Nocturia and Angelica

Nocturia is defined as the need to wake from sleep one or more times in order to urinate [1]. Having at least two voids per night is associated with impaired health-related quality of life [2]. The prevalence of nocturia increases with increasing age in both men and women. The bothersomeness of nocturia is largely due to the fact that it interferes with the quality of sleep, which may have a significant negative impact on how the individual feels the next day. Nocturia may affect not only nocturics, but also their partners, whose sleep may also be affected [3]. For patients who are aged 60–70 years, the prevalence of nocturia is between 11% and 50%; for those aged 80 years, the prevalence is between 80% and 90%, with about 30% experiencing two or more episodes nightly [4].

Important factors relating to nocturia include benign prostate enlargement and overactive bladder, diabetes mellitus, heart failure, renal failure, peripheral oedema, nephrotic syndrome, hyperproteinaemia and liver diseases [5].

The main causes of nocturia are global polyuria, nocturnal polyuria, decreased bladder capacity and sleep disorders [5]. Among the parameters used to assess the contribution of factors underlying nocturia are nocturnal polyuria index (NPi) and nocturnal bladder capacity (NBC) index [6]. The NPi is usually calculated by dividing the nocturnal urinary volume output by the total urinary output and thus a high NPi indicates increased nocturnal urine production. An NPi of 0.35 normally reflects nocturnal polyuria [6], although the limit may be lower or 0.2 for young people [7]. The NBC index is calculated from the actual number of nightly voids, nocturnal urine volume (nightly voided volume plus the first morning voided volume) and the functional bladder capacity. A high NBC index, which reflects reduced nocturnal bladder capacity, has been found to be more prevalent among Asian men suffering from nocturia than their Caucasian counterparts [8]. An NBC index of 1.3 has recently been suggested as a cut-off point above which reduced nocturnal bladder capacity should be investigated as a cause of nocturia [9].


SagaPro is a phytochemical product from Angelica archangelica leaf that has been used in Iceland for 6 years in the treatment of nocturia. The herb A. archangelica has been used both in folk medicine and as a vegetable. Extensive research has shown that A. archangelica contains several important bioactive compounds, including flavonoids and other polyphenols, terpenes, coumarins and polysaccharides, with various biological effects [10–12]. The roots, fruits and leaves of the herb have been used in folk medicine, and it is one of the most respected medicinal herbs in Nordic countries, where it was cultivated during the Middle Ages [13,14] and exported to other parts of Europe [15].

A water extract from A. archangelica leaf, as is SagaPro, has been found to have antitumour activity in vivo [16]. Among the many bioactive phytochemicals present in SagaPro is isoquercitrin (unpublished results), which could conceivably play a role in the effect of SagaPro on nocturia experienced by the users. Isoquercitrin is a flavonoid that influences the activity of leukotriene LTD4. Leukotrienes (LT) are compounds which are derived from arachidonic acid (20:4n-6) in smooth-muscle cells in the bladder and cause contractions by stimulating receptors. LTD4 also causes contraction in coronary arteries, pulmonary arteries and subcutaneous arterioles. Isoquercitrin inhibits the activity of leukotrienes (LTD4), either by inhibiting the production of LTD4 or by inhibiting binding to receptors in smooth-muscle cells in the bladder [17–19].


[1] Staskin D, Kelleher C, Avery K, Bosch R, Cotterill N, Coyne K, et al. Initial assessment of urinary and faecal incontinence in adult male and female patients. In: Abrams P, Cardozo L, Khoury S, Wein A, editors. Incontinence. 4th ed. Plymouth: Health Publications; 2009. 
[2] Tikkinen KA, Johnson TM, Tammela TL, Sintonen H, Haukka J, Huhtala H, et al. Nocturia frequency, bother, and quality of life: how often is too often? A population-based study in Finland. Eur Urol. 2010;57:488–96.  [PubMed]
[3] Chartier-Kastler E, Tubaro A. The measurement of nocturia and its impact on quality of sleep and quality of life in LUTS/BPH. Eur Urol Suppl. 2006;5:3–11.
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[6] Weiss JP, Blaivas JG, Stember DS, Chaikin DC. Evaluation of the etiology of nocturia in men: the nocturia and nocturnal bladder capacity indices. Neurourol Urodyn. 1999;18:559–65.  [PubMed]
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[9] Burton C, Weiss JP, Parsons M, Blaivas JG, Coats AC. Reference values for the nocturnal bladder capacity index. Neurourol Urodyn. 2011;30:52–7.  [PubMed]
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[11] Sigurdsson S, Ogmundsdottir HM, Gudbjarnason S. The cytotoxic effect of two chemotypes of essential oils from the fruits of Angelica archangelica L. Anticancer Res. 2005;25:1877–80.  [PubMed]
[12] Härmälä P, Vuorela H, Törnquist K, Hiltunen R. Choice of solvent in the extraction of Angelica archangelica roots with reference to calcium blocking activity. Planta Med. 1992;58:176–83.  [PubMed]
[13] Halldórsson B.  Grasnytjar. Copenhagen: August Friedrich Stein; 1783. 
[14] Bjarnason AH.  Íslensk flóra með litmyndum. Reykjavík: Iðunn; 1983. 
[15] Newall CA, Anderson LA, Phillipson JD.  Herbal medicines – a guide for health-care professionals.London: Pharmaceutical Press; 1996. 
[16] Sigurdsson S, Ogmundsdottir HM, Hallgrimsson J, Gudbjarnason S. Antitumour activity of Angelica archangelica leaf extract. In Vivo. 2005;19:191–4.  [PubMed]
[17] Piper PJ. Leukotrienes: possible mediators in bronchial asthma. Eur J Respir Dis Suppl. 1983;129:45–64.  [PubMed]
[18] Bjorling DE, Saban MR, Bruskewitz RC, Saban R. Response of the isolated guinea pig bladder to exogenous and endogenous leukotrienes. J Urol. 1994;152:1281–6.  [PubMed]
[19] Yoshimura N, Chancellor MB. Interstitial cystitis and bladder research: progress and future directions: highlights of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Interstitial Cystitis Association (ICA) International Research Symposium October 19–20, 2000, Minneapolis, MN. Rev Urol. 2001;3:146–51. [PMC free article]  [PubMed]
[20] Scheuermaier K, Meyers M, Surprise M, Loughlin KR, Duffy JF. Reciprocal relationship between age-related sleep disruption and urological symptoms. BJU Int. 2011;107:871–3. [PMC free article][PubMed]


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