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].
A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity published a guideline to harmonize the definition of the metabolic syndrome.[39] This definition recognizes that the risk associated with a particular waist measurement will differ in different populations. Whether it is better at this time to set the level at which risk starts to increase or at which there is already substantially increased risk will be up to local decision-making groups. However, for international comparisons and to facilitate the etiology, it is critical that a commonly agreed-upon set of criteria be used worldwide, with agreed-upon cut points for different ethnic groups and sexes. There are many people in the world of mixed ethnicity, and in those cases, pragmatic decisions will have to be made. Therefore, an international criterion of overweight (BMI≥25) may be more appropriate than ethnic specific criteria of abdominal obesity for an anthropometric component of this syndrome which results from an excess lipid storage in adipose tissue, skeletal muscle and liver.
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Type 2 diabetes is by far the most common form (around 90% of all cases) and the one which is increasing the most. It primarily affects overweight people in middle age or later. It’s not uncommon for the affected person to also have a high blood pressure and an abnormal lipid profile. Gestational diabetes is a temporary special case of type 2 diabetes.
Ketogenic diet could improve body composition: For some sports (such as gymnastics, cycling and some fighting sports), power to weight ratio is a key determinant of performance. Because the ketogenic diet has been associated with fat loss accompanied by lean muscle maintenance (or gain), it could thereby improve the power to weight ratio 21 ,22 and performance. 
Brain glucose and KB uptake was investigated in rats subjected to mild experimental ketonemia induced by 2 weeks on the KD or by 48 h fasting. To test this, researchers developed a carbon-11 labeled AcAc (11)C-AcAc for PET use. They found in rats that after 10 days of KD (11)C-AcAc brain uptake increased up to 8-fold, an increase comparable to those measured after 48 h of fasting (Pifferi et al., 2008).
Other mechanisms that have been suggested include: changes in ATP production making neurons more resilient in the face of metabolic demands, altered brain pH affecting neuronal activity, direct inhibitory effects of ketone bodies or fatty acids on ion channels, alterations in amino acid metabolism, and changes in synthesis of the inhibitory neurotransmitter GABA. (10)
Your first dietary step towards more balanced blood sugar: ditching (most of) the packaged foods and focusing on high-quality whole foods such as vegetables, fruits, whole grains, beans, nuts, seeds, and quality meats and fish. Many processed foods are high in sugar, refined grains and carbs, and artificial ingredients and flavorings, while being low in blood-sugar-stabilizing fiber and protein. Of course, it’s also important to be realistic. You’re probably not going to be able to nix packaged foods completely, so just make a point to select those that are made from mostly whole-food ingredients, like a bar that lists just nuts, seeds, and dried fruit on its label.

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 🙂

Blood pressure goals are generally set lower than 130/80. Some blood pressure medications offer more benefits than simply lowering blood pressure. For example, a class of blood pressure drugs called ACE inhibitors has been found to also reduce the levels of insulin resistance and actually deter the development of type 2 diabetes. This is an important consideration when discussing the choice blood pressure drugs in the metabolic syndrome.


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Overweight individuals with metabolic syndrome, insulin resistance, and type 2 diabetes are likely to see improvements in the clinical markers of disease risk with a well-formulated very-low-carbohydrate diet. Glucose control improves due to less glucose introduction and improved insulin sensitivity. In addition to reducing weight, especially truncal obesity and insulin resistance, low-carb diets also may help improve blood pressure, blood glucose regulation, triglycerides, and HDL cholesterol levels. However, LDL cholesterol may increase on this diet.

^ Feinman, R. D; Pogozelski, W. K; Astrup, A; Bernstein, R. K; Fine, E. J; Westman, E. C; Accurso, A; Frassetto, L; Gower, B. A; McFarlane, S. I; Nielsen, J. V; Krarup, T; Saslow, L; Roth, K. S; Vernon, M. C; Volek, J. S; Wilshire, G. B; Dahlqvist, A; Sundberg, R; Childers, A; Morrison, K; Manninen, A. H; Dashti, H. M; Wood, R. J; Wortman, J; Worm, N (2015). "Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base". Nutrition. 31 (1): 1–13. doi:10.1016/j.nut.2014.06.011. PMID 25287761.

Ketosis could benefit patients with PD, as ketones provide an alternative energy source to the brain and also have antiinflammatory effects. Several research groups have shown that the ketogenic diet can have manifold beneficial effects in animal models of PD: alleviating motor symptoms, reducing inflammation, decreasing neuronal loss 61 ,62. Also, an in vitro model of PD (neurons in culture treated with a drug called MPTP) was used to demonstrate that addition of 4 mM of BHB was protective against neurodegeneration52. An early study of the ketogenic diet in PD patients reported very promising results: patients improved their clinical PD ‘score,’ as classified by factors including tremor, balance and mood 63. Whilst there are promising results, further clinical studies are required to demonstrate if the ketogenic diet or exogenous ketones (either alone or in combination) are a tolerable and efficacious intervention for PD.            


PGC-1α coactivates all three known PPAR isoforms (PPARα, PPARδ, and PPARγ) [286]. Although each isoform is expressed in a variety of tissues, PPARα is prominently expressed in the liver, PPARδ in skeletal muscle, the heart, and the pancreas, and PPARγ in adipose [286, 296]. PGC-1α was discovered and named based on its promotion of brown adipose differentiation through coactivation of PPARγ and subsequent induction of mitochondrial biogenesis and UCP1 expression [297]. However, it is the PGC-1α coactivation of PPARα that is responsible for the upregulated transcription of many of the enzymes responsible for increased ketogenesis and fatty acid metabolism in response to a ketogenic diet [120]. Consistent with the role of PGC-1α in inducing mitochondrial biogenesis, it also shifts skeletal muscle fiber composition towards type I [298, 299] and type IIa [299], which are more oxidative. AMPK also contributes to fiber type changes and is required for the transition of highly glycolytic, type IIb fibers to more oxidative, type IIa fibers [276]. Although PGC-1α is primarily known for inducing transcription of nuclear DNA, it may also, in conjunction with SIRT1, induce expression of mtDNA [300].

The ketogenic diet can compromise high intensity sprint performance: High intensity exercise performance is heavily reliant on the ability to produce energy via anaerobic respiration (glycolysis), which requires carbohydrate as a substrate. Following a ketogenic diet causes a decrease in the amount/activity of the enzymes in the glycolysis pathway that decreases the rate that the pathway can proceed24. This could explain the decrease in anaerobic sprint performance consistently seen with athletes following a ketogenic diet 25 ,23. 
sdLDL. This is a measurement of the number of small dense low-density lipoprotein molecules a person has. LDL varies in size, and the smaller denser molecules, which tend to form when elevated triglycerides and VLDL are present in the blood, are thought to be more aggressive in causing atherosclerosis. This test is now commercially available, but is not performed by many laboratories and is not ordered frequently. Its ultimate clinical utility has yet to be determined. It may be evaluated in a LDL particle testing.

Acetone is a molecule that results from the breakdown of acetoacetate. Acetone is commonly referred to as a ‘waste product’ as it is less readily used as energy compared to BHB (although some studies have shown that acetone can be oxidised as a fuel4. That said, some evidence suggests that it is responsible for the antiseizure effects of ketogenic diets so in may not be completely inert. At low levels acetone in the breath corresponds well to levels of ketones in the blood 12,13, however this is not the case as blood BHB levels increase 13 and if the increase is rapid, such as with exogenous ketone consumption11. 


Mediterranean diet: Traditional cuisine of countries bordering the Mediterranean Sea, shown to reduce the risk for heart disease, diabetes, some cancers and dementia. On the menu: Plenty of fruits, vegetables and beans, along with olive oil, nuts, whole grains, seafood; moderate amounts of low-fat yogurt, low-fat cheese and poultry; small amounts of red meat and sweets; and wine, in moderation, with meals.
I read through aaaaallllll the comments for research before I made this bread, one thing I noticed when making your protein buns was – when I used 2 teaspoons of baking powder they deflated when exiting the oven. When I reduced the BP to 1.5 teaspoons, they turned out fine. I made two batches with 2 tsp of BP – they turned out like raisins, and 2 batches with 1.5 tsp of BP and they turned out fine. No one posting mentioned adjusting the baking powder – perhaps that would help in this recipe since deflating is a problem, maybe there is too much chemical loft for the non-gluten structure to handle?
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Hi Anita, I double checked my carton egg whites. 3/4 cup of egg whites is equivalent to 4 large whole eggs, not 4 large egg whites. Mine has a chart for converting whole eggs, and the conversion for egg whites only is below the chart. It says 2 tablespoons of liquid egg whites are equivalent to the egg white of 1 whole egg. So, 12 large egg whites would be 24 tablespoons, or 1 1/2 cups as written in the recipe. Hope this helps!
Thank you for the terrific recipe. I must admit that this really turned out to be “oopsie bread” for me. Due to the expensive nature of the recipe (organic eggs, almond flour, grass fed butter) I really attempted to follow the recipe perfectly instead of going with my usual improvisational style. I also do not have a food processor however that did not impede anything… a hand mixer and a deft hand did the trick. I did add the optional xanthum gum and erythritol but not the cream of tartar. The batter filled my silicone loaf pan to the top, I smoothed it out and popped it into the oven. Then, to my horror, I saw the little pot of melted butter still on the stovetop. There was nothing to be done except cross my fingers and hope for the best.
Theoretically, supplying ketones during this period of compromised glucose metabolism could prevent the energy deficit and reduce the likelihood of long-term brain damage. This could be because ketones can act as an alternative, highly energy efficient substrate7. Additionally, the antioxidant, antiinflammatory33 and anti-apoptosis properties of ketones (i.e ketones prevent the opening of the mitochondrial permeability transition pore, which causes cell death66) could protect against neuronal loss and damage. 
Moreover, in the above study of Sumithran et al. (2013), ketosis maintains post-prandial secretion of CCK as previously demonstrated by other researchers (Chearskul et al., 2008). Note that the orexigenic effect of BHB is blocked by transection of the common hepatic branch of the vagus nerve (Langhans et al., 1985). The hepatic branch contains fibers from the proximal small intestine, stomach and pancreas, and is sensitive to CCK (Horn and Friedman, 2004); ghrelin signals to brain are also transmitted via vagus nerve (Habara et al., 2014). Thus, the effects of ketosis on these two appetite-related hormones could be one of the many factors related to the effects of such nutritional regimen on food control.
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Acetone is a molecule that results from the breakdown of acetoacetate. Acetone is commonly referred to as a ‘waste product’ as it is less readily used as energy compared to BHB (although some studies have shown that acetone can be oxidised as a fuel4. That said, some evidence suggests that it is responsible for the antiseizure effects of ketogenic diets so in may not be completely inert. At low levels acetone in the breath corresponds well to levels of ketones in the blood 12,13, however this is not the case as blood BHB levels increase 13 and if the increase is rapid, such as with exogenous ketone consumption11. 
Has anyone tried this using a substitute for the eggs/egg whites? My husband seems to be sensitive to eggs (not sure which part, to be honest) and we’ve been making most recipes using agar agar as a substitute (for either whites or whole eggs) but this only works if the egg is a binder. I’m guessing that they are a leavening agent in the bread (please correct me if I’m wrong!) and I don’t know if agar would work in this recipe. I do have VersaWhip 600 – anyone ever tried that in a bread recipe?
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Although metabolic syndrome is a serious condition, you can reduce your risks significantly by reducing your weight; increasing your physical activity; eating a heart-healthy diet that's rich in whole grains, fruits, vegetables and fish; and working with your healthcare provider to monitor and manage blood glucose, blood cholesterol, and blood pressure.
An increase in fat burning ability could decrease the efficiency of exercise: one adaptation to a high fat diet is an increase in a process called mitochondrial uncoupling. This means that some of the stored energy from metabolic substrates is not used to generate ATP but is ‘dissipated’ leading to a decrease in efficiency of energy production 26 ,19.  

Jennifer, The yeast has no carbs. The coconut sugar does have carbs, but the yeast feeds on it and through the process of fermentation uses the sugar for energy and releases carbon dioxide gas as a result. The yeast is for flavor, aroma, and in our opinion does help with a little bit of rise. Additionally, we don’t like to consider any foods “bad”, “off-limits”, or not keto. Instead, we opt to mainly eat nourishing real foods that fit into our daily macro intake. We hope this helps! Best of luck on your keto journey.
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