Fatty acid synthase Inhibitors. - Advanced Prostate...

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Fatty acid synthase Inhibitors.

pjoshea13 profile image
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Recent media interest in the PCa study that showed that aggressive cancer cells are fat factories, is a reminder that fatty acid synthase [FAS / FASN] upregulation is a feature of a number of cancers, & has been the subject of cancer research for over 20 years.

If we can reduce FAS levels in PCa cells, we can slow progression & metastasis.

[1] (2004) - Belgium.

{Note that epigallocatechin-3-gallate [EGCG] is the important polyphenol in green tea.}

"Based on our previous finding that the cytotoxic effect of the flavanol epigallocatechin-3-gallate on prostate cancer cells correlates with its ability to inhibit fatty acid synthase (FAS, a key lipogenic enzyme overexpressed in many human cancers), we examined the anti-lipogenic effects of a panel of 18 naturally occurring polyphenolic compounds. In addition to epigallocatechin-3-gallate, five other flavonoids, more particularly luteolin, quercetin, kaempferol, apigenin, and taxifolin, also markedly inhibited cancer cell lipogenesis. Interestingly, in both prostate and breast cancer cells, a remarkable dose-response parallelism was observed between flavonoid-induced inhibition of fatty acid synthesis, inhibition of cell growth, and induction of apoptosis. In support for a role of fatty acid synthesis in these effects, the addition of exogenous palmitate, the end product of FAS, markedly suppressed the cytotoxic effects of flavonoids. Taken together, these findings indicate that the potential of flavonoids to induce apoptosis in cancer cells is strongly associated with their FAS inhibitory properties, thereby providing a new mechanism by which polyphenolic compounds may exert their cancer-preventive and antineoplastic effects."

Note that palmitate is a form of palmitic acid, a saturated fat with a backbone of 16 carbons. Palmitic acid is the favored energy source of normal prostate cells, & this generally remains so in PCa - i.e. they do not switch to glucose.

Palmitic acid is found in many foods. It is the major fatty acid in palm oil. Can we avoid it via a low-fat diet? Alas, "Excess carbohydrates in the body are converted to palmitic acid." [2] It is the starting point for the synthesis of more complex longer chain fatty acids.

Discussion of diet in the context of FASN diverts us from the serious issue - that PCa cells can make almost any fatty acid that they need (excluding the "essential" omega-3 & omega-6 fatty acids), & their needs ultimately outstrip what they have access to from the circulation. FAS upregulation is essential to aggressive PCa, so any degree of inhibition is worthwhile.

"... assays showed that after 5 h of exposure of LNCaP cells to luteolin, quercetin, or kaempferol, a significant decrease in lipid synthesis was already evident at a concentration of 6 μM. Higher concentrations further reduced lipogenesis in a dose-dependent way. A further decline was observed after 24 h of exposure. At 12 μM, luteolin reduced lipogenesis to less than 10% of the control levels, thereby making luteolin the most efficient inhibitor of the studied flavonoids. EGCG was clearly less active ..."

Luteolin (not to be confused with the useful lutein) - possible source: [3].

Other studies of FAS inhibitors report that they do not all work the same way. There may be synergy in combining flavonoid polyphenols. FAS inhibition increases with dosage, & polyphenols are generally well-tolerated at higher doses. Green tea is an exception - it can elevate liver enzymes.

-Patrick

[1] jbc.org/content/280/7/5636....

[2] en.wikipedia.org/wiki/Palmi...

[3] swansonvitamins.com/swanson...

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5 Replies
snoraste profile image
snoraste

Patrick -

I find this and nameless9999's post earlier on statins somewhat at odds. But getting back on the dietary aspect, do you know it factually that all types of carbohydrates can be converted into palmitic acid? Hard to imagine it is the same whether you eat processed white bread, vs whole wheat.

As for uteolin, quercetin, kaempferol, or flavonoid - I thought they are present in select fruits and vegetables. Is there a need to go the supplement route (higher dosage perhaps)?

pjoshea13 profile image
pjoshea13 in reply to snoraste

Snoraste,

Digestible carbohydrate provides energy in the form of glucose - blood sugar - which is the primary energy source for most of our cells. We basically eat carb to produce sugar for energy.

Glucose itself requires no digestion, so is instantly available. The glycemic index [GI] of a carb is given relative to glucose, which is given the GI of 100. Fructose takes a while to convert to glucose, & has a GI of only 25. Sucrose is glucose bound to fructose & has a GI of 65.

Complex carb takes longer to digest than refined carbs, such as simple sugars, but I reliably get a sugar high within 30 minutes of eating whole oat grain (groats) cooked in water - nothing added, & no other food in the meal. While it can take longer to digest a whole grain than a slice of white bread, that merely delays the glucose surge.

The body hates glucose spikes and tightly controls blood levels.

One of the things that happens to excess glucose in the blood is conversion to triglycerides. This is the source of the palmitic acid.

Take away the spike & you solve that problem (along with insulin resistance & diabetes.)

Those who adopt a low-fat diet will experience elevated triglycerides. A Dean Ornish 10% fat diet is a bad idea, since there will be glucose spikes after every meal.

With a 40% fat diet, glucose enters the blood slowly over a much longer period, & does not stress the body. Triglycerides do not become elevated & there is no creation/storage of palmitic acid.

Note that complex carbs produce the same glucose as glucose candy. It is in no way superior in terms of energy. Of course, it comes with other nutrients, but carb ---> glucose, & excess carb ---> palmitic acid.

-Patrick

dockam profile image
dockam

Thanks for the link, I just bought a bottle of the Luteolin and just added some Quercetin to get free shipping. I post PSA updates

Thanks again

Randy

rococo profile image
rococo in reply to dockam

Ditto Thanks Patrick for following up with the swanson source. Rocco

larry_dammit profile image
larry_dammit

Was drinking green tea and coffee when I was diagnosed. 😜😜

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