Serine is a nonessential amino acid that plays a role in synthesis of DNA and RNA, and is also involved in modulation of the NMDA receptor. While there are two main isomers of serine (D-serine and L-serine), humans metabolize the D-serine isomer better. Serine can be obtained from natural sources from the diet (mainly in meat, dairy and wheat based foods) or from supplementation (the most common way is via glycine supplementation). D-serine has been found to improve cognitive function with respect to attention, executive function and mood in many human subject studies.
Pharmacology of Serine
Serine is an amino acid that contains a hydroxymethyl group side chain. It is a nonessential amino acid synthesized in the human body. It is heavily involved in the biosynthesis of purines and pyrimidines, which are essential building blocks of DNA and RNA. Furthermore, D-serine is a co-agonist with glycine for the NMDA receptor. There are two isomers (D-serine and L-serine) of serine, however typically for supplementation humans metabolize L-serine. Upon ingestion, L-serine is racemized into D-serine.
Figure 1. Serine is an amino acid that contains a side chain in the form of hydroxymethyl group.
Furthermore, L-serine can be added to a glyercol lipid molecule to form phosphatidylserine. Phosphatidylserine plays a role in many bodily functions including nerve cell repair and structural integrity, improvement in nutrient absorption, and improvements in cognition with respect to memory, stress levels and mood.
L-serine vs. D-serine
It is important to note that there are two isomers of serine: L-serine and D-serine. L-serine is convereted to D-serine in the the glial cells (the support cells of the nervous system). Typically, L-serine is synthesized from other amino acids such as glycine, or from other protein metabolites.
L-serine typically sold as a dietary supplement, while D-serine is not. L-serine is classified as a Generally Regarded as Safe (GRAS) compound by the FDA, while D-serine is not. Despite the fact that D-serine is not a GRAS compound, there is a growing body of literature that suggests it is beneficial for boosting cognition with respect to attention, memory and mood.
Serine and Mental Performance
Serine has been found to improve memory and executive function in healthy adults. Most of the studies out there focus on the effects of D-serine.
In a study on 50 adults (mean age 70) it was found that D-serine administration at a dose of 30 mg/kg was found to improve performance on the Groton Maze Learning Test, when compared to placebo. Specifically, the participants undergoing D-serine administration exhibited 2 fewer legal errors compared to placebo (p = 0.03).
In a study on 35 adults aged 23-29, it was found that a daily administration of 2.1 g of D-serine was effective for improving attention as measured by the Continuous Performance Test–Identical Pairs (CPT-IP) test, and improving memory as measured by the Rey Auditory Verbal Learning Test (RAVLT). Specifically, there was a 10% improvement in performance (10% more items recalled) on the RAVLT (p <0.05; n=35). Furthermore, there was a 10% increase in performance on the CPT-IP test (p < 0.025; n=35). Finally, there was a 20% decrease in the Visual Analog Scale scores for “Sadness” with D-serine consumption, compared to placebo (p<0.01, n=35). These findings are consistent with current medical understanding, as serine deficiency has been known to be associated with depression and deficits in attention.
Figure 2. D-serine administration has been shown to increase scores on the Continuous Performance Test–Identical Pairs (CPT-IP) test, a test for working memory. Furthermore, D-serine administration led to a 10% improvement in performance on the Rey Auditory Verbal Learning Test (RAVLT) compared to placebo.
Furthermore, it was found that D-serine administration resulted in more significant decreases in scores for anxiety and sadness compared to placebo (Figure 3).
Figure 3. In a study of 35 young adults, it was found that administration of D-serine resulted in improvements in mood with respect to anxiety and sadness. Specifically, significant decreases in anxiety and sadness were seen after administration.
Sources of Serine
L-serine is naturally produced by glial cells of the nervous system. Glial cells are the support cells of the nervous system that aid in the potentiation of action potentials between neurons. L-serine is converted to D-serine in the glial cells via the enzyme serine racemetase.
For consumption, serine can be found in natural foods as well as supplements. In terms of food, the best sources of serine are in foods high in protein. Sources include egg whites (6g serine per 100g), white fish (2.3g serine per 100g), dairy products (1.5g serine per 100g in cheese), legumes (peanuts, almonds, sesame seeds, lentils, flax seed have approximately 1g serine per 100g), and wheat products (1g serine per 100g).
Regarding dietary supplementation, L-serine supplements can be consumed. Furthermore, serine can be found in soy protein powder (4.5g serine per 100g). Typically, L-serine is converted to D-serine in the body. D-serine in turn carries effects on cognition and metabolism.