Hagebutte (Rosa canina) – bei Arthrose, Rheuma, Ödemen, Magen- und Darmbeschwerden
Die traditionelle Anwendung der Hagebutte liegt im Einsatz gegen Erkältungskrankheiten. Neuerdings haben klinische Studien jedoch gezeigt, dass die Behandlung mit Hagebuttenpulver auch die Symptome der Arthrose deutlich zu reduzieren vermag. Hagebuttenpulver das nach einem patentgeschützen, schonenden Prozess, (bei einer Temperatur < 40°) hergestellt wird, ist als Nahrungsergänzung (Litozin®) im Handel.
Anwendung
Schmerzhafte Arthrose von Knie-, Hüft- und Handgelenken
Arteriosklerose
Wirkung
Als aktiver Wirkstoff wurde ein Galaktolipid angenommen – ein Molekül, das aus einem Zuckeranteil und Fettsäuren zusammengesetzt ist. Er zeigt eine antientzündliche Wirkung als Folge eines hemmenden Effektes auf die Chemotaxis menschlicher neutrophiler Leukozyten im peripheren Blut und verhindert die Bildung von toxischen freien Radikalen in polymorphkernigen Zellen. Auf diese Weise wird der gesunde Knorpel geschützt, die Schmerzen werden gelindert und die Beweglichkeit verbessert. Bei neueren invitro-Untersuchungen mit Methanol- und n-Hexan-Extrakten wurden neben einigen instabilen Bestanteilen alfa-Linolensäure, Linolsäure und Ölsäure identifiziert, die jedoch die Aktivität des Extrakts nicht erklären können. Daher vermutet man, dass ein noch nicht identifizierter lipophiler Bestandteil für die beobachtete inhibitorische Wirkung auf den Arachidonsäure-Metabolismus verantwortlich ist.
In klinischen Studien konnte gezeigt werden, dass bei Patienten mit Arthrose der Serumspiegel von C-reativem Protein (CRP) – einem Marker für entzündliche Vorgänge im Körper – sowie von Kreatinin durch die Einnahme von Hagebuttenpulver gesenkt wurden. Gleichzeitig verbesserten sich Symptome wie Gelenkschmerzen und Morgensteifigkeit. Der Verbrauch von zusätzlich eingenommenen Schmerzmitteln, wie Tramadol, Opioiden, Paracetamol oder NSARs konnte deutlich reduziert werden.
Als angenehmer Nebeneffekt wurde eine Senkung des LDL-Cholesterins beobachtet. Ob Hagebuttenpulver auch als wirksamer Gefäßschutz eingesetzt werden kann, muss in weiteren Untersuchungen geklärt werden.
Inhaltsstoffe
Vitamin C: bis 1,7 %, der Gehalt nimmt aber im Lauf der Lagerung ab. Carotine Galaktolipid (GOPO®), Pektine, Zucker, Fruchtsäuren, Gerbstoffe
Dosierung
5 g pro Tag über 3 Monate
Hinweise
GOPO® ist hitzelabil und darf nicht über 40° erhitzt werden. Die Zubereitung des Pulvers muss in einem schonenden Verfahren erfolgen – in Hagebuttentee oder Marmelade finden sich die wirkaktiven Komponenten daher nur in Spuren.
Quellen
Chrubasik, S.; Hagebuttenpulver: Die pflanzliche Arznei hält der wissenschaftlichen Prüfung stand, Studienpräsentationen am OARSI, Chicago, 2004.
Chrubasik, S.; Helfen pflanzliche Schmerzmittel bei Arthrose und Rückenschmerzen, Fortbildungsveranstaltung, Graz, 26.09.2006.
Rein, E.; Kharazmi, A.; Winther K.; A herbal remedy, Hyben Vital (stand. powder of a subspecies of Rosa canina fruits), reduces pain and improves general wellbeing in patients with osteoarthritis–a double-blind, placebo-controlled, randomised trial, Phytomedicine. 2004 Jul;11(5):383-91.
Wenzig, EM.; Widowitz, U.; Kunert, O.; Chrubasik, S.; Bucar, F.; Knauder, E.; Bauer, R.; Phytochemical composition and in vitro pharmacological activity of two rose hip (Rosa canina L.) preparations, Phytomedicine. 2008 Oct;15(10):826-35. Epub 2008 Aug 15.
De pitjes van de Rosa canina en Rosa rugosa zijn rijk aan vetten (10%). Verder bevatten ze vitamine A en E. Maar wat ze zo bijzonder in smaakwaarde maakt, ze bevatten vanilline. Vanilline is het hoofdbestanddeel van vanille en geeft de gemalen pitjes een zoet amandelachtig aroma. Je kan het meel verwerken in koek, brood en cake. Zowel in smaak als in structuur bijzonder mooi van kwaliteit, omdat de olierijke pitjes zorgen voor een smeuïg meel.
Vruchtvlees rozenbottels
De bottel is zeer rijk aan vitamine C, pectine (een voor de dikke darmflora fermenteerbare vezel en dus voedingsbron voor deze je gezondheid ondersteunende bacteriën) en looistoffen met een heilzame werking op de huid: een verstevigende en ontstekingsremmende werking op de haarvaatjes en een vertragende werking op de veroudering van celweefsel. Verder bevatten de bottels de stof glycolipide, wat een ontstekingswerende (antinflammatoire) werking op gewichtsontsteking heeft.
Je kan ook de hele rozenbottels met pitjes tot moes malen en vers verwerken in brood of er zo een confituur mee maken.
Dog Rose Hip Rosa canina
by Gayle Engels, Josef Brinckmann
HerbalGram. 2016; American Botanical Council
INTRODUCTION
Dog rose (Rosa canina, Rosaceae), also known by the common names dog brier, brier rose,1 or simply “rose hip,” refers to both the fruit and the entire plant. The species is native to Europe, and it is widely distributed throughout the continent. In fact, it is the most common Rosa species with the widest distribution in central Europe.2 Dog rose also grows wild throughout Central Asia and in parts of Mediterranean northern Africa.3 Hundreds of years ago, R. canina was introduced by European colonizers into the Americas, southern Australia, New Zealand, and southern Africa, where it escaped cultivation, naturalized, and now grows wild.3
Rosa canina is a large shrub or small tree with arching stems that grows rapidly up to 9 feet (2.74 meters) in height.4 Single or small clusters of five-petaled flowers ranging in color from white to pink appear in June and July and are followed by bright red persistent fruit or pseudofruit (hips) in September and October. The actual fruit is the small hairy structure within the hip that contains one seed.5 Dog rose reproduces by seed (generally dispersed by birds that eat the hips) and by suckering and layering. Its reproductive habits and large size make R. canina difficult to control. Some governments classify it as an invasive species and have implemented management plans to prevent its further spread.6
The commercial supply of R. canina is obtained primarily from wild-collection operations in Eastern Europe, particularly in Bulgaria, Hungary,7 the Czech Republic,8 and Romania;9 in southern Europe, especially Albania, Bosnia and Herzegovina, Croatia,10 Kosovo,11 Serbia,12 Slovenia,13 and Macedonia;14 in western Asia, including Armenia, Azerbaijan, Georgia,15 and Turkey;16 and in Central Asia, especially Uzbekistan.17 Cultivation also occurs in areas where wild-collection remains prominent, particularly in Bulgaria10 and Hungary.18 The raw material used to manufacture the most widely clinically tested dog rose hip product (Hyben Vital; produced by Hyben Vital Int. ApS; Tranekär, Denmark) is a selectively bred cultivated variety. In the 1990s, agronomists and botanists with Hyben Vital developed a distinct variety that they named “Rosa Canina Lito” (more properly written “Rosa canina ‘Lito’” taxonomically), which currently is grown in Denmark and in a few other European countries.19
There is significant commercial wild-collection in non-native regions where various species of Rosa escaped from domestication long ago, especially in Chile and Lesotho (in southern Africa),9 but also in Argentina and South Africa. Chile is a major exporter of “Rosa mosqueta,” a regional name used collectively for rose hips of at least three naturalized species: R. moschata (musk rose), R. rubiginosa (sweetbriar rose), and R. canina.20 These species, especially R. rubiginosa, increasingly are being cultivated in Chile.
The material of commerce is generally divided into four main quality grades. European Pharmacopoeia quality requires the “receptacle and the remains of the dried sepals with achenes removed” to contain a minimum of 0.3% ascorbic acid (vitamin C).21 The International Organization for Standardization (ISO) provides food quality specifications for the dried ripe fruits with “stems cut off and calyx ends removed” (ISO 23391) in three grades: “Extra class” grade must contain a minimum of 0.2% ascorbic acid, “Class I” specifies a minimum ascorbic acid content of 0.175%, and “Class II” grade has a minimum of 0.15% ascorbic acid.22
Biotype and altitude, depending on geographical origin, are the main factors impacting ascorbic acid content.23 Notably, researchers in Romania have found that higher harvesting altitudes correlate with higher ascorbic acid contents in R. canina. For example, in one study, the ascorbic acid content of fruit pulp was 0.27% when harvested at 630 meters (2,067 feet), but it was 0.45% when harvested at 807 meters (2,648 feet).24 Earlier experiments in the mid-20th century found that R. canina fruits harvested in the Caucasus Mountains contained more than three times the ascorbic acid of fruits harvested from the Black Sea shore.25 Another Romanian research group correlated higher ascorbic acid content with cold and rainy weather. Over a four-year period, R. canina was wild-collected from 42 biotypes during the second half of October and tested for ascorbic acid content. Fruits harvested in years with higher precipitation and colder temperatures showed higher vitamin C levels.26
While the European Pharmacopoeia includes both R. canina and R. pendulina (alpine rose) within the scope of its “Dog Rose – Rosae pseudo-fructus” monograph,21 this article does not specifically address the fruits of Rosa species other than R. canina. In the United States, three federal agencies define rose hip quite differently. The US Department of Agriculture (USDA), in its List of Approved Names, defines “rose hips” as either R. canina or R. rugosa (rugose rose);27 the US Food and Drug Administration (FDA) defines “rose fruit (hips)” as R. alba (white rose), R. centifolia (cabbage rose), R. damascena (damask rose), R. gallica (French rose), and varieties of these species;28 and the US Environmental Protection Agency (EPA) defines “rose hip” as R. rubiginosa.29
Rose hips used in the Asian systems of medicine are also imported into the United States. For example, “Rosae laevigatae fructus,” the dried ripe fruit of R. laevigata (Cherokee rose; Chinese: 旄憛磾, jinyingzi; Korean: 旎操濠, kumaengja), is specified in the Hong Kong Chinese Materia Medica Standards, the Korean Pharmacopoeia, the Pharmacopoeia of the People’s Republic of China, and Taiwan Herbal Pharmacopoeia. Additionally, “Rosae multiflorae fructus,” the pseudocarp of the fruit of R. multiflora (Japanese rose hip; Japanese: ⅷⅳⅨΔ; Korean: 艙褒), is specified in the Japanese Pharmacopoeia and in the Korean Herbal Pharmacopoeia. Furthermore, the “Fructus Rozae” monograph of the State Pharmacopoeia of the [former] USSR permitted the hips of 13 different species: R. acicularis (prickly wild rose), R. beggeriana (Begger’s rose), R. canina, R. corymbifera (pale rose), R. davurica (Amur rose), R. fedtschenkoana (Fedchenkovskiy rose), R. kokanica (Kokand rose), R. majalis (May rose), R. micrantha (smallflower sweetbriar rose), R. psammophila (now considered a synonym of R. micrantha), R. rugosa, R. tomentosa (whitewoolly rose), and R. zangezura (Zangezurian rose).30 Thus, what is traded and labeled as “rose hips” could be any of the many rose species in global commerce.
HISTORY AND CULTURAL SIGNIFICANCE
The species name canina stems from the Latin canis, meaning dog. The naming of this species may be attributed to writings of ancient Greek physician Hippocrates (460-377 BCE) and Roman naturalist Pliny the Elder (23-79 CE), in which it was suggested that a preparation of wild R. canina root could be used to treat the bite of a rabid dog.6,30 Another, and perhaps more likely, theory is that the species was formerly known as the “dag rose” (from the Italian daga, for dagger, referring to its stout thorns), which was changed to “dog rose” through misunderstanding.6
In the 9th century Zoroastrian scripture Bundahishn (“Original Creation”), written in the Pahlavi (Middle Iranian) language, each listed plant was associated with a particular angel. Dog rose (nestarun) belonged to Rashn, the Zoroastrian angel of justice, who judged souls of the dead.31 The dog rose was believed to acquire thorns only when evil appeared in the world.32 Some of the oldest documentation of traditional Bulgarian herbal remedies are found in a canon of early Bulgarian literature written in the Old Church Slavonic language. Here it is written that St. Ivan Rilski (876-946 CE) prepared communion bread from baked R. canina fruit powder. St. Rilski is known as Bulgaria’s first hermit and as one of the most important saints in the Bulgarian Orthodox Church.33 Rosa canina is also the second most frequently mentioned medicinal plant in the Chilandar Medical Codex, considered the most significant medieval Serbian pharmacological manuscript on European medical science from the 12th century to the 15th century.34 In Maister Constantini Buch — a Schwabian-language formulary published in 1472, which contains prescriptions attributed to Heinrich Steinhöwel (1412-1482 CE), the personal physician to Eberhard I, the Duke of Württemberg — a preparation of dog rose hip wine was indicated for stopping excessive menstrual bleeding. Curiously, another 15th century formulary in the Middle Franconian language, Bartholomäus-Handschrift, prescribed dog rose hip wine as an emmenagogue to stimulate menstrual flow.35
Traditional uses of rose hip were based on its astringency. It was believed to strengthen the stomach and alleviate diarrhea, dysentery, thirst, cough, and “spitting of blood.”6 The 17th century English herbalist, botanist, physician, and astrologer Nicholas Culpeper (1616-1654) stated that ripe hips made into a conserve (a preparation typically made with sugar or honey) would “gently bind the belly, and stay defluctions [the flow of humors, or body fluids] from the head upon the stomach, drying up the moisture thereof, and promoting digestion.”36 He also said that the dried, powdered hips would break up stones, promote urination, and ease colic.
In the 1885 edition of the British Pharmacopoeia, rose hips had official, listed uses for their refrigerant and astringent properties. However, rose hips are no longer used in conventional medicine or pharmacy in Britain, except as a flavoring for medicinal preparations (a confection of rose hips is used in which the pulp is separated from the skin and hairy seeds, and beaten with sugar).6
Today, rose hip preparations are used for colds, diabetes, diarrhea, edema, fever, gastritis, gout, polydipsia (abnormal thirst), rheumatism, sciatica, conditions of the kidneys and lower urinary tract, as a diuretic and laxative, and for “blood purification.”37-39
Rose hips are used in making jams, jellies, teas, soups,37 infusions, syrups, beverages, pies, bread, wine, and marmalade,40 sometimes just as flavoring, but often for their vitamin C content.
In northeastern Portugal, the fruit is eaten raw, and decoctions or brandy macerations are made with the fruit for their diuretic, antidiarrheal, antirheumatic, anti-inflammatory, respiratory, decongestant, stimulant, and tonic actions, as well as to treat skin infections.41 The young shoots and hips are eaten raw, and the hips are used in making cakes and spirits in rural communities in the Campoo (Cantabria) region of northern Spain.42
In 1990, the German Commission E published negative monographs for “Rosae pseudo-fructus” (dog rose hip without seeds), “Rosae pseudo-fructus cum fructibus” (dog rose hip with seeds), and “Rosae semen” (dog rose seed). At the time of the evaluation, there was insufficient evidence of therapeutic efficacy for any traditional uses. However, the Commission E stated that there were no objections against the use of dog rose as a component of non-medicinal beverage teas.43 That being said, the fruit of R. canina remains classified as both food and medicine, and appears on List B in the Government of Germany’s List of Substances, meaning that restricted use in foods is recommended because pharmacological effects occur above a certain dose.44 There is also a tradition in Germany of combining rose hip with “roselle flower” (calyces and epicalyces of Hibiscus sabdariffa, Malvaceae) as a so-called fruit tea (“Hagebutte-Hibiskus-Früchtetee”). In 2015, sales of rose hip/roselle flower combination teas accounted for 5.4% of all herbal and/or fruit tea sales in Germany in terms of volume (2,108 tons were sold out of a total of 39,249 tons of all herbal and/or fruit teas).45
CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES
In the United States, while the FDA does not expressly list R. canina as generally recognized as safe (GRAS) for use in food products, extracts and oils of rose hip (obtained from R. alba, R. centifolia, R. damascena, R. gallica, and varieties of these species) are listed as GRAS.28 The USDA, however, lists rose hips (obtained from R. canina or R. rugosa) as food.27 Rose hip, or an extract obtained from rose hip, is also permitted as a component of dietary supplement products, which require FDA notification within 30 days of marketing if a structure-function claim is made and product manufacturing according to current Good Manufacturing Practices (cGMPs). It is worth noting that “rosehips” is used 15 times in the preamble of the FDA’s cGMPs for dietary supplement regulation; the FDA provides a lengthy discussion to clarify the specifications and different labeling requirements for a “rosehips dietary supplement” versus a “vitamin C from rosehips dietary supplement.”46
In Canada, R. canina is regulated as an active ingredient of licensed natural health products (NHPs), requiring pre-marketing authorization from the Natural and Non-prescription Health Products Directorate (NNHPD). It is listed in Appendix 3 (“Other Medicinal Ingredients”) of the NHP “Antioxidants” monograph. At the prescribed dosage equivalents (100 g fresh, or 45 g dry), licensed dog rose NHPs may be marketed with antioxidant claim statements, (i.e., as a “source of antioxidants that help protect against cell damage caused by free radicals”).47 Additionally, “Rosa Canina Fruit Extract,” if used as the source of vitamin C for oral vitamin C NHPs, or for products making claims as per the NHP Vitamin C monograph, must declare R. canina as the source of vitamin C. Both “Rosa Canina Fruit Extract” and “Rosa Canina Fruit Oil” may also be used as non-medicinal components of topical NHPs for skin-conditioning purposes.48 At the time of this writing (July 2016), there were 512 licensed NHPs containing “rosehips”: 302 of those NHPs listed “R. canina” as a medicinal ingredient, 78 listed “rosehips” (without Latin name) as a medicinal ingredient, 60 listed “R. canina” as a non-medicinal ingredient, and 72 listed “rosehips” (without Latin name) as a non-medicinal ingredient.49
For herbal medicinal product companies in the European Union (EU), or in non-EU countries where the European Pharmacopoeia is an official compendium (e.g., in Australia and Canada), there is a quality standards monograph established by the European Directorate for the Quality of Medicines (EDQM) for “Rosae pseudo-fructus” that can be used as the basis for an active ingredient specification.21 The German Drug Codex (DAC) also provides a quality standards monograph for “Rosae pseudo-fructus cum fructibus.”50 For food applications, the aforementioned ISO 23391 standard can also be used as a basis for establishing quality specifications.22 In the EU, while it is possible to register an Herbal Medicinal Product (HMP), including dog rose hip, as an active ingredient, the European Medicines Agency (EMA) has yet to develop a labeling standards monograph. Even the most widely clinically tested dog rose hip product is not a registered medicine but is labeled and marketed as a food supplement product.51
As of July 2016, according to the drug information database of the German Federal Institute for Drugs and Medical Devices (BfArM), there were 1,959 medicinal products containing “Hagebutten” (dog rose hip) in Germany, but in most cases it is listed as a non-medicinal ingredient of the preparation. In Switzerland, there are some licensed non-prescription medicines containing “R. canina” as an active ingredient. For example, each 1.8-g teabag of Sidroga Erkältungstee (a traditional European herbal medicinal tea for feverish colds with cough; Sidroga AG; Rheinfelden, Switzerland) contains equal parts of five active ingredients: dog rose hips, European elder (Sambucus nigra, Adoxaceae) flower, German chamomile (Matricaria chamomilla, Asteraceae) flower, linden (Tilia cordata or T. platyphyllos, Tiliaceae) flower, and wild thyme (Thymus serpyllum, Lamiaceae) herb.52 For use in cosmetic products, the European Commission Health and Consumers Directorate lists “Rosa Canina Fruit Extract” for astringent, skin-conditioning, and tonic functions. “Rosa Canina Fruit Oil” is listed for emollient and skin-conditioning functions, and “Rosa Canina Fruit Juice” is listed for astringent functions.53
MODERN RESEARCH
In vivo and in vitro studies have confirmed the antibacterial, anti-inflammatory, antioxidant, and anti-obesogenic activities of rose hips. These actions have been attributed to galactolipids (namely GOPO), phenolics, and vitamin C, as well as carotenoids such as lycopene, lutein, and zeaxanthin.54 The hips also contain nutrients such as amino acids, bioflavonoids, pectins, sugars, tannins, tocopherol, beta-sitosterol, and long-chain polyunsaturated fatty acids,54,55 as well as vitamins A, B3 (niacin), D, and E, folate, and minerals magnesium and copper.37 Rose hips are considered to be one of the most abundant sources of vitamin C, second only to kakadu plum (Terminalia latipes ssp. psilocarpa, syn. T. ferdinandiana, Combretaceae) and camu-camu (Myrciaria dubia, Myrtaceae).56 The stability and bioavailability of vitamin C in rose hips is enhanced by the presence of flavonoids and organic acids that inhibit oxidation.55 There is a wide range in the content of chemical compounds in R. canina, presumably due to its great polymorphism (i.e., the appearance of different forms among the members of a specific population or colony).54
Known as Hyben Vital (HV) and Litozin in Europe, and as Litozin (until 2011) in the United States and Canada, a rose hip powder (RHP) made from the Lito variety of R. canina grown on the island of Langeland in Denmark is described by the company as a “biologically standardized powder” composed of the seeds and husks of the Langeland rose hip.57 With only the small hairs on the seeds removed, the remainder of the fruit is processed via a patented drying procedure at temperatures not exceeding 40°C (104°F). One hundred grams of the RHP contains at least 500 mg vitamin C, 5.8 g pectin, 5.8 mg beta-carotene, 50 mg beta-sitosterol, 0.2 mg folic acid, 4.6 mg vitamin E, 170 mg magnesium, 1 mg zinc, and 10.9 µg copper. At least nine double-blind, placebo-controlled clinical studies have investigated the efficacy of HV or Litozin RHP in treating osteoarthritis (OA), hypercholesterolemia (dyslipidemia), Crohn’s disease, chronic back and musculoskeletal pain, and reducing C-reactive protein (CRP), levels of which rise in blood plasma in response to inflammation. From 2011 forward, Litozin has been made with Chilean rose hip shell and no seed but with added vitamin C, carotenes, flavonoids, triterpenic acid, and galactolipids (trade name: Rosenoids), and has been studied only for its effect on OA. Therefore, studies using the “old” Litozin will refer to the product used as HV RHP or RHP.
In a 2013 randomized, double-blind, placebo-controlled (RDBPC) crossover study, 30 patients with OA of the dominant hand were randomized to take twice daily for three months either five 0.5 g-capsules of HV RHP or five placebo capsules (phase 1).58 Patients taking prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) were instructed to continue using them throughout the study, but patients using other analgesics (e.g., acetaminophen, codeine, or tramadol) were asked to reduce their consumption if possible. At the end of three months, patients in the HV group were switched to the placebo and vice versa and continued the study for an additional three months (phase 2). Joint pain in the dominant hand was evaluated by means of a 10-step categorical scale test prior to starting treatment, three weeks into treatment, and after three months of treatment in both phases. Test activities included various common actions: holding heavy items, opening containers, wringing a wet cloth, tying shoelaces, removing pills from a blister pack, and managing small items like forks or pens, among others. Patients also reported changes in joint stiffness during the pain assessment. Additionally, the use of rescue medications during the first 14 days of treatment was compared to the last 14 days of treatment.
In this study, after the first three months, the HV group reported a 90% reduction in pain, compared to a 36% reduction in the placebo group. The HV group continued to experience reduced pain for three weeks into phase 2 after they had switched to placebo. Reduction in pain during test activities varied, but was as high as 26% in the “handwriting a letter” task after three months. Stiffness declined after three weeks of treatment but did not attain statistical significance compared to placebo after three months. There was a 23% reduction in stiffness during test activities after three weeks, and a 25% reduction after three months. Additionally, treatment with HV resulted in a 33% decline in the number of analgesics used between the first 14 days and the last 14 days of phase 1. The authors opine that the consumption of analgesics may have “blunted some further impact on symptom scores from HV, but would have left us without the knowledge that HV treatment was strong enough to change the consumption of rescue medication.” Blood samples were collected and CRP was evaluated in patients prior to starting phase 1 and at the end of each treatment phase. CRP could be detected in only eight patients and, although pre-treatment values fell after active treatment, there was no statistically significant difference between HV treatment and placebo. The authors suggest that further research should include a comparison of rose hip products since their contents of anti-inflammatory constituents can vary greatly.
In another RDBPC parallel study published in 2009, 89 patients with rheumatoid arthritis (RA) were randomized for treatment with 5 g daily of RHP (five capsules in the morning and evening) or placebo for six months.59 At three and six months, scores on the Health Assessment Questionnaire (HAQ) disability index improved (i.e., numerically declined) in the experimental group, while they worsened in the placebo group. In the HAQ Patient Global Scale, a trend toward favoring treatment was seen after six months, but there were no significant differences between the treatment and placebo groups in the HAQ Patient Pain Scale. The disease activity score (DAS-28) for the treatment group showed greater improvement compared to placebo (P = 0.056), and the Physicians Global Scale showed strong improvement (approximately 30%) compared to placebo (7%) after six months. Quality of life assessments also showed improvement after treatment, but there was no significant reduction in pain medication. The authors recommended further studies with larger sample sizes and multivariate analyses, as well as studies on dose-finding and testing of different rose hip extractions.
A 2008 meta-analysis assessed three randomized, controlled trials (RCTs) discussed in the following paragraphs.60 It concluded that, despite a “sparse amount of data,” HV RHP reduces pain in OA patients but that its efficacy and safety required further study. A 2016 review of animal and human studies noted that rose hip preparations containing seeds and shells (HV RHP) are supported by meta-analyses and have substantial anti-inflammatory activities, but that claims for the shell only preparations (RHSP) are preliminary and lacking in “suitable placebo-controlled randomized clinical trials,” and thus cannot be advocated for in clinical settings.61
In 2005, a RDBPC crossover study showed that RHP reduced symptoms of knee and hip OA.62 Patients (N = 94) were randomized to take 5 g RHP per day (five 0.5 g-capsules taken in the morning and evening) or placebo for three months. After three months, the patients in the RHP group were switched to the placebo and vice versa. Patients taking prescribed NSAIDs were instructed to continue taking them, but patients taking other analgesics (e.g., acetaminophen or synthetic opioids) were requested to reduce their consumption, if possible, after the first three weeks of treatment. Patients were asked not to change or start any new pain medications during the study. At the beginning of the study, at three weeks, and at three months of both treatment periods, the researchers used the Western Ontario and McMaster Universities (WOMAC) questionnaire to assess pain, stiffness, disability, and global severity of the patients’ OA.
The RHP group experienced a statistically significant reduction in pain compared to the placebo group after three weeks. The same pattern was observed after three months of treatment, but it was not statistically significant, possibly because the patients were allowed to reduce their consumption of rescue medication after the first three weeks. Had they not reduced their consumption of analgesics, the reduced pain score might have been significant after three months and/or after three weeks. The RHP group also reduced its consumption of analgesics by 40% during the active treatment period. A sub-analysis of the consumption of analgesics in the first three months of treatment showed a significant reduction in the amount of pain medication taken during a two-week period in the RHP group, as opposed to an insignificant increase in the placebo group. Further, after three months, the active treatment group experienced a significant reduction in stiffness, less limitation of physical function, and a decline in the global assessment of disease severity compared to placebo. The authors suggested that future research should try to determine an optimal dose, test RHP impact in long-term treatment and compare that to NSAIDs, and investigate the biological activity of additional subtypes of rose hips.
Another RDBPC crossover study published in 2004 investigated HV’s efficacy in reducing pain and improving general wellbeing in 112 patients with OA of the hip, knee, hand, shoulder, neck, or some combination.63 Patients were randomly assigned to treatment with either five 0.5 g-capsules of HV (group B) daily or placebo (group A) for three months, after which patients in each group were switched to the other group. Additionally, patients were advised to continue taking prescription NSAIDs but, three weeks into the study, patients taking other pain relievers were requested to reduce their use if possible. The primary outcome measures were changes in joint pain and the amount of pain relievers the patients used. While there was a nonsignificant decline in the use of analgesics, there was a significant reduction in pain with HV treatment after three months, and the patients favored treatment with HV. End-of-treatment subjective assessments of the 85 patients who completed both phases of the study revealed that group A (placebo first) experienced a significant 50% reduction in pain after three months of treatment with HV, compared to just a 25% reduction in pain with placebo. Group B (HV first), on the other hand, experienced no significant difference between the HV and placebo treatments. The authors attribute this to a carryover effect of the HV treatment, a potential drawback of crossover studies.
Another RDBPC study in 2003 also assessed the effects of HV on knee and hip mobility, activities of daily living (ADL), quality of life, and pain in patients with OA.64 Two groups of 50 patients each took either five 0.5 g-capsules of HV or placebo twice daily for four months. Knee and hip mobility was measured at the beginning of the study and after four months of therapy. Hip joint mobility improved significantly in the HV group compared to placebo, but not knee mobility, which the authors were unable to explain. Patients gave a subjective categorical assessment of pain after four months of treatment, and it decreased significantly in the HV group compared to placebo, with 64% of patients in the HV group reporting some reduction in pain. Additionally, the HV treatment group showed significant improvement in ADL after one, two, and four months, compared with baseline.
In a small pilot study published in 1999, eight volunteers (four with clinically diagnosed OA, and four without) were treated with a high dose (45 g) of RHP daily for four weeks.65 Treatment was withdrawn for one month and restarted at a lower dose (10 g per day) for four more weeks. Chemotaxis (the movement of an organism in response to a substance; in this case, chemotaxis refers to a component of the inflammatory pathway) and CRP levels declined significantly during both the high-dose and the low-dose periods. A study published in 2011 was unable to reproduce the reduction in CRP with a 10.5-g dose of RHP over 28 days, leading the authors to opine that the dose was too low to have an anti-inflammatory or antioxidant effect.66
Chrubasik et al. (2008) conducted a one-year survey of patients with acute exacerbations of chronic pain in the back, hips, and knees.67 Based on previous studies, patients were recommended a dose of 5 g of RHP per day (10 capsules of 0.5 g each). Clinical symptoms and well-being were assessed every six weeks, and patients kept a record of their pain and use of rescue medications. The first six-week review revealed that the pain relief provided was not strong enough for some participants, so the starting dose was doubled for the next 75 participants if their symptoms appeared to be unduly severe or prolonged. Additionally, existing participants were encouraged to adjust the dosage up or down according to their symptoms. Multivariate analysis at the end of the surveillance indicated substantial improvement overall with RHP treatment.
In 2014, Chrubasik et al. conducted a pilot study that investigated the effectiveness of a rose hip shell powder (RHSP) in treating chronic musculoskeletal pain.68 Patients (N = 52, of whom 29 had participated in the 2008 survey) were provided up to 20 g RHSP without seed (“sine fructibus”; batch 119372 produced by Martin Bauer GmbH & Co. KG; Vestenbergsgreuth, Germany; no further information provided) per day for a period of three months. Patients were encouraged to adjust the dosage up or down according to their pain. At the beginning of the study and after six and 12 weeks, outcome variables (current pain, worst pain, and average pain over the preceding two weeks, disability component, aids/devices required to maintain quality of life, and patient assessment of treatment and tolerability) were assessed. During the three months of treatment, there were no differences in outcome measures between the RHSP study and the 2008 RHP survey. Participants in the 2014 study consumed significantly more RHSP than the 2008 participants consumed RHP, but the 2014 participants did not take any additional pain relievers. After three months of treatment, 12 of the 52 patients rated the effectiveness of RHSP as “very good,” 22 said it was “good,” and 14 thought it was “moderate.” Patients who participated in both studies did not express a preference for RHSP or RHP.
Presentations at two conferences addressed the effects of RHP on cholesterol. In the first, unpublished results of a RDBPC crossover trial involving patients with OA63 showed that three months of treatment with RHP resulted in a significant decline in LDL and total cholesterol, while no change was observed in HDL cholesterol levels.69 It was unclear if the cholesterol reduction was related to the treatment, or if it was a result of enhanced physical activity caused by a reduction of symptoms. The second conference presentation70 addressed the same cholesterol-lowering effects observed in patients with OA in another study62 in which a significant decline in total and LDL cholesterol levels were observed after three months of RHP treatment.
A RDBPC crossover study published in 2012 showed that daily consumption of rose hip powder drink over six weeks lowered systolic blood pressure (BP) and plasma cholesterol levels in 31 obese individuals with normal or impaired glucose tolerance.71 Subjects were randomly assigned to take either 5 dL (approximately 2 cups) per day of the control drink or the rose hip powder drink (equal to 40 g of Chilean R. canina rose hips with seeds removed, ground and mixed with apple [Malus spp., Rosaceae] juice, citric acid solution, and sugar, then heated, cooled, and aseptically packaged; no further information provided). Subjects were instructed to restrict their caloric intake to 75% of their resting metabolic rate × 1.3. Every two weeks, subjects visited the clinic to have body weight measured and blood drawn, to give adverse effect reports, and to receive test drinks for the next two weeks. In addition, a meal-based glucose tolerance test was performed at the beginning and end of each period. Consumption of the rose hip powder drink for six weeks resulted in a small but significant reduction in total plasma cholesterol (by 4.9%), LDL cholesterol (by 6%), and LDL/HDL ratio (by 6.5%) compared to placebo, while HDL cholesterol was unchanged. No changes were observed in plasma triglycerides. The intake of rose hip powder significantly lowered systolic BP by 3.4%. These findings suggest that rose hip powder consumption can significantly reduce cardiovascular risk by an estimated 17% in obese, non-diabetic people, according to the algorithm for Reynold’s risk assessment score.
A RDBPC study published in 2015 investigated the effects of daily intake of rose hip extract on abdominal visceral fat in pre-obese subjects.72 Volunteers (N = 32) who had a body mass index (BMI) of 25-29 were assigned to take rose hip extract (Rosehip Polyphenol EX; 100 mg rose hip with seed aqueous ethanol extract and no less than 0.1% tiliroside [a glycosidic flavonoid]; Morishita Jintan Co. Ltd.; Osaka, Japan) or placebo, once daily for 12 weeks with no dietary intervention. Men and women (n = 16 each) were divided equally between groups to avoid bias related to sex, body fat percentage, and BMI; there were no significant differences between groups in any of these parameters. Assessments and measurements were done at baseline, and on weeks four, eight, and 12, with measurements of abdominal fat and body fat percentage being the primary outcomes and body weight and BMI being secondary outcomes. The rose hip group experienced significant decreases in body weight and BMI by week 12, and the decreases were significantly higher than in the placebo group. Further, at weeks eight and 12, abdominal visceral fat area in the rose hip group had decreased significantly compared with baseline measurements, and this decrease was significantly greater than in the placebo group. These results, the authors note, show that rose hip extract may be useful as a supplement to reduce abdominal visceral fat in pre-obese persons, thus reducing risk of cardiovascular disease.
Published in 2015, a randomized, double-blind study assessed the effectiveness of HV on skin cell longevity, wrinkling, moisture, and elasticity.73 Thirty-four healthy subjects (35-65 years old) with well-defined crow’s feet or other well-defined wrinkles on the face were randomized to take 3 g of HV or 4 g of astaxanthin (Astawell; Nutramedica; Bangkok, Thailand) added to yogurt daily for eight weeks. In comparing the two groups at the beginning of the study, there were no statistical differences in the mean depth of crow’s feet, moisture content, or skin elasticity. After eight weeks of treatment, the HV group experienced a statistically significant reduction in the depth of crow’s feet and an increase in skin elasticity and the moisture content of the forehead. Similar improvement was seen in the astaxanthin group, and no significant difference was found between the two groups. In vitro assessment showed that HV reduced the flux of hemoglobin through cell membranes, reducing the disintegration of cells, suggesting that antioxidants such as RHP can contribute to keeping cell membranes intact and extending their life. The authors concluded that HV may support the skin and cell longevity, but they recommended that large-scale, placebo-controlled studies be conducted to confirm their findings, and that these studies should focus on the active components of HV.
FUTURE
The International Union for Conservation of Nature (IUCN) European Red List of Medicinal Plants assigns R. canina, R. pendulina, and R. rubiginosa to the conservation category of Least Concern (LC), meaning that these species are not threatened.74 While tens of millions of kilograms of rose hips are harvested annually, wild populations appear to be abundant and continue to serve as an important source of household income in rural areas throughout Eastern Europe, southern Europe, and western Asia. Sustainable wild-collection of dog rose fruit requires harvesting in such a way that does not destroy twigs and branches on which new flowers and fruits will be produced. For example, it is recommended to use scissors or clippers to collect mature red fruits without the stem. Because dog rose reproduces by seed, it is suggested that about 20% of the fruits should be left on each bush to facilitate regeneration, and that about 20% of all dog rose bushes in the controlled collection area should be left entirely unharvested.11,15
With the available data, it is not possible to separately quantify the total global export trade of R. canina hips, because only some countries report quantities, and the harmonized system (HS) tariff codes used for rose hips include fruits of all Rosa species and sometimes even include certain other unrelated fruits. For example, Switzerland’s tariff schedule lumps rose hips (of all species) together with European elderberries.75 Chile, possibly the world’s largest exporter of rose hip ingredients, uses codes for tracking exports of Rosa mosqueta (the hips of R. moschata, R. rubiginosa, and/or R. canina). Chile reportedly exports on average 6.8 million kg of rose hips annually, mainly to Germany,76 as well as substantial quantities of value-added forms, such as the fatty oil of rose hip seeds. In 2013, the reported customs value of Chile’s exports of various rose hip ingredients (classified under nine different HS codes) amounted to approximately $25.5 million.77*
In its native habitat, dog rose is one of the most important commercially-traded medicinal plants of Serbia,78 where, in 2007, an estimated 5 million kg were wild-collected.12 In 2005, Romania’s annual average harvest of wild R. canina fruits was 4.03 million kg.79 In 2003, dog rose hip was Bulgaria’s number-one medicinal plant in terms of volume, with an estimated 1 million kg wild-collected annually, plus another 300,000 kg obtained from cultivation.10 For the five-year period 2001-2005, Bulgaria’s Ministry of Environment and Water reported an average annual export of various dog rose ingredients (both wild-collected and cultivated) of 1,088,795 kg “Fructus Rosae cum semini” (dried ripe fruit with seed), 676,836 kg “Fructus Rosae semini” (seeds), 268,688 kg “Fructus Rosae (frozen),” and 25,231 kg “Fructus Rosae.”80 Fruits of R. canina are also among the most widely reported wild plants sold at markets on both sides of the Bulgarian-Turkish border.16
The annual quantity of R. canina hips collected in Hungary is estimated to be between 200,000 to 250,000 kg.81 Albania reportedly exports about 200,000 kg annually.10 In the Caucasus, four medicinal plants account for more than 80% of total tonnage that is wild-collected in Georgia, including R. canina hips and bilberry (Vaccinium myrtillus, Ericaceae) fruits, most of which is exported to Ukraine.82
There is evidence that dog rose production is occurring increasingly through sustainable wild-collection methods as well as through sustainable agriculture practices. Many wild-collection operations have implemented the “organic wild-crop harvesting practice standard” for certified organic wild-collected R. canina, particularly in Albania, Armenia, Bulgaria, Chile (mainly R. rubiginosa), Macedonia, Hungary, Romania, Serbia, and Turkey (also R. rubiginosa).83 An International Trade Centre (ITC) study estimated that in 2005 about 7.78 million kg of rose hips were wild-collected under organic certification rules, of which 3.51 million kg were wild-collected in Chile, 3.05 million kg in Romania, 1 million kg in Lesotho, 120,000 kg in Bulgaria, 50,000 kg in Albania, 10,000 kg in Macedonia, and 5,000 kg in Serbia and Montenegro.9 Some organic wild dog rose operations, particularly in Armenia, Bulgaria, Hungary, and Macedonia, have also implemented the FairWild Standard, which encompasses not only criteria for ecological sustainability but also economic and social sustainability for the harvesters and their communities.84 Wild R. canina hip with Fairtrade certification also comes from three operations in Uzbekistan.17 Given that the main Rosa species harvested and traded as “dog rose” are not endangered or threatened species, and that controlled cultivation is also increasing, ever more under organic agriculture rules, it appears that the huge global demand can still be met through sustainable production methods.
—Gayle Engels and Josef Brinckmann
REFERENCES
1. McGuffin M, Kartesz JT, Leung AY, Tucker AO. American Herbal Products Association’s Herbs of Commerce. 2nd ed. Silver Springs, MD: American Herbal Products Association; 2000.
2. Jürgens AH, Seitz B, Kowarik I. Genetic differentiation of Rosa canina (L.) at regional and continental scales. Plant Systematics and Evolution. 2007;269(1-2):39-53.
3. Cheikh-Affene ZB, Haouala F, Trabelsi N, Boulaaba M, Ksouri R, Harzallah-Skhiri F. Pomological description and chemical composition of rose hips gathered on four Rosa species section Caninae growing
wild in Tunisia. International Journal of Agricultural Science and Technology. 2013;1(3):43-50.
4. Grieve M. A Modern Herbal. Vol. 2. New York: Dover Books; 1971. Available at: www.botanical.com/botanical/mgmh/r/roses-18.html. Accessed May 24, 2016.
5. United States Department of Agriculture Natural Resources Conservation Service. Dog Rose Plant Guide. USDA NRCS website. Available at: http://plants.usda.gov/plantguide/pdf/pg_roca3.pdf. Accessed May
25, 2016.
6. Hunter I. Declared Plant Policy under the Natural Resources Management Act 2004: dog rose (Rosa canina). The Government of South Australia; 2014:4.
7. FairWild Foundation. FairWild-certified ingredients under production. FairWild Foundation website. Cambridge, UK: FairWild Foundation. Available at: www.fairwild.org/certification-overview. Accessed May 25,
2016.
8. Neugebauerová J, Vymyslický T, Růžičková G. Resource assessment and management planning: situation analysis of rosehip (Rosa canina agg.) in the Czech Republic. Brno, Czech Republic: Central Europe
Programme; October 2012. Available at: www.traditionalandwild.eu/en/images/Studies/RA/Act.4.4.7_Situation%20analysis%20of%20Rosehip_Mendel%20University.pdf. Accessed May 25, 2016.
9. Censkowsky U, Helberg U, Nowack A, Steidle M. Overview of world production and marketing of organic wild collected products. Geneva, Switzerland: International Trade Centre UNCTAD/WTO; 2007. MDS-
0139.E. Available at: www.intracen.org/uploadedFiles/intracenorg/Content/Exporters/Sectors/Fair_trade_and_environmental_exports/Biodiversity/Overview_World_Production_Marketing_Organic_Wild_Collected_Products.pdf.
Accessed May 25, 2016.
10. Kathe W, Honnef S, Heym A. Medicinal and Aromatic Plants in Albania, Bosnia-Herzegovina, Bulgaria, Croatia and Romania. Bonn, Germany: Bundesamt für Naturschutz (BfN); 2003.
11. Lonner J, Thomas M. A Harvester’s Handbook to Wild Medicinal Plant Collection in Kosovo. Pristina, Kosovo: Kosovo Business Support; August 2003. Available at: www.gowildconsulting.com/wp-content/uploads/2011/02/harvesters_handbook.pdf. Accessed May 25, 2016.
12. USAID Serbia. Herbs, Mushrooms, and Forest Fruit (Medicinal and Aromatic Plants): Value Chain Assessment. Belgrade, Serbia: USAID Agribusiness Project; June 2008.
13. Pogačnik L, Poklar Ulrih N. Influence of environmental factors on antioxidants content in rose hips. Bulletin of the Transilvania University of Brasov, Series VI: Medical Sciences. 2011;4(2):103-111.
14. USAID Macedonia. Macedonia’s Recent Trade Agreements: Opportunities and Threats for Bottled Wine, Table Grapes, Fresh Vegetables, Processed Vegetables and Wild Harvested Products. Washington DC: USAID AgBiz Program; April 2008.
15. Schindler H. Monographs for Selected Wild Collected Plants of Commercial Interest from the Caucasus Region. Eschborn, Germany: Deutsche Gesellschaft für Technische Zusammenarbeit (GTZ) GmbH; November 2010.
16. Dogan Y, Nedelcheva A. Wild plants from open markets on both sides of the Bulgarian-Turkish border. Indian Journal of Traditional Knowledge. 2015;14(3):351-358.
17. Brinckmann JA. Sustainable Sourcing: Markets for Certified Chinese Medicinal and Aromatic Plants. Geneva, Switzerland: International Trade Centre; 2016. SC-2016-5.E.
18. Porpáczy A, Kollányi G. Cultivation of Temperate Fruits of Peculiar Kind. Hungarian Agricultural Research. 2009;18(2):4-9.
19. Hyben Vital Int. ApS. Cultivation. 2016. Available at: www.hyben-vital.com/cultivation/. Accessed May 13, 2016.
20. Joublan JP, Berti M, Serri H, Wilckens R, Hevia F, Figueroa I. Wild rose germplasm evaluation in Chile. In: Janick J, ed. Progress in New Crops. Arlington, VA: ASHS Press; 1996.
21. European Pharmacopoeia Commission. European Pharmacopoeia (PhEur 8.0). Strasbourg, France: European Directorate for the Quality of Medicines; 2015:1228-1229.
22. International Organization for Standardization. ISO 23391: Rose hips – Specification and test methods. Geneva, Switzerland: International Organization for Standardization; 2006.
23. Roman I, Stănilă A, Stănilă S. Bioactive compounds and antioxidant activity of Rosa canina L. biotypes from spontaneous flora of Transylvania. Chemistry Central Journal. 2013;7(1):73.
24. Oprica L, Bucsa C, Zamfirache MM. Ascorbic acid content of rose hip fruit depending on altitude. Iranian Journal of Public Health. 2015;44(1):138-139.
25. Pyke M, Melville R. Vitamin C in rose hips. Biochemical Journal. 1942;36(3-4):336–339.
26. Ropciuc S, Cenuşă R, Caprita R, Creţescu I, Ion T. Influence of climatic factors on the nutritional value in Cynosbati Fructus. Scientific Papers: Animal Science and Biotechnologies. 2011;44(2):133-136.
27. US Department of Agriculture. Fresh Fruit and Vegetables Manual. 8th ed. Washington, DC: USDA; 2012.
28. US Food and Drug Administration. § 182.20 Essential oils, oleoresins (solvent-free), and natural extractives (including distillates). In: Code of Federal Regulations (21 CFR). Washington, DC: US FDA; 2015:477.
29. US Environmental Protection Agency. Part 180-Tolerances and Exemptions for Pesticide Chemicals in Food. In: Code of Federal Regulations (40 CFR). Washington, DC: US Government Printing Office; 2015:386-738.
30. Russian Pharmacopoeia Committee. State Pharmacopoeia of the Union of Soviet Socialist Republics. [in Russian] Vol. 2. 11th ed. Moscow: Medizina; 1990:294-7.
31. West EW, ed. Pahlavi Texts, vol. 5. Marvels of Zoroastrianism. In: Müller M, ed. Sacred Books of the East: Oxford University Press; 1897.
32. Touw M. Roses in the Middle Ages. Economic Botany. 1982;36(1):71-83.
33. Nedelcheva AM. Plants related to the life and medicinal practice of St. Ivan Rilski. In: Morel JP, Mercuri AM, eds. Plants and Culture: Seeds of the Cultural Heritage of Europe. Bari, Itlay: Centro Europeo per i Beni Culturali Ravello, Edipuglia; 2009:175-8.
34. Jarić S, Mitrović M, Djurdjević L, et al. Phytotherapy in medieval Serbian medicine according to the pharmacological manuscripts of the Chilandar Medical Codex (15-16th centuries). Journal of Ethnopharmacology. 2011;137(1):601-19.
35. Leidig D. Frauenheilkunde in volkssprachigen Arznei- und Kräuterbüchern des 12. bis 15. Jahrhunderts. Eine empirische Untersuchung. Würzburg, Germany: Julius-Maximilians-Universität Würzburg; 2004.
36. Culpeper N. Culpeper’s Complete Herbal. London, UK: Bloomsbury Books; 1992.
37. Cohen M. Rosehip: an evidence based herbal medicine for inflammation and arthritis. Australian Family Physician. July 2012;41(7):495-498.
38. Wichtl M, ed. Brinckmann JA, Lindenmaier MP, trans. Herbal Drugs and Phytopharmaceuticals. 3rd ed. Stuttgart, Germany: Medpharm GmbH Scientific Publishers; 2004.
39. British Herbal Medicine Association. British Herbal Pharmacopoeia. Dorset, UK: British Herbal Medicine Association; 1996.
40. Rodina K, ed. Common Useful Wild Plants in Central Europe: Promoting Traditional Collection and Use of Wild Plants to Reduce Social and Economic Disparities in Central Europe. Budapest, Hungary: TRAFFIC and WWF; 2013.
41. Carvalho AM, Barros L, Ferreira ICFR, Frazão-Moreira A. Folk Medicine of Trás-os-Montes (Portugal): Traditional Uses and Bioactive Compounds of Six Common Medicinal Species. Sesión 4 – Fitoterapia y Plantas Medicinales. 5th International Congress of Ethnobotany, San Carlos de Bariloche, Argentina. 2009.
42. Pardo-de-Santayana M, Tardío J, Morales R. The gathering and consumption of wild edible plants in the Campoo (Cantabria, Spain). International Journal of Food Science Nutrition. 2005;56(7):529-542.
43. Blumenthal M, Busse WR, Goldberg A, et al., eds. The Complete German Commission E Monographs — Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; Boston, MA: Integrative Medicine Communication; 1998.
44. Bundesamt für Verbraucherschutz und Lebensmittelsicherheit (BVL). List of Substances of the Competent Federal Government and Federal State Authorities: Category “Plants and plant parts”. Heidelberg, Germany: Bundesamt für Verbraucherschutz und Lebensmittelsicherheit (BVL); 2014:112.
45. Wirtschaftsvereinigung Kräuter – und Früchtetee e.V. 2015: Kräuter – und Früchtetees beliebter denn je / Trend zur Natur gibt neue Impulse. Hamburg, Germany: WKF; 2016.
46. US Food and Drug Administration. 21 CFR Part 111 Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements; Final Rule. Federal Register. 2007;72(121):34752-34958.
47. Natural and Non-prescription Health Products Directorate. Antioxidants. Ottowa, ON: Health Canada; 2015.
48. Natural and Non-prescription Health Products Directorate. Natural Health Products Ingredients Database. Ottowa, ON: Health Canada; 2016.
49. Natural and Non-prescription Health Products Directorate. Licensed Natural Health Products Databases. Ottawa, ON: Health Canada; 2016.
50. Kommission Deutscher Arzneimittel-Codex. Deutscher Arzneimittel-Codex (DAC) inkl. Neues Rezeptur-Formularium (NRF) Ergänzungsbuch zum Arzneibuch. Stuttgart, Germany: Deutscher Apotheker Verlag; 2015.
51. Hyben Vital Int. ApS. LitoFlex® brochure. Tranekär, Denmark; 2015.
52. Sidroga AG. Sidroga Erkältungstee. In: Patienteninformation des Arzneimittel-Kompendium der Schweiz®. Bern, Switzerland: HCI Solutions AG; 2015.
53. European Commission Health & Consumers Directorate. Cosmetic Ingredients and Substances (CosIng®) Database. Brussels, Belgium: European Commission; 2016.
54. Fan C, Pacier C, Martirosyan DM. Rose hip (Rosa canina L): a functional food perspective. Functional Foods in Health and Disease. 2014;4(11):493-509.
55. Adamczak A, Buchwald W, Zieliński J, Mielcarek S. Flavonoid and organic acid content in rose hips (Rosa L., sect. Caninae DC.EM. Christ.). Acta Biologica Cracoviensia Series Botanica. 2012;54(1):105-112.
56. Natural food – Fruit Viatmin C Content. The Natural Food Hub website. Available at: www.naturalhub.com/natural_food_guide_fruit_vitamin_c.htm. Accessed June 6, 2016.
57. Anon. Litozin® [product dossier]. Green Bay, WI: EuroPharma. (n.d.)
58. Winther K, Campbell-Tofte J, Hansen P. Rose hip powder that contains the natural amount of shells and seeds alleviated pain in osteoarthritis of the dominant hand — a randomized, double-blind, placebo-controlled, cross-over trial. Open Journal of Rheumatology and Autoimmune Diseases. 2013;3:172-180.
59. Willich SN, Rossnagel K, Roll S, et al. Rose hip herbal remedy in patients with rheumatoid arthritis — a randomised controlled trial. Phytomedicine. February 2010;17(2):87-93.
60. Christensen R, Bartels EM, Altman RD, Astrup A, Bliddal H. Does the hip powder of Rosa canina (rosehip) reduce pain in osteoarthritis patients? — a meta-analysis of randomized controlled trials. Osteoarthritis and Cartilage. 2008;16:965-972.
61. Marstrand K, Campbell-Tofte J. The role of rose hip (Rosa canina L) powder in alleviating arthritis pain and inflammation — part II animal and human studies. Botanics: Targets and Therapy. 2016;6:59-73.
62. Winther K, Apel K, Thamsborg G. A powder made from seeds and shells of a rose-hip subspecies (Rosa canina) reduces symptoms of knee and hip osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial. Scandanvaian Journal of Rheumatology. 2005;34:302-308.
63. Rein E, Kharazmi A, Winther K. A herbal remedy, Hyben Vital (stand. powder of a subspecies of Rosa canina fruits), reduces pain and improves general wellbeing in patients with osteoarthritis — a double-blind, placebo-controlled, randomised trial. Phytomedicine. 2004;11:383-391.
64. Warholm O, Skaar S, Hedman E, Mølmen HM. The effects of a standardized herbal remedy made from a subtype of Rosa canina in patients with osteoarthritis: a double-blind, randomized, placebo-controlled clinical trial. Current Therapeutic Research. January 2003;64(1):21-31.
65. Winther K, Rein E, Kharazmi A. The anti-inflammatory properties of rose-hip. Inflammopharmacology. 1999;7(1):63-68.
66. Kirkeskov B, Christensen R, Bügel S, et al. The effects of rose hip (Rosa canina) on plasma antioxidative activity and C-reactive protein in patients with rheumatoid arthritis and normal controls: a prospective cohort study. Phytomedicine. August 2011;18(11):953-958.
67. Chrubasik C, Wiesner L, Black A, Müller-Ladner U, Chrubasik S. A one-year survey on the use of a powder from Rosa canina lito in acute exacerbations of chronic pain. Phytotherapy Research. September 2008;22(9):1141-1148.
68. Chrubasik S, Chrubasik C, Neumann E, Müller-Ladner U. A pilot study on the effectiveness of a rose hip shell powder in patients suffering from chronic musculoskeletal pain. Phytotherapy Research. November 2014;28(11):1720-1726.
69. Rein E. Winther K. LDL-Cholesterol and C-reactive protein is influenced by rose-hip, a randomized, double-blind, placebo-controlled trial. Proceedings from XIV International Symposium on Drugs Affecting Lipid Metabolism; New York, NY: September 9-12, 2001.
70. Winther K, Kharazmi A, Rein E. A powder made from a subspecies of rose hip (Rosa canina) reduces WOMAC symptoms score as well as cholesterol level in patients suffering from osteoarthritis. [Conference abstract]. Presented at the OsteoArthritis Research Society International World Congress; Boston, MA: December 8-11, 2005.
71. Andersson U, Berger K, Högberg, Landin-Olsson M, Holm C. Effects of rose hip intake on risk markers of type 2 diabetes and cardiovascular disease: a randomized, double-blind, cross-over investigation in obese persons. European Journal of Clinical Nutrition. 2012;66:585-590.
72. Nagatomo A, Nishida N, Fukuhara I, et al. Daily intake of rosehip extract decreases abdominal visceral fat in preobese subjects: a randomized, double-blind, placebo-controlled clinical trial. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2015;8:147-156.
73. Phetcharat L, Wongsuphasawat K, Winther K. The effectiveness of a standardized rose hip posder, containing seeds and shells of Rosa canina, on cell longevity, skin wrinkles, moisture, and elasticity. Clinical Interventions in Aging. 2015;10:1849-1856.
74. Allen D, Bilz M, Leaman DJ, Miller RM, Timoshyna A, Window J. European Red List of Medicinal Plants. Luxembourg: Publications Office of the European Union; 2014:51.
75. Eidgenössische Zollverwaltung (EZV). List of Tariff Headings to the Electronic Customs Tariff Tares. Bern, Switzerland: Directorate General of Customs; Reprint, as of January 1, 2012.
76. Joublan JP, Rios D. Rose culture and industry in Chile. In: Nybom H, Rumpunen K, eds. I International Rose Hip Conference. Leuven, Belgium: International Society for Horticultural Science (ISHS); 2005:65-70.
77. Dirección Nacional de Aduanas. Estadísticos: Cuadros de Exportaciones por Productos (Monto FOB en dólares) — Ene-Dic 2013. Valparaíso, Chile: Gobierno de Chile; 2014.
78. Donnelly R, Helberg U. Balkans Herbal Development Initiative — Phase 1 Final Summary Report — Serbia and Montenegro. Southeast Europe Enterprise Development (SEED) and The Corporate Citizenship Facility (CCF); 2003.
79. Bouriaud L, Nichiforel L, Nastase C, Dragoi S, Padureanu L, Borlea GF. Romania. Acta Silv. Lign. Hung. Special Edition. 2005:643-694.
80. Evstatieva L, Hardalova R, Stoyanova R. Medicinal plants in Bulgaria: diversity, legislation, conservation and trade. Phytologia Balcanica. 2007;13(3):415-427.
81. Non-food Group Department of Agricultural Chemical Technology Budapest University of Technology and Economics. Report from the Republic of Hungary. Budapest, Hungary: Interactive European Network for Industrial Crops and their Applications; 2002 (with updates in January 2004):28.
82. Georgian National Investment Agency. Herbs and Medical Plants Sub-sector Overview 2011. Tblisi, Georgia: Georgian National Investment Agency; 2011.
83. United States Department of Agriculture. Organic INTEGRITY Database. USDA, Agricultural Marketing Service; 2016.
84. Brinckmann JA, Huggins K, Gardner ZE. Managing Natural Resources for Sustainable Livelihoods: Threats to the Future of Sustainable Wild Collection and Field Experience with Implementation of the Fair Wild Standard for Medicinal Plants. International Journal on Biodiversity Watch. January-March 2014;3:13-29.