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The coordinated effects of AMPK, SIRT1, and SIRT3 are primarily mediated through PGC-1α, which is activated through phosphorylation by AMPK [242, 265] and deacetylation by SIRT1 [77, 242, 266–269]. SIRT3 also increases PGC-1α activity [270], possibly through cAMP response element binding protein (CREB) [271, 272], but the exact mechanism has not been elucidated. In addition to phosphorylating PGC-1α, activated AMPK also increases PGC-1α expression [260, 273–276]. Activation of β2-adrenergic receptors [277–280] and the adiponectin AdipoR1 receptor [281] also increase PGC-1α expression, independently of AMPK activation [278, 281]. PGC-1α activity is increased by oxidative stress [76, 77, 282–284], possibly through activation of AMPK [259, 260] or p38 mitogen-activated protein kinase (MAPK) [283, 284], or inhibition of glycogen synthase kinase 3β, which inhibits PGC-1α through phosphorylation [77, 283]. In contrast, insulin decreases PGC-1α activity through phosphorylation by PKB [285]. Once activated, PGC-1α interacts with the PPAR family of nuclear receptors [286] and the FOXO family of transcription factors [287] to influence expression of a variety of bioenergetic and antioxidant proteins. PGC-1α most notably increases transcription of proteins involved in mitochondrial biogenesis and respiration [76, 242, 265, 267, 269, 274, 279, 282, 285, 288–293] but also increases transcription of antioxidant proteins including SOD1 [76], SOD2 [76, 282, 289, 292–294], catalase [282], GPx [76, 294], thioredoxins [282, 283, 292], TRXR [282, 292], Prx3 [282, 292], and Prx5 [282, 292], as well as the mitochondrial uncoupling proteins UCP2 [76, 265, 282, 288, 294], UCP3 [76, 265, 294], and ANT [76, 295].
Therefore the combustion enthalpy (∆H) of each fuel is an important factor in the energy it can provide to the cell. When expressed as the energy per 2 carbons in the molecule, ketones (BHB) have a higher combustion enthalpy (∆H) than pyruvate, lactate and glucose (see table). This means that the amount of energy that could possibly be transferred to ATP is higher than for those other substrates:
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More definitive evidence that metabolic syndrome per se predisposes to coronary heart disease and cerebrovascular disease has been reported. Thus a twofold to fourfold increase in subsequent cardiovascular events has been described in men and women with metabolic syndrome (modified WHO criteria) even in the absence of type 2 diabetes or impaired glucose tolerance.234-236 Qualitatively, similar results have been obtained when metabolic syndrome was defined by ATP III criteria237,238 (Fig. 43-9). In a compilation of multiple studies, the presence of metabolic syndrome had a greater impact on the risk for developing diabetes (fivefold) than ASCVD (twofold).22,182,199 In addition, where studied, the rate of cardiovascular events was higher in patients who had diabetes and metabolic syndrome than in individuals with only metabolic syndrome.22,239
I made two portions in flat soups bowls. Added a hard boiled egg & grilled onions from the pork rendering and sage dressing spices. It was awesome. The only thing I could have done to make it better would have been a quarter cup or less of water in the skillet for the flavor and poured it on top of the dressing. Don’t be afraid to experiment with this awesome bread recipe.
Ketone esters (BHB-BD) could help to accelerate glycogen resynthesis32. After exercise that depletes muscle glycogen, the muscle uses carbohydrate from the diet to replenish these stores. An experiment was carried out where athletes undertook depletive exercise and then were given a ketone drink (or carbohydrate placebo) as well as glucose intravenously to maintain a high blood level (10mM). In this experiment, when the recovery drink contained ketone ester, more glucose was infused in order to maintain blood glucose at 10 mM, and muscle glycogen levels were 50% higher. However, the evidence is not conclusive: another study. 31 found that adding ketone ester to a protein and carbohydrate recovery drink did not enhance the normal rate of glycogen re-synthesis.  
When preparing keto bread recipes, look out for low-carb ingredients that could contribute to brain fog and inflammation. Skip recipes that require conventional dairy or yeast, and avoid eating common keto bread ingredients like psyllium husk, xanthan gum, and nuts or nut butters too often — these can contain mold or irritate your gut. Grass-fed butter, ghee, and coconut flour are the few exceptions that will still produce a stellar loaf.
A reduced availability of dietary carbohydrates leads to an increased liver production of KBs. The liver cannot utilize KBs because it lacks the mitochondrial enzyme succinyl-CoA: 3-ketoacid (oxoacid) CoA transferase (SCOT) necessary for activation of acetoacetate to acetoacetyl CoA. KBs are utilized by tissues, in particularly by brain. KBs enter the citric acid cycle after being converted to acetyl CoA by hydroxybutyrate dehydrogenase (HBD), succinyl-CoA: 3–CoA transferase (SCOT), and methylacetoacetyl CoA thiolase (MAT). Modified from Owen (2005), Paoli et al. (2014).
But comprehensive transcriptional profiling of glucose-sensing neurons is challenging, as glucokinase (Gck) and other key proteins that transduce glucose signals are expressed at low levels. Glucose also exerts a hormonal-like action on neurons; electrophysiological recordings demonstrated, for example, that hypoglycemia activates growth hormone-releasing hormone (GHRH) neurons, suggesting a mechanistic link between low blood glucose levels and growth hormone release (Stanley et al., 2013).
This bread does have quite a few ingredients, but you’ll find that most are staple paleo and keto pantry ingredients. In the list below you’ll find details on several ingredients and possible subs. But if possible, please do try and make this recipe without any subs. As out of the 18 permutations we tried, this one really was terrific and the absolute best.

The prevalence of metabolic syndrome increases with age, with about 40% of people older than 60 years meeting the criteria. [26] However, metabolic syndrome can no longer be considered a disease of only adult populations. Alarmingly, metabolic syndrome and diabetes mellitus are increasingly prevalent in the pediatric population, again in parallel with a rise in obesity. [50]
LOVE this bread. As a pregnant type 1 diabetic, I was looking for something to toast. I’ve tried multiple different recipes from other sites, and the bread is always so crumbly that you can never spread anything on it. This one is AMAZING! I may have to experiment with more water so that it comes out less dense, but soooo happy to prevent blood sugar spikes with future sandwiches. I can even foresee being able to have traditional burgers again (not just wrapped in lettuce). My husband bakes his own “normal” bread, and now I get bread too and its even easier to make than his 🙂
In controlled studies on exercise-trained humans and animals, ketogenic diets have been shown to increase fat oxidation [8, 167] and expression or activity of carnitine palmitoyltransferase [167, 168] and β-HAD [168, 172], demonstrating that nutritional ketosis induces adaptation beyond exercise. Similarly, in a study comparing the independent and combined effects of exercise and a ketogenic diet on rats, the combination resulted in greater β-HAD and citrate synthase activities in skeletal muscle and higher maximal O2 consumption than either intervention alone, further indicating the potential for exercise to magnify adaptations induced by nutritional ketosis [156].
Thanks for replying. I guess I’ll just try it on both convection and regular and see which works out best! 🙂 I had made the sub roll in a regular oven with good results yet it didn’t turn out as well when baked on convection. That’s why I was wondering about the temperature and whether that was the culprit. Guess there’s only one way to find out. This experimenting can get expensive!
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Not so anymore. Thanks to the rising obesity epidemic in young people, kids and teens are getting these conditions — and they're getting them earlier than ever before. Some estimates say that nearly 1 in 10 teens — and over a third of obese teens — have metabolic syndrome. And a study of 375 second- and third-graders found that 5% had metabolic syndrome and 45% had one or two risk factors for it.

Ketosis is a sensitive state so as soon as you increase your carb intake above your carb tolerance, you’re out! You probably don’t want to continuously weigh and count your food for the rest of your life. So even if you stick to the approved list of ketogenic food, there is no guarantee that you will be in ketosis without interruption. That’s OK. Now if you’re in ketosis to manage cancer or epilepsy, that’s a different story obviously.
Version two was almond flour only. Right away I could tell the recipe would need some modifications. Almond flour doesn’t soak up nearly as much liquid as coconut flour, resulting in a very soupy batter. I added two more tablespoons of almond flour, which was double the amount of coconut flour, and it still wasn’t nearly as thick. After its short stint in the microwave, this bread turned out very moist, soft, and rather flimsy, but was pleasantly bland enough to go with any filling I wanted.
I just made this bread and it is beautiful! I cannot believe how well it rose-finally a nice rounded full loaf of bread! BUT…the bottom sticks and in order to get it out, I really have to abuse it, which causes some deflation and a not-as-pretty-as-it-should-be loaf. Ended up with a hole on the bottom that got stuck in the pan. I am using a coated aluminum pan with generous amount of coconut oil. Any tips? I put this loaf back in the oven on a cookie sheet to firm up the crust areas that are damaged. Thanks!
Dr. Campos, it is so discouraging to see that you disparage the ketogenic diet based on your assumption that it is very heavy in poor quality processed meats. No diet that relies on processed foods can be viewed as “healthy”. Become better informed by getting up to speed with what Jeff Volek, RD, PhD, calls a “well-formulated ketogenic diet.” Also, learn more about the potential of the diet to slow cancer progression (my specialty). You owe it to your patients who are depending on you for advice. Present them with facts, not opinions.
Fill half your plate with non-starchy vegetables. Split the other half in two between protein and whole-food carbs such as brown rice, quinoa, beans, legumes, or ancient grains such as amaranth, millet, or farro. These complex carbohydrates have more fiber and nutrients than processed carbs such as white rice, bread, and pasta, and the fiber helps control blood sugar levels.
Maria – I have been looking at this recipe for years. I have bought everything needed over time, down to the kitchen scale but never baked it. For some reason baking bread made me nervous! Well tonight I bit the bullet and tried it out. It was so easy!! I followed your recipe to a T, measured everything…it came our perfectly! Thank you for all you do! The bread is delicious it’s been years since I’ve enjoyed a slice of bread with butter on it! (Kerry a Gold of course!)
Ketosis is deliberately induced by use of a ketogenic diet as a medical intervention in cases of intractable epilepsy.[12] Other uses of low-carbohydrate diets remain controversial.[14][15] Carbohydrate deprivation to the point of ketosis has been argued to have both negative[16] and positive effects on health.[17][18] Ketosis can also be induced following periods of fasting (starvation),[19] and after consumption of ketogenic fats (such as medium chain triglycerides[citation needed]) or exogenous ketones.[20]
As you may recall, about 60% of the energy we expend, say 1,800 kcal/day for someone consuming 3,000 kcal/day in weight balance, is purely devoted to keeping us alive by generating enough ATP (“energy currency”) to do 2 things: allow ion gradients to function and allow muscular relaxation.  So, obviously, we can’t tolerate – literally even for one minute – insufficient ATP production.  In fact, one of the most potent toxins known to man (cyanide) exerts its effect on this process by inhibiting the electron transport chain which generates the bulk of the ATP our body produces.  Even the most transient interruption of this process is fatal.
I’m discouraged to see that nowhere in the article nor in the comments is there a mention of a diet’s best fit to genetics. Consider if someone is an APOE E2 carrier and/or has certain polymorphisms of the APO5 gene. These are quite rare in Okinawa but much more prevalent in the USA (12% of the population). According to a number of well-designed studies, these genetic characteristics point to a higher fat, lower carbohydrate diet as beneficial and even a “moderate” carb diet as problematic.

To get into ketosis without supplementation, you have to keep your insulin levels low. Supplementing with exogenous ketones can help get you into ketosis [17]. However, you won’t have achieved the same beneficial physiological changes as you would have from a well-formulated ketogenic diet or fasting. This is why we at Nutrita don’t recommend exogenous ketones as a substitute for a well-formulated ketogenic diet.
Basically, carbohydrates are the primary source of energy production in body tissues. When the body is deprived of carbohydrates due to reducing intake to less than 50g per day, insulin secretion is significantly reduced and the body enters a catabolic state. Glycogen stores deplete, forcing the body to go through certain metabolic changes. Two metabolic processes come into action when there is low carbohydrate availability in body tissues: gluconeogenesis and ketogenesis.[4][5]

For those, like myself, wanting a low-carb real bread I would recommend a proper low-carb yeast bread recipe with vital wheat gluten (the vast majority of people have zero gluten sensitivity, so the gluten-free fad is at best a waste and at worst a scam). Such breads have approx 1.5-2 grams more net carbs per 40g slice (5-6 grams total net carbs) than this recipe and I think it’s worth it.

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Like many variables in diet, health, and disease, it behooves us to look beyond the bumper sticker explanation. I want to highlight a couple of posts I wrote, to attempt to provide a little more nuance and understanding to the subject: “Ketosis — advantaged or misunderstood state?” Parts I and II. Part I follows below. I’m hoping to write more on the topic in the not-too-distant future since there’s been a number of intriguing papers published recently (certainly since 2012). But I also wanted to bring these back into focus in light of the information I’m seeing more of on the interwebz. (You can also visit the Ketosis section of the site to view more articles on the subject.)
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AGAIN I tried the protein bread, this time I even bought Jay Robb whey protein even though I have a huge container of whey protein, I thought I needed to try to do exactly what you were doing ;). And AGAIN my bread flopped. I whipped the egg whites very STIFF but as soon as I add the protein it breaks them down and it turns to a thick liquid. I bake it anyway and it comes out probably half the size of yours and there are spots through out that look dense like it’s not done. I love the bread and I need a bread substitute to feel satisfied. I’ll keep trying. sighhhhh.
This keto bread recipe delivers sweet heat with no corn whatsoever — instead, it uses a blend of coconut flour and sweetener to capture the same taste and texture for about 3 net carbs per serving. Add fresh cranberries and jalapeño slices for a fun twist that pairs well with holiday meals. To keep this recipe more Bulletproof, use grass-fed butter, swap almond milk with full-fat canned coconut milk, and skip the peppers if you have a nightshade sensitivity.
BMI (body mass index), an alternate measure of obesity that is used by many healthcare practitioners; it is calculated by taking: (Weight in pounds X 705) / (height in inches squared); for example: (150 pounds X 705) / (67 inches X 67 inches) = a BMI of 23.5. An adult with a BMI greater than 30 is considered obese. This calculation does not, however, describe where the excess weight is on the body.
An increase in fat burning ability could improve endurance capacity: as body fat represents a larger store of energy (150,000 kCal) compared to carbohydrate (2000 kCal), a greater ability to burn fat during exercise could prolong endurance performance. Whilst the theory appears sound, there is only one study showing an IMPROVEMENT in performance with a low carbohydrate diet18, with many showing no clear benefit of a low carbohydrate diet 19 ,20.    
Abundant data suggest that patients meeting these diagnostic criteria have a greater risk of significant clinical consequences, the 2 most prominent of which are the development of diabetes mellitus [6] and of coronary heart disease. Pooled data from 37 studies involving more than 170,000 patients have shown that metabolic syndrome doubles the risk of coronary artery disease. [7] It also increases risk of stroke, fatty liver disease, and cancer. [8] (See Prognosis.)
For those, like myself, wanting a low-carb real bread I would recommend a proper low-carb yeast bread recipe with vital wheat gluten (the vast majority of people have zero gluten sensitivity, so the gluten-free fad is at best a waste and at worst a scam). Such breads have approx 1.5-2 grams more net carbs per 40g slice (5-6 grams total net carbs) than this recipe and I think it’s worth it.

Our keto bread recipe has a beautiful golden crust. It has great structure with a lovely rise and perfect bread-like crumb. It slices well for sandwiches or toasting, but you don’t have to toast or grill it to make it taste good. Sliced with a smear of salted butter is keto perfection. And it actually tastes like bread, not eggs or almonds or coconut. Additionally, this bread will keep well wrapped in the fridge for up to a week!