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GARLIC, BITTER MELON, AND CREATINE

Da ria Bib a n , Fa rin Fa ra h z a d i,& Da n ie lle Tra ffic a n d a

Garlic, Creatine, & Bitter Melon Content


Introduction Uses and Claims Contraindications Interactions Recent Research

Creatine

Introduction
Creatine is a naturally occurring amino acid that our body produces or ingested through dietary sources.
The best sources are: lean red meats, fish, and especially wild game (Ehrlich, 2011).

Creatines role in the body is to supply energy quickly to the muscle in a one step energy system. Supplemental Creatine started to gain popularity in the 1990s An ergogenic supplement Use is allowed by the International Olympic Committee & National Collegiate Athletic Association

Active Ingredient
Creatine supplement is commonly sold as Creatine Monohydrate (CM). Creatine supplement is most often sold in powdered form.
Also comes as liquids, tablets, energy bars, drink mixes, etc.

CM is manufactured in the laboratory usually in a secret patented way.


Supplement companies do not have to disclose how the supplement is made as long as they are following GMPs.

A common way of producing CM is by combining cyanamide and sarcosinate using the cyanamide route
This is the procedure Creapure uses

Uses and Claims


Natural Medicines Comprehensive Database rates the effectiveness of supplements (based off scientific evidence) as: Effective, possibly effective, likely effective, possibly ineffective, ineffective, and insufficient evidence. Possibly effective
Increasing strength and endurance in people with heart failure Slow the worsening symptoms of Parkinsons disease Creatine is most commonly used to improve exercise performance during brief high intense activity and increase muscle strength

Insuffiecient evidence for effectiveness


High cholesterol Depression Huntingtons disease

Uses and Claims


How Creapure Works http://www.creapure.c om/en/creapureevery-day/why-doescreapure-work

(Intergratedsupplements, 2013, 100% Creapure Creatine)

Uses and Claims


The recommended dose is 2-5g (or 0.03g/kg weight) daily

To improve physical performance a loading dose of 20g daily for 5 days, followed by the recommended dose.

(Medline Plus, 2011)

Contraindications
People with kidney disease or diabetes
High doses could cause worsen of disease

Pregnant and breastfeeding women

No recommended for athletes under 18

Interactions
Interactions with medications
NSAIDS Diuretics H2 blockers

Interactions with supplements


Caffeine Coenzyme Q10

Interactions with nutrients


Carbohydrates

Hickner, R. C., Dyck, D. J., Hatley, H., & Byrd, P. (2010). The effect of 28 days creatine ingestion on muscle metabolism and performance of a simulated cycling road race. Journal of International Society of Sports Nutrition, 7(26). Retrieved October 27, 2013, from the PubMed.gov database.

Purpose: The effects of creatine supplementation on muscle metabolism and exercise performance during a simulated endurance road race was investigated.

Conclusion: Creatine supplementation may increase resting muscle total creatine, muscle creatine phosphate, and plasma volume, it does not improve sprint performance at the end of endurance cycling exercise.

Lugareal, R., & al. (2013). Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein diet? Journal of International Society of Sports Nutrition, 10(26). Retrieved October 28, 2013, from http://www.jissn.com/content/10/1/36

Purpose: Determine the effects of long term creatine supplementation on kidney function in resistance-trained individuals ingesting a high protein diet. Conclusion: After 12 weeks of supplementation creatine supplementation (20g for 5 days followed maintenance of 5g/ day) did not affect kidney function versus placebo

Fumagalli, S., Fattirolli, F., Guarducci, L., Cellai, T., Baldasseroni, S., Tarantini, F., Di Bari, M., Masotti, G. and Marchionni, N. (2011). Coenzyme Q10 terclatrate and creatine in chronic heart failure: A randomized, placebo-controlled, doubleblind study. Clinical Cardiology, 34: 211217. doi: 10.1002/clc.20846

Purpose: Evaluate the effects of the combination of oral supplemental coenzyme Q10 and creatine in patients with stable chronic heart failure Conclusion: After 2 months of taking a combination of 320mg coenzyme Q10 and 340mg creatine daily, along with conventional drug therapy, participants showed an improvement in total work capacity and peak VO2 levels

Summary
Creatine monohydrate (CM) is generally recognized as safe for short term use It is most effective for improving muscle strength and physical performance People with kidney disease or diabetes are not advised to take creatine supplement because the risk of worsening disease May interaction with drugs, nutrients, and other supplements More research is needed

Bitter Melon

Bitter Melon
Introduction Uses and Claims Active Ingredients Contraindications Interactions Recent Research

Bitter Melon
Momordica charantia Grown in tropical climates of Asia, East Africa, Caribbean, and South America All parts of the plant are used: root, leaves, fruit, juice, and seeds

Active ingredients of bitter melon


Active Ingredients:
Charantin (seeds, leaves, and fruit)
hypoglycemic properties

Polypeptide-p (seeds, leaves, and fruit)


an insulin-like hypoglycemic protein mimics the action of human insulin in the body

Vicine (seeds)
a glycoalkaloid, a pyrimidine nucleoside induces hypoglycemia

Antioxidants:
Linolenic Acid Curcubitacins
(momordicosides, momordicines, karavilosides, charnatosides)

Uses and Claims


India:
Used in Ayurvedic medicine to treat diabetes, liver disease, gout, and arthritis

Thailand:
Herb specialists use the leaves in a green recipe to help with fever relief; and the root for blood disorders

Home remedies:
Use of the whole fruit and juice to treat upset stomach, ulcers, and menstrual disorders Recommended Dosage:
3.5 oz. of whole fruit or 2 oz. of fresh juice daily

Evidence showing the phytochemicals in bitter melon may help with psoriasis, leukemia, and cancer. Has been used as supportive treatment for HIV/AIDS

Uses and Claims Bitter Melon


Claims:
Fruit to be among the most bitter foods Traditional Ayurvedic herb for healthy glucose metabolism

Capsules
Dosage: 1(500mg) capsule 2X daily

Fresh freeze-dried Powder

Contraindications
Toxicity from seeds seen in children
Found to cause vomiting, diarrhea, and death

Further toxicity from seeds in individuals lacking glucose6-phosphate-dehydrogenase


Vicine found in the seeds, also found in fava beans, may cause fauvism.

Pregnant women
induction of contractions and bleeding

Interaction with Herbs/supplements


Cinnamon bark Flaxseed Fenugreek Alphalipoic acid

Interaction with Medications


Anti-diabetic drugs:
Glipizide, Glimepride, Glyburide, Metformin, Repaglinide, Nateginide, Ploglitazone, Exenatide, Sliagliptin, Insulin, and other glucose lowering drugs

Possible interaction with drugs used to treat:


HIV, cholesterol, arthritis, cancer, fever, pain, and blood pressure

Nivitabishekan, N., Asad, M., & Prasad, V.S. (2009). Pharmacodynamic interaction of Momordica charantia with rosiglitazone in rats. ChemicoBiological Interactions 177, 247253. Purpose: To determine the interaction between Rosiglitazone (antidiabetic drug) given at two different dosages and bitter melon extract, using Type I & Type II diabetic induced rats Results: Found both Rosiglitazone and bitter melon lower blood glucose levels when given separately. A more significant (p < 0.05) and additive effect was seen when bitter melon and Rosiglitazone were combined. Conclusion: Bitter Melon augments the hypoglycemic effect of Rosiglitazone. A reduction in dosage of medication will achieve enhanced therapeutic effect when supplemented with bitter melon (0.51%) Charantin extract, and reduce side effects from medication.

Fuangchan, A., Sonthisombat, P., Seubnukarn, T., Chanouan, R., Chotchaisuwat, P., et al. (2011). Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients. Journal of Ethnopharmacology, 134(2), 422-428.

Purpose: To determine the efficacy and safety of three different daily doses (500,1000, & 2000mg) of bitter melon, compared to daily dose of 1000mg of Metformin for 4 weeks Conclusion: Found bitter melon group & Metformin group at daily dose of 2000mg had a significant (p<0.05) decline in fructosamine levels. However, the hypoglycemic effect of bitter melon at 2000mg was less than that of Metformin at 1000mg

Kwatra, D., Subramaniam, D. , Ramamoorthy, P., Standing, D., Moran, E., et al. (2013). Methanolic extracts of bitter melon inhibit colon cancer stem cells by affecting energy homeostasis and autophagy. Evidence-based Complementary and Alternative Medicine : ECAM, 2013, 702869.

Purpose:
Results: Whole fruit and skin extracts of bitter melon showed significant inhibition of cell proliferation and colony formation, with whole fruit of bitter melon showing greater efficacy. Cells were arrested at the S phase of cell cycle. Found extracts target stem cells within cancer, thus cells were undergoing autophagy and not apoptosis. Found extract to effect cellular ATP through AMPKmediated pathway Conclusion: Whole fruit and skin extract can be an effective, preventative/therapeutic agent for colon cancer.

Summary
Both natural and supplemental forms of bitter melon provided a variety of therapeutic effects Most prominent: lowering/maintaining blood glucose levels Studies suggest bitter melon extract may be helpful to supplement with anti-diabetic medication (taking caution w/ attention to dosage management) Further research needed to determine bitter melons cytotoxic properties inhibiting cancer cells. Contraindicated for children, pregnant women, individuals susceptible to fauvism, and individuals taking anti-diabetic medication

GARLIC
Introduction Uses and Claims Contraindications Interactions Recent Research

Introduction
Allium sativum One of the most popular herbal remedies
Used for thousands of years for treating various ailments

Supplement is derived from the bulb of the plant


Available in the form of powder, tablets, oily preparations, and aqueous alcoholic extracts of fresh or aged garlic

Introduction
Active compounds: Alliin Alicin Organosulfur compounds such as: Diallyl sulfide confer the main Diallyl disulfide pharmacological Diallyl trisulfide effect Different garlic preparations have different chemical composition and bioavailability

Uses and Claims


Recommended dose: 4 g fresh garlic
equivalent to 8 mg garlic oil or 600 to 900 mg garlic powder standardized to 1.3 % alliin content

There is a discrepancy between the dose used in in vitro and in vivo studies and the dose used in clinical trials
This lead to conflicting results regarding the benefits of garlic

Uses and Claims


Antioxidative, antibacterial, antiparasitic, antilipidemic, antihypertensive, antiatherosclerotic, antithrombotic, antidiabetic, and anticancer properties Has an effect on different factors related to cardiovascular disease such as: Suppressing platelet aggregation Inhibiting angiogenesis Preventing cardiac hypertrophy Preventing hyperlipidemia Preventing hyperglycemia Inducing vasorelaxation

Claims

Contraindications
Common side effect is breath and body odor; odorless products are available Raw garlic can cause gastrointestinal upset, flatulence, and changes in the intestinal flora Due to its antiplatelet properties, it is advised to stop garlic intake 10 days before surgery to avoid postoperative bleeding One case study suggested that garlic increased INR of patients taking Warfarin
More studies are needed to clarify this possible interaction Patients on blood thinners should avoid garlic

Interactions
HIV-protease inhibitors
Garlic inhibits Pgp and CYP3A4 activity, leading to possible toxic levels of HIV-inhibitors such as Saquinavir

Calcium channel antagonists


Used for management of hypertension and angina (e.g. Nifedipine) Garlic inhibits intestinal CYP3A, therefore less drug will be metabolized, so its oral availability will be increased, leading to a possible toxicity

Blood thinners
One case report suggested garlic interacted with Warfarin by potentiation

Berginc, K., Milisav, I., Kristl, A. (2010). Garlic flavonoids and organosulfur compounds: Impact on the hepatic pharmacokinetics of Saquinavir and Darunavir. Drug Metab Pharmacokinet 25(6), 521-530

Purpose: To evaluate the effect of different garlic phytochemicals on the pharmacokinetics of saquinavir (Saq) and darunavir (Dar) Results: Garlic constituents modify Pgp activity and inhibits CYP3A4 activity The intracellular concentrations of Saq metabolites significantly decreased in the aged garlic extract treated cells (from 16.8 * 10 14 mol/mg in Saq only group to 11.6 * 10 -14 mol/mg in garlic plus Saq group) less Saq was metabolized, so more of the drug is available to exert its effect

Wang, Y. Et al. (2011). Effect of diallyl trisulfide on the pharmacokinetics of nifedipine in rats. J food sci 76(1), 30-34 Purpose: evaluated the effect of diallyl trisulfide (DATS) on the pharmacokinetics of nifedipine in rats Nifedipine is a calcium channel antagonist used in the management of hypertension and angina

Conslusion: DATS significantly enhanced oral availability of nifedipine, possibly by inhibition of intestinal CYP3A, while the pharmacokinetics of i.v. nifedipine was not altered. Findings of this study suggest that co-administration of garlic supplements and nifedipine has a potential for nutrient-drug interaction and close monitoring is recommended

Asdaq, S. M. & Inamdar, M. N. (2011). The potential benefits of a garlic and hydrochlorothiazide combination as antihypertensive and cardioprotective in rats. J nat med 65(1), 81-88.

Purpose: to investigate the protective effects of combined therapy of hydrochlorothiazide (HCTZ) and garlic HCTZ is a potent diuretic used for treatment of hypertension

Conslusion: garlic in moderate dose (250 mg/kg) with added HCTZ has a synergistic effect, restoring normal values of systolic blood pressure (from 165 to 124 in garlic and HCTZ group, compared with 130 in HCTZ only group).

Poonam, T., Prakash, G. P., Kumar, L. V. (2013). Influence of allium sativum extract on the hypoglycemic activity of glibenclamide: an approach to possible her-drug interaction. Drug metabol drug interaction 11, 1-6.
Purpose: to investigate the synergistic effects of garlic and glibenclamide in rats Glibenclamide is a sulfonylurea or antidiabetic drug Conclusion: The hypoglycemic effect observed in the glibenclamide plus garlic group was greater than in either glibenclamide or garlic alone groups this synergistic effect could be used to reduce the dose of glibenclamide to achieve a therapeutic effect with minimal side effects

Summary
Many proposed health effects such as cardioprotective benefits, antioxidant activity, and anticancer properties
However, there are conflicting results coming from in vitro and in vivo studies versus clinical trials regarding its benefits and drugnutrient interactions

To be on the safe side, it is best to take into account all the possible interactions of garlic with drugs such as warfarin, saquinovir, and nifedipine It is recommended to inform the consumers about the possible risks and benefits of taking garlic supplements or consuming garlic frequently

References
Agins, A. P. (2011). ADA quick guide to drug-supplement interactions: American Dietetic Association Asdaq, S. M. & Inamdar, M. N. (2011). The potential benefits of a garlic and hydrochlorothiazide combination as antihypertensive and cardioprotective in rats. J Nat Med 65(1), 81-88. Berginc, K., Milisav, I., Kristl, A. (2010). Garlic flavonoids and organosulfur compounds:Impact on the hepatic pharmacokinetics of saquinavir and darunavir. Drug Metab Pharmacokinet 25(6), 521530. Chan, J. Y., Yuen, A. C., Chan R. Y., Chan, S. (2013). A review of the cardiovascular benefits and antioxidant properties of allicin. Phytother Res 27(5), 637-646. Creapure - The reason, why Creapure improves your performance. (n.d.). Creapure - The reason, why Creapure improves your performance. Retrieved October 27, 2013, from http://www.creapure.com/en/creapure-every-day/why-does-creapure-work Creapure - Quality Management. (n.d.). Creapure - Quality Management. Retrieved October 27, 2013, from http://www.creapure.com/en/creapure-every-day/manufacturer/quality-management Creatine: MedlinePlus Supplements. (2012). U.S National Library of Medicine. Retrieved October 13, 2013, from http://www.nlm.nih.gov/medlineplus/druginfo/natural/873.html Ehrlich, S. (2011). Creatine. University of Maryland Medical Center. Retrieved October 27, 2013, from http://umm.edu/health/medical/altmed/supplement/creatine Fuangchan, A., Sonthisombat, P., Seubnukarn, T., Chanouan, R., Chotchaisuwat, P., et al. (2011). Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients. Journal of Ethnopharmacology, 134(2), 422-428.

References
Fumagalli, S., Fattirolli, F., Guarducci, L., Cellai, T., Baldasseroni, S., Tarantini, F., Di Bari, M., Masotti, G. and Marchionni, N. (2011). Coenzyme Q10 terclatrate and creatine in chronic heart failure: A randomized, placebo-controlled, double-blind study. Clinical Cardiology, 34: 211217. doi: 10.1002/clc.20846 Gaikwad, A.B., Singh, A.K., Behera, T.K., Chandel, D., Staub, J.E. (2008). AFLP Analysis Provides Strategies for Improvement of Momordica Charantia L. (Bitter Gourd). HortScience, 43(1), 127133. Grossberg, G.T. & Fox, B. (2008). The Essential Herb-Drug-Vitamin Interaction Guide: The safe way to use medications and supplements together. Random House. Hermann, R., von Richter, O. (2012). Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med 78(13), 1458-1477. Hickner, R. C., Dyck, D. J., Hatley, H., & Byrd, P. (2010). The effect of 28 days creatine ingestion on muscle metabolism and performance of a simulated cycling road race. Journal of International Society of Sports Nutrition, 7(26). Retrieved October 27, 2013, from the PubMed.gov database. Integrated Supplements 100% Creapure Creatine. (n.d.). Integrated Supplements. Retrieved November 16, 2013, from http://www.integratedsupplements.com/intsup/intsup0011.C Jiratchariyakul, W., Mahady, G.B. (2013). Overview of Botanical Status in EU, USA, and Thailand. Evidence-Based Complementary and Alternative Medicine, 2013, 17-34. Kwatra, D., Subramaniam, D. , Ramamoorthy, P., Standing, D., Moran, E., et al. (2013). Methanolic extracts of bitter melon inhibit colon cancer stem cells by affecting energy homeostasis and autophagy. Evidence-based Complementary and Alternative Medicine : ECAM, 2013, 702869.

References
Lugareal, R., & al. (2013). Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein diet? Journal of International Society of Sports Nutrition, 10(26). Retrieved October 28, 2013, from http://www.jissn.com/content/10/1/36 Malik, S., Riaz-ur-Rehman, M. Z., & Chaudhary, M. F. ( 2007). In vitro Plant Regeneration from Direct and Indirect Organogenesis of Memordica charantia. Pakistan Journal of Biological Sciences, 10, 4118-4122. Nivitabishekan, N., Asad, M., & Prasad, V.S. (2009). Pharmacodynamic interaction of Momordica charantia with rosiglitazone in rats. Chemico-Biological Interactions 177, 247253. Ooi, C.P., Yassin, Z., & Hamid, T.A. (2010). Momordica charantia for type 2 diabetes mellitus. Cochrane Database System Review, Feb 17, 2. Poonam, T., Prakash, G. P., Kumar, L. V. (2013). Influence of Allium sativum extract on the hypoglycemic activity of glibenclamide: an approach to possible her-drug interaction. Drug Metabol Drug Interaction 11, 1-6. Tattelman, E. (2005). Health effects of garlic. Am Fam Physician, 72(1), 103-106. Wang, Y. et al. (2011). Effect of Diallyl Trisulfide on the Pharmacokinetics of Nifedipine in Rats. J Food Sci 76(1), 30-34. Zeng, T., Zhang, C., Zhao, X., Xie, K. (2013). The roles of garlic on the lipid parameters:A systematic review of the literature. Crit Rev Food Sci Nutr 53(3), 215-230.