Creatine

1. Creatine How Creatine affects homeostasis in the human body.

2. What is Creatine? • Creatine is a nitrogenous organic acid, it’s naturally found in the body. • Creatine helps to supply energy to the cells in your body, primarily muscle cells by increasing the formation of Adenosine triphosphate (ATP) which is considered to be the energy currency of life. • ATP is a high-energy molecule that stores the energy for pretty well everything we need to do.

3. More about Creatine • There are three amino acids that make up creatine; L-arginine, glycine and L-methionine. • Creatine is produced in the body from amino acids from the kidney and liver. It is then transported through blood flow to the muscles that are being used. Roughly 95% of the human body’s creatine is located in the skeletal muscle. • Your body produces creatine naturally; it is not an essential nutrient. However, humans get approximately half of their body’s creatine from meat.

4. Who uses Creatine? • Creatine is used by athletes, bodybuilders and others who wish to gain muscle, strength or body size. • They will typically consume two to fifteen times as much creatine as a regular healthy diet would give you. • Like many supplements, using more then recommended by the bottle or your doctor can lead to health problems, and people using it should use it in cycles (e.g. 3 weeks using, 1 week off).

5. Anyone taking creatine as a supplement should be consuming 2-4 litres of water a day, depending on how much their taking and how much they weigh. • Initially when somebody starts to use creatine they will do a loading phase, where they have 20g of creatine everyday for five days before reducing that to 5g everyday. • If you don’t use creatine in cycles, your body could stop producing it, or you could have health problems.

8. Homeostasis • Homeostasis is the body’s maintenance of a relatively stable internal physiological environment. Generally, homeostatic regulation is maintained by releasing hormones into the bloodstream. • An example of your body working to maintain it’s stable state would be if you have just finished a long run and you are very warm. To get rid of the heat, your body releases sweat onto the skin, and as the sweat evaporates, your skin cools down.

9. The Central Nervous system • The nervous system is divided into two parts; the central nervous system (CNS) and the peripheral nervous system (PNS). • The central nervous system is made up of the brain and the spinal cord. This is where nerve impulses are interpreted. • The CNS is wrapped in meninges (connective tissue coverings) and the space between the meninges are filled with cerebrospinal fluid, which is used to cushion and protect the CNS.

10. The Peripheral Nervous system • The Peripheral nervous system (PNS) consists of the nerves and ganglia (mass of nerve cell bodies) outside of the brain and the spinal cord. • The main task of the PNS is to connect the CNS to the limbs and organs of the body. • Unlike the CNS, the PNS is not protected by bone, skull or meninges.

11. The Endocrine system • The Endocrine system works with the nervous system to maintain homeostasis. • It does so by releasing chemical substances (hormones) which trigger certain actions in specific targeted cells.

12. A good example is if you are exercising, your endocrine system will release hormones to regulate oxygen consumption, basic metabolic rate, etc. • The Endocrine system is composed of a number of glands and tissues (pituitary gland, thyroid gland, adrenal gland…)

13. Reported negative effects of Creatine (from users) • Stomach cramps (due to the creatine not completely dissolving prior to digestion). • Bloating (due to water retention), in face or other areas. • Anger and aggressive behaviour. • Increased urination and dehydration. • Weight gain. • Once you stop taking creatine, you tend to “deflate” and will lose weight, strength and size.

14. Creatine experiment (rats) • An experiment was conducted to determine creatines effect on insulin secretion, glucose tolerance, and quadriceps glycogen metabolism. • Insulin is a hormone central which regulates carbohydrate and fat metabolism in the body. Insulin is responsible for causing cells in the liver, muscle, and fat tissue to take up glucose from the blood, and storing it as glycogen in the liver and muscle. • Glucose tolerance is checking to see how quickly glucose is removed from the blood stream after being given. • Glycogen is a molecule manufactured in the liver and muscles, and it is a long term energy storage molecule. • Metabolism is the amount of energy or calories that your body burns to do things. • Quadriceps are a leg main leg muscle.

15. How the rats were affected? • There were six groups of 8 rats. The rats were fed a diet supplemented of 2% creatine for 2, 4 or 8 weeks (one of the groups was not fed creatine). Glucose tolerance tests were performed, and the pancreas and quadriceps muscles were collected. • The insulin response to glucose had significantly increased in the rats that were given creatine for 4 and 8 weeks. • Fasting insulin levels also increased in the rats that were on the diet for 8 weeks. • Glucose tolerance was not affected until the 8 week period at which point the peak plasma glucose was elevated in the 8 week diet rats. • A significant increase in pancreatic total creatine content was seen in all the rats that were given creatine.

17. What the results mean? • The results in this experiment show that (on rats) prolonged creatine supplementation induces abnormalities in pancreatic insulin secretion and changes in glucose homeostasis. • The hormone insulin could be affected in the pancreas which could lead to pancreas problems. Examples of pancreas problems are pancreatic cancer, pancreatitis, acute pancreatitis, gallstones, chronic pancreatitis etc. This is not to say that creatine will lead to any of those problems in humans. • If your glucose levels are not regulated they could also lead to serious problems. Too little glucose will lead to starvation, and to much glucose is toxic. When glucose enters the bloodstream, it is detected by specialized cells in the pancreas. These cells respond by releasing insulin, which then signals to other cells that there is glucose to be taken in and stored as energy.

18. Creatine experiment (humans) • An experiment was conducted by Darren G. Burke, Truis Smith-Palmer, Laurence E. Holt, Brian Head, and Philip D. Chilibeck. The purpose of the experiment was to determine how much of the creatine supplement that people take is wasted, and removed through urine less then 24 hours after initially taking the creatine. • Although the results of their experiment did not show how or where the creatine was stored, they showed that dosages used led to a significant removal through the kidneys, with roughly a 50% retention rate meaning half the creatine was wasted.

20. This is tough on your kidneys because they have to work harder to remove the excess creatine, and if the dosage was too high, it could potentially result in kidney failure. • The professors who conducted this experiment were unable to detect where the retained creatine was stored, but based on previous research they concluded it was stored in muscle cells. • Their conclusion was that when taking 7g, or 0.1g/Kg of body weight of creatine a day, you will retain roughly half of that after the first 24 hours, the rest being waste.

21. Creatine experiment (mice) • Researchers gave the mice asthma by injecting a large quantity of the protein ovalbumin directly into their gut a couple of times. This made the mice allergic to ovalbumin, and then the researchers could induce asthma attacks by spraying ovalbumin powder. • Some of the mice were also given creatine. The researchers gave the mice 0.5 g creatine per kg bodyweight five times a week.

22. The graph shows what happened when the mice were exposed to provocholine, a substance that constricts your airways if you are asthmatic. The graph shows the difficulty four groups of lab animals had with breathing as they were given an increasing dose of provocholine. • Methacholine (provocholine) is a synthetic choline ester that acts as a non-selective muscarinic receptor agonist in the parasympathetic nervous system.

24. Creatine experiment on brain performance • A study was conducted by the Caroline Rae, Alison L. Digney, Sally R. McEwan and Timothy C. Bates to determine whether or not creatine supplements would increase brain performance. • Subjects were given 5g of creatine monohydrate for every day. Subjects completed timed (10 min) parallel versions of Raven’s Advanced Progressive Matrices (RAPMs) constructed to have equal levels of difficulty based on the published normative performance data and verified by us on an independent sample of 20 subjects.

25. This intelligence test is well validated as a measure of general ability with minimal dependence on cultural factors. Versions of these tests were assigned evenly across the four visits. • Subjects also completed the Wechsler Auditory backward digit span (BDS) task. This subtest of the Wechsler Adult Intelligence Scales loads on both short-term storage and verbal working memory functions supported by mid-ventrolateral and dorsolateral prefrontal cortex. • The results were that the subjects using creatine significantly increased their intelligence. Individuals using creatine achieved better results on both tests, the RAPMs and the BDS`, which goes to show that creatine can improve your intelligence.

26. Questions to ask? • There are still a lot of questions that can’t yet be fully answered, or they have been answered, but with many different conclusions and results. • Even if you cycle it, are there long term consequences from using creatine? At what age is it okay to use it? • How serious can the imbalance in your body get after using creatine? • How much creatine would need to be consumed before your body will no longer return to it’s normal, stable state?

27. Conclusion In conclusion, there are the possible benefits to supplementing creatine, and there are possible detriments to using creatine. Creatine has different effects on people, whether they be positive or negative. Using creatine excessively or for an extended period of time has proved to be unhealthy, and could lead you to seriously harming your body. Your body can only be pushed so far to maintain its stable state, and when pushed beyond that (using creatine too much or for too long), there are many different problems your body could have (kidneys, liver, brain, nervous systems) all which could be fatal.

28. References • J. David Branch. (2003). Effect of Creatine Supplementation on Body Composition and Performance: A Meta-analysis. Retrieved from www.ux1.eiu.edu/~cfje/5230/Cr%20Meta%20Analysis.pdf • Richard B. Kreider. (1998). Creatine, the Next Ergogenic Supplement? Retrieved from www.sportsci.org/traintech/creatine/rbk.html • Personal Health Zone. (2011). Creatine Side Effects, Interactions and Warnings. Retrieved from http://www.personalhealthzone.com/herbal_medicine/side_effects/creatine_side_effects.html • The Royal Society. (2003). Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1691485/pdf/14561278.pdf