Сахар и фруктоза

Источники

1. Независимое

   Hannou SA, Haslam DE, McKeown NM, Herman MA. Fructose metabolism and metabolic disease Journal of Clinical Investigation, 2018.

   doi:10.1172/JCI96702PubMed 29388924

   Финансирование и результат

   Финансирование

   This work is supported by American Heart Association 16CSA28590003 (to MAH and NMM), NIH R01DK100425 (to MAH), NIH 5T32HL069772-15 (to DEH), and US Department of Agriculture Agricultural Research Service agreement 58-1950-4-003 (to NMM).

   Результат

   Narrative review. Sucrose is composed of equal portions of glucose and fructose. GLUT5 (SLC2A5) absorbs fructose with a Km of 6 mM; healthy adults absorb from less than 5 g to more than 50 g of free fructose. The liver extracts about 70% of an oral fructose load and 15% to 30% of an oral glucose load; the intestine metabolises up to 30% of an oral fructose load. KHK phosphorylates fructose to fructose 1-phosphate; the C isoform (liver, kidney, intestine) has a Km of 0.8 mM, the A isoform 8 mM. ALDOB cleaves fructose 1-phosphate to dihydroxyacetone phosphate and glyceraldehyde, which TKFC phosphorylates to glyceraldehyde 3-phosphate, so fructose carbon enters below phosphofructokinase. Fructose activates ChREBP and SREBP1c; malonyl-CoA inhibits CPT1A. Falling intracellular phosphate activates AMP deaminase and AMP is catabolised to uric acid; Mendelian randomisation studies do not strongly support a causal role for circulating uric acid in cardiometabolic disease. KHK loss of function causes essential fructosuria with no documented adverse effects. Large long-term randomised trials of added sugars on cardiometabolic risk are lacking.

2. Регуляторное

   EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck D, Bohn T, Castenmiller J, de Henauw S, Hirsch-Ernst KI, et al. Tolerable upper intake level for dietary sugars EFSA Journal, 2022.

   doi:10.2903/j.efsa.2022.7074PubMed 35251356

   Финансирование и результат

   Финансирование

   European Food Safety Authority. Requestor: European Commission, following a request from the national food competent authorities of Denmark, Finland, Iceland, Norway and Sweden (question EFSA-Q-2016-00414).

   Результат

   Systematic reviews of 49 RCTs and 66 cohorts on metabolic endpoints. Added sugars are mono- and disaccharides added during processing or preparation or at the table; free sugars are added sugars plus sugars naturally present in honey, syrups, fruit juices and juice concentrates. Sucrase-isomaltase hydrolyses sucrose; glucose enters enterocytes by SGLT1, fructose by facilitated diffusion through GLUT5, incompletely and enhanced by co-ingested glucose; GLUT2 moves all three monosaccharides into portal blood. Hepatic glycolysis is restrained at phosphofructokinase by ATP and citrate, fructolysis is not; almost all fructose entering hepatocytes becomes triose phosphates, from which lactate, glucose, glycogen, glycerol and fatty acids are formed. Large fructose loads transiently deplete hepatic ATP, with AMP formation and purine degradation. Dietary sugars are a well-established hazard for dental caries: plaque bacteria convert sugars to organic acids that demineralise enamel and dentine, and about 30% of plaque is matrix largely of glucans made from sucrose by bacterial glucosyltransferases. Certainty of a causal relationship for added and free sugars (RCTs on surrogate endpoints): moderate for obesity and dyslipidaemia, low for NAFLD and type 2 diabetes, very low for hypertension; too few RCTs below 10% of energy. Cohorts did not support a relationship of dietary sugars in isocaloric exchange with chronic metabolic disease. In RCTs, free fructose and free glucose had similar effects on body weight, liver fat, glucose tolerance, blood lipids and blood pressure, while free fructose increased hepatic insulin resistance and uric acid more; certainty for fructose and gout moderate (cohorts). Sugar-sweetened beverages: high certainty for obesity, type 2 diabetes, hypertension and cardiovascular disease, moderate for gout. Glucose-fructose syrups are made by hydrolysing starch to glucose and converting about half enzymatically to fructose; most contain 42% fructose (processed foods) or 55% (sugar-sweetened beverages), as free monosaccharides; called high-fructose corn syrup in the United States and isoglucose in the EU. No tolerable upper intake level could be set; intake of added and free sugars should be as low as possible in a nutritionally adequate diet.

3. Справочное издание

   Gaughan S, Ayres L, Baker PR II. Hereditary Fructose Intolerance GeneReviews, University of Washington, Seattle, 2021.

   PubMed 26677512

   Финансирование и результат

   Финансирование

   not stated

   Результат

   Initial posting 17 December 2015; last update 18 February 2021. Autosomal recessive; biallelic pathogenic ALDOB variants. Prevalence estimated from carrier testing: 1 in 18,000 (United Kingdom), 1 in 26,000 (Germany), 1 in 31,000 (Poland), 1 in 60,000 (United States). p.Ala150Pro (legacy Ala149Pro) is the most common variant in all studies. Accumulated fructose 1-phosphate inhibits gluconeogenesis and glycogenolysis, causes overuse and reduced regeneration of ATP, and impairs protein glycosylation. After fructose, sucrose or sorbitol, untreated patients develop hypoglycaemia, vomiting and metabolic disturbances, and may progress to hepatic and renal failure; with early dietary restriction of fructose, sucrose, sorbitol and sucralose, quality of life and life expectancy are normal.

4. Независимое

   de Ruyter JC, Olthof MR, Seidell JC, Katan MB. A trial of sugar-free or sugar-sweetened beverages and body weight in children New England Journal of Medicine, 2012.

   doi:10.1056/NEJMoa1203034PubMed 22998340

   Финансирование и результат

   Регистрация

   NCT00893529

   Участники

   641

   Наблюдение

   18 months

   Финансирование

   Supported by grants from the Netherlands Organization for Health Research and Development (120520010), the Netherlands Heart Foundation (2008B096), and the Royal Netherlands Academy of Arts and Sciences (ISK/741/PAH). The investigators hired Refresco Benelux to produce the beverages; the manufacturer had no role in the design of the study, the accrual or analysis of the data, or the preparation of the manuscript.

   Результат

   Double-blind; one 250 ml can per day of a sugar-free drink (34 mg sucralose, 12 mg acesulfame potassium) or a matching drink with 26 g sucrose (104 kcal). With imputation for the 26% who stopped drinking the beverages, BMI z score rose by 0.02 SD in the sugar-free group and 0.15 SD in the sugar group (95% CI of the difference -0.21 to -0.05); weight rose by 6.35 kg and 7.37 kg (difference 1.01 kg; 95% CI -1.54 to -0.48).

5. Независимое

   Ebbeling CB, Feldman HA, Chomitz VR, Antonelli TA, Gortmaker SL, Osganian SK, et al. A randomized trial of sugar-sweetened beverages and adolescent body weight New England Journal of Medicine, 2012.

   doi:10.1056/NEJMoa1203388PubMed 22998339

   Финансирование и результат

   Регистрация

   NCT00381160

   Участники

   224

   Наблюдение

   2 years: 1-year intervention, then 1 year without intervention

   Финансирование

   Supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK073025 and K24DK082730, to Dr. Ludwig) and from the National Center for Research Resources to the Boston Children's Hospital General Clinical Research Center (M01RR02172), the Harvard Catalyst Clinical and Translational Science Center (UL1RR025758), and the New Balance Foundation. Beverages for the intervention group were purchased from an online delivery service.

   Результат

   Home delivery of noncaloric beverages, telephone calls with parents and check-in visits for 1 year. Change in experimental minus control group: at 1 year, BMI -0.57 (P=0.045) and weight -1.9 kg (+1.6 against +3.5 kg; P=0.04); at 2 years, the primary outcome, BMI -0.30 (P=0.46) and weight -0.8 kg (+4.3 against +5.1 kg; P=0.55). Retention 97% at 1 year and 93% at 2 years.

6. Независимое

   Stanhope KL, Schwarz JM, Keim NL, Griffen SC, Bremer AA, Graham JL, et al. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans Journal of Clinical Investigation, 2009.

   doi:10.1172/JCI37385PubMed 19381015

   Финансирование и результат

   Участники

   39

   Наблюдение

   10 weeks of sugar-sweetened beverages: 8 weeks outpatient with ad libitum diet, then 2 weeks inpatient with energy-balanced diet

   Финансирование

   This research was supported with funding from NIH grant R01 HL-075675 and grant UL1 RR024146 from the National Center for Research Resources, a component of the NIH, and the NIH Roadmap for Medical Research. P.J. Havel's laboratory also receives support from NIH grants HL-091333, AT-002599, AT-002993 and AT-003545 and the American Diabetes Association; N.L. Keim's research is supported by intramural USDA-ARS CRIS 5306-51530-016-00D.

   Поддержка в натуральной форме

   Postheparin total and hepatic lipase activity was assayed by Asahi Kasei Pharma; payment terms are not stated.

   Результат

   Beverages provided 25% of energy requirements as fructose (17 completers) or glucose (15 completers). Change at 10 weeks, fructose against glucose: body weight +1.4% and +1.8%; intra-abdominal fat volume +14.0% (P<0.01) and +3.2% (not significant); fasting LDL cholesterol +13.9% and +3.6%; fasting apoB +27.2% and +3.0%; fasting triglyceride +3.9% and +9.7%; insulin sensitivity index -17.3% and +1.1%. Postprandial fractional hepatic de novo lipogenesis rose from 11.4% to 16.9% with fructose (P=0.021) and from 13.4% to 14.2% with glucose (P=0.31); the 16-hour DNL AUC increased more with fructose (P=0.016) in the 18 participants with isotope data.

7. Независимое

   Geidl-Flueck B, Hochuli M, Németh Á, Eberl A, Derron N, Köfeler HC, et al. Fructose- and sucrose- but not glucose-sweetened beverages promote hepatic de novo lipogenesis: A randomized controlled trial Journal of Hepatology, 2021.

   doi:10.1016/j.jhep.2021.02.027PubMed 33684506

   Финансирование и результат

   Регистрация

   NCT01733563

   Участники

   126

   Наблюдение

   7 weeks

   Финансирование

   This study was funded by the Swiss National Science Foundation (No. 144204), Vontobel Foundation, Rhyner Bangerter Foundation, Promedica Foundation, Uniscientia Foundation, Prof. Otto Beisheim-Foundation, Jubiläumsstiftung Swiss Life, Philhuman Foundation and the Austrian Federal Ministry of Education (No. BMWFW-10.420/0005-WF/V/3c/2017).

   Поддержка в натуральной форме

   Molkerei Biedermann AG provided the beverages in coded containers; the Swiss technology testing service, Dietikon, performed quality control; payment terms are not stated.

   Результат

   Described as double-blind; the control group abstained from sugar-sweetened beverages and received no placebo. 80 g per day of fructose, sucrose or glucose in three 200 ml beverages for 7 weeks. Median basal hepatic fractional secretion rate of newly synthesised VLDL palmitate (%/day): fructose 19.7 (P=0.013), sucrose 20.8 (P=0.0015), glucose 11.0 (P=0.16), control 9.1. Total energy intake did not change; fasting triglyceride, glucose and insulin did not change; liver fat was not measured.

8. Независимое

   Kearns CE, Schmidt LA, Glantz SA. Sugar Industry and Coronary Heart Disease Research: A Historical Analysis of Internal Industry Documents JAMA Internal Medicine, 2016.

   doi:10.1001/jamainternmed.2016.5394PubMed 27617709

   Финансирование и результат

   Финансирование

   This work was supported by the UCSF Philip R. Lee Institute for Health Policy Studies, a donation by the Hellmann Family Fund to the UCSF Center for Tobacco Control Research and Education, the UCSF School of Dentistry Department of Orofacial Sciences and Global Oral Health Program, National Institute of Dental and Craniofacial Research grant DE-007306 and National Cancer Institute Grant CA-087472. The funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

   Результат

   In 1965 the Sugar Research Foundation approved Project 226, a literature review by Hegsted and McGandy overseen by Stare, and paid $6500 ($48,900 in 2016 dollars). The foundation set the review's objective, contributed articles for inclusion and received drafts. The two-part review, published in the New England Journal of Medicine in 1967, discounted studies linking sucrose to coronary heart disease and concluded that reducing dietary cholesterol and substituting polyunsaturated for saturated fat was the only dietary intervention needed; the foundation's funding and role were not disclosed. The authors state that evidence of industry influence on the review's conclusions is circumstantial. In 1971 the industry influenced the National Caries Program of the National Institute of Dental Research to shift its emphasis to interventions other than restricting sucrose.

9. Независимое

   Bes-Rastrollo M, Schulze MB, Ruiz-Canela M, Martinez-Gonzalez MA. Financial conflicts of interest and reporting bias regarding the association between sugar-sweetened beverages and weight gain: a systematic review of systematic reviews PLoS Medicine, 2013.

   doi:10.1371/journal.pmed.1001578PubMed 24391479

   Финансирование и результат

   Финансирование

   No funding was received for this work.

   Результат

   17 systematic reviews with 18 conclusions on sugar-sweetened beverages and weight gain or obesity. Five of 6 conclusions (83.3%) from reviews disclosing a financial conflict of interest with the food industry found insufficient evidence of a positive association; 10 of 12 conclusions (83.3%) from reviews reporting no such conflict found a potential risk. Relative risk of a conclusion of no positive association 5.0 (95% CI 1.3 to 19.3).

10. Финансировано индустрией

    Choi HK, Curhan G. Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study BMJ, 2008.

    doi:10.1136/bmj.39449.819271.BEPubMed 18244959

    Финансирование и результат

    Участники

    46 393

    Наблюдение

    12 years

    Финансирование

    This work was supported in part by grants from the National Institutes of Health (DK58573, AA11181, HL35464, and CA55075) and TAP Pharmaceuticals. The funding sources had no role in the design, conduct, or reporting of the study or in the decision to submit the manuscript for publication.

    Результат

    755 incident cases of gout. Sugar-sweetened soft drinks, 2 or more servings per day against less than 1 per month: multivariate relative risk 1.85 (95% CI 1.08 to 3.16); 16 cases in 7392 person-years against 279 cases in 158,891 person-years. Highest against lowest fifth of free fructose intake: 2.02 (1.49 to 2.75). Diet soft drinks were not associated with gout (P for trend 0.99).

11. Консенсус

    World Health Organization. Guideline: Sugars Intake for Adults and Children World Health Organization, Geneva, 2015.

    PubMed 25905159

    Финансирование и результат

    Финансирование

    WHO expresses special appreciation to the following for providing financial support for the guideline development work: the Ministry of Health, Labour and Welfare of the Government of Japan; the Korean Food and Drug Administration, through grants to the Korea Health Industry Development Institute; Zhejiang University in Hangzhou, China; and the WHO Regional Office for Europe.

    Результат

    WHO recommends a reduced intake of free sugars throughout the lifecourse (strong recommendation) and, in adults and children, reducing free sugars to less than 10% of total energy intake (strong recommendation); WHO suggests a further reduction to below 5% (conditional recommendation). The 10% limit rests on moderate-quality evidence from observational studies of dental caries and the 5% limit on very-low-quality evidence from ecological studies. The excess body weight associated with free sugars results from excess energy intake.