L-Serine

L-serine is a non-essential amino acid produced by the body and found in various foods. It is an isomer of D-serine and has benefits such as improved sleep quality, helping the central nervous system function, aiding creatine absorption, and promoting cerebral blood flow.

So, if L-serine has so many potential benefits, is there scientific evidence to support these claims? This article will take you through all of the research conducted to verify or dispute its potential benefits and whether it is safe to take.

What Is L-Serine?

L-serine is the L-enantiomer of serine and, therefore, one of two stereoisomers that mirror each other.

Serine comes in the form of L-serine and D-serine, with both being made up of the same atoms, but those atoms are arranged differently. L-serine can be consumed through diet and produced in the body, while D-serine can be made in the body from L-serine (1).

Serine is a non-essential amino acid that is present and functionally important in many proteins. The body can synthesize it. It plays a major role in the metabolism of fats, fatty acids, and cell membranes. It also affects muscle growth and plays a role in maintaining a healthy immune system. It is found at the active site of the serine protease enzyme class (1).

Furthermore, it plays a major role in the biosynthetic pathways for pyrimidine, purine, creatine, and porphyrin (1).

L Serine & D Serine

Serine molecules come in two forms: L-serine and D-serine. They are known as stereoisomers – they are isomers of each other. This means they consist of the same atoms, which are arranged differently.

Your body’s cells use L-serine to synthesize other amino acids like cysteine and tryptophan, and proteins like this are typically involved in many enzymatic and hormonal reactions within the body. When present in our neural tissues, L-serine becomes D-serine as it is triggered by the enzyme serine-racemase. D-serine fulfills critical functions such as supporting the brain and nervous system as a neurotransmitter (1).

Foods High In L-Serine

You can rely on your body to produce L-serine on its own, but it’s also possible to get it from your diet or oral supplements. These are a few of the foods that are high in L-serine:

• Eggs
• Soy protein
• Seaweed
• Spirulina
• Dairy
• Turkey
• Beef
• Seafood/shellfish
• Peanuts
• Almonds
• Seeds
• Chickpeas
• Lentils

What Are The Potential Benefits Of L-Serine?

There has been extensive research conducted over L-serine’s potential benefits, and some people claim that it could enhance brain function, improve sleep quality, protect the nervous system, and boost muscular endurance.

However, despite the research and information available, the evidence that backs these claims is not comprehensive enough to consider scientifically irrefutable. So, always consult with a medical practitioner before using L-serine and L-serine-derived products to ensure that it’s safe to use.

Helps Central Nervous System Diseases And Injuries

L-serine has been identified as an indispensable neurotrophic factor and precursor for neurotransmitters. And although it is a native amino supplement, the associated metabolic products have been demonstrated to be essential for cell proliferation and neuronal development, among other specific functions in the brain (2).

A growing body of evidence suggests that L-serine regulates the release of various cytokines in the brain under certain neurological conditions to recover cognitive function, improve cerebral blood flow, inhibit inflammation, promote remyelination, and exert other neuroprotective effects that neurological injuries have caused (2).

L-serine can also be an effective neuroprotective agent due to its broad spectrum of functions.

Research into long-term treatments with L-serine has demonstrated an increase in neurotrophic factors in the injured side of the brain, which promotes the proliferation of endogenous neural stem cells (NSCs) and the repair of neurological functions (2).

L-serine also regulates microglial polarization and promotes the repair of damaged white matter while reducing inflammation. It also releases neurotoxicity and inhibits the release of inflammatory agents by activating the glycine receptor. L-serine also activates potassium and calcium channels in an ischemic brain injury model (2).

As an endogenous amino acid, L-serine has been tested in a clinical trial, demonstrating that it’s a safe treatment after secondary treatment for repairing neurological function. Its neuroprotective effects are so compelling that human trials for the clinical use of L-serine are being strongly considered (2). However, further studies are needed to determine where and when the levels of L-serine change during disease progression.

Injuries to the central nervous system (CNS), such as cerebral ischemia, anoxia, stroke, and TBI, are common clinical-pathological phenomena that cause differing degrees of damage to the brain.

And in the cascade that follows most hypoxic-ischemic brain injuries, neurons and glial cells will fulfill the function of releasing many excitatory amino acids like glutamate while the uptake of them is reduced.

Therefore, the accumulation of glutamate in the extracellular space increases the excitatory amino acid concentration (2). This is related to the injury mechanism caused by intracellular calcium overload, free radical proliferation, and increased nitric oxide production.

As a neurotrophic actor, L-serine is an antagonist of the glycine receptor, a neurotransmitter receptor that inhibits hyperpolarization of membranes when activated. It, therefore, reduces excitable neurons, triggering a neuroprotective effect. L–serine is also the main source of nucleotides and deoxythymidine monophosphate, which major cell proliferation (2).

In addition to this, further research has found that L-serine treatment in Proximal Middle Cerebral Artery Occlusion (pMCAO) rats has reduced brain injury and facilitated neurorestorative (3). This is also partially associated with the proliferation of NSCs and micro vessels, along with the reconstruction of neurovascular units, which results in neuro repair.

L-serine’s benefits for endogenous NSC proliferation and microvascular proliferation allow it to effectively synthesize purine and pyrimidine and modulate the expression of endogenous nerve growth-related factors (3).

By activating glycine receptors, L-serine alleviates neuronal ecotoxicity, which is a secondary brain injury process. This reduces the activation of astrocytes and microglial cells and the secretion of proinflammatory cytokines while inhibiting neuronal apoptosis (4).

Therefore, the current evidence suggests that L-serine treatment can lead to the neuroprotection of brain tissue by reducing inflammatory responses. It has been demonstrated to recover neurological functions in mice following traumatic brain injuries (4).

Improve Quality Of Sleep

Findings from research into the effects of L-serine on human sleep have suggested it improves sleep initiation and nighttime awakening, which results in more sleep satisfaction when subjects wake up in the morning (5). Therefore, L-serine could be an effective treatment for people that struggle to sleep.

More research into L-serine’s effects on sleep demonstrated in chicks that received an injection of L-serine analogs, and its derivatives took on a sedative state, and it had hypnotic effects under an acute stressful condition, which doesn’t involve the hypothalamic-pituitary-adrenal axis. The study concluded that L-serine might effectively treat anxiety and sleeping disorders triggered by psychological stressors (6).

Mental Health

Data from another study suggests that bright light may elicit antidepressant-like effects via enhanced 5-HT signals and that L-serine could enhance those effects (7).

Assists With Creatine Absorption

L-serine is a prerequisite for the body to synthesize and absorb creatine – which supplies energy to the muscles and helps maintain healthy muscle functionality. Therefore, high levels of L-serine could also lead to more energy and muscle fiber development (8).

Promotes Cerebral Blood Flow

To supply your brain with oxygen- and nutrient-rich blood, you need good cerebral circulation, which also helps to reduce carbon dioxide and other waste products from your brain. Impaired circulation could lead to several serious health conditions (9).

Research suggests that L-serine has a neuroprotective effect by improving cerebral blood flow after cerebral ischemia (2).

Assists With Brain Function Memory

As the precursor for D-serine, L-serine is essential for brain function and helps to establish memories. Therefore, reduced activity in these receptors can be caused by producing fewer L-serine acolytes. This alters neuronal plasticity and memory capacity (10).

May Be Able To Help Treat Seizures

Serine deficiency can cause symptoms such as Congenital microcephaly, seizures, and severe psychomotor retardation; therefore, L-serine, along with glycine, could be an effective treatment for people who experience seizures. Research has demonstrated that L-serine and L-serine-derived metabolites play important roles in the CNS in subjects with serine deficiencies (11).

Another study of patients with two different serine synthesis defects found that L-serine treatment led to a reduction of seizures and an improvement of spasticity. However, it did fail to achieve any substantial neurocognitive improvement (12).

Therefore, we can deduce that Cerebrospinal fluid (CSF) and plasma serine levels should be measured in all severe microcephaly cases at birth as a screen for serine deficiency. Early treatment could significantly impact the outcome of this disease, and physicians may also diagnose reduced serine levels in fetal cord blood as early as 30 weeks into the pregnancy (13).

Alzheimer’s Disease

The neurological hallmarks of Alzheimer’s disease and another rare paralytic illness by residents of the Chamorro village in Guam are Neurofibrillary tangles (NFTs) and β-amyloid plaques. It was found that, in some of the Chamorro villagers, a quarter of the adults died from this disease. However, administering L-serine with l-BMAA led to a significant reduction in the density of NFTs.

The findings indicate that while chronic exposure to the toxin BMAA can trigger neurodegeneration, increasing L-serine in vulnerable individuals can reduce the associated risks (14).

Chronic Fatigue Syndrome

Some Chronic Fatigue Syndrome (CFS) symptoms include extreme tiredness, pain, and discomfort. And preliminary research has linked this to low blood levels of serine. Therefore, increasing serine levels could alleviate the symptoms of CFS (15).

Is L-Serine Safe?

WebMD states that serine is likely safe for most people who orally consume approximately 3.5-8 grams (0.12-0.28 ounces) of this promising amino acid (16).

However, no clinical studies have tested the safety of supplementing healthy adults’ diets with L-serine. A phase 1 clinical trial  found that doses of up to 15g (0.52oz) twice a day appear to be safe in patients with ALS. However, two of the 20 study participants presented gastrointestinal side effects and withdrew from the trial (17).

Therefore, you must consult with a medical professional before using L-serine supplements.

Conclusion

Retaining adequate levels of L-serine is critical for your general health because it is crucial for several bodily functions, such as manufacturing cysteine, tryptophan, and lipids. These are necessary for the enzymatic and hormonal reaction, while the isomer D-serine is required for brain and nervous system support.

L-serine also facilitates creatine production, which is important for bone and muscle growth. L-serine also aids in immunoglobins and antibodies that promote a healthy immune system. However, more scientific research is necessary to certify certain benefits, and none of the potential benefits have yet been scientifically proven.