“Prevent cardiovascular disease, understand the causes, empower yourself to take action”
Atherosclerosis is the leading cause of cardiovascular disease and mortality in the industrialized world. Current theories on the etiology of CVD formation include the endotoxin theory of damage to the tunica, the inflammation and oxidation of cholesterol theory and the hydroxyapatite theory of calcium formation. This literature review explores six leading phytonutrients and minerals, Bear garlic (Allium ursinum), Garlic (Allium Sativum), Turmeric (Curcuma longa), Delta Tocotrienol, and Vitamin D3 and Coral Calcium, shown effective against the causes of atherosclerosis. Along with a healthy diet, exercise and stress management we found that phytonutrients from plants and minerals are effective in the prevention and treatment of atherosclerosis.
Theories of Atherosclerosis Development
The endotoxin theory of atherosclerosis development postulates that the endothelium becomes injured from lipopolysaccharides (LPS), a component of the cell wall of gram negative bacteria (Wang, Si, Wu et al 2012) (and other environmental toxins), damaging the delicate tunica intima. Anilhovskaia, Kubatiev, and Llakoviev (2015) observed bacterial LPS in the blood of volunteers with atherosclerotic risk factors including obesity, diabetes, stress, kidney and intestinal disorders. Wang et al (2015) found LPS could induce lipid deposition in fibroblasts, a trigger for atherosclerosis plague formation and foam cells (Wang et al. 2012).
Inflammation and Cholesterol Theory
The inflammation and cholesterol theory is well documented and supported. Cholesterol and its byproducts form bulging atherosclerotic plaque within the arteries preventing blood flow (Tan, 2015). Free radical induced blood lipid peroxidation and peroxidized low density lipoproteins (LDL) play a central role in the pathogenesis of atherosclerosis contributing to apolipoprotein B (apo B) formation and macrophage proliferation (Bosca et al, 2000).
Vascular Calcification Theory
The vascular calcification theory shows the accumulation of calcium plaque formation. Calcium nanoparticles (CNP’s) serve as mineral chaperones which potentiate the accumulation of smooth muscle apoptotic bodies accelerating vascular calcification (Hunter et al 2014). This process leads to elevated blood pressure as the walls of the arteries thicken and become less elastic, further thickening plaque resulting in instability and probability of plaque rupture (Marieb, 2013). Coronary arterial calcification score (CACS) measures the density of coronary calcification.
In a meta-analysis of six studies among 27,622 subjects global CV risk increases as CACS scores increase (Ulusoy, Yolcu, Ipek et al 2015). Vascular calcification has recently been shown to be caused by the deposition of calcium hydroxyapatite crystals within the arterial intima (Durcan et al 2014) contributing to inflammation and atherosclerosis plaque formation (Kurabayashi, 2015). An in vitro study on rat vascular smooth muscle cells by Lei, Sinha, Nosoudi, et al (2014) showed that vascular calcification by hydroxyapatite like crystals occur on degraded elastin resulting in osteogenic transformation. Lei et al (2014) also found that removal of calcified conditions resulted in cells reverting back to normal SMC-like behavior and conditions.
Phytonutrient and Mineral Support
Bear garlic (Allium ursinum) has been used for centuries for its cardiovascular benefits and has been clinically shown to have high potential for the prevention and treatment of CVD (Sobolewska, Podolak and Makowska-Was, 2015). Its active constituents contain antimicrobial, antioxidant and other cardio-protective properties. The antimicrobial activity of Bear garlic was shown to inhibit the growth of bacteria including, Staphylococcus aureaus, Bacillus subtilis, Escherichia coli, Proteus mirabilis, and Salmonella enteritis’s. It has been shown effective against fungi including Cladosporim sp., Asperigillys niger, Rhizopus nigricans, Geotrichum candidum, Penicillim expansum, Candid lipolytica, Mycoderma, and Saccharomycopsis fibuligera (Sobolewska et al, 2015).
Antioxidant properties contained within the flavonoid and carotenoid show free radical scavenging activity. Phenolic compounds found in the leaves are high in antioxidant enzymes including catalase and peroxidase and the bulb contains superoxide dismutase (Sobolewska et al, 2013). Studies tested in vitro on human platelet aggregation showed significant inhibitory activity on ADP-induced aggregation resulting in anti-inflammatory activity (Sobolewska et al 2013).
Other cardio protective effects are reduction in blood pressure and cholesterol. In vitro studies of the leaves showed the inhibition of Angiotensin-converting enzyme which increases blood pressure by vessel constriction. Essential oils in the leaves may also play a role in regulation of the membrane functions in hypertension (Sobolewska et al, 2015). Studies on rats showed a 6 mmHg reduction in mean systolic blood pressure from rats fed Bear garlic after 45 days (Sobolewska et al 2013). Bear garlic decreased elevated circulating insulin and total cholesterol, while increasing HDL (Sobolewska et al 2015) and inhibiting cholesterol synthesis.
Garlic, (Allium sativum) Allium sativum is well researched and contains antimicrobial (Goncagul, 2010) anti hyperlipidemic, antihypertensive and anti-inflammatory (Capasso, 2013) properties. As an antimicrobial, it has been shown effect against many gram negative bacteria (Goncagul, 2010). Garlic blocks quorum sensing, the bacterial communication signal to reproduce. Jacobsen, Gennip Phipps et al (2013) found the sulfur containing ajoene in the garlic bulb is active in quorum sensing and the treatment of bacterial infections.
Turmeric, (Curcuma longa) has both antimicrobial and anti-inflammatory effects on the cardiovascular system (Hanses, 2015). Quiles et al (2002) found Curcuma longa reduces oxidative stress and damage to the thoracic and abdominal aorta of rabbits fed an atherogenic diet high in cholesterol. Curcuma longa decreases the levels of blood lipid peroxides, oxidized lipoproteins and fibrinogen (Basca et al, 2000) and significantly decreases LDL and apo B.
Delta Tocotrienol from the oils of the Annatto plant is a superior source of Vitamin E containing both Delta T3 and Gamma T3. It is a powerful antioxidant of cholesterol that supports both carotid and arterial coronary health by reducing many inflammatory biomarkers (Tan, 2015). Tocotrienol is a protease inhibitor of nitric oxide (NO) and C reactive protein mediated inflammation found in CVD (Qureshi, Khan, Mahjabeen et al 2013). Recently Tan reports on a study done by Qureshi in 2015, which found tocotrienol reduced inflammatory cytokinetic activity from 35 to 60 percent (Tan, 2015). Reduced cytokines and their role include; TNF alpha, which contributes to atherosclerotic lesion development, IL-2, elevated in patients with stable angina, IL-4, activates collagen synthesis in cardiac fibrosis, IL-6, promotes myocardial injury involved in cardiac hypertrophy, IL-8, found in vascular injury sites, and IL-10, increased in premature coronary artery disease (Tan, 2015).
Vitamin D, Calcium with Vitamin K prevent mineral decalcification and release of hydroxyapatite from the bone. Carmeliet, Dermauw, and Bouillon (2015) found that vitamin D3 deficiency may decrease bone quality and lead to osteomalacia, osteoporosis and bone fracture. A large meta-analysis found Vitamin D with calcium enhanced benefits in reducing osteoporotic non vertebrae and non-hip fractures in elderly women (Bergman, Fan, McFetridge et al, 2010). Intestinal calcium absorption is a primary target of vitamin D3. Low calcium intake will increase bone resorption and decrease bone mineralization (Carmeliet et al. 2015). Natural Medicines Database (2015) reported clinical trials and observational studies have shown calcium modestly reduces blood pressure in patients with or without hypertension and woman over the age of 45 taking dietary or supplemental calcium had lower risk of developing hypertension than woman with low calcium intake.
Anikhovskaia, A., Kubatiev, A. A., & Lakoyley, M. (2015). Endotoxin theory of atherosclerosis. Fiziologiia Cheloveka, 4(1), 106-16. Abstract retrieved from PMID: 25857184
Bergman, G. J., Fan, T., McFetridge, J. T., & Sen, S. S. (2010). Efficacy of vitamin D3 supplementation in preventing fractures in elderly women: a meta-analysis [Abstract]. Current Medical Research and Opinion, 5, 1193-201. doi:10.1185/03007991003659814
Bosca, A. R., Soler, A., Carrion, M., Diaz-Alperi, J., Bernd, A., Quintanilla, C., . . . Miquel, J. (2000). An hydroalcoholic extract of Curcuma longa lowers the apo B/apo A ratio: Implications for atherogenesis prevention [Abstract]. Mechanisms of Ageing and Development, 119(1), 41-47. doi:10.1016/S0047-6374(00)00169-X
Calcium. (2015). In Natural Medicine Data Base. Retrieved August 16, 2015, from Natural Medicines website: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=781
Capasso, A. (2013). Antioxidant action and therapeutic efficacy of Allium sativum. Molecules, 690-700. doi:10.3390/molecules18010690
Carmeliet, G., Dermauw, V., & Bouillon, R. (2015). Vitamin D signaling in calcium and bone homeostasis: A delicate balance [Abstract]. Best Practice and Research: Clinical Endocrinology Metabolism, 621-31. doi:10.1016/j.beem.2015.06.001
Durcan, L., Bolster, F., Kavanagh, E. C., & McCarthy, G. M. (2014). The structural consequences of calcium crystal deposition [Abstract]. Rheumatic Diseases Clinics of North America, 40(2), 311-28. doi:10.1016/j.rdc.2014.01.007
Goncagul, G., & Ayaz, A. (2010). Antimicrobial effect of garlic (Allium sativum). Recent Patterns in Antiinfection Drug Discoveries, 91-3. Retrieved from PMID:19929845
Hanses, M. (2015, February). Cardiovascular health nutrients [Healthy Heart Webinar]. Retrieved from www.prlabs.com
Hunter, L. W., Charlesworth, J. E., Yu, S., Lieske, J. C., & Miller, V. M. (2014). Calcifying nanoparticles promote mineralization in vascular smooth muscle cells: implications for atherosclerosis [Abstract]. International Journal of Nanomedicine, 9, 2689-98. doi:10.2147/IJN.S63189
Jakobsen, T. H., Van Gennip, M., Phipps, R. K., Shanmugham, M. S., Christensen, L. D., Alhede, M., . . . Givskov, M. (2012). AAjoene, a sulfur-rich molecule from garlic, inhibits genes controlled by quorum sensing. Antimicrobial Agents Chemotherapy, 2314-25. doi:10.1128/AAC.05919-11
Kurabayashi, M. (2015). Vascular calcification – pathological mechanism and clinical application. Role of vascular smooth muscle cells in vascular calcification [Abstract]. Clinical Calcium, 25(5), 661-9. doi:CliCa1505661669
Lei, Y., Sinha, A., Nosoudi, N., Grover, A., & Vyavahare, N. (2014). Hydroxyapatite and calcified elastin induce osteoblast-like differentiation in rat aortic smooth muscle cells. Experimental Cell Research, 323(1), 198-208. doi:10.1016/j.yexcr.2014.01.011
Marieb, E., & Hoehn, K. (2013). The cardiovascular system: blood vessels. In S. Beauparlant & G. Puttkamer (Eds.), Human Anatomy & Physiology (9th, pp. 692-745). Glenview, IL: Pearson Education, Inc.
Quiles, J., Mesa, M. D., Ramirez-Tortosa, C., Aguilera, C., Battino, M., Gil, A., & Ramirez-Tortosa, M. C. (2002). Curcuma longa extract supplementation reduces oxidaative stress and attenuates aortic fatty streak development in Rabbits [Abstract]. Arteriosclerosis, Thrombosis, and Vascular Biology, 1225-1231. doi:10.1161/01.ATV.0000020676.11586.F2
Qureshi, A., Khan, D., Mahjabeen, W., Papasian, C., & Qureshi, N. (2013). Nutritional supplement-5 with a combination of proteasome inhibitors (Resveratrol, Quercetin, & Tocotrienol) modulate age-associated biomarkers and cardiovascular lipid parameters in human subjects. Journal of Clinical Exploratory Cardiology, 4(3). doi:10: 4172/2155-9880.1000238
Sobolewska, D., Podolak, I., & Was, J. M. (2015). Allium ursinum: botanical, phytochemical and pharmacological overview. Phytochemistry Reviews: Proceedings of the Phytochemical Society of Europe, 14(1), 81-97. Retrieved from PMID: 25774103
Tan, B. (2015, February). Delta Tocotrienol and Cardiovascular Protection [Healthy Heart Webinar]. Retrieved from www.prlabs.com
Ulusoy, F., Yolcu, M., Ipek, E., Korkmaz, A., Gurler, M., & Gulbaran, M. (2015). Coronary artery disease risk factors, coronary artery calcification and coronary bypass surgery [Abstract]. Journal of Clinical Diagnostic Research, 9(5), 6-10. doi:10.7860/JCDR/2015/12081.5989
Wang, J., Si, Y., Wu, C., Sun, L., Ma, Y., Ge, A., & Li, B. (2012). Lipopolysaccharide promotes lipid accumulation in human adventitial fibroblasts via TLR4-NF-kB pathway. Lipids in Health and Disease, 11(139). doi:10.1186/1476-511X-11-139