L-Serine Additional Information
L-serine is a nonessential amino acid that is synthesized from other amino acids. L-serine plays an important role in cell proliferation and the production of proteins, DNA, and cell membranes. L-serine is the predominant source of one-carbon groups for the synthesis of purines, and the amino acids L-Tryptophan, L-Cystine, and Serotonin. (1,2,3,4,5) Although termed as “nonessential”, L-serine has long been recognized as a conditional essential amino acid as it cannot be synthesized in sufficient quantities to meet cellular demands. (1,2)
L-serine is currently classified as a Generally Regarded as Safe (GRAS) compound by the FDA. This is following trials on animals and clinical trials on humans that have investigated the therapeutic effects of L-serine. (1)
L-Serine vs. D-Serine
Serine exists as two isomers, L-serine or D-serine. Whereas L-serine is synthesized from other amino acids (such as glycine), D-serine is synthesized in the body from L-serine. This occurs in the glial cells which are support cells of the central nervous system and acts as one of L-serine’s mechanisms of action.
While L-serine plays a role in cell proliferation and the production of proteins, D-serine is a neurotransmitter that plays a central role in information processing and modulates synaptic plasticity and memory. D-serine is not commonly found as a supplement as it has poor absorption.
L-Serine Benefits
Several benefits of L-serine are in its production of other enzymes, phospholipids, neurotransmitters, and proteins and the benefits associated with them as well as its role in forming the five bases that make up DNA and RNA (1,8)
L-Serine produces the following compounds when taken as a supplemement: (1,4,9,10):
- Tryptophan - a biological precursor to several key compounds and proteins as well as a sleep aid.
- Glycine - an amino acid that is used as a building block of protein.
- L-Cystine - functions as an antioxidant and protects tissues against pollution and radiation.
- Serotonin - monoamine neurotransmitter that modulates cognition and contributes to feelings of well-being.
One key benefit of L-serine is that once in the body, it is synthesized into D-serine which has the added benefits of:
- Increases the speed of glutaminergic signaling which can enhance memory formation (19,20)
- Binds with agonist glutamate to activate NMDA receptors which applies antidepressant effects (21)
L-serine has also been shown to have the following benefits that will be discussed further in “L-Serine Research”:
- Improved sleep quality (4,9,15)
- Acts as a neuroprotectant (16)
- Enhanced mood (9)
- Cell membrane integrity (13,18)
How to Use L-Serine
L-serine for dietary supplementation is commonly found as a powder or powdered capsule. Although L-serine can be found in food sources, its typically in trace amounts and not sufficient. L-serine is water soluble and therefore can be taken without food. As L-serine has a beneficial effect on sleep through its mechanism of increasing levels of L-Tryptophan and Serotonin, it is recommended to be taken in the evening before bed.
L-Serine Dosage Guidelines
Standard L-serine dosages are normally between 500mg – 2,000mg daily. There have been reported dosages as high as 48g per day and it has shown to be safe in dosages as high as 30g per day. (14) It is important to note that higher doses lead to an increased risk of side effects.
Half Life and Duration of Effects
The half-life of L-serine has not been adequately studied to form a firm conclusion. One study noted that on average it took L-serine 14 minutes to take effect and the half life once converted to phosphatidylserine was an average of 8.2 hours. (25)
L-Serine Safety and Side Effects
L-serine is generally reported to be very safe. At dosages as high as 15 g, twice daily, were well-tolerated with no safety concerns. (24) As L-Serine hasn’t been studied much at higher doses, we don’t recommend exceeding our recommended dosage of 2000 mg per day.
Although L-serine is reported to be well tolerated, side effects have been reported at high dosages. Gastrointestinal issues including constipation, nausea, and diarrhea have been shown to occur. (23) These side effects are very unlikely to be experienced if using L-Serine at our recommended dosage of 2000 mg per day.
How L-Serine Works
L-serine has numerous mechanisms of actions that play different roles throughout the body:
DNA Production (1,8): There are five nucleobases that are the fundamental units of DNA and RNA. They are; adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U). L-serine plays a role in forming all five bases, with the interaction energy of serine and guanine being the highest, and with uracil being the lowest.
This was strengthened by an in vivo study on sheep where the foetal placenta produced glycine that was used in the foetal liver to produce L-serine. The hepatic serine production reflects the role of L-serine as a precursor to DNA and RNA.
Production of Tryptophan and Serotonin (4,9): Tryptophan is an α-amino acid that is used in the biosynthesis of proteins. As tryptophan is an essential amino acid, it is not synthesized in the human body and needs to be obtained through diet or supplementation.
Tryptophan functions as a biochemical precursor to several key compounds including;
- Serotonin: a neurotransmitter that affects mood, digestion, and sleep.
- Melatonin: a hormone that regulates sleep-wake cycles.
- Niacin: an organic compound that is an essential human nutrient.
Precursor to Other Amino Acids (1,10): Some biproducts of L-serine metabolism include the amino acids, cysteine and glycine. Both cysteine and glycine act as precursors for the synthesis of glutathione. There are numerous benefits associated with glutathione that include but are not limited to; aiding in the production of DNA, supporting immune function, and breaking down free radicals.
Conversion to D-Serine (7,11,12): L-serine converts to D-serine via the enzyme serine racemase. Serine racemase is found in neurons and glial cells, with the highest levels being found in glial cells. This is expressed highly in the forebrain.
Potentially through glutamate-receptor-interacting protein (GRIP), there is an activation of AMPA receptors which cause a 5-fold increase in D-serine. AMPA receptors are responsible for fast synaptic transmission in the central nervous system.
Phosphatidylserine Formation (13): L-serine is essential for the synthesis of phosphatidylserine. Phosphatidylserine consists of two fatty acids attached to the first and second carbon of glycerol and L-serine. Phosphatidylserine is vitally important for regulating which molecules can enter and leave cells through the cell membrane.
L-Serine Research
Improved Sleep Quality (4,9,15)
L-serine is used by the body to produce L-tryptophan which is a fundamental precursor for neurotransmitters in the brain that aid to regulate sleep. Low levels of tryptophan can cause disruptive sleep behaviors. Several studies have been aimed at the impact of L-serine on sleep quality via the mechanism of increasing tryptophan levels.
Two of these studies were randomized, double-blinded crossover studies. One study was aimed at individuals who had reported being dissatisfied with their sleep and were measured subjectively via the Ogri-Shirakawa-Azumi sleep rating scale. The second study was measured using a questionnaire along with objective parameters such as sleep initiation time, number of nighttime wakings, and hours of sleep.
Study 1 observed that individuals who were administered L-serine reported significantly improved sleep satisfaction compared to the placebo group. In study 2, subjective sleep quality was demonstrated to be higher than placebo via the sleep questionnaire while the objective factors tended to decrease. These factors all point to L-serine improving sleep quality.
Acts as a Neuroprotectant (16)
A group of rats had focal cerebral ischemia induced by the occlusion of the middle cerebral artery to examine the neuroprotective effects of L-serine. Once the occlusion occurred, rats were given either a dosage of L-serine or a placebo. The rats were measured via the neurological deficit score and brain infarct volume before and after injection of L-serine.
The treatment with L-serine both reduced the neurological deficit score and infarct volume. There was also an increase in cerebral blood flow in the cortex. This combination of effects leads to the thought that L-serine can aid as a neuroprotectant for the brain.
Enhanced Mood (9,22)
Within the body, L-serine is used to create the neurotransmitter, serotonin. While a shortage of serotonin has shown to cause symptoms of depression and anxiety, an increase in serotonin has shown to enhance mood.
One study aimed at observing the effects of a decrease in serotonin. Tryptophan is a necessary precursor to serotonin and acute tryptophan depletion (ATD) lowers central serotonin levels. Participants with ATD were tasked with viewing two morphed faces and were instructed to choose between the faces based on the intensity of the emotional expression. Individuals with lower levels of serotonin where shown to not accurately choose pictures that had a negative emotion. This is explained by a mood-induced bias driven by negative emotions.
Cell Membrane Integrity (13,18)
L-serine is essential to the synthesis of phosphatidylserine as it binds to two fatty acids to form the phospholipid. One of the key role’s phosphatidylserine plays in the body is that of maintaining cell membrane integrity and regulation.
By forming phosphatidylserine, L-serine is able to assist in cell signaling during cell death to act as a signal for macrophages to engulf cells.
L-Serine FAQ
What foods are high in L-serine?
While traditionally known as being a non-essential amino acid, L-serine is more commonly thought of as a conditionally essential as the body produces some, but not enough. Although L-serine is found in food sources, its normally in trace amounts which is why supplementation is recommended. Food sources that do contain the highest levels of L-serine are; eggs, milk, cheese, seeds, pork, beef, or chicken.
Is L-serine safe?
Even though it is not regulated by the FDA, it is labeled as Generally Regarded as Safe (GRAS) and has shown to be very well tolerated even at extremely high doses.
What is L-serine made from?
L-serine is synthesized from amino acids, primarily glycine.
Is L-serine the same as phosphatidylserine?
L-serine is not the same as phosphatidylserine, but it is used to synthesize phosphatidylserine.
Does L-serine need to be taken with food?
L-serine is water soluble and therefore does not need to be taken with food.
Can I take L-serine if pregnant?
Like all dietary supplements, you should consult with a physician prior to supplementation of L-serine. However, it is not recommended to take if pregnant.
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