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Sports Nutrition: HMB -- The Book

Building Muscle Mass,

Performance and Health

with

HMB

by

Richard A. Passwater, Ph.D.

and

John Fuller, Jr., Ph.D.

ISBN: 0-87983-867-1

8 1997 Richard A. Passwater and John Fuller, Jr.

Copyright assigned to Keats Publishing, New Canaan, CT

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The Body Builder

The newest athletic supplement on the market, safe, legal and nourishing HMB has shown muscle-building powers comparable to illegal and dangerous steroids. As a natural substance, HMB is a legitimate and safe athletic aid, used by the US Olympic team in 1996, and rapidly finding use in pro football and other sports, and in body building.

Dr. Richard Passwater and Dr. John Fuller both explore the benefits, uses and dosage of HMB and give a fascinating account of the scientific quest that established its worth.

About the Authors

Richard A. Passwater, Ph.D. is one of the world’s most called-upon authorities in preventive health care. A noted biochemist, he is credited with popularizing the term “supernutrition” in such books as Supernutrition: Megavitamin Revolution and the New Supernutrition. He is the discoverer of antioxidant synergism and the role of selenium in reducing cancer incidence. He has written several dozen books and hundreds of articles on nutrition. Dr. Passwater lives in Berlin, Maryland, where he is the director of a nutritional research laboratory.

John C. Fuller, Jr., M.S., Ph.D. has been involved in many of the studies on HMB detailed in this book. He has been a co-author on many of the research related HMB publications. Dr. Fuller has graduate degrees in nutrition and muscle biology and is especially interested in how nutrition affects muscle protein metabolism and health. He lives in Zearing, Iowa and is Director of Animal Research at Metabolic Technologies Inc.

Introduction...... 3

What is HMB?...... 4

What does HMB do?...... 4

How is HMB made?...... 6

Where is HMB made?...... 9

How does HMB work?...... 9

HMB Research...... 10

Solving the Mystery...... 13

Animal Studies...... 14

Human Studies...... 16

Building Massive Muscles...... 16

Study Results...... 19

Olympic and Professional Athletes...... 30

Animal Athletes ...... 31

Aerobics...... 32

Exercise is required...... 34

HMB Helps AMelt@ Body-fat...... 34

HMB Lowers Cholesterol...... 35

HMB Enhances the Immune System...... 35

Cancer, AIDS, Dystrophies, and other muscle-wasting diseases...... 37

How to take HMB supplements...... 37

HMB Safety...... 39

Summary...... 41

Bibliography...... 42

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Introduction

HMB is the common name for an exciting new food supplement. An ideal supplement improves your health while improving your appearance. If you look good, you are inspired to keep up your good health habits. HMB is a supplement that makes you look good by improving your physique, while simultaneously improving your body chemistry. The early research on HMB (actually named -Hydroxy--Methylbutyrate) showed that HMB supplementation lowered total and LDL cholesterol levels in blood and helped strengthen the immune system, while building muscles and burning body fat. This news is certainly of interest to body builders and other athletes, but it may also become of interest to cancer, AIDS and muscular dystrophy patients.

From antiquity, health has been associated with a Ahealthy looking@ body. Eating and exercise habits that lead to Ahealthy looking@ bodies usually are the same habits that lead to good health. It was the physical culturists such as Paul Bragg that had a lot to do with the beginning of the health movement. It has long intrigued us why, after the mid-twenties, athletic performance declined with age -- even though the athlete trained just as hard and ate just as well. This question is responsible for leading one of you co-authors (RP) to study the aging process in 1959. Today there is even a specialized field called sports nutrition that interests young people in nutrition and health, hopefully an interest that will stay with them throughout life.

HMB has been available as a supplement targeted for building muscles and suppressing protein breakdown since October 1995, but because the early research studies were animal studies, HMB did not receive widespread attention until later. Eventually, brief abstracts of human clinical trials were presented at scientific meetings, and this information quickly found its way to several elite athletes who immediately benefitted from HMB. Now detailed, full publications of the human clinical studies are available to allow independent scientific review. Other researchers are following the leads generated by the HMB pioneers and their confirmatory studies are being readied for scientific publication as this book is being printed. These clinical results are very exciting indeed, as are the anecdotal reports from users. We are able to report these results in this book.

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In addition to the research on HMB for building muscles, there are several decades of research behind HMB, arising primarily from its role in cholesterol metabolism. Scientists had noted the role of HMB in cholesterol synthesis in the early 1950s when it was known as 3-hydroxyisovaleric acid. Although the most important factor about HMB may be that it is a health builder in that it builds the immune system and lowers cholesterol, most people are interested in its muscle-building and fat-burning actions.

Before we get into the HMB story, let=s take a brief overview by looking at the answers to some frequently asked questions.

What is HMB?

HMB is the acronym for a very important compound made in our bodies called beta-hydroxy-beta-methylbutyrate. HMB is a metabolite of the essential amino acid leucine. In addition to that made in our bodies, we can use HMB from food. HMB is present in small quantities in both plant and animal foods. HMB is also available as a dietary supplement. HMB is not a steroid or drug, and in fact, HMB is a natural component of mother=s milk, which substantiates HMB=s nutrient role.

What does HMB do?

HMB is of particular importance to us because it helps strengthen our immune system, lowers blood cholesterol, protects against stress and builds strong muscles. Studies with body-builders have shown that HMB can, on average, speed muscle mass and strength gains by 50 percent. HMB also has other nutritional functions such as it is found in the milk of lactating women.

Later, we will look into these functions in more detail, but for now let=s just take a quick look at Figure 1 to see why HMB is needed to produce muscles.

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Figure 1. The role of HMB and exercise in increasing Muscle mass. Both HMB and exercise are important for building muscles. You can exercise a lot, but if your body doesn=t make enough HMB, your muscle growth will be restricted.

Protein Amino acids Leucine HMB

HMB-CoA

HMG-CoA

Mevalonate

ExerciseIntra-cellular Cholesterol

Muscle cell growth

INCREASED MUSCLE MASS

The immune system protects us against invaders such as bacteria and viruses. The immune system also destroys mutated cells such as cancer cells. In essence, the immune system tries to destroy anything in your body that shouldn=t be there. It protects you by attacking anything that is not you. Whether or not your immune system can protect you against these and cancer depends on the strength of the immune system. HMB strengthens your immune system by allowing it to produce white blood cells as quickly as needed. Figure 2 shows how HMB is involved in building immune system cells.

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Figure 2. The role of HMB in strengthening the immune system to prevent disease.

HMB

HMB-CoA

HMG-CoA

Mevalonate

Germs or other challenge

to the immune systemIntra-cellular Cholesterol

Increased production of

Immune System Cells

REDUCED ILLNESS AND LONGER LIFE

We will also discuss the roles of HMB in lowering blood cholesterol and fighting stress in later sections.

How is HMB made?

We produce our own HMB from the amino acid leucine after leucine has been metabolized to a compound called alpha-ketoisocaproate (KIC). An amino acid is a small compound containing both an acid group and an amino group, thus the term Aamino acid.@ The amino group contains nitrogen. You will see why this fact is important when we discuss proteins and muscles in term of nitrogen balance.

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Leucine is vital to our health, yet we can not make leucine in our bodies. We depend on our diet for the leucine, just as we do for vitamins. Leucine is called a Adietary essential@ amino acid for that very reason. Besides leucine, there are eight other amino acids that are considered essential. Eleven other amino acids can be made in the body from the nine essential amino acids. These common amino acids are Abuilding blocks@ that can be linked together to form thousands of different proteins. Thus, proteins, the most abundant biochemicals in the body, are very long chains of amino acids linked together.

Plants and animals make proteins from the amino acids. Then we eat the proteins and digest them, which breaks them apart to the individual amino acids (or at least to smaller linkages of two or three amino acids). These groups of two or three amino acids are called Apeptides.@ We call the individual amino acids Afree@ amino acids to distinguish them from amino acids that are joined together. Free amino acids do not widely occur in nature, as the vast majority of amino acids are tied up in proteins.

Free amino acids and peptides are absorbed from the digestive tract into the bloodstream where they are transported to the liver. The liver uses some amino acids and circulates others to cells throughout the body for use as needed. The liver can complete the task of breaking down peptides into individual amino acids and the liver can assemble the amino acids into new protein.

Many of the enzymes that drive the thousands of chemical reactions of life are made in the liver. Enzymes are proteins, and thus made from amino acids. The free amino acids that circulate in the bloodstream are available for use by the appropriate cells for such things as building our muscles and making the cells of the immune system.

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Leucine is called a Abranched-chain@ amino acid (BCAA), as are the essential amino acids isoleucine and valine. BCAA are so-called because they have carbon atoms that branch out from the main Abackbone@ of carbon atoms. The three BCAA have been considered together to have anabolic effects similar to those of insulin. BCAA are important constituents of muscle fibers, but that is not why leucine is so important to building massive muscles. The leucine obtained from our diet is used for several purposes in the body. Leucine can become a structural part of the many thousands of different proteins in the body, including muscles and enzymes. When early research showed that leucine was critical to muscle building, it was assumed that it was just because it was needed for the protein in muscle fibers. Now, we know that it is much more than that.

When we have adequate amounts of leucine in our diet, some is transported into muscle cells. Within muscle cells leucine can be converted into KIC. In turn, if there is enough produced, some KIC can be converted into HMB. Under optimal conditions, about five percent of dietary leucine is converted to HMB. It is estimated that one would have to eat almost five pounds (2,300 grams) of meat to get about two ounces (60 grams) of leucine to make about three grams of HMB in the young healthy male. If you could eat that much, you would be getting a lot of calories and fat that you didn=t need. Figure 3 reviews the basic steps in how the body makes HMB.

Supplemental HMB is probably needed to permit the rapid growth of muscle cells. As we will discuss in detail later, HMB is needed in the production of the muscle cell membranes. Muscle cells have an especially intricate membrane system which is vital to their function.

Figure 3. The production of HMB from food proteins.

Food ProteinBody protein turnover (degradation)

Leucine

KIC

HMB

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Where is HMB made?

Muscle and liver are the major sites of HMB production although this hasn=t been extensively studied. In humans it has been estimated that we make somewhere between 1/4 of a gram to one gram of HMB per day, depending on the protein intake. If we were to eat extremely high levels of leucine-rich protein, we theoretically could produce up to several grams of HMB per day.

Most foods have very low HMB concentrations (about one part per million). However, in some plant products such as alfalfa, some fermentation products, and some meats such as catfish, concentrations can reach greater than 20 times higher than most foods. Nonetheless, foods are not a significant source of HMB under normal circumstances. Since dietary HMB is low and HMB production in the body is limited by protein intake, better results can be obtained with the use of HMB supplements.

How does HMB work?

Who cares? Well, the scientists have to know how HMB works so that they can continue discover how to gain more benefits from specific dietary supplements such as HMB. The more we know about building muscles and strengthening the immune system, the more we can improve the process. In fact, the researchers studying HMB have had to make educated guesses (hypothesis) and then test these hypothesis to see if they are right. As they have gained more experimental data, they then Aadjust@ their hypothesis as to how HMB works.

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In building muscles, what is important is that more cell protein is made than destroyed. You can improve the protein balance either by slowing the degradation (catabolism) or by speeding up the production (anabolism) of cell proteins. While it has been shown that HMB improves this balance through a slowing of protein degradation, it was not known how this occurred. At first, it was thought that HMB might be blocking the enzymes that carry out this catabolic process or that HMB itself may be an integral part of cell membranes. While neither of these hypotheses has been completely ruled out, the scientists now believe that the most likely action of HMB is as a precursor to an important part of muscle cell membranes. The most likely mechanism for this is via the intra-cellular synthesis of cholesterol which is a vital component of cell membranes.

However, no one has to know how HMB works to benefit from it. What is important to know is that several studies have verified that HMB does indeed work to build massive muscles, strengthen the immune system and lower blood cholesterol levels. These studies will be examined shortly. However, many people like to have a conceptual explanation as to what is going on in the body with HMB. They know it is not magic, so what is involved?

Figures 1 and 2 illustrate that HMB can be used to make muscles and white blood cells of the immune system. The story as to how they do this is much more complicated. Later in this book we will examine the research that made the exciting discoveries that lead to our understanding of how HMB functions to do these tasks. It=s not that we don=t want to spoil the story by telling the ending first, it is just that some more background is required for the non-specialist to fully understand the question of Ahow.@ If the experts have had difficulty in figuring it out, you can see that it is complex. If we tried to explain it now, it might sound confusing. However, the key is that HMB is needed to produce a compound critical for cell growth. What might be especially confusing to non-specialists, is that the compound stimulated by HMB may be plentiful in the blood, but it is difficult to get this compound into the cell where it is needed. HMB helps produce this compound right where it is needed and in ample amounts, as long as there is HMB.

HMB Research

The scientist who discovered that HMB helps build muscles quicker than any supplement yet known is Dr. Steven L. Nissen, D.V.M., Ph.D. Dr. Nissen received his Doctorate of Veterinary Medicine in 1976, his Masters of Science in 1977, and his Doctorate of Philosophy in 1981, all from IowaStateUniversity. Dr. Nissen has been a Postdoctoral research fellow and a National Institutes of Health-Diabetes fellow at the Mayo Clinic in Rochester from 1979 to 1982. Dr. Nissen has been an Assistant Professor (1982-1987), Associate Professor (1987-1993), and since 1993, is a Professor in the Department of Animal Science at IowaStateUniversity.

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Dr. Nissen has published over 40 scientific studies in peer-reviewed journals and has been granted eleven patents, several of which are Ause patents@ on HMB and, beside his duties as a professor and researcher, is concurrently the CEO of Metabolic Technologies Inc. Dr. Nissen has won the Outstanding Graduate Student Research Award at ISU in 1979, and the Walnut Grove Outstanding Research Award in 1992. He has also been recognized in the scientific community for his research by receiving the National Institutes of Health Young Investigator Award in 1982.

Dr. Nissen devoted most of his academic career doing research related to muscle and amino acid metabolism. Specifically, he directed his research on the amino acid leucine and how it=s metabolized in muscle and how it regulates muscle growth. So it was a natural extension of this work that led him down the metabolic pathway to the leucine metabolite HMB.

Initially, Dr. Nissen=s interests in HMB were related to animal meat production. He was interested in helping farmers raise leaner, more efficient cattle and other farm animals. Dr. Nissen started his HMB research after brainstorming with graduate students in 1988. They were doing another experiment related to soybean meal and protein nutrition. They had three sheep that were not assigned to that experiment and thus were available for other studies. They decided to make some HMB and feed it to the sheep. The results, although extremely preliminary, were very encouraging. The sheep gained muscle and lost fat.