PROFESSIONAL USE ONLY

APPLICATIONS• Cardiovascular and Metabolic Support• Microbial Support• Infl mmatory Response Support• Antioxidant Support

STEVIA

INTRODUCTIONStevia is a hydro-ethanol extract from Stevia leaf (Stevia rebaudiana). S. rebaudiana, formerly known as Eupatorium rebaudiana1, is part of the Asteraceae/Compositae family, native to Brazil and Paraguay, and used as a dietary supplement as well as a sweetener. The constituents responsible for the sweet taste are steviol glycosides, including stevioside, rebaudiosides A-F, steviolbioside, isosteviol, and dulcoside A, of which stevioside and rebaudioside A are the most abundant.2, 3 Steviol glycosides are approximately 250-300 times sweeter than sucrose.3 S. rebaudiana also contains phytosterols such as stigmasterol, beta-sitosterol, and campesterol,2 as well as flavonoids, diterpenes, triterpenes, vitamins, and minerals.2

Stevia is made at our U.S. manufacturing facility and because our extracts are made in our own facility, we control all aspects of quality, including stringent ID testing, microbial testing, and heavy metal testing. NutraMedix rigorously follows current good manufacturing practices (cGMP), as do our suppliers.

CARDIOVASCULAR AND METABOLIC SUPPORTStevioside within S. rebaudiana may help to maintain healthy blood pressure levels already within the normal range.*4 Blood pressure support from steviol glycosides may be related to alterations in glomerular filtration rate and transport of water and salt in renal tubules, resulting in changes to sodium and potassium excretion.*5 Stevioside may support vasodilation through changes

in Ca2+ ion inflow to vascular smooth muscle, and may help to maintain angiotensin II levels already within the normal range.*7

Stevioside within S. rebaudiana may help to maintain cholesterol levels already within the normal range.*7 It may help to maintain total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL), very low density lipoprotein (VLDL), and LDL/HDL ratios within the normal range. It may also help to maintain HDL levels already within a healthy range.*8,9 Additionally, Stevia may help to support hepatic cellular health.*10

S. rebaudiana may help to maintain a healthy energy intake and support satiety.*11,12

Colonic microbiota convert steviol glycosides into steviol glucuronides, which are then excreted into the urine.1 In a human study comparing Stevia to control without dietary restrictions, a 24-hour diet recall was used to track calories, carbohydrates, protein, fat, and fiber. The Stevia group was found to have a higher protein intake, lower carbohydrate intake, and lower overall calorie intake, compared to control.*9 In animal studies, S. rebaudiana has shown support of a healthy body weight.*13

S. rebaudiana may help with blood glucose support, helping to maintain both fasting and postprandial glucose levels already within the normal range.*9,14,15 It may help to decrease the intestinal absorption of glucose.*16 Steviol glycosides such as stevioside and rebaudioside A may help to support pancreatic health and maintain both insulin and glucagon levels already within the normal range.*9,17,18

S. rebaudiana extract may also help to maintain healthy insulin sensitivity in 3T3-L1 adipocytes.*19 Lastly, S. rebaudiana may help to support healthy glycogen levels in both liver and muscles.*20

MICROBIAL SUPPORTS. rebaudiana leaf extract may help with microbial support for a variety of morphological forms, including biofilms.*21, 22 In diverse morphological forms, S. rebaudiana extract exhibited strong microbial support.*21 Stevia extract may also contribute microbial support for organisms with capsids.*1,22,23

OTHER USESInflammatory Response SupportS. rebaudiana may help with inflammatory response support.*25 Stevioside and its metabolite steviol may help with cytokine support, helping to maintain healthy levels of TNF-alpha, IL-1-beta, IL-6 and NF-kappaB already within their normal ranges.*25 It may also help to maintain levels of cytokine-governing lipopolysaccharides already within the normal range.*1

Antioxidant SupportPolyphenols and flavonoids in S. rebaudiana leaves may contribute antioxidant support, helping with protection in oxidative stress.*25,26

SAFETY AND CAUTIONSS. rebaudiana is generally well tolerated. Nausea and dizziness have been known to occur, though at a similar rate to placebo, and usually resolves after the first week of use.4 While one study found S. rebaudiana to weakly inhibit CYP3A4 and CYP2C928, another concluded that there were only minor or no changes to CYP activity or expression, and thus unlikely to cause cytochrome P450 interactions with pharmaceuticals.29 S. rebaudiana may theoretically increase lithium levels due to increased diuresis and decreased lithium excretion.30 S. rebaudiana may theoretically have additive effects when taken concurrently with antidiabetic and antihypertensive medications.

* These statements have not been evaluated by the Food and Drug Administration. This product is not intended to treat, cure, or prevent any diseases.

PROFESSIONAL USE ONLY

REFERENCES

Lot #

Exp.

Jupiter, Florida 33458 USAwww.nutramedix.com561-745-2917

Dietary Supplement2 fl oz. (60 mL)

V000

000Supplement Facts

Serving Size 30 dropsServings Per Container 40Amount Per Serving

Stevia leaf extract*Daily Value not established

Other ingredients: water, ethanol (20-24%)

SHAKE WELL BEFORE EACH USE.Put 1 to 30 drops in 4 oz (1 20 mL) of water and wait one minute before drinking. Start with 1 drop (30 min. before meals) increasing slowly up to 30 drops 2-4 times per day or as directed by your physician. Do not use if pregnant or nursing. Stop use if adverse reactions develop. Keep out of reach of children.

†This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

STEVIAMICROBIAL SUPPORT †

1.5 mL*

1 Marcinek, K. & Krejpcio, Z. (2016). Stevia rebaudiana Bertoni: health promoting properties and therapeutic applications. Journal für verbraucherschutz und lebensmittelsicherheit, 11, 3-8.2 Goyal, S. K., Samsher, & Goyal, R. K. (2010). Stevia (Stevia rebaudiana) a bio-sweetener: a review. International Journal of Food Sciences and Nutrition, 61(1), 1-10.3 Momtazi-Borojeni, A. A., Esmaeili, S. A., Abdollahi, E., & Sahebkar, A. (2017). A Review on the Pharmacology and Toxicology of Steviol Glycosides Extracted from Stevia rebaudiana. Current pharmaceutical design, 23(11), 1616–1622.4 Chan, P., Tomlinson, B., Chen, Y. J., Liu, J. C., Hsieh, M. H., & Cheng, J. T. (2000). A double-blind placebo-controlled study of the effectiveness and tolerability of oral stevioside in human hypertension. British journal of clinical pharmacology, 50(3), 215–220.5 Melis M. S. (1997). Effects of Steviol on renal function and mean arterial pressure in rats. Phytomedicine : international journal of phytotherapy and phytopharmacology, 3(4), 349–352.6 Wong, K. L., Lin, J. W., Liu, J. C., Yang, H. Y., Kao, P. F., Chen, C. H., Loh, S. H., Chiu, W. T., Cheng, T. H., Lin, J. G., & Hong, H. J. (2006). Antiproliferative effect of isosteviol on angiotensin-II-treated rat aortic smooth muscle cells. Pharmacology, 76(4), 163–169.7 Adisakwattana, S., Intrawangso, J., Hemrid, A., Chanathong, B., & Mäkynen. (2012). Extracts pf edible plants inhibit pancreatic lipase, cholesterol esterase, and cholesterol micellization and bind to bile acids. (2012). Food Technology & Biotechnology, 50(1):11-16.8 Ahmad, U., Ahmad, R. S., Arshad, M. S., Mushtaq, Z., Hussain, S. M., & Hameed, A. (2018). Antihyperlipidemic efficacy of aqueous extract of Stevia rebaudiana Bertoni in albino rats. Lipids in health and disease, 17(1), 175.9 Ritu, M., & Nandini, J. (2016). Nutritional composition of Stevia rebaudiana, a sweet herb, and its hypoglycaemic and hypolipidaemic effect on patients with non-insulin dependent diabetes mellitus. Journal of the science of food and agriculture, 96(12), 4231–4234.10 Holvoet, P., Rull, A., García-Heredia, A., López-Sanromà, S., Geeraert, B., Joven, J., & Camps, J. (2015). Stevia-derived compounds attenuate the toxic effects of ectopic lipid accumulation in the liver of obese mice: a transcriptomic and metabolomic study. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 77, 22–33.11 Farhat, G., Berset, V., & Moore, L. (2019). Effects of Stevia Extract on Postprandial Glucose Response, Satiety and Energy Intake: A Three-Arm Crossover Trial. Nutrients, 11(12), 3036.12 Stamataki, N. S., Scott, C., Elliott, R., McKie, S., Bosscher, D., & McLaughlin, J. T. (2020). Stevia Beverage Consumption prior to Lunch Reduces Appetite and Total Energy Intake without Affecting Glycemia or Attentional Bias to Food Cues: A Double-Blind Randomized Controlled Trial in Healthy Adults. The Journal of nutrition, 150(5), 1126–1134.13 Jeppesen, P. B., Hong, J., Abudula, R., & Hermansen, K. (2008). Isosteviol increases insulin sensitivity and changes gene expression of key insulin regulatory genes and transcription factors in islets of the diabetic KKAy mouse. Diabetes, Obesity, and Metabolism, 10(10), 939-949.14 Pane, Y. S., Ganie, R. A., Lindarto, D., & Lelo, A. (2018). The effect of gambier extract on the levels of malondialdehyde, superoxide dismutase, and blood glucose in type 2 diabetes mellitus patients. Asian Journal of Pharmaceutical and Clinical Research, 11(10), 121.15 Gregersen, S., Jeppesen, P. B., Holst, J. J., & Hermansen, K. (2004). Antihyperglycemic effects of stevioside in type 2 diabetic subjects. Metabolism: clinical and experimental, 53(1), 73–76.16 Toskulkao, C., Sutheerawatananon, M., Wanichanon, C., Saitongdee, P., & Suttajit, M. (1995). Effects of stevioside and steviol on intestinal glucose absorption in hamsters. Journal of nutritional science and vitaminology, 41(1), 105–113.17 Philippaert, K., Pironet, A., Mesuere, M., Sones, W., Vermeiren, L., Kerselaers, S., Pinto, S., Segal, A., Antoine, N., Gysemans, C., Laureys, J., Lemaire, K., Gilon, P., Cuypers, E., Tytgat, J., Mathieu, C., Schuit, F., Rorsman, P., Talavera, K., Voets, T., & Vennekens, R. (2017). Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. Nature communications, 8, 14733. 18 Jeppesen, P. B., Dyrskog, S. E., Agger, A., Gregersen, S., Colombo, M., Xiao, J., & Hermansen, K. (2006). Can stevioside in combination with a soy-based dietary supplement be a new useful treatment of type 2 diabetes? An in vivo study in the diabetic goto-kakizaki rat. The review of diabetic studies : RDS, 3(4), 189–199. 19 Watal, G., Dhar, P., Srivastava, S. K., & Sharma, B. (2014). Herbal medicine as an alternative medicine for treating diabetes: the global burden. Evidence-based complementary and alternative medicine : eCAM, 2014, 596071.20 Aghajanyan, A., Movsisyan, Z., & Trchounian, A. (2017). Antihyperglycemic and Antihyperlipidemic Activity of Hydroponic Stevia rebaudiana Aqueous Extract in Hyperglycemia Induced by Immobilization Stress in Rabbits. BioMed research international, 2017, 9251358.21 Theophilus, P. A., Victoria, M. J., Socarras, K. M., Filush, K. R., Gupta, K., Luecke, D. F., & Sapi, E. (2015). Effectiveness of Stevia Rebaudiana Whole Leaf Extract Against the Various Morphological Forms of Borrelia Burgdorferi in Vitro. European journal of microbiology & immunology, 5(4), 268–280.22 Preethi, D., Sridhar, T. M., Josthna, P., & Naidu, C. V. (2011). Studies on antibacterial activity, phytochemical analysis of stevia rebaudiana (Bert.) – an important calorie free biosweetner. (2011). Journal of Ecobiotechnology, 3(7):05-10.23 Debnath, M. (2008). Clonal propagation and antimicrobial activity of an endemic medicinal plant Stevia rebaudiana. Journal of medicinal plants research, 1(2), 045-051.24 Jayaraman, S., Manoharan, M. S., & Illanchezian, S. (2008). In-vitro antimicrobial and antitumor activities of Stevia rebaudiana (Asteraceae) leaf extracts. Tropical Journal of Pharmaceutical Research, 7(4), 1143-1149.25 Boonkaewwan, C., & Burodom, A. (2013). Anti-inflammatory and immunomodulatory activities of stevioside and steviol on colonic epithelial cells. Journal of the science of food and agriculture, 93(15), 3820–3825.26 Marcinek, K., & Krejpcio, Z. (2015). Stevia rebaudiana Bertoni - chemical composition and functional properties. Acta scientiarum polonorum. Technologia alimentaria, 14(2), 145–152.27 El-Mesallamy, A., Mahmoud, S. A., Elazab, K. M., Hussein, S., & Hussein, A. M. (2018). Attenuation of metabolic dysfunctions in the skeletal muscles of type 1 diabetic rats by Stevia rebaudiana extracts, via AMPK upregulation and antioxidant activities. Acta scientiarum polonorum. Technologia alimentaria, 17(3), 289–297.28 Dusek, J., Carazo, A., Trejtnar, F., Hyrsova, L., Holas, O., Smutny, T., Micuda, S., & Pavek, P. (2017). Steviol, an aglycone of steviol glycoside sweeteners, interacts with the pregnane X (PXR) and aryl hydrocarbon (AHR) receptors in detoxification regulation. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 109(Pt 1), 130–142.29 Thøgersen, R., Petrat-Melin, B., Zamaratskaia, G., Grevsen, K., Young, J. F., & Rasmussen, M. K. (2018). In vitro effects of rebaudioside A, stevioside and steviol on porcine cytochrome p450 expression and activity. Food chemistry, 258, 245–253.30 Natural Medicines. (2021, March 27). Stevia [monograph]. http://naturalmedicines.therapeuticresearch.com.31 National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 12875216. Retrieved March 28, 2021 from https://pubchem.ncbi.nlm.nih.gov/compound/12875216.