Breath acetone is a reliable indicator of ketosis in adults consuming ketogenic meals

BACKGROUND: Ketogenic diets are used therapeutically to treat intractable seizures. Clinically, it appears that the maintenance of ketosis is crucial to the efficacy of the diet in ameliorating seizures. To understand how ketosis and seizure protection are related, a reliable, noninvasive measure of ketosis that can be performed frequently with minimal discomfort is needed. OBJECTIVE: The objective was to determine which index, breath acetone or urinary acetoacetate, is more strongly related to the plasma ketones acetoacetate and beta-hydroxybutyrate. DESIGN: After fasting overnight for 12 h, 12 healthy adults consumed 4 ketogenic meals over 12 h. Blood, breath, and urine samples were collected hourly. Blood was analyzed for plasma acetoacetate and beta-hydroxybutyrate, breath for acetone, and urine for acetoacetate. RESULTS: By the end of the 12-h dietary treatment, plasma acetoacetate, plasma beta-hydroxybutyrate, and breath acetone had increased 3.5-fold, whereas urinary acetoacetate increased 13-fold when measured enzymatically and 25-fold when measured with urinary ketone dipsticks. Plasma acetoacetate was best predicted by breath acetone (R(2) = 0.70, P < 0.0001). Plasma beta-hydroxybutyrate was equally predicted by breath acetone and urinary acetoacetate (R(2) = 0.54, P = 0.0040). CONCLUSIONS: Breath acetone is as good a predictor of ketosis as is urinary acetoacetate. Breath acetone analysis is noninvasive and can be performed frequently with minimal discomfort to patients. As an indicator of ketosis in epilepsy patients consuming a ketogenic diet, breath acetone may be useful for understanding the mechanism of the diet, elucidating the importance of ketosis in seizure protection, and ultimately, enhancing the efficacy of the diet by improving patient monitoring.     

Changes in growth and seizure reduction in children on the ketogenic diet as a treatment for intractable epilepsy

OBJECTIVE: To assess growth and seizure reduction in epileptic children using the ketogenic diet as a treatment for intractable epilepsy. DESIGN: A retrospective chart review was designed to evaluate urinary ketone levels, height and weight z scores and percentiles, and seizure reduction. Data were collected at baseline and at 6 and 12 months. SUBJECTS/SETTINGS: Fifty-seven subjects, ages 1 to 26 years old, started the ketogenic diet at Rush University Medical Center between August 1995 and December 2001. Thirty-nine subjects stayed on the diet for 6 months, and five more were lost by the 12th month of follow-up. Statistical analysis Mann-Whitney U tests assessed differences between male and female subjects and between subjects with high ketosis and moderate ketosis. Friedman tests followed by Wilcoxon sign rank tests assessed the significance of changes in growth at baseline and at 6 and 12 months. Associations between seizure reduction and growth and urinary ketone levels were determined using chi 2 tests. A binary logistic regression model identified potential predictors of growth and seizure reduction. RESULTS: Height-for-age z scores significantly decreased ( P < or =.0005) from -0.30+/-1.19 to -0.99+/-1.13 among subjects on the diet for 12 months. Subjects with high ketosis (80 to 160 mg/dL) experienced a significant decrease ( P < or =.0005) in height-for-age z scores from -0.45+/-1.28 to -1.1+/-1.23, whereas subjects with moderate ketosis did not. Observed percent seizure reduction was similar to those of other published studies. CONCLUSIONS: Subjects on the ketogenic diet showed a delay in growth. More research is needed to evaluate the relationship between ketosis and growth.     

Implementing A Ketogenic Diet Based on Medium-chain Triglyceride Oil in Pediatric Patients with Cancer

Traditionally, a ketogenic diet is given to drug-resistant children with epilepsy to improve seizure control. Inducing a ketogenic state in patients with cancer may be a useful adjunct to cancer treatment by affecting tumor glucose metabolism and growth while maintaining the patient's nutritional status. A ketogenic diet consisting of 60% medium-chain triglyceride (MCT) oil, 20% protein, 10% carbohydrate, and 10% other dietary fats was provided to a select group of pediatric patients with advanced-stage cancer to test the effects of dietary-induced ketosis on tumor glucose metabolism. Issues of tolerance and compliance for patients consuming an oral diet (consisting of normal table foods and daily MCT oil “shakes”) and for patients receiving an enteral formula are reviewed. Preliminary use of the MCT oil-based diet suggests a potential in pediatric patients with cancer. J Am Diet Assoc. 1995; 95:693-697.     

A Hypomethylating Ketogenic Diet in Apolipoprotein E-Deficient Mice: A Pilot Study on Vascular Effects and Specific Epigenetic Changes

Hyperhomocysteneinemia (HHcy) is common in the general population and is a risk factor for atherosclerosis by mechanisms that are still elusive. A hypomethylated status of epigenetically relevant targets may contribute to the vascular toxicity associated with HHcy. Ketogenic diets (KD) are diets with a severely restricted amount of carbohydrates that are being widely used, mainly for weight-loss purposes. However, studies associating nutritional ketosis and HHcy are lacking. This pilot study investigates the effects of mild HHcy induced by nutritional manipulation of the methionine metabolism in the absence of dietary carbohydrates on disease progression and specific epigenetic changes in the apolipoprotein-E deficient (apoE^–/–) mouse model. ApoE^–/– mice were either fed a KD, a diet with the same macronutrient composition but low in methyl donors (low methyl KD, LMKD), or control diet. After 4, 8 or 12 weeks plasma was collected for the quantification of: (1) nutritional ketosis, (i.e., the ketone body beta-hydroxybutyrate using a colorimetric assay); (2) homocysteine by HPLC; (3) the methylating potential S-adenosylmethionine to S-adenosylhomocysteine ratio (AdoHcy/AdoMet) by LC-MS/MS; and (4) the inflammatory cytokine monocyte chemoattractant protein 1 (MCP1) by ELISA. After 12 weeks, aortas were collected to assess: (1) the vascular AdoHcy/AdoMet ratio; (2) the volume of atherosclerotic lesions by high-field magnetic resonance imaging (14T-MRI); and (3) the content of specific epigenetic tags (H3K27me3 and H3K27ac) by immunofluorescence. The results confirmed the presence of nutritional ketosis in KD and LMKD mice but not in the control mice. As expected, mild HHcy was only detected in the LMKD-fed mice. Significantly decreased MCP1 plasma levels and plaque burden were observed in control mice versus the other two groups, together with an increased content of one of the investigated epigenetic tags (H3K27me3) but not of the other (H3K27ac). Moreover, we are unable to detect any significant differences at the p < 0.05 level for MCP1 plasma levels, vascular AdoMet:AdoHcy ratio levels, plaque burden, and specific epigenetic content between the latter two groups. Nevertheless, the systemic methylating index was significantly decreased in LMKD mice versus the other two groups, reinforcing the possibility that the levels of accumulated homocysteine were insufficient to affect vascular transmethylation reactions. Further studies addressing nutritional ketosis in the presence of mild HHcy should use a higher number of animals and are warranted to confirm these preliminary observations.     

Slow but Steady—The Responsiveness of Sympathoadrenal System to a Hypoglycemic Challenge in Ketogenic Diet-Fed Rats

The sympathoadrenal counterregulatory response to hypoglycemia is critical for individuals with type 1 diabetes due to impaired ability to produce glucagon. Ketogenic diets (KD) are an increasingly popular diabetes management tool; however, the effects of KD on the sympathoadrenal response are largely unknown. Here, we determined the effects of KD-induced ketosis on the sympathoadrenal response to a single insulin-induced hypoglycemic challenge. We investigated how a 3 week KD feeding regimen affected the main components of the sympathoadrenal counterregulatory response: adrenal sympathetic nerve activity (ASNA), adrenal gland activity, plasma epinephrine, and brainstem glucose-responsive C1 neuronal activation in anesthetized, nondiabetic male Sprague-Dawley rats. Rats on KD had similar blood glucose (BG) levels and elevated ketone body β-hydroxybutyrate (BHB) levels compared to the control Chow diet group. All KD rats responded to hypoglycemia with a robust increase in ASNA, which was initiated at significantly lower BG levels compared to Chow-fed rats. The delay in hypoglycemia-induced ASNA increase was concurrent with rapid disappearance of BHB from cerebral and peripheral circulation. Adrenal gland activity paralleled epinephrine and ASNA response. Overall, KD-induced ketosis was associated with initiation of the sympathoadrenal response at lower blood glucose levels; however, the magnitude of the response was not diminished.     

Cancer cachexia: influence of systemic ketosis on substrate levels and nitrogen metabolism

The aim of this study was to determine whether a ketogenic diet could decrease nitrogen losses in cachectic cancer patients and at the same time reduce the supply of glucose for tumor energy metabolism. Five patients with malignant disease and severe weight loss (mean 32%) were fed via a fine bore nasogastric tube. A normal diet was given for 6 d and this was followed by 7 d of an isonitrogenous, isocaloric, ketogenic diet. Both diets were well tolerated. At 7 d the mean ketone body concentration in the blood of patients fed the ketogenic diet was 1.21 +/- 0.33 mM. This ketosis was associated with a significant reduction of the concentration in blood of glucose, lactate, and pyruvate (p less than 0.05). There was, however, no significant alteration in host N balance or whole-body protein synthesis, degradation, or turnover rates. Whether the change from glucose- to fat-derived energy substrates might reduce tumor growth rates in the long term remains to be determined.     

Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum

BACKGROUND: Altering the macronutrient composition of the diet influences hunger and satiety. Studies have compared high- and low-protein diets, but there are few data on carbohydrate content and ketosis on motivation to eat and ad libitum intake. OBJECTIVE: We aimed to compare the hunger, appetite, and weight-loss responses to a high-protein, low-carbohydrate [(LC) ketogenic] and those to a high-protein, medium-carbohydrate [(MC) nonketogenic] diet in obese men feeding ad libitum. DESIGN: Seventeen obese men were studied in a residential trial; food was provided daily. Subjects were offered 2 high-protein (30% of energy) ad libitum diets, each for a 4-wk period-an LC (4% carbohydrate) ketogenic diet and an MC (35% carbohydrate) diet-randomized in a crossover design. Body weight was measured daily, and ketosis was monitored by analysis of plasma and urine samples. Hunger was assessed by using a computerized visual analogue system. RESULTS: Ad libitum energy intakes were lower with the LC diet than with the MC diet [P=0.02; SE of the difference (SED): 0.27] at 7.25 and 7.95 MJ/d, respectively. Over the 4-wk period, hunger was significantly lower (P=0.014; SED: 1.76) and weight loss was significantly greater (P=0.006; SED: 0.62) with the LC diet (6.34 kg) than with the MC diet (4.35 kg). The LC diet induced ketosis with mean 3-hydroxybutyrate concentrations of 1.52 mmol/L in plasma (P=0.036 from baseline; SED: 0.62) and 2.99 mmol/L in urine (P<0.001 from baseline; SED: 0.36). CONCLUSION: In the short term, high-protein, low-carbohydrate ketogenic diets reduce hunger and lower food intake significantly more than do high-protein, medium-carbohydrate nonketogenic diets.     

Breath acetone predicts plasma ketone bodies in children with epilepsy on a ketogenic diet

OBJECTIVE: The high-fat ketogenic diet has long been used to treat refractory childhood seizures, but whether there is a relation between the degree of ketosis and effectiveness of seizure control remains unclear. Frequent measurements of plasma ketones are difficult in children so the goal was to determine the utility of breath acetone as a marker of systemic ketosis and seizure control in children given the ketogenic diet because of seizures refractory to medication. METHODS: In experiment I, breath acetone and plasma ketones were assessed every 2 h during an 8-h test day in seven children. In experiment II, a preliminary assessment of the possible relation between breath acetone and seizure frequency was made over 14 d in five children and one adolescent on the ketogenic diet. RESULTS: Breath acetone was positively and curvilinearly related to plasma acetone (r2 = 0.99, P < 0.0001), plasma acetoacetate (r2 = 0.89, P < 0.0001), and plasma beta-hydroxybutyrate (r2 = 0.94, P < 0.0001). No significant relation was found between breath acetone and seizure frequency or change in seizure frequency. CONCLUSIONS: Breath acetone is indicative of systemic ketosis while on the ketogenic diet. However, owing to the wide range of seizure types and plasma acetone, more subjects will be needed to determine whether there is a clear link between breath acetone and seizure frequency or decreased seizure frequency while on the high-fat ketogenic diet.     

Ketogenic Diet Decreases Alcohol Intake in Adult Male Mice

The classic ketogenic diet is a diet high in fat, low in carbohydrates, and well-adjusted proteins. The reduction in glucose levels induces changes in the body’s metabolism, since the main energy source happens to be ketone bodies. Recent studies have suggested that nutritional interventions may modulate drug addiction. The present work aimed to study the potential effects of a classic ketogenic diet in modulating alcohol consumption and its rewarding effects. Two groups of adult male mice were employed in this study, one exposed to a standard diet (SD, n = 15) and the other to a ketogenic diet (KD, n = 16). When a ketotic state was stable for 7 days, animals were exposed to the oral self-administration paradigm to evaluate the reinforcing and motivating effects of ethanol. Rt-PCR analyses were performed evaluating dopamine, adenosine, CB1, and Oprm gene expression. Our results showed that animals in a ketotic state displayed an overall decrease in ethanol consumption without changes in their motivation to drink. Gene expression analyses point to several alterations in the dopamine, adenosine, and cannabinoid systems. Our results suggest that nutritional interventions may be a useful complementary tool in treating alcohol-use disorders.     

The Association between Australian Childcare Centre Healthy Eating Practices and Children’s Healthy Eating Behaviours: A Cross-Sectional Study within Lunchbox Centres

The association between healthy eating practices and child dietary intake in childcare centres where parents pack foods from home has received little attention. This study aimed to: (1) Describe the nutritional content of foods and beverages consumed by children in care; and (2) Assess the association between centre healthy eating practices and child intake of fruit and vegetable servings, added sugar(grams), saturated fat(grams) and sodium(milligrams) in care. A cross-sectional study amongst 448 children attending 22 childcare centres in New South Wales, Australia, was conducted. Child dietary intake was measured via weighed lunchbox measurements, photographs and researcher observation, and centre healthy eating practices were assessed via researcher observation of centre nutrition environments. Children attending lunchbox centres consumed, on average 0.80 servings (standard deviation 0.69) of fruit and 0.27 servings (standard deviation 0.51) of vegetables in care. The availability of foods within children’s lunchboxes was associated with intake of such foods (p < 0.01). Centre provision of intentional healthy eating learning experiences (estimate −0.56; p = 0.01) and the use of feeding practices that support children’s healthy eating (estimate −2.02; p = 0.04) were significantly associated with reduced child intake of saturated fat. Interventions to improve child nutrition in centres should focus on a range of healthy eating practices, including the availability of foods packed within lunchboxes.     

A prospective study: growth and nutritional status of children treated with the ketogenic diet

OBJECTIVE: To assess the nutritional status of children treated with the classic and medium-chain triglyceride (MCT) ketogenic diets. DESIGN: A prospective, nonrandomized study design was used to measure nutrient intakes, growth, and biochemical indexes of children, age 1 to 16 years, with intractable epilepsy before and after 4 months' treatment with the classic and MCT ketogenic diets. None of the children had been on earlier dietary regimens. SUBJECTS: Of 58 children asked to participate in the study between September 1998 and July 2000, consent was obtained for 30 children. Fourteen children on the classic diet and 11 children on the MCT diet completed the study (83% completed). Statistical analysis performed Paired t tests were done on anthropometric and biochemical indexes. Nutrient intakes were compared with Dietary Reference Intakes (DRIs). RESULTS: Both groups had statistically significant height increases of 2 to 3 cm (P<.05), but did not have significant increases in height/age percentiles. Weight percentiles decreased by approximately 10 percentiles for both diets; P=.043 for classic diet and.051 for MCT diet. Nutrient intakes from the diet and vitamin and mineral supplements met the DRIs except for phosphorus (both diets) and folate (classic diet). All biochemical indexes, including albumin, remained within the normal range. For the MCT diet, there was a 0.7 decrease in the ratio of total cholesterol to high-density lipoprotein ratios (P<.0009) at 4 months. APPLICATIONS: When treating children on a ketogenic diet, clinicians should recommend adequate intake of energy and protein, a higher proportion of unsaturated to saturated dietary fats, and consider vitamin and mineral supplements.     

The Ketogenic Diet: A Practical Guide for Caregivers

The ketogenic diet is a high-fat, low-carbohydrate diet that results in ketosis. It has been in use for nearly 70 years. Several modifications of the diet's original form, including the medium-chain triglyceride (MCT) diet, have been made in an attempt to overcome the obstacles of compliance and acceptance, which have been critical factors in determining its success. The practical guide for caregivers that is presented here uses elements of both the original ketogenic diet and the MCT diet, with added ideas. Our modified diet has been in use for more than 3 years at Columbia Presbyterian Medical Center Babies and Children's Hospital of New York. The majority of parents and children find our diet more acceptable and/or more user friendly than other types of ketogenic diets. Thus, compliance is better. The variety of foods offered is greater and provides a more normal diet than the other types of ketogenic diets. In addition, the calculations for nutritionists are easier, and parents are able to adjust the diet without the fear that their child will lose ketones. J Am Diet Assoc. 1998;98:316-321.     

A ketogenic diet increases protein phosphorylation in brain slices of rats

Ketogenic diets have been used to treat seizure disorders of children and recently it was shown to increase the drug-induced seizure threshold in rats. Protein phosphorylation is a major regulatory mechanism of signal transduction that has been implicated in modulating neuronal excitability. We investigated the basal protein phosphorylation in microslices from different brain regions (hippocampus, cerebral cortex and cerebellum) of young rats fed a ketogenic diet, and we evaluated the effect of this diet on weight development and health of these rats based on serum biochemistry. Thirty-day-old rats consumed ad libitum ketogenic (high fat) or control diets for 8 wk. Rats consuming the high fat diet had ketonemia without signs of undernutrition or illness. Microslices were incubated in media containing (32)P-phosphate, and (32)P-phosphoprotein content was analyzed by one- or two-dimensional electrophoresis followed by autoradiography. Basal protein phosphorylation was greater in brain slices from ketogenic rats. Different increments of synapsin I, GAP-43 and GFAP phosphorylation were observed in two-dimensional autoradiography. A ketogenic diet induced metabolic changes affecting the basal status of protein phosphorylation. This change could affect the mechanisms of signal transduction in neural cells involved in the increase in the seizure threshold.     

Effects of low carbohydrate diets on energy and nitrogen balance and body composition in rats depend on dietary protein-to-energy ratio

ObjectivesTruly ketogenic rodent diets are low in carbohydrates but also low in protein. The aim of this study was to differentiate effects of ketosis, low carbohydrate (LC) and/or low-protein intake on energy and nitrogen metabolism.MethodsWe studied the nitrogen balance of rats fed LC diets with varying protein contents: LC diets consisted of 75/10, 65/20 and 55/30 percent of fat to protein (dry matter), respectively, and were iso-energetically pair-fed to a control (chow) diet to 12-wk-old male Wistar rats (n = 6 per diet).Previous studies demonstrated only LC75/10 was truly ketogenic. Food, fecal, and urine samples, as well as carcasses were collected and analyzed for heat of combustion and nitrogen (Kjeldahl method). Blood samples were analyzed for plasma protein, albumin, and triacylglycerol.ResultsAll LC groups displayed less body weight gain, and the degree of reduction was inversely related to digestible crude protein intake (daily weight gain compared with chow: LC75/10: −50%; LC55/30: −20%). Nitrogen excretion by urine was related to digestible protein intake (chow: 0.23 ± 0.02 g nitrogen/d; LC75/10: 0.05 ± 0.01 g nitrogen/d). Renal energy excretion was closely associated with intake of digestible crude protein (r = 0.697) and renal nitrogen excretion (r = 0.769). Energy-to-nitrogen ratio in urine was nearly doubled with LC75/10 compared with all other groups. Total body protein was highest with chow and lowest with LC75/10. Rats fed with LC75/10 displayed features of protein deficiency (reduced growth and nitrogen balance, hypoproteinemia, depletion of body protein, and increased body and liver fat), whereas the effects with the non-ketogenic diets LC65/20 and LC55/30 were less pronounced.ConclusionThese results suggest that truly ketogenic LC diets in growing rats are LC diets that are also deficient in protein for growth.     

Adenosine Receptors Modulate the Exogenous Ketogenic Supplement-Evoked Alleviating Effect on Lipopolysaccharide-Generated Increase in Absence Epileptic Activity in WAG/Rij Rats

It has been previously demonstrated that KEKS food containing exogenous ketogenic supplement ketone salt (KS) and ketone ester (KE) decreased the lipopolysaccharide (LPS)-generated increase in SWD (spike-wave discharge) number in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats, likely through ketosis. KEKS-supplemented food-generated ketosis may increase adenosine levels, and may thus modulate both neuroinflammatory processes and epileptic activity through adenosine receptors (such as A1Rs and A2ARs). To determine whether these adenosine receptors are able to modify the KEKS food-generated alleviating effect on LPS-evoked increases in SWD number, an antagonist of A1R DPCPX (1,3-dipropyl-8-cyclopentylxanthine; 0.2 mg/kg) with LPS (50 µg/kg) and an antagonist of A2AR {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304"}}SCH58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine; 0.5 mg/kg) with LPS were co-injected intraperitoneally (i.p.) on the ninth day of KEKS food administration, and their influence not only on the SWD number, but also on blood glucose, R-beta-hydroxybutyrate (R-βHB) levels, and body weight were measured. We showed that inhibition of A1Rs abolished the alleviating effect of KEKS food on LPS-generated increases in the SWD number, whereas blocking A2ARs did not significantly modify the KEKS food-generated beneficial effect. Our results suggest that the neuromodulatory benefits of KEKS-supplemented food on absence epileptic activity are mediated primarily through A1R, not A2AR.     

Effect of Anti-Inflammatory Diets on Pain in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

Various nutritional therapies have been proposed in rheumatoid arthritis, particularly diets rich in ω-3 fatty acids, which may lead to eicosanoid reduction. Our aim was to investigate the effect of potentially anti-inflammatory diets (Mediterranean, vegetarian, vegan, ketogenic) on pain. The primary outcome was pain on a 10 cm visual analogue scale. Secondary outcomes were C-reactive protein levels, erythrocyte sedimentation rate, health assessment questionnaire, disease activity score 28, tender/swollen joint counts, weight, and body mass index. We searched MEDLINE (OVID), Embase (Elsevier), and CINAHL for studies published from database inception to 12 November 2021. Two authors independently assessed studies for inclusion, extracted study data, and assessed the risk of bias. We performed a meta-analysis with all eligible randomized controlled trials using RevMan 5. We used mean differences or standardized mean differences and the inverse variance method of pooling using a random-effects model. The search retrieved 564 unique publications, of which we included 12 in the systematic review and 7 in the meta-analysis. All studies had a high risk of bias and the evidence was very low. The main conclusion is that anti-inflammatory diets resulted in significantly lower pain than ordinary diets (−9.22 mm; 95% CI −14.15 to −4.29; p = 0.0002; 7 RCTs, 326 participants).     

High-fat versus high-carbohydrate enteral formulae: effect on blood glucose, C-Peptide, and ketones in patients with type 2 diabetes treated with insulin or sulfonylurea

Recently, two commercial enteral formulae for diabetic patients have been made available in Spain: a high-complex-carbohydrate, low-fat formulation (HCF) and a low-carbohydrate formulation (RCF). This study compares the effects of the two enteral nutritional formulae in patients with non–insulin-dependent diabetes mellitus (type 2 diabetes) treated with sulfonylurea or insulin. Fifty-two type 2 diabetes patients were randomly assigned to receive one of the two enteral formulae. Test enteral formula breakfast (250 cc) were consumed at approximately 0900 h after routine medications (insulin or oral agents) had been taken. Venous blood samples were obtained during fasting, before medication, and at 30 and 120 min after the start of the meal. The glycemic response of patients to the HCF was significantly greater than to RCF, but lower than in the sulfonyl type 2 diabetes treated groups. The incremental glucose response was within acceptable levels except in insulin treatment type 2 diabetes patients given HCF. Glucose, insulin, and C-peptide responses were higher in HCF than RCF groups. Two-factor analysis of variance on mean increments of blood glucose and C-peptide from basal levels to 30 min show the type of enteral nutrition as the main factor (P = 0.0010 and P = 0.0005, respectively). The RCF formula supplies 50.0% of energy as fat and 33.3% as carbohydrates, so it may be a ketogenic diet. It was found that both ketone bodies were higher after RCF than after HCF ingestion, but without statistical significance. We conclude that the partial replacement of complex digestible carbohydrates with monounsaturated fatty acids in the enteral formulae for supplementation of oral diet may improve glycemic control in patients with type 2 diabetes. The long-term effects of enteral diets high in monounsaturated fatty acids need further evaluation in patients with type 2 diabetes.     

Consumption Patterns of Fruit and Vegetable Juices and Dietary Nutrient Density among French Children and Adults

Background: Fruit and vegetable consumption is a marker of higher-quality diets; less is known about the contribution of 100% fruit and vegetable juices (FVJ) to diet quality. Objective: To explore FVJ consumption patterns in relation to dietary nutrient density among French children (aged 3–14 years old) and adults (≥21 years old). Methods: Analyses were based on the nationally representative 2013 CCAF (Comportements et Consommations Alimentaires en France) survey of 1930 respondents, stratified by age group, FVJ consumption, and socioeconomic status (SES). Dietary nutrient density was based on the Nutrient Rich Food (NRF9.3) index, adjusted for gender and age. Results: Mean total consumption of fruits and vegetables was 2.6 servings/day for children and 3.8 servings/day for adults. Mean population consumption of FVJ was 83 mL/day for children and 54.6 mL/day for adults, equivalent to 0.4 servings/day and 0.3 servings/day respectively. FVJ consumers had higher quality diets than did non-consumers, after adjusting for covariates. The respective NRF9.3 values were 486.4 ± 4.3 vs. 428.7 ± 7.5 for children and 460.7 ± 4.4 vs. 435.4 ± 4.4 for adults. FVJ consumers had similar or higher intakes of fruits and vegetables than did non-consumers. The socioeconomic gradient for FVJ consumption was much weaker (p < 0.046) than for whole fruit (p < 0.01). Conclusions: In a nationally representative sample of French children and adults, fruit and vegetable consumption fell short of recommended values. Higher FVJ consumption was associated with higher-quality diets and better compliance with the French National Plan for Nutrition and Health (PNNS).     

A Comparison of the Effects of Young-Child Formulas and Cow’s Milk on Nutrient Intakes in Polish Children Aged 13–24 Months

Adequately balanced daily food rations that provide the body with sufficient amounts of energy and nutrients, including minerals, are particularly important in early childhood when rapid physical, intellectual and motor development takes place. Cow’s milk (CM) and young-child formulas (YCFs) are introduced to a child’s diet past the first year of age. The main aim of the present study was to perform a qualitative and a quantitative analysis of daily food rations of young children based on the recommendations of the daily food ration model. An attempt was also made to determine whether the type of consumed milk (YCF or CM) adequately meets young children’s energy demands and contributes to the incorporation of different food groups into a balanced and healthy diet for children aged 13–24 months. A total of 714 parents between October 2019 and March 2020 filled out a food frequency questionnaire. In the second stage of the study, the parents participated in a dietary recall and were asked to keep diaries of all meals and foods consumed by children over a period of three days. The mean daily intake of CM/YCF and fermented milks was determined at 360 mL ± 128 mL, and it accounted for 55.4% of the guideline values. Flavored dairy products were consumed more frequently than fermented milks without added sugar or flavoring (94 ± 17 g vs. 56 ± 26 g, p < 0.05). Diets incorporating CM were significantly more abundant in protein than YCF diets (29.3 g vs. 21.9 g; p < 0.01). Liquid intake was somewhat higher in children fed YCFs (1280.8 mL vs. 1120.1; p < 0.05), mainly due to the higher consumption of fruit juice, nectars and sweetened hot beverages (246 ± 35 mL in the YCF group vs. 201 ± 56 mL in the CM group; p < 0.05). Children fed YCF consumed significantly larger amounts of sweetened beverages such as tea sweetened with sugar or honey, sweetened hot chocolate or instant teas (OR = 2.54; Cl: 1.32–3.26; p < 0.001), than children receiving CM. This group was also characterized by higher consumption of sweetened dairy products, mainly cream cheese desserts, fruit yogurt and yogurt with cereal (OR = 1.87; Cl: 1.36–2.54; p < 0.01), as well as a lower daily intake of plain fermented milks (OR = 0.56; Cl: 0.21–0.79; p < 0.001). The daily food intake and the quality of the diets administered to children aged 13–24 months were evaluated and compared with the model food ration. It was found that milk type influenced children’s eating habits and preference for sweet-tasting foods. The study also demonstrated that Polish parents and caregivers only have limited knowledge of nutritional guidelines for toddlers.     

The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer

Background

Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the second leading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting the health and vitality of normal brain cells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growth and survival, normal brain cells can metabolize both glucose and ketone bodies for energy. This study evaluated the efficacy of KetoCal^®, a new nutritionally balanced high fat/low carbohydrate ketogenic diet for children with epilepsy, on the growth and vascularity of a malignant mouse astrocytoma (CT-2A) and a human malignant glioma (U87-MG).

Methods

Adult mice were implanted orthotopically with the malignant brain tumors and KetoCal^® was administered to the mice in either unrestricted amounts or in restricted amounts to reduce total caloric intake according to the manufacturers recommendation for children with refractory epilepsy. The effects KetoCal^® on tumor growth, vascularity, and mouse survival were compared with that of an unrestricted high carbohydrate standard diet.

Results

KetoCal^® administered in restricted amounts significantly decreased the intracerebral growth of the CT-2A and U87-MG tumors by about 65% and 35%, respectively, and significantly enhanced health and survival relative to that of the control groups receiving the standard low fat/high carbohydrate diet. The restricted KetoCal^® diet reduced plasma glucose levels while elevating plasma ketone body (β-hydroxybutyrate) levels. Tumor microvessel density was less in the calorically restricted KetoCal^® groups than in the calorically unrestricted control groups. Moreover, gene expression for the mitochondrial enzymes, β-hydroxybutyrate dehydrogenase and succinyl-CoA: 3-ketoacid CoA transferase, was lower in the tumors than in the contralateral normal brain suggesting that these brain tumors have reduced ability to metabolize ketone bodies for energy.

Conclusion

The results indicate that KetoCal^® has anti-tumor and anti-angiogenic effects in experimental mouse and human brain tumors when administered in restricted amounts. The therapeutic effect of KetoCal^® for brain cancer management was due largely to the reduction of total caloric content, which reduces circulating glucose required for rapid tumor growth. A dependency on glucose for energy together with defects in ketone body metabolism largely account for why the brain tumors grow minimally on either a ketogenic-restricted diet or on a standard-restricted diet. Genes for ketone body metabolism should be useful for screening brain tumors that could be targeted with calorically restricted high fat/low carbohydrate ketogenic diets. This preclinical study indicates that restricted KetoCal^® is a safe and effective diet therapy and should be considered as an alternative therapeutic option for malignant brain cancer.