Effect of Korean red ginseng on cold hypersensitivity in the hands and feet: study protocol for a randomized controlled trial

Kyoung-Sun Park, Jin-Woo Kim, Jun-Young Jo, Deok-Sang Hwang, Chang-Hoon Lee, Jun-Bock Jang, Kyung-Sub Lee, Inkwon Yeo, Jin-Moo Lee, Kyoung-Sun Park, Jin-Woo Kim, Jun-Young Jo, Deok-Sang Hwang, Chang-Hoon Lee, Jun-Bock Jang, Kyung-Sub Lee, Inkwon Yeo, Jin-Moo Lee

Abstract

Background: Cold hypersensitivity in the hands and feet (CHHF) is one of the most common complaints among Asians, especially in women. Korean red ginseng (KRG), which is a steamed form of Panax ginseng, has vasodilating action in the peripheral vessels and increases blood flow under cold stress. However, few studies have evaluated the effect of KRG on cold hypersensitivity.

Methods/design: This trial is a randomized, double-blind, placebo-controlled trial in 80 CHHF patients. The trial will be implemented at Kyung Hee University Hospital at Gangdong in Seoul, Korea. The participants will take KRG or a placebo for eight weeks, after which they will be followed-up for four weeks. During the administration period, six capsules of 500 mg KRG or placebo will be provided twice a day. The primary outcome is change of skin temperature in the hands between baseline and after treatment. The secondary outcomes include the visual analogue scale scores of cold hypersensitivity in the hands, change of skin temperature and the VAS scores of cold hypersensitivity in the feet, the recovery rate of the skin temperature by the cold stress test of the hands, the distal-dorsal difference of the hands, power variables of heart rate variability, and the 36-item short form health survey.

Discussion: This study is the first trial to evaluate the efficacy of KRG on CHHF by using infrared thermography. Our study will provide basic evidence regarding CHHF.

Trial registration: CliniacalTrials.gov NCT01664156.

Figures

Figure 1
Figure 1
Study flow chart. CHHF, cold hypersensitivity in the hands and feet; KRG, Korean red ginseng.

References

    1. Hur YM, Chae JH, Chung KW, Kim JJ, Jeong HU, Kim JW, Seo SY, Kim KS. Feeling of cold hands and feet is a highly heritable phenotype. Twin Res Hum Genet. 2012;14:166–169. doi: 10.1375/twin.15.2.166.
    1. Lee SL, Lee KS, Song BK. The literature review on the cold hypersensitivity of women. J Korean Gynecol. 1996;14:55–80.
    1. Bae GM, Cho HS, Kim KK, Lee IS. The research on the cold hypersensitivity of patients in the gynecology clinic. J Korean Gynecol. 2002;14:101–113.
    1. Kim DH, Kim YS, Lee KS. Standardization of diagnosis of cold hypersensitivity of hands and feet by D.I.T.I. J Korean Gynecol. 2001;14:129–134.
    1. Vuksan V, Sung MK, Sievenpiper JL, Stavro PM, Jenkins AL, Di Buono M, Lee KS, Leiter LA, Nam KY, Arnason JT. Korean red ginseng (Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebo-controlled study of efficacy and safety. Nutr Metab Cardiovasc Dis. 2008;14:46–56. doi: 10.1016/j.numecd.2006.04.003.
    1. Kim SY, Seo SK, Choi YM, Jeon YE, Lim KJ, Cho S, Choi YS, Lee BS. Effects of red ginseng supplementation on menopausal symptoms and cardiovascular risk factors in postmenopausal women: a double-blind randomized controlled trial. Menopause. 2012;14:461. doi: 10.1097/gme.0b013e3182325e4b.
    1. Helms S. Cancer prevention and therapeutics: Panax ginseng. Altern Med Rev. 2004;14:259–274.
    1. Park JD. Recent studies on the chemical constituents of Korean ginseng (Panaxginseng CA Meyer) Korean J Ginseng Sci. 1996;14:389–415.
    1. Kim WY, Kim JM, Han SB, Lee SK, Kim ND, Park MK, Kim CK, Park JH. Steaming of ginseng at high temperature enhances biological activity. J Nat Prod. 2000;14:1702–1704. doi: 10.1021/np990152b.
    1. Kaneko H, Nakanishi K. Vasodilator action of ginsenosides. Clin Study. 1984;14:2657–2662.
    1. Chen X. Cardiovascular protection by ginsenosides and their nitric oxide releasing action. Clin Exp Pharmacol Physiol. 1996;14:728–732. doi: 10.1111/j.1440-1681.1996.tb01767.x.
    1. Kim ND, Kim EM, Kang KW, Cho MK, Choi SY, Kim SG. Ginsenoside Rg3 inhibits phenylephrine‒induced vascular contraction through induction of nitric oxide synthase. Br J Pharmacol. 2003;14:661–670. doi: 10.1038/sj.bjp.0705490.
    1. Sung J, Han KH, Zo JH, Park HJ, Kim CH, Oh BH. Effects of red ginseng upon vascular endothelial function in patients with essential hypertension. Am J Chin Med. 2000;14:205–216. doi: 10.1142/S0192415X00000258.
    1. Jovanovski E, Jenkins A, Dias AG, Peeva V, Sievenpiper J, Arnason JT, Rahelic D, Josse RG, Vuksan V. Effects of Korean red ginseng (Panax ginseng C. A. Mayer) and its isolated ginsenosides and polysaccharides on arterial stiffness in healthy individuals. Am J Hypertens. 2010;14:469–472. doi: 10.1038/ajh.2010.5.
    1. Kwan C. The effects of different ginseng extracts on vascular contraction in vitro: evidence for Yin-Yang principle. Acta Phytother. 1999;14:73–77.
    1. Kaneko H, Nakanishi K. Proof of the mysterious efficacy of ginseng: basic and clinical trials: clinical effects of medical ginseng, Korean red ginseng: specifically, its anti-stress action for prevention of disease. J Pharmacol Sci. 2004;14:158–162. doi: 10.1254/jphs.FMJ04001X5.
    1. Clark S, Hollis S, Campbell F, Moore T, Jayson M, Herrick A. The distal-dorsal difference as a possible predictor of secondary Raynaud's phenomenon. J Rheumatol. 1999;14:1125–1128.
    1. Pauling JD, Flower V, Shipley J, Harris ND, McHugh NJ. Influence of the cold challenge on the discriminatory capacity of the digital distal-dorsal difference in the thermographic assessment of Raynaud's phenomenon. Microvasc Res. 2011;14:364–368. doi: 10.1016/j.mvr.2011.03.007.
    1. Anderson M, Moore T, Lunt M, Herrick A. The ‘distal–dorsal difference’: a thermographic parameter by which to differentiate between primary and secondary Raynaud's phenomenon. Rheumatology. 2007;14:533–538. doi: 10.1093/rheumatology/kel330.
    1. Montano N, Ruscone TG, Porta A, Lombardi F, Pagani M, Malliani A. Power spectrum analysis of heart rate variability to assess the changes in sympathovagal balance during graded orthostatic tilt. Circulation. 1994;14:1826–1831. doi: 10.1161/01.CIR.90.4.1826.
    1. Perini R, Veicsteinas A. Heart rate variability and autonomic activity at rest and during exercise in various physiological conditions. Eur J Appl Physiol. 2003;14:317–325. doi: 10.1007/s00421-003-0953-9.
    1. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care. 1992;14:473–483. doi: 10.1097/00005650-199206000-00002.
    1. Levien TL. Advances in the treatment of Raynaud’s phenomenon. Vasc Health Risk Manag. 2010;14:167.
    1. Cooke JP, Marshall JM. Mechanisms of Raynaud’s disease. Vasc Med. 2005;14:293–307. doi: 10.1191/1358863x05vm639ra.
    1. Gayraud M. Raynaud's phenomenon. Joint Bone Spine. 2007;14:e1–e8. doi: 10.1016/j.jbspin.2006.07.002.
    1. Wigley FM. Raynaud's phenomenon. N Engl J Med. 2002;14:1001–1008. doi: 10.1056/NEJMcp013013.
    1. Choi WS, Ock SM, Byeon JH, Jung SH, Park KS, Park JW, Yoo DJ, Lee JB, Kim CM. The prevalence of diagnosis as Raynaud’s disease among the people complaint of abnormal sensation on hands and feet. Korean J Fam Med. 2003;14:1085–1091.
    1. Zaproudina N, Varmavuo V, Airaksinen O, Närhi M. Reproducibility of infrared thermography measurements in healthy individuals. Physiol Meas. 2008;14:515. doi: 10.1088/0967-3334/29/4/007.
    1. Murray AK, Moore TL, Manning JB, Taylor C, Griffiths CEM, Herrick AL. Noninvasive imaging techniques in the assessment of scleroderma spectrum disorders. Arthritis Rheum. 2009;14:1103–1111. doi: 10.1002/art.24645.
    1. Di Carlo A. Thermography and the possibilities for its applications in clinical and experimental dermatology. Clin Dermatol. 1995;14:329. doi: 10.1016/0738-081X(95)00073-O.
    1. Polunina A, Gugleta K, Kochkorov A, Katamay R, Flammer J, Orgül S. Relationship between peripheral blood flow in extremities and choroidal circulation. Klin Monatsbl Augenheilkd. 2011;14:302–305. doi: 10.1055/s-0031-1273211.
    1. O'Reilly D, Taylor L, El-Hadidy K, Jayson M. Measurement of cold challenge responses in primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis. Ann Rheum Dis. 1992;14:1193–1196. doi: 10.1136/ard.51.11.1193.
    1. Schuhfried O, Vacariu G, Lang T, Korpan M, Kiener HP, Fialka-Moser V. Thermographic parameters in the diagnosis of secondary Raynaud's phenomenon. Arch Physical Med Rehabil. 2000;14:495–499. doi: 10.1053/mr.2000.4870.
    1. Coughlin P, Chetter I, Kent P, Kester R. The analysis of sensitivity, specificity, positive predictive value and negative predictive value of cold provocation thermography in the objective diagnosis of the hand–arm vibration syndrome. Occup Med. 2001;14:75–80. doi: 10.1093/occmed/51.2.075.
    1. Han JY, Joe JH, Jang JB, Kim YS, Lee KS. Cold stress test for the diagnosis of cold hypersensitivity on hands. J Oriental Med Thermol. 2003;14:17–23.
    1. Kistler A, Mariauzouls C, von Berlepsch K. Fingertip temperature as an indicator for sympathetic responses. Int J Psychophysiol. 1998;14:35–41. doi: 10.1016/S0167-8760(97)00087-1.
    1. Faes TJ, Wagemans MF, Cillekens JM, Scheffer GJ, Karemaker JM, Bertelsmann FW. The validity and reproducibility of the skin vasomotor test—studies in normal subjects, after spinal anaesthesia, and in diabetes mellitus. Clin Auton Res. 1993;14:319–324. doi: 10.1007/BF01827333.
    1. Zaproudina N, Lipponen JA, Eskelinen P, Tarvainen MP, Karjalainen PA, Närhi M. Measurements of skin temperature responses to cold exposure of foot and face in healthy individuals: variability and influencing factors. Clin Physiol Funct Imaging. 2011;14:307–314. doi: 10.1111/j.1475-097X.2011.01018.x.
    1. Abramson DI. Neural regulation of cutaneous circulation. Adv Biol Skin. 1972;14:207.
    1. Olsen N, Petring OU, Rossing N. Exaggerated postural vasoconstrictor reflex in Raynaud's phenomenon. Br Med J (Clin Res Ed) 1987;14:1186–1188. doi: 10.1136/bmj.294.6581.1186.
    1. Nielsen S, Christensen N, Olsen N, Lassen N. Raynaud's phenomenon: peripheral catecholamine concentration and effect of sympathectomy. Acta Chir Scand Suppl. 1980;14:57.
    1. Koszewicz M, Gosk-Bierska I, Bilinska M, Podemski R, Budrewicz S, Adamiec R, Slotwinski K. Autonomic dysfunction in primary Raynaud's phenomenon. Int Angiol. 2009;14:127–131.
    1. Brändström H, Wiklund U, Karlsson M, Ängquist KA, Grip H, Haney M. Autonomic nerve system responses for normal and slow rewarmers after hand cold provocation: effects of long-term cold climate training. Int Arch Occup Environ Health. 2013;14:357–365. doi: 10.1007/s00420-012-0767-3.
    1. Yook TH, Yu JS, Lee HY, Song BY, Kim LH, Roh JD, Shin JC, Lim ST. Comparing the effects of distilled Rehmanniaglutinosa, wild ginseng and astragali radix pharmacopuncture with Heart Rate Variability (HRV): a randomized, sham-controlled and double-blind clinical trial. J Acupunct Meridian Stud. 2009;14:239–247. doi: 10.1016/S2005-2901(09)60061-3.
    1. Zheng A, Moritani T. Effect of the combination of ginseng, oriental bezoar and glycyrrhiza on autonomic nervous activity and immune system under mental arithmetic stress. J Nutr Sci Vitaminol. 2008;14:244–249. doi: 10.3177/jnsv.54.244.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する