L-Serine Unflavored by California Gold Nutrition

POSSIBLY EFFECTIVE

• Schizophrenia. Meta-analyses of small clinical studies suggest that oral D-serine, taken with standard antipsychotic therapy, may improve positive and negative symptoms in patients with schizophrenia. Details: Observational research has found that patients with schizophrenia have lower serum D-serine levels when compared with healthy controls (102201). Results from several small clinical trials assessing the impact of oral D-serine supplements on symptoms of schizophrenia are mixed (102202,102208,102214,102215,102216,102217,102237). However, meta-analyses of these and other small clinical studies in patients with schizophrenia show that taking D-serine as adjunct to antipsychotic therapy modestly improves negative symptoms when compared with placebo (102201,102214,102224). Some analyses have also found an improvement in positive symptoms (102201). Doses of D-serine assessed in clinical studies include 30 mg/kg daily for 4-12 weeks (102202,102208,102215), 60-120 mg/kg daily for 4 weeks (102215), and 2 grams daily for 6-16 weeks (102214,102216,102217,102237). Limited research shows that serine supplementation alone is inferior to antipsychotic treatment. A small clinical study in patients with treatment-resistant schizophrenia shows that taking D-serine 3 grams daily for 10 weeks is less effective for improving symptoms than olanzapine 30 mg (102203).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). It is unclear if oral L-serine is beneficial in patients with ALS. Details: Observational research in patients with ALS has found that taking L-serine 0.5-15 grams twice daily for 4 months is associated with a dose-dependent reduction in the rate of disease progression when compared with historical controls (102200).
• Alzheimer disease. It is unclear if oral serine is beneficial for the prevention or treatment of Alzheimer disease. Details: A small observational study in a group of patients with Alzheimer disease or mild cognitive impairment has found that increased blood levels of D-serine are associated with improved cognition, especially improved word recall, orientation, comprehension, and word-finding difficulty (102221). However, not all research agrees. Another small observational study in patients with Alzheimer disease found no correlation between levels of D-serine in cerebrospinal fluid and Alzheimer disease or level of cognitive function (102198). While clinical trials on the use of serine alone for improving cognitive function in patients with Alzheimer disease are lacking, serine has been evaluated in combination with other ingredients for this purpose. A small clinical study in patients with Alzheimer disease shows that taking a combination of L-serine 12.35 grams, N-acetyl cysteine 2.55 grams, nicotinamide riboside 1 gram, and L-carnitine tartrate 3.73 grams once daily for 4 weeks then twice daily for 8 weeks improves cognitive function, as measured using the ADAS-Cog score, in patients with greater baseline cognitive impairment when compared with placebo. However, taking this combination product did not improve cognitive function in patients with lower cognitive impairment at baseline (110623). It is unclear if these effects are due to serine, other ingredients, or the combination.
• Back pain. Oral L-serine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy adults with chronic low back pain and knee pain that is primarily neuropathic in nature shows that taking L-serine 594 mg with eicosapentaenoic acid (EPA) 149 mg daily for 8 weeks decreases back pain scores by 50% at week 8, compared with a 30% reduction in those taking placebo. However, there was no difference between groups at 4 weeks, and improvements were not maintained 4 weeks after treatment discontinuation (105831). It is unclear if these effects are due to serine, EPA, or the combination.
• Circadian rhythm sleep disorders. It is unclear if oral serine is beneficial in patients with circadian rhythm sleep disorders. Details: A small clinical study in healthy adults shows that taking L-serine 3 grams at bedtime daily for 2 weeks does not alter sleep habits, including bedtime, wake time, and time in bed, when compared with placebo. However, dim light melatonin onset, used as a marker of the circadian phase, was delayed in the placebo group, but not in the L-serine group, suggesting that L-serine may attenuate circadian phase delay (111267). The validity of these findings is limited by the small study size and short duration. Further, it is unclear if these findings can be generalized to patients with circadian rhythm sleep disorders.
• Cognitive function. Small clinical studies suggest that a single dose of oral D-serine may improve some, but not all, measures of cognitive function in adults. Details: A small clinical study in healthy adults shows that taking a single dose of D-serine 2.1 grams improves attention, vigilance, and verbal memory, but not visual memory, when compared with placebo (102219). Another small clinical study in healthy older adults shows that taking a single dose of D-serine 30 mg/kg improves spatial memory, learning, and problem solving, but does not affect executive function, working memory, or visual attention, when compared with placebo (102197). These studies are limited by small sample size and short duration. Serine has also been evaluated in combination with other ingredients for this purpose. A small clinical study in healthy adults with fatigue shows that taking serine, alanine, glutamate, aspartate, and tyrosine daily for 4 weeks improves measures of cognitive function including attention, spatial cognition, orientation, motivation, and time management when compared with placebo (111249). It is unclear if these effects are due to serine, other ingredients, or the combination.
• Depression. It is unclear if oral serine is beneficial in patients with depression. Details: A small observational study in patients with major depressive disorder has found that lower concentrations of D-serine in the cerebrospinal fluid are associated with greater depression severity. However, when cerebrospinal fluid levels of L-serine or D-serine were compared between healthy controls and patients with major depressive disorder, there was no significant between-group difference (102211).
• Fatigue. Oral serine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy adults with fatigue shows that taking serine, alanine, glutamate, aspartate, and tyrosine daily for 4 weeks does not improve subjective or objective measures of fatigue when compared with placebo (111249).
• Hereditary motor and sensory neuropathy. It is unclear if oral L-serine is beneficial in patients with hereditary motor and sensory neuropathy. Details: A very small clinical study in patients with hereditary sensory autonomic neuropathy type I (HSAN1) shows that taking L-serine 400 mg/kg daily for one year modestly reduces neuropathy severity when compared with placebo (102204).
• Inflammatory bowel disease (IBD). Although there has been interest in using oral serine for IBD, there is insufficient reliable information about the clinical effects of serine for this purpose.
• Insomnia. It is unclear if oral L-serine is beneficial in patients with insomnia. Details: A small clinical study in healthy patients dissatisfied with their sleep shows that taking L-serine 3 grams 30 minutes before going to bed seems to improve falling asleep, staying asleep, and subjective sleep quality when compared with placebo (102212). It is uncertain if patients with insomnia would also have the same benefits from L-serine.
• Knee pain. Oral L-serine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy adults with knee pain and chronic low back pain that is primarily neuropathic in nature shows that taking L-serine 594 mg with eicosapentaenoic acid (EPA) 149 mg daily for 8 weeks decreases knee pain scores by 36% and 43% at weeks 4 and 8, respectively, compared with changes of 24% and 29%, respectively, in those taking placebo. At 4 weeks after treatment discontinuation, pain reductions were maintained in both groups (105831). It is unclear if these effects are due to serine, EPA, or the combination.
• Muscle fatigue. Oral serine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy male volunteers shows that taking serine 200 mg, arginine 3600 mg, and valine 2200 mg daily for 14 days reduces fatigue and perceived exertion after 120 minutes on a cycle ergometer when compared with placebo (102234). It is unclear if these findings are due to serine, other ingredients, or the combination.
• Parkinson disease. It is unclear if oral D-serine is beneficial in patients with Parkinson disease. Details: A small clinical study in patients with Parkinson disease shows that taking D-serine 30 mg/kg daily for 6 weeks modestly improves involuntary movements and behavioral symptoms when compared with placebo (102206).
• Post-traumatic stress disorder (PTSD). It is unclear if oral D-serine is beneficial in patients with PTSD. Details: A small clinical study in patients with PTSD shows that taking D-serine 30 mg/kg daily for 6 weeks improves symptoms of anxiety and depression when compared with placebo (102209).
• Tourette syndrome. It is unclear if oral D-serine is beneficial in children with Tourette syndrome. Details: A very small clinical study in children 8-17 years of age with Tourette syndrome shows that taking D-serine up to 30 mg/kg daily for 8 weeks does not improve symptoms when compared with placebo (102218). This study is limited by a small sample size and insufficient power to detect differences between groups. More evidence is needed to rate serine for these uses.

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LIKELY SAFE ...when L-serine is used orally in food amounts. Average dietary consumption of L-serine from combined food and supplemental sources ranges from 3.5-8 grams daily (91405).

POSSIBLY SAFE ...when used orally in medicinal amounts. D-serine 30 mg/kg (about 2 grams) orally daily for 6-16 weeks or 60 mg/kg (about 4 grams) daily for 4 weeks has been used with apparent safety (102202,102206,102214,102215,102237). L-serine up to 400 mg/kg (about 25 grams) daily for up to 1 year has been used with apparent safety (102204,102220,108550).

POSSIBLY UNSAFE ...when used orally in large doses. L-serine in doses greater than 400 mg/kg (about 25 grams) daily has caused reversible side effects including nausea, vomiting, nystagmus, and seizures (102204). D-serine 120 mg/kg (about 8 grams) or more daily might increase the risk of nephrotoxicity (102215).

PREGNANCY AND LACTATION:
Insufficient reliable information available. Animal research in lactating mice shows that dietary L-serine transfers to milk and increases free L-serine while decreasing glutamic acid, L-alanine, D-alanine, and taurine levels in milk. However, this does not affect serine levels in the offspring (102228). It is unknown what effect supplemental serine may have in humans. Avoid using in amounts greater than those found in food.

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General ...Orally, L-serine and D-serine seem to be well tolerated in medicinal doses. Side effects appear to be dose-dependent.
Most Common Adverse Effects:
Orally: Gastrointestinal distress, including abdominal pain, bloating, dyspepsia, loss of appetite, and nausea.
Serious Adverse Effects (Rare):
Orally: Seizures with high doses of L-serine.

Gastrointestinal ...Orally, D-serine 120 mg/kg (about 8 grams) daily has been reported to cause gastrointestinal distress (102215). L-serine 5-30 grams daily has been reported to cause abdominal pain, dyspepsia, bloating, nausea, and loss of appetite (102204,102220).

Genitourinary ...Orally, D-serine 120 mg/kg (about 8 grams) daily for 4 weeks has been reported to cause proteinuria without glycosuria or creatine elevation. Proteinuria resolved completely after discontinuation of serine (102215).

Hepatic ...Orally, D-serine 120 mg/kg (about 8 grams) daily has been reported to cause asymptomatic transaminitis which resolved after discontinuation of serine (102215).

Immunologic ...Orally, in one very small, exploratory study, patients taking L-serine 400 mg/kg (about 25 grams) daily for one year had a higher rate of localized infections than those taking placebo (102204). Whether ingestion of L-serine caused or increased the risk of these infections is unknown.

Neurologic/CNS ...Orally, D-serine 120 mg/kg (about 8 grams) daily has been reported to cause insomnia after a single dose (102215). Taking L-serine in doses greater than 400 mg/kg (about 25 grams) can cause reversible nystagmus and seizures (102204).

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