Scientifically formulated recipe for a dietary supplement for immunonutrition during surgery

Abstract

Formula of a dietary supplement for immunonutrition (support of the immune system through nutrients), consisting of proteins, omega-3 fatty acids, creatine, vitamin C, zinc, vitamin D, folic acid, vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B12, vitamin E, iron, beta-alanine, arginine, calcium, prebiotics: inulin, probiotics: Bifidobacterium animalis ssp. lactis; Bifidobacterium breve; Lactobacillus acidophilus; Lactiplantibacillus plantarum; Limosilactobacillus reuteri; Lacticaseibacillus rhamnosus.

Description

Rationale / underlying problem:

[0001] Thanks to modern medicine, humanity was able to overcome deadly diseases just over 100 years ago. Advances in surgery have played a significant role in this. Nevertheless, despite intensive efforts, residual risks of complications during surgery ("perioperative") remain.

[0002] The most feared complication by both patients and surgeons is infection of the surgical site, usually caused by bacteria. Despite modern antibiotics and hygiene measures during the procedure, the risk of infection can be as high as 11% for complex procedures (1).

[0003] Many risk factors have been scientifically researched and confirmed. For example, significant overweight, nicotine abuse, or comorbidities such as diabetes mellitus and cardiovascular diseases are considered prognostically unfavorable factors (2-3). Furthermore, existing malnutrition has been confirmed as a risk factor for perioperative infection (4). Malnutrition here does not refer to being underweight, but rather to a poor diet with a deficiency of nutrients that positively influence the immune system. For example, most significantly overweight people are malnourished (5-7).

[0004] International studies, based on the finding that a large proportion of the population suffers from at least some form of malnutrition, have now shown that the intake of nutrients that strengthen the immune system can lead to a lower infection rate (8,9). This applies both after serious accidents and during surgeries that put a strain on the immune system. This type of additional nutrient intake is called immunonutrition. State of the art:

[0005] Currently, various products for immunonutrition (technical) are available on the market (Table 1). These generally cover specific aspects of the scientifically documented malnutrition mentioned above. These products are usually only used within the context of specialized treatment processes, such as in intensive care units (10,11). Table 1. State of the art. Product name Main ingredients (per serving / day) Nestle, Impact Arginine (~4.5 g), Omega-3 (EPA / DHA~1.5-2 g), Nucleotides (~0.2 g), Antioxidants (Vit. C, E, Selenium, Zinc) Nestle, Oral Impact Arginine, EPA / DHA, nucleotides, selenium, zinc, vitamin C / E Nestle, modules TGF-β-rich proteins, medium-chain fats, easily digestible carbohydrates Fresenius Kabi, Reconvan Arginine, omega-3, nucleotides, vitamin C, vitamin E, selenium, zinc, copper Fresenius Kabi, Survimed Arginine (~4g), Omega-3 (~2g), Vitamin A, C, E, Selenium, Nucleotides Nutricia, Cubison High in protein, zinc, arginine, vitamin C Nutricia, Fortimel High protein (~20g), vitamin D, calcium, zinc, omega-3 Smartfish AS, Remune Omega-3 (EPA / DHA), highly bioavailable antioxidants, vitamin D, whey protein Abbott Nutrition, NeproHP High in calories, high in protein, vitamin B complex, omega-3, low in phosphorus / potassium / sodium Abbott Nutrition, EnsurePlus Advance HMB (β-Hydroxy-β-methylbutyrate), Vit. D, Protein (~20 g), Ca, Zinc

[0006] The aforementioned link between infection risk and malnutrition is not sufficiently known to most people, and those affected by a postoperative infection often feel helpless and wonder why it happened to them. Similarly, surgeons are frequently confronted with the consequences of such complications, and even among these specialists, the field of immunonutrition still does not receive enough attention. Invention / Problem solving:

[0007] Taking the above points into account, the applicants (licensed physicians, including a specialist in orthopedics and trauma surgery with additional qualifications in nutritional medicine and sports medicine) conducted a comprehensive analysis of existing evidence-based studies (sufficiently valid and robust according to international criteria) on this topic. Based on this analysis, a unique formula was developed that combines all nutrients known to date as having evident benefits into a single dietary supplement. Clear scientific evidence exists for each of the nutrients (Table 2). Table 2. Recipe of the novel product. protein 12, 13 Omega-3 fatty acids 14, 15 Creatine 16, 17 Vitamin C 18, 19 zinc 20, 21 Vitamin D 22, 23 Folic acid 24 Vitamin B1 25-29 Vitamin B2 Vitamin B3 Vitamin B5 Vitamin B6 Vitamin B12 Vitamin E 30, 31 iron 32, 33 Beta-alanine 34 Arginine 35, 36 Calcium 37 Inulin (prebiotics) 38, 39 Probiotics (active strains of bacteria that support the intestinal flora) 40, 41 Achievable benefits:

[0008] The product, currently under development for market readiness and based on the aforementioned formula, is intended to help reduce the perioperative risk of infection in the future. Depending on pre-existing conditions and the underlying surgery, a reduction of up to 45% has been described in the literature (42-44).

[0009] The use of this product therefore contributes to the prevention of complications for every patient and, in the best-case scenario, can even prevent the considerable costs of a perioperative infection. The KRINKO (Commission for Hospital Hygiene and Infection Prevention) and the KISS surveillance system estimate that there are approximately 195,000 surgical site infections (SSIs) annually in German acute care hospitals. These infections prolong hospital stays, increase morbidity and mortality, and, according to estimates, cause total costs in the range of several billion euros per year (approximately €1-3 billion) (45). References: 1. Gillespie BM, Harbeck E, Rattray M, Liang R, Walker R, Latimer S, Thalib L, Andersson AE, Griffin B, Ware R, Chaboyer W. Worldwide incidence of surgical site infections in general surgical patients: A systematic review and meta-analysis of 488,594 patients. Int J Surg. 2021 Nov;95:106136. doi: 10.1016 / j.ijsu.2021.106136. Epub 2021 Oct 13. PMID: 34655800. 2. Bagheri A, Sharifi Niknafs A, Farhadi B, Mazhari SA, Karimian P, Hekmati Pour N, Hojjati H, Nosratabadi I, Emami A, Salehi R. Incidence and Risk Factors of Surgical Site Infection After Knee Arthroplasty; a Systematic Review and Meta-Analysis. Arch Acad Emerg Med. 2025 Jan 18;13(1):e28. doi: 10.22037 / aaemj.v13i1.2543. PMID: 40027221; PMCID: PMC11870287. 3. Garale MN, Rewatkar AK, Moktali AV, Dalvi A. Incidence and Risk Factors for Surgical Site Infections Following Emergency Laparotomies: A Prospective Observational Study. Cureus. 2025 Mar 9;17(3):e80283. doi: 10.7759 / cureus.80283. PMID: 40201888; PMCID: PMC11977445. 4. Lasithiotakis, K., Andreou, A., Migdadi, H. et al. Malnutrition and perioperative nutritional rehabilitation in major operations. Eur Surg (2025). doi.org / 10.1007 / s10353-025-00863-4 5. Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BW, Zitman FG. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry. 2010 Mar;67(3):220-9. doi: 10.1001 / archgenpsychiatry.2010.2. PMID: 20194822. 6. Kobylińska M, Antosik K, Decyk A, Kurowska K. Malnutrition in Obesity: Is It Possible? Obes Facts. 2022;15(1):19-25. doi: 10.1159 / 000519503. Epub 2021 Nov 8. PMID: 34749356; PMCID: PMC8820192. 7. Freeman AM, Aggarwal M. Malnutrition in the Obese: Commonly Overlooked But With Serious Consequences. J Am Coll Cardiol. 2020 Aug 18;76(7):841-843. doi: 10.1016 / j.jacc.2020.06.059. PMID: 32792082. 8. Wu D, Lewis ED, Pae M, Meydani SN. Nutritional Modulation of Immune Function: Analysis of Evidence, Mechanisms, and Clinical Relevance. Front Immunol. 2019 Jan 15;9:3160. doi: 10.3389 / fimmu.2018.03160. PMID: 30697214; PMCID: PMC6340979. 9. Bourke CD, Berkley JA, Prendergast AJ. Immune Dysfunction as a Cause and Consequence of Malnutrition. Trends Immunol. 2016 Jun;37(6):386-398. doi: 10.1016 / j.it.2016.04.003. Epub 2016 May 26. PMID: 27237815; PMCID: PMC4889773. 10. Preiser JC, Arabi YM, Berger MM, Casaer M, McClave S, Montejo-González JC, Peake S, Reintam Blaser A, Van den Berghe G, van Zanten A, Wernerman J, Wischmeyer P. A guide to enteral nutrition in intensive care units: 10 expert tips for the daily practice. Crit Care. 2021 Dec 14;25(1):424. doi: 10.1186 / s13054-021-03847-4. PMID: 34906215; PMCID: PMC8669237 11. Ochoa Gautier JB, Berger A, Hussein R, Huhmann MB. Safety of increasing protein delivery with an enteral nutrition formula containing very high protein (VHP) and lower carbohydrate concentrations compared to conventional standard (SF) and high protein (HP) formulas. Clin Nutr. 2022 Dec;41(12):2833-2842. doi: 10.1016 / j.clnu.2022.10.020. Epub 2022 Nov 5. PMID: 36402010. 12. Zhang B, Najarali Z, Ruo L, Alhusaini A, Solis N, Valencia M, Sanchez MIP, Serrano PE. Effect of Perioperative Nutritional Supplementation on Postoperative Complications-Systematic Review and Meta-Analysis. J Gastrointest Surg. 2019 Aug;23(8):1682-1693. doi: 10.1007 / s11605-019-04173-5. Epub 2019 May 6. PMID: 31062270. 13. Srinivasaraghavan N, Das N, Balakrishnan K, Rajaram S. Effect of Whey Protein Supplementation on Perioperative Outcomes in Patients with Cancer-A Systematic Review and Meta-Analysis (PROSPERO 2020: CRD42020188666). Nutr Cancer. 2022;74(7):2351-2364. doi: 10.1080 / 01635581.2021.2020302. Epub 2021 Dec 28. PMID: 34961401. 14. Mohsen G, Stroemer A, Mayr A, Kunsorg A, Stoppe C, Wittmann M, Velten M. Effects of Omega-3 Fatty Acids on Postoperative Inflammatory Response: A Systematic Review and Meta-Analysis. Nutrients. 2023 Jul 31;15(15):3414. doi: 10.3390 / nu15153414. PMID: 37571352; PMCID: PMC10421202. 15. Sorensen LS, Thorlacius-Ussing O, Schmidt EB, Rasmussen HH, Lundbye-Christensen S, Calder PC, Lindorff-Larsen K. Randomized clinical trial of perioperative omega-3 fatty acid supplements in elective colorectal cancer surgery. Br J Surg. 2014 Jan;101(2):33-42. doi: 10.1002 / bjs.9361. Epub 2013 Nov 26. PMID: 24281905. 16. Bredahl EC, Eckerson JM, Tracy SM, McDonald TL, Drescher KM. The Role of Creatine in the Development and Activation of Immune Responses. Nutrients. 2021 Feb 26;13(3):751. doi: 10.3390 / nu13030751. PMID: 33652752; PMCID: PMC7996722. 17. Di Biase S, Ma X, Wang X, Yu J, Wang YC, Smith DJ, Zhou Y, Li Z, Kim YJ, Clarke N, To A, Yang L. Creatine uptake regulates CD8 T cell antitumor immunity. J Exp Med. 2019 Dec 2;216(12):2869-2882. doi: 10.1084 / jem.20182044. Epub 2019 Oct 18. PMID: 31628186; PMCID: PMC6888972. 18. Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017 Nov 3;9(11):1211. doi: 10.3390 / nu9111211. PMID: 29099763; PMCID: PMC5707683. 19. Ramón R, Holguín E, Chiriboga JD, Rubio N, Ballesteros C, Ezechieli M. Anti-Inflammatory Effect of Vitamin C during the Postoperative Period in Patients Subjected to Total Knee Arthroplasty: A Randomized Controlled Trial. J Pers Med. 2023 Aug 25;13(9):1299. doi: 10.3390 / jpm13091299. PMID: 37763067; PMCID: PMC10532858. 20. Wessels I, Maywald M, Rink L. Zinc as a Gatekeeper of Immune Function. Nutrients. 2017 Nov 25;9(12):1286. doi: 10.3390 / nu9121286. PMID: 29186856; PMCID: PMC5748737. 21. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998 Aug;68(2 Suppl):447S-463S. doi: 10.1093 / ajcn / 68.2.447S. PMID: 9701160. 22. Iglar PJ, Hogan KJ. Vitamin D status and surgical outcomes: a systematic review. Patient Saf Surg. 2015 Apr 30;9:14. doi: 10.1186 / s13037-015-0060-y. PMID: 25926889; PMCID: PMC4413543. 23. Birinci M, Hakyemez ÖS, Geçkalan MA, Mutlu M, Yildiz F, Bilgen ÖF, Azboy I. Effect of Vitamin D Deficiency on Periprosthetic Joint Infection and Complications After Primary Total Joint Arthroplasty. J Arthroplasty. 2024 Sep;39(9S2):S151-S157. doi: 10.1016 / j.arth.2024.05.012. Epub 2024 May 10. PMID: 38734328. 24. Myles PS, Chan MT, Forbes A, Leslie K, Paech M, Peyton P. Preoperative folate and homocysteine status in patients undergoing major surgery. Clin Nutr. 2006 Oct;25(5):736-45. doi: 10.1016 / j.clnu.2006.04.003. PMID: 16766094. 25. Sander J, Torensma B, Siepe J, Schorp T, Schulte T, Schmeer C, Gögele H, Böckelmann I, Grabenhorst A, Ockert-Belz I, Berends F, Aarts E. Assessment of Preoperative Multivitamin Use on the Impact on Micronutrient Deficiencies in Patients with Obesity Prior to Metabolic Bariatric Surgery. Obes Surg. 2025 May;35(5):1818-1826. doi: 10.1007 / s11695-025-07853-1. Epub 2025 Apr 8. Erratum in: Obes Surg. 2025 Jun 11. doi: 10.1007 / s11695-025-07970-x. PMID: 40199822; PMCID: PMC12065735. 26. Zhang L, Zhang F, Li S, Xu F, Zheng X, Huang T, Lyu J, Yin H. Thiamine supplementation may be associated with improved prognosis in patients with sepsis. Br J Nutr. 2023 Jul 28;130(2):239-248. doi: 10.1017 / S0007114522003373. Epub 2022 Oct 19. PMID: 36259460; PMCID: PMC10277660. 27. Mitra S, Paul S, Roy S, Sutradhar H, Bin Emran T, Nainu F, Khandaker MU, Almalki M, Wilairatana P, Mubarak MS. Exploring the Immune-Boosting Functions of Vitamins and Minerals as Nutritional Food Bioactive Compounds: A Comprehensive Review. Molecules. 2022 Jan 16;27(2):555. doi: 10.3390 / molecules27020555. PMID: 35056870; PMCID: PMC8779769. 28. Yoshii K, Hosomi K, Sawane K, Kunisawa J. Metabolism of Dietary and Microbial Vitamin B Family in the Regulation of Host Immunity. Front Nutr. 2019 Apr 17;6:48. doi: 10.3389 / fnut.2019.00048. PMID: 31058161; PMCID: PMC6478888. 29. Mikkelsen K, Stojanovska L, Prakash M, Apostolopoulos V. The effects of vitamin B on the immune / cytokine network and their involvement in depression. Maturitas. 2017 Feb;96:58-71. doi: 10.1016 / j.maturitas.2016.11.012. Epub 2016 Nov 19. PMID: 28041597. 30. Fan Y, Yuh J, Lekkala S, Asik MD, Thomson A, McCanne M, Randolph MA, Chen AF, Oral E. The efficacy of vitamin E in preventing arthrofibrosis after joint replacement. Animal Model Exp Med. 2024 Apr;7(2):145-155. doi: 10.1002 / ame2.12388. Epub 2024 Mar 25. PMID: 38525803; PMCID: PMC11079150. 31. Asbaghi O, Sadeghian M, Nazarian B, Sarreshtedari M, Mozaffari-Khosravi H, Maleki V, Alizadeh M, Shokri A, Sadeghi O. The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials. Sci Rep. 2020 Oct 14;10(1):17234. doi: 10.1038 / s41598-020-73741-6. PMID: 33057114; PMCID: PMC7560744 32. Czempik PF, Wiórek A. Iron deficiency in sepsis patients managed with divided doses of iron dextran: a prospective cohort study. Sci Rep. 2023 Mar 31;13(1):5264. doi: 10.1038 / s41598-023-32002-y. PMID: 37002279; PMCID: PMC10066317. 33. Ni S, Yuan Y, Kuang Y, Li X. Iron Metabolism and Immune Regulation. Front Immunol. 2022 Mar 23;13:816282. doi: 10.3389 / fimmu.2022.816282. PMID: 35401569; PMCID: PMC8983924. 34. Dolan E, Swinton PA, Painelli VS, Stephens Hemingway B, Mazzolani B, Infante Smaira F, Saunders B, Artioli GG, Gualano B. A Systematic Risk Assessment and Meta-Analysis on the Use of Oral β-Alanine Supplementation. Adv Nutr. 2019 May 1;10(3):452-463. doi: 10.1093 / advances / nmy115. PMID: 30980076; PMCID: PMC6520041. 35. Aghaeepour N, Kin C, Ganio EA, Jensen KP, Gaudilliere DK, Tingle M, Tsai A, Lancero HL, Choisy B, McNeil LS, Okada R, Shelton AA, Nolan GP, Angst MS, Gaudilliere BL. Deep Immune Profiling of an Arginine-Enriched Nutritional Intervention in Patients Undergoing Surgery. J Immunol. 2017 Sep 15;199(6):2171-2180. doi: 10.4049 / jimmunoi.1700421. Epub 2017 Aug 9. PMID: 28794234; PMCID: PMC5807249. 36. Marik PE, Zaloga GP. Immunonutrition in high-risk surgical patients: a systematic review and analysis of the literature. JPEN J Parenter Enteral Nutr. 2010 Jul-Aug;34(4):378-86. doi: 10.1177 / 0148607110362692. PMID: 20631383. 37. Diercks BP. The importance of Ca 2+ microdomains for the adaptive immune response. Biochim Biophys Acta Mol Cell Res. 2024 Jun;1871(5):119710. doi: 10.1016 / j.bbamcr.2024.119710. Epub 2024 Mar 23. PMID: 38522726. 38. Sheng W, Ji G, Zhang L. Immunomodulatory effects of inulin and its intestinal metabolites. Front Immunol. 2023Aug 10;14:1224092. doi: 10.3389 / fimmu.2023.1224092. PMID: 37638034; PMCID: PMC10449545. 39. De Giani A, Sandionigi A, Zampolli J, Michelotti A, Tursi F, Labra M, Di Gennaro P. Effects of Inulin-Based Prebiotics Alone or in Combination with Probiotics on Human Gut Microbiota and Markers of Immune System: A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Subjects. Microorganisms. 2022 Jun 20;10(6):1256. doi: 10.3390 / microorganisms10061256. PMID: 35744774; PMCID: PMC9229734. 40. Heckmann ND, Culler MW, Mont MA, Lieberman JR, Parvizi J. Emerging Concepts in Periprosthetic Joint Infection Research: The Human Microbiome. J Arthroplasty. 2025 Jul;40(7):1821-1826. doi: 10.1016 / j.arth.2025.01.001. Epub 2025 Jan 9. PMID: 39798621. 41. Tzikos G, Tsalkatidou D, Stavrou G, Thoma G, Chorti A, Tsilika M, Michalopoulos A, Papavramidis T, Giamarellos-Bourboulis EJ, Kotzampassi K. A Four-Probiotic Regime to Reduce Surgical Site, Infections in Multi-Trauma Patients. Nutrients. 2022 Jun 24;14(13):2620. doi: 10.3390 / nu14132620. PMID: 35807801; PMCID: PMC9268677. 42. Slim K, Badon F, Vacheron CH, Occean BV, Dziri C, Chambrier C. Umbrella review of the efficacy of perioperative immunonutrition in visceral surgery. Clin Nutr ESPEN. 2022 Apr;48:99-108. doi: 10.1016 / j.clnesp.2022.02.015. Epub 2022 Feb 24. PMID: 35331540. 43. Buzquurz F, Bojesen RD, Grube C, Madsen MT, Gögenur I. Impact of oral preoperative and perioperative immunonutrition on postoperative infection and mortality in patients undergoing cancer surgery: systematic review and meta-analysis with trial sequential analysis. BJS Open. 2020 Oct;4(5):764-775. doi: 10.1002 / bjs5.50314. Epub 2020 Jun 23. PMID: 32573977; PMCID: PMC7528521. 44. Shen J, Dai S, Li Z, Dai W, Hong J, Huang J, Chen J. Effect of Enteral Immunonutrition in Patients Undergoing Surgery for Gastrointestinal Cancer: An Updated Systematic Review and Meta-Analysis. Front Nutr. 2022 Jun 29;9:941975. doi: 10.3389 / fnut.2022.941975. PMID: 35845793; PMCID: PMC9277464. 45. Association of the Scientific Medical Societies in Germany (AWMF). S3 Guideline: Perioperative and Periinterventional Antibiotic Prophylaxis (PAP). AWMF Registry No. 067-009. Version 5.0. Published December 20, 2024. Available at: https: / / register.awmf.org / de / leitlinien / detail / 067-009 QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Zitierte Nicht-Patentliteratur

[0000] Gillespie BM, Harbeck E, Rattray M, Liang R, Walker R, Latimer S, Thalib L, Andersson AE, Griffin B, Ware R, Chaboyer W. Worldwide incidence of surgical site infections in general surgical patients: A systematic review and meta-analysis of 488,594 patients. Int J Surg. 2021 Nov;95:106136. doi: 10.1016 / j.ijsu.2021.106136. Epub 2021 Oct 13. PMID: 34655800

[0009] Bagheri A, Sharifi Niknafs A, Farhadi B, Mazhari SA, Karimian P, Hekmati Pour N, Hojjati H, Nosratabadi I, Emami A, Salehi R. Incidence and Risk Factors of Surgical Site Infection After Knee Arthroplasty; a Systematic Review and Meta-Analysis. Arch Acad Emerg Med. 2025 Jan 18;13(1):e28. doi: 10.22037 / aaemj.v13i1.2543. PMID: 40027221; PMCID: PMC11870287

[0009] Garale MN, Rewatkar AK, Moktali AV, Dalvi A. Incidence and Risk Factors for Surgical Site Infections Following Emergency Laparotomies: A Prospective Observational Study. Cureus. 2025 Mar 9;17(3):e80283. doi: 10.7759 / cureus.80283. PMID: 40201888; PMCID: PMC11977445

[0009] Lasithiotakis, K., Andreou, A., Migdadi, H. et al. Malnutrition and perioperative nutritional rehabilitation in major operations. Eur Surg (2025). doi.org / 10.1007 / s10353-025-00863-4

[0009] Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BW, Zitman FG. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry. 2010 Mar;67(3):220-9. doi: 10.1001 / archgenpsychiatry.2010.2. PMID: 20194822

[0009] Kobylińska M, Antosik K, Decyk A, Kurowska K. Malnutrition in Obesity: Is It Possible? Obes Facts. 2022;15(1):19-25. doi: 10.1159 / 000519503. Epub 2021 Nov 8. PMID: 34749356; PMCID: PMC8820192

[0009] Freeman AM, Aggarwal M. Malnutrition in the Obese: Commonly Overlooked But With Serious Consequences. J Am Coll Cardiol. 2020 Aug 18;76(7):841-843. doi: 10.1016 / j.jacc.2020.06.059. PMID: 32792082

[0009] Wu D, Lewis ED, Pae M, Meydani SN. Nutritional Modulation of Immune Function: Analysis of Evidence, Mechanisms, and Clinical Relevance. Front Immunol. 2019 Jan 15;9:3160. doi: 10.3389 / fimmu.2018.03160. PMID: 30697214; PMCID: PMC6340979

[0009] Bourke CD, Berkley JA, Prendergast AJ. Immune Dysfunction as a Cause and Consequence of Malnutrition. Trends Immunol. 2016 Jun;37(6):386-398. doi: 10.1016 / j.it.2016.04.003. Epub 2016 May 26. PMID: 27237815; PMCID: PMC4889773

[0009] Preiser JC, Arabi YM, Berger MM, Casaer M, McClave S, Montejo-González JC, Peake S, Reintam Blaser A, Van den Berghe G, van Zanten A, Wernerman J, Wischmeyer P. A guide to enteral nutrition in intensive care units: 10 expert tips for the daily practice. Crit Care. 2021 Dec 14;25(1):424. doi: 10.1186 / s13054-021-03847-4. PMID: 34906215; PMCID: PMC8669237

[0009] Ochoa Gautier JB, Berger A, Hussein R, Huhmann MB. Safety of increasing protein delivery with an enteral nutrition formula containing very high protein (VHP) and lower carbohydrate concentrations compared to conventional standard (SF) and high protein (HP) formulas. Clin Nutr. 2022 Dec;41(12):2833-2842. doi: 10.1016 / j.clnu.2022.10.020. Epub 2022 Nov 5. PMID: 36402010

[0009] Zhang B, Najarali Z, Ruo L, Alhusaini A, Solis N, Valencia M, Sanchez MIP, Serrano PE. Effect of Perioperative Nutritional Supplementation on Postoperative Complications-Systematic Review and Meta-Analysis. J Gastrointest Surg. 2019 Aug;23(8):1682-1693. doi: 10.1007 / s11605-019-04173-5. Epub 2019 May 6. PMID: 31062270

[0009] Srinivasaraghavan N, Das N, Balakrishnan K, Rajaram S. Effect of Whey Protein Supplementation on Perioperative Outcomes in Patients with Cancer-A Systematic Review and Meta-Analysis (PROSPERO 2020: CRD42020188666). Nutr Cancer. 2022;74(7):2351-2364. doi: 10.1080 / 01635581.2021.2020302. Epub 2021 Dec 28. PMID: 34961401

[0009] Mohsen G, Stroemer A, Mayr A, Kunsorg A, Stoppe C, Wittmann M, Velten M. Effects of Omega-3 Fatty Acids on Postoperative Inflammatory Response: A Systematic Review and Meta-Analysis. Nutrients. 2023 Jul 31;15(15):3414. doi: 10.3390 / nu15153414. PMID: 37571352; PMCID: PMC10421202

[0009] Sorensen LS, Thorlacius-Ussing O, Schmidt EB, Rasmussen HH, Lundbye-Christensen S, Calder PC, Lindorff-Larsen K. Randomized clinical trial of perioperative omega-3 fatty acid supplements in elective colorectal cancer surgery. Br J Surg. 2014 Jan;101(2):33-42. doi: 10.1002 / bjs.9361. Epub 2013 Nov 26. PMID: 24281905

[0009] Bredahl EC, Eckerson JM, Tracy SM, McDonald TL, Drescher KM. The Role of Creatine in the Development and Activation of Immune Responses. Nutrients. 2021 Feb 26;13(3):751. doi: 10.3390 / nu13030751. PMID: 33652752; PMCID: PMC7996722

[0009] Di Biase S, Ma X, Wang X, Yu J, Wang YC, Smith DJ, Zhou Y, Li Z, Kim YJ, Clarke N, To A, Yang L. Creatine uptake regulates CD8 T cell antitumor immunity. J Exp Med. 2019 Dec 2;216(12):2869-2882. doi: 10.1084 / jem.20182044. Epub 2019 Oct 18. PMID: 31628186; PMCID: PMC6888972

[0009] Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017 Nov 3;9(11):1211. doi: 10.3390 / nu9111211. PMID: 29099763; PMCID: PMC5707683

[0009] Ramón R, Holguín E, Chiriboga JD, Rubio N, Ballesteros C, Ezechieli M. Anti-Inflammatory Effect of Vitamin C during the Postoperative Period in Patients Subjected to Total Knee Arthroplasty: A Randomized Controlled Trial. J Pers Med. 2023 Aug 25;13(9):1299. doi: 10.3390 / jpm13091299. PMID: 37763067; PMCID: PMC10532858

[0009] Wessels I, Maywald M, Rink L. Zinc as a Gatekeeper of Immune Function. Nutrients. 2017 Nov 25;9(12):1286. doi: 10.3390 / nu9121286. PMID: 29186856; PMCID: PMC5748737

[0009] Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998 Aug;68(2 Suppl):447S-463S. doi: 10.1093 / ajcn / 68.2.447S. PMID: 9701160

[0009] Iglar PJ, Hogan KJ. Vitamin D status and surgical outcomes: a systematic review. Patient Saf Surg. 2015 Apr 30;9:14. doi: 10.1186 / s13037-015-0060-y. PMID: 25926889; PMCID: PMC4413543

[0009] Birinci M, Hakyemez ÖS, Geçkalan MA, Mutlu M, Yildiz F, Bilgen ÖF, Azboy I. Effect of Vitamin D Deficiency on Periprosthetic Joint Infection and Complications After Primary Total Joint Arthroplasty. J Arthroplasty. 2024 Sep;39(9S2):S151-S157. doi: 10.1016 / j.arth.2024.05.012. Epub 2024 May 10. PMID: 38734328

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[0009]

Claims

[1] Formula of a food supplement for immunonutrition (support of the immune system through nutrients), consisting of proteins, omega-3 fatty acids, creatine, vitamin C, zinc, vitamin D, folic acid, vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B12, vitamin E, iron, beta-alanine, arginine, calcium, prebiotics: inulin, probiotics: Bifidobacterium animalis ssp. lactis; Bifidobacterium breve; Lactobacillus acidophilus; Lactiplantibacillus plantarum; Limosilactobacillus reuteri; Lacticaseibacillus rhamnosus. [2] Formulation of a food supplement for immunonutrition (support of the immune system by nutrients) according to claim 1, characterized in that the formulation contains, in addition to nutrients, vitamins and trace elements, probiotics and prebiotics (also referred to as synbiotically active) as active ingredients.