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Raspberry

Scientific Name(s): Rubus Bushii L.H. Bailey, Rubus idaeus L., Rubus occidentalis H. Lev., Rubus strigosus Michx.
Common Name(s): Black raspberry, Bokbunja, Red raspberry

Clinical Overview

Use

Little pharmacologic evidence is available to support the use of raspberry leaf in pregnancy, menstruation, or during childbirth. Evidence suggests dried black raspberries may improve vascular endothelial function, decrease total serum cholesterol level, and decrease inflammatory cytokines in adults with metabolic syndrome. Raspberry fruit and leaf extracts have shown activity on cancer cell lines, possibly due to an antioxidant effect; however, no clinical trials exist.

Dosing

Traditional dosages include 5 to 10 mg (1 to 2 tsp) crushed leaf per 240 mL of water up to 6 times per day, or up to 12 g dry leaf. For improvement of vascular endothelial function and lipid changes in patients with metabolic syndrome, 750 mg of dried black raspberries each day for a period of 12 weeks has shown to be effective. However, substantiated clinical applications for dosage recommendations are lacking.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Avoid use during pregnancy; adverse effects have been documented. Information regarding safety during lactation is lacking.

Use of raspberry leaf preparations has been promoted by nurse-midwives for strengthening the uterus and shortening the duration of labor. However, there are too few studies upon which to substantiate either the efficacy or the safety of this practice.

Interactions

None well documented.

Adverse Reactions

Information regarding adverse reactions with the use of raspberry fruit is limited. No adverse events were reported in a clinical study evaluating the effect of raspberry tea during pregnancy.

Toxicology

Information is generally lacking for raspberry leaf; raspberry fruit is considered nontoxic.

Scientific Family

  • Rosaceae (rose)

Botany

The cultivated red raspberry R. idaeus (Eurasian) or R. strigosus (North American, also known as R. idaeus var. strigosus) are 2 of many Rubus species worldwide. While the berries are cultivated as food items, the leaves have been used medicinally. Raspberries grow as brambles with thorny canes bearing 3-toothed leaflets and stalked white flowers with 5 petals. The red berries detach easily from their cores when ripe. While some species of Rubus primarily reproduce clonally and commercial red raspberries are propagated as clones, DNA fingerprinting has indicated that wild R. idaeus populations exhibit substantial genetic diversity. 1, 2

History

Red raspberry leaves were used for their astringent properties to treat diarrhea in the 19th century. A strong tea of raspberry leaves was used in painful or profuse menstruation and to regulate labor pains in childbirth. A decoction of the leaves to suppress nausea and vomiting was used by the Eclectic medical movement of the late 19th and early 20th centuries. A gargle of raspberry leaf infusion has been used for sore throats and mouths, and to wash wounds and ulcers, while Mongolian herdsmen have used the roots for symptoms of hypertension and hepatitis.3, 4, 5, 6

Chemistry

The fruit of the raspberry plant is a rich source of a diverse range of polyphenols and flavonoids (ie, anthocyanins, ellagitanins), as well as carbohydrates and glycosides. Carotenoid and tocopherol content have also been reported.7, 8, 9, 10

The principal compounds isolated from red raspberry leaves include aliphatic hydrocarbons, fatty acids, ketones, wax esters, and terpenoids, as well as hydrolysable tannins.7, 11

Analytical methods have been described.7 Storage of the fruit and its irradiation to kill pathogens have been shown to affect the total phenolic content and antioxidant capacity to a limited extent.12

Uses and Pharmacology

Anti-inflammatory effect

Animal data

In vitro studies show inhibition of inflammatory mediators.13 In a rat model of antigen-induced arthritis, raspberry extract reduced inflammation and damage to the cartilage at higher dosages.14 Anti-inflammatory effects were demonstrated in a study with mouse models with ulcerative colitis administered black raspberry powder. Reductions in proinflammatory mediators and inflammatory response on histological examination were reported.15

Clinical data

A small open-label, randomized crossover trial conducted in 10 healthy men 55 to 72 years years of age investigated the effect of black raspberry (R. occidentalis) consumption on postprandial inflammation in overweight and obese participants. Diet restrictions during the 14-day study included low-phenolic foods and avoidance of strenuous exercise, alcohol, and excess salt. Participants were randomized into 2 groups that consumed either a high-fat, high-caloric breakfast alone or 15 minutes after consuming lyophilized black raspberries (45 g in approximately 1 cup of water), and then crossed over. Changes in the area under the curve (AUC) were significantly lower for serum IL-6 during the postprandial period with raspberry consumption compared to baseline. No other significant changes were noted in AUCs for tumor necrosis factor-alpha or for C-reactive protein with or without raspberry consumption. Adverse events related to treatment included dark stools (8), mild constipation (1), loose stools (2), and hematoma at injection site (2).50

Cardiovascular

Animal data

Extracts of the fruit and seed oil have been evaluated in mice, hamsters, and rats for their effect on blood pressure and plasma lipid profiles with equivocal results.6, 16, 17, 18, 19 Limited in vitro studies have also been conducted.20

Clinical data

Plant roots of raspberry have been used traditionally by Mongolian herdsmen for symptoms of hypertension.6 A placebo-controlled trial suggests the dried raspberries themselves can cause favorable lipid changes.49

A prospective randomized, double-blind, placebo-controlled trial in adults with metabolic syndrome (N = 77) identified significant improvements from baseline with the use of black raspberry (750 mg/day × 12 weeks) in total cholesterol (−22.8 vs −1.9 mg/dL), total cholesterol/high-density lipoprotein ratio (−0.31 vs 0.07), brachial artery flow-mediated dilatation (0.33 vs 0.1 mm), and cellular inflammatory parameters such as IL-6 (−0.4 vs −0.1 pg/mL) and tumor necrosis factor-alpha (−2.9 vs 0.1 pg/mL) (P < 0.05 for each).49

Cancer

Animal data

In vitro and animal studies investigating the effect of raspberry fruit and leaf extracts on cancer cell lines have shown activity including inhibition of proliferation and antiangiogenesis, regulation or induction of apoptosis, and inhibitory effects on transcription factor. An antioxidant mechanism of action is primarily suggested, as well as anti-inflammatory and synergistic activity. Antiandrogenic activity has also been demonstrated. Stomach, colon, breast, hepatic, and dermal cancer cell lines have been investigated.21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32

Clinical data

There are no clinical data regarding raspberry for use in cancer.

Diabetes

Animal data

Blackberry (R. strigosus) leaves, which have similar chemistry to raspberry leaves, had a slight hypoglycemic activity in rabbit models; however, the chemistry responsible for this effect was not elucidated.33, 34

Clinical data

In a small clinical study (N = 12), the addition of raspberries to the diet had no effect on the glycemic response.35

Pregnancy

Use of raspberry leaf preparations during pregnancy and prior to labor has been promoted by nurse-midwives for strengthening the uterus and shortening the duration of labor.36, 37, 38 However, there are too few studies upon which to substantiate either the efficacy or the safety of this practice.36, 37

Animal data

Studies have shown that commercial red leaf preparations promote contractions in animal and human uterine tissue. However, the concentrations used to achieve these effects are higher than would usually be consumed, and not all in vitro and animal studies found similar results.36, 39 Effects of raspberry leaf consumption during pregnancy have been demonstrated on the offspring of the maternal rats (see Toxicology).

Clinical data

Very limited case reports exist together with the findings from 1 retrospective and 1 prospective study. The data from the retrospective study (N = 57) suggested an association for red leaf tea consumption and shortened labor, as well as a decreased need for intervention. Similarly, the prospective study (N = 96 in both intervention and comparator groups) found a nonsignificant trend toward a shortened second stage of labor and the need for assisted delivery.36, 37, 38

Other uses

A hepatoprotective effect of raspberry ketone in rats with nonalcoholic steatohepatitis suggested mechanisms that include decreased inflammation and improved antioxidant capacity.40

Intravenous extract of R. idaeus roots reduced formation of calcium oxalate nephrolithiasis in mice.41 Hair growth–promoting activity42 and depigmentation43 by raspberry ketone has been described in rodent studies.

Root polyphenols have been shown to exert strong antibacterial activity, including against methicillin-resistant Staphylococcus aureus, in limited in vitro studies.13

Dosing

Traditional dosages include 5 to 10 mg (1 to 2 tsp) crushed leaf per 240 mL of water up to 6 times per day, or up to 12 g dry leaf.5 For improvement of vascular endothelial function and lipid changes in patients with metabolic syndrome, 750 mg of dried black raspberries each day for a period of 12 weeks has been shown to be effective.49 However, substantiated clinical studies for dosage recommendations are lacking.

Commercial raspberry leaf preparations have been studied using 1.5 to 2.4 g/day.36, 44

Pregnancy / Lactation

Information regarding safety during lactation is lacking. Avoid use during pregnancy; documented adverse effects include antigonatographic activity and stimulation of contraction in pregnant human uterine tissue.30, 36, 45

Briggs Book Link

Interactions

None well documented.

Adverse Reactions

Information regarding adverse reactions with the use of raspberry fruit is limited.4 No adverse events were reported in a clinical study evaluating the effect of raspberry tea during pregnancy.44 An outbreak of a strain of norovirus in 2009 was associated with the importation of frozen raspberries in Finland.46

Toxicology

Information is generally lacking for raspberry leaf; raspberry fruit is considered nontoxic.4, 47

Limited studies in rats have demonstrated effects of raspberry leaf consumption during pregnancy in offspring. One study reports early reproductive maturity in the first generation female offspring and decreased body weight in the second generation, while another study reported effects on the cytochrome P450 system in both the male and female offspring of maternal rats.39, 48

Index Terms

  • Rubus idaeus var. strigosus

References

1. Rubus idaeus L. USDA, NRCS. 2013. The PLANTS Database (http://plants.usda.gov, 27 June 2013). National Plant Data Team, Greensboro, NC 27401-4901 USA. Accessed June 27, 2013.
2. Erichsen-Brown C. Medicinal and Other Uses of North American Plants. New York, NY: Dover Publications; 1989:471-473.
3. Grieve M. A Modern Herbal. London, England: J. Cape; 1931:671-672.
4. Blumenthal M, Busse WR, et al. The Complete German Commission E Monographs. Austin, TX: American Botanical Council; 1998.
5. Duke JA. Handbook of Medicinal Herbs. 2nd ed. Boca Raton, FL: CRC Press; 2002:609-610.
6. Jia H, Liu JW, Ufur H, He GS, Liqian H, Chen P. The antihypertensive effect of ethyl acetate extract from red raspberry fruit in hypertensive rats. Pharmacogn Mag. 2011;7(25):19-24.21472074
7. Patel AV, Rojas-Vera J, Dacke CG. Therapeutic constituents and actions of Rubus species. Curr Med Chem. 2004;11(11):1501-1512.15180580
8. Dobson P, Graham J, Stewart D, Brennan R, Hackett CA, McDougall GJ. Over-seasons analysis of quantitative trait loci affecting phenolic content and antioxidant capacity in raspberry. J Agric Food Chem. 2012;60(21):5360-5366.22583495
9. Bradish CM, Perkins-Veazie P, Fernandez GE, Xie G, Jia W. Comparison of flavonoid composition of red raspberries (Rubus idaeus L.) grown in the southern United States. [published online December 15, 2011]. J Agric Food Chem.22128912
10. Carvalho E, Fraser PD, Martens S. Carotenoids and tocopherols in yellow and red raspberries. Food Chem. 2013;139(1-4):744-752.23561169
11. Venskutonis, A. Dvaranauskaite, J. Labokas, Radical scavenging activity and composition of raspberry (Rubus idaeus) leaves from different locations in Lithuania. Fitoterapia. 2007;78(2):162-165.17215088
12. Verde SC, Trigo MJ, Sousa MB, et al. Effects of gamma radiation on raspberries: safety and quality issues. J Toxicol Environ Health A. 2013;76(4-5):291-303.23514071
13. Kim SK, Kim H, Kim SA, Park HK, Kim W. Anti-inflammatory and anti-superbacterial activity of polyphenols isolated from black raspberry. Korean J Physiol Pharmacol. 2013;17(1):73-79.2344062510.4196/kjpp.2013.17.1.73
14. Jean-Gilles D, Li L, Ma H, Yuan T, Chichester CO, Seeram NP. Anti-inflammatory effects of polyphenolic-enriched red raspberry extract in an antigen-induced arthritis rat model. [published online December 1, 2011]. J Agric Food Chem.22111586
15. Montrose DC, Horelik NA, Madigan JP, et al. Anti-inflammatory effects of freeze-dried black raspberry powder in ulcerative colitis. Carcinogenesis. 2011;32(3):343-350.2109864310.1093/carcin/bgq248
16. Suh JH, Romain C, Gonzalez-Barrio R, et al. Raspberry juice consumption, oxidative stress and reduction of atherosclerosis risk factors in hypercholesterolemic golden Syrian hamsters. Food Funct. 2011;2(7):400-405.21894327
17. Prior RL, Wilkes S, Rogers T, et al. Dietary black raspberry anthocyanins do not alter development of obesity in mice fed an obesogenic high-fat diet. J Agric Food Chem. 2010;58(7):3977-3983.20201554
18. Ash MM, Wolford KA, Carden TJ, Hwang KT, Carr TP. Unrefined and refined black raspberry seed oils significantly lower triglycerides and moderately affect cholesterol metabolism in male Syrian hamsters. J Med Food. 2011;14(9):1032-1038.21548801
19. Wang LS, Kuo CT, Cho SJ, et al. Black raspberry-derived anthocyanins demethylate tumor suppressor genes through the inhibition of DNMT1 and DNMT3B in colon cancer cells. Nutr Cancer. 2013;65(1):118-125.2336892110.1080/01635581.2013.741759
20. Bhandary B, Lee GH, So BO, et al. Rubus coreanus inhibits oxidized-LDL uptake by macrophages through regulation of JNK activation. Am J Chin Med. 2012;40(5):967-978.22928828
21. Mallery SR, Budendorf DE, Larsen MP, et al. Effects of human oral mucosal tissue, saliva, and oral microflora on intraoral metabolism and bioactivation of black raspberry anthocyanins. Cancer Prev Res (Phila). 2011;4(8):1209-1221.2155841210.1158/1940-6207
22. God J, Tate PL, Larcom LL. Red raspberries have antioxidant effects that play a minor role in the killing of stomach and colon cancer cells. Nutr Res. 2010;30(11):777-782.21130297
23. Durgo K, Belščak-Cvitanović A, Stančić A, Franekić J, Komes D. The bioactive potential of red raspberry (Rubus idaeus L.) leaves in exhibiting cytotoxic and cytoprotective activity on human laryngeal carcinoma and colon adenocarcinoma. J Med Food. 2012;15(3):258-268.22082102
24. Chen HS, Liu M, Shi LJ, et al. Effects of raspberry phytochemical extract on cell proliferation, apoptosis, and serum proteomics in a rat model. J Food Sci. 2011;76(8):T192-T198.22417609
25. Chen L, Xin X, Yuan Q, Su D, Liu W. Phytochemical properties and antioxidant capacities of various colored berries. [published online May 7, 2013]. J Sci Food Agric.2365322310.1002/jsfa.6216
26. Zikri NN, Riedl KM, Wang LS, Lechner J, Schwartz SJ, Stoner GD. Black raspberry components inhibit proliferation, induce apoptosis, and modulate gene expression in rat esophageal epithelial cells. Nutr Cancer. 2009;61(6):816-826.20155622
27. Woode DR, Aiyer HS, Sie N, et al. Effect of berry extracts and bioactive compounds on fulvestrant (ICI 182,780) sensitive and resistant cell lines. [published online December 31, 2012]. Int J Breast Cancer.2334640610.1155/2012/147828
28. Zhang Z, Knobloch TJ, Seamon LG, et al. A black raspberry extract inhibits proliferation and regulates apoptosis in cervical cancer cells. Gynecol Oncol. 2011;123(2):401-406.21831414
29. Ravoori S, Vadhanam MV, Aqil F, Gupta RC. Inhibition of estrogen-mediated mammary tumorigenesis by blueberry and black raspberry. J Agric Food Chem. 2012;60(22):5547-5555.22571764
30. Ogawa Y, Akamatsu M, Hotta Y, Hosoda A, Tamura H. Effect of essential oils, such as raspberry ketone and its derivatives, on antiandrogenic activity based on in vitro reporter gene assay. Bioorg Med Chem Lett. 2010;20(7):2111-2114.20226658
31. Madhusoodhanan R, Natarajan M, Singh JV, et al. Effect of black raspberry extract in inhibiting NFkappa B dependent radioprotection in human breast cancer cells. Nutr Cancer. 2010;62(1):93-104.20043264
32. Liu Y, Liu M, Li B, et al. Fresh raspberry phytochemical extract inhibits hepatic lesion in a Wistar rat model. Nutr Metab (Lond). 2010;7:84.21108811
33. Alonso R, Cadavid I, Calleja JM. A preliminary study of hypoglycemic activity of Rubus fruticosus. Planta Med. 1980;Suppl:102-106.7454877
34. Swanston-Flatt SK, Day C, Bailey CJ, Flatt PR. Traditional plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetologia. 1990;33(8):462-464.2210118
35. Clegg ME, Pratt M, Meade CM, Henry CJ. The addition of raspberries and blueberries to a starch-based food does not alter the glycaemic response. Br J Nutr. 2011;106(3):335-338.2173682810.1017/s0007114511001450
36. Holst L, Haavik S, Nordeng H. Raspberry leaf--should it be recommended to pregnant women? Complement Ther Clin Pract. 2009;15(4):204-208.19880082
37. Dante G, Pedrielli G, Annessi E, Facchinetti F. Herb remedies during pregnancy: a systematic review of controlled clinical trials. J Matern Fetal Neonatal Med. 2013;26(3):306-312.22928540
38. Zheng J, Pistilli MJ, Holloway AC, Crankshaw DJ. The effects of commercial preparations of red raspberry leaf on the contractility of the rat's uterus in vitro. Reprod Sci. 2010;17(5):494-501.
39. Johnson JR, Makaji E, Ho S, Boya X, Crankshaw DJ, Holloway AC. Effect of maternal raspberry leaf consumption in rats on pregnancy outcome and the fertility of the female offspring. Reprod Sci. 2009;16(6):605-609.19276407
40. Wang L, Meng X, Zhang F. Raspberry ketone protects rats fed high-fat diets against nonalcoholic steatohepatitis. J Med Food. 2012;15(5):495-503.2255141210.1089/jmf.2011.1717
41. Ghalayini IF, Al-Ghazo MA, Harfeil MN. Prophylaxis and therapeutic effects of raspberry (Rubus idaeus) on renal stone formation in Balb/c mice. Int Braz J Urol. 2011;37(2):259-266; discussion 267.21557843
42. Harada N, Okajima K, Narimatsu N, Kurihara H, Nakagata N. Effect of topical application of raspberry ketone on dermal production of insulin-like growth factor-I in mice and on hair growth and skin elasticity in humans. Growth Horm IGF Res. 2008;18(4):335-344.18321745
43. Lin CH, Ding HY, Kuo SY, Chin LW, Wu JY, Chang TS. Evaluation of in vitro and in vivo depigmenting activity of raspberry ketone from Rheum officinale. Int J Mol Sci. 2011;12(8):4819-4835.2195432710.3390/ijms12084819
44. Simpson M, Parsons M, Greenwood J, Wade K. Raspberry leaf in pregnancy: its safety and efficacy in labor. J Midwifery Womens Health. 2001;46(2):51-59.11370690
45. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. 2002;109(3):227-235.11950176
46. Sarvikivi E, Roivainen M, Maunula L, et al. Multiple norovirus outbreaks linked to imported frozen raspberries. Epidemiol Infect. 2012;140(2):260-267.21418716
47. British Herbal Pharmacopoeia 1990. Dorset, Great Britian: British Herbal Medicine Association; 1990.
48. Makaji E, Ho SH, Holloway AC, Crankshaw DJ. Effects in rats of maternal exposure to raspberry leaf and its constituents on the activity of cytochrome p450 enzymes in the offspring. Int J Toxicol. 2011;30(2):216-224.21115944
49. Jeong HS, Hong SJ, Lee TB, et al. Effects of black raspberry on lipid profiles and vascular endothelial function in patients with metabolic syndrome. Phytother Res. 2014;28:1492-1498.24706588
50. Sardo CL, Kitzmiller JP, Apseloff G, et al. An open-label randomized crossover trial of lypophilized black raspberries on postprandial inflammation in older overweight males: a pilot study. Am J Ther. 2016;23(1):e86-e91.23982695

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

Further information

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