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Serina

Also known as: L-Serine, D-Serine, Serine, 2-amino-3-hydroxypropanoic acid

Overview

Serine is a non-essential amino acid that exists in two forms: L-serine and D-serine. L-serine is a proteinogenic amino acid, meaning it is incorporated into proteins, and is synthesized endogenously and found in dietary proteins. D-serine, produced from L-serine, acts as a neuromodulator in the brain. Serine supplements, particularly D-serine, have been investigated for neurological and psychiatric conditions such as schizophrenia, cognitive function, and neurodegenerative diseases. D-serine acts as a co-agonist at the NMDA receptor, modulating glutamatergic neurotransmission. Research on serine is moderately mature, with several clinical trials and meta-analyses, especially regarding schizophrenia, but evidence is still emerging and not definitive for many indications. The quality of available evidence is strongest for schizophrenia symptom improvement with D-serine supplementation combined with antipsychotics.

Benefits

The most evidence-based benefit of D-serine is in patients with schizophrenia, where supplementation alongside antipsychotic therapy has shown improvements in both negative and positive symptoms. A meta-analysis of 20 studies demonstrated that D-serine supplementation, when combined with antipsychotics, significantly improved negative symptoms (SMD = -0.319, 95% CI = -0.576 to -0.061) and positive symptoms (SMD = -0.211, 95% CI = -0.413 to -0.009). L-serine supplementation may have neuroprotective effects by reducing neurotoxic metabolite production, potentially benefiting neurodegenerative conditions, though clinical evidence is limited. Effect sizes for symptom improvement in schizophrenia are small to moderate but statistically significant, indicating a potentially meaningful adjunctive benefit. Clinical trials typically assess effects over weeks, with benefits observed within this timeframe.

How it works

D-serine primarily works by acting as a co-agonist at the glycine site of the N-methyl-D-aspartate receptor (NMDAR) in the brain. This enhances receptor activation and glutamatergic neurotransmission, which plays a crucial role in synaptic plasticity, learning, memory, and psychiatric symptomatology. By modulating central nervous system excitatory signaling, D-serine influences various brain functions. Oral D-serine is absorbed and crosses the blood-brain barrier, allowing it to directly impact NMDAR activity. Further research is needed to fully characterize its bioavailability and optimal dosing.

Side effects

Serine supplementation is generally considered safe at moderate doses. L-serine is commonly consumed in the diet, and D-serine supplementation at doses up to 2-4 grams daily for up to 4 weeks has been used safely in clinical trials. The most common side effect is gastrointestinal upset, such as bloating and stomach discomfort. Uncommon side effects are not well documented, but higher doses may increase the risk of adverse effects. Rarely, very high doses of D-serine (above 8 grams daily) may increase the risk of seizures. D-serine may interact with antipsychotics, although it is often used adjunctively; caution is advised for individuals prone to seizures. Contraindications are not well-established, but caution is advised for individuals with seizure disorders or kidney impairment. Limited data are available for pregnant or breastfeeding women, children, and the elderly.

Dosage

Clinical studies suggest that 2 grams daily of D-serine may be effective as adjunctive therapy in schizophrenia. Optimal dosage ranges are 2-4 grams daily for D-serine, while L-serine doses up to 25 grams daily have been used safely in some studies. D-serine doses above 8 grams daily may increase the risk of adverse effects, and L-serine doses above 25 grams daily are considered possibly unsafe. Serine is typically administered orally, and divided doses may improve tolerability. D-serine supplements are preferred for neurological effects, while L-serine is more common in general amino acid supplementation. Food intake may affect absorption, and no specific cofactors are required.

FAQs

Is serine supplementation safe?

Yes, at moderate doses, but high doses may cause gastrointestinal discomfort or seizures. Follow recommended dosage guidelines.

Does serine cure schizophrenia?

No, D-serine is an adjunct that may improve symptoms when combined with antipsychotics, not a standalone cure.

When should serine be taken?

As directed by clinical protocols; typically daily dosing with meals to reduce stomach upset.

How soon are benefits seen?

Improvements in schizophrenia symptoms may be observed within weeks of consistent D-serine supplementation.

Is there a difference between L-serine and D-serine?

Yes, D-serine modulates brain NMDA receptors, while L-serine is primarily a proteinogenic amino acid.

Research Sources

https://pubmed.ncbi.nlm.nih.gov/27717827/ – This meta-analysis included 20 studies and found significantly lower serum D-serine levels in schizophrenia patients compared to controls. D-serine supplementation, when used as an adjunct to antipsychotics, improved both positive and negative symptoms, with small to moderate effect sizes. The study highlights the potential of D-serine as an adjunctive treatment for schizophrenia.
https://www.webmd.com/vitamins/ai/ingredientmono-1615/serine – WebMD summarizes clinical trial data supporting the safety and efficacy of D-serine at 2-4 grams daily for up to 4 weeks as an adjunct therapy for schizophrenia. It notes potential side effects and dose limits, while also highlighting the lack of strong evidence for other indications. This source provides a general overview of serine supplementation based on available research.
https://pubmed.ncbi.nlm.nih.gov/29508691/ – This systematic review supports the role of amino acid supplementation in improving muscle mass and function. While not specific to serine, it indirectly supports the safety and utility of amino acids like serine in broader nutritional contexts. The review provides evidence for the benefits of amino acid supplementation in overall health and well-being.
https://www.mdpi.com/2072-6643/13/9/3054 – This study investigates the effects of L-serine supplementation on metabolic health and muscle function. It provides insights into the potential benefits of L-serine in improving metabolic parameters and muscle performance. The research contributes to the understanding of L-serine's role in overall health and well-being.
https://ous-research.no/home/pc/Group+members/12039 – This is a research group page that may provide additional information on serine research. It could offer insights into ongoing studies and the researchers involved in serine-related projects. The page may contain links to publications and other relevant resources.