coffee induces autophagy

[Kasper]

http://www.ncbi.nlm.nih.gov/pubmed/24769862

What do you think of drinking coffee RRM? This study talks about the polyphenols of coffee inducing autophagy, I also read that caffeine itself induces autophagy.

I understand that coffee is not part of the wai diet, but would you recommend someone eating a normal western diet, to drink coffee, or do you think it's very unhealthy?

[Oscar]

You might wanna check your autocorrect

[Kasper]

Haha, added wai to my dictionary

[Xplorer]

Coffee induces autophagy in vivo:
https://www.landesbioscience.com/journa ... cle/28929/
"Abstract:
Epidemiological studies and clinical trials revealed that chronic consumption coffee is associated with the inhibition of several metabolic diseases as well as reduction in overall and cause-specific mortality. We show that both natural and decaffeinated brands of coffee similarly rapidly trigger autophagy in mice. One to 4 hours after coffee consumption, we observed an increase in autophagic flux in all investigated organs (liver, muscle, heart) in vivo, as indicated by the increased lipidation of LC3B and the reduction of the abundance of the autophagic substrate sequestosome 1 (p62/STQM1). These changes were accompanied by the inhibition of the enzymatic activity of mammalian target of rapamycin complex 1 (mTORC1), leading to the reduced phosphorylation of p70S6K, as well as by the global deacetylation of cellular proteins detectable by immunoblot. Immunohistochemical analyses of transgenic mice expressing a GFP–LC3B fusion protein confirmed the coffee-induced relocation of LC3B to autophagosomes, as well as general protein deacetylation. Altogether, these results indicate that coffee triggers 2 phenomena that are also induced by nutrient depletion, namely a reduction of protein acetylation coupled to an increase in autophagy. We speculate that polyphenols contained in coffee promote health by stimulating autophagy."

[Xplorer]

" Caffeine prevents human prion protein-mediated neurotoxicity through the induction of autophagy.
http://www.ncbi.nlm.nih.gov/m/pubmed/24938171/

Abstract
The human prion protein (PrP) fragment PrP(106‑126) possesses the majority of the pathogenic properties associated with the infectious scrapie isoform of PrP, known as PrPSc. The accumulation of PrPSc in the brain of humans and animals affects the central nervous system. Recent epidemiological studies have suggested that caffeine, one of the major components of coffee, exerts protective effects against the development of neurodegeneration. However, the protective effects of caffeine against prion disease have not been reported to date. In this study, we therefore investigated the effects of caffeine on PrP-mediated neurotoxicity. The protein expression of the autophagosomal marker, LC3-II, was increased by caffeine in a dose-dependent manner, and the autophagy induced by caffeine protected the neuronal cells against PrP(106‑126)‑induced cell death. On the contrary, the downregulation of LC3-II using the autophagy inhibitors, 3-methyladenine (3-ΜΑ) and wortmannin, prevented the caffeine-mediated neuroprotective effects. To the best of our knowledge, the present study provides the first evidence that treatment with caffeine protects human neuronal cells against prion‑mediated neurotoxicity and these neuroprotective effects are mediated by caffeine-induced autophagy signals. Our data suggest that treatment with caffeine may be a novel therapeutic strategy for prion peptide‑induced apoptosis.

PMID 24938171 [PubMed - in process]
Full text: Spandidos Publications http://www.spandidos-publications.com/ijmm/34/2/553 "

[Xplorer]

" Caffeine stimulates hepatic lipid metabolism by the autophagy-lysosomal pathway in mice.
http://www.ncbi.nlm.nih.gov/m/pubmed/23929677/

Abstract
Caffeine is one of the world's most consumed drugs. Recently, several studies showed that its consumption is associated with lower risk for nonalcoholic fatty liver disease (NAFLD), an obesity-related condition that recently has become the major cause of liver disease worldwide. Although caffeine is known to stimulate hepatic fat oxidation, its mechanism of action on lipid metabolism is still not clear. Here, we show that caffeine surprisingly is a potent stimulator of hepatic autophagic flux. Using genetic, pharmacological, and metabolomic approaches, we demonstrate that caffeine reduces intrahepatic lipid content and stimulates β-oxidation in hepatic cells and liver by an autophagy-lysosomal pathway. Furthermore, caffeine-induced autophagy involved down-regulation of mammalian target of rapamycin signaling and alteration in hepatic amino acids and sphingolipid levels. In mice fed a high-fat diet, caffeine markedly reduces hepatosteatosis and concomitantly increases autophagy and lipid uptake in lysosomes.

CONCLUSION: These results provide novel insight into caffeine's lipolytic actions through autophagy in mammalian liver and its potential beneficial effects in NAFLD.

© 2014 by the American Association for the Study of Liver Diseases.
PMID 23929677 [PubMed - indexed for MEDLINE]
Full text: John Wiley & Sons, Inc. http://dx.doi.org/10.1002/hep.26667 "

[Xplorer]

" Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition.
http://www.ncbi.nlm.nih.gov/m/pubmed/21081844/

Abstract
Caffeine is one of the most frequently ingested neuroactive compounds. All known mechanisms of apoptosis induced by caffeine act through cell cycle modulation or p53 induction. It is currently unknown whether caffeine-induced apoptosis is associated with other cell death mechanisms, such as autophagy. Herein we show that caffeine increases both the levels of microtubule-associated protein 1 light chain 3-II and the number of autophagosomes, through the use of western blotting, electron microscopy and immunocytochemistry techniques. Phosphorylated p70 ribosomal protein S6 kinase (Thr389), S6 ribosomal protein (Ser235/236), 4E-BP1 (Thr37/46) and Akt (Ser473) were significantly decreased by caffeine. In contrast, ERK1/2 (Thr202/204) was increased by caffeine, suggesting an inhibition of the Akt/mTOR/p70S6K pathway and activation of the ERK1/2 pathway. Although insulin treatment phosphorylated Akt (Ser473) and led to autophagy suppression, the effect of insulin treatment was completely abolished by caffeine addition. Caffeine-induced autophagy was not completely blocked by inhibition of ERK1/2 by U0126. Caffeine induced reduction of mitochondrial membrane potentials and apoptosis in a dose-dependent manner, which was further attenuated by the inhibition of autophagy with 3-methyladenine or Atg7 siRNA knockdown. Furthermore, there was a reduced number of early apoptotic cells (annexin V positive, propidium iodide negative) among autophagy-deficient mouse embryonic fibroblasts treated with caffeine than their wild-type counterparts. These results support previous studies on the use of caffeine in the treatment of human tumors and indicate a potential new target in the regulation of apoptosis.

PMID 21081844 [PubMed - indexed for MEDLINE]
PMCID PMC3039768 Free Full Text
http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21081844/

Free full text: Landes Bioscience
http://www.landesbioscience.com/journal ... p?id=14074 "

[Xplorer]

Coffee is beneficial for fat-burning, especially during a fast.
http://www.ncbi.nlm.nih.gov/pubmed/2405717 study found that an infusion of epinephrine – a hormone which coffee increases – during “starvation” enhanced its lipolytic and thermogenic effects.

In other words, fat-burning and metabolism up-regulated in response to epinephrine (more so than usual).

Epinephrine lowers appetite.

[RRM]

What do you think of drinking coffee RRM?

Coffee contains a large number of active compounds, including:
- caffeine
- toxic HCA (the beans are roasted)
- phenols

They induce both apoptosis and autophagy, so the effects of coffee are mixed (good and bad).
It depends on which one dominates, which may be individually different.

Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition.

Apoptosis is cell death (contributing to ageing of cell-line)
Autophagy is cell clean up (cell remaining alive, slowing down ageing of cell-line)
Multiple processes involved in apoptosis are also involved in autophagy.
If processes dominate that also lead to apoptosis, the induced effects including autophagy may or may not be beneficial.
Many toxins induce both apoptosis and autophagy.

Coffee is beneficial for fat-burning, especially during a fast.

For most people here, that is not a good thing, actually.

[Xplorer]

Coffee may promote a "positive" apoptosis which is a required function where and when needed...

"Cells - too many, aka Cell senescence:
This is a phenomenon where the cells are no longer able to divide, but also do not die and let others divide. They may also do other things that they’re not supposed to, like secreting proteins that could be harmful. Cell senescence has been proposed as cause or consequence of type 2 diabetes. Immune senescence is also caused by this. ApoptoSENS (cell senescence) – Cells that become old and no longer divide (senescent cells) produce inflammatory substances that contribute to many of the diseases of aging. ApoptoSENS would eliminate senescent cells by inducing such cells to “commit suicide” (apoptosis)."

[Xplorer]

I think that burning fat is a positive thing on a high carbohydrate diet which contains lots of fresh fruits and/or fruit juices, and where lots of exercising is not a too high priority.

[Xplorer]

Re: the "toxic HCA - the beans are roasted"..., according to citations below, a frequent consumption of acrylamide in coffee (the darker the roast the better) is associated with a decreased cancer incidence:

http://jnci.oxfordjournals.org/content/ ... 3.abstract

http://aje.oxfordjournals.org/content/1 ... 3.full.pdf

http://link.springer.com/article/10.102 ... 5.28319.c1

http://www.nature.com/bjc/journal/v88/n ... 00726a.pdf

[Xplorer]

To clarify. I am not a coffee addict, not even for a "moderate" / "infrequent" coffee drinking...

I have experimented with drinking one cup of (organic) espresso daily for a period of 1 month at a time. I have ended this experiment a few days ago.

I as well have experimented with eating 50gr of (organic) dark 85-87% chocolate daily for ca 1 month.

These stimulants ("super-foods") are usually promoted and discussed for their "health promoting" effects in various forums and groups, incl related to IF and CR, etc

However, my concerns from experimenting with these are related to the obvious toxicity effects combined with absent or unclear positive effects so far...

[Xplorer]

Coffee kahweol cafestol cholesterol-raising negative effects vs anti mycotoxins positive effects

Cholesterol-raising effect of coffee :

In this summary, trials using a control group that consumed decaffeinated coffee identified no effect of drinking regular coffee on serum cholesterol. This suggests that the cholesterol-raising effect of coffee is not due to the caffeine itself but to another ingredient of coffee (46, 47). 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). Boiled coffee has a higher concentration of coffee oils because of the higher temperatures used during its preparation (17) and the longer contact time between the coffee grounds and water (17, 38). Filtration of coffee through a paper filter removes the cholesterol-raising fraction from the coffee extract (22, 32). Consistent with these observations, trials using boiled or nonfiltered coffee had a stronger cholesterol-raising effect than did those using filtered coffee (table 3).

Source: http://m.aje.oxfordjournals.org/content/153/4/353.full

"The lipid-raising effects of coffee drinking have been reported to be primarily due to coffee oils, such as cafestol and kahweol, that increase the synthesis of cholesterol by decreasing excretion of bile acids and neutral sterols. Boiled coffee has a higher concentration of coffee oils because of the higher temperatures used during its preparation and the longer contact time between the coffee grounds and water."

Besides caffeine, the kahweol and cafestol is shown to counter the negative effects of mycotoxins (aflatoxin, ochratoxin, trichothecene - produced by fungi and moulds) which are found in 30% of coffee. Roasting may neutralize only a part of mycotoxins.

So, the coffee oils - cafestol and kahweol, have positive effects in neutralizing mycotoxins, while increasing the level of LDL cholesterol...

Mycotoxins are found as well in many other foods, such as - peanut butter, nuts, seeds, beer, wine, raisins, dried fruits, chocolate, grains, wheat products, etc Mycotoxins are shown to be carcinogenic, harming kidneys, etc

[RRM]

Coffee may promote a "positive" apoptosis

Senescent cells produce inflammatory substances not as a result of their age, but as a result of poorer functioning, due to damaged organelles (due to aging).
Apoptosis is "positive" if aging cells cannot be repaired through autophagy.
There is no selective mechanism between "postive" and "negative" apoptosis.