Reformulation initiative for partial replacement of saturated with unsaturated fats in dairy foods attenuates the increase in LDL cholesterol and improves flow-mediated dilatation compared with conventional dairy: the randomized, controlled REplacement of SaturatEd fat in dairy on Total cholesterol (RESET) study

Dafni Vasilopoulou, Oonagh Markey, Kirsty E Kliem, Colette C Fagan, Alistair S Grandison, David J Humphries, Susan Todd, Kim G Jackson, David I Givens, Julie A Lovegrove, Dafni Vasilopoulou, Oonagh Markey, Kirsty E Kliem, Colette C Fagan, Alistair S Grandison, David J Humphries, Susan Todd, Kim G Jackson, David I Givens, Julie A Lovegrove

Abstract

Background: Modifying dairy fat composition by increasing the MUFA content is a potential strategy to reduce dietary SFA intake for cardiovascular disease (CVD) prevention in the population.

Objectives: To determine the effects of consuming SFA-reduced, MUFA-enriched (modified) dairy products, compared with conventional dairy products (control), on the fasting cholesterol profile (primary outcome), endothelial function assessed by flow-mediated dilatation (FMD; key secondary outcome), and other cardiometabolic risk markers.

Methods: A double-blind, randomized, controlled crossover 12-wk intervention was conducted. Participants with a 1.5-fold higher (moderate) CVD risk than the population mean replaced habitual dairy products with study products (milk, cheese, and butter) to achieve a high-fat, high-dairy isoenergetic daily dietary exchange [38% of total energy intake (%TE) from fat: control (dietary target: 19%TE SFA; 11%TE MUFA) and modified (16%TE SFA; 14%TE MUFA) diet].

Results: Fifty-four participants (57.4% men; mean ± SEM age: 52 ± 3 y; BMI: 25.8 ± 0.5 kg/m2) completed the study. The modified diet attenuated the rise in fasting LDL cholesterol observed with the control diet (0.03 ± 0.06 mmol/L and 0.19 ± 0.05 mmol/L, respectively; P = 0.03). Relative to baseline, the %FMD response increased after the modified diet (0.35% ± 0.15%), whereas a decrease was observed after the control diet (-0.51% ± 0.15%; P< 0.0001). In addition, fasting plasma nitrite concentrations increased after the modified diet, yet decreased after the control diet (0.02 ± 0.01 μmol/L and -0.03 ± 0.02 μmol/L, respectively; P = 0.01).

Conclusions: In adults at moderate CVD risk, consumption of a high-fat diet containing SFA-reduced, MUFA-enriched dairy products for 12 wk showed beneficial effects on fasting LDL cholesterol and endothelial function compared with conventional dairy products. Our findings indicate that fatty acid modification of dairy products may have potential as a public health strategy aimed at CVD risk reduction. This trial was registered at clinicaltrials.gov as NCT02089035.

Keywords: cardiovascular disease risk; cholesterol profile; dairy fat; flow-mediated dilatation; food chain approach; monounsaturated fatty acids; reformulation; saturated fatty acids; vascular function.

Copyright © The Author(s) 2020.

Figures

FIGURE 1
FIGURE 1
Δ fasting cholesterol profile after 12-wk diets that incorporated modified and control dairy products. Values are unadjusted means ± SEMs. n = 54. Linear mixed-model analyses were used to calculate overall effect of treatment based on Δ values, with adjustments made for fixed effects of baseline values of the assessed variable, period, treatment sequence, gender, age, and BMI. Participant was included as a random effect. The Δ values after each 12-wk dietary intervention were calculated by subtracting week 0 from week 12 values; and week 20 from week 32 values. No period effects were observed in the model for any outcome measure. *< 0.05. HDL-C, HDL cholesterol; LDL-C, LDL cholesterol; TC, total cholesterol; Δ, change-from-baseline.

References

    1. Mensink RP, Zock PL, Kester AD, Katan MB. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr. 2003;77(5):1146–55.
    1. Joris PJ, Mensink RP. Role of cis-monounsaturated fatty acids in the prevention of coronary heart disease. Curr Atheroscler Rep. 2016;18(7):38.
    1. Roberts C, Steer T, Maplethorpe N, Cox L, Meadows S, Nicholson S, Page P, Swan G. National Diet and Nutrition Survey. Results from Years 7–8 (combined) of the Rolling Programme (2014/2015 to 2015/2016). London: Public Health England; 2018.
    1. Lovegrove JA, Givens DI. Dairy food products: good or bad for cardiometabolic disease?. Nutr Res Rev. 2016;29(2):249–67.
    1. Thorning TK, Bertram HC, Bonjour J-P, de Groot L, Dupont D, Feeney E, Ipsen R, Lecerf JM, Mackie A, McKinley MC et al. .. Whole dairy matrix or single nutrients in assessment of health effects: current evidence and knowledge gaps. Am J Clin Nutr. 2017;105(5):1033–45.
    1. Feeney EL, Barron R, Dible V, Hamilton Z, Power Y, Tanner L, Flynn C, Bouchier P, Beresford T, Noronha N et al. .. Dairy matrix effects: response to consumption of dairy fat differs when eaten within the cheese matrix—a randomized controlled trial. Am J Clin Nutr. 2018;108(4):667–74.
    1. Siri-Tarino PW, Sun Q, Hu FB, Krauss RM. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Am J Clin Nutr. 2010;91(3):535–46.
    1. Chowdhury R, Warnakula S, Kunutsor S, Crowe F, Ward HA, Johnson L, Franco OH, Butterworth AS, Forouhi NG, Thompson SG et al. .. Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. Ann Intern Med. 2014;160(6):398–406.
    1. Scientific Advisory Committee on Nutrition. Saturated fats and health: draft SACN report. [Internet] London: Government Digital Service; 2018; [cited 29 April 2019]. Available from: .
    1. World Health Organization. Draft Guidelines on Saturated Fatty Acid and trans-fatty Acid Intake for Adults and Children [Internet]. Geneva: WHO; 2018; [cited 29 April 2019]. Available from: .
    1. Vafeiadou K, Weech M, Altowaijri H, Todd S, Yaqoob P, Jackson KG, Lovegrove JA. Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin, and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study. Am J Clin Nutr. 2015;102(1):40–8.
    1. de Souza RJ, Mente A, Maroleanu A, Cozma AI, Ha V, Kishibe T, Uleryk E, Budylowski P, Schünemann H, Beyene J et al. .. Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. BMJ. 2015;351:h3978.
    1. Jakobsen MU, O'Reilly EJ, Heitmann BL, Pereira MA, Bälter K, Fraser GE, Goldbourt U, Hallmans G, Knekt P, Liu S et al. .. Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies. Am J Clin Nutr. 2009;89(5):1425–32.
    1. Hooper L, Martin N, Abdelhamid A, Davey Smith G. Reduction in saturated fat intake for cardiovascular disease. Cochrane Database Syst Rev. 2015;(6):CD011737.
    1. Kliem KE, Humphries DJ, Markey O, Vasilopoulou D, Fagan CC, Grandison AS, Jackson KG, Todd S, Givens DI, Lovegrove JA. Food chain approach to lowering the saturated fat of milk and dairy products. Int J Dairy Technol. 2019;72:100–9.
    1. Markey O, Vasilopoulou D, Givens DI, Lovegrove JA. Dairy and cardiovascular health: friend or foe?. Nutr Bull. 2014;39(2):161–71.
    1. Anderson CA, Thorndike AN, Lichtenstein AH, Van Horn L, Kris-Etherton PM, Foraker R, Spees C. Innovation to create a healthy and sustainable food system: a Science Advisory from the American Heart Association. Circulation. 2019;139(23):e1025–32.
    1. Livingstone KM, Lovegrove JA, Givens DI. The impact of substituting SFA in dairy products with MUFA or PUFA on CVD risk: evidence from human intervention studies. Nutr Res Rev. 2012;25(2):193–206.
    1. Inaba Y, Chen JA, Bergmann SR. Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis. Int J Cardiovasc Imaging. 2010;26(6):631–40.
    1. Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol. 2003;23(2):168–75.
    1. Markey O, Vasilopoulou D, Kliem KE, Koulman A, Fagan CC, Summerhill K, Wang LY, Grandison AS, Humphries DJ, Todd S et al. .. Plasma phospholipid fatty acid profile confirms compliance to a novel saturated fat-reduced, monounsaturated fat-enriched dairy product intervention in adults at moderate cardiovascular risk: a randomized controlled trial. Nutr J. 2017;16(1):33.
    1. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97(18):1837–47.
    1. Markey O, Souroullas K, Fagan CC, Kliem KE, Vasilopoulou D, Jackson KG, Humphries DJ, Grandison AS, Givens DI, Lovegrove JA et al. .. Consumer acceptance of dairy products with a saturated fatty acid–reduced, monounsaturated fatty acid–enriched content. J Dairy Sci. 2017;100(10):7953–66.
    1. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499–502.
    1. Brady LM, Gower BA, Lovegrove SS, Williams CM, Lovegrove JA. Revised QUICKI provides a strong surrogate estimate of insulin sensitivity when compared with the minimal model. Int J Obes Relat Metab Disord. 2004;28(2):222–7.
    1. Bryan NS, Grisham MB. Methods to detect nitric oxide and its metabolites in biological samples. Free Radic Biol Med. 2007;43(5):645–57.
    1. Müller H, Kirkhus B, Pedersen JI. Serum cholesterol predictive equations with special emphasis on trans and saturated fatty acids. An analysis from designed controlled studies. Lipids. 2001;36:783–91.
    1. Soininen P, Kangas AJ, Würtz P, Suna T, Ala-Korpela M. Quantitative serum nuclear magnetic resonance metabolomics in cardiovascular epidemiology and genetics. Circ Cardiovasc Genet. 2015;8(1):192–206.
    1. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D et al. .. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002;39(2):257–65.
    1. Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, Csiba L, Desvarieux M, Ebrahim S, Hernandez Hernandez R et al. .. Mannheim carotid intima-media thickness and plaque consensus (2004–2006–2011). An update on behalf of the advisory board of the 3rd, 4th and 5th Watching the Risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovasc Dis. 2012;34(4):290–6.
    1. Keys A, Anderson JT, Grande F. Serum cholesterol response to changes in the diet: IV. Particular saturated fatty acids in the diet. Metabolism. 1965;14(7):776–87.
    1. De Roos NM, Bots ML, Schouten EG, Katan MB. Within-subject variability of flow-mediated vasodilation of the brachial artery in healthy men and women: implications for experimental studies. Ultrasound Med Biol. 2003;29(3):401–6.
    1. Streiner DL. Best (but oft-forgotten) practices: the multiple problems of multiplicity—whether and how to correct for many statistical tests. Am J Clin Nutr. 2015;102(4):721–8.
    1. Welch RW, Antoine J-M, Berta J-L, Bub A, de Vries J, Guarner F, Hasselwander O, Hendriks H, Jäkel M, Koletzko BV et al. .. Guidelines for the design, conduct and reporting of human intervention studies to evaluate the health benefits of foods. Br J Nutr. 2011;106(S2):S3–S15.
    1. Hegsted DM, McGandy RB, Myers ML, Stare FJ. Quantitative effects of dietary fat on serum cholesterol in man. Am J Clin Nutr. 1965;17(5):281–95.
    1. Mensink RP, Katan MB. Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Arterioscler Thromb. 1992;12(8):911–19.
    1. Clarke R, Frost C, Collins R, Appleby P, Peto R. Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies. BMJ. 1997;314(7074):112–17.
    1. Howell WH, McNamara DJ, Tosca MA, Smith BT, Gaines JA. Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta-analysis. Am J Clin Nutr. 1997;65(6):1747–64.
    1. Fernandez ML, West KL. Mechanisms by which dietary fatty acids modulate plasma lipids. J Nutr. 2005;135(9):2075–8.
    1. Silva KD, Kelly CN, Jones AE, Smith RD, Wootton SA, Miller GJ, Williams CM. Chylomicron particle size and number, factor VII activation and dietary monounsaturated fatty acids. Atherosclerosis. 2003;166(1):73–84.
    1. Jackson KG, Maitin V, Leake DS, Yaqoob P, Williams CM. Saturated fat-induced changes in Sf 60–400 particle composition reduces uptake of LDL by HepG2 cells. J Lipid Res. 2006;47(2):393–403.
    1. Desroches S, Lamarche B. Diet and low-density lipoprotein particle size. Curr Atheroscler Rep. 2004;6(6):453–60.
    1. Gayet-Boyer C, Tenenhaus-Aziza F, Prunet C, Marmonier C, Malpuech-Brugère C, Lamarche B, Chardigny JM. Is there a linear relationship between the dose of ruminant trans-fatty acids and cardiovascular risk markers in healthy subjects: results from a systematic review and meta-regression of randomised clinical trials. Br J Nutr. 2014;112(12):1914–22.
    1. Keogh JB, Grieger JA, Noakes M, Clifton PM. Flow-mediated dilatation is impaired by a high–saturated fat diet but not by a high-carbohydrate diet. Arterioscler Thromb Vasc Biol. 2005;25(6):1274–9.
    1. Fuentes F, López-Miranda J, Sánchez E, Sánchez F, Paez J, Paz-Rojas E, Marín C, Gómez P, Jimenez-Perepérez J, Ordovás JM et al. .. Mediterranean and low-fat diets improve endothelial function in hypercholesterolemic men. Ann Intern Med. 2001;134(12):1115–19.
    1. Tentolouris N, Arapostathi C, Perrea D, Kyriaki D, Revenas C, Katsilambros N. Differential effects of two isoenergetic meals rich in saturated or monounsaturated fat on endothelial function in subjects with type 2 diabetes. Diabetes Care. 2008;31(12):2276–8.
    1. Moreno-Luna R, Muñoz-Hernandez R, Miranda ML, Costa AF, Jimenez-Jimenez L, Vallejo-Vaz AJ, Muriana FJ, Villar J, Stiefel P. Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension. Am J Hypertens. 2012;25(12):1299–304.
    1. Lundberg JO, Weitzberg E. NO generation from nitrite and its role in vascular control. Arterioscler Thromb Vasc Biol. 2005;25(5):915–22.
    1. Fuentes F, López-Miranda J, Pérez-Martínez P, Jiménez Y, Marín C, Gómez P, Fernández J, Caballero J, Delgado-Lista J, Pérez-Jiménez F. Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with α-linolenic acid on postprandial endothelial function in healthy men. Br J Nutr. 2008;100(1):159–65.
    1. Stranieri S, Ricci EC, Banterle A. Convenience food with environmentally-sustainable attributes: a consumer perspective. Appetite. 2017;116:11–20.

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