Is Supplementing Vit E Actually Bad For You?

[Obi-wan]

Picture would not display . Has High Gamma Tocotrienols 20mgs

 

[Wagner83]

Perhaps this is relevant to the discussion:

Gamma and delta tocopherol are toxic in ways alpha tocopherol isn't, according to this paper.

The cytotoxicity of vitamin E is both vitamer- and cell-specific and involves a selectable trait.

During a study of the effect of vitamin E in activated mouse macrophages, we observed a reduction in the viability of cells treated with various forms of vitamin E. We show in this report that some tocopherols (both gamma- and delta-tocopherol) are cytotoxic to some but not all cell types. Mouse macrophages were especially sensitive (40 micromol/L), whereas human hepatocytes and bovine endothelial cells were almost completely refractory (90 micromol/L). The fully methylated tocopherol, alpha-tocopherol (alpha-Toc), was not cytotoxic in any cell type tested. The cytotoxicity observed with delta-tocopherol (delta-Toc) was associated with 2 markers of apoptosis. Vitamer-specific cytotoxicity was not due to differences in cellular uptake/accumulation because both alpha-Toc and delta-Toc accumulated equally in any cell type tested. In contrast, the cell-specific cytotoxicity was related in part to uptake/accumulation of the tocopherols. Macrophages accumulated nearly 5 times more tocopherol compared with hepatocytes cultured under similar conditions. To address the hypothesis that uptake accounted for the cell-specific sensitivity, we developed a macrophage "subtype" that was markedly resistant (>150 micromol/L) to delta-Toc. Under many different cell culture conditions (including human serum) uptake/accumulation of tocopherols was reduced in this subtype by approximately 50%. Further selection and evaluation of this phenotype, however, demonstrated no cytotoxicity even when cellular levels were elevated. Our results show that undermethylated tocopherols are cytotoxic to macrophages and that there are independent and selectable processes that determine cellular tocopherol uptake/accumulation and delta-Toc cytotoxicity.

Oh well, maybe there is a point where keeping taking mixed tocopherols is bad, and we don't know what that is.

An other one:
https://raypeatforum.com/community/...otrienol-preparation-in-rats.3953/#post-47503

 

[Obi-wan]

Perhaps this is relevant to the discussion:

"We show in this report that some tocopherols (both gamma- and delta-tocopherol) are cytotoxic to some but not all cell types." - if it is cancer cells that is great...

 

[MrSmart]

"We show in this report that some tocopherols (both gamma- and delta-tocopherol) are cytotoxic to some but not all cell types." - if it is cancer cells that is great...

Abnormalities in endothelium-dependent arterial relaxation develop early in atherosclerosis and may, in part, result from the effects of modified low-density lipoprotein (LDL) on agonist-mediated endothelium-derived relaxing factor (EDRF) release and EDRF degradation. alpha-Tocopherol (AT) is the main lipid-soluble antioxidant in human plasma and lipoproteins, therefore, we investigated the effects of AT on endothelium-dependent arterial relaxation in male New Zealand White rabbits fed diets containing (a) no additive (controls), (b) 1% cholesterol (cholesterol group), or 1% cholesterol with either (c) 1,000 IU/kg chow AT (low-dose AT group) or (d) 10,000 IU/kg chow AT (high-dose AT group). After 28 d, we assayed endothelial function and LDL susceptibility to ex vivo copper-mediated oxidation. Acetylcholine-and A23187-mediated endothelium-dependent relaxations were significantly impaired in the cholesterol group (P < 0.001 vs. control), but preserved in the low-dose AT group (P = NS vs. control). Compared to the control and cholesterol groups, vessels from the high-dose AT group demonstrated profound impairment of arterial relaxation (P < 0.05) and significantly more intimal proliferation than other groups (P < 0.05). In normal vessels, alpha-tocopherol had no effect on endothelial function. LDL derived from both the high- and low-dose AT groups was more resistant to oxidation than LDL from control animals (P < 0.05). These data indicate that modest dietary treatment with AT preserves endothelial vasodilator function in cholesterol-fed rabbits while a higher dose of AT is associated with endothelial dysfunction and enhanced intimal proliferation despite continued LDL resistance to ex vivo copper-mediated oxidation.

Keaney, John F., et al. "Low-dose alpha-tocopherol improves and high-dose alpha-tocopherol worsens endothelial vasodilator function in cholesterol-fed rabbits." The Journal of clinical investigation 93.2 (1994): 844-851.

 

[Waynish]

It has been shown that circulating oleic acid will enter the brain, and I think oleamide could partialy explain 'Italian psychology:' dramatic behavior, over-emotionality, impulsiveness, rudeness, and absurd language are all Italian archetypes (see Goodfellas);⁽¹⁾⁽²⁾⁽³⁾ the list of famous scientists who claim Italy as a homeland is disproportionately small. But what the high-sertotonin brain lacks in logic it can make-up for in poetry, music, and art. (I'm a German descendant myself, and like the Peter Duesberg's personality much more than his unscrupulous Italian rival: Robert Gallo.)

Fun post - and of course Duesberg > Gallo, since Duesberg has contributed, and Gallo is a fraud.

I find the reductionism of oleamide causing 'Italian behavior' to be significantly more extreme than many of the central dogma of biology.

 

[Travis]

Fun post - and of course Duesberg > Gallo, since Duesberg has contributed, and Gallo is a fraud.

I find the reductionism of oleamide causing 'Italian behavior' to be significantly more extreme than many of the central dogma of biology.

How else can one even begin to explain these people?

 

[sladerunner69]

How else can one even begin to explain these people?

Neither Travolta nor Olivia Newton John claim to have Italian ancestry...

And I can name multiple legendary scientific minds from Italy off the top of my mind: Galileo, DaVinci, Petrarch, Lagrange, Grimaldi, Cabot...

Upon further review I can't find any data concerning the number of Italian scientists being "disproportionately small" relative other nationalities... Was this remark founded in data or merely instinctual?

 

[Travis]

Neither Travolta nor Olivia Newton John claim to have Italian ancestry...

Doesn't his name, face, and manner of speech obviously give that away?

'His [Travolta] father was a second-generation Italian American (with roots in Godrano, Sicily).' ―Wiki

'Just don't go busting my balls, Billy, okay?' ―Joe Pesci​

Has John Travolta actually denied being Italian in the past, or are you confabulating things just to be argumentative?

Was this remark founded in data or merely instinctual?

It's founded on freely available and easy-to-find published lists of scientists, as well as memory, yet that remark had obviously been somewhat facetious.

The point is that oleamide has been shown to potentiate three distinct serotonin receptor subtypes at nanomolar concentrations, and with great effect, making this molecule arguably more serotonergic than serotonin itself. It does not antagonize indole ligands yet binds allosterically to an adjacent site. While true that it's powerful sleep promoting effects in rats and cats may not be shared with humans, there is also a good deal of interspecies variation in the distribution of: melatonin receptors, serotonin receptors, and endocannibinoid receptors as well as the respective G proteins they're coupled to. Nonetheless: oleamide can still be expected to potentiate three separate human 5-hydroxytryptophan receptors in nanomolar concentrations, regardless of whether or not they're associated with sleep promoting brain regions.

 

[MrSmart]

The point is that oleamide has been shown to potentiate three distinct serotonin receptor subtypes at nanomolar concentrations, and with great effect, making this molecule arguably more serotonergic than serotonin itself. It does not antagonize indole ligands yet binds allosterically to an adjacent site. While true that it's powerful sleep promoting effects in rats and cats may not be shared with humans, there is also a good deal of interspecies variation in the distribution of: melatonin receptors, serotonin receptors, and endocannibinoid receptors as well as the respective G proteins they're coupled to. Nonetheless: oleamide can still be expected to potentiate three separate human 5-hydroxytryptophan receptors in nanomolar concentrations, regardless of whether or not they're associated with sleep promoting brain regions.

Wouldn't that explain sleep deprivation's effect on depression though?

 

[Wagner83]

I'm not sure I would associate serotonin with joy, libido and dancing, but I don't know much.

How else can one even begin to explain these people?

I had posted this somewhere else.

 

[Travis]

Wouldn't that explain sleep deprivation's effect on depression though?

It could, but the more established effect of melatonin perhaps needs to be considered as well.

Oleamide's discovery sparked a good deal of research in the 1990s, yet after this initial wave it has been mostly ignored. Oleamide has been found to potently-induce sleep in cats, and enzyme studies reveal that it's synthesized using oleic acid and ammonia as substrates. Plasma ammonia concentrations increase after a high protein meal, largely derived from the hydrolysis of primary amino groups, and this could explains the post-meal somnolence observed in cats: Meat provides both substrates of oleamide simultaneously, the most potent sleep-inducer of that suborder. Yet the sleep–wake activity in the cat appears more under dietary influence than humans, a species who's diurnal pattern is primarily regulated by melatonin. Many rodent breeds are nocturnal and found to be low-excretors of melatonin, perhaps making a person wonder if other sleep control mechanisms have evolved in these species. [?] Owls secrete practically no melatonin at night.

Nonetheless: the same serotonin receptors can be found in the human brain where they've been shown to influence behavior; these receptors can be potentiated by nanomolar concentrations of oleamide, a lipid that can cross the blood–brain barrier.

Here are two good ones:

García-Huidobro Toro. "Brain lipids that induce sleep are novel modulators of 5-hydroxytryptamine receptors." Proceedings of the National Academy of Science (1996)

Thomas, Elizabeth. "Unique allosteric regulation of 5-hydroxytryptamine receptor-mediated signal transduction by oleamide." Proceedings of the National Academy of Sciences (1997)​

 

[Travis]

I'm not sure I would associate serotonin with joy, libido and dancing, but I don't know much.

I had posted this somewhere else.

Okay, perhaps John Travolta could have been 'just acting;' but is there any other way to explain Frankie Vallie?

 

[Wagner83]

Okay: Perhaps John Travolta could have been 'just acting,' but is there any other way to explain Frankie Vallie?

Oh my.. This is terrible, and yet slightly better than expected as I had thought he would give us a garage-band, beef tallow (olive oil?) hair-styling and falsetto rendition of Vivaldi' s famous piece. I guess la Mama had to be there and loudly applaud any chance she had.

 

[Wagner83]

Peatarian Reviews: Tocotrienols and red palm oil have more beneficial effects than expected

 

[Arrade]

Is there like a TL;DR of this thread?
@Obi-wan I was interested in Vit E, both tocovit and Ultra E by Thorne’s.
What is the conclusions so far?

 

[Obi-wan]

Is there like a TL;DR of this thread?
@Obi-wan I was interested in Vit E, both tocovit and Ultra E by Thorne’s.
What is the conclusions so far?

IMO high gamma Vit. E mixed Tocopherols in MCT oil and dry e succinate

 

[Arrade]

IMO high gamma Vit. E mixed Tocopherols in MCT oil and dry e succinate

Thanks for the response

 

[Obi-wan]

@Travis can ROS and RNS be a good thing for cancer in killing it? See https://cancerandmetabolism.biomedcentral.com/articles/10.1186/2049-3002-2-17. Maybe I should not be doing any Vit. E...

 

[Travis]

@Travis can ROS and RNS be a good thing for cancer in killing it? See https://cancerandmetabolism.biomedcentral.com/articles/10.1186/2049-3002-2-17. Maybe I should not be doing any Vit. E...

But this kills all cells, right? My justification for taking γ-tocopherol is that it adducts with peroxynitrite and nitrogen dioxide, which are powerful mutagens shown to initiate cancer. There's a considerable amount of evidence for γ-tocopherol preventing cancer, yet it may not be the most effective thing for reversing it. I had just read a considerable amount about sodium, potassium, cell membrane potential, and mitosis. Sodium is actually considered a mitotic growth factor by Clarence Cone—head of the Biochemistry & Biophysics Department at NASA's Langley Research Center—and many others.

Intracellular sodium is seen to spike at a time preceding the dNA replication stage of the cell cycle; intracellular [Na⁺] also corresponds directly the cell membrane potential (Ψ). Graphs of Ψ and cytosolic [Na⁺] vs time are superimposable, and tumor biopsies consistently report elevated intracellular [Na⁺]. Neurons rarely divide, if ever, and have Ψs around −70 mV. Somatic cells range between −40 and −50 mV, and often divide, and carcinoma cells are lower yet: between about −10 and −20 mV.

So how does a monovalent ion do it? The sodium ion does have a higher osmotic potential than potassium, making a person wonder what causes the force to expand the cell membrane. Yet! the ends of telomeres bind sodium and do change their configuration, perhaps unwinding chromosomal ends for dNA duplication. This would jive with Dr. Cone's data proving the [Na⁺] influx directly precedes the synthesis step of the cell cycle.

Sodium, of course, is not always growth factor and is more-or-less harmless when found in the extracellular space. Potassium is sodium's counterion, and is partially responsible for excluding it. From reading these classic studies, and many modern ones, I think any logical person would adjust their diet to achieve a high K⁺/Na⁺ ratio. Most natural foods have ratios between about 7∶1 and 11∶1, yet many Americans consume ratios closer to unity. A person could of course avoid all salt, or alternatively: They could take a few grams of K⁺ per day, perhaps as the iodide/chloride salt or bound to an organic acid—i.e. potassium ascorbate, potassium acetate, potassium citrate.

 

[Obi-wan]

Membrane potential -Wikipedia

is the difference in electric potential between the interior and the exterior of a biological cell. With respect to the exterior of the cell, typical values of membrane potential range from –40 mV to –80 mV.

All animal cells are surrounded by a membrane composed of a lipid bilayer with proteins embedded in it. The membrane serves as both an insulator and a diffusion barrier to the movement of ions. Transmembrane proteins, also known as ion transporter or ion pump proteins, actively push ions across the membrane and establish concentration gradients across the membrane, and ion channels allow ions to move across the membrane down those concentration gradients. Ion pumps and ion channels are electrically equivalent to a set of batteries and resistors inserted in the membrane, and therefore create a voltage between the two sides of the membrane.

Virtually all eukaryotic cells (including cells from animals, plants, and fungi) maintain a non-zero transmembrane potential,[citation needed] usually with a negative voltage in the cell interior as compared to the cell exterior ranging from –40 mV to –80 mV. The membrane potential has two basic functions. First, it allows a cell to function as a battery, providing power to operate a variety of "molecular devices" embedded in the membrane. Second, in electrically excitable cells such as neurons and muscle cells, it is used for transmitting signals between different parts of a cell. Signals are generated by opening or closing of ion channels at one point in the membrane, producing a local change in the membrane potential. This change in the electric field can be quickly affected by either adjacent or more distant ion channels in the membrane. Those ion channels can then open or close as a result of the potential change, reproducing the signal.

In non-excitable cells, and in excitable cells in their baseline states, the membrane potential is held at a relatively stable value, called the resting potential. For neurons, typical values of the resting potential range from –70 to –80 millivolts; that is, the interior of a cell has a negative baseline voltage of a bit less than one-tenth of a volt. The opening and closing of ion channels can induce a departure from the resting potential. This is called a depolarization if the interior voltage becomes less negative (say from –70 mV to –60 mV), or a hyperpolarization if the interior voltage becomes more negative (say from –70 mV to –80 mV). In excitable cells, a sufficiently large depolarization can evoke an action potential, in which the membrane potential changes rapidly and significantly for a short time (on the order of 1 to 100 milliseconds), often reversing its polarity. Action potentials are generated by the activation of certain voltage-gated ion channels.

Resting potential[edit]
When the membrane potential of a cell goes for a long period of time without changing significantly, it is referred to as a resting potential or resting voltage. This term is used for the membrane potential of non-excitable cells, but also for the membrane potential of excitable cells in the absence of excitation. In excitable cells, the other possible states are graded membrane potentials (of variable amplitude), and action potentials, which are large, all-or-nothing rises in membrane potential that usually follow a fixed time course. Excitable cells include neurons, muscle cells, and some secretory cells in glands. Even in other types of cells, however, the membrane voltage can undergo changes in response to environmental or intracellular stimuli. For example, depolarization of the plasma membrane appears to be an important step in programmed cell death.[22]

The interactions that generate the resting potential are modeled by the Goldman equation.[23] This is similar in form to the Nernst equation shown above, in that it is based on the charges of the ions in question, as well as the difference between their inside and outside concentrations. However, it also takes into consideration the relative permeability of the plasma membrane to each ion in question.

The three ions that appear in this equation are potassium (K+), sodium (Na+), and chloride (Cl−). Calcium is omitted, but can be added to deal with situations in which it plays a significant role.[24] Being an anion, the chloride terms are treated differently from the cation terms; the intracellular concentration is in the numerator, and the extracellular concentration in the denominator, which is reversed from the cation terms. Pi stands for the relative permeability of the ion type i.

In essence, the Goldman formula expresses the membrane potential as a weighted average of the reversal potentials for the individual ion types, weighted by permeability. (Although the membrane potential changes about 100 mV during an action potential, the concentrations of ions inside and outside the cell do not change significantly. They remain close to their respective concentrations when then membrane is at resting potential.) In most animal cells, the permeability to potassium is much higher in the resting state than the permeability to sodium. As a consequence, the resting potential is usually close to the potassium reversal potential.[25][26] The permeability to chloride can be high enough to be significant, but, unlike the other ions, chloride is not actively pumped, and therefore equilibrates at a reversal potential very close to the resting potential determined by the other ions.

Values of resting membrane potential in most animal cells usually vary between the potassium reversal potential (usually around -80 mV) and around -40 mV. The resting potential in excitable cells (capable of producing action potentials) is usually near -60 mV—more depolarized voltages would lead to spontaneous generation of action potentials. Immature or undifferentiated cells show highly variable values of resting voltage, usually significantly more positive than in differentiated cells.[27] In such cells, the resting potential value correlates with the degree of differentiation: undifferentiated cells in some cases may not show any transmembrane voltage difference at all.

Maintenance of the resting potential can be metabolically costly for a cell because of its requirement for active pumping of ions to counteract losses due to leakage channels. The cost is highest when the cell function requires an especially depolarized value of membrane voltage.

On the other hand, the high resting potential in undifferentiated cells can be a metabolic advantage. This apparent paradox is resolved by examination of the origin of that resting potential. Little-differentiated cells are characterized by extremely high input resistance,[27] which implies that few leakage channels are present at this stage of cell life. As an apparent result, potassium permeability becomes similar to that for sodium ions, which places resting potential in-between the reversal potentials for sodium and potassium as discussed above. The reduced leakage currents also mean there is little need for active pumping in order to compensate, therefore low metabolic cost.

Graded potentials[edit]
As explained above, the potential at any point in a cell's membrane is determined by the ion concentration differences between the intracellular and extracellular areas, and by the permeability of the membrane to each type of ion. The ion concentrations do not normally change very quickly (with the exception of Ca2+, where the baseline intracellular concentration is so low that even a small influx may increase it by orders of magnitude), but the permeabilities of the ions can change in a fraction of a millisecond, as a result of activation of ligand-gated ion channels. The change in membrane potential can be either large or small, depending on how many ion channels are activated and what type they are, and can be either long or short, depending on the lengths of time that the channels remain open. Changes of this type are referred to as graded potentials, in contrast to action potentials, which have a fixed amplitude and time course.

As can be derived from the Goldman equation shown above, the effect of increasing the permeability of a membrane to a particular type of ion shifts the membrane potential toward the reversal potential for that ion. Thus, opening Na+ channels pulls the membrane potential toward the Na+ reversal potential, which is usually around +100 mV. Likewise, opening K+ channels pulls the membrane potential toward about –90 mV, and opening Cl− channels pulls it toward about –70 mV (resting potential of most membranes). Because –90 to +100 mV is the full operating range of membrane potential, the effect is that Na+ channels always pull the membrane potential up, K+ channels pull it down, and Cl− channels pull it toward the resting potential.

Graded membrane potentials are particularly important in neurons, where they are produced by synapses—a temporary change in membrane potential produced by activation of a synapse by a single graded or action potential is called a postsynaptic potential. Neurotransmitters that act to open Na+ channels typically cause the membrane potential to become more positive, while neurotransmitters that act on K+ channels typically cause it to become more negative.

Whether a postsynaptic potential is considered excitatory or inhibitory depends on the reversal potential for the ions of that current, and the threshold for a cell to fire an action potential (around –50mV). A postsynaptic potential with a reversal potential above threshold, such as a typical Na+ current, is considered excitatory. A potential with a reversal potential below threshold, such as a typical K+ or Cl− current, is considered inhibitory. Even if a current depolarizes a cell, it will inhibit the cell if its reversal potential is below threshold. This is due to the fact that multiple postsynaptic potentials do not have an added effect but average, so a current with a reversal potential above the resting potential, but below threshold, will not contribute to reaching threshold. Thus, neurotransmitters that act to open Na+ channels produce excitatory postsynaptic potentials, or EPSPs, whereas neurotransmitters that act to open K+ or Cl− channels produce inhibitory postsynaptic potentials, or IPSPs. When multiple types of channels are open within the same time period, their postsynaptic potentials summate (add) nonlinearly.

Excitation of a cell pulls sodium into the cell. Continues excitation causes a cell to swell with long term implications of cancer metabolism...what causes continues excitation?

"Somatic cells range between −40 and −50 mV, and often divide, and carcinoma cells are lower yet: between about −10 and −20 mV." -@Travis

But apple cider vinegar in alkaline form has a millivolt charge of over -200 easy. -Ted from Bangkok

"But this kills all cells, right? My justification for taking γ-tocopherol is that it adducts with peroxynitrite and nitrogen dioxide, which are powerful mutagens shown to initiate cancer. There's a considerable amount of evidence for γ-tocopherol preventing cancer, yet it may not be the most effective thing for reversing it." -Travis

From https://cancerandmetabolism.biomedcentral.com/articles/10.1186/2049-3002-2-17

ROS contribute to mitogenic signaling, and thus decreasing intracellular ROS levels is an attractive method for inhibiting cancer growth. With this in mind, several large-scale studies have investigated whether supplementation with antioxidant vitamins, including β-carotene and vitamin A or vitamin E can reduce cancer risk in humans. Contrary to the expected result, supplementation increased the risk of cancer in both cases [96, 97]. In agreement with these results, in genetic mouse models of K-Ras- or B-Raf-induced lung cancer, treatment with NAC or vitamin E markedly enhanced tumor growth and accelerated mortality [98]. These results show that the potential use of antioxidants for cancer therapy is complex and needs to be carefully validated before being applied. One possibility for the failure of these antioxidants as cancer treatments is their lack of specificity. Treatment of patients with general antioxidants may modulate many physiological processes that are relevant to cancer growth. For example, the immune system, an important modulator of cancer growth, has been shown to be sensitive to ROS levels [99]. Another possibility is that general antioxidants are differentially effective than targeted antioxidants. Mitochondrial-targeted versions of antioxidants have been shown to be potent inhibitors of cancer cell growth in vitro and in vivo[69, 100]. Thus, further investigation needs to be considered to determine if targeted antioxidants are a viable method to treat cancer.

Increasing ROS to selectively kill cancer cells
Considering that cancer cells have increased ROS levels, they may be selectively sensitive to the damaging effects of further increasing ROS. Increasing ROS production specifically in cancer cells is likely difficult to accomplish, although it is one proposed mechanism for how many current chemotherapeutics function [108]. Alternatively, since cancer cells frequently have increased expression of antioxidants to maintain homeostasis, a promising therapeutic approach is to inhibit antioxidants to expose cancer cells to endogenously produced ROS [109]. In support of this model, several small molecule screens identifying compounds that specifically inhibit growth of transformed cells have converged upon glutathione utilization [110, 111, 112]. In all cases, treatment with the identified small molecules decreased glutathione levels, increased ROS, and could be rescued by treatment with NAC. In addition, inhibition of antioxidant pathways has also been shown to be effective for inhibiting cancer growth. Genetic knockout of NRF2 inhibited disease progression in mouse models of pancreatic and lung cancer [31, 32]. Inhibition of SOD1 by the small molecule ATN-224 was shown to cause ROS-dependent cancer cell death in vitro and decreased tumor burden in advanced K-Ras-driven lung cancers in vivo[113]. These recent examples provide further proof of principle that increasing ROS, whether by increasing production or inhibiting antioxidants, is a promising approach for targeting cancer cells (Figure 6). Further research is warranted to determine which components of the antioxidant pathway are selectively essential for tumor growth.

Figure 6
Targeting cancer cells by modifying ROS levels. Normal cells have decreased amounts of both ROS and antioxidants relative to cancer cells. Loss of either ROS or antioxidants therefore causes only small changes in ROS homeostasis, leaving cells viable and functional. However, since cancer cells have more ROS and antioxidants, they may be more susceptible to changes in ROS levels. Treatment with antioxidants or prevention of ROS generation will cause cells to lose sufficient ROS signaling to maintain growth. The result is cytostasis and possibly senescence. Alternatively, inhibition of antioxidants or increasing ROS generation will result in excess ROS in cancer cells and cause cancer-specific oxidative cell death.