Populations living further north had much less edible vegetation available for gathering. Thankfully for us, animals that lived in these areas ate the vegetation inedible to us, effectively transforming it into fatty meat we could hunt and enjoy. These people most certainly relied on high levels of fat and protein, thus likely spending most of their time in ketosis.
In the previously described C. elegans experiments demonstrating mitohormesis, knockout of the NFE2L2 homologue SKN-1 attenuated the increases in antioxidant enzyme activity and lifespan [73], indicating that mitohormesis may, at least in part, be dependent on NFE2L2 signaling. Similarly, a ketogenic diet (Bio-Serv F3666) increased nuclear content of NFE2L2 and expression of its target NQO1 in the hippocampi of rats, all of which occurred after an initial increase in mtROS [96]. This increase in NFE2L2 content appears to have mediated the subsequent decrease in mtROS to a level below baseline [96], thereby further indicating a likely role of NFE2L2 in the induction of mitohormesis during a ketogenic diet.
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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].
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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:
It looks and smells beautiful when baking. The bottom of my loaves is heavy and dense. The top rises and makes an air pocket. As a result, it’s just not really pleasant to eat with it being so dense and solid even though it tastes good. The few good pieces at the very ends were yummy. I really don’t know what to do. Almond flour is expensive to be going through it like this. 🙁
Ultimately, cancer is highly complex, whereas some tumors may be highly responsive to carbohydrate restriction, others may become adapted to utilise fats or ketones. Cancer, and the treatments currently in use cause unpleasant systemic effects such as muscle wasting and compromise of the immune system, therefore any interventions should be undertaken under the guidance of a doctor. There are limited treatment options available for some types of cancer, many drugs have toxic side effects and many types of cancer have a poor prognosis. In these cases, considering metabolism as an adjunct to conventional treatments is interesting, and offers the potential of another avenue of attack on cancer.  
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This was a great read. I aim to restrict carbs always because I believe most are why the American population is obese. I would very much like to hear more about carb restriction excluding the discussion on processed meats and processed high salt content foods because I consume neither. I also don’t consume dairy or eggs. So can you provide some substance.
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People suffering from diabetes and taking insulin or oral hypoglycemic agents suffer severe hypoglycemia if the medications are not appropriately adjusted before initiating this diet. The ketogenic diet is contraindicated in patients with pancreatitis, liver failure, disorders of fat metabolism, primary carnitine deficiency, carnitine palmitoyltransferase deficiency, carnitine translocase deficiency, porphyrias, or pyruvate kinase deficiency. People on a ketogenic diet rarely can have a false positive breath alcohol test. Due to ketonemia, acetone in the body can sometimes be reduced to isopropanol by hepatic alcohol dehydrogenase which can give a false positive alcohol breath test result. 
Hi Melissa, Are you beating the whole eggs? It needs to be egg whites only. Whole eggs will never form peaks. Adding a little cream of tartar helps, as well as making sure you start with a very clean bowl (preferably not plastic if you’re having issues). Having the egg whites at room temperature can be a little easier, too, though I usually don’t need to. Hope this answers your question!
Losing weight is 80% diet. Volek and Phinney did a study where they put people on a High fat (65-80% of calories from fat, 50-75 grams protein and low carb) and had one group do no exercise, one do resistance training and one to resistance training and cardio. All 3 groups lost the same amount of weight on average. But the resistance training group lost almost entirely fat while preserving muscle mass, which is important. So I always advocate some resistance training. 🙂

“Whole fruit is nothing but good for people who have prediabetes,” Wright says. Just don't consume produce in the form of juice or smoothies. “Though a smoothie does give one a concentrated source of nutrients, they are often packed with calories that don’t satisfy our hunger as there is little fiber in them,” Denison says. So rather than drinking your fruit, eat it, spacing it out over your day.
High-density lipoprotein (HDL – the "good" cholesterol) ordinarily transports excess cholesterol from the tissues back to the liver. In the liver, the cholesterol is either recycled for future use or excreted into bile. HDL's reverse transport is the only way that cells can get rid of excess cholesterol. It helps protect the arteries and, if there is enough HDL present, it can even reverse the build up of fatty plaques in the arteries. When there are excessive amounts of VLDL and triglyceride present, however, HDL concentrations in the blood decrease.
tips for making this bread with coconut flour and those getting purple results! i made half the recipe and made the following changes: 3/4 cups of water, 1 teaspoon baking powder, 1/2 teaspoon baking soda. my bread which previously came out purple and with very dense patches came up much fluffier and with more bread like ‘holes’ and also had the colour of normal brown bread! i baked it in a small loaf and the bread rose a lot but the top half was basically a tunnel. the rest of it is good ‘bread’ though! 🙂

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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].
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 🙂

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!!!!!!!!!!!!!


To figure out how many calories you need from each macronutrient group, first figure out how many calories you should be eating in total for weight maintenance or loss. You can use an online calculator, such as the one created by the National Institute of Health found here to help determine your energy/calorie needs. Then split up your calorie intake into fats, proteins and carbs.
In addition, as early as in 2008, the Swedish Board of Health and Welfare examined and approved advice on LCHF within the health care system. Advice on LCHF is, according to the Swedish Board of Health and Welfare’s review, in accordance with science and proven knowledge. In other words, certified healthcare professionals, who give such advice (for example myself) can feel completely confident.
I have made your sub bread a few times with not good results. Tasted ok but it was gummy in the middle. Tonight I made the bread and it looked beautiful in the oven but when I took it out it deflated and was completely hollow in the middle. lol. This time I weighed everything to the T. I used Honeyville almond flour, liquid egg whites, and psyllium powder. Think I will skip trying the bread and try the sub bread again one more time. Probably made the sub bread 4x and all times came out gummy….grrrr. Hate to give up because the taste was good. Any suggestions??
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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.

143. Echtay K. S., Winkler E., Frischmuth K., Klingenberg M. Uncoupling proteins 2 and 3 are highly active H+ transporters and highly nucleotide sensitive when activated by coenzyme Q (ubiquinone) Proceedings of the National Academy of Sciences. 2001;98(4):1416–1421. doi: 10.1073/pnas.98.4.1416. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Note that urine measurements may not reflect blood concentrations. Urine concentrations are lower with greater hydration, and after adaptation to a ketogenic diet the amount lost in the urine may drop while the metabolism remains ketotic. Most urine strips only measure acetoacetate, while when ketosis is more severe the predominant ketone body is β-hydroxybutyrate.[36] Unlike glucose, ketones are excreted into urine at any blood level. Ketoacidosis is a metabolic derangement that cannot occur in a healthy individual who can produce insulin, and should not be confused with physiologic ketosis.


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Long-term compliance is low and can be a big issue with a ketogenic diet, but this is the case with any lifestyle change.  Even though the ketogenic diet is significantly superior in the induction of weight loss in otherwise healthy patients with obesity and the induced weight loss is rapid, intense, and sustained until at least 2 year, the understanding of the clinical impacts, safety, tolerability, efficacy, duration of treatment, and prognosis after discontinuation of the diet is challenging and requires further studies to understand the disease-specific mechanisms.


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.  
The difference between ketosis and ketoacidosis is the level of ketones in the blood. Ketosis is a physiological adaptation to a low carbohydrate environment like fasting or a ketogenic diet. There are situations (such as treatment-resistant epilepsy) where ketosis can be beneficial to health. Ketoacidosis is an acute life-threatening state requiring prompt medical intervention; its most common form is diabetic ketoacidosis where both glucose and ketone levels are significantly elevated.
In order to best investigate the efficiency of different fuels, one needs a closed system, where the substrate conditions can be changed and the oxygen consumption and work done can be accurately measured. Isolated (ex-vivo) animal hearts are the best model to study these variables, as it is easy to manipulate the fuel provided (i.e glucose, ketones), to measure the oxygen use and also the amount of work (how much fluid is pumped). 
^ Bechtel PJ (2 December 2012). Muscle as Food. Elsevier Science. pp. 171–. ISBN 978-0-323-13953-3. Retrieved 19 May 2014. Freezing does stop the postmortem metabolism but only at about −18ºC and lower temperatures. Above −18ºC increasing temperatures of storage cause an increasing rate of ATP breakdown and glycolysis that is higher in the comminuted meat than in the intact tissue (Fisher et al., 1980b). If the ATP concentration in the frozen tissue falls below ~ 1 µmol/g no contraction or rigor can occur because they are prevented by the rigid matrix of ice.
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The last issue is your consumption of “residual” carbohydrates—the carbs you’re not even aware you’re eating, like those in nuts and meal-replacement shakes. It’s OK to have some nuts, but you should rely more on other fat sources that are carb-free like oils and cheeses. Remember that meal replacement shakes and protein shakes are not the same. The typical meal-replacement powder contains up to half your day’s intake of carbs. Instead, opt for a scoop of regular protein powder after your workout. Make these changes and you’ll see your six-pack soon enough.
Many questions about the role of such an important intermediate of lipid metabolism remains unanswered, e.g., the role of BHB in food control. For example, whether or not BHB could act as a satiety signal in the brain, considering its role in energy supply to CNS. We have to consider that the effects of KBs on hunger reduction can only be seen after many days following fasting or KD initiation (Paoli et al., 2010); this is consistent with the abovementioned threshold of brain utilization of KB as an energy source, i.e., 4 mmol/L (Veech, 2004), which is close to the Km for the monocarboxylate transporter (Leino et al., 2001). During the first days of fasting or KD there is a rise of BHB and adiponectin concentrations (Halberg et al., 2005). One of the putative causes of hunger in starved humans may be due—together with other causes—to adiponectin. When adiponectin binds to its receptor AdipoR1, AMP-activated protein kinase (AMPK) is phosphorylated in the ARC of the hypothalamus (Valassi et al., 2008). The increase of AMPK activity in the hypothalamus may increase food intake and hepatic glucose output in mice while the decrease seems to reduce food intake (Zhang et al., 2009). KDs can also act similarly to a caloric restriction on AMPK (Newman and Verdin, 2014). Interestingly, AMPK seems to have opposing actions on the liver, muscle tissues and the brain: in liver and muscle AMPK activation increases FA oxidation by decreasing malonyl-CoA concentrations (Malonyl-CoA is the first intermediate in the lipogenic pathway and is also an inhibitor of carnitine palmitoyltransferase-1 (CPT-1). CPT-1 activity can be limiting for FA oxidation), through the inactivation of the acetyl-CoA carboxylase 1 (ACC1). AMPK can also increase the activity of malonyl-CoA decarboxylase (MCD), which enhances the decrease of malonyl-CoA levels.
Add mozzarella and cream cheese to a large microwave-safe bowl. Cover the cream cheese with mozzarella (this will prevent the cream cheese from overheating and making a mess in your microwave). Melt in the microwave at 30 second intervals. After each 30 seconds, stir cheese until cheese is completely melted and uniform and resembles a dough in appearance (see photo for reference). This should only take around 1 minute total cooking time. Do not try to microwave the full time at once because some of the cheese will overcook. You can also melt the cheeses over the stove in a double boiler.
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