What's the Optimal Dose of Vitamin D3 for Lean, Normal-, Overweight & Obese Women With Established Vitamin D Deficiency to Get 25OHD Back into the Normal Range?

Both ladies are D-ficient, but will probably need profoundly different amounts of D3 to get their 25OHD back in range.

Actually, I guess, I don't really have to tell you that there is not going to be guest post by Adelfo Cerame, today. Adelfo is busy with the last weeks of school, but will be back as soon as he has passed all the tests. And while I am not sure, whether or not you would call the latest on vitamin D supplementation an adequate replacement for a contest prep update from "your's truly", I suppose that it's better than nothing to bridge the time that still remains until the SuppVersity  Science Round-Up on the Super Human Radio Network is going to air (the show starts at 12PM, EST; the Science-Round-Up airs in the 2nd hour and will thus begin at 1PM, EST; click here to listen live or wait for the podcast // update: now available).

I am honestly not yet sure what exactly we will cover today, but among the things I am still thinking about how we can squeeze them into a 1h show are...

• methylxanthines caffeine, theobromine and theophylline can bind to human DNA - what does that tell us about the purported health benefits of caffeine & co?
• caffeine prevents memory impairment - in this case in a model of sporadic Alzheimer's disease
• anti-Alzheimer's effect of CLA - plus a list of supplements that have been implicated in the prevention of Alzheimer's and other amyloid diseases such as Parkinson's, Cerebellar Ataxis, Amyotrophic lateral sclerosis and (hardly recognized as an amyloid disease) diabetes type II
• the effect of body weight on the benefits of circuit training in older women - turns out that those who need it the most, namely the obese, also see the greatest benefits
• Gum arabicum to ward off holiday weight gain - that this could actually work is at least what a recent human study would suggest
• more on vitamin E, resveratrol, soldiers don't get hurt in battle, but by geranium (DMAA), ...

I think there should be something for everyone of you. Plus: If everything works out, this is going to be the first show to air live via Skype, so no nagging land line echoes and noise any more.

Let's get to the D-news, now

The general consensus among the vitamin D advocates currently is that 2,000 IU of vitamin D3/day is the minimum you need to bring low levels of 25OHD back into the normal range. A soon-to-be-published study by Gallagher, Yalamanchili and Smith that's available ahead of print on the website of the Journal of Steroid Biochemistry and Molecular Biology does yet contradict this notion - at least for women with a body mass <25kg/m² even the meager RDA of 400IU would be enough (Gallagher. 2012). That said the concise paper actually describes the results of two, not just one experiment, with

• study 1 (ViDOS) being a one-year randomized, double-blind placebo controlled study (ViDOS – Vitamin D supplementation in Older Subjects) of increasing doses of vitamin D3 (400,  800, 1600, 2400, 3200, 4000 or 4800 IU/day vitamin D3 vs. placebo + calcium supplements to maintain calcium intake between 1,200-1,400mg/day) in 163 Caucasians, age 57–90 years; all vitamin D insufficienty, i.e. serum 25OHD ≤ 20 ng/ml (50 nmol/l), and 
• study 2 (STOP IT) being a 3-year intervention study of calcitriol 0.25 mcg (the active form of vitamin D) twice daily, conjugated estrogens 0.625 mg  daily, a combination of both and placebo in 488 elderly women, age 65–77 years

Body composition indices for the studies at hand (i.e. percentages of total and regional fat and fat-free mass) were measured by dual energy X-ray absorptiometry (DEXA Hologic Delphi) at baseline and after 12 months.

Figure 1: Mean total body weight, total body lean mass, total body fat mass and serum 25OHD in different BMI subgroups of study 2 (STOPIT); right, corresponding calculated ratios (based on Gallagher. 2012).

Even the baseline data in figure 1 does actually yield some insights into the relation of BMI, adiposity and 25OHD levels. While the data on the left already shows that the fat mass increases almost linearly across the BMI levels, while the lean mass remains relatively stable (with the highest value in the overweight group, though), the ratios I calculated and plotted on the right-hand side of figure 1 make it even more obvious clear: The lean / fat mass ratio scales with the BMI. With identical levels in the normal- and overweight individuals and significant increases and declines in the lightest and heaviest study participants. Moreover, the 25OHD vitamin D to fat mass ratio drops most significantly between the low BMI and the upper normal zone, where I suppose even most of the "healthy" individuals will be hovering around these days.

Being lean is a positive predictor of increases in 25OHD with supplementation

That this latent "chubbiness" of the average Westerner may be of particular significance in view of the negative / non-significant outcomes in many of the vitamin D supplementation trials, becomes self-evident, when you take a closer look at the data in figure 2, however you will have to realize that my plot which comprises above all the highly relevant relative changes (middle, marked in red) tells a different story than the original plot from the study showing only the absolute changes (left, but in form of a line graph).

Absolute, relative (compared to baseline) changes and total 25OHD levels (ng/ml) after supplementation with low, medium and high amounts of vitamin D3 in lean, normal, overweight and obese women (based on Gallagher. 2012)

Accordingly, the conclusion of the abstract, which says that "the response to vitamin D is dependent on body weight" and that "women with BMI <25 kg/m² develop much higher levels of serum 25OHD after vitamin D supplementation compared to those with BMI of >25 kg/m²" (Gallagher. 2012) may be correct, but is somewhat misleading as it is open to be interpreted as 'lean women respond most favorably to vitamin D supplementation' - an interpretation that is not really sustainable in view of the relative changes I calculated for figure 2  (middle), yet by no means as incredible as the abstract of another vitamin D study, I dessicated back in September (see "Stronger & Leaner or Fatter & Less Muscular W/ 4,000IU Vitamin D3 - What if Abstract and Data Tell Different Stories?")

Bottom line: The data from this most recent investigation into the differential response of lean, normal, overweight and obese women to vitamin D3 supplementation shows that the absolute increases appear on BMI and that...

• 

  Always take vitamin D with fatty foods! (see "A Fat D-Ficiency")

  low dose supplementation (400 or 800IU/day) is probably only sufficient to rise and maintain adequate vitamin D levels in lean women,
• medium dose supplementation (1,400 or 2,400IU/day) yields the most favorable outcomes in total 25OHD levels and 
• high dose supplementation (3,200, 4,000 or 4,800IU/day) does not yield additional benefits in either the the normal-, overweight and obese subgroup and only marginally higher levels in the lean women.

Overall the study at hand would thus support the notion that a daily vitamin D supplement containing ~2,000IU is the best way to get deficient levels back up, esp. for lean women it should be no problem to cut back to 2x the RDA, i.e. 800IU after normal vitamin D levels are achieved. For the rest, future studies will have to show if low dose supplementation is enough.

These longissimus dorsi slices of mice on a normal and a vitamin D3 supplemented diet show that supplemental vitamin D3 can be used as a fat synthesizer and meat tenderizer in "meat-producing animals". (learn more)

The often-heard hypothesis that the decreased response to vitamin D supplementation in the obese would be a result of the preferential storage of vitamin D in the adipose tissue was not supported by data of the Ghallagher study "there is no evidence from the dose response curves that in obesity serum 25OHD is being deposited in fat" (Gallagher. 2012). In view of the fact that contrary to total vitamin D, which is in fact preferentially stored in adipose tissue (78%) over lean muscle (14%), 25OHD stores are distributed much more evenly with 33% being stored in body fat and 20% in muscle tissue in omnivores like humans and swine (the data is in fact based on a study in pigs; cf. Jakobsen. 2007).

Lastly, a beneficial effect of increase / normalized vitamin D levels on lean or fat mass was (once again) not observed in any of the studies; and that despite the fact that "body fat was an independent predictor of serum PTH", which decreased in response to calcitriol supplementation in study 2 (which is actually more of an adjunct for correlative analysis and as a data source to compare the results of study 1 to). In other words, normalizing your vitamin D levels without taking appropriate measures to counter what's probably behind both, the nasty body fat and the low vitamin D level is not going to make you lean or musclar - at least as of now, it rather appears as if this was yet another instance, where we are - if anything - treating isolated symptoms instead of the root causes of the obesity epidemic.

References

• Gallagher JC, Yalamanchili V, Smith LM. The Effect Of Vitamin D Supplementation On Serum 25OHD In Thin And Obese Women. J Steroid Biochem Mol Biol. 2012 Dec 11.
• Jakobsen H, Maribo A, Bysted HM, Sommer OH. 25-Hydroxyvitamin D3 affects vitamin D status similar to vitamin D3 in pigs – but the meat produced has a lower content of vitamin D. British Journal of Nutrition. 2007; 98 908–913.
• Shephard RJ. Limits to the measurement of habitual physical activity by questionnaires. Br J Sports Med. 2003 Jun;37(3):197-206; discussion 206.

More Protein = Less Fat: Additional(!) Whey, But Not Soy, Induces Slight Body Fat Decrease in Obese Individuals Without Conscious Dietary Intervention(s)

Image 1: Whey proteins are cheap,
many are tasty and as this study
shows, effective not only for increases
in lean, but also for reductions in fat mass.

As a faithful visitor of the SuppVersity, it won't surprise you to read about the counter-intuitive effects the addition of 56g of whey protein to the diet of ninety overweight and obese patients (BMI ~30kg/m²; age 51y) had in a study the results of which have finally been published in the Journal of Nutrition on June 15 (Baer. 2011). What could be news to you, however, is that the same amount of soy protein failed to induce similar changes.

David J. Baer and his colleagues from the Human Nutrition Research Center in Beltsville (note: this institute is financed by the USDA) instructed the participants of the study to add 56g of a supplement containing either whey (WP), soy protein (SP) or carbohydrate (CHO) to their regular diets for 23 weeks - other than that participants were not provided any dietary advice and were supposed to continue to consume their free-choice diets.

The supplements were supposed to be taken in divided doses with breakfast and dinner, respectively. Most subjects chose to consume their protein either before of with those meals (breakfast: 80%; dinner: 72%). Yet other than one would have suspected...

[t]he dietary treatments did not affect hunger (P = 0.11), desire to eat (P = 0.11), prospective consumption (P = 0.38), or stomach fullness (P = 0.62).

Unfortunately, the study is lacking objective information about the effective macronutrient intake of the individuals. Based on the very subjective visual analogue scale (VAS) questionnaire that was used to 'measure' satiety it is however impossible to exclude the possibility that the subjects just (over-)compensated for the additional 417kcal they consumed in form of supplements. This holds especially true in view of the fact that over a time course of 23 weeks, even a minimal reduction of 42.5-52.5 kcal/day should (assuming the flawed calories in vs. calories out hypothesis were true) have facilitated the exact same weight reductions.

The lack of information about the overall caloric value and macronutrient composition of the subjects' diets is thus a very unfortunate shortcoming of the study, you should keep in mind, when looking at the changes in body composition, which as a closer look at the data in figure 1 shows were marginal [0.1% fat mass lost per week is not really impressive, is it?], anyway.

Figure 1: Changes in body composition and waist circumference relative to baseline in obese individuals supplemented with carbohydrate, whey or soy protein beverage over the course of 23 weeks (data calculated on the basis of Baer. 2011)

Despite the fact that the abolute effect of this 'dietary intervention' was relatively small, the relative changes in body composition and morphology, I calculated and plotted in figure 1, make it quite obvious that only individuals consuming the whey protein shakes saw beneficial effects on both their body fat, as well as the circumference of their waistline. On the other hand, the addition of soy protein produced the largest increases in IGF-1 (cf. figure 2), yet without any statistically significant effect on body composition or morphology. The carbohydrate group, lastly, experienced a significant, yet completely undesirable recompositioning effect with an overall increase in body fat of >3.5%. In view of the negligible increase in waist circumference, it is worth to note that their bodies obviously distributed evenly across all fat depots.

Figure 2: Serum markers of the three groups after 23 weeks of supplemental carbohydrate, whey or soy protein (data adapted from Baer. 2011)

With the differences between blood parameters other than IGF-1 and ghrelin being non-significant [especially the metabolically relevant thyroid hormones T3 & T4], it is difficult to find any reasons other than compensatory effects due to (unconscious, but well existent) increases in satiety. This holds especially true, in view of the fact that "[b]ased on the length of the treatment and the daily energy provided from the supplement", the scientists had estimated that "weight gain would exceed ~10 kg without any compensation for the additional energy of the supplement." If we now have a look at the hunger-hormone ghrelin (cf. figure 2), its elevation, or reduction (vs. soy protein as a median that left the weight of the participants unchanged) in the carbohydrate and whey group, respectively, this would corroborate my initial hypothesis that the 90 men and women participating in this study may, without even noticing it, have reduced their total caloric intake by exactly those 42.5-52.5 kcal/day that, in conjunction with an overall improvement in the macronutrient composition of their meals (meaning a higher protein content), allowed them to drop those 2.3kg of fat in the course of those 23 weeks on whey protein supplements.

Edit: My buddy Sean from CasePerformance reminded me of a study by Hartman et al. (Hartman. 2007) from the McMaster University Medical Center in Hamilton, ON, Canada from 2007. Despite being published in the "Pre-SuppVersity Ages" some of you may remember this study, as it triggered a series of reports that brought milk back to the radar as a potent post-workout supplement. The study showed that compared to a soy formula a milk-derived post-workout shake (17.5 g protein, 25.7 g carbohydrate, 0.4 g fat) facilitated greater increases in type II muscle size and lean mass while reducing fat gain at roughly equal overall body weight gains. Sean also points out that - other than in the study at hand - Hartman et al. also recorded total caloric intake and found no statistical significant differences between the two groups, whether or not this allows for any inferences on the actual caloric intake of the obese subjects in the Baer study is questionable, however. After all, you ought to be hungry after a workout and you probably know that no matter how large your post-workout drink may be, you're going to be hungry again about 1h after...

Binging Counter-Indicated Not Even, but Especially in Pregnancy: Excessive Gestational Weight Gain Associated With Higher Body Fat in Infants

A recent study conducted by a group of researchers from New York (Hull. 2011) found that excessive gestational weight gain in already overweight women had detrimental consequences on the body composition of their offspring:

[I]nfants from obese mothers had greater percent fat (%fat) and FM than offspring from normal and overweight mothers. Within the excessive group, infants from normal mothers had less %fat and FM than infants from overweight and obese mothers.

This is alarming news, especially if one takes into consideration the results of Conan et al. from Harvard (Conan. 2010) who found that "birth weight [and I would suppose body fat even more so] is significantly associated with incident AF [arterial fibration]" in later life.

Figure 1: Infant body fat [%] in formerly normal, overweight and obese women with either appropriate of excessive gestational weight gain

These results should remind mothers-to-be that the good old saying "you are what you eat" is and will be true not only for themselves, but for their children and maybe even their grand children, as well. Furthermore, following a healthy pregnancy diet and throwing overboard old over- as well as undereating (many women are on a life-long calorie restriction and begin binging when they are pregnant and finally "allowed" to) habits will give both your children, as well as yourself a headstart into a "new" life. Consider that before you dip the next potato chip into a pot of sugar-loaden peanut butter.

On a side note: If you have a closer look at the data in figure 1, you will notice that gestational overeating is most detrimental for the children of mothers who are "only" overweight. While this would of course warrant further investigations, I would suspect that this is the group to which most of the the aforementioned life-long-dieters belong. Many of these women literally switch their calorie intake from 0 to 1000 and "jojo" back up far beyond any healthy settling point - with all the corresponding ill effects on their as well as on the health of their unborn children.

Fat or Fire, What Comes First? Scientists Answer: Obesity Alone Triggers Inflammatory Signaling in Mice

The metabolic syndrome, i.e. the combination of obesity, inflammation and insulin resistance, is at the center of contemporary medical research. In my appearance on Carl Lenore's Super Human Radio, I already mentioned that from a logical perspective the mainstream belief, inflammation was the root of all evil, must be flawed. How should the reaction to a problem be the cause of the very problem itself? A recent study coming from a group of Korean scientists strengthens my conviction that out of the triad that not inflammation, but rather obesity or - one step further up in the genesis of the pathology - the combination of an unhealthy diet and a sedentary lifestyle is at the heart of the triad we now call the "metabolic syndrome".

Kim et al. investigated the pro-inflammatory signaling cascade in either diet-induced (DIO) or leptin gene deficient (ob/ob) obese mice and found that obesity alone ...

[...] up-regulated the expression of TLR1–9 and TLR11–13 in murine adipose tissues, a phenomenon linked with downstream nuclear factor κB [inflammatory protein linked to linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development], interferon regulatory factors, and STAT-1 activation, and up-regulated the expression of cytokines and chemokines via MyD88-dependent and MyD88-independent cascades [activate NF-κB].

Thus, obesity sets the scene for inflammation and inflammation in turn triggers a cascade of unfavorable metabolic and hormonal changes which in and out of themselves result in further weight gain...

Here, we have a self-enhancing pathologic circle, which - and this is probably an even more important result of the study - was especially "effective" in the group of diet-induced obese mice:

The magnitudes of the obesity-induced up-regulation of the TLR1, TLR4, TLR5, TLR8, TLR9 and TLR12 genes in the visceral adipose tissue were greater in the DIO mice than in the ob/ob mice. Similarly, the expression of the IFNα and IFNβ genes significantly increased in the adipose tissues of the DIO mice but did not change in the adipose tissues of the ob/ob mice.

So, its not in your genes, but in your hands, feet and mouth to ward off the plague of the 21st century: Exercise and eat healthy to get lean and/or stay lean and stave off inflammation and diabetes.

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

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