Assessing the impact of concurrent high-fructose and high-saturated fat diets on pediatric metabolic syndrome: A review

Table 1 Results of some clinical studies in pediatric populations with fructose consumption or restriction, consumption of foods with saturated fat or ultra-processed foods

MetS inductors and interventions	Population (age, n)	Measured parameters	Outcomes	Type of study	Ref.
Saturated fatty acids	6-16 (n = 108); OB children	lipid profiles	High saturated fat intake was associated with higher BMI, NAFLD positivity. TG, total cholesterol, LDL-C and HOMA-IR were significantly higher in SFA consumption group	Cross-sectional study	Maffeis et al[81]
Fructose restriction	8-18 (n = 20) Children with obesity and MetS	Lactate in serum (related with liver fat fraction and visceral adipose tissue)	Fructose restriction produced a 50% decrease in lactate, which was related with decreased de novo lipogenesis and insulin sensitivity	Clinical trial	Erkin-Cakmak et al[85]
Sugar sweetened beverages (Fructose)	6-12 (n = 1,087); OB children	Adiposity (BMI, WC), cardiovascular risk markers (glucose, insulin, HOMA-IR, TG, LDL-C, HDL)	TG, insulin, TC and LDL concentrations and HOMA-IR were significantly higher in OB children	Association study	Huerta-Ávila et al[86]
Moderate fruit consumption	5-19 (n = 14, 755)	Lipid Profile (TC, TG), fasting serum insulin (HOMA-IR)	Moderate fruit consumption (1.5 serving per day 6-7 d a week) was associated with lower odds of lipid disorders, improving the childhood lipid profiles	Cluster-controlled trial	Liu et al[87]
Fructose restriction	3-18 (Latino children n = 2; African-American children n = 16)	Anthropometric parameters (BW, WC, BMI), BP, biochemical measurements (serum lactate, TG, cholesterol and others), glucose and HOMA-IR	Fructose restriction (reduction from 28% to 10%) in children showed reductions in diastolic BP, serum lactate, TG, LDL-C. Glucose tolerance and hyperinsulinemia	Clinical trial	Lustig et al[90]
Fructose	12-16 (n = 1454)	HOMA-IR, uric acid, anthropometric parameters (BW, WC, BMI, body fat percentage)	High consumption of sugar sweetened beverages (> 350 mL/d) were more likely to have elevated fasting serum insulin and HOMA-IR, WC and serum uric acid compared to those not having fructose consumption	Cross-sectional study	Lin et al[96]
UPC foods (high fructose-high fat)	4-8 (n = 307)	Anthropometric parameters (BW, WC, BMI, WHR) and glucose profile	An increase in WC was observed in children with a higher UPC consumption. Not a direct association with altered glucose metabolism was observed	Longitudinal study	Costa et al[97]
UPC foods (high fructose-high fat)	3-4 (n = 346); 7-8 (n = 307)	Lipid profile (TC, TG, HDL, LDL-C)	The higher consumption of UPC, the higher increase in total cholesterol and LDL-C and altered lipoprotein profiles in children	Longitudinal study	Rauber et al[99]
UPC foods (high fructose-high fat)	12-19 (n = 210) Children from Brazilian family program	Urinary fructose excretion Anthropometric parameters and biochemical parameters	Significant association between MetS and the consumption of UPC foods	Cross- sectional study	Tavares et al[100]
Fructose	7-12 (n = 27); 13-15 (n = 25); 16-16 (n = 32); OB children	Anthropometric parameters (BW, Hgt, WC, BMI and WHR), serum lipid profiles	Higher fructose intake from beverages correlate positively with the percentage of body fat, WC, WHR, TC, TG and increased atherogenic indices	Observational study	Czerwonogrodzka-Senczyna et al[101]
Fructose	9-16 (n = 246)	Urinary fructose excretion	Metabolic dysfunctions and urinary excretion only at very high fructose intake levels (> 25% of total energy intake) or hypercaloric diets	Cohort study (DONALD)	Perrar et al[102]
Trans fatty acids	6-13 (n = 54); OB children	Anthropometric parameters, glucose and insulin. HOMA-IR, total lipids, postprandial levels of trans fatty acids	Obese children showed hyperinsulinemia and increased insulin resistance compared with controls. No differences for fasting plasma tFA or dietary tFA intake were observed	Clinical trial	Larqu et al[103]
High dairy fat products (total and saturated fat intake)	4-13 (n = 174) Intervention with low dairy fat products	Anthropometric parameters Pentadecanoic acid and lipid profile	Total fat and saturated fat intakes from dairy foods were lower in the intervention group (low fat dairy products consumption) but did not alter energy intakes or measures of adiposity	Randomized controlled trial	Hendrie and Golley[104]

OB: Obese; BW: Body weight (kg); Hgt: Height (cm); WC: Waist circumference (cm); BMI: Body mass index; WHR: Waist-to-height ratio; TC: Total cholesterol; TG: Triglycerides; HOMA-IR: Homeostasis Model Assessment of Insulin Resistance; LDL-C: Low-density lipoprotein cholesterol; HDL: High density lipoproteins; ALT: Alanine aminotransferase; AST: Aspartate amino transferase; NAFLD: Non-alcoholic fatty liver disease; SFA: Saturated fatty acid; tFA: Trans fatty acids; UPC: Ultra-processed; DONALD: The Dortmund Nutritional and Anthropometric Longitudinally Designed ongoing study; MetS: Metabolic syndrome.

Table 2 Recent studies focus on new therapeutic alternatives for obesity, metabolic syndrome, and Non-alcoholic fatty liver disease

Model/population	Treatment	Outcomes	Ref.
Fructose-induced NAFLD; Neonatal rats	Oleanolic acid	Attenuates the subsequent development of HFr diet-induced NAFLD	Nyakudya et al[143]
HFr induced metabolic dysfunction; Rats (Rattus norvegicus)	Oleanolic acid (60 mg/kg); metformin (500 mg/kg)	Both treatments increased mono- and polyunsaturated FFAs, associated with increased glut-4, glut-5 and nrf-1 and decreased acc-1 and fas	Molepo et al[144]
MetS induced by HFr diet; female mice	Tyrosol, hydroxytyrosol and salidroside	Improved glucose metabolism and lipid metabolism, including reduced levels of total cholesterol insulin, uric acid, LDL-C, and aspartate aminotransferase	Zhan et al[145]
Obesity and related diseases in humans	Olive oil triterpenic acids	Improves glucose and insulin homeostasis, lipid metabolism, adiposity and cardiovascular dysfunction in obesity	Claro-Cala et al [146]
HF and HFr diets induced metabolic dysfunction; Sprague dawley rat	Wheat flour, enriched with γ-oryzanol, phytosterol, and ferulic acid	Alleviates hepatic lipid accumulation and insulin resistance through their elevation in the phosphorylation of AMPK and Akt	Guo et al[147]
HF diet induced NAFLD; C57BL/6J mice	Quercetin	Decreased insulin resistance and NAFLD activity score, by reducing the intrahepatic lipid accumulation through its ability to modulate lipid metabolism gene expression, cytochrome P450 2E1 (CYP2E1)-dependent lipoperoxidation and related lipotoxicity	Porras et al[148]
HFr induced NAFLD; Sprague dawley rats	Ursolic acid	Ursolic acid administration against dietary fructose-induced NAFLD in newborn rats by reducing fructose-induced hepatic lipid accumulation	Mukonowenzou et al[149]
Mouse 3T3-L1 fructose-induced NAFLD	Citrulline	Prevented hypertriglyceridemia and attenuated liver fat accumulation	Jegatheesan et al[150]
Sprague-Dawley rats MetS; in vitro and in vivo studies	Nanoformulations of herbal extracts	Decrease the lipid profile, inflammation, oxidative damage, and insulin resistance in in vitro and in vivo models of MetS-related complications	Nouri et al[151]
MetS humans	Pharmabiotics	Improves gut microbiota profile wich influence serum lipid levels, BP, neuroendocrine cells and immune functions via regulating the metabolism of the host	Nguyen et al[152]
MetS; in vivo studies	Seaweed-derived bioactive components	Modulate the gut microbiota by reversing the Firmicutes/Bacteroidetes ratio, increasing the relative abundance of beneficial bacteria and decreasing the abundance of harmful bacteria; these compounds increase the production of short-chain fatty acids and influence glucose and lipid metabolism	Zang et al[153]
HFr induced adiposity	Valsartan; Amlodipine	Both treatment reduced triacylglycerol storage in adipocytes by inhibiting PU.1	Chou et al[154]
Hepatic steatosis induced by HFr diet; Wistar rats	β-catenin	Mediates the effect of GLP-1 receptor agonist on ameliorating hepatic steatosis	Gao et al[155]
NAFLD and nonalcoholic steatohepatitis Humans	Acetyl-CoA Carboxylase inhibitors	Therapeutic target for MetS as a key regulatory role in fatty acid synthesis and oxidation pathways	Chen et al[156]

BP: Blood pressure; HFr: High-fructose; FFA: Free fatty acids; NAFLD: Non-alcoholic fatty liver disease; HF: High-saturated fat; LDL-C: Low-density lipoprotein cholesterol; MetS: Metabolic syndrome.