Let's start with a few questions. Would you re-wrap your presents the day after Christmas? Or tie one hand behind your back before you head to the gym? Or perhaps tie up your girlfriend before you... okay, so that one's a different story. But you get the point. We generally don't bind things up if we want to get their full effect.
Is it any different with Testosterone? Although debatable, probably not much. And yet the main focus in bodybuilding circles seems to be on adding more T rather than freeing-up what we have. It's no secret to many T-mag readers that nearly all of the circulating androgens in the bloodstream are bound to transport proteins – notably sex hormone binding globulin, or SHBG. Other proteins also exist in the serum, carrying around other hormones, various nutrients, etc. But SHBG is of particular interest. Along with albumin, it ties up about 98% of our bodies' circulating Testosterone, keeping it from doing its anabolic work.
Imagine if we could reduce the percentage of SHBG-bound Testosterone to 90% or even 96%. The biological impact could be huge. It's fairly well established that by unbinding Testosterone from SHBG, the free hormone exerts greater effects when compared to total T.(3, 7, 12, 14, 28) Ah, if only it could be done via practical means. Normal endogenous (gonadal) production could be all the more effective and any supplemental androgens may have noticeably greater effects. This latter scenario results in saved money and/ or extended use of one's person androgen cache. These are not trivial matters.
Before I get into the concept of "unleashing the hostage," let me make a few comments to naysayers – and admit that I'm about to wax a bit theoretical here. Although albumin also binds Testosterone, it generally doesn't keep the T from dissociating in local tissue capillary beds and reaching its cellular target – or prevent its bioavailability.(1, 10, 16, 19, 26) Better to consider albumin as a transport protein rather than a binding protein, as there are different affinities among such serum proteins for our beloved T.(10, 18, 23) Nonetheless, I can certainly see why the role of serum proteins as "kidnappers" has been overstated in the past. TC pointed this out in Estrogen's Dirty Little Secret. Indeed, the truth is that – as far as serum proteins go – albumin just isn't a major concern; it even appears to be a good thing.(3)
SHBG, conversely, has a very high affinity for Testosterone. Because of it's greediness for Testosterone, it's generally considered to reduce the physiologic effects of T. So much so in fact, that the term "non-SHBG-bound Testosterone" is now common, rather than simply "free Testosterone." This protein, also known as "TeBG" (Testosterone-estrogen Binding Globulin) has such high affinity for Testosterone that it can even suck T out of red blood cells where it is also transported in the bloodstream.(4) And here's a very cool fact: SHBG binds tighter to T than to estradiol and estrone.(18, 23, 29) We can, however, take advantage of this. Check out this quote from the text I use in my graduate Nutritional Biochemistry course (Murray, R., et al, 2000):
Testosterone binds to SHBG with higher affinity than does estradiol. Therefore, a change in the level of SHBG causes a greater change [decline] in the free Testosterone level than in the free estradiol level. An increase of SHBG may contribute to the increased free estradiol: Ttestosterone ratio... and hence contribute to the attendant signs and symptoms of "estrogenization."
Wow. Sounds like bad medicine. I figure that, although it has been overstated by some, it's still generally a good thing to reduce SHBG if you're a bodybuilder. Just remember that the "free-hormone hypothesis" remains a hot debate among science geeks.(17) Hell, now even TC and I are being sucked into it. Luckily, T-men can "go take downs" to resolve their issues. (NOTE: This is not the method by which science geeks usually settle debates... ) Anyway, bear with my concept that SHBG may in fact be a thorn in the side of certain bodybuilders...
Okay, by now I know what you're thinking. "Spill it. How do I keep SHBG at bay and unleash the Testosterone I already have?" Well, not to disappoint, let's look at a few research supported facts:
• Under-eating is related to higher SHBG concentrations.
• Over-training is related too.
• Over-eating, conversely, lowers SHBG.
• Insulin is inversely related to SHBG levels.
• Particular supplements appear to reduce SHBG binding.
Panning down this list, we learn that periods of massive eating kick up the anabolic drive in a variety of ways. Conversely, eating like a wussy (you know, only when you're hungry) threatens to leave you somewhere around "dough boy" on the androgen-estrogen continuum.
Let's tackle these five concepts one-by-one. Under-eating, "dieting," has been shown in research to be associated with higher SHBG.(15, 22, 24) Extended periods (weeks) of drastic caloric and/or fat restriction appear to raise the binding protein, presumably reducing Testosterone's effects.
This knowledge supports the concept of cyclical dieting such as the popular cyclic ketogenic diets. These diets aren't strictly starvation-driven. Those critical power-eating weekends, after one is depleted all week, may well prevent SHBG elevation just as they help prevent the triiodothyronine (T3) suppression that is common to "dieting."
Similar to under-eating is over-training. More than a few weeks of excessive volume training not only raise basal concentrations of cortisol in the blood, but also increase SHGB (5), interfering with androgen function. Talk about a catabolic scenario! No wonder pre-competition bodybuilders often lose so much muscle mass despite the self-administration of androgens. They're BOTH under-eating AND over-training. Perhaps the best term for this under-eating/over-training phenomenon is "negative energy balance." The take home message? If you're in a state of frequent, long duration, and/or super-heavy training YOU HAD BETTER EAT.
Regarding points three and four above, it appears that bulking-up has endocrinologic merit. Excess calorie (kcal) intake beyond maintenance needs actually seems to upregulate one's anabolic hormone profile, converting the food into muscle mass. In agriculture, the ease of which feed becomes bodily tissue is called "feed efficiency." It's one of the ways substances like clenbuterol and even conjugated linoleic acid (CLA) work. But even without such adjuncts, the simple act of over-eating triggers physiologic anabolism. Part of this may be explained by improved Testosterone function (less SHBG). Let's look into this concept...
Endogenous (internally produced) insulin concentrations are higher throughout any given day of large frequent feedings (say, every two hours). This is simply a fact unless you're a Type-I diabetic without a functioning pancreas. Insulin is, of course, highly anabolic/ anticatabolic in it's own right – but it also appears to reduce SHBG synthesis (20, 22, 24), and is otherwise related negatively to SHBG levels in the blood.(2,25)
The net result appears to be an unleashing of Testosterone to do its anabolic work! In support of this, an over-eating study in identical twins, involving 1000 kcal excess (and plenty of insulin secretion) per day over 100 days did, in fact result in lower SHBG.(21) So in theory, large, regular meals may aid muscle growth in part via increased Testosterone bioavailability.
This is not to say that indiscriminate pigging-out is advisable or even allowable; the choice of nutrients that accompany periods of "hyperinsulinemia" is paramount. Powering back a couple Big Macs, a supersized fries, and a quart of cola every few hours is clearly better at building your gut than your guns. Providing plenty of high-fructose corn syrup, high-glycemic starch and common fat in the presence of high circulating insulin is a ticket to Pudge World. Don't go there. One needs only to drive down the street to see the super effective "crash weight gain plan" that most Americans self-administer.
Weight alone is not where it's at. This is obvious to most T-mag readers, but I do know lifters who obsess over getting bigger at all costs. Over-emphasis on the scale is a precarious way to judge progress. Even those feed-efficiency substances like clen' and CLA also partition nutrients into muscle tissue. No farmer is going to over feed his critters just to make them fat. He's after BEEF, just like us. (Of course, this is why bodybuilders started taking clen' and CLA.)
I'm not trying to confuse you regarding insulin. It's simply a Jeckyl and Hyde hormone. The pancreas will kick out plenty of it in response to a variety of stimuli. It can make you fat or it can help make you muscular. You can "naturally" manipulate this hormone like few others, but it can't be done the easy way. Toying with higher insulin concentrations is touchy business; the trick is to garner its anabolic benefits without allowing it to indiscriminately build all bodily tissues (e.g. adipose). If you do choose to keep insulin high "the hard way," your Testosterone will start to break from its bonds.
So what nutrients should be coursing through your veins along with high insulin concentrations? Principally amino acids with some, but not too many carbs. A meal of 30-50 grams of protein with perhaps 50-75 grams of complex carbs, eaten to the tune of an alarm wrist watch every two-three hours, is a good bet. Food choices like water-packed tuna, salmon, poultry, fish and 93% lean beef, or a whey-casein shake, are all great protein choices. When co-consumed with whole grains, red potatoes and other starchy carbs, or even fruit mixed-in with your protein shakes, you're telling your pancreas it's time to rock. My friend and colleague, John Berardi formulated Surge for Biotest for just this kind of effect. Insulin levels will kick up in about 30-60 minutes and stay up for about 2-3 hours. Check out the figure from some of my own data.
There will be amino acids available for the insulin to drive into muscle tissue and just enough glucose to fill-out your glycogen stores without much left for adipose tissue lipogenesis (fat building from the blood glucose). And more relevant to our androgen discussion, even an acute rise of insulin appears to be enough to lower SHBG! (11)
Oh, and one last thing. I'm certainly no high-carb nut. For those of you wondering where fat and protein fit into this insulin-SHBG scenario, good for you. A high-carb intake meant to raise insulin levels in a "bodybuilder friendly way" only works well the first half of the day. By mid afternoon, glucose tolerance is already starting to lessen (8), potentially increasing the risk of carbs becoming body fat. Thus, a greater reliance on fat as an energy source appears wise as evening approaches.
Although not as insulinogenic as carbs, "good fat" choices like olive oil, flax, canola and fish oils make a nice addendum to protein in the evenings. Insulin concentrations are lower in the evening anyhow (8), so pounding carbs at this time probably won't smack down SHBG much more. Keeping the protein high throughout the day is a good bet in any case, however, as it has been shown to have a stronger inverse relationship with SHBG than carbs or fats.(14)
In a nutshell, consuming two to three protein-carb meals before lunch and two protein-fat meals after lunch seems a decent "androgen emancipation" strategy. It should keep insulin levels reasonably high while providing both proper substrates to muscle and reducing SHBG. The probable free-Testosterone elevation over time should help the higher circulating insulin that you're cultivating do it's anabolic/ anti-catabolic thing. And let's not forget, early or late, workouts generally enable an additional carb meal post-exercise, so take advantage of them. Getting an insulin spike when Testosterone and GH are also high is like hiring three construction workers at once!
Okay, now that we know how to carefully jack-up insulin regularly enough to keep SHBG from hog tying our precious T, let's briefly talk supplements. Perhaps the most interesting is Avena sativa, or green oat, like that found in Biotest's Tribex-500. Data on this stuff are sparse but there is some suggestion that it combats SHBG. An often touted but unpublished report from the Institute for Advanced Study of Human Sexuality in San Francisco suggests that green-oat extracts do release Testosterone from its binding proteins.
And as a side note, Japanese research suggests increased luteinizing hormone (LH) secretion as well, via interactions with the anterior pituitary gland itself (6, 9). Yeah, these latter studies were done in amenorrheic women, but I told you the data were sparse! Anyhow, the combined effect could well be higher circulating concentrations of free T, even in men.
The other general approach is to simultaneously raise total T and free-T via prohormones. Although unpublished, I've seen first hand that androstenediol, for example, can raise serum Testosterone levels with the bound (SHBG-tied) and unbound levels rising simultaneously. One could very well speculate that a prohormone (or other steroid), combined with green oat supplementation and natural (or unnatural) insulin elevation could be quite the ticket for muscle anabolism.
To summarize our "unleashing" plan, we need to 1) Eat every 2-3 hours, focusing on protein with carbs in the morning and protein with "healthier fats" in the evening 2) Allow for adequate rest – perhaps two "off" days weekly – to prevent over-training 3) Limit high-volume training cycles to just a few weeks, and 4) Possibly consider a 2-4 week course of Avena sativa along with the frequent eating to see if one's prohormones, (etc.) are more effective.
With the person-to-person variation in SHBG being on the order of 40-50% (27), these "unleashing" suggestions may be just the ticket for those of you who have high SHBG and don't even know it. Although the "free hormone hypothesis" debate rages on, it is an interesting scenario – especially if we can control it. If you get less progress from a cycle of androgens than your gloating training buddy, SHBG may be involved. Perhaps the data mentioned here is your missing factor. In any case, the research suggests a new mechanism for the wonders of massive, disciplined eating.
Now go track down some of that leftover beef carcass in the fridge, will ya?
1. Belgorosky A. Validity of the calculation of non-sex hormone-binding globulin-bound estradiol from total testosterone, total estradiol and sex hormone-binding globulin concentrations in human serum J Steroid Biochem 1987 Oct;28(4):429-32.
2. Buyalos R., et al. The influence of luteinizing hormone and insulin on sex steroids and sex hormone-binding globulin in the polycystic ovarian syndrome. Fertil Steril 1993 Oct;60(4):626-633.
3. Demisch K, and Nickelsen T. Distribution of testosterone in plasma proteins during replacement therapy with testosterone enanthate in patients suffering from hypogonadism Andrologia 1983;15 Spec No:536-41.
4. Egloff M. Influence of sex hormone binding globulin and serum albumin on the conversion of androstenedione to testosterone by human erythrocytes Acta Endocrinol (Copenh) 1981 Jan;96(1):136-40.
5. Fry, A. American Society of Exercise Physiologists Fourth Annual Meeting, Memphis, TN: September 27-29, 2001.
6. Fukushima, M. et al. J Exp Med Jun 1976; 119(2): 115-122.
7. Gandar R. Interpretation of the blood level of a steroid Rev Fr Gynecol Obstet 1985 Aug-Sep;80(8-9):635-40.
8. Grabner, W., et al. Diurnal variation of glucose tolerance and insulin secretion in man. Klin Wochenschr 1975 Aug 15;53(16):773-8.
9. Hasegawa, T., Hayashi, M., Ebling, F. and Henderson, I. (Eds.) Fertility and Sterility. Proceedings of the Seventh World Congress, Tokyo and Kyoto, Oct 17-25, Amsterdam, Exerpta Medica, 1973, 632-633.
10. Hobbs, C., Jones, R., and Plymate, S. The effects of sex hormone binding globulin (SHBG) on testosterone transport into the cerebrospinal fluid J Steroid Biochem Mol Biol 1992 Jul;42(6):629-35.
11. Katsuki, A., et al. Acute and chronic regulation of serum sex hormone-binding globulin levels by plasma insulin concentrations in male noninsulin-dependent diabetes mellitus patients Journal of Clinical Endocrinology & Metabolism, Vol 81, 2515-2519.
12. Legrand E., et al. Osteoporosis in men: a potential role for the sex hormone binding globulin Bone 2001 Jul;29(1):90-5.
13. Longcope C., et al. Androgens, estrogens, and sex hormone-binding globulin in middle-aged men J Clin Endocrinol Metab 1990 Dec;71(6):1442-6.
14. Longcope C., et al. Diet and sex hormone-binding globulin. J Clin Endocrinol Metab 2000 Jan;85(1):293-296.
15. Lovejoy J. et al. Effects of experimentally induced mild hyperthyroidism on growth hormone and insulin secretion and sex steroid levels in healthy young men. Metabolism 1997 Dec;46(12):1424-1428.
16. Manni A, et al. Bioavailability of albumin-bound testosterone. J Clin Endocrinol Metab 1985 Oct;61(4):705-10.
17. Mendel C. The free hormone hypothesis: a physiologically based mathematical model. Endocr Rev 1989 Aug;10(3):232-74.
18. Murray, R., et al. (Eds.) Harper's Biochemistry, 25th Edition, 2000, Appleton and Lange: New York, NY.
19. Nankin HR, Calkins JH. Decreased bioavailable testosterone in aging normal and impotent men. J Clin Endocrinol Metab 1986 Dec;63(6):1418-20.
20. Pasquali R, et al. Insulin regulates testosterone and sex hormone-binding globulin concentrations in adult normal weight and obese men. J Clin Endocrinol Metab 1995 Feb;80(2):654-658.
21. Pritchard J, et al. Plasma adrenal, gonadal, and conjugated steroids before and after long-term overfeeding in identical twins. J Clin Endocrinol Metab 1998 Sep;83(9):3277-3284.
22. Pugeat M, et al. Interrelations between sex hormone-binding globulin (SHBG), plasma lipoproteins and cardiovascular risk. J Steroid Biochem Mol Biol 1995 Jun;53(1-6):567-572.
23. Shanbhag VP, Sodergard R. The temperature dependence of the binding of 5 alpha-dihydrotestosterone, testosterone and estradiol to the sex hormone globulin (SHBG) of human plasma. J Steroid Biochem 1986 Feb;24(2):549-55.
24. Strain G, et al. The relationship between serum levels of insulin and sex hormone-binding globulin in men: the effect of weight loss. J Clin Endocrinol Metab 1994 Oct;79(4):1173-1176.
25. Tymchuk C. et al. Effects of diet and exercise on insulin, sex hormone-binding globulin, and prostate-specific antigen. Nutr Cancer 1998;31(2):127-131.
26. Umstot ES, Baxter JE, Andersen RN. A theoretically sound and practicable equilibrium dialysis method for measuring percentage of free testosterone. J Steroid Biochem 1985 May;22(5):639-48.
27. Valero-Politi J, and Fuentes-Arderiu X. Within- and between-subject biological variations of follitropin, lutropin, testosterone, and sex-hormone-binding globulin in men. Clin Chem 1993 Aug;39(8):1723-1725.
28. van den Beld AW Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men J Clin Endocrinol Metab 2000 Sep;85(9):3276-82.