Supplementation & Nutrition

Caffeine Anhydrous – Uses, Differences, Side Effects, Benefits – Everything You Need to Know

Caffeine has been used for thousands of years as a stimulant and cognitive enhancer.

Today, it is the worlds most popular bioactive substance, with millions consuming it each day.

However, beverages such as coffee and tea are not the only way to get your daily caffeine fix. 

Take a quick glance at the supplement facts of many products and you will find caffeine anhydrous listed as one of the major ingredients.

From pre-workout powders and energy drinks to weight loss and nootropic supplements, caffeine anhydrous is used in abundance.

The popularity of caffeine anhydrous raises important questions regarding its effectiveness and safety.

Is it as good as natural caffeine found in our favorite beverages? What are the benefits of consumption?

How safe is it?

Below we address these questions in great detail as well as provide useful background information about caffeine anhydrous, so that you can determine if it is right for you.

What is Caffeine Anhydrous?

First, caffeine, the component that we are all familiar with, is a naturally occurring substance belonging to a family of compounds called xanthines.

More specifically, because caffeine contains methyl groups at different positions, it is classified as a methylxanthine.

These methyl groups is what gives caffeine its bioactive properties, and the three that it contains is what differentiates it from other well know xanthines such as theobromine and theophylline (1).

Second, the word anhydrous means; in the absence of water - making caffeine anhydrous simply dehydrated, concentrated, water soluble caffeine powder.

It is usually synthesized but it can be derived from natural sources such as coffee beans/seeds or tea leaves (2).

Take Away

Caffeine anhydrous is a potent, dehydrated form of caffeine that is either synthesized or extracted from natural sources.

What Products Is Caffeine Anhydrous In?

Many types of soda, energy drinks, alcoholic beverages, and even some breakfast bars contain caffeine, usually in the form of caffeine anhydrous. 

The list does not stop there.

Over the years caffeine anhydrous has made its way into many products including pre-workout powders and drinks, weight loss supplements, nootropics/brain-related blends, and performance enhancing supplements.

How Does Caffeine Anhydrous Work?

Caffeine's most well known effect is its ability to reduce the feeling of fatigue. It is not technically a stimulant, but is indirectly stimulating to the brain because it promotes wakefulness and increased energy.  

There are other ways that caffeine affects the body, specifically within the peripheral nervous system (PNS), which will be discussed later on in this article.

The major and most well studied mechanism of caffeine is its ability to inhibit certain adenosine receptors in the brain.

Adenosine, a neurotransmitter, is mainly responsible for causing feelings of tiredness and fatigue.

There is also some evidence that caffeine increases the amount of other neurotransmitters in the central nervous system (CNS) like serotonin and catecholamines such as dopamine, but more studies in need to be done in humans to determine how significant this effect is (3).

Lastly, caffeine may also have other cellular mechanisms such as impacting calcium kinetics and increasing sodium/potassium ATPase activity, but again, more studies need to be done to verify these findings (4).

Take Away

Caffeine works by inhibiting adenosine receptors in the brain, promoting wakefulness and indirectly increasing energy levels. It may also increase levels of different neurotransmitters, which may also contribute to its effects. 

Caffeine Anhydrous vs. "Regular" caffeine

It is important to understand that the caffeine in caffeine anhydrous powder or concentrated liquid caffeine products is the exact same chemical structure as "regular" caffeine. 

They share the same bioactivity, and work by the same main mechanism in the body, blocking adenosine receptors (3, 4).

anhydrous caffeine vs regular caffeine

However, there are major differences between the two forms. The four most important ones are: 1) Source, 2) Concentration, 3) Convenience, and 4) Cost

1) Source

"Regular" caffeine is naturally-occurring and extracted from coffee beans and tea leaves, and therefore undergoes no synthetic or chemical processing.

On the other hand, caffeine anhydrous, usually undergoes some kind of manipulation in the laboratory, including dehydration and other separation techniques, all aimed at obtaining “pure caffeine".

2) Concentration

To put the concentration difference between  "regular" caffeine and caffeine anhydrous into perspective - according to the Federal Drug Administration (FDA), using one teaspoon of powdered caffeine anhydrous is equivalent to drinking 28 cups of coffee!

The purity of caffeine anhydrous may vary, but that is the major difference between the two forms of caffeine, with the anhydrous version being almost 30 times stronger.

3) Convenience

Caffeine anhydrous comes in more convenient dosage forms than "regular" caffeine. This variety includes tablets, gums, liquids, and gels.

This point could be debated, as simply drinking some coffee or tea may be seen by some as easier than taking it through another route, but generally speaking these alternative forms of caffeine anhydrous are considered more convenient due to their versatility.

A Word of Caution

The fact that anhydrous caffeine is so concentrated and can easily be added to a lot of different things also adds an element of danger to its use, which we will discuss in further detail below. If manufacturers or individuals improperly dose it, overdoses and toxicity can occur. This is not so much an issue for producers of caffeinated products, as most manufacturers have strict practices in place to make sure this does not happen. However, individual users that purchase and add anhydrous caffeine to foods or drinks must take extreme caution and make sure they are measuring a safe amount of caffeine anhydrous.

4) Cost

Sourcing natural forms of caffeine is quite expensive. Making synthetic caffeine in the laboratory, however, is a lot cheaper. To put in perspective just how cheap it is, you can get about a 100,000 milligram (mg) bag of anhydrous caffeine for around $10.

Types of Caffeine Anhydrous

Anhydrous caffeine, after the removal of water and other components, usually appears in a white crystalline powdered form.

For easier dosage calculation, safety, and convenience, this powdered form is usually converted to other forms. Again, these include tablets, capsules, gums, gels, and liquids.

Apart from these, caffeine anhydrous is also used in small doses as an ingredient in a variety of other supplements. These types of caffeine anhydrous usually appear as either dicaffeine malate, caffeine citrate, or caffeine pterostilbene co-crystal.

Dicaffeine Malate – Dicaffeine malate consists of two caffeine molecules conjoined to a malic acid molecule.

This is done to prevent upset stomach, prevent the "crash" associated with "regular" caffeine, and malic acid itself has some additional benefits associated with it including increased endurance and energy production. 

Few clinical studies have looked at dicaffeine malate's safety and effectiveness, so it is suggest to use with a bit of caution. However, it is generally considered safe and as effective as standard caffeine.

Caffeine Pterostilbene Co-Crystal – This form of caffeine is a patented form of caffeine combined with the antioxidant pterostilbene. This unique combination prolongs its absorption and half-life allowing the caffeine to have a more sustained effect without the crash.

Caffeine Citrate – Caffeine citrate consists of caffeine and two other compounds – citric acid monohydrate and sodium citrate dihydrate, in a 2 – 1 – 1 ratio.

This form of caffeine is isn't actually used in over the counter (OTC) supplements but rather as a medication to open airways and improve breathing for patients in need.

Caffeine Anhydrous Benefits

It has been proposed that because caffeine anhydrous is better absorbed, it may actually produce more pronounced benefits over "regular" caffeine.

However, the very few studies that have been published have produced conflicting results and therefore caffeine anhydrous and "regular" caffeine are thought to produce the same results and benefits.

Caffeine improves exercise performance

1) Enhances Exercise Performance

Caffeine is ergogenic, which means it enhances exercise performance (endurance, strength, recovery, or a combination of one or more).

The most pronounced benefit of caffeine consumption is improved acute exercise performance. According to the International Society of Sports Nutrition, caffeine has been shown to improve exercise performance for a variety of parameters in many, but not all studies (5).

Exercises like the Bulgarian Split Squat or Arnold Presses and Military Presses are great examples of lifting techniques that may be improved with caffeine use.

It is important to remember that individual results will vary with caffeine consumption. Why? The answer is rather complex and depends on five main factors.

Caffeine response is dependent on pharmacokinetics (how the body processes substances), pharmacodynamics (how the body responds to substances), genetics, physiology (any present disorders,  conditions, or environmental factors like history of smoking), timing of consumption, and the interplay between the five. 

The three main pharmacokinetic factors that impact caffeine response are absorption, metabolism, and elimination/clearance.

The main pharmacodynamic mechanism involved with caffeine consumption is tolerance and adenosine receptor down or upregulation.

Genetics, physiological circumstances, and timing play a role along the entire spectrum of caffeine response (5, 6).

Aerobic Endurance

There is a solid amount of evidence that moderate caffeine consumption (3 - 6 mg/kg) improves aerobic stamina.

Again, individual results will vary, but the improvement in performance is in the 2 - 4% range for different exercises such as running, cycling, swimming, and cross-country skiing, or rowing (5, 7, 8, 910).

Muscular Endurance

The literature on whether caffeine improves muscular endurance is somewhat mixed, but meta-analyses (study of studies) found that it increases muscular endurance by 6 - 7% (510).


Like with muscular endurance different meta-analyses again found caffeine to improve strength, but only to a small degree (510).


Studies looking at power output after caffeine consumption have been mixed with further research needed. Therefore, some individuals may experience benefits and others may not (5, 10).

2) Improves Cognitive Function

When looking at caffeine's effect on cognitive function it is often analyzed by looking at its ability to improve "lower" vs. "higher" cognitive function.

In respect to "lower" cognitive processes such as reaction time, attention, arousal, and vigilance, caffeine has been shown to improve these aspects in a dose dependent manner at moderate dosage ranges between 32 to 300 mg (10).

For "higher" cognitive functions such as memory, problem solving, decision making, executive function the data is less clear and studies have produced mix results, with some individuals experiencing benefits and others not (10).

Generally speaking, caffeine's ability to promote wakefulness whether an individual is sleep-deprived or not will ultimately improve overall cognitive function.

3) Reduces Fatigue

There is little debate in the clinical and scientific communities about caffeine's most well know effect - indirectly reducing fatigue by promoting wakefulness and arousal. It has been shown over many decades to increase wakefulness through the inhibition of adenosine receptors (10).

4) Helps Relieve Headaches

Caffeine alone and in combination with analgesics such as ibuprofen, acetaminophen, and aspirin can help with alleviating headaches.

How does caffeine work to help get rid of headaches? The mechanism is two fold. 1) It is vasoconstrictive or constrictive to blood vessels, and 2) Caffeine is thought to be anti-inflammatory.

With increased blood flow and inflammation present in almost all types of headaches, it makes sense that caffeine could help with these symptoms. 

Much of the evidence that exists for caffeine alleviating headaches is anecdotal - however, several studies have found caffeine to be effective at relieving pain associated with migraines and tension-type headaches (11).

5) May Increase Fat Burning And Metabolism

Aside from caffeine affecting the CNS, it also stimulates a wide range of physiological functions throughout the PNS. One beneficial action is that it may increase fat burning and metabolism by increasing the release of epinephrine into the blood (12, 13). 

Clinical studies have been somewhat mixed, however some found caffeine consumption to increase fat burning and metabolism (14, 15, 16, 17, 18).

Another study found no significant difference in fat burning and metabolism after caffeine consumption (19).

So, all in all, it is still unclear to what degree caffeine increases fat burning and metabolism and larger, more definitive studies need to be done.

6) May Protect against oxidative stress and inflammation

Oxidative stress and inflammation have been linked to many disorders over the years ranging from neurodegenerative and cardiovascular diseases to diabetes and cancer.

The idea that caffeine may reduce oxidative stress and inflammation throughout the body is a relatively new, but exciting one.

Oxidative stress and inflammatory processes are related and very complicated. Exactly how caffeine interacts with these pathways is not well understood and a lot of research still needs to be done (20).

Coffee reduces oxidative stress

7) Other Coffee and Tea Related Benefits

Caffeine may have a host of other benefits, however, it is difficult to determine if the following potential benefits are caffeine related or due to a host of anti-oxidants and anti-inflammatories found in coffee and tea.

In addition, the combination of caffeine with these other beneficial substances may be synergistic. Regardless, if either is found to be the case these benefits may not be observed with just consuming caffeine alone.

Therefore for clarity, all of these potential benefits are related to coffee and tea, not caffeine specifically.


There have been few studies investigating the neuroprotective properties of caffeine and the ones that have been conducted have only looked coffee intake. 

Three long-term studies found that prolonged coffee consumption decreased the risk of Alzheimer's disease (AD) and one concluded it decreased the risk of both AD and dementia.

In addition, a meta-analysis determined that long-term coffee consumption resulted in a 18% drop in neurodegenerative related conditions such as AD and dementia, but this decrease was not considered statistically significant.

Coffee and tea also decrease the risk for Parkinson's disease (PD), another neurodegenerative disorder (21, 22).

The mechanism by which caffeine may be neuroprotective lies in its ability to block adenosine receptors, which are thought to involved in the formation of beta-amyloid plagues, a hallmark of several neurogenerative disorders. (21, 23).

Helps Prevent Cardiovascular-Related Diseases

Both coffee and tea drinkers have been found to have a lower risk of developing cardiovascular-related diseases such as heart disease and stroke (24, 25, 26).

These findings seem counter intuitive given that caffeine can raise blood pressure.

The data on this topic is somewhat mixed with some studies concluding that tolerance develops after regular caffeine consumption and others finding that tolerance only occurs in certain individuals where the elevation in blood pressure caffeine causes persists.

The reason for varying responses is thought to be related to differences in genetic make-up (27, 28, 29, 30).

Therefore, patients with high blood pressure should take caution and consult with their health care provider before consuming coffee and/or caffeine daily. For those without hypertension, the small increase that caffeine causes should not be significant, but individuals with high blood pressure it could be an issue.

Ultimately, it is unknown how chronic coffee intake lowers the risk of cardiovascular-related diseases. The mechanism is most likely not related to caffeine itself, but to all the anti-oxidants and anti-inflammatories that coffee contains.

Reduces All Cause Mortality

According to The New England Journal of Medicine "drinking 2 to 5 standard cups of coffee per day has been associated with reduced all cause mortality in cohort studies across the world" (31). 

This effect was independent from genetic variations in caffeine metabolism, and included participants without any underlying diseases (31).

May Help Prevent Diabetes

One study found that prolonged coffee consumption decreased the risk for developing type 2 diabetes (31). 

Caffeine can decrease insulin sensitivity, but this effect is transitory and tolerance develops with continued use (31).

Again, it is not well understood how coffee can protect against the onset of type 2 diabetes. Like with cardiovascular-related disorders, it is likely due to the fact that coffee is chalked full of anti-oxidants and anti-inflammatories.

May Decrease Risk Of Cancer

There is a good amount of evidence that coffee consumption decreases the risk for certain types of cancer. The following list are different types where coffee intake is associated with a slightly decreased risk (31):

  • Breast cancer
  • Prostate cancer
  • Melanoma
  • Nonmelanoma skin cancer

Cancer types with a more decreased risk after long-term coffee consumption (31):

  • Endometrial cancer
  • Hepatocellular carcinoma

May Protect the liver

Finally coffee consumption can also help improve liver health. It decreases the risk of liver fibrosis and cirrhosis, and can lower enzymes associated with liver damage (31).

Take Away

Caffeine's established benefits include reduced fatigue, improved cognitive function ("lower" brain processes), and enhanced exercise performance (aerobic and muscular endurance). 

Other, less established positives of caffeine use may exist including; improved exercise power and strength, relief from headaches, increased fat burning and metabolism, anti-oxidation and anti-inflammation.

In addition, prolonged coffee intake may help reduce the risk of neurodegenerative disorders, cardiovascular-related diseases, all cause mortality, diabetes, and liver disease.

Caffeine Anhydrous Side Effects

After reading about all the benefits of caffeine and coffee consumption it is also important to keep in mind that caffeine is still considered a stimulant, has many different effects on the body, and must be used in moderation.

Different individual responses and sensitivities to caffeine make this point even more relevant because some users can experience side effects at any dose, especially when consuming highly concentrated caffeine anhydrous.

Therefore, the most significant consideration with caffeine anhydrous is dosage.

Caffeine anhydrous is very strong and must be measured in appropriate amounts to prevent any dose related side effects that we will discuss in further detail below.

This also means that the potential for caffeine overdose is more profound with anhydrous caffeine than it is with "regular" caffeine (31).

General Caffeine Side Effects

Caffeine can affect many systems throughout the body and below they are broken down based on each of those areas. Withdrawal symptoms are also discussed for each section when relevant.

1) Brain-Related

Confusion, Headaches, Irritability, and Drowsiness

Caffeine overstimulation can cause confusion and unclear thinking. Headaches can occur with too much caffeine and too little can result in caffeine withdrawal headaches, irritability, and drowsiness.

Anxiety, Insomnia, and Hallucinations

Too much caffeine can cause feelings of nervousness or "jitteriness", insomnia, and in rare cases hallucinations.

2) Cardiovascular System

Caffeine in general is a vasoconstrictor, meaning that it contracts blood vessels and can raise blood pressure. Therefore, it should always be used in moderation, or avoided all together in individuals with chronic hypertension or high blood pressure. It also acts as a positive chronotrope, which simply means it can increase heart rate.

Finally, caffeine related overstimulation can cause dysrhythmias, or irregular heartbeats.

3) Gastrointestinal Tract

Excess caffeine can cause various gut-related side effects including heartburn, nausea, vomiting, and diarrhea.

4) Urinary Tract and Kidneys

Bladder issues and increased urination can occur with too much caffeine use.

5) Musculoskeletal System

Muscle twitch and bone thinning can result with too much caffeine consumption.

When To Limit or Avoid Caffeine

There are certain populations that should limit or avoid caffeine anhydrous and caffeine in general. They include:

  • Pregnant and breast feeding women, or women who are trying to get pregnant - Amounts up to 300 mg of caffeine a day are considered safe for women that fall into these three categories. However, caffeine amounts exceeding 300 mg are not recommended.
  • Children - Few studies have looked at caffeine consumption in children. Therefore, it is recommended that they should avoid caffeine all together, just to be on the safe side.
  • Individuals with chronic high blood pressure and history of irregular heartbeat, osteoporosis, anxiety or bipolar disorders, diabetes, bleeding disorders, glaucoma, and irritable bowel syndrome (IBS) are all recommended to use caffeine with caution or to avoid it all together.
  • There are also a host of drug interactions with caffeine, so be sure to consult with your physician if you are taking any medications.

Caffeine Anhydrous and Regulations

Caffeine anhydrous, like caffeine, is one of the most loosely regulated bioactive substances in the world with little to zero regulation among general governing bodies. However, it can provide an advantage for athletes, and is regulated to some degree by different athletic governing bodies.

Although not outright banned or outlawed in any jurisdiction, caffeine anhydrous and caffeine use in general should always be done with proper dosage considerations and side effect awareness. 

Caffeine Anhydrous Regulation in Sports

When it comes to sports and performance enhancement, the NCAA includes caffeine on their list of banned substances with "a threshold of 15 micrograms per milliliter (mcg/mL) not be exceeded in a urine sample".

The World Anti-Doping Agency (WADA), is more relaxed when it comes to caffeine use prior to competition and does not consider it a banned substance. It does, however, have caffeine in a "monitoring program" that keeps track of substances that are not currently banned, but are being monitored to see if a ban is warranted in the future.

Final Thoughts

Caffeine anhydrous and caffeine consumption in general has several well established benefits. Further benefits are experienced when coffee is consumed over longer periods of time.

It is unknown if these benefits are due to substances in coffee other than caffeine, caffeine itself, or a combination of the two.

Both caffeine anhydrous and "regular" caffeine must always be used with some degree of caution to prevent overdoses and side effects.

Like almost any substance, if used appropriately and in moderation, all of caffeine's benefits can be experienced without any its side effects.

Ben Mayz

Hi there! I'm Ben, main author and chief editor at I have been obsessed with Strength Training and Fitness for 18 years now.
My passion for living a happy fit lifestyle is what made me realize that fitness is what I wanted for my future.
I went on to earn my Masters in Sports Training & Biomechanics.
My passion for Strength training & fitness and my love of helping others is what made me start Fitlifefanatics.
Here, myself, and a team of specialist aim to provide the most accurate, and actionable information possible in hopes to help foster the fitness community forward.
You can learn more about Fitlifefanatics on our About Page

johnathan Ritter, Pharm.D., Ph.D., MIMFA

Jonathan Ritter Pharm.D., Ph.D., MIMFA

Dr. Ritter has served as an expert scientific and medical reviewer, editor, writer, and consultant on topics ranging from natural substances, medications, and biomarkers to disease states and genetics.

With over 10 years of supplement-related experience, and having always been a proponent for natural substances and supplementation, he founded Eneuvos Bionutriceuticals in 2019, a company dedicated to creating next-generation, comprehensive nutritional dietary supplements.