Loose Skin autophagy vs muscle loss


(Jane) #81

The first one I ordered off Amazon was cheaper but hasn’t been available lately. I just re-ordered this one. Not sure what you can get over in Asia

(Hyperbole- it’s the best thing in the universe! ) #82

Thanks! I’ll check taobao.

(Jenny) #83

you can purchase on Mark’s daily apple primal kitchen as well. the chocolate coconut is amazing.


Dunno how big of a benefit this actually gives but some say taking good care of ur skin helps, having skin oils in balance, using creams after shower, specially if u get ashy etc.

(Jane) #85

Oh it does.

But I am 60 and didn’t do all that when I was young, so hoping to repair some of the damage from the inside out.

(Troy) #86


Thomas Delauer goes in to the benefits🙂

The sciency
HSP’s - Heat Shock Proteins


(Karim Wassef) #87

Sauna is awesome for muscle growth. I am specifically looking for mechanisms that allow me to grow muscle while also reducing excess loose skin. Doesn’t sound like sauna would help with loose skin reduction?

(Troy) #88

Yeah. Agree, not to sure about loose skin reduction
But, if I can acquire abs like Thomas from saunas
I’m gonna join all gyms to sauna up :rofl:

(Karim Wassef) #89

So here is an interesting look at autophagy…

the concept is regionalization of hormones… simultaneous signaling of mToR in muscles and signaling with AMPK in fat and damaged cells. I’ve always looked at hormones as systemic drivers that effect all cells at once, but if there’s a regional distribution and that distribution can be “directed”, then it’s possible to achieve both without cycling.

So exercise triggers mToR in muscles… that’s one driver.

Is there a symmetric driver for skin catabolism through regionalized AMPK? UV exposure? Heat exposure? Cold exposure? Red light exposure? Physical abrasion or damage (brushing or needling)? Chemical exposure (creams, astringents)? Hydration (internal or external)? Fluid redistribution (mud, mineral baths like Mg or salts in general), Flushing & blood flow drivers (Niacin?).

I think I’ll start looking deeper into safe “skin stressors” while pushing mToR through more heavy exercise.

(Doug) #90

Karim, the Siim Land stuff has no guarantee of accuracy - I’ve seen some flat out falsehoods spouted therein. I think he/they are just trying to crank out a huge amount of videos.


Ok. I just got in some powdered beef collagen peptides to help with my joints (shoulder arthritis) and loose skin from extended fasting. So should I just skip it’s use during EF so as to preserve autophagy? And resume it during re-feeding and only with meals?

(Jane) #92

That’s what I do. I don’t want the protein in the collagen shutting down autophagy.

(Karim Wassef) #93

I don’t think amino acids are all that bad…

(Karim Wassef) #94

This has echoes of Dr Bikman’s results too:

They also reference that the up regulation of AMPK varies by cell type (liver vs muscle) adding credence to the idea that these effects are not systemic. Even if the chemicals are systemic, their effects may be cell specific and could therefore be directed differently.

Here’s an extract:

Maintaining appropriate nitrogen balance is crucial to the fitness of an organism. The decision to deaminate amino acids to use their carbon skeleton for oxidative and/or synthetic purposes is tightly regulated. Excessive amino acid catabolism not only generates toxic nitrogenous waste but also could jeopardize the ability to generate or maintain protein levels.

The liver is unique in its capacity to detoxify nitrogenous waste through the energy-requiring synthesis of urea. Accounting for nearly a third of hepatic metabolism, ureagenesis consumes three ATPs per urea produced and has an overall flux comparable to that of gluconeogenesis (1, 2). Importantly, the ligation of citrulline to aspartate via argininosuccinate synthetase (ASS) hydrolyzes one ATP into AMP per turn of the ornithine cycle, making ASS a predominant hepatocellular contributor of AMP. Hence, a metabolic signal generated through the AMP-generating ornithine cycle could be intrinsic to preserving nitrogen balance.

In oxidative tissues such as muscle, AMPK helps balance energy homeostasis by detecting fluctuations in the [AMP]:[ATP] ratio. Phosphorylation of AMPK by upstream kinases such as liver kinase B1 enhance AMPK activity, and AMP binding to an allosteric site stabilizes a conformation that supports phosphorylation and protects AMPK from dephosphorylation (3). The canonical view of AMPK activation is that, following global shifts in energy balance (e.g., excessive energy demand during exercise), adenylate kinase (AK) increases AMP synthesis to salvage ATP from ADP (4). As a consequence, the AMPK-mediated phosphorylation of sterol regulatory element-binding protein 1 (SREBP-1), acetyl-CoA carboxylase 1 (ACC1), and acetyl-CoA carboxylase 2 (ACC2), then switches metabolism from lipogenesis to lipid oxidation (58).

We hypothesized that the extremes in energy demand experienced in exercising muscle that would require AK rescue are much less likely in the liver and that there is a greater possibility that other AMP-generating pathways activate hepatic AMPK. In principle, a shift toward lipid oxidation would support gluconeogenesis and ketogenesis during times of high organismal energy demand. Similarly, the liver could activate lipid oxidation following protein-rich meals to support the repackaging of the surfeit of amino acid carbon into glucose for export and storage while at the same time detoxifying ammonia.

In humans, disruptive mutations in the ASS1 gene cause type I citrullinemia, an inborn error in metabolism marked by hyperammonemia (9, 10). Interestingly, ASS deficiency also is associated with reduced AMPK activation and decreased fatty acid oxidation in mice (11) and with fatty liver in humans (12). Here we propose that ASS is an important physiological regulator of hepatic AMPK, effectively coupling lipid oxidation to ornithine cycle activity.

Amino Acids Activate AMPK in Primary Hepatocytes.

Amino acids stimulate hepatic gluconeogenesis and ureagenesis during both fasting and protein feeding (13). As expected, both glucose and urea production increased following the addition of L-glutamine to primary rat hepatocytes (Fig. 1 A and B ). Intriguingly, despite the nutrient excess, AMPK was phosphorylated, and its physiologic activation was confirmed by the phosphorylation of its substrate acetyl-CoA carboxylase (ACC) (Fig. 1 C and D ). Inhibition of glutamate dehydrogenase (GDH) activity by epigallocatechin gallate (EGCG) (14) diminished gluconeogenesis and ureagenesis from 10 mM L-glutamine and decreased both AMPK and ACC phosphorylation. Conversely, enhancing GDH-mediated ammonialysis with the nonmetabolizable leucine analog 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH) (15) augmented both L-glutamine–dependent glucose and urea production and amplified AMPK and ACC phosphorylation. The concentration of ornithine cycle intermediates paralleled the increase in urea production (Fig. S1). Thus, there is a strong positive correlation between L-glutamine metabolism and AMPK activation in primary hepatocytes.

(Bacon is the new bacon) #95

Benjamin Bikman appears to believe that mTOR is not really an issue when the insulin/glucagon ratio is low, in any case.

(Karim Wassef) #96

Here’s my simplistic view - autophagy breaks down both fat and protein. The release of amino acids & ketones has a feedback loop that can both enhance further AMPK autophagy in some cells but could also trigger mToR in other cells.

The urea nitrogen balance component is new to me and so I’m trying to understand and study it… sorry if it’s not too helpful just yet. I am hopeful though.

(Karim Wassef) #97

Yes. That’s why I think the two are aligned. Whether it’s a correlation between the i/G ratio and the AMPK protein autophagy or actual causation, the results are the same.

Bikman’s simple explanation (that I like) is that in the low glucose low insulin fasted state, (i.e. the body is already in autophagy), the exogenous amino acids cannot trigger an insulin response that would drop blood glucose to dangerously low levels and you would become unconscious. Instead, the body does the safest thing and that is use fat oxidation to generate the energy needed to incorporate the new amino acids - and that’s what the glucagon is already primed to do in that state.

I can’t find where he explicitly says that, but if the amino acids are not being used to drive more energy, then mToR would be needed to incorporate them.

This makes sense with exogenous amino acids. But the urea feedback loop in these other papers throws another variable during fasting… basically, the amino acids come from autophagy (not exogenous)… but the effect can be the same. The body would rather not waste the precious nitrogen and would try to reuse it. The same effect as before should make the body burn more fat (in the liver) in order to incorporate the amino acids (in the muscle).

I know amino acids don’t turn into glucose directly, but they are usually anabolic.

So whether you take in protein as food or consume loose skin through fasting, the amino acids would trigger more fat loss and build new tissue vs. waste the nitrogen. This is only true if the insulin stays low though = fasting.

So maybe I just need to double down on my heavy lifting while fasting deeper (longer EF). I know it sounds like both extremes but that should trigger both supply and demand sides of both nitrogen and energy loops…

(Bacon is the new bacon) #98

That makes a lot of sense, Karim.

I can’t find the reference offhand, but I read a paper in the last couple of weeks that states there is a certain minimal level of deamination always occurring, which is one of the reasons protein intake is essential—to replenish the lost nitrogen.

They also posited, however, some reaction (the name of which I cannot remember, but you are familiar with it, I am sure) that could serve as a sort of storage mechanism for hanging on to amino acids in excess of what the labile pool can hold.

Can muscle tissue grow in the absence of branched-chain amino acids? Particularly in the absence of leucine, iso-leucine, and valine? I’m not a body-builder, so I’ve never had to study this before.

(Karim Wassef) #99

So I’m going to make two amino acid exceptions during my prolonged fast …

I’m going to supplement carnitine and leucine

My thinking is that I’ll be taking very small supplementary amounts with the purpose of unlocking fat (carnitine) and driving anabolic hypertrophy (leucine). If I do this while fasted (low insulin) and lifting (muscle stress and damage), it should push the machine hard…

The hardcore fasting cynic in me says it’s an excuse to cheat during fasting and autophagy should supply those amino acids too… but if I’m lifting heavy while extended fasting, I’m going to err on the side of caution so I can repair that damage.

I’m doing DEX before and after anyway… so we’ll have the data.

(Karim Wassef) #100

By the way- I did cringe when I said that whether it was correlation or causation didn’t matter… I had a little angry emoji of Peter Attia on my shoulder screaming “confounding factors matter, you dolt!” And it really does help me appreciate how little I understand the underlying biochemistry…

Damnit, Jim… I’m a physicist, not a doctor! :smiley: