HOW MUCH CREATINE? "How much creatine - How to take it, when to take it, why to take it" By: Brad Pilon, Author of Eat Stop Eat

Transcription

1 HOW MUCH CREATINE? "How much creatine - How to take it, when to take it, why to take it" By: Brad Pilon, Author of Eat Stop Eat

2 How Much Creatine? Brad Pilon

3 Copyright 2013 by StrengthWorks International Publishing, Inc. All rights Reserved No portion of this book may be used, reproduced, or transmitted in any form or by any means, electronic or mechanical, including fax, photocopy, recording, or any information storage and retrieval system by anyone but the purchaser for their own personal use. This manual may not be reproduced in any form without the express written permission of Brad Pilon, except in the case of a reviewer who wishes to quote brief passages for the sake of a review written for inclusion in a magazine, newspaper, or journal, and all of these situations require the written approval of Brad Pilon prior to publication. The information in this book is for educational purposes only. The information in this book is based on my own personal experiences and my own interpretation of available research. It is not medical advice and I am not a medical doctor. The information within this book is meant for healthy adult individuals. You should consult with your physician to make sure it is appropriate for your individual circumstances. Keep in mind that nutritional needs vary from person to person, depending on age, sex, health status and total diet. If you have any health issues or concerns please consult with your physician. Always consult your physician before beginning or making any changes in your diet or exercise program, for diagnosis and treatment of illness and injuries, and for advice regarding medications.

4 INTRODUCTION What exactly is building muscle? Is it an increase in size? Weight? Both? I wish we had all the answers to muscle, but we really don t. What we do know is that muscle will increase in size as a response to weight training. However, even this is a bit of an incorrect way of looking at the problem. In fact, a more accurate statement would be that muscles will increase in size as response to eating protein, thanks to the anabolic sensitizing affect of resistance training. Now, I won t bore you with any more protein studies as I m sure you ve heard more than enough about eating protein to build muscle, however I will say that protein isn t the only thing associated with muscle growth. We know that testosterone and other anabolic hormones build muscle, but there use is illegal without a doctor s prescription and are generally not an option for the average person. Therefore, what I would like to show you is some very interesting research on the one specific dietary supplement that is legal in

5 most countries that can actually increase the size of your muscles - good old creatine monohydrate a dietary supplement that is legal for use in most countries. Many people think that it was the passing of the Dietary Supplement Health and Education Act (DSHEA) back in 1994 that allowed the nutritional supplement industry to become the juggernaut that it is today, but in my opinion, the discovery of the muscle building effect of creatine monohydrate played just as large a role. In fact, my opinion is that there would be no supplement industry without creatine. From the pioneering research conducted by Dr. Eric Hultman and Dr. Roger Harris, to the ongoing work being conducted by Dr. Paul Greenhaff and many others, the scientific research behind the muscle building effects of creatine is very impressive. So impressive that I believe the effectiveness of creatine created a belief that all supplements could work this well with no side effects and be safe and inexpensive. Creatine is truly the poster child for the supplement industry and how amazingly effective a product could be. Unfortunately 16 years later it is still one of the only supplements that can make this claim.

6 There are hundreds of scientific papers on creatine, and easily over a dozen published books, and for good reason - In almost every clinical trial on creatine I have ever reviewed, the men (and women) taking creatine always gain impressive amounts of lean mass and they have gained strength a lot of it. Interestingly, these people do this without any other post-workout supplements or changes to their normal diets. They gain weight and strength without any extra calories or protein (creatine does not contain any useable calories). People in creatine research trials gained muscle WITHOUT high protein diets. postworkout protein meals, or massive amounts of calories more proof that you may not need these things to gain muscle size. Now, it may seem odd that creatine could be considered a protein. Creatine is actually a tri-pepitde made of 3 amino acids, and that it is naturally found in our diets in most red meats (which is the main reason why it s considered a supplement and not a drug). (creatine) Creating is formed by combining the amino acids glycine, arginine, and methionine and is produced in physiologic amounts by the liver, kidneys, and

7 pancreas. So creatine is not essential since we do have the ability to make it within our own bodies [Balsom PD 1994]. It was largely thought that the reason helped you gain muscle was simply by adding water weight [Hultman E, 1996]. However, we know now this is not true, and we know that creatine use is associated with an actual increase in muscle fiber diameter [Volek JS, 1999; Tarnopolsky MA 2001]. So the weight added by creatine is not simply bloating or only water (as we will discuss later) but actual muscle mass. The bottom line is that any supplement with a twenty-year track record of success with little to no side effects is definitely worth investigating.

8 CREATINE AND MUSCLE MASS If you measure the surrogate endpoints like amino acid flux or nitrogen balance, creatine has no effect [Louis M, 2003]. But, when you measure the true endpoint of increased muscle weight and muscular strength, creatine does very well, creating clear improvements in the majority of research studies. So while creatine may not actually build new muscle in the classical sense, it does increase the size and weight of muscles, and that by itself is an excellent achievement. In fact, creatine performs so well that people in creatine research trials typically gain much more muscle than people in research trials who take protein after their workouts. In general it seems that the use of creatine can add 2 to 5 pounds of weight in 4 to 28 days, and that this weight is mostly in the form of fat free mass. This seems to be in addition to the 2 to 5 pounds we would expect from weight training alone. For instance, in a trial published in 2000, 23 men taking creatine gained over 3.5 pounds of lean mass over 6 weeks. The impressive part is that they only exercised their arms during this 6 week period! That s right, 6 weeks of only blasting their biceps and triceps and the men in this study still gained 3.5 a

9 pound of lean mass! In a measure of upper arm muscle area they gained over 2 square inches of muscle size! [Becque DM, 200] In a trial published in 2001, researchers gave creatine to a group of football players for 9 weeks. During this time these red-shirt freshmen were weight training 4 times per week. At the end of the 9 weeks, the creatine group gained over 8 pounds of lean mass [Bemben MG 2001]. In another trial using creatine combined with resistance training (this time in older men in their 70 s), after 12 weeks of resistance training and taking creatine (no post-workout protein) the creatine group gained over 7 pounds of lean tissue mass! [Chrusch MJ 2001]. What you need to know about this study: It s important to note that in this study the subjects were of advanced age (70 s). This study was funded by MuscleTech Research and Development, Inc. So to put it all into perspective, from what I can tell from reviewing clinical research, working out alone should cause you to gain between 2-5 pounds of lean mass (remember our baseline with no supplemental protein).

10 Adding a protein shake after your workout won t provide any extra benefit and you should still expect to gain around 2-5 pounds (you just might gain it quicker). If you increase your overall protein intake you may gain more muscle mass, possibly increasing the amount you gain over several months by as much as 2 extra pounds. If you take creatine in conjunction with your workout program you can expect to gain as much as 10 pounds of muscle mass. The variation in these numbers (whether you gain 2 or 10 pounds) is most likely dependant on your training status and the design of your workout program. Simply put, the better the workout program design, the better the weight gain. This has even been shown in research where better-designed workout programs have caused larger increases in lean mass [Kraemer WJ, 2003]. And, no matter how great your workout program is, adding creatine into the mix will increase the amount of muscle you gain. The interesting thing with creatine research is that it doesn t matter whether you take your creatine alone, in combination with carbs or protein, or a combination of the two. The research suggests that in any of these styles of dosing creatine you end up gaining around 7-9 pounds. The protein and carbs don t seem to make that much of a difference. In the conclusion section of a research paper published in 2004, the authors stated, It is likely that a significant portion of any increases in fat free mass that

11 occurs with a supplement containing creatine, protein, amino acids and carbohydrates is due to the creatine. [Chromiak, J. 2004] What you need to know about this study: The quote from Chromiak comes from a 2004 study that was funded by Numico USA. During the Early 2000 s Numico owned Met-Rx and GNC. Based on my findings, I couldn t agree more. In fact, Here s a quick insider tip for you if a protein powder has a claim on its label that it builds muscle look in its ingredient list chances are, you will find creatine monohydrate as an ingredient. As far as I am aware, creatine is one of the only ingredients to have enough evidence behind it to make this strong claim. Supplementing with creatine can increase the size and weight of your muscles and cause an increase in overall strength. Now, you may be wondering if all the results come from the creatine alone, then why is everyone always talking about taking creating WITH something to make it better?. And the answer of course, is money.

12 Creatine is interesting because not only does it work well, and is cheap to make, but there is also a lot of intellectual property surrounding creatine. A quick search of the US patent data base shows that there are hundreds of patents on the use of creatine, on combining creatine with certain ingredients and on specific forms of creatine. These patents are typically created or bought by supplement companies. So if my supplement company has the patent on selling creatine combined with blueberry extract, this would mean that no one else can sell creatine combined with blueberry extract. So you can bet your bottom dollar I m going to do everything in my power to convince you that taking creatine with blueberry extract is the ONLY way to take creatine. Despite all of these patents, if you review the research and ignore the advertising it seems logical to say that if you are interested in gaining muscle mass then simply taking creatine monohydrate is your best option. After all, why eat tons of extra calories or excessive amounts of protein or pay for special types of creatine if they don t make a difference (and instead may even increase your chance of gaining body fat)?

13 TYPES OF CREATINE New fancy forms of creatine are coming out every day, Usually accompanied by the claim that they have somehow improved on one of the weaknesses of creatine monohydrate. However, most of these weaknesses are actually myths. We know that creatine is very bioavailable with the overall bioavailability of standard creatine monohydrate being from 80% [Macneil L, 2005] upwards to near 100% [Jager R, 2011] depending on dose ingested. While mega dosing with creatine monohydrate is associated with a slightly lower creatine bioavailabilty, the standard dose of 5-10 grams of creatine monohydrate per day is associated with a bioavailability ~99% [Jager R, 2007]. This means that close to 100% of the creatine you ingest will eventually make it to your muscles. Another myth about Creatine monohydrate powder is that it degrades very quickly. However, stability research has shown us that creatine monohydrate is very stable - showing no signs of degradation over years, even at elevated temperatures. Even when mixed with water, creatine degrades very slowly, and

14 can be kept dissolved in water in your fridge for several days before you lose significant amounts of creatine to breakdown. Even though creatine monohydrate has an exceptional track record, with excellent support from both clinical research and anecdotal evidence from users, the market has still seen dozens of new types of creatine appear over the years. To date, I have not seen any of the fancy creatines out perform good ol creatine monohydate. From all the different salts of creatine such as creatine malate, creatine citrate, creatine ascorbate to the newer buffered creatines none of these ingredients have outperformed creatine monohydrate in any markers of lean body mass or strength measured. In addition to the creatine salts, newer derivatives of creatine such as creatine ester or even creatine alcohols are currently available in the USA and Canada. Interestingly, neither of these ingredients actually contain any creatine, but rather a chemically altered version of creatine. While it is assumed that the human body will transform these molecules into creatine upon intake, there are no published data available confirm this expectation. The bottom line is that the vast majority of research showing benefits of

15 creatine supplementation was completed using creatine monohydrate. And to date, no other creatine form has vastly outperformed creatine monohydrate when it comes to gains in lean body mass or strength. Based on this, I am still convinced that creatine monohydate is the form to beat and I can see no reason to spend extra money on some of the fancier creatine forms.

16 NEW THEORIES ON HOW CREATINE WORKS Recent research has shed some light on why creatine may be so effective, and it will probably come to no surprise to you that it involves the effect that creatine has on muscle satellite cells. In this study, 41 men ranging from 19 to 28 years old (our proverbial sweet spot of muscle growth) were divided into 4 groups. Group 1 took a supplement containing 6 grams of creatine + 14 grams of carbohydrate every day. They also took 80 grams of carbohydrate after their workouts. Group 2 took a supplement containing 14 grams of carbohydrate everyday and took 20 grams of protein and 60 grams of carbohydrate after each workout. Group 3 took a supplement containing 14 grams of carbohydrate every day and took 80 grams of carbohydrate after their workout. Group 4 had no supplements and also did no training. The creatine group (group 1) did a traditional loading phase where they took 5 grams of creatine 4 times per day for the first 7 days of the study. After the loading phase they took a supplement containing 6 grams of creatine plus 14 grams of carbohydrate (flavor) once per day.

17 The protein group (group 2) did not receive any creatine and instead took 20 grams of protein with 60 grams of carbohydrates as their post-workout supplement. The carbohydrate group (group 3) did not receive any creatine or extra protein and instead took 80 grams of carbohydrate as their post workout supplement. The final group, was the control group and received no supplements, nor did they workout. The men in the first three groups trained 3 times per week for a total of 16 weeks. ALL of these workouts were leg workouts. So these men trained legs 3 days per week. Muscle biopsies were taken at weeks 0, 4, 8 and 16 so that the researchers could measure the changes that were occurring inside the subjects muscles. What was found shouldn t be too surprising The creatine group saw the best increase in the size of their muscles, at weeks 4, 8 and 16. What s very interesting is that the creatine group also saw the largest increase in satellite cells and number of myonuclei per muscle fiber (remember muscles need new nuclei in order to grow). The group not receiving creatine or protein saw no increase in myonuclei, but still did see a transient increase in muscle size (in

18 line with our theory that the existing nuclei you already have do have some capacity to increase their domain and thus muscle size) [Kadi 2004] Interestingly the satellite cell content was no longer significantly elevated at week 16 in the creatine group, suggesting that the creatine supplementation accelerated the incorporation of Satellite Cell derived myonuclei to the growing muscles. So it happened quicker than in the other groups, but still had a defined limit. It has long been accepted that the main action of creatine in the body is to increase the amount of energy provided to your muscles. Specifically increasing the store of high-energy phosphate groups in the form of phosphocreatine. This is the energy source that your muscles use during short-term exercise (around 10 seconds or less). During periods of stress, phosphocreatine releases this energy to aid cellular function. Based on this theory it s long been accepted that the way creatine works is by allowing you lift more weight in the gym, and do more volume (more sets and reps) and that was how it increased lean body mass. In other words it allowed you to do more work in the gym and that is why your muscles grew larger.

19 While this explanation is most likely true to some extent, the actions of creatine on satellite cells provides a much more feasible and complete explanation for the muscle growth associated with creatine intake. Another interesting line of research involves the ability of creatine to increase the amount of protein signaling molecules in your muscles. Proteins like mtor are extremely important to the muscle building process, acting as a relay that gets the muscle building signal from your body to the nucleus of your muscles fibers, thus allowing for growth to be initiated. Scientists have found that creatine may not increase the sensitivity of mtor, and it also may not actually activate mtor, instead (and this could even be better for your long term muscle gains) creatine may increase the amount of signaling molecules in this pathway leading to the idea that creatine can cause a better or louder muscle growth signal in your muscles [Safdar A, 2008].

20 ISN T IT JUST WATER WEIGHT? Regarding the increase in muscle size that is associated with creatine use; the argument that it is mostly water weight is a bit misleading. It s misleading because your muscles are mostly water weight to begin with. Human muscle is anywhere from 75 to 80% water. And the amount of water within each muscle tends to increase in more heavily muscled individuals. Saying creatine adds water weight is very similar to saying creatine adds muscle weight. When scientists looked at actual muscle fibers it was found that Creatine supplementation was able to increase muscle fiber size. Even if this increase in muscle fiber weight was a result of an increase in hydration (water in the muscle) it s important to realize that this was in the actual muscle fibers. This means the diameter of the muscle fiber was increasing it wasn t just water around the muscle, or in between the fibers but an actual true increase in muscle fiber diameter [Safdar A, 2009]. Finally, this increase in muscle fiber hydration has been speculated to decrease protein oxidation rates, which lead to increases in nitrogen balance and indirectly increases muscle mass [Parise G, 2001; Berneis, K 1999]. In fact cellular swelling has been described as being similar to fasting in that it demonstrates a metabolic adaptation that results in protein sparing associated

21 with increased lipolysis, ketogenesis and lipid oxidation (three markers of fat burning) [Keller U, 2003; Bilz S, 1999]. The argument that the weight added by creatine is mostly water seems to be a nonsensical argument seeing as ANY increase in muscle size is mostly water and there may be a slight anabolic and even fat burning advantage to having well or properly hydrated muscle fibers. Interestingly, it is exactly this chronic increase in muscle hydration that may be at least partially responsible for the activatation of satellite cells we see with creatine use. A satellite cell is responsible for the inner-workings of a certain amount or length of a muscle fiber. The best example would be to think of a ruler. The ruler would represent your muscle fiber, and each inch mark would be a satellite cell. The space between each inch would be the area that each specific satellite cell would be responsible for. This area is called the myonuclear domain. When creatine hydrates a muscle this myonuclear domain increases, but each nucleus can only handle so much domain, and once the domain becomes too larg then another nuclei will be needed to split the domain into so that each nucleus can properly oversee all of the metabolic happenings of that specific

22 area. Therefore, it is completely plausible that simply by chronically hydrating an actual muscle fiber, creatine is able to force the activation of satellite cells to provide more nuclei to control the new domain. An increase in the water weight of a muscle itself may be the key to the muscle building potential of creatine.

23 TECHNIQUES FOR OPTIMIZING CREATINE It is believed that you begin to see the benefits of taking creatine once your internal stores are maximized, and once your internal levels of creatine reach their peak, they simply cannot go any higher. Creatine follows a dose-dependent relationship, meaning the more creatine you ingest the more your serum levels increases. However the rate of creatine uptake and storage into your muscle cells may be maximized at a serum concentration achievable with 5 grams per day. While early research on creatine suggested the need for a loading phase taking 5 grams of creatine 4 times per day for the first 5 days of use, the more recent research on creatine has found that a dose of 3 grams of creatine monohydrate per day for 30 days is enough creatine to maximize internal stores. The benefit of loading is that it gets you to the maximal internal levels of creatine in the quickest possible way. However, the research showing that 3 grams of creatine for 30 days was enough to maximize muscle stores was conducted on ~70 kilogram men (about 155 pounds). So men heavier than this weight, or with more Lean Body Mass then

24 would be considered average may have to take a higher dose for this affect to occur. The safest bet would be 5 grams per day for well muscle men. Realistically, over the course of a week weight training period, you will probably see little to no difference between the two methods of creatine supplementation. Finally, with regards to the use of creatine for muscle building there are a number of important facts that you need to know if you plan on optimizing your creatine intake. It is true that resistance exercise enhances the rate of creatine uptake into muscle cells, but this is ONLY true for the muscles that were actively engaged during the workout. In other words creatine uptake in the muscle is specific to the muscle that was recently trained with resistance exercise. Initially thought to be a byproduct of enhanced blood flow [Harris RC, 1992], the enhanced creatine uptake is now thought to be due to changes in the creatine transporter, which enhance its maximal capacity [Robinson TM, 1999]. This line of research shows us a new way we could use creatine monohydrate to reach our goals. If your goal is to maximize the size of a specific muscle or

25 group of muscles you could try training that muscle group 3 to 4 times in one week, while at the same time doing a loading phase with creatine monohydrate. This theoretically should then provide those specific muscles with a creatine induced anabolic advantage over the next several weeks of training. We know that the elevated creatine levels that occur after creatine supplementation tend to return to baseline after roughly 30 days (4 weeks) without creatine supplementation [Preen D, 2003; Febbraio MA, 1995]. However, despite creatine levels returning to baseline their ergogenic effects seems to continue for a period, and the increase in lean body mass also seems to be mostly maintained [Rawson ES, 2004]. Based on the above information, it would be best to only attempt this approach once every 6 weeks, and only taking creating during each loading phase. If your goal is overall gains in lean body mass then you could try a whole body approach. Research has shown that creatine uptake can be increased by near supraphsyiological amounts of the hormone insulin. Research has also shown that this level can be reached with a dose of ~100 grams of dextrose (Sugar) or 50 grams of protein combined with 50 grams of carbohydrate. If your goal is to get a whole body balanced muscle growth then you should take your creatine with high doses of carbohydrates or a carbohydrate protein blend to ensure a whole body uptake of creatine monohydrate. At the very least this should occur during the loading phase period.

26 If you do not want to follow either of these more aggressive protocols then you could simply take 5-10 grams of creatine, once a day, either with food, or after your workouts. It is important to remember that we have not seen any evidence that these dramatic muscle-building effects are repeatable. In other words, in almost every research paper studying the benefits of creatine, the subjects were using creatine for the very first time. If the people in a creatine trial were to enroll in a second research study examining the effects of creatine on muscle building I would be very surprised if they were able to gain the same amount of muscle. So while creatine has been shown to be effective in many different research studies, it is always important to remember that it has not been shown to be continually effective for gaining measureable amounts of muscle mass the results may lessen over time. This may reflect a limit to the ability of creatine to increase muscle size via satellite cell incorporation, or it may have been a limitation of the way we have

27 been using creatine perhaps not allowing enough time inbetween doses or cycles. While we don t really have a consensus as to the perfect way to take creatine, we do know that there are multiple ways to use creatine to build muscle, and there are ways to target and direct the effect.

28 CONCLUSIONS Creatine is a dietary supplement that is legal in most countries, has almost 20 years of proven results, with little-to-no side effects. It has countless imitators and improvements all of which seem unnecessary for the most part. It seems to work through several mechanisms, from supplying more energy for your workouts to activating satellite cells to be incorporated into your muscle fibers, thereby allowing for more growth. It can be dosed differently depending on your needs and there is even the possibility that how we use creatine (taking a little bit every day for months on end) may not be the optimal way to use creatine to change the look of our bodies. The bottom line is that is a cheap, effective supplement than can come in both pill and powder form that seems to have the ability to increase the size your muscles above and beyond any other legal supplement to date.

29 REFERENCES Balsom PD, Soderlund K, Ekblom B Creatine in humans with special reference to creatine supplementation. Sports Med 1994; 18: Hultman, E, Soderlund K, Timmons A, Cedarblad JG, and Greenhaff PL. Muscle creatine loading in men. J Appl Physiol 81: , 1996 Volek JS, Duncan ND, Mazzetti SA, Staron RS, Putukian M, Gomez AL, Pearson DR, Fink WJ, Kraemer WJ. Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc Aug;31(8): Tarnopolsky MA, Parise G, Yardley NJ, Ballantyne CS, Olatinji S, Phillips SM. Creatinedextrose and protein-dextrose induce similar strength gains during training. Med Sci Sports Exerc Dec;33(12): Safdar A, et al. Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation. Physiol Genomics. (2008) Jagim AR, Oliver JM, Sanchez A, Galvan E, Fluckey J, Riechman S, Greenwood M, Kelly K, Meininger C, Rasmussen C, Kreider RB. A buffered form of creatine does not promote greater changes in muscle creatine content, body composition, or training adaptations than creatine monohydrate. J Int Soc Sports Nutr Sep 13;9(1):43. doi: / Ralf Jäger Martin Purpura Andrew Shao Toshitada Inoue Richard B. Kreider Analysis of the efficacy, safety, and regulatory status of novel forms of creatineamino Acids (2011) 40:

30 Safdar A, et al. Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation. Physiol Genomics. (2008) Berneis K, Ninnis R, Häussinger D, Keller U. Effects of hyper- and hypoosmolality on whole body protein and glucose kinetics in humans. Am J Physiol Jan;276(1 Pt 1):E Parise G, Mihic S, MacLennan D, Yarasheski KE, Tarnopolsky MA. Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis. J Appl Physiol Sep;91(3): Harris RC, Söderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Lond). (1992) Rawson ES, et al. Effects of repeated creatine supplementation on muscle, plasma, and urine creatine levels. J Strength Cond Res. (2004) Preen D, et al. Creatine supplementation: a comparison of loading and maintenance protocols on creatine uptake by human skeletal muscle. Int J Sport Nutr Exerc Metab. (2003) Febbraio MA, et al. Effect of creatine supplementation on intramuscular TCr, metabolism and performance during intermittent, supramaximal exercise in humans. Acta Physiol Scand. (1995) Robinson TM, Sewell DA, Hultman E, Greenhaff PL. Role of submaximal exercise in promoting creatine and glycogen accumulation in human skeletal muscle. J Appl Physiol Aug;87(2): Jäger R, et al. Comparison of new forms of creatine in raising plasma creatine levels. J Int Soc Sports Nutr. (2007)

31 MacNeil L, et al. Analysis of creatine, creatinine, creatine-d3 and creatinine-d3 in urine, plasma, and red blood cells by HPLC and GC-MS to follow the fate of ingested creatined3. J Chromatogr B Analyt Technol Biomed Life Sci. (2005) Keller U, Szinnai G, Bilz S, Berneis K. Effects of changes in hydration on protein, glucose and lipid metabolism in man: impact on health. Eur J Clin Nutr Dec;57 Suppl 2:S Bilz S, Ninnis R, Keller U. Effects of hypoosmolality on whole-body lipolysis in man. Metabolism Apr;48(4):472-6.