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Building Muscle

The 10 Best Muscle-Building Supplements: A 2021 Science-Based Review

There’s no getting around it, if you want to build muscle, you need to be eating and training right. In fact, if you're not challenging yourself both in the kitchen and the weight room, it’s going to be very difficult to build any size or strength at all.

But even with your diet and workout routine dialed in, it can still be tough to achieve the kind of gains in lean body mass that many folks are after.  Ultimately, that’s one of the main reasons people looking to build muscle become interested in dietary supplements.

The only issue is that there are hundreds of supplements out there with all sorts of different claims as to their benefits.  So what are the best muscle-building supplements? To answer this question, we’ve developed an efficacy rating system we call ‘Does it Work’,or DIW for short.         

Determining the Best Muscle-Building Supplements

Our rating system ranges from 1 to 4, with 1 representing the least effective supplements and 4 representing those that are most effective for muscle growth. Each supplement’s rating is determined by a couple of different factors.

First, we’ve taken into consideration the number of randomized, prospective, and blind studies that have been published on each substance. If there aren’t many studies on a particular supplement, the overall rating for that substance will be lower and vice versa.

Secondly, we consider the results of the studies. If most studies on a particular supplement demonstrated positive effects with high significance, that supplement would rank highly. If numerous studies demonstrated only modest improvements, the ranking would be lowered somewhat. If there is a high degree of mixed results in the studies-- i.e. some of the studies are positive, while others are not -- it lowers the DIW score further.

Now that we’ve covered how we actually came up with our ratings, let’s get into our evaluation of the best muscle-building supplements.

What Are the Best Muscle-Building Supplements?

best muscle building supplements

1. Whey Protein

What is it?

Whey is a dairy-based protein.  Milk consists of two types of protein: whey and casein.  Whey is a faster-digesting protein, meaning that it is more rapidly absorbed in comparison to casein.  While supplementing with casein may also have some benefits, particularly when it comes to recovery, it’s hard to deny that whey protein is the best muscle-building supplements.  

As far as proteins go, whey is categorized as a complete protein because it contains all of the 9 essential amino acids that your body can’t make on its own.  On top of that, it contains more of the BCAAs leucine, isoleucine, and valine than any other complete protein source.

How does it work?

All of the muscles throughout your body are going through a constant state of turnover.  At the cellular level, they’re made up of proteins, which are constantly being broken down by physical stressors.  Your body also naturally breaks down proteins to be used in other important bodily processes as well.

Muscle protein breakdown (MPB) which is also known as protein degradation,  happens to all of us on a daily basis. Luckily though, it’s only half of the equation.  In response to this natural process, your body uses dietary protein to repair and rebuild the damaged proteins in your muscles, which is known as muscle protein synthesis (MPS).         

MPS is the key to muscle growth.  In the most basic of terms, muscle growth happens when the amount of protein synthesized within your muscles eclipses the amount that is broken.  In order for that to happen though, your body needs an adequate supply of dietary protein.

While you can get all of the protein you need from solid food sources like meats, many may find it difficult to do so.  Building muscle requires a high-protein intake, oftentimes at or above 1g of protein per pound of body weight each day.  

So, if you’re 180 lbs, that’d be around 180g of protein per day, which would be quite a lot of meat. For example, that’d translate to over 20 ozs of chicken per day.  

However, that’s where supplementing with whey comes into the picture.  One serving of most high-quality whey products contains around 25g of protein, which can be effortlessly mixed in with water.  Adding a couple of scoops of whey into your daily diet makes hitting your protein goal that much easier day in and day out.

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It’s not just the ease of use that makes whey protein such a popular supplement either; it also has a rapid absorption rate.  On top of that, a number of studies have demonstrated that whey produces greater spikes in MPS than just about any other type of complete protein.    

Scientists have revisited these results in a variety of tests, and have consistently found that on average, whey produces more muscle biosynthesis in comparison to other complete protein sources.  

2. BCAAs

What are they?

Branched-chain amino acids (BCAAs) are like the name implies, amino acids (AAs). There are two kinds of AAs: essential and non-essential.  Your body can produce non-essential amino acids all on its own, whereas essential AAs can only be obtained through food sources.

There are 9 different essential amino acids, 3 of which are classified as BCAAs due to their molecular structures.  The 3 BCAAs are leucine, valine, isoleucine.

How Do They Work?

BCAAs play an important role in muscle protein synthesis.  Leucine, in particular, helps to set off a series of signaling events in your body designed to kick start the rebuilding process within your muscle cells.  

It directly activates what’s known as the mTOR cascade, which is the process responsible for stimulating muscle growth.  mTOR, which is short for the mammalian target of rapamycin, refers to a series of signaling pathways within your body that help to coordinate the transportation of protein and other nutrients to your muscles.  

While leucine does appear to play the most critical role when it comes to muscle growth, research shows that all 3 BCAAs have synergistic effects when taken together.   When combined with isoleucine and valine, leucine produces greater spikes in MPS compared to when taken on its own.

It is important to point out though that some researchers have argued that BCAAs may not be as effective at stimulating muscle protein synthesis when compared to whey protein.  However, most studies have found that supplementing with BCAAs before and/or after a workout helps to decrease exercise-induced muscle damage.

BCAAs are oxidized by your muscles during exercise and your muscles’ store of them can be easily depleted by an intense workout.  Without an adequate supply of BCAAs, your muscles won’t be able to kick start the process to repair and rebuild after your workout.

3. Creatine

What is it?

Creatine is a naturally occurring amino acid-like substance that’s produced in small amounts in the human body.  Minimal quantities can be obtained through certain food sources as well.

It’s also one of the most popular, most well-researched, and best muscle-building supplements on the market.  That's because numerous studies have demonstrated that creatine has positive effects on both exercise performance and muscle growth in a wide variety of different test subjects.  

How does it work?

One way creatine works is by increasing your body’s levels of adenosine triphosphate (ATP).  ATP is an energy-providing biochemical that plays an important role in muscle contractions.  More available energy in your muscles during your workout ultimately translates into more training volume.  Adding more sets, reps, and weight into your routine, leads to significant increases in size and strength over time.   

Some research shows that creatine may also help to increase levels of insulin-like growth factor (IGF) in your muscles during exercise.  IGF plays an important role in muscle growth and those with higher concentrations of IGF in their muscles, on average, demonstrated significantly greater gains in lean body mass.  

4. Beta-Alanine

What is it?

Beta-alanine (BA) is a non-essential amino acid, meaning it’s produced in small amounts in the human body.  It can also be found in some food sources. Beta-alanine plays a direct role in your body’s production of the molecule carnosine.  

And with a sizeable and growing body of evidence as to its significant effects on the muscle-building process, beta-alanine also has to be considered one of the best muscle-building supplements currently on the market.

How does it work?

Carnosine plays a buffering role within your muscles cells, helping to block the build-up of lactic acid during intensive exercise.  Reducing the amount of lactic acid in your muscles ultimately helps you to work at higher intensities for longer periods of time, thus increasing the time you have before exhaustion sets in.  

A number of studies have demonstrated that BA supplementation significantly improves exercise performance.  Researchers have found positive effects on populations ranging from those with no previous training experience all the way up to top-level athletes.  

On top of that, other research has also demonstrated that over time, study participants who supplemented with beta-alanine on average also saw significantly greater gains in lean body mass compared to those who were given only a placebo.            

5. HMB

What is it?

HMB, which is short for β-hydroxy-β-methylbutyrate, is a metabolite of the BCAA leucine.  Although it may share some similar functions with leucine, HMB plays its own unique role within the body.  Somewhere around 5% of the leucine that is consumed through your daily diet is ultimately converted by your body into HMB.       

In recent years, it's continued to grow in popularity as a muscle-building supplement do to the growing body of evidence that taking HMB may lead to greater gains in size and strength compared to diet and exercise alone.

How does it work?

HMB plays a buffering role in your muscles’ metabolism, preventing the build-up of enzymes that directly contribute to muscle protein breakdown (MPB).  It’s also believed to stimulate MPS through the activation of certain biochemical pathways within your body.

In particular, HMB is believed to activate the mammalian target of rapamycin (mTOR) pathways. Once activated, these pathways help to facilitate the delivery of fresh nutrients to damaged muscle tissues during protein synthesis, helping to replace old broken down muscle proteins with fresh new ones.  


What is it?

Alpha-hydroxy-isocaproic acid, or HICA, is a naturally occurring amino acid metabolite.  It’s also sometimes referred to as DL-α-hydroxy-isocaproic acid, leucic acid or DL-2-hydroxy-4-methylvaleric acid.   

Like HMB, it’s produced during the metabolism of the BCAA leucine.  80% of the leucine absorbed in your diet is used to make muscle proteins. The remainder is metabolized in the muscle into α-ketoisocaproate (α-KIC) and β-hydroxy-β-methylbutyrate (HMB). Along the α-KIC pathways, some of the KIC is also converted into HICA, although it’s a pretty small amount.

How does it work?

HICA works as an anti-catabolic agent, inhibiting certain enzymes that contribute to the degradation of muscle tissues and a number of experimental and clinical studies have found that it helps to prevent muscle protein breakdown in both animal and human subjects.

Some research has also demonstrated that HICA may increase muscle protein synthesis as well.  Like it’s closely related cousin HMB, it’s also believed to activate mTOR pathways, although through different mechanisms than HMB.  

While the findings up to this point seem to be promising, there simply hasn’t been as much research on HICA as there has been on other supplements like creatine.  Some believe it will eventually surpass HMB as a muscle-building supplement and at half the dose required by HMB. Yet without the depth of clinical research, it’s a little more difficult to make definitive conclusions about its effectiveness on muscle growth.  

7. Phosphatidic Acid

What is it?

Another promising muscle-building supplement is Phosphatidic acid (PA), a natural compound and important signaling lipid found throughout most of your body’s cells.   PA plays a critical function in mTOR signaling, which in turn helps to regulate cell growth throughout your entire body.

How does it work?

mTOR plays a central role in muscle protein synthesis (MPS), helping to set off a series of signaling events drawing nutrients and oxygen into muscle tissues in need of repair.  

Researchers have found a positive correlation between PA and the activation of mTOR signaling pathways, which are directly involved in MPS.  Several double-blind studies have found that supplementing with PA lead to significantly greater increases in lean muscle mass compared to a placebo.

In fact, several studies evaluating high-intensity training protocols that typically lead to net muscle loss found that those who supplemented with phosphatidic acid not only avoided losing muscle, they actually saw some net gains.  

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8. Testosterone Boosters (D-Aspartic Acid, ZMA & NMDA)

What is it?

Testosterone plays a key role in muscle growth and numerous studies have demonstrated that boosting testosterone levels can have positive effects on both exercise performance and overall body composition.  So much so that taking substances like steroids and human growth hormone has become a banned practice in pretty much all major sport.

How Does it Work?

With that being said, some supplements claim to boost your testosterone the natural way.  Several substances, such as d-aspartic acid, ZMA, and NMDA have been said to be ‘natural testosterone boosters’, with several different supplements touting them as “muscle-building” ingredients.

However, there simply isn’t any scientific evidence to support these kinds of claims.  Up until this point, there has been no clear evidence to support the basic premise behind the idea of a “natural testosterone booster”.

9. Arginine

What is it?

Arginine is an amino acid that aids in your body’s production of nitric oxide, which plays an important role in cell signaling.  Arginine synthesis begins in your intestines, where citrulline is formed. From there, citrulline is transported to your kidneys where it’s converted into arginine and sent back out into your bloodstream.  

How Does it Work?

Several studies have shown that in its supplemental form, arginine is poorly absorbed by the intestinal tract.  Some research has also found that arginine supplementation may lead to stomach pain and discomfort for some.

Furthermore, there doesn’t appear to be any scientific evidence to support the claim that arginine is an effective muscle-building supplement.  Researchers have generally found that its effects are minimal when taken as a supplement and no study has clearly demonstrated a significant correlation between arginine supplementation and muscle growth.  

10. Citrulline

What is It?

Citrulline is a naturally occurring amino acid.  When taken in the supplemental form, citrulline is converted by your body into arginine (and ornithine).  Research has clearly demonstrated that citrulline is more effectively absorbed by your body than arginine when taken as a supplement.  

How Does it Work?

Some studies have demonstrated that citrulline may help to improve aerobic and/or anaerobic endurance in athletes.  However, its effects on muscle growth have yet to be fully demonstrated.

Athletes primarily supplement with nitric oxide boosters for the vasodilation effect they produce in the muscles.  This effect is often referred to as the “pump”. While it’s a sensation many gym-goers may enjoy, there isn’t much scientific evidence that a more intense pump leads to greater gains in size and strength.    

wrap up

While a number of different natural substances have been touted as muscle-building supplements, the research shows that some ingredients work better than others.  Amongst them, whey protein and creatine are without a doubt the most well-researched supplements, with numerous studies highlighting their positive effects on muscle growth.

Along with whey and creatine, there also appears to be a substantial body of evidence that beta-alanine, HMB, and phosphatidic acid can have significant effects on the size and strength of your muscles as well.

Although BCAAs have been extensively studied, there is still some debate when it comes to their effectiveness on muscle protein synthesis.  Some researchers argue that compared to BCAAs, whey protein is far more effective at stimulating MPS. Even so, there is ample evidence to suggest that BCAAs play an important role in preventing the breakdown of muscle tissues.     

While there is a growing cache of research on the positive effects of HICA, there simply haven’t been as many studies on it to make the same kind of conclusions we were able to make for substances like HMB.  

For other supplements like testosterone boosters and arginine, there is little if any reliable scientific evidence to suggest that they are effective substances for increasing the size and strength of your muscles.  Most studies demonstrating positive findings appear to have conflicts of interest.

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