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Home / Equine Research Bank / Equine Vet J / Leucine, pyridoxine and resveratrol supplementation alter me...
Equine veterinary journal2025; doi: 10.1002/evj.70135

Leucine, pyridoxine and resveratrol supplementation alter metabolic parameters in ponies with equine metabolic syndrome.

Abstract: Supplements claiming to improve metabolic profiles in equine metabolic syndrome (EMS) often lack scientific validation. Objective: To evaluate the effect of a supplement containing leucine, resveratrol and pyridoxine on the metabolic profile in ponies with EMS. Methods: Unmasked randomised, placebo-controlled field trial. Methods: Thirty-eight ponies completed the trial across five farms. Ponies were age and sex matched per farm and randomly assigned to the supplement (n = 20) or placebo group (n = 18) with owners masked to group assignments. Ponies were sampled at days -1/0 (T1), 7/8 (T2), 30/31 (T3) and 60/61 (T4). Measurements included morphometrics, insulin, triglycerides, nonesterified fatty acids, leptin and adiponectin, a two-step insulin tolerance test and oral sugar test (OST). Biochemical and dynamic testing results were compared across groups and times using pairwise comparisons of the estimated marginal means from mixed model, with significance set at a Tukey corrected p-value of <0.05. Chi analyses assessed group differences from the trial onset and conclusion, with significance set at a p-value of <0.05. Results: In the supplement group, maximum insulin post-OST was significantly reduced between T1/T2 and T3/T4, and bodyweight (bwt) decreased significantly between T1 and T4. By T4, more ponies in the supplement group lost ≥2% of their bwt (p = 0.006), with an average reduction of 8.1 kg (95% CI: -11.4, -4.7) while the placebo group gained an average of 2.6 kg (95% CI: -4.2, 9.4). Additionally, more ponies in the supplement group reduced maximum insulin post-OST by ≥40% (p = 0.01 average decrease 36.6 μU/mL; 95% CI: -60.8, -12.3), compared with the placebo group (average decrease of 3.5 μU/mL; 95% CI: -24.8, 17.8). Conclusions: Small sample size across multiple farms may have increased variability and masked some effects. Conclusions: Supplementation with leucine, pyridoxine and resveratrol may support weight loss and reduce post-prandial insulin concentrations in ponies with EMS.
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Publication Date: 2025-12-08 PubMed ID: 41358782DOI: 10.1002/evj.70135Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study tested whether a supplement containing leucine, pyridoxine (vitamin B6), and resveratrol can improve metabolic health in ponies diagnosed with equine metabolic syndrome (EMS), a condition linked to obesity and insulin resistance.
  • The researchers conducted a randomized controlled trial and found that ponies receiving the supplement showed reduced body weight and lower insulin levels after eating compared to ponies given a placebo.

Background and Objective

  • Equine metabolic syndrome (EMS) is characterized by obesity, insulin resistance, and increased risk of laminitis (a painful hoof condition).
  • Various supplements claim to improve metabolic health in EMS ponies but often lack scientific evidence supporting their effectiveness.
  • This study aimed to rigorously evaluate the effects of a supplement containing leucine (an amino acid), pyridoxine (vitamin B6), and resveratrol (an antioxidant compound) on metabolic parameters in ponies with EMS.

Methods

  • The trial was an unmasked randomized placebo-controlled field study conducted on five farms with a total of 38 ponies completing the trial.
  • Ponies were matched by age and sex within each farm and randomly assigned to either the supplement group (20 ponies) or placebo group (18 ponies).
  • Owners were blinded to treatment assignments to minimize bias.
  • Sampling occurred at four time points: baseline (day -1/0, T1), after one week (day 7/8, T2), after one month (day 30/31, T3), and after two months (day 60/61, T4).
  • At each time point, researchers measured:
    • Body morphometrics (weight and body condition)
    • Blood levels of insulin, triglycerides, nonesterified fatty acids, leptin, and adiponectin (hormones related to metabolism and fat regulation)
    • Dynamic tests including a two-step insulin tolerance test and an oral sugar test (OST) to assess insulin sensitivity and secretion.
  • Data analysis used mixed models with pairwise comparisons adjusted for multiple testing (Tukey correction), and chi-squared tests to assess group differences over time.

Key Results

  • Ponies receiving the supplement showed:
    • A significant reduction in maximum insulin concentration after the oral sugar test, particularly notable between baseline and week 1 (T1 to T2) and between one month and two months (T3 to T4).
    • A significant decrease in bodyweight from baseline to two months (T1 to T4).
    • At two months, a larger proportion of supplement-fed ponies lost at least 2% of their body weight compared to placebo ponies (statistically significant with p = 0.006).
    • The average weight loss in the supplement group was about 8.1 kg, whereas the placebo group on average gained weight (~2.6 kg).
    • More ponies in the supplement group achieved a ≥40% reduction in maximum insulin post-OST, indicating improved insulin response (p = 0.01).
  • The placebo group showed very little change in weight or insulin levels.
  • No significant differences were reported for other metabolic hormones or fatty acids.

Interpretation and Conclusions

  • The findings suggest that supplementation with leucine, pyridoxine, and resveratrol can support weight loss and improve insulin regulation after meals in ponies with EMS.
  • Reducing post-prandial (after meal) insulin spikes is important in managing EMS because high insulin can increase the risk of laminitis and other complications.
  • The study helps provide scientific validation for a supplement often marketed to improve metabolic health in EMS-affected equids.
  • Limitations included:
    • A relatively small sample size spread across multiple farms, which may have introduced variability and obscured some potential effects.
    • The trial was unmasked (except for owner blinding), which could introduce some bias.
  • Further larger-scale studies could help confirm and expand upon these results.

Significance for Equine Health Management

  • Managing EMS mainly involves dietary control and exercise; this study identifies a potential supplemental strategy to aid weight loss and improve insulin dynamics.
  • Supplementing with leucine, pyridoxine, and resveratrol could be a promising adjunct therapy to help reduce EMS-associated risks, especially in ponies that are difficult to manage by diet alone.
  • Veterinarians and equine managers should consider scientific evidence when choosing supplements for metabolic disease management.

Cite This Article

APA
Norton EM, Plumb S, Shane D, Smalley L, McKendry K, Scharf B, Zemel M. (2025). Leucine, pyridoxine and resveratrol supplementation alter metabolic parameters in ponies with equine metabolic syndrome. Equine Vet J. https://doi.org/10.1002/evj.70135

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

Norton, Elaine M
  • Department of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, Arizona, USA.
Plumb, Sydney
  • Department of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, Arizona, USA.
Shane, Douglas
  • Cornerstone Animal Health, Denton, Texas, USA.
Smalley, Lowell
  • Smalley Equine Veterinary Consulting, LLC, Omaha, Nebraska, USA.
McKendry, Kent
  • John Ewing Company, LaSalle, Colorado, USA.
Scharf, Bob
  • John Ewing Company, LaSalle, Colorado, USA.
Zemel, Michael
  • NuSirt Biopharma, Knoxville, Tennessee, USA.

Grant Funding

  • John Ewing Company

References

This article includes 57 references
  1. Durham AE, Frank N, McGowan CM, Menzies‐Gow NJ, Roelfsema E, Vervuert I. ECEIM consensus statement on equine metabolic syndrome. J Vet Intern Med 2019;33(2):335–349.
  2. Karikoski NP, Horn I, McGowan TW, McGowan CM. The prevalence of endocrinopathic laminitis among horses presented for laminitis at a first‐opinion/referral equine hospital. Domest Anim Endocrinol 2011;41(3):111–117.
  3. McGowan CM, Dugdale AH, Pinchbeck GL, Argo CM. Dietary restriction in combination with a nutraceutical supplement for the management of equine metabolic syndrome in horses. Vet J 2013;196(2):153–159.
  4. Manfredi JM, Stapley ED, Nadeau JA, Nash D. Investigation of the effects of a dietary supplement on insulin and adipokine concentrations in equine metabolic syndrome/insulin dysregulation. J Equine Vet Sci 2020;88:102930.
  5. Elzinga SE, Betancourt A, Stewart JC, Altman MH, Barker VD, Muholland M. Effects of docosahexaenoic acid‐rich microalgae supplementation on metabolic and inflammatory parameters in horses with equine metabolic syndrome. J Equine Vet Sci 2019;83:102811.
  6. Pinnell EF, Hostnik LD, Watts MR, Timko KJ, Thriffiley AA, Stover MR. Effect of 5′‐adenosine monophosphate‐activated protein kinase agonists on insulin and glucose dynamics in experimentally induced insulin dysregulation in horses. J Vet Intern Med 2024;38(1):102–110.
  7. Zemel MB, Bruckbauer A. Effects of a leucine and pyridoxine‐containing nutraceutical on fat oxidation, and oxidative and inflammatory stress in overweight and obese subjects. Nutrients 2012;4(6):529–541.
  8. Lal KJ, Sharma SK, Dakshinamurti K. Regulation of calcium influx into vascular smooth muscle by vitamin B6. Clin Exp Hypertens 1993;15(3):489–500.
  9. Dakshinamurti K, Lal KJ, Ganguly PK. Hypertension, calcium channel and pyridoxine (vitamin B6). Mol Cell Biochem 1998;188(1–2):137–148.
  10. Kalogeropoulou D, Lafave L, Schweim K, Gannon MC, Nuttall FQ. Leucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucose. Metabolism 2008;57(12):1747–1752.
  11. Sun X, Zemel MB. Leucine and calcium regulate fat metabolism and energy partitioning in murine adipocytes and muscle cells. Lipids 2007;42(4):297–305.
  12. Floyd ZE, Wang ZQ, Kilroy G, Cefalu WT. Modulation of peroxisome proliferator‐activated receptor γ stability and transcriptional activity in adipocytes by resveratrol. Metabolism 2008;57:S32–S38.
  13. Gomez‐Zorita S, Tréguer K, Mercader J, Carpéné C. Resveratrol directly affects in vitro lipolysis and glucose transport in human fat cells. J Physiol Biochem 2013;69:585–593.
  14. Batista‐Jorge GC, Barcala‐Jorge AS, Lelis DF, Santos DE, Jorge AH, Monteiro‐Junior RS. Resveratrol effects on metabolic syndrome features: a systematic review and meta‐analysis. Endocrine 2024;5(2):225–243.
  15. Adams A, Siard M, Reedy S, Stewart C, Betancourt A, Sanz M. Identifying the role of a ‘caloric restriction mimetic’, resveratrol, in equine metabolic syndrome and its implications for targeted therapy. J Equine Vet Sci 2013;5(33):346–347.
  16. Kreidler SM, Muller KE, Grunwald GK, Ringham BM, Coker‐Dukowitz ZT, Sakhadeo UR, et al. GLIMMPSE: online power computation for linear models with and without a baseline covariate. J Stat Softw. 2013;54(10):i10.
  17. R Core Team. R: a language and environment for statistical computing Vienna: R Foundation for Statistical Computing; 2024.
  18. Henneke DR, Potter GD, Kreider JL, Yeates BF. Relationship between condition score, physical measurements and body fat percentage in mares. Equine Vet J. 1983;15(4):371–372.
  19. Carter RA, Geor RJ, Staniar WB, Cubitt TA, Harris PA. Apparent adiposity assessed by standardised scoring systems and morphometric measurements in horses and ponies. Vet J. 2009;179(2):204–210.
  20. Bertin FR, Sojka‐Kritchevsky JE. Comparison of a 2‐step insulin‐response test to conventional insulin‐sensitivity testing in horses. Domest Anim Endocrinol. 2013;44(1):19–25.
  21. Hackett ES, McCue PM. Evaluation of a veterinary glucometer for use in horses. J Vet Intern Med. 2010;24(3):617–621.
  22. Schuver A, Frank N, Chameroy KA, Elliott SB. Assessment of insulin and glucose dynamics by using an oral sugar test in horses. J Equine Vet Sci. 2014;34(4):465–470.
  23. Jocelyn NA, Harris PA, Menzies‐Gow NJ. Effect of varying the dose of corn syrup on the insulin and glucose response to the oral sugar test. Equine Vet J. 2018;50(6):836–841.
  24. Wooldridge AA, Edwards HG, Plaisance EP, Applegate R, Taylor DR, Taintor J, et al. Evaluation of high‐molecular weight adiponectin in horses. Am J Vet Res. 2012;73(8):1230–1240.
  25. Yang X, Alexander VJ, Xia S, Tsimikas S. Effect of olezarsen on lipoprotein‐associated ApoC‐III levels in patients with familial chylomicronemia syndrome. Atherosclerosis. 2025;408:120462.
  26. Waitt LH, Cebra CK. Characterization of hypertriglyceridemia and response to treatment with insulin in horses, ponies, and donkeys: 44 cases (1995–2005). J Am Vet Med Assoc. 2009;234(7):915–919.
  27. Sundra T, Kelty E, Rendle D. Preliminary observations on the use of ertugliflozin in the management of hyperinsulinaemia and laminitis in 51 horses: a case series. Equine Vet Educ. 2023;35(6):311–320.
  28. Bamford NJ, Potter SJ, Baskerville CL, Harris PA, Bailey SR. Influence of dietary restriction and low‐intensity exercise on weight loss and insulin sensitivity in obese equids. J Vet Intern Med. 2019;33(1):280–286.
  29. Ungru J, Coenen M, Vervuert I, Blüher M, Raila J, Boston R. Effects of body weight reduction on blood adipokines and subcutaneous adipose tissue adipokine mRNA expression profiles in obese ponies. Vet Rec. 2012;171(21):528.
  30. Knowles EJ, Harris PA, Elliott J, Menzies‐Gow NJ. Use of the oral sugar test in ponies when performed with or without prior fasting. Equine Vet J. 2017;49(4):519–524.
  31. Frank N, Walsh DM. Repeatability of oral sugar test results, glucagon‐like peptide‐1 measurements, and serum high‐molecular‐weight adiponectin concentrations in horses. J Vet Intern Med. 2017;31(4):1178–1187.
  32. Piccione G, Arfuso F, Giudice E, Aragona F, Pugliatti P, Panzera MF, et al. Dynamic adaptation of hematological parameters, albumin, and non‐esterified fatty acids in Saddlebred and Standardbred horses during exercise. Animals (Basel). 2025;15(3):300.
  33. Misra A, Alappan NK, Vikram NK, Goel K, Gupta N, Mittal K, et al. Effect of supervised progressive resistance‐exercise training protocol on insulin sensitivity, glycemia, lipids, and body composition in Asian Indians with type 2 diabetes. Diabetes Care. 2008;31(7):1282–1287.
  34. Lee MY, Koh JH, Nam SM, Jung PM, Sung JK, Kim SY, et al. Short insulin tolerance test can determine the effects of thiazolidinediones treatment in type 2 diabetes. Yonsei Med J. 2008;49(6):901–908.
  35. Bates D, Mächler M, Bolker B, Walker S. Fitting linear mixed‐effects models using lme4. J Stat Softw. 2015;67(1):1–48.
  36. Lenth R. emmeans: estimated marginal means, aka least‐squares means. R package version 1.11.2; 2025. https://CRAN.R‐project.org/package=emmeans
  37. Martinson KL, Coleman RC, Rendahl AK, Fang Z, McCue ME. Estimation of body weight and development of a body weight score for adult equids using morphometric measurements1. J Anim Sci. 2014;92(5):2230–2238.
  38. Pratt‐Phillips SE, Owens KM, Dowler LE, Cloninger MT. Assessment of resting insulin and leptin concentrations and their association with managerial and innate factors in horses. J Equine Vet Sci. 2010;30(3):127–133.
  39. Buff PR, Dodds AC, Morrison CD, Whitley NC, McFadin EL, Daniel JA, et al. Leptin in horses: tissue localization and relationship between peripheral concentrations of leptin and body condition. J Anim Sci. 2002;80(11):2942–2948.
  40. Arvidsson E, Viguerie N, Andersson I, Verdich C, Langin D, Arner P. Effects of different hypocaloric diets on protein secretion from adipose tissue of obese women. Diabetes. 2004;53(8):1966–1971.
  41. Garaulet M, Viguerie N, Porubsky S, Klimcakova E, Clement K, Langin D, et al. Adiponectin gene expression and plasma values in obese women during very‐low‐calorie diet. Relationship with cardiovascular risk factors and insulin resistance. J Clin Endocrinol Metab. 2004;89(2):756–760.
  42. Kovacikova M, Vitkova M, Klimcakova E, Polak J, Hejnova J, Bajzova M, et al. Visfatin expression in subcutaneous adipose tissue of pre‐menopausal women: relation to hormones and weight reduction. Eur J Clin Invest. 2008;38(7):516–522.
  43. Capel F, Viguerie N, Vega N, Dejean S, Arner P, Klimcakova E, et al. Contribution of energy restriction and macronutrient composition to changes in adipose tissue gene expression during dietary weight‐loss programs in obese women. J Clin Endocrinol Metab. 2008;93(11):4315–4322.
  44. Ramel A, Parra D, Martinéz JA, Kiely M, Thorsdottir I. Effects of seafood consumption and weight loss on fasting leptin and ghrelin concentrations in overweight and obese European young adults. Eur J Nutr. 2009;48(2):107–114.
  45. Van Weyenberg S, Hesta M, Buyse J, Janssens GPJ. The effect of weight loss by energy restriction on metabolic profile and glucose tolerance in ponies. J Anim Physiol Anim Nutr (Berl). 2008;92(5):538–545.
  46. Macon EL, Harris P, Barker VD, Adams AA. Seasonal insulin responses to the oral sugar test in healthy and insulin dysregulated horses. J Equine Vet Sci. 2022;113:103945.
  47. Cohen PA, Schneidman K, Ginsberg‐Fellner F, Sturman JA, Knittle J, Gaull GE. High pyridoxine diet in the rat: possible implications for megavitamin therapy. J Nutr. 1973;103(1):143–151.
  48. Hagiwara S, Gohda T, Tanimoto M, Ito T, Murakoshi M, Ohara I, et al. Effects of pyridoxamine (K‐163) on glucose intolerance and obesity in high‐fat diet C57BL/6J mice. Metabolism. 2009;58(7):934–945.
  49. Haidari F, Mohammadshahi M, Zarei M, Haghighizadeh MH, Mirzaee F. The effect of pyridoxine hydrochloride supplementation on leptin, adiponectin, glycemic indices, and anthropometric indices in obese and overweight women. Clin Nutr Res. 2021;10(3):230–242.
  50. Mourier A, Bigard AX, de Kerviler E, Roger B, Legrand H, Guezennec CY. Combined effects of caloric restriction and branched‐chain amino acid supplementation on body composition and exercise performance in elite wrestlers. Int J Sports Med. 1997;18(1):47–55.
  51. He X, Duan Y, Yao K, Li F, Hou Y, Wu G, et al. β‐Hydroxy‐β‐methylbutyrate, mitochondrial biogenesis, and skeletal muscle health. Amino Acids. 2016;48(3):653–664.
  52. Nairizi A, She P, Vary TC, Lynch CJ. Leucine supplementation of drinking water does not alter susceptibility to diet‐induced obesity in mice. J Nutr. 2009;139(4):715–719.
  53. Zhang Y, Guo K, LeBlanc RE, Loh D, Schwartz GJ, Yu Y‐H. Increasing dietary leucine intake reduces diet‐induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes. 2007;56(6):1647–1654.
  54. Zemel MB, Bruckbauer A. Effects of a leucine and pyridoxine‐containing nutraceutical on body weight and composition in obese subjects. Diabetes Metab Syndr Obes. 2013;6:309–315.
  55. Murphy M, Bartges JW, Zemel MB, Kirk CA, Witzel‐Rollins A. Effect of a leucine/pyridoxine nutraceutical on caloric intake and body composition of obese dogs losing weight. Front Vet Sci. 2020;7:7.
  56. Mukherjee S, Dudley JI, Das DK. Dose‐dependency of resveratrol in providing health benefits. Dose Response. 2010;8(4):478–500.
  57. Bruckbauer A, Zemel MB. Synergistic effects of polyphenols and methylxanthines with leucine on AMPK/sirtuin‐mediated metabolism in muscle cells and adipocytes. PLoS One. 2014;9(2):e89166.

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