L-Serine: Benefits, Side Effects, Best Time to Take It & More

L-Serine

(Serine)

Evidence: High
Possible Benefits: High
Safety: High

What is L-serine?

L-serine is a non-essential amino acid that can be synthesized in the body from glycine. As a supplement, it is often used for improving focus, cognition, and well-being. This article is about the main benefits of L-serine, its potential side effects, the best time to take it, and more.

What does L-serine do for the body?

Since serine is a non-essential amino acid, you do not need to consume it to survive. It can be synthesized from glycine.

L-serine plays a critical role in protein synthesis and intracellular metabolism, and it’s also involved in the functioning of RNA, DNA, immune function, and muscle formation.

Some of the L-serine converts to D-serine in the body. D-serine enhances NMDA receptor (NMDAR) function by inhibiting glycine uptake. This can result in promising anti-schizophrenic effects and cognitive enhancement.

Possible benefits

All of the potential benefits mentioned below are dose-dependent. Generally, the higher the dose, the more pronounced the effects are. However, they do reach a plateau at a certain point. We will discuss the best dosing protocol later in this article.

Major benefits

Improved cognition – L-serine supplements are associated with an improvement in many markers of cognition, including memory, learning capacities, attention, mental flexibility, number processing, calculation, and more. Supplementation can support acetylcholine release, monoamine oxidase B (MAO-B), brain glucose metabolism, and increase BDNF (brain-derived neurotrophic factor).
Reduced symptoms of schizophrenia – L-serine can be about as effective as glycine and sarcosine for reducing the symptoms of schizophrenia. It is not as reliable as sarcosine as many people don’t respond to L-serine supplements positively. On the other hand, L-serine is much more practical than glycine for this purpose because glycine can only reduce symptoms of schizophrenia when taken at extremely high doses (800+ mg/kg/d). This dose seems too impractical and may not be safe to take in the long term.

Minor benefits

Increased exercise performance – L-serine supports resistance to exhaustion and healthy stress responses to exercise.
Reduced anxiety – A moderate-high dose can lower stress and anxiety to at least some degree.
Improved well-being – At least one study has shown that serine supplements can reduce the intensity of sad feelings and supports healthy stress response.
Reduced symptoms of Parkinson’s disease – While more research is necessary to prove this effect, at least one study shows that D-serine can alleviate some symptoms of Parkinson’s disease. This effect likely applies to L-serine as well.

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.

Amino acid imbalance – Essential and non-essential amino acids should be kept in balance as they act synergistically in many ways. Too much of one amino acid can sometimes cause side effects if there isn’t enough of another amino acid. For example, this principle applies to glycine and methionine, lysine and arginine, and the BCAA trio. There are many other proven and unproven examples. Food or a protein powder is usually a better choice for getting enough amino acids unless you have a specific goal in mind targeted by a particular amino acid/s.
Toxicity – While acute toxicity has never been reported, taking high amounts of L-serine could lead to chronic toxicity and cause some health problems. To prevent chronic toxicity, it is best to stay below 3 grams 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.

Who should not take L-serine?

You should probably avoid taking the supplement if you:

get enough serine from food
experience a severe adverse reaction after taking the amino acid
are on a tight supplement budget (since there are more cost-effective supplements on the market for most people)

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)
suffer from schizophrenia

How much L-serine should you take?

Since this amino acid can be found in food or synthesized in the body, you may already get sufficient amounts without taking it as a supplement. About 0.36 grams of protein/pound of body weight should generally be enough to prevent any symptom deficiency.

If you plan to take L-serine as a supplement, 500-1000 mg appears to be the best daily target for most people. This amount should provide most of the benefits without meaningful side effects.

Schizophrenics may benefit from doses higher than 1 gram/day. The benefits may not plateau even beyond 3 grams/day.

The upper safety limit for L-serine is not well-established. To stay on the safe side, don’t take more than 3 grams daily unless you have a great reason to do so. Higher amounts may cause problems if you take the supplement for a prolonged period.

Food sources of serine

Serine is found in all whole foods that contain dietary protein.

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

The easiest way to find out exactly how much serine or other amino acids 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 L-serine

Like most other amino acids, L-serine is water-soluble, so you don’t have to take it with food to absorb it well. Taking the supplement with food is better if it causes stomach upset when you take it on an empty stomach.

To maximize the benefits, take L-serine in the morning or before a cognitively demanding task.

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

Interactions

Ginkgo biloba
The two supplements act synergistically for improving memory.
DHA
The combination is effective for improving memory and cognitive health.
Other amino acids
Essential and non-essential amino acids should be kept in balance as they act synergistically in many ways. Too much of one amino acid can sometimes cause side effects if there isn’t enough of another amino acid. For example, this principle applies to glycine and methionine, lysine and arginine, and the BCAA trio. There are many other proven and unproven examples. Food or a protein powder is usually a better choice for getting enough amino acids unless you have a specific goal in mind targeted by a particular amino acid/s.

Where to buy L-serine

Amazon is the best option for ordering L-serine supplements 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 amino acid daily and do not need to cycle it. However, it is certainly not a problem if you don’t take it daily. 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.

While L-serine absorbs and gets digested well if you take it before falling asleep, it is better to take the amino acid early in the day or before a cognitively demanding task.

This amino acid should not become harmful once it exceeds the expiration date but can 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 toxicity is rare, too much L-serine in the system can cause some health problems, often related to causing an imbalance in other amino acids. It is best to stay below 3 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)
– suffer from schizophrenia

The half-life of L-serine in the body is about 1.5 hours. This amino acid stays in your system for about half a day after you consume it.

In the long term, you need to take the supplement for about 2-4 weeks to begin noticing the benefits.

You can easily find vegan-friendly L-serine pills and powders but always check the label to be sure. If you buy the amino acid in a capsulated form, beware that the capsules often contain animal-based gelatin. Instead, find a brand that puts its products into cellulose capsules.

Like most other amino acids, L-serine is water-soluble, so you don’t have to take it with food to absorb it well.

Unless you take very high doses at once, L-serine should not break your fast. If you practice time-restricted eating, take this amino acid 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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