Docosahexaenoic acid (DHA) is Essential and Critical for Brain Development and Maintenance

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Docosahexaenoic acid (DHA) in Evolution

The life forms of the first 2.5 billion years after the origin of life on Earth were anaerobic, single celled systems.  The Cambrian fossil record represents an abrupt change in the fossil record from the previous 2.5 billion years. 

About 500 to 600 million years ago, air-breathing life forms became thermodynamically possible and intracellular detail not seen in previous life forms began to appear.  In fact, 32 phyla appeared at this time as evidenced in the Cambria record, also known as the Cambrian explosion.

Image result for cambrian explosion

The fossil records from the Cambria explosion has shown changes from the previous 2.5 billion years with the appearance of intracellular compartmentalization provided by cell membranes which constitute of lipids (fatty acids). These lipids formed the membranes of cells that housed the transporters, ion channels, signaling, and cell recognition systems.

As such, lipids made intracellular specialization possible, and have been integral to specialization and multicellular evolution. Prior to the Cambria explosion, lipids did not play a role in the evolution of life. 

In particular, it was marine lipids that were the drivers in the Cambrian explosion.

Image result for cambrian explosion marine lipids

Art from What Sparked the Cambrian Explosion? – Scientific American

A certain marine lipid called Docosahexaenoic acid (DHA) played a key and significant role in human evolution and specifically the development of the brain.  DHA provided the membrane backbone for the emergence of new photoreceptors that converted photons into electricity, laying the foundation for the evolution of other signalling systems, the nervous system and the brain. 

Docosahexaenoic acid (DHA)

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, and retina. It can be synthesized from alpha-linolenic acid or obtained directly from maternal milk (breast milk), fish oil, or algae oil. 

There is also clear evidence from molecular biology that DHA is a determinant of neuronal migration, neurogenesis and the expression of several genes involved in brain growth and function. That same process was essential to the ultimate cerebral expansion in human evolution.  1 

DHA provided the basic membrane backbone of new photoreceptors that converted photons into electricity.  This is why experts state that DHA must have played a role in the evolution of the human brain. The biological science supports the view that a powerful evolutionary advantage for cerebral expansion would have come from a regular, food-rich source of DHA and associated trace elements.  2

Modern humans have evolved with a staple source of preformed docosahexaenoic acid (DHA) in the diet. An important turning point in human evolution was the discovery of high-quality, easily digested nutrients from coastal seafood and inland freshwater sources.  3

Docosahexaenoic acid (DHA) as an Essential Brain Nutrient

DHA is most abundant in the:

  • brain
  • eyes
  • heart

It is integral in:

  • learning and memory ability
  • brain and mental development
  • visual acuity
  • prevention and management of cardiovascular disease

Image result for benefits of dha

(Source)

DHA is the most abundant omega-3 fatty acid in the brain and retina. DHA comprises:

  • 40% of the polyunsaturated fatty acids (PUFAs) in the brain
  • 60% of the PUFAs in the retina

Fifty percent of the weight of a neuron’s plasma membrane is composed of DHA.  4

Multiple studies indicate that brain tissue contains the highest concentration of DHA in the body.  5  In fact, 60 percent of the brain is composed of structural fat (the gray matter), of which nearly half is composed of DHA. Due to this fact, it is an essential building block for early brain development, as well as a key structural element in maintaining healthy brain functioning through all stages of life.

Image result for development of the brain and DHA

(Source)

DHA has the most influence on the brain and how it develops and functions.  It assists in the determination of brain structure and protects brain tissue from damage. DHA protects the brain in three major areas:

Protects brain tissue from inflammatory damage

DHA promotes the development of anti-inflammatory molecules while suppressing pro-inflammatory molecules in brain cell membranes.  6 

DHA protects learning and memory

The regions with the greatest concentrations of DHA are closely related to memory.  It is often recognized that those people that show cognitive deficiencies and an increased risk for dementia and Alzheimer’s disease have a DHA deficiency.  7

Since DHA is a major lipid in the cell membrane, it maintains the fluidity of the neuron which is required for a properly functioning memory.  It also promotes rapid signal transduction across synapses.

DHA also promotes the outgrowth of neurites which is involved in forming new memories.  8   It also concentrates in the synaptic membranes.

DHA promotes the healing of damaged brain tissue

If brain tissue is damaged, brain cell membranes release DHA in massive amounts for conversion into compounds called protectins9 

The Need for Continuous Dietary DHA for Brain Health

DHA turns over very fast in the brain, especially in the hippocampus region of the brain.  This is especially true in the aging brain where DHA normally drops off quite quickly.

Since DHA is a fat that is not stored in fat cells but instead resides exclusively in cell membranes, it needs to be replenished on a continuous basis.  The need for constant supplementation of DHA is due to the cell membrane undergoing continuous degradation and renewal.

It is therefore necessary to have a constant dietary supply of DHA to avoid depletion and injury to the cells of the brain.

Consuming Fish Oil as Dietary DHA is the Best Bioavialable Form

It is widely accepted that the best way to obtain dietary DHA is to consume marine animals and/or to supplement with EPA/DHA rich fish oil or algae oil. Consuming plant based omega-3 fatty acids will provide a limited amount of DHA.

Omega-3 fatty acids are polyunsaturated fatty acids and consist of:

  • alpha-linolenic acid (ALA)
  • eicosapentaenoic acid (EPA)
  • docosahexaenoic acid (DHA)

The are two primary sources of omega-3 fatty acids, animal and plant sources.  Marine animals such as fish and krill provide eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).  Plant foods, such as flaxseed and chia seed provide alpha-linolenic acid (ALA).  When consuming plant-based omega-3 fatty acids, the body has to convert the ALA into EPA and DHA, which can be limited.

Plant and Animal Based Omega-3 Fatty Acids

Plant Based Omega-3 Fatty Acid

  • Flaxseed/oil
  • Hemp seed/oil
  • Canola oil
  • Mustard oil
  • Algae oil
  • Chia seed
  • Chicken egg
  • Broccoli
  • Walnuts
  • Soybeans
  • Microalgae (oil) (Crypthecodinium cohnii, Schizochytrium, brown algae and Nannochloropsis)
  • Perilla (Perilla frutescens)
  • Edible seaweeds (e.g., Wakame, Hijiki, Kombu)
  • Camelina
  • Lingon Berry  (Vaccinium vitis-idaea)
  • Purslane  (Portulaca oleracea)
  • Kiwifruit seed oil  (Actinidia deliciosa)

Animal Based Omega-3 Fatty Acids

  • Fish (oily fish)
  • Fish oil
  • Krill oil
  • Cod Liver oil
  • Greenshell/lipped mussels
  • Fish roe (eggs) (Both red and black caviar)
  • Turkey (limited)
  • Grass fed lean red meat (The omega-6:omega-3 ratio of grass-fed beef is about 2:1, making it a more useful source of omega-3 than grain-fed beef, which usually has a ratio of 4:1.)

ALA is converted into EPA and DHA in your body through desaturations (addition of a double bond) and elongation (addition of two carbon atoms) enzymes.  However, this process results in a very low ratio of EPA and DHA. 

This means that even when consuming large quantities of ALA (e.g., flaxseeds/oil or chia seeds), the body can only convert a relatively small amount into EPA and DHA, and only when there are sufficient enzymes.

Linoleic Acid (LA), (which is also called omega-6 fatty acid) and ALA compete for the same elongase and desaturase enzymes in the synthesis of longer polyunsaturated fatty acids, such as Arachidonic acid (AA) and EPA.

Figure 3. Desaturation and Elongation of Essential Fatty Acids. Humans can synthesize longer omega-6 and omega-3 fatty acids from the essential fatty acids LA and ALA through a series of desaturation (addition of a double bond) and elongation (addition of two carbon atoms) reactions. Delta-6 desaturase (FADS2) is considered the rate-limiting enzyme in this metabolic pathway. Retroconversion of DHA to EPA in peroxisomes occurs at low basal rates and following DHA supplementation.

Desaturation and Elongation of Essential Fatty Acids  (Source)

In addition to the fact that LA and ALA compete for the same elongase and desaturase enzymes in the synthesis of longer polyunsaturated fatty acids, namely AA and EPA, there are two other factors that influence the ability to generate long-chain polyunsaturated fatty acids (LC-PUFA).   These two factors include:

  • Gender
  • Genetic variability

The capacity to generate DHA from ALA differs based on gender.  The capacity is higher in women than men:

  • Women  10
    • 21% of ALA converted to EPA
    • 9% of ALA converted to DHA
  • Men  11
    • 8% of ALA converted to EPA
    • 0-4% of ALA converted to DHA

Estrogens cause higher DHA concentrations in women than in men, probably by upregulating synthesis of DHA from vegetable precursors.  12

The two key enzymes in fatty acid metabolism include:

  • delta-6 desaturase (FADS2)
  • delta-5 desaturase (FADS1)

The single nucleotide polymorphisms (SNPs) in the FADS gene differ dramatically in their ability to generate Long Chain Polyunsaturated Fatty Acids (LC-PUFA), which include AA, EPA and DHA.  With these FADS polymorphisms there may be up to 30% of the variability in blood levels of omega-3 and omega-6 fatty acids among individuals.

The FADS2 gene converts the omega-3 fatty acid ALA to EPA and downstream to DHA.  FADS2 is responsible for elongating ALA and converting it into eicosapentenoic acid (EPA). 

The minor “G” allele in the FADS2 gene is associated with a lower rate of ALA conversion to EPA and a decrease in the conversion of EPA to DHA.  As a result, only a small percentage of ALA can be changed via the enzymes produced by FADS1 and FADS2 genes into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

The U.S. Office of Disease Prevention and Health Promotion published Nutrition and Your Health:  Dietary Guidelines for Americans which provides a list of EPA and DHA content of Fish Species.

The Table below provides the data from this list from the U.S. Office of Disease Prevention and Health Promotion.  (Source)

EPA and DHA Levels in Marine Animals

Fish Species and DescriptionDHA per 100 gEPA per 100 gDHA+EPA per 100 gDHA+EPA per 85 g (3 oz.)
Crustaceans, crab, Alaska king, cooked, moist heat0.1180.2950.4130.351
Crustaceans, crab, blue, cooked, moist heat0.2310.2430.4740.403
Crustaceans, crab, Dungeness, cooked, moist heat0.1130.2810.3940.335
Crustaceans, crab, queen, cooked, moist heat0.1450.3320.4770.405
Crustaceans, crayfish, mixed species, farmed, cooked, moist heat0.0380.1240.1620.138
Crustaceans, crayfish, mixed species, wild, cooked, moist heat0.0470.1190.1660.141
Crustaceans, lobster, northern, cooked, moist heat0.0310.0530.0840.071
Crustaceans, shrimp, mixed species, cooked, moist heat0.1440.1710.3150.268
Crustaceans, spiny lobster, mixed species, cooked, moist heat0.1390.3410.480.408
Fish, anchovy, European, raw0.9110.5381.4491.232
Fish, anchovy, European, canned in oil, drained solids1.2920.7632.0551.747
Fish, bass, freshwater, mixed species, cooked, dry heat0.4580.3050.7630.649
Fish, bass, striped, cooked, dry heat0.750.2170.9670.822
Fish, bluefish, cooked, dry heat0.6650.3230.9880.84
Fish, turbot, cooked, dry heat0.1230.090.2130.181
Fish, carp, cooked, dry heat0.1460.3050.4510.383
Fish, catfish, channel, farmed, cooked, dry heat0.1280.0490.1770.15
Fish, catfish, channel, wild, cooked, dry heat0.1370.10.2370.201
Fish, caviar, black and red, granular3.82.7416.5415.56
Fish, cod, Atlantic, cooked, dry heat0.1540.0040.1580.134
Fish, cod, Pacific, cooked, dry heat0.1730.1030.2760.235
Fish, croaker, Atlantic, raw0.0970.1230.220.187
Fish, dolphin fish, cooked, dry heat0.1130.0260.1390.118
Fish, drum, freshwater, cooked, dry heat0.3680.2950.6630.564
Fish, eel, mixed species, cooked, dry heat0.0810.1080.1890.161
Fish, fish portions and sticks, frozen, preheated0.1280.0860.2140.182
Fish, flatfish (flounder and sole species), cooked, dry heat0.2580.2430.5010.426
Fish, grouper, mixed species, cooked, dry heat0.2130.0350.2480.211
Fish, haddock, cooked, dry heat0.1620.0760.2380.202
Fish, halibut, Atlantic and Pacific, cooked, dry heat0.3740.0910.4650.395
Fish, halibut, Greenland, cooked, dry heat0.5040.6741.1781.001
Fish, herring, Atlantic, cooked, dry heat1.1050.9092.0141.712
Fish, herring, Atlantic, kippered1.1790.972.1491.827
Fish, herring, Pacific, cooked, dry heat0.8831.2422.1251.806
Fish, lingcod, cooked, dry heat0.130.1330.2630.224
Fish, mackerel, Atlantic, cooked, dry heat0.6990.5041.2031.023
Fish, mackerel, king, cooked, dry heat0.2270.1740.4010.341
Fish, mackerel, Pacific and jack, mixed species, cooked, dry heat1.1950.6531.8481.571
Fish, mackerel, Spanish, cooked, dry heat0.9520.2941.2461.059
Fish, mullet, striped, cooked, dry heat0.1480.180.3280.279
Fish, ocean perch, Atlantic, cooked, dry heat0.2710.1030.3740.318
Fish, perch, mixed species, cooked, dry heat0.2230.1010.3240.275
Fish, pike, northern, cooked, dry heat0.0950.0420.1370.116
Fish, pike, walleye, cooked, dry heat0.2880.110.3980.338
Fish, pollock, Atlantic, cooked, dry heat0.4510.0910.5420.461
Fish, pompano, Florida, cooked, dry heat??????0.620 est
Fish, rockfish, Pacific, mixed species, cooked, dry heat0.2620.1810.4430.377
Fish, roe, mixed species, cooked, dry heat1.7471.263.0072.556
Fish, roe, mixed species, raw1.3630.9832.3461.994
Fish, roughy, orange, raw00.0010.0010.001
Fish, sablefish, cooked, dry heat0.920.8671.7871.519
Fish, sablefish, smoked0.9450.8911.8361.561
Fish, salmon, Atlantic, farmed, cooked, dry heat1.4570.692.1471.825
Fish, salmon, Atlantic, wild, cooked, dry heat1.4290.4111.841.564
Fish, salmon, Chinook, cooked, dry heat0.7271.011.7371.476
Fish, salmon, chum, cooked, dry heat0.5050.2990.8040.683
Fish, salmon, chum, drained solids with bone0.7020.4731.1750.999
Fish, salmon, coho, farmed, cooked, dry heat0.8710.4081.2791.087
Fish, salmon, coho, wild, cooked, dry heat0.6580.4011.0590.9
Fish, salmon, pink, cooked, dry heat0.7510.5371.2881.095
Fish, salmon, sockeye, cooked, dry heat0.70.531.231.046
Fish, sardine, Atlantic, canned in oil, drained solids with bone0.5090.4730.9820.835
Fish, scup, raw (Porgy—assigned to low omega-3 group)no datano datano datano data
Fish, sea bass, mixed species, cooked, dry heat0.5560.2060.7620.648
Fish, sea trout, mixed species, cooked, dry heat0.2650.2110.4760.405
Fish, shad, American, raw1.3211.0862.4072.046
Fish, shark, mixed species, raw0.5270.3160.8430.717
Fish, sheepshead, cooked, dry heat0.1070.0830.190.162
Fish, smelt, rainbow, cooked, dry heat0.5360.3530.8890.756
Fish, snapper, mixed species, cooked, dry heat0.2730.0480.3210.273
Fish, spot, cooked, dry heat0.5260.2820.8080.687
Fish, sturgeon, mixed species, cooked, dry heat0.1190.2490.3680.313
Fish, sucker, white, cooked, dry heat0.3710.2440.6150.523
Fish, sunfish, pumpkin seed, cooked, dry heat0.0920.0470.1390.118
Fish, swordfish, cooked, dry heat0.6810.1380.8190.696
Fish, tilefish, cooked, dry heat0.7330.1720.9050.769
Fish, trout, mixed species, cooked, dry heat0.6770.2590.9360.796
Fish, trout, rainbow, farmed, cooked, dry heat0.820.3341.1540.981
Fish, trout, rainbow, wild, cooked, dry heat0.520.4680.9880.84
Fish, tuna, fresh, bluefin, cooked, dry heat1.1410.3631.5041.278
Fish, tuna, light, canned in oil, drained solids0.1010.0270.1280.109
Fish, tuna, light, canned in water, drained solids0.2230.0470.270.23
Fish, tuna, skipjack, fresh, cooked, dry heat0.2370.0910.3280.279
Fish, tuna, white, canned in water, drained solids0.6290.2330.8620.733
Fish, tuna, yellowfin, fresh, cooked, dry heat0.2320.0470.2790.237
Fish, whitefish, mixed species, cooked, dry heat1.2060.4061.6121.37
Fish, whiting, mixed species, cooked, dry heat0.2350.2830.5180.44
Fish, wolffish, Atlantic, cooked, dry heat0.4050.3930.7980.678
Frog legs, raw0.0340.02
Mollusks, abalone, mixed species, raw00.0490.0490.042
Mollusks, clam, mixed species, cooked, moist heat0.1460.1380.2840.241
Mollusks, conch, baked or broiled0.0720.0480.120.102
Mollusks, cuttlefish, mixed species, cooked, moist heat0.1320.0780.210.179
Mollusks, mussel, blue, cooked, moist heat0.5060.2760.7820.665
Mollusks, octopus, common, cooked, moist heat0.1620.1520.3140.267
Mollusks, oyster, eastern, farmed, cooked, dry heat0.2110.2290.440.374
Mollusks, oyster, eastern, wild, cooked, dry heat0.2910.260.5510.468
Mollusks, oyster, Pacific, cooked, moist heat0.50.8761.3761.17
Mollusks, scallop, mixed species, cooked, breaded and fried0.1030.0860.180.161
Mollusks, whelk, unspecified, cooked, moist heat0.0120.0080.020.017

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