View source for Dietary supplement against atherosclerosis

A scientifically proven dietary supplement that will allow people with initial forms of atherosclerosis to prolong their lives:

1. ß-cyclodextrin (a cheap prophylactic agent that reduces blood cholesterol levels);

2. acarbose (a prophylactic agent that reduces blood glucose levels);

3. homogenate of 2-3 week old red cabbage sprouts (contains sulforaphane, tocopherols and flavones);

4. celery homogenate (contains apigenin - protects NAD+, quercetin - senolytic); resveratrol metabolite Lunularin (Unfortunately, can cause severe allergies)

5. Nicotinic acid (a cheap precursor to NAD+); GPR109A receptor activator.

6. Homogenate of a mixture of hazelnuts (its oil contains palmitoleic acid) with flax seeds (20%). This homogenate gives a pleasant taste to the product. You can use macadamia nuts instead of hazelnuts.

7. Cocoa powder. Gives a pleasant taste to the product and is also rich in microelements (such as calcium, magnesium, copper, phosphorus, potassium, zinc). Contains flavonoids, caffeine and theobromine.

This cheap and effective dietary supplement against aging and for the prevention of cardiovascular diseases - the main cause (about 50%) of all deaths can be stored in a refrigerator for a long time in disposable vacuum packagings. All components are natural, cheap and easy to produce. Take 1-2 times a week with food.
== JUSTIFICATION ==
'''ß-cyclodextrin''' allows you to quickly turn into powder the liquid homogenates listed below and therefore serves as the basis of the drug, and also contributes to the safety of all the listed components during storage. In addition, feeding ß-cyclodextrin leads to a decrease in blood cholesterol levels and promotes regression of atherosclerotic plaques.<ref>Mahjoubin-Tehran, M., Kovanen, P. T., Xu, S., Jamialahmadi, T., & Sahebkar, A. (2020). Cyclodextrins: Potential therapeutics against atherosclerosis. Pharmacology & Therapeutics, 214, 107620. PMID: 32599008 [https://doi.org/10.1016/j.pharmthera.2020.107620 DOI: 10.1016/j.pharmthera.2020.107620]</ref><ref>Coisne, C., Tilloy, S., Monflier, E., Wils, D., Fenart, L., & Gosselet, F. (2016). Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases. Molecules, 21(12), 1748. DOI:10.3390/molecules21121748</ref><ref>Yao, J., Ho, D., Calingasan, N. Y., Pipalia, N. H., Lin, M. T., & Beal, M. F. (2012). Neuroprotection by cyclodextrin in cell and mouse models of Alzheimer disease. The Journal of experimental medicine, 209(13), 2501-2513. DOI:10.1084/jem.20121239</ref><ref>Sebastian Zimmer, Alena Grebe, Siril S. Bakke et al., and Eicke Latz (2016). Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming. Science Translational Medicine: 8(333), 333ra50 DOI:10.1126/scitranslmed.aad6100</ref><ref>Mistry, R. H., Verkade, H. J., & Tietge, U. J. (2017). Absence of intestinal microbiota increases ß-cyclodextrin stimulated reverse cholesterol transport. Molecular Nutrition & Food Research. DOI:10.1002/mnfr.201600674</ref>

ß-cyclodextrin is an approved food additive under the code '''E 459'''. It is an excellent ingredient for masking the unpleasant taste of celery homogenate & an excellent preservative that protects other components from exposure to light and also improves the absorption of other components (for example, apigenin) - they dissolve better in the stomach.<ref>Wu, W., Zu, Y., Zhao, X., Zhang, X., Wang, L., Li, Y., ... & Lian, B. (2017). Solubility and dissolution rate improvement of the inclusion complex of apigenin with 2-hydroxypropyl-β-cyclodextrin prepared using the liquid antisolvent precipitation and solvent removal combination methods. Drug Development and Industrial Pharmacy, 1-30. http://www.tandfonline.com/…/…/10.1080/03639045.2017.1318900</ref><ref>Aytac, Z., & Uyar, T. (2016). Antioxidant activity and photostability of α-tocopherol/β-cyclodextrin inclusion complex encapsulated electrospun polycaprolactone nanofibers. European Polymer Journal, 79, 140-149. http://www.sciencedirect.com/…/article/pii/S0014305716303111</ref>

'''Cavadex''' is a Beta-Cyclodextrin based product developed by the Australian biopharmaceutical company [https://www.cholrem.com Cholrem]. It is designed to remove cholesterol from damaged and narrowed arteries, leading to increased blood flow. CAVADEX daily ('''RemChol''') demonstrated reduced cholesterol levels and plaque reduction within two months.<ref>István Puskás (2022). [https://cyclodextrinnews.com/2022/10/25/australian-company-pioneering-cavadextrin-to-reversing-the-effects-of-hart-disease/ Australian company pioneering Cavadextrin for regression of atherosclerosis]. Cyclodextrin News</ref><ref>[https://www.heartfixer.com/Cyclodextrin.htm Cyclodextrin Therapy to Rapidly Reverse Atherosclerotic Vascular Disease]</ref>
 
'''Acarbose''' is a medicine used under the name glucobay to prevent diabetes. In small quantities - 25 mg (1/4 of the usual medicinal dose) it can be used by healthy people. From the official instructions: “In patients with impaired glucose tolerance, regular administration of acarbose leads to a reduction in the risk of developing type 2 diabetes mellitus by 25%. In addition, they significantly reduce the incidence of cardiovascular diseases (by 49%) and heart attack myocardium (by 91%)." The intestinal environment – the microbiome – also improves.<ref>Hanefeld, M., Cagatay, M., Petrowitsch, T., Neuser, D., Petzinna, D., & Rupp, M. (2004). Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. European heart journal, 25(1), 10-16.</ref><ref>Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M, et al. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: The STOP-NIDDM trial. JAMA. 2003;290:486–94. doi: 10.1001/jama.290.4.486</ref><ref>Zhang, X., Fang, Z., Zhang, C., Xia, H., Jie, Z., Han, X., ... & Ji, L. (2017). Effects of Acarbose on the Gut Microbiota of Prediabetic Patients: A Randomized, Double-blind, Controlled Crossover Trial. Diabetes Therapy, 8(2), 293-307. doi:10.1007/s13300-017-0226-y https://link.springer.com/article/10.1007/s13300-017-0226-y</ref>

In the future, it is planned to replace acarbose with a homogenate of buckwheat sprouts treated with 0.05% NaHCO3 for 96 hours before harvesting.<ref>Qin, P., Wei, A., Zhao, D., Yao, Y., Yang, X., Dun, B., & Ren, G. (2017). Low concentration sodium bicarbonate improves the bioactive compound levels and antioxidant and α-glucosidase inhibitory activities of tartary buckwheat sprouts. Food Chemistry, 224, 124-130.
https://doi.org/10.1016/j.foodchem.2016.12.059</ref>

'''Homogenate of red cabbage sprouts''' - retains a huge amount of vitamins, contains many times more carotene and vitamin C (compared to traditional white cabbage). In addition, anthocyanins - substances that color cabbage in its characteristic color - protect the walls of blood vessels, strengthen and make them elastic. In addition, sprouts are rich in tocopherol, 40 times more than in mature cabbage<ref>(https://agnr.umd.edu/news/mighty-microgreens)</ref>  and reduce inflammatory processes. To facilitate homogenization, the starting material can be cooled with liquid nitrogen or carbon dioxide (dry ice) and then mixed with ß-cyclodextrin.<ref>Huang, H., Jiang, X., Xiao, Z., Yu, L., Pham, Q., Sun, J., ... & Wang, T. T. (2016). Red Cabbage Microgreens Lower Circulating Low-Density Lipoprotein (LDL), Liver Cholesterol, and Inflammatory Cytokines in Mice Fed a High-Fat Diet. Journal of Agricultural and Food Chemistry, 64(48), 9161-9171. DOI: 10.1021/acs.jafc.6b03805</ref><ref>Jiang, X., Huang, H., Xiao, Z., Yu, L., Pham, Q., Yu, L. L., ... & Wang, T. T. (2016). Lipids and Cholesterol-Lowering Activity of Red Cabbage Microgreens. The FASEB Journal, 30(1 Supplement), 431-8. http://www.fasebj.org/content/30/1_Supplement/431.8.short</ref>

'''Celery homogenate''' contains apigenin (4', 5, 7-trihydroxyflavone) - a flavone that is reported to have anti-inflammatory, antioxidant and anti-carcinogenic properties, and also protects the skin from aging. Apigenin is an inhibitor of [[CD38]] NADase (activity which increases with aging and leads to an age-related decrease in NAD and mitochondrial dysfunction) protects the body from premature aging.<ref>Camacho-Pereira, J., Tarrago, M. G., Chini, C. C., Nin, V., Escande, C., Warner, G. M., ... & Chini, E. N. (2016). CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell metabolism, 23(6), 1127-1139. http://doi.org/10.1016/j.cmet.2016.05.006</ref><ref>Escande, C., Nin, V., Price, N. L., Capellini, V., Gomes, A. P., Barbosa, M. T., ... & Chini, E. N. (2013). Flavonoid Apigenin Is an Inhibitor of the NAD+ ase CD38. Diabetes, 62(4), 1084-1093. https://doi.org/10.2337/db12-1139</ref><ref>Choi, S., Youn, J., Kim, K., Joo, D. H., Shin, S., Lee, J., ... & Ahn, K. J. (2016). Apigenin inhibits UVA-induced cytotoxicity in vitro and prevents signs of skin aging in vivo. International journal of molecular medicine, 38(2), 627-634.</ref><ref>Tang, D., Chen, K., Huang, L., & Li, J. (2017). Pharmacokinetic properties and drug interactions of apigenin, a natural flavone. Expert Opinion on Drug Metabolism & Toxicology, 13(3), 323-330.http://dx.doi.org/10.1080/17425255.2017.1251903</ref><ref>Zhou, X., Wang, F., Zhou, R., Song, X., & Xie, M. (2017). Apigenin: A current review on its beneficial biological activities. Journal of Food Biochemistry. DOI: 10.1111/jfbc.12376</ref><ref>Kevin M Perrott, Christopher D Wiley... Judith Campisi (2017). Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells. Geroscience 39:2 161-173 https://link.springer.com/article/10.1007/s11357-017-9970-1</ref>

In addition, celery contains '''Lunularin''', a derivative of [[resveratrol]]. 

Unfortunately, celery can cause a severe allergic reaction and is therefore not suitable for everyone.

In addition to apigenin, celery contains [[quercetin]], a [[Senolytics|senolytic]] that destroys old cells that harm the body with their secretions. For its better absorption, ß-cyclodextrin is also required.<ref>Kleemann, R., Verschuren, L., Morrison, M., Zadelaar, S., van Erk, M. J., Wielinga, P. Y., & Kooistra, T. (2011). Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models. Atherosclerosis, 218(1), 44-52.</ref><ref>Lin, W., Wang, W., Wang, D., & Ling, W. (2017). Quercetin protects against atherosclerosis by inhibiting dendritic cell activation. Molecular Nutrition & Food Research. DOI: 10.1002/mnfr.201700031</ref><ref>Aytac, Z., Kusku, S. I., Durgun, E., & Uyar, T. (2016). Quercetin/β-cyclodextrin inclusion complex embedded nanofibres: Slow release and high solubility. Food chemistry, 197, 864-871. http://www.sciencedirect.com/…/article/pii/S0308814615301965</ref>
 
'''Celery''' contains dietary fiber, reduces hypertension and prevents platelet aggregation (because it contains coumarin derivatives).<ref>Santoso, M. B., Bangun, A. V., & Hakim, L. G. (2016). COMBINATION EFFECTS CELERY AND CARROTS TO DECREASE BLOOD PRESSURE IN THE ELDERLY WITH HYPERTENSION GRADE I. http://eprints.ners.unair.ac.id/353/</ref>
 
'''Nicotinic acid''', also known as '''niacin''', (a cheap precursor to NAD+); its benefits are known - nicotinic acid, through its receptor '''GPR109A, fights atherosclerosis'''.<ref>Lukasova, M., Malaval, C., Gille, A., Kero, 1. J., & Offermanns, S. (2011). Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cells. The Journal of clinical investigation, 121(3), 1163-1173. http://www.jci.org/articles/view/41651</ref> It is important to note that unlike nicotinic acid, nicotinamide does not directly affect the GPR109A receptor.<ref>Santolla, M. F., De Francesco, E. M., Lappano, R., Rosano, C., Abonante, S., & Maggiolini, M. (2014). Niacin activates the G protein estrogen receptor (GPER)-mediated signaling. Cellular signaling, 26(7), 1466-1475. https://doi.org/10.1016/j.cellsig.2014.03.011</ref>
 
Additionally, niacin supplementation is known to increase NAD+ levels as well as DNA repair efficiency and improve genomic stability.<ref>Weidele, K., Beneke, S., & Bürkle, A. (2017). The NAD+ precursor nicotinic acid improves genomic integrity in human peripheral blood mononuclear cells after X-irradiation. DNA repair, 52, 12-23. http://doi.org/10.1016/j.dnarep.2017.02.001</ref>
 
Palmitoleic acid from '''hazelnut homogenate''' (or macadamia nuts) protects the body from type 2 diabetes and chronic inflammation, and prevents atherosclerosis.<ref>Yang, Z. H., Miyahara, H., & Hatanaka, A. (2011). Chronic administration of palmitoleic acid reduces insulin resistance and hepatic lipid accumulation in KK-A y Mice with genetic type 2 diabetes. Lipids in health and disease, 10(1), 120.</ref><ref>Çimen, I., Kocatürk, B., Koyuncu, S., Tufanlı, Ö., Onat, U. I., Yıldırım, A. D., ... & Watkins, S. M. (2016). Prevention of atherosclerosis by bioactive palmitoleate through suppression of organelle stress and inflammasome activation. Science Translational Medicine, 8(358), 358ra126-358ra126. DOI: 10.1126/scitranslmed.aaf9087</ref><ref>Frigolet, M. E., & Gutiérrez-Aguilar, R. (2017). The Role of the Novel Lipokine Palmitoleic Acid in Health and Disease. Advances in Nutrition: An International Review Journal, 8(1), 173S-181S. doi: 10.3945/an.115.011130</ref><ref>Souza, C. O., Teixeira, A. A., Biondo, L. A., Silveira, L. S., Calder, P., & Rosa Neto, J. C. (2017). Palmitoleic acid reduces the inflammation in LPS stimulated macrophages by inhibition of NFκB, independently of PPARs. Clinical and Experimental Pharmacology and Physiology. DOI: 10.1111/1440-1681.12736</ref>

'''Cocoa powder''' reduces the risk of stroke (at least in women) and improves taste.<ref>Steinberg, F. M., Bearden, M. M., & Keen, C. L. (2003). Cocoa and chocolate flavonoids: implications for cardiovascular health. Journal of the American Dietetic Association, 103(2), 215-223.</ref><ref>Dong, J. Y., Iso, H., Yamagishi, K., Sawada, N., Tsugane, S., & Japan Public Health Center–based Prospective Study Group. (2017). Chocolate consumption and risk of stroke among men and women: A large population-based, prospective cohort study. Atherosclerosis, 260, 8-12.http://doi.org/10.1016/j.atherosclerosis.2017.03.004</ref>
 
In the future, it may be possible to partially replace cocoa powder with sorghum seed bran extract (sorghum bran is known to be rich in flavonoids - there are more of them than in blueberries.<ref>http://edaplus.info/produce/sorghum.html)</ref><ref>김주연, 노상규, 우관식, & 서명철. (2016). 흰쥐에서 수수추출물이 트랜스지방산이 함유된 지방과 콜레스테롤의 흡수에 미치는 영향. (Sorghum Extract Lowers Lymphatic Absorption of Trans Fat and Cholesterol in Rats) 한국식품영양과학회지,45(6), 783-788.</ref><ref>Noh, S. K., Kong, D., & Kim, J. (2015). Filtered Coffee Lowers the Intestinal Absorption of Cholesterol in Rats. 한국식품영양과학회 학술대회발표집, 384-384.</ref>  Luteolinidin from ''Sorghum'' extract is a powerful CD38 inhibitor.<ref>Boslett, J., Hemann, C., Zhao, Y. J., Lee, H. C., & Zweier, J. L. (2017). Luteolinidin protects the postischemic heart through CD38 inhibition with preservation of NAD (P)(H). Journal of Pharmacology and Experimental Therapeutics, 361(1), 99-108. PMID: 28108596 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363772/ PMC5363772] DOI: 10.1124/jpet.116.239459</ref>

== Expected life years gained for 60-year-olds who change from a typical Western diet to an optimized diet (changes indicated in gram) ==

Expected life years gained for 60-year-old female adults (left forest plot) and males (right forest plot)] from the United States who change from a typical Western diet to an optimized or feasible approach diet with changes indicated in gram.<ref>Fadnes LT, Økland J-M, Haaland ØA, Johansson KA (2022) Estimating impact of food choices on life expectancy: A modeling study. PLoS Med 19(2): e1003889. https://doi.org/10.1371/journal.pmed.1003889</ref> See: [https://commons.wikimedia.org/wiki/File:Expected_life_years_gained_for_60-year-olds_in_U.S._who_change_from_a_typical_Western_diet_to_an_optimized_diet_(changes_indicated_in_gram).png Original file ]

== References ==
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