AA/EPA Ratio: A Major Marker of Cellular Inflammation

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Cellular or Chronic Inflammation

According to Life Extension® cellular or chronic low-level inflammation contributes to the pathogenesis of at least seven of the ten leading causes of mortality, which include:  1

  • heart disease
  • cancer
  • chronic lower respiratory disease
  • stroke
  • Alzheimer’s disease
  • diabetes
  • nephritis

There are two types of inflammation:

  • acute inflammation
  • chronic inflammation

Acute inflammation is a short term response to tissue injury that produces symptoms of pain.  Acute inflammation usually resolves rather quickly depending on the nature of the injury.

Chronic inflammation is usually triggered by cellular stress and dysfunction and plays a major role in the development of degenerative diseases and loss of normal functions. 

Chronic inflammation is silent in its nature and thus usually shows no signs of pain or at least acute pain.  Because it is below the perception of pain, it tends to have a very destructive power and often disrupts hormonal signaling at the cellular level.  This often leads to the following:

  • increased fat accumulation
  • acceleration of the development of chronic disease
  • decreased physical performance

Measuring Cellular or Chronic Inflammation

Even though cellular or chronic inflammation is silent (absent of pain signals), it can be measured with a number of medical tests.

The three most common tests for cellular inflammation include:

  • hs-C-reactive protein (hs-CRP)
  • Nuclear factor kappa-B (NF-kB)
  • AA/EPA Ratio

hs-C-reactive protein (hs-CRP)

hs-C-reactive protein (hs-CRP) is one of the earliest and often used marker of inflammation.  It is a very effective measure of cellular inflammation.  

hs-CRP is a protein that is synthesized in the liver in response to elevated levels of IL-6 in the blood.  Since hs-CRP is a long-lived protein in the blood, as opposed to others that have a short half life, it is easily measured. 

The two drawbacks to hs-CRP is that a slight bacterial infection can elevate its levels; and, it is a late downstream marker of cellular inflammation rather than an early warning sign.  2

Nuclear factor kappa-B (NF-kB)

Nuclear factor kappa-B (NF-kB) is important in the initiation of the inflammatory response. When cells are exposed to damage signals (such as TNF-α, IL-1β, IL-6 or oxidative stress), they activate NF-kB.  3 

The drawback to Nuclear factor kappa-B (NF-kB) is that their levels in the blood are very low and they have very short half-lives.  4

AA/EPA Ratio

The AA/EPA ratio in the blood is considered the best marker of cellular inflammation in the body.

The AA/EPA ratio is the ratio of two fatty acids in the blood, the omega-6 fatty acid arachidonic acid (AA) and the omega-3 fatty acid eicosapentaenoic acid (EPA). 

Focus on Omega-6 Fatty Acids/Arachidonic acid (AA) and Omega-3 Fatty Acids/Eicosapentaenoic acid (EPA)

Omega-6 Fatty Acids and Arachidonic acid (AA)

Arachidonic acid (AA) is a polyunsaturated omega-6 fatty acid.  It is either synthesized in the human body or obtained via the diet.  

AA is synthesized from the consumption of linoleic acid known as omega-6 fatty acids.   Dietary sources of omega-6 fatty acids include:

Plant based omega-6 fatty acids:

  • nuts
  • hulled sesame seeds
  • pumpkin seeds
  • sunflower seeds
  • almonds
  • cereals
  • durum wheat
  • whole-grain breads
  • grape seed oil
  • evening primrose oil
  • borage oil
  • blackcurrant seed oil
  • flax/linseed oil
  • rapeseed or canola oil
  • hemp oil
  • soybean oil
  • cottonseed oil
  • sunflower seed oil
  • corn oil
  • safflower oil
  • Salicornia oil
  • poppy seed oil
  • sunflower oil
  • Barbary Fig Seed Oil
  • wheat germ oil
  • cottonseed oil
  • walnut oil
  • sesame oil
  • rice bran oil
  • Argan oil
  • pistachio oil
  • peanut oil
  • olive oil (small amounts)

Animal based omega-6 fatty acids:

  • poultry
  • chicken fat
  • egg yolk
  • lard

Image result for omega 6

Figure 1.  Omega-6 Fatty Acid Food Sources

Arachidonic acid is also found in certain foods and can be consumed directly.  Arachidonic acid is found in the following foods:

  • meat
  • poultry
  • eggs

Image result for AA/EPA ratio

Figure 2.  Arachidonic acid in foods and their inflammatory cascade  (Source)

Even though a certain level of arachidonic acid is necessary in the body, an excess of AA in the blood is the building block of pro-inflammatory eicosanoids that stimulate cellular inflammation.

Ideally the AA levels in the blood should be between 7 and 9% of the total fatty acids.

Omega-3 Fatty Acids and Eicosapentaenoic acid (EPA)

Omega-3 fatty acids are polyunsaturated fatty acids (PUFAs).  They consist of:

  • alpha-linolenic acid (ALA); (found in plant oils)
  • eicosapentaenoic acid (EPA); (found in marine oils)
  • docosahexaenoic acid (DHA); (found in marine oils)

Alpha-linolenic acid (ALA) is converted into EPA and DHA in the body through desaturations (addition of a double bond) and elongation (addition of two carbon atoms) enzymes.  However, this process results in a very low ration of EPA and DHA. 

This means that even consuming large quantities of ALA, the body can only convert a relatively small amount into EPA and DHA, and only when there are sufficient enzymes.

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

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-linoleic acid (ALA).

Plant based omega-3 fatty acids:

  • 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  5
  • 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
  • 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.)

EPA is a very powerful anti-inflammatory mediator and also acts as a competitive inhibitor of AA for the enzymes necessary for the production of inflammatory eicosanoids.

Since the AA/EPA ratio provides a specific indicator of the balance between omega-6 and omega-3 fatty acids in circulation, when this ratio is higher, there is preferred incorporation of AA into membranes over EPA, leading to a pro-inflammatory environment.  6

The ideal AA/EPA ratio is between 1.5 and 3 which is often found in the Japanese population.  In the American population the AA/EPA ratio is often found around 15.

Image result for AA/EPA ratio

Figure 3.  Typical AA/EPA Ratios  (Source)

The higher the AA/EPA ratio, the higher are the levels of cellular inflammation.  The Table below lists the ranges of AA/EPA and the corresponding cellular inflammation and future states of wellness:

AA/EPA Ranges Cellular Inflammation Future state of wellness
1.5 to 3 Low Excellent
3 to 6 Moderate Good
7 to 15 Elevated Moderate
> than 15 High Poor

(Source)

The higher the levels of cellular inflammation, the more likely the future development of chronic disease will be accelerated. Populations with an AA/EPA ratio greater than 12 are often associated with chronic diseases.  7 

Image result for AA/EPA ratio

Figure 4.  AA to EPA Ratio – Biomarker of Inflammatory Status  (Source)

How to Reduce and Improve the AA/EPA Ratio Through Dietary Methods

The AA/EPA ratio can be modulated strictly through diet, and not through pharmaceuticals or nutraceuticals.

According to Dr. Barry Sears, a leading authority on the dietary control of hormonal and inflammatory responses and considered the founder of anti-inflammatory nutrition, he states that:

“If the AA levels in the blood are greater than 9% of the total fatty acids, then a more restrictive anti-inflammatory diet is required to lower insulin and a greater restriction of omega-6 fatty intake is also required. 

If the EPA levels are less than 4% of the total fatty acids, then greater consumption of fatty fish or omega-3 fatty concentrates is required.”  8 

Significant changes to the AA/EPA ratio can occur in 60 days of dietary changes, since the ratio reflects the previous 30 days of dietary intake.

The fastest way to reduce the AA/EPA ratio is to increase the intake of high-purity omega-3 fatty acid concentrates rich in EPA.  The other way to reduce the AA/EPA ratio is to reduce the consumption of arachidonic acid (AA) and omega-6 fatty acids (LA). 

Practicing both dietary changes (increasing EPA and reducing AA and LA consumption) is the primary method to reduce the AA/EPA ratio.

The Table below lists the EPA and DHA levels in marine animals and can be used as a guide to increase consumption of EPA: 

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

The Table below lists the omega-3 fatty acids in various foods:

Omega-3 in Certain Various Foods

CategoryFoodServing SizeOmega-3 fatty acids (g)
FishBluefish, fresh and frozen, cooked4 oz1.7
FishCod, fresh and frozen4 oz0.6
FishCrab, soft shell, cooked4 oz0.6
FishLobster, cooked4 oz0.12
FishMackerel, canned, drained4 oz2.2
FishSalmon, canned, drained4 oz2.2
FishSalmon, wild, raw4 oz (113g)2.3
FishSardines, canned in oil, drained4 oz1.8
FishScallops, Maine, fresh and frozen, cooked4 oz0.5
FishSmelt, rainbow4 oz0.5
FishSwordfish, fresh and frozen, cooked4 oz1.7
FishTuna, canned in oil, drained4 oz0.2
FishTrout, rainbow100 g0.986
FishBass, freshwater100 g0.79
FishDemersal fish100 g0.388
FishFlatfish, flounder and sole 100 g0.253
FishHalibut100 g0.522
FishPelagic fish3100 g0.989
FishTuna, bluefin 100 g1.298
FishCod, Atlantic100 g0.195
FishPollock, Atlantic 100 g0.443
FishCrustaceans, shrimp 100 g0.54
FishMollusks, mussel 100 g0.483
FishTuna, canned in water, drained4 oz0.3
Grains & BeansMatpe (Vigna mungo bean), boiled1 cup0.6
Grains & BeansPeanut, All types,raw1/2 cupTrace
Grains & BeansSoybeans, dried, cooked1/2 cup0.5
Grains & BeansTofu, regular4 oz0.3
Grains & BeansNatt ō , regular1 cup1.3
Grains & BeansChickpeas, mature seeds, cooked, boiled, without salt1 cup0.07
Green leafy vegetablesArugula raw1 cup34
Green leafy vegetablesGreen leaf lettuce, fresh, raw1 cupTrace
Green leafy vegetablesRed leaf lettuce, fresh, raw1 cupTrace
Green leafy vegetablesBoston lettuce or Bibb lettuce, fresh, raw1 cupTrace
Green leafy vegetablesBrussels sprouts cooked1 cup270
Green leafy vegetablesCabbage red, raw1 cup40
Green leafy vegetablesChinese cabbage cooked, boiled, drained, without salt1 cup69.7
Green leafy vegetablesChard, cooked, boiled, drained, without salt1 cup5.3
Green leafy vegetablesSauerkraut, canned, low sodium1 cup36
Green leafy vegetablesSpinach, cooked, boiled, drained, without salt1 cup166
Green leafy vegetablesTurnip greens, cooked1/2 cupTrace
Green leafy vegetablesDandelion greens, cooked1/2 cup0.1
Green leafy vegetablesKale, cooked1/2 cup0.1
Green leafy vegetablesKohlrabi raw1 cup35
Green leafy vegetablesBeet greens, cooked1/2 cupTrace
Green leafy vegetablesCollard greens, cooked, boiled, drained, without salt1 cup177
Green leafy vegetablesMustard greens, cooked, boiled, drained, without salt1 cup30.8
MeatsPoultry meats3100 g0.121
MeatsChicken, with skin100 g0.19
MeatsChicken, without skin 100 g0.08
MeatsTurkey with skin 100 g0.15
MeatsTurkey, without skin100 g0.06
MeatsPig meats100 g0.065
MeatsPork loin, without fat100 g0.024
MeatsPork loin, without fat100 g0.02
MeatsPork, with fat100 g0.09
MeatsEggs100 g0.081
MeatsBovine meats100 g0.122
MeatsBeef rib eye100 g0.029
MeatsBeef rib eye100 g0.01
MeatsBeef sirloin100 g0.05
MeatsLamb loin chop100 g0.076
MeatsLamb steak leg100 g0.292
Nuts & SeedsAlmonds, dry roasted1 oz0.002
Nuts & SeedsCashews1 oz0.017
Nuts & SeedsChia seeds1 oz4.915
Nuts & SeedsCoconut, raw1 oztrace
Nuts & SeedsFlax seeds1 oz6.388
Nuts & SeedsHazelnuts, filberts1 oz0.024
Nuts & SeedsPecans1 oz0.276
Nuts & SeedsPistachios, raw1 oz0.071
Nuts & SeedsPoppy seed1 oz0.076
Nuts & SeedsPumpkin seeds, whole, roasted, without salt1 oz0.021
Nuts & SeedsSesame seeds, whole, dried1 oz0.105
Nuts & SeedsSunflower seeds, kernels, dried1 oz0.021
Nuts & SeedsWalnuts1 oz2.542
Nuts & SeedsSacha Inchi seeds1 oz4.771
Nuts & SeedsLentils, mature seeds, cooked, boiled, without salt1 oz10.4
OlisAvocado Oil0.14
OlisButter
OlisCanola oil1 Tbsp1.3
OlisCoconut oil
OlisCod liver oil1 Tbsp2.8
OlisCorn oil
OlisCotton seed
OlisFlax seed oil1 Tbsp6.9
OlisGhee
OlisGrape seed
OlisLard
OlisOlive oil1 Tbsp0.1
OlisPalm oil (Hydrogenated)
OlisPeanut oil1 TbspTrace
OlisSardine oil1 Tbsp3.7
OlisSoybean oil, (Unhydrogenated)1 Tbsp0.9
OlisTallow (Grain Fed)0.002
OlisTallow (Grass Fed)0.008
OlisWalnut oil1 Tbsp (15 g)1.4
Pumpkin & squashesButternut squash, Squash, winter, butternut, cooked, baked, without salt1 cup0.0492
Pumpkin & squashesZucchini, Squash, summer, zucchini, includes skin, raw1 cup0.0583
Pumpkin & squashesAcorn squash, Squash, winter, acorn, cooked, baked, without salt1 cup0.0759
Pumpkin & squashesTomatoes, Tomatoes, red, ripe, raw1 cup0.045
Root vegetablesCarrots, raw1 cup0.0026
Root vegetablesBeets, raw1 cup0.0068
Root vegetablesParsley, raw1 cup0.0048
Root vegetablesTurnips, raw1 cup0.052

A guideline (based on an Italian study) provided by Dr. Barry Sears, indicates (in the Table below) how much EPA and DHA to consume to reduce the AA/EPA ratio.

Grams of EPA and DHA supplemented per day AA/EPA Ratio
0 12.1
0.8 4.7
2.5 2.6
5.0 1.3
7.5 1.2

This data indicates that a daily dosage of EPA and DHA of 2.5 grams was sufficient to bring the AA/EPA ratio into the desired range for excellent wellness for these healthy individuals. This level of EPA and DHA recommendation correlates well with an Italian study that demonstrated in patients with various chronic diseases having an elevated AA/EPA ratio (>15) lowered their elevated AA/EPA ratio to approximately 5 with daily supplementation of 2.5 grams of EPA and DHA (1). This is also indicative that a person with an existing chronic disease may need greater amounts of EPA and DHA to get them into an excellent wellness range compared to a healthy individual.  9

Even though these are guidelines for daily EPA and DHA supplementation, Dr. Barry Sears recommends that an individual test for the AA/EPA ratio every six to twelve months in order to optimize the AA/EPA ratio.