Cardiometabolic Benefits of a Weight-Loss Mediterranean Diet/Lifestyle Intervention in Patients with Obstructive Sleep Apnea: The “MIMOSA” Randomized Clinical Trial
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Participants
2.3. Randomization
2.4. Interventions
2.5. Assessments
2.6. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Greenstone, M.; Hack, M. Obstructive sleep apnoea. BMJ 2014, 348, g3745. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gaines, J.; Vgontzas, A.N.; Fernandez-Mendoza, J.; Bixler, E.O. Obstructive sleep apnea and the metabolic syndrome: The road to clinically-meaningful phenotyping, improved prognosis, and personalized treatment. Sleep Med. Rev. 2018, 42, 211–219. [Google Scholar] [CrossRef] [PubMed]
- Romero-Corral, A.; Caples, S.M.; Lopez-Jimenez, F.; Somers, V.K. Interactions between obesity and obstructive sleep apnea: Implications for treatment. Chest 2010, 137, 711–719. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vgontzas, A.N.; Gaines, J.; Ryan, S.; McNicholas, W.T. CrossTalk proposal: Metabolic syndrome causes sleep apnoea. J. Physiol. 2016, 594, 4687–4690. [Google Scholar] [CrossRef]
- Levy, P.; Bonsignore, M.R.; Eckel, J. Sleep, sleep-disordered breathing and metabolic consequences. Eur. Respir. J. 2009, 34, 243–260. [Google Scholar] [CrossRef] [Green Version]
- Epstein, L.J.; Kristo, D.; Strollo, P.J., Jr.; Friedman, N.; Malhotra, A.; Patil, S.P.; Ramar, K.; Rogers, R.; Schwab, R.J.; Weaver, E.M.; et al. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J. Clin. Sleep Med. 2009, 5, 263–276. [Google Scholar]
- Feng, Y.; Zhang, Z.; Dong, Z.Z. Effects of continuous positive airway pressure therapy on glycaemic control, insulin sensitivity and body mass index in patients with obstructive sleep apnoea and type 2 diabetes: A systematic review and meta-analysis. NPJ Prim. Care Respir. Med. 2015, 25, 15005. [Google Scholar] [CrossRef]
- Jullian-Desayes, I.; Joyeux-Faure, M.; Tamisier, R.; Launois, S.; Borel, A.L.; Levy, P.; Pepin, J.L. Impact of obstructive sleep apnea treatment by continuous positive airway pressure on cardiometabolic biomarkers: A systematic review from sham CPAP randomized controlled trials. Sleep Med. Rev. 2015, 21, 23–38. [Google Scholar] [CrossRef]
- Araghi, M.H.; Chen, Y.F.; Jagielski, A.; Choudhury, S.; Banerjee, D.; Hussain, S.; Thomas, G.N.; Taheri, S. Effectiveness of lifestyle interventions on obstructive sleep apnea (OSA): Systematic review and meta-analysis. Sleep 2013, 36, 1553–1562, 1562A–1562E. [Google Scholar] [CrossRef]
- Mitchell, L.J.; Davidson, Z.E.; Bonham, M.; O’Driscoll, D.M.; Hamilton, G.S.; Truby, H. Weight loss from lifestyle interventions and severity of sleep apnoea: A systematic review and meta-analysis. Sleep Med. 2014, 15, 1173–1183. [Google Scholar] [CrossRef]
- Chirinos, J.A.; Gurubhagavatula, I.; Teff, K.; Rader, D.J.; Wadden, T.A.; Townsend, R.; Foster, G.D.; Maislin, G.; Saif, H.; Broderick, P.; et al. CPAP, Weight Loss, or Both for Obstructive Sleep Apnea. N. Engl. J. Med. 2014, 370, 2265–2275. [Google Scholar] [CrossRef] [Green Version]
- Tuomilehto, H.P.; Seppa, J.M.; Partinen, M.M.; Peltonen, M.; Gylling, H.; Tuomilehto, J.O.; Vanninen, E.J.; Kokkarinen, J.; Sahlman, J.K.; Martikainen, T.; et al. Lifestyle intervention with weight reduction: First-line treatment in mild obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 2009, 179, 320–327. [Google Scholar] [CrossRef] [PubMed]
- Barnes, M.; Goldsworthy, U.R.; Cary, B.A.; Hill, C.J. A diet and exercise program to improve clinical outcomes in patients with obstructive sleep apnea--a feasibility study. J. Clin. Sleep Med. 2009, 5, 409–415. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nerfeldt, P.; Nilsson, B.Y.; Mayor, L.; Udden, J.; Friberg, D. A two-year weight reduction program in obese sleep apnea patients. J. Clin. Sleep Med. 2010, 6, 479–486. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dobrosielski, D.A.; Papandreou, C.; Patil, S.P.; Salas-Salvado, J. Diet and exercise in the management of obstructive sleep apnoea and cardiovascular disease risk. Eur. Respir. Rev. 2017, 26. [Google Scholar] [CrossRef]
- World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. JAMA 2013, 310, 2191–2194. [Google Scholar] [CrossRef] [Green Version]
- Han, B.; Enas, N.H.; McEntegart, D. Randomization by minimization for unbalanced treatment allocation. Stat. Med. 2009, 28, 3329–3346. [Google Scholar] [CrossRef]
- Kushida, C.A.; Chediak, A.; Berry, R.B.; Brown, L.K.; Gozal, D.; Iber, C.; Parthasarathy, S.; Quan, S.F.; Rowley, J.A.; Positive Airway Pressure Titration Task Force of the American Academy of Sleep Medicine. Clinical guidelines for the manual titration of positive airway pressure in patients with obstructive sleep apnea. J. Clin. Sleep Med. 2008, 4, 157–171. [Google Scholar]
- Wadden, T.A.; Webb, V.L.; Moran, C.H.; Bailer, B.A. Lifestyle modification for obesity: New developments in diet, physical activity, and behavior therapy. Circulation 2012, 125, 1157–1170. [Google Scholar] [CrossRef] [Green Version]
- Wadden, T.A.; Butryn, M.L.; Wilson, C. Lifestyle modification for the management of obesity. Gastroenterology 2007, 132, 2226–2238. [Google Scholar] [CrossRef]
- Wadden, T.A.; Foster, G.D. Behavioral treatment of obesity. Med. Clin. N. Am. 2000, 84, 441–461. [Google Scholar] [CrossRef]
- Bach-Faig, A.; Berry, E.M.; Lairon, D.; Reguant, J.; Trichopoulou, A.; Dernini, S.; Medina, F.X.; Battino, M.; Belahsen, R.; Miranda, G.; et al. Mediterranean diet pyramid today. Science and cultural updates. Public Health Nutr. 2011, 14, 2274–2284. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- World Health Organization. Global Recommendations on Physical Activity for Health; World Health Organization: Geneva, Switzerland, 2010. [Google Scholar]
- Watson, N.F.; Badr, M.S.; Belenky, G.; Bliwise, D.L.; Buxton, O.M.; Buysse, D.; Dinges, D.F.; Gangwisch, J.; Grandner, M.A.; Kushida, C.; et al. Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society. Sleep 2015, 38, 843–844. [Google Scholar] [CrossRef] [PubMed]
- Bountziouka, V.; Bathrellou, E.; Giotopoulou, A.; Katsagoni, C.; Bonou, M.; Vallianou, N.; Barbetseas, J.; Avgerinos, P.C.; Panagiotakos, D.B. Development, repeatability and validity regarding energy and macronutrient intake of a semi-quantitative food frequency questionnaire: Methodological considerations. Nutr. Metab. Cardiovasc. Dis. 2012, 22, 659–667. [Google Scholar] [CrossRef] [PubMed]
- Panagiotakos, D.B.; Pitsavos, C.; Arvaniti, F.; Stefanadis, C. Adherence to the Mediterranean food pattern predicts the prevalence of hypertension, hypercholesterolemia, diabetes and obesity, among healthy adults; the accuracy of the MedDietScore. Prev. Med. 2007, 44, 335–340. [Google Scholar] [CrossRef]
- Jonnalagadda, S.S.; Mitchell, D.C.; Smiciklas-Wright, H.; Meaker, K.B.; Van Heel, N.; Karmally, W.; Ershow, A.G.; Kris-Etherton, P.M. Accuracy of energy intake data estimated by a multiple-pass, 24-h dietary recall technique. J. Am. Diet. Assoc. 2000, 100, 303–308, quiz 309–311. [Google Scholar] [CrossRef]
- Carlson, R.V.; van Ginneken, N.H.; Pettigrew, L.M.; Davies, A.; Boyd, K.M.; Webb, D.J. The three official language versions of the Declaration of Helsinki: What’s lost in translation? J. Med. Ethics 2007, 33, 545–548. [Google Scholar] [CrossRef] [Green Version]
- Papathanasiou, G.; Georgoudis, G.; Georgakopoulos, D.; Katsouras, C.; Kalfakakou, V.; Evangelou, A. Criterion-related validity of the short International Physical Activity Questionnaire against exercise capacity in young adults. Eur. J. Cardiovasc. Prev. Rehabil. 2010, 17, 380–386. [Google Scholar] [CrossRef]
- Friedewald, W.T.; Levy, R.I.; Fredrickson, D.S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem. 1972, 18, 499–502. [Google Scholar] [CrossRef]
- Matthews, D.R.; Hosker, J.P.; Rudenski, A.S.; Naylor, B.A.; Treacher, D.F.; Turner, R.C. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28, 412–419. [Google Scholar] [CrossRef] [Green Version]
- Muntner, P.; Shimbo, D.; Carey, R.M.; Charleston, J.B.; Gaillard, T.; Misra, S.; Myers, M.G.; Ogedegbe, G.; Schwartz, J.E.; Townsend, R.R.; et al. Measurement of Blood Pressure in Humans: A Scientific Statement From the American Heart Association. Hypertension 2019, 73, e35–e66. [Google Scholar] [CrossRef] [PubMed]
- Alberti, K.G.; Eckel, R.H.; Grundy, S.M.; Zimmet, P.Z.; Cleeman, J.I.; Donato, K.A.; Fruchart, J.C.; James, W.P.; Loria, C.M.; Smith, S.C. Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009, 120, 1640–1645. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, S.; Wan, Y.; Xu, M.; Ming, J.; Xing, Y.; An, F.; Ji, Q. The association between obstructive sleep apnea and metabolic syndrome: A systematic review and meta-analysis. BMC Pulm. Med. 2015, 15, 105. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Esposito, K.; Kastorini, C.M.; Panagiotakos, D.B.; Giugliano, D. Mediterranean diet and metabolic syndrome: An updated systematic review. Rev. Endocr. Metab. Disord. 2013, 14, 255–263. [Google Scholar] [CrossRef]
- Little, R.J.; D’Agostino, R.; Cohen, M.L.; Dickersin, K.; Emerson, S.S.; Farrar, J.T.; Frangakis, C.; Hogan, J.W.; Molenberghs, G.; Murphy, S.A.; et al. The prevention and treatment of missing data in clinical trials. N. Engl. J. Med. 2012, 367, 1355–1360. [Google Scholar] [CrossRef] [Green Version]
- Bland, J.M.; Altman, D.G. Multiple significance tests: The Bonferroni method. BMJ 1995, 310, 170. [Google Scholar] [CrossRef] [Green Version]
- Coughlin, S.; Calverley, P.; Wilding, J. Sleep disordered breathing--a new component of syndrome x? Obes. Rev. 2001, 2, 267–274. [Google Scholar] [CrossRef]
- Yu, J.; Zhou, Z.; McEvoy, R.D.; Anderson, C.S.; Rodgers, A.; Perkovic, V.; Neal, B. Association of Positive Airway Pressure With Cardiovascular Events and Death in Adults With Sleep Apnea: A Systematic Review and Meta-analysis. JAMA 2017, 318, 156–166. [Google Scholar] [CrossRef]
- Patil, S.P.; Ayappa, I.A.; Caples, S.M.; Kimoff, R.J.; Patel, S.R.; Harrod, C.G. Treatment of Adult Obstructive Sleep Apnea With Positive Airway Pressure: An American Academy of Sleep Medicine Systematic Review, Meta-Analysis, and GRADE Assessment. J. Clin. Sleep Med. 2019, 15, 301–334. [Google Scholar] [CrossRef]
- Yumuk, V.; Tsigos, C.; Fried, M.; Schindler, K.; Busetto, L.; Micic, D.; Toplak, H. European Guidelines for Obesity Management in Adults. Obes. Facts 2015, 8, 402–424. [Google Scholar] [CrossRef]
- Lin, X.; Zhang, X.; Guo, J.; Roberts, C.K.; McKenzie, S.; Wu, W.C.; Liu, S.; Song, Y. Effects of Exercise Training on Cardiorespiratory Fitness and Biomarkers of Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J. Am. Heart Assoc. 2015, 4. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Henst, R.H.P.; Pienaar, P.R.; Roden, L.C.; Rae, D.E. The effects of sleep extension on cardiometabolic risk factors: A systematic review. J. Sleep Res. 2019, 28, e12865. [Google Scholar] [CrossRef] [PubMed]
Total (n = 187) | SCG (n = 65) | MDG (n = 62) | MLG (n = 60) | p * | |
---|---|---|---|---|---|
Age, years | 49 ± 10 | 48 ± 10 | 50 ± 9.1 | 48 ± 10 | 0.2 |
Male sex, n (%) | 141 (75) | 51 (79) | 44 (71) | 46 (77) | 0.6 |
Current smokers, n (%) | 61 (33) | 19 (29) | 26 (42) | 16 (27) | 0.2 |
BMI, kg/m2 | 35.6 ± 6.0 | 36.1 ± 6.4 | 34.9 ± 5.9 | 35.8 ± 6.0 | 0.5 |
Obesity, n (%) a | 150 (80) | 52 (80) | 48 (77) | 50 (83) | 0.7 |
Energy intake, kJ/day | 9699 ± 3117 | 9326 ± 3029 | 10071 ± 3427 | 9719 ± 2879 | 0.4 |
MedDietScore (0–55) | 32.1 ± 4.4 | 32.2 ± 4.5 | 31.7 ± 4.4 | 32.4 ± 4.5 | 0.7 |
Physical activity, min/day | 13 (2.9, 34) | 11 (0.0, 34) | 11 (0.0, 30) | 17 (6.4, 40) | 0.2 |
Sleep duration, h/day | 6.1 ± 1.5 | 6.0 ± 1.8 | 6.1 ± 1.2 | 6.2 ± 1.5 | 0.8 |
AHI, events/h | 58 (31, 85) | 52 (31, 87) | 60 (35, 81) | 62 (21, 89) | 0.9 |
Severe OSA, n (%) b | 143 (77) | 50 (78) | 50 (81) | 42 (70) | 0.4 |
CPAP therapy, n (%) | 142 (76) | 53 (82) | 43 (69) | 46 (77) | 0.2 |
Increased WC, n (%) c | 169 (90) | 59 (91) | 53 (86) | 57 (95) | 0.1 |
Increased TG, n (%) d | 81 (43) | 34 (52) | 20 (32) | 27 (45) | 0.1 |
Decreased HDLC, n (%) e | 102 (55) | 37 (57) | 31 (50) | 34 (57) | 0.7 |
Hypertension, n (%) f | 135 (72) | 45 (69) | 47 (76) | 43 (72) | 0.7 |
Hyperglycemia, n (%) g | 45 (24) | 13 (20) | 16 (26) | 16 (27) | 0.5 |
Presence of MS, n (%) h | 115 (62) | 42 (65) | 31 (50) | 42 (70) | 0.1 |
MDG vs. SCG | MLG vs. SCG | MLG vs. MDG | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
MD | 95%CI | p * | p ** | MD | 95%CI | p * | p ** | MD | 95%CI | p * | p ** | |
Body weight, kg | −8.96 | −12.6, −6.33 | <0.001 | - | −12.6 | −15.3, −9.93 | <0.001 | - | −3.63 | −6.29, −0.97 | 0.004 | - |
BMI, kg/m2 | −3.07 | −3.93, −2.22 | <0.001 | - | −4.21 | −5.07, −3.35 | <0.001 | - | −1.14 | −2.00, −0.27 | 0.005 | - |
WC, cm | −5.51 | −8.50, −2.51 | <0.001 | - | −7.74 | −10.8, −4.71 | <0.001 | - | −2.23 | −5.26, 0.80 | 0.2 | - |
Glucose, mmol/L a | −0.26 | −0.47, −0.05 | 0.006 | 0.1 | −0.17 | −0.38, 0.05 | 0.2 | >0.9 | 0.10 | −0.11, 0.31 | 0.6 | 0.4 |
Insulin, pmol/L b | −24.4 | −47.1, −1.64 | 0.002 | 0.7 | −51.8 | −74.8, −28.8 | <0.001 | 0.05 | −27.4 | −50.3, −4.59 | 0.05 | 0.4 |
HOMA-IR | −1.10 | −2.10, −0.10 | 0.001 | 0.5 | −2.19 | −3.21, −1.17 | <0.001 | 0.05 | −1.09 | −2.11, −0.08 | 0.02 | 0.8 |
TC, mmol/L c | −0.27 | −0.57, 0.02 | 0.08 | >0.9 | −0.10 | −0.40, 0.20 | 0.5 | >0.9 | 0.17 | −0.13, 0.47 | >0.9 | 0.3 |
LDLC, mmol/L c | −0.15 | −0.41, 0.12 | 0.6 | 0.8 | −0.02 | −0.28, 0.25 | >0.9 | >0.9 | 0.13 | −0.14, 0.40 | 0.7 | 0.8 |
HDLC, mmol/L c | 0.05 | −0.01, 0.11 | 0.1 | 0.08 | 0.15 | 0.09, 0.21 | <0.001 | <0.001 | 0.09 | 0.03, 0.15 | 0.001 | <0.001 |
nHDLC, mmol/Lc | −0.34 | −0.62, −0.06 | 0.01 | 0.3 | −0.24 | −0.53, 0.04 | 0.1 | >0.9 | 0.10 | −0.19, 0.38 | >0.9 | 0.8 |
TG, mmol/L d | −0.41 | −0.68, −0.14 | <0.001 | 0.1 | −0.49 | −0.76, −0.21 | <0.001 | 0.01 | −0.07 | −0.35, 0.20 | >0.9 | >0.9 |
TC/HDLC | −0.59 | −0.93, −0.24 | <0.001 | 0.01 | −0.74 | −1.09, −0.39 | <0.001 | 0.004 | −0.15 | −0.50, 0.20 | 0.9 | >0.9 |
TG/HDLC | −0.52 | −0.84, −0.20 | <0.001 | 0.01 | −0.72 | −1.05, −0.40 | <0.001 | 0.01 | −0.20 | −0.52, 0.13 | 0.4 | >0.9 |
ALT, U/L | −2.14 | −4.32, −0.04 | 0.008 | 0.2 | −3.42 | −5.64, −1.12 | <0.001 | 0.08 | −1.28 | −3.50, 0.93 | 0.5 | >0.9 |
AST, U/L | −4.60 | −7.79, −1.41 | 0.001 | 0.4 | −6.98 | −10.2, −3.75 | <0.001 | 0.2 | −2.38 | −5.62, 0.86 | 0.5 | >0.9 |
GGT, U/L | −10.1 | −17.8, −2.39 | <0.001 | 0.3 | −9.66 | −17.4, −1.89 | <0.001 | >0.9 | 0.43 | −7.36, 8.22 | >0.9 | 0.3 |
SBP, mmHg | −7.29 | −12.2, −2.43 | 0.001 | 0.5 | −6.93 | −11.8, −2.04 | 0.002 | >0.9 | 0.37 | −4.49, 5.22 | >0.9 | >0.9 |
DBP, mmHg | −9.52 | −13.4, −5.63 | <0.001 | 0.001 | −6.70 | −10.6, −2.81 | <0.001 | 0.01 | 2.82 | −1.08, 6.71 | 0.3 | 0.6 |
MDG vs. SCG | MLG vs. SCG | MLG vs. MDG | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
RR | 95%CI | p * | p ** | RR | 95%CI | p * | p ** | RR | 95%CI | p * | p ** | |
Increased WC a | 0.68 | 0.17, 2.70 | 0.6 | 0.9 | 0.22 | 0.06, 0.85 | 0.02 | 0.2 | 0.33 | 0.12, 0.91 | 0.04 | 0.2 |
Increased TG b | 0.51 | 0.26, 0.99 | 0.08 | >0.9 | 0.46 | 0.24, 0.90 | 0.05 | >0.9 | 0.92 | 0.45, 1.85 | 0.8 | >0.9 |
Decreased HDLC c | 0.54 | 0.30, 0.98 | 0.04 | 0.01 | 0.27 | 0.14, 0.52 | <0.001 | <0.001 | 0.51 | 0.29, 0.90 | 0.03 | 0.01 |
Hypertension d | 0.60 | 0.35, 0.99 | 0.09 | >0.9 | 0.38 | 0.23, 0.64 | <0.001 | >0.9 | 0.64 | 0.39, 1.06 | 0.09 | >0.9 |
Hyperglycemia e | 0.68 | 0.39, 1.19 | 0.3 | 0.7 | 0.60 | 0.34, 1.07 | 0.2 | 0.7 | 0.88 | 0.49, 1.59 | 0.7 | 0.7 |
Presence of MS f | 0.58 | 0.34, 0.99 | 0.04 | 0.4 | 0.30 | 0.17, 0.52 | <0.001 | 0.05 | 0.52 | 0.30, 0.89 | 0.04 | 0.08 |
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Georgoulis, M.; Yiannakouris, N.; Kechribari, I.; Lamprou, K.; Perraki, E.; Vagiakis, E.; Kontogianni, M.D. Cardiometabolic Benefits of a Weight-Loss Mediterranean Diet/Lifestyle Intervention in Patients with Obstructive Sleep Apnea: The “MIMOSA” Randomized Clinical Trial. Nutrients 2020, 12, 1570. https://0-doi-org.brum.beds.ac.uk/10.3390/nu12061570
Georgoulis M, Yiannakouris N, Kechribari I, Lamprou K, Perraki E, Vagiakis E, Kontogianni MD. Cardiometabolic Benefits of a Weight-Loss Mediterranean Diet/Lifestyle Intervention in Patients with Obstructive Sleep Apnea: The “MIMOSA” Randomized Clinical Trial. Nutrients. 2020; 12(6):1570. https://0-doi-org.brum.beds.ac.uk/10.3390/nu12061570
Chicago/Turabian StyleGeorgoulis, Michael, Nikos Yiannakouris, Ioanna Kechribari, Kallirroi Lamprou, Eleni Perraki, Emmanouil Vagiakis, and Meropi D Kontogianni. 2020. "Cardiometabolic Benefits of a Weight-Loss Mediterranean Diet/Lifestyle Intervention in Patients with Obstructive Sleep Apnea: The “MIMOSA” Randomized Clinical Trial" Nutrients 12, no. 6: 1570. https://0-doi-org.brum.beds.ac.uk/10.3390/nu12061570