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1. Enter your Windows 8 Installation Disk on DVD Drive.
2. Now run Command Prompt as Administrator. (Hint: Start > Type cmd > Now right click on Command Prompt and hit on Run as Administrator from the bottom)
3. Now copy the following command and paste it in the command prompt window. Or type the following line in command prompt. Press Enter (To paste the command in command prompt, click the right button of mouse and select paste)
4. Now .Net Framework will be installed within few minutes. 

Stay with Marks PC Solution to get more interesting IT topics!

1. Open Command prompt as Administrator. XP users dont require Administrative mode. 
2. Now type this command and press enter- net user
3. Now type another command and press enter- net user Administrator *
4. Type the new password and press enter.
5. Retype the password and press enter.
6. If password is changed then you will see the message- the command completed successfully. 

Stay with Marks PC Solution to get more interesting IT topics!

Creatine is a dangerous steroid? Well, the study at hand shows that it will prevent not promote hepatic lipid accumulation as you will see it with many oral steroids.

You can learn more about creatine at the SuppVersity

Creatine Doubles Ur GainZ!

Creatine, DHT & Broscience

Creatine Better After Workout

ALA + Creatine = Max Uptake?

Creatine lowers cortisol!

Build Ur Own Buffered Creatine

Suggested Read: "Supercharging Creatine With Baking Soda: Study Shows Increased Peak Power and Endurance - Plus: How Bicarbonate Could Help You Lose Fat & Build Muscle" | read more

Figure 1: The reduced hepatic lipid accumulation in the cell study at hand is a consequence of (A) reduced synthesis and (B) increased secretion of triglycerides (da Silva. 2014b)

Figure 2: Increased triglyceride oxidation, yes, increased AMPK & ACC, no (da Silva. 2014b)

Bottom line: The study at hand adds weight to the previously formulated hypothesis that creatine supplementation (obviously cheap, but pure creatine monohydrate) is not for muscle-headz, only.

Figure 3: Creatine monohydrate supplementation increases glucose uptake via GLUT-4 receptor expression in immobilized and active human skeletal muscle (Opt Eijnde. 2001)

On the contrary! In conjunction with the previously established anti-oxidant effects and its ability to improve glucose management via increases in AMPK and GLUT-4 (glucose receptor) expression in skeletal muscle cells (see Figure 3), the data from this recent study by scientists from the University of Alberta should eventually shut the critics, who still claim creatine was a "dangerous steroid" or at least a "gateway drug to steroid abuse" up. Unfortunately, something in the back of my head tells me that studies are less convincing to the medical orthodoxy than the glossy product flyers for the latest patentable diabesity and NAFLD drugs | Comment on Facebook!

• da Silva, Robin, Karen Kelly, and Rene Jacobs. "Hepatic carbohydrate and lipid metabolism are altered in rats fed creatine-supplemented diets (LB151)." The FASEB Journal 28.1 Supplement (2014a): LB151.
• da Silva, Robin P., et al. "Creatine reduces hepatic TG accumulation in hepatocytes by stimulating fatty acid oxidation." Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids (2014b). 
• Engelhardt, Martin, et al. "Creatine supplementation in endurance sports." Medicine and Science in Sports and Exercise 30.7 (1998): 1123-1129.
• Jacobs, Rene L., Robin da Silva, and Randy Nelson. "Creatine Supplementation may prevent NAFLD by stimulating fatty acid oxidation." The FASEB Journal 27 (2013): 222-2.
• Opt Eijnde, B., et al. "Effect of oral creatine supplementation on human muscle GLUT4 protein content after immobilization." Diabetes 50.1 (2001): 18-23.

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.

If its not testosterone its usually meat thats blamed to increase your cancer risk.

Meat-Love: You May Eat Pork, too!

You Eat What You Feed!

Meat & Prostate Cancer?

Meat - Is cooking the problem

Meat Packaging = Problem?

Grass-Fed Pork? Is it Worth it?

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

• 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%.

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?

• 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)

• 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.

This article will teach you how to make sure youll see your great, great grand children.

You can learn more about the secrets of longevity at the SuppVersity

Are You Stressed Enough to Live Forever?

Suffocated Mitochondria Live Longer

Get Lean & Live Longer With I. Fasting

Can You add 9 Years to your Life W/ Glucosamine?

The Soccer Molecule - C60 Fullerene

Is a Latent Acidosis Killing You Softly?

• Use the available medical care to your advantage: Within the health and fitness community, the things our regular doctors can do for us have gotten a surprisingly bad rep. It does however stand out of question that the availability and use of modern medicine is one of the cornerstones of the ever-increasing longevity in centennials and other healthy elderly. From basic treatments to complicated operations, all these things the availability of which we usually take for granted has helped us (and the living centenarians) to do what Thomas Perls calls "to ‘compress morbidity’ and live most of our lives in good health, with only a short period of ill health at the end." (Perls. 1999)

  Figure 1: Luckily, your place of birth is not the only determinant of life expectancy; map depicts life expectancy (in years) at birth (created by Panagiotis V. Lazaridis based on WHO & CIA data in 2008)

  At first this may contradict findings Engberg et al. present in a paper with data from a 29-year follow-up of hospitalizations among 40 000 Danes born in 1905, but in the end, it should be obvious that the low hospitalization rates, the Danish researchers observed in centenarians and almost centenarians were rather a consequence than a cause of their longevity and probably also due to timely non-stationary medical interventions, when one of them actually got sick (Engberg. 2009)
• Dont smoke, or quit smoking: I know this should be obvious, but I guess too many people still believe that they must belong to the lucky few Lewin and Crimmins, the authors of a recent paper with the intruiging title "Not All Smokers Die Young: A Model for Hidden Heterogeneity within the Human Population." (Lewin. 2014) are interested in. Contrary to these (allegedly) genetic outliers, the majority of us will suffer a significant reduction in life expectancy. Estimations of the number of years youll lose range from a handful of years to up to 25% (Rogers. 1991). For a US citizen the latter would equal almost 16 years! Years, of which Susan T. Stewart et al. (2009) say that the average 18-year-old may reclaim 3.76 life-years and, more importantly, 5.16 quality-adjusted years, in which he or she is not hospitalized and wasting away, if they managed to avoid the getting overweight / obese instead.

• In fact, the increase in BMI after smoking sessation "overwhelmed the positive effects of declines in smoking in multiple scenarios" Stewart et al. calculated and reduced the benefits for an 18-year old to 0.71 years or 0.91 (Stewart. 2009).
  
  But dont worry, other studies report much more beneficial effects. Taylor et al. (2002), for example, estimate that the life expectancy among smokers who quit at age 35 will exceeded that of continuing smokers by 6.9 to 8.5 years for men and 6.1 to 7.7 years for women. And in spite of the fact that early smokers will obviously realize greater gains in life expectancy, even those even those who quit much later in life gained some benefits: among smokers who quit at age 65 years, men gained 1.4 to 2.0 years of life, and women gained 2.7 to 3.7 years.
• Avoid drinking alcohol in amounts >0.5 glasses of wine per day: Notwithstanding the overcited epidemiological evidence which suggests that a moderate alcohol consumption will have beneficial effects on your life-expectancy, the margin between "just enough" and "already too much" is simply too narrow for me to suggest you drink more than the literal half glass of wine thats supposed to lower the all-cause mortality risk of women by ~20-25% (Streppel. 2009).
  
  

  Table 1: Relative Risk for Major Chronic Disease Categories, by Gender and Average Drinking Category (Rehm. 2002)

  A high(er) level of alcohol consumption, on the other hand, has been found to be associated with a higher risk of hypertension, alcoholic cardiomyopathy, cancer, cerebrovascular events and dementia (Kloner. 2007) - a fact that should remind you that (a) the evidence regarding the possible health benefits of alcohol is uncertain, and that (b) alcohol may not benefit everyone who drink. Theoretically, genetic polymorphisms that make alcohol the panacea for one, could turn an in innocent glass of wine into a deadly poison for someone else (Hashimoto. 2002).
  
  And just in case the ambiguity of data aint reason enough for you to let go of all alcoholic beverages on at least360 of 365 days of the year, the data in Table 1 may convince you.
  
  If you take a closer look at "Drinking Category I", where youll find all the women who consume 0–19.99 g pure alcohol and all the men who consume 0–39.99 g pure alcohol every day (a glass of wine has ~13g), you will see that alcohol increases the risk of liver cirrhosis by 26%, hypertensive diseases and other CVD by 40% and 50%, is associated with 34% and 23% higher risk of epilepsy for women and men, respectively and increases the risk of all cancers esp. those of the esophagus (+80%) significantly.
  
  I am not sure about you, but for me this alone would be enough to get my sleep, diet and exercise regimen in check instead of trying to use alcohol as a means to reduce my CVD risk.
• Attend to relationships and friends: Individuality has become on of the / the (choose for yourself) highest good(s) of Western civilization and few people are aware that we are paying a very high price for that. The influence of social relations on mortality is, after all, well documented. A meta-analysis of 148 studies (308,849 participants followed for an average of 7.5 years) confirms that the quality of our social networks significantly predicts mortality (Holt-Lunstad. 2010).

  Figure 2: Weighted avg. effect sizes across different measures of social relationships (Holt-Lunstad. 2010).

  People with social relationships defined as adequate are 50% more likely to survive than older adults with social relationships defined as poor or insufficient. The overall effect remains consistent across age (see Figure 2).
  
  It is yet still unclear whether specific types of relationships are more advantageous than others. Giles et al. (2005) showed that the beneficial association between social networks and survival among elderly people may be restricted to relationships with friends and confidants rather than with children and relatives. In a meta-analysis of 53 prospective observational studies on older adults, marriage or support from a partner was found be a significant independent predictor of survival; the overall reduction in mortality risk was 9–15%. However, this association was statistically significant in only half of the studies (Manzoli. 2007).

• As Rizzuto & Fratiglioni (2014) point out, one hypothesis suggests that strong social connec tions can buffer significant stress and protect against ne ative stress-related outcomes:
  

  "People might be protected from adopting stress-related lifestyle choices that are detrimental to health, such as smoking, excessive alcohol consumption and sleep loss." (Rizzuto. 2014)

  The main-effect hypothesis postulates that social support is beneficial regardless of the stress level a person is experiencing; in other words, social support can act protectively even before a stressor is experienced. For instance, persons with social support could be influenced to engage in protective be haviors such as exercise.
  
  Moreover, having a wide range of social ties also provides multiple sources of information that could result in more effective use of available health care and services (Cohen. 2004). No wonder, you have, after all, read only a couple of days ago that education is what protects "poor women from fattening effects of rising wealth" in the SuppVersity Facebook News (read more).
• Stay lean and be avtive, God damnit! There is this unfortunate and die-hard myth of something scientists refer to as the obesity paradox. A term that is misrepresented by overweight journalists and doctors and misunderstood by the ever-increasing number of obese average Joes, for whom the misleading connotations of terms such as "healthy obese" are downright life-threatening. 
  
  And this is not an exaggeration, by the way. If you look at the 30% increase in mortality risk Whitlock et al. (2009) calculated based on a meta-analysis of data from 57 prospective studies that included almost 900,000 adults for every 5-point increase in BMI the attribute "life-threatening" is by no means an exaggeration.

Ladies, listen up! Being underweight is unhealthier than being obese. Trying to equal the anorexic Hollywood "stars" could cost your life! It sounds drastic, but with a 47% increase in mortality risks being underweight underweight women (BMI <18.4) have a higher mortality risk than obese ones (+44% for BMI 30.0 to 34.9; see Berrington de Gonzalez. 2010)

• Although the proportional increase was greater at younger ages (35–59 years), the corresponding increase in mortality for those in their 70s was nearly 30%, and for those in their 80s, it was still 15% - the notion that older people would benefit from being fat is thus simply hilarious.
  
  Whats not hilarious, though, is that a certain amount of healthy, well-distributed body fat thats complemented by a decent amount of life-extending muscle mass (20% reduction in all cause-mortality for men >55years w/ a decent amount of lean mass; see  SuppVersity Facebook News | learn more) and a corresponding BMI between 20-27 offers enough energy reserves to draw on, when youre sick and old. It is thus also not surprising that being slightly overweight (obesity starts with BMI >30) is not a risk factor for people aged ? 65 years (Heiat. 2001) and certainly better than being what scientists call "underweight", when its actually only "undermuscled" for the vast majority of elderly individuals who are affected.

• As a SuppVersity reader you know: The risk for both, being underweight and overweight can be reduced if not nullified by a high amount of daily physical activity (the 10,000 steps mantra) and working out regularly. Being moderately active, alone, for example, was found to be associated with a 3.6x higher chance of "successful [=healthy] aging" in a recent study from the University of Ibadan - for regular vigorous activity, the chance of aging healthily increased by 711% (Gureje. 2014)!

• Miscellaneous, but worth mentioning: This is where I will list everything that popped up on my radar while doing the research, but did not really appear to make a good standalone item in the list. Things like having sex, for example. At least twice a week, to make sure that you dont increase your risk of  fatal coronary heart disease by 180%, guys (Ebrahim. 2002). And ther results Smith et al. presented 5 years before are even more promising: According to their study, each increase of 100 orgasms per year is associated with a 46% reduction in all-cause mortality risk (Smith. 1997)!

"[...]female centenarians likely exploited a healthier life-style and more favorable environmental conditions, owing to gender-specific cultural and anthropological characteristics" (Franceschi. 2000) 

Figure 5: Yes, genes matter, but there is more (Franceschi. 2003)

• Berrington de Gonzalez, Amy, et al. "Body-mass index and mortality among 1.46 million white adults." New England Journal of Medicine 363.23 (2010): 2211-2219.
• Bonafè, Massimiliano, et al. "A gender–dependent genetic predisposition to produce high levels of IL?6 is detrimental for longevity." European journal of immunology 31.8 (2001): 2357-2361. 
• Cohen, Sheldon. "Social relationships and health." American psychologist 59.8 (2004): 676.
• Ebrahim, S., et al. "Sexual intercourse and risk of ischaemic stroke and coronary heart disease: the Caerphilly study." Journal of epidemiology and community health 56.2 (2002): 99-102.
• Flachsbart, Friederike, et al. "Association of FOXO3A variation with human longevity confirmed in German centenarians." Proceedings of the National Academy of Sciences 106.8 (2009): 2700-2705.
• Franceschi, C., et al. "Do men and women follow different trajectories to reach extreme longevity?." Aging Clinical and Experimental Research 12.2 (2000): 77-84. 
• Franceschi, C., and M. Bonafe. "Centenarians as a model for healthy aging." Biochemical Society Transactions 31.2 (2003): 457-461. 
• Giles, Lynne C., et al. "Effect of social networks on 10 year survival in very old Australians: the Australian longitudinal study of aging." Journal of Epidemiology and Community Health 59.7 (2005): 574-579. 
• Gureje, Oye, et al. "Profile and Determinants of Successful Aging in the Ibadan Study of Ageing." Journal of the American Geriatrics Society (2014).
• Heiat, Asefeh, Viola Vaccarino, and Harlan M. Krumholz. "An evidence-based assessment of federal guidelines for overweight and obesity as they apply to elderly persons." Archives of internal medicine 161.9 (2001): 1194-1203.
• Holt-Lunstad, Julianne, Timothy B. Smith, and J. Bradley Layton. "Social relationships and mortality risk: a meta-analytic review." PLoS medicine 7.7 (2010): e1000316. 
• Kilpeläinen, Tuomas O., et al. "Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children." PLoS medicine 8.11 (2011): e1001116.
• Kloner, Robert A., and Shereif H. Rezkalla. "To drink or not to drink? That is the question." Circulation 116.11 (2007): 1306-1317.
• Larkin, Marilynn. "Centenarians point the way to healthy ageing." The Lancet 353.9158 (1999): 1074.
• Manzoli, Lamberto, et al. "Marital status and mortality in the elderly: a systematic review and meta-analysis." Social science & medicine 64.1 (2007): 77-94. 
• Oliveira, Aldair J., et al. "The influence of social relationships on obesity: sex differences in a longitudinal study." Obesity 21.8 (2013): 1540-1547.
• Panza, Francesco, et al. "Decreased frequency of apolipoprotein E ?4 allele from Northern to Southern Europe in Alzheimers disease patients and centenarians." Neuroscience letters 277.1 (1999): 53-56.
• Perls, Thomas T., Margery Hutter Silver, and John F. Lauerman. Living to 100: Lessons in living to your maximum potential at any age. 1st ed. New York: Basic Books, 1999.
• Rehm, Jürgen, et al. "Alcohol-related morbidity and mortality." Mouth 140.208 (2002): C00-C97. 
• Rizzuto, D., and L. Fratiglioni. "Lifestyle Factors Related to Mortality and Survival: A Mini-Review." Gerontology (2014).
• Rodriguez, Beatriz L., et al. "Fish Intake May Limit the Increase in Risk of Coronary Heart Disease Morbidity and Mortality Among Heavy Smokers The Honolulu Heart Program." Circulation 94.5 (1996): 952-956. 
• Rogers, Richard G., and Eve Powell-Griner. "Life expectancies of cigarette smokers and nonsmokers in the United States." Social science & medicine 32.10 (1991): 1151-1159.
• Sebastiani, Paola, et al. "Genetic signatures of exceptional longevity in humans." Science 10 (2010): 1126. 
• Smith, George Davey, Stephen Frankel, and John Yarnell. "Sex and death: are they related? Findings from the Caerphilly cohort study." Bmj 315.7123 (1997): 1641-1644.
• Stewart, Susan T., David M. Cutler, and Allison B. Rosen. "Forecasting the effects of obesity and smoking on US life expectancy." New England Journal of Medicine 361.23 (2009): 2252-2260.
• Streppel, Martinette T., et al. "Long-term wine consumption is related to cardiovascular mortality and life expectancy independently of moderate alcohol intake: the Zutphen Study." Journal of epidemiology and community health 63.7 (2009): 534-540.

Todays SuppVersity News will provide you with "confirmation" rather than "innovation", I suppose

Avoid protein wasting post workout.

Why do I even mention the Aragon + Schoenfeld study? The reason is that I already read how people were going on about how this "stupid review" got it all wrong on Facebook. And though I know that SuppVersity readers are not as ignorant as the average gymbro (watch what I am talking about, here) I wanted to make sure that (a) this study is not about the post-workout anabolic window Aragon & Schoenfeld wrote about and that (b) the tow actually argued that spreading your protein intake across the day instead of placing it in the "anabolic window", should yield superior results.

Figure 1: Fractional protein synthesis at breakfast (left), when the difference was most pronounced (+30%) and rel. calculated 24h fractional protein synthesis (right) with EVEN vs. SKEWED protein distribution (Mamerow. 2014)

Table 1: Seven-day mean energy and macronutrient intake in healthy adults consuming diets with an EVEN or SKEW protein distribution (Mamerow. 2014)

"Both diets exceeded the RDA for protein [0.8 g/(kg d)] by ~50%. The SKEW diet met the RDA for protein during the evening meal alone. In all versions of the EVEN and SKEW menus used in this study, the animal-to-vegetable protein ratio was ~2:1." (Mamerow. 2014)

"Fat Loss Principles That Work: 10g+ of EAA W/ Every Meal" | read more

Bottom line: You have already seen the outcome of the three FSR measurement in Figure 1 and there is actually not much to add to what youre seeing there already.

In view of the fact that I gather that youd expected a result like this, I dont feel inclined to repeat that I have been suggesting for years to consume 30g+ of quality protein ("quality" = 10g+ of EAAs per 30g serving) with every meal.

If you stick to this simple principle, its going to help you build muscle and lose fat (see "Fat Loss Principles That Work: 10g+ of EAA W/ Every Meal" | read more).

• Aragon, Alan Albert, and Brad Jon Schoenfeld. "Nutrient timing revisited: is there a post-exercise anabolic window?." Journal of the International Society of Sports Nutrition 10.1 (2013): 5.
• Mamerow, Madonna M., et al. "Dietary Protein Distribution Positively Influences 24-h Muscle Protein Synthesis in Healthy Adults". J. Nutr. January 29, 2014 jn.113.185280 [ahead of print].