Casein Protein: Benefits, Side Effects, Best Time to Take It & More

Casein Protein

(Casein Protein Powder)

Evidence: High
Possible Benefits: Very High
Safety: Reasonable

What is casein protein?

Casein protein is a protein powder extracted from milk. About 80% of total protein in milk is casein protein. It contains all 9 essential amino acids (lysine, histidine, threonine, methionine, tryptophan, phenylalanine, leucine, isoleucine, and valine) as well as many non-essential amino acids. Because there are so many individual amino acids in the protein powder, it can have a wide variety of effects on the body. This article is about the main benefits of casein protein, its potential side effects, the best time to take it, and more.

What does casein protein do for the body?

Casein protein contains 9 essential and many non-essential amino acids. Since there are so many components and all have their unique properties, casein protein can have a wide variety of pleasant and unpleasant effects.

Here is a list of the most important amino acids in the protein powder and how they can affect the body:

Leucine is the main activator of protein synthesis. It also helps activate the SIRT1 gene. This effect may be associated with slowing down aging but more research is needed to prove this.

Isoleucine has strong anti-catabolic effects, which means it slows down the breakdown of muscle mass, amongst other things in the body.

Valine shares similar properties to those of isoleucine and leucine but to a lesser extent. Its effects are not as pronounced as those of leucine and isoleucine.

Phenylalanine mainly plays a role in adrenergic and dopaminergic neurotransmission. The body converts L-phenylalanine into L-Tyrosine, which is then converted into L-DOPA. Decarboxylation of L-DOPA results in the synthesis of dopamine. Dopamine can then convert into adrenaline and noradrenaline through the dopamine-beta-hydroxylase enzyme.

Tryptophan can be converted into 5-HTP, which acts as a precursor to serotonin. Serotonin can then convert into melatonin, which is why people often take tryptophan to enhance sleep quality. The body can also make NAD+ molecules from tryptophan through a series of biological reactions. This pathway is most active in the morning when as much as 95% of tryptophan consumed is used directly for this purpose.

Lysine serves as a building block for many proteins in the body. This amino acid interacts with arginine in many ways and should be kept in balance unless you have a strong reason to off-balance them (such as herpes simplex). Taking too much of one can override the functions of the other. For example, high doses of lysine could hinder the ability of arginine to produce nitric oxide.

Histidine helps regulate and metabolize trace minerals, such as copper, zinc, iron, manganese, and more. This amino acid is used by the body to make specific hormones and metabolites that impact kidney function, the transmission of nerves, stomach secretions, and the immune system.

Threonine acts as a precursor to glycine. Among other roles, glycine works in the brain to reduce unwanted muscle contraction. This is why people sometimes take threonine to prevent muscle weakness or muscle spasms. Unfortunately, the amino acid doesn’t seem effective in this regard.

Methionine is a “methyl donor” and plays an important part in the methylation process. Because of this, it can speed up or help maintain many chemical reactions in the body. This amino acid acts as an antioxidant and helps protect damaged tissues.

Amino acid profile of casein protein

Contrary to popular belief, the amount of amino acids per gram of protein powder is similar among all protein powders. Animal-based protein powders generally have slightly more “protein” in them, but the difference is not nearly as big as some people claim.

Here is the amino acid content of 100 grams of casein protein and other protein powders:

	Leucine	Isoleucine	Valine	Lysine	Methionine	Phenylalanine	Threonine	Tryptophan	Histidine
Pea	5.9 g	2.7 g	3.7 g	5.3 g	1.3 g	3.0 g	3.4 g	0.9 g	2.0 g
Soy	8.4 g	4.2 g	4.2 g	6.6 g	1.8 g	3.4 g	5.5 g	1.1 g	2.0 g
Whey	8.4 g	4.6 g	4.6 g	8.0 g	2.2 g	3.9 g	6.3 g	1.3 g	2.3 g
Rice	5.3 g	2.8 g	3.4 g	4.8 g	1.4 g	2.7 g	3.1 g	0.9 g	1.8 g
Hemp	6.3 g	3.6 g	3.6 g	5.9 g	1.6 g	3.1 g	3.9 g	1.0 g	1.9 g
Sunflower	6.6 g	4.8 g	5.7 g	3.5 g	2.2 g	4.8 g	3.7 g	1.3 g	2.6 g
Casein	8.9 g	5.2 g	6.4 g	7.6 g	2.8 g	4.8 g	3.9 g	1.2 g	2.9 g
Pumpkin	7.2 g	4.6 g	5.1 g	3.6 g	1.9 g	5.1 g	2.8 g	4.4 g	2.2 g
Almond	6.9 g	3.4 g	3.9 g	2.8 g	0.8 g	5.4 g	3.0 g	0.9 g	2.7 g
Sesame	6.7 g	3.4 g	4.3 g	1.3 g	2.4 g	5.6 g	3.6 g	1.9 g	3.0 g
Egg	7.5 g	4.6 g	6.4 g	6.3 g	3.2 g	5.4 g	4.0 g	1.4 g	2.0 g

Whey vs. casein protein

Both whey and casein come from milk. They are the two main types of protein in milk, with whey making up about 20% of the protein and casein making up about 80%.

The main difference between whey and casein protein is the rate at which they are absorbed by the body.

Whey protein digests much faster and most people absorb it relatively well.

Casein protein, on the other hand, is absorbed more slowly by the body. It forms a gel-like substance in the stomach when mixed with water, which can make you feel fuller for longer. Casein is often taken before bed as a way to provide the body with a slow and steady supply of protein while you sleep.

Most people are intolerant to casein than to whey protein. Whey protein may also be slightly better when taken right before or after a workout.

Possible benefits

It is important to note that all of the potential benefits mentioned below are dose-dependent. Generally, the higher the dose, the more pronounced the effects are. However, most of these benefits do reach a plateau at a certain point. We will discuss the best dosing protocol later in this article.

Major benefits

Correcting a protein deficiency – The body needs at least some amount of protein to survive and function properly Not getting enough protein can lead to multiple health problems, some of which can become serious. Fortunately, a severe protein deficiency is relatively rare and shouldn’t happen unless you consume very low amounts of protein. In most cases, 0.36 grams/pound of body weight is sufficient to prevent a deficiency.
Improved muscle protein synthesis – This effect is mainly due to leucine. However, casein protein can improve muscle protein synthesis to a greater degree than leucine itself or even the BCAA trio (leucine, valine, and isoleucine).

Minor benefits

Reduced fatigue – Leucine, isoleucine, and leucine from casein protein or BCAA supplements can reduce both mental and physical fatigue after a workout when taken at doses of 10+ grams (combined). This benefit directly leads to other proven benefits, such as improved processing accuracy and reaction time.
Increased fat oxidation and weight loss – When combined with aerobic exercise (such as running, swimming, or riding a bike), the BCAA trio can aid the fat-burning effect by preserving glucose and helping the body utilize fat as a fuel source.
Improved aerobic exercise – This effect mainly applies to untrained or lightly trained individuals. Whether or not casein protein can increase cardio and time to exhaustion in athletes is not yet clear.
Improved carbohydrate absorption – BCAAs in casein protein promote insulin secretion from the pancreas and help the body utilize carbohydrates. Taking these amino acids before a carbohydrate-rich meal lowers the blood glucose spike from it.
Improved mood and well-being – Phenylalanine obtained from food or protein powders can improve well-being mainly for people with depression but also for non-depressed individuals. L-lysine supports emotional processing and healthy functional connectivity between the default mode network and emotion-related brain regions. This results in a calmer mood, improved well-being, and greater life satisfaction.
Improved social cognition – L-tryptophan has been shown by multiple studies to support prosocial interactions and increase people’s motivation to socialize. Those who consume more tryptophan also tend to be more empathetic, charitable, and altruistic.
Reduced appetite – Protein is generally more satiating than fat or carbohydrates. This is likely due to L-tryptophan. This amino acid is fairly effective at suppressing appetite and reducing food cravings. Those who tend to overeat as a coping mechanism tend to eat less when they take tryptophan.
Weight loss – This effect is due to multiple amino acids in casein protein. For example, histidine has a very mild but beneficial effect on weight loss in obese women with metabolic syndrome. It is somewhat effective at lowering insulin resistance and fat mass. L-tryptophan can also aid fat loss but the benefit is secondary to the reduction of appetite. If you take casein protein or isolated tryptophan but eat the same amount of calories, it will not have a notable impact on your weight.
Improved sleep quality – 5-HTP, a byproduct of tryptophan, helps synthesize serotonin, which can turn into melatonin at night. Those who take the supplement often have deeper and more restorative sleep. One study has also found that taking L-tryptophan reduces sleep terrors. If you take the supplement to improve sleep quality, take it 30-60 minutes before bedtime.
Improved exercise performance – Multiple studies support that L-tryptophan is at least mildly effective at increasing power output and delaying time to exertion during exercise sessions.
Reduced symptoms of depression – This effect is mostly due to phenylalanine and the main reason is an increase in dopamine levels. About 80% of those who take the supplement notice an improvement in their well-being. It is important to note that this improvement happens in the short term and likely won’t last once you stop taking the supplement.
Reduced stress – L-phenylalanine is somewhat effective at reducing acute stress when taken at low doses. Higher doses may actually increase stress response because of elevated adrenaline levels.
Treatment of vitiligo – Several studies show that L-phenylalanine may be helpful for people with vitiligo when paired with ultraviolet A light.
Reduced pain – D-Phenylalanine (DPA) slows the action of the enzymes carboxypeptidase A or endorphinase and enkephalinase, which can directly reduce pain. The research on this effect is rather limited.
Reduced symptoms of ADHD – People with ADHD have a general deficit in amino acid transport, absorption, or both. This often leads to significantly lower levels of phenylalanine and tyrosine in the body.
Reduced birth defects – Eating more methionine during pregnancy can lower the risk of neural tube birth defects.
Improved working memory – L-phenylalanine is a precursor to L-tyrosine, which has been shown to preserve working memory during acute stressors. These two amino acids do not seem to have a memory-boosting effect outside stressful situations.
Reduced muscle contractions in people with spinal spasticity – Taking 2 grams of L-threonine 3 times a day has been shown to reduce muscle contractions in people with spinal spasticity caused by spinal cord injury. Unfortunately, the benefit is only modest and there is not much evidence to support it.

Possible side effects

These side effects are dose-dependent. The risk for them increases (often linearly but sometimes exponentially) as you increase the dose. Some of the side effects only apply to very high doses.

Drowsiness
Stomach pain
Nausea
Vomiting
Diarrhea
Blurry vision
Casein or milk intolerance or allergy – Casein intolerance is very common and so is milk intolerance in general. In some individuals, casein protein may cause an allergic reaction, which can be more severe. If you don’t know how well you tolerate casein protein, start with a small dose and increase it gradually if you do not notice any side effects that would imply intolerance or allergy.
Excessive anabolism – Many amino acids in casein protein have anabolic effects. This can be great for multiple functions of the body but it can also speed up the aging process and the onset and growth of many diseases.
Increased levels of homocysteine – Even low doses of methionine can elevate homocysteine levels in the blood. This is especially the case for people with impaired methylation due to genetics or deficiency in certain nutrients, most notably B vitamins.
Worsened symptoms of ALS – L-threonine found in casein protein may worsen lung function in those suffering from ALS. This was observed when people took 2-4 grams of L-threonine daily for up to 12 months.
FIGLU – If you are deficient in vitamin B9 (folate), too much protein (histidine, specifically) can cause an unwanted chemical called formiminoglutamic acid (FIGLU) to build up in the body. People with a vitamin B9 deficiency should avoid histidine or high doses of casein protein.
Toxicity – While acute toxicity from any individual amino acid in casein protein is rare, taking high amounts of this protein powder could lead to chronic toxicity and cause multiple health problems. For example, high doses can cause increases in serum ammonia in the body. To prevent chronic toxicity, it is best to stay below 40 grams of casein protein a day unless you have a great reason to take more.
Contamination – Contaminated supplements are uncommon in the USA and other well-regulated countries. However, if you wish to buy products from China, India, or other countries without strict regulations, beware that the supplements may be contaminated. Either way, you need to choose the brand you order from wisely. It is highly recommended to check the certificates or read through some reviews for the specific product before you buy it. The FDA (Food and Drug Administration) has the power to regulate dietary supplements but can only do so after they have been on the market for a while. That’s because supplement companies are not obligated to announce to the FDA when releasing a new product on the market. The FDA has to discover the product and test it for potential impurities, which can take a lot of time. During that time, the supplement can be sold on the market even if it’s impure. Also, supplement companies can change their manufacturers without announcing it to the FDA.
Heavy metals – Protein powders in general tend to be somewhat high in heavy metals which requires some attention, especially if you already have high levels of heavy metals in the body.

Who should not take casein protein?

You should probably avoid taking the protein powder if you:

eat high amounts of protein from food (most whole foods contain at least some amount of each essential amino acid)
have casein or milk allergy or intolerance
experience a severe adverse reaction after taking the supplement
are deficient in folate (vitamin B9)
are on a supplement budget (there are cheaper protein powders that can be just as good if not better, such as soy protein)
have high blood pressure and-or take drugs for high blood pressure
suffer from schizophrenia
are inactive

Who will benefit the most?

You should consider taking the supplement if you:

consume very little protein (less than 0.3 grams/pound of body weight)
are on a vegetarian diet but don’t eat legumes
are muscular and work out a lot
wish to reduce appetite and food cravings
suffer from depression or generalized anxiety disorder
often experience uncontrolled muscle contractions
are an older person (older people need up to 2 times more protein than young adults for similar activations of muscle protein synthesis and to reduce age-related catabolic effects)

How much casein protein should you take?

The optimal protein intake is highly individual and can range anywhere from 0.36-1 gram of protein/pound of body weight, depending on your age, gender, activity levels, genes, goals, and more.

If you plan to get additional protein through a casein protein supplement, 20 grams appears to be the best daily target for most people. This amount should provide most of the benefits without meaningful side effects.

Some people may benefit from doses higher than 20 grams. These include older people, bodybuilders, very physically active individuals, and those on a low-protein diet.

Each essential amino acid in casein protein has an RDA (recommended daily allowance). The RDAs for all adult men and most adult women are:
14 mg/kg/day of histidine
19 mg/kg/day of isoleucine
42 mg/kg/day of leucine
38 mg/kg/day of lysine
19 mg/kg/day of methionine + cysteine
33 mg/kg/day of phenylalanine + tyrosine
20 mg/kg/day of threonine
5 mg/kg/day of tryptophan
24 mg/kg/day of valine

The RDAs for pregnant women are:
18 mg/kg/day of histidine
25 mg/kg/day of isoleucine
56 mg/kg/day of leucine
51 mg/kg/day of lysine
25 mg/kg/day of methionine + cysteine
44 mg/kg/day of phenylalanine + tyrosine
26 mg/kg/day of threonine
7 mg/kg/day of tryptophan
31 mg/kg/day of valine

The RDAs for lactating women are:
19 mg/kg/day of histidine
30 mg/kg/day of isoleucine
62 mg/kg/day of leucine
52 mg/kg/day of lysine
26 mg/kg/day of methionine + cysteine
51 mg/kg/day of phenylalanine + tyrosine
30 mg/kg/day of threonine
9 mg/kg/day of tryptophan
35 mg/kg/day of valine

Since these amino acids are found in almost every food, you probably already get sufficient amounts from food alone. About 0.36 grams of protein/pound of body weight should be enough to prevent a deficiency in all of these.

Each essential amino acid has a safety limit, whether it is well-established or not. To stay on the safe side, don’t take more than 50 grams of protein from protein powders daily unless you have a great reason to do so.

Food sources of protein

All essential amino acids are found in all foods containing dietary protein.

The amount of amino acids per gram of protein varies from food to food but a general rule of thumb is that the more protein you eat, the more amino acids you are getting from food.

The easiest way to find out exactly what amount of total protein and each amino acid you are getting from food is with Cronometer.com. This free app allows you to track all vitamins, minerals, and more.

Best time to take casein protein

All amino acids in casein protein powder are at least somewhat water-soluble, so you don’t have to take it with food to absorb it well. Taking a protein powder on empty stomach is generally better for the absorption of these amino acids because they do not compete for absorption with amino acids from food.

To maximize the benefits, take casein protein before or after a workout.

Whether you take the supplement in the morning or the evening doesn’t matter much. The supplement should not impact sleep quality in any negative way and may slightly improve it because of the calming effects of glycine, tryptophan, and other amino acids.

If you practice time-restricted eating, take the protein powder during your eating window to guarantee it won’t break your fast.

Unless it feels too impractical, spread the daily dose into 2+ smaller doses throughout the day.

Interactions

Carbohydrates
BCAAs in casein protein promote insulin secretion from the pancreas and help the body utilize glucose. Taking this amino acid before a carbohydrate-rich meal lowers the blood glucose spike from it and increases muscle protein synthesis.
Resveratrol
Both resveratrol and leucine can activate the SIRT1 gene and act synergistically in doing so when taken together. Whether or not this effect is of practical significance is not yet clear.
Vitamin B9
If you are deficient in vitamin B9 (folate), too much histidine can cause an unwanted chemical called formiminoglutamic acid (FIGLU) to build up in the body. People with a vitamin B9 deficiency should avoid the supplement.
TMG
Trimethylglycine (TMG) can greatly mitigate the side effects associated with methionine supplementation. TMG is also the most effective supplement we know of for lowering homocysteine levels.
Sedatives
Phenylalanine and tryptophan from the protein powder may increase the effects and side effects of sedatives.
SSRIs
Taking SSRIs together with high doses of L-tryptophan (whether it is isolated or from food and protein powders) may lead to serotonin syndrome. The same applies to some other groups of anti-depressants, such as SNRIs and tricyclic antidepressants (TCAs).

Which protein powder is the best?

Contrary to popular belief, all protein powders are roughly equal in their amino acid content per gram of protein.

While whey protein is the most popular type of protein powder, most people have at least a mild intolerance to it.

The same is the case for casein protein, where intolerance is even more common. In addition, these two forms are among the more expensive ones and don’t have many benefits over the cheaper ones, such as rice and soy proteins.

Since soy protein is usually the cheapest and most people digest it well, it is the best option if you tolerate soy well and are on a budget.

Protein concentrate vs. protein isolate

Protein concentrate and protein isolate are forms of protein derived from whole food sources and processed to remove non-protein components.

Protein concentrate typically contains around 70-80% protein and has a slightly higher fat and carbohydrate content.

It is often used in supplements because it has a more natural flavor and retains some of the beneficial components of the whole food source.

Protein isolate contains 90-95% protein and has a low fat and carbohydrate content. It is often used in supplements because it is very high in protein and has a more neutral flavor.

The benefits of these two forms are roughly equal but if you take the isolated form, you can get more protein from the same dose.

Where to buy casein protein

Amazon is the best option for ordering casein protein in most countries. They offer some very affordable products backed by many positive reviews. Also, you can choose from a wide range of brands without having to search through other markets on the internet.

Beware some brands display the dosage per serving instead of per pill or capsule. Therefore, you may accidentally buy something less potent than you intended. Do not fall for this marketing trick.

FAQ

You can take the protein powder daily and do not need to cycle it. However, it is certainly not a problem if you don’t take it every day. Not taking the supplement every once in a while could lead to better absorption. That is yet to be proven or disproven.

All of these options are fine. The two most important things to consider are the price and dosing. Powders are almost always the cheapest form. However, you may need a highly accurate scale to dose them correctly (preferably 0.001g). You can get one for as little as $20 from Amazon. Dosing the powders also takes some time that can add up over months or years. The disadvantage of capsules is that they often contain bovine gelatin, which rarely comes from an ethical source.

Yes. Most amino acids in casein protein absorb and digest well if you take them before falling asleep. The supplement should not impact sleep quality in any negative way and may even improve it because of amino acids like glycine and L-tryptophan.

Casein protein should not become harmful once it exceeds the expiration date but can become moldy or lose potency over time.

Keep the supplement in a cold, dark, and dry place, and it should remain just as potent for many months or even years.

While acute toxicity is extremely rare, too much protein in the system can cause some health problems over time, often related to speeding up the aging process due to excessive anabolism. It is best to stay below 50 grams a day to prevent these side effects.

You may need more of this amino acid if you:
– eat very little protein (less than 0.3 grams/pound of body weight)
– are on a plant-based diet and avoid legumes
– suffer from depression or anxiety
– are muscular and work out a lot
– are an older person (older people need up to 2 times more protein than young adults for similar activations of muscle protein synthesis and the anti-catabolic effects)

Most essential amino acids get metabolized within a day after you consume them.

If you take the supplement before a workout, you may notice a mild increase in power output. Another short-term effect you may notice almost immediately is an increase in well-being, mainly due to L-tryptophan and phenylalanine. In the long term, you need to take protein for a few weeks to begin noticing the benefits.

Unfortunately, casein protein is not vegan-friendly. However, there are vegan alternatives that can be just as good if not better. These include soy protein and pumpkin protein.

All essential amino acids are at least somewhat water-soluble, so you don’t have to them with food to absorb them well.

While low doses may not break a fast when taken close to your workout, higher doses certainly can. If you practice time-restricted eating, take casein protein during your eating window so it doesn’t break your fast.

References

Most of the information provided in this guide is supported by scientific research that can be found and verified in the PubMed medical library. We highly encourage you to use the library to verify anything said in this article. We excluded from consideration studies that are either confounded or have a high conflict of interest.

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