Another aspect of mitochondrial function influenced by ketones is the mitochondrial permeability transition pore (mPTP). Prolonged opening of the mPTP is one of the mechanisms through which mtROS can induce cellular injury and promote disease [114]. In neurons isolated from rat brain slices, treatment with BHB + ACA has decreased the mtROS production, mPTP opening, and cell death induced by H2O2 [115]. This protective effect was duplicated with catalase, even in conjunction with diamide-induced opening of the mPTP, indicating that the protective effect of BHB and ACA is at least partly due to defense against ROS [115]. In a mouse model of epilepsy, this decrease in mPTP opening was found to be induced exclusively by BHB, and in a manner dependent on the cyclophilin D subunit of the mPTP [116]. BHB in combination with ACA also appears to promote opening of mitochondrial ATP-sensitive K+ (mtKATP) channels [117], which in heart mitochondria is known to protect against Ca+ overload [118] and dissipate membrane potential (ΔΨ) [119]. Since high ΔΨ promotes mtROS production, dissipation of ΔΨ through mtKATP channels may partly explain the potential for ketones to decrease mtROS production. However, opening of mtKATP channels by pinacidil decreases mitochondrial ATP production [119], which is consistent with dissipation of ΔΨ and suggests a compromise between ATP and mtROS production.
The FOXO family of transcription factors is highly conserved and promotes longevity and resistance to cellular stress. Although there are a variety of FOXO isoforms with varying tissue distribution [318–320], FOXO3a has been the most thoroughly studied in relation to energy sensing, mitochondrial function, and antioxidant defense. Similar to PGC-1α, FOXO3a is activated through phosphorylation by AMPK [321–323] and deacetylation by SIRT1 [324, 325] and SIRT3 [326–329], and its transcriptional activity is at least partly dependent on AMPK [322] and SIRT1 [325]. In a variety of organisms, tissues, and cell types, FOXO3a increases mitochondrial biogenesis and expression of TFAM [329], but is more known for increasing expression of antioxidant and repair proteins, including SOD2 [287, 330, 331], catalase [287, 330, 332, 333], glutathione S-transferase (GST) [322], thioredoxins [287, 323], Prx3 [287, 334], Prx5 [287], and metallothioneins I and II [322], as well as UCP2 [287, 322] and the DNA repair enzyme growth arrest and DNA damage-inducible 45 (GADD45) [322, 324, 335, 336]. FOXO3a is also activated by oxidative stress [324, 331, 333], possibly in a SIRT1-dependent manner [324], and likely mediated through c-Jun N-terminal protein kinase (JNK), which allows FOXOs to translocate to the nucleus by promoting dissociation of 14-3-3 [337, 338]. Furthermore, FOXO3a and SIRT3 interact in mitochondria to induce mitochondrial gene expression in an AMPK-dependent manner [339]. FOXO3a also induces expression of LKB1 [340] and NAMPT [341], indicating a feed-forward cycle of activation with AMPK and sirtuins. Like PGC-1α, FOXO3a transcriptional activity is inhibited by insulin through PKB [331].
This “lazy” keto bread recipe is anything but boring: Crumbling the butter directly into the dough creates moist and tender biscuits for all your sweet and savory recipes. Plus, this recipe takes 30 minutes from start to finish and keeps each biscuit macro-friendly at 3 net carbs. Stay more Bulletproof and use the sour cream and whey protein swaps suggested in the recipe, plus avoid eating flaxseed too often.

Keto is not hard to follow at all. See, this is why I took my diet and nutrition into my own hands. I have PCOS and the ketogenic diet has worked wonders for me. I’m finally pregnant at the age of 32 and after 11 years of marriage because the ketogenic diet made me lose over 100 lbs and brought my insulin resistance under control. I feel better than I’ve ever felt. Sometimes doctors don’t seem to know as much as they should, or as much as they assume they do, and that’s pretty disturbing. Just like they’re still using the old school and very inaccurate BMI charts that are just pure bs. I’ll just take care of myself outside of certain situations involving illness or injury. I’m doing great on my own.
When the kidneys filter blood, metabolic substrates such as glucose and ketones are re-absorbed to prevent energy wastage. If blood levels of a metabolite exceed the capacity of the kidney to reabsorb them, then a ‘spillover’ effect occurs and the metabolite (i.e. glucose or ketones) appear in the urine. However, urine is not a very reliable measure. Firstly, whilst following a ketogenic diet, adaptation occurs over time that means more ketones are reabsorbed in comparison to the early phase of the diet9. Furthermore, at higher levels of ketones, the appearance in the urine does not correlate to levels in the blood10. Similarly, after consumption of exogenous ketones, urine ketone levels were not in proportion to the levels in the blood11 this may be because of the rapid onset of ketosis in comparison to when ketosis is achieved with fasting or diet. Therefore urine test strips are useful as a guide but have several disadvantages to their use to accurately quantify levels of ketosis. 
BHB, in addition to being an important energy substrate, is also a signaling molecule [100–102]. Although not induced through mtROS, BHB inhibits class I and II histone deacetylases (HDACs) in a dose-dependent manner, resulting in greater histone acetylation regardless of whether BHB is elevated through fasting, caloric restriction, or infusion [103]. This inhibition is associated with increased expression of forkhead box O (FOXO) 3a and metallothionein II and increased protein content of FOXO3a, SOD2, and catalase [103]. Consistent with these changes, the kidneys of mice with elevated blood BHB concentrations (∼1.2 mM) were protected from paraquat-induced (50 mg/kg) oxidative damage to proteins and lipids, which was indicated by lower levels of protein carbonyls, 4-HNE, and lipid peroxides [103]. Upregulation of antioxidant defense by BHB-induced HDAC inhibition also appears to be the mechanism through which exogenous BHB extends lifespan in C. elegans [95]. The dependence of this response on FOXO3a, NFE2L2, and several bioenergetic signaling proteins that influence the activities of these two transcription factors [95] is indicative of the overlap between bioenergetics and antioxidant defense that is characteristic of mitohormesis.
Maria I have ALL your books, except your 30 day cleanse, and I have attempted the 7 day weight loss and healing plan, and dairy free I might add, but was so hungry and dizzy on it! My husband pointed out the the “lunch” area, item, says Side. Well I’ve read it 3 times – the front of the book and such, it doesn’t say add food to the “SIDE”…it says use this plan. Also you maybe have said elsewhere, but the math is wrong on the second page for total calories….lastly the intermittent fasting – I thought I read previously in the Metabolism book that you shouldn’t fast more than 3 days at a time, but this book doesn’t mention that. Have you updated your thoughts?
The brain is different as it is dependent on carbohydrates as a fuel source. This is because fats cannot easily cross the blood-brain barrier. The inability to make use of energy within fat poses a problem during periods where there is limited carbohydrate in the diet. If blood glucose levels fall to low, brain function declines. Relatively little energy is stored as carbohydrate (2,000 kCal) compared to fat (150,000 kCal). The body's store of carbohydrates runs out with a few days of carbohydrate restriction. Once glycogen is depleted, a cascade of hormonal signals causes the body to increase the release of stored fats (from adipose tissue). Signals include the fall in blood insulin, rise in a hormone called glucagon and an increase in cortisol (stress hormone) 1. The increase in blood fatty acids is a key trigger for ketone production (ketogenesis). Unlike fats, ketones are readily used as a fuel in the brain. Fatty acids are converted into ketone bodies in the liver, and ketones can provide up to 60% of the brain's energy requirements during starvation 2. The graph below shows how BHB (black triangles) builds up in the blood over many days until it reaches a level of around 6 mM.
I’m following the ketogenic diet and I find it very easy, pleasant and varied. I can even say that my diet today is more varied than the previous one. I do not intend to leave this diet and I cannot really see why. My initial focus was not to lose weight, I’ve always been lean, but to feel better, well disposed. And I got it! I am very pleased, I have read a lot about it (including scientific literature) and I have influenced other people who need to lose weight or improve some aspects of their health. But from the beginning I went on my own way, without the help of a nutritionist because I did not want to suffer the influence of others’ ideas.
I saw this recipe today and went out and bought the ingredients. I made it exactly like the instructions state. Mine actually did rise while it baked. But there is no yeast in this. Was it the baking powder and egg whites? It’s still fluffy and light. But all I taste is egg whites and coconut from. The coconut flour. I could definitely see how this will be an amazing bread… But I’m not sure what I did wrong. I used 12 egg whites just like the recipe called for. I also used the suggested items. Any idea on what I did wrong? I had to have messed up something…

People who have metabolic syndrome typically have apple-shaped bodies, meaning they have larger waists and carry a lot of weight around their abdomens. It's thought that having a pear-shaped body — that is, carrying more of your weight around your hips and having a narrower waist — doesn't increase your risk of diabetes, heart disease and other complications of metabolic syndrome.

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!)
One particular concern to be aware of is the risk for ketoacidosis, which especially applies to diabetics. Ketoacidosis is a dangerous metabolic state in which excessive amounts of ketones are produced. In mostly healthy individuals, ketosis is regulated by insulin, which is the hormone that controls the creation of ketone bodies and regulates the flow of fatty acids into the blood.
People with type 1 diabetes do not produce enough insulin, so their bodies are unable to regulate ketones, which can lead to a dangerous environment. Always consult with your doctor if you have diabetes before changing your diet, and look out for warning signs of ketoacidosis including: excessive thirst, increased urination, nausea, vomiting, abdominal pain, shortness of breath, weakness, fatigue and confusion.
Hi Maria, I love your bread recipes but can’t get over the one thing, the gritty texture you get in one every couple bites due to the psyllium husk, I have tried different brands and all have it. I haven’t tried Jay Robs yet. But have you tried ground up chia seeds instead by any chance? I read somewhere to just add twice the amount of water. Thanks
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.
So when i made this bread it didnt really stay the way i wanted it to be because when i took it out it looked like regular bread but after like 5-10 minutes it sunk down and mine turned blueish-purpleish….is that good?? I dont think i will be making this again….and i measured out all the ingredients too so i dont know what i did wrong…. PLEASE HELP!!!!!!!!!!!!!
So when i made this bread it didnt really stay the way i wanted it to be because when i took it out it looked like regular bread but after like 5-10 minutes it sunk down and mine turned blueish-purpleish….is that good?? I dont think i will be making this again….and i measured out all the ingredients too so i dont know what i did wrong…. PLEASE HELP!!!!!!!!!!!!!
I don’t usually cook making things from scratch. Glad I did this to replace high carb bread! Made my first bread plain this am in microwave using all the ingredients with 1 sub – olive oil no butter. Worked Great! Toasted it and had it with sliced egg, bacon and mayo instead of butter. Nice and firm and the taste, Fabulous! Very satisfying. Thanks for sharing this and making it so easy for us guys that don’t cook from scratch. Appreciate it much 🙂

One of the foods that people tell us they miss most after going keto is bread. (And cookies or cakes, but you get the idea.) We get it, bread is undeniably comfort food. Growing up, it wasn’t unheard of to eat toast for breakfast, a sandwich for lunch, and maybe even a slice of buttered bread along with dinner. Not only is that ton of carbs, but it’s also a lot of empty calories when we could have been eating real-food alternatives, like this bread made from nutrient-dense ingredients!