Sugar, cancer and mitochondria

I've had stuff up here over the years (e.g. here and here)about how cancer cells seem to survive by burning sugar and not fat and so some doctors have tried to starve cancers by using a ketogenic diet, with some success.

Anyway, here is a video outlining new research into this same topic:



The research is reported here and the full article is available here

Cancer cells tend to take up more glucose than healthy cells, and researchers are increasingly interested in exploiting this tendency with drugs that target cancer cells' altered metabolism.

Cancer cells' sugar cravings arise partly because they turn off their mitochondria, power sources that burn glucose efficiently, in favor of a more inefficient mode of using glucose. They benefit because the byproducts can be used as building blocks for fast-growing cells.

Drugs or diet, if this knowledge can help find a solution to cancer then that is good.

Ketosis and Sleep Quality

Sleep Warrior has an interesting article on ketosis and sleep:

Ultimately, I think there’s something about the insulin roller coasters we put ourselves on by constantly consuming sugary or starchy foods — and it seems to be impairing how our brains function. The idea is that by fueling our brain cells with an “alternative” source of energy (ketones) we allow them to operate more efficiently, perhaps despite any damage done from too much glucose and insulin.

ketogenic diet plus weight training

So, it seems (for overweight women)

• Resistance exercise in combination with a ketogenic diet reduces body fat without significantly changing Lean body mass (LBM)
  
• Resistance exercise on a regular diet may increase LBM without significantly affecting fat mass.

So to lose fat and maintain muscle do weights on a low carb diet?

The full text is available:


Resistance training in overweight women on a ketogenic diet conserved lean body mass while reducing body fat

More health benefits for a low carb diet - protection against mitochondrial mallfunction

Here is another one to think about with respect to the protective aspects of a low carb / primal / paleo diet (I know it is mice and we are not mice....but still worth thinking about):

Ketogenic diet slows down mitochondrial myopathy progression in mice

Mitochondrial dysfunction is a major cause of neurodegenerative and neuromuscular diseases of adult age and of multisystem disorders of childhood. However, no effective treatment exists for these progressive disorders. Cell culture studies suggested that ketogenic diet, with low glucose and high fat content, could select against cells or mitochondria with mutant mitochondrial DNA (mtDNA), but proper patient trials are still lacking. We studied here the transgenic Deletor mice, a disease model for progressive late-onset mitochondrial myopathy, accumulating mtDNA deletions during aging and manifesting subtle progressive respiratory chain deficiency. We found that these mice have wide-spread lipidomic and metabolite changes, including abnormal plasma phospholipid and free amino acid levels and ketone body production. We treated these mice with presymptomatic long-term and post-symptomatic shorter term ketogenic diet. The effects of the diet for disease progression were followed by morphological, metabolomic and lipidomic tools. We show here that the diet decreased the amount of cytochrome-c-oxidase negative muscle fibers, a key feature in mitochondrial respiratory chain deficiencies, and prevented completely the formation of the mitochondrial ultrastructural abnormalities in the muscle. Furthermore, most of the metabolic and lipidomic changes were cured by the diet to wildtype levels. The diet did not, however, significantly affect the mtDNA quality or quantity, but rather induced mitochondrial biogenesis and restored liver lipid levels. Our results show that mitochondrial myopathy induces widespread metabolic changes, and that ketogenic diet can slow down progression of the disease in mice. These results suggest that ketogenic diet may be useful for mitochondrial late-onset myopathies.

Cancer and carbs

I've had stuff up here before on treating cancer with low carb diets - like this.

Here us a new study that looks a bit more deeply at the whole area. Much of it is beyond me, but there is some interesting stuff there.

Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including aerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease will impact approaches to cancer management and prevention.

The whole paper is available as pdf

Ketogenic Diet as a cancer treatment

I've had stuff on this on the blog before - e.g. here.

Via facebook - thanks Richard - I learned that Jimmy Moore has posted an interview with

Dr. Thomas Seyfried, a researcher from Boston College who runs the Seyfried Laboratory dedicated specifically to taking a closer look at such diseases as epilepsy and brain cancer.

you can listen to the interview here - Definitely worth it.

I'd given up reading Jimmy's blog for a few reasons (his whole folksy style irritates me and his diet winds me up - lots of artificial sweeteners / low carb products and little real food) BUT he works hard on the blog and gives some great information for free.

Low Carb diets and diabetes

Research is catching up with what people like Bernstein have been saying for years....

Therapeutic role of low-carbohydrate ketogenic diet in diabetes.

INTRODUCTION: Changes in dietary habits influence the glycemic level. Preliminary studies using the low-carbohydrate ketogenic diet (LCKD) were found to be quite promising in controlling diabetes mellitus. Therefore, the objectives of this study are to investigate the therapeutic effects of LCKD in experimental diabetic rats following the administration of streptozotocin (STZ).
MATERIALS AND METHODS: Adult rats were divided into three groups: normal diet, LCKD, and high-carbohydrate diet. Each group was subdivided into normal, sham, and diabetic groups. Diabetes was induced by a single intraperitoneal injection of STZ (55mg/kg). Specific diets were given to each group of animals for a period of 8 wk and then the animals were sacrificed. The rats were monitored daily for food and water intake, whereas body weight, urine output, and blood glucose levels were monitored weekly. The histology of the islets of Langerhans was studied by histochemical methods.
RESULTS: The results showed that LCKD was effective in bringing blood glucose level close to normal (P<0.01). Food and water intake and urine output were increased in all groups except the LCKD group (P<0.01). The body weight was significantly reduced in all diabetic animals except in the LCKD group (P<0.01). Histologic studies showed significant decrease in the islet size and number of beta cells in all the diabetic groups.
CONCLUSION: This study indicates that LCKD has a significant beneficial effect in ameliorating the diabetic state and helping to stabilize hyperglycemia.

Low Carb Research

Does anyone have access to this full paper? It looks interesting:

Low-carbohydrate diets: an update on current research.

The diabetes and obesity epidemics have stimulated research to assess the benefits and potential risks of low-carbohydrate diets. Carbohydrate comprises less than 45% of calories in carbohydrate-restricted diets, but very low carbohydrate ketogenic diets may restrict carbohydrate to 20 g initially with variability in the carbohydrate level subsequently. Some research suggests that low-carbohydrate diets may achieve better early weight loss than comparison diets higher in carbohydrate. Studies of up to 1 year suggest that weight loss on low-carbohydrate diet is comparable with fat-restricted diets with higher carbohydrate content. Limited research has been conducted to evaluate low-carbohydrate diets in managing type 2 diabetes. Although science continues to advance in this field, current research suggests that low-carbohydrate diets can be a viable option for achieving weight loss and may have beneficial effects on glycemic control, triglyceride levels, and high-density lipoprotein cholesterol levels in some patients.

Does a very low carb diet limit your propensity to exercise?

....er no. Low-carbohydrate, ketogenic diets give greater weight loss in the short-term than low-fat, calorie-restricted diets. This experiment shows that such diets do not result in decreased voluntary exercise....Well at least not if you are a rat:

Maintenance on a ketogenic diet: voluntary exercise, adiposity and neuroendocrine effects

Background:

Adherence to low-carbohydrate, ketogenic diets (KDs) has been associated with greater weight loss in the short-term than low-fat, calorie-restricted diets. However, consumption of KDs may result in decreased voluntary exercise and thus render long-term weight loss and maintenance of weight loss difficult.

Methods:

Rats were maintained on either a non-ketogenic chow (CH) diet or a low-carbohydrate, KD for 6 weeks. Half of each dietary group was sedentary, whereas the other half was given access to a running wheel. Running wheel activity (total distance and meters per minute), plasma leptin and insulin, adiposity, and hypothalamic mRNA for neuropeptide Y and proopiomelanocortin (POMC) were measured to assess activity-related effects in animals maintained on KD.

Results:

With access to a running wheel, rats on KD engaged in similar levels of voluntary activity as CH rats and both dietary groups decreased caloric intake. Caloric intake increased over time such that it was significantly greater than sedentary controls after 1 month of access to the wheels, however body weight remained decreased. Sedentary rats maintained on KD had increased adiposity and plasma leptin levels and decreased hypothalamic POMC mRNA, as compared to sedentary CH rats. KD rats with access to a running wheel had similar levels of adiposity and plasma leptin levels as CH rats with access to running wheels, but significantly increased POMC mRNA in the arcuate.

Conclusion:

We demonstrate that maintenance on KD does not inhibit voluntary activity in a running wheel. Furthermore, prevention of KD-related increased adiposity and plasma leptin, as measured in sedentary KD rats, significantly increases levels of the anorexigenic neuropeptide POMC mRNA.

A couple more low carb studies

First one says that a low carb diet including eggs - i.e. adding cholesterol - has good effects on both insulin resistance and the hormones that make you feel full.

Carbohydrate restriction (with or without additional dietary cholesterol provided by eggs) reduces insulin resistance and plasma leptin without modifying appetite hormones in adult men.

Carbohydrate-restricted diets (CRDs) have been shown to reduce body weight, whereas whole egg intake has been associated with increased satiety. The purpose of this study was to evaluate the effects of additional dietary cholesterol and protein provided by whole eggs while following a CRD on insulin resistance and appetite hormones. Using a randomized blind parallel design, subjects were allocated to an egg (640 mg/d additional dietary cholesterol) or placebo (0 mg/d additional dietary cholesterol) group for 12 weeks while following a CRD. There were significant reductions in fasting insulin (P < .025) and fasting leptin concentrations (P < .01) for both groups, which were correlated with the reductions in body weight and body fat (P < .05 and P < .01, respectively). Both groups reduced insulin resistance as measured by the homeostatic model assessment of insulin resistance (P < .025). There was a significant decrease in serum glucose levels observed after the intervention. We did not observe the expected increases in plasma ghrelin levels associated with weight loss, suggesting a mechanism by which subjects do not increase appetite with CRD. To confirm these results, the subjective measures of satiety using visual analog scale showed that both groups felt more "full" (P < .05), "satisfied" (P < .001), and "wanted to eat less" (P < .001) after the intervention. These results indicate that inclusion of eggs in the diet (additional dietary cholesterol) did not modify the multiple beneficial effects of CRD on insulin resistance and appetite hormones.


Second one is low carb in people with Diabetes (Type II). Limiting your carbs is a good as taking insulin.... Full study available


Effects of a low-carbohydrate diet on glycemic control in outpatients with severe type 2 diabetes

We previously demonstrated that a loosely restricted 45%-carbohydrate diet led to greater reduction in hemoglobin A1c (HbA1c) compared to high-carbohydrate diets in outpatients with mild type 2 diabetes (mean HbA1c level: 7.4%) over 2 years. To determine whether good glycemic control can be achieved with a 30%-carbohydrate diet in severe type 2 diabetes, 33 outpatients (15 males, 18 females, mean age: 59 yrs) with HbA1c levels of 9.0% or above were instructed to follow a low-carbohydrate diet (1852 kcal; %CHO:fat:protein = 30:44:20) for 6 months in an outpatient clinic and were followed to assess their HbA1c levels, body mass index and doses of antidiabetic drugs. HbA1c levels decreased sharply from a baseline of 10.9 +/- 1.6% to 7.8 +/- 1.5% at 3 months and to 7.4 +/- 1.4% at 6 months. Body mass index decreased slightly from baseline (23.8 +/- 3.3) to 6 months (23.5 +/- 3.4). Only two patients dropped out. No adverse effects were observed except for mild constipation. The number of patients on sulfonylureas decreased from 7 at baseline to 2 at 6 months. No patient required inpatient care or insulin therapy. In summary, the 30%-carbohydrate diet over 6 months led to a remarkable reduction in HbA1c levels, even among outpatients with severe type 2 diabetes, without any insulin therapy, hospital care or increase in sulfonylureas. The effectiveness of the diet may be comparable to that of insulin therapy.

Low Carb diet for mental health.....

I had a post up a few days ago about low carb diets making people happier. And then there was the post about cholesterol and mental function.

Here is another:

Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature

It is a case study of a schizophrenic who is "cured" after adopting a low carbohydrate diet. Very interesting stuff.

Low Carb wins again

The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus.


OBJECTIVE: Dietary carbohydrate is the major determinant of postprandial glucose levels, and several clinical studies have shown that low-carbohydrate diets improve glycemic control. In this study, we tested the hypothesis that a diet lower in carbohydrate would lead to greater improvement in glycemic control over a 24-week period in patients with obesity and type 2 diabetes mellitus. Research design and methods: Eighty-four community volunteers with obesity and type 2 diabetes were randomized to either a low-carbohydrate, ketogenic diet (<20 g of carbohydrate daily; LCKD) or a low-glycemic, reduced-calorie diet (500 kcal/day deficit from weight maintenance diet; LGID). Both groups received group meetings, nutritional supplementation, and an exercise recommendation. The main outcome was glycemic control, measured by hemoglobin A1c.
RESULTS: Forty-nine (58.3%) participants completed the study. Both interventions led to improvements in hemoglobin A1c, fasting glucose, fasting insulin, and weight loss. The LCKD group had greater improvements in hemoglobin A1c (-1.5% vs. -0.5%, p=0.03), body weight (-11.1 kg vs. -6.9 kg, p=0.008), and high density lipoprotein cholesterol (+5.6 mg/dL vs. 0 mg/dL, p<0.001) compared to the LGID group. Diabetes medications were reduced or eliminated in 95.2% of LCKD vs. 62% of LGID participants (p<0.01).
CONCLUSIONS: Dietary modification led to improvements in glycemic control and medication reduction/elimination in motivated volunteers with type 2 diabetes. The diet lower in carbohydrate led to greater improvements in glycemic control, and more frequent medication reduction/elimination than the low glycemic index diet. Lifestyle modification using low carbohydrate interventions is effective for improving and reversing type 2 diabetes.

Selenium - eat your liver and eggs

A couple of things to think about in terms of making sure your diet has sufficient selenium - especially if it is a low carb / ketogenic diet.


Sudden cardiac death in association with the ketogenic diet.


Selenium May Slow March Of AIDS

These things actually reminded me of something I read on Barry Groves' site years ago:

A Cheap Way to Prevent AIDS and Bird Flu

Selenium

Selenium is present in a wide variety of foods and it can also be obtained in supplements. The best source of natural selenium is liver and other organ meats, particularly from grass-fed animals, although it does depend on how much selenium is in the soil. Next come fish and shellfish, followed by muscle meats. The soil most likely to have a high selenium content is one that is rich in organic matter, and no pesticides. Organic meats are most likely to be the best.

Tuna and eggs are also very good suppliers of selenium and they also contain sulphur, which helps the absorption and utilisation of selenium.

Selenium is also available in plants, but in much smaller quantities and it is much less available than that from animal sources. However, depending again on the levels of selenium in the soil where plants are grown, grains, mushrooms, asparagus, broccoli, onions and tomatoes do contain some selenium.

If selenium is taken in supplements, you should avoid taking more than 200 mcg per day as this mineral can be toxic in overdose.

Amino acids

The best source of the three amino acids mentioned has to be meat, although grains may help to boost tryptophan levels.

The reason cysteine is included may be because it contains sulphur which, as was mentioned above, increases the effectiveness of the selenium. The reason for other two is unclear.

Anti-viral fatty acids

Lastly, short-chain fatty acids having four to six carbon atoms are also antiviral. These fats are always saturated. Four-carbon butyric acid is found mostly in butterfat from cows, and six-carbon capric acid is found mostly in butterfat from goats. Butter, cream and full-fat cheeses are the best sources.

Liver, meat, eggs, butter....sounds good

More on low carb diet as a cancer treatment

we have touched on this before.

unlike healthy cells, which generate energy by metabolizing sugar in their mitochondria, cancer cells appeared to fuel themselves exclusively through glycolysis, a less-efficient means of creating energy through the fermentation of sugar in the cytoplasm. The theory is simple: If most aggressive cancers rely on the fermentation of sugar for growing and dividing, then take away the sugar and they should stop spreading. Meanwhile, normal body and brain cells should be able to handle the sugar starvation; they can switch to generating energy from fatty molecules called ketone bodies — the body's main source of energy on a fat-rich diet — an ability that some or most fast-growing and invasive cancers seem to lack.

Here is another study which works on the same idea.: (full text)



Drug/diet synergy for managing malignant astrocytoma in mice: 2-deoxy-D-glucose and the restricted ketogenic diet.

ABSTRACT: BACKGROUND: Astrocytomas are largely dependent on glycolysis to satisfy their bioenergetic requirements for growth and survival. Therapies that target glycolysis can potentially manage astrocytoma growth and progression. Dietary restriction of the high fat/low carbohydrate ketogenic diet (KD-R) reduces glycolysis and is effective in managing experimental mouse and human astrocytomas. The non-metabolizable glucose analogue, 2-deoxy-D-glucose (2-DG), is a potent glycolytic inhibitor that can mimic effects of energy restriction both in vitro and in vivo, but can also produce adverse effects when administered at doses greater than 200 mg/kg. The goal here was to determine if low doses of 2-DG could act synergistically with the KD-R to better manage growth of the CT-2A malignant mouse astrocytoma. METHODS: The therapeutic effect of a KD-R supplemented with a low dose of 2-DG (25 mg/kg) was examined in adult C57BL/6J mice bearing the syngeneic CT-2A malignant astrocytoma grown orthotopically. Mice were fed the standard unrestricted diet for the first 3 days after tumor implantation prior to their separation into one of four diet groups fed either a standard rodent diet in unrestricted amounts (SD-UR) or a KD-R with or without 2-DG for 10 days. The KD-R was restricted to reduce body weight by about 20%. 2-DG was initiated 6 days after tumor implantation and was continued for 7 days. Brain tumors were excised and weighed. RESULTS: Energy intake, body weights, and CT-2A tumor weights were similar in the SD-UR and the SD-UR+2-2DG mouse groups over the dietary treatment period (days 3-13). Tumor weights were about 48% and 80% lower in the KD-R and in the KD-R+2-DG groups, respectively, than in the SD-UR group. Mouse health and vitality was better in the KD-R group than in the KD-R+2-DG group. CONCLUSION: Astrocytoma growth was reduced more in the KD-R mouse group supplemented with 2-DG than in the mouse groups receiving either dietary restriction or 2-DG alone, indicating a synergistic interaction between the drug and the diet. The results suggest that management of malignant astrocytoma with restricted ketogenic diets could be enhanced when combined with drugs that inhibit glycolysis.

Ketogenic Mediterranean diet: a healthy cardiovascular diet for weight loss

Or so this new study says.....

It is interesting to look at the background:

Ketogenic diets are an effective healthy way of losing weight since they promote a non-atherogenic lipid profile, lower blood pressure and decrease resistance to insulin with an improvement in blood levels of glucose and insulin.

you don't hear that very often in the mainstream!

The whole article is currently available as a pdf

Here is the abstract:

Spanish Ketogenic Mediterranean diet: a healthy cardiovascular diet for weight loss

Background
Ketogenic diets are an effective healthy way of losing weight since they promote a non-atherogenic lipid profile, lower blood pressure and decrease resistance to insulin with an improvement in blood levels of glucose and insulin. On the other hand, Mediterranean diet is well known to be one of the healthiest diets, being the basic ingredients of such diet the olive oil, red wine and vegetables. In Spain the fish is an important component of such diet. The objective of this study was to determine the dietary effects of a protein ketogenic diet rich in olive oil, salad, fish and red wine.

Methods
A prospective study was carried out in 31 obese subjects (22 male and 19 female) with the inclusion criteria whose body mass index and age was 36.46 +/- 2.22 and 38.48+/-2.27, respectively. This Ketogenic diet was called "Spanish Ketogenic Mediterranean Diet" (SKMD) due to the incorporation of virgin olive oil as the principal source of fat ([greater than or equal to]30ml/day), moderate red wine intake (200-400ml/day), green vegetables and salads as the main source of carbohydrates and fish as the main source of proteins. It was an unlimited calorie diet. Statistical differences between the parameters studied before and after the administration of the "Spanish Ketogenic Mediterranean diet" (week 0 and 12) were analyzed by paired Student's t test.

Results
There was an extremely significant (p<0.0001)> 94.48 kg), body mass index (36.46 kg/m2->31.76 kg/m2), systolic blood pressure (125.71 mmHg->109.05 mmHg), diastolic blood pressure (84.52 mmHg-> 75.24 mmHg), total cholesterol (208.24 mg/dl->186.62 mg/dl), triacylglicerols (218.67 mg/dl->113.90 mg/dl) and glucose (109.81 mg/dl-> 93.33 mg/dl). There was a significant (p=0.0167) reduction in LDLc (114.52 mg/dl->105.95 mg/dl) and an extremely significant increase in HDLc (50.10 mg/dl->54.57 mg/dl). The most affected parameter was the triacylglicerols (47.91% of reduction).

Conclusions
The SKMD is safe, an effective way of losing weight, promoting non-atherogenic lipid profiles, lowering blood pressure and improving fasting blood glucose levels. Future research should include a larger sample size, a longer term use and a comparison with other ketogenic diets.

Eat Fat to Lower your Cholesterol?

I've noted before that a ketogenic diet (low carb, high fat) is often used to treat epilepsy in children.

It is also potentially a healthy diet, as I've also pointed out before. For those worried that a ketogenic diet might not be healthy, here is an interesting study:

High cholesterol levels drop naturally in children on high-fat anti-seizure diet, Hopkins study show

Elevated cholesterol levels return to normal or near normal levels over time in four out of 10 children with uncontrollable epilepsy treated with the high-fat ketogenic diet, according to results of a Johns Hopkins Children's Center study reported in the Journal of Child Neurology. The study appears online ahead of print here.

Here is the abstract:

A prospective study was performed of all children started on the ketogenic diet at our institution for intractable epilepsy from January 2003 to March 2007 (n = 137), examining for baseline and follow-up total cholesterol and triglyceride levels. Interventions for dyslipidemia were analyzed for their effectiveness. At baseline, 25% of children had hypercholesterolemia (>200 mg/dL), which increased to 60% for those receiving the ketogenic diet. Children receiving a solely formula-based ketogenic diet were less likely to have hypercholesterolemia than those eating solid food after adjusting for age and initial ketogenic ratio (P < .001). Only a slightly higher likelihood of a 20% decrease in cholesterol occurred for those children in whom a dietary intervention was made compared with observation alone (60% vs 41%; P = .11). Hypercholesterolemia occurs in most children receiving a solid food based ketogenic diet but improved in approximately half, even without interventions.

Arguments In Favor Of Ketogenic Diets

I spotted this review that is worth a read (the full article is available)

Arguments In Favor Of Ketogenic Diets Abstract

Many negative comments have been made about the use of ketogenic diets (KDs) and experts today believe that the best way to lose weight is by cutting back on calories, chiefly in the form of fat. The international consensus is that carbohydrates are the basis of the food pyramid for a healthy diet. However, this review will clarify that low-carbohydrate diets are, from a practical and physiological point of view, a much more effective way of losing weight. It is also argued that such diets provide metabolic advantages, for example: they help to preserve muscle mass, reduce appetite, diminish metabolic efficiency, induce metabolic activation of thermogenesis and favor increased fat loss and even a greater reduction in calories. These diets are also healthier because they promote a non-atherogenic lipid profile, lower blood pressure and decrease resistance to insulin with an improvement in blood levels of glucose and insulin. Low-carbohydrate diets should therefore be used to prevent and treat type II diabetes and cardiovascular problems. Such diets also have neurological and antineoplastic benefits and diet-induced ketosis is not associated with metabolic acidosis, nor do such diets alter kidney, liver or heart functions.

More ketogenic diet reseach

I've pointed out recently that keotgenic diets are used to treat epilepsy and possibly benefit other neurological conditions. However each time this is mentioend the science will often say something like:

However, the mechanism(s) by which the Ketogenic Diet achieves neuroprotection and/or seizure control are not yet known.

Here is a study which makes a guess at what is going on. Increases in ATP - the basic fuel of cells

Are purines mediators of the anticonvulsant/neuroprotective effects of ketogenic diets?

Abnormal neuronal signaling caused by metabolic changes characterizes several neurological disorders, and in some instances metabolic interventions provide therapeutic benefits. Indeed, altering metabolism either by fasting or by maintaining a low-carbohydrate (ketogenic) diet might reduce epileptic seizures and offer neuroprotection in part because the diet increases mitochondrial biogenesis and brain energy levels. Here we focus on a novel hypothesis that a ketogenic diet-induced change in energy metabolism increases levels of ATP and adenosine, purines that are critically involved in neuron-glia interactions, neuromodulation and synaptic plasticity. Enhancing brain bioenergetics (ATP) and increasing levels of adenosine, an endogenous anticonvulsant and neuroprotective molecule, might help with understanding and treating a variety of neurological disorders.


And another one - look at the sentence I've put in bold in this abstract:



Effect of weight loss and ketosis on postprandial cholecystokinin and free fatty acid concentrations.


BACKGROUND: Weight regain after weight loss may not be due primarily to voluntary return to social habits but may be explained by changes in peripheral hormonal signals activating hunger and encouraging feeding behavior. OBJECTIVE: The objective of this study was to investigate physiologic adaptations to weight loss that may encourage weight regain. DESIGN: The study had a within-subject repeated-measure design [12 healthy, obese men, 33-64 y, body mass index (in kg/m(2)) 30-46] and was a clinical intervention investigation of circulating metabolites and hunger-satiety responses before and after weight loss. Measures included anthropometry (bioelectrical impedance, body weight, and waist circumference), concentrations of circulating hormones and metabolites [ketone bodies, free fatty acids (FFAs), insulin, leptin, glucose, and cholecystokinin (CCK)], and measures of hunger and satiety at baseline, 8 wk after weight loss with a very-low-energy diet, and 1 wk after weight maintenance. RESULTS: Weight loss led to a reduction in postprandial CCK secretion (P = 0.016). However, when subjects were ketotic (elevated circulating beta-hydroxybutyrate concentrations), CCK secretion was sustained at concentrations before weight loss. After weight loss, there were reduced postprandial FFA concentrations (P = 0.0005). The presence of ketosis sustained FFA to concentrations before weight loss (P = 0.60). CONCLUSION: Rapid weight loss of approximately 10% of initial body weight results in a reduction in postprandial CCK and FFA concentrations.

.....when subjects were ketotic (elevated circulating beta-hydroxybutyrate concentrations), CCK secretion was sustained at concentrations before weight loss.

What is CCK?

Cholecystokinin (CCK; from Greek chole, "bile"; cysto, "sac"; kinin, "move"; hence, move the bile-sac (gallbladder)) is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein. Cholecystokinin, previously called pancreozymin, is synthesised by I-cells in the mucosal epithelium of the small intestine and secreted in the duodenum, the first segment of the small intestine, and causes the release of digestive enzymes and bile from the pancreas and gallbladder, respectively. It also acts as a hunger suppressant. Recent evidence has suggested that it also plays a major role in inducing drug tolerance to opioids like morphine and heroin, and is partly implicated in experiences of pain hypersensitivity during opioid withdrawal.[1][2]

So reading this abstract in the light of this it seems that the weight loss causes a reduction in CCK - and therefore an increase in hunger.....unless you are in ketosis, when hunger is suppressed?

a ketogenic diet is good for you....

well ok it is good for rats.

It increases the level of Glutathione, an important antioxidant. So forget your 5 a day, just dump the carbs?

The Ketogenic Diet Increases Mitochondrial Glutathione Levels.

The ketogenic diet (KD) is a high-fat, low carbohydrate diet that is used as a therapy for intractable epilepsy. However, the mechanism(s) by which the KD achieves neuroprotection and/or seizure control are not yet known. We sought to determine whether the KD improves mitochondrial redox status. Adolescent Sprague-Dawley rats (P28) were fed a KD or control diet for 3 weeks and ketosis was confirmed by plasma levels of beta-hydroxybutyrate (BHB). KD-fed rats showed a 2-fold increase in hippocampal mitochondrial glutathione (GSH) and GSH/GSSG ratio compared to control diet-fed rats. To determine whether elevated mitochondrial GSH was associated with increased de novo synthesis, the enzymatic activity of glutamate cysteine ligase (GCL) (the rate limiting enzyme in GSH biosynthesis) and protein levels of the catalytic (GCLC) and modulatory (GCLM) subunits of GCL were analyzed. Increased GCL activity, as well as upregulated protein levels of GCL subunits in KD-fed, but not control rats, was observed. Reduced coenzyme A (CoASH), an indicator of mitochondrial redox status, and lipoic acid, a thiol antioxidant, were also significantly increased in the hippocampus of KD-fed rats compared to controls. Since GSH is a major mitochondrial antioxidant that protects mitochondrial DNA (mtDNA) against oxidative damage, we measured mitochondrial hydrogen peroxide (H(2)O(2)) production and H(2)O(2)-induced mtDNA damage. Isolated hippocampal mitochondria from KD-fed rats showed functional consequences consistent with the improvement of mitochondrial redox status i.e. decreased H(2)O(2) production and mtDNA damage. Together, the results demonstrate that the KD upregulates GSH biosynthesis, enhances mitochondrial antioxidant status, and protects mtDNA from oxidant-induced damage.

UPDATE - Emma has written more about a ketogenic diet in the last couple of days here and here

Ketogenic diet and epilepsy

I really didn't think this was news, but it was on the radio this morning

Diet treatment call for epilepsy
A special high-fat diet helps to control fits in children with epilepsy, a UK trial suggests.
The number of seizures fell by a third in children on the "ketogenic" diet, where previously they had suffered fits every day despite medication.
The diet alters the body's metabolism by mimicking the effects of starvation, the researchers reported in the Lancet Neurology.
The researchers called for the diet to be more widely available on the NHS.

A further story gives a case of a young child who improved with the diet and an example of it.

The abstract of the study is here.

Lyle McDonald explains the history of this diet:

The ketogenic diet has been used to treat a variety of clinical conditions, the most well known of which is childhood epilepsy. Writings as early as the middle ages discuss the use of fasting as a treatment for seizures. The early 1900's saw the use of total fasting as a treatment for seizures in children. However, fasting cannot be sustained indefinitely and only controls seizures as long as the fast is continued.

Due to the problems with extended fasting, early nutrition researchers looked for a way to mimic starvation ketosis, while allowing food consumption. Research determined that a diet high in fat, low in carbohydrate and providing the minimal protein needed to sustain growth could maintain starvation ketosis for long periods of time. This led to development of the original ketogenic diet for epilepsy in 1921 by Dr. Wilder. Dr. Wilder's ketogenic diet controlled pediatric epilepsy in many cases where drugs and other treatments had failed. The ketogenic diet as developed by Dr. Wilder is essentially identical to the diet being used in 1998 to treat childhood epilepsy.

The ketogenic diet fell into obscurity during the 30's, 40's and 50's as new epilepsy drugs were discovered. The difficulty in administering the diet, especially in the face of easily prescribed drugs, caused it to all but disappear during this time.

So it has been around since 1921 and it is now rediscovered...