Although the ketogenic diet has been used in the therapy for epilepsy for more than 50 years, there are few studies concerned with the effects of this diet on the central nervous system. Recent attempts to unravel the biochemical effects of the ketogenic diet on the brain seem to be a fruitful approach to understanding how the ketogenic diet causes anticonvulsant effects. Another exciting approach is the development of animal models in which various effects of the diet can be correlated with changes in seizure protection. It would be useful to determine whether the diet produces any neurophysiological effects that could account for some, or all, of its antiseizure properties. Finally, the efficacy of the diet is impressive. It is likely that the ketogenic diet will never be of major therapeutic importance because of the expense and commitment required of the patient and the family. Nevertheless, it appears obvious that continued study of a therapy which seems to work so well will give us some valuable clues as to the mechanism of seizures and their control. Further investigations into the mechanism of action of the ketogenic diet should be encouraged.

Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving "aging retardant" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.

OBJECTIVE: The objective of this study was to test the hypothesis whether a maternal dietary pattern is associated with the risk of spina bifida (SB) in the offspring.

DESIGN: Case-control study.

SETTING: Eight clinic sites in the Netherlands, 1999-2001. SAMPLE: A total of 50 mothers of children with SB and 81 control mothers.

METHODS: Maternal food intakes were obtained by food frequency questionnaires at the standardised study moment of 14 months after the birth of the index child. Principal component factor analysis (PCA) and reduced rank regression (RRR) were used to identify dietary patterns.

MAIN OUTCOME MEASURES: Maternal biomarkers were used as response measures in the RRR analysis and composed of serum and red blood cell (RBC) folate, serum vitamin B12 and total plasma homocysteine. The strength of the use of the dietary pattern in association with SB risk was estimated by odds ratios and 95% CI with the highest quartiles of the dietary pattern as reference.

RESULTS: A predominantly Mediterranean dietary pattern was identified by both PCA and RRR. Those dietary patterns were highly correlated (r = 0.51, P<0.001) and characterised by joint intakes of fruit, vegetables, vegetable oil, alcohol, fish, legumes and cereals and low intakes of potatoes and sweets. We observed a significantly increased risk of SB offspring in mothers with a weak use of the Mediterranean dietary pattern, OR 2.7 (95% CI 1.2-6.1) and OR 3.5 (95% CI 1.5-7.9). The Mediterranean dietary pattern was correlated with higher levels of serum and RBC folate, serum vitamin B12 and lower plasma homocysteine.

CONCLUSION: The Mediterranean dietary pattern seems to be associated with reduction in the risk of offspring being affected by SB.

The present study assessed the long-term (i.e., 24months) efficacy of the ketogenic diet (KD) as an add-on therapy in children with refractory epilepsy, with focus on seizure frequency, seizure severity, and tolerability. Most patients were treated with the MCT-diet. At one and two years, 33% and 23%, respectively, of the 48 included patients were still on the KD. After three months, one year, and two years of treatment, 16.7% of the patients were responders. The highest responder rate (i.e., 22.9%) was seen at six and nine months of treatment. Of the fifteen patients with seizure clusters during baseline, 60% were responders after three months when looking at cluster reduction and most of them were not responders for the total seizure frequency. From three months of treatment onwards, most of the patients had a relevant decrease in seizure severity which was mainly related to the most severe seizure type. Gastrointestinal dysfunction was often reported, especially in the first six weeks of treatment. Growth deceleration was present in 30% of the patients, and weight reduction in 15%. Improved arousal was mentioned in 30% of patients. No patients developed ECG abnormalities or kidney stones. Increase in lipid profile was rare. The KD is an effective therapy for children with therapy-resistant epilepsy. Effectiveness is reflected in the reduction of seizure frequency as well as in the reduction of seizure severity. After 6months of treatment, it is obvious which patients are responders and tolerate the treatment well. Most of these patients will continue to benefit from the KD for a longer time. Long-term use of the diet was well tolerated.

Ancient Greece was the cradle of the Mediterranean food tradition, characterized by the Mediterranean"eternal trinity"wheat - olive oil - wine, the very essence of the country's traditional agricultural and dietary regime, enriched by a culture of sharing and commensality. This food model, subsequently adopted and spread by the Romans, was rediscovered at the end of the Second World War by two American researchers, Leland Allbaugh and Ancel Keys. With the famous Seven Countries Study, Keys demonstrated for the first time that populations practicing a Mediterranean diet - such as the Greeks and southern Italians - showed low mortality rates from ischemic heart disease compared to the peoples of Northern Europe and North America. Since then, numerous subsequent epidemiological studies and randomized clinical trials have confirmed the beneficial effects of the Mediterranean diet both in primary and secondary prevention of cardiovascular diseases. This review will focus on the origins of the Mediterranean diet from its roots and its relationship to cardiovascular disease, with a brief overview of the nutritional mechanisms that influence atherosclerosis.

This study aimed to assess the potential association between dietary patterns (i.e., the Mediterranean Diet (MedDiet) and healthy eating) and patient-reported quality of life (QoL) and treatment satisfaction (TS) in adults with type 1 diabetes (T1D). A food frequency questionnaire, the Audit of Diabetes-Dependent Quality of Life (ADDQoL-19), and the Diabetes Treatment Satisfaction Questionnaire-status version (DTSQ-s) were administered via personal interviews to 258 participants with T1D. Multivariable analysis showed that a moderate or high adherence to the MedDiet was associated with greater diabetes-specific QoL (β = 0.32, 95% CI = 0.03; 0.61;= 0.029). None of the dietary quality indexes (i.e., the alternate Mediterranean Diet Score (aMED) and the alternate Healthy Eating Index (aHEI)) were associated with the overall TS. However, the aHEI was positively associated with the specific items of TS"convenience"and"flexibility"(β = 0.03, 95% CI = 0.00; 0.06;= 0.042 andβ = 0.04; 95% CI = 0.01; 0.06;= 0.011, respectively). On the other hand, the aHEI was negatively associated with the dimension"recommend to others"(β = -0.5, 95% CI = -0.99; -0.02;= 0.042). In conclusion, a moderate and high adherence to the MedDiet was associated with greater QoL. Although neither aMED nor aHEI were associated with the overall TS, some specific items were positively (i.e.,"convenience","flexibility") or negatively ("recommend to others") related to the aHEI. Further research is needed to assess how to improve medical nutrition therapy and its impact on patient-reported outcomes in people with T1D.

The aging population is rapidly increasing all over the world. This results in significant implications for the planning and provision of health and social care. Aging is physiologically characterized by a decrease in lean mass, bone mineral density and, to a lesser extent, fat mass. The onset of sarcopenia leads to weakness and a further decrease in physical activity. An insufficient protein intake, which we often observe in patients of advanced age, certainly accelerates the progression of sarcopenia. In addition, many other factors (e.g., insulin resistance, impaired protein digestion and absorption of amino acids) reduce the stimulation of muscle protein synthesis in the elderly, even if the protein intake is adequate. Inadequate intake of foods can also cause micronutrient deficiencies that contribute to the development of frailty. We know that a healthy eating style in middle age predisposes to so-called"healthy and successful"aging, which is the condition of the absence of serious chronic diseases or of an important decline in cognitive or physical functions, or mental health. The Mediterranean diet is recognized to be a"healthy food"dietary pattern; high adherence to this dietary pattern is associated with a lower incidence of chronic diseases and lower physical impairment in old age. The aim of our review was to analyze observational studies (cohort and case-control studies) that investigated the effects of following a healthy diet, and especially the effect of adherence to a Mediterranean diet (MD), on the progression of aging and on onset of frailty.

OBJECTIVE: Field studies of twentieth century hunter-gathers (HG) showed them to be generally free of the signs and symptoms of cardiovascular disease (CVD). Consequently, the characterization of HG diets may have important implications in designing therapeutic diets that reduce the risk for CVD in Westernized societies. Based upon limited ethnographic data (n=58 HG societies) and a single quantitative dietary study, it has been commonly inferred that gathered plant foods provided the dominant energy source in HG diets.

METHOD AND RESULTS: In this review we have analyzed the 13 known quantitative dietary studies of HG and demonstrate that animal food actually provided the dominant (65%) energy source, while gathered plant foods comprised the remainder (35%). This data is consistent with a more recent, comprehensive review of the entire ethnographic data (n=229 HG societies) that showed the mean subsistence dependence upon gathered plant foods was 32%, whereas it was 68% for animal foods. Other evidence, including isotopic analyses of Paleolithic hominid collagen tissue, reductions in hominid gut size, low activity levels of certain enzymes, and optimal foraging data all point toward a long history of meat-based diets in our species. Because increasing meat consumption in Western diets is frequently associated with increased risk for CVD mortality, it is seemingly paradoxical that HG societies, who consume the majority of their energy from animal food, have been shown to be relatively free of the signs and symptoms of CVD.

CONCLUSION: The high reliance upon animal-based foods would not have necessarily elicited unfavorable blood lipid profiles because of the hypolipidemic effects of high dietary protein (19-35% energy) and the relatively low level of dietary carbohydrate (22-40% energy). Although fat intake (28-58% energy) would have been similar to or higher than that found in Western diets, it is likely that important qualitative differences in fat intake, including relatively high levels of MUFA and PUFA and a lower omega-6/omega-3 fatty acid ratio, would have served to inhibit the development of CVD. Other dietary characteristics including high intakes of antioxidants, fiber, vitamins and phytochemicals along with a low salt intake may have operated synergistically with lifestyle characteristics (more exercise, less stress and no smoking) to further deter the development of CVD.

Most patients with irritable bowel syndrome (IBS) believe that diet plays a significant role in inducing IBS symptoms and desire to know what foods to avoid. It has been found that the intake of calories, carbohydrates, proteins and fat by IBS patients does not differ from that of the background population. IBS patients were found to avoid certain food items that are rich in fermentable oligo-, di- and monosacharides and polyols (FODMAPs), but they did have a high consumption of many other FODMAP-rich food items. The diet of IBS patients was found to consist of a low calcium, magnesium, phosphorus, vitamin B2 and vitamin A content. There is no consistent evidence that IBS patients suffer from food allergy, nor is there documented evidence that food intolerance plays a role in IBS symptoms. Abnormalities in gut hormones have been reported in IBS patients. As gut hormones control and regulate gastrointestinal motility and sensation, this may explain the abnormal gastrointestinal motility and visceral hypersensitivity reported in these patients. Guidance concerning food management which includes individually based restrictions of FODMAP-rich food items and individual evaluation of the effects ofprotein-, fat- and carbohydrate-rich/poor diets may reduce IBS symptoms.

OBJECTIVE:The aim of this study was to evaluate the efficacy of the ketogenic diet (KD) on the clinical and electroencephalographic (EEG) features of Lennox-Gastaut syndrome (LGS) and explore the relationships between EEG changes and clinical efficacy.

METHODS:We retrospectively studied 47 patients with LGS who accepted KD therapy between May 2011 and May 2015. Clinical efficacy and EEG features such as background activity, abnormal interictal epileptic discharges (IEDs) and the discharge location were evaluated prior to and at 3 and 6 months after therapy. Responders were defined as ≥50% seizure reduction.

RESULTS:At 3 months of treatment, 23 patients (48.9%) had≥50% seizure reduction. Seven patients (14.9%) discontinued treatment between 3 and 6 months because of lack of efficacy or inability to adhere to the diet. At 6 months of treatment, 4 patients (10%) were seizure free, 5 (12.5%) had ≥90% seizure reduction, 12 (30%) had a reduction of 50-89%, and19 (47.5%) had<50% reduction. Patients with improved EEG background and reduced IEDs had an improved seizure reduction rate compared with patients without change in EEG background or IEDs (p<0.01).

CONCLUSIONS:The results show that the KD is effective in LGS. It can control seizures and improve EEG abnormalities. Early improvement in the EEG background and a reduction in IEDs may be predictors of a patient's response to diet.

Prevalence of mild hyperhomocysteinemia in vegetarians and vegans is a consequence of vitamin B12 deficiency. Clinical study of homocysteine reduction by vitamin B12 consisted of subjective healthy adults on alternative nutrition (n = 9) with vitamin B12 deficiency and with mild hyperhomocysteinemia. Vitamin B12 treatment was implemented by 5 intramuscular cyanocobalamin injections of a total content of 2200 micrograms during two weeks. Homocysteine level was significantly reduced (from 22 mumol/l to 11.7 mumol/l; individual reduction 29-55%). Vitamin B12 concentration in blood was significantly increased (from 152 pmol/l to 277 pmol/l; individual % of increase 63-150). The results show a high effect of vitamin B12 treatment in homocysteine value reduction of subjects on alternative nutrition.

Abstract Background. Liver involvement in celiac disease (CD) is clinically relevant and could require specific treatment in addition to gluten-free diet (GFD). Transient elastography (TE), a noninvasive tool for assessing liver stiffness (LS), has widely been reported as an accurate surrogate marker of liver fibrosis. Aims. To prospectively identify celiac patients with liver involvement by TE and to assess the effect of GFD. Material and methods. Ninety-five histologically confirmed CD patients (24 newly diagnosed) were consecutively evaluated by TE and compared with 146 patients with chronic hepatitis C (HCV) and 54 healthy subjects. Results. LS ranged between 2.8 and 6.7 kPa (median 4.9) in healthy subjects, defining 6.9 kPa as the upper reference limit (2 SD above the mean levels). TE was above 6.9 kPa in 10 (10.5%) CD patients. Median TE values resulted significantly higher in CD patients with hypertransaminasemia than those without [6.1 vs. 4.2 kPa (p<0.01)]. Among the 24 newly diagnosed patients with CD, median TE values declined from 4.4 to 4 kPa, after 6 months of GFD, resulting below 6.9 kPa in 100% of the patients. Conclusions. A subset of CD patients with hypertransaminasemia showed liver involvement by TE. Accordingly, based on its accuracy in predicting liver fibrosis, TE could be used to identify those CD patients suitable for liver biopsy.

Twenty-six nitrogen balance studies were performed in 15 patients with severe uremia (Ccr mean value 5.1, range 2.3-8.5 ml/min) treated with an unselected protein-poor (16-20 g protein/day corresponding to 2.6-3.2 g N/day) diet and oral supply of the essential amino acids including histidine (2.6 g N/day). The general condition improved and the concentration of serum urea nitrogen decreased. The nitrogen balance, corrected for changes in total urea pool, was negative on the diet alone,-1.46 plus or minus 1.15 g N/day (mean plus or minus SD), but was positive when the essential amino acids were supplied, plus 0.84 plus or minus 0.68 g N/day. In four patients studied after 3 to 26 months of diet and amino acid therapy, during which time a further deterioriation of the renal function had occurred, the nitrogen balance was around zero in three and negative in one patient (-1.2 g N/day). The results show that it is possible with our new regimen to attain positive nitrogen balance or nitrogen equilibrium in severely uremic patients without excessive accumulation of urea in the body fluids.

Twenty-six uremic patients - serum urea nitrogen (SUN) 110 MG/100 ml plus or minus 22.8 (mean plus or minus SD), serum cretinine (S-Creat) 13.2 mg/100 ml plus or minus 2.27, ratio SUN/S-Creat 8.6 plus or minus 2.26, and endogenous creatinine clearance (Ccr) 3.86 plus or minus 1.41 ml/min - were treated for three months or longer with an unselected protein-poor (16-20 g protein/day) diet with oral supply of the essential amino acids including histidine in high doses as coated tablets. The amino acids were instituted after an initial diet only period (mean 0.4 months). The average treatment time was 8.4 months (range 2.7-33.6). An improvement of the general condition was obtained, persisting for several months. SUN and SUN/S-Creat decreased on the diet alone, continued to decrease after one month, and increased slightly again after three months of treatment, but did not reach the initial levels for several months in spite of an almost doubled nitrogen intake. S-Creat increased after six months indicating a further deterioration of the renal function. In patients with initially low serum total protein (smaller than 6.5 g/100 ml, 9 patients), albumin (smaller than 3.5 g/100 ml, 10 patients), and total iron-binding capacity (smaller than 260 mug/100 ml, 11 patients) the values increased after one month on amino acids and were thereafter stable. No signs of bleeding tendency, progressive muscle atrophy, or progressive peripheral neuropathy were observed. - Five patients died due to cardiovascular maladies. A further 13 patients were withdrawn for medical reasons (overhydration, 4 patients; hypertension, 1 patient; nausea and vomiting, 7 patients; and pericarditis, 1 patient). - The renal function improved in one patient. Four patients received home dialysis training, three a kidney transplant. - The results indicate that it is possible to keep severely uremic patients free from uremic symptoms, counteract protein depletion, and even improve the nutritional status during long-term treatment with an unselected protein-poor diet supplementd with essential amino acids.

BACKGROUND:Eosinophilic esophagitis (EE) is a recently described disorder identified in patients with symptoms suggestive of gastroesophageal reflux disease (GERD) but unresponsive to conventional reflux therapies. Therapies have included corticosteroids, elemental diet, and diet restriction. We report our experience with skin prick and atopy patch testing and food elimination diets in patients diagnosed as having EE.

OBJECTIVE:To identify food antigens that cause EE and the characteristics of patients who respond to food elimination vs those who are unresponsive.

METHODS:Patients diagnosed as having EE had restricted diets based on skin prick and atopy patch testing results. Additional biopsies were performed after 4 to 8 weeks of restricted diet. Demographics, atopic tendencies, and food antigens were identified retrospectively in our food allergy database.

RESULTS:A total of 146 patients diagnosed as having EE were evaluated with skin prick and atopy patch testing. Thirty-nine patients had unequivocal demonstration of food causing EE, with normalization of biopsy results on elimination and reoccurrence on reintroduction. An additional 73 patients, for a total 112 (77%) of 146 patients, had resolution of their EE as demonstrated by biopsy results. Fifteen (10%) of 146 patients were nonresponders manifested by no significant reduction in esophageal eosinophils despite restricted diet based on skin prick and atopy patch testing. Egg, milk, and soy were identified most frequently with skin prick testing, whereas corn, soy, and wheat were identified most frequently with atopy patch testing.

CONCLUSION:In more than 75% of patients with EE, both symptoms and esophageal inflammation can be significantly improved with dietary elimination of foods. Skin prick and atopy patch testing can help identify foods in most patients.

PURPOSE: Tuberous sclerosis complex (TSC) is a condition that is frequently associated with intractable, early-onset epilepsy, and often is first seen as infantile spasms. If medications fail and no clear epileptogenic tuber is identified, nonpharmacologic therapies are often attempted. The use of the ketogenic diet specifically for children with TSC and epilepsy has not been previously described.

METHODS: A chart review was performed of patients with TSC treated with the ketogenic diet over a 5-year period at Johns Hopkins Hospital and Massachusetts General Hospital.

RESULTS: Twelve children, ages 8 months to 18 years, were identified. Eleven (92%) children had a >50% reduction in their seizures at 6 months on the diet, and 8 (67%) had a >90% response. Five children had at least a 5-month seizure-free response. Diet duration ranged from 2 months to 5 years (mean, 2 years).

CONCLUSIONS: In this limited-duration case series of 12 patients, the ketogenic diet was a generally effective therapeutic modality for the intractable epilepsy occasionally seen in children with TSC.

Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD). The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such asβ-hydroxybutyrate (βHB) in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.

Recent evidence suggested a protective role of dietary monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) intakes against several chronic diseases and, therefore, an increased human longevity. After a median follow-up of 8.5 years, we investigated the possible role of MUFA, PUFA, and other selected food groups in protecting against all-causes mortality in a population-based, prospective study, conducted in one of the eight centers of the Italian Longitudinal Study on Aging (ILSA), Casamassima, Bari, Italy. Out of 704 elderly subjects (65-84 years), 278 nondemented persons agreed to participate at the first survey (1992-1993). During the follow-up, there were 91 deaths. A semi-quantitative food frequency questionnaire evaluating macronutrient daily intakes were performed at the first survey. Higher MUFA intake was associated with an increase of survival (hazard ratio 0.81, 95% CI 0.66-0.99), a higher unsaturated fatty acids (UFA) to SFA ratio (hazard ratio 1.20, 95% CI 0.99-1.45) increased total mortality only marginally, while no effect about other selected food groups were found. In conclusion, in this prospective study on older nondemented subjects with a typical Mediterranean diet, a higher MUFA intake increased survival, while a higher UFA/SFA ratio increased total mortality, but only marginally.