haidut

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The study below directly contradicts a mantra commonly repeated in nutrition circles - restrict glucose and increase fat oxidation in order to lose body fat. In fact, this idea is so ingrained into the minds of most people that I often get hate mail from people all over the world angrily admonishing me that without increasing fat oxidation weight loss will become impossible.
Well, I suggest carefully reading the study below. First, it shows that FAO is independent of energy expenditure. This directly suggests that FAO has a role that is not so much about supplying energy but likely more as a signalling mechanism - i.e. a stress signal. As such, you'd expect increasing the stress signal (in this case FAO) to NOT lead to weight loss. The study found that increasing FAO by 30%+ did not lead to any weight/fat loss. What it did do is decrease glucose oxidation by the exact same percentage as the increase in FAO, thus confirming nicely the Randle cycle (which the study explicitly mentions). While the study did not look at what happened after the study ended, I'd venture a guess that the poor rodents subjected to pharmacologically increased FAO became insulin-resistant and gained even more weight than the control group after the torture ended. Hopefully, there will be a follow up study that will look at the long-term effects AFTER the stress signal (FAO) is no longer present, and what interventions could restore metabolism back to normal. The study did mention that the role of FAO in diabetes and obesity is "controversial" with some studies finding benefit while others finding FAO detrimental. The current study did NOT find any benefit of increased FAO for insulin sensitivity. So, until we see more follow up studies, the conclusion I'd draw from this study is that stress and its resulting increase in FAO ("endurance" exercise anyone?) is not only not a healthy way to lose weight, but for most people likely won't even work.

Acute or chronic upregulation of mitochondrial fatty acid oxidation has no net effect on whole-body energy expenditure or adiposity. - PubMed - NCBI

"...Body weight and fat mass in mammals are highly robust parameters. Fat mass is very well defended rendering many lifestyle interventions ineffective and so there is a growing need for new therapies. The hypothesis that manipulations which enhance fat burning will reduce adiposity has provided novel avenues and new hope for the treatment of obesity. Indeed there is a link between AMPK activation and leanness (Lage et al., 2008; Narkar et al., 2008). Currently the precise mechanism linking AMPK to leanness is unknown as AMPK activity has both short and long-term effects. On one hand AMPK rapidly increases FAO, primarily via its inhibition of ACC. On the other its prolonged activity regulates many other pathways such as mitochondrial biogenesis (Bergeron et al., 2001; Winder et al., 2000), uncoupling protein expression (Narkar et al., 2008; Suwa et al., 2003), GLUT4 expression (Winder et al., 2000), and the SIRT1 pathway (Canto et al., 2009). Hence, it is unclear if AMPK agonists promote leanness via the FAO pathway or an alternate route (Fig 4G)."

"...To address this question we used pharmacological and genetic manipulations in rodents to increase FAO upstream or downstream of AMPK. We used AICAR to activate AMPK acutely and chronically for 10 days. There was no change in body composition, substrate utilization, or energy expenditure following AICAR treatment at either time point, but there was a clear stimulation of mitochondrial biogenesis in skeletal muscle after 10 days. To test the effects of long-term changes in FAO independently of AMPK we directly targeted ACC2 in mice. ACC2 inhibition led to reduced intracellular malonyl-CoA levels and a concomitant increase in FAO in skeletal muscle without any change in energy expenditure or adiposity. Rather, in both acute and chronic settings, our data show that increased FAO is offset by an alteration in the handling of other macronutrients. Our findings are consistent with previous studies using a non-selective ACC1/2 inhibitor in rats. This inhibitor decreased RER over a 3 h period without altering energy expenditure (Harwood et al., 2003). Secondly, reduced ACC1/2 expression in rat liver and fat using antisense oligonucleotides was without effect on body weight (Savage et al., 2006). This illustrates that increased FAO is insufficient to promote energy expenditure or weight loss. Rather, the inherent flexibility in the metabolic system compensates for enforced FAO by altering carbohydrate metabolism. Such an effect is consistent with the glucose-FA cycle first proposed by Randle (Randle, 1963)."

"...Excess adiposity and lipid accumulation in non-adipose tissues are linked to insulin resistance (Savage et al., 2007). However the effect of increasing FAO on insulin sensitivity is controversial in that some studies indicate that enhancing FAO protects against HFD-induced insulin resistance (Bruce et al., 2009), while other studies show that excessive FAO in fact promotes insulin resistance (Koves et al., 2008). In our study we were unable to observe any protective effect of increased FAO against HFD-induced insulin resistance."

"...Based on the present study it is unlikely that increasing lipid oxidation alone is sufficient to cause leanness. In view of the fact that increased FAO was considered one of the major mechanisms of AMPK in fat reduction and leanness, this leaves open the possibility that the adipose lowering effects of chronic AMPK activation are mediated via an alternate pathway such as increased mitochondrial biogenesis or increased expression of uncoupling proteins."
 

Hans

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Good study. Cardio and especially fasted cardio will drop the metabolic rate whereas feeding and correct training increases the metabolic rate.
In the long run a higher resting metabolic rate will promote to fat loss, while maintaining good health and muscle mass. A great example is DNP.
 

jb116

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Probably the other hidden variable is the composition of fat in an organism. May be why some lose weight with increased FAO and get away with it relatively unscathed is less pufa in their tissues. At any rate higher metabolism and oxidative sugar burning is a much better solution ultimately.

DNP? Ah! I say caffeine FTW ;)
 

haidut

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In the long run a higher resting metabolic rate will promote to fat loss, while maintaining good health and muscle mass. A great example is DNP.

Yep, and I would also add good liver function to that. Many people believe that the only way fat can be lost is through metabolism/oxidation. Not so, a significant amount can be glucuronidated by liver and excreted with urine. The better the liver function the more glucuronidation of FFA it can perform. And also carb supply matters as glucuronic acid is synthesized from glucose.
 

Hans

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DNP? Ah! I say caffeine FTW ;)
Lol yeah caffeine's good, but still a stimulant, whereas I think that most people might actually do better on a pure uncoupler than a stimulant.
Fat loss from DNP seems almost effortless and easy. It's just hard to try to replicate it with other substances which never give the same result.
 

jb116

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Lol yeah caffeine's good, but still a stimulant, whereas I think that most people might actually do better on a pure uncoupler than a stimulant.
Fat loss from DNP seems almost effortless and easy. It's just hard to try to replicate it with other substances which never give the same result.
The interesting thing for me has been I've successfully reduced weight for myself and two others using caffeine but of course with either sufficient carbs or a well-fed state. I was a "hidden" fat type. Didn't look at all, but the visceral fat was there. Went from 183 down to 167, the weight I was basically for most of my 30s. The other is a 70 year old female, started around 68 with a course of caffeine and MCT as well. Over a course of a year she safely shed a good 15 pounds and overall 20 to 25 lbs after 2 years. All this as well as diet overall, removal of pufa, etc. Pre-diabetes gone, arthritic pains way under control. Point is, getting to carb burning and using something metabolically useful such as caffeine did a world of good, and in a safe (but slower) way. But also, with the right fuel, the caffeine wasn't so much stimulating as it was actually relaxing. As far as ease, I don't doubt DNP.
 

Dobbler

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Lol yeah caffeine's good, but still a stimulant, whereas I think that most people might actually do better on a pure uncoupler than a stimulant.
Fat loss from DNP seems almost effortless and easy. It's just hard to try to replicate it with other substances which never give the same result.
Have you actually tried DNP?
 

tankasnowgod

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Nice study. Looking around the forum, it seems that people either mention both niacinamide and aspirin together as hindering fat loss, or simply niacinamide (usually in a higher dose). There are actually a fair amount of testimonials on the forum of aspirin (sans niacinamide) helping people to lose weight. I know at one point, I was using two aspirins a day, and still losing weight.

One issue that has been brought up before, and applies to all of the pro-metabolic substances, is that you need proper fuel, or they can trigger a stress response. With anything that lowers FAO or FFA in the blood, this is easy to see. Stop burning of fat without adequate sugar intake or glycogen, and you've really put your body in a no win situation.

This point was made in a thread about Pregnenolone-

Just want to note. I wrote earlier about pregnenolone raising estrogen etc and making me feel like rubbish.

Well, I have trialed preg again. As usual it raised my temps, energy etc for the first few days. Then I fell back into the bloated, cold, high estrogen effects i get from preg. However, i realized if preg doesnt directly raise estrogen something else was doing it.

What was happening was preg was raising my metabolism. This was causing a release of PUFA's as my detox systems etc ramped up. The increased PUFA's then caused high estrogen, serotonin, low metabolism etc.

After supplementing with a high dose of vitamin E, aspirin, coconut oil etc., my temperatures started to come back up and my distended stomach started to shrink back down.


So, the lesson from that is, increasing your metabolism can cause an increase in circulating PUFA's making you worse off than when you started..

I also think that lower dose niacinamide (meaning about 50-100mg) with carby meals might be a better approach than going for the 500mg or more in a single dose, if trying to lose weight. I have been using this approach along with adding aspirin, and have noticed likely uncoupling effects multiple times during the day, and seemingly after almost any meal. I used to only notice this in meals that included some coconut oil.
 

Hans

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The interesting thing for me has been I've successfully reduced weight for myself and two others using caffeine but of course with either sufficient carbs or a well-fed state. I was a "hidden" fat type. Didn't look at all, but the visceral fat was there. Went from 183 down to 167, the weight I was basically for most of my 30s. The other is a 70 year old female, started around 68 with a course of caffeine and MCT as well. Over a course of a year she safely shed a good 15 pounds and overall 20 to 25 lbs after 2 years. All this as well as diet overall, removal of pufa, etc. Pre-diabetes gone, arthritic pains way under control. Point is, getting to carb burning and using something metabolically useful such as caffeine did a world of good, and in a safe (but slower) way. But also, with the right fuel, the caffeine wasn't so much stimulating as it was actually relaxing. As far as ease, I don't doubt DNP.
Cool, what dose did you use?
 
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Lol yeah caffeine's good, but still a stimulant, whereas I think that most people might actually do better on a pure uncoupler than a stimulant.
Fat loss from DNP seems almost effortless and easy. It's just hard to try to replicate it with other substances which never give the same result.

I heard DNP is super dangerous and risky. Whats your opinion on that?
 

jb116

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Cool, what dose did you use?
For myself I started at 100mg capsules twice a day. I would open the capsule and use the powder. Then after 1 month or so I went to 200mg twice a day. After a couple weeks went to 200mg 3 times a day. This lasted for several months and then I did 400mg may be for a week or two. I found I like 200 or 300mg a few times a day ever since. Within year or so for me my weight was finding equilibrium. Diet and being conscientious as I said was all part of it. Incidentally this also helped me in coffee drinking. I attribute caffeine, taurine and k2 to vast change in liver health. I still think I can improve (crohns from the past can make it a more uphill battle).
 

milkboi

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When I do decide to be a pig, and eat a starch + fat meal, how to mitigate the damage from FFAS + glucose in the blood?
 

Hans

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When I do decide to be a pig, and eat a starch + fat meal, how to mitigate the damage from FFAS + glucose in the blood?
Fats from a meal only appear in the blood about 2 hours after the meal has been eaten so you should be fine.
Muscles burn fat at rest and should help get rid of the fat. Also the liver helps get rid of the PUFAs.

The problems comes in when you deprive yourself of carbs and then increase the oxidation of fat through stress.
 

miki14

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What is about increasing fat metabolism by mild cold exposure , championed by Ray Cronise? Stimulating brown adipose tissue by exposing the body to cold?
 

tankasnowgod

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What is about increasing fat metabolism by mild cold exposure , championed by Ray Cronise? Stimulating brown adipose tissue by exposing the body to cold?

I'm still a bit on the fence about the idea of "cold thermogenesis." I have largely stopped doing it. It's fairly easy to see that it can be a stressor in many situations, especially the more extreme protocols. However, I have noticed getting very warm overall when I get the uncoupling effects I described earlier in the thread. At that point, I have naturally sought out cooler environments, and it is very complementary. Things like going for a swim to cool down, being in heavy air conditioning, or even wearing a cooling vest in these situations is likely beneficial. But forcing yourself into an ice bath or locking yourself in a sub zero meat locker is likely not.

And I would think any use of cold to "force" FAO is bad.
 
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