26 The Nurse Practitioner • Vol. 41, No. 11
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Inte g
ies ser
e health v i t ra
part 2
Herbal supplements used to treat common chronic conditions Abstract: This is part 2 of a three-part series designed to provide clinicians with a working knowledge of the use of herbal supplements for health and disease states. Part 2 of the series focuses on the efficacy of herbal supplements used in the treatment of common chronic conditions. By Saun-Joo Yoon, PhD, RN; Susan D. Schaffer, PhD, ARNP; and Kim Curry, PhD, ARNP
ore than half of the adults in the United States have at least one chronic condition, and one-quarter of adults have two or more chronic conditions.1 According to the National Health Interview Survey, the following chronic conditions were found to be most prevalent in adults age 18 and older: hypertension (23.9%), arthritis (20.6%), heart disease (10.8%), diabetes mellitus (8.6%), and cancer (8.1%).2 Chronic conditions in adults age 57 and older were reported in the National Social Life, Health, and Aging Project. The most prevalent conditions found in this age group included hypertension (59.9%), incontinence (45.8%), arthritis (34.9%), cardiac conditions (29.9%), cancer (27.8%), and diabetes (22.1%).3
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M
The five chronic conditions shared by these two major national data sets are hypertension, other cardiac conditions, arthritis, cancer, and diabetes mellitus. To manage these chronic conditions, adults often use herbal products in addition to conventional treatments, such as prescription pharmaceuticals. Herbal supplements commonly used for these conditions and the efficacy of these supplements is discussed in the following sections. This article focuses on studies of human subjects, rather than animal or lab studies. Multiple PubMed searches were performed to identify systematic reviews and metaanalyses, with single randomized controlled trials (RCTs) utilized if higher-level evidence was not identified. The
Keywords: chronic conditions, complementary and alternative medicine, evidence-based practice, health promotion, herbal medicine, herbal supplements
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The Nurse Practitioner • November 2016 27
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Herbal supplements used to treat common chronic conditions
960 mg daily to treat hypertension. Ried and colleagues conducted an RCT of 79 patients with uncontrolled systolic hypertension.7 Aged garlic extract was found to be effective and well tolerated in patients with uncontrolled hypertension. Mean systolic BP was significantly reduced in patients consuming 480 mg of garlic per day for 12 weeks. Garlic was found to be a safe complementary therapy.7 However, garlic may prolong bleeding and therefore should be stopped at least 2 weeks before a scheduled surgery. In addition, garlic may reduce the amount of isoniazid absorbed by the body and may decrease the effectiveness of antiviral medications used for HIV, such as nevirapine, delavirdine, and Level 1 evidence supports the use of certain efavirenz.8 Adverse reactions related to garlic preparations include gastrogarlic preparations as a complementary intestinal symptoms such as bloating, therapy for hypertension. flatulence, reflux, and mild abdominal discomfort.6 It is recommended to use garlic preparations with caution if an Level 3. Case-series, case-controlled studies, or historically individual is taking any antiplatelet, anticoagulant, anticontrolled studies are categorized into Level 4, whereas diabetic, antiretroviral, or anti-inflammatory medications.5 4 mechanism-based reasoning work is Level 5. However, Ginseng (Korean red ginseng). Level 2 evidence was suplevels of evidence do not constitute a recommendation for plied by Rhee and colleagues in a study of the effects of Kotreatment. Clinicians must utilize their knowledge of indirean red ginseng on arterial stiffness in 80 individuals with vidual patients before recommending for or against using hypertension who were taking traditional antihypertensive these herbals for any of the chronic conditions discussed medications.9 No significant differences in BP changes or in this article. arterial stiffness were noted after 3 months of intervention between the group treated with 3 g/day of Korean ■ Hypertension red ginseng and the placebo group, which remained on A number of different herbal preparations have been studied their prescribed traditional antihypertensive medication.9 for hypertension, but not all of them are supported by curPatients should be advised that there is no good evidence rent clinical evidence. supporting the use of ginseng for hypertension. Allium sativum (garlic). Level 1 evidence supports the use Hibiscus sabdariffa L. (Sudan tea, sour tea). A tropical of certain garlic preparations as a complementary therapy plant, H. sabdariffa L. has been used as a food, beverage, for hypertension. One of the mechanisms of action of garlic and medicinal herb, particularly for hypertension. A recent in lowering BP seems to involve endothelium-dependent systematic review and meta-analysis of five RCTs with a total vasodilation and relaxation of the vascular smooth muscle of 390 subjects provided Level 1 evidence that H. sabdariffa L. cells.5 Recently, a meta-analysis of nine RCTs with 482 pasignificantly lowers both systolic and diastolic BP.10 Doses tients was conducted by Rohner and colleagues. The duraand durations included in this analysis varied greatly and tion of the study periods was from 8 to 26 weeks.6 ranged from 3.75 g/day to 100 mg of aqueous H. sabdariffa L. extract for 15 days to 6 weeks (depending on the clinical The types of garlic preparation used among the trials trial). The authors concluded that H. sabdariffa L. showed were dried garlic powder (Kwai), time-released garlic powpromise in managing hypertension safely, but further inder (Allicor), aged garlic extract, or crushed garlic. Dosages vestigation is needed to determine potential interactions ranged from 240 to 2,400 mg daily. The authors concluded with other conventional medications and optimal dose of that garlic preparations showed some evidence of lowering H. sabdariffa L. the BP, lowering systolic BP by 9.1 mm Hg and diastolic BP by 3.8 mm Hg; however, more research is needed to confirm ■ Hyperlipidemia these findings.6 Studies using aged garlic preparations demAllium sativum (garlic). Level 1 evidence supports the efonstrated greater efficacy.6 ficacy of garlic for lowering lipid levels. A meta-analysis Level 2 evidence was provided by a dose response study of 39 trials including 2,298 participants found that garlic involving the use of garlic in doses of 240 mg, 480 mg, or Cochrane Database of Systematic Reviews and the National Center for Complementary and Integrative Health were also consulted for all herbs considered for inclusion. Levels of evidence as described by the Oxford Centre for Evidence-Based Medicine 2011 working group were used to appraise the evidence with particular attention to potential harms or risks. In this rating scale, systematic reviews of RCTs are considered to be Level 1 evidence, while a Level 2 designation is used for individual RCTs. Nonrandomized controlled cohort/follow-up studies are considered to be
28 The Nurse Practitioner • Vol. 41, No. 11
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Herbal supplements used to treat common chronic conditions
reduced total serum cholesterol by 17 ± 6 mg/dL and lowdensity lipoprotein (LDL) cholesterol by 9 ± 6 mg/dL in individuals with elevated cholesterol who used it for more than 2 months.11 Studied daily doses were as follows: garlic powder (600 to 5,600 mg/day), garlic oil (9 to 18 mg/day), aged garlic extract (1,000 to 7,200 mg/day), and raw garlic (4 to 10 mg/day [one clove equals approximately 1 g]).11 Adverse reactions reported were consisted with those reported in studies of garlic for hypertension. An earlier systematic review of 10 RCTs found that 6 of the studies reported efficacy, with an average drop in total cholesterol of 24.8 mg/dL.12 Garlic supplements may be considered for patients with mild hyperlipidemia, although adverse reactions may limit adherence and potential drug interactions must be considered. Red yeast rice (RYR). This product has become popular for treatment of dyslipidemia, particularly in those who have experienced myopathies from HMG CoA reductase inhibitor (statin) drugs or in those who believe they are a safer alternative to statins. The recommended dosage is 1,200 to 2,400 mg once or twice daily.8 The use of RYR grew nearly 80% from 2005 to 2008 in the United States, with sales of $20 million reported in 2008.8 A meta-analysis of 93 randomized trials (primarily published in Chinese), including 9,625 participants, assessed the effectiveness and safety of three proprietary RYR preparations on primary hyperlipidemia.13 The duration of the interventions in these trials ranged from 4 to 24 weeks, and designs varied. Although some of the trials compared RYR with placebo, 37 trials compared xuezhikang 1.2 g and zhibituo 3.15 g variously with simvastatin, pravastatin, lovastatin, or other statins and
There is some Level 2 evidence of effectiveness of curcumin for the management of OA. found they were equivalent in lipid-lowering efficacy, lowering total cholesterol by about 10%.13 Incidence of adverse reactions ranged from 1.3% to 36% and included dizziness, anorexia, nausea, and abdominal distension. A reportedly “small” number of participants experienced increased serum blood urea nitrogen and alanine aminotransferase levels. This trial concluded that long-term effects and safety should be explored before RYR preparations were recommended as an alternative treatment for primary hyperlipidemia.13 A more recent meta-analysis of 13 RCTs (804 participants) with duration of at least 4 weeks demonstrated
significant lowering of total cholesterol, LDL cholesterol, and triglyceride compared with placebo. High-density lipoprotein levels were unaffected. RYR doses in these trials ranged from 200 to 3,600 mg/day, and all but four trials utilized combination products, including garlic, soybean, niacin, or artichoke leaf extract. No serious adverse reactions on hepatic function, kidney function, muscle (as measured by creatine kinase), or fasting blood glucose were reported in the analyses.14 Although RYR has generally been found to be effective in treating dyslipidemia, patients need to be aware that RYR products contain the naturally occurring form of lovastatin in inconsistent amounts, may potentially be adulterated with citrinin, a hepatotoxin, and nephrotoxin, and should not be combined with other statins or other medications that increase the risk of adverse reactions when combined with statins.15,16 These medications include the antidepressant nefazodone, anticoagulants, certain antibiotics, and drugs used to treat fungal and HIV infections. ■ Arthritis Although there are several different types of arthritis, the focus of most herbal therapy has been on osteoarthritis (OA) and age-related joint disease. Since there is no known cure for OA, symptom management focuses on reducing pain with pharmacologic therapies alone or in combination with nonpharmacologic methods, according to the OA Research Society International Treatment Guidelines Committee.17 Harpagophytum procumbens (Devil’s claw). Iridoid glycosides and phenylpropanoid glycosides of Devil’s claw have shown anti-inflammatory as well as analgesic properties biologically and have long been used for various ailments in South African regions.18 However, there is little clinical evidence supporting use of Devil’s claw for the treatment of OA pain. Brien and colleagues conducted a systematic review of relevant trials over a 10-year period. Fourteen studies were reviewed, including four RCTs; methodological quality was poor. The authors concluded that while the evidence showed some support for the use of Devil’s claw, it was insufficient to recommend benefit for OA.19 In an open-label study of 42 patients with degenerative joint disease, investigators studied a marketed mixture of Devil’s claw, turmeric, and bromelain. Results in this small sample revealed a significant reduction in pain as measured with a visual analogue scale, thus providing Level 3 evidence of some effectiveness when combined with select other plant products.20 Further investigation is warranted to ensure that
30 The Nurse Practitioner • Vol. 41, No. 11
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Herbal supplements used to treat common chronic conditions
that use of B. serrata reduced pain and slightly improved RCTs support the use of this herb. The most commonly physical function.27 reported adverse reactions of Devil’s claw is gastrointestinal 21 discomfort. Salix alba (willow bark). Willow bark, from the white ■ Cancer willow, contains the active ingredient salicin, which is a Many oncology experts advise against taking any type of 22 precursor to aspirin. Known to be an antipyretic agent, supplement, including herbal supplements and antioxidants, during cancer treatment—particularly during chemotherasalicin has Level 1 evidence to support its use for muscupy or radiation therapy due to lack of scientific evidence.28 loskeletal pain management, such as low back pain and arthritis pain. A systematic review of seven clinical trials There is also a theoretical concern that antioxidants may related to the use of willow bark for musculoskeletal pain repair the damage to cancer cells caused by cancer treatindicated that willow bark extract inhibited COX-2, showed ments, rendering these treatments less effective.28 an antioxidant effect in animal models, and reduced inflamDespite this, many patients with cancer make use of mation and pain.23 supplements. While the American Cancer Society recommends against the use of herbal supplements, the Society An open-label observational study with willow bark of Integrative Oncology (SIO) proposed a list of potentially extract STW33-I provided Level 3 evidence of the effectivebeneficial dietary supplements. Among the list the SIO sugness of willow bark. The authors used a willow bark dose gested were curcumin, Maitake mushrooms, green tea, and equivalent to 240 mg salicylic alcohol in 436 outpatients. Astragalus.29 Patients received two tablets a day for 6 months to manage arthritis pain. Results of the study indicated steady and Curcuma longa (turmeric [curcumin]). Curcumin has significant reduction of pain throughout the study with shown radioprotective and chemoprotective functions in mild adverse reactions, such as gastrointestinal discomfort, fatigue, flulike symptoms, and arthralgia.24 Green tea leaves have been used widely Curcuma longa (turmeric [curcumand known to have an antioxidant and in]). Curcumin is the active ingredient proapoptotic effect. of the turmeric plant. There is some Level 2 evidence of effectiveness of curcumin for the management of OA. Panahi and colleagues conducted a single RCT including 40 preventing toxicity from chemotherapy or radiotherapy patients with knee OA. Patients in the study arm received in some studies. 30 No Level 1 or Level 2 studies docu500 mg of curcuminoid capsules three times per day. Curmenting the effectiveness of curcumin in the treatment cumin demonstrated measurable antioxidant effects and of cancer in humans were located. Use of curcumin may provided symptom relief.25 In a prospective clinical trial increase the risk of bleeding when it is used with anticoagulants, antiplatelet drugs, nonsteroidal anti-inflammatory involving a more bioavailable form of curcumin, 50 patients drugs, herbs (such as ginkgo biloba and garlic), and saw with osteoarthritis of the knee were administered 180 mg/ palmetto.29 day of a proprietary curcumin compound. After 8 weeks of treatment, knee pain was significantly lower as measured Maitake mushrooms. These mushrooms have been with a visual analogue scale. The investigators concluded used in Asia to promote health for many years. Maitake that curcumin displayed modest potential for treating knee mushrooms contain a polysaccharide, D fraction, that has OA.26 This provides additional Level 2 evidence that this been studied for its effectiveness in treating several forms of cancer, including breast and lung cancers. The D fraction herb may be effective. compound appears to induce apoptosis, or programmed cell Boswellia serrata. This gummy tree resin has long been death, in cancer cells, among other mechanisms of action.31 used in Ayurvedic medicine. Level 1 evidence was provided by a systematic review of multiple studies of patients who No systematic reviews or RCTs were found that demonstrattook enriched B. serrata 100 mg/day for osteoarthritis.27 ed specific efficacy of maitake mushrooms in the treatment of tumors in patients. Overall results indicated that pain was lowered 17/100 Camellia sinensis (green tea). Green tea leaves have been points on a pain scale of 0 to 100 (lower scores indicatused widely and known to have an antioxidant and proing reduced pain). Physical function was improved by apoptotic effect.29 Green tea has largely been studied for 8 points (on a scale of 0 to 100 with lower scores indicating improved function) after 90 days of herbal therapy. cancer prevention rather than treatment. Even with regard to The authors concluded that there is high-quality evidence prevention, results have been inconsistent and conflicting.32 www.tnpj.com
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Herbal supplements used to treat common chronic conditions
with nondiabetic patients) with a total of 311 subjects, five of the eight trials demonstrated a reduction in fasting blood glucose; however, only two of those demonstrated a statistically significant difference when compared with placebo.35 Three studies demonstrated no significant difference. All three of the studies that failed to demonstrate significance were conducted with patients with diabetes. Doses of cinnamon (usMany herbal products confer significant ing C. cassia or C. verum) used in the studies varied. The authors concluded pharmacologic effects and may interact with that definitive conclusions could not prescription and nonprescription drugs. be drawn concerning cinnamon as therapy for diabetes mellitus.35 Further trials are needed to determine the benefits and risks of using cinnamon for diabetes mellitus.34 cell carcinoma of the lung. McCulloch and colleagues conducted a meta-analysis in 2006 of 34 studies representing Trigonella foenum-graecum (fenugreek). This fiber-rich 2,815 patients.33 All patients were taking platinum-based plant is popular in many regions of the world including Egypt, India, and Middle Eastern countries for glycemic chemotherapy. control.36,37 There is Level 1 evidence supporting the use Twelve studies reported reduced risk of death at 12 months, while 30 studies reported improved tumor reof fenugreek for glycemic control in patients with diabetes sponse data, over chemotherapy alone. Doses of astragamellitus. Neelakantan and colleagues conducted a metalus root varied, and it was administered as a mixture with analysis of 10 clinical trials that demonstrated significantly other Chinese herbs. McCulloch and colleagues concluded lowered fasting glucose, 2-hour postprandial glucose load, that astralagus-based herbal therapy may increase the efand hemoglobin A1C compared with controls.37 Fenugreek fectiveness of traditional chemotherapy but further closely preparations ranged from seeds to gum isolate to leaves, and controlled studies are warranted.33 dosages ranged from 1 g (seeds) to 100 g (leaves) per day. The authors concluded that a beneficial effect was demonstrated but that further trials were needed with a consistent ■ Diabetes mellitus preparation of the herb.37 Many herbal products have been studied in the treatment of diabetes mellitus, including bitter melon, cinnamon, dandelion, fenugreek, burdock, and onion. Although most ■ Implications for NPs of these herbs lack any recent well-documented clinical triAlthough many studies have been conducted to test the als, there is some evidence in the literature that can provide effectiveness of various types of herbal supplements for guidance on the use of cinnamon and fenugreek. treating chronic conditions, more studies are warranted with Cinnamomum cassia or Cinnamomum verum (cinnamon rigorous designs, large sample sizes, consistent preparations bark). Clinical evidence does not support the use of cinnaand dosages, and specific outcome measures. Particularly, mon bark to treat diabetes mellitus. This popular treatment clinical studies need to provide information about safety has been said to improve glycemic control, but has not been and tolerability. Potential drug-herb interactions should shown to differ from placebo in one meta-analysis of 10 be taken into consideration if adults take multiple medicaRCTs.34 A total of 577 patients received cinnamon (pretions or complex treatments such as chemotherapies with multiple agents. dominantly C. cassia) orally at an average dose of 2 g per It is imperative to have open communication with day for up to 16 weeks. patients to prevent adverse outcomes, maintain safety of Cinnamon was compared with placebo, no medication, treatments, and improve quality of life. The use of any or another medication and did not change glycemic control oral herbal supplements to treat chronic diseases, with or in any of the three circumstances. The included studies were without the use of prescription pharmaceuticals, should judged to lack quality, and none of the studies investigated be managed on an individual case-by-case basis with each morbidity, mortality, cost of care, or quality of life. The patient. Providers should expect patients with chronic conauthors concluded that cinnamon was not effective but that ditions to use, or at least consider, herbal adjunctive therapy, further rigorous studies are needed.34 and they should be prepared to initiate a discussion of the In an earlier systematic review of eight clinical trials benefits and risks. (five with patients with type 2 diabetes mellitus and three No high-level evidence was found supporting the use of green tea in cancer treatment. Astragalus root (milk vetch or huang qi). This herb has shown immunomodulatory properties and may be used along with chemotherapy.29 There is Level 1 evidence to support the use of astragalus root for advanced non–small
32 The Nurse Practitioner • Vol. 41, No. 11
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Herbal supplements used to treat common chronic conditions
■ Conclusion The use of herbal supplements to treat chronic conditions is a long-standing practice. Patients suffering from a chronic condition are motivated to try a variety of traditional and nontraditional methods to relieve symptoms and reverse the disease course. Clinicians should keep in mind that many herbal products confer significant pharmacologic effects, and may exhibit interactions with prescription and nonprescription drugs. The final part of this three-part series will focus on existing clinical guidelines for the use of herbal products.
18. Mncwangi N, Chen W, Vermaak I, Viljoen AM, Gericke N. Devil’s claw—a review of the ethnobotany, phytochemistry and biological activity of Harpagophytum procumbens. J Ethnopharmacol. 2012;143(3):755-771. 19. Brien S, Lewith GT, McGregor G. Devil’s claw (Harpagophytum procumbens) as a treatment for osteoarthritis: a review of efficacy and safety. J Altern Complement Med. 2006;12(10):981-993. 20. Conrozier T, Mathieu P, Bonjean M, Marc JF, Renevier JL, Balblanc JC. A complex of three natural anti-inflammatory agents provides relief of osteoarthritis pain. Altern Ther Health Med. 2014;20(suppl 1):32-37. 21. Warnock M, McBean D, Suter A, Tan J, Whittaker P. Effectiveness and safety of Devil’s claw tablets in patients with general rheumatic disorders. Phytother Res. 2007;21(12):1228-1233. 22. Sego S. Willow bark relieves pain and inflammation. Clin Advisor. 2011; 14(6):129. 23. Vlachojannis JE, Cameron M, Chrubasik S. A systematic review on the effectiveness of willow bark for musculoskeletal pain. Phytother Res. 2009;23(7): 897-900.
REFERENCES 1. Ward BW, Schiller JS. Prevalence of multiple chronic conditions among US adults: estimates from the National Health Interview Survey, 2010. Prev Chron Dis. 2013;10:120203. 2. National Center for Health Care Statistics. Data file documentation, National Health Interview Survey 2012. Hyattsville, MD: National Center for Health Care Statistics, Centers for Disease Control and Prevention; 2013. 3. Vasilopoulos T, Kotwal A, Huisingh-Scheetz MJ, Waite LJ, McClintock MK, Dale W. Comorbidity and chronic conditions in the National Social Life, Health and Aging project (NSHAP), Wave 2. J Gerontol B Psychol Sci Soc Sci. 2014;69(suppl 2):S154-S165. 4. Centre for Evidence-Based Medicine. OECBM levels of evidence. 2011. www.cebm.net/index.aspx?o=5653. 5. Ried K, Fakler P. Potential of garlic (Allium sativum) in lowering high blood pressure: mechanisms of action and clinical relevance. Integr Blood Press Control. 2014;7:71-82.
24. Uehleke B, Müller J, Stange R, Kelber O, Melzer J. Willow bark extract STW 33-I in the long-term treatment of outpatients with rheumatic pain mainly osteoarthritis or back pain. Phytomedicine. 2013;20(11):980-984. 25. Panahi Y, Alishiri GH, Parvin S, Sahebkar A. Mitigation of systemic oxidative stress by curcuminoids in osteoarthritis: results of a randomized controlled trial. J Diet Suppl. 2016;13(2):209-220. 26. Nakagawa Y, Mukai S, Yamada S, et al. Short-term effects of highlybioavailable curcumin for treating knee osteoarthritis: a randomized, double-blind, placebo-controlled prospective study. J Orthop Sci. 2014;19(6):933-939. 27. Cameron M, Chrubasik S. Oral herbal therapies for treating osteoarthritis. The Cochrane Collaboration. 2014. www.cochrane.org/CD002947/MUSKEL_oralherbal-therapies-for-treating-osteoarthritis. 28. Rock CL, Doyle C, Demark-Wahnefried W, et al. Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin. 2012;62(4):242-274. 29. Frenkel M, Abrams DI, Ladas EJ, et al. Integrating dietary supplements into cancer care. Integr Cancer Ther. 2013;12(5):369-384.
6. Rohner A, Ried K, Sobenin IA, Bucher HC, Nordmann AJ. A systematic review and metaanalysis on the effects of garlic preparations on blood pressure in individuals with hypertension. Am J Hypertens. 2015;28(3): 414-423.
30. Goel A, Aggarwal BB. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer. 2010;62(7):919-930.
7. Ried K, Frank OR, Stocks NP. Aged garlic extract reduces blood pressure in hypertensives: a dose-response trial. Eur J Clin Nutr. 2013;67(1):64-70.
31. Soares R, Meireles M, Rocha A, et al. Maitake (D fraction) mushroom extract induces apoptosis in breast cancer cells by BAK-1 gene activation. J Med Food. 2011;14(6):563-572.
8. Natural Medicines Comprehensive Database. Herbs and supplements. 2016. www.nlm.nih.gov/medlineplus/druginfo/herb_All.html. 9. Rhee MY, Kim YS, Bae JH, et al. Effect of Korean red ginseng on arterial stiffness in subjects with hypertension. J Altern Complement Med. 2011;17(1):45-49. 10. Serban C, Sahebkar A, Ursoniu S, Andrica F, Banach M. Effect of sour tea (Hibiscus sabdariffa L.) on arterial hypertension: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2015;33(6): 1119-1127. 11. Ried K, Toben C, Fakler P. Effect of garlic on serum lipids: an updated metaanalysis. Nutr Rev. 2013;71(5):282-299. 12. Alder R, Lookinland S, Berry JA, Williams M. A systematic review of the effectiveness of garlic as an anti-hyperlipidemic agent. J Am Acad Nurse Pract. 2003;15(3):120-129. 13. Liu J, Zhang J, Shi Y, Grimsgaard S, Alraek T, Fønnebø V. Chinese red yeast rice (Monascus purpureus) for primary hyperlipidemia: a meta-analysis of randomized controlled trials. Chin Med. 2006;1:4. 14. Li Y, Jiang L, Jia Z, et al. A meta-analysis of red yeast rice: an effective and relatively safe alternative approach for dyslipidemia. PLoS One. 2014;9(6): e98611. 15. Childress L, Gay A, Zargar A, Ito MK. Review of red yeast rice content and current Food and Drug Administration oversight. J Clin Lipidol. 2013;7(2): 117-122. 16. Gordon RY, Cooperman T, Obermeyer W, Becker DJ. Marked variability of monacolin levels in commercial red yeast rice products: buyer beware! Arch Intern Med. 2010;170(19):1722-1727. 17. Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence. Osteoarthritis Cartilage. 2007;15(9):981-1000.
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32. Boehm K, Borrelli F, Ernst E, et al. Green tea (Camellia sinensis) for the prevention of cancer. Cochrane Database Syst Rev. 2009;(3):CD005004. 33. McCulloch M, See C, Shu XJ, et al. Astragalus-based Chinese herbs and platinum-based chemotherapy for advanced non-small-cell lung cancer: meta-analysis of randomized trials. J Clin Oncol. 2006;24(3):419-430. 34. Leach MJ, Kumar S. Cinnamon for diabetes mellitus. The Cochrane Collaboration. 2012. www.cochrane.org/CD007170/ENDOC_cinnamon-fordiabetes-mellitus. 35. Kirkham S, Akilen R, Sharma S, Tsiami A. The potential of cinnamon to reduce blood glucose levels in patients with type 2 diabetes and insulin resistance. Diabetes Obes Metab. 2009;11(12):1100-1113. 36. National Center for Complementary and Integrative Health. Fenugreek. 2012. https://nccih.nih.gov/sites/nccam.nih.gov/files/Herbs_At_A_Glance_ Fenugreek_06-15-2012_0.pdf. 37. Neelakantan N, Narayanan M, de Souza RJ, van Dam RM. Effect of fenugreek (Trigonella foenum-graecum L.) intake on glycemia: a meta-analysis of clinical trials. Nutr J. 2014;13:7. Saun-Joo Yoon is an associate professor at the University of Florida, College of Nursing, Gainesville, Fla. Susan D. Schaffer is a clinical associate professor at the University of Florida, College of Nursing, Gainesville, Fla. Kim Curry is a clinical associate professor at the University of Florida, College of Nursing, Gainesville, Fla. The authors have disclosed that they have no financial relationships related to this article. DOI-10.1097/01.NPR.0000502793.50737.2f
The Nurse Practitioner • November 2016 33
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Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
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Inte g
ies ser
e health v i t ra
part 2
Herbal supplements used to treat common chronic conditions Abstract: This is part 2 of a three-part series designed to provide clinicians with a working knowledge of the use of herbal supplements for health and disease states. Part 2 of the series focuses on the efficacy of herbal supplements used in the treatment of common chronic conditions. By Saun-Joo Yoon, PhD, RN; Susan D. Schaffer, PhD, ARNP; and Kim Curry, PhD, ARNP
ore than half of the adults in the United States have at least one chronic condition, and one-quarter of adults have two or more chronic conditions.1 According to the National Health Interview Survey, the following chronic conditions were found to be most prevalent in adults age 18 and older: hypertension (23.9%), arthritis (20.6%), heart disease (10.8%), diabetes mellitus (8.6%), and cancer (8.1%).2 Chronic conditions in adults age 57 and older were reported in the National Social Life, Health, and Aging Project. The most prevalent conditions found in this age group included hypertension (59.9%), incontinence (45.8%), arthritis (34.9%), cardiac conditions (29.9%), cancer (27.8%), and diabetes (22.1%).3
Photo by Elena the Wise / iStock ©
M
The five chronic conditions shared by these two major national data sets are hypertension, other cardiac conditions, arthritis, cancer, and diabetes mellitus. To manage these chronic conditions, adults often use herbal products in addition to conventional treatments, such as prescription pharmaceuticals. Herbal supplements commonly used for these conditions and the efficacy of these supplements is discussed in the following sections. This article focuses on studies of human subjects, rather than animal or lab studies. Multiple PubMed searches were performed to identify systematic reviews and metaanalyses, with single randomized controlled trials (RCTs) utilized if higher-level evidence was not identified. The
Keywords: chronic conditions, complementary and alternative medicine, evidence-based practice, health promotion, herbal medicine, herbal supplements
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The Nurse Practitioner • November 2016 27
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Herbal supplements used to treat common chronic conditions
960 mg daily to treat hypertension. Ried and colleagues conducted an RCT of 79 patients with uncontrolled systolic hypertension.7 Aged garlic extract was found to be effective and well tolerated in patients with uncontrolled hypertension. Mean systolic BP was significantly reduced in patients consuming 480 mg of garlic per day for 12 weeks. Garlic was found to be a safe complementary therapy.7 However, garlic may prolong bleeding and therefore should be stopped at least 2 weeks before a scheduled surgery. In addition, garlic may reduce the amount of isoniazid absorbed by the body and may decrease the effectiveness of antiviral medications used for HIV, such as nevirapine, delavirdine, and Level 1 evidence supports the use of certain efavirenz.8 Adverse reactions related to garlic preparations include gastrogarlic preparations as a complementary intestinal symptoms such as bloating, therapy for hypertension. flatulence, reflux, and mild abdominal discomfort.6 It is recommended to use garlic preparations with caution if an Level 3. Case-series, case-controlled studies, or historically individual is taking any antiplatelet, anticoagulant, anticontrolled studies are categorized into Level 4, whereas diabetic, antiretroviral, or anti-inflammatory medications.5 4 mechanism-based reasoning work is Level 5. However, Ginseng (Korean red ginseng). Level 2 evidence was suplevels of evidence do not constitute a recommendation for plied by Rhee and colleagues in a study of the effects of Kotreatment. Clinicians must utilize their knowledge of indirean red ginseng on arterial stiffness in 80 individuals with vidual patients before recommending for or against using hypertension who were taking traditional antihypertensive these herbals for any of the chronic conditions discussed medications.9 No significant differences in BP changes or in this article. arterial stiffness were noted after 3 months of intervention between the group treated with 3 g/day of Korean ■ Hypertension red ginseng and the placebo group, which remained on A number of different herbal preparations have been studied their prescribed traditional antihypertensive medication.9 for hypertension, but not all of them are supported by curPatients should be advised that there is no good evidence rent clinical evidence. supporting the use of ginseng for hypertension. Allium sativum (garlic). Level 1 evidence supports the use Hibiscus sabdariffa L. (Sudan tea, sour tea). A tropical of certain garlic preparations as a complementary therapy plant, H. sabdariffa L. has been used as a food, beverage, for hypertension. One of the mechanisms of action of garlic and medicinal herb, particularly for hypertension. A recent in lowering BP seems to involve endothelium-dependent systematic review and meta-analysis of five RCTs with a total vasodilation and relaxation of the vascular smooth muscle of 390 subjects provided Level 1 evidence that H. sabdariffa L. cells.5 Recently, a meta-analysis of nine RCTs with 482 pasignificantly lowers both systolic and diastolic BP.10 Doses tients was conducted by Rohner and colleagues. The duraand durations included in this analysis varied greatly and tion of the study periods was from 8 to 26 weeks.6 ranged from 3.75 g/day to 100 mg of aqueous H. sabdariffa L. extract for 15 days to 6 weeks (depending on the clinical The types of garlic preparation used among the trials trial). The authors concluded that H. sabdariffa L. showed were dried garlic powder (Kwai), time-released garlic powpromise in managing hypertension safely, but further inder (Allicor), aged garlic extract, or crushed garlic. Dosages vestigation is needed to determine potential interactions ranged from 240 to 2,400 mg daily. The authors concluded with other conventional medications and optimal dose of that garlic preparations showed some evidence of lowering H. sabdariffa L. the BP, lowering systolic BP by 9.1 mm Hg and diastolic BP by 3.8 mm Hg; however, more research is needed to confirm ■ Hyperlipidemia these findings.6 Studies using aged garlic preparations demAllium sativum (garlic). Level 1 evidence supports the efonstrated greater efficacy.6 ficacy of garlic for lowering lipid levels. A meta-analysis Level 2 evidence was provided by a dose response study of 39 trials including 2,298 participants found that garlic involving the use of garlic in doses of 240 mg, 480 mg, or Cochrane Database of Systematic Reviews and the National Center for Complementary and Integrative Health were also consulted for all herbs considered for inclusion. Levels of evidence as described by the Oxford Centre for Evidence-Based Medicine 2011 working group were used to appraise the evidence with particular attention to potential harms or risks. In this rating scale, systematic reviews of RCTs are considered to be Level 1 evidence, while a Level 2 designation is used for individual RCTs. Nonrandomized controlled cohort/follow-up studies are considered to be
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Herbal supplements used to treat common chronic conditions
reduced total serum cholesterol by 17 ± 6 mg/dL and lowdensity lipoprotein (LDL) cholesterol by 9 ± 6 mg/dL in individuals with elevated cholesterol who used it for more than 2 months.11 Studied daily doses were as follows: garlic powder (600 to 5,600 mg/day), garlic oil (9 to 18 mg/day), aged garlic extract (1,000 to 7,200 mg/day), and raw garlic (4 to 10 mg/day [one clove equals approximately 1 g]).11 Adverse reactions reported were consisted with those reported in studies of garlic for hypertension. An earlier systematic review of 10 RCTs found that 6 of the studies reported efficacy, with an average drop in total cholesterol of 24.8 mg/dL.12 Garlic supplements may be considered for patients with mild hyperlipidemia, although adverse reactions may limit adherence and potential drug interactions must be considered. Red yeast rice (RYR). This product has become popular for treatment of dyslipidemia, particularly in those who have experienced myopathies from HMG CoA reductase inhibitor (statin) drugs or in those who believe they are a safer alternative to statins. The recommended dosage is 1,200 to 2,400 mg once or twice daily.8 The use of RYR grew nearly 80% from 2005 to 2008 in the United States, with sales of $20 million reported in 2008.8 A meta-analysis of 93 randomized trials (primarily published in Chinese), including 9,625 participants, assessed the effectiveness and safety of three proprietary RYR preparations on primary hyperlipidemia.13 The duration of the interventions in these trials ranged from 4 to 24 weeks, and designs varied. Although some of the trials compared RYR with placebo, 37 trials compared xuezhikang 1.2 g and zhibituo 3.15 g variously with simvastatin, pravastatin, lovastatin, or other statins and
There is some Level 2 evidence of effectiveness of curcumin for the management of OA. found they were equivalent in lipid-lowering efficacy, lowering total cholesterol by about 10%.13 Incidence of adverse reactions ranged from 1.3% to 36% and included dizziness, anorexia, nausea, and abdominal distension. A reportedly “small” number of participants experienced increased serum blood urea nitrogen and alanine aminotransferase levels. This trial concluded that long-term effects and safety should be explored before RYR preparations were recommended as an alternative treatment for primary hyperlipidemia.13 A more recent meta-analysis of 13 RCTs (804 participants) with duration of at least 4 weeks demonstrated
significant lowering of total cholesterol, LDL cholesterol, and triglyceride compared with placebo. High-density lipoprotein levels were unaffected. RYR doses in these trials ranged from 200 to 3,600 mg/day, and all but four trials utilized combination products, including garlic, soybean, niacin, or artichoke leaf extract. No serious adverse reactions on hepatic function, kidney function, muscle (as measured by creatine kinase), or fasting blood glucose were reported in the analyses.14 Although RYR has generally been found to be effective in treating dyslipidemia, patients need to be aware that RYR products contain the naturally occurring form of lovastatin in inconsistent amounts, may potentially be adulterated with citrinin, a hepatotoxin, and nephrotoxin, and should not be combined with other statins or other medications that increase the risk of adverse reactions when combined with statins.15,16 These medications include the antidepressant nefazodone, anticoagulants, certain antibiotics, and drugs used to treat fungal and HIV infections. ■ Arthritis Although there are several different types of arthritis, the focus of most herbal therapy has been on osteoarthritis (OA) and age-related joint disease. Since there is no known cure for OA, symptom management focuses on reducing pain with pharmacologic therapies alone or in combination with nonpharmacologic methods, according to the OA Research Society International Treatment Guidelines Committee.17 Harpagophytum procumbens (Devil’s claw). Iridoid glycosides and phenylpropanoid glycosides of Devil’s claw have shown anti-inflammatory as well as analgesic properties biologically and have long been used for various ailments in South African regions.18 However, there is little clinical evidence supporting use of Devil’s claw for the treatment of OA pain. Brien and colleagues conducted a systematic review of relevant trials over a 10-year period. Fourteen studies were reviewed, including four RCTs; methodological quality was poor. The authors concluded that while the evidence showed some support for the use of Devil’s claw, it was insufficient to recommend benefit for OA.19 In an open-label study of 42 patients with degenerative joint disease, investigators studied a marketed mixture of Devil’s claw, turmeric, and bromelain. Results in this small sample revealed a significant reduction in pain as measured with a visual analogue scale, thus providing Level 3 evidence of some effectiveness when combined with select other plant products.20 Further investigation is warranted to ensure that
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Herbal supplements used to treat common chronic conditions
that use of B. serrata reduced pain and slightly improved RCTs support the use of this herb. The most commonly physical function.27 reported adverse reactions of Devil’s claw is gastrointestinal 21 discomfort. Salix alba (willow bark). Willow bark, from the white ■ Cancer willow, contains the active ingredient salicin, which is a Many oncology experts advise against taking any type of 22 precursor to aspirin. Known to be an antipyretic agent, supplement, including herbal supplements and antioxidants, during cancer treatment—particularly during chemotherasalicin has Level 1 evidence to support its use for muscupy or radiation therapy due to lack of scientific evidence.28 loskeletal pain management, such as low back pain and arthritis pain. A systematic review of seven clinical trials There is also a theoretical concern that antioxidants may related to the use of willow bark for musculoskeletal pain repair the damage to cancer cells caused by cancer treatindicated that willow bark extract inhibited COX-2, showed ments, rendering these treatments less effective.28 an antioxidant effect in animal models, and reduced inflamDespite this, many patients with cancer make use of mation and pain.23 supplements. While the American Cancer Society recommends against the use of herbal supplements, the Society An open-label observational study with willow bark of Integrative Oncology (SIO) proposed a list of potentially extract STW33-I provided Level 3 evidence of the effectivebeneficial dietary supplements. Among the list the SIO sugness of willow bark. The authors used a willow bark dose gested were curcumin, Maitake mushrooms, green tea, and equivalent to 240 mg salicylic alcohol in 436 outpatients. Astragalus.29 Patients received two tablets a day for 6 months to manage arthritis pain. Results of the study indicated steady and Curcuma longa (turmeric [curcumin]). Curcumin has significant reduction of pain throughout the study with shown radioprotective and chemoprotective functions in mild adverse reactions, such as gastrointestinal discomfort, fatigue, flulike symptoms, and arthralgia.24 Green tea leaves have been used widely Curcuma longa (turmeric [curcumand known to have an antioxidant and in]). Curcumin is the active ingredient proapoptotic effect. of the turmeric plant. There is some Level 2 evidence of effectiveness of curcumin for the management of OA. Panahi and colleagues conducted a single RCT including 40 preventing toxicity from chemotherapy or radiotherapy patients with knee OA. Patients in the study arm received in some studies. 30 No Level 1 or Level 2 studies docu500 mg of curcuminoid capsules three times per day. Curmenting the effectiveness of curcumin in the treatment cumin demonstrated measurable antioxidant effects and of cancer in humans were located. Use of curcumin may provided symptom relief.25 In a prospective clinical trial increase the risk of bleeding when it is used with anticoagulants, antiplatelet drugs, nonsteroidal anti-inflammatory involving a more bioavailable form of curcumin, 50 patients drugs, herbs (such as ginkgo biloba and garlic), and saw with osteoarthritis of the knee were administered 180 mg/ palmetto.29 day of a proprietary curcumin compound. After 8 weeks of treatment, knee pain was significantly lower as measured Maitake mushrooms. These mushrooms have been with a visual analogue scale. The investigators concluded used in Asia to promote health for many years. Maitake that curcumin displayed modest potential for treating knee mushrooms contain a polysaccharide, D fraction, that has OA.26 This provides additional Level 2 evidence that this been studied for its effectiveness in treating several forms of cancer, including breast and lung cancers. The D fraction herb may be effective. compound appears to induce apoptosis, or programmed cell Boswellia serrata. This gummy tree resin has long been death, in cancer cells, among other mechanisms of action.31 used in Ayurvedic medicine. Level 1 evidence was provided by a systematic review of multiple studies of patients who No systematic reviews or RCTs were found that demonstrattook enriched B. serrata 100 mg/day for osteoarthritis.27 ed specific efficacy of maitake mushrooms in the treatment of tumors in patients. Overall results indicated that pain was lowered 17/100 Camellia sinensis (green tea). Green tea leaves have been points on a pain scale of 0 to 100 (lower scores indicatused widely and known to have an antioxidant and proing reduced pain). Physical function was improved by apoptotic effect.29 Green tea has largely been studied for 8 points (on a scale of 0 to 100 with lower scores indicating improved function) after 90 days of herbal therapy. cancer prevention rather than treatment. Even with regard to The authors concluded that there is high-quality evidence prevention, results have been inconsistent and conflicting.32 www.tnpj.com
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Herbal supplements used to treat common chronic conditions
with nondiabetic patients) with a total of 311 subjects, five of the eight trials demonstrated a reduction in fasting blood glucose; however, only two of those demonstrated a statistically significant difference when compared with placebo.35 Three studies demonstrated no significant difference. All three of the studies that failed to demonstrate significance were conducted with patients with diabetes. Doses of cinnamon (usMany herbal products confer significant ing C. cassia or C. verum) used in the studies varied. The authors concluded pharmacologic effects and may interact with that definitive conclusions could not prescription and nonprescription drugs. be drawn concerning cinnamon as therapy for diabetes mellitus.35 Further trials are needed to determine the benefits and risks of using cinnamon for diabetes mellitus.34 cell carcinoma of the lung. McCulloch and colleagues conducted a meta-analysis in 2006 of 34 studies representing Trigonella foenum-graecum (fenugreek). This fiber-rich 2,815 patients.33 All patients were taking platinum-based plant is popular in many regions of the world including Egypt, India, and Middle Eastern countries for glycemic chemotherapy. control.36,37 There is Level 1 evidence supporting the use Twelve studies reported reduced risk of death at 12 months, while 30 studies reported improved tumor reof fenugreek for glycemic control in patients with diabetes sponse data, over chemotherapy alone. Doses of astragamellitus. Neelakantan and colleagues conducted a metalus root varied, and it was administered as a mixture with analysis of 10 clinical trials that demonstrated significantly other Chinese herbs. McCulloch and colleagues concluded lowered fasting glucose, 2-hour postprandial glucose load, that astralagus-based herbal therapy may increase the efand hemoglobin A1C compared with controls.37 Fenugreek fectiveness of traditional chemotherapy but further closely preparations ranged from seeds to gum isolate to leaves, and controlled studies are warranted.33 dosages ranged from 1 g (seeds) to 100 g (leaves) per day. The authors concluded that a beneficial effect was demonstrated but that further trials were needed with a consistent ■ Diabetes mellitus preparation of the herb.37 Many herbal products have been studied in the treatment of diabetes mellitus, including bitter melon, cinnamon, dandelion, fenugreek, burdock, and onion. Although most ■ Implications for NPs of these herbs lack any recent well-documented clinical triAlthough many studies have been conducted to test the als, there is some evidence in the literature that can provide effectiveness of various types of herbal supplements for guidance on the use of cinnamon and fenugreek. treating chronic conditions, more studies are warranted with Cinnamomum cassia or Cinnamomum verum (cinnamon rigorous designs, large sample sizes, consistent preparations bark). Clinical evidence does not support the use of cinnaand dosages, and specific outcome measures. Particularly, mon bark to treat diabetes mellitus. This popular treatment clinical studies need to provide information about safety has been said to improve glycemic control, but has not been and tolerability. Potential drug-herb interactions should shown to differ from placebo in one meta-analysis of 10 be taken into consideration if adults take multiple medicaRCTs.34 A total of 577 patients received cinnamon (pretions or complex treatments such as chemotherapies with multiple agents. dominantly C. cassia) orally at an average dose of 2 g per It is imperative to have open communication with day for up to 16 weeks. patients to prevent adverse outcomes, maintain safety of Cinnamon was compared with placebo, no medication, treatments, and improve quality of life. The use of any or another medication and did not change glycemic control oral herbal supplements to treat chronic diseases, with or in any of the three circumstances. The included studies were without the use of prescription pharmaceuticals, should judged to lack quality, and none of the studies investigated be managed on an individual case-by-case basis with each morbidity, mortality, cost of care, or quality of life. The patient. Providers should expect patients with chronic conauthors concluded that cinnamon was not effective but that ditions to use, or at least consider, herbal adjunctive therapy, further rigorous studies are needed.34 and they should be prepared to initiate a discussion of the In an earlier systematic review of eight clinical trials benefits and risks. (five with patients with type 2 diabetes mellitus and three No high-level evidence was found supporting the use of green tea in cancer treatment. Astragalus root (milk vetch or huang qi). This herb has shown immunomodulatory properties and may be used along with chemotherapy.29 There is Level 1 evidence to support the use of astragalus root for advanced non–small
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Herbal supplements used to treat common chronic conditions
■ Conclusion The use of herbal supplements to treat chronic conditions is a long-standing practice. Patients suffering from a chronic condition are motivated to try a variety of traditional and nontraditional methods to relieve symptoms and reverse the disease course. Clinicians should keep in mind that many herbal products confer significant pharmacologic effects, and may exhibit interactions with prescription and nonprescription drugs. The final part of this three-part series will focus on existing clinical guidelines for the use of herbal products.
18. Mncwangi N, Chen W, Vermaak I, Viljoen AM, Gericke N. Devil’s claw—a review of the ethnobotany, phytochemistry and biological activity of Harpagophytum procumbens. J Ethnopharmacol. 2012;143(3):755-771. 19. Brien S, Lewith GT, McGregor G. Devil’s claw (Harpagophytum procumbens) as a treatment for osteoarthritis: a review of efficacy and safety. J Altern Complement Med. 2006;12(10):981-993. 20. Conrozier T, Mathieu P, Bonjean M, Marc JF, Renevier JL, Balblanc JC. A complex of three natural anti-inflammatory agents provides relief of osteoarthritis pain. Altern Ther Health Med. 2014;20(suppl 1):32-37. 21. Warnock M, McBean D, Suter A, Tan J, Whittaker P. Effectiveness and safety of Devil’s claw tablets in patients with general rheumatic disorders. Phytother Res. 2007;21(12):1228-1233. 22. Sego S. Willow bark relieves pain and inflammation. Clin Advisor. 2011; 14(6):129. 23. Vlachojannis JE, Cameron M, Chrubasik S. A systematic review on the effectiveness of willow bark for musculoskeletal pain. Phytother Res. 2009;23(7): 897-900.
REFERENCES 1. Ward BW, Schiller JS. Prevalence of multiple chronic conditions among US adults: estimates from the National Health Interview Survey, 2010. Prev Chron Dis. 2013;10:120203. 2. National Center for Health Care Statistics. Data file documentation, National Health Interview Survey 2012. Hyattsville, MD: National Center for Health Care Statistics, Centers for Disease Control and Prevention; 2013. 3. Vasilopoulos T, Kotwal A, Huisingh-Scheetz MJ, Waite LJ, McClintock MK, Dale W. Comorbidity and chronic conditions in the National Social Life, Health and Aging project (NSHAP), Wave 2. J Gerontol B Psychol Sci Soc Sci. 2014;69(suppl 2):S154-S165. 4. Centre for Evidence-Based Medicine. OECBM levels of evidence. 2011. www.cebm.net/index.aspx?o=5653. 5. Ried K, Fakler P. Potential of garlic (Allium sativum) in lowering high blood pressure: mechanisms of action and clinical relevance. Integr Blood Press Control. 2014;7:71-82.
24. Uehleke B, Müller J, Stange R, Kelber O, Melzer J. Willow bark extract STW 33-I in the long-term treatment of outpatients with rheumatic pain mainly osteoarthritis or back pain. Phytomedicine. 2013;20(11):980-984. 25. Panahi Y, Alishiri GH, Parvin S, Sahebkar A. Mitigation of systemic oxidative stress by curcuminoids in osteoarthritis: results of a randomized controlled trial. J Diet Suppl. 2016;13(2):209-220. 26. Nakagawa Y, Mukai S, Yamada S, et al. Short-term effects of highlybioavailable curcumin for treating knee osteoarthritis: a randomized, double-blind, placebo-controlled prospective study. J Orthop Sci. 2014;19(6):933-939. 27. Cameron M, Chrubasik S. Oral herbal therapies for treating osteoarthritis. The Cochrane Collaboration. 2014. www.cochrane.org/CD002947/MUSKEL_oralherbal-therapies-for-treating-osteoarthritis. 28. Rock CL, Doyle C, Demark-Wahnefried W, et al. Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin. 2012;62(4):242-274. 29. Frenkel M, Abrams DI, Ladas EJ, et al. Integrating dietary supplements into cancer care. Integr Cancer Ther. 2013;12(5):369-384.
6. Rohner A, Ried K, Sobenin IA, Bucher HC, Nordmann AJ. A systematic review and metaanalysis on the effects of garlic preparations on blood pressure in individuals with hypertension. Am J Hypertens. 2015;28(3): 414-423.
30. Goel A, Aggarwal BB. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer. 2010;62(7):919-930.
7. Ried K, Frank OR, Stocks NP. Aged garlic extract reduces blood pressure in hypertensives: a dose-response trial. Eur J Clin Nutr. 2013;67(1):64-70.
31. Soares R, Meireles M, Rocha A, et al. Maitake (D fraction) mushroom extract induces apoptosis in breast cancer cells by BAK-1 gene activation. J Med Food. 2011;14(6):563-572.
8. Natural Medicines Comprehensive Database. Herbs and supplements. 2016. www.nlm.nih.gov/medlineplus/druginfo/herb_All.html. 9. Rhee MY, Kim YS, Bae JH, et al. Effect of Korean red ginseng on arterial stiffness in subjects with hypertension. J Altern Complement Med. 2011;17(1):45-49. 10. Serban C, Sahebkar A, Ursoniu S, Andrica F, Banach M. Effect of sour tea (Hibiscus sabdariffa L.) on arterial hypertension: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2015;33(6): 1119-1127. 11. Ried K, Toben C, Fakler P. Effect of garlic on serum lipids: an updated metaanalysis. Nutr Rev. 2013;71(5):282-299. 12. Alder R, Lookinland S, Berry JA, Williams M. A systematic review of the effectiveness of garlic as an anti-hyperlipidemic agent. J Am Acad Nurse Pract. 2003;15(3):120-129. 13. Liu J, Zhang J, Shi Y, Grimsgaard S, Alraek T, Fønnebø V. Chinese red yeast rice (Monascus purpureus) for primary hyperlipidemia: a meta-analysis of randomized controlled trials. Chin Med. 2006;1:4. 14. Li Y, Jiang L, Jia Z, et al. A meta-analysis of red yeast rice: an effective and relatively safe alternative approach for dyslipidemia. PLoS One. 2014;9(6): e98611. 15. Childress L, Gay A, Zargar A, Ito MK. Review of red yeast rice content and current Food and Drug Administration oversight. J Clin Lipidol. 2013;7(2): 117-122. 16. Gordon RY, Cooperman T, Obermeyer W, Becker DJ. Marked variability of monacolin levels in commercial red yeast rice products: buyer beware! Arch Intern Med. 2010;170(19):1722-1727. 17. Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence. Osteoarthritis Cartilage. 2007;15(9):981-1000.
www.tnpj.com
32. Boehm K, Borrelli F, Ernst E, et al. Green tea (Camellia sinensis) for the prevention of cancer. Cochrane Database Syst Rev. 2009;(3):CD005004. 33. McCulloch M, See C, Shu XJ, et al. Astragalus-based Chinese herbs and platinum-based chemotherapy for advanced non-small-cell lung cancer: meta-analysis of randomized trials. J Clin Oncol. 2006;24(3):419-430. 34. Leach MJ, Kumar S. Cinnamon for diabetes mellitus. The Cochrane Collaboration. 2012. www.cochrane.org/CD007170/ENDOC_cinnamon-fordiabetes-mellitus. 35. Kirkham S, Akilen R, Sharma S, Tsiami A. The potential of cinnamon to reduce blood glucose levels in patients with type 2 diabetes and insulin resistance. Diabetes Obes Metab. 2009;11(12):1100-1113. 36. National Center for Complementary and Integrative Health. Fenugreek. 2012. https://nccih.nih.gov/sites/nccam.nih.gov/files/Herbs_At_A_Glance_ Fenugreek_06-15-2012_0.pdf. 37. Neelakantan N, Narayanan M, de Souza RJ, van Dam RM. Effect of fenugreek (Trigonella foenum-graecum L.) intake on glycemia: a meta-analysis of clinical trials. Nutr J. 2014;13:7. Saun-Joo Yoon is an associate professor at the University of Florida, College of Nursing, Gainesville, Fla. Susan D. Schaffer is a clinical associate professor at the University of Florida, College of Nursing, Gainesville, Fla. Kim Curry is a clinical associate professor at the University of Florida, College of Nursing, Gainesville, Fla. The authors have disclosed that they have no financial relationships related to this article. DOI-10.1097/01.NPR.0000502793.50737.2f
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