ONLINE DRIVERS MEDIA

Dont fall for someone who overgeneralizes, misreports or -interprets study results to tell you that healthy mid-range testosterone levels were a major trigger of cancer development.

I just got an email from my good friend Carl Lanore who hosts the Super Human Radio Show I am sure you have already seen in the sidebar of the SuppVersity. He pointed me towards the results of a recent study from the Copenhagen University Hospital saying "Adel have you seen this? Im sure the media will be all over it." Since Carl is usually pretty good at identifying things that "news" make headlines, I would like to leapfrog the mass media craze before any of you consider cutting off their best parts to end up in the allegedly healthy depth of quasi zero testosterone.

You have no clue what I am talking about? Well, I am about to elaborate. You just have to stay with me for the rest of a comparatively long, but insightful (I promise) analysis of the study and related contemporary evidence.
So, where do I begin?  The "mass media compatible message" of the abstract (and this is usually not even as far as most headline producers read) says: Having normal testosterone levels increases your risk of dying from cancer before your time by at least 30%! The more testosterone, the likelier you will pass away before your expiry date."

Well, as I said, this is the mainstream interpretation. And interpretation anyone could identify as being fundamentally flawed by simply reading the abstract carefully. In fact, you dont even have to read the whole 268 words! It would suffice to read the end of the first line of the result section, where it says:

"For risk of early death after cancer, for men [...]" (Ørsted. 2014)

Did you notice it? There is an "after cancer" in this sentence. This means, your risk of dying, if you develop cancer is increased, if [whatever follows]. Now, that which follows is ...

• if you are in the 2nd quartile, your risk will be increased by 30%,
• if you are in the 3rd quartile, your risk will be increased by 31%,
• if you are in the 4th quartile, your risk will be increased by 52% and
• if you are in the 5th quartile, your risk will be increased by 80%.

So, if you happen to be unlucky enough to develop cancer and your testosterone levels are high there is in fact an increased risk you could die from cancer.

So testosterone is still bad, right? Yes, but anything that is "anabolic", i.e. promotes the growth of all cells in your body is "bad" for someone who has cancer. Guess what chemotherapy will to do your testosterone levels and the amount of other pro-anabolic factors in your body? It will wreak havoc on your testes (Wallace. 1997), reduce their size to that of dried raisins, increase your risk of gynecomastia and reduce your testosterone levels to exactly those 6-10 nmol/L (Whitehead. 1982) of which the previously cited study by Ørsted et al. found that they are associated with the least risk of dying from already existing cancer in your body.

Figure 1: If you look at a random assemble of the myriad of risk associations that have been established for low T, the results of the study at hand do no longer appear to be that frightening - right?

A result that conceals the established negative effects of having low testosterone (see Figure 1) or depressing it which androgen deprivation therapy which may reduce the testosterone levels to the allegedly desirable range, but is associated with a 350% (!) increased risk of dieing from cardiovascular disease in prostate cancer patients (Tsai. 2007). I guess this should make you reconsider the "usefulness" of low testosterone levels.

But there is also an increase in cancer risk, no?

Yes, there is. According to the scientists it is (I quote) "1.07 (95% CI 0.98–1.18) and 1.06 (0.93–1.22) for men and women" if you compare say a man with 10nmol/L to a man with 20nmol/L. Now, as far as I can remember a 95% confidence interval, which is what you see in brackets, i.e. for men 0.98-1.18, defines the range in which the chance that the hypothesis that is tested, i.e. "testosterone influences the risk of prostate cancer" has a 5% chance of not being bullocks... ah, I mean statistical significant.
So, the scientists are 95% sure that a 2x higher testosterone level will be associated with a 2% decrease and 18% increase in... does this ring a bell? Yeah, thats not exactly a reliable prediction considering the fact that the researchers adjusted for smoking status, cumulative smoking, body mass index, alcohol consumption, level of education, and level of income for men and women, but "forgot" to adjust for...

• family history of cancer, which is one of the, if not the main correlate of your risk of developing various cancer, such as prostate cancer (1000% increase, no typo | Steinberg. 1990), colon cancer (up to 59% risk increase depending on the region | Slattery. 1994) or breast cancer (145% risk increase with first-degree relative having breast cancer | Slattery. 1993) 
• diabetes, which has been found to be associated with a 60% increase in colorectal cancer risk in patients who have been diagnosed with diabetes 10+ years ago (La Vecchia. 1997), a
• the level of visceral fat, where high levels (relative to total body fat) are associated with 850% increased risk of breast cancer (Schapira. 1994) and up to 1000% increased prostate cancer risk (Hafe. 2004)
• low sleep duration and quality, which has been associated with an increased risk of developing almost every form of cancer you can think of (Blask. 2009), including 60% increased breast cancer risk for women working the "graveyard shift" (Davis. 2001)

I could go on with all sorts of nutritional factors, medication (specifically hormonal contraceptives) the amount of exercise, the area you live in, your year of birth and hundreds of other factors that have previously been associated with an increase of cancer risk, but I guess the above should suffice to make you less confident that a "confidence interval" of 0.98–1.18 in men and 0.93–1.22 in women was enough to make the claim that "having a high testosterone level would [mechanistically!] trigger the development of cancer.
References:

• Araujo, Andre B., et al. "Endogenous testosterone and mortality in men: a systematic review and meta-analysis." The Journal of Clinical Endocrinology & Metabolism 96.10 (2011): 3007-3019.
• Blask, David E. "Melatonin, sleep disturbance and cancer risk." Sleep medicine reviews 13.4 (2009): 257-264.
• Davis, Scott, Dana K. Mirick, and Richard G. Stevens. "Night shift work, light at night, and risk of breast cancer." Journal of the national cancer institute 93.20 (2001): 1557-1562.
• Garavello, Werner, et al. "Family history and the risk of oral and pharyngeal cancer." International journal of cancer 122.8 (2008): 1827-1831.
• Hafe, Pedro, et al. "Visceral fat accumulation as a risk factor for prostate cancer." Obesity research 12.12 (2004): 1930-1935.
• La Vecchia, Carlo, et al. "Diabetes mellitus and colorectal cancer risk." Cancer Epidemiology Biomarkers & Prevention 6.12 (1997): 1007-1010.
• Morgentaler, Abraham. "Testosterone and prostate cancer: an historical perspective on a modern myth." european urology 50.5 (2006): 935-939.
• Raynaud, Jean-Pierre. "Prostate cancer risk in testosterone-treated men." The Journal of steroid biochemistry and molecular biology 102.1 (2006): 261-266.
• Roddam, Andrew W., et al. "Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies." Journal of the National Cancer Institute 100.3 (2008): 170-183.
• Slattery, Martha L., and Richard A. Kerber. "A comprehensive evaluation of family history and breast cancer risk: the Utah Population Database." Jama 270.13 (1993): 1563-1568.
• Slattery, Martha L., and Richard A. Kerber. "Family history of cancer and colon cancer risk: the Utah Population Database." Journal of the National Cancer Institute 86.21 (1994): 1618-1626.
• Schapira, David V., et al. "Visceral obesity and breast cancer risk." Cancer 74.2 (1994): 632-639.
• Shores, Molly M., et al. "Low serum testosterone and mortality in male veterans." Archives of internal medicine 166.15 (2006): 1660-1665.
• Stattin, Pär, et al. "High levels of circulating testosterone are not associated with increased prostate cancer risk: a pooled prospective study." International journal of cancer 108.3 (2004): 418-424.
• Steinberg, G. D., Carter, B. S., Beaty, T. H., Childs, B. and Walsh, P. C. (1990), Family history and the risk of prostate cancer. Prostate, 17: 337–347. doi: 10.1002/pros.2990170409 
• Tsai, Henry K., et al. "Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality." Journal of the National Cancer Institute 99.20 (2007): 1516-1524. 
• Ujpál, Márta, et al. "Diabetes and Oral Tumors in Hungary Epidemiological correlations." Diabetes care 27.3 (2004): 770-774.
• Wallace, Euan M., et al. "Effects of chemotherapy-induced testicular damage on inhibin, gonadotropin, and testosterone secretion: a prospective longitudinal study." The Journal of Clinical Endocrinology & Metabolism 82.9 (1997): 3111-3115.
• Whitehead, E., et al. "The effects of Hodgkins disease and combination chemotherapy on gonadal function in the adult male." Cancer 49.3 (1982): 418-422.

The study tested only leg exercises, but you can safely expect increased reps on other exercises, as well.

Citrulline? Yes thats the stuff the supplement industry claims to be a better version of arginine. A "super pump supplement", but not necessarily an ergogenic - in spite of the fact that corresponding evidence from rodent and human studies (Briand. 1992; Pérez-Guisado. 2010; Giannesini. 2011) existed years before the study at hand was published (Wax. 2014).

Benjamin Wax and his colleagues from the Mississippi State University and the Auburn University  investigated the effects of citrulline malate supplementation on lower-body resistance exercise performance, blood lactate, heart rate, and blood pressure.

Based on citrulline malate’s chemical composition and a review of the current literature Wax et al. hypothesized that citrulline malate supplementation would mitigate fatigue occurring to the working muscle; therefore, augmenting resistance training performance.
To test their hypothesis the researchers recruited 12 advanced resistance trained male subjects (85kg body weight; <12% body fat; 22.1 ± 1.4 years) and conducted a randomized, counterbalanced, double blind study.

The subjects were randomly assigned to placebo or citrulline malate (8 g; 60 minutes before the workout) groups and then performed repeated bouts of multiple lower body resistance exercise:

"Subjects warmed up on an upright stationary bike (Life Fitness, Brunswick Corporation, Lake Fores, IL) for five minutes, at 60 – 70 revolution/minute with a mass of 3 – 5 kg. Following this warm up, subjects performed two warm up sets (10 repetitions at 90.9 kg and 8 repetitions at 136.4 kg) on the leg press machine. Subjects rested three minutes between sets during the warm up and trial sets.

Next, 60% of each subject’s predetermined 1RM was loaded on the leg press machine and the subject completed as many repetitions as possible until failure occurred. This process was completed for 4 additional sets for a total of 5 sets on the leg press. Next, the subjects performed one warm upset (10 repetitions) on the hack squat machine at a mass of 40.9 kg. This warm up set was followed by 5 sets of 60% of their predetermined 1RM to failure. Finally, following one warm up set (10 repetitions at 36.4 kg) on the leg extension, subjects completed 5 sets of 60% of their 1RM to failure." (Wax. 2014)

The rest periods (recovery periods between sets of exercise), exercise order, and number of sets performed were the same for all subjects in this investigation, for sessions 2 and 3. Blood lactate, heart rate, systolic blood pressure, and diastolic blood pressure were determined pre and post exercise.
The exercise protocol resulted in sequential significant (p < 0.05) decrease in the number of repetitions in all three exercises. However, subjects in the citrulline malate group performed significantly (p < 0.05) higher number of repetitions during all three exercises compared to placebo group.

Figure 1: Wax et al. observed significant increases in maximal leg press, hack squat, and leg extension (not shown) repetitions in response to the ingestion of 8g of citrulline malate 60min before exercise (Wax. 2014)

Blood lactate and heart rate, on the other hand, were significantly increased (p < 0.05) post-exercise in both groups with no significant inter-group differences between citrulline malate and placebo (p > 0.05).
References:

• Briand, Joël, et al. "Use of a microbial model for the determination of drug effects on cell metabolism and energetics: Study of citrulline?malate." Biopharmaceutics & drug disposition 13.1 (1992): 1-22.
• Hickner, Robert C., et al. "L-citrulline reduces time to exhaustion and insulin response to a graded exercise test." Medicine and science in sports and exercise 38.4 (2006): 660-666.
• Giannesini, Benoît, et al. "Citrulline malate supplementation increases muscle efficiency in rat skeletal muscle." European journal of pharmacology 667.1 (2011): 100-104.
• Pérez-Guisado, Joaquín, and Philip M. Jakeman. "Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness." The Journal of Strength & Conditioning Research 24.5 (2010): 1215-1222.
• Verleye, M., et al. "Effects of citrulline malate on bacterial lipopolysaccharide induced endotoxemia in rats." Arzneimittelforschung 45.6 (1995): E712.
• Wax, Benjamin, et al. "Effects of Supplemental Citrulline Malate Ingestion During Repeated Bouts of Lower-body Exercise in Advanced Weight Lifters." The Journal of Strength & Conditioning Research (2014).

Voluntary & NMES contractions for Monster Quads?

You are always looking for new ways to improve your training outcome? Scientists from the Department of Physiotherapy at the University Cardenal Herrera-CEU might have something for you, then. In their latest study, V. Benavent-Caballer, P. Rosado-Calatayud, E. Segura-Ortí, J.J. Amer-Cuenca, and J.F. Lisón tried to elucidate, whether conducting low intensity resistance training in conjunction with  neuromuscular electrical stimulation (NMES) would provide not just an additional growth stimulus, but also corresponding increases in physical performance, muscle cross-sectional area (CSA) and the capacity to perform daily tasks 22 in exactly those subjects researchers will resort to, when theyre looking for generous funding for studies the outcome of which is not going to pay off in form of scripts for a new patentable drug: Older adults living in a geriatric nursing home.
What? Yeah... I have to admit, the subjects are not exactly bodybuilders and a regular high intensity control is missing, but even if it wasnt for the necessary fact that youll belong to the group of "older adults" in 50 years from now, the results of the study at hand would still have a certain relevance for younger trainees. Why? Well, something that makes the elderly grow will certainly do the same in young people. Whether it does so at the same or even higher rates than "regular" strength training will obviously have to be elucidated in future studies.

Table 1: Subject characteristics;  VC = volitional contraction; NMES = neuromuscular electrical stimulation; NMES+ = NMES superimposed onto voluntary contraction. SD = standard deviation (Benavent-Caballer. 2014)

For now, all I can tell you is that the three weekly supervised 30-35 min exercise sessions the 89 participants of the study at hand performed in the course of this 16-week study lead to significantly more pronounced strength and size gains, when the exercise was performed using both voluntary contractions and the forced contractions, the researchers produced by attaching their subjects to the surface electrodes of a portable NMES devices (TensMed S82).
The four adhesive surface electrodes (5 × 5 cm) were placed on the distal medial and proximal lateral portions of the subjects anterior thigh, when they performed their three sets of knee extensions (15 reps each) in a single-leg fashion with 3-minute rest between sets.

Figure 2: Changes in muscle strength (hand grup) and size (rectus femoris), as well as changes in parameters of physical functioning in response to the three training modalities (Benavent-Caballer. 2014)

The participants were instructed to raise the weight in 1 s (concentric phase), keep a full knee extension for 3 s (isometric phase) and slowly lower the weight in 2 s to the starting position (eccentric phase). Each contraction was followed by a 2-second rest period, and the training intensity was set at 40% of 1RM... and yeas, this sounds pretty much like peak contractions, an intensity technique which may in fact be the reason that the old trainees in the study at hand recorded highly significant increases in muscle size even when the peak contraction or rather the whole movement was not superimposed with NMES which was delivered with a ramp-up time of 1 s increasing intensity as the knee was extended from 90° to full extension that was followed by 3 s keeping the knee in full extension and 2 s of a ramp-down with gradually decreasing intensity (see Figure 2, yellow).
References:

• Babault N, Cometti G, Bernardin M, et al. "Effects of electromy ostimulation training on muscle strength and power of elite rugby players." J Strength Cond Res 21 (2007): 431-7.
• Bezerra, Pedro, et al. "Effects of unilateral electromyostimulation superimposed on voluntary training on strength and cross?sectional area." Muscle & nerve 40.3 (2009): 430-437.
• Brocherie F, Babault N, Cometti G, et al. "Electromyostimulation training effects on the physical performance on ice hockey players." Med Sci Sports Exerc 37 (2005): 455-60.
• Delitto A, Brown M, Strube MJ, et al." Electrical stimulation of quadriceps femoris in an elite weight lifter: a single subject experiment." Int J Sports Med 10 (1989): 187-91.
• Dervisevic E, Bilban M, Valencic V." The influence of low-frequency electrostimulation and isokinetic training on the maximal strength of m. quadriceps femoris." Isokinet Exerc Sci 10 (2002): 203-9. 
• Hortobágyi, Tibor, Jean Lambert, and Kevin Scott. "Incomplete muscle activation after training with electromyostimulation." Canadian journal of applied physiology 23.3 (1998): 261-270. 
• Maffiuletti NA, Cometti G, Amiridis IG, et al. "The effects of electromyostimulation training and basket practice on muscle strength and jumping ability. Int J Sports Med 21 (2000): 437-
  43. 
• Malatesta D, Cattaneo F, Dugnani S, et al. "Effects of electromyostimulation training and volley practice on jumping abilities." J Strength Cond Res 17 (2003): 573-9.
• Herrero JA, Izquierdo M, Maffiuletti N, et al. "Electromyostimu lation and plyometric training effects on jumping and sprint time." Int J Sports Med 27 (2006): 533-9.
• Paillard, Thierry, et al. "Effects of two types of neuromuscular electrical stimulation training on vertical jump performance." The Journal of Strength & Conditioning Research 22.4 (2008): 1273-1278.
• Pichon F, Chatard JC, Martin A, et al. "Electrical stimulation and swimming performance." Med Sci Sports Exerc 27 (1995): 1671-6.
• Venable MP, Collins MA, O’Bryant HS, et al. "Effect of supplemental electrical stimulation on the development of strength, vertical jump performance and power." J Appl Sport Sci Res 5 (1991): 139-43

NEMS devices are usually marketed as "ab trainers" - do you own one?

Convenience above everything! Although I personally believe that this mantra is to blame for most of the modern health issues, scientists from the Department of Biomedical Engineering and Institute for Convergence Study of Bio-Medical Wellness at the Yonsei University in Korea have now been able to demonstrate that you can counter part of the negative side effects of our post-modern convenience culture quite conveniently.

Plug an NMES device into your convenient outlet, attach it to your biceps, sit down conveniently in front of your television screen and have the device train your muscles.
You dont believe that this works? Well, basically this is what the seven healthy male subjects who were recruited for the study did at the laboratory. The participants were trained two times per week (three subjects: Mondays and Thursdays; and four subjects: Tuesdays and Fridays) for 12 weeks. Each exercise session was performed for 30 min with no rest interval.

You could do this in front of your TV at home (image from Son. 2014)

"During the training, the subject was required to maintain a shoulder joint angle of 90° in the sagittal plane. The electrical stimulation (pulse width: 200?s; and frequency: 20 Hz (Dreibati et al., 2010)) was delivered through a pair of 5 × 5 cm gelcoated electrodes attached to the region of the biceps brachii muscle belly. The magnitude of the stimulation was determined as the subjects maximum comfortable current level, but no more than 80 mA, with complete elbowflexion from the fully extended state; the mean value was 57.00 (SD 4.28) mA." (Son. 2014)

I am not sure if this hurts, but based on my experience with a friends NMES ab trainer, I suppose it did... not convenient, ok, but still better than actually moving for most of the the members of the convenience generation, Id guess - And I mean, you cant argue with results, right?

Figure 1: Maximal force and muscle thickness before and after the NMES training (Son. 2014)

I must admit I was quite impressed with the 8% increase in muscle size and the 23% increase in performance. Ok, the study doesnt tell us anything about the training experience of the subjects, but even if they were noobs thats more than Id expected to see from two weekly sessions of NMES.
Reference:

• Jongsang Son, Dongyeop Lee, Youngho Kim, Effects of involuntary eccentric contraction training by neuromuscular electrical stimulation on the enhancement of muscle strength, Clinical Biomechanics, Available online 10 June 2014.

Taking vitamin D pills on their own may be less effective than taking them with a meal containing 30% of the calories from fat - at least for older men & women and high doses of vitamin D3

This is science. Only 6 months ago, I wrote in an article about the effects of fat on the absorption and bioavailability of fat soluble vitamins that vitamin D would be the fat soluble vitamin with the lowest dependence on the co-administration of fat. Rather than the amount, it appeared as if the change in plasma 25OHD (nanograms per milliliter) during vitamin D supplementation was rather associated with the types of fat, i.e. MUFA = increased absorption vs. PUFA = decreased absorption (Niramitmahapanya. 2011).

Now, half a year later, it appears as if another, previously overlooked variables would force me to reformulate previous recommendations: Age and dosage!
In contrast to previous studies, Bess Dawson- Hughes and colleagues investigated the influence of fat on the absorption of vitamin D3 in older, not young men and women. In that, inclusion criteria for the study were

• no use of not more than 400 IU vitamin D or 1,000 mg calcium per day,
• serum 25(OH)D level in the range 20 to 29.5 ng/mL (49.9 to 73.6 nmol/L),and
• a body mass index in the range 20 to 29.5 (normal weight)

Subjects with kidney problems, hypercalcemia, general issues with malabsorption, Crohn’s disease, disorders of bone metabolism, kidney stones, cancer and those who were using proton pump in hibitors, lipid-lowering medications, fish oil, or flaxseed oil, hormones, osteoporosis medications, or high-dose thiazide diuretic therapy were equally excluded as those subjects who attended tanning salons, regularly.
This was yet not the only difference. Next to the subjects age, the amount of vitamin D3 in the capsules the subjects received differed, as well. While previous studies that reported little to no effect of fat on the absorption of vitamin D3 used small(er) amounts of vitamin D, like 1,000, 2,000 or 5,000 IU per serving, Dawson-Hughes et al. used a single serving of 50,000 IU(!) and thus more than 10x higher dosages than previous studies.

Figure 1: Composition of the test breakfast, lunch, and dinner meals, expressed as % of total energy the 50 healthy older adults consumed in the study at hand (Dawson-Hughes. 2014)

Alongside said vitamin D3 super-dose all 50 subjects ingested one out of three randomly selected meals that were either fat free or contained 30% of the total calories in form of dietary fat - albeit at two different PUFA:MUFA ratios (see Figure 1)

"[The m]eals were provided by the metabolic kitchen and consisted of real food. For example, breakfast consisted of egg whites flavored with small amounts of onion and tomato, fruit, toast, and cranberry juice. The groups were balanced for energy by adjusting the amount of sugar in the cranberry juice (diet or regular juice or a mixture of the two). Protein and fiber were balanced across all groups. MUFA:PUFA was manipulated by adding varying amounts of MUFA (olive oil) and PUFA (corn oil) to achieve a ratio of 1:4 in the low and 4:1 in the high MUFA:PUFA diets. The boxed lunch and the dinner provided to the study subjects on the test day had fat/protein/carbohydrate content similar to that of the test breakfast meals.

Importantly, the subjects were required to (a) eat all of the food provided and (b) refrain from pigging out on anything that was not on the menu for the study day.

Figure 2: Serum vitamin D3 levels in subjects after consuming fat-free or -containing meals (Dawson-Hughes. 2014)

What the scientists found, when they analyzed the vitamin D response of the subjects depending on (a) the fat content and (b) the type of the fat, Dawson-Hughes et al. found:

• In analyses of vitamin D absorption at baseline and the three follow-up time points, there was a significant interaction of fat-free vs fat-containing meal group with time (P < 0.001). As shown in [figure 2], there was no significant difference in plasma vitamin D-3 levels at baseline, but the fat-containing meal group had significantly higher plasma vitamin D-3 concentrations than the fat-free meal group at each time point thereafter.
  
  At 12 hours, the fat-containing vs fat-free meal mean difference in plasma D-3 concentration was 26.9 ng/mL (95% CI 9.6 to 44.1 ng/mL) (69.9 nmol/L). Differences at the other time points were for 10 hours, 30.5 ng/mL (95% CI 14.4 to 46.7 ng/mL) (79.3 nmol/L) and for 14 hours, 21.3 ng/mL (95% CI 4.6 to 37.9 ng/mL) (55.4 nmol/L).

• Vitamin D-3 levels at 12 hours after the dose were 116.0 3 ng/mL (301.5 nmol/L) in the low MUFA:PUFA group and 104.2 ng/mL (270.8 nmol/L) in the high MUFA: PUFA group.
  
  Potential covariates, body mass index, total body fat mass, and screening plasma 25(OH)D level were not associated with vitamin D absorption and neither modified the effect of fat on vitamin D absorption.

As the researchers point out, "[t]here were no serious adverse events during the study" and "[c]ompliance with the vitamin D supplement was 100%" (Dawson-Hughes. 2014). So, non of these obvious, but undesirable confounding factors could explain the observed differences between (a) the non-fat vs. fat-meals and (b) the influence of the PUFA:MUFA ratio.
References:

• Dawson-Hughes, Bess, et al. "Dietary Fat Increases Vitamin D-3 Absorption." Journal of the Academy of Nutrition and Dietetics (2014).
• Niramitmahapanya, Sathit, Susan S. Harris, and Bess Dawson-Hughes. "Type of dietary fat is associated with the 25-hydroxyvitamin D3 increment in response to vitamin D supplementation." The Journal of Clinical Endocrinology & Metabolism 96.10 (2011): 3170-3174. 
• Wortsman, Jacobo, et al. "Decreased bioavailability of vitamin D in obesity." The American journal of clinical nutrition 72.3 (2000): 690-693.