Elsevier

Nutrition

Volume 31, Issue 6, June 2015, Pages 781-786
Nutrition

Review
Phosphatidylserine and the human brain

https://doi.org/10.1016/j.nut.2014.10.014Get rights and content

Abstract

Objective

The aim of this study was to assess the roles and importance of phosphatidylserine (PS), an endogenous phospholipid and dietary nutrient, in human brain biochemistry, physiology, and function.

Methods

A scientific literature search was conducted on MEDLINE for relevant articles regarding PS and the human brain published before June 2014. Additional publications were identified from references provided in original papers; 127 articles were selected for inclusion in this review.

Results

A large body of scientific evidence describes the interactions among PS, cognitive activity, cognitive aging, and retention of cognitive functioning ability.

Conclusion

Phosphatidylserine is required for healthy nerve cell membranes and myelin. Aging of the human brain is associated with biochemical alterations and structural deterioration that impair neurotransmission. Exogenous PS (300–800 mg/d) is absorbed efficiently in humans, crosses the blood–brain barrier, and safely slows, halts, or reverses biochemical alterations and structural deterioration in nerve cells. It supports human cognitive functions, including the formation of short-term memory, the consolidation of long-term memory, the ability to create new memories, the ability to retrieve memories, the ability to learn and recall information, the ability to focus attention and concentrate, the ability to reason and solve problems, language skills, and the ability to communicate. It also supports locomotor functions, especially rapid reactions and reflexes.

Introduction

Phosphatidylserine (PS) is the major acidic phospholipid in human membranes and constitutes 2% to 20% of the total phospholipid mass of adult human plasma and intracellular membranes [1], [2], [3]. Within the healthy human brain, myelin is enriched in PS [4], [5] and the PS content of gray matter doubles from birth to age 80 y [4]. Throughout the human body, PS is a structural component of endoplasmic reticulum, nuclear envelopes, Golgi apparati, inner (cytosolic) leaflets of plasma membranes, outer mitochondrial membranes, and myelin [1], [2], [3], [4], [5], [6], [7], [8], [9].

About 20% to 30% of the PS in human gray matter is in the form of 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphoserine [4], [10], [11], [12], [13]. The docosahexaenoic acid (DHA) content of neuronal PS is of functional importance [12]; in the cortex of the brain, a reduction in the DHA content of PS is associated with the progression of mild cognitive impairment to Alzheimer's disease [14]. Consequently, the incorporation of PS into human membranes is sensitive to the availability of both PS and DHA [4], [10], [11]. Additionally, fatty-acid recycling at the sn-1 and sn-2 positions of PS is frequent, rapid and energy-consuming, allowing co-accumulation of DHA and PS [10], [11], [15] and facilitating DHA enrichment of PS molecules within membranes [11].

Section snippets

Phosphatidylserine synthesis and incorporation into membranes

Most PS that is synthesized de novo, including that synthesized within the central nervous system, results from the PS synthase 1- (PSS1-) catalyzed substitution of serine for choline on PS within mitochondria-associated membrane (MAM) domains of the endoplasmic reticulum (ER) [13], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25]. Some newly synthesized PS is transported from the ER to the inner (cytosolic) leaflet of the plasma membrane [1], where thermodynamic barriers minimize its

Phosphatidylserine and neurotransmission

The incorporation of PS into neuronal cell membranes influences the metabolism of the neurotransmitters acetylcholine (ACh), norepinephrine, serotonin, and dopamine [63], [64], [65]. Adequate amounts of DHA-enriched PS are required for the fusion of intraneuronal secretory granules with the presynaptic membrane, the subsequent release of neurotransmitter molecules into the synaptic cleft during the intracellular transmission of action potentials and proper postsynaptic neurotransmitter-receptor

Aging and deterioration of the human brain

Aging of the human brain is associated with loss of neurons, dendritic atrophy, loss of synaptic connections, decreased synaptic density, decreased synthesis of ACh and other neurotransmitters, abnormal neuronal membrane lipid composition (especially decreased membrane PS content and increased membrane cholesterol content), and reduced sensitivity of postsynaptic membranes to ACh [63], [64], [75], [76], [77], [78], [79], [80], [81]. A decrease in the ratio of PS to cholesterol within neuronal

Phosphatidylserine in the deteriorating brain

In intact aged rats, ingested PS increases interneuronal communication by increasing the fluidity of cell membranes [59], [63], [64], eliminates the typical age-dependent decreases in stimulus-evoked ACh release, cholinergic functioning, and cognitive problem solving [82], [83], [84], and stimulates enhanced performance on tasks that test learning ability and short-term memory [82], [85], [86], [87]. These beneficial outcomes have been associated with rapid incorporation of supplemental PS into

Safety of dietary supplementation with phosphatidylserine

In addition to the absence of reports in the published scientific literature of adverse reactions concerning oral supplementation with PS, the safety of dietary supplementation with PS has been demonstrated in many human clinical trials [57], [63], [65], [93], [94], [95], [96], [97], [98], [99], [100], [101], [102], [103], [104], [105], [106], [107], [108], [109], [110], [111], [112], [119], [120], [121], [122], [123], [124], [125], [126], [127] and has been documented in detail by several

Conclusions

Phosphatidylserine is required for healthy nerve cell membranes and myelin. Oral PS is absorbed efficiently in humans and crosses the blood–brain barrier following its absorption into the bloodstream, increasing the supply of PS to the brain. Increasing the supply of PS increases the incorporation of it into neuronal cell membranes. The incorporation of adequate amounts of PS within nerve cell membranes is required for efficient neurotransmission throughout the human nervous system.

Aging of the

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    Support for this project was received from Progressive Laboratories, Inc., Irving, Texas.

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