Although the majority of links between energy sensing and antioxidant defense are manifested further downstream, there is some direct influence at the level of AMPK and sirtuins. AMPK is activated by oxidative stress [259, 260], likely through ATP depletion and a subsequent increase in the AMP to ATP ratio, or facilitation of tyrosine phosphorylation, which occurs independently of AMP and ATP concentrations [259]. SIRT3 contributes more directly to antioxidant defense by deacetylating and activating SOD2 [261–263]. The overlapping effect of SIRT3 on antioxidant defense and bioenergetics is further supported by SIRT3 knockout increasing lipid peroxidation in conjunction with decreased O2 consumption in mouse skeletal muscle and also by SIRT3 knockdown increasing H2O2 production and decreasing O2 consumption in myoblasts [264].

As previously discussed, RET is a prominent source of mtROS and is dependent on a high Δp across the inner mitochondrial membrane. During ATP production, Δp is dissipated as H+ enters the mitochondrial matrix through ATP synthase. Mitochondrial uncoupling also dissipates Δp, but by allowing translocation of H+ into the matrix independent of ATP synthase. Uncoupling is therefore regarded as an antioxidant defense in that it can mitigate mtROS production [122–126]. In fact, only a small dissipation of ΔΨ or ΔpH (components of Δp) is needed for a large decrease in mtROS production [57–60, 127].


Ketogenic diets have become popular in recent decades for their demonstrated positive effects on weight loss (Bueno et al., 2013), though the precise mechanism of action is not fully understood (Paoli, 2014). In fact there is contradictory data about KD in mice and rats. In fact, there are contradictory data about KD in mice and rats. For example whilst a huge amount of data confirm that KD in humans is effective in weight reduction, improving lipidemia and glucose tolerance (Bueno et al., 2013), it has been recently demonstrated that a long-term KD (22 weeks) caused dyslipidemia, a pro-inflammatory state, hepatic steatosis, glucose intolerance and a reduction in beta and alpha cell mass, all without weight loss in mice (Ellenbroek et al., 2014). Two considerations should be made: (1) the induction of ketosis and the response to ketosis in humans and mice are quite different and (2) mice and humans have different life spans, and results obtained in mice after several weeks on the diet can correspond to months on the diet in humans (Demetrius, 2005, 2006).
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.

So, if I’m deprived of a dietary source of glucose, I depend solely on my liver to release glycogen (a process known as hepatic glucose output, or HGO).  How long can HGO supply my brain with sufficient glucose? It depends on a few things that impact both the “source” and the “sink” of glucose.  Other competing sinks for glucose (e.g., activity level, thermogenic needs) and sources (e.g., glycerol and gluconeogenic amino acid availability) can make a difference for a while. But, in a state of starvation we’ve only got about one to three days before we’re in trouble.  If our brain doesn’t get a hold of something else, besides glucose, we will die quite unceremoniously.
289. Kukidome D., Nishikawa T., Sonoda K., et al. Activation of AMP-activated protein kinase reduces hyperglycemia-induced mitochondrial reactive oxygen species production and promotes mitochondrial biogenesis in human umbilical vein endothelial cells. Diabetes. 2006;55(1):120–127. doi: 10.2337/diabetes.55.1.120. [PubMed] [CrossRef] [Google Scholar]
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We’ve longed been told that calorie restriction, increasing exercise and reducing dietary fat intake are the keys to weight loss. But, if you’ve ever attempted to control your weight by subsisting on fewer calories — especially from mostly bland “diet foods”— you’re already probably aware that this typically produces minimal results and is extremely hard to stick with long-term or consistently.
Eggs and hash browns are the quintessential American breakfast—but carb-loaded potatoes are a definite no-go on the keto diet. Luckily, with a little creativity, you can whip up a delicious low-carb alternative using cauliflower. These hash browns from Keto Connect are made with just cauliflower, shredded cheese, and an egg (plus any seasonings you want), and contain just 3.2 grams of net carbs per serving. They’re the perfect bed for other breakfast ingredients, like eggs, bacon, and avocado, or ground beef, sour cream, and guacamole.
Mohanraj, R., & Sivasankar, S. (2014, June). Sweet Potato (Ipomoea batatas [L.] Lam) – a valuable medicinal food: A review.  Journal of Medicinal Food, 17(7), 733–741. Retrieved from https://www.researchgate.net/profile/Remya_Mohanraj2/publication/263096030_Sweet_Potato_Ipomoea_batatas_L_Lam_-_A_Valuable_Medicinal_Food_A_Review/links/54ee2b8b0cf2e55866f22c1a.pdf

In addition to BHB inducing upregulation of antioxidant defense, ketones have direct antioxidant capacity. BHB scavenges •OH, as does ACA, although to a lesser extent [108]. The applicability of this antioxidant capacity has been investigated in vitro and in vivo in the context of hypoglycemia. In cultured hippocampal neurons, treatment with BHB or ACA decreased ROS during hypoglycemia induced through inhibition of glycolysis, and in hypoglycemic rats, infusion of BHB decreased hippocampal lipid peroxidation [108].
I’m so glad you love it, Tanya! Yes, $17 sounds like a lot for xanthan gum. I use this one here. Swerve is sweeter than erythritol, so you’d need less of it – I have a conversion chart here. You’re absolutely right about the xanthan gum and texture – it will make the bread more chewy. It will still be more of a “light and fluffy” bread, but definitely less muffin-like with the xanthan gum. I haven’t tried add-ins yet – let me know how it goes if you try!
You can’t find Jay Robb Psyllium Husk anywhere online. I called their company today and they have no idea when it will be back in stock. They said they were restructuring, whatever that means. So my question is this, is there a similar brand I can try that won’t turn my bread purple. It tastes great, but I’m not crazy about the color. Thanks for this recipe, it’s just wonderful!
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Hi Maria, glad you like the bread! Good question about the olive oil – on the one hand using the same amount as butter would mean you stick with the same wet/dry ratio, on the other had olive oil doesn’t firm up at room temperature, but butter and coconut oil do. Therefore, I’d try using a bit less olive oil than butter, maybe 40g instead of 60g. You could also get hold of refined coconut oil, which does not have the coconut taste, for example this one.
Clinical trials of various ketogenic agents have shown promising outcomes in AD. Recently, a case report was published describing a dramatic improvement in cognitive function in a patient consuming daily drinks of a ketone ester of beta-hydroxybutyrate-butanediol54. This corroborates evidence from animal studies of AD, which showed behavioural and anatomical improvements in AD mice treated with the same ketone ester55. Also, medical foods containing medium chain triglycerides can give an acute improvement in cognitive scores in AD patients 56 ,57. The effectiveness of this treatment was found to depend on the absence of a gene variant that has been associated to increased chance of AD, called APOE4. Finally, following a ketogenic diet for 6 weeks improved the symptoms of mild cognitive impairment58. It is still early days, but the use of ketogenic diets and exogenous ketones may help to improve the quality of life of patients with dementia and their caregivers.             
Hello, I’m sure you must roll your eyes at getting yet another post about glitches when making this bread. Unlike the first loaf I made I had four loaves turn out gummy. it still makes reasonable toast but I’d like to avoid this the next time I make the bread. I used your recommended almond flour, and I really ground the psyllium. However in narrowing things down there are two factors that may have contributed to the problem: 1) I mixed up two loaves at a time and I wonder if the dough was too heavy for my mixer and did not combine sufficiently. 2) I may have let a very small amount of yolk fall into the whites. Would either of these caused the gummy texture? Thanks for this amazing website. We purchased all your books and find them a wealth of information. Liz
Thanks for this article. I just started a Keto diet so found it appropriate to my current lifestyle. Though I don’t believe your bottom line is strong enough since you simply stating that the diet is “hard to follow” and food is “notoriously unhealthy” without evidence going deeper into why those “notoriously unhealthy” foods are worse than keeping carbohydrate-heavy food that are addictive and give the body a quick sugar high for energy. I believe “hard to follow” is your opinion only, since acceptable Keto foods are found at all restaurants easily and also all grocery stores. All the foods you mention: “rich in very colorful fruits and vegetables, lean meats, fish, whole grains, nuts, seeds, olive oil, and lots of water” are all Keto-friendly. Many people have been on a Keto-diet for years. A healthy lifestyle is a healthy mindset change and making right choices – it’s not going to be easy.

Ceejoy – Please don’t give into fear mongering. There is nothing wrong with the microwave. It is 100% safe to use. If you still want to not use one, that’s your choice but please don’t spread incorrect information and try and get people to be fearful of something that is safe. If you have any legit studies to prove this (recent ones) please share those.
Angie, I’m happy to hear you and your hubby enjoyed the taste, but sorry to hear the bread was flat! The egg whites don’t need to be whipped for this recipe, but I’ll try to help you troubleshoot…first I would check to make sure that your baking powder is fresh. Also, did you use the full cup of egg whites? Did you make any ingredient substitutions or adjustments? Did you use a 9 by 5-inch loaf pan? Did you cook it at 350F and is your oven properly calibrated? Did you bake it for the amount of time the recipe calls for? I hope this helps!
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