Turn Off The Catabolic Switch

[nrage04]

I have read and re-read the following article and found it very interesting. I thought others would find this useful/interesting also. read and enjoy.

--

Turn Off The Catabolic Switch
By Robbie Durand, MA (originally written for MD)

"Your bleeding man", says the private. "I aint got time to bleed" replies Jesse Ventura in the move "Predator", as bullets and bombs explode around him. The alien predator stood over 7 feet tail and wa built like a brick house. The predator must have been on some potent alien supplements, because real space-flight causes rapid activation of muscle proteases that break down muscle tissue. The predator would probably have looked more like a skinny extraterretrial without the use of alien anti-catabolic agents. During spaceflight, or any form of traumatic injury involving muscle wasting - cancer, AIDS, burns and hospital immobilization - all kind of catabolic and muscle atrophy (increased myostatin production: a negative growth regulator) pathways are turned on. The ubiquitin-proteasome pathway (PPP) for muscle breakdown. Myostatin turns on the UPP pathway and breaks down muscle tissue. Unfortunatley, the UPP pathway also becomes activated during periods of high-intensity exercise and stress, when cortisol is being secreted. UPP is a mahor enemy for anyone trying to get ripped up without losing muscle. Its no coincidence that marathon runners are mostly skin and bones; marathon runners and o ther endurance athletes have an increase in UPP from not eating enough and excess training, which causes exce muscle breakdown. Most people on diets make the mistake of losing too much muscle mas when trying to get ripped up, but fear not - this article will give you the inside edge to turning off the catabolic switch.

Triggers of UPP

Everyone knows that cortisol is a catabolic hormone. Cortisol breaks down muscle tissue and can be overactive during periods of elecated stress i.e. overtraining, diet, emotional stress. Cortisol causes muscle tissue breakdown through the activiation of UPP. Researchers have discovered a few other mechanisms that trigger the UPP pathway. The thyroid has potent fatloss properties, as elevated thyroid levels result in increased calorie burned, particularly in the form of heat. People with excess thyroid production are often in a catabolic tate, a exce thyroid hormone production can cause muscle protein breakdown, mainly mediated by increaing UPP activity. Additionally, a low level of plasma insulin triggers protein breakdown in muscle through activation of the UPP. As you know insulin is an anti-catabolis hormone and suppreses protein breakdown. Its interesting that diabetics or patients with insulin resistance have increaes muscle protein breakdown and increased msucle atrophy due to defects in insulin signaling. The increaed breakdown of muscle in diabetics is also due to elecated UPP levels. Low-carb diets are highly effective for losing fat by controlling insulin. Some diet gurus recommend periodic high glycemic meals, which spike insulin - especially post-workout; this is not only effective for maintaining an anabolic state, bbut insulin shuts down the UPP pathway. A new study published in BMC Molecular Biology also report that increasing amino acids or leucine alone acts additively with insulin to downregulate protein breakdown and reduce UPP. The use of L-leucine while dieting seems to be effective for reducing muscle tissue breakdown by reducing UPP. IN addition to hormonal stimulators of UPP, resistance exercise also increases UPP, which is a normal adaption to exercise.

Resistance Exercise And UPP

Strenous resitance exerise stimulates adaption in skeletal muscle. UPP is part of the normal adaptions to exercise, but overtraining can significantly increase UPP and stop muscle gains. Muscles have a memory system that further protects it from muscular damage from exerise . An increase in UPP has been found to occur after intense resistance exercise. This increase in UPP mediates a rise in protein breakdown, followed by an immediate increase in protein synthesis required for mucle adaption in orderfor exercise to occur. It has been reported that an increase in UPP is associated with post-exercise increases in damaged muscle fibers. Eccentric exercise also increase UPP. Thompson and cordalis evaluated msucle biopsies obtained from the biceps two days after a bout of damaging, eccentric exercise. They found a 55 percent increase in UPP after exercise, relative to nonexercised control muscle; however, after repeated eccentric exercise bouts, there seems to be a muscle adaption that takes place, protecting mucle from further damage and increases in UPP activity. Willoughby and colleagues measured muscle UPP after eccentric knee extension exercises performed by healthy volunteers on two successive trials. They observed that an increase in UPP wa larger after the first trial then the second. This means muscle tries to "protect" itself from further muscular damage. Eccentric exercise produces the most robust changes, whereas concentric exercise tasks stimulate UPP, but appear to have a lesser effect. Acute increases in UPP art part of the normal adaption to resitance exercise, but chronically elecated levels caused by diet and stress (physical and emotional) lead to excess muscle tissue breakdown.

Pt 1

[nrage04]

The Burn Victim Anti-Catabolic Diet

While trying to get ripped up, the reduced amount of calories combined with cardio and resistance exercise can lead to an increase in cortisol, which can lead to a catabolic condition. Did you know that there is an anti-catabolic diet that was specially formulated for burn victims to reverse muscle catabolism? The Shriners' Burn Diet consists of high protein and fats high in anti-inflammatory omega-3 fatty acids that are low in pro-inflammatory omega-6 fatty acids. The diet also has been shown to enhance muscle recuperation from burns compared to the standard hospital diet.

Dr Cutler To The Burn Unit!

When reducing calories and increasing cardio to lose fat, the use of agents that reduce mucle catabolism is beneficial. It should be of no surprise that tesosterone administration has been shown to decrease UPP. The use of clenbuterol is known to exert its anabolic effects largely through reduced protein muscle breakdown. Clenbuterol has been shown to significantly reduce UPP; it also appear that clenbuterol preferentially inhibits the UPP in the fast twitch muscles. Reducing muscle catabolism is eential in the medical field, as trauma doctor know that reversing the catabolic tate in trauma victims is a matter of life and death. In severe injury such as burns, skeletal muscle breakdown far exceeds synthesis, even during feeding. The traumatic insult is also associated with increased cortisol secretion. The increase in blood cortisol concentrations correlates with the severity of the injury and often persists for weeks after injury. Although trauma is accompanied y increased circulating concentrations of glucagons and catecholamines, the loss of muscle mass is likely due primarily to the effects of cortisol. The effect of cortisol on skeletal muscle is to increase protein breakdown, which increases UPP production.

Do you that there is a specially formulated medical drink called Juven to reverse catabolic conditions? Juven is a therapeutic drink clinically proven to help build muscle in cancer and HIV/AIDS patients. The best part about it is that you can all the ingrediants at a local health food store. Juven contains a patented blend of three key ingrediants: HMB, argnine and glutamine. The exact dosing in all the research studies to prevent muscle loss is 3 grams HMB, 14 grams of L-glutamine and 1 gram of L-argnine. Most of the studies to date have adminitered this blend twice a day. Some of the studies are showing increases in lean muscle mass with this supplementation without the use of resistance exercise. It is important to note that all three componnents work through different metabolic pathways and have synergistic effects. Pretty soon, your local emergency room doctors may be Jay Cutler, Ronnie Coleman and the rest of the MD gang due to their expertise with anti-catabolic supplements!

Pt 2

[nrage04]

Gllutamine

Muscle cell concentrations of glutamine are far higher than blood levels. PLasma and intramuscular glutamine concentrations drop during metabolic stresses such as surgery, burns or trauma. Glutamine also increaes heat-shock proteins, which increase muscle hypertrophy. Heat-shock proteins are "celluar chaperones" involved in the management of stress-induced protein cell destruction. Glutamine depletion results in dminised synthesis of heat-shock proteins. Recently, Glutamine has been shown to increase heat-shock protein approximately fourfold in critical illnes. Glutamine can also increase tissue glutethione levels and enhance antioxidant capacity. The use of Glutamine seems to be especially warranted during dieting when caloric restriction, exercise frequency and exercise intensity are at their highest.

Argnine

Dietary supplementation with argnine has also been shown to safely induce positive nitrogen balance in humans by increasing muscle protein synthesis and inhibiting muscle proteasome acitivity. The most important pathway of argnine metabolism appears to be its conversion to orthinine in the liver, which is a precursor for protein synthesis. Arginine supplementation, usually up to 20 grams per day, has been reported to reduce weight loss and nutrogen loss and improve nitrogen retention and wound healing. The mechanism for this action is unclear. One mechanism may be stimulation of the release of growth hormone. Another mechanism may be through stimulation of nitric oxide (NO) production, as NO is directly involved in many physiological mechanisms relevant to hormone release and muscle regeneration. For example, the enhanced musle regeneration effects of L-argninine appear to be dependent on the NO pathway, as supplemental dietary arginine enhances muscle regeneration in normal people, but not those who are deficient in NO.

HMB

HMB is a metabolite of the branched-chained amino acid, leucine. Leucine alone can stimulate protein synthesis, inhibit protein breakdown and reduce activation of UPP. You probably remember hearing about HMB a few years ago, but it kind of just faded away.Its importance should not be underestimated. It seems that HMB may e making a comeback. IN the Journal of Trauma, the use of HMB was found to significantly improve nitrogen retention in patients who were seriously injured. This effect may be meiated by the actions of increasing leucine metabolism. Also, HMB has been shown to reduce muscle tissue breakdown by inhibiting UPP. One study looked at the validity of several supplements (creatine, HMB, chromium, DHEA, androstenedione and protein) for increasing lean muscle mass. Creatine and HMB were the only supplements with data supporting their use to augment lean mass and strength gains with resistance training.

Pt 3

[simon m]

Good post.

I better buy some more supplements!

[allthegoodnamesaregone]

nrage have you tried this combo during pct?

[nrage04]

Quote

nrage have you tried this combo during pct?

I take it your talking about the Juven formulation. I've not tried it as I am currently bulking and will be right up until Jan08 now but when I start dieting I plan on using that formulation.

If you try it before then let me know how it goes.

[Bison]

Quote

Gllutamine

Muscle cell concentrations of glutamine are far higher than blood levels. PLasma and intramuscular glutamine concentrations drop during metabolic stresses such as surgery, burns or trauma. Glutamine also increaes heat-shock proteins, which increase muscle hypertrophy. Heat-shock proteins are "celluar chaperones" involved in the management of stress-induced protein cell destruction. Glutamine depletion results in dminised synthesis of heat-shock proteins. Recently, Glutamine has been shown to increase heat-shock protein approximately fourfold in critical illnes. Glutamine can also increase tissue glutethione levels and enhance antioxidant capacity. The use of Glutamine seems to be especially warranted during dieting when caloric restriction, exercise frequency and exercise intensity are at their highest.

Does the article provide any proof to these claims about Glutamine? I'm very sceptical about any claims with this stuff.

Loving the idea about the drink though, who wouldn't?

As for the Arginine do you think it matters about the form it's in? I mean Arginine Alpha-Ketoglutarate (AAKG) compared to Arginine Ethyl-Ester HCl (AEE) or Di-Arginine Malate?

How about a similar drink using Leucine instead of HMB? It works out quite a bit cheaper if you buy in bulk as there's no discount on HMB, that's what puts me off it.

[nrage04]

Quote

Does the article provide any proof to these claims about Glutamine? I'm very sceptical about any claims with this stuff.

Loving the idea about the drink though, who wouldn't?

As for the Arginine do you think it matters about the form it's in? I mean Arginine Alpha-Ketoglutarate (AAKG) compared to Arginine Ethyl-Ester HCl (AEE) or Di-Arginine Malate?

How about a similar drink using Leucine instead of HMB? It works out quite a bit cheaper if you buy in bulk as there's no discount on HMB, that's what puts me off it.

I know what you mean. The article as a whole has 46 references. The following are just the ones relevant to the Glutamine information:

9.Powell-Tuck J. Nutritional interventions in critical illnes. Proc Nutr Soc, 2007 Feb;66(1):16-24.

10.Murlasits Z, Cutlip RG, Geronilla KB, Rao KM, Wonderlin WF, Alway SE, Resistance training increases heat shock protein levels in skeletal muscle of young and old rats. Exp Gerontol, 2006 Apr;41(4):398-406.

11.Kawada S, Ishii N. Skeletal muscle hypertrophy after chronic restriction of venous blood flow in rats. Med Sci Sports Exerc. 2005 Jul;37(7):1144-50. Erratum in: Med Sci Sports Exerc, 2005 Oct;37(10):1824.

12.Ziegler TR, Ogden LG, Singleton KD, Luo M, Fernandez-Estivariz C, Griffith DP, Galloway JR & Wischmeyer PE (2005) Paranteral glutamine increases serum heat shock protein 70 in critically ill patients. Intensive Care Medicine 31, 1079-1086.

Below I have added the references to the text so you know which reference relates to what part:

--

Gllutamine

Muscle cell concentrations of glutamine are far higher than blood levels. PLasma and intramuscular glutamine concentrations drop during metabolic stresses such as surgery, burns or trauma(9). Glutamine also increaes heat-shock proteins, which increase muscle hypertrophy(10,11). Heat-shock proteins are "celluar chaperones" involved in the management of stress-induced protein cell destruction. Glutamine depletion results in dminised synthesis of heat-shock proteins. Recently, Glutamine has been shown to increase heat-shock protein approximately fourfold in critical illnes(12). Glutamine can also increase tissue glutethione levels and enhance antioxidant capacity. The use of Glutamine seems to be especially warranted during dieting when caloric restriction, exercise frequency and exercise intensity are at their highest.

--

Regarding the Arginine I have no idea mate to be honest. I can email the guy who originally wrote the article to ask as the article doesnt mention any specific type (maybe it doesnt matter?)

Yeah HMB is after all a metabolite of leucine, and HMB's actions (it says in the article) may be beause it increases leucine metabolism. I wouldnt like to say but you could try it. I would have thought though, that the company that hold the patent for the formulation of Juven, would have tried leucine as it'd also be cheaper to purchase at wholesale?

All I can suggest is to try it. I plan on trying this formulation next time I'm dieting, which should be around Jan08.

[Bison]

Thanks mate

I'm now going on another cut for a month or two and I'll be trying this. Going to place an order at the end of the week and get the ingredients in. Not made my mind up on exact formula I'll use yet but will give updates

EDIT-
I'm thinking:
L-Glutamine 1kg
AAKG 100g
HMB 100g - I've got about 50g left here aswell
Leucine 500g

Might use a lower dosage of HMB but top up with Leucine. So 1.5g HMB + 5g Leucine.

Was going to order most of that anyway, the only real addition is the glutamine as I don't use this.

[nrage04]

sounds good! The addition of leucine can only help. The article says at the hospitals they give the formula twice per day.

Defo keep us updated! This'll be very interesting