Everything You Need to Know About the Safety and Benefits of Phospholipids (Part 2)

The Components of Phosphatidylserine

Phospholipids, including phosphatidylserine, might sound like scary toxic chemicals, but every single cell in your body requires phospholipids to function. Phospholipids are present in nearly all food too, so you eat them daily!

Thank you for joining us as we learn more about the components of phosphatidylserine and continue our exciting blog series about the safety and benefits of phospholipids!

Review from Part 1 – What is Phosphatidylserine?

Phosphatidylserine (PS) is an essential phospholipid that contains one amino acid (serine) and two fatty acids. Up to 10% of the phospholipid content present in the phospholipid bilayer in your cell membranes is phosphatidylserine, and PS is necessary for proper cell-to-cell recognition and communication. PS regulates cell receptors, enzymes, ion channels, and signaling molecules to directly affect the function of your hormones and intellectual abilities.¹

Here is a picture of the phospholipid bilayer with parallel layers of phospholipids:

PS is most concentrated in the cells of your organs with high metabolic demand, including your brain, heart, lungs, liver, and skeletal muscles. PS is also a dietary nutrient found in high concentrations in fish, meat, and egg yolks. Smaller amounts of PS are present in many other common foods.¹

Results of numerous clinical trials indicate that supplemental PS provides metabolic support for cognitive functions that tend to decline with age, including memory, learning, language skills, concentration, reasoning, and decision-making. Indeed, phosphatidylserine is the only dietary supplement that boasts FDA-qualified health claims for reducing the risk of cognitive dysfunction and dementia.¹

According to research, phosphatidylserine supplements also appear to effectively support adaptability to stress, moderate the perception of stress load, and enhance actual performance and recovery in a variety of stressful situations, including intensive exercise training and demanding mental and emotional tasks.¹

The structure of phosphatidylserine consists of a phosphorylated serine head group, a glycerol backbone, and two fatty acid tails.¹

The Components of Phosphatidylserine

What is serine?

Serine is an amino acid that was first discovered in 1865 by Emil Cramer. Amino acids are the building blocks of proteins. Serine is present in many foods, and good sources of serine include eggs, fish, milk, nuts, and soybeans.²

What does serine do?

In addition to being required for protein synthesis in the body, research indicates serine supplementation could offer benefits for certain health conditions. Clinical trials, animal studies, and population-based cohort studies suggest serine could be beneficial for those who have amyotrophic lateral sclerosis (ALS), insulin resistance, diabetes, neuropathy, steatohepatitis (fatty liver disease), a liver injury, or a circadian rhythm disorder.²

Is serine safe?

Serine is well-tolerated at suggested doses, but an exceptionally large dose of serine can cause side effects. So, always take serine in the amount recommended on the supplement label or by your trusted healthcare provider. The U.S. Food and Drug Administration (FDA) has classified L-serine as “generally recognized as safe (GRAS)” for human consumption when it does not exceed 8.4% of total dietary protein.³

What is phosphorylated serine?

Phosphorylated serine is also known as phosphoserine.¹ Phosphoserine is produced by adding a phosphate group to the amino acid serine; therefore, phosphoserine is an amino acid that has been phosphorylated.⁴

Phosphorylation is essential for normal cellular processes, and the process of phosphorylation occurs by transferring a phosphate group from ATP (adenosine triphosphate), your cellular energy molecule, to an amino acid or protein. Approximately 30% of all proteins in your body are phosphorylated.⁵

Threonine, serine, and tyrosine are the most commonly phosphorylated amino acids.⁵ Phosphoserine plays a fundamental role in the synthesis of neurotransmitters and is embedded within the structural matrix of all cell membranes.⁶

What does phosphorylated serine do?

Phosphoserine improves the function of neurons and amplifies mental aptitude. Furthermore, phosphoserine has been shown to enhance immune function and could improve mood in some people.⁶

A clinical study assessed the effect of supplemental phosphoserine on patients with primary open-angle glaucoma, which is the most common form of glaucoma. The study determined that, compared to placebo, supplementation with phosphoserine induced a significant clinical improvement in patients with glaucoma. The results suggest phosphoserine offers a potential neuroprotective, or “nerve-protecting,” effect.⁶

Research also suggests phosphoserine could support bone health when applied directly to bone cells. A study that assessed the effects of phosphoserine on bone cells found that collagen mRNA expression was notably increased in the phosphoserine-treated groups compared with the untreated group.⁷

According to the researchers, this increased collagen mRNA expression suggests that phosphoserine treatment promotes bone cell maturation. The phosphoserine also enhanced bone mineralization, so; phosphoserine may strengthen bones. When applied to the injured bone in an animal model, treatment with phosphoserine significantly increased new bone formation.⁷ Today, phosphoserine is added to bone cement blends used for osteopathic and dental applications due to its significant and beneficial effects on bone health.^7,8

Is phosphorylated serine safe?

Phosphorylated serine (phosphoserine) is a natural product. According to safety data, pure phosphoserine can act as a lung, skin, or eye irritant if inhaled or applied topically.⁹ When taken as a supplement at suggested doses, phosphorylated serine tends to be well-tolerated and has been administered to humans in clinical trials with no reports of adverse effects.⁶

What is glycerol, and is it safe?

Glycerol is a molecule that is naturally present in the human body and acts as the backbone structure in phosphatidylserine since the phosphoserine head group and fatty acid tails are attached to the glycerol.^1,10

Intravenous infusion and ingestion of glycerol have been used in research settings and as a treatment for certain health conditions for over 60 years. Since 1987, a technique called glycerol hyper-hydration has been used to increase the amount of water stored in an athlete’s body, thereby providing the benefit of improved exercise tolerance in hot environments.¹⁰

Glycerol is also known as glycerin, which is “generally recognized as safe (GRAS)” as a food additive by the FDA.^11,12

What are fatty acids, and are they safe?

Fatty acids are the building blocks required to produce lipids, which are fats. Fatty acids have many diverse functions in cells, which include supporting the structure of cell membranes, storing and supplying energy, and acting as signaling molecules.¹³ Most of us have heard of “omega-3 fatty acids,” which are incorporated into phosphatidylserine as the fatty acid tails of the phospholipid.¹⁴

Increased intake of omega-3 fatty acids via diet or supplementation does increase their incorporation into the phospholipids in your cell membranes. Omega-3 fatty acids are less inflammatory than other types of fatty acids, and their incorporation into phospholipids is one way your daily diet can directly affect your cellular health and overall well-being.¹⁴

Fatty acids are found in healthy whole foods like fish and walnuts and are essential and safe when consumed in optimal amounts.

We hope you will join us for part 3 of our blog series about phospholipids, where we will thoroughly discuss the components of phosphatidylethanolamine!

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References:

1. Canar, L. Phosphatidylserine: Cell Membrane Nutrient for Stress Resiliency. Chronobiology. 2016;1(23):1-2. Accessed July 22, 2022.
2. Jiang J, Li B, He W, et al. Dietary serine supplementation: Friend or foe?. Curr Opin Pharmacol. 2021;61:12-20. doi:10.1016/j.coph.2021.08.011
3. Serine. (2021, November 28). Retrieved July 18, 2022, from https://naturalmedicines.therapeuticresearch.com/.
4. Kurmangaliyev YZ, Goland A, Gelfand MS. Evolutionary patterns of phosphorylated serines. Biol Direct. 2011;6:8. doi:10.1186/1745-6150-6-8
5. Singh V, Ram M, Kumar R, et al. Phosphorylation: Implications in Cancer. Protein J. 2017;36(1):1-6. doi:10.1007/s10930-017-9696-z
6. Scalinci SZ, Lugaresi M, Scorolli L, et al. Neuroprotective role of phosphoserine in primary open-angle glaucoma patients. Eur Rev Med Pharmacol Sci. 2020;24(19):9780-9786. doi:10.26355/eurrev_202010_23186
7. Park JW, Kim YJ, Jang JH, et al. MC3T3-E1 cell differentiation and in vivo bone formation induced by phosphoserine. Biotechnol Lett. 2011;33(7):1473-1480. doi:10.1007/s10529-011-0565-0
8. Kesseli FP, Lauer CS, Baker I, et al. Identification of a calcium phosphoserine coordination network in an adhesive organo-apatitic bone cement system. Acta Biomater. 2020;105:280-289. doi:10.1016/j.actbio.2020.01.007
9. Phosphoserine. National Center for Biotechnology Information. PubChem Compound Database. Published July 15, 2022. Accessed July 21, 2022.
10. Robergs RA, Griffin SE. Glycerol. Biochemistry, pharmacokinetics and clinical and practical applications. Sports Med. 1998;26(3):145-167. doi:10.2165/00007256-199826030-00002
11. The Federal Register. Federal Register. Published August 18, 2022. Accessed August 23, 2022.
12. Becker LC, Bergfeld WF, Belsito DV, et al. Safety Assessment of Glycerin as Used in Cosmetics. Int J Toxicol. 2019;38(3_suppl):6S-22S. doi:10.1177/1091581819883820
13. de Carvalho CCCR, Caramujo MJ. The Various Roles of Fatty Acids. Molecules. 2018;23(10):2583. doi:10.3390/molecules23102583
14. Senkal M, Geier B, Hannemann M, et al. Supplementation of omega-3 fatty acids in parenteral nutrition beneficially alters phospholipid fatty acid pattern. JPEN J Parenter Enteral Nutr. 2007;31(1):12-17. doi:10.1177/014860710703100112