A down side to omega 3 FAs in E4s?

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circular
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A down side to omega 3 FAs in E4s?

Post by circular »

Apolipoprotein E potently inhibits ferroptosis by blocking ferritinophagy (April 2022)
Using postmortem inferior temporal brain cortex tissue from deceased subjects from the Rush Memory and Aging Project (MAP) (N = 608), we found that the association of iron with pathologically confirmed clinical Alzheimer's disease was stronger among those with the adverse APOE-ε4 allele. While protection against ferroptosis did not differ between apoE isoforms in vitro, other features of ε4 carriers, such as low abundance of apoE protein and higher levels of polyunsaturated fatty acids (which fuel ferroptosis) could mediate the ε4 allele's heighted risk of AD. These data support ferroptosis as a putative pathway to explain the major genetic risk associated with late onset AD. [Emphasis added]
The full text isn't easily available, and this abstract doesn't say whether they just mean omega 6 polyunsaturated fatty acids fuel ferroptosis. Does anyone know anything about this? I did a quick search but didn't scare anything out of the internet.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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Re: A down side to omega 3 FAs in E4s?

Post by Quantifier »

A quick search got me to Differential effects of saturated and unsaturated free fatty acids on ferroptosis in rat β-cells:
Abstract
Elevated plasma concentrations of saturated free fatty acids (SFAs) are involved in pancreatic β-cell dysfunction and apoptosis, referred to as lipotoxicity. However, in contrast to apoptosis, the involvement of ferroptosis, as a distinct type of oxidative regulated cell death in β-cell lipotoxicity remains elusive. Therefore, the aim of this study was to determine the effects of various free fatty acids on ferroptosis induction in rat insulin-producing β-cells. Herein, rat insulin-producing β-cells underwent lipid peroxidation in the presence of long-chain SFAs and ω-6-polyunsaturated fatty acids (PUFAs), but only the latter induced ferroptosis. On the other hand, the ω-3-PUFA α-linolenate did not induce ferroptosis but sensitized insulin-producing β-cells to SFA-mediated lipid peroxidation. While the monounsaturated fatty acid oleate, overexpression of glutathione peroxidase 4, and the specific ferroptosis inhibitor ferrostatin-1 significantly abrogated lipid peroxidation, neither glutathione peroxidase 4 nor ferrostatin-1 affected palmitate-mediated toxicity. Site-specific expression of catalase in cytosol, mitochondria, and ER attenuated lipid peroxidation, indicating the contribution of metabolically generated H2O2 from all three subcellular compartments. These observations suggest that only ω-6-PUFAs reach the thresholds of lipid peroxidation required for ferroptosis, whereas SFAs favour apoptosis in β-cells. Hence, avoiding an excessive dietary intake of ω-6-PUFAs might be a crucial prerequisite for prevention of reactive oxygen species-mediated ferroptosis in insulin-producing cells.
This is in rat pancreatic cells, no idea how it works out in whole animals, let alone in humans. But it does look like there is a difference between omega 6 and omega 3 fatty acids in this regard.
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Re: A down side to omega 3 FAs in E4s?

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Quantifier wrote: Wed Oct 05, 2022 7:31 pm A quick search got me to Differential effects of saturated and unsaturated free fatty acids on ferroptosis in rat β-cells:
Abstract
Elevated plasma concentrations of saturated free fatty acids (SFAs) are involved in pancreatic β-cell dysfunction and apoptosis, referred to as lipotoxicity. However, in contrast to apoptosis, the involvement of ferroptosis, as a distinct type of oxidative regulated cell death in β-cell lipotoxicity remains elusive. Therefore, the aim of this study was to determine the effects of various free fatty acids on ferroptosis induction in rat insulin-producing β-cells. Herein, rat insulin-producing β-cells underwent lipid peroxidation in the presence of long-chain SFAs and ω-6-polyunsaturated fatty acids (PUFAs), but only the latter induced ferroptosis. On the other hand, the ω-3-PUFA α-linolenate did not induce ferroptosis but sensitized insulin-producing β-cells to SFA-mediated lipid peroxidation. While the monounsaturated fatty acid oleate, overexpression of glutathione peroxidase 4, and the specific ferroptosis inhibitor ferrostatin-1 significantly abrogated lipid peroxidation, neither glutathione peroxidase 4 nor ferrostatin-1 affected palmitate-mediated toxicity. Site-specific expression of catalase in cytosol, mitochondria, and ER attenuated lipid peroxidation, indicating the contribution of metabolically generated H2O2 from all three subcellular compartments. These observations suggest that only ω-6-PUFAs reach the thresholds of lipid peroxidation required for ferroptosis, whereas SFAs favour apoptosis in β-cells. Hence, avoiding an excessive dietary intake of ω-6-PUFAs might be a crucial prerequisite for prevention of reactive oxygen species-mediated ferroptosis in insulin-producing cells.
This is in rat pancreatic cells, no idea how it works out in whole animals, let alone in humans. But it does look like there is a difference between omega 6 and omega 3 fatty acids in this regard.
Thanks for taking the time to pull that up Quantifier. At least it suggests what would seem to be common sense, if there is such a thing in medicine. I started looking into it because I periodically see someone saying (not here) to get ferritin above 100 for thyroid function, but that seems narrow-sighted given the problems iron can pose to the brain. I thought I'd try to find some sort of guidance as to what iron/ferritin levels might be safe for brain health. I remember a very old thread in these forums about it and I'll try to find that.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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Re: A down side to omega 3 FAs in E4s?

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circular wrote: Wed Oct 05, 2022 7:50 pm I thought I'd try to find some sort of guidance as to what iron/ferritin levels might be safe for brain health. I remember a very old thread in these forums about it and I'll try to find that.
FWIW, Circ, target range for ferritin on ReCODE Reports is 40-160.
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circular
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Re: A down side to omega 3 FAs in E4s?

Post by circular »

floramaria wrote: Fri Oct 07, 2022 8:49 pm
circular wrote: Wed Oct 05, 2022 7:50 pm I thought I'd try to find some sort of guidance as to what iron/ferritin levels might be safe for brain health. I remember a very old thread in these forums about it and I'll try to find that.
FWIW, Circ, target range for ferritin on ReCODE Reports is 40-160.
Thanks floramaria! Mine is only about 56, so maybe I have more room to work with than I thought. I still should see what was discussed about it in that old thread when I get a chance, as well as learn more about the rest of the “iron panel” too.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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Re: A down side to omega 3 FAs in E4s?

Post by Maria4/4 »

Hi everyone,

My ferritin is 16 😞. Should I take a supplement?

I feel fine and eat well, but if the recommended lower level is 40, I am far behind...

Thanks for your help,
Maria 4/4
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Re: A down side to omega 3 FAs in E4s?

Post by Plumster »

Maria4/4 wrote: Sat Jan 21, 2023 9:53 am Hi everyone,

My ferritin is 16 😞. Should I take a supplement?

I feel fine and eat well, but if the recommended lower level is 40, I am far behind...

Thanks for your help,
Maria 4/4
Maria4/4, you could supplement with iron bisglycinate 25 mg -- that is what my doctor has me on (I use Thorne's brand). My ferritin is typically below 30, usually in the 20s. Sometimes I feel tired and attribute it to low iron. Here's a good account of low and high ferritin.
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Re: A down side to omega 3 FAs in E4s?

Post by Maria4/4 »

Plumster wrote: Thu Jan 26, 2023 7:18 am
Maria4/4 wrote: Sat Jan 21, 2023 9:53 am Hi everyone,

My ferritin is 16 😞. Should I take a supplement?

I feel fine and eat well, but if the recommended lower level is 40, I am far behind...

Thanks for your help,
Maria 4/4
Maria4/4, you could supplement with iron bisglycinate 25 mg -- that is what my doctor has me on (I use Thorne's brand). My ferritin is typically below 30, usually in the 20s. Sometimes I feel tired and attribute it to low iron. Here's a good account of low and high ferritin.
Thank you Plumster for the useful information!

Grateful,
Maria 4/4
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