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1.
Ketogenic diet for epilepsy and obesity: Is it the same?
Tagliabue, A, Armeno, M, Berk, KA, Guglielmetti, M, Ferraris, C, Olieman, J, van der Louw, E
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2024;(3):581-589
Abstract
The term "ketogenic diet" (KD) is used for a wide variety of diets with diverse indications ranging from obesity to neurological diseases, as if it was the same diet. This terminology is confusing for patients and the medical and scientific community. The term "ketogenic" diet implies a dietary regimen characterized by increased levels of circulating ketone bodies that should be measured in blood (beta-hydroxybutyrate), urine (acetoacetate) or breath (acetone) to verify the "ketogenic metabolic condition". Our viewpoint highlights that KDs used for epilepsy and obesity are not the same; the protocols aimed at weight loss characterized by low-fat, low-CHO and moderate/high protein content are not ketogenic by themselves but may become mildly ketogenic when high calorie restriction is applied. In contrast, there are standardized protocols for neurological diseases treatment for which ketosis has been established to be part of the mechanism of action. Therefore, in our opinion, the term ketogenic dietary therapy (KDT) should be reserved to the protocols considered for epilepsy and other neurological diseases, as suggested by the International Study Group in 2018. We propose to adjust the abbreviations in VLCHKD for Very Low CarboHydrate Ketogenic Diet and VLEKD for Very Low Energy Ketogenic Diet, to clarify the differences in dietary composition. We recommend that investigators describe the researchers describing efficacy or side effects of KDs, to clearly specify the dietary protocol used with its unique acronym and level of ketosis, when ketosis is considered as a component of the diet's mechanism of action.
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2.
Novel insight into GLUT1 deficiency syndrome: screening for emotional and behavioral problems in youths following ketogenic diet.
Varesio, C, Zanaboni, MP, Pasca, L, Provenzi, L, Ferraris, C, Tagliabue, A, Pezzotti, E, Carpani, A, Veggiotti, P, DE Giorgis, V
Minerva pediatrics. 2024;(2):189-196
Abstract
BACKGROUND Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare disorder with a broad spectrum of neurological manifestations. The ketogenic diet (KD) is, to date, the gold standard treatment. Behavioral problems, well recognized in patients with chronic conditions, have not been, so far, deeply investigated in GLUT1DS patients. We performed an exploratory study to assess the risk of emotional and behavioral problems and investigated the potential role of influencing factors related to the pathology itself or KD treatment. METHODS This was a mono-center retrospective study involving youths with GLUT1Ds treated with KD and a group of migraine patients age- and gender-matched. Patients were included if the main caregiver completed the Child Behavior Check List 6-18 (CBCL). Descriptive statistics for demographic and clinical data and questionnaire scores were computed. Correlational analyses were used to assess the potential associations of clinical variables and age and time from KD introduction with CBCL scores in GLUT1DS patients. RESULTS We enrolled nine youths with GLUT1DS and 9 with migraine. In the GLUT1DS group, none of the mean scores of the CBCL items fell within the borderline/clinical range, except for social problems located in the borderline range. Investigation for influencing factors revealed the patient's age related to withdrawn/depressive (r=0.709, P=0.032) and social problems (r=.684, P=0.042). Time from the introduction of KD was related to social problems (r=.827, P=0.006). From the comparison with the scores obtained from migraine patients, significantly higher scores emerged in the latter group in internalizing problems (Z=-2.48, P=0.01), externalizing problems (Z=-3.49, P<0.001), anxious/depressed subscale (Z=-2.37, P=0.014), somatic complaints subscale (Z=-2.624, P=0.008), aggressive behavior subscale (Z=-2.539, P=0.011). CONCLUSIONS Although highly exploratory in its nature, this study provides a novel insight into GLUT1DS. Our data suggested that the risk for internalizing problems in GLUT1DS youths was related to higher age and higher time elapsed from KD introduction. They occurred at a sub-clinical level, making them difficult to detect, if not expressly and systematically investigated.
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3.
Adherence to ketogenic dietary therapies in epilepsy: A systematic review of literature.
Lopes Neri, LC, Guglielmetti, M, Fiorini, S, Pasca, L, Zanaboni, MP, de Giorgis, V, Tagliabue, A, Ferraris, C
Nutrition research (New York, N.Y.). 2024;:67-87
Abstract
Treatment adherence, defined as the degree to which the patient actively follows the plan of care, is very difficult for subjects undergoing ketogenic dietary therapies (KDTs). This is a relevant issue because adherence to dietary therapies is considered 1 of the primary determinants of the treatment's success. This paper aimed to review the literature evidence about KDT adherence according to age and diagnosis of patients. Performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method, this systematic review included clinical trials and observational studies. The risk of bias was assessed by the RoB 2.0 Cochrane tool and the quality of evidence according to the Mixed Methods Appraisal Tool system. Twenty-two articles were included, with more than half (n = 12) having average quality (2-3 stars). The studies' heterogeneity in measuring adherence and diagnosis made it difficult to compare results. Mean adherence rates were 71.5%, 66%, and 63.9% for children, adolescents, and adults, respectively. Adherence and compliance rates varied according to the follow-up period (79.7%, 66.7%, and 37.7% at 6, 24, and 36 months, respectively). The most frequent reasons for low adherence were linked to inefficacy in seizure control, adverse effects, food refusal, difficulty in preparing KDT meals or diet restrictiveness, lack of motivation, poor parental compliance, or cost of the diet. To conclude, there is a lack of standardized tools to measure adherence. Several studies highlighted the families' challenges in adhering to KDTs. These factors should be considered when creating strategies and resources on family education.
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4.
Nutritional counseling in childhood and adolescence: a systematic review.
Neri, LCL, Guglielmetti, M, Fiorini, S, Quintiero, F, Tagliabue, A, Ferraris, C
Frontiers in nutrition. 2024;:1270048
Abstract
UNLABELLED Healthy eating habits are the basis for good health status, especially for children and adolescents, when growth and development are still ongoing. Nutrition educational programs are essential to prevent and treat chronic diseases. Nutritional counseling (NC), as a collaborative process between the counselor and the client process, could help to achieve better outcomes. This review aims to collect information about the utilization of NC during childhood and adolescence and to highlight its possible impact on adherence/compliance rates, nutrition knowledge, status and dietary intake. The methods applied in this systematic review followed the instruction of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search in PubMed/Medline, Scopus, Web of Science, LILACS, and Science Direct included observational or randomized studies. RoB 2.0 and Robins-I tools was used for the risk of bias assessment in randomized and non-randomized studies, respectively. The quality of evidence was checked by the Mixed Methods Appraisal Tool system. A total of 21 articles were selected, computing 4,345 individuals. 11 achieved at least 4 stars quality level. The highest risk of bias for randomized studies was related to the randomization process. 42.9% of non-randomized studies had some concerns of bias, mainly because of a lack of control of all confounding factors. Different strategies of NC were used in children and adolescents with positive results for health or diseases. NC strategies can be effectively used in children and adolescents. In general, NC showed benefits in pediatrics age for anthropometric or body composition parameters, dietary intake, nutrition knowledge and physical activity improvement. Performing NC in pediatrics is challenging due to the counseling strategies that must be adapted in their contents to the cognitive ability of each age. More structured research must be done focused on this population. Investments in healthy eating behaviors in pediatrics can lead to better health outcomes in the future population with substantial benefits to society. SYSTEMATIC REVIEW REGISTRATION [https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42022374177].
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5.
Ultra-processed foods consumption is associated with multiple sclerosis severity.
Guglielmetti, M, Grosso, G, Ferraris, C, Bergamaschi, R, Tavazzi, E, La Malfa, A, Wahidah, HA, Tagliabue, A
Frontiers in neurology. 2023;:1086720
Abstract
BACKGROUND MS is a chronic inflammatory neurological and immune-mediated disease of multifactorial etiology. Ultra-processed foods (UPFs) have been generally considered unhealthy due to their poor nutritional value. Emerging evidence suggests that factors other than their nutritional content may play an additional role toward chronic inflammation. AIM: To investigate the potential association of UPF consumption and MS severity in a group of MS Italian consecutive patients. METHODS Demographic (age, sex, marital status, educational level), neurological (EDSS, MSSS), and nutritional (anthropometric measures, dietary habits) information were collected. Physical activity and smoking habits were also investigated. Food items were grouped according to the NOVA classification. Patients were classified in two groups based on MS severity ("mild" and "moderate to high"). RESULTS Higher UPF consumption was associated with moderate-to-high MS severity compared to lower consumption in both the unadjusted model (OR = 2.28, 95% CI: 1.04-5.01) and after adjustment for potential background (OR = 2.46, 95% CI: 1.04-5.83) and clinical confounding factors (OR = 2.97, 95% CI: 1.13-7.77). CONCLUSIONS Although these results are only preliminary and hypothesis generating, it is important to explore how various aspects of the diet may relate to MS severity in order to identify the best strategy to support MS patients over the disease course.
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6.
Adherence to Mediterranean Diet Is Associated with Multiple Sclerosis Severity.
Guglielmetti, M, Al-Qahtani, WH, Ferraris, C, Grosso, G, Fiorini, S, Tavazzi, E, Greco, G, La Malfa, A, Bergamaschi, R, Tagliabue, A
Nutrients. 2023;(18)
Abstract
Currently available data suggest that the union of a balanced diet and an overall healthy lifestyle may determine an amelioration in several clinical parameters and in the quality of life for patients with MS (pwMS). The study objective was to investigate the possible difference in MS severity in a group of Italian patients with MS based on their adherence to Mediterranean Diet (MedDiet). Eating habits were collected through a validated 110-items Food Frequency Questionnaire, the Medi-Lite score was used for adherence to MedDiet evaluation. MS severity was graded according to Herbert's severity scale, based on the MSSS. 106 patients were classified in 3 groups according to their MedDiet adherence (low/medium/high). Higher adherence was associated with a 6.18 (95% CI: 1.44, 26.59) higher probability of having a mild-to-moderate MS. When studying the single constituents of the Medi-Lite score, none of them was individually associated with MS severity. It remains unclear whether effects of specific dietary components included in the MedDiet may impact the health status at disease onset or can slow down the symptoms due course of disease. Future studies are needed to reproduce our findings and should focus on answering the latter raised question.
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7.
Nutritional counseling in athletes: a systematic review.
Fiorini, S, Neri, LCL, Guglielmetti, M, Pedrolini, E, Tagliabue, A, Quatromoni, PA, Ferraris, C
Frontiers in nutrition. 2023;:1250567
Abstract
UNLABELLED Many studies report poor adherence to sports nutrition guidelines, but there is a lack of research on the effectiveness of nutrition education and behavior change interventions in athletes. Some studies among athletes demonstrate that nutrition education (NE), often wrongly confused with nutritional counseling (NC), alone is insufficient to result in behavior change. For this reason, a clear distinction between NC and NE is of paramount importance, both in terms of definition and application. NE is considered a formal process to improve a client's knowledge about food and physical activity. NC is a supportive process delivered by a qualified professional who guides the client(s) to set priorities, establish goals, and create individualized action plans to facilitate behavior change. NC and NE can be delivered both to individuals and groups. To our knowledge, the efficacy of NC provided to athletes has not been comprehensively reviewed. The aim of this study was to investigate the current evidence on the use and efficacy of nutritional counseling within athletes. A systematic literature review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method. The search was carried out in: PubMed, Scopus, Web of Science, Science Direct, Cochrane Library between November 2022 and February 2023. Inclusion criteria: recreational and elite athletes; all ages; all genders; NC strategies. The risk of bias was assessed using the RoB 2.0 Cochrane tool. The quality of evidence checking was tested with the Mixed Methods Appraisal Tool system. From 2,438 records identified, 10 studies were included in this review, with athletes representing different levels of competition and type of sports. The most commonly applied behavior change theory was Cognitive Behavioral Theory. NC was delivered mainly by nutrition experts. The duration of the intervention ranged from 3 weeks to 5 years. Regarding the quality of the studies, the majority of articles reached more than 3 stars and lack of adequate randomization was the domain contributing to high risk of bias. NC interventions induced positive changes in nutrition knowledge and dietary intake consequently supporting individual performance. There is evidence of a positive behavioral impact when applying NC to athletes, with positive effects of NC also in athletes with eating disorders. Additional studies of sufficient rigor (i.e., randomized controlled trials) are needed to demonstrate the benefits of NC in athletes. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/, identifier CRD42022374502.
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8.
A Review of Ketogenic Dietary Therapies for Epilepsy and Neurological Diseases: A Proposal to Implement an Adapted Model to Include Healthy Mediterranean Products.
Ferraris, C, Guglielmetti, M, Neri, LCL, Allehdan, S, Mohsin Albasara, JM, Fareed Alawadhi, HH, Trentani, C, Perna, S, Tagliabue, A
Foods (Basel, Switzerland). 2023;(9)
Abstract
Based on the growing evidence of the therapeutic role of high-fat ketogenic dietary therapies (KDTs) for neurological diseases and on the protective effect of the Mediterranean diet (MD), it could be important to delineate a Mediterranean version of KDTs in order to maintain a high ketogenic ratio, and thus avoid side effects, especially in patients requiring long-term treatment. This narrative review aims to explore the existing literature on this topic and to elaborate recommendations for a Mediterranean version of the KDTs. It presents practical suggestions based on MD principles, which consist of key elements for the selection of foods (both from quantitative and qualitative prospective), and indications of the relative proportions and consumption frequency of the main food groups that constitute the Mediterranean version of the KDTs. We suggest the adoption of a Mediterranean version of ketogenic diets in order to benefit from the multiple protective effects of the MD. This translates to: (i) a preferential use of olive oil and vegetable fat sources in general; (ii) the limitation of foods rich in saturated fatty acids; (iii) the encouragement of high biological value protein sources; (iv) inserting fruit and vegetables at every meal possible, varying their choices according to seasonality.
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9.
Ketosis and migraine: a systematic review of the literature and meta-analysis.
Neri, LCL, Ferraris, C, Catalano, G, Guglielmetti, M, Pasca, L, Pezzotti, E, Carpani, A, Tagliabue, A
Frontiers in nutrition. 2023;:1204700
Abstract
INTRODUCTION Headaches are a prevalent disorder worldwide, and there is compelling evidence that certain dietary interventions could provide relief from attacks. One promising approach is ketogenic therapy, which replaces the brain's glucose fuel source with ketone bodies, potentially reducing the frequency or severity of headaches. AIM: This study aims to conduct a systematic review of the scientific literature on the impact of ketosis on migraine, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. RESULTS After a careful selection process and bias evaluation, 10 articles were included in the review, primarily from Italy. The bias assessment indicated that 50% of the selected articles had a low risk of bias in all domains, with the randomization process being the most problematic domain. Unfortunately, the evaluation of ketosis was inconsistent between articles, with some assessing ketonuria, some assessing ketonemia, and some not assessing ketosis levels at all. Therefore, no association could be made between the level of ketosis and the prevention or reduction of migraine attacks. The ketogenic therapies tested in migraine treatments included the very low-calorie ketogenic diet (VLCKD, n = 4), modified Atkins diet (MAD, n = 3), classic ketogenic diet (cKDT, n = 2), and the administration of an exogenous source of beta-hydroxybutyrate (BHB). The meta-analysis, despite reporting high heterogeneity, found that all interventions had an overall significant effect (Z = 9.07, p < 0.00001; subgroup differences, Chi2 = 9.19, dif = 3, p = 0.03; I2, 67.4%), regardless of the type of endogenous or exogenous induction of ketosis. CONCLUSION The initial findings of this study suggest that metabolic ketogenic therapy may provide some benefit in treating migraines and encourage further studies, especially randomized clinical trials with appropriate and standardized methodologies. The review strongly recommends the use of the adequate measurement of ketone levels during ketogenic therapy to monitor adherence to the treatment and improve knowledge of the relationship between ketone bodies and efficacy. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/, identifier: CRD42022330626.
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10.
Validation of an Italian Questionnaire of Adherence to the Ketogenic Dietary Therapies: iKetoCheck.
Lopes Neri, LC, Guglielmetti, M, De Giorgis, V, Pasca, L, Zanaboni, MP, Trentani, C, Ballante, E, Grumi, S, Ferraris, C, Tagliabue, A, et al
Foods (Basel, Switzerland). 2023;(17)
Abstract
Ketogenic dietary therapies (KDTs) are an effective and safe non-pharmacological treatment for drug-resistant epilepsy, but adherence can be challenging for both patients and caregivers. In Europe, there are no adequate tools to measure it other than monitoring ketosis. This study aimed to adapt and validate the Brazilian adherence questionnaire, Keto-check, into the Italian version: iKetoCheck. Using the Delphi technique, 12 judges validated the contents through agreement rates and the Content Validity Index (CVI). The iKetocheck was self-completed electronically by 61 drug-resistant epilepsy or GLUT1 deficiency patients within an interval of 15 days to measure its reproducibility. The test-retest reliability was evaluated using Pearson's correlation and relative significance test. Exploratory and confirmatory factorial analyses were made using Factor software version 12.03.02. The final tool, iKetoCheck, consists of 10 questions with 5-point Likert scale answers. It evaluates various aspects such as informing caregivers about the diet, organization of meals, measurement of ketosis, weighing food consumed, diet negligence, use of carbohydrate-free medications, attending follow-up visits, reading food labels, consulting an expert for dietary concerns, and cooking at home. The factorial analysis resulted in three factors: "attention," "organization," and "precision," with satisfactory results for indices in exploratory and confirmatory analyses. Although higher mean values of ketonemia measurement were observed in patients with a higher adherence score, these values were not statistically significant (p = 0.284). In conclusion, despite the small sample size, iKetoCheck is a valid tool for evaluating KDTs' adherence in Italian drug-resistant epilepsy or GLUT1 deficiency patients. It can provide valuable information to improve patient management and optimize the effectiveness of KDTs.