Lipids / Fats

How much Omega 3 (EPA + DHA) fatty acids should you consume? [Source: Dr. Sears presentation on "Silent Inflammation"]

The half life of omega 3s is two days, so if you stop supplementing your blood levels will decrease by 50% in two days and after four days would be down to 25%.

Higher levels of omega 3 fatty acids (DHA & EPA) is associated with slower loss of telemere length. This may be due to reduced oxidative stress. (oxidative stress is known to accelerate telemere shortening) [Journal of the American Medical Association 303(3):250-257, 2010]

Many people consume GLA (gamma linolenic acid) (Evening Primrose Oil / Borage Oil) to generate the anti-inflammatory DGLA (Dihomo gamma Linolenic Acid). However excess GLA can spill over into creating inflammatory AA (Arachidonic Acid). Combining sesame oil with GLA helps to prevent this spill over.

Biosynthetic pathways for polyunsaturated fatty acids (PUFAs):

Plant Only Metabolism
Fatty Acid Common Name Enzyme Next Metabolite
18:0 Stearic Acid 9-desaturase Oleic Acid
18:1 n-9 Oleic Acid 12-desaturase Linoleic Acid
18:2 n-6 Linoleic Acid 15-desaturase alpha Linolenic Acid (ALA)

 

"Omega 6" Pathways
Fatty Acid Common Name Enzyme Next Metabolite
18:2 n-6 Linoleic Acid 6-desaturase gamma Linolenic Acid (GLA)
18:3 n-6 gamma Linolenic Acid (GLA) elongase Dihomo gamma Linolenic Acid
20:3 n6 Dihomo gamma Linolenic Acid 5-desaturase Arachidonic Acid (AA)
20:4 n-6 Arachidonic Acid (AA) elongase Adrenic Acid
22:4 n-6 Adrenic Acid elongase 24:4 n-6
24:4 n-6 none * Docosapentaenoic Acid (22:5 n-6)

* 6-desaturase peroxisomal beta oxydation

"Omega 3" Pathways
Fatty Acid Common Name Enzyme Next Metabolite
18:3 n-3 alpha Linolenic Acid (ALA) 6-desaturase Stearidonic Acid
18:4 n-3 Stearidonic Acid elongase Eicosatetraenoic Acid
20:4 n-3 Eicosatetraenoic Acid 5-desaturase Eicosapentaenoic Acid (EPA)
20:5 n-3 Eicosapentaenoic Acid (EPA) elongase Docosapentaenoic Acid
22:5 n-3 Docosapentaenoic Acid elongase 24:5 n-3
24:5 n-3 none * Docosahexaenoic Acid (22:6 n-3) (DHA)

* 6-desaturase peroxisomal beta oxydation

Note: the omega-6 and omega-3 pathways compete for the same enzymes. This results in supplementation of one suppressing the other and hence the importance of the ratio of consumption.

Arachidonic Acid is the relatively famous precursor of the COX and LOX inflammation pathways (for which asprin, ibuprofen, Celebrex, etc are prescribed to block).

Eicosanoid Synthesis
GLA (y-Linolenic Acid)
DGLA ->
Arachidonic Acid
EPA
COX
5-LOX
15-LOX
COX
5-LOX
COX
5-LOX
PGE1
LTB3
15-OH-DGLA
PGE2
LTB4
PGE3
LTB5
TXA1
LTC3
TXA2
LTC4
TXA3
LTC5
LTD4
LTD5
LTE4
LTE5
5-HETE
Arachidonic Acid (in more detail)
COX
12-LOX
15-LOX
5-LOX
PGG2
12-HPETE
15-HPETE
5-HPETE
PGD2
PGH2
12-HETE
15-HETE
LTA4
5-HETE
PGJ2
PGE2; PGI2; PGF2a; TXA2
LTC4
LTB4
Lipoxin A4 & B4
LTD4
LTE4

Monocytes and Macrophages produce large amounts of PGE2 and PGF2.

Neutrophils produce moderate amounts of PGE2.

Mast cells produce PGD2.

12-LOX and 15-LOX is found primarily in epithelial cells.

5-LOX is found primarily in mast cells, monocytes, macrophages and granulocytes.

Eicosanoids (primarily PGE2 and LTx4 series) are involved in modulating the intensity and duration of immune response and inflammation.

PGE2:

15-HETE reduces lymphcyte production, 5-HETE increases lymphocyte production.

Consuming fish oil (high in omega-3) results in a decrease in the amount of arachodonic acid in most cell membranes (specifically those involved in immunity and inflammation). The eicosanoids produced from EPA are usually less potent (example: LTB5 is only 10% as potent as LTB4). The most popular concept is that omega-3 consumption results in less PGE2 production and thus is anti-inflammatory. This is true, however it is a simplistic view and overlooks numerous other factors.

Production of PGE2 was shown to be highest in a low-fat corn oil diet, then Safflower oil, then Olive Oil, then significantly lower with Coconut Oil and finally dramatically lower in the fish oil diet.

Rheumatoid Arthritis: "the evidence for a beneficial effect of fish oil is strongest in rheumatoid arthritis".

Cancer: Supplementation of omega-3 produces increased natural killer cell cytotoxicity, more CD8+ and CD28+ cells activated, increased nitric oxide and IL-2 production.

Phosphatidylserine - is a phospholipid, an essential component of cell membranes and is related to lecithin. The FDA has allowed the health claims of "may reduce the risk of cognitive dysfunction" and "may reduce the risk of dementia in the elderly" as proven facts. Scientific speculation is that phosphatidylserine encourages the regrowth of damaged nerve networks. Suggested dosage: 300 mg to 600 mg per day in divided doses. ["Memory Loss is Not Inevitable" Dr. Allen Josephs 2007]