 |hdl-access=free }}</ref> No DNA of ''E. coli'' (used for production of the enzyme) was found in the enzyme preparation, and no match was found in the enzyme amino acid sequence with those of known allergens.<ref name=EFSA/>

==History==

Allulose was first discovered in the 1940s.<ref name="ChicagoTribune2019" /> The first mass-production method for allulose was established when Ken Izumori at [[Kagawa University]] in Japan discovered the key enzyme, <small>D</small>-tagatose 3-epimerase, to convert fructose to allulose in 1994.<ref>{{Cite journal |last1=Itoh |first1=Hiromichi |last2=Okaya |first2=Hiroaki |last3=Khan |first3=Anisur Rahman |last4=Tajima |first4=Shigeyuki |last5=Hayakawa |first5=Shigeru |last6=Izumori |first6=Ken |display-authors=3 |year=1994 |title=Purification and characterization of D-tagatose 3-epimerase from ''Pseudomonas'' sp. ST-24 |journal=Biosci Biotechnol Biochem |volume=58 |issue=12 |pages=2168–2171 |doi=10.1271/bbb.58.2168 }}</ref><ref>{{cite journal |last1=Itoh |first1=Hiromichi |last2=Sato |first2=Tomoko |last3=Izumori |first3=Ken |title=Preparation of d-psicose from d-fructose by immobilized d-tagatose 3-epimerase |journal=Journal of Fermentation and Bioengineering |date=January 1995 |volume=80 |issue=1 |pages=101–103 |doi=10.1016/0922-338X(95)98186-O }}</ref> This method of production has a high yield, but has a very high production cost.

=== Regulatory history ===

In June 2012, the U.S. [[Food and Drug Administration]] (FDA) accepted the assertion of [[CJ CheilJedang]], Inc. of South Korea that allulose is [[generally recognized as safe]] (GRAS) as a sugar substitute in various specified food categories.<ref name=GRN400/> In June 2014, a similar GRAS letter was issued to Matsutani Chemical Industry Company, Ltd. of Japan.<ref name=GRN498/> Non-GMO allulose manufactured by Samyang Corp. of South Korea was approved as GRAS in March 2020.<ref name=GRAS828>{{Cite web|title=GRAS Notice GRN 000828|url=https://www.fda.gov/media/137310/download}}</ref>

In the [[European Union]], although allulose is a naturally-occurring saccharide, under their regulations, monosaccharides and other saccharides are not considered food additives, and thus cannot be approved as such, but must be approved as ingredients.<ref name=EUnovel>{{cite web| url=https://food.ec.europa.eu/system/files/2019-05/novel-food_sum_ongoing-app_2018-0394.pdf | title=Application for the Approval of Allulose as a Novel Food Ingredient in the European Union | date=25 April 2018}}</ref> CJ-Tereos Sweeteners of France filed for such an approval in April 2018.<ref name=EUnovel/> The Allulose Novel Food Consortium (ANFC) was formed in 2021 by four Japanese, Korean, U.S. and European food ingredient companies to speed its approval as an ingredient in Europe, including exemption from sugar labelling.<ref name=ANFC>{{cite web| url=https://www.ingredion.com/na/en-us/news-events/news/Ingredient-Companies-Create-Consortium-to-Put-Allulose-on-European-Menus1.html |title=Ingredient Companies Create Consortium to Put Allulose on European Menus |date= 29 November 2021 |publisher=Ingredion Incorporated}}</ref>

The U.S. FDA in October 2019 announced the exemption of allulose from total and added sugars on nutritional labels, but manufacturers must continue to include allulose in the total carbohydrates declaration, with a value of 0.4kcal/g, "0.4 calories per gram of allulose".<ref name=NutrFactsRuling/>

==Manufacturing==

Allulose is produced by an enzymatic reaction that converts fructose into allulose.<ref name="HossainYamaguchi2015" /> As of 2018, most commercially available allulose uses corn (maize) as the source of fructose.<ref>[https://www.fooddive.com/news/a-new-way-to-make-allulose-may-not-sweeten-the-sugars-appeal/526732/ A new way to make allulose may not sweeten the sugar's appeal]</ref> Another source of fructose is from [[sugar beet]].<ref>{{cite web |url=https://www.savanna-ingredients.com/en/food/allulose/ |title=Allulose |access-date=2019-11-10}}</ref>

==Commercial application ==

Commercial manufacturers and food laboratories are looking into properties of allulose that may differentiate it from sucrose and fructose sweeteners, including an ability to induce the high foaming property of [[egg white]] protein and the production of antioxidant substances produced through the [[Maillard reaction]].<ref name=foodnavigator>{{cite news|last1=Daniells|first1=Stephan|title=Rare sugar may replace sucrose for bakery and beyond|url=http://www.foodnavigator.com/Science/Rare-sugar-may-replace-sucrose-for-bakery-and-beyond|access-date=12 July 2015|publisher=Food Navigator|date=9 June 2008}}</ref>

Commercial uses of allulose include [[low-calorie]] sweeteners in beverages, yogurt, ice cream, baked goods, and other typically high-calorie items. London-based [[Tate & Lyle]] released its proprietary variant of allulose, known as Dolcia Prima allulose,<ref name="T&L">{{cite web |last= Watson |first= Elaine |title= Tate & Lyle unveils Dolcia Prima allulose low-calorie-sugar: 'We believe this will change the food and beverage landscape forever' |website= foodnavigator-usa.com |publisher= William Reed Business Media SAS |date= 25 Feb 2015 |url= http://www.foodnavigator-usa.com/Suppliers2/Tate-Lyle-unveils-Dolcia-Prima-allulose-low-calorie-sugar}}</ref> and U.S.-based Anderson Global Group released its own proprietary variant into the North American market in 2015.<ref name=newfootnote1>{{cite news|last1=Gelski|first1=Jeff|title=New low-calorie sweetener to launch at I.F.T.|url=http://www.foodbusinessnews.net/articles/news_home/Supplier-Innovations/2015/06/New_lowcalorie_sweetener_to_la.aspx?ID={C0B602CE-EFF5-4686-81B7-B8382DFF113F}|access-date=12 July 2015|publisher=Food Business News|date=30 June 2015}}</ref><ref name="Anderson Global Group">{{cite web|title=AllSweet|url=http://www.andersonglobalgroup.com/products/allsweet.php|publisher=Anderson Global Group}}</ref> The first major food company to adopt allulose as a sweetener was [[Quest Nutrition]] in some of their [[protein bar]] products.<ref name="ChicagoTribune2019">{{Cite web|url=https://www.chicagotribune.com/business/ct-biz-allulose-sugar-substitute-20190822-ayfcmkmol5a33jziuoguubrt7i-story.html|title = A natural sweetener with a tenth of sugar's calories. Allulose, developed in Hoffman Estates, could be 'breakthrough ingredient.'}}</ref>

On April 16, 2019, [[Food and Drug Administration|US Food and Drug Administration (FDA)]] issued a draft guidance, allowing food manufacturers to exclude allulose from total and added sugar counts on [[Nutrition facts label|Nutrition and Supplement Facts]] labels.<ref name="FDA2019">{{Cite web|url=https://www.fda.gov/NewsEvents/Newsroom/FDAInBrief/ucm636183.htm|title=FDA In Brief - FDA In Brief: FDA allows the low-calorie sweetener allulose to be excluded from total and added sugars counts on Nutrition and Supplement Facts labels when used as an ingredient|last=Commissioner|first=Office of the|website=www.fda.gov|language=en|access-date=2019-04-17}}</ref> Like sugar alcohols and dietary fiber, allulose will still count towards total carbohydrates on nutrition labels.<ref name="FDA2019" /> This, combined with the GRAS designation, has increased interest in including allulose in food products instead of sucrose.

==References==

{{Reflist}}

{{Carbohydrates}}

[[Category:Ketohexoses]]

[[Category:Pyranoses]]

[[Category:Furanoses]]