Is Supplementing Vit E Actually Bad For You?

[Obi-wan]

Also:

Vitamin K2 Induces Mitochondria-Related Apoptosis in Human Bladder Cancer Cells via ROS and JNK/p38 MAPK Signal Pathways
Vitamin K2 Induces Mitochondria-Related Apoptosis in Human Bladder Cancer Cells via ROS and JNK/p38 MAPK Signal Pathways

I have stopped taking all Vit E. Context, I have prostate cancer and want ROS...subjects without cancer would want to lower ROS with antioxidants

Succinate-Q oxidoreductase (complex II)

also known as complex II or succinate dehydrogenase, is a second entry point to the electron transport chain.[24] It is unusual because it is the only enzyme that is part of both the citric acid cycle and the electron transport chain. Complex II consists of four protein subunits and contains a bound flavin adenine dinucleotide (FAD) cofactor, iron–sulfur clusters, and a heme group that does not participate in electron transfer to coenzyme Q, but is believed to be important in decreasing production of reactive oxygen species.[25][26] It oxidizes succinate to fumarate and reduces ubiquinone. As this reaction releases less energy than the oxidation of NADH, complex II does not transport protons across the membrane and does not contribute to the proton gradient. -Wikipedia

 

[Hans]

From what I've read, compex II contributes to a significant part to ROS production at the Q couple compared to the other inputs such as glycerol 3 phosphate dehydrogenase and electron transfer flavoprotein dehydrogenase (ETFdh). But if you're on a low fat diet, there will not be much activity at compex II, because oxaloacetate and malonyl-coa both inhibit complex II. By increasing saturated fat intake will increase complex II activity and also input at ETFdh, which will lead to more reverse electron transport and more ROS production.
I think this effect will be greatest with longer chain saturated fat such as stearic acid.
The superoxide that is produced by the electron transport chain will be rapidly converted to hydrogen peroxide by superoxide dismutase, which will then leave the mitochondria. In the cytosol, the hydrogen peroxide will rapidly be converted to water by catalase or by neutralized by glutathione.
But I think for the highest ROS output will be generated by fructose and saturated fat.

Xanthine oxidase is also a minor site of hydrogen peroxide generation

 

[Obi-wan]

From what I've read, compex II contributes to a significant part to ROS production at the Q couple compared to the other inputs such as glycerol 3 phosphate dehydrogenase and electron transfer flavoprotein dehydrogenase (ETFdh). But if you're on a low fat diet, there will not be much activity at compex II, because oxaloacetate and malonyl-coa both inhibit complex II. By increasing saturated fat intake will increase complex II activity and also input at ETFdh, which will lead to more reverse electron transport and more ROS production.
I think this effect will be greatest with longer chain saturated fat such as stearic acid.
The superoxide that is produced by the electron transport chain will be rapidly converted to hydrogen peroxide by superoxide dismutase, which will then leave the mitochondria. In the cytosol, the hydrogen peroxide will rapidly be converted to water by catalase or by neutralized by glutathione.
But I think for the highest ROS output will be generated by fructose and saturated fat.

Xanthine oxidase is also a minor site of hydrogen peroxide generation

Thanks@salmonamb. Aren’t All electron transports reverse from NADH?

 

[Hans]

Thanks@salmonamb. Aren’t All electron transports reverse from NADH?

Complex I and III are the major contributes to superoxide. But I think electron leak can happen at complex I, II & III. If both glucose and fats are eaten, ROS will complex I and II will contribute to a significant degree.
Also NOX4 is a major contributor to ROS production. See my post here:
High-Fructose-High-Coconut-Oil Diet Disregulates Leptin, Stearoyl-CoA Desaturase, And Spatial Memory

 

[Obi-wan]

Complex I and III are the major contributes to superoxide. But I think electron leak can happen at complex I, II & III. If both glucose and fats are eaten, ROS will complex I and II will contribute to a significant degree.
Also NOX4 is a major contributor to ROS production. See my post here:
High-Fructose-High-Coconut-Oil Diet Disregulates Leptin, Stearoyl-CoA Desaturase, And Spatial Memory

“ROS will oxidize the free PUFAs in the cell as well as in the cell membranes and also the cardiolipin, leading to mitochondrial dysfunction and cell death. ”- interesting

Also “A loss of electron chain complexes increase ROS production, because of a high ubiquinol to ubiquinone ratio.”

I now take ubiquinol with my ACV/BS drink

 

[Hans]

“ROS will oxidize the free PUFAs in the cell as well as in the cell membranes and also the cardiolipin, leading to mitochondrial dysfunction and cell death. ”- interesting

From: Functional role of cardiolipin in mitochondrial bioenergetics - ScienceDirect
MPTP is mitochondrial permeability transition pore.
"The synergistic effect of Ca2 + and oxidized CL in the induction of MPTP opening and in the release of cytochrome c from mitochondria (Fig. 3) may have important implications in cell death, as well as in those physiopathological situations characterized by alterations in Ca2 +homeostasis and accumulation of oxidized CL in mitochondria, such as aging [48], [49], [50], heart ischemia/reperfusion [38], [40], [42], [114] and other degenerative diseases"

"There is continued interest in discovering new antioxidants or free radical scavengers of high potency and low toxicity that are effective in preventing CL oxidation in mitochondria. Among these compounds, melatonin [115] and plastoquinones [116], [117] have been shown to be particularly effective in preventing CL oxidation in mitochondria by ROS attack."

Cardiolipin will consist of saturated and monounsaturated in a PUFA depleted state, which will significantly reduce the amount of oxidized cardiolipin.
Ca2+ alone does not cause MPTP opening directly and flood the mitochondria, but requires ROS and oxidized cardiolipin.

In one of my previous messages I said that fructose and stearic acid would produce the most ROS, but because lauric acid is oxidized much more rapidly than longer chain saturated fats, lauric acid will make more ROS compared to stearic acid. But this is just theoretical.

 

[Wagner83]

If the last bit about alpha-tocopherol is relevant for us humans:

Fluorescence spectroscopic analysis of the interaction of papain and bromelain with l-ascorbic acid, α-tocopherol, β-carotene and astaxanthin. - PubMed - NCBI

Fluorescence spectroscopic analysis of the interaction of papain and bromelain with l-ascorbic acid, α-tocopherol, β-carotene and astaxanthin. - PubMed Li X , et al. 2 minutes Abstract In this study, the interaction between four classic dietary antioxidants (including l-ascorbic acid, α-tocopherol, β-carotene and astaxanthin) and papain/bromelain was investigated by fluorescence spectroscopy. The results show that the quenching mechanisms are all static quenching at lower concentrations of antioxidants, but at higher concentrations of antioxidants, predominantly by the "sphere of action" quenching mechanisms. The binding processes of the four antioxidants to papain/bromelain are all synergistically driven by enthalpy and entropy, and the major driving forces are electrostatic effect and hydrophobic interactions. The binding constants of papain/bromelain with the four antioxidants are in the following order as: astaxanthin-papain >β-carotene-papain > astaxanthin-bromelain >l-ascorbic acid-papain >l-ascorbic acid-bromelain >β-carotene-bromelain >α-tocopherol-papain >α-tocopherol-bromelain. Synchronous fluorescence spectroscopy shows the interaction between l-ascorbic acid/β-carotene/astaxanthin and papain/bromelain decreases the hydrophobicity of the microenvironment of tryptophan (Trp) and tyrosine (Tyr) residues. The hydrophobicity of Trp is increased while the hydrophility of Tyr is increased in the presence of α-tocopherol.​

 

[High_Prob]

This seems like a good product: Tocotrienols

It is a blend of both Tocotrienols and Tocopherols. Extracted from Rice Bran only. There are no soy derivatives as confirmed by Pure Encapsulations Customer Service.

Note: There is no break down of how much of each type of tocopherol/tocotrienol but when I asked about this the rep stated that there is an even profile...

 

[Obi-wan]

I stopped taking ubiquinol since it is also an antioxidant and have switched from BS to potassium bicarbonate so ACV/potassium bicarbonate then do K2 on my gums since K2 increases ROS. See Vitamin K2 Induces Mitochondria-Related Apoptosis in Human Bladder Cancer Cells via ROS and JNK/p38 MAPK Signal Pathways

 

[Obi-wan]

Cancer is a metabolic defect thereby causing glycolysis to produce lactic acid from pyruvate instead of acetyl CoA which is a necessary component of the Krebs Cycle. Acetyl CoA is the only enzyme that the Krebs cycle will accept. If there is no acetyl CoA then the cytosol is uncoupled from the Krebs cycle and electron chain transport does not happen (Warburg effect) and there is not enough ATP produced. ATP drives membrane potential. Since the cell likes to be in the resting potential it has lots of potassium on the inside and sodium on the outside giving it a negative potential of -70 to -80 mVolts. When mitochondria is uncoupled and ATP drops the potential changes and sodium rushes in causing the cell to swell signaling the stress hormones. Cancer is stuck in this mode. Apple cider vinegar and potassium bicarbonate creates potassium acetate creating acetyl CoA and much needed potassium... ROS is a byproduct of oxidative phosphorylation. Scientists are starting to reconsider the role of ROS as a good thing. K2 would be beneficial for higher ROS. Antioxidants like Vitamin A, E, and C could be a detriment…

 

[Wagner83]

Serum alpha-tocopherol and subsequent risk of lung cancer among male smokers. - PubMed - NCBI

 

[High_Prob]

This seems like a good product: Tocotrienols

It is a blend of both Tocotrienols and Tocopherols. Extracted from Rice Bran only. There are no soy derivatives as confirmed by Pure Encapsulations Customer Service.

Note: There is no break down of how much of each type of tocopherol/tocotrienol but when I asked about this the rep stated that there is an even profile...

@Obi-wan I apologize for the above post - I haven't been keeping up with your more recent posts so didn't realize that you were stopping all vitamin E supplementation...

 

[Mito]

Cancer is a metabolic defect thereby causing glycolysis to produce lactic acid from pyruvate instead of acetyl CoA which is a necessary component of the Krebs Cycle.

But you can still synthesize acetyl CoA from fat or protein correct?

 

[Obi-wan]

But you can still synthesize acetyl CoA from fat or protein correct?

At high glucose levels, acetyl-CoA is produced through glycolysis.[10] Pyruvate undergoes oxidative decarboxylation in which it loses its carboxyl group (as carbon dioxide) to form acetyl-CoA, giving off 33.5 kJ/mol of energy. The oxidative conversion of pyruvate into acetyl-CoA is referred to as the pyruvate dehydrogenase reaction. It is catalyzed by the pyruvate dehydrogenase complex. Other conversions between pyruvate and acetyl-CoA are possible. For example, pyruvate formate lyase disproportionates pyruvate into acetyl-CoA and formic acid.

Pyruvic acid can be made from glucose through glycolysis, converted back to carbohydrates (such as glucose) via gluconeogenesis, or to fatty acids through a reaction with acetyl-CoA.[3] It can also be used to construct the amino acid alanine and can be converted into ethanol or lactic acid via fermentation.

Pyruvic acid supplies energy to cells through the citric acid cycle (also known as the Krebs cycle) when oxygen is present (aerobic respiration), and alternatively ferments to produce lactate when oxygen is lacking (lactic acid fermentation).[4]

At low glucose levels, the production of acetyl-CoA is linked to β-oxidation of fatty acids. Fatty acids are first converted to acyl-CoA. Acyl-CoA is then degraded in a four-step cycle of dehydrogenation, hydration, oxidation and thiolysis catalyzed by four respective enzymes, namely acyl-CoA dehydrogenase, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and thiolase. The cycle produces a new acyl-CoA with two fewer carbons and acetyl-CoA as a byproduct.[11]

But secondary lipid oxidation products can also inactivate LDH (Lactate dehydrogenase) and impact its ability to regenerate NADH,[27] directly disrupting the enzymes ability to convert lactate back to pyruvate.

Cut and pasted from Wilkipedia

So you have continuous lactic acid fermentation but not enough ATP produced to keep a high negative membrane potential

Bicarbonate reduces lactic acid, ACV/potassium bicarbonate increases acetyl-CoA which increases ATP. K2 increases ROS...keep glucose high​

 

[Obi-wan]

Serum alpha-tocopherol and subsequent risk of lung cancer among male smokers. - PubMed - NCBI

"These findings suggest that high levels of alpha-tocopherol, if present during the early critical stages of tumorigenesis, may inhibit lung cancer development"-Wonder how high?

Plus this: Mitochondrial reactive oxygen species and cancer | Cancer & Metabolism | Full Text

It is becoming increasingly apparent that ROS play an important role in the biology of tumorigenesis. While several mechanisms have been presented here, the bulk of ROS-mediated signaling targets are largely unknown. However, the frequency of cancer-associated mutations that increase ROS levels suggests that increased production of ROS may be a common output of a large fraction of cancer-associated mutations in oncogenes and tumor suppressors. In addition, the apparent selection for mitochondrial mutations that increase ROS at the detriment of metabolic flexibility suggests that ROS are strongly selected for in these cancer cells. An emerging model is that cancer cells increase the production of ROS to activate localized pro-tumorigenic signaling but balance the increased ROS with elevated antioxidant activity to maintain redox balance. As with all studies in cancer, the final goal will be to design therapeutics that can take advantage of these discoveries. Both the suppression of ROS to prevent activation of pro-tumorigenic signaling pathways and the exacerbation of ROS by disabling antioxidants to induce cell death represent promising approaches in this regard. Future work is needed to better understand ROS-targeted pathways. In addition, future studies need to determine what sources of ROS and what specific antioxidants are required for homeostasis. With this knowledge, we can better understand cancer biology and design novel therapeutics to specifically treat cancer cells

Antioxidants work for prevention but not for deactivation of cancer cells...​

 

[Braveheart]

"These findings suggest that high levels of alpha-tocopherol, if present during the early critical stages of tumorigenesis, may inhibit lung cancer development"-Wonder how high?

Plus this: Mitochondrial reactive oxygen species and cancer | Cancer & Metabolism | Full Text

It is becoming increasingly apparent that ROS play an important role in the biology of tumorigenesis. While several mechanisms have been presented here, the bulk of ROS-mediated signaling targets are largely unknown. However, the frequency of cancer-associated mutations that increase ROS levels suggests that increased production of ROS may be a common output of a large fraction of cancer-associated mutations in oncogenes and tumor suppressors. In addition, the apparent selection for mitochondrial mutations that increase ROS at the detriment of metabolic flexibility suggests that ROS are strongly selected for in these cancer cells. An emerging model is that cancer cells increase the production of ROS to activate localized pro-tumorigenic signaling but balance the increased ROS with elevated antioxidant activity to maintain redox balance. As with all studies in cancer, the final goal will be to design therapeutics that can take advantage of these discoveries. Both the suppression of ROS to prevent activation of pro-tumorigenic signaling pathways and the exacerbation of ROS by disabling antioxidants to induce cell death represent promising approaches in this regard. Future work is needed to better understand ROS-targeted pathways. In addition, future studies need to determine what sources of ROS and what specific antioxidants are required for homeostasis. With this knowledge, we can better understand cancer biology and design novel therapeutics to specifically treat cancer cells​

The stress from trying to understand all this ***t is going to give me cancer....health for the knowledgeable at least

 

[Elephanto]

Daily supplementation of vitamin E does not decrease the risk of prostate cancer, and may increase it. -Wikipedia

It could be because most Vitamin E supplements include anti-androgenic substances (soybean oil, rice bran oil and other high O6 oils) and bad excipients. It's also not a consistent result, the largest epidemiological study had 60% lower risks with combined Vitamin E and Selenium supplementation but increased risks with either Vit E or Selenium alone. Others found decreased risks with Vit E alone.
Vitamin E and the Risk of Prostate Cancer: Updated Results of The Selenium and Vitamin E Cancer Prevention Trial (SELECT)

I use this one since it's the purest I could find :
Cococare, 100% Vitamin E Oil, .5 fl oz (15 ml)

 

[yomama]

Vit. E increases risk of prostate cancer

 

[Elephanto]

View attachment 10486

I also wonder if the prostate doesn't preferentially take up Vitamin E since it's so protective, and along with it are transported the O6 oils with phytoestrogens in Vit E supps so they can exert their estrogenic/anti-androgenic effects directly.

 

[Obi-wan]

The stress from trying to understand all this ***t is going to give me cancer....health for the knowledgeable at least

Sorry John. This is what I was concluding to "Antioxidants work for prevention but not for deactivation of cancer cells..." Context is everything...