Zinc Supplementation Might Not Affect Serum Leptin and Adiponectin Levels in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials
Abstract
Background: Zinc as one of the important trace elements in human health has been suggested to be a supplement for modifying the level of adipokines, whereas findings from studies have been inconsistent. This study aimed to systematically review the evidence provided by randomized controlled trials (RCTs) regarding the effect of zinc supplementation on serum adipokines levels.
Methods: PubMed, Google Scholar, Web of Science, and Scopus were systematically searched up to June 2019. The mean differences and their corresponding standard deviations (SDs) of changes in serum adipokines levels were used as effect size.
Results: Eight eligible RCTs (leptin n=6, adiponectin n=3) were included in the current study. There were no significant changes in serum leptin levels [weighted mean difference (WMD) =0.60 ng/ml, 95% confidence interval (CI): -1.78, 2.99; I-squared (I2) = 64.3%] and adiponectin levels (WMD = 1.09 ng/ml, 95% CI: -0.76, 3.18, I2 = 78.8%) following zinc supplementation compared to placebo group. These findings did not change after considering several subgroups including gender, study duration, health status, body weight and the type of zinc used for supplementation.
Conclusion: No evidence was found to support the efficacy of dietary zinc supplements on serum levels of adipokines. Further, high-quality, long-term controlled clinical trials are warranted to confirm these findings.
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2. Bell JA, Kivimaki M, Hamer M (2014). Metabolically healthy obesity and risk of incident type 2 diabetes: a meta-analysis of prospective cohort studies. Obes Rev, 15 (6): 504-15.
3. Abdullah A, Peeters A, de Courten M, et al (2010). The magnitude of association between overweight and obesity and the risk of diabetes: A meta-analysis of prospective cohort studies. Diabetes Res Clin Pract, 89 (3): 309-19.
4. Dattilo AM, Kris-Etherton PM (1992). Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr, 56 (2): 320-8.
5. Fan J, Song Y, Chen Y, et al (2013). Combined effect of obesity and cardio-metabolic abnormality on the risk of cardiovascular disease: A meta-analysis of prospective cohort studies. Int J Cardiol, 168 (5): 4761-8.
6. Moghaddam AA, Woodward M, Huxley R (2007). Obesity and Risk of Colorectal Cancer: A Meta-analysis of 31 Studies with 70,000 Events. Cancer Epidemiol Biomarkers Prev, 16 (12): 2533-47.
7. Larsson SC, Wolk A (2007). Obesity and the risk of gallbladder cancer: a meta-analysis. Br J Cancer, 96 (9): 1457-1461.
8. Larsson SC, Wolk A (2007). Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies. Br J Cancer, 97 (7): 1005-1008.
9. WHO (2016). Obesity and overweight fact sheet [Available from: http://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
10. Marti A, Martinez-Gonzalez MA, Martinez JA (2008). Interaction between genes and lifestyle factors on obesity. Proc Nutr Soc, 67 (1): 1-8.
11. Morton GJ, Cummings D, Baskin D, et al (2006). Central Nervous System Control of Food Intake and body Weight. Nature, 443 (7109): 289-95.
12. Halaas JL, Gajiwala KS, Maffei M, et al (1995). Weight-reducing effects of the plasma protein encoded by the obese gene. Science, 269 (5223): 543-6.
13. Maffei M, Halaas J, Ravussin E, et al (1995). Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med, 1 (11): 1155-61.
14. Pelleymounter MA, Cullen MJ, Baker MB, et al (1995). Effects of the obese gene product on body weight regulation in ob/ob mice. Science, 269 (5223): 540-3.
15. Campfield LA, Smith FJ, Guisez Y, et al (1995). Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science, 269 (5223): 546-9.
16. Weigle DS, Bukowski TR, Foster DC, et al (1995). Recombinant ob protein reduces feeding and body weight in the ob/ob mouse. J Clin Invest, 96 (4): 2065-70.
17. Mantzoros CS, Qu D, Frederich RC, et al (1996). Activation of beta(3) adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice. Diabetes, 45 (7): 909-14.
18. Caro JF, Sinha MK, Kolaczynski JW,et al (1996). Leptin: the tale of an obesity gene. Diabetes, 45 (11): 1455-62.
19. Havel PJ (2004). Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes, 1:S143-51.
20. Einollahi N, Alirezaee A (2016). A review of adipose tissue hormones and their functions in the body. Journal of Laboratory and Diagnosis, 8 (33): 23-34.
21. Tinkov AA, Sinitskii AI, Popova EV, et al (2015). Alteration of local adipose tissue trace element homeostasis as a possible mechanism of obesity-related insulin resistance. Med Hypotheses, 85 (3): 343-7.
22. Vallee BL, Falchuk KH (1993). The biochemical basis of zinc physiology. Physiol Rev, 73 (1): 79-118.
23. Baltaci AK, Mogulkoc R, Halifeoglu I (2005). Effects of zinc deficiency and supplementation on plasma leptin levels in rats. Biol Trace Elem Res, 104 (1): 41-6.
24. Vallee BL, Auld DS (1990). Zinc coordination, function, and structure of zinc enzymes and other proteins. Biochemistry, 29 (24): 5647-59.
25. Soheilykhah S, Dehestani MR, Mohammadi SM, et al (2012). The Effect of Zinc Supplementation on Serum Adiponectin Concentration and Insulin Resistance in First Degree Relatives of Diabetic Patients. IJDO, 4 (2): 57-62.
26. Payahoo L, Ostadrahimi A, Mobasseri M, et al (2014). Effects of zinc supplementation on serum leptin level and insulin sensitivity in obese people. Trace Elements and Electrolytes, 31 (1): 27-32.
27. Argani H, Mandavi R, Ghorbani-haghjo A, et al (2014). Effects of zinc supplementation on serum zinc and leptin levels, BMI, and body composition in hemodialysis patients. J Trace Elem Med Biol, 28 (1): 35-8.
28. Garcia OP, Long KZ, Rosado JL (2009). Impact of micronutrient deficiencies on obesity. Nutr Rev, 67 (10): 559-72.
29. Mantzoros CS, Prasad AS, Beck FWJ, et al (1998). Zinc May Regulate Serum Leptin Concentrations in Humans. J Am Coll Nutr, 17 (3): 270-5.
30. Prasad AS (1991). Discovery of human zinc deficiency and studies in an experimental human model. Am J Clin Nutr, 53 (2): 403-12.
31. Halas ES, Wallwork JC, Sandstead HH (1982). Mild zinc deficiency and undernutrition during the prenatal and postnatal periods in rats: effects on weight, food consumption, and brain catecholamine concentrations. J Nutr, 112 (3): 542-51.
32. Mazloomi S, Alizadeh N, Aminzare M, et al (2018). RETRACTED ARTICLE: Serum Zinc and Adiponectin Levels in Patients with Polycystic Ovary Syndrome, Adjusted for Anthropometric, Biochemical, Dietary Intake, and Physical Activity Measures. Biol Trace Elem Res, 181 (2): 388.
33. Yang WS, Jeng CY, Wu TJ, et al (2002). Synthetic peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients. Diabetes Care, 25 (2): 376-80.
34. Sarraf P, Frederich RC, Turner EM, et al (1997). Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia. J Exp Med, 185 (1): 171-5.
35. Kirchgessner TG, Uysal KT, Wiesbrock SM, et al (1997). Tumor necrosis factor-alpha contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes. J Clin Invest, 100 (11): 2777-82.
36. Ueda H, Nakai T, Konishi T,et al (2014). Effects of Zinc Deficiency and Supplementation on Leptin and Leptin Receptor Expression in Pregnant Mice. Biol Pharm Bull, 37 (4): 581-7.
37. Baltaci AK, Mogulkoc R (2012). Leptin and zinc relation: In regulation of food intake and immunity. Indian J Endocrinol Metab, 16(Suppl 3): S611–S616.
38. Roshanravan N, Tarighat-Esfanjani A, Alamdari NM, et al (2018). The Effects of zinc supplementation on inflammatory parameters in pregnant women with impaired glucose tolerance: A randomized placebo controlled clinical trial. Progr Nutr, 20(1-S):330-6.
39. Bribiescas RG (2003). Effects of oral zinc supplementation on serum leptin levels in Ache males of eastern Paraguay. Am J Hum Biol, 15 (5): 681-7.
40. Kim J, Ahn J (2014). Effect of Zinc Supplementation on Inflammatory Markers and Adipokines in Young Obese Women. Biol Trace Elem Res, 157 (2): 101-6.
41. Marreiro DD, Geloneze B, Tambascia MA, et al (2006). Effect of zinc supplementation on serum leptin levels and insulin resistance of obese women. Biol Trace Elem Res, 112 (2): 109-18.
42. Khorshidi M, Zarezadeh M, Sadeghi A, et al (2019). The Effect of Zinc Supplementation on Serum Leptin Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Horm Metab Res, 51 (8): 503-510.
43. Liberati A, Altman DG, Tetzlaff J, et al (2009). The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ, 339: b2700.
44. Pt Higgins J, Green S (2009). Cochrane Handbook for Systematic Reviews of Interventions. https://training.cochrane.org/cochrane-handbook-systematic-reviews-interventions
45. Follmann D, Elliott P, Suh I, et al (1992). Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol, 45 (7): 769-73.
46. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7 (3): 177-88.
47. Egger M, Davey Smith G, Schneider M, et al (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315 (7109): 629-634.
48. Egger M, Smith GD, Altman DG (2001). Systematic reviews in health care : meta-analysis in context. 2nd ed. ISBN: 978-0-727-91488-0.
49. Gomez-Garcia A, Hernandez-Salazar E, Gonzalez-Ortiz M, et al (2006). Effect of oral zinc administration on insulin sensitivity, leptin and androgens in obese males. Rev Med Chil, 134 (3): 279-84.
50. Asghari S, Mohajeri Tehrani MR, Sadegh M (2011). The effect of zinc supplementation on plasma adiponectin and insulin resistance in type 2 diabetic patients. Iranian Journal of Diabetes and Lipid Disorders, 10 (4): 398-406.
2. Bell JA, Kivimaki M, Hamer M (2014). Metabolically healthy obesity and risk of incident type 2 diabetes: a meta-analysis of prospective cohort studies. Obes Rev, 15 (6): 504-15.
3. Abdullah A, Peeters A, de Courten M, et al (2010). The magnitude of association between overweight and obesity and the risk of diabetes: A meta-analysis of prospective cohort studies. Diabetes Res Clin Pract, 89 (3): 309-19.
4. Dattilo AM, Kris-Etherton PM (1992). Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr, 56 (2): 320-8.
5. Fan J, Song Y, Chen Y, et al (2013). Combined effect of obesity and cardio-metabolic abnormality on the risk of cardiovascular disease: A meta-analysis of prospective cohort studies. Int J Cardiol, 168 (5): 4761-8.
6. Moghaddam AA, Woodward M, Huxley R (2007). Obesity and Risk of Colorectal Cancer: A Meta-analysis of 31 Studies with 70,000 Events. Cancer Epidemiol Biomarkers Prev, 16 (12): 2533-47.
7. Larsson SC, Wolk A (2007). Obesity and the risk of gallbladder cancer: a meta-analysis. Br J Cancer, 96 (9): 1457-1461.
8. Larsson SC, Wolk A (2007). Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies. Br J Cancer, 97 (7): 1005-1008.
9. WHO (2016). Obesity and overweight fact sheet [Available from: http://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
10. Marti A, Martinez-Gonzalez MA, Martinez JA (2008). Interaction between genes and lifestyle factors on obesity. Proc Nutr Soc, 67 (1): 1-8.
11. Morton GJ, Cummings D, Baskin D, et al (2006). Central Nervous System Control of Food Intake and body Weight. Nature, 443 (7109): 289-95.
12. Halaas JL, Gajiwala KS, Maffei M, et al (1995). Weight-reducing effects of the plasma protein encoded by the obese gene. Science, 269 (5223): 543-6.
13. Maffei M, Halaas J, Ravussin E, et al (1995). Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med, 1 (11): 1155-61.
14. Pelleymounter MA, Cullen MJ, Baker MB, et al (1995). Effects of the obese gene product on body weight regulation in ob/ob mice. Science, 269 (5223): 540-3.
15. Campfield LA, Smith FJ, Guisez Y, et al (1995). Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science, 269 (5223): 546-9.
16. Weigle DS, Bukowski TR, Foster DC, et al (1995). Recombinant ob protein reduces feeding and body weight in the ob/ob mouse. J Clin Invest, 96 (4): 2065-70.
17. Mantzoros CS, Qu D, Frederich RC, et al (1996). Activation of beta(3) adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice. Diabetes, 45 (7): 909-14.
18. Caro JF, Sinha MK, Kolaczynski JW,et al (1996). Leptin: the tale of an obesity gene. Diabetes, 45 (11): 1455-62.
19. Havel PJ (2004). Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes, 1:S143-51.
20. Einollahi N, Alirezaee A (2016). A review of adipose tissue hormones and their functions in the body. Journal of Laboratory and Diagnosis, 8 (33): 23-34.
21. Tinkov AA, Sinitskii AI, Popova EV, et al (2015). Alteration of local adipose tissue trace element homeostasis as a possible mechanism of obesity-related insulin resistance. Med Hypotheses, 85 (3): 343-7.
22. Vallee BL, Falchuk KH (1993). The biochemical basis of zinc physiology. Physiol Rev, 73 (1): 79-118.
23. Baltaci AK, Mogulkoc R, Halifeoglu I (2005). Effects of zinc deficiency and supplementation on plasma leptin levels in rats. Biol Trace Elem Res, 104 (1): 41-6.
24. Vallee BL, Auld DS (1990). Zinc coordination, function, and structure of zinc enzymes and other proteins. Biochemistry, 29 (24): 5647-59.
25. Soheilykhah S, Dehestani MR, Mohammadi SM, et al (2012). The Effect of Zinc Supplementation on Serum Adiponectin Concentration and Insulin Resistance in First Degree Relatives of Diabetic Patients. IJDO, 4 (2): 57-62.
26. Payahoo L, Ostadrahimi A, Mobasseri M, et al (2014). Effects of zinc supplementation on serum leptin level and insulin sensitivity in obese people. Trace Elements and Electrolytes, 31 (1): 27-32.
27. Argani H, Mandavi R, Ghorbani-haghjo A, et al (2014). Effects of zinc supplementation on serum zinc and leptin levels, BMI, and body composition in hemodialysis patients. J Trace Elem Med Biol, 28 (1): 35-8.
28. Garcia OP, Long KZ, Rosado JL (2009). Impact of micronutrient deficiencies on obesity. Nutr Rev, 67 (10): 559-72.
29. Mantzoros CS, Prasad AS, Beck FWJ, et al (1998). Zinc May Regulate Serum Leptin Concentrations in Humans. J Am Coll Nutr, 17 (3): 270-5.
30. Prasad AS (1991). Discovery of human zinc deficiency and studies in an experimental human model. Am J Clin Nutr, 53 (2): 403-12.
31. Halas ES, Wallwork JC, Sandstead HH (1982). Mild zinc deficiency and undernutrition during the prenatal and postnatal periods in rats: effects on weight, food consumption, and brain catecholamine concentrations. J Nutr, 112 (3): 542-51.
32. Mazloomi S, Alizadeh N, Aminzare M, et al (2018). RETRACTED ARTICLE: Serum Zinc and Adiponectin Levels in Patients with Polycystic Ovary Syndrome, Adjusted for Anthropometric, Biochemical, Dietary Intake, and Physical Activity Measures. Biol Trace Elem Res, 181 (2): 388.
33. Yang WS, Jeng CY, Wu TJ, et al (2002). Synthetic peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients. Diabetes Care, 25 (2): 376-80.
34. Sarraf P, Frederich RC, Turner EM, et al (1997). Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia. J Exp Med, 185 (1): 171-5.
35. Kirchgessner TG, Uysal KT, Wiesbrock SM, et al (1997). Tumor necrosis factor-alpha contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes. J Clin Invest, 100 (11): 2777-82.
36. Ueda H, Nakai T, Konishi T,et al (2014). Effects of Zinc Deficiency and Supplementation on Leptin and Leptin Receptor Expression in Pregnant Mice. Biol Pharm Bull, 37 (4): 581-7.
37. Baltaci AK, Mogulkoc R (2012). Leptin and zinc relation: In regulation of food intake and immunity. Indian J Endocrinol Metab, 16(Suppl 3): S611–S616.
38. Roshanravan N, Tarighat-Esfanjani A, Alamdari NM, et al (2018). The Effects of zinc supplementation on inflammatory parameters in pregnant women with impaired glucose tolerance: A randomized placebo controlled clinical trial. Progr Nutr, 20(1-S):330-6.
39. Bribiescas RG (2003). Effects of oral zinc supplementation on serum leptin levels in Ache males of eastern Paraguay. Am J Hum Biol, 15 (5): 681-7.
40. Kim J, Ahn J (2014). Effect of Zinc Supplementation on Inflammatory Markers and Adipokines in Young Obese Women. Biol Trace Elem Res, 157 (2): 101-6.
41. Marreiro DD, Geloneze B, Tambascia MA, et al (2006). Effect of zinc supplementation on serum leptin levels and insulin resistance of obese women. Biol Trace Elem Res, 112 (2): 109-18.
42. Khorshidi M, Zarezadeh M, Sadeghi A, et al (2019). The Effect of Zinc Supplementation on Serum Leptin Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Horm Metab Res, 51 (8): 503-510.
43. Liberati A, Altman DG, Tetzlaff J, et al (2009). The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ, 339: b2700.
44. Pt Higgins J, Green S (2009). Cochrane Handbook for Systematic Reviews of Interventions. https://training.cochrane.org/cochrane-handbook-systematic-reviews-interventions
45. Follmann D, Elliott P, Suh I, et al (1992). Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol, 45 (7): 769-73.
46. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7 (3): 177-88.
47. Egger M, Davey Smith G, Schneider M, et al (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315 (7109): 629-634.
48. Egger M, Smith GD, Altman DG (2001). Systematic reviews in health care : meta-analysis in context. 2nd ed. ISBN: 978-0-727-91488-0.
49. Gomez-Garcia A, Hernandez-Salazar E, Gonzalez-Ortiz M, et al (2006). Effect of oral zinc administration on insulin sensitivity, leptin and androgens in obese males. Rev Med Chil, 134 (3): 279-84.
50. Asghari S, Mohajeri Tehrani MR, Sadegh M (2011). The effect of zinc supplementation on plasma adiponectin and insulin resistance in type 2 diabetic patients. Iranian Journal of Diabetes and Lipid Disorders, 10 (4): 398-406.
| Files | ||
| Issue | Vol 50 No 2 (2021) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v50i2.5337 | |
| PMCID | PMC7956100 | |
| PMID | 33747988 | |
| Keywords | ||
| Zinc Adipokines Leptin Adiponectin Meta-analysis | ||
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How to Cite
1.
TABATABAIE M, SOLTANI S, MOZAFFARI-KHOSRAVI H, SALEHI-ABARGOUEI A. Zinc Supplementation Might Not Affect Serum Leptin and Adiponectin Levels in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. Iran J Public Health. 2021;50(2):245-256.
