DHA

2022-02-08 links: PUFA reference: https://tanyewwei.com/blog/dha/ https://forum.jackkruse.com/index.php?threads/dha-a-cancer-causing-killer-ray-peat-says.17123/#post-182111

DHA (22:6ω-3) #

• Formation of isoprostane-like compounds (neuroprostanes) in vivo from docosahexaenoic acid
  • F2-isoprostanes are PGF2α-like compounds that are formed nonenzymatically by free radical-induced oxidation of Arachidonic Acid.
  • Oxidation of DHA yields a series of F4-neuroprostanes. The amounts formed exceed that of the F2 from AA 3.4-fold.
  • Cerebrospinal fluid levels are detected in patients with Alzheimer’s, significantly higher in age-matched controls. Furthermore, the formation of F4-neuroprostane-containing aminophospholipids might adversely effect neuronal function as a result of alterations they induce in the biophysical properties of neuronal Membranes.
• Jack Kruse:
  • *“The fish oil used in studies is not in triglyceride form and is in ethyl ester form which increases inflammation. This means it cannot be in the SN-2 position in our body. And the SN-2 is required to get into the CNS and PNS.”
    • sn = stereospecific numbering = location in a glycerol-based molecule, from top to bottom or something.
  • DHA in the TG or ethyl ester form outside of its other chemicals photo-oxidizes under blue light.
• Docosahexaenoic Acid (DHA): An Ancient Nutrient for the Modern Human Brain
  • 4.6mg turnover a day. Arachidonic Acid is 17.8mg/day.
  • DHA’s half-life in the human brain is ~2.5 years, and there is about 5g total.
• Docosahexaenoic acid: one molecule diverse functions very pro-DHA
• Order from disorder, corralling cholesterol with chaotic lipids The role of polyunsaturated lipids in membrane raft formation
  • Phospholipase D1 has been shown to be displaced from rafts in the presence of DHA.
  • Interaction of cholesterol with a docosahexaenoic acid-containing phosphatidylethanolamine: Trigger for microdomain/raft formation?
    • DHA-containing phospholipids have been postulated to be involved in promoting lateral segregation within membranes into cholesterol-rich and CHOL-poor lipid microdomains.
• How polyunsaturated fatty acids modify molecular organization in 3 membranes: Insight from NMR studies of model systems
• Docosahexaenoic acid affects cell signaling by altering lipid rafts
• Wtf? A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution (Crawford 2013)
• An introduction to a theory on the role of π-electrons of docosahexaenoic acid in brain function (Crawford 2017)

Synthesis #

• ALA via Δ6 Desaturase -> Stearidonic Acid; via Δ6 Elongase -> Eicosatetraenoic Acid (ETA); via Δ5 desaturase ->EPA; via Δ5 elongase -> Docosapentaenoic Acid; via Δ4 desaturase -> DHA.
  • ω−6 fatty acids eventually displace the ω−3 fatty acids under an unfavourable dietary ratio by occupying our elongase and desaturase enzymes by competition, to some extent, I think you can make the case that ω−6 restriction is both more important and safer than ω−3 supplementation.
• Pely: Brain penetrance of exogenous DHA is around 1% and without it and with controlled omega 6 intake endogenous DHA synthesis surpasses that up to 6 fold depending on genetics

Enhanced level of n-3 fatty acid in membrane phospholipids induces lipid peroxidation in rats fed dietary docosahexaenoic acid oil #

• In male rats, DHA-triglycerides (DHA-TG), DHA-ethyl esters (DHA-EE) or DHA-phospholipids (DHA-PL). Control is palm oil supplemented with 20% soybean oil, which isn’t exactly flattering.
• Phospholipid peroxidation in plasma and liver was significantly higher than control in rats fed DHA-TG or DHA-EE, but not DHA-PL.
  • Consistent with increased thiobarbituric acid reactive substances (TBARS) and decreased α-tocopherol levels in plasma and liver.
• Liver microsomes from rats of each group were exposed to a mixture of chelated iron (Fe(3+)/ADP) and NADPH to determine the rate of peroxidative damage.
  • During NADPH-dependent peroxidation of microsomes, the accumulation of phospholipid hydroperoxides, as well as TBARS, were elevated and α-tocopherol levels were significantly exhausted in DHA-TG and DHA-EE groups.
  • During microsomal lipid peroxidation, there was a greater loss of n-3 fatty acids (mainly DHA) than of n-6 fatty acids, including arachidonic acid. These results indicate that polyunsaturation of n-3 fatty acids is the most important target for Lipid Peroxidation.

Brain #

• Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals

  • A journal review, so more complexity to deal with.

• Docosahexaenoic acid: membrane properties of a unique fatty acid.

  • The solubility of Cholesterol in 16:0-18:1 Phosphatidylethanolamine bilayers is ∼51 mol%, in 16∶0-22∶6 PE the value is reduced to 32 mol%… unlike in PC bilayers where a marked reduction in solubility requires polyunsaturation at sn-1 and sn-2 positions, DHA at the sn-2 position with a saturated sn-1 chain is sufficient in PE to trigger exclusion of the sterol.

• Decrease in neuron size in docosahexaenoic acid-deficient brain

  • Without DHA or its precursor α-linolenic acid, omega−6 fatty acids will preferentially become incorporated into the cell membrane. This extra double bond of DHA and its position affords this lipid the greatest ability to exclude cholesterol from cell membranes.
  • ~90% decrease of rat brain DHA. 17.1 vs 1.2 n-6/n-3 ratio. Dafuq? There are 4 graphs each for 21 day and 68 day old groups.
    • Order from disorder, corralling cholesterol with chaotic lipids: The role of polyunsaturated lipids in membrane raft formation.
      • Constitutes the most highly unsaturated naturally occuring fatty acid. Our experiments… support the idea that steric incompatibility of the rigid steroid moiety for highly disordered PUFA chains promotes lateral segregation of lipids into PUFA-rich/sterol-poor and PUFA-poor/sterol-rich regions. The solubility of cholesterol is low in polyunsaturated bilayers.

• MRI evidence that docosahexaenoic acid ethyl ester improves myelination in generalized peroxisomal disorders

• Vasodilator

Supplements #

Ethyl ester form is ~36% less efficient absorption, and oxidizes faster, than triglyceride form (such as what’s used by Omegavia).

• https://shop.omegavia.com/products/omegavia-vegan-omega-3 their fish oil was quite pure (i.e. mostly DHA as advertised) according to Sirsadalot’s testing. You want to minimize EPA and any oxidized DHA. It’s also IFOS tested (international fish oil standards) but idk how relevant that is.
• Performance Lab is also very good according to Uxküll. https://www.performancelab.com/products/omega-3 90 capsules for $50.
• https://profuel.de/omega-3-vegan-60-kapseln
  • Supposed to be 600 + 300, but it’s 525 DHA + 250mg EPA. Then there’s like 120 of mystery ω-9, 25 of ω-6, and then 50ish mg of random ω-3. So pretty pure honestly.