Successful improved peripheral tissue perfusion was seen in patients with atherosclerosis after 12 months of treatment with aged garlic extract

Sandra Lindstedt, Martiné Wlosinska, Ann-Christin Nilsson, Joanna Hlebowicz, Mohammed Fakhro, Rafi Sheikh, Sandra Lindstedt, Martiné Wlosinska, Ann-Christin Nilsson, Joanna Hlebowicz, Mohammed Fakhro, Rafi Sheikh

Abstract

Patients with arteriolosclerosis have impaired microvascular perfusion leading to impaired wound healing. Aged garlic extract has shown to have a positive impact on vascular elasticity. The present study aimed to assess the effect of long-term treatment with AGE on peripheral tissue perfusion in patients with confirmed atherosclerosis. Ninety three patients with a CT-scan confirmed coronary artery arteriolosclerosis were randomised in a double-blind manner to placebo or 2400 mg AGE daily for 1 year. Peripheral tissue perfusion was evaluated at 0- and 12-months using Laser Speckle Contrast Imaging. Measurement of post occlusive reactive hyperemia (PORH) and cutaneous vascular conductance (CVC) using acetylcholine iontophoresis (Ach) was conducted. After 12 months a significant increase of 21.6% (95% CI 3.2%-40.0%, P < .05) was seen in the relative change of PORH in the AGE compared with the placebo group. The same response was seen for CVC and Ach with an increase of 21.4% (95% CI 3.4%-39.4%, P < .05) in the AGE group compared with the placebo group. Aged garlic extract regenerated peripheral tissue perfusion and increase microcirculation in patients with arteriolosclerosis. Adequate peripheral tissue perfusion and tissue oxygen tension are important prerequisites for successful tissue repair. Restored microcirculation in patients could hypothetically facilitate wound healing.

Keywords: aged garlic extract; atherosclerosis; double blinded; laser speckle contrast imaging; peripheral tissue perfusion.

Conflict of interest statement

Dr Lindstedt has received a grant to support this research from Wakunaga of America LTD. None of the other authors has conflicts of interest to disclose.

© 2021 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Illustration of the clinical Laser speckle contrast imaging (LSCI) setup for post occlusive reactive hyperemia (PORH) analysis (A). The LSCI camera was framed at the forearm of the study subjects, the red aiming beams are visualised. A blood pressure cuff was inflated to cause occlusion of the blood flow. The measurements, here illustrated with a representative example (B), were made on the forearm before before (B), during (O) and after (P) blood flow occlusion, to estimate the PORH. The time of interest for the measurements are illustrated with the colour bars in the in (B) and the region of interest are illustrated with the green circles in both (A) and the LSCI images in (B)
FIGURE 2
FIGURE 2
CONSORT statement (consolidated standards of reporting trials) flow chart. Showing demographics and baseline clinical information of the study cohort
FIGURE 3
FIGURE 3
Increased post occlusive reactive hyperemia (PORH) response in patients treated with AGE. Peripheral tissue perfusion was measured at 0‐ and 12‐months. Measurements were done before, during and after partial occlusion using a blood pressure cuff creating a post occlusive reactive hyperemia (PORH) response. A significant increase in relative change in PORH was seen in the AGE group compared with the placebo group (P < .05)
FIGURE 4
FIGURE 4
Improved endothelial function in patients treated with AGE. Endothelial function and vascular response were measured at 0‐ and 12‐months using iontophoresis and acetylcholine (Ach) provocation. Measurements, cutaneous vascular conductance (CVC) was calculated at rest and at peak vasodilatation in the first 5 minutes following ACh iontophoresis. A significant increase in relative change in CVC was seen in the AGE group compared with the placebo group (P < .05)

References

    1. Leys D. Atherothrombosis: a major health burden. Cerebrovasc Dis. 2001;11(Suppl 2):1‐4.
    1. Singh RB, Mengi SA, Xu YJ, Arneja AS, Dhalla NS. Pathogenesis of atherosclerosis: a multifactorial process. Exp Clin Cardiol. 2002;7(1):40‐53.
    1. Glass CK, Witztum JL. Atherosclerosis: the road ahead. Cell. 2001;104(4):503‐516.
    1. Levy BI, Schiffrin EL, Mourad JJ, et al. Impaired tissue perfusion: a pathology common to hypertension, obesity, and diabetes mellitus. Circulation. 2008;118(9):968‐976.
    1. Bottino DA, Lopes FG, de Oliveira FJ, Mecenas Ade S, Clapauch R, Bouskela E. Relationship between biomarkers of inflammation, oxidative stress and endothelial/microcirculatory function in successful aging versus healthy youth: a transversal study. BMC Geriatr. 2015;15:41.
    1. Hartman J, Frishman WH. Inflammation and atherosclerosis: a review of the role of interleukin‐6 in the development of atherosclerosis and the potential for targeted drug therapy. Cardiol Rev. 2014;22(3):147‐151.
    1. Machin DR, Phuong TT, Donato AJ. The role of the endothelial glycocalyx in advanced age and cardiovascular disease. Curr Opin Pharmacol. 2019;45:66‐71.
    1. Strain WD, Paldanius PM. Diabetes, cardiovascular disease and the microcirculation. Cardiovasc Diabetol. 2018;17(1):57.
    1. Lauten A, Ferrari M, Goebel B, et al. Microvascular tissue perfusion is impaired in acutely decompensated heart failure and improves following standard treatment. Eur J Heart Fail. 2011;13(7):711‐717.
    1. Bult H. Nitric oxide and atherosclerosis: possible implications for therapy. Mol Med Today. 1996;2(12):510‐518.
    1. Ide N, Lau BH. Garlic compounds minimize intracellular oxidative stress and inhibit nuclear factor‐kappa b activation. J Nutr. 2001;131(3s):1020S‐1026S.
    1. Imai J, Ide N, Nagae S, Moriguchi T, Matsuura H, Itakura Y. Antioxidant and radical scavenging effects of aged garlic extract and its constituents. Planta Med. 1994;60(5):417‐420.
    1. Ahmadi N, Nabavi V, Hajsadeghi F, et al. Aged garlic extract with supplement is associated with increase in brown adipose, decrease in white adipose tissue and predict lack of progression in coronary atherosclerosis. Int J Cardiol. 2013;168(3):2310‐2314.
    1. Allison GL, Lowe GM, Rahman K. Aged garlic extract inhibits platelet activation by increasing intracellular cAMP and reducing the interaction of GPIIb/IIIa receptor with fibrinogen. Life Sci. 2012;91(25–26):1275‐1280.
    1. Budoff M. Aged garlic extract retards progression of coronary artery calcification. J Nutr. 2006;136(3 Suppl):741S‐744S.
    1. Zeb I, Ahmadi N, Flores F, Budoff MJ. Randomized trial evaluating the effect of aged garlic extract with supplements versus placebo on adipose tissue surrogates for coronary atherosclerosis progression. Coron Artery Dis. 2018;29(4):325‐328.
    1. Zeb I, Ahmadi N, Nasir K, et al. Aged garlic extract and coenzyme Q10 have favorable effect on inflammatory markers and coronary atherosclerosis progression: a randomized clinical trial. J Cardiovasc Dis Res. 2012;3(3):185‐190.
    1. Budoff MJ, Ahmadi N, Gul KM, et al. Aged garlic extract supplemented with B vitamins, folic acid and L‐arginine retards the progression of subclinical atherosclerosis: a randomized clinical trial. Prev Med. 2009;49(2–3):101‐107.
    1. Ried K. Garlic lowers blood pressure in hypertensive subjects, improves arterial stiffness and gut microbiota: a review and meta‐analysis. Exp Ther Med. 2020;19(2):1472‐1478.
    1. Wlosinska M, Nilsson AC, Hlebowicz J, et al. The effect of aged garlic extract on the atherosclerotic process—a randomized double‐blind placebo‐controlled trial. BMC Complement Med Ther. 2020;20(1):132.
    1. Wlosinska M, Nilsson AC, Hlebowicz J, Malmsjo M, Fakhro M, Lindstedt S. Aged garlic extract preserves cutaneous microcirculation in patients with increased risk for cardiovascular diseases: a double‐blinded placebo‐controlled study. Int Wound J. 2019;16(6):1487‐1493.
    1. Hutchins E, Shaikh K, Kinninger A, et al. Aged garlic extract reduces left ventricular myocardial mass in patients with diabetes: a prospective randomized controlled double‐blind study. Exp Ther Med. 2020;19(2):1468‐1471.
    1. Hamal S, Cherukuri L, Birudaraju D, et al. Short‐term impact of aged garlic extract on endothelial function in diabetes: a randomized, double‐blind, placebo‐controlled trial. Exp Ther Med. 2020;19(2):1485‐1489.
    1. Kodera Y, Kurita M, Nakamoto M, Matsutomo T. Chemistry of aged garlic: diversity of constituents in aged garlic extract and their production mechanisms via the combination of chemical and enzymatic reactions. Exp Ther Med. 2020;19(2):1574‐1584.
    1. Tsuneyoshi T. BACH1 mediates the antioxidant properties of aged garlic extract. Exp Ther Med. 2020;19(2):1500‐1503.
    1. Ahmadi N, Tsimikas S, Hajsadeghi F, et al. Relation of oxidative biomarkers, vascular dysfunction, and progression of coronary artery calcium. Am J Cardiol. 2010;105(4):459‐466.
    1. Weiss N, Ide N, Abahji T, Nill L, Keller C, Hoffmann U. Aged garlic extract improves homocysteine‐induced endothelial dysfunction in macro‐ and microcirculation. J Nutr. 2006;136(3 Suppl):750S‐754S.
    1. Kim KM, Chun SB, Koo MS, et al. Differential regulation of NO availability from macrophages and endothelial cells by the garlic component S‐allyl cysteine. Free Radic Biol Med. 2001;30(7):747‐756.
    1. Zografos GC, Martis K, Morris DL. Laser Doppler flowmetry in evaluation of cutaneous wound blood flow using various suturing techniques. Ann Surg. 1992;215(3):266‐268.
    1. Schabauer AM, Rooke TW. Cutaneous laser Doppler flowmetry: applications and findings. Mayo Clin Proc. 1994;69(6):564‐574.
    1. Anesater E, Borgquist O, Torbrand C, et al. The use of a rigid disc to protect exposed structures in wounds treated with negative pressure wound therapy: effects on wound bed pressure and microvascular blood flow. Wound Repair Regen. 2012;20(4):611‐616.
    1. Lindstedt S, Malmsjo M, Hansson J, Hlebowicz J, Ingemansson R. Microvascular blood flow changes in the small intestinal wall during conventional negative pressure wound therapy and negative pressure wound therapy using a protective disc over the intestines in laparostomy. Ann Surg. 2012;255(1):171‐175.
    1. Sheikh R, Memarzadeh K, Torbrand C, Blohme J, Lindstedt S, Malmsjo M. Blood perfusion in a full‐thickness eyelid flap, investigated by laser Doppler Velocimetry, laser speckle contrast imaging and thermography. Eplasty. 2018;18:e9.
    1. Lindstedt S, Hlebowicz J. Blood flow response in small intestinal loops at different depths during negative pressure wound therapy of the open abdomen. Int Wound J. 2013;10(4):411‐417.
    1. Malmsjo M, Ingemansson R, Lindstedt S, Gustafsson L. Comparison of bacteria and fungus‐binding mesh, foam and gauze as fillers in negative pressure wound therapy—pressure transduction, wound edge contraction, microvascular blood flow and fluid retention. Int Wound J. 2013;10(5):597‐605.
    1. Lindstedt S, Malmsjo M, Hlebowicz J, Ingemansson R. Comparative study of the microvascular blood flow in the intestinal wall, wound contraction and fluid evacuation during negative pressure wound therapy in laparostomy using the V.a.C. abdominal dressing and the ABThera open abdomen negative pressure therapy system. Int Wound J. 2015;12(1):83‐88.
    1. Schulz KF, Altman DG, Moher D, Group C . CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c332.
    1. Puissant C, Abraham P, Durand S, et al. Assessment of endothelial function by acetylcholine iontophoresis: impact of inter‐electrode distance and electrical cutaneous resistance. Microvasc Res. 2014;93:114‐118.
    1. Budoff MJ, Takasu J, Flores FR, et al. Inhibiting progression of coronary calcification using aged garlic extract in patients receiving statin therapy: a preliminary study. Prev Med. 2004;39(5):985‐991.
    1. Tsuchida Y. Age‐related changes in skin blood flow at four anatomic sites of the body in males studied by xenon‐133. Plast Reconstr Surg. 1990;85(4):556‐561.
    1. Roustit M, Blaise S, Millet C, Cracowski JL. Reproducibility and methodological issues of skin post‐occlusive and thermal hyperemia assessed by single‐point laser Doppler flowmetry. Microvasc Res. 2010;79(2):102‐108.
    1. Roustit M, Cracowski JL. Assessment of endothelial and neurovascular function in human skin microcirculation. Trends Pharmacol Sci. 2013;34(7):373‐384.
    1. Puissant C, Abraham P, Durand S, et al. Reproducibility of non‐invasive assessment of skin endothelial function using laser Doppler flowmetry and laser speckle contrast imaging. PLoS One. 2013;8(4):e61320.
    1. Yvonne‐Tee GB, Rasool AH, Halim AS, Rahman AR. Reproducibility of different laser Doppler fluximetry parameters of postocclusive reactive hyperemia in human forearm skin. J Pharmacol Toxicol Methods. 2005;52(2):286‐292.
    1. Patterson GC. The role of intravascular pressure in the causation of reactive hyperaemia in the human forearm. Clin Sci. 1956;15(1):17‐25.
    1. Kontos HA, Mauck HP Jr, Patterson JL Jr. Mechanism of reactive hyperemia in limbs of anesthetized dogs. Am J Physiol. 1965;209(6):1106‐1114.
    1. Lorenzo S, Minson CT. Human cutaneous reactive hyperaemia: role of BKCa channels and sensory nerves. J Physiol. 2007;585(Pt 1):295‐303.
    1. Strain WD, Chaturvedi N, Bulpitt CJ, Rajkumar C, Shore AC. Albumin excretion rate and cardiovascular risk: could the association be explained by early microvascular dysfunction? Diabetes. 2005;54(6):1816‐1822.
    1. Yamamoto‐Suganuma R, Aso Y. Relationship between post‐occlusive forearm skin reactive hyperaemia and vascular disease in patients with type 2 diabetes—a novel index for detecting micro‐ and macrovascular dysfunction using laser Doppler flowmetry. Diabet Med. 2009;26(1):83‐88.
    1. Durand S, Tartas M, Bouye P, Koitka A, Saumet JL, Abraham P. Prostaglandins participate in the late phase of the vascular response to acetylcholine iontophoresis in humans. J Physiol. 2004;561(Pt 3):811‐819.
    1. Katz A, Ekberg K, Johansson BL, Wahren J. Diminished skin blood flow in type I diabetes: evidence for non‐endothelium‐dependent dysfunction. Clin Sci (Lond). 2001;101(1):59‐64.
    1. Jagren C, Gazelius B, Ihrman‐Sandal C, Lindblad LE, Ostergren J. Skin microvascular dilatation response to acetylcholine and sodium nitroprusside in peripheral arterial disease. Clin Physiol Funct Imaging. 2002;22(6):370‐374.
    1. Ried K, Frank OR, Stocks NP, Fakler P, Sullivan T. Effect of garlic on blood pressure: a systematic review and meta‐analysis. BMC Cardiovasc Disord. 2008;8:13.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren