Coffee and AMPK
-
If I heard correctly Heidut mentioned that AMPK is a hallmark of cancer?
Also I read that coffee stimulates AMPK. Is that a bad thing? -
@Osteo said in Coffee and AMPK:
If I heard correctly Haidut mentioned that AMPK is a hallmark of cancer?
I won’t formulate it so. Sorry, but there is no single answer.
AMPK is a central regulator of cell growth and metabolism.
AMPK must be seen as a sensor and a coordinator. It has thus a key role in maintaining the balance between anabolic and catabolic programs for cellular homeostasis in response to metabolic stress.
The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status expressed in essentially all eukaryotic cells.
Once stress is detected by AMPK, in case of lack of energy (AMP:ATP and ADP:ATP ratios), AMP kinase inhibits ATP consumption: It switches off anabolic (building) processes and other cellular activities that consume ATP, such as cell growth and biosynthesis.
AMPK can also stimulate ATP production: It promotes catabolic pathways that generate ATP, such as the oxidation of fats and the uptake of glucose into cells.
Once active, AMPK phosphorylates various downstream targets to increase ATP production or decrease ATP consumption, according to the situation.
However, cancer is trying to take control of the process as it derives the usual way for glucose to reach the cells. Cancer dampens oxidative enzymes too.
At one moment cancer will be attempting to moderate and counteract the switching off ATP-consuming processes. Tumor is very hungry. Tumor cells appear to downregulate the function of AMPK to its profit, thus limiting its restraining influence on cell growth and proliferation, according to the situation.
Otherwise expressed, AMPK can therefore be either a friend or a foe in cancer, depending on the context.
From Google AI
My quote: “Why a low level of ampk could be required in cancer?”Answer of Google AI:
The paradoxical effect of AMPK
Tumor Suppressor:
High levels of AMPK activation are typically associated with a tumor suppressor role, as it inhibits anabolic processes like cell growth and proliferation and promotes energy production via catabolism.
However, the dual role of AMPK means that targeting this pathway requires careful consideration of the context. Maintaining NADPH and metabolic adaptation is also required. A low AMPK level helps maintain NADPH, an essential molecule for cell survival under metabolic stress.
NB: Here we try to calm down and restrain the capacity of the tumor cell to proliferate. Defensive tactics, in order to allow the immune system to get rid of dysfunctional cells.Dual tactics
A low level of AMPK can be helpful in certain contexts of cancer, particularly in cancers where the LKB1 pathway is lost, because it can sensitize tumor cells to chemotherapeutic agents. While a highly active AMPK typically suppresses tumor growth by restraining proliferation and inducing cell death, paradoxically, a low residual level of AMPK function can enable tumor cells to survive and adapt to the metabolic stresses of a tumor environment, potentially making them more vulnerable to treatments that exploit these energetic weaknesses.AMPK: A "double-edged sword" in cancer:
Instead of trying to eradicate the tumor completely, adaptive therapies use intermittent treatment to maintain a balance, delaying tumor progression by controlling the competitive relationship between sensitive and resistant cancer cells.
It makes it easier to recover (homeostasis). The immune system has to remain efficient, which can’t be met in cachexia (denutrition and loss of muscle mass).Sources:
- Molecular Cell Biology 2011
http://www.ncbi.nlm.nih.gov/pubmed/21157483 - Clin Cancer Res; 21(17); 3836–40. 2015
DOI: 10.1158/1078-0432. CCR-14-3300
http://clincancerres.aacrjournals.org/content/21/17/3836
- Molecular Cell Biology 2011
-
@Osteo said in Coffee and AMPK:
Also I read that coffee stimulates AMPK.
In short:
Caffeine impacts the AMPK sensor, in energy metabolism (through the regulation of muscle and liver metabolism), in autophagy and cellular protection (antioxidant)
If you want more details, make a Google search with:
Does caffeine impact AMPK sensor ?So, yes it's protective, as long you don't abuse (2 or 3 cups), you drink one cup every 4-5 hours (half-life) to avoid to be accustomed (drug).
As long your liver can manage well caffeic acid.
Dose-Dependent Effects
At very high concentrations, polyphenols can become pro-oxidants, leading to cellular damage by triggering DNA breaks, protein modification, and lipid peroxidation. -
@Osteo said in Coffee and AMPK:
If I heard correctly Heidut mentioned that AMPK is a hallmark of cancer?
An imbalance with ATP may be the issue. Haidut wrote:
It is also worth noting that reduction of the ATP/AMP ratio (by lowering ATP) and thus activation of AMPK is currently all the rage in medicine and longevity research, with methods such as fasting, low-carb diets, exhaustive exercise, taking AMPK-mimetics such as metformin, etc being hailed as the key to a very long and healthy life. Yet, behind the scenes, all those interventions may be working to destabilize the organism by increasing baseline inflammation and risk of cancer by lowering mitochondrial production of ATP.
-
@LucH said in Coffee and AMPK:
Does caffeine impact AMPK sensor
Thank you! -
@DavidPS Thank you!
-
Guys what do you think about those papers claiming that coffee diminishes blood flow to the brain?
https://www.researchgate.net/publication/10874668_Field_AS_Laurienti_PJ_Yen_YF_Burdette_JH_Moody_DM_Dietary_caffeine_consumption_and_withdrawal_Confounding_variables_in_quantitative_cerebral_perfusion_studies_Radiology_227_129-135
https://pubmed.ncbi.nlm.nih.gov/19219847/ -
@Osteo
Too complicate to analyze and justify without spending too much energy.
Still have to answer to another forumer
Conversation with ChatGPT
Context
The effect of daily caffeine use on cerebral blood flow: How much caffeine can we tolerate? Hum Brain Mapp. 2009; Merideth A Addicott et al.
DOI: 10.1002/hbm.20732
Question:
Apart from a withdrawal effect by high caffeine users (150 mg caffeine x 6), when stopping, and the consecutive impact on cerebral blood flow (CBF) seen in the study, how can we interpret the effect on moderate caffeine users (half the dose) (3 cups), each take being spaced from 4H to limit drug-accustom and serotonin impact.
Additional info
Caffeine's effects, such as increased alertness, are due to its ability to block adenosine receptors in the brain, preventing adenosine—a natural sedative—from binding and promoting drowsiness. This constant blockage signals the brain to adapt by creating more adenosine receptors, leading to caffeine tolerance and increased sleepiness when the drug wears off. This process also influences the release of other important neurotransmitters, impacting mood and cognitive function.Answer from ChatGPT – Summary
Moderate coffee use still allows the adenosine system to adapt without overwhelming it.
Neurochemical balance beyond CBF
• Serotonin, dopamine, norepinephrine release is influenced by caffeine, but moderate spaced intake avoids constant overstimulation.
• Moderate use maintains alertness and mood elevation without producing the high receptor upregulation (and subsequent withdrawal rebound) seen in heavy users.Overall interpretation: For moderate caffeine users (~3 cups/day spaced 4h apart):
• CBF decreases transiently after each dose (~27% drop), but cerebrovascular adaptation is not maxed out.
• Between doses, partial recovery occurs, preventing cumulative suppression of CBF.
• Long-term, this pattern strikes a balance: you get the stimulant benefits of caffeine while minimizing chronic vasoconstriction and receptor overcompensation.
• In contrast, heavy use overwhelms the compensatory system, leading to greater risk of chronic CBF suppression and stronger withdrawal effects. -
@Osteo - Coffee is not considered bad for the brain. In fact, a review of the literature suggests that coffee has protective qualities for the brain. Studies have found that people who drink more than five cups of coffee a day have lower incidences of Alzheimer's disease, Parkinson's disease, and other conditions. Coffee is also noted to stimulate brain metabolism, increase blood volume in the brain, and decrease the resistance of blood vessels, which can be beneficial. Additionally, caffeine in coffee can improve mood, increase metabolic energy, and help alleviate symptoms of depression by stimulating the uptake of serotonin.
Dr. Peat wrote a balanced article on caffeine in 2006:
-
@DavidPS This is exactly what I knew about coffee.
That's why I'm confused reading articles about how coffee diminishes cerebral blood flow... Or how coffee changes behavior.. -
@Osteo said in Coffee and AMPK:
That's why I'm confused reading articles about how coffee diminishes cerebral blood flow... Or how coffee changes behavior..
Context matters.
Coffee is beneficial if you maintain a proper diet and a healthy lifestyle.
For someone (most average people?) who eats junk food, fast, or does keto, and undersleeps, coffee may be problematic...
