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Sunday, January 20, 2013

Serious Lifting Increases SHBG, Muscle & Total Mass, While Decreasing Total and Trunk Fat in Overweight Young Men. Plus: Why an Increase in SHBG is Nothing to Be Afraid Of

Posted by Unknown at 11:27 PM
Warning: Used correctly, this dumbbell will increase your BMI, your glucose sensitivity and - at least if you still got some fat to shed - your SHBG! And what's the result? Metabolic health, strength and a significantly improved body composition!
If you read the headline of today's news closely and did not freak out due to bro-scientific indoctrination and the firmly held believe that "SHGB is bad for you, bro. I'll bind your testosterone, bro!" you will probably have noticed that the 12-week resistance training regimen 36 of the 49 participants (BMI 31.4 kg/m² age 22 years) of a recently published study by Roberts et al. underwent would have to be considered an epic fail, if we went for the mainstream assessment of workout / dietary success - the infamous body mass index. If the add the broscientific notion that you best reduce your SHBG to zero (or into the negative range, if you find a way to do so), squats, deadlifts, lunges, rows, side raises, overhead presses, triceps extensions and biceps curls appear to be the worst thing you can do for your health and physique!

Yep, there is no debating: The overweight guys gained even more weight...

... and this change in BMI was statistically significant (p = 0.03). In kilograms that means the average 21.5 year old member of the resistance training group gained 1.8kg body weight, but at the same time he lost 1kg of body fat, reduced his waist circumference by 0.55cm and gained a whopping 2.7kg of lean body mass (p < 0.0001; see figure 1, right).
Figure 1: Changes in body composition and strength in the course of the 12-week study period (Roberts. 2013)
As the data in figure 1 (left) goes to show, the resistance training protocol, which comprised three pases with a 2-week introductory period of 12-15 reps to failure, a second hypertrophy phase from week 3-7, in the course of which they lifted in the 8-12 rep range and a subsequent heavier lifting phase with 6-8 reps during phase 3 (weeks 8-12).
"As participants adapted to the training overload, the weight was increased to maintain the prescribed training intensity. All participants trained on 3 non-consecutive days/week, rotating between two daily workout regimens. Workout I consisted of dumbbell (DB) squat, cable row, DB front lunge, DB row, barbell (BB) deadlift, DB triceps extension, and DB curl.Workout II was DB step-up, BB chest press, machine squat, DB overhead press, DB incline chest press, DB side raise, DB reverse fly, and abdominal crunches. A certified personal trainer led all training sessions with a maximum 3:1 participant to trainer ratio." (Roberts. 2013)
You see, real training yields real results. And while diets (in the study at hand "participants were instructed tomaintain their normal ad-libitum diet") are necessary to cut weight and lose fat in those who are already lean, healthy (not metabolically deranged) overweight individuals can achieve a whole lot by just lifting their behind off the couch and into the gym thrice a week.

Aesthetics are not all that counts

That said, in addition to the aesthetic improvements due to the changes in body composition, it should not be forgotten that despite the weight gain that would have discouraged many uneducated dieters, the resistance training only program yielded similar beneficial effects as far as the glucose management and insulin sensitivity of the participants is concerned.
Figure 2: Relative (% baseline) changes in response to oral glucose tolerance test (OGGT) and hormone levels after 12 weeks of resistance training (Roberts. 2013)
How and if this has any direct relation to the hormonal changes (figure 2, right) in general and the increase in SHBG, in particular, is as of now, not 100% certain.
"The function of SHBG has classically been ascribed to the binding of steroid hormones in circulation to regulate their bioavailability. Because SHBG is decreased with obesity, it was thought that SHBG may be a marker for obesity in relation to T2D risk. However, evidence suggests that SHBG independently affects glycemic control and predicts both  T2D and metabolic syndrome. In addition, it is known that insulin and glucose also have reciprocal action on SHBG to regulate SHBG production in the liver." (Roberts. 2012)
Despite the fact that the perception of SHBG as an inactive binding protein is changing as of late, the study at hand does not provide clear cut evidence that the improvements in insulin tolerance occur in response to the changes in SHBG. This result matches perfectly with human data by Daka et al. and a study Simó et al. In those two 2012 paper, the researchers state that type I diabetics (=low to no insulin) have very high, type II diabetics, on the other hand, very low SHBG levels (Daka. 2012), and that the inflammatory cytokine TNF-alpha and a hallmark feature of diabesity directly represses SHBG production, as well (Simó. 2012; check out the blue infobox below to get a "feeling" for further things that are related by one way or another to SHBG).

Increasing SHBG levels in the lower third of the normal range are nothing to worry about

SHBG does also figure (unsorted list; (+) = positive association meaning high SHBG high whatever, (-) = neg. association, meaning low SHBG high whatever) in ... Bone density (+) in male prostate cancer patients (Varsavsky. 2012) as well as US men in general (Trabert. 2012) || BMI, BP and HOMAR-IR (+) in postmenopausal women (Davis. 2012), in premenopausal women from the Japanese Saku cohort, the exact opposite was the case, i.e. high SHBG = low risk of type II diabetes (Gota. 2012) || breast cancer risk (-) based on data from the Nurses Health Study (Zhang. 2013) || prostate cancer (+ when abnormally high and testosterone low; García-Cruz. 2012) || weight loss after gastric bypass (+), obese women (Ernst. 2012) || peripheral artery disease (-) in older men and women (Maggio. 2012) || vascular dementia (-) in men (Xing . 2013)
In view of the results of previous studies which had a resistance training component, involved healthy, normalweight young (McCall. 1999), middle-aged (Cadore. 2008) or old individuals (Hakkinen. 2002) and had no effect on SHBG levels, it appears way more likely that increased insulin sensitivity in response to the resistance training lead to increases in SHBG and not vice-versa. This hypothesis would be supported by a rodentt study Roberts and his co-workers refer to in the conclusion of their paper:
"Selva et al. [Selva. 2007] elegantly demonstrated that elevated glucose (and fructose), rather than insulin might be the primary stimulus to lower SHBG. In this study, transgenic mice expressing different SHBG transgenes exposed to diets with elevated monosaccharides led to large decreases in SHBG." (Roberts. 2013)
This alone still does not suffice to shed more light on the SHBG <> diabesity connection, it should yet be enough to finally draw the curtain over the initially mentioned broscientific myth that SHBG was your enemy. As long as it's within the lower third of the normal range (which was the case in the study at hand) any further decrease is almost certainly going to have more negative than positive effects on your overall health - and if it impairs insulin sensitivity, your physique, as well (important note: both age and sex appear to modify the role of SHBG, for examples see in the infobox to the right)

Bottom line: Whether SHBG is an active modulator or passive indicator of efficient / inefficient glucose management has not been fully understood. It does yet appear to be more likely that changes in SHBG occur in response to changes in blood glucose. In any way, you certainly don't have to worry about the potential increase in SHBG in response to resistance training. Ah,... and in case you are wondering at least in obese postmenopausal women the same increases in SHBG occur in response to aerobic exercise, as well (Kim. 2012)

References:
  • Cadore EL, Lhullier FL, Brentano MA, da Silva EM, Ambrosini MB, Spinelli R, Silva RF, Kruel LF. Hormonal responses to resistance exercise in long-term trained and untrained middle-aged men. J Strength Cond Res. 2008 Sep;22(5):1617-24.
  • Daka B, Rosen T, Jansson PA, Råstam L, Larsson CA, U Lindblad. Inverse association between serum insulin and sex hormone-binding globulin in a population survey in Sweden Endocr Connect. 2013;1:129-133.
  • Davis SR, Robinson PJ, Moufarege A, Bell RJ. The contribution of SHBG to the variation in HOMA-IR is not dependent on endogenous oestrogen or androgen levels in postmenopausal women. Clin Endocrinol (Oxf). 2012 Oct;77(4):541-7. 
  • Ernst B, Wilms B, Thurnheer M, Schultes B. Reduced Circulating Androgen Levels After Gastric Bypass Surgery in Severely Obese Women. Obes Surg. 2012 Nov 29.
  • García-Cruz E, Carrión Puig A, García-Larrosa A, Sallent A, Castañeda-Argáiz R, Piqueras M, Ribal MJ, Leibar-Tamayo A, Romero-Otero J, Alcaraz A. Higher sex hormone-binding globulin and lower bioavailable testosterone are related to prostate cancer detection on prostate biopsy. Scand J Urol. 2012 Nov 27.
  • Goto A, Morita A, Goto M, Sasaki S, Miyachi M, Aiba N, Terauchi Y, Noda M, Watanabe S; the Saku Cohort Study Group. Associations of sex hormone-binding globulin and testosterone with diabetes among men and women (the Saku Diabetes study): a case control study. Cardiovasc Diabetol. 2012 Oct 16;11(1):130.
  • Hakkinen K, Kraemer WJ, Pakarinen A, et al. Effects of heavy resistance/power training on maximal strength, muscle morphology, and hormonal response patterns in 60–75-year-old men and women. Can J Appl Physiol 2002;27:213–31.
  • Kim JW, Kim DY. Effects of aerobic exercise training on serum sex hormone binding globulin, body fat index, and metabolic syndrome factors in obese postmenopausal women. Metab Syndr Relat Disord. 2012 Dec;10(6):452-7.
  • Maggio M, Cattabiani C, Lauretani F, Artoni A, Bandinelli S, Schiavi G, Vignali A, Volpi R, Ceresini G, Lippi G, Aloe R, De Vita F, Giallauria F, McDermott MM, Ferrucci L, Ceda GP. The relationship between sex hormones, sex hormone binding globulin and peripheral artery disease in older persons. Atherosclerosis. 2012 Dec;225(2):469-74.
  • McCall GE, Byrnes WC, Fleck SJ, Dickinson A, Kraemer WJ. Acute and chronic hormonal responses to resistance training designed to promote muscle hypertrophy. Can J Appl Physiol. 1999 Feb;24(1):96-107.
  • Roberts CK, Croymans DM, Aziz N, Butch AW, Lee CC. Resistance training increases SHBG in overweight/obese, young men. Metabolism. 2013 Jan 11.
  • Selva DM, Hogeveen KN, Innis SM, Hammond GL. Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene. J Clin Invest 2007;117:3979–87. 
  • Simó R, Barbosa-Desongles A, Sáez-Lopez C, Lecube A, Hernandez C, Selva DM. Molecular Mechanism of TNFα-Induced Down-Regulation of SHBG Expression. Mol Endocrinol. 2012 Mar;26(3):438-46. 
  • Trabert B, Graubard BI, Nyante SJ, Rifai N, Bradwin G, Platz EA, McQuillan GM, McGlynn KA. Relationship of sex steroid hormones with body size and with body composition measured by dual-energy X-ray absorptiometry in US men. Cancer Causes Control. 2012 Dec;23(12):1881-91.
  • Varsavsky M, Reyes-García R, García-Martín A, Ramírez RG, Avilés-Perez MD, Muñoz-Torres M. SHBG levels are associated with bone loss and vertebral fractures in patients with prostate cancer. Osteoporos Int. 2012 May 16.
  • Xing Y, Qin W, Li F, Jia XF, Jia J. Associations between sex hormones and cognitive and neuropsychiatric manifestations in vascular dementia (VaD). Arch Gerontol Geriatr. 2013 Jan-Feb;56(1):85-90.
  • Zhang X, Tworoger SS, Eliassen AH, Hankinson SE. Postmenopausal plasma sex hormone levels and breast cancer risk over 20 years of follow-up. Breast Cancer Res Treat. 2013 Jan 3

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