Dietary Intake and Circulating Concentrations of Carotenoids and Risk of Type 2 Diabetes: A Dose-Response Meta-Analysis of Prospective Observational Studies.

Previous meta-analysis studies have indicated inverse associations between some carotenoids and risks of metabolic syndrome, cardiovascular disease, cancer, and all-cause mortality. However, the results for associations between carotenoids and type 2 diabetes (T2D) remain inconsistent and no systematic assessment has been done on this topic. We conducted a systematic review and meta-analysis to examine the associations of dietary intakes and circulating concentrations of carotenoids with risk of T2D. We searched PubMed and Ovid Embase from database inception to July 2020. Prospective observational studies of carotenoids and T2D risk were included. Random-effects models were used to summarize the RRs and 95% CIs. Thirteen publications were included. Dietary intake of β-carotene was inversely associated with the risk of T2D, and the pooled RR comparing the highest with the lowest categories was 0.78 (95% CI: 0.70, 0.87; I2 = 13.7%; n = 6); inverse associations were also found for total carotenoids (n = 2), α-carotene (n = 4), and lutein/zeaxanthin (n = 4), with pooled RRs ranging from 0.80 to 0.91, whereas no significant associations were observed for β-cryptoxanthin and lycopene. Circulating concentration of β-carotene was associated with a lower risk of T2D, and the pooled RR comparing extreme categories was 0.60 (95% CI: 0.46, 0.78; I2 = 56.2%; n = 7); inverse associations were also found for total carotenoids (n = 3), lycopene (n = 4), and lutein (n = 2), with pooled RRs ranging from 0.63 to 0.85, whereas no significant association was found for circulating concentrations of α-carotene and zeaxanthin when comparing extreme categories. Dose-response analysis indicated that nonlinear relations were observed for circulating concentrations of α-carotene, β-carotene, lutein, and total carotenoids (all P-nonlinearity < 0.05), but not for other carotenoids or dietary exposures. In conclusion, higher dietary intakes and circulating concentrations of total carotenoids, especially β-carotene, were associated with a lower risk of T2D. More studies are needed to confirm the causality and explore the role of foods rich in carotenoids in prevention of T2D. This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42020196616.

[1]  J. Danesh,et al.  Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries , 2020, BMJ.

[2]  A. J. Meléndez-Martínez,et al.  Comparison of the bioavailability and intestinal absorption sites of phytoene, phytofluene, lycopene and β-carotene. , 2019, Food chemistry.

[3]  J. Sassi,et al.  Microalgal Carotenoids: A Review of Production, Current Markets, Regulations, and Future Direction , 2019, Marine drugs.

[4]  O. Franco,et al.  Dietary antioxidant capacity and risk of type 2 diabetes mellitus, prediabetes and insulin resistance: the Rotterdam Study , 2019, European Journal of Epidemiology.

[5]  J. Manson,et al.  Application of blood concentration biomarkers in nutritional epidemiology: example of carotenoid and tocopherol intake in relation to chronic disease risk. , 2019, The American journal of clinical nutrition.

[6]  A. Tamakoshi,et al.  Fat-soluble vitamins from diet in relation to risk of type 2 diabetes mellitus in Japanese population. , 2019, The British journal of nutrition.

[7]  E. Riboli,et al.  Dietary intake and blood concentrations of antioxidants and the risk of cardiovascular disease, total cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective studies , 2018, The American journal of clinical nutrition.

[8]  J. Ilonen,et al.  Carotenoid Intake and Serum Concentration in Young Finnish Children and Their Relation with Fruit and Vegetable Consumption , 2018, Nutrients.

[9]  A. Zonderman,et al.  Carotenoids, vitamin A, and their association with the metabolic syndrome: a systematic review and meta-analysis , 2018, Nutrition reviews.

[10]  Elizabeth J Johnson,et al.  Intrinsic and Extrinsic Factors Impacting Absorption, Metabolism, and Health Effects of Dietary Carotenoids. , 2018, Advances in nutrition.

[11]  Changfu Zhu,et al.  A global perspective on carotenoids: Metabolism, biotechnology, and benefits for nutrition and health. , 2018, Progress in lipid research.

[12]  Xinchun Shen,et al.  Carotenoid supplementation and retinoic acid in immunoglobulin A regulation of the gut microbiota dysbiosis , 2018, Experimental biology and medicine.

[13]  I. Kimura,et al.  Gut Microbiota Dysbiosis Drives and Implies Novel Therapeutic Strategies for Diabetes Mellitus and Related Metabolic Diseases , 2017, Front. Immunol..

[14]  P. Balagopal,et al.  Effects of Mixed Carotenoids on Adipokines and Abdominal Adiposity in Children: A Pilot Study , 2017, The Journal of clinical endocrinology and metabolism.

[15]  Georg Hoffmann,et al.  Food groups and risk of type 2 diabetes mellitus: a systematic review and meta-analysis of prospective studies , 2017, European Journal of Epidemiology.

[16]  L. Dragsted,et al.  Host‐related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans , 2017, Molecular nutrition & food research.

[17]  Y. Ikoma,et al.  High-serum carotenoids associated with lower risk for developing type 2 diabetes among Japanese subjects: Mikkabi cohort study , 2015, BMJ Open Diabetes Research and Care.

[18]  S. Xie,et al.  Higher intake of fruits, vegetables or their fiber reduces the risk of type 2 diabetes: A meta‐analysis , 2015, Journal of diabetes investigation.

[19]  A. Palou,et al.  Carotenoids and their conversion products in the control of adipocyte function, adiposity and obesity. , 2015, Archives of biochemistry and biophysics.

[20]  D. van der A,et al.  Dietary intake of carotenoids and risk of type 2 diabetes. , 2015, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[21]  S. Sharp,et al.  The association between a biomarker score for fruit and vegetable intake and incident type 2 diabetes: the EPIC-Norfolk study , 2014, European Journal of Clinical Nutrition.

[22]  C. Cooper,et al.  Dietary total antioxidant capacity is related to glucose tolerance in older people: the Hertfordshire Cohort Study. , 2014, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[23]  D. Jacobs,et al.  Dietary intakes of zinc and heme iron from red meat, but not from other sources, are associated with greater risk of metabolic syndrome and cardiovascular disease. , 2012, The Journal of nutrition.

[24]  D. Panagiotakos,et al.  Dietary antioxidant capacity is inversely associated with diabetes biomarkers: the ATTICA study. , 2011, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[25]  L. Arab,et al.  Racial differences in correlations between reported dietary intakes of carotenoids and their concentration biomarkers. , 2011, The American journal of clinical nutrition.

[26]  D. Albanes,et al.  Intake of antioxidants and risk of type 2 diabetes in a cohort of male smokers , 2011, European Journal of Clinical Nutrition.

[27]  Tak Yee Aw,et al.  Reactive oxygen species, cellular redox systems, and apoptosis. , 2010, Free radical biology & medicine.

[28]  J. Manson,et al.  Effects of vitamins C and E and beta-carotene on the risk of type 2 diabetes in women at high risk of cardiovascular disease: a randomized controlled trial. , 2009, The American journal of clinical nutrition.

[29]  A. Galano,et al.  What is important to prevent oxidative stress? A theoretical study on electron-transfer reactions between carotenoids and free radicals. , 2009, The journal of physical chemistry. B.

[30]  D. Moher,et al.  Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement , 2009, BMJ : British Medical Journal.

[31]  Michael T Brannick,et al.  A SAS macro for statistical power calculations in meta-analysis , 2009, Behavior research methods.

[32]  D. Albanes,et al.  Effect of α-tocopherol and β-carotene supplementation on the incidence of type 2 diabetes , 2007, Diabetologia.

[33]  R. Curi,et al.  Diabetes associated cell stress and dysfunction: role of mitochondrial and non‐mitochondrial ROS production and activity , 2007, The Journal of physiology.

[34]  C. Perera,et al.  Functional Properties of Carotenoids in Human Health , 2007 .

[35]  A. Rao,et al.  Carotenoids and human health. , 2007, Pharmacological research.

[36]  J. Manson,et al.  Plasma lycopene, other carotenoids, and the risk of type 2 diabetes in women. , 2006, American journal of epidemiology.

[37]  P. Galan,et al.  Antioxidant supplementation does not affect fasting plasma glucose in the Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) study in France: association with dietary intake and plasma concentrations. , 2006, The American journal of clinical nutrition.

[38]  D. Jacobs,et al.  Associations of serum carotenoid concentrations with the development of diabetes and with insulin concentration: interaction with smoking: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. , 2006, American journal of epidemiology.

[39]  J. Manson,et al.  The consumption of lycopene and tomato-based food products is not associated with the risk of type 2 diabetes in women. , 2006, The Journal of nutrition.

[40]  E. Lyden,et al.  Plasma Carotenoid and Vitamins A and E Concentrations in Older African American Women after Wheat Bran Supplementation: Effects of Age, Body Mass and Smoking History , 2005, Journal of the American College of Nutrition.

[41]  A. Reunanen,et al.  Dietary Antioxidant Intake and Risk of Type 2 Diabetes , 2004 .

[42]  L. Hedges,et al.  The power of statistical tests in meta-analysis. , 2001, Psychological methods.

[43]  I. Olkin,et al.  Meta-analysis of observational studies in epidemiology - A proposal for reporting , 2000 .

[44]  J. Manson,et al.  Long-term β-Carotene Supplementation and Risk of Type 2 Diabetes Mellitus: A Randomized Controlled Trial , 1999 .

[45]  David B. Haytowitz,et al.  Carotenoid Content of U.S. Foods: An Update of the Database , 1999 .

[46]  P. Wilson,et al.  Carotenoid intakes, assessed by dietary questionnaire, are associated with plasma carotenoid concentrations in an elderly population. , 1999, The Journal of nutrition.

[47]  A. Reunanen,et al.  Serum antioxidants and risk of non‐insulin dependent diabetes mellitus , 1998, European Journal of Clinical Nutrition.

[48]  L. Skibsted,et al.  Comparative mechanisms and rates of free radical scavenging by carotenoid antioxidants , 1997, FEBS letters.

[49]  H. Gerster The potential role of lycopene for human health. , 1997, Journal of the American College of Nutrition.

[50]  A. Ben‐Amotz,et al.  Bioavailability of a natural isomer mixture compared with synthetic all-trans beta-carotene in human serum. , 1996, The American journal of clinical nutrition.

[51]  P. Taylor,et al.  Relationship between dietary intake and plasma concentrations of carotenoids in premenopausal women: application of the USDA-NCI carotenoid food-composition database. , 1994, The American journal of clinical nutrition.

[52]  S. Greenland,et al.  Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. , 1992, American journal of epidemiology.

[53]  P. Tugwell,et al.  The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses , 2014 .

[54]  J. Ärnlöv,et al.  Serum and dietary β-carotene and α-tocopherol and incidence of type 2 diabetes mellitus in a community-based study of Swedish men: report from the Uppsala Longitudinal Study of Adult Men (ULSAM) study , 2008, Diabetologia.

[55]  D. Leibfritz,et al.  Free radicals and antioxidants in normal physiological functions and human disease. , 2007, The international journal of biochemistry & cell biology.

[56]  N. Pellegrini,et al.  The total antioxidant capacity of the diet is an independent predictor of plasma β-carotene , 2007, European Journal of Clinical Nutrition.

[57]  Joseph L Evans,et al.  Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? , 2003, Diabetes.