By Dr Elizabeth Owings, MD “A stroke occurs when blood flow is cut off to neural tissue. It is most commonly assumed to occur in the brain, but can also occur in the spinal cord as a “spinal stroke”. Approximately 80% of cerebral strokes are ischemic (blood flow is blocked off), and about 20% are hemorrhagic (a blood vessel bursts causing localized pressure injury). The cellular cause of death is lack of oxygen and glucose: the brain requires glucose but does not store glucose and cannot make glucose, so the obstruction of blood flow in an ischemic stroke, or inability to overcome the pressure gradient in a hemorrhagic stroke results in the same lack of oxygen and glucose causing rapid injury or death of neural tissue.
Treatable risk factors include hypertension, smoking, heart disease (including arrhythmias or abnormal heart rhythms), diabetes, cholesterol imbalance, and physical inactivityi. Hypertension is an abnormal elevation of blood pressure due to a myriad of factors, but generally associated with endothelial dysfunction. Endothelial dysfunction may be a precursor of hypertension; or, subsequent to its development, endothelial dysfunction may occur in accelerated form. The endothelium is the name of the lining of blood vessels, and it is arguably the largest organ in the body, lining 100,000 miles of blood vessels and covering roughly a soccer field in surface area. This lining is responsible for producing nitric oxide, which then relaxes the blood vessel, allowing more blood to flow through it. When the endothelium is dysfunctional, it does not recognize or cannot respond to the need for blood flow, and the vessel remains in a constricted state. Additionally, this dysfunctional endothelium is more susceptible to cholesterol plaquing, and these plaques are more likely to rupture, triggering a local clot, or even allowing this clot to travel to another area of the body. This is how an “ulcerated” plaque in a vessel of the neck can cause a stroke in the brain.
Endothelial dysfunction is worsened by diabetesii, kidney failureiii, elevatated LDL cholesteroliv, elevated homocysteine levelsv, smokingvi, lack of antioxidant consumptionvii, and high salt diet.viii It is endothelial dysfunction which signals the initiation and progression of atherosclerosisix, contributing to worsening high blood pressure, heart attack, stroke, peripheral vascular disease, and erectile dysfunction. Furthermore, endothelial dysfunction underlies microvascular (microscopic blood vessels) disease such as multi-infarct dementia and microvascular angina. These vessels are too small to be aided by procedures such as stents, endarterectomyx, or bypass operations. It is this microvascular endothelial dysfunction which is believed to underlie a condition known as “leukoaraiosis”, a finding on brain MRI’s associated with cognitive dysfunction, which is not explained by ischemia of larger vessels supplying the brain.xi
Panoxol™, a patented combination of L-arginine, L-citrulline, horse chestnut seed extract, Ginkgo biloba, cayenne pepper, and red yeast rice, provides a novel non-prescription supplement to support the body’s natural repair mechanisms. Combined with appropriate blood pressure control, diet, and exercise, this product can be expected to assist in the prevention as well as recovery from stroke. Each ingredient works at multiple points in the progression of endothelial dysfunction and atherosclerotic disease, and the combination is synergistic in effect.
L-arginine is an amino acid, which means it is found in protein, in dilute form. It is the precursor to nitric oxide and the only substrate needed to synthesize nitric oxide. Supplementing the diet with purified L-arginine helps increase nitric oxide levels, thus ameliorating endothelial dysfunction.
L-Citrulline has been shown to both inhibit arginase (which would turn arginine into uric acid instead of nitric oxide) and to improve arginine stores better than arginine itself.
The combination of citrulline and arginine have been shown to reverse endothelial dysfunction.xii In addition, it has been shown that the combination of citrulline and arginine enhances nitric oxide bioavailabilityxiii.
Horse chestnut is best known for improving ankle swelling and shrinking swollen leg veins. It has been shown to protect the endotheliumxiv, and also has an important role in stroke prevention and recovery. Aescin, the active ingredient, has been shown to prevent damaging inflammation and actually downregulates inflammatory genes and upregulates healing genes in a mouse model of stroke.xv
Cayenne, a potent antioxidantxvi, has been shown to improve not only stroke risk, but several contributory risk factors, such as hypertension, atherosclerosis, diabetes, and obesity.xvii
Red Yeast Rice improves cholesterol profile, as well as diminishing oxidation and limiting the expression of cell adhesion molecules, effectively making the endothelium less ‘sticky’ and therefor less likely form cholesterol plaque.
Gingko biloba is widely recognized as a neuroprotective supplement, protecting the brain from injury in cases of absent or diminished blood flow.xviii It improves blood flow to the brain in patients who have experienced a hemorrhagic strokexix, and has been extensively studied and found helpful in both ischemic and hemorrhagic strokes.xx In recent randomized, double blind, placebo-controlled study of ischemia stroke, Gingko biloba administration tripled the likelihood of 4 month improvement to half the original NIHSS score.xxi”
i From the National Institute of Neurological Disorders and Stroke website (http://www.ninds.nih.gov/disorders/stroke/preventing_stroke.htm)
ii Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag. 2007 Dec; 3(6): 853–876. Hadi AR ,Hadi and Jassim Al Suwaidi
iii Mechanism of endothelial dysfunction in chronic kidney disease. Clin Chim Acta. 2010 Oct 9;411(19- 20):1412-20. doi:10.1016/j.cca.2010.06.019. Epub 2010 Jun 22. Malyszko J
iv New mechanisms of LDL-cholesterol induced endothelial dysfunction; correction by statins. Bull Mem Acad R Med Belg. 2002;157(10-12):427-31; discussion 431-4. Balligand JL
v Homocysteine and endothelial dysfunction: a link with cardiovascular disease. J Nutr. 2000 Feb;130(2S Suppl):369S- 372S. McDowell IF,Lang D.
vi Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol. 2014 Mar;34(3):509-15. doi: 10.1161/ATVBAHA.113.300156. Messner B, Bernhard D
vii Acute reversal of endothelial dysfunction in the elderly after antioxidant consumption. Hypertension. 2012 Apr;59(4):818- 24. Wray DW1,Nishiyama SK, Harris RA, Zhao J, McDaniel J, Fjeldstad AS, Witman MA, Ives SJ, Barrett-O’Keefe Z, Richardson RS.
viii Vascular Endothelial Function and Hypertension: Insights and Directions. Curr Hypertens Rep. 2010 Dec; 12(6): 448– 455. Kodlipet Dharmashankar and Michael E. Widlansky
ix Arterial endothelial dysfunction in baboons fed a high-cholesterol, high-fat diet; Am J Clin Nutr. 2005 Oct; 82(4): 751–759. Qiang Shi, et al.
x Endarterectomy is a surgical procedure in which the plaque is actually removed from the wall of the vessel, usually in the neck.
xi Pathogenesis of Leukoaraiosis: A Review. Stroke 1997; 28:652-659. Leonardo Pantoni, MD; Julio H. Garcia, MD
xii Meta Gene. 2013 Oct 15;1:8-14. doi: 10.1016/j.mgene.2013.09.001. ECollection 2013. The effect of citrulline and arginine supplementation on lactic acidemia in MELAS syndrome. El-Hattab AW1, Emrick LT2, Williamson KC2, Craigen WJ2, Scaglia F2.
xiii Oral supplementation with a combination of l-citrulline and l-arginine rapidly increases plasma l-arginine concentration and enhances NO bioavailability. Biochemical and Biophysical Research Communications. Volume 454, Issue 1, 7, November 2014, Pages 53–57.Masahiko Morita, Toshio Hayashi, Masayuki Ochiai, Morihiko Maeda, Tomoe
xiv Endothelial function impairment in chronic venous insufficiency: effect of some cardiovascular protectant agents. Angiology. 2009 Dec-2010 Jan;60(6):763-71. Carrasco OF1, Ranero A, Hong E, Vidrio H.
xv Escin attenuates cognitive deficits and hippocampal injury after transient global cerebral ischemia in mice via regulating certain inflammatory genes. Neurochemistry 57(2):119-127. Sept 2010. International.Leiming Zhang, Fenghua Fu , Xiumei Zhang, Mei Zhu,Tian Wang, Huaying Fan
xvi Antioxidant activity of capsinoids. J Agric Food Chem. 2002 Dec 4;50(25):7396-401. Rosa A, Deiana M, Casu V, Paccagnini S, Appendino G, Ballero M, Dessí MA
xvii Capsaicin may have important potential for promoting vascular and metabolic health. Open Heart. 2015 Jun 17;2(1):e000262.McCarty MF1, DiNicolantonio JJ2, O’Keefe JH2. xviii Neuroprotective effects of bilobalide on cerebral ischemia and reperfusion injury are associated with inhibition of pro-inflammatory mediator production and down-regulation of JNK1/2 and p38 MAPK activation.J Neuroinflammation. 2014 Sep 26;11:167. doi: 10.1186/s12974-014-0167-6. Jiang M, Li J, Peng Q, Liu Y, Liu W, Luo C, Peng J, Li J, Yung KK, Mo Z.
xix Effect of ginkgolide B on brain metabolism and tissue oxygenation in severe haemorrhagic stroke.Int J Clin Exp Med. 2015 Mar 15;8(3):3522-9. Chi CL, Shen DF, Wang PJ, Li HL, Zhang L
xx Neuroprotective Effects of Ginkgolide B Against Ischemic Stroke: A Review of Current Literature.Curr Top Med Chem.2015;15(21):2222-32. Nabavi SM, Habtemariam S, Daglia M, Braidy N, Loizzo MR, Tundis R, Nabavi SF
xxi The Effect of Ginkgo biloba on Functional Outcome of Patients with Acute Ischemic Stroke: A Double- blind, Placebo-controlled, Randomized Clinical Trial. November 2013; Volume 22, Issue 8, Pages e557–e563 Darioush Savadi Oskouei, MD,Reza Rikhtegar, MD, Mazyar Hashemilar, MD, Homayoun Sadeghi-Bazargani, MD, PhD, Mohsen Sharifi-Bonab, MD, Elyar Sadeghi-Hokmabadi, MD, Sina Zarrintan, MD, Ehsan Sharifipour, MD