Alzheimer’s Disease: Is A Dysfunctional Mevalonate Biosynthetic Pathway The Master-Inducer Of Delete

[yerrag]

It’s not a study, it’s a publication. And yes, de Loof admits he doesn’t know farnesols exact role and action - only that he thinks it could be very important in human physiology too.

Sorry, it's a publication.

I have to read the abstract and the discussion/conclusion again as I had difficulty understanding the abstract. The use of double negatives is making it hard and I get the impression that the abstract is intending to say "is" and then writing "is not."

It says:

A dysfunctional mevalonate biosynthetic pathway, with farnesol at its very heart, can disturb “Golgicrine” activity, reduce mitochondrial multiplication, alter Ca2+ homeostasis, and cause massive apoptosis in specific tissues.

So dysfunctional mevalonate biosynthetic pathway = massive apoptosis

Then it says:

It became undeniably established that the absence of endogenous sesquiterpenoids farnesol and its JH esters is the direct inducer of complete metamorphosis.

So, the absence of farnesol(endogenous) = complete metamorphosis

It says:

In insects, the administration of farnesol/JH temporarily prevents all mentioned changes

Meaning that farnesol = prevention of metamorphosis (is this what all mentioned changes mean?)

It then says:

The absence of farnesol/JH was not observed in insects with incomplete metamorphosis; hence, there is no massive apoptosis.

Which means: Farnesol = incomplete metamorphosis, yet there is a contradiction : there is incomplete metamorphosis, yet there no apoptosis.

This paper is poorly proofed and edited.

In the end, I just have to make sense of it it. Luckily this makes sense:

Neither do vertebrates have a period in their development in which the mevalonate biosynthetic pathway—that synthesizes farnesyl pyrophosphate, farnesol, and cholesterol— comes to a complete halt. Hence, there exists a difficulty in uncovering the other functions of farnesol, besides being an intermediate in the mevalonate pathway.

So, in conclusion, I now understand what the author is trying to convey. That farnesol is producted in a functioning mevalonate pathway, and that it may play a key role in the prevention of AD. And why it does so is because it keeps the cell from being filled with calcium.

 

[Tristan Loscha]

Farnesol - Wikipedia

Among other interesting tidbits in the article, this one caught my eyeball.

"In a 1994 report released by five top cigarette companies, farnesol was listed as one of 599 additives to cigarettes.[1] It is a flavoring ingredient."

Seems like I remember reading that smokers rarely get AD. Is that correct?

Smokers have increased incidence and severity and shortened time to onset of disease. Smokers have slightly reduced incidence of Parkinsons Disease though.

 

[LeeLemonoil]

@yerrag

De Loofs English isn’t very good, I had mail-contact with him once. Those postulation-publications usually are indeed poorly edited and proof read.

Nontheless, De Loof‘s stuff is very interesting, especially since he is an „outsider“ to human life sciences but prolific in evolutionary theory, where he is critical to neo-Darwinism.

@Diokine
Exactly. This entire field is mind-blowing, so little really understood but so much „thinkable“ - a huge field that plays a major role in physiology and amends canonical functional knowledge.

 

[Juniper]

A great study, which both highlights the dangers of statins while also providing a plausible mechanism for those side effects that both FDA and Big Pharma vehemently continue to dispute. This plausible mechanism involves the inhibition of vitamin K2 (MK-4) synthesis, which requires the same enzymes that synthesize cholesterol. As the authors themselves state, vitamin K is crucial for proper glucose metabolism. One of the key roles of vitamin K is as a co-factor for the synthesis of osteocalcin and it is the latter that is a powerful regulator of both insulin as well as gonadal steroid synthesis, both of which heavily influence glucose homeostasis. Perhaps studies like this will finally convince the FDA to get off of its high horse and admit that vitamin K is not just some puny vitamin used clinically by "an obscure Asian country" but rather a powerful regulator of systemic health.

Statin use is associated with insulin resistance in participants of the Canadian Multicentre Osteoporosis Study
Statin use may lead to ‘unintended consequence’ of insulin resistance

"...A cohort of Canadian adults prescribed statins, and hydrophilic statins, in particular, had higher levels of insulin resistance compared with non-statin users, according to findings published in the Journal of the Endocrine Society. “There is emerging data to suggest that by inhibiting the production of intermediates of cholesterol biosynthesis, statins also inhibit the mevalonate pathway and impede the production of vitamin K2 in peripheral tissues,” Rachel M. Holden, MD, a nephrologist and associate professor in the department of medicine at Queen’s University in Kingston, Ontario, Canada, and colleagues wrote in the study background. “There is growing evidence to suggest that vitamin K2 plays a key role in glucose homeostasis as well as vascular calcification. On this background, we hypothesized that statin use would be associated with both insulin resistance and vascular calcification in community-dwelling participants of a large longitudinal study of osteoporosis.”

"...“Statins, widely prescribed drugs to lower cholesterol, may have unintended consequences related to glucose homeostasis that could be relevant in healthy aging,” the researchers wrote. “In those individuals with risk factors for diabetes, consideration for choosing non-lipophilic statins and avoidance of rosuvastatin and lipophilic statins may provide the intended cardiovascular protection without the increased incidence of insulin resistance.”

Was reading through this thread and saw the mevalonate pathway mentioned in a study Hiadut posted a few weeks ago! What caught my eye was the following:

“statins also inhibit the mevalonate pathway and impede the production of vitamin K2 in peripheral tissues...”

 

[Drareg]

Could explain why smokers are more immune to COVID-19? @Drareg

It’s in the lancet study on covid mortality, smokers less likely to die.

The mechanism isn’t explained in the study buts it’s clearly the nicotine acting similarly to niacinamide/nicotinamide.

 

[yerrag]

It’s in the lancet study on covid mortality, smokers less likely to die.

The mechanism isn’t explained in the study buts it’s clearly the nicotine acting similarly to niacinamide/nicotinamide.

@GAF @yerrag
Please keep this thread updated with your findings farnesol and citronella

I wouldn’t use citronella oil excessively topically, there ain’t much farnesol in it

Bummer. Guess I'll have to order the farnesol then from Amazon.

It’s in the lancet study on covid mortality, smokers less likely to die.

The mechanism isn’t explained in the study buts it’s clearly the nicotine acting similarly to niacinamide/nicotinamide.

But farnesol may have a role, as it's used as an additive in cigarettes.

 

[Drareg]

Bummer. Guess I'll have to order the farnesol then from Amazon.

But farnesol may have a role, as it's used as an additive in cigarettes.

I don’t know about farnesol , I haven’t read through the thread.
That’s why it’s safer to use niacinamide , longer half life also.

I think once the structure of the Alzheimer’s brain is damaged you need to be careful what you try on people, the brain starts to break down, speeding things up too quick once it’s advanced could be uncomfortable for the patient.

 

[yerrag]

I don’t know about farnesol , I haven’t read through the thread.
That’s why it’s safer to use niacinamide , longer half life also.

I think once the structure of the Alzheimer’s brain is damaged you need to be careful what you try on people, the brain starts to break down, speeding things up too quick once it’s advanced could be uncomfortable for the patient.

It's just the post I shared with you from GAF. It mentions the anti-inflammatory effect of farnesol, and that it's used as an additive in making cigarettes. That it is used in cigarettes and that smoking is correlated with better survival outcomes in COVID may have to do with farnesol just as it may have to do with niacinamide. So I'm passing to you as you posted about smoking and COVID in another thread. So if you take any interest, that's up to you.

 

[Drareg]

It's just the post I shared with you from GAF. It mentions the anti-inflammatory effect of farnesol, and that it's used as an additive in making cigarettes. That it is used in cigarettes and that smoking is correlated with better survival outcomes in COVID may have to do with farnesol just as it may have to do with niacinamide. So I'm passing to you as you posted about smoking and COVID in another thread. So if you take any interest, that's up to you.

Interesting ,could be multiple factors, don’t cigarettes contain mao inhibitors also?

 

[yerrag]

Interesting ,could be multiple factors, don’t cigarettes contain mao inhibitors also?

That I'm not aware of.

 

[yerrag]

The supplier of farnesol in Amazon doesn't charge for shipping when you order direct from them.

www.consoludated-chemical.com

Funny, it makes up for it by tacking the shipping onto the price lol.

 

[High_Prob]

It's just the post I shared with you from GAF. It mentions the anti-inflammatory effect of farnesol, and that it's used as an additive in making cigarettes. That it is used in cigarettes and that smoking is correlated with better survival outcomes in COVID may have to do with farnesol just as it may have to do with niacinamide. So I'm passing to you as you posted about smoking and COVID in another thread. So if you take any interest, that's up to you.

Wait, does tobacco have niacin (anamide) in it?

Niacin

‘The term ‘niacin’ is often used to refer to nicotinic acid (pyridine-3-carboxylic acid) only, although other vitamers with a pyridine ring, including nicotinamide (pyridine-3-carboxamide) and nicotinamide riboside, also contribute to NAD+ formation (1). None of the vitamers are related to the nicotine found in tobacco, although their names are similar. Likewise, nicotine — but not nicotinic acid — is an agonist of the nicotinic receptors that respond to the neurotransmitter, acetylcholine.’

 

[High_Prob]

Nev

Wait, does tobacco have niacin (anamide) in it?

Niacin

‘The term ‘niacin’ is often used to refer to nicotinic acid (pyridine-3-carboxylic acid) only, although other vitamers with a pyridine ring, including nicotinamide (pyridine-3-carboxamide) and nicotinamide riboside, also contribute to NAD+ formation (1). None of the vitamers are related to the nicotine found in tobacco, although their names are similar. Likewise, nicotine — but not nicotinic acid — is an agonist of the nicotinic receptors that respond to the neurotransmitter, acetylcholine.’

Never mind...You were most likely just referring to the B3 content that is typical of all plants (including tobacco)...

 

[LeeLemonoil]

Tobacco contains mao-inhibitors, one of them is a farnesol-derivate/farnesoid

Farnesol itself is discussed as a Mao-B inhibitor

 

[LeeLemonoil]

Farnesol is a major part of that

Why flavored vape products may be attractive: Green apple tobacco flavor elicits reward-related behavior, upregulates nAChRs on VTA dopamine neurons, and alters midbrain dopamine and GABA neuron function - PubMed

While nicotine is the primary addictive component in tobacco products, additional flavors have become a concern with the growing popularity of electronic nicotine delivery systems (ENDS). For this reason, we have begun to investigate popular tobacco and ENDS flavors. Here, we examined farnesol, a chemical flavorant used in green apple and fruit flavors in ENDS e-liquids, for its ability to produce reward-related behavior. Using male and female 3-6 month old C57BL/6 J mice and farnesol doses of 0.1, 1, and 10 mg/kg we identified a sex-dependent effect in a conditioned place preference assay: farnesol-alone produces reward-related behavior in only male mice. Despite this sex-dependent effect, 1.0 mg/kg farnesol enhances locomotor activity in both male and female mice. To understand farnesol's effect on reward-related behavior, we used whole-cell patch-clamp electrophysiology and confocal microscopy to investigate changes in putative dopamine and GABA neurons. For these approaches, we utilized genetically modified mice that contain fluorescent nicotinic acetylcholine receptors (nAChRs). Our electrophysiological assays with male mice revealed that farnesol treatment increases ventral tegmental area (VTA) dopamine neuron firing frequency and this may be due to a decrease in inhibitory tone from GABA neurons. Our microscopy assays revealed that farnesol treatment produces a significant upregulation of α6* nAChRs in male mice but not female mice. This was supported by an observed increase in α6* nAChR function in additional electrophysiology assays. These data provide evidence that popular tobacco flavorants may alter smoking-related behavior and promote the need to examine additional ENDS flavors.


Some more pubmed-publications available on farnesol/mao-I and its occurrence in tobacco

 

[GAF]

While waiting for my farnesol to arrive, i bought some lemongrass oil to try out.

 

[rei]

.

 

[LeeLemonoil]

While waiting for my farnesol to arrive, i bought some lemongrass oil to try out.

EOs are Great, but only minuscule traces of farnesol in it, won’t give you any „farnesol-effects“

 

[Tristan Loscha]

Interesting ,could be multiple factors, don’t cigarettes contain mao inhibitors also?

They do, of the Harmalin type/Norharman. I saw that also for Coffee, iirc.

 

[GAF]

EOs are Great, but only minuscule traces of farnesol in it, won’t give you any „farnesol-effects“

Farnesol arrived. Couple days of topical on wrist, behind ears. Virtually no smell. No skin reactions. Using straight so far.

Any suggestions for amounts to use or carrier oil usage such as mct oil or just add to lemongrass EO.

No negatives so far. No dramatic effects so far. 2 days.