There are more benefits to Vitis vinifera than red wine
by Lucy Youle
Vitis vinifera L. and its many varieties have been cherished throughout history for their medicinal properties and role in recreation. Today, the leaves of this plant (red vine leaf) are used medicinally for chronic venous insufficiency and products can be found in pharmacies and health food shops. Vitis vinifera can be characterised by its lobed leaves and fruits of varying colours. Red vine leaf extract – the extract from the plant’s colourful autumn leaves – may not be what comes to one’s mind first, but it has become an important herbal treatment for a range of chronic inflammatory conditions, most notably chronic venous insufficiencies of the lower limbs. Reported side effects are relatively mild and rare, though more studies are needed. Overall, there is sufficient evidence to suggest that using red vine leaf extract may be beneficial for sufferers of chronic venous insufficiency.
Popular History and Contemporary Use
Wine has been met with reverential respect throughout the course of history; with its origins in Northern China, from the Neolithic archaeological site of Jiahu (c. 13000 BCE). It has also appeared in ancient Egyptian medicinal recipes inscribed within the tomb of Ptahhotep (the vizier of Ancient Egypt) (c. 4000 BCE) and on Egyptian papyri (c. 2000 BCE) (Fig. 1.). Wine has also been found within prescriptions given by Hippocrates (460-377 BCE) himself for the treatment of wounds and fevers (Norrie, 2019). V. vinifera L. is the species of grape from which wine is produced, and the leaves of this plant (red vine leaf), despite comparatively humble beginnings as an offering to the dead in ancient Egypt (Mercuri et al., 2018), have formed their own medicinal journey.
Galen (129- c. 216 CE), a prominent Greek physician who first demonstrated that the arteries carry blood and not air (which had been the view before) (Nutton, 2020), often used red vine leaf in his treatments (Lotter, 2016). More recently, it has been noted that French wine farmers frequently ingested small amounts of red vine leaf infusions and pastes for the treatment of painful swelling in the legs, and, as a result, has been used in France for over 70 years (EMA, 2016). Today, red vine leaf extract is used in herbal medicines for venous diseases (Rabe et al., 2011) and is also sold as a food supplement and massage gel (extract: AS195).
The most prominent venous disease for which red vine leaf is used is chronic venous insufficiency (CVI); characterised by tingling sensations and painful heaviness and swelling in the legs (EMA, 2016). CVI is caused by damage to the one-way venous valves in the legs, which are meant to carry blood black to the heart. This results in some blood going back down into the legs (known as regurgitation) and accumulating; inducing swelling (WebMD, 2018). CVI is said to be caused by deep vein thrombosis and even lack of exercise, both of which can raise blood pressure in the legs and weaken the valves (WebMD, 2018). Currently, CVI is treated with lifestyle changes such as regular exercise and losing weight, the use of compression stockings and medications that prevent the formation of blood clots (Cleveland Clinic, 2019).
Biological Characteristics and Identification
V. vinifera (Fig. 2.; Vitaceae) is more commonly referred to as either: grape vine, cultivated grape, wine grape and/or European grape (RHS, 2020). This plant can grow up to 18m, showcasing large 3- or 5-lobed leaves; small, green flowers (RHS, 2020) and grapes with colours ranging from bright greens and golden/rouge tones to deep purples (BBC Gardeners World, 2020).
The identification of specific grapevine cultivars is a specific field of economic botany (ampelography from ἄμπελος, – vine and γράφος, -writing) noting physical attributes and using tools such as the V. International Variety Catalogue at: www.vivc.de/index.php?r=site%2Findex (OSU, 2020), Or alternatively, you could send samples for DNA testing to one of many plant identification research centres in the UK, such as Fera (OSU, 2020; Fera, 2020).
Red Vine Leaf Phytochemistry
Flavonoids are the essential group of biologically active metabolites and quercetin-3-Oβ-D-glucuronide,Q3GA (Fig. 3.) is the most abundant one present in red vine leaf (EMA, 2016). Flavonoids are a group of phytochemicals present in most whole foods and are renowned for their anti-inflammatory, anti-carcinogenic and anti-oxidative properties, to name a few (Panche, Diwan and Chandra, 2016). In plants, flavonoids are classed as secondary metabolites and are used in processes such as: growth, defence and the production of pigments in most angiosperms (Panche, Diwan and Chandra, 2016). Studies on the effects of Q3GA have also found that the compound boasts preventative effects on atherosclerosis (Ishizawa et al., 2011) and, interestingly, inhibitory activity on cellular senescence (ageing) (Yang et al., 2014). Flavonoids, in general, have been praised for their cardiovascular protective effects and have even been thought to play a crucial role in the foundations of the ‘French Paradox’ (Ferrières, 2004). This phenomenon calls attention to the low coronary heart disease incidence and mortality rates in France, despite diets high in cholesterol and saturated fats, and is (partly) thought to be down to the considerable consumption of red wine.
Red Vine Leaf Pharmacology
Studies carried out on the effects of red vine leaf for the treatment of chronic venous insufficiency (CVI) have yielded promising results. One study comparing once-daily doses of 360 and 720 mg of commercial preparation indicated the product being as effective as compression stockings in reducing oedema, and that both doses had a significant effect compared to placebo (Kiesewetter et al., 2000). The larger dose also resulted in greater improvement and was tolerated as well as the lower dose. In addition to this, Rabe et al. (2011) found that taking 720 mg of AS195 for 84 days resulted in a 20ml reduction in limb volume compared to a placebo group. Numerous studies have extensively researched the pharmacodynamics of red vine leaf extract, allowing for a clearer understanding of the biological mechanisms that are involved with CVI.
Nees et al. (2003) found that a chemically well characterised extract (AS195) repaired damaged venular endothelial cells when applied directly, in vitro. To expand, the aforementioned risk factors (sedentary lifestyle; thrombotic occlusion etc.) signal for inflammatory mediators, from chronically activated blood cells and/or polymorphonuclear leukocytes, to accumulate at the site of damage. This, in turn, leads to the breakdown of venous endothelia. AS195, in this case, showed significant signs of repair, though the exact mechanism is not fully understood. In theory; if damage to the cells covering the small blood vessels (venular endothelial cells) is reduced, the one-way valves should remain intact and allow for normal blood flow; reducing chances of regurgitation (blood travelling in the wrong direction). This protective effect is thought to be attributed to red vine leaf’s anti-inflammatory flavonoids, mainly quercetin-3-Oβ-D-glucuronide (Q3GA) and isoquercitrin.
From another perspective, Grau et al. (2016) concluded that red vine leaf extract (AS195) increases NOS (nitric oxide synthase) activation and decreases oxidative stress. NOS is an enzyme that produces nitric oxide (NO), a compound which induces vasodilation. This subsequently delays endothelial damage by lowering blood pressure (Chen, Pittman and Popel, 2008). With regards to oxidative stress, NO bioavailability has been shown to be affected by the presence of reactive oxygen species (ROS), thus, it has also been hypothesised that red vine leaf increases NO by reducing ROS (Grau et al., 2016). Interestingly, one study on Q3GA found the compound significantly inhibited lipid peroxidation (Shirai et al., 2001), a process by which ROS causes tissue damage via destruction of cellular membranes (Mylonas and Kouretas, 1999). As a result, there is compelling evidence to suggest that red vine leaf may reduce ROS significantly and consequently protect venous integrity, though, as stated above, some studies have been performed in vitro and may not be entirely reliable with regards to application in everyday life.
Information regarding the safety of V. vinifera as red vine leaf is slightly convoluted due to its specificity and association with wine and grapes. It has been stated on the PILs for products containing AS195. Due to lack of data, pregnant or breastfeeding women should avoid these products. Nausea, stomach discomfort, generalised pruritic (itching) rash, urticaria (hives) and hypersensitivity may be experienced. It is not clear whether these effects are due to the red vine leaf extract itself or any of the other excipients present within these products (such as talc) (Sanofi Consumer Health INC, 2017). Any effects on fertility and the ability to drive and use heavy machinery have not been studied, but seem unlikely. In general, regulated products with a well-defined chemical profile seem to be very safe.
By decreasing endothelial damage and increasing vasodilation, red vine leaf has the potential to encourage normal venous function and reduce hypertension in the legs. Taking red vine leaf extract could also reduce the need for compression stockings and other edema related medicines. Despite some reported side effects, evidence from numerous studies suggest that red vine leaf could be beneficial for sufferers of chronic venous insufficiency and related conditions.
More research, however, is needed regarding side effects, interactions and most importantly: red vine leaf’s exact mechanism of action. It is hard to monitor the effects of red vine leaf as optimal dosages have not yet been determined, due to the complexities of red vine leaf’s path within the body and the plant’s rich phytochemistry. As always, products regulated as (herbal) medicines or under some other form of regulation, are preferable. In quite a few European countries licensed medicines based on red wine leaf are available (Edwards et al 2015), but as of 2020 not in the UKAs of now, red vine leaf is not available as a prescription drug due to these limitations, though a red vine leaf supplement may be all that you need. It is within your best interest to consult with a doctor, prior to taking, if you are uncertain.
In this essay we do not advise or recommend herbs for medicinal or health use. This information is intended for educational purposes only and should not be considered as a recommendation or an endorsement of any particular medical or health treatment. The use of any such product should be based on the appropriate advice of a healthcare professional or based on the information available in the patient information leaflets (i.e. for THR products).
Written by Lucy Youle, a MSc Medicinal Natural Products and Phytochemistry at the UCL School of Pharmacy (2019 – 2020). She has a BSc (Hons) in Biological Sciences.
© Lucy Youle, 2020. All rights reserved.
BBC. 2020. Vitis vinifera. [online]. Immediate Media Company Ltd 2020. Available at: https://www.gardenersworld.com/plants/vitis-vinifera/ [20.3.20]
Chen, K., Pittman, R.N., Popel, A.S. 2008. Nitric Oxide in the Vasculature: Where Does It Come From and Where Does It Go? A Quantitative Perspective. [online]. Antioxid Redox Signal, 10(7), pp. 1185-1198. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2932548/ [19.3.20]
Cleveland Clinic. 2019. Chronic Venous Insufficiency (CVI): Management and Treatment. [online]. Cleveland Clinic. Available at: https://my.clevelandclinic.org/health/diseases/16872-chronic-venous-insufficiency-cvi/management-and-treatment [21.3.20]
Edwards, S., I. da Costa-Rocha, E.M. Williamson and M. Heinrich (2015) Phytopharmacy – an evidence-based guide to herbal medicines. Wiley, Chichester.
EMA. 2016. Assessment report on Vitis vinifera L., folium. [online]. EMA. Available at: https://www.ema.europa.eu/en/documents/herbal-report/draft-assessment-report-vitis-vinifera-l-folium_en.pdf [20.3.20]
Fera. 2020. Plant Clinic. [online]. Fera. Available at: https://www.fera.co.uk/crop-health/plant-clinic#videos [19.3.20]
Ferrières, J. 2004. The French paradox: lessons for other countries. [online]. Heart, 90(1), pp. 107-111. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1768013/ [22.3.20]
Grau, M., Bolck, B., Bizjak, D.A., Stabenow, C.J., Block, W. 2016. The red-vine-leaf extract AS195 increases nitric oxide synthase-dependent nitric oxide generation and decreases oxidative stress in endothelial and red blood cells. [online]. Pharmacol Res Perspect, 4(1). Available at: https://www.ncbi.nlm.nih.gov/pubmed/26977302 [19.3.20]
Ishizawa, K., Yoshizumi, M., Kawal, Y., Terao, J., Kihira, Y., Ikeda, Y., Tomita, S., Minakuchi, K., Tsuchiya, K., Tamaki, T. 2011. Pharmacology in Health Food: Metabolism of Quercetin In Vivo and Its Protective Effect Against Arteriosclerosis. [online]. Journal of Pharmacological Sciences, 115(4), pp. 466-470. Available at: https://www.sciencedirect.com/science/article/pii/S1347861319307406 [23.3.20]
Kiesewetter, H., Koscielny, J., Kalus, U., Vix, J.M., Peil, H., Petrini, O., Van Toor, B.S., De Mey, C. 2000. 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. [online]. Arzneimittel-Forschung, 50(2), pp. 109-17. Available at: https://www-thieme-connect-de.libproxy.ucl.ac.uk/products/ejournals/pdf/10.1055/s-0031-1300174.pdf [25.3.20]
Lotter, E. 2016. How red vine leaf can improve your circulation. [online]. Health24. Available at: https://www.health24.com/Medical/Leg/Varicose-veins/red-vine-leaf-for-varicose-veins-20160114 [18.3.20]
Mercuri, A.M., Catherine, D.A., Formaciaria, R., Hohn, A. 2018. Plants and People in the African Past: Progress in African Archaeobotany. [online]. Springer. Available at: https://books.google.co.uk/books?id=lftmDwAAQBAJ&pg=PA47&lpg=PA47&dq=red+vine+leaf+recipe+in+egyptian+papyri&source=bl&ots=cH1P8AKVS0&sig=ACfU3U2q6eO4jKXspDrerpzQjm3Qy2nwqQ&hl=en&sa=X&ved=2ahUKEwigypyluJLoAhWBh1wKHfjbBs8Q6AEwHXoECAsQAQ#v=snippet&q=red%20vine%20leaves&f=false [23.3.20]
Mylonas, C., Kouretas, D. 1999. Lipid peroxidation and tissue damage. [online]. In Vivo, 13(3), pp. 295-309. Available at: https://www.ncbi.nlm.nih.gov/pubmed/10459507 [24.3.20]
Nees, S., Weiss, D.R., Reichenbach-Klinke, E., Rampp, F., Heilmeier, B., Kanbach, J., Esperester, A. 2003. Protective effects of flavonoids contained in the red vine leaf on venular endothelium against the attack of activated blood components in vitro. [online]. Arzneimittelforschung, 53(5), pp. 330-41. Available at: https://www-thieme-connect-de.libproxy.ucl.ac.uk/products/ejournals/pdf/10.1055/s-0031-1297117.pdf [27.3.20]
Norrie, P. 2019. The History of Wine as a Medicine. [online]. Cambridge Scholars Publishing. Available at: https://www.cambridgescholars.com/download/sample/65052 [20.3.20]
Nutton, V. 2020. Galen. [online]. Encyclopedia Britannica, Inc. Available at: https://www.britannica.com/biography/Galen [19.3.20]
OSU. 2020. Grape Variety Identification. [online]. Oregon State University. Available at: https://extension.oregonstate.edu/crop-production/wine-grapes/grape-variety-identification [19.3.20]
Panche, A.N., Diwan, A.D., Chandra, S.R. Flavonoids: an overview. [online]. J Nutr Sci. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465813/ [25.3.20]
Rabe, E., Stucker, M., Esperester A., Schafer, E., Ottillinger, B. 2011. Efficacy and Tolerability of a Red-vine-leaf Extract in Patients Suffering from Chronic Venous Insufficiency e Results of a Double-blind Placebo-controlled Study. [online]. Eur J Vasc Endovasc Surg, 41, pp. 540-547. Available at: https://core.ac.uk/download/pdf/82140643.pdf [26.3.20]
RHS. 2020. Vitis vinifera. [online]. The Royal Horticultural Society 2020. Available at: https://www.rhs.org.uk/Plants/134401/Vitis-vinifera/Details [23.3.20]
Sanofi Consumer Health INC. (2017). Antistax® Tablets Product Information. [online]. Sanofi. Available at:https://www.antistax.ca/en/product/info.htm [20.3.20]
Shirai, M., Moon, J.H., Tsushida, T., Terao, J. 2001. [online]. Inhibitory Effect of a Quercetin Metabolite, Quercetin 3-O-β-d-Glucuronide, on Lipid Peroxidation in Liposomal Membranes. Journal of Agricultural and Food Chemistry, 49(11), pp. 5602-5608. Available at: https://pubs-acs-org.libproxy.ucl.ac.uk/doi/abs/10.1021/jf010713g [25.3.20]
WebMD. 2018. What Is Chronic Venous Insufficiency? [online]. WebMD. Available: https://www.webmd.com/dvt/dvt-venous-insufficiency#1 [26.3.20]
Yang, H.H., Hwangbo, K., Zheng, M.S., Cho, J.H., Son, J.K., Kim, H.Y., Baek, S.H., Choi, H.C., Park, S.Y., Kim, J.R. 2014. Quercetin-3-O-β-D-glucuronide isolated from Polygonum aviculare inhibits cellular senescence in human primary cells. [online]. Archives of Pharmacal Research, 37, pp. 1219-1233. Available at: https://link-springer-com.libproxy.ucl.ac.uk/article/10.1007/s12272-014-0344-2 [26.3.20]