Raspberry leaf tea

Raspberry, an edible fruit from the Rubus genus, is known to posses many health benefits, it is a powerful antioxidant properties, has anti-proliferative activity against cancer in vitro [1], increases fertility, suppress induced hepatic lesions (in rats), reduces weight via raspberry leaf ketones, helps pregnant women during labor, this last due to certain uterine relaxant effects [5,38,39], and some of its phytochemicals are even used as the source of aromatic compounds used by the industry in many commercial products...etc., but what scientific and medical evidence is behind all these claimed benefits?

In this article we try to document the evidence behind the claimed properties of raspberry tea and raspberry leaf.

RUBUS IDAEUS

Family: Rosaceae
Genus: Rubus
Common name: Red raspberry

RASPBERRY LEAF TEA ANTIOXIDANT PROPERTIES

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In spite many fruits and vegetables are known to also exert powerful antioxidant properties, recent studies done on berries such as blackberries, raspberries, strawberries and blueberries [17] showed that these ones are specially rich in polyphenols, very powerful and naturally occurring antioxidants able to combat free radicals and prevent, up to a certain level, the occurrence of some types of cancer.

A recent study by Halvorsen et al confirmed also that fruits from the Rosaceae family, as raspberries, were particularly rich in antioxidants [17], raspberry leaf tea may have inherited those properties too.

As we mentioned, raspberries and raspberry leaf tea are a rich source of antioxidant compounds, and not only polyphenols, raspberries are also rich in anthocyanins and ellagitannins. The anthocyanins found in raspberry leaf tea are the most abundant type of flavonoid [6] and they are also responsible for the blue or purple color present in blueberries, cherries, grapes, blackberries and other fruits [7]. Actually a little bit more than 500 anthocyanins have been found [8] in different herbs, plants and natural sources, including raspberry leaf.

In pomegranate anthocyanins are the only fatty acid that is believed to play an important role in the health benefits exerted by this fruit (apart from the  polyphenolic content found on it and more specifically punicalagins, punicalins, gallagic acid, and ellagic acid that act as powerful antioxidants).

THE MOST ABUNDANT TYPE OF ANTHOCYANIN IN RASPBERRY

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The most abundant anthocyanin found in raspberry leaf tea was cyanidin-3-O-sophoroside, followed by cyanidin-3-O-(2G)-glucosylrutinoside and cyanidin-3-O-glucoside, pelargonidin-3-O-sophoroside, cyanidin-3-O-rutinoside, pelargonidin-3-O-(2G)-glucosylrutinoside. Smaller amounts of pelargonidin-3-O-glucoside and pelargonidin-3-O-rutinoside eluted later and could be confirmed by searching the MS data at their relevant masses [2].

RED RASPBERRY LEAF TEA AND CANCER

• RASPBERRY LEAF FOR DIGESTIVE TRACT CANCERS

It is widely known that diets rich in fruits and vegetables are associated with a lower incidence of cancer and a lower cancer risk, more particularly the digestive tract cancer [2].  This anti-cancer activity has been attributed in part to antioxidants present in these foods. Raspberries and raspberry leaf in particular are a rich source of the antioxidant compounds, such as polyphenols, anthocyanins and ellagitannins [2].

But in order to be able to fight cancer and in particular certain cancer cell lines, Raspberry Leaf Extracts and their phytochemicals need to reach the areas where cancer cells are. In the case of colon cancer, raspberry leaf active constituents need to reach colon. In a study done on Colon Available Raspberry Extracts (CARE) [2], it was discovered that raspberry phytochemicals likely to reach the colon are capable of inhibiting several important stages in colon carcinogenesis in vitro [2], another further evidence on how raspberry leaf extracts can help to prevent and fight certain types of cancer in future.

Raspberry leaf tea is also said to be useful against minor digestive tract inflammation problems and diarrhea [39].

• RASPBERRY FOR LIVER CANCER

Four varieties of raspberry significantly inhibited the proliferation of HepG2 human liver cancer cells. Red raspberry extract significantly inhibited the proliferation of human hepatic cancer HepG2 and human colon cancer CaCo-2 cells in a dose-dependent manner [32,33].

Raspberry compounds from raspberry leaf are metabolized by the liver, implying the liver is directly exposed to these compounds by compounds themselves or metabolites, which may explain why the raspberry diet so effectively protected the liver lesions against a DEN (diethylnitrosamine) insult [1].

• RASPBERRY LEAF FOR COLON CANCER

The red raspberry extract was also able to inhibit cell proliferation of HT-29 colon cancer mainly via the p21WAF1 pathway [34]. The red raspberry extract and its components reduced endogenous oxidative DNA damage in vitro and in vivo [35]. Another study showed how raspberry leaf extracts exerted cytotoxic activity against human colon adenocarcinoma cell line SW 480 [41].

• RASPBERRY LEAF IN ORAL, BREAST, COLON AND PROSTATE CANCERS

The potent capacity of red raspberry diet could not only suppress DEN-induced hepatic lesions in rats, but also reduce the definite diagnostic features of neoplasm the red raspberry extract showed a significant inhibition of growth of human oral (KB, CAL-27), breast (MCF-7), colon (HT-29, HCT116), and prostate (LNCaP) tumor cell lines.

In one of the studies done on raspberry extracts, a mixture of 15 anthocyanidin 3-O-glycosides, cyaniding 3-glucoside, ellagic acid, and gallic acid decreased the proliferation of HT-29 cells in a dose - dependent manner [26].

Polyphenolic profile and antioxidative properties of red raspberry leaf extract, cytotoxic effect, antioxidative/prooxidative effect, and effect on total glutathione concentration were determined in human laryngeal carcinoma (HEp2) and colon adenocarcinoma (SW 480) cell lines [41].

The results obtained confirmed the biological activity of red raspberry leaf polyphenols and showed that this traditional plant can supplement the daily intake of valuable natural antioxidants, which exhibit beneficial health effects [45].

In May 2012, researchers at the James Graham Brown Cancer Center, at the University of Louisville, Kentucky, discovered in a study performed in rats that a blueberry diet showed efficacy in reducing mammary tissue proliferation in estrogen-mediated mammary tumorigenesis, with tumor latency delayed efficently by black raspberry powder [42].

RASPBERRY LEAF ACTIVE CONSTITUENTS

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The major groups of phenolic compounds present in red raspberries are reported to be anthocyanins, flavonols, flavanols, ellagitannins, gallotannins, proanthocyanidins, and phenolic acids [35].

The major anthocyanins [8] and tannins [8, identified in raspberry leaf are as follows: cyanidin-3-sophoroside, cyanidin-3-glucoside, pelargonidin-3-glucoside and predominantly hydrolyzable tannins (ellagitannins and gallotannins) as well as ellagic and gallic acid. Other specific flavonoids found in raspberry leaf tea include kaempferol and quercetin [8]. Quercetin glucuronide, quercetin-3-O-glucoside and rutin were identified also in raspberry extracts.

Raspberry leaf contains also Vitamins A, B, C, D and F, as well as phosphorus, calcium and magnesium [40].

DOES RASPBERRY LEAF TEA CONTAINS CATECHINS?

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As you may already know, catechins are another type of flavonoids that can be found in apples, cherries, pears, tea and even in wine [10]. Their properties are well known and are certainly one of the reasons tea is believed to exert most of its health benefits, however the amount of catechins present in raspberry leaf tea are not as much as those found in tea (Camelia sinensis) as raspberry leaf tea doesn't belong to the Camelia sinensis family.

RASPBERRY TEA FOR DELIVERY

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Raspberry leaf tea is found in many herbal remedies formulations, some of them suggesting its use as a uterine tonic that may help pregnant women to deliver, but was that property documented in scientific studies or clinical trails?

• RASPBERRY LEAF EXTRACTS - THE AUSTRALIAN CASE -
  

In the search for biologically active compounds, one of the most frequently documented species of the genus is the raspberry plant, raspberry leaf and the red raspberries (Rubus idaeus) [1], the leaves of which have been used traditionally as a uterine relaxant and stimulant during confinement, for the treatment of diarrhea and similar enteric disorders and as an astringent [47].

One of the best documented studies on the effect of raspberry leaf in facilitating labor was carried out by Simpson et al. [36,37] in Australia. The study involved the observation of the effects of raspberry leaf in 192 multiparous women in a double-blind, randomized, placebo-controlled trial.

In the study raspberry leaf was consumed in tablet form from 32 weeks of gestation until labor. Contrary to popular belief, raspberry leaf did not shorten the first stage of labor but rather the second, and also lowered the rate of forceps deliveries (19.3% vs. 30.4%) [36,37].

The study showed that the most common herbal supplements taken by pregnant women were raspberry leaf (14%), followed by ginger (12%) and chamomile (11%) [9].

Raspberry leaf tea contains uterine muscle relaxants that are used in pregnancy teas, said to ease delivery [5], however the difficulty with herbal remedies is that there is very little information and documentation on clinical trials and scientific studies on the subject, and even fewer on the active constituents or phytochemicals involved in those effects, letting scientists investigate on an easier way the toxicity of those compounds and potential side effects.

Raspberry leaves are reported to have a double effect, from one side raspberry leaf seems to exert a stimulant effect on the uterus and from the other they seem to act as a uterus musculature relaxant (Bamforf et al 1970) [38].

Other clinical studies performed in rat models using raspberry leaf tea and capsules caused weak contractions, pretreatment with tea did not alter the ability of oxytocin to initiate contractions [11], however further searches done on medical libraries and databases suggest a lack of evidence for safety and efficacy such recommendations are questionable [12].

RASPBERRY LEAF TEA CONSUMPTION DURING PREGNANCY, A NOT SO SAFE PRACTICE?

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The use of herbal medicines, such as raspberry leaf extracts, by pregnant women reported a considerable increase over the last years. Many women consume raspberry leaf teas during their pregnancies in the belief that it may help to shorten labor and make labor "easier".

Some studies done on raspberry leaf use during gestation suggest that raspberry leaf extracts use during pregnancy was associated with increased gestation length and accelerated reproductive development in a study.

In another study done on 192 low-risk, nulliparous women who birthed their babies between May 1999 and February 2000, on the effect and safety of raspberry leaf tablets (2 x 1.2 g per day), consumed from 32 weeks' gestation until labor, on labor and birth outcomes, raspberry leaf, consumed in tablet form, was found to cause no adverse effects for mother or baby, but contrary to popular belief, did not shorten the first stage of labor either  [37].

The majority of women (62%) used both a vitamin or mineral supplement and a herbal preparation during the course of pregnancy. Folate (70%), iron (38%) and multivitamins (27%) were the vitamin and mineral supplements most frequently taken by pregnant women. Ginger (20%) and raspberry leaf (9%) were the most frequently used herbal preparations. Women relied on advice from friends and relatives in deciding to use herbal preparations. [35].

SAFETY AND EFFICACY OF RASPBERRY LEAF PRODUCTS

A study aimed to evaluate the safety and efficacy of raspberry leaf products consumed by a group of mothers during their pregnancy, by comparison with a group of mothers who did not and consisting of 108 mothers; 57 (52.8%) consumed raspberry leaf products while 51 (47.2%) were in the control group, showed as findings that the ingestion of the drug might decrease the likelihood of pre and post-term gestation.

An unexpected finding in this study seems to indicate that women who ingest raspberry leaf might be less likely to receive an artificial rupture of their membranes, or require a cesarean section, forceps or vacuum birth than the women in the control group [38].

Among the most used herbal preparations to stimulate labor, 64% used blue cohosh, 45% used black cohosh, 63% used red raspberry leaf, 93% used castor oil, and 60% used evening primrose oil [39].

Raspberry leaf tea is one of the most commonly used tonic drinks among pregnant women [48], however its safety and contraindications haven't been yet documented enough. As with many other herbal teas and natural remedies, extreme care should be taken on the administration and usage of herbs and herbal remedies, as some of the active constituents and phytochemicals may have interactions.

Raspberry leaf use during pregnancy can have long-term consequences for the health of the offspring and raise concerns about the safety of this herbal preparation for use during pregnancy [8].

RASPBERRY KETONES

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Raspberry ketone (RK) is a natural phenolic compound of the red raspberry responsible for the raspberry aroma and widely used in industry.

The structure of raspberry ketone is similar to the structures of capsaicin (the active constituent found in hot peppers and responsible for their spicy taste) and synephrine (a drug commonly used to reduce weight), compounds known to exert anti-obese actions and alter the lipid metabolism.

Raspberry ketone prevents and improves obesity and fatty liver. These effects appear to stem from the action of raspberry ketone in altering the lipid metabolism, or more specifically, in increasing norepinephrine-induced lipolysis in white adipocytes [44].

Raspberry ketone is also frequently used in products such as soft drinks, sweets, puddings and ice creams. The compound can be either produced by organic synthesis or extracted naturally from raspberry extracts. Demand for "natural" raspberry ketone is growing considerably, however, this product is extremely expensive [51].

• STRUCTURE OF RASPBERRY KETONE

The structure of raspberry ketone is similar to the structures of capsaicin and synephrine, compounds known to exert anti-obese actions and alter the lipid metabolism.  [52]

Raspberry ketone 4-(4 ´-hydroxyphenyl)-butan-2-one is a major aromatic compound of red raspberry (Rubus idaeus), has a structure similar to that of capsaicin. Thus, it is possible that raspberry ketone activates sensory neurons, thereby increasing skin elasticity and promoting hair growth by increasing dermal IGF-I production. In a study on this subject this possibility in mice and humans.

Raspberry ketones for hair growth and skin

Raspberry ketone at concentrations higher than 1 microM, significantly increased CGRP release from dorsal root ganglion neurons (DRG) isolated from wild-type (WT) mice and this increase was completely reversed by capsazepine, an inhibitor of vanilloid receptor-1 activation. Topical application of 0.01% RK increased dermal IGF-I levels and promoted hair re-growth in WT mice at 4 weeks after the application.

When applied topically to the scalp and facial skin, 0.01% raspberry ketone promoted hair growth in 50.0% of humans with alopecia (n=10) at 5 months after application and increased cheek skin elasticity at 2 weeks after application in 5 females (p<0.04). These observations strongly suggest that raspberry ketone might promote hair growth and increase skin elasticity [41].

Raspberry ketone is an important compound for the flavor industry. It is frequently used in products such as soft drinks, sweets, puddings and ice creams.

The compound can either be produced by organic synthesis or synthesized, however industry prefers the natural raspberry ketone for many different uses [50]. The difference in price is considerably big, being the price of the naturally extracted raspberry ketone a hundred times higher than the artificially synthesised, 100 USD vs 1000 USD per Kilogram.  Demand for "natural" raspberry ketone is growing considerably. However, this product is extremely expensive [42].

As a curiosity we can mention that Bulbophyllum apertum flower (Orchidaceae) releases raspberry ketone (RK) in its fragrance, to attract males of several fruit fly species belonging to the genus Bactrocera [43].

Disclaimer

REFERENCES

[1] Fresh raspberry phytochemical extract inhibits hepatic lesion in a Wistar rat model Yan Liu,#1 Ming Liu,corresponding author#1 Bin Li,#1 Jin-Lu Zhao,1 Chun-Peng Zhang,1 Luo-Qiang Lin,1 Hong-Sheng Chen,1 Shu-Jun Zhang,1 Jun-Chao Jin,1 Lei Wang,1 Le-Jing Li,2 and Jia-Ren Liucorresponding author3,4 1Treatment Center of Oncology, the Fourth Affiliated Hospital of Harbin Medical University, 37 YiYuan Street, NanGang District, Harbin, 150001, The People's Republic of China 2The Affiliated Tumor Hospital of Harbin Medical University, 6 BaoJian Road, NanGang District, Harbin, 150086, The People's Republic of China 3Public Health College, Harbin Medical University, 157 BaoJian Road, NanGang District, Harbin, 150081, The People's Republic of China 4Jia-Ren Liu at Harvard Medical School, 300 Longwood Ave, Boston, MA, USAthe potent capacity of red raspberry diet could not only suppress DEN-induced hepatic lesions in rats, but also reduce the definite diagnostic features of neoplasm

[2] Colon-available raspberry polyphenols exhibit anti-cancer effects on in vitro models of colon cancer Emma M Coates,#1 Gina Popa,#1 Chris IR Gill,corresponding author1 Mark J McCann,1 Gordon J McDougall,2 Derek Stewart,2 and Ian Rowland1 1Northern Ireland Centre for Food and Health (NICHE), University of Ulster (Coleraine), Cromore Road, Coleraine, Co. Londonderry BT52 1SA, Northern Ireland, United Kingdom. 2Scottish Crop Research Institute (SCRI) Quality, Health and Nutrition Programme, Mylnefield, Invergowrie, Dundee DD2 5DA, Scotland, United Kingdom

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