Spheres represent proteins, lines are relationships between proteins and green triangles indicate proteins which are drug target. Seed proteins are colored in dark green. The overlaying image shows the location and density of the diabetes cluster on the ketogenic-diet map.
The main objective of these analyses is to identify whether the molecular events responsible for diabetes are indeed present, in a significant manner, in the ketogenic-diet map. With this purpose, the relationship at cell network level between the metabolic state of ketosis and diabetes was assessed by presence, centrality and clustering analysis.
Centrality analysis gives us an idea of the topological proximity at map level between diabetes and the ketosis status. The most representative proteins for each of the states are used for the measurement.
The ketosis state induced by protein-sparing modified fast is represented by the seed proteins, while diabetes is represented by the 19 effector proteins present in the map. The distance Hausdorff distance between the two groups of proteins of interest is of 1. To assess the statistical significance of this topological proximity, we calculated the general distribution of Hausdorff distances for each pair of physiological conditions contained in our database Figure 2A , finding that a distance of 1.
Probability Density Function of Hausdorff distances. The Hausdorff distance between any pair of physiological conditions is calculated as the average number of jumps between each protein contained in the first physiological condition against the closest proteins in the second physiological condition and vice versa. It comprises a total of 12, comparisons that give a normal distribution with an average distance of 2.
It comprises a total of comparisons. The clustering analysis identifies cores or groups of effector proteins of diabetes present in the ketogenic-diet map that are topologically relevant by MDS transformation Figure 1B. The next step is to address whether the macromolecular components, constitutive of diabetes, identified in the ketogenic-diet map are indeed related to type 2 diabetes, as the clinical observations indicate.
Accordingly, we conducted similar analyses to those described above but, this time, analyzing each of the type 2 diabetes pathophysiological pathways motives independently. See Table 1 for details. The distance analysis between the proteins of the different KEGG pathways selected as seed proteins and the proteins of the two physiological pathways related to type 2 diabetes did not identify significant differences between the pathways analyzed data not shown , since all KEGG pathways studied showed a close relationship to both type 2 diabetes motives.
The beneficial effects of ketogenic diets observed in clinical studies on patients with type 2 diabetes has been typically attributed to the low carbohydrate content of this type of diets, and the concomitant weight loss.
However, there is still a significant beneficial contribution that cannot be directly attributed to the previously mentioned aspects, and that some authors relate to the ketosis status [ 25 , 29 , 30 ].
In order to explore this hypothesis further, we have centered the analysis of distances and relationships at a protein level on the two main pathways of the ketosis state: the synthesis and degradation of ketone bodies and the fatty acid metabolism, and we left for coming projects exploration of the relationships with the other metabolic pathways used in the map construction.
The distance analysis of the two main pathways of the ketosis state used to construct the map i. The existence of nuclei or sets of diabetes effector proteins from the two physiological pathways of type 2 diabetes that have a topological relationship on the map was also analyzed by clustering analysis. The highest level of clustering is found in proteins that define the route of insulin resistance Figure 3 , concluding thus that it is, indeed, this pathological process the one that is the most embedded within the ketogenic-diet map.
Clusters of the different type 2 diabetes motifs on a 2D projection of ketogenic-diet map. The underlying image represents the ketogenic-diet map obtained through MDS transformation. The color grading of the image gives us an idea of the protein density, from black, no protein, until yellow areas of high protein density. Overlaying this image the localization of the protein clusters for the different type 2 diabetes motifs is presented. The analysis of the relationship between effector proteins of diabetes and seed proteins of ketogenic map was also conducted.
We found a total of relationships between seed proteins used to build the ketogenic-diet map and diabetes effector proteins. Of those relationships, 33 are direct, i. In summary, this analysis of direct interactions at the protein level indicates that type 2 diabetes motive, insulin resistance, is in close relationship with proteins in the ketosis pathway Figure 4.
Protein relationship between effector proteins involved in the insufficient insulin production motive of diabetes and the key pathways of the ketogenic diet.
Two complementary hypothesis of functional relationship between the molecules involved in both physiological processes have evolved: a Elements of lipid metabolism may facilitate proper cellular localization of glucose transporter and recycling and b Ketone bodies can alleviate certain inflammatory processes by blocking specific cytokines. Clinical trials provide evidence of benefits of very-low-carbohydrate ketogenic diets in terms of clinical outcomes of type 2 diabetes patients.
Recently, advances in systems biology and disease network analysis allow new approaches to understand and reveal the complex and intricate relationships between molecular network and different metabolic phenotypes.
In this sense, our aim was to reveal such relationship between ketogenic diet and type 2 diabetes by means of systems biology methodologies, and specifically, by topological analysis of the diabetes effector proteins in the ketogenic diet molecular network map. Our analysis suggests that, from the innovative perspective of the global topological analysis of molecular networks describing the two conditions, the relationship between the ketosis status induced by protein-sparing modified fast and type 2 diabetes is closer to the insulin resistance pathway than to insufficient insulin production.
Our studies at the protein level have identified that one of the effector proteins of the insulin resistance pathway, GLUT4, has a direct relation with proteins of the fatty acids metabolism HADH1 and ACOX1 a key pathway of the ketogenic diet Figure 3.
GLUT4, Glucose transporter type 4, facilitates glucose transport into the cell in an insulin-responsive manner. Insulin increases intracellular glucose concentration by transferring GLUT4 to the plasma membrane localization where it exerts its function via vesicles that require acylated lipid. HADH, encodes for the enzyme 3-hydroxyacyl-coenzyme A dehydrogenase and catalyses the penultimate reaction in the beta-oxidation of fatty acids.
Defects in HADH are the cause of familial hyperinsulinemic hypoglycemia type 4. It has been hypothesized that HADH deficiency causes modulation of other genes associated with the insulin secretion apparatus and thus triggers insulin secretion [ 42 ], however, the mechanism remains unclear [ 43 ].
Actually, the GLUT4- HADH interaction has been anticipated earlier and a role in priming fatty acids for protein acylation by adjusting acyl chain length by b-oxidation has been proposed [ 44 ]. The interaction may be part of the regulatory mechanisms that modulate the catalytic activity of GLUT4 or it could participate on the recycling between stocks and functional storage in the membrane.
The analysis at the molecular level also provided another provable way in which ketone bodies and insulin resistance can be related. Conditions in which inflammatory cytokines are elevated insulin resistance has also been shown to occur [ 29 ]. Ketone bodies reportedly counteract certain inflammatory processes by blocking the proinflammatory cytokine, macrophage migration inhibitory factor MIF [ 45 ]. KAT5 is the catalytic subunit of NuA4 histone acetyltransferase complex that is involved in the acetylation of nucleosomal histone H4 and H2A producing an activation of transcription of selected genes.
No previous relation with bodies or lipid metabolism has been identified for KAT5. On the other hand, a recent publication has shown that TRAF6, an adapter protein for the TNF receptor and interleukin-1R receptor, has a role in immunity by modulating fatty acid metabolism [ 48 ]. These set of relations offer another feasible way by which ketone bodies palliate the effects of elevated insulin resistance states.
CBL is an E3 ubiquitin-protein ligase involved on glucose uptake stimulated by insulin. Its inhibition is associated with insulin resistance [ 49 ]. Finally, it is worth stressing that neither of the hypotheses raised by our approach relates the beneficial effects described in type 2 diabetes with the significant weight loss achieved as a consequence of the diet itself, which correlates well with clinical observations that uncouple these two effects, since the improvements in the glycemic state are detected before a significant reduction of weight.
The global molecular network analysis of conditions, diseases and treatments either pharmacological or based in changes in life style are bound to provide new insights and help in a better understanding of clinical, metabolic, and molecular relationships between them.
The analysis of the ketogenic-diet map from the diabetes perspective offers interesting results and insights on the mechanism of action, but also opens new possibilities to study the applications of the ketogenic diet in other situations such as CNS or other metabolic dysfunctions.
One reason we think a ketogenic metabolism is normal and desirable, is that human newborns are in ketosis. Despite the moderate sugar content of human breast milk, breastfeeding is particularly ketogenic.
This period of development is crucial, and there is extensive brain growth during it. Although the composition of breast milk can be affected by diet [1], it is reasonable to assume that breast milk has always been ketogenic, and this is not an effect of modernisation.
When the brain is in its period of highest growth, and when the source of food is likely to be close to what it evolved to be for that period, ketones are used to fuel that growth. If nothing else, this suggests that learning is well supported by a ketogenic metabolism.
It is also consistent with the ability of ketogenic diets to treat a variety of seemingly unrelated brain disorders and brain trauma. Newborn infants are in ketosis. This is their normal state. Breastfeeding is particularly ketogenic compared to formula feeding.
Breastfeeding longer up to a point is associated with better health outcomes. This suggests the hypothesis that weaning onto a ketogenic diet would be healthier than weaning onto a high-carb diet. Mark-up ours Human babies are in ketosis Soon after birth, human babies are in ketosis, and remain so while breastfeeding [2].
They use ketones and fats for energy and for brain growth. When this has been studied, in the first couple of hours after birth, babies aren't immediately in ketosis. There is a short delay [3]. Ketogenic diets are all the rage lately, but do they really work? Will it get you shredded, or will it leave you flat? A nutritional trend that has persisted for several years, and has seen countless bodybuilders and hopeful dieters lose valuable muscle tissue and get weaker in the gym — all in an attempt to become leaner — is low, or zero, carbohydrate consumption.
This is often referred to as a ketogenic diet, or just plain keto for short. It has even been argued that by replacing carbohydrates with fats, and keeping protein consumption consistent the so called ketogenic diet, during which the user is thought to become more efficient at mobilizing fats for energy while their insulin levels are down-regulated to further lessen fat storage , we can become leaner and more muscular.
While low carb eating plans may work for some people, a meal plan which emphasizes higher complex carbohydrates and proteins, and moderate fats, has been proven by many an athlete to be very effective, and most importantly, sustainable. It involves the use of pharmaceutical grade meal replacements in the form of shakes, soups and bars. The program typically runs weeks and a person can expect to lose approximately 5 pounds a week on average. This protocol is not suitable for all patients and requires a thorough evaluation by the physician to determine eligibility.
When following this protocol, the patient requires to be regularly monitored by the physician to ensure safety. This protocol forces the body to selectively burn its fat stores while preserving the lean body mass to generate energy by a process called ketosis leading to rapid loss of excess fat deposits. Option 2: Low Calorie Diet Low Calorie Diet is a less aggressive protocol and the weight loss is at a more moderate pace. Other than the usage of meal replacements, the protocol allows the usage of one's own regular, but low calorie food.
This program typically runs for weeks and one can expect to lose approximately pounds per week on average. Majority of the patients qualify to follow this program, however the details vary depending upon the patients needs and co-morbid conditions.
As before, this requires a thorough physical evaluation before starting and a regular follow-up by the physician usually once a month. Weight Loss Medications Medications may be used as an adjunct to meal replacement options, exercise and other regular low calorie food.
Their usage is based on scientifically proven guidelines and the best clinical judgment of the physician. If you want to lose weight or build muscle faster and think the ketogenic diet might help, you want to read this article. How did a diet meant for treating epileptic seizures turn into a popular weight loss fad?
Henry Geyelin. Geyelin, presenting at the annual meeting of the American Medical Association, explained that the ancient Greeks had discovered that fasting was an effective method of managing epileptic seizures. Hippocrates wrote about it and, like Geyelin, found that the seizures would return once eating resumed.
What was it about fasting that suppressed the seizures? Well, epileptic seizures are triggered by electrical abnormalities in the brain. The causes can vary, from genetics to brain injury, but more common is chronic inflammation throughout the body.
Hyperproteic and normoproteic ketogenic diets KD have long been used in the treatment of pharmacoresistant epilepsy. In more recent times, some preclinical and clinical evidence support the use of ketogenic diets also in other areas, such as neurodegenerative diseases Alzheimer's disease, Parkinson's disease , neurocognitive disorders Mild cognitive impairment, MCI , brain trauma Traumatic brain injury, TBI even if the most interesting data come from their use in the neuro-oncological field.
There are several studies published on experimental models of different types of malignant neoplasms, treated with the ketogenic diet or in combination with standard therapy radio and chemotherapy Figure 2. Without entering into the details of each individual study and the type of neoplasm taken into account, the effects are globally positive on the survival or reduction of the tumor mass, with some exceptions concerning some melanoma and renal cell lines where the ketogenic diet has a promoter effect against the cancer 30 , Several therapeutic mechanisms exist: the reduction of the angiogenic process of the neoplasm, the radiosensitization, the chemosensitization in particular to the PI3K inhibitors, the reduction of the inflammatory processes of the tumor microenvironment and the conservation of the lean mass.
Figure 2. Pre-clinical studies on the ketogenic diet as antineoplastic therapy, adapted The promoter effects are unclear, as different tumors with similar alterations in mitochondrial oxidative metabolism have produced opposite results with such diets, as in the case of gliomas anti-neoplastic effect and renal carcinoma pro-neoplastic effect. In a breast cancer model, although the neoplastic cells had an enzyme kit capable of using ketones BDH-1 and OXCT-1, which convert ketone bodies back to Ac-CoA , there was no promoter effect of ketones.
On the other hand, an antineoplastic effect has not even been observed Considering studies on glioma and astrocytoma models, the most used metabolic treatment is the classic 4: 1 or 3: 1 ketogenic diet, ad libitum or energy-restricted.
Studies were conducted with both the ketogenic regimen as a unique therapy and in combination with chemotherapy CT or radiation therapy RT. Although the premises based on in vitro models have been very optimistic about the antineoplastic role of beta-hydroxy-methyl-butyrate BHB or of aceto-acetate, the results are not always as expected in vivo.
Taking into account the experimental models with control group KD vs. The effect also occurs in the absence of traditional RT or CT Temozolomide if it is administered with metabolism antagonists of glutamine 6 - diazo - 5 - oxo - L - norleucine, DON or glucose 2-deoxyglucose , indicating how these models of gliomas are greatly influenced by the host's metabolic and nutritional status 33 , The available human studies are currently very heterogeneous because there is no standardized therapeutic protocol.
Ongoing clinical trials seem to favor modified ketogenic diets MKD , with a less extreme ketogenic ratio 3: 1, 2: 1 or variable as in the modified Atkins diet and integration of nutritional supplements with MCT to facilitate ketogenesis and l adherence to the diet protocol.
Besides anecdotal studies, most prospective studies are open. Nine patients were selected, of whom 6 concluded the study period 14 months, of which 12 in ketosis Quality of life and neurological aspects did not change during the study and the average survival was The authors stressed, as already described by Schwartz et al.
The only clinical trial published to date, is a pilot study conducted on 20 patients with recurrent GBM, including 8 on the modified ketogenic diet with MCT drink without calorie restriction. Patients were monitored and the ketogenic regimen showed higher latency to tumor growth recovery progression-free survival compared to untreated patients median 6 vs.
The patients, following the progression of the neoplasm, resumed a cycle of CT Bevacizumab, anti VEGF drug maintaining the ketogenic diet and arriving at a survival median of According to a systematic review of the literature on clinical and pre-clinical studies, KD is effective and safe in experimental models, and of possible benefit and safe in patients as adjuvant and neo-adjuvant therapy for the control of neoplasm and associated complications of type neurological.
A number of clinical trials are underway to verify safety, compliance and efficacy in enhancing survival Table 2 summarizes the clinical trials. Table 2. Published clinical studies on Eucaloric Ketogenic diet in Neurological cancers, adapted from The protocols used are still very heterogeneous with one another, both in terms of ketogenic ratio and calorie intake. The choice of the protocol in addition to ensuring adequate ketosis, requires high patient adherence.
This aspect is actually essential for benefiting from the metabolic modulation aspect on healthy tissues and for enhancing the effects of therapy on the tumor. Scientifically verified low-carbohydrate diets include the Atkins diet such as Plack, Scarsdale, etc.
The most used variant in clinical practice is the one called Atkins diet. Therefore, there is a spontaneously reduced caloric intake due to anorectic effect of ketones and proteins. Endogenous lipolysis provides the necessary Ac-CoA for ketogenesis 38 associated with a high amount of lipids.
Popular low-protein high-protein diets, such as Atkins or Zone, produce a significant weight loss in the short term 39 , 40 , increasing satiety and energy expenditure and body composition On the other hand, in the long term in clinical trials longer than 1—2 years there are no differences in weight loss 39 , 40 , 42 — Furthermore, hyperlipidic high-protein diets have a higher intake of saturated fats and animal proteins and are associated with an increase in LDL cholesterol values LDL cholesterol 5 , 45 — The Paleolithic diet, also called Paleo or Paleodiet, is based on foods of daily use that imitate the food groups of the Paleolithic hunter-gatherers 49 , Paleodiet trials showed positive effects in metabolic syndrome 52 , increased insulin sensitivity 53 reduced cardiovascular risk factors 54 , 55 , increased satiety 56 , 57 and beneficial modulation of the intestinal microbiota In particular, regarding the Paleodiet for weight loss, scientific evidence indicates a constant reduction of body weight and body fat mass in short 55 , 59 — 61 or long-term studies 62 , Moreover, poor adherence over time 59 , poor palatability, the presence of a potential risk of deficiency which includes vitamin D, calcium 60 and iodine 64 , and high costs are important factors limiting the use of this diet In conclusion, in the short term, hyperlipidic diets with high protein content with low carbohydrate content show greater effectiveness in terms of weight loss.
Furthermore, negative effects on the metabolic level and the microbiota could be considered as a short-term therapeutic tool, but not as a dietary model for life. In addition, in the long term, it has been shown that diets with a different macro-nutrient composition do not have a different efficiency in weight loss.
Apart from the physiological fasting, many treatments have tried over time to achieve the benefits that the fasting condition produces. The basic purpose of fasting is to promote changes in metabolic pathways, cellular processes and hormone secretions The major physiological responses of fasting on health indicators include better insulin sensitivity 67 , improved blood pressure levels 68 , reduced body fat 69 , blood sugar 70 , atherogenic lipids 71 and inflammation In the animal model, fasting is associated with interesting outcomes in correcting type 2 diabetes 73 and cardiovascular disease Under these conditions, the transition to ketogen metabolism occurs In oncology, in preclinical studies, h water fasting is able to prevent DNA damage in healthy cells, usually induced by chemotherapy agents but, in addition to being difficult to accept and completed by patients, it can cause macro and micro-nutritional deficiencies 75 — For this reason, another method of daily calorie restriction can be carried out by manipulating meal times and frequencies over time daily, weekly, monthly.
This method refers to calorie restriction and therefore the length of fasting between meals to establish a new kind of strategy. Intermittent fasting is the most cited among these methodologies and consists in abstaining from food and calorie drinks for a certain period of time 83 , Different variants of intermittent fasting differ in the duration and frequency of fasting cycles.
In addition, modified intermittent fasting allows small contributions from energy foods to reduce hunger stimulation The most common types of intermittent fasting include periodic 5: 2 fasting, alternating fasting Figure 3 , hourly food restriction e.
In the experimental animal the effects are contradictory: in mice, alternating fasting is not able to reduce muscle insulin resistance induced by high fat diets and is not able to promote changes in weight loss 70 , 86 , In several clinical studies, the absence of adequate control groups suggests that intermittent fasting has not yet been rigorously studied in the long term.
Two recent meta-analyses provided a summary of the effects of intermittent energy restriction in intervention studies 84 , Both analyses found that no intermittent or continuous calorie restriction was greater than the other for weight loss. Moreover, in a recent comparative real life study of the Mediterranean diet, Paleo diet and intermittent fasting for a period of 1 year, it has been observed that the Mediterranean diet and intermittent fasting give similar results in terms of weight loss but the Mediterranean diet allows a greater benefit in the glycemic control in relation to the consumption of plant foods with a higher fiber content Finally, as regards religious fasts, the data are inconclusive: as regards Ramadan, several studies have reported weight loss , , while others have not shown any significant changes 90 , , Very often weight recovery is observed a few weeks after the fasting period 91 , , while weight loss for daily calorie restriction periods is observed but the results are still short-term.
Finally, it should be stressed that fasting without adequate protein content can be harmful for some populations such as children, the elderly and underweight patients. Patients receive standardized portions of vegetable broths, soups, juices, dried fruit bars, herbal teas and in addition micronutrient supplements.
Protocols provide that fast-mimicking diet is observed for 2—5 consecutive days a month. Several studies have shown efficacy in the experimental animal in various morbid conditions such as diabetes and tumors, but in humans the data are limited to open studies or case reports.
The only randomized phase 2 study is a cross over that compared a group treated with three cycles of FMD with a group treated with a normal calorie diet Subsequently, the group with normocaloric diet was treated with 3 cycles of FMD and the FMD group with control diet, which also was normocaloric. The result is easy to interpret: with the cross over it simply doubled in number of patients but the comparison between FMD remained the normocaloric diet. Obviously it is paradoxical to think that a fast is compared with a normocaloric diet because the results are necessarily spurious.
The absence of comparison between a low-calorie diet and a FMD is a severe bias. As a matter of facts the study demonstrated that a 3 cycles of fasting reduce body weight, waist circumference, BMI, total body and trunk fat, systolic blood pressure and IGF-1 compared to a normocaloric diet. But not only, although there is no real control group, the authors also point out that, from a post-hoc analysis, the subjects who had high risk factors or metabolic markers associated with metabolic syndrome and age-related diseases such as a high body mass index, elevated blood pressure, high blood glucose levels, triglycerides, CRP, cholesterol and IGF-1 , were significantly improved compared with non-risk individuals In fact, the same results could be observed with any low-calorie regimen conducted for the same period, even more on high-risk individuals, where it is well-known that weight loss is related to the reduction of metabolic risk factors and pressure.
Consequently, it is necessary that rigorous studies are conducted with real control arms with low calorie diets. This study simply strengthens the evidence for calorie restriction in preventing chronic degenerative diseases, malignant tumors and longevity. As regards tumors, several preclinical studies have shown that fasting diets or fast-mimicking diets exert powerful anticancer effects in experimental animals, both in solid tumor models such as breast, lung, and gliomas and in hematological tumors.
In fact, fasting can activate a sustained evolutionary molecular response to metabolic stress in normal cells, inhibiting their proliferation, increasing the maintenance of self with effect of protection from chemotherapy and toxic agents This mechanism can be noteworthy if we consider the damage often caused by these drugs, the side effects of which can be serious or even lethal for the lesions suffered by epithelial and non-epithelial tissues. In this way, it is possible, at least in part, to explain the observed reduction of the side effects of anti-cancer treatments if the fasting mimic diet is simultaneously followed.
On the contrary, cancer cells have a reverse effect differential stress response with inhibition of stress response. The reduction in the availability of glucose in neoplastic cells determined by FMD causes a switch from aerobic glycolysis Warburg effect Figure 5 toward oxidative phosphorylation and beta-oxidation of fatty acids, a necessary condition to allow cell growth in a nutrient-poor environment Figure 5. Warburg effect. The Warburg effect is a form of modified cell metabolism observed in many neoplastic cells where, unlike normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, relies on aerobic glycolysis.
Aerobic glycolysis is an apparently inefficient way of generating adenosine 5'-triphosphate ATP , compared to oxidative phosphorylation which allows the production of ATP by the oxidative disruption of pyruvate in mitochondria. However, the rate of glucose metabolism through aerobic glycolysis is higher, so that lactate production from glucose takes place 10— times faster than complete glucose oxidation in mitochondria.
The metabolic difference observed by Warburg adapts cancer cells to hypoxic oxygen deficient conditions within solid tumors and derives largely from the same mutations of oncogenes and tumor suppressor genes that cause the other abnormal characteristics of cancer cells.
Hypoxic conditions could induce HIF1A, a major regulator of glucose metabolism, and activate the expression of key enzymes for glycolysis. The high use of glucose in aerobic glycolysis, in addition to the high production of ATP, and the increase in the pathway of pentose phosphates, both essential for the anabolic processes necessary to support cell proliferation, is associated with the production of high levels of lactate and the acidification of the tumor microenvironment which plays a favorable role to the growth of neoplastic.
The increase in beta-oxidation in the mitochondria, in turn, causes an increase in ROS production and, at the same time a decrease in the cell's antioxidant defenses glutathione occurs; the two processes amplify oxidative stress and promote the activity of chemotherapy Figure 6. Reverse Warburg effect. Cells within tumors interact metabolically with the transfer of catabolites from supporting stromal cells to adjacent tumor cells. The reverse Warburg effect describes when the aerobic glycolysis of stromal fibroblasts associated with cancer metabolically supports adjacent cancer cells.
The stromal-cancer metabolic coupling, allows cancer cells to generate ATP from substrates lactate, pyruvate, ketonic bodies provided by stromal cells, increase proliferation and reduce apoptosis. If left untreated, this condition can lead to a diabetic coma or death.
Signs of diabetic ketoacidosis include a high blood glucose level, a high ketone level, dehydration , frequent urination , nausea, difficulty breathing, and dry skin.
A ketone level between 1. A ketone level higher than 3. Some people intentionally achieve ketosis to lose weight by eating a low-carb, high-fat diet. Make sure your carbohydrate intake is 45 to 65 percent of your total daily calories, fat 20 to 35 percent of your total daily calories, and protein 10 to 35 percent of your total daily calories.
Shifting your metabolism and achieving ketosis may speed up weight loss and result in other health benefits, like more energy and a lower blood pressure. By subscribing you agree to the Terms of Use and Privacy Policy.
Health Topics. Health Tools. Ketogenic Diet. Reviewed: January 25, Medically Reviewed. Editorial Sources and Fact-Checking. The Diabetes Council. December 7, Ketone Testing.
0コメント