Sugars, obesity, and cardiovascular disease: results from recent randomized control trials

Rippe, James M.; Angelopoulos, Theodore J.

doi:10.1007/s00394-016-1257-2

Cited by 88Diet, Metabolism, and DiseaseNutritional Studies and DietBiochemical Analysis and Sensing Techniques

Sugars, obesity, and cardiovascular disease: results from recent randomized control trials

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Rippe, James M., Angelopoulos, Theodore J.·2016·European Journal of Nutrition

DOI 10.1007/s00394-016-1257-2PMC PMC5174142

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Abstract

The relationship between sugar consumption and various health-related sequelas is controversial. Some investigators have argued that excessive sugar consumption is associated with increased risk of obesity, coronary heart disease, diabetes (T2D), metabolic syndrome, non-alcoholic fatty liver disease, and stimulation of reward pathways in the brain potentially causing excessive caloric consumption. These concerns have influenced organizations such as the World Health Organization, the Scientific Advisory Committee on Nutrition in England not to exceed 5 % of total energy and the Dietary Guidelines for Americans Advisory Committee 2015 to recommend upper limits of sugar consumption not to exceed 10 % of calories. Data from many randomized control trials (RCTs) do not support linkages between sugar consumption at normal levels within the human diet and various adverse metabolic and health-related effects. Fructose and glucose are typically consumed together in roughly equal proportions from high-fructose corn syrup (also known as isoglucose in Europe) or sucrose. The purpose of this review is to present data from recent RCTs and findings from recent systematic reviews and meta-analyses related to sugar consumption and its putative health effects. This review evaluates findings from recent randomized controlled trials, systematic reviews and meta-analyses into the relationship of sugar consumption and a range of health-related issues including energy-regulating hormones, obesity, cardiovascular disease, diabetes, and accumulation of liver fat and neurologic responses. Data from these sources do not support linkages between sugar consumption at normal levels within the human diet and various adverse metabolic and health-related effects.

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The Legume-Nut dietary pattern's high carbohydrate and sugar content, particularly from potatoes and certain legumes, may lead to rapid blood sugar spikes in the absence of sufficient dietary fiber, increasing metabolic syndrome risk.
“This diet is predominantly characterized by a high intake of carbohydrates and sugars, particularly from potatoes and certain legumes that naturally contain significant amounts of starches and sugars [29,30]. In the absence of sufficient dietary fiber to mitigate these effects, there is an elevated risk of rapid blood sugar spikes [31].”
From Impact of Dietary Patterns on Metabolic Syndrome in Young Adults: A Cross-Sectional Study (2024) · cites this paper as [29]
The citation is attached to the claim that insufficient dietary fiber increases the risk of rapid blood-sugar spikes. The paper’s “Sugars and diabetes” section discusses sugar intake, glucose tolerance, and diabetes risk, but does not address whether fiber mitigates blood-sugar spikes from potatoes or legumes. Searches for dietary fiber, postprandial glucose, starch, and legumes found no passage establishing that mechanism. (LLM, conf=0.76)
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Method
Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study
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Method
Dietary sugars and cardiometabolic risk: systematic review and meta-analyses of randomized controlled trials of the effects on blood pressure and lipids
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“* James M. Rippe jrippe@rippelifestyle.com Theodore J. Angelopoulos tangelopoulos@ehc.edu 1 Rippe Lifestyle Institute, 21 North Quinsigamond Avenue, Shrewsbury, MA 01545, USA 2 School of Health Sciences, Emory and Henry College, Emory, VA 24327, USA 1 3 fatty liver disease (NAFLD) now represents the leading cause of l…”
BackgroundInfluential
Dietary Sugar and Body Weight: Have We Reached a Crisis in the Epidemic of Obesity and Diabetes?
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Background
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Background
Low to moderate sugar-sweetened beverage consumption impairs glucose and lipid metabolism and promotes inflammation in healthy young men: a randomized controlled trial
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Background
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Background
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BackgroundMethod
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Background
A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans
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Background
Fructose ingestion acutely elevates blood pressure in healthy young humans
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Background
Endocrine and metabolic effects of consuming beverages sweetened with fructose, glucose, sucrose, or high-fructose corn syrup
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Background
Moderate Amounts of Fructose Consumption Impair Insulin Sensitivity in Healthy Young Men
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“[81] reported a systematic review and metaanalysis of RCTs and non-randomized controlled trials of fructose and diabetes and reported no adverse impact on glycemic control.”
Background
High fructose corn syrup and diabetes prevalence: A global perspective
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“Several recent ecological analyses have reported that the prevalence of diabetes is correlated with sugar consumption in various countries [24, 25].”
Background
No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men.
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“[90] showed that overweight men with increased abdominal girth had no increase in either hepatic or total body insulin resistance when studied in a weight stable environment.”
Background
Effect of fructose on postprandial triglycerides: A systematic review and meta-analysis of controlled feeding trials
David Wang, D., Sievenpiper, J. L., de Souza, R. J., Cozma, A. I., Chiavaroli, L., Ha, V., Mirrahimi, A., Carleton, A. J., Di Buono, M., Jenkins, A. L., et al. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.10.019 · Cited by 191 · see citing works
Impaired cellular insulin binding and insulin sensitivity induced by high-fructose feeding in normal subjects.
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Effect of Fructose on Blood Pressure: A Systematic Review and Meta-Analysis of Controlled Feeding Trials
Ha, V., Sievenpiper, J., de Souza, R., Chiavaroli, L., Wang, D., Cozma, A., Mirrahimi, A., Yu, M. E., Carleton, A., Buono, M. D., et al. (2012) · HYPERTENSION · doi:10.1161/hypertensionaha.111.182311 · Cited by 180 · cited 1× · see citing works
“[63] performed a meta-analysis of 13 randomized and nonrandomized controlled feeding trials where subjects were given an isocaloric exchange of fructose for carbohydrates and found no increases in blood pressure.”
Method
Functional magnetic resonance imaging of human hypothalamic responses to sweet taste and calories
Smeets, P. A. M., de Graaf, C., Stafleu, A., van Osch, M. J. P., & van der Grond, J. (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/82.5.1011 · Cited by 170 · see citing works
A prospective study of sugar intake and risk of type 2 diabetes in women.
Janket, S.-J., Manson, J., Sesso, H., Buring, J., & Liu, S.-M. (2003) · Diabetes Care · doi:10.2337/diacare.26.4.1008 · Cited by 158 · cited 2× · see citing works
“Moreover, another study published by the same group did not show a relationship between sugar consumption and diabetes risk [76].”
Background
Added Fructose
DiNicolantonio, J. J., O’Keefe, J. H., & Lucan, S. C. (2015) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2014.12.019 · Cited by 154 · see citing works
Will reducing sugar‐sweetened beverage consumption reduce obesity? Evidence supporting conjecture is strong, but evidence when testing effect is weak
Kaiser, K. A., Shikany, J. M., Keating, K. D., & Allison, D. B. (2013) · Obesity Reviews · doi:10.1111/obr.12048 · Cited by 147 · see citing works
The plausibility of sugar addiction and its role in obesity and eating disorders
Benton, D. (2010) · Clinical Nutrition · doi:10.1016/j.clnu.2009.12.001 · Cited by 144 · see citing works
Calorie‐sweetened beverages and fructose: what have we learned 10 years later
Bray, G. A., & Popkin, B. M. (2013) · Pediatric Obesity · doi:10.1111/j.2047-6310.2013.00171.x · Cited by 144 · cited 1× · see citing works
“Some epidemiologic studies have linked consumption of added sugars to increased risk of weight gain and obesity [14–16], increased risk factors for cardiovascular disease (CVD) [17] including hypertension [18–20] and dyslipidemia [21, 22], and increased risk factors for diabetes [23–25].”
Background
No differences in satiety or energy intake after high-fructose corn syrup, sucrose, or milk preloads.
Soenen, S., & Westerterp-Plantenga, M. (2007) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.5.1586 · Cited by 142 · see citing works
Effects of high-fructose corn syrup and sucrose consumption on circulating glucose, insulin, leptin, and ghrelin and on appetite in normal-weight women.
Melanson, K., Zukley, L., Lowndes, J., Nguyễn, V., Angelopoulos, T., & Rippe, J. (2007) · Nutrition (Burbank, Los Angeles County, Calif.) · doi:10.1016/j.nut.2006.11.001 · Cited by 142 · cited 1× · see citing works
“[41], we demonstrated that there we no different acute impacts (24 h) when comparing 25 % of calories either from HFCS or sucrose on insulin, glucose, leptin, or ghrelin in non-smoking women 20–60 years of age with body mass indexes of 19–25 kg/m(2).”
BackgroundSelf-citation
Soft drink intake in relation to incident ischemic heart disease, stroke, and stroke subtypes in Japanese men and women: the Japan Public Health Centre–based study cohort I
Eshak, E. S., Iso, H., Kokubo, Y., Saito, I., Yamagishi, K., Inoue, M., & Tsugane, S. (2012) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.112.037903 · Cited by 111 · cited 1× · see citing works
“[52] reported a large prospective cohort study and found no association between SSB consumption and myocardial infarction.”
Background
Food addiction: is there a baby in the bathwater?
Ziauddeen, H., Farooqi, I. S., & Fletcher, P. C. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3212-c2 · Cited by 105 · see citing works
The wrong white crystals: not salt but sugar as aetiological in hypertension and cardiometabolic disease
DiNicolantonio, J., & Lucan, S. (2014) · Open Heart · doi:10.1136/openhrt-2014-000167 · Cited by 104 · see citing works
Exercise Prevents Fructose-Induced Hypertriglyceridemia in Healthy Young Subjects
Egli, L., Lecoultre, V., Theytaz, F., Campos, V., Hodson, L., Schneiter, P., Mittendorfer, B., Patterson, B. W., Fielding, B. A., Gerber, P. A., et al. (2013) · Diabetes · doi:10.2337/db12-1651 · Cited by 102 · see citing works
Fructose and Risk of Cardiometabolic Disease
Bray, G. A. (2012) · Current Atherosclerosis Reports · doi:10.1007/s11883-012-0276-6 · Cited by 94 · cited 2× · see citing works
“Some epidemiologic studies have linked consumption of added sugars to increased risk of weight gain and obesity [14–16], increased risk factors for cardiovascular disease (CVD) [17] including hypertension [18–20] and dyslipidemia [21, 22], and increased risk factors for diabetes [23–25].”
Background
Dietary Sugar and Body Weight: Have We Reached a Crisis in the Epidemic of Obesity and Diabetes?
Kahn, R., & Sievenpiper, J. L. (2014) · Diabetes Care · doi:10.2337/dc13-2506 · Cited by 93 · see citing works
Misconceptions about fructose-containing sugars and their role in the obesity epidemic
van Buul, V. J., Tappy, L., & Brouns, F. J. P. H. (2014) · Nutrition Research Reviews · doi:10.1017/s0954422414000067 · Cited by 89 · cited 1× · see citing works
“[73] in one of these studies, in European countries, the authors confused sugar consumption with sugar production.”
Background
Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans
Purnell, J. Q., Klopfenstein, B. A., Stevens, A. A., Havel, P. J., Adams, S. H., Dunn, T. N., Krisky, C. M., & Rooney, W. D. (2010) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2010.01340.x · Cited by 87 · cited 1× · see citing works
“[100] explored neurologic responses to 25 g of either fructose or glucose delivered as intravenous boluses.”
Background
Consumption of sucrose and high-fructose corn syrup does not increase liver fat or ectopic fat deposition in muscles
Bravo, S., Lowndes, J., Sinnett, S., Yu, Z., & Rippe, J. (2013) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2012-0322 · Cited by 86 · cited 1× · see citing works
“A RCT from our research laboratory which compared either 8, 18, or 30 % of calories from HFCS or sucrose did not find any accumulation in liver fat over a 10 week, free living trial [95].”
MethodSelf-citation
Metabolic responses to prolonged consumption of glucose- and fructose-sweetened beverages are not associated with postprandial or 24-h glucose and insulin excursions
Stanhope, K. L., Griffen, S. C., Bremer, A. A., Vink, R., Schaefer, E. J., Nakajima, K., Schwarz, J., Beysen, C., Berglund, L., Keim, N. L., et al. (2011) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.002246 · Cited by 82 · see citing works
Very high fructose intake increases serum LDL-cholesterol and total cholesterol: a meta-analysis of controlled feeding trials.
Zhang, Y.-H., An, T., Zhang, R., Zhou, Q., Huang, Y., & Zhang, J. (2013) · Journal of NutriLife · doi:10.3945/jn.113.175323 · Cited by 82 · see citing works
The Australian Paradox: A Substantial Decline in Sugars Intake over the Same Timeframe that Overweight and Obesity Have Increased
Barclay, A., & Brand-Miller, J. (2011) · Nutrients · doi:10.3390/nu3040491 · Cited by 76 · see citing works
The Effects of Fructose-Containing Sugars on Weight, Body Composition and Cardiometabolic Risk Factors When Consumed at up to the 90th Percentile Population Consumption Level for Fructose
Lowndes, J., Sinnett, S., Yu, Z., & Rippe, J. M. (2014) · Nutrients · doi:10.3390/nu6083153 · Cited by 60 · cited 1× · see citing works
“In a mildly hypercaloric trial, however, a 10 % increase in TGs occurred driven largely by individuals who consumed 30 % of those calories from either HFCS or sucrose [60, 61].”
BackgroundSelf-citation
High-fructose corn syrup and sucrose have equivalent effects on energy-regulating hormones at normal human consumption levels
Yu, Z., Lowndes, J., & Rippe, J. M. (2013) · Nutrition Research · doi:10.1016/j.nutres.2013.07.020 · Cited by 58 · cited 1× · see citing works
“A third study in our laboratory showed that there were no differences when comparing 8 % of calories from either HFCS or sucrose (25th percentile population consumption level) to 18 % of calories from these two sugars (50th population level in the United States) and 30 % of calories from these two sugars (90th percent…”
BackgroundSelf-citation
The Effect of Normally Consumed Amounts of Sucrose or High Fructose Corn Syrup on Lipid Profiles, Body Composition and Related Parameters in Overweight/Obese Subjects
Lowndes, J., Sinnett, S., Pardo, S., Nguyen, V., Melanson, K. J., Yu, Z., Lowther, B., & Rippe, J. M. (2014) · Nutrients · doi:10.3390/nu6031128 · Cited by 58 · see citing works
Self-citation
Fructose, High Fructose Corn Syrup, Sucrose and Health
Rippe, J. (2014) · Springer eBooks · doi:10.1007/978-1-4899-8077-9 · Cited by 50 · see citing works
Self-citation
Genes required for fructose metabolism are expressed in Purkinje cells in the cerebellum.
Funari, V., Herrera, V., Freeman, D., & Tolan, D. (2005) · Brain Research. Molecular Brain Research · doi:10.1016/j.molbrainres.2005.09.019 · Cited by 49 · cited 1× · see citing works
“Some animal experiments have suggested differences in brain responses to fructose compared to glucose [96, 97].”
Background
Fructose Containing Sugars Do Not Raise Blood Pressure or Uric Acid at Normal Levels of Human Consumption
Angelopoulos, T., Lowndes, J., Sinnett, S., & Rippe, J. (2014) · The Journal of Clinical Hypertension · doi:10.1111/jch.12457 · Cited by 41 · see citing works
Self-citation
Dietary treatment of thrombogenic disorders related tothe metabolic syndrome
Marckmann, P. (2000) · British Journal of Nutrition · doi:10.1017/s0007114500001057 · Cited by 37 · cited 1× · see citing works
“Some epidemiologic studies have linked consumption of added sugars to increased risk of weight gain and obesity [14–16], increased risk factors for cardiovascular disease (CVD) [17] including hypertension [18–20] and dyslipidemia [21, 22], and increased risk factors for diabetes [23–25].”
Background
No Effect of Added Sugar Consumed at Median American Intake Level on Glucose Tolerance or Insulin Resistance
Lowndes, J., Sinnett, S., & Rippe, J. M. (2015) · Nutrients · doi:10.3390/nu7105430 · Cited by 35 · see citing works
Self-citation
Scientific Opinion on the substantiation of health claims related to fructose and reduction of post-prandial glycaemic responses (ID 558) pursuant to Article 13(1) of Regulation (EC) No 1924/2006
Products, E. P. O. D. (2011) · EFSA Journal · doi:10.2903/j.efsa.2011.2223 · Cited by 26 · see citing works
Are Sugars Addictive? Perspectives for Practitioners
Corwin, R. L., & Hayes, J. E. (2014) · Springer eBooks · doi:10.1007/978-1-4899-8077-9_13 · Cited by 15 · see citing works
Does Fructose Consumption Elicit a Dose-response Effect on Fasting Triglycerides? A Systematic Review and Meta-regression of Controlled Feeding Trials
Chiavaroli, L., Mirrahimi, A., de Souza, R., Cozma, A., Ha, V., Wang, D. D., Yu, M. E., Carleton, A., Beyene, J., Kendall, C., et al. (2012) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2012.07.330 · Cited by 10 · see citing works
Consumption of beverages sweetened with high fructose corn syrup and sucrose produce similar levels of glucose, leptin, insulin and ghrelin in obese females.
Zukley, L., Lowndes, J., Nguyễn, V., Brosnahan, J., Summers, A., Melanson, K., Angelopoulos, T., & Rippe, J. (2007) · The FASEB Journal · doi:10.1096/fasebj.21.5.a328-d · Cited by 7 · cited 1× · see citing works
“Subsequent research trials in our laboratory evaluated energy-regulating hormones in obese individuals and found no differences between HFCS and sucrose [42].”
BackgroundSelf-citation
No Dose Response Relationship in the Effects of Commonly Consumed Sugars on Risk Factors for Diabetes across a Range of Typical Human Consumption Levels
Lowndes, J., Kawiecki, D., Yu, Z., & Rippe, J. M. (2015) · Food and Nutrition Sciences · doi:10.4236/fns.2015.61011 · Cited by 5 · see citing works
Self-citation
Barclay, A.W. and Brand-Miller, J. The Australian Paradox: A Substantial Decline in Sugars Intake over the Same Timeframe that Overweight and Obesity Have Increased. Nutrients 2011, 3, 491-504
Barclay, A., & Brand-Miller, J. (2011) · Nutrients · doi:10.3390/nu3080734 · Cited by 3
No Dose‐Response Relationship in the Effect of Commonly Consumer Sugars on Insulin Sensitivity Across a Range of Typical Human Consumption Levels
Lowndes, J., Yu, Z.-P., & Rippe, J. (2015) · doi:10.1096/fasebj.29.1_supplement.596.11 · Cited by 1 · cited 1×
“A study conducted in our research laboratory examined HFCS or sucrose given at 18 % of calories compared to 9 % of fructose or glucose in low-fat milk compared to unsweetened milk in the context of mixed nutrient meals and showed no differences in hypothalamic blood flow [104].”
Self-citation

Flagged first, then by citations

7 of the 104 references couldn’t be matched to a known paper.

Research works printed but not linked: 4

[26]World Health Organization (2015) Guideline: sugars intake for adults and children. World Health Organization, Geneva. http://who.int/nutrition/publications/guidelines/sugars_intake/en/ 25905159
[31]Institute of Medicine (U.S.) (2005) Panel on Macronutrients, Institute of Medicine (U.S.). Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. Chapter 6—dietary carbohydrates: sugars and starches. National Academies Press, Washington
[46]American Medical Association. Report of the council on science and public health [cited December 9, 2015]. http://www.ama-assn.org/ama1/pub/upload/mm/467/csaph12a07.doc
[77]de Koning L Malik VS Kellogg MD Rimm EB Willett WC Hu FB Sweetened beverage consumption, incident coronary heart disease and biomarkers of risk in men Circulation 2012 25 1735–1741 S1731 PMC3368965 22412070

Sorted by citations

Fructose Consumption, Lipogenesis, and Non-Alcoholic Fatty Liver Disease
ter Horst, K. W., & Serlie, M. J. M. (2017) · Nutrients · doi:10.3390/nu9090981 · Cited by 365 · see citing works
“Rippe and Angelopoulos [156] evaluated recent observations from randomized controlled trials and meta-analyses into the effects of sugar consumption on important metabolic outcomes and health-related issues.”
Background
Excessive intake of sugar: An accomplice of inflammation
Ma, X., Nan, F., Liang, H., Shu, P., Fan, X., Song, X., Hou, Y., & Zhang, D. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.988481 · Cited by 338 · see citing works
Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease
Aragno, M., & Mastrocola, R. (2017) · Nutrients · doi:10.3390/nu9040385 · Cited by 239 · see citing works
“Excessive soft drink consumption has only been associated with increased risk for metabolic disorders such as obesity and insulin resistance [98,99], but their effects are often attributed to an unspecific calorie excess [100,101].”
Background
Triglyceride-glucose index is associated with symptomatic coronary artery disease in patients in secondary care
da Silva, A., Caldas, A., Hermsdorff, H. H., Bersch-Ferreira, Â., Torreglosa, C., Weber, B., & Bressan, J. (2019) · Cardiovascular Diabetology · doi:10.1186/s12933-019-0893-2 · Cited by 234 · see citing works
The Association between Chronotype and Dietary Pattern among Adults: A Scoping Review
Mazri, F. H., Manaf, Z. A., Shahar, S., & Mat Ludin, A. F. (2019) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17010068 · Cited by 198 · see citing works
“Nonetheless, evening chronotypes were linked to detrimental eating habits of sucrose which have notable negative effects on the health such as obesity, diabetes, an increase in cholesterol and blood pressure levels [78,79].”
Background
Recent advances in fructose intake and risk of hyperuricemia
Zhang, C., Li, L., Zhang, Y., & Zeng, C. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110795 · Cited by 142 · see citing works
Dietary Composition Independent of Weight Loss in the Management of Non-Alcoholic Fatty Liver Disease
Eslamparast, T., Tandon, P., & Raman, M. (2017) · Nutrients · doi:10.3390/nu9080800 · Cited by 108 · see citing works
“High sugar intake is associated with dyslipidemia, insulin resistance and central obesity [78]; (v) Higher intake of calcium and magnesium content of the DASH diet may have beneficial effects on insulin sensitivity and the anti-inflammatory response by decreasing oxidative activity and restoring anti-oxidative enzymes…”
Background
Added sugars and sugar-sweetened beverage consumption, dietary carbohydrate index and depression risk in the Seguimiento Universidad de Navarra (SUN) Project
Sánchez‐Villegas, A., Zazpe, I., Santiago, S., Perez‐Cornago, A., Martínez‐González, M. Á., & Lahortiga‐Ramos, F. (2017) · British Journal Of Nutrition · doi:10.1017/s0007114517003361 · Cited by 124 · see citing works
“Consumption of processed and sugary foods and beverages has exponentially increased worldwide, being in part responsible for the obesity and childhood obesity epidemic, and other non-communicable diseases such as type 2 diabetes mellitus and CHD((4)).”
Background
The Dose Makes the Poison: Sugar and Obesity in the United States – a Review
Faruque, S., Tong, J., Lacmanovic, V., Agbonghae, C., Minaya, D. M., & Czaja, K. (2019) · Polish Journal of Food and Nutrition Sciences · doi:10.31883/pjfns/110735 · Cited by 100 · see citing works
“…and meta-analyses of cohort studies and randomized control trials have reported that the link between consumption of AHA-recommended amounts of dietary sugars and obesity does not exist [Khan & Sievenpiper, 2016; Rippe & Angelopoulos, 2016; Te Morenga et al., 2012; Khan & Sievenpiper, 2014].”
Background
Food Addiction Support: Website Content Analysis
McKenna, R. A., Rollo, M., Skinner, J., & Burrows, T. (2018) · JMIR Cardio · doi:10.2196/cardio.8718 · Cited by 72 · see citing works
“CVD: cardiovascular disease DSM: Diagnostic and Statistical Manual of Mental Disorders OA: Overeaters Anonymous YFAS: Yale Food Addiction Scale JMIR Cardio 2018 | vol. 2 | iss.”
Background
Assessing the Influence of Visual-Taste Congruency on Perceived Sweetness and Product Liking in Immersive VR
Chen, Y., Huang, A. X., Faber, I., Makransky, G., & Pérez-Cueto, F. J. A. (2020) · Foods · doi:10.3390/foods9040465 · Cited by 82 · see citing works
NLRP3-inflammasome inhibition prevents high fat and high sugar diets-induced heart damage through autophagy induction
Pavillard, L. E., Cañadas-Lozano, D., Alcocer‐Gómez, E., Marín‐Aguilar, F., Pereira, S., Robertson, A. A. B., Muntané, J., Ryffel, B., Cooper, M. A., Quiles, J. L., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.20763 · Cited by 72 · see citing works
“Corroborating existing literature, all these physical and metabolic alterations have been observed in HFD and HSD, and both have been closely linked to an increased obesityrisk, cardiac disease, diabetes (T2D), metabolic syndrome, non-alcoholic fatty liver disease [26].”
Uric acid and hypertension
Becker, B. D., Borghi, C., Burnier, M., & van de Borne, P. (2018) · Journal of Hypertension · doi:10.1097/hjh.0000000000001980 · Cited by 85 · see citing works
Dietary sugars and cardiometabolic risk factors: a network meta-analysis on isocaloric substitution interventions
Schwingshackl, L., Neuenschwander, M., HOFFMANN, G. E., Buyken, A. E., & Schlesinger, S. (2019) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz273 · Cited by 73 · see citing works
Toxic AGE (TAGE) Theory for the Pathophysiology of the Onset/Progression of NAFLD and ALD
Takeuchi, M., Takino, J.-I., Sakai, A., Takata, T., & Tsutsumi, M. (2017) · Nutrients · doi:10.3390/nu9060634 · Cited by 40 · see citing works
In Defense of Sugar: A Critique of Diet-Centrism.
Archer, E. C. (2018) · Progress in cardiovascular diseases · doi:10.1016/j.pcad.2018.04.007 · Cited by 36 · see citing works
Associations Between Added Sugar Intake and Risk of Four Different Cardiovascular Diseases in a Swedish Population-Based Prospective Cohort Study
Janzi, S., Ramne, S., González-Padilla, E., Johnson, L., & Sonestedt, E. (2020) · Frontiers in Nutrition · doi:10.3389/fnut.2020.603653 · Cited by 43 · see citing works
“Further, a majority of studies have primarily focused on the intake of sugar-sweetened beverages (SSBs) (3, 5), rather than the totality of added sugars.”
Background
High-intensity interval training has beneficial effects on cardiac remodeling through local renin-angiotensin system modulation in mice fed high-fat or high-fructose diets
Sá, G. D. O., Neves, V. D. S., Fraga, S. R. D. O., Souza‐Mello, V., & Barbosa‐da‐Silva, S. (2017) · Life Sciences · doi:10.1016/j.lfs.2017.09.012 · Cited by 38 · see citing works
Habitual Fructose Intake Relates to Insulin Sensitivity and Fatty Liver Index in Recent-Onset Type 2 Diabetes Patients and Individuals without Diabetes
Weber, K., Simon, M., Strassburger, K., Markgraf, D., Buyken, A., Szendroedi, J., Müssig, K., & Roden, M. (2018) · Nutrients · doi:10.3390/nu10060774 · Cited by 25 · see citing works
“Fructose overconsumption increased hepatocellular fat content in some, but not all intervention studies [5,6].”
Background
The function, mechanisms, and clinical applications of metformin: potential drug, unlimited potentials
Liu, J., Zhang, M., Deng, D., & Zhu, X. (2023) · Archives of pharmacal research · doi:10.1007/s12272-023-01445-2 · Cited by 23 · see citing works
“2012; Rippe and Angelopoulos 2016; Stanhope 2016; Sigala et al.”
Background
Carbohydrates in nutrition: friend or foe?
Großkopf, A., & Simm, A. (2020) · Zeitschrift für Gerontologie und Geriatrie (Print) · doi:10.1007/s00391-020-01726-1 · Cited by 20 · see citing works
Substituting Sugar in Pastry and Bakery Products with Functional Ingredients
Dana, H., & Sonia, A. (2024) · Applied Sciences · doi:10.3390/app14188563 · Cited by 19 · see citing works
Impact of Dietary Patterns on Metabolic Syndrome in Young Adults: A Cross-Sectional Study
Liu, J., Lu, W., Lv, Q., Wang, Y., Xu, X., He, Y., Chang, H., Zhao, Y., Zhang, X., Zang, X., et al. (2024) · Nutrients · doi:10.3390/nu16172890 · Cited by 18 · see citing works
“This diet is predominantly characterized by a high intake of carbohydrates and sugars, particularly from potatoes and certain legumes that naturally contain significant amounts of starches and sugars [29,30].”
Background
Blood Pressure and Tooth Loss: A Large Cross-Sectional Study with Age Mediation Analysis
Mendes, J., Viana, J., Cruz, F., Pereira, D., Ferreira, S., Pereira, P., Proença, L., Machado, V., Botelho, J., Rua, J., et al. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18010285 · Cited by 16 · see citing works
Relevance of control diet choice in metabolic studies: impact in glucose homeostasis and vascular function
González-Blázquez, R., Alcalá, M., Fernández-Alfonso, M., Villa-Valverde, P., Viana, M., Gil-Ortega, M., & Somoza, B. (2020) · Scientific Reports · doi:10.1038/s41598-020-59674-0 · Cited by 16
Olfactory–gustatory cross-modal integration: mechanisms of aroma-induced sweetness enhancement, sensory evaluation methodologies, neuroimaging evidence and advances in influencing factors
Tan, Y., & Pang, X. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.09.043 · Cited by 8 · see citing works
Effect of High-Sucrose Diet on the Occurrence and Progression of Diabetic Retinopathy and Dietary Modification Strategies
Yang, C., Yu, Y., & An, J. (2024) · Nutrients · doi:10.3390/nu16091393 · Cited by 14 · see citing works
“…excessive intake of carbohydrates, which is a high-sucrose diet (HSD), especially foods containing high amounts of glucose and fructose, can lead to increased sugar intake and cause metabolic disorder, cardiovascular abnormalities [2], neurological disturbances [1,3] and inflammation [4–6].”
Background
Falsehoods and facts about dietary sugars: a call for evidence-based policy
Archer, E., & Arjmandi, B. H. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2020.1804320 · Cited by 13 · see citing works
Added sugar intake and its associations with incidence of seven different cardiovascular diseases in 69,705 Swedish men and women
Janzi, S., González-Padilla, E., Ramne, S., Bergwall, S., Borné, Y., & Sonestedt, E. (2024) · Frontiers in Public Health · doi:10.3389/fpubh.2024.1452085 · Cited by 16 · see citing works
Plant-based diets and body composition in Chinese omnivorous children aged 6–9 years old: A cross-sectional study
Chen, G., Su, M., Chu, X., Wei, Y., Chen, S., Zhou, Y., Liu, Z., & Zhang, Z. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.918944 · Cited by 11 · see citing works
Nε-(carboxymethyl)lysine formation from the Maillard reaction of casein and different reducing sugars
Park, H.-Y., Oh, M.-J., Park, Y., & Kim, Y. (2019) · Food Science and Biotechnology · doi:10.1007/s10068-019-00689-3 · Cited by 10 · see citing works
Neurosecretory Protein GL Accelerates Liver Steatosis in Mice Fed Medium-Fat/Medium-Fructose Diet
Narimatsu, Y., Ukena, K., Naito, M., Moriwaki, S., Furumitsu, M., & Ukena, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042071 · Cited by 8 · see citing works
“Introduction Diets with unbalanced nutrients lead to obesity and ectopic fat deposition, resulting in metabolic syndrome [1,2].”
Background
Kinome profiling reveals abnormal activity of kinases in skeletal muscle from adults with obesity and insulin resistance.
Qi, Y., Zhang, X.-M., Seyoum, B., Msallaty, Z., Mallisho, A., Caruso, M., Damacharla, D., Ma, D.-J., Al-Janabi, W., Tagett, R., et al. (2020) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/clinem/dgz115 · Cited by 9 · see citing works
Natural sweetener agave inhibits gastric emptying in rats by a cholecystokinin-2- and glucagon like peptide-1 receptor-dependent mechanism.
Gürler, E. B., Özbeyli, D., Buzcu, H., Bayraktar, S., Carus, I., Dağ, B., Geriş, Y., Jeral, S., & Yeğen, B. (2017) · Food & Function · doi:10.1039/c6fo01438k · Cited by 9 · see citing works
Association between Free Sugars Intake and Risk of Metabolic Syndrome in Chinese Adults: Results from the China Health and Nutrition Survey, 2000–2018
Pan, F., Wang, Z.-H., Wang, H.-J., Su, C., Zhang, J.-G., Du, W., Jia, X.-F., Wang, L.-S., Jiang, H.-R., Li, W.-Y., et al. (2022) · Nutrients · doi:10.3390/nu14245385 · Cited by 8
“Data from some RCTs and meta-analyses showed that there are no significant linkages between various adverse metabolic health effects and sugar consumption at normal levels within diets [14].”
Background
More pieces of the fructose puzzle
Stanhope, K. L. (2017) · Journal of Internal Medicine · doi:10.1111/joim.12644 · Cited by 7 · see citing works
Polarimetric and fluorescence spectroscopic based classification of mono and disaccharide solutions.
Ullah, R., Faisal, M., & Ullah, R. (2023) · Spectrochimica Acta Part A - Molecular and Biomolecular Spectroscopy · doi:10.1016/j.saa.2023.122490 · Cited by 7 · see citing works
FRUCTOSE-INDUCED ALTERATION OF THE HEART AND VESSELS HOMEOSTASIS.
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Influential
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Empfehlungen zur Ernährung von Personen mit Typ-1-Diabetes mellitus
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Empfehlungen zur Ernährung von Personen mit Typ-1-Diabetes mellitus
Rubin, D. F., Bosy‐Westphal, A., Kabisch, S., Kronsbein, P., Müssig, K., Simon, M., Tombek, A., Weber, K. S., & Skurk, T. (2026) · Die Diabetologie · doi:10.1007/s11428-026-01471-w
Nutritional Recommendations for People with Type 1 Diabetes Mellitus
Rubin, D., Bosy‐Westphal, A., Kabisch, S., Kronsbein, P., Simon, M., Tombek, A., Weber, K. S., & Skurk, T. (2023) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-1946-3753 · Cited by 1 · see citing works
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Empfehlungen zur Ernährung von Personen mit Diabetes mellitus Typ 1
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Empfehlungen zur Ernährung von Personen mit Typ-1-Diabetes mellitus
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Background
Diyetle Alınan Fruktozun Kronik Hastalıkların Gelişmesinde ve Prognozunda Etkisi Var mıdır?
Yuruk, A. A., & Ünal, R. (2019) · Florence Nightingale Hemşirelik Dergisi · doi:10.26650/fnjn346677
Sehr geehrte Kolleginnen und Kollegen,
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Sehr geehrte Kolleginnen und Kollegen,
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“Auf der anderen Seite war eine geringere Mahlzeitenfrequenz mit einer geringeren Energieaufnahme bei der Frühstücksmahl-zeit oder dem kompletten Auslassen des Frühstücks in prospekti-ven Langzeituntersuchungen mit einer höheren Gewichtszunah-me und einem Anstieg des Risikos für Diabetes, Herzinfarkt und Schlaganfall a…”

Authors: Rippe, J. M., & Angelopoulos, T. J.
Affiliations: Rippe Health (US)
Emory and Henry College (US)
Corresponding author: Rippe, James M.
ORCID: Rippe, James M.
Venue: European Journal of Nutrition
Publisher: Springer Science and Business Media LLC
Published: 2016-07-14
Volume: 55
Issue: S2
Pages: 45-53
ISSN: 0044-264X (ISSN-L)
1436-6207
1435-1293
DOI: 10.1007/s00394-016-1257-2
PMC: PMC5174142
OpenAlex: W2469191570
Cited by: 88
References: 104
Citations by year: 2026: 5 · 2025: 7 · 2024: 10 · 2023: 8 · 2022: 12 · 2021: 8 · 2020: 12 · 2019: 8 · 2018: 8 · 2017: 9 · 2016: 1
FWCI: 1.28
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (unspecified)
Locations: Zeitschrift für Ernährungswissenschaft (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
Keywords: sugar consumption, fructose, glucose, high fructose corn syrup, sucrose, obesity, cardiovascular disease, coronary artery disease, type 2 diabetes, metabolic syndrome, non-alcoholic fatty liver disease, brain reward system, dietary guidelines
MeSH terms: Animals, Blood Pressure, Brain, Energy Intake, Cardiovascular Diseases, Diabetes Mellitus, Type 1, Energy Metabolism, Fructose, Glucose, Humans, Lipids, Obesity, Meta-Analysis as Topic, Randomized Controlled Trials as Topic, Dietary Sucrose, Non-alcoholic Fatty Liver Disease, High Fructose Corn Syrup

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Sugars, obesity, and cardiovascular disease: results from recent randomized control trials

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