Body Weight Variation Patterns as Predictors of Cognitive Decline over a 5 Year Follow-Up among Community-Dwelling Elderly (MAPT Study)
Abstract
:1. Introduction
2. Methods
2.1. Study Population
2.2. Confounders
2.3. Weight Variation Patterns
2.4. Outcomes: Cognitive Score and Hippocampal Volume
2.5. Statistical Analysis
3. Results
3.1. Characterization of the Sample
3.2. Changes in Cognitive Z-score According to Body Weight Variation Patterns
3.3. Changes in Hippocampus Volume According to Body Weight Variation Patterns
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
MAPT/DSA Group
References
- Guh, D.P.; Zhang, W.; Bansback, N.; Amarsi, Z.; Birmingham, C.L.; Anis, A.H. The incidence of co-morbidities related to obesity and overweight: A systematic review and meta-analysis. BMC Public Health 2009, 9, 88. [Google Scholar] [CrossRef] [PubMed]
- Kivipelto, M.; Ngandu, T.; Fratiglioni, L.; Viitanen, M.; Kåreholt, I.; Winblad, B.; Helkala, E.L.; Tuomilehto, J.; Soininen, H.; Nissinen, A. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch. Neurol. 2005, 62, 1556–1560. [Google Scholar] [CrossRef] [PubMed]
- Tolppanen, A.-M.; Ngandu, T.; Kåreholt, I.; Laatikainen, T.; Rusanen, M.; Soininen, H.; Kivipelto, M. Midlife and late-life body mass index and late-life dementia: Results from a prospective population-based cohort. J. Alzheimer’s Dis. 2014, 38, 201–209. [Google Scholar] [CrossRef] [PubMed]
- Dorrance, A.M.; Matin, N.; Pires, P.W. The effects of obesity on the cerebral vasculature. Curr. Vasc. Pharmacol. 2014, 12, 462–472. [Google Scholar] [CrossRef] [PubMed]
- Arnoldussen, I.A.C.; Kiliaan, A.J.; Gustafson, D.R. Obesity and dementia: Adipokines interact with the brain. Eur. Neuropsychopharmacol. 2014, 24, 1982–1999. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Anjum, I.; Fayyaz, M.; Wajid, A.; Sohail, W.; Ali, A. Does Obesity Increase the Risk of Dementia: A Literature Review. Cureus 2018, 10, e2660. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Greenwood, C.E.; Winocur, G. High-fat diets, insulin resistance and declining cognitive function. Neurobiol. Aging 2005, 26 (Suppl. 1), 42–45. [Google Scholar] [CrossRef] [PubMed]
- Watson, G.S.; Craft, S. The role of insulin resistance in the pathogenesis of Alzheimer’s disease: Implications for treatment. CNS Drugs 2003, 17, 27–45. [Google Scholar] [CrossRef]
- Bell, S.P.; Liu, D.; Samuels, L.R.; Shah, A.S.; Gifford, K.A.; Hohman, T.J.; Jefferson, A.L. Late-Life Body Mass Index, Rapid Weight Loss, Apolipoprotein E ε4 and the Risk of Cognitive Decline and Incident Dementia. J. Nutr. Health Aging 2017, 21, 1259–1267. [Google Scholar] [CrossRef]
- Cronk, B.B.; Johnson, D.K.; Burns, J.M. Alzheimer’s Disease Neuroimaging Initiative. Body mass index and cognitive decline in mild cognitive impairment. Alzheimer Dis. Assoc. Disord. 2010, 24, 126–130. [Google Scholar] [CrossRef]
- Gustafson, D.R.; Bäckman, K.; Joas, E.; Waern, M.; Östling, S.; Guo, X.; Skoog, I. 37 years of body mass index and dementia: Observations from the prospective population study of women in Gothenburg, Sweden. J. Alzheimer’s Dis. 2012, 28, 163–171. [Google Scholar] [CrossRef] [PubMed]
- Chang, K.-V.; Hsu, T.-H.; Wu, W.-T.; Huang, K.-C.; Han, D.-S. Association between Sarcopenia and Cognitive Impairment: A Systematic Review and Meta-Analysis. J. Am. Med. Dir. Assoc. 2016, 17, 1164.e7–1164.e15. [Google Scholar] [CrossRef] [PubMed]
- Memel, M.; Bourassa, K.; Woolverton, C.; Sbarra, D.A. Body Mass and Physical Activity Uniquely Predict Change in Cognition for Aging Adults. Ann. Behav. Med. 2016, 50, 397–408. [Google Scholar] [CrossRef] [PubMed]
- Strandberg, T.E.; Stenholm, S.; Strandberg, A.Y.; Salomaa, V.V.; Pitkälä, K.H.; Tilvis, R.S. The “obesity paradox” frailty, disability, and mortality in older men: A prospective, longitudinal cohort study. Am. J. Epidemiol. 2013, 178, 1452–1460. [Google Scholar] [CrossRef] [PubMed]
- Driscoll, I.; Espeland, M.A.; Wassertheil-Smoller, S.; Gaussoin, S.A.; Ding, J.; Granek, I.; Ockene, J.K.; Phillips, L.S.; Yaffe, K.; Resnick, S.M.; et al. Weight Change and Cognitive Function: Findings from the Women’s Health Initiative Study of Cognitive Aging. Obesity 2011, 19, 1595–1600. [Google Scholar] [CrossRef]
- Cova, I.; Clerici, F.; Rossi, A.; Cucumo, V.; Ghiretti, R.; Maggiore, L.; Pomati, S.; Galimberti, D.; Scarpini, E.; Mariani, C.; et al. Weight Loss Predicts Progression of Mild Cognitive Impairment to Alzheimer’s Disease. PLoS ONE 2016, 11, e0151710. [Google Scholar] [CrossRef] [PubMed]
- Jimenez, A.; Pegueroles, J.; Carmona-Iragui, M.; Vilaplana, E.; Montal, V.; Alcolea, D.; Videla, L.; Illán-Gala, I.; Pané, A.; Casajoana, A.; et al. Weight loss in the healthy elderly might be a non-cognitive sign of preclinical Alzheimer’s disease. Oncotarget 2017, 8, 104706–104716. [Google Scholar] [CrossRef]
- Gauthier, S.; Gélinas, I.; Gauthier, L. Functional disability in Alzheimer’s disease. Int. Psychogeriatr. 1997, 9 (Suppl. 1), 163–165. [Google Scholar] [CrossRef]
- Vellas, B.; Carrie, I.; Gillette-Guyonnet, S.; Touchon, J.; Dantoine, T.; Dartigues, J.F.; Cuffi, M.N.; Bordes, S.; Gasnier, Y.; Robert, P.; et al. MAPT STUDY: A multidomain approach for preventing alzheimer’s disease: Design and baseline data. J. Prev. Alzheimer’s Dis. 2014, 1, 13–22. [Google Scholar]
- Andrieu, S.; Guyonnet, S.; Coley, N.; Cantet, C.; Bonnefoy, M.; Bordes, S.; Bories, L.; Cufi, M.N.; Dantoine, T.; Dartigues, J.F.; et al. Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): A randomised, placebo-controlled trial. Lancet Neurol. 2017, 16, 377–389. [Google Scholar] [CrossRef]
- Folstein, M.F.; Folstein, S.E.; McHugh, P.R. “Mini-mental state”—A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 1975, 12, 189–198. [Google Scholar] [CrossRef]
- Galasko, D.; Bennett, D.A.; Sano, M.; Marson, D.; Kaye, J.; Edland, S.D. ADCS Prevention Instrument Project: Assessment of instrumental activities of daily living for community-dwelling elderly individuals in dementia prevention clinical trials. Alzheimer Dis. Assoc. Disord. 2006, 20 (Suppl. 3), S152–S169. [Google Scholar] [CrossRef] [PubMed]
- World Health Organization (WHO). World Report on Ageing and Health; World Health Organization: Geneva, Switzerland, 2015. [Google Scholar]
- Lankisch, P.; Gerzmann, M.; Gerzmann, J.F.; Lehnick, D. Unintentional weight loss: Diagnosis and prognosis. The first prospective follow-up study from a secondary referral centre. J. Intern. Med. 2001, 249, 41–46. [Google Scholar] [CrossRef]
- Newman, A.B.; Yanez, D.; Harris, T.; Duxbury, A.; Enright, P.L.; Fried, L.P.; Cardiovascular Study Research Group. Weight change in old age and its association with mortality. J. Am. Geriatr. Soc. 2001, 49, 1309–1318. [Google Scholar] [CrossRef] [PubMed]
- McMinn, J.; Steel, C.; Bowman, A. Investigation and management of unintentional weight loss in older adults. BMJ 2011, 342, d1732. [Google Scholar] [CrossRef] [PubMed]
- Chupin, M.; Hammers, A.; Liu, R.S.N.; Colliot, O.; Burdett, J.; Bardinet, E.; Duncan, J.S.; Garnero, L.; Lemieux, L. Automatic segmentation of the hippocampus and the amygdala driven by hybrid constraints: Method and validation. NeuroImage 2009, 46, 749–761. [Google Scholar] [CrossRef] [PubMed]
- Ganguli, M.; Belle, S.; Ratcliff, G.; Seaberg, E.; Huff, F.J.; von der Porten, K.; Kuller, L.H. Sensitivity and specificity for dementia of population-based criteria for cognitive impairment: The MoVIES project. J. Gerontol. 1993, 48, M152–M161. [Google Scholar] [CrossRef]
- Sobów, T.; Fendler, W.; Magierski, R. Body mass index and mild cognitive impairment-to-dementia progression in 24 months: A prospective study. Eur. J. Clin. Nutr. 2014, 68, 1216–1219. [Google Scholar] [CrossRef]
- Albanese, E.; Taylor, C.; Siervo, M.; Stewart, R.; Prince, M.J.; Acosta, D. Dementia severity and weight loss: A comparison across eight cohorts. The 10/66 study. Alzheimer’s Dement. 2013, 9, 649–656. [Google Scholar] [CrossRef] [Green Version]
- Park, S.; Jeon, S.-M.; Jung, S.-Y.; Hwang, J.; Kwon, J.-W. Effect of late-life weight change on dementia incidence: A 10-year cohort study using claim data in Korea. BMJ Open 2019, 9, e021739. [Google Scholar] [CrossRef]
- Witte, A.V.; Fobker, M.; Gellner, R.; Knecht, S.; Flöel, A. Caloric restriction improves memory in elderly humans. Proc. Natl. Acad. Sci. USA 2009, 106, 1255–1260. [Google Scholar] [CrossRef] [Green Version]
- Siervo, M.; Nasti, G.; Stephan, B.C.M.; Papa, A.; Muscariello, E.; Wells, J.C.K.; Prado, C.M.; Colantuoni, A. Effects of intentional weight loss on physical and cognitive function in middle-aged and older obese participants: A pilot study. J. Am. Coll. Nutr. 2012, 31, 79–86. [Google Scholar] [CrossRef] [PubMed]
- Horie, N.C.; Serrao, V.T.; Simon, S.S.; Gascon, M.R.P.; dos Santos, A.X.; Zambone, M.A.; del Bigio de Freitas, M.M.; Cunha-Neto, E.; Marques, E.L.; Halpern, A.; et al. Cognitive Effects of Intentional Weight Loss in Elderly Obese Individuals With Mild Cognitive Impairment. J. Clin. Endocrinol. Metab. 2016, 101, 1104–1112. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bales, C.W.; Ritchie, C.S. Sarcopenia, weight loss, and nutritional frailty in the elderly. Annu. Rev. Nutr. 2002, 22, 309–323. [Google Scholar] [CrossRef]
- Locher, J.L.; Roth, D.L.; Ritchie, C.S.; Cox, K.; Sawyer, P.; Bodner, E.V.; Allman, R.M. Body mass index, weight loss, and mortality in community-dwelling older adults. J. Gerontol. A Biol. Sci. Med. Sci. 2007, 62, 1389–1392. [Google Scholar] [CrossRef] [PubMed]
- Ensrud, K.E.; Ewing, S.K.; Taylor, B.C.; Fink, H.A.; Cawthon, P.M.; Stone, K.L.; Hillier, T.A.; Cauley, J.A.; Hochberg, M.C.; Rodondi, N.; et al. Comparison of 2 frailty indexes for prediction of falls, disability, fractures, and death in older women. Arch. Int. Med. 2008, 168, 382–389. [Google Scholar] [CrossRef] [PubMed]
- Wilson, D.; Jackson, T.; Sapey, E.; Lord, J.M. Frailty and sarcopenia: The potential role of an aged immune system. Ageing Res. Rev. 2017, 36, 1–10. [Google Scholar] [CrossRef] [PubMed]
- Rolland, Y.; Kim, M.-J.; Gammack, J.K.; Wilson, M.-M.G.; Thomas, D.R.; Morley, J.E. Office management of weight loss in older persons. Am. J. Med. 2006, 119, 1019–1026. [Google Scholar] [CrossRef] [PubMed]
- Wilkins, C.H.; Roe, C.M.; Morris, J.C.; Galvin, J.E. Mild physical impairment predicts future diagnosis of dementia of the Alzheimer’s type. J. Am. Geriatr. Soc. 2013, 61, 1055–1059. [Google Scholar] [CrossRef] [PubMed]
- Tolea, M.I.; Galvin, J.E. Sarcopenia and impairment in cognitive and physical performance. Clin. Interv. Aging 2015, 10, 663–671. [Google Scholar] [CrossRef]
- Waters, D.L.; Ward, A.L.; Villareal, D.T. Weight loss in obese adults 65 years and older: A review of the controversy. Exp. Gerontol. 2013, 48, 1054–1061. [Google Scholar] [CrossRef] [PubMed]
- Veronese, N.; Facchini, S.; Stubbs, B.; Luchini, C.; Solmi, M.; Manzato, E.; Sergi, G.; Maggi, S.; Cosco, T.; Fontana, L. Weight loss is associated with improvements in cognitive function among overweight and obese people: A systematic review and meta-analysis. Neurosci. Biobehav. Rev. 2017, 72, 87–94. [Google Scholar] [CrossRef] [PubMed]
- Napoli, N.; Shah, K.; Waters, D.L.; Sinacore, D.R.; Qualls, C.; Villareal, D.T. Effect of weight loss, exercise, or both on cognition and quality of life in obese older adults. Am. J. Clin. Nutr. 2014, 100, 189–198. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Handley, J.D.; Williams, D.M.; Caplin, S.; Stephens, J.W.; Barry, J. Changes in Cognitive Function Following Bariatric Surgery: A Systematic Review. Obes. Surg. 2016, 26, 2530–2537. [Google Scholar] [CrossRef] [PubMed]
- Thiara, G.; Cigliobianco, M.; Muravsky, A.; Paoli, R.A.; Mansur, R.; Hawa, R.; McIntyre, R.S.; Sockalingam, S. Evidence for Neurocognitive Improvement After Bariatric Surgery: A Systematic Review. Psychosomatics 2017, 58, 217–227. [Google Scholar] [CrossRef] [PubMed]
- Kelaiditi, E.; Cesari, M.; Canevelli, M.; van Kan, G.A.; Ousset, P.-J.; Gillette-Guyonnet, S.; Ritz, P.; Duveau, F.; Soto, M.E.; Provencher, V.; et al. Cognitive frailty: Rational and definition from an (I.A.N.A./I.A.G.G.) international consensus group. J. Nutr. Health Aging 2013, 17, 726–734. [Google Scholar] [CrossRef]
- Bobb, J.F.; Schwartz, B.S.; Davatzikos, C.; Caffo, B. Cross-sectional and longitudinal association of body mass index and brain volume. Hum. Brain Mapp. 2014, 35, 75–88. [Google Scholar] [CrossRef]
- Driscoll, I.; Gaussoin, S.A.; Wassertheil-Smoller, S.; Limacher, M.; Casanova, R.; Yaffe, K.; Resnick, S.M.; Espeland, M.A. Obesity and Structural Brain Integrity in Older Women: The Women’s Health Initiative Magnetic Resonance Imaging Study. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 2016, 71, 1216–1222. [Google Scholar] [CrossRef]
- Prehn, K.; Jumpertz von Schwartzenberg, R.; Mai, K.; Zeitz, U.; Witte, A.V.; Hampel, D.; Szela, A.M.; Fabian, S.; Grittner, U.; Spranger, J.; et al. Caloric Restriction in Older Adults-Differential Effects of Weight Loss and Reduced Weight on Brain Structure and Function. Cereb. Cortex 2017, 27, 1765–1778. [Google Scholar] [CrossRef]
- Haigis, M.C.; Guarente, L.P. Mammalian sirtuins—Emerging roles in physiology, aging, and calorie restriction. Genes Dev. 2006, 20, 2913–2921. [Google Scholar] [CrossRef]
- Wang, F.; Nguyen, M.; Qin, F.X.-F.; Tong, Q. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. Aging Cell 2007, 6, 505–514. [Google Scholar] [CrossRef] [PubMed]
- Chang, Y.-T.; Chang, W.-N.; Tsai, N.-W.; Huang, C.-C.; Kung, C.-T.; Su, Y.-J.; Lin, W.C.; Cheng, B.C.; Su, C.M.; Chiang, Y.F.; et al. The roles of biomarkers of oxidative stress and antioxidant in Alzheimer’s disease: A systematic review. BioMed Res. Int. 2014, 2014, 182303. [Google Scholar] [CrossRef] [PubMed]
- Herranz, D.; Muñoz-Martin, M.; Cañamero, M.; Mulero, F.; Martinez-Pastor, B.; Fernandez-Capetillo, O.; Serrano, M. Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat. Commun. 2010, 1, 3. [Google Scholar] [CrossRef] [PubMed]
Total n = 1394 | Weight Variation Patterns | |||
---|---|---|---|---|
Weight Loss | Stable | Weight Gain | ||
n = 76 | n = 1193 | n = 125 | ||
Mean ± SD * | Meean ± SD * | Meean ± SD * | Meean ± SD * | |
Female sex | 890 (63.9%) | 48 (63.2%) | 747 (62.6%) | 95 (76.0%) † |
Age (years) | 75.2 ± 4.3 | 75.9 ± 4.3 a | 75.2 ± 4.4 | 74.6 ± 4.0 a |
Education (n = 1375) | ||||
No diploma or primary school certificate | 298 (21.7%) | 18 (23.7%) | 260 (22.2%) | 20 (16.0%) |
Secondary education | 468 (34.0%) | 22 (29.0%) | 400 (34.1%) | 46 (36.8%) |
High school diploma | 204 (14.8%) | 13 (17.1%) | 178 (15.2%) | 13 (10.4%) |
University level | 405 (29.5%) | 23 (30.3%) | 336 (28.6%) | 46 (36.8%) |
Weight (kg) | 68.6 ± 12.9 | 70.9 ± 13.6 a | 68.9 ± 12.8 b | 64.4 ± 12.4 a,b |
Height (m) | 1.62 ± 0.09 | 1.61 ± 0.09 | 1.62 ± 0.09 a | 1.60 ± 0.08 a |
Body mass index (kg/m2) | 26.1 ± 4.0 | 27.3 ± 4.5 a,b | 26.2 ± 4.0 a,c | 25.0 ± 4.0 b,c |
Cognition | ||||
Composite Z-score ** | 0.02 ± 0.66 | −0.13 ± 0.70 a | 0.03 ± 0.65 a | 0.01 ± 0.66 |
Free and total recall of the Free and Cued Selective Reminding test score | 73.1 ± 9.5 | 70.6 ± 11.6 a,b | 73.2 ± 9.2 a | 73.6 ± 10.1 b |
Ten Mini-Mental State Examination orientation items score | 9.8 ± 0.5 | 9.8 ± 0.5 | 9.8 ± 0.5 | 9.8 ± 0.5 |
Digit Symbol Substitution Test score | 38.1 ± 9.9 | 35.7 ± 9.6 a | 38.3 ± 9.9 a | 38.2 ± 9.7 |
Category Naming Test score | 26.1 ± 7.4 | 25.7 ± 6.9 | 26.3 ± 7.4 | 25.1 ± 8.1 |
Estimated Mean Within-Group 5 Year Change from Baseline * (95% CI); p-Value | Between-Group Differences in Cognitive Score after 5 Year Follow-Up (95% CI); p-Value | ||||||
---|---|---|---|---|---|---|---|
Weight Loss | Stable | Weight Gain | Weight Loss vs. Stable | Weight Gain vs. Stable | |||
Unadjusted Model | Adjusted Model ** | Unadjusted Model | Adjusted Model ** | ||||
Composite cognitive score | −0.47 (−0.61, −0.33); <0.0001 | −0.21 (−0.24, −0.18); <0.0001 | −0.14 (−0.25, −0.04); 0.007 | −0.26 (−0.40, −0.11); 0.001 | −0.24 (−0.41, −0.07); 0.006 | 0.07 (−0.04, 0.18); 0.222 | 0.07 (−0.06, 0.19); 0.287 |
Estimated Mean Within-Group 5 Year Change from Baseline * (95% CI); p-Value | Between-Group Differences in Cognitive Score after 5 Year Follow-Up (95% CI); p-Value | ||||||
---|---|---|---|---|---|---|---|
Weight Loss | Stable | Weight Gain | Weight Loss vs. Stable | Weight Gain vs. Stable | |||
Unadjusted Model | Adjusted Model ** | Unadjusted Model | Adjusted Model ** | ||||
Composite cognitive score | −0.42 (−0.56, −0.29); <0.0001 | −0.21 (−0.24, −0.18); <0.0001 | −0.15 (−0.25, −0.05); 0.005 | −0.21 (−0.36, −0.07); 0.003 | −0.19 (−0.35, −0.02); 0.028 | 0.06 (−0.04, 0.17); 0.244 | 0.06 (−0.06, 0.19); 0.305 |
Estimated Mean Within-Group 3 Year Change from Baseline * (95% CI); p-Value | Between-Group Differences in Hippocampal Volume after 3 Year Follow-Up (95% CI); p-Value | ||||||
---|---|---|---|---|---|---|---|
Weight Loss | Stable | Weight Gain | Weight Loss vs. Stable | Weight Gain vs. Stable | |||
Unadjusted Model | Adjusted Model ** | Unadjusted Model | Adjusted Model ** | ||||
Hippocampal volume (cm3) | −0.14 (−0.21, −0.08); <0.0001 | −0.12 (−0.14, −0.11); <0.0001 | −0.10 (−0.14, −0.06); <0.0001 | −0.02 (−0.09, 0.05); 0.536 | 0.01 (−0.06, 0.08); 0.788 | 0.02 (−0.02, 0.06); 0.379 | 0.00 (−0.05, 0.04); 0.912 |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Giudici, K.V.; Guyonnet, S.; Rolland, Y.; Vellas, B.; de Souto Barreto, P.; Nourhashemi, F.; on behalf of the MAPT/DSA Group. Body Weight Variation Patterns as Predictors of Cognitive Decline over a 5 Year Follow-Up among Community-Dwelling Elderly (MAPT Study). Nutrients 2019, 11, 1371. https://doi.org/10.3390/nu11061371
Giudici KV, Guyonnet S, Rolland Y, Vellas B, de Souto Barreto P, Nourhashemi F, on behalf of the MAPT/DSA Group. Body Weight Variation Patterns as Predictors of Cognitive Decline over a 5 Year Follow-Up among Community-Dwelling Elderly (MAPT Study). Nutrients. 2019; 11(6):1371. https://doi.org/10.3390/nu11061371
Chicago/Turabian StyleGiudici, Kelly Virecoulon, Sophie Guyonnet, Yves Rolland, Bruno Vellas, Philipe de Souto Barreto, Fati Nourhashemi, and on behalf of the MAPT/DSA Group. 2019. "Body Weight Variation Patterns as Predictors of Cognitive Decline over a 5 Year Follow-Up among Community-Dwelling Elderly (MAPT Study)" Nutrients 11, no. 6: 1371. https://doi.org/10.3390/nu11061371