Abstract
Obesity can lead children and adolescents to an increased cardiovascular disease (CVD) risk. A diet supplemented with Plantago psyllium has been shown to be effective in reducing LDL-C and IL-6 in adolescents. However, there are no studies that have explored small-dense LDL (sdLDL) or HDL subclasses. The aim of this study was to evaluate the impact of a fiber dietary intervention on LDL and HDL subclasses in adolescents with obesity. In this parallel, double blind, randomized clinical trial, the participants were assigned to Plantago psyllium or placebo (10g/day for 7 weeks). We randomized 113 participants, and evaluated and analyzed 100 adolescents (50 in each group), 15 to 19 years with a body mass index of 29–34. We measured biochemical markers LDL and HDL subclasses using the Lipoprint system (Quantimetrix) and IL-6 by ELISA. Post-treatment there was a decrease in sdLDL between the groups 2.0 (0–5.0) vs 1 (0–3.0) mg/dl (p = 0.004), IL-6 median 3.32 (1.24–5.96) vs 1.76 (0.54–3.28) pg/ml, p <0.0001. There were no differences in HDL subclasses and no adverse effects were reported in either group.
Conclusions: Small dense LDL and IL-6 reduced in adolescents with obesity when consuming Plantago psyllium. This may be an early good strategy for the reduction of cardiovascular disease risk in this vulnerable population.
Trial registration: ISRCTN # 14180431. Date assigned 24/08/2020
What is Known: • Supplementing the diet with Plantago psyllium lowers LDL-C levels. What is New: • First evidence that soluble fiber supplementation like Plantago psyllium decreases small dense LDL particles in association with lowered IL-6, reducing the risk of cardiovascular disease in obese adolescents. |
Similar content being viewed by others
Availability of data and material
Data and material available by request to Ma. Eugenia Garay-Sevilla (megaray@ugto.mx).
Code availability
Not applicable.
Abbreviations
- AI:
-
Atherogenic index
- BMI:
-
Body mass index
- CETP:
-
Cholesteryl ester transfer protein
- CHO:
-
Carbohydrates
- CVD:
-
Cardiovascular disease
- FA:
-
Fatty acid
- GLUT-4:
-
Glucose transporter type 4
- HDL:
-
High-density lipoproteins
- IL-6:
-
Interleukin-6
- IQR:
-
Interquartile range
- IR:
-
Insulin resistance
- LCAT:
-
Lecithin cholesterol acyltransferase
- LDL:
-
Low-density lipoprotein
- RRCT:
-
Remnant reverse cholesterol transport
- SCFA:
-
Short chain fatty acids
- SdLDL:
-
Small dense low density lipoprotein
- VLDL:
-
Very low-density lipoproteins
References
World Health O (2017) Report of the Commission on Ending Childhood Obesity: implementation plan: executive summary World Health. World Health Organization. License: CC BY-NC-SA 3.0 IGO. https://apps.who.int/iris/handle/10665/259349. Accessed 31 May 2017
Duffey KJ, Rivera JA, Popkin BM (2014) Snacking is prevalent in Mexico. J Nutr 144:1843–1849. https://doi.org/10.3945/jn.114.198192
Aceves-Martins M, Llauradó E, Tarro L, Solà R, Giralt M (2016) Obesity-promoting factors in Mexican children and adolescents: challenges and opportunities. Glob Health Action 9:1–13. https://doi.org/10.3402/gha.v9.29625
Hoogeveen RC, Gaubatz JW, Sun W, Dodge RC, Crosby JR, Jiang J, Couper D, Virani SS, Kathiresan S, Boerwinkle E, Ballantyne CM (2014) Small dense LDL cholesterol concentrations predict risk for coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb Vasc Biol 34:1069–1077. https://doi.org/10.1161/ATVBAHA.114.303284
Collins R, Armitage J, Parish S, Sleight P, Peto R (2002) MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360:7–22. https://doi.org/10.1016/S0140-6736(02)09327-3
Liou L, Kaptoge S (2020) Association of small, dense LDL-cholesterol concentration and lipoprotein particle characteristics with coronary heart disease: a systematic review and meta-analysis. PLoS One 15:1–16. https://doi.org/10.1371/journal.pone.0241993
Ivanova EA, Myasoedova VA, Melnichenko AA, Grechko AV (2017) Orekhov AN (2017) Small dense low-density lipoprotein as biomarker for atherosclerotic diseases. Oxidative Med Cell Longev 2017:1–10. https://doi.org/10.1155/2017/1273042
Miyashita M, Okada T, Kuromori Y, Harada K (2006) LDL particle size, fat distribution and insulin resistance in obese children. Eur J Clin Nutr 60:416–420. https://doi.org/10.1038/sj.ejcn.1602333
Rodríguez-Mortera R, Luevano-Contreras C, Solorio-Meza S, Caccavello R, Bains Y, Garay-Sevilla ME, Gugliucci A (2018) Higher D-lactate levels are associated with higher prevalence of small dense low-density lipoprotein in obese adolescents. Clin Chem Lab Med 56:1100–1108. https://doi.org/10.1515/cclm-2017-0733
Talebi S, Bagherniya M, Atkin SL, Askari G, Orafai HM, Sahebkar A (2020) The beneficial effects of nutraceuticals and natural products on small dense LDL levels, LDL particle number and LDL particle size: A clinical review. Lipids Health Dis 19:1–21. https://doi.org/10.1186/s12944-020-01250-6
Muchová J, Andrezálová L, Oravec S, Nagyová Z, Garaiova I, Duracková Z (2016) High density lipoprotein subfractions and paraoxonase 1 in children. Acta Biochim Pol 63:555–563. https://doi.org/10.18388/abp.2015_1230
Mietus-Snyder ML, Shigenaga MK, Suh JH, Shenvi SV, Lal A, McHugh T, Olson D, Lilienstein J, Krauss RM, Gildengoren G, McCann JC, Ames BN (2012) A nutrient-dense, high-fiber, fruit-based supplement bar increases HDL cholesterol, particularly large HDL, lowers homocysteine, and raises glutathione in a 2-wk trial. FASEB J 26:3515–3527. https://doi.org/10.1096/fj.11-201558
Barbora K, Magdaléna V, Iveta W, Stanislav O, Iveta G, Zuzana N, Nataša H, Zdenka Ď, Jana T (2020) Lipid profile, lipoprotein subfractions, and fluidity of membranes in children and adolescents with depressive disorder: effect of omega-3 fatty acids in a double-blind randomized controlled study. Biomolecules 10:1–19. https://doi.org/10.3390/biom10101427
Parikh S, Pollock NK, Bhagatwala J, Guo DH, Gutin B, Zhu H, Dong Y (2012) Adolescent fiber consumption is associated with visceral fat and inflammatory markers. J Clin Endocrinol Metab 97:1451–1457. https://doi.org/10.1210/jc.2012-1784
Barquera S, Rivera JA, Safdie M, Flores M, Campos-Nonato I, Campirano F (2003) Energy and nutrient intake in preschool and school age Mexican children: National Nutrition Survey 1999. Salud Publica Mex 45:540–550. https://doi.org/10.1590/s0036-36342003001000010
McRae MP (2017) Dietary fiber is beneficial for the prevention of cardiovascular disease: an umbrella review of meta-analyses. J Chiropr Med 16:289–299. https://doi.org/10.1016/j.jcm.2017.05.005
Ribas SA, Cunha DB, Sichieri R, Santana Da Silva LC (2015) Effects of psyllium on LDL-cholesterol concentrations in Brazilian children and adolescents: a randomised, placebo-controlled, parallel clinical trial. Br J Nutr 113:134–141. https://doi.org/10.1017/S0007114514003419
de Bock M, Derraik JGB, Brennan CM, Biggs JB, Smith GC, Cameron-Smith D, Wall CR, Cutfield WS (2012) Psyllium supplementation in adolescents improves fat distribution & lipid profile: a randomized, participant-blinded, placebo-controlled, crossover trial. PLoS One 7:e41735. https://doi.org/10.1371/journal.pone.0041735
Swann OG, Breslin M, Kilpatrick M, O’Sullivan TA, Mori TA, Beilin LJ, Oddy WH (2020) Dietary fibre intake and its association with inflammatory markers in adolescents. Br J Nutr 125:329–336. https://doi.org/10.1017/S0007114520001609
Lottenberg AMP, Fan PLT, Buonacorso V (2010) Effects of dietary fiber intake on inflammation in chronic diseases. Einstein (São Paulo) 8:254–258. https://doi.org/10.1590/s1679-45082010md1310
Maliachova O, Stabouli S (2018) Familial hypercholesterolemia in children and adolescents: diagnosis and treatment. Curr Pharm Des 24:3672–3677. https://doi.org/10.2174/1381612824666181010145807
Garoufi A, Vorre S, Soldatou A, Tsentidis C, Kossiva L, Drakatos A, Marmarinos A, Gourgiotis D (2014) Plant sterols-enriched diet decreases small, dense LDL-cholesterol levels in children with hypercholesterolemia: A prospective study. Ital J Pediatr 40:1–6. https://doi.org/10.1186/1824-7288-40-42
Jovanovski E, Yashpal S, Komishon A, Zurbau A, Mejia SB, Ho HVT, Li D, Sievenpiper J, Duvnjak L, Vuksan V (2018) Effect of psyllium (Plantago ovata) fiber on LDL cholesterol and alternative lipid targets, non-HDL cholesterol and apolipoprotein B: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr 108:922–932. https://doi.org/10.1093/ajcn/nqy115
Moreno LA, Tresaco B, Bueno G, Fleta J, Rodríguez G, Garagorri JM, Bueno M (2003) Psyllium fibre and the metabolic control of obese children and adolescents. J Physiol Biochem 59:235–242. https://doi.org/10.1007/BF03179920
Cicero AFG, Colletti A, Bajraktari G, Descamps O, Djuric DM, Ezhov M, Fras Z, Katsiki N, Langlois M, Latkovskis G, Panagiotakos DB, Paragh G, Mikhailidis DP, Mitchenko O, Paulweber B, Pella D, Pitsavos C, Reiner Ž, Ray KK, Rizzo M, Sahebkar A, Serban MC, Sperling LS, Toth PP, Vinereanu D, Vrablík M, Wong ND, Banach M (2017) Lipid lowering nutraceuticals in clinical practice: Position paper from an International Lipid Expert Panel. Arch Med Sci 13:965–1005. https://doi.org/10.5114/aoms.2017.69326
Riley M, Hernandez AK, Kuznia AL (2018) High blood pressure in children and adolescents. Am Fam Physician 98:486–494
Rodríguez-Morán M, Guerrero-Romero F, Aradillas-García C, Bermudez-Peña C, Simental-Mendia LE, Vargas Morales JM, Torres Rodríguez ML, De La Cruz Mendoza E (2013) Atherogenic indices and prehypertension in obese and non-obese children. Diab Vasc Dis Res 10:17–24. https://doi.org/10.1177/1479164112440713
Takumansang R, Warouw SM, Lestari H (2013) Interleukin-6 and insulin resistance in obese adolescents. Paediatr Indones 53:268. https://doi.org/10.14238/pi53.5.2013.268-72
Hoefner DM, Hodel SD, O’Brien JF, Branum EL, Sun D, Meissner I, McConnell JP (2001) Development of a rapid, quantitative method for LDL subfractionation with use of the quantimetrix lipoprint LDL system. Clin Chem 47:266–274. https://doi.org/10.1093/clinchem/47.2.266
Xiao Z, Chen H, Zhang Y, Deng H, Wang KW, Bhagavathula AS, Almuhairi SJ, Ryan PM, Rahmani J, Dang M, Kontogiannis V, Vick A, Wei Y (2020) The effect of psyllium consumption on weight, body mass index, lipid profile, and glucose metabolism in diabetic patients: a systematic review and dose-response meta-analysis of randomized controlled trials. Phytother Res 34:1237–1247. https://doi.org/10.1002/ptr.6609
Austin MA, Breslow JL, Hennekens CH, Buring JE, Willett WC, Krauss RM (1988) Low-density lipoprotein subclass patterns and risk of myocardial infarction. JAMA 260:1917–1921. https://doi.org/10.1001/jama.1988.03410130125037
Zaki Khalil RMA, Al-Azab DAM, Akl OA (2017) Is sdLDL a valuable screening tool for cardiovascular disease in patients with metabolic syndrome? Alexandria J Med 53:299–305. https://doi.org/10.1016/j.ajme.2017.01.002
Packard CJ, Boren J, Taskinen MR (2020) Causes and consequences of hypertriglyceridemia. Front Endocrinol (Lausanne) 11:1–15. https://doi.org/10.3389/fendo.2020.00252
Anderson JW (1987) Dietary fiber, lipids and atherosclerosis. Am J Cardiol 60:G17–G22. https://doi.org/10.1016/0002-9149(87)90587-X
National Research Council (US) Committee on Diet and Health (1989) Diet and health: implications for reducing chronic disease risk. National Academies Press (US), Washington (DC)
Nishina PM, Freedland RA (1990) The effects of dietary fiber feeding on cholesterol metabolism in rats. J Nutr 120:800–805. https://doi.org/10.1093/jn/120.7.800
Schneeman BO, Gallaher D (1985) Effects of dietary fiber on digestive enzyme activity and bile acids in the small intestine. Proc Soc Exp Biol Med 180:409–414. https://doi.org/10.3181/00379727-180-42197
Slavin J, Green H (2007) Dietary fibre and satiety. Nutr Bull 32:32–42. https://doi.org/10.1111/j.1467-3010.2007.00603.x
Kontush A, Chapman MJ (2006) Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. Pharmacol Rev 58:342–374. https://doi.org/10.1124/pr.58.3.1
Oravec S, Dukat A, Gavornik P, Kucera M, Gruber K, Gaspar L, Rizzo M, Toth PP, Mikhailidis DP, Banach M (2014) Atherogenic versus non-atherogenic lipoprotein profiles in healthy individuals. Is There a need to change our approach to diagnosing dyslipidemia? Curr Med Chem 21:2892–2901. https://doi.org/10.2174/0929867321666140303153048
Zeljkovic A, Vekic J, Spasojevic-Kalimanovska V, Jelic-Ivanovic Z, Bogavac-Stanojevic N, Gulan B, Spasic S (2010) LDL and HDL subclasses in acute ischemic stroke: prediction of risk and short-term mortality. Atherosclerosis 210:548–554. https://doi.org/10.1016/j.atherosclerosis.2009.11.040
Lopez-Sandoval J, Sanchez-Enriquez S, Rivera-Leon EA, Bastidas-Ramirez BE, Garcia-Garcia MR, Gonzalez-Hita ME (2018) Cardiovascular risk factors in adolescents: Role of insulin resistance and obesity. Acta Endocrinol 14:330–337. https://doi.org/10.4183/aeb.2018.330
Pires A, Martins P, Pereira AM, Silva PV, Marinho J, Marques M, Castela E, Sena C, Seiça R (2015) Insulin resistance, dyslipidemia and cardiovascular changes in a group of obese children. Arq Bras Cardiol 104:266–273. https://doi.org/10.5935/abc.20140206
Davy BM, Davy KP, Ho RC, Beske SD, Davrath LR, Melby CL (2002) High-fiber oat cereal compared with wheat cereal consumption favorably alters LDL-cholesterol subclass and particle numbers in middle-aged and older men. Am J Clin Nutr 76:351–358. https://doi.org/10.1093/ajcn/76.2.351
Vega-López S, Vidal-Quintanar RL, Femandez ML (2001) Sex and hormonal status influence plasma lipid responses to psyllium. Am J Clin Nutr 74:435–441. https://doi.org/10.1093/ajcn/74.4.435
Marcos-Gómez B, Bustos M, Prieto J, Martínez JA, Moreno-Aliaga MJ (2008) Obesity, inflammation and insulin resistance: Role of gp 130 receptor ligands. An Sist Sanit Navar 31:113–123
Negre-Salvayre A, Dousset N, Ferretti G, Bacchetti T, Curatola G, Salvayre R (2006) Antioxidant and cytoprotective properties of high-density lipoproteins in vascular cells. Free Radic Biol Med 41:1031–1040. https://doi.org/10.1016/j.freeradbiomed.2006.07.006
González Hernández MA, Canfora EE, Jocken JWE, Blaak EE (2019) The short-chain fatty acid acetate in body weight control and insulin sensitivity. Nutrients 11. https://doi.org/10.3390/nu11081943
da Silva ST, dos Santos CA, Bressan J (2013) Intestinal microbiota; relevance to obesity and modulation by prebiotics and probiotics. Nutr Hosp 28:1039–1048. https://doi.org/10.3305/nh.2013.28.4.6525
Song YJ, Sawamura M, Ikeda K, Igawa S, Yamori Y (2000) Soluble dietary fibre improves insulin sensitivity by increasing muscle GLUT-4 content in stroke-prone spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 27:41–45. https://doi.org/10.1046/j.1440-1681.2000.03198.x
Bozzetto L, Costabile G, Della Pepa G, Ciciola P, Vetrani C, Vitale M, Rivellese AA, Annuzzi G (2018) Dietary fibre as a unifying remedy for the whole spectrum of obesity-associated cardiovascular risk. Nutrients 10. https://doi.org/10.3390/nu10070943
Funding
University of Guanajuato (DAIP 211/2019 and 195/2020), Mining Company Santa María de la Paz, SLP, México, Touro-University California, Vallejo Ca. USA.
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design; material preparation, data collection, and analysis were performed by Alma Patricia González, Anaisa Flores Ramírez, Karla Paola Gutiérrez Castro, Claudia Luévano Contreras, Russell Caccavello, Ma Eugenia Garay-Sevilla, and Alejandro Gugliucci]; the first draft of the manuscript was written by Alma Patricia González mentored by Ma Eugenia Garay-Sevilla and Alejandro Gugliucci, and all authors gave their input. All authors read and approved the final manuscript.
Corresponding authors
Ethics declarations
Ethics approval
Ethics approval for this study was provided by the Locals Ethics Committees [University of Guanajuato (CIBIUG-P40-2017) and the Mexican Institute of Social Security, (R-2018-1002-052)] ISRCTN # 14180431.
Consent to participate
Written informed consent was obtained from the parents, and from all individual participants included in the study.
Consent for publication
All adolescents and their parents gave consent for the publication of their data anonymously if is necessary.
Conflicts of interest
The authors declare no competing interests.
Additional information
Communicated by Peter de Winter
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
ESM 1
(DOCX 13 kb)
Rights and permissions
About this article
Cite this article
González, A.P., Flores-Ramírez, A., Gutiérrez-Castro, K.P. et al. Reduction of small dense LDL and Il-6 after intervention with Plantago psyllium in adolescents with obesity: a parallel, double blind, randomized clinical trial. Eur J Pediatr 180, 2493–2503 (2021). https://doi.org/10.1007/s00431-021-04064-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00431-021-04064-5