What is Indrepta?

INDREPTA: A dietary supplement designed to promote lung heath

Indrepta is available in three versions A, B & C.

Purchase Indrepta here…

Frequently asked questions here…


Scientific and technical data

Dietary polyphenols are molecules found in abundance in brightly colored fruits and vegetables, and are associated with many of the health benefits of these foods. Diets rich in polyphenols are demonstrated to provide protection from a wide range of diseases including cancer, diabetes, osteoporosis and dementia.1 Food can indeed be medicine.

Some plant extracts take center stage in commercial products currently sold in drug stores. For example, the popular expectorant MucinexTM is simply a natural plant compound, guaifenesin, re-formulated as a time-release ‘drug’.


Sourcing reliable high quality supplements available to all patients has also been challenging for those who wish to study supplement benefits. The New York Attorney General’s office found in 2015 that few supplements offered by the largest US retailers contain ingredients listed on the label.8 By placing control of the formulation and manufacture of supplements within patient stakeholder organizations, quality concerns can be addressed. For example to create Indrepta, the Certificates of Analysis (COA’s) from multiple manufacturers were compared to select the best products regardless of cost. Ingredients used in Indrepta have each been subjected to individual analysis for quality and purity, and ingredients are standardized by HPLC to ensure consistency from batch to batch. Microbiology reports for ingredients are carefully reviewed.

Indrepta was created to supply dietary polyphenols in a consistent, standardized formula three times a day. Indrepta combines several individual natural therapies with good literature support and positive feedback regarding benefit from patients. The goal of initial Indrepta formulations is to maximize the potential to successfully reduce inflammation and oxidation. Further laboratory research and feedback from patients will allow further refinement of supplements.

We are releasing A and B versions of Indrepta, which share most of their ingredients but differ by substitution of Alpha Lipoic Acid and Naringin found in version A in with the B version herbal ingredients Amentoflavone and Forskolin.   Although specific health claims for supplements are prohibited, it is permissible to report independent third party research findings with regard to supplement activity and health benefits.

Each Indrepta ingredient is listed individually below with evidence to support its inclusion in the supplement. Supplement Information panels from product labels are also provided.

  1. Curcumin – Archives of NACFC meetings indicate that in 2008, curcumin was listed as a pipeline CF drug.9 Curcumin, a well-studied food spice with multiple known health benefits, was given a small CF clinical trial. Lasting only 2 weeks and enrolling 14 subjects, 9 of whom completed the study, this curcumin trial did not pair oral administration of curcumin with any additives known to increase its systemic bioavailability. For example, a black pepper extract (piperine), included in Indrepta’ s formulation, is demonstrated to increase curcumin bioavailability by 20 fold.10 Oral curcumin is poorly absorbed from the gut without specific measures to improve its absorption. Piperine was not used in the curcumin clinical trials. Not surprisingly, undetectable levels of curcumin were found in serum of all but one CF patient in the trial, and levels were therefore insufficient to significantly impact the study endpoint, nasal potential difference (PD).11 For a compound to be effective, it must reach its target tissue at an adequate concentration. The single CF patient who achieved measurable blood levels of curcumin (83 ng/ml, lower level of detection=2.0 ng/ml) had forced vital capacity increased by 3.3%, enough to reach statistical significance (p=0.05). 11 Indrepta is formulated with curcumin and piperine, a combination reported by patients to produce desirable results in terms of reduction of sweat chlorides, reduced aquagenic wrinkling of the palms, weight gain and improved overall wellness. Curcumin is also reported to improve GI issues of patients with CF.
  1. Resveratrol – Resveratrol is a promising corrector/potentiator12,13 already used by patients, with good response reported. However, resveratrol is poorly absorbed through the gut. Resveratrol is reported to receive enhancement in permeability when combined with quercetin (310%), curcumin (300%), and piperine (350%),14 all of which are included in Indrepta.
  1. Naringin – Naringin is a flavone glycoside found naturally in citrus fruits. Naringin is structurally similar to apigenin, one of the most potent activating natural compounds used by researchers in drug screening experiments. 15, 16 Naringen demonstrates protective effects in diabetes and elevated oxidative stress,17, 18  and is believed to act, like apigenin, by increasing channeling activity. 19
  1. Quercetin – Quercetin is demonstrated to activate channeling20 and is also reported to increase ciliary beat frequency. 21 Quercetin is known to increase bioavailability of other co-administered supplements including resveratrol14 and green tea polyphenols which are components of the Indrepta formulation.
  1. Bioperine™ – Bioperine is a registered trademark for a black pepper extract molecule known as piperine, which is demonstrated to increase oral bioavailability of some co-administered supplements. For example co-administration of 20 mg of piperine with 2 g curcumin (the Indrepta dose) caused 2000% increase in curcumin bioavailability in humans. 10 For this reason, modest doses of curcumin are used in Indrepta.
  1. Silymarin – Silymarin from milk thistle has been administered for more than 2,000 years, primarily to treat liver dysfunction. 23 The German Commission E for natural compounds recommends milk thistle use for dyspeptic complaints, toxin-induced liver damage and as supportive therapy for chronic inflammatory liver conditions. 24 Silymarin is included in Indrepta to protect against liver disease and also toxic effects of pharmaceutical drugs.
  1. EGCG – Epigallocatechin gallate (EGCG) is an antioxidant and herbal derivative of green tealeaves (Camellia sinensis). EGCG was tested in clinical trials to correct CFTR splicing defects 25 and also to enhance benefit of cysteamine administration; in this capacity, EGCG is proposed to act via autophagy-dependent rescue of class II-mutated ABC proteins. 26-27
  1. Hawthorne – Hawthorne, also known by its botanical name Crataegus, is a flowering plant with berries. Crataegus preparations have been consistently proven to be well tolerated with low or negligible side effects. 28-30 Both flowers and leaves are rich sources of polyphenolic compounds. Since the fruits and plant parts of Hawthorne differ in their polyphenolic composition, 31,32 standardized extracts of both fruits and leaf/flower were included to increase polyphenolic diversity in the formulation.
  1. Alpha Lipoic Acid – Alpha Lipoic Acid (ALA) is a potent antioxidant. As a supplement, it has shown benefit against oxidative stress and inflammation. In vivo and in vitro studies demonstrate that ALA exhibits ability to scavenge free radicals, regulate the detoxification of heavy metals, and modulate various pathways in pathological conditions. 33Lipoic acid is demonstrated to be highly effective in preventing cataract formation, 34 a reported side effect of Kalydeco.
  1. Amentoflavone – Apigenin is one of the most potent natural potentiators.15,16 Amentoflavone is a biflavonoid of apigenin, and is also known as bis-apigenin. Amentoflavone is demonstrated to be a phosphodiesterase inhibitor35 (PDE) that can break down enzymes that destroy cyclic AMP (cAMP).
  1. Forskolin – Forskolin is an herbal compound which directly activates the adenylate cyclase enzyme, thereby generating cAMP from ATP and raising intracellular cAMP Forskolin is a mainstay channel-activating compound used by laboratory researchers as well as an ancient remedy used to support lung, heart, and urinary health, among numerous other uses.36 As an oral supplement, forskolin has been used to treat asthma. 37 Forskolin increases cAMP, and then the other side of the coin, amentoflavone, is added to Indrepta B to prevent cAMP breakdown. The desired net effect of the combination of Amentoflavone and Forskolin is increased and extended overall channel activity.

Natural compounds used in Indrepta are time-tested for safety in humans and inexpensive.  Currently it is impossible to predict without a cell biopsy which patients will respond most favorably to natural and/or synthetic polyphenolic compounds. Because we have included powerful antioxidants in our supplements, we believe Indrepta will benefit the health of many people. For example, it has recently been demonstrated that dietary polyphenols are protective against drug induced hearing loss. 39,40

Sharktank Research Foundation is committed to continued research to develop and refine nutritional supplements. We do this work in the first stakeholder funded and managed CF research laboratory we established in Research Triangle Park, North Carolina.  You can help our effort by joining Sharktank and by making tax-deductible donations to Sharktank Research Foundation.


  1. Pandey, KB and SI Rizvi. (2009) Oxid Med Cell Longev. Nov-Dec; 2(5): 270–278.
  2. Illek B, Fischer H, Santos GF, Widdicombe JH, Machen TE, Reenstra WW. (1995) cAMP-independent activation of CFTR Cl channels by the tyrosine kinase inhibitor genistein. Am J Physiol. Apr;268(4 Pt 1):C886-93.
  3. Sears CL, Firoozmand F, Mellander A, Chambers FG, Eromar IG, Bot AG, Scholte B, De Jonge HR, Donowitz M. (1995) Genistein and tyrphostin 47 stimulate CFTR-mediated Cl- secretion in T84 cell monolayers. Am J Physiol. Dec;269(6 Pt 1):G874-82.
  4. Egan ME, Pearson M, Weiner SA, Rajendran V, Rubin D, Glöckner-Pagel J, Canny S, Du K, Lukacs GL, Caplan MJ. (2004) Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science. Apr 23;304(5670):600-2.
  5. Hamdaoui N, Baudoin-Legros M, Kelly M, Aissat A, Moriceau S, Vieu DL, Colas J, Fritsch J, Edelman A, Planelles G. 2011. Resveratrol rescues cAMP-dependent anionic transport in the cystic fibrosis pancreatic cell line CFPAC1. Br J Pharmacol. Jun;163(4):876-86.
  6. Rapino D1, Sabirzhanova I1, Lopes-Pacheco M1, Grover R1, Guggino WB2, Cebotaru L3. (2015) Rescue of NBD2 mutants N1303K and S1235R of CFTR by small-molecule correctors and transcomplementation. PLoS One. 2015 Mar 23;10(3):e0119796.
  7. Dekkers JF, Van Mourik P, Vonk AM, Kruisselbrink E, Berkers G, de Winter-de Groot KM, Janssens HM, Bronsveld I, van der Ent CK, de Jonge HR, Beekman JM. (2016) Potentiator synergy in rectal organoids carrying S1251N, G551D, or F508del CFTR mutations. J Cyst Fibros. Sep;15(5):568-78.
  8. Washington Post. GNC, Target, Wal-Mart, Walgreens accused of selling adulterated ‘herbals.’ (2015) https://www.washingtonpost.com/news/morning-mix/wp/2015/02/03/gnc-target-wal-mart-walgreens-accused-of-selling-fake-herbals/. Accessed 10/28/2016.
  9. Archives, NACFC: https://www.nacfconference.org/plen.archive.html. Dr. Preston Campbell powerpoint slides, 2008. Accessed 2/18/16.
  10. Shoba G1, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. 1998. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998 May;64(4):353-6.
  11. Goss CH, Genatossio A, Rowbotham RK, Hamblett N, McNamara S, Knowles M, Brass-Ernst L, Aitken ML, Zeitlin PL, Boyle MP. (2006) A phase I safety and dose finding study of orally administered curcuminoids in adult subjects with cystic fibrosis who are homozygous for ΔF508 cystic fibrosis transmembrane conductance regulator. Ped Pulmonol Suppl 41: 247.
  12. Hamdaoui N, Baudoin-Legros M, Kelly M, Aissat A, Moriceau S, Vieu DL, Colas J, Fritsch J, Edelman A, Planelles G. 2011. Resveratrol rescues cAMP-dependent anionic transport in the cystic fibrosis pancreatic cell line CFPAC1. Br J Pharmacol. Jun;163(4):876-86.
  13. Dhooghe B, Bouckaert C1, Capron A2, Wallemacq P2, Leal T1, Noel S3. 2015. Resveratrol increases F508del-CFTR dependent salivary secretion in cystic fibrosis mice. Biol Open. Jun 19;4(7):929-36.
  14. Lund, K.C.; Pantuso, T. (2014) Combination Effects of Quercetin, Resveratrol and Curcumin on In Vitro Intestinal Absorption. Journal of Restorative Medicine, Volume 3, Number 1, 1 April, pp. 112-120(9).
  15. Ma T, Vetrivel L, Yang H, Pedemonte N, Zegarra-Moran O, Galietta LJ, Verkman AS. High-affinity activators of cystic fibrosis transmembrane conductance regulator (CFTR) chloride conductance identified by high-throughput screening. 2002. J Biol Chem. Oct 4;277(40):37235-41.
  16. Caci E, Folli C, Zegarra-Moran O, Ma T, Springsteel MF, Sammelson RE, Nantz MH, Kurth MJ, Verkman AS, Galietta LJ. 2003. CFTR activation in human bronchial epithelial cells by novel benzoflavone and benzimidazolone compounds. Am J Physiol Lung Cell Mol Physiol. Jul;285(1):L180-8.
  17. Kandhare AD, Raygude KS, Ghosh P, Ghule AE, Bodhankar SL (2012). “Neuroprotective Effect of Naringin by Modulation of Endogenous Biomarkers in Streptozotocin Induced Painful Diabetic Neuropathy”. Fitoterapia. 83 (4): 650–9.
  18. Kumar A, Dogra S, Prakash A (2010). “Protective Effect of Naringin, a Citrus Flavonoid, against Colchicine-Induced Cognitive Dysfunction and Oxidative Damage in Rats”. Journal of Medicinal Food. 13 (4): 976–84. 20673063.
  19. Yang ZH1, Yu HJ, Pan A, Du JY, Ruan YC, Ko WH, Chan HC, Zhou WL. (2008) Cellular mechanisms underlying the laxative effect of flavonol naringenin on rat constipation model. PLoS One. Oct 3;3(10):e3348.
  20. Pyle LC1, Fulton JC, Sloane PA, Backer K, Mazur M, Prasain J, Barnes S, Clancy JP, Rowe SM. (2010) Activation of the cystic fibrosis transmembrane conductance regulator by the flavonoid quercetin: potential use as a biomarker of ΔF508 cystic fibrosis transmembrane conductance regulator rescue. Am J Respir Cell Mol Biol. Nov;43(5):607-16.
  21. Zhang S1, Smith N, Schuster D, Azbell C, Sorscher EJ, Rowe SM, Woodworth BA. (2011) Quercetin increases cystic fibrosis transmembrane conductance regulator-mediated chloride transport and ciliary beat frequency: therapeutic implications for chronic rhinosinusitis. Am J Rhinol Allergy. Sep-Oct;25(5):307-12.
  22. Wang, PA ,Hebera D and  M. Henning (2012) Quercetin increased bioavailability and decreased methylation of green tea polyphenols in vitro and in vivo. Food Funct.,3, 635-642.
  23. Flora K, Hahn M, Rosen H, et al. (1998) Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 93 (2): 139-43.
  24. Blumenthal M, Busse WR, et al., eds. (1998) The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, Tex: American Botanical Council.
  25. gov: https://clinicaltrials.gov/ct2/show/NCT00889434 . Accessed 10/28/2016.
  26. De Stefano D, Villella VR, Esposito S, Tosco A, Sepe A, De Gregorio F, Salvadori L, Grassia R, Leone CA, De Rosa G, Maiuri MC, Pettoello-Mantovani M, Guido S, Bossi A, Zolin A, Venerando A, Pinna LA, Mehta A, Bona G, Kroemer G, Maiuri L, Raia V. (2014) Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation. Autophagy. 2014;10(11):2053-74.
  27. Tosco A, De Gregorio F, Esposito S, De Stefano D, Sana I, Ferrari E, Sepe A, Salvadori L, Buonpensiero P, Di Pasqua A, Grassia R, Leone CA, Guido S, De Rosa G, Lusa S, Bona G, Stoll G, Maiuri MC, Mehta A, Kroemer G9, Maiuri L Raia V (2016) A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR. Cell Death Differ. Aug; 23(8):1380-93.
  28. Tauchert M. (2002) Efficacy and safety of crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure. Am Heart J;143: 910–5. [PubMed]
  29. Degenring FH, Suter A, Weber M, Saller R. (2003) A randomised double blind placebo controlled clinical trial of a standardised extract of fresh Crataegus berries (Crataegisan) in the treatment of patients with congestive heart failure NYHA II. Phytomedicine;10: 363–9.
  30. Rigelsky JM, Sweet BV. (2002) Hawthorn: pharmacology and therapeutic uses. Am J Health Syst Pharm;59: 417–22.
  31. Svedström, U., Vuorela, H., Kostiainen, R., Tuominen, J., Kokkonen, J., Rauha, J., Laakso, I. and Hiltunen, R. (2002). Isolation and identification of oligomeric procyanidins from Crataegus leaves and flowers. Phytochemistry, 60(8), 821–825.
  32. Barros L1, Carvalho AM, Ferreira IC. (2011) Comparing the composition and bioactivity of Crataegus Monogyna flowers and fruits used in folk medicine. Phytochem Anal. Mar-Apr;22 (2):181-8.
  33. Salinthone S, Yadav V, Bourdette DN, Carr DW. (2008) Lipoic acid: a novel therapeutic approach for multiple sclerosis and other chronic inflammatory diseases of the CNS. Endocr Metab Immune Disord Drug Targets;8(2):132-142.
  34. Packer L. (1994) Antioxidant properties of lipoic acid and its therapeutic effects in prevention of diabetes complications and cataracts. Ann NY Acad Sci. 1994;738: 257-264.
  35. Saponara R1, Bosisio E. (1998) Inhibition of cAMP-phosphodiesterase by biflavones of Ginkgo biloba in rat adipose tissue. J Nat Prod. 1998 Nov;61(11):1386-7.
  36. Alasbahi RH, Melzig MF. (2010) Plectranthus barbatus: a review of phytochemistry, ethnobotanical uses and pharmacology – Part 1. Planta Med. May;76(7):653-61.
  37. González-Sánchez R1, Trujillo X, Trujillo-Hernández B, Vásquez C, Huerta M, Elizalde A. (2006) Forskolin versus sodium cromoglycate for prevention of asthma attacks: a single-blinded clinical trial. J Int Med Res. Mar-Apr;34(2):200-7.
  38. Awatade NT1, Uliyakina I1, Farinha CM1, Clarke LA1, Mendes K1, Solé A2, Pastor J3, Ramos MM1, Amaral MD1. (2015) Measurements of Functional Responses in Human Primary Lung Cells as a Basis for Personalized Therapy for Cystic Fibrosis. EBioMedicine. 2014 Dec 17;2(2):147-53.
  39. Gu LT, Yang J, Su SZ, Liu WW, Shi ZG, Wang QR. (2015) Green Tea Polyphenols Protects Cochlear Hair Cells from Ototoxicity by Inhibiting Notch Signalling. Neurochem Res. 2015 Jun;40(6):1211-9.
  40. Yazici ZM1, Meric A, Midi A, Arınc YV, Kahya V, Hafız G. (2012) Reduction of cisplatin ototoxicity in rats by oral administration of pomegranate extract. Eur Arch Otorhinolaryngol. Jan;269(1):45-52.