Insulin as an Anabolic Agent

by William Llewellyn

Insulin is definitely the new kid on the block when it comes to anabolic agents. Although it’s been available for decades as a prescription drug, it really did not start appearing in the bodybuilding subculture until the late 1990s. And despite the serious potential dangers of the non-medical use of insulin, including the possibility of death from overdose or miscalculation, its popularity has only increased. Several letters appeared in medical journals in the late 1990’s, warning doctors of this scary and relatively new abuse phenomenon. One in particular actually went on to question if insulin is even capable of offering an athletic benefit at all.1 The authors wrote, “Although there is some evidence in favor of testosterone increasing fat-free mass and muscle storage when combined with strength training, there is no evidence that other drugs do the same… We could find no evidence in the literature to support the use of insulin in this context.” This is indeed a strong statement and it poses a very serious question. Have we in fact latched on to a new drug without having so much as a shred of solid data to support what we are using it for?

Anabolic Activities
A quick perusal through the medical journals does reveal several studies showing activities inherent in insulin that are seemingly attractive for building muscle. One study looked at the effects of insulin on skeletal muscle and whole body protein turnover, noting strong anabolic properties in this hormone.2 In this investigation, eight health volunteers (two women, six men) were given infusions of tracer-labeled amino acids (phenylalanine and leucine), with and without infused glucose and insulin. Amino acid turnover was measured in the leg. The dosage of insulin given was sufficient to raise blood levels to the high end of normal (physiologic hyperinsulinemia).

With insulin infusion there was a marked 30 percent decrease in leucine breakdown, and a 13 percent increase in its incorporation into muscle tissue. Phenylalanine breakdown, on the other hand, was reduced only 9 percent, however its incorporation into new muscle protein was bumped up a dramatic 30 percent. A strong net positive protein balance was reached in this investigation, which was accomplished by a reduction of amino acid release (anti-catabolism) and an increase in its incorporation into new muscle protein (anabolism).

Anti-Catabolic Activities
There are also studies with insulin demonstrating this hormone to support a positive protein balance in skeletal muscle mainly through anti-catabolic action. One such investigation looked at amino acid turnover in the forearm muscle of seven healthy male subjects.3 Here again, tracer-labeled phenylalanine and leucine were infused to help determine amino acid turnover. Measures were taken before and after insulin infusion, and reported a strong positive effect on protein balance with insulin administration.

This was demonstrated clearly in the figures for the disposal (muscle intake of amino acid) and production (muscle release of amino acid) of phenylalinine and leucine. Initially, the reported disposal rate was 43 nmol/100ml and 113 nmol/100ml for phenylalinine and leucine, respectively, a figure that was not significantly altered by insulin infusion (42 nmol/100ml and 124 nmol/100ml). Production, however, went from 57 nmol/100ml and 126 nmol/100ml for the two amino acids to only 33 nmol/100ml and 63 nmol/100ml. As in the first study, we see a strong shift in favor of increased protein storage. Unlike the first study, however, it was achieved primarily by inhibiting protein breakdown instead of stimulating new protein synthesis.

Post-Exercise Loading
Going one step further, although admittedly to studies conducted after the letter in question, we can also find support for the most common method of insulin use among bodybuilders, namely as a post-exercise nutrient-loading and partitioning agent. As the suggestion goes, insulin is most anabolic when taken directly after a bout of resistance exercise and accompanied by ample amounts of amino acids and carbohydrates. Athletes have long understood that there’s a vital window of time after training for replacing lost glycogen and protein, and many believe this same window is the optimal time to exploit the nutrient loading and anabolic/anti-catabolic properties of insulin. (This is by far the most accepted practice).

One study, published in the journal Diabetes, supports this practice extremely well.4 In this comprehensive investigation, five healthy male subjects were studied on three separate occasions, once at rest (with and without insulin) and twice after an intense 40-minute bout of lower body resistance exercise (with and without insulin). Tracer-labeled phenylalanine, leucine, lysine and alanine were used during all to measure amino acid turnover and transport. The investigators noted that insulin-stimulated glucose uptake and alanine transport was a remarkable three times greater after exercise. The rate of protein degradation, normally heightened during recovery, was also effectively blunted by insulin administration.

Another paper, published about a year later in the same journal, looked more narrowly at insulin’s role in the resynthesis of muscle glycogen after resistance training.5 The investigators wanted to know specifically if exercise would increase the sensitivity for glycogen synthase (an enzyme pivotal to glycogen storage) activation by insulin. Seven healthy male volunteers participated, and their blood was measured before, and at various points after, resistance exercise (one-leg knee extensions) for glucose, insulin concentrations, hemoglobin content, blood oxygen saturation and pulmonary oxygen uptake. Muscle glycogen content was also measured, but by needle biopsy.

The study demonstrated that in the exercised leg there was a striking two- to four-fold increase of insulin-stimulated glucose uptake and glycogen synthase activity. The one failing in this investigation, however, is that subjects remained in a euglycemic state (normal glucose levels). As a result, muscle glycogen content was not able to be fully restored during the course of the experiment. This is in contrast to studies in which a hyperglycemic-hyperinsulinemic state (elevated blood glucose and insulin levels) was maintained, and full glycogen repletion occurring within two hours.6

In Closing
To answer the original question of whether or not we’ve been using a drug with nothing to support what we’re doing, the answer would have to be an emphatic no. The cited studies are extremely supportive here, and represent only a few of many pertaining to the anabolic, anti-catabolic and nutrient-loading effects of insulin. In reviewing the literature, we are left to conclude a few very important things about this hormone:

1. It exerts both anabolic and anti-catabolic effects in skeletal muscle tissue.
2. It increases the skeletal muscle uptake of glucose and certain amino acids.
3. It increases glycogen synthase activity and the rate of glycogen storage in muscle.
4. Its positive effects are largely enhanced in the post-training recovery state.

Given the medical studies available at the time, I’m actually at a loss for how the authors of our original warning letter could have even made the statement they did. Perhaps, as was the situation for a long time with anabolic steroids, they were simply looking for the definitive double-blind placebo-controlled study (with strength and muscle mass increases both measured in healthy trained subjects) that did not exist. With the amount of telling data available on this hormone, however, I think there’s little doubt what the results would be if such a study were ever undertaken.

William Llewellyn is widely regarded as one of the world’s foremost authorities on the use of performance-enhancing substances. He is the author of the bestselling anabolic steroid reference guide ANABOLICS and CEO of Molecular Nutrition. William is an accomplished researcher/developer in the field of anabolic substances, and is also a longtime advocate for harm reduction and legislative change. He built the website, an extensive online database of information on anabolic steroids and other performance-enhancing drugs.

1. Bodybuilders find it easy to obtain insulin to help them in training. Elkin S L, Brady S, Williams I P. BMJ 1997;314:1280
2. Euglycemic hyperinsulinemia augments amino acid uptake by human leg tissues during hyperaminoacidemia. Bennet WM, Connacher AA, Scrimgeour CM, Jung RT, Rennie MJ. Am J Physiol 1990 Aug;259(2 Pt 1):E185-94
3. Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man. Gelfand RA, Barrett EJ. Clin Invest 1987 Jul;80(1):1-6
4. Insulin action on muscle protein kinetics and amino acid transport during recovery after resistance exercise. Biolo G, Williams BD, Fleming RY, Wolfe RR. Diabetes 1999 May;48(5):949-57
5. Insulin signaling and insulin sensitivity after exercise in human skeletal muscle. Wojtaszewski JF, Hansen BF, Gade, Kiens B, Markuns JF, Goodyear LJ, Richter EA. Diabetes 2000 Mar;49(3):325-31
6. Glycogen concentrations in human skeletal muscle: effect of prolonged insulin and glucose infusion. Hansen BF, Asp S, Kiens B, Richter EA. Scand J Med Sci Sports 9:209-13, 1999