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I've read on different blogs that intermittent fasting puts a strain on the adrenals since it requires them to release cortisol to maintain steady blood sugar levels. Since a ketogenic diet has a similar effect on the body as fasting, does this also strain the adrenals? Does this diet require the adrenals to release enough cortisol to break down our muscles to provide enough amino acids for use in gluconeogenesis? Or do cortisol levels remain stable since there aren't insulin spikes like there are when eating foods high in sugar or starch? I guess it comes down to this question: how much does gluconeogenesis rely on cortisol during a state of fasting or on a ketogenic diet?

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7 Answers

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Chris excellent question. Plus one for it. In the brain, Neurons determine how much CBF they need based upon their own metabolic demands. CBF is tightly coupled to CMRO2 given the wide variations in blood pressures. A ketogenic diet works by uncoupling CBF from CMRO2! This means that eating a ketogenic diet allows a higher CBF while having a lower resting cerebral metabolism. Carbohydrates and proteins have never shown this benefit in any study I know of testing cerebral autoregulation. This means that a low carb, high MCT fat diet confers a significant metabolic advantage to the brain at all times. The brain directly controls all efferent and afferent pathways of metabolism via its leptin receptor stimulation. The implications are big if that receptor is not functioning because the outflow of that stimulus will not match the desired response of the 20 trillion cells it controls. This is what people refer to as LR. I don't. LR for me is a receptor dysfunction issue. Remember that food is really only a substrate source of electrons for our mitochondria’s electron transport chain in organic chemistry terms. This also means that somehow the electrons that come from these ketone bodies affects the neuronal ATP requirement of cerebral mitochondria.

Matt Lalonde and Lucas Tafur have posted on this topic as well. During oxidative phosphorylation, almost all of the reducing equivalents produced by glucose metabolism in the Krebs cycle are in the form of NADH with the exception of the succinate dehydrogenase step, which takes place in mitochondrial complex II and makes FADH2. Metabolism of one molecule of glucose produces an NADH:FADH2 ratio of 5:1 whereas fatty acid metabolism in beta oxidation and the Krebs cycle will produce a ratio of ≤3:1 depending on the length of the fatty acid. NADH is oxidized only in mitochondrial complex I whereas FADH2 is oxidized only in complex II. Complex I produces more reactive oxygen species than complex II. As such, production of a specific number of ATP molecules from glucose has the potential to generate more reactive oxygen species compared to the generation of the same number of ATP molecules from fatty acids.

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A ketogenic diet decrease the energy mismatch and it lowers the sympathetic outflows out of the brain that innervate the adrenal gland. These do not stimulate the adrenals, they infact protect them at a resting state. – The Quilt Nov 4 2011 at 14:59
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Cortisol can be elevated for many reasons but the key point when considering a diets effect on the brain is about what is happening at the inner mitochondrial membrane. This ultimately will determine the gene transcription (epigenetic swtiches) and the hormone response. Central effects of a ketogenic diet is to decrease sympathetic outflow. – The Quilt Nov 4 2011 at 16:03
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If the liver is also LS and not LR there is no gluconeogenic signal of hypoglycemia and the adrenals are not run ragged. If you are LR or you are overtraining and driving your cortisol up via another pathway then you may cause trouble. I see many believe that ketogenic diets cause adrenal problems. I dont see it and I have a ton of people on them who are LR too. People who believe this seem to forget that their are other pathways that can drive cortisol higher besides the central sympathetic pathways. Ketogenic diets are energy sparing and this is why the brain works better on them. – The Quilt Nov 4 2011 at 16:09
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Its an organ that makes up 2% of our weight and pulls 20% of our cardiac output. It is the quintesential energy hog. Anything that spares it energy makes it work better. And this biochemical truth is laid out above and is well known. Another myth out there is the brain needs exogenous glucose. No it does not ever. It runs perfectly fine on a complete ketogenic diet. In fact all mental functions improve on it because of how it uncouples CMRO2 from CBF. The brain can still draw any glucose it might use from the liver. P – The Quilt Nov 4 2011 at 16:13
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Thanks for your detailed answer Dr. K. I'm with you on most of the biochem, but are you saying that by producing more ROS, glucose, and therefore a non-ketogenic diet, is more inflammatory and requires more cortisol to reduce the inflammation? Basically it seems you're saying that the answer is either you're LR or LS, and if you're the latter then your mitochondria are efficient enough on a ketogenic diet to produce energy without having blood glucose levels fluctuate significantly and thus leave the adrenals unaffected. – Chris Antenucci Nov 4 2011 at 20:38
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There is a detailed question and answer about this topic here.

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Good question. I'd love to hear everyone's thoughts on this. I've been gaining weight not losing! The only thing I hadn't given up was dairy (I had given up milk though). So after 10 mths Archevore, I stopped dairy and in 2 wks lost 4 lbs and then stalled for 2 more wks. I reintroduced dairy and have not gained back. Dr. Kruse suggested thyroid issues might be at work. I've been reading the pop thyroid and adrenal books, websites, etc. and I'm very much concerned about stressing my adrenals too. I feel much better eating 50-75g protein within 3 hrs of waking and am sated until dinner at 6:30. I had been IF using a window from 2pm to 7pm but I found myself stressing physically. I was also VLC to LC and just started increasing at dinner time to see if I'd feel better. Also gave up my Primal beginner workouts as I gained weight in the following wks! I was doing 2 twenty minute WOs/wk, then cut it to once a week and even that fatigued me for a whole wk after. It gets soooo complicated...and I know my docs would never entertain my musings with Paleo, thyroid, adrenals, underlying immune issues, etc. Can't afford to see my neuropath either. Not sure how we recommend Paleo to anyone if we can't get it to work for us...I only had 20 lbs to lose and I gained 4; albeit it may all be muscle as body measurements keep going down. But trying to understand muscle gain is as complicated as trying to understand underlying thyroid, adrenal, immune issues on Paleo.

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instead of trying weird protocols why dont you just do normal paleo i.e. 3 consistent meals made up of fruit, meat, tubers etc. All the fasting and restriction isn't helping imo – cliff Nov 4 2011 at 12:29
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Whoa! You lost size and you're still concerned about weight? I couldn't care less about my scale weight except as a poor proxy for fat mass. What do you think makes you look hotter: a slimmer waist or a lower scale weight? Isn't your size the whole point? – Ambimorph Nov 4 2011 at 17:58
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+1 Sandra, but weird comments, huh? – The Loon Nov 5 2011 at 0:59
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Sorry. Didn't mean to be weird (or rude for that matter). "Weight" just seems irrelevant here -- Sandra is winning, and it would be sad for her to miss that because of relying on a poor measurement. – Ambimorph Nov 5 2011 at 17:22
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Well, I did the normal Paleo for a few mths before tweaking since normal Paleo wasn't dropping the wt everyone raves about. Unfortunately, when you do down the Paleo path you don't read all your options in a nice organized manner. So when you read about IF, you try it! When you read about Primal workouts, you try it. Unfortunately, if you have existing cortisol or thyroid issue you aren't savvy about and don't realize VLC can adversely affect you, you end up trying crazy protocols. – Sandra Brigham Nov 6 2011 at 14:26
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To Sandra Brigham (and others):

You are on a road to big FAIL if you keep fasting when having thyroid issues. I've went through the same.

You should have a minimum, I repeat, a minimum of 3 meals a day not to further screw up your thyroid and adrenals. And understand this: it's the calories, not the fasting, there is nothing magical going on.

Even though meal frequency does not affect body composition (looking good naked), it can affect your health. Less frequent meals and fasting push up your cortisol even though some people may say it doesn't, much like Martin Berkhan cherry picking studies stating cortisol doesn't elevate with IF, to support his whole fan boy base.

Remember there's money to be had with sites, people, supps and consultations and communities like our own. I'm not here to take away your money, just making sure you don't end up doing the mistakes I did.

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Keto per se is an adrenals stressor. That doesn't make keto bad; not all "adrenal stress" is problematic. There's a ratcheting effect, in both directions. Add insufficient sleep/rest to keto and you can skirt cortical overload. Adequate sleep, rest, serene time, will mitigate stress including adrenal. There are very few unlinear causal chains that exist outside of the mind's desire to postulate them. Which is to say: causality is almost always invariably multifactorial.

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I disagree with this. – The Quilt Nov 4 2011 at 15:58
Well isn't that special. – Satchmo Apr 5 2012 at 1:59
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I have no categorical proof, but I guarantee if you are in keto, your adrenals ain't exactly relaxed.

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I disagree with this too. – The Quilt Nov 4 2011 at 15:59
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I like it because of ain't and adrenals in the same sentence. – Cacktus Wayfinder Nov 4 2011 at 18:39
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Thanks. I like your response for the same reason. – Gabriel Nov 6 2011 at 2:29
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Thanks again Quilt. Always with the sharing. Maybe if we paid you $3000 you'd be more helpful. – Satchmo Apr 5 2012 at 2:00
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is there ever a situation where the cortisol/adrenal stress of a ketogenic diet may in fact be a helpful balance to someone who may have lazy adrenals does the term lazy adrenals exist because i know you can almost use the prefix hypo or hyper to most anything in science and i think balance is the key.

this is compared to the above a very layman post i will admit but less science more understanding of the real life picture can provide useful indeed.

ive read about carbs being parasympathetic in general and that parasympathetic dominant types would get a parasympathetic overload when ingesting carbs compared to sympathetic types.

adopting this cns/ans approach to ketogenic diets seems to explain why carbs make me sleepy all the time and a ketogenic diet makes me feel like i just drank eight cups of coffee.

but i would like to hear from the scientist on this one it just seems that to say these cortisol related issues are bad which occur on a ketogenic diet may actually be beneficial to someone who needs such an effect to balance out their already low cortisol i mean it has some use or it wouldn't even exist. and most things in the body revolve around finding balance so i thought i would inquire along these purely non scientific speculative ramblings

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