The Travis Corner

[hang loose]

Hi Travis,

I posted the following already in another thread. Maybe it’s better to ask it here. I am just super curious about more info on acne.
Many other users and readers are interested as well, IMO.

„Thanks for sharing your thoughts and research on acne.
I also found those studies linking acne to an imbalance of Lipids some time ago.
Dr. Peat has said a couple of times that supplementing thyroid and vitamin A (or eating liver on a weekly basis) will (most likely) clear acne.

What are your thoughts on this?
I would be very grateful about your opinion.“

 

[Wagner83]

(4) Wheat is so terrible that it actually has a disease named after it: celiac disease. Everyone knows about this, and it involves immunogenic self‐destruction of enteral crypts through ill‐defined cytokine and prostaglandin mechanisms (but could it be autoantibodies?).
​

Luckily, we only have four foods to worry about. Only A1 cow's milk and soy has been shown to release μ‐opiate peptides, and only wheat and spinach have δ‐exorphins. I think most people would avoid wheat and soy anyway since they are immunogenic, but dairy does have some things going for it. For those people, I would say that goat and sheep cheese certainly have less opiate potential.

Don't you think that a lot of the research has been done to condemn wheat and fuel the whole grains / other grains / gluten-free "propaganda", with many products being possibly terrible for health?

About spinach, what would be the effects to look out for to know if they have a bad effect? From what I remember you eat them yourself and said kale and spinach are "pretty mild".

 

[Travis]

Hi Travis,

I posted the following already in another thread. Maybe it’s better to ask it here. I am just super curious about more info on acne.
Many other users and readers are interested as well, IMO.

„Thanks for sharing your thoughts and research on acne.
I also found those studies linking acne to an imbalance of Lipids some time ago.
Dr. Peat has said a couple of times that supplementing thyroid and vitamin A (or eating liver on a weekly basis) will (most likely) clear acne.

What are your thoughts on this?
I would be very grateful about your opinion.“

I guess the preliminary logic would be dependent on how it influences SREBP and the skin lipids.

I have seen studies showing that it increases skin turnover, roughly twofold. Is this why retinoic acid is used for this condition, just to regenerate skin at a faster rate? (or is there something more to it?)

Goldstein, Jay A. "Comparative effect of isotretinoin and etretinate on acne and sebaceous gland secretion." Journal of the American Academy of Dermatology (1982)​

Here we have a study using two retinoids, and there does appear to be 'something else to it' besides simply skin turnover (i.e. keratin synthesis):

'Isotretinoin has a profound inhibitory effect on sebaceous gland secretion, and this action may be partly or fully responsible for the beneficial clinical response. Similar to the results obtained in the present study, Farrell observed that a dose of 1 mg/kg/day reduced sebaceous gland secretion by almost 70% after only 2 weeks of therapy; this inhibition was seen to increase to 90% after 12 weeks of therapy.' ―Goldstein

'There are morphologic alterations in the glands themselves from isotretinoin administration 12-~ which can be correlated with the marked inhibition of sebaceous gland secretion. [...] Patients treated with isotretinoin (oral dose of 1 to 2 mg/kg/day) manifested a reduction in size of the sebaceous glands of up to 50% after 3 to 4 weeks of treatment, and up to 90% after 12 weeks of treatment.' ―Goldstein​

So it looks like the cis isomer of retinoic acid works, and it likely works mostly by reducing sebum. Although isotretinoin is commonly though of a 'synthetic vitamin A' of sorts, it is actually produced in the body in small amounts (yet it is synthetically produced commercially).

But there is a difference between cis and trans retinoic acid; one binds to the RAR and one to the RXR only. These are the two nuclear retinoic acid receptors, which are also transcription factors. Upon binding ligand, these nuclear‐receptor–transcription‐factors physically interact with DNA itself in the cell's nucleus and can determine which segments are replicated. Details of the nuclear DNA mechanics are murky, but this much is certain. These receptors with the help of retinoic acids change the transcriptome: the quantity and quality of messenger RNA which diffuses out of the nucleus. This mRNA then creates proteins and enzymes which physically catalyze molecular transformations.

'The RARs directly bind all-trans-retinoic acid and as a consequence of this binding become transcriptionally active. The RXRs differ from the RARs in that they are incapable of binding trans-retinoic acid, but they bind and are activated by the 9-cis stereoisomer of retinoic acid (20, 21).' ―Allenby

'The results demonstrate that the RXRs are selective for 9-cis-retinoic acid and 9-cis-dehydroretinoic acid but that the RARs effectively bind and are activated by 9-cis-retinoic acid as well as trans-retinoic acid. These results suggest a role for 9-cis-retinoic acid in the induction of RA target gene responses through RAR, RXR, or RAR-RXR heterodimer pathways.' ―Allenby

click to embiggen: images showing isotretinoin to be weak agonists of RAR and RXR.
​

'Thus, the RXRs demonstrate a striking selectivity for 9-cis isomers...' ―Allenby

'The binding of 9-cis-retinoic acid to RXRs is specific and saturable. Scatchard analyses of the binding of 9-cis-retinoic acid to RXRs α, β, and γ yield Kd values of 15.7, 18.3, and 14.1 nM, respectively. These data indicate that 9-cis-retinoic acid binds with relatively high affinity to all three mouse RXRs. Human RXRa binds 9-cis-retinoic acid with Kd values in the 10 nM range (20, 21).' ―Allenby
​

So the cis isomers are more active since they can activate both receptor forms while the trans isomers can only activate one (RAR). So you might think that isotretinoin (13‐cis) would be the most active, but this is not so. The most active renoic acid appears to be 9‐cis, followed by 11‐cis, and these can be produced in the body from retinol. So not only is isotretinoin relatively more expensive and harder to obtain, it is actually not even a particularly powerful retinoid.

But it does exemplify what can happen with retinoids. Retinoic acid (13‐cis) has been shown to lower sebum production and acne, as you would predict from the IGF‐1 and androgen‐mediated SREBP‐driven sebum viscosity theory. The following quote illustrates that we are on the right track:

'A marked decrease in wax esters, a slight decrease in squalene and a relative increase in cholesterol level have been detected in skin surface lipids [12]. Oral isotretinoin was also shown to decrease the triglyceride fraction, whereas, free sterols and total ceramides were found increased in comedonal lipids [15].' ―Zouboulis ​

But things get tricky, because a relatively weak retinoic acid—as determined by receptor‐binding studies—is actually found to be the most effective. This perhaps makes one wonder if isotretinoin is actually antagonizing natural vitamin A signalling?:

'Tretinoin and 9-cis-retinoic acid have recently been found to be inferior to isotretinoin in sebum suppression [16, 17].' ―Orfanos

'Since isotretinoin has low affinity for nuclear retinoid receptors and cellular retinoic acid-binding proteins [24, 25], it is likely that sebosuppression is not a directly receptor-mediated retinoid effect.' ―Orfanos

'Systemic isotretinoin is today the regimen of choice in severe seborrhoea, since it reduces sebum excretion rates by 75% with daily doses as low as 0.1 mg/kg [28] and by 90% with 0.3–0.5 mg/kg after 4 weeks [17, 31]. No other known agent can influence sebaceous lipids to the same extent.' ―Orfanos

'The second- and third-generation aromatic retinoids did not significantly reduce sebum synthesis in several clinical studies. Etretinate (1 mg/kg/day for 8 weeks) [32], acitretin (0.3–1 mg/kg/day for 6 weeks) and arotinoid ethylester (1 µg/kg/day for 6 weeks) [33], esarotene (100 mg/day for 6 weeks) [23] and temarotene (1 mg to 2 g/day for 8–12 weeks) [34, 35] did not reveal notable sebosuppressive activity.' ―Orfanos

'Isotretinoin is an extremely effective drug if given systemically in severe forms of seborrhoea and acne, being the only retinoid with potent sebostatic properties. Its unique activity on the sebaceous gland still remains unclear since isotretinoin barely binds to cellular retinoic-acid-binding proteins and to retinoic acid receptors.' ―Orfanos

'The molecular basis for its antisebotrophic activity has not been fully elucidated.' ―Orfanos​

So it seems as if Orfanos has noticed this discrepancy with receptor binding as well, and also admits to having no clear idea why 13‐cis retinoic acid and no other can powerfully reduce sebum excretion. Other indications that isotretinoin does not work through the retinoic acid receptors (RXR or RAR) is the fact that these—in tandem with liver X receptors—are actually responsible for transcribing for SREBP‐1, the transcription factor necessary for wax ester and squalene synthesis. Since unsaturated fatty acids have been shown to antagonize liver X receptors (LXRs) and unsaturated fatty acids are structurally similar to cis‐retinoic acid, you might expect that isotretinoin could be antagonizing liver X receptors and working in that manner.

'Sterol regulatory element binding protein-1c (SREBP-1c) (1), also known as ADD-1 (2), is a membrane-bound transcription factor that functions at the interface between sterol and fatty acid metabolism. SREBP-1c enhances fatty acid synthesis by activating the genes encoding acetyl CoA carboxylase, fatty acid synthase (FAS), stearoyl CoA desaturase-1 (SCD-1), and other enzymes (3). The SREBP-1c gene is activated by insulin [and IGF‐1], which helps to explain the classic ability of insulin to enhance the conversion of glucose to fatty acids (4–6). In contrast, mRNA levels for SREBP-1c are decreased when cells are exposed to unsaturated fatty acids, the end products of SREBP-1c action (7–9).' ―Ou​

click to embiggen​

'The current results establish that unsaturated fatty acids can act as competitive antagonists of LXR in cultured rat hepatoma and human HEK-293 cells and in cell-free assays that reflect LXR activation. This antagonism appears to explain, at least partially, the ability of unsaturated fatty acids to lower the levels of mRNA for SREBP-1c (7–9), the transcription of which has been shown to depend on an endogenous LXR ligand (11). The lowered SREBP-1c, in turn, leads to a fall in mRNAs for enzymes responsible for synthesizing unsaturated fatty acids, thus completing a feedback loop.' ―Ou​

This is important, because if isotretinoin is working through a LXR then there is little reason to think that consuming vitamin A would be particularly helpful in acne. I am almost getting the impression that such an idea could merely be the conflation of the two retinoic acid isomers while also assuming that 13‐cis retinoic acid works through same receptors. As already shown, the isotretinoic experts aren't certain of its mechanism of action and express the very same doubts. Since the liver X receptors transcribe for SREBP—which is a prerequisite for acne as far as I am concerned—and this receptor has ligands structurally similar to the retinoids (see above), I would be willing to bet that isotretinoin is an antagonist of a liver X receptor. This also means that you wouldn't much expect retinol to work unless you can be certain that your body will create this one retinoid specifically in high amounts.

Also worth mentioning is the observation of increased serum trigylecerides observed with oral isotretinoin—what you might expect if it were antagonizing a liver X receptor.

'Hyperlipidaemia is one of the most common acute toxicities of systemic isotretinoin, usually occurring more often as increased serum triglycerides (19%) than with cholesterol increase (12%) [51]. The increase in serum triglycerides and cholesterol is proportional to the dosage and usually reverses after discontinuation of treatment.' ―Orfanos

'Treatment of adipocytes and sebocytes with LXR agonists causes a decrease in lipogenesis [18].' ―Cemil​

There seems to be no evidence that vitamin A would even be particularly effective; a person could be better‐off taking zinc.

'The effects of oral zinc sulfate (corresponding to 135 mg of zinc daily) alone and in combination with vitamin A (300,000 international units) daily on acne lesions have been compared with those of vitamin A alone and of a placebo. The number of comedones, papules, pustules, and infiltrates were counted at each visit. After four weeks, there was a significant decrease in the number of papules, pustules, and infiltrates in the zinc-treated groups. The effect of zinc plus vitamin A was not better than zinc alone. After 12 weeks of treatment, the mean acne score had decreased from 100% to 15%. The mechanism for the effect of zinc therapy in acne, to our knowledge, is not presently known.' —Michaëlsson​

The people with acne already consume far more vitamin A than the millions of Africans, Asians, and Islanders without acne. Taking vitamin A for acne could be dangerous, as this is certainly the most dangerous vitamin; being lipid‐soluble, it builds‐up in the liver over time. Concentrations found on autopsy vary considerably, yet the blood levels are kept in a surprisingly tight range. Not only would this be somewhat risky, there is little evidence that it would even work. The idea that vitamin A would work for acne appears to be based simply on the similarity between vitamin A and isotretinoin; though similar in name, the 13‐cis double bond appears to lend it rather different shape and binding characteristics―abrogating the RXR and RAR binding propensity you'd expect from a retinoid while perhaps giving it the ability to antagonize LXR, or perhaps even PPARα.

Orfanos, C. "Oral Retinoids in the Treatment of Seborrhoea and Acne." Dermatology (1998)
Michaëlsson, Gerd "Effects of Oral Zinc and Vitamin A in Acne." Archives of Dermatology (1977)
Goldstein, Jay A. "Comparative effect of isotretinoin and etretinate on acne and sebaceous gland secretion." Journal of the American Academy of Dermatology (1982)
Allenby, Gary. "Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids." Proceedings of the National Academy of Sciences (1993)
Cemil, Bengu Cevirgen. "Effects of isotretinoin on body mass index, serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients." Advances in Dermatology and Allergology (2016)
Yoshikawa, Tomohiro. "Polyunsaturated fatty acids suppress sterol regulatory element-binding protein 1c promoter activity by inhibition of liver X receptor (LXR) binding to LXR response elements." Journal of Biological Chemistry (2002)
Ou, Jiafu "Unsaturated fatty acids inhibit transcription of the sterol regulatory element-binding protein-1c (SREBP-1c) gene by antagonizing ligand-dependent activation of the LXR." Proceedings of the National Academy of Sciences (2001)​

 

[charlie]

The French press is versatile.

Travis, have you seen this?

Filtered Vs Un-filtered Coffee And Cholesterol

 

[Such_Saturation]

Sunflower oil is used for almost all processed foods in Europe, especially now that companies are running away from palm oil. Sunflower oil is basically what canola and rapeseed are in the States.

 

[Diokine]

@Travis

What about retinoic acid signalling and cholinesterease expression? Cholinergic signalling has been shown to involved in sebum production and lipid profiles.

This paper gives evidence for cholinergic influence

Regulation of lipid production by acetylcholine signalling in human sebaceous glands.​

And there is evidence for intimate involvement of retinoic acid and cholinesterase expression and neuronal topography.

Regulation of neuronal differentiation by retinoic acid alone and in cooperation with thyroid hormone or hydrocortisone.​

My hypothesis is that proper activity of retinoic acid is important for proper levels of acetylcholinesterase and this may help to explain efficacy of retinoic acid in acne. I would love to hear any thoughts on the subject.





Retinoic acid in the development, regeneration and maintenance of the nervous system.



Retinoic acid as a therapeutic option in Alzheimer's disease: a focus on cholinergic restoration.

 

[Travis]

Don't you think that a lot of the research has been done to condemn wheat and fuel the whole grains / other grains / gluten-free "propaganda", with many products being possibly terrible for health?

About spinach, what would be the effects to look out for to know if they have a bad effect? From what I remember you eat them yourself and said kale and spinach are "pretty mild".

I was eating spinach because the store stopped selling organic kale; but I am back eating kale because they are selling good kale again. The δ-exorphins in spinach are more mild than the μ-exorphins in soy and milk, and an entire pound of spinach is only about 12‧g of protein. So even though spinach has a confirmed opiate, it is of a weaker type and harder to consume in high amounts (relative to A1 cheese and tofu).

I think if any one food should be condemned it should be wheat. I honestly cannot think of anything worse than many baked products on the shelves. Besides having the most immunogenic food protein, having exorphins, and actually having a disease named it, wheat is very often adulterated with micron-sized iron particles. But it gets worse! because aluminum phosphate double-acting baking powder is used for nothing else; only gluten is sticky enough to rise in the oven, making wheat flour one of the only foods commonly adulterated with aluminum ions.

To make wheat better, a person could find non-adulterated flour and use sourdough fermentation to reduce the size of the immunogenic peptides and exorphins down to more manageable levels. This can and has been done, and wheat can perhaps even be considered 'healthy' with the proper steps taken.

But its easier to just eat potatoes, rice, or corn. I think most people on this forum eat potatoes and rice, which seem to be better choices with less linoleic acid than whole-grain wheat flour and less iron particles than the refined version.

 

[Travis]

Travis, have you seen this?

Filtered Vs Un-filtered Coffee And Cholesterol

Looks like there must be some lipids in the coffee. I am glad that I had read Pauling, or it could be overly worried about cholesterol like some people still are. But this is still important, because cholesterol can probably be considered a plus.

I wonder if it's working through the liver, or through the plasma? I do know that many plants have phytosterols very similar to cholesterol, and perhaps . . . coffee does actually has some cholesterol, perhaps formed upon roasting from a phytosterol:

'Albeit the method is sound and well established, a previous study on the accuracy based on recovery assays from spiked samples was done. Four additions of standard mixtures of the studied sterols were spiked on samples of extracted coffee oils, and then, the analytical method was applied. Average recoveries (in %) for each sterol were calculated therefrom and are presented as follows: cholesterol (106.2%), campesterol (98.0%), campestanol (91.2%), stigmasterol (96.1%), Δ⁷‐campesterol (99.0%), chlerosterol (97.9%), β‐sitosterol (99.7%), sitostanol (93.9%), Δ⁵‐avenasterol (94.6%), Δ⁵˙²⁴‐stigmastadienol (98.5%), Δ⁷‐stigmastenol (98.0%) and Δ⁷‐avenasterol (100.9%). These results show that the analytical procedure can be considered accurate according to the AOAC guidelines.

Data analysis: Twelve sterols have been analysed in the roasted coffee mixtures and considered as chemical descriptors. These sterols will be viewed as follows: cholesterol (COL), campesterol (CPR), campestanol (CPN), stigmasterol (STR), Δ⁷‐campesterol (D7C), chlerosterol (CLE), β‐sitosterol (BSIT), sitostanol (SIT), Δ⁵‐avenasterol (D5), Δ⁵˙²⁴‐stigmastadienol (D524), Δ⁷‐stigmastenol (D7S) and Δ⁷‐avenasterol (D7A). Table 1 shows the content of the sterols found in the analysed blends, indicating the percentage of arabica in each of the mixtures. PCR calculations were made for the compositional analysis of the blends, using the statistical package CSS: STATISTICA from StafsoftTM.' ―Pablos​

​

'The analysis of the sterolic fraction of the oil of roasted coffee blends provides a very useful tool for establishing the percentage of arabica–robusta. D5 is the most adequate chemical descriptor for predicting the arabica–robusta content in coffee samples.' ―Pablos​

It makes me wonder if some of these sterols had actually been measured and simply assumed to be cholesterol. The one existing in highest amounts, sitostanol, is quite similar to cholesterol. It would be interesting to look at the materials & methods section of that article to see if the technique they had used could have made this distinction.

Pablos, F. "Determination of the arabica/robusta composition of roasted coffee according to their sterolic content." Analyst (1999)​

 

[CLASH]

@Travis
As always thanks for your reply and your time/ research, its much appreciated and very helpful. The next question is a bit off topic but what do you think about cane sugar in the diet as a carb source to increase calories?

 

[Travis]

@Travis

What about retinoic acid signalling and cholinesterease expression? Cholinergic signalling has been shown to involved in sebum production and lipid profiles.

This paper gives evidence for cholinergic influence

Regulation of lipid production by acetylcholine signalling in human sebaceous glands.​

And there is evidence for intimate involvement of retinoic acid and cholinesterase expression and neuronal topography.

Regulation of neuronal differentiation by retinoic acid alone and in cooperation with thyroid hormone or hydrocortisone.​

My hypothesis is that proper activity of retinoic acid is important for proper levels of acetylcholinesterase and this may help to explain efficacy of retinoic acid in acne. I would love to hear any thoughts on the subject.





Retinoic acid in the development, regeneration and maintenance of the nervous system.



Retinoic acid as a therapeutic option in Alzheimer's disease: a focus on cholinergic restoration.

This is interesting, because this would provide a direct link between Accutane™ and the psychological problems it has induced in some people. I think I had mentioned earlier that perhaps linking something directly to a neurotransmitter needs no further explanation since neurotransmitters are fundamental and effect psychology on an axiomatic level. I remember reading a study involving Accutane™ and and MRI.. .

' RESULTS: Isotretinoin but not antibiotic treatment was associated with decreased brain metabolism in the orbitofrontal cortex (–21% change versus 2% change for antibiotic), a brain area known to mediate symptoms of depression. There were no differences in the severity of depressive symptoms between the isotretinoin and antibiotic treatment groups before or after treatment.'​

So isotretinoin decreases forebrain metabolism by a full twenty percent; and isn't the frontal cortex the area with the most cholinergic receptors? I think your article on Alzheimer's would tell us:

'Under resting conditions, the brain consumes about 20% of the whole body glucose and the oxygen supply [6,13]. Glucose is almost exclusive energy precursor in the brain, which through glycolytic pathway in cytoplasm is converted to pyruvate.' ―Szutowicz​

'Over 70% of energy produced in neurons is utilized for restoration of their membrane potentials, after depolarization takes place with a frequency of 10–50 Hz' ―Szutowicz​

Depolarization of nerves appears to be caused by acetylcholine. This neurotransmitter can cause muscles to move as it splits in two—discharging a nerve.

​

Microtubules are found inside of nerves surrounded by myelin; this is the only thing I can imagine which could transmit nerve energy, perhaps by tryptophan‐to‐tryptophan Förster resonance energy transfer (tryptophan indoles line the interior of microtubules). The enzyme which dischanges a nerve is presumed to be acetylcholinesterase, or something close, and acetylcholinesterase contacts the choline‐part through a tryptophan:

'Trp84 has been shown to be responsible for the binding of the cationic charge of the substrate in the enzyme active site by chemical modification [39] and site directed mutagenesis [25,37]. The substitution of Trp84 by alanine results in a 3000-fold decrease in the reactivity of human AChE towards acetylthiocholine due to the decrease in the binding affinity, but only has a small effect on the reactivity towards uncharged substrates [25,37]. According to the X-ray structure of AChE the Trp84 side-chain is located in a position spatially suitable for the interaction with the cationic pole of acetylcholine.' ―Tougu​

​

'There is no doubt that Trp84 is the key residue interacting with the cationic ammonium moiety of the substrate and is responsible for the molecular recognition of cationic substrates at least in most cholinesterases [11]. However, it is not a part of catalytic machinery of the enzyme: it contributes neither to the catalytic constant of the substrate hydrolysis nor to the high rate of the hydrolysis of neutral substrates [37,38]. The calculations of the catalytic effect of AChE show [28] that replacement of Trp84 to alanine reduces both the bound state and the transition state energies by 4-5 kcal/mol, which corresponds to the observation that this mutant reduces kII by approximately 3 × 10³ due to lower binding affinity. The role of Trp84 is clearly of entropic nature – it is necessary for bringing the cationic substrates to the close proximity of the catalytic groups of the enzyme and it is not directly involved in the catalysis i.e. in the transformation of chemical bonds.' ―Tougu​

They tryptophan is necessary but this fact doesn't fit into their enzymatic model, which doesn't actually involve an energy transfer. According to them, the splitting of acetylcholine is the main purpose of the enzyme. The hydrolysis of acetylcholine is though by some as a way of 'detoxifying' excessive acetylcholine, keeping the levels in range.

Perhaps acetylcholine could be seen a creating a temporary bridge between two neural circuits, yet quickly splitting in two as to not overload the circuit? The cleavage of a chemical bond does not normally cause nerve transmission; this only happens with acetylcholine in acetylcholine receptors. This is a unique neurotransmitter for this reason.

​

So the brain needs all this glucose so it can create acetyl‐CoA, and this acetyl group forms half of acetylcholine—other half being supplied by membrane lipid phosphotidylcholine, cleaved off by phospholipase D.

'ACh release were observed in cultured hybridoma SN56 cells originating from mouse septum upon their exposition to supraphysiological concentrations of retinoic acid. Those effects were mediated by retinoic acid binding to different RAR and RXR nuclear receptor heterodimer complexes, activating or suppressing broad range of multiple nuclear promoter sites including cholinergic locus [49,53,61,63,65].' ―Szutowicz​

'RA caused morphologic and biochemical differentiation of SH-SY5Y toward morphologically mature neuronal cells with markedly increased cholinergic and noradrenergic/dopaminergic phenotypes and elevations of mRNAs for choline acetyltransferase (6×) and tyrosine hydroxylase (3×).' ―Szutowicz​

'The loss of the cholinergic phenotype is a key feature of AD being associated tightly with deficits of memory and spatial learning [11].' ―Szutowicz​

So this is another reason why isotretinoin should not be seen as 'upregulated vitamin A'—these two molecules seem to have somewhat opposite effects in the brain. I am fairly certain that forebrain metabolism is correlated with cholinergic activity here and that a decrease in forebrain acetylcholine receptors is a consistent finding in dementia. Although aluminum seems almost necessary for neurofibrillary tangles, many people having simple dementia are diagnosed with "Alzheimer's." I think there could be multiple causes for receiving such a diagnosis, including homocysteine and iron.

Since isotretinoin doesn't seem to work on the RAR or RXR receptors, then perhaps it is slowing brain metabolism simply by displacing 9‐cis and all‐trans‐retinoic acid from serum albumin?

The ability of vitamin A to upregulate the cholinergic system seems undeniable, but blood levels are normally kept in a very narrow range. Excessive retinol appears to all go to the liver for storage, and the two‐step synthesis to retinoic acid occurs with multiple feedback mechanisms the entire way. This isn't like taking vitamin C or a B vitamin, where serum levels can increase tenfold, and taking retinol doesn't have much effect on blood levels. But perhaps supplemental retinol it is forced into the tissues anyway—regardless of near‐steady‐state blood levels—simply by creating greater flux?

Szutowicz, Andrzej. "Retinoic acid as a therapeutic option in Alzheimer’s disease: a focus on cholinergic restoration." Expert review of neurotherapeutics (2015)
Tougu, V. "Acetylcholinesterase: mechanism of catalysis and inhibition." Current Medicinal Chemistry-Central Nervous System Agents 1.2 (2001): 155-170.
Bremner, J. Douglas. "Functional brain imaging alterations in acne patients treated with isotretinoin." American Journal of Psychiatry (2005)​

 

[Diokine]

This is interesting, because this would provide a direct link between Accutane™ and the psychological problems it has induced in some people.

Exactly right and I'm thoroughly convinced it plays a major role. A few weeks after I started taking Accutane I developed pretty severe symptoms of OCD.

I've been trying to understand the cholinergic system in context for a bit now, and big pieces are coming together.

So the cholinergic system is involved in memory and learning in the higher brain centers, essentially establishing circuits based on the perceived outcome of events and also predicting outcomes of future events. I think the main reason we do not have any memories of when we are very young is because cholinergic nerve transmission hasn't yet been established, and is also the reason why we build a system of interpreting reality so quickly.

Modeling the cholinergic innervation in the infant cortico-hippocampal system and its contribution to early memory development and attention
​

This establishing of circuits happens in centers controlling metabolism as well. The cholinergic system creates perceptual memory, and also creates physiological memory. Excessive activation and a reduction in feedback into the systems controlling it creates an inability for the body to create new patterns of neural activity which govern moment to moment metabolism. This seems like a very bad thing for a system as complicated as our bodies.

Alzheimer's as a physiological manifestation of learned helplessness?

The enzyme which dischanges a nerve is presumed to be acetylcholinesterase, or something close, and acetylcholinesterase contacts the choline‐part through a tryptophan

'Trp84 has been shown to be responsible for the binding of the cationic charge of the substrate in the enzyme active site by chemical modification [39] and site directed mutagenesis [25,37]. The substitution of Trp84 by alanine results in a 3000-fold decrease in the reactivity of human AChE towards acetylthiocholine due to the decrease in the binding affinity, but only has a small effect on the reactivity towards uncharged substrates [25,37]. According to the X-ray structure of AChE the Trp84 side-chain is located in a position spatially suitable for the interaction with the cationic pole of acetylcholine.' ―Tougu

This connection is so money.


___



Found these links, maybe you'll find something exceptionally interesting?

Acetylcholinesterase

Acetylcholinesterase: Molecular Modeling with the Whole Toolkit

Structure-reactivity Relationships as Probes to Acetylcholinesterase Inhibition Mechanisms by Aryl Carbamates. II. Hammett-Taft Cross-interaction Correlations


​

 

[Koveras]

There seems to be no evidence that vitamin A would even be particularly effective; a person could be better‐off taking zinc.

Kligman, A. M., Mills, O. H., Jr., Leyden, J. J., Gross, P. R., Allen, H. B., & Rudolph, R. I. (1981). Oral vitamin A in acne vulgaris. Preliminary report. Int J Dermatol, 20(4), 278-285.

"Oral vitamin A (retinol) is generally not considered useful in the treatment of acne vulgaris. We conducted a study which showed that retinol was indeed ineffective at the usual doses of 50,000 to 100,000 IU daily. Retinol was highly efficacious in doses of 300,000 units for women and 400,000 to 500,000 units for men, toxicity was slight and limited mainly to skin (xerosis) and mucous membranes (cheilitis). The danger of hypervitaminosis A in this dosage range has been exaggerated. Retinol is a valuable drug for treating stubborn, severely inflammatory acne vulgaris. It is administered until the disease is brought under control, usually within three to four months. Then the dosage is progressively reduced relying on conventional drugs to keep the disease in abeyance."

 

[Travis]

Considering the Amazon reviews for 25,000‧IU tablets, I would would be apprehensive to take even that.

 

[Koveras]

Travis, have you seen this?

Filtered Vs Un-filtered Coffee And Cholesterol

Looks like there must be some lipids in the coffee. I am glad that I had read Pauling, or it could be overly worried about cholesterol like some people still are. But this is still important, because cholesterol can probably be considered a plus.

I wonder if it's working through the liver, or through the plasma? I do know that many plants have phytosterols very similar to cholesterol, and perhaps . . . coffee does actually has some cholesterol, perhaps formed upon roasting from a phytosterol:

'Albeit the method is sound and well established, a previous study on the accuracy based on recovery assays from spiked samples was done. Four additions of standard mixtures of the studied sterols were spiked on samples of extracted coffee oils, and then, the analytical method was applied. Average recoveries (in %) for each sterol were calculated therefrom and are presented as follows: cholesterol (106.2%), campesterol (98.0%), campestanol (91.2%), stigmasterol (96.1%), Δ⁷‐campesterol (99.0%), chlerosterol (97.9%), β‐sitosterol (99.7%), sitostanol (93.9%), Δ⁵‐avenasterol (94.6%), Δ⁵˙²⁴‐stigmastadienol (98.5%), Δ⁷‐stigmastenol (98.0%) and Δ⁷‐avenasterol (100.9%). These results show that the analytical procedure can be considered accurate according to the AOAC guidelines.

Data analysis: Twelve sterols have been analysed in the roasted coffee mixtures and considered as chemical descriptors. These sterols will be viewed as follows: cholesterol (COL), campesterol (CPR), campestanol (CPN), stigmasterol (STR), Δ⁷‐campesterol (D7C), chlerosterol (CLE), β‐sitosterol (BSIT), sitostanol (SIT), Δ⁵‐avenasterol (D5), Δ⁵˙²⁴‐stigmastadienol (D524), Δ⁷‐stigmastenol (D7S) and Δ⁷‐avenasterol (D7A). Table 1 shows the content of the sterols found in the analysed blends, indicating the percentage of arabica in each of the mixtures. PCR calculations were made for the compositional analysis of the blends, using the statistical package CSS: STATISTICA from StafsoftTM.' ―Pablos​

View attachment 8082​

'The analysis of the sterolic fraction of the oil of roasted coffee blends provides a very useful tool for establishing the percentage of arabica–robusta. D5 is the most adequate chemical descriptor for predicting the arabica–robusta content in coffee samples.' ―Pablos​

It makes me wonder if some of these sterols had actually been measured and simply assumed to be cholesterol. The one existing in highest amounts, sitostanol, is quite similar to cholesterol. It would be interesting to look at the materials & methods section of that article to see if the technique they had used could have made this distinction.

Pablos, F. "Determination of the arabica/robusta composition of roasted coffee according to their sterolic content." Analyst (1999)​

I wrote something about this awhile back

Italian-style coffee could halve the risk of prostate cancer

"They prepare coffee [the] rigorously Italian way: high pressure, very high water temperature, and with no filters,"

Pounis, G., Tabolacci, C., Costanzo, S., Cordella, M., Bonaccio, M., Rago, L., . . . Moli-sani study, i. (2017). Reduction by coffee consumption of prostate cancer risk: Evidence from the Moli-sani cohort and cellular models. Int J Cancer, 141(1), 72-82. doi:10.1002/ijc.30720​

Cholesterol/Unfiltered

De Roos, B., Van Tol, A., Urgert, R., Scheek, L. M., Van Gent, T., Buytenhek, R., . . . Katan, M. B. (2000). Consumption of French-press coffee raises cholesteryl ester transfer protein activity levels before LDL cholesterol in normolipidaemic subjects. J Intern Med, 248(3), 211-216.

Moeenfard, M., Erny, G. L., & Alves, A. (2016). Variability of some diterpene esters in coffee beverages as influenced by brewing procedures. J Food Sci Technol, 53(11), 3916-3927. doi:10.1007/s13197-016-2378-6

Naidoo, N., Chen, C., Rebello, S. A., Speer, K., Tai, E. S., Lee, J., . . . van Dam, R. M. (2011). Cholesterol-raising diterpenes in types of coffee commonly consumed in Singapore, Indonesia and India and associations with blood lipids: a survey and cross sectional study. Nutr J, 10, 48. doi:10.1186/1475-2891-10-48
​

Cafestol and Kahweol are interesting for a number of reasons... such as protection against cancer

Cardenas, C., Quesada, A. R., & Medina, M. A. (2014). Insights on the antitumor effects of kahweol on human breast cancer: decreased survival and increased production of reactive oxygen species and cytotoxicity. Biochem Biophys Res Commun, 447(3), 452-458. doi:10.1016/j.bbrc.2014.04.026
Cavin, C., Holzhaeuser, D., Scharf, G., Constable, A., Huber, W. W., & Schilter, B. (2002). Cafestol and kahweol, two coffee specific diterpenes with anticarcinogenic activity. Food Chem Toxicol, 40(8), 1155-1163.
Chae, J. I., Jeon, Y. J., & Shim, J. H. (2014). Anti-proliferative properties of kahweol in oral squamous cancer through the regulation specificity protein 1. Phytother Res, 28(12), 1879-1886. doi:10.1002/ptr.5217
Choi, D. W., Lim, M. S., Lee, J. W., Chun, W., Lee, S. H., Nam, Y. H., . . . Park, S. C. (2015). The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression. Biomol Ther (Seoul), 23(2), 128-133. doi:10.4062/biomolther.2014.133
Choi, M. J., Park, E. J., Oh, J. H., Min, K. J., Yang, E. S., Kim, Y. H., . . . Kwon, T. K. (2011). Cafestol, a coffee-specific diterpene, induces apoptosis in renal carcinoma Caki cells through down-regulation of anti-apoptotic proteins and Akt phosphorylation. Chem Biol Interact, 190(2-3), 102-108. doi:10.1016/j.cbi.2011.02.013
Hammons, G. J., Fletcher, J. V., Stepps, K. R., Smith, E. A., Balentine, D. A., Harbowy, M. E., & Kadlubar, F. F. (1999). Effects of chemoprotective agents on the metabolic activation of the carcinogenic arylamines PhIP and 4-aminobiphenyl in human and rat liver microsomes. Nutr Cancer, 33(1), 46-52. doi:10.1080/01635589909514747
Higgins, L. G., Cavin, C., Itoh, K., Yamamoto, M., & Hayes, J. D. (2008). Induction of cancer chemopreventive enzymes by coffee is mediated by transcription factor Nrf2. Evidence that the coffee-specific diterpenes cafestol and kahweol confer protection against acrolein. Toxicol Appl Pharmacol, 226(3), 328-337. doi:10.1016/j.taap.2007.09.018
Huber, W. W., McDaniel, L. P., Kaderlik, K. R., Teitel, C. H., Lang, N. P., & Kadlubar, F. F. (1997). Chemoprotection against the formation of colon DNA adducts from the food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the rat. Mutat Res, 376(1-2), 115-122.
Huber, W. W., & Parzefall, W. (2005). Modification of N-acetyltransferases and glutathione S-transferases by coffee components: possible relevance for cancer risk. Methods Enzymol, 401, 307-341. doi:10.1016/S0076-6879(05)01020-7
Huber, W. W., Prustomersky, S., Delbanco, E., Uhl, M., Scharf, G., Turesky, R. J., . . . Schulte-Hermann, R. (2002). Enhancement of the chemoprotective enzymes glucuronosyl transferase and glutathione transferase in specific organs of the rat by the coffee components kahweol and cafestol. Arch Toxicol, 76(4), 209-217. doi:10.1007/s00204-002-0322-1
Huber, W. W., Rossmanith, W., Grusch, M., Haslinger, E., Prustomersky, S., Peter-Vorosmarty, B., . . . Schulte-Hermann, R. (2008). Effects of coffee and its chemopreventive components kahweol and cafestol on cytochrome P450 and sulfotransferase in rat liver. Food Chem Toxicol, 46(4), 1230-1238. doi:10.1016/j.fct.2007.09.094
Huber, W. W., Scharf, G., Nagel, G., Prustomersky, S., Schulte-Hermann, R., & Kaina, B. (2003). Coffee and its chemopreventive components Kahweol and Cafestol increase the activity of O6-methylguanine-DNA methyltransferase in rat liver--comparison with phase II xenobiotic metabolism. Mutat Res, 522(1-2), 57-68.
Huber, W. W., Scharf, G., Rossmanith, W., Prustomersky, S., Grasl-Kraupp, B., Peter, B., . . . Schulte-Hermann, R. (2002). The coffee components kahweol and cafestol induce gamma-glutamylcysteine synthetase, the rate limiting enzyme of chemoprotective glutathione synthesis, in several organs of the rat. Arch Toxicol, 75(11-12), 685-694.
Huber, W. W., Teitel, C. H., Coles, B. F., King, R. S., Wiese, F. W., Kaderlik, K. R., . . . Kadlubar, F. F. (2004). Potential chemoprotective effects of the coffee components kahweol and cafestol palmitates via modification of hepatic N-acetyltransferase and glutathione S-transferase activities. Environ Mol Mutagen, 44(4), 265-276. doi:10.1002/em.20052
Jeon, Y. J., Bang, W., Cho, J. H., Lee, R. H., Kim, S. H., Kim, M. S., . . . Chae, J. I. (2016). Kahweol induces apoptosis by suppressing BTF3 expression through the ERK signaling pathway in non-small cell lung cancer cells. Int J Oncol, 49(6), 2294-2302. doi:10.3892/ijo.2016.3727
Kim, H. G., Hwang, Y. P., & Jeong, H. G. (2009). Kahweol blocks STAT3 phosphorylation and induces apoptosis in human lung adenocarcinoma A549 cells. Toxicol Lett, 187(1), 28-34. doi:10.1016/j.toxlet.2009.01.022
Kotowski, U., Heiduschka, G., Seemann, R., Eckl-Dorna, J., Schmid, R., Kranebitter, V., . . . Thurnher, D. (2015). Effect of the coffee ingredient cafestol on head and neck squamous cell carcinoma cell lines. Strahlenther Onkol, 191(6), 511-517. doi:10.1007/s00066-014-0807-x
Lee, K. A., Chae, J. I., & Shim, J. H. (2012). Natural diterpenes from coffee, cafestol and kahweol induce apoptosis through regulation of specificity protein 1 expression in human malignant pleural mesothelioma. J Biomed Sci, 19, 60. doi:10.1186/1423-0127-19-60
Lima, C. S., Spindola, D. G., Bechara, A., Garcia, D. M., Palmeira-Dos-Santos, C., Peixoto-da-Silva, J., . . . Bincoletto, C. (2017). Cafestol, a diterpene molecule found in coffee, induces leukemia cell death. Biomed Pharmacother, 92, 1045-1054. doi:10.1016/j.biopha.2017.05.109
Miller, E. G., Formby, W. A., Rivera-Hidalgo, F., & Wright, J. M. (1988). Inhibition of hamster buccal pouch carcinogenesis by green coffee beans. Oral Surg Oral Med Oral Pathol, 65(6), 745-749.
Miller, E. G., McWhorter, K., Rivera-Hidalgo, F., Wright, J. M., Hirsbrunner, P., & Sunahara, G. I. (1991). Kahweol and cafestol: inhibitors of hamster buccal pouch carcinogenesis. Nutr Cancer, 15(1), 41-46. doi:10.1080/01635589109514110
Moeenfard, M., Cortez, A., Machado, V., Costa, R., Luis, C., Coelho, P., . . . Santos, A. (2016). Anti-Angiogenic Properties of Cafestol and Kahweol Palmitate Diterpene Esters. J Cell Biochem, 117(12), 2748-2756. doi:10.1002/jcb.25573
Neuwirthova, J., Gal, B., Smilek, P., & Urbankova, P. (2017). [Coffee in Cancer Chemoprevention]. Klin Onkol, 30(2), 106-114. doi:doi: 10.14735/amko2017106
Oh, J. H., Lee, J. T., Yang, E. S., Chang, J. S., Lee, D. S., Kim, S. H., . . . Kwon, T. K. (2009). The coffee diterpene kahweol induces apoptosis in human leukemia U937 cells through down-regulation of Akt phosphorylation and activation of JNK. Apoptosis, 14(11), 1378-1386. doi:10.1007/s10495-009-0407-x
Park, G. H., Song, H. M., & Jeong, J. B. (2016). The coffee diterpene kahweol suppresses the cell proliferation by inducing cyclin D1 proteasomal degradation via ERK1/2, JNK and GKS3beta-dependent threonine-286 phosphorylation in human colorectal cancer cells. Food Chem Toxicol, 95, 142-148. doi:10.1016/j.fct.2016.07.008
Park, G. H., Song, H. M., & Jeong, J. B. (2017). Kahweol from Coffee Induces Apoptosis by Upregulating Activating Transcription Factor 3 in Human Colorectal Cancer Cells. Biomol Ther (Seoul), 25(3), 337-343. doi:10.4062/biomolther.2016.114
Pounis, G., Tabolacci, C., Costanzo, S., Cordella, M., Bonaccio, M., Rago, L., . . . Moli-sani study, i. (2017). Reduction by coffee consumption of prostate cancer risk: Evidence from the Moli-sani cohort and cellular models. Int J Cancer, 141(1), 72-82. doi:10.1002/ijc.30720
Scharf, G., Prustomersky, S., Knasmuller, S., Schulte-Hermann, R., & Huber, W. W. (2003). Enhancement of glutathione and g-glutamylcysteine synthetase, the rate limiting enzyme of glutathione synthesis, by chemoprotective plant-derived food and beverage components in the human hepatoma cell line HepG2. Nutr Cancer, 45(1), 74-83. doi:10.1207/S15327914NC4501_9
Schilter, B., Perrin, I., Cavin, C., & Huggett, A. C. (1996). Placental glutathione S-transferase (GST-P) induction as a potential mechanism for the anti-carcinogenic effect of the coffee-specific components cafestol and kahweol. Carcinogenesis, 17(11), 2377-2384.
Steinkellner, H., Hoelzl, C., Uhl, M., Cavin, C., Haidinger, G., Gsur, A., . . . Knasmuller, S. (2005). Coffee consumption induces GSTP in plasma and protects lymphocytes against (+/-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide induced DNA-damage: results of controlled human intervention trials. Mutat Res, 591(1-2), 264-275. doi:10.1016/j.mrfmmm.2005.04.016
Tao, K. S., Wang, W., Wang, L., Cao, D. Y., Li, Y. Q., Wu, S. X., & Dou, K. F. (2008). The multifaceted mechanisms for coffee's anti-tumorigenic effect on liver. Med Hypotheses, 71(5), 730-736. doi:10.1016/j.mehy.2008.06.026
Um, H. J., Oh, J. H., Kim, Y. N., Choi, Y. H., Kim, S. H., Park, J. W., & Kwon, T. K. (2010). The coffee diterpene kahweol sensitizes TRAIL-induced apoptosis in renal carcinoma Caki cells through down-regulation of Bcl-2 and c-FLIP. Chem Biol Interact, 186(1), 36-42. doi:10.1016/j.cbi.2010.04.013
Um, H. J., Park, J. W., & Kwon, T. K. (2011). Melatonin sensitizes Caki renal cancer cells to kahweol-induced apoptosis through CHOP-mediated up-regulation of PUMA. J Pineal Res, 50(4), 359-366. doi:10.1111/j.1600-079X.2010.00851.x
Wang, S., Yoon, Y. C., Sung, M. J., Hur, H. J., & Park, J. H. (2012). Antiangiogenic properties of cafestol, a coffee diterpene, in human umbilical vein endothelial cells. Biochem Biophys Res Commun, 421(3), 567-571. doi:10.1016/j.bbrc.2012.04.046
Wattenberg, L. W. (1983). Inhibition of neoplasia by minor dietary constituents. Cancer Res, 43(5 Suppl), 2448s-2453s.
Wattenberg, L. W., Hanley, A. B., Barany, G., Sparnins, V. L., Lam, L. K., & Fenwick, G. R. (1985). Inhibition of carcinogenesis by some minor dietary constituents. Princess Takamatsu Symp, 16, 193-203.
Woo, S. M., Min, K. J., Seo, B. R., Nam, J. O., Choi, K. S., Yoo, Y. H., & Kwon, T. K. (2014). Cafestol overcomes ABT-737 resistance in Mcl-1-overexpressed renal carcinoma Caki cells through downregulation of Mcl-1 expression and upregulation of Bim expression. Cell Death Dis, 5, e1514. doi:10.1038/cddis.2014.472
Yew, Y. W., Lai, Y. C., & Schwartz, R. A. (2016). Coffee Consumption and Melanoma: A Systematic Review and Meta-Analysis of Observational Studies. Am J Clin Dermatol, 17(2), 113-123. doi:10.1007/s40257-015-0165-1​

 

[Koveras]

Considering the Amazon reviews for 25,000‧IU tablets, I would would be apprehensive to take even that.

I was digging into vitamin A toxicity a bit as well.

Vitamin E seems to lower the risk to the liver (via reduction in lipid peroxidation)

Vitamin D seems to lower the risk to the bone and general toxicity

Certainly wouldn't be playing around with massive doses unless there was a really clear indication for it.

None the less

The “Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc” (Institute of Medicine (US) Panel on Micronutrients, 2001) states "Chronic toxicity is usually associated with ingestion of large doses greater than or equal to 30,000 μg/day for months or years. Both acute and chronic vitamin A toxicity are associated with increased plasma retinyl ester concentrations (Krasinski et al., 1989; Ross, 1999).”​

30,000 μg/day = 100,000 IU/day ("for months or years")

Digging a bit deeper the Krasinski reference states

"For elderly people, greater fasting plasma retinyl esters were associated with long-term vitamin A supplement use (greater than 5 y) and biochemical evidence of liver damage.​

Krasinski, S. D., Russell, R. M., Otradovec, C. L., Sadowski, J. A., Hartz, S. C., Jacob, R. A., & McGandy, R. B. (1989). Relationship of vitamin A and vitamin E intake to fasting plasma retinol, retinol-binding protein, retinyl esters, carotene, alpha-tocopherol, and cholesterol among elderly people and young adults: increased plasma retinyl esters among vitamin A-supplement users. Am J Clin Nutr, 49(1), 112-120.

"Because of the accumulation of retinoids in the liver, chronic toxicity can arise at intake levels much lower than those causing acute toxicity. The duration of intake is crucial, and chronic toxicity occurs after months or years of increased consumption (139). The lowest dose causing chronic hypervitaminosis A in humans is not known. It usually appears at doses of 100,000 IU (>30 times RDI) per day and above (81), but has been reported at intake levels as low as 25,000-50,000 IU daily (141-143). The suggested threshold dose for teratogenicity is 3 mg or 10,000 IU per day (144). Vitamin A in water-miscible, emulsified and solid forms are more toxic than oil-based preparations or retinol in liver, and result in higher peak plasma values, higher liver concentrations and lower fecal losses (145).

"In vivo, a high level of vitamin A intake has been shown to reduce the toxicity associated with hypervitaminosis D in the rat (193) and the turkey poult (194) and to increase the need for dietary vitamin D in the chicken (195) and the poult (194). Hypervitaminosis D similarly diminishes vitamin A toxicity symptoms, such as reduced bone ash, in the chicken (196). In rats, an antagonistic relationship has been demonstrated in bone and intestine by Rohde et al 1999 (197). The possible interaction between vitamin A and D in man had not been investigated when this project was initiated. In 2003, a review of all hitherto published case reports of vitamin A intoxication found that the mean dose causing chronic toxicity was lower for patients taking vitamin A only, compared to patients taking supplements containing both vitamin A and vitamin D (145). This finding is in agreement with competi- tive antagonism between the vitamins."​

Johansson, S. (2004). Vitamin A and osteoporosis: experimental and Clinical Studies. Acta Universitatis Upsaliensis,

"Retinol was taken together with vitamin D or alone in 39 and 42 chronic cases, respectively (Table 1). Vitamin D appears to protect against retinol toxicity because the median dose was significantly higher when the vitamins were combined (0.7 mg/kg; P 0.020; 95% CI: 0.082, 1.56 mg/kg). The effect of vitamin D was independent of the physical form of the sup- plement. Of the subjects who took retinol together with vitamin D, 13 took oil-based preparations, 8 took water-miscible or emulsified preparations, and 18 took preparations for which the form was unknown. For subjects who did not take vitamin D preparations in combination with retinol, 1 subject took an oil-based preparation, 5 subjects took water-miscible or emul- sified preparations, 2 subjects took solid tablets, and 34 sub- jects took preparations for which the form was unknown."​

Myhre, A. M., Carlsen, M. H., Bohn, S. K., Wold, H. L., Laake, P., & Blomhoff, R. (2003). Water-miscible, emulsified, and solid forms of retinol supplements are more toxic than oil-based preparations. Am J Clin Nutr, 78(6), 1152-1159.

 

[Obi-wan]

Hey Travis,

You can click on any of the foods that are in my linoleic list above to get a complete breakdown of their fats, etc. For example a cashew is:
Stearic 3.22g
Linoleic 7.48g
Threoine . .69g

Thoughts...

 

[Obi-wan]

The French Press seems to be the new "in" in coffee preparation. Our small town coffee shop now offers it. Thanks for the info Koveras. I see you put in bold "and no filters"

 

[Obi-wan]

The fatty acid composition of the egg fat corresponded with that of the diets: groundnut feeding produced a high oleic acid content of the eggs, soya bean feeding resulted in a high level of linoleic acid and linseed feeding raised the level of α-linolenic acid. Incorporation of groundnut versus linseed into the diet raised the arachidonic acid content of the eggs. Feeding the linseed diet produced higher contents of eicosapentaenoic and docosahexaenoic acid. The three experimental diets did not differently influence the cholesterol and fat contents of the eggs, but linseed versus soya bean significantly reduced egg weight by on average 3.4%. - Science Direct

What's in your egg?

 

[Wagner83]

Travis, have you seen this?

Filtered Vs Un-filtered Coffee And Cholesterol

Cafestol and Kahweol are interesting for a number of reasons... such as protection against cancer

...​

In addition to those above:

Cafestol Increases Serum Cholesterol Levels in Apolipoprotein E*3-Leiden Transgenic Mice by Suppression of Bile Acid Synthesis

In conclusion, cafestol increases serum cholesterol levels in apoE*3-Leiden mice by suppression of the major regulatory enzymes in the bile acid synthesis pathways, leading to decreased LDLR mRNA levels and increased secretion of hepatic cholesterol esters. We suggest that suppression of bile acid synthesis may provide an explanation for the cholesterol-raising effect of cafestol in humans.
​

Coffee Consumption and Serum Lipids: A Meta-Analysis of Randomized Controlled Clinical Trials | American Journal of Epidemiology | Oxford Academic

The lipid-raising effects of coffee drinking have been reported to be primarily due to coffee oils, such as cafestol and kahweol (12, 13), that increase the synthesis of cholesterol by decreasing excretion of bile acids and neutral sterols (48).
​

Here is a source of 48: COLON CANCER AND BLOOD-CHOLESTEROL - ScienceDirect
Those guys think the same, less bile acid synthesis, less colon cancer, more cholesterol Coffee, cholesterol, and colon cancer: is there a link.

 

[Travis]

Hey Travis,

You can click on any of the foods that are in my linoleic list above to get a complete breakdown of their fats, etc. For example a cashew is:
Stearic 3.22g
Linoleic 7.48g
Threoine . .69g

Thoughts...

That's quite the list; I hadn't realized that these were 'clickable,' with more details forthcoming upon clicking.

Someone needs to make a Fernstrom calculator, which calculates the tryptophan/Σ(CAA) ratio for every food. This is the best measure for brain serotonin synthesis.