Workout Supplement Cautions

preworkout safety

DHEA (Dehydroepiandrosterone)

DHEA is a common supplement used by bodybuilders because of its effect on testosterone and strength. DHEA levels drop beginning at the age of 30, causing decreased muscle mass and libido.

DHEA seems to be a great addition to a workout stack, but there are several reported side effects. Due to the fluctuation of testosterone levels, DHEA can cause psychological disturbances including anger and insomnia. Supplementing with DHEA can also cause gender-specific alterations such as shrinking of testes or unwanted hair growth.

DHEA is likely safe when taken as directed; however, it is important to contact a physician prior to use.

Vitamins C and E

VitaminC[1]These vitamins are found in most workout supplements acting as natural antioxidants. Both vitamins C and E offer many benefits including weight management support, healthy skin, and improved immune function.

It is safe to use vitamins C and E; however, it is much more beneficial to consume these vitamins through whole foods rather than supplements. Overdoing these supplements can result in fewer mitochondria meaning less energy and growth.

Tribulus Terrestris

Tribulus Terrestris is a common ingredient in testosterone boosters and pre workout supplements. Tribulus claims state that the supplement increases testosterone levels, thus improving strength, muscle mass, and sex drive.

There have been no dangerous side effects reported from Tribulus supplementation, so it appears safe to consume. The problem with Tribulus is that there are very little studies to back up the claims stating this supplement supports testosterone or performance enhancement.

Yohimbe

Yohimbine is a popular supplement taken to increase energy and fat loss, which is why yohimbine is a common ingredient in weight loss and pre workout supplements.

This supplement needs to be treated just like other stimulants. Too many stimulating supplements can cause anxiety, high blood pressure, increased heart rate, and insomnia. When using supplements in this category, it is always wise to start at the lowest dose possible to assess tolerance.

Effective and Safe Pre-Workout Supplements

Whey Protein Make sure you have some whey protein and some Branched-Chain Amino Acids (BCAA) like isoleucine, leucine, and valine. The whey is the same protein you needed when you were a child to help you grow big and strong while the BCAA’s help your body use the protein more effectively and reduce delayed muscle soreness.

While some workout supplements have approximately 900,000 ingredients, taking the time to make sure you know what each one is and what it does can not only give you a better workout, it can save your life. Also remember that any of the beneficial ingredients – such as caffeine – can be harmful if taken in improper amounts.

The Bottom Line

Taking supplements daily is an excellent way to feel better and work harder; however, some dietary supplements do have side effects. It is always recommended to speak with a doctor before taking any dietary supplement.

Pre-Workout Supplements: Do I need anything more than caffeine or am I wasting money?

caffeine is found in coffee

With the flashy marketing and high-pressure sales tactics favored by supplement companies, pre-workout supplements may come off as snake oil. And to be honest, some pre-workout supplements are ineffective, overpriced, and full of nasty filler that will do more harm than good (see: belly fat).

That being said, there are a few supplements that I highly suggest including in your pre-workout blend in addition to caffeine. We all know that caffeine supplements can boost your energy levels, but what other supplements can have an impact on your workout? Let’s take a look at my three favorite pre-workout supplements other than caffeine: L-arginine, creatine, and beta-alanine.

L-arginine

 

Muscle growth
L-arginine can help with muscle growth

L-arginine is an amino acid that shows significant promise in increasing natural production of growth hormone, boosting testosterone levels, and reducing fatigue. L-arginine is the precursor to nitric oxide, and increased nitric oxide production is a great thing for exercise.Why? Nitric oxide is responsible for vasodilation.

When vasodilation occurs, blood vessels widen. Wider blood vessels equal better blood flow. Better blood flow equals more effective oxygen transportation. More oxygen equals more intense workouts. It is as simple as that! Also, for you men out there, I can report that l-arginine is a big boost in the bedroom!

Creatine

Creatine can be added to protein shakes
Creatine can be added to protein shakes

If you’ve spent any time in the workout community, you’ve heard about creatine. Creatine is an organic acid found in many foods, especially fish. Creatine powder’s main function is to supply energy to the cells, in particularly to muscle.

If you eat meat on a regular basis, your body probably has a standard supply of creatine. If you don’t… well, I hate to tell you, but you’re probably deficient. That being said, even meat eaters can benefit from a creatine supplement regimen because the more creatine your body has, the more energy is supplied to your cells. More energy translates into more intense and productive workouts. Great deal, right?

Beta-Alanine

Beta-alanine is another amino acid, and if you’ve ever taken a pre-workout blend before, then you know EXACTLY what beta-alanine does. You know that tingly, powerful, stimulant feeling you get after taking your pre-workout? That’s beta-alanine doing its job.

 

Beta-alanine can help increase muscular endurance
Beta-alanine can help increase muscular endurance

Beta-alanine is all-around my favorite supplement other than caffeine because it helps with weight-loss, stamina, and muscle recovery. It is an all-in-one miracle supplement, and I say that with 100 percent sincerity.

Conclusion

So, knowing that these three supplements (plus caffeine) are decent is one thing, but how do you go about introducing them to your workouts? You can do what I do, which is buy the bulk supplement powders and cap my own pre-workout pills, but I recognize that the capping process is labor intensive and some of you may have busy schedules. So what do you do? Simple, check out the nutrition labels on pre-workout blends and keep an eye out for these supplements. Speaking from experience, both MusclePharm Assault and Cellucor C4 are good choices.

How to Survive on a College Student Budget while Still Buying Supplements

supplements on a college budget

If you are a typical broke college student or recent graduate, then you certainly do not have any extra money to throw around. And for those of us concerned about working out and keeping healthy, there is one huge additional expense that eats into our food budget: supplements.

Come on, you are already paying through the nose for tuition, books, and room and board. You do not need to keep paying more than you should for these big name-brand supplements. Do not sacrifice your monthly or weekly food budget any more, forcing yourself to live on ramen noodles and that famous protein pill that you just have to have.

Did you know that most nationally-known big-brand supplements cost a lot more than they need to? A large portion of the product prices are based on the flashy packaging that you see in the stores and the magazine ads which are meant to catch your eye. Well, who do you think pays for all that? You do through higher prices.

Beating the System:

The first step to getting around the seeming monopoly of these big brands is to step back and consider what you really need. It might not be as easy to do as it seems, especially since the big supplement companies have been brainwashing you into thinking that you really NEED their stuff. A solid research tool is the site Examine.com. Spend a little bit of time here and you will have a much clearer idea of what you ultimately “need” in terms of supplementation. It will most likely be a lot less than you thought.

After doing this research, let’s say you have decided to buy beta-alanine, creatine monohydrate, and bulk caffeine powder. It should also be pointed out here that the powder versions tend to be the most economical. You not only end up spending less money on a cost per use basis, but you generally get a lot more product as well. Sure, it is a little less convenient to actually take an extra couple seconds and mix this up in a blender or by hand, but the significant savings are certainly worth it.

Your Supplement War Chest:

The first supplement you decided upon was Beta-Alanine. This is a non-essential amino acid which is a hybrid between powerful neurotransmitters L-glycine and GABA. When it is consumed as a dietary supplement, beta-alanine is transported into your skeletal muscles through the use of sodium and chloride. Once it enters into the muscle, it binds with the essential amino acid histidine and forms the dipeptide carnosine. Without getting overly technical, by increasing the muscular concentrations of carnosine, it helps to fight off muscular fatigue. This fight allows you to train harder and longer before getting tired.

The second supplement chosen was bulk creatine monohydrate powder. Creatine is one of most well-researched supplements around and it just plain works. Creatine helps to increase the body’s ability to produce energy. This energy is transported directly into the working muscle cells, which allows you to train harder, longer, and even more often. You will likely find yourself being able to lift an extra rep or two, or add 5 more pounds to the bar.

The third supplement you are using is bulk caffeine powder. Of course everyone knows that coffee and tea have naturally-occurring amounts of caffeine in them. But as a supplement, caffeine powder is actually quite useful and effective. This usefulness includes being able to increase the capacity of a workload someone can handle and building extra muscle fibers. These increases will allow you to have more energy, work out more intensely, have increased alertness and endurance, and improve your concentration. Many people will also see an increased uptake of oxygen and it can help to spare glycogen usage.

Give these a try and we think you will find out very quickly that you can still have some money left over for other things. Things like eating and paying for school!

Pre-Workout Supplements for Weight Loss vs. Muscle Building

supplements for muscle building and weight loss

Pre-workout supplements are a popular choice among weight lifters and among those who are trying to lose weight. The purpose of these supplements is to improve workouts and help attain the best results. There are two main kinds of pre-workout supplements: weight-loss supplements and muscle-building supplements.

The following are some of the benefits from using such supplements:

  • Increased strength and endurance;
  • Faster metabolic rate;
  • Enhanced energy and focus;
  • Overall better performance.

Before one decides to use any pre-workout supplements, pre-workout nutrition ought to be considered. Carbohydrates are essential as they are your body’s fuel source. It is recommended that you eat your carbs before your workout so that they can be utilized as fuel in your body. Protein is another must-have food.

Supplements for Weight Loss

Creatine for Weight Loss

Supplementing with creatine increases the body’s creatine stores which results in an increased level of phosphocreatine that in turn helps regenerate muscles’ energy source, ATP. According to a study conducted on 17 subjects, a dosage of 5g of creatine produced an increase in the total creatine content of the muscles. Recommended dosage is 3g per day.

Caffeine for Weight Loss

Caffeine is one of the most popular pre-workout supplements for weight loss. Caffeine can be obtained from coffee, tea, chocolate, or through energy drinks. This very popular supplement works by inhibiting the enzyme that blocks degradation of cAMP therefore allowing energy levels to remain high for extended periods of time. A study on the efficacy of caffeine in increased exercise performance showed increased performance after an intake of caffeine before workout. Typical dosage rages from 100-200 mg.

Glutamine:

As you work-out, the levels of glutamine in the body falls and using this as a pre-workout supplement can help delay fatigue during workout by producing more energy and reducing muscle fatigue.

Supplements for Muscle Building

Arginine:

This is a very popular pre-workout supplement for weight lifters because it allows more blood to flow to the muscles by dilating vessels and thereby allowing more nutrients to be absorbed. Results of a study on the effect arginine as a supplement 10 minutes before work-outs showed enhanced performance during workouts. Recommended dosage before a workout is 2-3g.

Citrulline Malate:

Supplementation with Citrulline Malate can increase the levels of arginine which is necessary after an intense workout. Breakdown of amino acids and increased levels of ammonia cause a reduction in arginine levels. Studies show that aerobic energy production is also promoted because of the muscle metabolism promoted by citrulline malate.

Tyrosine:

This supplement helps improve perceived level of fatigue and cognitive and physical performance during stressful conditions. It increases mental alertness and the ability to concentrate which can help one perform more strenuous workouts. Doses of 500 to 1000mg per day before workouts are recommended.

Whether or not to take pre-workout supplements will be totally up to you and will greatly depend on how you feel during your workout when you are taking these supplements.

Pre-Workout Supplements for Beginners

pre workout supplements for beginners

If you’re not using pre workout supplements, you’re cheating yourself in the gym. The addition of pre workout supplements can make your time in the gym more efficient and more effective, meaning you will build more muscle and lose more fat in a shorter amount of time. Just like you make sure your car has all the proper fluids and fuel it needs before going on a road trip, there are pre workout supplements that will help your body run at its optimal levels while you exercise. Basically, pre workout supplements will give you the boost you need and get the right nutrients into your muscles so you can get bigger and stronger. There are a variety of pre workout supplements available, but for the beginner, there are a few basics you should keep on hand.

Why Use Pre Workout Supplements?

Anyone can benefit from proper pre workout nutrition. Whether you’re a weekend warrior trying to lose some belly fat or a professional athlete, the advantages of proper pre workout supplementation are solid.

  • Energy and focus: When you enter the gym with pep in your step and laser focus on the workout ahead of you, you’re much more likely to give it your all and enjoy your time there. Having the same levels of energy for the last exercise as you did for your first will be crucial in a well balanced physique and training regimen.
  • Build more strength: Pre workout supplements can help you move more volume while training, which results in more muscle fiber growth and stronger muscles. Even if your initial goal isn’t to build strength, being stronger definitely won’t hurt.
  • Get bigger, faster: Between getting the right nutrients in your muscles, getting the right pump and having the energy to move more weight, pre workout supplements will help increase hypertrophy.
  • Lose fat: The right pre workout supplementation will increase lipolysis, or fatty acid mobilization, and your body will burn more fat for fuel. There’s a common misconception that having supplements before a workout may decrease fat loss, but if done right, it can only help. A lot.
  • Faster recovery: Soreness after a hard workout can be annoying and can get in the way of your next training session. Correct supplementation can speed up the recovery process and get you ready for your next workout faster.

Recommended Pre Workout Supplements for Beginners

If you’re a newcomer to pre workout nutrition, here are some good pre workout supplements that will serve as a solid foundation to your regimen.

Caffeine Benefits: Taking caffeine in your pre workout stack can serve multiple purposes. First, as you’re well aware, it will give you energy and focus. Second, it will help ramp up your metabolism and increase fat loss. Dosage can vary based on caffeine tolerance, so start low if you’re not used to caffeine. A good starting dose is 100mg (about the caffeine in a cup of coffee.

Creatine Benefits: Overall work capacity is crucial in the gym. Creatine increases ATP energy, giving your muscles more fuel for the extra reps or the extra lap. And when you’re done working out, creatine will help you recover faster and prevent soreness.

Arginine Benefits: By boosting nitric oxide levels, arginine helps improve blood flow into the muscles so more oxygen and nutrients are delivered to your muscles during your workout. This is a great synergistic addition since it works well on its own to reduce fatigue, but helps other supplements become more effective.

Creatine and Caffeine for Strength and Energy

During a workout session, many of us begin to feel sapped of energy and experience feelings of fatigue and exhaustion. This can lead to less productive time in the gym, less muscle gains, and, ultimately, can hinder our ability to reach our goals. A healthy diet can be fortified with beneficial supplements to help our body adapt to increased intensity during training when working towards a set of goals. Two different compounds, Creatine and Caffeine, when included as part of a workout stack or as daily supplements, can help the body combat fatigue and increase the overall performance of our bodies.

What is Creatine Supplement? What is Caffeine Supplement?

Creatine [1,2] is an amino acid that occurs naturally in humans and is found in different organs in the body- the liver, kidneys, and pancreas. Creatine supplement is used as an energy source by skeletal muscles during intensive exercise and is transported easily and efficiently through the bloodstream. Since its discovery in the early 1800s, Creatine is known to be significant in the proper functioning of the skeletal muscles as roughly 95% of the body’s supply is stored in these muscles. Additional supplementation of Creatine has not been shown to have high chances of toxicity in the body.

caffeine powder for energyCaffeine [3,4] is a natural alkaloid that is widely used for its stimulant effects on the central nervous system which help alleviate symptoms of sleepiness and fatigue. Caffeine supplements are derived from a number of sources including the coffee bean, leaves of different types of teas, guarana berries, and numerous others. While intensive amounts of Caffeine supplements are not recommended, moderate levels have been shown to improve different aspects of our body’s performance and concentration.

How can these supplements help?

Creatine and Caffeine supplements can be taken at varying periods of the day depending on your workout schedule, diet, and sleep habits. When taken as part of a supplement schedule, the two compounds work to provide our bodies with energy and prevent early feelings of fatigue. During a workout, the stress we exert on our bodies and muscles can create a need for quick energy resources to help keep our current pace and stay on target. Creatine [1,2] fills in these gaps by helping to energize our muscles to help prolong and increase performance. Additionally, Creatine is reported to increase the body’s ability to build and retain lean muscle. Caffeine also helps [3,4] to energize our bodies by stimulating different systems of our body to alleviate feelings of fatigue during especially intensive exercise regimens. Caffeine can provide faster reaction time, increased concentration, and boost total time spent in the gym. This combination can help us to meet our fitness and health goals, but as with any supplement, the body requires both adequate hydration during exercise and recovery time to ensure optimum performance of our bodies.

Sources

  1. www.umm.edu
  2. https://en.wikipedia.org/wiki/Creatine
  3. www.ncbi.nlm.nih.gov/pubmed/12439084
  4. https://en.wikipedia.org/wiki/Caffeine

Pre-Workout Stack: Creatine, Caffeine, and DMAA

pre-workout stack: creatine, caffeine, DMAA

Caffeine supplements, creatine supplements, and DMAA are already included in many generic proprietary blend pre-workout formulas, and there is good reason why. The combination of these three supplements work very well together to provide the energy, focus, and recovery that are essential to a great workout and great results. To effectively evaluate this particular stack let’s take a look at the individual supplements and the specific research behind their effectiveness.

Creatine

According to the International Society of Sports and Nutrition the supplementation of creatine is the most effective performance enhancing nutritional supplement when it comes increasing high-intensity exercise capacity and building lean body mass. In addition, creatine is produced naturally in the body and can be found in some foods. Research involving both novice and experienced athletes has shown creatine to increase power output, muscular endurance, anaerobic running capacity, and lean mass. Increased power output and anaerobic running capacity are among the most heavily researched effects when it comes to studying creatine and both areas have shown significant results. We’ll look at how it interacts with caffeine and DMAA in a moment.

Caffeine Powder

Pure caffeine powder is arguably one of the most popular stimulants in the world at present and there is good reason why. Its effects are potent and they work fast; this coupled with the fact that caffeine is legal and unregulated make it an extremely popular choice in the stimulatory world. Research has shown caffeine to increase focus, reduce physical and mental fatigue, restore alertness, increase general coordination, and it allows for faster and clearer thoughts.

DMAA

DMAA is often one of the main ingredients in many pre-workout supplements you may have already tried and is enjoyed by many people around the world every day. Currently the only significant effects found through research relate to DMAA’s ability to raise blood pressure while not increasing the subject’s heart rate. While this may be beneficial to those with low blood pressure, I’m guessing that’s not why you’re here. In regards to training, DMAA is used in conjunction with caffeine to boost mood, confidence, and energy. In addition, it has been shown to be more potent than caffeine in related areas, essentially meaning less is more when it comes to DMAA supplementation.

This pre-workout stack will not leave you wondering if it is working or not 30 minutes in to your workout. It is most effective in boosting energy, focus, and strength and preparing your body for recovery so that you can get back to training as soon as possible. One should always exercise caution when trying a new stack and do their own research on each individual component they wish to implement. Individual responses will always be different and should be taken into account. This stack is a great option to cycle with any other stacks you may have tried and liked. Give it a shot and let us know about your results.

Sources

Caffeine: https://intraspec.ca/1981-v10n03-p202.pdf

Creatine: https://www.ncbi.nlm.nih.gov/pubmed/7714837

DMAA: https://physsportsmed.org/doi/10.3810/psm.2011.09.1927

Best Caffeine Free Pre Workout Supplements

pre-workout supplements without caffeine

Caffeine powder is widely used as a pre-workout stimulant. It’s taken through energy drinks, coffee, or supplement stacks. There are benefits to using caffeine before a workout. In the very least, it gives your muscles the extra energy to keep going and also helps get your blood pumping faster.

However, there are times when using caffeine may not be the best idea. For example, if you train later in the evening, a high dose of caffeine may interfere with your sleep. Or, for anyone particularly sensitive to caffeine, the effects can be over stimulating and become more of a hindrance in the gym. Regardless of your situation, you shouldn’t feel slighted during your workout. There are several alternatives to caffeine in pre-workout supplements that can help you keep your edge and help you reach your goals faster.

Citrulline Malate Powder

Citrulline Malate is a form of the amino acid citrulline and provides energy to the muscles and promotes endurance for both aerobic and anaerobic athletes. Citrulline malate powder works in two main ways. First, it increases intramuscular ATP energy. This is what you use each time you lift a rep or run a lap. The more ATP in your muscles, the longer they will function at optimal levels.

Citrulline malate takes that a step further by helping you function on an even higher level. In a study performed on athletes using the chest press as a test exercise, participants were given citrulline malate or placebo. Then their work output and recovery times were measured. Users given citrulline malate were able to do 52% more repetitions and had a 40% reduction in soreness, so they were stronger during their workout and recovered faster too. [1]

Beta-Alanine Supplement

Beta-alanine is another great caffeine-free pre-workout supplement that also promotes muscular endurance.  Beta-alanine works a bit differently than citrulline malate. Supplementing with beta-alanine helps increase intramuscular carsonine levels [2].

During exercise, carsonine helps remove lactic acid from muscles, which can cause a burning sensation and muscle fatigue. Without acid buildup and muscular fatigue, beta-alanine helps you get stronger and build muscle mass.

Beta-alanine can help improve your overall body composition too. Research performed on athletes has shown that beta-alanine can increase lean muscle mass and decreasing body fat percentage [2]. Since this is a popular reason for using caffeine pre-workout, you can now work toward your fat-burning goals without stimulant supplements.

L-Arginine Supplement

As the two supplements mentioned above, L-Arginine supplement, also simply known as Arginine, is also an alternative to caffeine for increasing endurance, increasing strength and reducing fatigue. Arginine works differently as well. It’s is responsible for boosting nitric oxide flow into the body after exercise. Higher nitric oxide levels relax blood vessels which allows for more blood flow. The increased blood flow delivers oxygen and nutrients to the muscles more efficiently to prevent muscle fatigue. Arginine also boosts growth hormone production and helps you recover quicker. [3] [4]

Caffeine Free Pre Workout Stacks

You can also try pre-workout stacks which are often available without caffeine. Stacks take the guesswork out of pre-workout supplementation. I found a great pre-workout stack called Muscle Maxx Pro. This pre-workout stack contains L-Arginine, Astragalus, Tongkat Ali (Longjack), Maca, and Tribulus. These ingredients work together synergistically to enhance the body’s muscle building capacity.

Whatever your reasons are for wanting to cut caffeine out of your pre-workout stack, there are alternatives. With muscular endurance and energy being the main benefits, the options for replacement are well represented. A stimulant-free pre-workout stack can help you reach your goals just as fast and without any of the negative side-effects of caffeine use.

Sources

[1] https://www.ncbi.nlm.nih.gov/pubmed/20386132

[2] https://en.wikipedia.org/wiki/Beta-Alanine

[3] https://l-arginineguide.com/facts-about-l-arginine-and-working-out.html

[4] https://www.livestrong.com/article/6135-need-l-arginine-bodybuilding/

Importance of Pre-Workout Nutrition and Supplementation

The importance of nutrition isn’t foreign to anyone in the health and fitness community. You, like many athletes, surely know the right meals and supplements are essential to maximizing strength and power.  Lack of proper supplement timing, however, may be holding you back from your goals. For a long time there was an understanding that the most important time to take supplements was post-workout. There is now a new school of thought that says taking supplements before you work can be even more effective.

Why Pre-Workout Supplements?

Priming your body and your muscles properly is akin to making sure your car has enough gas in it before a long car trip. Pre-workout supplements can help you in multiple ways by fueling you with the nutrients you need at the very moment you need them, not just after you’re depleted.

Benefits of good pre-workout supplements include[1]:

  • More strength and performance. Lift more weight, work out for a longer period of time and reduce muscle fatigue.
  • Improved energy and reaction time. Do you work out early in the morning or after a long day’s work? You probably need an energy boost to perform at your best.
  • Better focus. Give yourself a mental edge for overcoming barriers. Having a focused, determined attitude is essential to success in the gym. Focus on your plan and execute.
  • Increased protein synthesis. Build muscle more efficiently and recover faster by getting nutrients to muscles immediately.
  • Improved fat burning. Get full advantage of your workout and maximize your body composition.

As you can see, these are very wide in scope so they can benefit athletes at any level. It’s not just anecdotal evidence either – clinical studies have shown that the proper pre-workout supplements can provide significant results. In one study, subjects performed 50% more bench press repetitions and had a 40% reduction in DOMS (delayed onset muscle soreness) when they used citrulline malate powder pre-workout[2].

What to supplement with?

There are a wide variety of pre-workout supplements available, so it’s essential to do research and read up on some of the options to make sure you’re getting the most out of your time in the gym and getting the right supplements to meet your goals. Below are some options and good places to start with pre-workout supplements:

Strength and performance: Citrulline Malate powder, Creatine supplement (or the faster absorbed derivative, creatine ethyl ester), Beta Alanine supplement, L-Arginine supplement, Beta-Ecdysterone supplements

Energy and focus: Caffeine supplements, DS Craze pre workout supplement, C-vitamins

Increased protein synthesis: Whey Protein, Branched Chain Amino Acids

Improved fat burning: Caffeine supplements

Keep in mind that with certain supplements you may want to stagger the dosage. For example, users should take arginine powder should be taken about an hour before exercise, but branched chain amino acids are digested quickly, so those should be consumed just before your workout.

Now that you know the benefits of  pre-workout nutrition and what to use, go pick up some new pre-workout supplements to add to your routine and see your gains skyrocket!

Sources

[1] https://www.nutritionandmetabolism.com/content/9/1/28

[2] https://www.ncbi.nlm.nih.gov/pubmed/20386132