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Arachidonic Acid

07.30.2020


Arachidonic Acid




ARA is an integral constituent of biological cell membrane, conferring it with fluidity and flexibility, so necessary for the function of all cells, especially in nervous system, skeletal muscle, and immune system. Arachidonic acid is obtained from food or by desaturation and chain elongation of the plant-rich essential fatty acid, linoleic acid.

ARA is obtained from food such as poultry, animal organs and meat, fish, seafood, and eggs and is incorporated in phospholipids in the cells' cytosol, adjacent to the endoplasmic reticulum membrane that is studded with the proteins necessary for phospholipid synthesis and their allocation to the diverse biological membranes. Of note, glycerophospholipids are composed of a glycerol backbone esterified to two hydrophobic fatty acids tails at sn-(stereospecifically numbered) 1 and 2 position and a hydrophilic head-group at sn-3. The membrane and cytosolic phospholipids of mammalian cells and tissues are rich in ARA, usually localized in the glycerol backbone sn-2 position. Platelets, mononuclear cells, neutrophils, liver, brain and muscle have up to 25% phospholipid fatty acids as ARA. Arachidonic acid participates in the Lands cycle, a membrane phospholipids' reacylation/deacylation cycle, which serves to keep the concentration of free ARA in cells at a very low level. Since ARA is a fundamental constituent of cell structure, it will particularly be needed for during development and growth and upon severe or widespread cell damage and injury.

Arachidonic acid physiological functions:

Cell membrane fluidity

Arachidonic acid four cis double bonds endow it with mobility and flexibility conferring flexibility, fluidity and selective permeability to membranes. ARA control of membrane fluidity influences the function of specific membrane proteins involved in cellular signaling and plays a fundamental role in maintenance of cell and organelle integrity and vascular permeability. These properties might explain ARA critical role in neuron function, brain synaptic plasticity, and long-term potentiation in the hippocampus.

Ion channels

Non-esterified, free ARA affects neuronal excitability and synaptic transmission via acting on most voltage-gated ion (Nav, Kv, Cav, Clv, proton Hv) channels, responsible for regulating the electric activity of excitable tissues, such as the brain, heart and muscles. Ion channels are large families of integral membrane proteins that form a selective pore for ions to cross the lipid bilayer, via undergoing conformational changes in response to alteration in the cell transmembrane electrical potential. These channels gate passage of specific ions and thus control the propagation of nerve impulses, muscle contraction, and hormone secretion.

Receptors and enzymes

Exogenous or endogenously produced ARA was discovered to greatly enhance the functional activity of ligand-gated ion channels, namely the γ-amino butyric acid receptor (GABA-R) located on the neuronal membrane, via modulating the GABA-R interaction characteristics with its ligands . Free ARA exposure essentially led to inhibiting the muscle and neuronal nicotinic acetylcholine receptor (nAChR), an integral membrane protein deeply embedded in the postsynaptic region, with two agonist binding sites and a central ion pore. The receptor inhibition resulted from ARA displacing lipids from their sites in the plasma membrane and direct acting as antagonist at the PUFA-protein interface.

PUFA, especially ARA, are documented activators of membrane-associated, magnesium-dependent, neutral sphingomyelinases. ARA was recently documented as activator of Schistosoma mansoni and S. haematobium tegument-associated neutral sphingomyelinase in a dose-dependent manner, eventually leading to their attrition in vitro and in vivo.

A most needed nutritional supplement:

Newborns

Polyunsaturated fatty acids (PUFAs), especially ARA, affect the function of numerous ion channels, the activity of various enzymes and are implicated in cell apoptosis, necrosis and death, events of critical importance during embryogenesis, thereby have significant physiological and pharmacological impact on the health of newborns. ARA and docosahexaenoic acid (DHA, 22:6 ω3) are important components of human milk but are lacking in cow milk and most commercial infant formula in developing countries. Due to its importance in development especially of the central nervous system and retina, the Food and Agricultural Organization (FAO)/World Health Organization (WHO) recommended that infant formula, unless specifically added, should be supplemented with ARA. Decreased postnatal ARA and DHA blood levels in premature infants were found to be associated with neonatal morbidities, while adding DHA and ARA to preterm-infant formulas led to improved visual acuity, visual attention and cognitive development. The ARA levels in human milk and ARA requirements, essentiality in pre- and neonatal life and during development, and inclusion in infant formulas have recently been reviewed challenged and discussed.

Neurological disorders

ARA does not only influence cell membrane fluidity and the activity of ion channels, especially in the brain, it constitutes together with DHA 20% of the human brain dry weight, concentrated in the neurons outer membrane and in the myelin sheath. Additionally, positron emission tomography was used to show that the brain of human healthy volunteers consumes ARA at a rate of 17.8 mg/d. Accordingly, ARA was recommended for management of central nervous system, visual and auditory damage in preterm infants via supporting neurovascular membrane integrity. Children with autism had lower levels of blood PUFA, especially ARA, than normal children, and showed notable improvement after dietary PUFA intake. In the elderly too, ARA supplementation improved cognitive functions, perhaps via increasing the proliferation of neural stem/progenitor cells or newborn neurons and general hippocampal neurogenesis. The charged ARA displayed beneficial effects on epileptic seizures and cardiac arrhythmia by electrostatically affecting the kV channel's voltage sensor, thus regulating neuronal excitability.

Exercise

In skeletal muscles, ARA has been found to make up to 15–17% of total fatty acids, thus explaining why ARA supplementation affected body composition, muscle function and power output in strength-training individuals. It is also possible that ARA modulates neuromuscular signaling through its incorporation into cell membranes, and/or increases neurotransmitter firing from nerve cells.

The Clinical Trials of ARA:

Effects of different arachidonic acid supplementation on psychomotor development in very preterm infants; a randomized controlled trial

Background & aims:

Nutritional supplementation with polyunsaturated fatty acids is important in preterm infants neurodevelopment, but it is not known if the omega-6/omega-3 ratio affects this process. This study was designed to determine the effects of a balanced contribution of arachidonic acid in very preterm newborns fed with formula milk.

Methods:

This was a randomized trial, in which newborns <1500g and/or <32 weeks gestational age were assigned to one of two groups, based on the milk formula they would receive during the first year of life. Initially, 60 newborns entered the study, but ultimately, group A was composed of 24 newborns, who were given formula milk with an ω-6/ω-3 ratio of 2/1, and Group B was composed of 21 newborns, given formula milk with an ω-6/ω-3 ratio of 1/1. The infants were followed up for two years: growth, visual-evoked potentials, brainstem auditory-evoked potentials, and plasma fatty acids were periodically measured, and psychomotor development was assessed using the Brunet Lézine scale at 24 months corrected age. A control group, for comparison of Brunet Lézine score, was made up of 25 newborns from the SEN1500 project, who were fed exclusively with breast milk.

Results:

At 12 months, arachidonic acid values were significantly higher in group A than in group B (6.95 ± 1.55 % vs. 4.55 ± 0.78 %), as were polyunsaturated fatty acids (41.02 ± 2.09 % vs. 38.08 ± 2.32 %) achieved a higher average. Group A achieved a higher average Brunet Lézine score at 24 months than group B (99.9 ± 9 vs. 90.8 ± 11, p =0.028). The Brunet Lézine results from group A were compared with the control group results, with very similar scores registered between the two groups (99.9 ± 9 vs. 100.5 ± 7). There were no significant differences in growth or evoked potentials between the two formula groups.

Conclusions:

Very preterm infants who received formula with an ω-6/ω-3 ratio of 2/1 had higher blood levels of essential fatty acids during the first year of life, and better psychomotor development, compared with very preterm newborns who consumed formula with an ω-6/ω-3 of 1/1. Therefore, formula milk with an arachidonic acid quantity double that of docosahexaenoic acid should be considered for feeding very preterm infants.

Kangcare Arachidonic Acid Specifications:

OliginTM Arachidonic Acid Powder 10%

It is powder form product, made from nutritional oil derived from the marine alga, mortierella alpina, a rich source of Arachidonic Acid (ARA). Tocopherols and ascorbyl palmitate, as antioxidants, are added to provide stability. It is contain Triglyceride(Contain ARA), Starch, Maltodextrin, Sucrose and others.

OliginTM Arachidonic Acid Oil 40%

Nutritional oil derived from the marine alga, mortierella alpina, a rich source of Arachidonic Acid (ARA).Tocopherols and ascorbyl palmitate, as antioxidants, are added to provide stability. It is contain ARA Oil, Tocopherols and Ascorbyl Palmitate (as antioxidants).

The attentions for storage:

OliginTM Arachidonic Acid Powder 10% is 12 months under room temperature conditions inclosed container, while 24 months if stored under refrigerated conditions (0~10°C). It should be used in one week after opened.

OliginTM Arachidonic Acid Oil 40% is six months in cool condition(4℃). The shelf life of the product is one month under room temperature(25℃). It should be used in one week after opened.




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