Most of the brain consists of fat. Signals traveling away from the cell body require insulation to prevent short circuiting. This targeted delivery is made possible by a type of fat, myelin, which coats the projecting axons. Fatty matter constitutes the membranes around each neuron forming a convoluted surface that sends out dendritic processes allowing for synaptic communication.
Chemical signals are passed across synapses when lipid packages containing small molecules fuse with the membranes of the transmitting cell, dumping molecules into the synaptic gap such as acetylcholine, dopamine and norepinephrine which then activate the receiving cell. The ability of these lipid packages to fuse and reform critically depends on the constituent fatty content of the membranes. The fatty content must be exactly right for proper fusion and reformation of these synaptic vesicles. Too waxy or too liquid prevents proper function.
The fats contained in neuronal membranes also serve as a source of either inflammatory precursors or anti-inflammatory agents; arachidonic acid constitutes the former, while docosahexaenoic acid (DHA) promotes resolution of inflammation. If this yin and yang is out of balance, the brain may become enraged with an inflammatory overdrive. DHA is also a natural antioxidant that can neutralize toxic agents that are created by haphazard mitochondrial fuel production.
We must understand a bit more about membrane structure to picture how fats actually exist in the brain. We all know that the liquid form of a fat, in the form of an oil, does not mix with water. Oil hates water, it is “hydrophobic.” Soap on the other hand can mix with oil or water because it is a molecule that has a hydrophilic head that loves water and a lipophilic tail that loves oil. The purpose of membranes is to create a biological wall that separates extracellular water and intracellular water so that the body can compartmentalize different activities – the same way that the walls in your house separate the bathroom from the kitchen; the solution is to use what is called a glycerol phospholipid which looks like a 3-fingered hand with the thumb being the hydrophilic phosphate head and the pinky and ring fingers being the lipophilic tails.
The 2 hydrophobic tails intermingle with each other on the interior of the membrane and hydrophilic heads happily interfacing with the water containing spaces on each side. The middle attachment point, the ring finger or R2, is where your body stores most of your essential polyunsaturated fatty acids, like arachidonic acid or DHA. When the arachidonic acid is released by an enzyme, phospholipase, we are off to the inflammatory races. When there is more DHA, inflammation may be subdued. The head group, the thumb or R3, position contains the hydrophilic phosphate group and the anchor lipophilic tail, the pinky finger or R1 position contains a saturated or monounsaturated fatty acid or fatty alcohol (called a plasmalogen). Plasmalogens are the master regulator of membrane structures and fluidity. Their unique vinyl ether bond drastically changes the phospholipid three dimensional configuration and promotes exactly the degree of membrane fluidity that is required for the fusing of synaptic vesicles, thereby facilitating information processing in the normal brain.
Most of the materials that your body uses to make membranes are abundant in our food supply – except plasmalogens. Their unique vinyl ether bond gets oxidized and destroyed by your stomach acids. Accordingly, virtually all of the plasmalogens in your body are made in your body. Certain diseases and getting old can reduce your body’s ability to make all of the plasmalogens that your body needs. Low plasmalogen levels are linked to many diseases, including Alzheimer’s and dementia. Later, we will discuss how plasmalogens are important to brain health and how they may protect from aging related memory impairment or even progression of Alzheimer’s disease.
Dietary intake of animal fats including beef, pork, lamb and dairy products will provide a large quantity of arachidonic acid which then becomes a component of triglycerides stored in adipose tissue and in cell membranes. Even a low animal fat diet does not protect against adipose deposition because any excess of calories gets turned into body fat. Animals make arachidonic acid, an omega 6 fatty acid and so do humans. The inflammatory profile of these deposits may activate immune cells, spreading these influences throughout the body, including, the brain. DHA and EPA are both omega 3 fatty acids, so named for the desaturated carbon to carbon bond at the number three location from the hydrophobic end of the molecule. As previously noted, DHA (and to some extent EPA) are likely to balance out the inflammatory nature of arachidonic acid. Interestingly, the same part of your body that is responsible for making plasmalogens is also responsible for making DHA and EPA, so low plasmalogens and low DHA often go hand in hand. Although dietary sources of DHA and EPA are readily available, unfortunately, DHA and EPA supplements are poorly absorbed. Large doses above 2 grams per day are required to achieve apparent clinical benefit or even to show potential delivery to the brain. Doses above 3 grams per day may cause bleeding. Even at lower doses, diarrhea, belching, bloating, and bruising may occur.
This year, an exciting new development has occurred in both plasmalogen and omega-3 science. Researchers at Prodrome Sciences have developed a natural plasmalogen precursor that does not get oxidized in the stomach and which has DHA pre-packaged at the R2 position so that it can be directly incorporated into membranes. This new omega-3 formulation is available as a dietary supplement, so no prescription is needed.
In addition, blood testing services are available so that plasmalogen and other membrane phospholipid DHA levels can be measured before and after supplementation.
This absorbable plasmalogen precursor with DHA allows for eventual replenishment of brain membranes required for optimizing synaptic connections, reducing oxidative stress and resolving inflammation. Such a precursor may be used to correct the plasmalogen deficiency that has been observed with the form of dementia seen with Alzheimer’s disease. It is anticipated that early deployment of plasmalogen supplementation efforts may minimize progressive deterioration in middle aged and older folks who begin to show mild memory loss and word finding difficulties characteristic of mild cognitive impairment.
Clinical studies are now ongoing to determine proper dosing, tolerability, improvement in biochemical markers and possible improvements in cognitive function.
Click here to learn more about The Regenesis Project and Prodrome Sciences’ clinical trial on ProdomeNeuro Plasmalogen supplement.
Click here to contact The Regenesis Project about enrollment in this or other clinical trials
-Sheldon Jordan MD and Dayan Goodenowe PhD