What is the truth about ouabain bioavailability?

This time I would like to discuss the issue of the bioavailability of strophanthin, also known as ouabain. This topic has been a source of controversy for decades, and much of the information presented in medical literature is repeated uncritically and without verification, creating a distorted picture of the situation. It’s time to set the facts straight and consider what we actually know for certain about the absorption of this substance when taken orally in drop form.

What is strophanthin?

Strophanthin (g-strophanthin, ouabain) is a cardiac glycoside derived from the plant *Strophanthus gratus*. Although it was long regarded merely as a drug with effects similar to digitalis, modern research shows that its mechanism of action and effects are actually different.

Strophanthin Bioavailability – Facts, Not Myths

Textbooks still often claim that orally administered strophanthin has very low bioavailability. This is simply not true. There are over 20 studies that show quite the opposite. Examples? Here you go:

• Ouabain absorption in the small intestine reaches 24–48% in rodents (Forth et al.).
• Marchetti et al. (1972) demonstrated a stable presence of the substance in tissues after oral administration.
• Leuschner & Winkler (2001) confirmed 50% absorption in the organs of rodents after oral administration.
• Kitano et al. (1998) demonstrated high oral bioavailability of ouabain, comparable to that of digoxin.

Moreover, studies from the 1970s and 1980s (Erdle, Belz, Dohrmann) showed stable and predictable levels of ouabain in the blood after oral administration – without significant fluctuations. These are just a few examples; there are many more.

Yes, I’m aware that most of the data mentioned above come from animal model studies, but in my opinion, their results are all the more reason to finally carry out reliable, independent research in accordance with modern scientific standards—without cheap manipulation or bias.

So where did the claim of weak absorption come from?

It originates from a single, frequently misquoted study from the 1970s (Greeff, 1974), which was actually based on an earlier doctoral thesis. In that thesis, data from two different groups (fasted and fed) were combined and presented as a single average. This is a fundamental methodological error that, unfortunately, has influenced decades of clinical decision-making.

What is the clinical relevance of this bioavailability?

• Therapeutic Effect – even at standard doses (3–12 mg), clinical effects have been observed in angina pectoris and in the prevention of heart attacks.
• Speed of Action – strophanthin acts within 5–10 minutes after sublingual administration.
• Low Risk of Drug Interactions – it can be used alongside other medications (with some exceptions!).
• Oral dosing makes sense – confirmed clinical effects do not require injectable forms.
• Absorption Mechanism – active transport and endocytosis

As early as the 1960s, Lauterbach suggested the existence of an active transport mechanism for glycosides such as ouabain. This has also been supported by studies on endocytosis in heart muscle cells.

Strophanthin in Practice – Clinical Observation Data

• Dohrmann (1984): 146 out of 148 patients with angina pectoris experienced improvement after 1–2 weeks of therapy.
• At the Gelsenkirchen coal mine, the number of deaths due to heart attacks dropped from three per year to zero over the following 10 years after the introduction of oral strophanthin therapy.
• In the study by Belz et al. (1984), improved hemodynamic parameters were observed in healthy volunteers after oral administration.

Conclusion

The claim of low oral bioavailability of strophanthin is, at best, incorrect. It is based on a flawed source that has gained disproportionately high significance in the literature. In reality, strophanthin is absorbed effectively and exhibits strong therapeutic effects – as confirmed by numerous studies and clinical observations.

Let’s not keep repeating myths (there are more of them, as you’ll read in future articles). Let’s focus on the data. Let’s evaluate substances not through the lens of textbook simplifications, but through evidence. Oral strophanthin—especially in the form of sublingual drops—works. And it works well.

Sources:

• R.E.Dohrmann & M.Dohrmann: Neuere Therapie der instabilen Angina pectoris bei koronarer Herzerkrankung, Erfahrungsheilkunde – acta medica empirica 33: 183-190, 1984
• R.E.Dohrmann; H.D.Janisch & M.Kessel: Klinisch-poliklinische Studie über die Wirksamkeit von g-Strophanthin bei Angina pectoris und Myokardinfarkt, Cardiol Bull (Cardiologisches Bulletin) 14/15: 183-187, 1977
• R.E.Dohrmann & R.F.Heller: Therapeutische Ergebnisse bei akutem Myokardinfarkt unter Anwendung hoch-dosierter Steroidgaben und fluiditätsbeeinflussender Pharmaka – Ergebnisse einer 10-Jahres-Studie, Cardiol Bull 24: 17, 1987
• H.J.Avenarius, H.Poliwoda & B.Schneider: Unersuchungen zum klinischen Verlauf des akuten Myokardinfarkts. Med Klin 72: 459-464, 1977
• Prof. Quantiliano de Mesquita, Professor Honorario de Faculdade de Medicina de Universidade Federal de Paraiba. Chefo do Instituto de Angio Cardiologia de Hospital Matarazzo e Cas de Saude Matarazzo Sao Paulo: Teoria miogenico do enfarte miocardio. Verlag: Gemini, Sao Paulo (Brasilien), 1979, in Rundbrief 42 der Int.Gesellschaft für Infarktbekämpfung, Febr.1980 (später umbenannt in Gesellschaft für Infarktbekämpfung, weitere Umbenennung in Gesellschaft für Infarktverhütung. Sitz: Schorndorf-Haubersbronn, ausleihbar in Bilbliotheken (evtl. Fernleihe)
• H.Brembach: Infarktvorbeugung in der Arbeitsmedizin, notabene medici 7: 613-616, 1984
• Eine Dokumentation ambulanzkardiologischer Therapie-Ergebnisse nach Anwendung oralen g-Strophanthins, Herbert Pharma GmbH, Wiesbaden, 1984
• Gao et al. (New York): Isoform-specific stimulation of cardiac Na/K pumps by nanomolar concentrations of glycosides. J Gen Physiol 119(4): 297-312, 2002
• Stephen J.McGarry & Alan J.Williams: Digoxin activates sarcoplasmatic reticulum Ca++-release channels: a possible role in cardiac inotropy. Br J Pharmacol 108: 1043-1050, 1993
• Masako Fujino & Sumiko Fujino: An immunohistochemical study of the significance of a new 31,5 kD ouabainreceptor protein isolated from cat cardiac muscle. Jpn J Pharmacol 67: 125-135, 1995
• L.F.Santana, A.M.Gomez & W.J.Lederer Ca++ flux through promiscuos cardiac Na+ channels: slip-mode conductance. Science 279: 1027-33, 1998
• Virendra K.Sharma, Lorelle A.Pottick & Shailesh Banerjee (New York): Ouabain stimulation of noradrenaline transport in guinea pig heart. Nature 286: 817-819, 1980
• Yehuda Gutman & Punya Boonyaviroj: Mechanism of inhibition of catecholamine release from adrenal medulla by diphenylhydantoin and by low concentration of ouabain (10 (-10) M). Naunyn-Schmiedebergs Arch Pharmacol 296: 293-296, 1977
• M.v.Ardenne, W.-K. Mayer, J.Schmidt, G.Rostock & W.Mohnike (Dresden): Klinische Prüfung des perlingual applizierten g-Strophanthin-Präparats Strodival (R) spezial mit Hilfe der 99 mTc-Myospect-Herztomographie. Z Klin Med 46: 667-669, 1991
• S.F.Vatner & H.Baig (Harvard): Comparison of the effects of ouabain and isoproterenol on ischemic myocardium of conscious dogs, Circulation, 58: 654, 1978
• M.von Ardenne: Research on the mechanism of myocardial infarctions and on counteracting measures, a new galenic form of the fast acting g-strophanthin, Agressologie 19: 13-22, 1978
• D.Branco & W.Osswald: Ouabain-induced efflux of catecholaminess and metabolites from blood vessels of normotensive and hypertensive dogs, in E.Erdmann, K.Greeff, J.C.Skou: Cardiac Glycosides 1785-1985, Steinkopff Verlag, Darmstadt, 1986
• Henry DeMots, Shabudin H.Rahimtoola, John H.McAnulty, George A.Porter (Portland / USA): Effects of ouabain on coronary and systemic vascular resistance and myocardial oxygen consumption in patients without heart failure, Am J Cardiol 41: 88-93, 1978
• H.J.Marjorie G.Nelissen-Vrancken, Ju-Feng Wang, Harry A.J.Struijker Boudier, Regien G.Schoemaker, Jos S.F.Smits: Ouabain improves cardiac functionin vivo in rats with heart failure after chronic but not acute treatment. Naunyn-Schmiedebergs Arch Pharmacol 356: 203-209, 1997
• W.Strobelt, U.Karsten, W.Lohmann (Giessen): Biophysikalische Untersuchungen an Erythrocyten mit äquivalenten Dosen von g-Strophantin perlingual und Digitoxin zur Frage der Flexibilität und Mikroperfusion, Rundbrief 68 (April 1986) der Internat. Gesellschaft für Infarktbekämpfung, Schorndorf
• E.Ernst & T.Saradeth (Vienna): Hämorheologische Effekte durch g-Strophanthin, Erfahrungsheilkunde 40: 775-776, 1991
• L.R.Erhardt, G.Unge, G.Boman (Stockholm): Formation of coronary arterial thrombi in relation to onset of necrosis in acute myocardial infarction in man. Am Heart J 91: 592-598, 1976
• L.R.Erhardt, T.Lundmann & H.Mellstedt (Stockholm): Incorporation of 125 I-labelled fibrinogen into coronary arterial thrombi in acute myocardial infarction in man. Lancet 1: 387-390, 1973
• Akira Matsumori, Koh Ono, Ryosuke Nishio, Hiseki Igata, Tetsuo Shioi, Shigeo Matsui, Yutaka Furukawa, Atsushi Iwasaki, Yoshisuke Nose, Shigetake Sasayama (Kyoto / Japan): Modulation of cytokine production and protection against lethal endotoxemia by the cardiac glycoside ouabain. Circulation 96: 1501-6, 1997
• H.Salz & B.Schneider: Perlinguales g-Strophanthin bei stabiler Angina pectoris, Z Allg Med (Zeitschrift für Allgemeinmedizin) 61: 1223-1228, 1985
• F.Kubicek, Th.Reisner: Hypoxietoleranz bei koronarer Herzkrankheit unter der Einwirkung von Digoxin, ß-methyl-Digoxin und g-Strophanthin, Ther d.Gegenw (Therapie der Gegenwart) Heft 5 1973, S.747-768
• B.Sharma, P.A.Majid, M.K.Meeran; W.Whitaker & S.H.Taylor (Leeds / GB): Clinical, electrocardiographic, and haemodynamic effects of digitalis (ouabain) in angina pectoris, Br Heart J 34: 631-637, 1972
• G.G.Belz, J.Mathews, U.Sauer, H.Stern & B.Schneider (Wiesbaden /Germany): Pharmacodynamic effects of ouabain following single sublingual and intravenous doses in normal subjects. Eur J Clin Pharmacol 26: 287-292, 1984
• R.E.Dohrmann und E.Schlief-Pflug (Berlin): Echokardiographische Studie zum Wirkungsnachweis äquivalenter Dosierungen von Nitrolingual und Strodival spezial bei Patienten mit koronarer Herzkrankheit Cardiol.-Angiol Bull 23: 18-22, 1986
• Aristides G.Gousios, James M.Felts, Richard J.Havel (San Francisco + Bethesda) 1967 Circ Res 21: 445-448, Effects of ouabain on force of contraction, oxygen consumption, and metabolism of free fatty acids in the perfused rabbit heart.Naunyn-Schmiedebergs Arch Pharmacol 356: 203-209, 1967
• M.Horackova, S.Mullen (Halifax,Kanada): The dual effects of ouabain on 45Ca++ transport and contractility in adult rat ventricular myocytes. Pflügers Archiv 412: 277-284, 1988
• W.D.Heiss, Th.Reisner, H.Reisner, L.Havelec, F.Kubicek & K.Dietmann (Wien): Effect of ouabain on cerebral blood flow, Wiener klinische Wochenschrift 88: 171-174, 1976
• Krishna P.Agrawal, Charles E.Reed, Robert E.Hyatt, Wayne E.Imber, Willane S.Krell: Airway responses to inhaled ouabain in subjects with and without asthma, Mayo Clin Proc 61: 778-784, 1986
• M.Michalik, R.Uebelhack, I.Grote, G.Ehle & K.Seidel: Das Verhalten vegetativer Parameter unter Anwendung von Ouabain (g-Strophanthin) bei endogen depressiven Patienten. Schweizer Archiv für Neurologie, Neurochirurgie und Psychiatrie 125: 163-178, 1979
• A.Marzo, P.Ghirardi & G.Marchetti: The absorption, distribution and excretion of k-strophanthoside-3H in guinea-pigs afterparenteral administration, J Pharmacol Exp Ther 183: 185-193, 1974
• Norton J.Greenberger, Richard P.MacDermott, James F.Martin & Saradindu Dutta (Chicago): Intestinal absorption os six tritium-labeled digitalis glycosides in rats and guinea pigs, J Pharmacol Exp Ther 167: 265-273
• W.Forth, E.Furukawa & W.Rummel: Comparative studies of the absorption and elimination of tritium-labelled cardiac glycosides, Naunyn-Schmiedebergs Arch Pharmak 263: 206-208, 1969
• W.Forth & W.Rummel: Vergleichende Untersuchung der intestinalen Resorption von 3H-markierten Herzglykosiden in vitro und in vivo. Naunyn-Schmiedebergs Archiv 260: 112-114, 1968
• W.Forth, E.Furukawa, W.Rummel & H.Andres: Intestinale Resorption von Herzglykosiden in vitro und in vivo. Naunyn-Schmiedebergs Arch Pharmak Exp Pathol 262: 53-72, 1969
• W.Forth, E.Furukawa, W.Rummel & H.Andres: Die Bestimmung der intestinalen Resorption von Herzglykosiden durch Messung der 3H-markierten Glykoside im Portalvenenblut und in der Darmlymphe bei Katzen. Naunyn-Schmiedebergs Archiv 264 (1969) 406, 1969
• K.Buchtela, K.Drexler, A.Fehringer, H.Hackl, M.Königstein & J.Schläger: Vergleichende Untersuchung über Resorption, Verteilung und Ausscheidung einiger herzwirksamer Glykoside im Tierversuch. Wien Z Inn Med 51: 227, 1970
• H.Ohlmeier & A.Ruiz-Torres: Die Digitoxin- und g-Strophanthin-Resorption an der perfundierten Dünndarmschlinge der Ratte. Arzneim-Forsch 22 :1874, 1972
• F.W.Hempelmann, N.Heinz & H.Flasch: Lipophilie und enterale Resorption bei Cardenoliden), Arzneimittelforschung / Drug Research 28: 2182, 1978
• A.Garbe & H.Nowak: Zur Pharmakokinetik des Peruvosid. Arzneimittel-Forsch 18: 1597, 1968
• Shoichi Kitano, Shigeto Morimoto, Akira Nishibe, Keisuke Fukuo, Atushi Hirotani, Takeshi Nakahashi, Osamu Yasuda & Toshio Ogihara: Exogenous Ouabain is accumulated in the adrenals and mimics the kinetics of endogenous digitalis-like-factor in rats. Hypertens Res 21: 47-56, 1998
• J.Leuschner & A.Winkler (Hamburg): Toxicological studies with ouabain. Naunyn-Schmiedeberg´s Arch Pharmacol 363 (4) Suppl.: 139, abstract 544, 2001
• Fritz Lauterbach, Günther Vogel & Ingeborg Baumann: Die Abhängigkeit der enteralen Wirkungsquote kardiotoner Steroide von der angebotenen Dosis, Naunyn-Schmiedebergs Arch Pharmak exp Pathol 259: 248-259, 1968
• Fritz Lauterbach in Kurt Greeff (ed.): „Handbook of Experimental Pharmacology”, Vol. 56/II, 1981
• Harol Nunez-Duran, Laura Riboni, Ernestina Ubaldo, Emilio Kabela, & Laura Barcenas-Ruiz: Ouabain uptake by endocytosis in isolated guinea pig atria. J Am Physiol 255: C479-C485, 1988
• H.P.Erdle, K.D.Schultz, E.Wetzel & F.Gross: Resorption und Ausscheidung von g-Strophanthin nach intravenöser und perlingualer Gabe, Dtsch Med Wschr. (Deutsche Medizinische Wochenschrift) 104: 976-979, 1979
• G.V.Marchetti, A.Marzo, C.de Ponti, A.Scvalvini, L.Merlo & V.Noseda: Blood levels and tissue distribution of 3H-Ouabain administered per os, Arzneim Forsch (Drug Res) 21: 1399-1403, 1972
• K.Greeff & K.E.Wirth: Pharmacokinetics of strophantus glykosides, in Kurt Greeff: Handbook of Experimental Pharmacology, Band 56 II : Cardiac Glykosides, S.56-85, Springer B-Hdlbg-N.Y., 1981
• H.Lahrtz, R.W.Sattler & P.A.van Zwieten: Über den Blutspiegel und die Ausscheidung radioaktiv markierter Herzglykoside nach deren intraduodenaler Applikation bei der Katze, Z ges exp Med (Zeitschrift für die gesamte experimentelle Medizin) 148: 210-222, 1968
• F.Piscitello & G.C.Maggi: Effectiveness of orally administered g-Strophanthin on haemodynamics in cardiac patients, Arzneim.-Forsch (Drug Res) 23: 1546-1547, 1973
• K.Greeff, E.Köhler, H.Strobach, E.Verspohl: Zur Pharmakokinetik des g-Strophanthins, Verh Dtsch Ges Kreislaufforschg (Verhandlungen der Deutschen Gesellschaft für Kreislaufforschung) 40: 301-305, 1974
• H.Strobach, K.E.Wirth & K.Rojsathaporn: absorption, metabolism and elimination of strophanthus glycosides in man, Naunyn-Schmiedebergs Arch Pharmacol 334: 496-500, 1986
• M.Riehle, J.Bereiter-Hahn & B.Boller: Effects of ouabain and digitoxin on the respiration of chick embryo cardiomyocytes in culture, Arzneim-Forsch / Drug Res 41: 378-384, 1991
• M.Riehle and J.Bereiter-Hahn: Ouabain and Digitoxin as modulators of chick embryo cardiomyocyte energy metabolism, Arzneim-Forsch 44: 943-947, 1994
• E.Verspohl: Entwicklung radioimmunologischer Methoden zur Bestimmung von Herzglykosiden des Digitoxigenins, g-Strophanthins und k-Strophantidins mit Untersuchungen zur Pharmakokinetik des Digitoxins und g-Strophanthins. Inaugural-Dissertation, Düsseldorf 1973
• M.Tamura, H.Utsunomiya, M.Nakamura & E.J.Landon (Nashville / USA): Effect of dietary glycosides on blood pressure regulation in rats: Can J Physiol Pharmacol 78(7): 548-56, 2000
• Christina M.Yuan, Paolo Manunta, John M.Hamlyn, Shanwan Chen, Erin Bohen, Jane Yeun, Francis J.Haddy & Motilal B.Pamnani (Bethesda, Washington, Baltimore / USA): Long-term ouabain administration produces hypertension in rats. Hypertension 22: 178-187, 1993
• E.Moskopf & H.Dietz: Experimentelle u. klinische Untersuchungen über eine zuverlässige orale Strophanthintherapie. Die Medizinische Welt 1955, p. 1375-77
• G.Kuschinsky: Die Verhütung von Erschöpfungszuständen des Herzens. Klin Wschr 24/25 (1947) 502-503

Disclaimer:
The content in this article is for informational and educational purposes only. The purpose of the material is to increase awareness of the substance discussed, and not to promote any specific product. The information presented in the text is based on available scientific research and does not constitute medical advice. It should also not be considered an encouragement to self-diagnose or treat any ailments. In case of any health problems or concerns, it is recommended to consult a doctor or other qualified specialist.