Studi clinici

Evidenze scientifiche sui principi attivi

• Akzo Nobel Functional Chemicals October 5, 2007. APPLICATION FOR THE APPROVAL OF FERRAZONE® FERRIC SODIUM EDTA AS A SOURCE OF IRON FOR USE IN THE MANUFACTURE OF PARNUTS PRODUCTS, FOOD SUPPLEMENTS AND FORTIFIED FOODS
• World Health Organization. (2006). Guidelines on food fortification with micronutrients / edited by Lindsay Allen et al.
• EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS); Scientific Opinion on the use of ferric sodium EDTA as a source of iron added for nutritional purposes to foods for the general population (including food supplements) and to foods for particular nutritional uses. EFSA Journal 2010;8(1):1414. [32 pp.]. doi: 10.2903/j.efsa.2010.1414
• Evaluations of the Joint FAO/WHO Expert Committee on Food Additives (JECFA) 2007
• Marchitto N. et al. A pilot study on secondary anaemia in “frailty” patients treated with the Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine: safety of treatment explored by HRV non-linear analysis as predictive factor of cardiovascular tolerability. Eur Rev Med Pharmacol Sci, 2020 in press.
• Marchitto N. et al. Role of Ferric Sodium EDTA associated with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine administration in patients with secondary anaemia. Effects on hemoglobin value and cardiovascular risk. Health Sci J. 2019, 13 (5), 682.
• Marchitto N. et al. Effect of Ferric Sodium EDTA administration, in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine, on cardiovascular risk evaluation: exploration of the HRV frequency domain. Clinical Practice, 2019, 16(5), 1245-1251.
• Curcio A. et al. Efficacy and Safety of a New Formulation of Ferric Sodium EDTA Associated with Vitamin C, Folic Acid, Copper Gluconate, Zinc Gluconate and Selenomethionine Administration in Patients with Secondary Anaemia. J Blood Lymph. 2018, 8: 224.
• Alessandra Graziottin. Ferro (NaFe3+EDTA), Lattoferrina, Vitamina C e Vitamina B12: sinergie farmacologiche: Per ottimizzare prevenzione e cura dell’anemia prima, durante e dopo la gravidanza.
• Ai Guo Ma et al. Supplementation of iron alone and combined with vitamins improves haematological status, erythrocyte membrane fluidity and oxidative stress in anaemic pregnant women. British Journal of Nutrition (2010), 104, 1655-1661.
• Hallberg L. et al. The role of vitamin C in iron absorption. Int J Vitam Nutr Res Suppl. 1989;30:103-8.
• Reeves P.G. et al. Dietary Copper Deficiency Reduces Iron Absorption and Duodenal-Enterocyte Hephaestin Protein in Male and Female Rats. J Nutr. 2005, 135(1):92-8.
• National Institutes of Health, Office of Dietary Supplements, (2006), “Dietary Supplement Fact Sheet: Selenium,”
• Phuong Nguyen, Ruben Grajeda, PaulMelgar, JessicaMarcinkevage,Rafael Flores ,Usha Ramakrishnan, and Reynaldo Martorell. Effect of Zinc on Efficacy of Iron Supplementation in Improving Iron and Zinc Status in Women. Journal of Nutrition and Metabolism,Volume 2012.
• Munro I.C., SODIUM IRON EDTA, CanTox Inc., Mississauga, Ontario Canada. 796. Sodium iron EDTA (WHO Food Additives Series 32)
• Appel, M.J.; Kuper, C.F.; Woutersen, R.A. 2001. Disposition, accumulation and toxicity of iron fed as iron (11) sulfate or as sodium iron EDTA in rats. Food Chem Toxicol 39(3):261-269.
• Scholl, TO., 2005, Iron status during pregnancy: setting the stage for mother and infant, Am J Clin Nutr, vol. 81(5 suppl), pp. 1218S-1222S.
• Wang, B., Siyan, Z., Yinyin, X., and Liming, L., 2008, Effect of sodium iron ethylenediaminetetra- acetate (NaFe3+EDTA) on haemoglobin and serum ferritin in iron-deficient populations: a systematic review and meta-analysis of randomised and quasi-randomised controlled trials, Br J Nutr, vol. 100, pp. 1169-1178.
• Anupam Aditi et al. Vitamin C, Gastritis, and Gastric Disease: A Historical Review and update. Dig Dis Sci. 2012, 57:2504-2515.
• Rodrigo R. et al. Cardioprotection against ischaemia/reperfusion by vitamins C and E plus n-3 fatty acids: molecular mechanisms and potential clinical applications. Clin Sci (Lond). 2013, 124(1):1-151968.
• Ryszard Rutkowski et al. Vitamin C: is it time to re-evaluate its role in health and disease? Postep. Derm. Alergol. 2012; XXIX, 6: 456-460.
• Select Committee on GRAS Substances (SCOGS) Opinion: L-ascorbic acid
• Padayatty S.J. et al. Vitamin C pharmacokinetics: implications for oral and intravenous use. Annals of Internal Medicine 2004; 140:533-7.
• Rumbold A, Ota E, Nagata C, Shahrook S, Crowther CA-Vitamin C supplementation in pregnancy.
• Scheers N. Regulatory Effects of Cu, Zn, and Ca on Fe Absorption: The Intricate Play between Nutrient Transporters. Nutrients 2013, 5(3), 957-970.
• Linee guida Ministero della salute reperibili al sito:
• López de Romaña D. et al. Risks and benefits of copper in light of new insights of copper homeostasis. Journal of Trace Elements in Medicine and Biology, 25 (2011) pp. 3-13.
• Select Committee on GRAS Substances (SCOGS) Opinion: Copper (cupric) sulfate
• Hazra, A. Tripathi, S.K. Folic Acid Revisited. Indian Journal of Pharmacology, 2001,(5), pp.322-342
• Letter Regarding Dietary Supplement Health Claim for Folic Acid With Respect to Neural Tube Defects (Docket No. 91N-100H).
• Lumley J. et al., (2001). Periconceptional Supplementation with Folate and/or Multivitamins for Preventing Neural Tube Defects. Cochrane Database Syst.Rev 2011.
• Weekly Iron-Folic Acid Supplementation (Wifs) in Women of Reproductive Age: its Role in Promoting Optimal Maternal and Child Health. World Health Organization 2009, Who/Nmh/Nhd/Mnm/09.2.
• Richard D. Semba, Luigi Ferrucci, Anne R. Cappola4, Michelle O. Ricks, Amanda L. Ray, Qian-Li Xue, Jack M. Guralnik, and Linda P. Fried. Low Serum Selenium Is Associated with Anemia Among Older Women Living in the Community: The Women’s Health and Aging Studies I and II.
• EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)
• Select Committee on GRAS Substances (SCOGS) Opinion: Magnesium gluconate; Potassium gluconate; Sodium gluconate; Zinc gluconate.
• Chaffee BW, King JC. Effect of zinc supplementation on pregnancy and infant outcomes: a systematic review. Paediatric and Perinatal Epidemiology. 2012, 26 (Suppl. 1):118-137.
• WHO: e-Library of Evidence for Nutrition Actions (eLENA)
• Andrews NC. Forging a field: the golden age of iron biology. Blood 2008; 112(2): 219–230
• Crichton R. Inorganic Biochemistry of Iron Metabolism – From Molecular Mechanisms to Clinical Consequences. 2nd edition. England: John Wiley & Sons, Ltd.; 2001.
• Dunn LL et al. Iron uptake and metabolism in the new millennium. Trends Cell Biol 2007;17(2): 93-100.
• Crichton R et al. Iron Therapy With Special Emphasis on Intravenous Administration. 4th edition. London, Boston: International Medical Publishers; 2008.
• Ovidio Brignoli Società Italiana di Medicina Generale. Anemia e terapia marziale I dati di Health Search - Società Italiana di Medicina Generale.
• “La carenza di ferro”, di Nevin S. Scrimshaw, pubbl. su “Le Scienze (Scientific American)”, num.280, dic.1991, pag.16-22.
• Triolo G. et al. Linee Guida per il trattamento dell’anemia nell’insufficienza renale cronica. Giornale Italiano di Nefrologia, 2003, 20, S-24, pp. S61-S82.
• Rockey DC. Occult and obscure gastrointestinal bleeding: causes and clinical management. Nat Rev Gastroenterol Hepatol 2010;7:265-79.
• Hershko C, Skikne B. Pathogenesis and management of iron deficiency anemia: emerging role of celiac disease, Helicobacter pylori, and autoimmune gastritis. Semin Hematol 2009;46:339-50.
• Clark SF. Iron deficiency anemia: diagnosis and management. Curr Opin Gastroenterol 2009;25.
• Pasricha SR, Flecknoe-Brown SC, Allen KJ, et al. Diagnosis and management of iron deficiency anaemia: a clinical update. Med J Aust 2010;193:525-32.
• Paesano R. et al. Ipoferremia e anemia da carenza di ferro in gravidanza. Il Ginecologo, 2008, 3 (Suppl 1), pp. 1-6.
• Van Thuy P, Berger J, Nakanishi Y, Khan NC, Lynch S, Dixon P. The use of NaFeEDTAfortified fish sauce is an effective tool for controlling iron deficiency in women of childbearing age in rural Vietnam.
• Xiu X Han MD, Yong Y Sun, Ai G Ma, Fang Yang, Feng Z Zhang, Dian C Jiang, Yong Li. Moderate NaFeEDTA and ferrous sulfate supplementation can improve both hematologic status and oxidative stress in anemic pregnant women.
• Saaka M. Combined Iron and Zinc Supplementation Improves Haematologic Status of Pregnant Women in Upper West Region of Ghana. Ghana Med J. 2012 Dec; 46(4): 225-233.
• Shubhada J. Kanani,Rashmi H. Poojara. Supplementation with Iron and Folic Acid Enhances Growth in Adolescent Indian Girls. J Nutr. 2000 Feb.
• Bier-Ulrich A.M. et al. The impact of intensive serial plasmapheresis on iron metabolism and Hb concentration in menstruating women: a prospective randomized placebo-controlled double-blind study.Transfusion 2003; 43:405-401.
• Kapur G. et al. Iron supplementation in children with celiac disease. Indian J Pediatr. 2003 Dec;70(12):955-8.
• Yang Y. et al. Efficacy and safety of iron supplementation for the elderly patients undergoing hip or knee surgery: a meta-analysis of randomized controlled trials. The Journal of Surgical Research 2011, 171(2):e201-7.

• Romano A. et al. A topical combination of blackberry, Centella asiatica, sodium hyaluronate, vitamin E and Melilotus to relieve legs symptoms of venous insufficiency Veins&Lymph 2020, 9(1), pp. 15-17.
• Cesarone M.R. et al. Microcirculatory effects of total triterpenic fraction of Centella asiatica in chronic venous hypertension: measurement by laser Doppler, TcPO2-CO2, and leg volumetry. Angiology 52 Suppl 2:S45-48, 2001.
• Aguilar-Peralta G.R. et al. Clinical and capillaroscopic evaluation in the treatment of chronic venous insufficiency with Ruscus aculeatus, hesperidin methylchalcone and ascorbic acid in venous insufficiency treatment of ambulatory patients. Int Angiol. 26(4):378-384, 2007.
• Rabe et al. Eur J Vasc Endovasc Surg (2011) 41, 540e547.
• Marco Basile, Stefano Gidaro, Massimo Pacella, Paolo M. Biffignandi and Giacomo S. Gidaro Parenteral Troxerutin and Carbazochrome Combination in the Treatment of Posthemorrhoidectomy Status: A Randomized, Double blind, Placebo-controlled, Phase IV Study Current Medical Research And Opinion Vol. 17, No. 4, 2001, 256-261.
• Y.-H. Ho, C.L. Foo, F. Seow-Choen and H.S. GOH Prospective randomized controlled trial of a micronized flavonidic fraction to reduce bleeding after haemorrhoidectomy British Journal of Surgery 1995, 82, 1034-1035.
• Galley P., Thiolet M.: A double-blind, placebocontrolled trial of a new veno-active fraction (S5682) in the treatment of symptomatic capillary fragility. Int Angiol 1993;12:69-72.
• Cesarone M.R., Belcaro G., Pellegrini L., Ledda A., Di Renzo A., Vinciguerra G., Ricci A., Gizzi G., Ippolito E., Fano F., Dugall M., Acerbi G., Cacchio M. H.R., 0-(betahydroxyethyl)- rutosides, in comparison with diosmin+hesperidin in chronic venous insufficiency and venous microangiopathy: an independent, prospective, comparative registry study. Angiology. 2005 Jan-Feb;56(1):1-8.
• Kiesewetter H., Koscielny J., Kalus U., Vix J.M., Peil H., Petrini O., van Toor B.S., de Mey C. Efficacy of orally administered extract of red vine leaf AS 195 (folia vitis viniferae) in chronic venous insufficiency (stages I-II). A randomized, double-blind, placebo-controlled trial. Arzneimittelforschung. 2000 Feb;50(2):109-17.
• Greeske K., Pohlmann B.K. Rosskastaniensamenextrakt-ein wirksames Therapieprinzip in der Praxis. Fortschr Med 1996; 114:196-200.
• Martinez-Zapata MJ, Vernooij RWM, Uriona Tuma SM, Stein AT, Moreno RM, Vargas E, Capellà D, Bonfill Cosp X. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev. 2016 Apr 6;4:CD003229. doi: 10.1002/14651858.CD003229.pub3. Review.
• Widmer LK. Pheripheral venous disorders: prevalence and socio-medical importance. Hans Huber, Bern 1978.
• Amisano GC, Amisano MF. Flebologia, da ieri al domani. L’insufficienza venosa ed una sua complicanza: “l’ulcera”. Casa di Cura Salus, Alessandria.
• Scortecci V. Chirurgia generale - Patologia chirurgica per apparati. Raffaello Cortina Editore. Milano, 1996.
• Garreu C, Garreu Gomez B, Domenjou JM, Bianchi D, Portail M. Venous insufficiency and varicouse disease. Sequelae of lower limb thrombosis. The role of crenotherapy. Phlebologie, 1993 Apr, Jun 46 (2):303-11.
• Nyuk Jet Chong and Zoriah Aziz. A Systematic Review of the Efficacy of Centella asiatica for Improvement of the Signs and Symptoms of Chronic Venous Insufficiency. Evidence-Based Complementary and Alternative Medicine Volume 2013, Article ID 627182, 10 pages http://dx.doi. org/10.1155/2013/627182.
• Ulbricht et al. An Evidence-Based Systematic Review of Bilberry (Vaccinium myrtillus) by the Natural Standard Research Collaboration. Journal of Dietary Supplements, Vol. 6(2), 2009.
• Assessment report for the development of community monographs and for inclusion of herbal substance(s), preparation (s) or combinations thereof in the list.
• Merita F., Se le vene delle gambe soffrono, su Sapere&Salute, anno 4, num. 21, luglio 1999, pagg. 48-50.
• Pigozzi P., Causa, prevenzione e cure naturali delle vene varicose, Demetra.
• Rosellò R., Curare le gambe stanche e le varici con trattamenti naturali, Macro Edizioni.

• Werner Englisch, Christoph Beckers, Markus Unkauf, Michel Ruepp, and Vsevolod Zinserling Efficacy of Artichoke Dry Extract in Patients with Hyperlipoproteinemia. Arzneim.-Forsch./Drug Res. 50 (I), Nr. 3 (2000).
• Hye Duck Choi & Yeo Kyu Youn &Wan Gyoon Shin Positive Effects of Astaxanthin on Lipid Profiles and Oxidative Stress in Overweight Subjects. Plant Foods Hum Nutr (2011) 66:363–369.
• Stacey Lockyer, Ian Rowland, Jeremy Paul Edward Spencer Parveen Yaqoob, Welma Stonehouse. Impact of phenolic‑rich olive leaf extract on blood pressure, plasma lipids and infammatory markers: a randomised controlled trial. Eur J Nutr (2017) 56:1421–1432.
• Giuseppe Derosa, Aldo Bonaventura, Lucio Bianchi, Davide Romano, Angela D’Angelo, Elena Fogari & Pamela Maffioli Berberis aristata/Silybum marianum fixed combination on lipid profile and insulin secretion in dyslipidemic patients Expert Opin. Biol. Ther. (2013) 13(11):1495-1506.
• Schmelzer C1, Niklowitz P, Okun JG, Haas D, Menke T, Döring F. Ubiquinol-induced gene expression signatures are translated into altered parameters of erythropoiesis and reduced low density lipoprotein cholesterol levels in humans. IUBMB Life. 2011 Jan;63.
• Rayman MP, Stranges S, Griffin BA, Pastor-Barriuso R, Guallar E. Effect of supplementation with high-selenium yeast on plasma lipids: a randomized trial. Ann Intern Med. 2011 May 17;154(10):656-65.
• Mahmoud Bahmani, Hedayatollah Shirzad, Mahmoud Mirhosseini, Endocrinologist, Azadeh Mesripour, and Mahmoud Rafieian-Kopaei A Review on Ethnobotanical and Therapeutic Uses of Fenugreek (Trigonella foenum-graceum L). Journal of Evidence-Based Complementary & Alternative Medicine 2016, Vol. 21(1) 53-62.
• Kaikkonen J, Nyyssönen K, Tomasi A, Iannone A, Tuomainen TP, Porkkala-Sarataho E, Salonen JT. Antioxidative efficacy of parallel and combined supplementation with coenzyme Q10 and d-alpha-tocopherol in mildly hypercholesterolemic subjects: a randomized placebo-controlled clinical study. Free Radic Res. 2000 Sep; 33(3): 329-40.
• Rezazadeh K, Rahmati-Yamchi M, Mohammadnejad L, Ebrahimi-Mameghani M, Delazar A. Effects of artichoke leaf extract supplementation on metabolic parameters in women with metabolic syndrome: Influence of TCF7L2-rs7903146 and FTO-rs9939609 polymorphisms. Phytother Res. 2018 Jan;32(1):84-93.
• Hiroshi Yoshida, Hidekatsu Yanai, Kumie Ito, Yoshiharu Tomono, Takashi Koikeda Hiroki Tsukahara Norio Tada. Administration of natural astaxanthin increases serum HDL-cholesterol and adiponectin in subjects with mild hyperlipidemia. Atherosclerosis 209 (2010) 520–523.

• Romano A. et al. The association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine for the treatment of Non-Alcoholic Fatty Liver Disease. Journal of Gastrointestinal and Digestive System 2019, Vol 9(1), 589.
• Hajaghamohammadi A., Ziaee A., Raei R. The efficacy of Silymarin in Decreasing Transaminase Activities in Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial. Hepatitis Monthly Sett. 2008.
• Stephen A. Harrison, Sigurd Torgerson, Paul Hayashi et al. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. The American Journal of Gastroenterology (2003).
• Ales Vidlara, Jitka Vostalovab, Jitka Ulrichovab et al. The safety and efficacy of a silymarin and selenium combination in men after radical prostatectomy- a six month placebo-controlled double-blind clinical trial. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010 Sep.
• Farsi F., Mohammadshahi M., Alavinejad P. et al. Functions of Coenzyme Q10 Supplementation on Liver Enzymes, Markers of Systemic Inflammation, and Adipokines in Patients Affected by Nonalcoholic Fatty Liver Disease: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial. J Am Coll Nutr. 2015 Jul 9.
• P. Ferenci , B. Dragosics , H. Dittrich. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol. 1989 Jul.
• Ales Vidlara, Jitka Vostalovab, Jitka Ulrichovab et al. The safety and e_cacy of a silymarin and selenium combination in men after radical prostatectomy-a six month placebo-controlled double-blind clinical trial. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010 Sep.
• The Efficacy of Silybum marianum (L.) Gaertn. (Silymarin) in the Treatment of Type II Diabetes: A Randomized, Double-blind, Placebo-controlled, Clinical Trial.
• Paolisso G1, Balbi V, Volpe C, Varricchio G, Gambardella A, Saccomanno F, Ammendola S, Varricchio M, D’Onofrio F. Metabolic benefits deriving from chronic vitamin C supplementation in aged non-insulin dependent diabetics. J Am Coll Nutr. 1995 Aug;14.
• Ajda Skarlovnik, Miodrag Janic,Mojca Lunder Martina Turk,and Mišo Šabovic. Coenzyme Q10 Supplementation Decreases Statin-Related Mild-to-Moderate Muscle Symptoms: A Randomized Clinical Study. Med Sci Monit. 2014; 20: 2183-2188.

• Renzini G., Varengo M. The absorption of tetracyclin in conbination with bromelain by oral application. Arzneim-Forsch 1972;22:410-412.
• Gregory S. Kelly, N.D.: Bromelain: A Literature Review and Discussion of its Therapeutic Applications; Alt Med Rev 1996;1(4):243-257.
• Baskanchiladze G.Sh., Khurtsilava L.A., Gelovani I.A., Asatiani M.V., Rossinskii V.I. Chemotherapeutic effectiveness of antibiotics in combination with papain in experimental septicemia-Antibiotiki. 1984 Jan;29(1):33-5.
• Snowden H.M. et al. Treatments for breast engorgement during lactation. Cochrane database of systematic reviews. 2005, Issue 1, pp. 1-24.
• Murata T. et al. The clinical effects of “protease complex” on postpartum breast engorgement. J Jap Obstet Gynaecol Soc. 1965,12(3), pp. 139-47.
• Pavan R. et al. Properties and Therapeutic Application of Bromelain: A Review. Biotechnology Research International. 2012, Volume 2012, Article ID 976203, 6 pages.
• Maurer H.R. Bromelain: biochemistry, pharmacology and medical use. CMLS, Cell. Mol. Life Sci. 2001, 58, pp. 1234-1245.
• Howat R.C.L. and Lewis G.D. The effect of bromelain therapy on episiotomy wounds – A double blind controlled clinical trial. J Obstet Gynaecol BR Commonw. 1972, 79, pp. 951-953.
• Zatuchni G.I. and Colombi D.J. Bromelain therapy for the prevention of episiotomy pain. Obstetrics and Gynecology. 1967, 29(2), pp. 275-278
• Netti C., Bandi G.L., Pecile A.: Anti-inflammatory action of proteolytic enzymes of animal vegetable or bacterial origin administered orally compared with that of known anti-phlogistic compounds. Farmaco Prat. 1972 Aug;27(8):453-66.
• Ryan R.E. A double-blind clinical evaluation of bromelains in the treatment of acute sinusitis. Headache. 1967, 7(1):13-7.
• Tassman G., Zafran J., Zayon G. A double-blind crossover study of plant proteolytic enzymes of animal vegetable or bacterial origin administered orally compared with tat of known anti-phlogistic compounds. Farmaco Prat. 1972 Aug;27(8);453-66.
• Luerti M, Vignali ML. Influence of bromelain on penetration of antibiotics in uterus, salpinx and ovary. Drugs Expt Clin Res 1978;4:45-48.
• Baskanchiladze GSh, Khurtsilava LA, Gelovani IA, Asatiani MV, Rossinskii VI. Chemotherapeutic Effectiveness of antibiotics in combination with papain in experimental septicemia-Antibiotiki. 1984 Jan;29(1):33-5.
• Neubauer R.A., “A plant protease for potentiation of and possible replacement of antibiotics” Experimental Medicine and Surgery, 1961, 19, pp. 143-160.

• Shokes D. A. et al. Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial. Urology 1999, 54 (6): 960-963.
• Netti C. et al. Anti-inflammatory action of proteolytic enzymes of animal vegetable or bacterial origin administered orally compared with that of known anti-phlogistic compounds. Farmaco Prat. 1972 Aug; 27(8):453-66.
• Tassman G., et al. A double-blind crossover study of plant proteolytic enzyme in oral surgery. J Dent Med 1965; 20:51-54.
• Kamenícek V., et al. Systemic enzyme therapy in the treatment and prevention of post-traumatic and postoperative swelling]. Acta Chir Orthop Traumatol Cech. 2001;68(1):45-9.
• Blonstein J. Control of swelling in boxing injuries. Practitioner 1960, 203, pp. 206.
• Luerti M. et al. Influence of bromelain on penetration of antibiotics in uterus, salpinx and ovary. Drugs Expt Clin Res 1978; 4:45-48.
• Renzini G., Varengo M. The absorption of tetracyclin in combination with bromelain by oral application. Arzneim-Forsch 1972; 22: 410-412. Gregory S. Kelly, N.D. Bromelain: A Literature Review and Discussion of its Therapeutic Applications; Alt Med Rev 1996;1(4):243-257.
• Baskanchiladze G.Sh., et al. Chemotherapeutic effectiveness of antibiotics in combination with papain in experimental septicemia-Antibiotiki. 1984 Jan; 29(1):33-5.
• Pendzhiev A.M. Proteolytic enzymes of Papaya: Medical applications. Pharmaceutical Chemistry Journal, 2002, Vol. 36, No. 6, 32-34.
• MacKay D. and Miller A. Nutritional Support for Wound Healing Alternative Medicine Review - Volume 8, Number 4 - 2003.
• Bahmani F. et al. The effects of selenium supplementation on biomarkers of inflammation and oxidative stress in patients with diabetic nephropathy: a randomised, double-blind, placebo-controlled trial. British Journal of Nutrition (2016), 116, 1222-1228.
• Guardia T. et al. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Il Farmaco 2001; 56: 683-687.
• Javadi F. M. The Effect of Quercetin on Inflammatory Factors and Clinical Symptoms in Women with Rheumatoid Arthritis: A Double-Blind, Randomized Controlled Trial. Journal of the American College of Nutrition Journal of the American College of Nutrition 2016: 1-7.

• Serpell M, et al. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. Eur J Pain. 2014 Aug;18(7):999-1012.
• Blake DR, et al. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford). 2006 Jan;45(1):50-2.
• Wetzel D, et al. Escin/diethylammonium salicylate/heparin combination gels for the topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study. Br J Sports Med 2002;36:183-188.
• Belcaro G, et al. Management of osteoarthritis (OA) with the pharma-standard supplement FlexiQule (Boswellia): a 12-week registry. Minerva Gastroenterol Dietol. 2015 Oct 2.
• Brien S, et al. Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies. Evid Based Complement Alternat Med. 2004 Dec; 1(3): 251-257.
• Kim LS, et al.Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. Osteoarthritis Cartilage. 2006 Mar;14(3):286-94.
• Debbi EM, et al. Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study. BMC Complement Altern Med. 2011 Jun 27;11:50.
• Drovanti A, et Al. Therapeutic activity of oral glucosamine sulfate in osteoarthrosis: a placebo-controlled, double blind investigation. Clinical Therapeutics, 1980; 3 ( 4 ): 260-272.
• Usha P.R., Naidu MUR. Randomised, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine, Methylsulfoylmethane and their Combination in Osteoarthritis. Clinical Drug Investigation 24 ( 6 ): 353-363, 2004.
• Higashi Y, et al. Efficacy and Safety Profile of a Topical Methyl Salicylate and Menthol Patch in Adult Patients With Mild to Moderate Muscle Strain: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multicenter Study. Clin Ther. 2010 Jan;32(1):34-43.
• Study Evaluating the Influence of Vehicle in the Permeability Process of a Topical Composition Containing Cannabis Sativa Oil, Escin, Bromelain, Glucosamine Sulphate, Methylsulfonylmethane, Methylsalicylate and Boswellia Extract, Designed for Local Treatment of Musculoskeletal Painful and Inflammatory Conditions

• James M. Jay, A. Tedesco, P.M. Falcone, E. Gala, Martin J. Loessner, F. Licciardello, David A. Golden. Microbiologia degli alimenti. Springer p. 341.
• Generally recognized as safe (gras) determination for cow’s milk-derived lactoferrin as a component of cow’s milk products and chewing gum. http://www.accessdata.fda.gov/scripts/fcn/gras_notices/GRN000464.pdf
• Manzoni et al.: Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA. 2009 Oct 7;302(13):1421-8. doi: 10.1001/jama.2009.1403.
• Artym J, Zimecki M. The role of lactoferrin in the proper development of newborns. Postepy Hig Med Dosw. 2005;59:421-32. Review. Polish.
• Paesano R. et Al. Ipoferremia e anemia da carenza di ferro in gravidanza. Evidenze cliniche della maggiore efficacia della lattoferrina, somministrata per os, rispetto al solfato ferroso. Il Ginecologo. Rivista di Ostetricia e Ginecologia 3 (suppl. al n. 1):1-6, 2008.
• Paesano R. et Al. Oral administration of lactoferrin increases hemoglobin and total serum iron in pregnant women. Biochem. Cell. Biol. 84: 377- 380, 2006.
• Costantino D, Guaraldi C. Lattoferrina e anemia in gravidanza. Rivista Italiana Di Medicina Perinatale 2005, Settembre, vol. 7, n.3, 15-20.
• Valenti et al, 2008 Valenti P, Pacifici E, Pietropaoli M et al. La lattoferrina per os, un’importante alternativa priva di effetti indesiderati, nella prevenzione e trattamento dell’ipoferremia ed anemia da carenza di ferro in gravidanza. Riv It Ost Gin 2008.
• D., Guaraldi C. Anemia sideropenica in gravidanza: Lattoferrina vs ferro in varie formulazioni e idrolizzato di cartilagine di pesce marino. Il Ginecologo, Rivista di Ostetricia e Ginecologia Vol 4, Suppl. al No. 1 Marzo 2009.
• Hiraku Onishi Lactoferrin delivery systems: approaches for its more effective use.
• Suzuki Y.A., Lopez V., Lönnerdal B. Mammalian lactoferrin receptors: structure and function. Cell Mol Life Sci. 2005; 62(22): 2560-75.
• Ashida K., Sasaki H., Suzuki Y.A. et al. Cellular internalization of lactoferrin in intestinal epithelial cells. Biometals. 2004; 17(3): 311-5.
• Vicariotto F. Lattoferrina: l’alternativa alla terapia marziale. Edit-Symposia Ginecologia & Ostetricia 2008/1.
• World Health Organization (WHO). The prevalence of Anaemia in women: a tabulation of available information. Geneva, Switzerland: WHO; 1992. WHO/MCH/ MSM/92.2.
• Feirbanks V.F., Beutler E. Iron deficiency. In: Beutler E., Lichtman M.A., Coller B.S., Kipps T.J., eds. Williams Hematology. New York: McGraw-Hill; 2001. p. 447-70.
• Bothwell T.H. Iron requirements in pregnancy and strategies to meet them. Am J Clin Nutr. 2000; 72(suppl): 257-64.
• Harris E.D. New insights into placental iron transport. Nutr Rev. 1992; 50(11): 329-31.
• Cheng Y., Zak O., Aisen P. et al. Structure of the human transferrin receptor-transferrin complex. Cell. 2004; 116: 565 76.
• Allen L.H. Anemia and iron deficiency: effects on pregnancy outcome. Am J Clin Nutr. 2000; 71(Suppl): 1280-4.
• School T.O. Iron status during pregnancy: setting the stage for mother and infant. Am J Clin Nutr. 2005; 81: 1218-2.
• Leidi L. 2007, Lattoferrina: un nuovo approccio terapeutico per il trattamento dell’anemia sideropenia. Integratori terapeutici e fitoterapici nell’età riproduttiva, dello sviluppo ed avanzata. Ed 2007.