Article

Kidney Stones and the Ketogenic Diet: Risk Factors and Prevention

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Abstract

A cohort study was performed of children started on the ketogenic diet for intractable epilepsy from 2000 to 2005 (n = 195). Children who developed kidney stones were compared with those without in terms of demographics, urine laboratory markers, and intervention with urine alkalinization (potassium citrate). Thirteen children (6.7%) developed kidney stones. The use of oral potassium citrate significantly decreased the prevalence of stones (3.2% vs 10.0%, P = .049) and increased the mean time on the ketogenic diet before a stone was first noted (260 vs 149 patient-months, P = .29). The prevalence of kidney stones did not correlate with younger age or use of carbonic anhydrate inhibitors (eg, topiramate or zonisamide) but trended toward higher correlation with the presence of hypercalciuria (92% vs 71%, P = .08). No child stopped the diet due to stones; in fact, the total diet duration was longer (median 26 vs 12 months, P < .001). Kidney stones continue to occur in approximately 1 in 20 children on the ketogenic diet, and no statistically significant risk factors were identified in this cohort. As oral potassium citrate was preventative, prospective studies using this medication empirically are warranted.

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... The aim of these variants is to increase the variability, the palatability, and the tolerability of the diet [2], improving the compliance, an important factor for a successful dietary treatment. However, a recent meta-analysis of 11 studies on adult patients reveals a compliance rate of 45% for KDs [35]. Such adherence decreases to 38% when considering only the CKD [35]. ...
... However, a recent meta-analysis of 11 studies on adult patients reveals a compliance rate of 45% for KDs [35]. Such adherence decreases to 38% when considering only the CKD [35]. This relatively low compliance is related to diet ineffectiveness or diet-intolerability because of severe side-effects or discontinuation caused by psychosocial factors and the restrictiveness of the diet [35]. ...
... Such adherence decreases to 38% when considering only the CKD [35]. This relatively low compliance is related to diet ineffectiveness or diet-intolerability because of severe side-effects or discontinuation caused by psychosocial factors and the restrictiveness of the diet [35]. ...
Article
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The ketogenic diet (KD) is the first line intervention for glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency, and is recommended for refractory epilepsy. It is a normo-caloric, high-fat, adequate-protein, and low-carbohydrate diet aimed at switching the brain metabolism from glucose dependence to the utilization of ketone bodies. Several variants of KD are currently available. Depending on the variant, KDs require the almost total exclusion, or a limited consumption of carbohydrates. Thus, there is total avoidance, or a limited consumption of cereal-based foods, and a reduction in fruit and vegetable intake. KDs, especially the more restrictive variants, are characterized by low variability, palatability, and tolerability, as well as by side-effects, like gastrointestinal disorders, nephrolithiasis, growth retardation, hyperlipidemia, and mineral and vitamin deficiency. In recent years, in an effort to improve the quality of life of patients on KDs, food companies have started to develop, and commercialize, several food products specific for such patients. This review summarizes the foods themselves, including sweeteners, and food products currently available for the ketogenic dietary treatment of neurological diseases. It describes the nutritional characteristics and gives indications for the use of the different products, taking into account their metabolic and health effects.
... The KD has been associated with an increased occurrence of renal stones. 93 This is a well-established phenomenon in children receiving a KD that was first reported in 1972. 94 Kidney stones are believed to occur in 1 in 20 children on a KD. ...
... 94 Kidney stones are believed to occur in 1 in 20 children on a KD. 93 However, some reports have suggested that the occurrence of kidney stones is as high as 25% in children on KD over 6 years. 49 Hypercalciuria associated with KD is believed to have some role in this increased occurrence. ...
... 96 The general acidosis associated with KD leads to more acidic urine in which uric acid is less soluble, more readily forms crystals and can act as a nidus for calcium stone formation. 93,96 Fluid restriction, especially in children on a KD, is also a risk factor for renal stones. 93 Alkalization of the urine using oral potassium citrate has been found to be beneficial in reducing renal stone formation in people on KD. ...
Article
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The use of ketogenic diets (KDs) for the management of type 2 diabetes mellitus (T2DM) and in weight-loss programs is long established, but high-quality data supporting them are limited and they remain controversial. In recent years there has been a trend towards individual, patient-centered medical nutrition therapy in which KD regimens have been adapted to the specific needs of individuals. Every patient with type 1 diabetes mellitus (T1DM) or T2DM should have a dietary regimen that is specific to their needs in addition to their continuing medications, and KD may have an important role in this aspect of disease management. KD regimens consist of low carbohydrate intake (<5%) with high fat (70-75%) and moderate protein (20-25%). The low carbohydrate content assists with weight loss and glycemic control while the relatively high protein content can increase satiety and thus assist adherence to the diet, reduce food intake, and decrease weight. These factors are beneficial in individuals with reduced insulin secretion or reduced response to insulin. In KDs, the oxidation of fat mass in the body is desirable but leads to ketone body generation and potentially to ketosis. This and raised levels of free fatty acids, can cause negative cardiovascular, renal, bone mineral, liver, and other effects, which discourage some physicians from recommending this diet for their patients. The KD, however, has reported positive neurological effects and is used in the treatment of epilepsy and some other neurological conditions in addition to weight-loss and diabetes regimens. It is clear that more studies are needed to provided better evidence in support or against a KD in diabetes therapy. Until this is available, KD use is likely to remain a matter of opinion and its true potential value, particularly in T2DM management, may not be realized.
... 7,8 Citrate is also used to prevent nephrolithiasis by counteracting urinary acidosis and hypocitraturia induced by the ketogenic diet. [9][10][11] In this study, we defined 'uncompensated' metabolic acidosis as a state with clinical signs of metabolic acidosis (nausea, vomiting, and somnolence) accompanied by a blood pH of less than 7.30. The aim of this study was to investigate if potassium citrate supplementation can prevent uncompensated metabolic acidosis and related symptoms without affecting seizure frequency in ketogenic diet treatment for intractable epilepsy. ...
... In 2007, we became aware of a report suggesting that potassium citrate could prevent nephrolithiasis caused by the ketogenic diet. 9 This prompted us to start oral administration of potassium citrate in participants starting the ketogenic diet after April 2007. Potassium citrate was administered as oral Polycitra-K crystals (2mEq/kg/d up to a maximum dose of 60mEq/d) and was started simultaneously with the ketogenic diet in 22 participants. ...
... None of the 22 patients started on potassium citrate developed nephrolithiasis during the 7 months follow-up, compared to two of the 29 not treated with potassium citrate, a non-significant result (p=0.5). According to earlier studies, [9][10][11] citrate supplementation protects against nephrolithiasis in ketogenic diet treatment. ...
Article
Aim: To investigate if potassium citrate, a mild alkaline compound, can prevent metabolic acidosis in children with epilepsy treated with the ketogenic diet without reducing antiepileptic efficacy. Method: In this prospective controlled study, we investigated the frequency of initial uncompensated metabolic acidosis in 51 participants. There were 22 participants with and 29 without potassium citrate supplementation. The ketogenic diet was used as add-on treatment to children with drug resistant epilepsy. We also estimated the proportion of participants with a greater than 50% seizure reduction after 7 months. Results: None of the 22 participants (15 males, seven females; median age 1y 7mo, interquartile range [IQR] 3y 3mo) with, and 10 of 29 (12 males, 17 females; median age 6y 1mo, IQR 4y 8mo) without potassium citrate developed metabolic acidosis (odds ratio=0.04, 95% CI 0.00-0.75 [p<0.01]); median pH 7.32 vs 7.24; [p<0.001]), and median bicarbonate 19.7mmol/L vs 14.0mmol/L (p<0.001). The number of seizures was reduced by more than 50% in 9 of 22 with potassium citrate and 8 of 29 participants without potassium citrate, 7 months after introducing a ketogenic diet (p=0.4). Interpretation: In the ketogenic diet, potassium citrate supplementation can prevent metabolic acidosis, without reducing antiepileptic efficacy. What this paper adds: Citrate supplementation prevents metabolic acidosis in children treated with a ketogenic diet. Efficacy of the ketogenic diet is not affected by supplementation with citrate. Citrate supplementation does not affect beta-hydroxybuturate concentration. Potassium citrate reduces the time needed to reach an optimal ketogenic ratio.
... [10][11][12] However, during long-term follow-up of KDT, an increased incidence of kidney stones have also been found, mostly due to hypercalciuria. 13,14 This makes prophylactic supplementation of calcium and vitamin D challenging. ...
... 17,18 on the use of other relevant drugs, like potassium citrate and hydrochloorthiazide, which are prescribed to prevent renal complications of KDT, were also collected. 14 ...
... More recently we started with the use of oral citrates to prevent the formation of kidney stones. 13,14,17,21 There are no studies on the use of bisphosphonates in children with KDT. 15 Treatment with intravenous biphosphonates should be considered in patients with genetic forms of osteoporosis or those whose risk factor cannot be mitigated or when there is a low likelihood of spontaneous recovery. 22 The primary function of bisphosphonates is to inactivate osteoclasts which results in cortical and trabecular bone thickening. ...
Article
Background During long-term follow-up of children treated with the ketogenic diet therapy (KDT) have an increased incidence of bone fractures. However, the exact contribution of KDT to a decreased bone mineral density (BMD) remains unclear. Objective This study aimed to evaluate (changes in) BMD in children treated with KDT and to evaluate whether intravenous bisphosphonate therapy may be effective. Design In this retrospective, observational cohort study, all children treated with KDT from 2010 until 2018 at the Radboudumc Amalia Children's hospital were included. Patients who were on KDT for more than 6 months and who had at least two dual-energy X-ray (DXA)-scans were eligible for inclusion for longitudinal analysis. Z-scores of DXA-scans were compared over the course of time. Results In 34 out of 68 patients, one or more lumbar DXA-scans were performed, with a mean lumbar Z-score of −1.32 ± 1.74. Of these 68 patients, 8.8% got a fracture during KDT, and also 8.8% got kidney stones. In 20 patients, more than one DXA-scan was performed. A statistically not significant decrease in BMD (0.22 Z-score/year) was found. However, there was an increase in BMD in the five patients treated with intravenous bisphosphonate therapy. This was statistically significant in comparison to the nonbisphosphonate treated group (p = 0.034). Conclusion Children on KDT have low normal BMD which may decrease further during KDT. For this reason monitoring of BMD is crucial, as is monitoring of kidney stones and hypercalciuria. Intravenous bisphosphonate therapy may have a positive effect, when other therapies have failed.
... KDs are accepted clinical treatments for pediatric epilepsy or weight reduction and are emerging as potentially beneficial in several other diseases [17][18][19][20]. Nonetheless, adverse effects like hyperlipidemia, a higher risk for kidney stones and other temporary symptoms can occur and have been controversially discussed as safety concerns [21][22][23]. ...
... reported new HIs that raised safety concerns. One participant reported the finding of kidney stones, which has been associated with KDIs [21]. Kidney stones are also common in PKD [42], and it is unclear whether they were related to the KDI in this case. ...
Article
Full-text available
Background Our laboratory published the first evidence that nutritional ketosis, induced by ketogenic diet (KD) or time-restricted diet (TRD), ameliorates disease progression in PKD animal models. We reasoned that, due to their frequent use for numerous health benefits, some ADPKD patients may already have had experience with ketogenic dietary interventions (KDIs). This retrospective case series study is designed to collect first real-life observations of ADPKD patients about safety, feasibility, and possible benefits of KDIs in ADPKD as part of a translational project pipeline. Methods Patients with ADPKD who had already used KDIs were recruited to retrospectively collect observational and medical data about beneficial or adverse effects, the feasibility and safety of KDIs in questionnaire-based interviews. Results 131 ADPKD patients took part in this study. 74 executed a KD and 52 TRD, for 6 months on average. 86% of participants reported that KDIs had improved their overall health. 67% described improvements in ADPKD-associated health issues. 90% observed significant weight loss. 64% of participants with hypertension reported improvements in blood pressure. 66% noticed adverse effects that are frequently observed with KDIs. 22 participants reported safety concerns like hyperlipidemia. 45 participants reported slight improvements in eGFR. 92% experienced KDIs as feasible while 53% reported breaks during their diet. Discussion Our preliminary data indicate that KDIs may be safe, feasible, and potentially beneficial for ADPKD patients highlighting that prospective clinical trials are warranted to confirm these results in a controlled setting and elucidate the impact of KDIs specifically on kidney function and cyst progression.
... In most studies concerning KD negative effects such as: occurrence of kidney stones, decreased weight gain and deficiencies of mineral substances were observed when the diet was applied for 1 -6 years [9,71]. In the literature the following are described as the adverse effects: torpor, nausea and vomiting caused by intolerance of the diet, especially in children. ...
... There is a risk of kidney damage caused by nitrogenous waste products excretion. The authors do not demonstrate definite certainty of the occurrence of KD-related kidney damage, but in 6% of children kidney stones were noted while applying the diet for 1 -5 years [71]. Introduction of KD may be related to occurrence of elevated concentration of ketone No 4 compounds in blood which is in particular undesired in the case of patients with diabetes in whom there is an increased risk of ketoacidosis -a state that is potentially life-threatening. ...
Article
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The differences between the metabolism and the physiology of cancer cells and the cells of the human body are assessed and used in most anticancer treatments. These differences encompass, among others, increased glucose metabolism in the changed cells. The aim of the paper was to discuss the results of studies concerning the relationship between lowcarbohydrate diets and fasting and the course of cancer. An inappropriately composed diet consisting of high amounts of simple sugars supplies cancer cells with nutrients, which may impair the effectiveness of cancer patients treatment. Lowcarbohydrate diets may, therefore, constitute an element of supplementary therapy in cancer treatment. The mechanism of low-carbohydrate diets in combination with standard treatment has not been completely explained, though. In initial studies it was proven that patients who were able to continue low-carbohydrate diets showed improvement in health and reduction of tumor mass or its slower growth. Moreover, it was observed that the inability of cancer cells to adapt in new environmental conditions that occur while fasting may have toxic effect on them. Introduction of fasting may sensitize cancer cells to chemotherapy, decrease concentration of growth factors and lead to repair of normal cells. On the other hand, fasting may also promote autophagy and, as can be concluded from the literature, its mechanism may have twofold activity: as a process impacting the survival or death of cancer cells.
... However, a case series found no negative effects on bone mineral content or density in 3 adults with G1DS who had followed the diets for >5 years 46 (Class III evidence). Nephrolithiasis occurs in 2%-7% of KDT-treated children, 47 resulting from hypercalciuria. The risk of nephrolithiasis may be increased with the use of carbonic anhydrase inhibitors such as topiramate and zonisamide 48 (Class III evidence). ...
... Comparable to pediatric recommendations, carnitine monitoring and supplementation remains controversial with limited evidence of carnitine deficiency developing in patients following KDT long term 55 (Class III evidence). Supplementation with citrates reduces the incidence of nephrolithiasis to 0.9% by the process of urine alkalinization 47,56 in children on a CKD and therefore may be used in adults prescribed a CKD as well and less often for modified KD variants. Gastrointestinal symptoms such as nausea, indigestion, and reflux have been reported during the initiation phase; however, a gradual introduction of ketogenic meals into the diet may help minimize these symptoms. ...
Article
Objective To evaluate current clinical practices and evidence-based literature to establish preliminary recommendations for the management of adults using ketogenic diet therapies (KDTs). Methods A 12-topic survey was distributed to international experts on KDTs in adults consisting of neurologists and dietitians at medical institutions providing KDTs to adults with epilepsy and other neurologic disorders. Panel survey responses were tabulated by the authors to determine the common and disparate practices between institutions and to compare these practices in adults to KDT recommendations in children and the medical literature. Recommendations are based on a combination of clinical evidence and expert opinion regarding management of KDTs. Results Surveys were obtained from 20 medical institutions with >2000 adult patients treated with KDTs for epilepsy or other neurologic disorders. Common side effects reported are similar to those observed in children and recommendations for management are comparable with important distinctions, which are emphasized. Institutions differ with regard to recommended biochemical assessment, screening, monitoring, and concern for long-term side effects and further investigation is warranted to determine the optimal clinical management. Differences also exist between screening and monitoring practices among adult and pediatric providers. Conclusions KDTs may be safe and effective in treating adults with drug-resistant epilepsy and there is emerging evidence supporting the use in other adult neurologic disorders and general medical conditions as well. Therefore, expert recommendations to guide optimal care are critical as well as further evidence-based investigation.
... A systemic ketosis can be obtained through the maintenance of a high fat, low CHO, and restricted protein intake, with a beneficial effect on raising seizure threshold [141]. However, a chronic ketoacidosis state may create the conditions for both a negative balance of bone mineral ions (buffering capacity) and a decreased renal conversion of 25OHD to its active metabolite 1,25(OH)2D [142]. Of course, the presence of cerebral palsy as comorbidity further increases the risk of BMD decrease likely through an increased bone turnover during a ketonic state in epileptic adults [143]. ...
... One hundred ninety-five US children on the KD for intractable epilepsy from 2000 to 2005 [142] Cohort study kidney stones formers vs. not kidney stones formers Demographics, urine laboratory markers, and intervention with urine alkalization (potassium citrate) ...
Article
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The existence of a common mesenchymal cell progenitor shared by bone, skeletal muscle, and adipocytes cell progenitors, makes the role of the skeleton in energy metabolism no longer surprising. Thus, bone fragility could also be seen as a consequence of a "poor" quality in nutrition. Ketogenic diet was originally proven to be effective in epilepsy, and long-term follow-up studies on epileptic children undergoing a ketogenic diet reported an increased incidence of bone fractures and decreased bone mineral density. However, the causes of such negative impacts on bone health have to be better defined. In these subjects, the concomitant use of antiepileptic drugs and the reduced mobilization may partly explain the negative effects on bone health, but little is known about the effects of diet itself, and/or generic alterations in vitamin D and/or impaired growth factor production. Despite these remarks, clinical studies were adequately designed to investigate bone health are scarce and bone health related aspects are not included among the various metabolic pathologies positively influenced by ketogenic diets. Here, we provide not only a narrative review on this issue, but also practical advice to design and implement clinical studies on ketogenic nutritional regimens and bone health outcomes. Perspectives on ketogenic regimens, microbiota, microRNAs, and bone health are also included.
... The adverse effects of KDT are quite common. Digestive [25,26], hepatic [26], and kidney problems [27][28][29] can appear, but are generally mild and easy to manage. In our cohort CKD seems to be as safe as MAD. ...
... In our cohort CKD seems to be as safe as MAD. Dyslipidemia [30,31] and kidney stones [27][28][29] are some of the most relevant long-term side effects. Hypercholesterolemia was very frequent in our cohort, but no patients were treated with lipid-lowering drugs, and, although CKD has a higher fat content diet, cholesterol was significantly higher in children who were on a MAD in the first few months. ...
Article
Background: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is caused by mutations in the SLC2A1 gene and produces seizures, neurodevelopmental impairment, and movement disorders. Ketogenic dietary therapies (KDT) are the gold standard treatment. Similar symptoms may appear in SLC2A1 negative patients. The purpose is to evaluate the effectiveness of KDT in children with GLUT1DS suspected SLC2A1 (+) and (-), side effects (SE), and the impact on patients nutritional status. Methods: An observational descriptive study was conducted to describe 18 children (January 2009-August 2020). SLC2A1 analysis, seizures, movement disorder, anti-epileptic drugs (AEDS), anthropometry, SE, and laboratory assessment were monitored baseline and at 3, 6, 12, and 24 months after the onset of KDT. Results: 6/18 were SLC2A1(+) and 13/18 had seizures. In these groups, the age for debut of symptoms was higher. The mean time from debut to KDT onset was higher in SLC2A1(+). The modified Atkins diet (MAD) was used in 12 (5 SLC2A1(+)). Movement disorder improved (4/5), and a reduction in seizures >50% compared to baseline was achieved in more than half of the epileptic children throughout the follow-up. No differences in effectiveness were found according to the type of KDT. Early SE occurred in 33%. Long-term SE occurred in 10, 5, 7, and 5 children throughout the follow-up. The most frequent SE were constipation, hypercalciuria, and hyperlipidaemia. No differences in growth were found according to the SLC2A1 mutation or type of KDT. Conclusions: CKD and MAD were effective for SLC2A1 positive and negative patients in our cohort. SE were frequent, but mild. Permanent monitoring should be made to identify SE and nutritional deficits.
... One major issue of concerns, however, is the long-term safety of very low-carb "keto" diets. Sampath et al. suggested that "keto" diets, mainly used in the long term for therapeutic purposes in drug refractory epilepsy in children, can increase the risk of KSD due to hypercalciuria [33]. Maintaining sufficient fluid intake for adequate urine production, and urine alkalinization, in addition to periodic renal ultrasound to screen for stones, are all recommended measures [33,34]. ...
... Sampath et al. suggested that "keto" diets, mainly used in the long term for therapeutic purposes in drug refractory epilepsy in children, can increase the risk of KSD due to hypercalciuria [33]. Maintaining sufficient fluid intake for adequate urine production, and urine alkalinization, in addition to periodic renal ultrasound to screen for stones, are all recommended measures [33,34]. ...
Article
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Objectives: Kidney stone disease (KSD) has a strong association with diet metabolic syndrome. This review aims at exploring the lithogenic risk posed by the current most popular diets. Our approach was to search for the effect of each diet type on the major urinary risk factors, to try to draw conclusions regarding the association of a specific diet type and KSD. Methods: This systematic review searched for the available literature exploring the association between the existing popular fad diets and KSD. Articles in English, French and Spanish were included, without restriction of the search period with the final search done in August 2021. Results: Total number of studies and studies for each diet type was as follows: 22 articles for the low carbohydrate diet, 20 articles for high protein diets, 26 articles for vegetarian and vegan diets. There exists a substantial variability in different low carbohydrate and high protein diets, and considerable overlap between modern popular fad diets. High carbohydrate intake might increase urine uric acid, calcium and oxalate levels. High protein diets increase urine calcium and uric acid and lower urine pH and citrate. Consumption of fruits and vegetables increases the urinary volume and urinary citrate. In vegan diets, sufficient daily calcium intake is important to avoid possible secondary hyperoxaluria. Conclusions: Few studies evaluated the direct relationship between modern fad diets and KSD. In general, the reduction of carbohydrate in the diet, and counterbalancing protein rich diets with sufficient intake of fruits and vegetables, seem to play a protective role against KSD formation. Maintaining sufficient calcium intake in vegan and vegetarian diets is important. Additional research is needed to directly evaluate the link between KSD and each diet type.
... Post-only studies (N = 134) 76, 82, 87, 104, 109, 112, 116, 119-121, 127, 128, 133, 134, 142, 145, 146, 148, 152, 155, 160, 167, 170, 172, 173, 175, 180, 183, 187, 189, 191, 192, 195, 199, 201, 202, 206, 209, 211, 214, 216, 217, 220, 224, 228, 229, 231, 234-236, 239, 243-246, 249, 250, 257, 259-262, 267, 269, 270, 275, 276, 286, 289, 291, 297, 300, 303, 305, 307, 310-312, 314-316, 319, 321, 325, 332, 334, 335, 337, 340, 341, 344, 345, 347-349, 351-353, 358, 361, 367, 370, 372-375, 380, 381, 383, 386-389, 392-394, 396, 399, 406, 414, 415, 419, 427, 433, 437, 442, 444, 449, 450, 462-465, 470 Infants (N = 7) 76,128,189,381,419,462,463 Pediatric mix (N = 38) 82, 119, 121, 133, 152, 167, 172, 192, 211, 216, 224, 228, 229, 234, 236, 239, 243- 245, 250, 260, 262, 267, 291, 297, 303, 305, 310, 314, 321, 325, 335, 345, 373, 380, 383 Partially included (N = 37) 104,109,112,134,146,160,173,180,187,195,199,201,202,217,220,231,235,246,249,275,286,311,332,334,337,344,347,352,367,370,372,374,375,387,389,396 Unclear (N = 52) 87, 116, 120, 127, 142, 145, 148, 155, 170, 175, 183, 191, 206, 209, 214, 257, 259, 261, 269, 270, 276, 289, 300, 307, 312, 315, 316, 319, 340, 341, 348, 349, 351, 353, 358, 361, 386, 388, 392-394, 399, 406, 414, 427, 433, 442, 444, 449, 464, 465, 470 Lacosamide, 76 Case-control studies (N = 4) 140, 147 ,203, 204 Infants (N = 0) Pediatric mix (N = 1) 147 Partially included (N = 0) Unclear (N = 3) 140,203,204 Not applicable ...
... The evidence base includes other relevant research studies that could be, at least partially, included in an evidence review on infantile epilepsy. 89,94,119,124,132,133,137,151,152,156,166,167,169,192,193,200,205,213,223,229,233 77, 78, 80, 84, 85, 91, 95, 97, 100, 107, 109, 114, 115, 117, 118, 129, 130, 134, 138, 143, 146, 149, 162, 165, 171, 173, 186, 198, 199, 201, 202, 215, 218, 221, 230, 238, 242, 246, 251, 255, 263, 264, 266, 272, 275, 277, 281, 282, 284, 286, 288, 293, 294, 298, 304, 306, 309, 311, 328, 330, 334, 337, 342, 344, 347, 352, 355, 356, 363, 366, 367, 372, 375, 376, 396, 398, 402-404, 407, 411, 413, 415, 416, 428, 432 N = 102 74, 87, 92, 93, 99, 106, 116, 126, 131, 140-142, 144, 155, 164, 175, 182, 183, 191, 204, 212, 222, 247, 256, 259, 261, 270, 271, 274, 278, 280, 285, 289, 290, 295, 296, 302, 307, 312, 313, 315-319, 322-324, 326, 327, 329, 331, 333, 338, 340, 341, 343, 348, 349, 351, 353, 354, 358, 359, 361, 362, 365, 368, 369, 394, 397 90, 96, 98, 103, 105, 108, 110, 111, 122, 125, 135, 136, 158-161, 163, 177, 181, 184, 188, 195, 197, 225, 252, 292, 332 N = 13 127,145,179,185,190,203,208,227,241,248,269,276,279 Medical devices The studies exclusively in infants evaluated different medications, including levetiracetam (N = 3), 83, 102, 189 adjunctive levetiracetam (N = 1), 176 topiramate (N = 1), 237 adjunctive topiramate (N = 3), 139, 153, 168 lamotrigine (N = 1), 258 adjunctive lamotrigine (N = 1), 194 lacosamide (N = 1), 76 liposteroid (dexamethasone palmitate) (N = 1), 210 multiple anticonvulsants (N = 1), 128 oxcarbazepine (N = 1), 226 and antiepileptic treatment not further specified (N = 1). 157 Two studies evaluated the ketogenic diet (N = 2), 377, 382 1 focused on vagus nerve stimulation (N = 1), 381 and 2 focused on surgery. ...
Technical Report
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Epilepsy is more common in children than in adults, with several unique childhood-onset epilepsy syndromes. Despite its significant prevalence, limited research exists on infantile epilepsy. The objective of the topic brief is to identify and categorize the existing literature on management strategies for infantile epilepsy to help the Patient-Centered Outcomes Research Institute (PCORI) and the American Epilepsy Society determine whether there is sufficient literature to warrant a systematic review on the topic. We identified 401 empirical published or ongoing research studies that include children up to 3 years of age in a scoping search in June 2019. Most studies used an uncontrolled postintervention design. Only 21 identified studies were exclusively in the age group of interest (ie, aged 0-3), with 16 focused on pharmaceutical interventions. A systematic review of infantile epilepsy appears to be feasible, especially if the literature search is combined with an effort of contacting authors of existing studies to request data from the subgroup of infants and reviewing the existing evidence base on pediatric samples for generalizability to infants. The results of the topic brief are only an estimate of the available literature; a systematic review will likely identify additional relevant publications.
... Autori smatraju da je u takvim slu~ajevima kao profilakti~ka mjera apsolutno nu`na adekvatna hidratacija te korekcija metaboli~ke acidoze i puferiranje urina dodatkom kalijeva-citrata, kao i primjena redovite kontrole kalcija, kreatinina i citrata u urinu. Rezultati retrospektivne studije Sampath i suradnika u potpunosti podr`avaju navedene preporuke (49). ...
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UVOD Historijat ketogene dijete Ketogena dijeta podrazumijeva prehranu siroma{nu ugljikohidratima i bogatu mastima, koje ~ine najve}i dio kalorijske vrijednosti prehrane. Takav na~in prehrane zapravo imitira stanje gladovanja, pri ~emu metabolizam masti postaje osnovni izvor energije, potiskuju}i glukozu i ostale ugljikohidrate. Ketogena je dijeta razvijena u Mayo klinici kao terapijski tretman za kontrolu refraktorne epilepsije u djece po~etkom dvadesetih godina pro{loga stolje}a (1), u vrijeme ograni~ene dostupnosti i u~inkovitosti antiepileptika. Mogu}a korist od posta u tretmanu epilepsije opisana je jo{ u Bibliji, dok se u suvre-menoj medicinskoj literat uri sli~an pristup prvi put spominje u radovima Guelpa i Mariea iz 1911. (1). Sljede}a dva desetlje}aobiljèili su brojni izvje{taji o djelotvornosti ketogene dijete u tretmanu epilepsije. Otkri}e fenitoina 1938. bitno mijenja takav trend, a novaistràivanja i terapijska doktrina usmjereni su na fenitoin i nove antiepileptike. U usporedbi s novom farmakoterapijom, ketogena je dijeta ocijenjena kao zahtjevna, slabo podno{ljiva i skupa. Sve manja primjena, kao i veoma slaba preciznost i kontrola tretmana kona~no je krajem 90-tih godina pro{loga stolje}a rezultirala stavom mnogih lije~nika da primjena ketogene dijete vi{e nije opravdana (2). Ipak, primjena ketogene dijete u tretmanu epilepsije u djece nastavljena je u bolnici Johns Hopkins (Maryland), podjednako dob-rim rezultatima kakvi su opisivani i prethodnih desetlje}a. Ponovnoj aktualizaciji keto-gene dijete krajem 20. i po~etkom 21. stolje}a pridonio je hollywoodski producent Jim Abrahams, ~iji je sin Charlie bolovao od farmakorezistentne epilepsije. Budu}i da prim-jena mnogih antiepileptika i razli~itih terapijskih tretmana nije zaustavila konvulzivne napade, Abrahams je sina odveo u bolnicu Johns Hopkins, gdje su napadi u djeteta u potpunosti zaustavljeni ubrzo nakon uvo|enja ketogene dijete (3). Nakon takvog uspjeha, Abrahams je osnovao fondaciju (Charlie Foundation) kojapodràva i poti~e kontinuirani rad na terapijskoj primjeni ketogene dijete. Iznimna popularnost uslijedila je nakon medijske promocije i rezultirala velikim zanimanjem roditelja za takav vid lije~enja. Stoga su 1994. zapo~eli multicentri~nu studiju u sedam klini~kih centara i financirali je iz Charlie fondacije. Rezultati te studije (4), kao i rezultati primjene ketogene dijete u 150 djece u bolnici Johns Hopkins (5,6) bili su prvi objavljeni rezultati klini~kih studija o efi-kasnosti ketogene dijete, nakon ~ega je uslijedio dramati~an porast zanimanja stru~ne i znanstvene javnosti za tu temu. U usporedbi s prethodnim desetlje}ima, nakon 1996. mnogostruko je porastao broj objavljenih apstrakta i ~lanaka prikazanih Ameri~kom P R E G L E D N I R A D O V I 613
... 45 Renal As high as 3-7% of the children on KD therapy may develop renal calculi, the risk of which is reportedly decreased by co-administration of oral citrates. 47 ...
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Drug-refractory epilepsy is a commonly prevalent pediatric neurological illness of global significance. Ketogenic diet (KD) is a time-tested therapeutic modality for refractory epilepsy, which has reemerged as a robust alternative to anti-epileptic pharmacotherapy. There is a growing body of evidence which supports the anti-seizure efficacy, safety profile and feasibility of KD use in childhood epilepsy. In addition, this modality has been recognized to reduce anti-epileptic exposure, improve cognition and behavioral profile of patients as well as improve the quality-of-life of care-givers. Current indications of KD include refractory epilepsy syndromes, selected metabolic disorders (such as pyruvate dehydrogenase deficiency) and a host of varied neurological entities. KD research has broadened the knowledge-base about its mechanisms of action. Four types of KD are in vogue currently with varying nutritional constitution, palatability, administration protocols and comparable efficacy. KD initiation and maintenance are the result of concerted effort of a team of pediatric neurologist/epileptologist, nutritionist and patient’s primary care-giver. Consensus is being formulated about various practical aspects of KD such as patient-selection, parental counseling, baseline work-up, dietary prescription, nutritional supplementation, concurrent anti-epileptic drug administration, follow-up and treatment-duration. Novel applications of KD include its use in neonatal epilepsy and super-refractory status epilepticus and tailor-made formulations such as cooking oil-based KD in predominantly rice-fed populations. Increasing body of clinical experience, improved nutritional designs and translational research are promoting KD as a major therapeutic modality. Currently, KD forms a core essence in the armamentarium against refractory epilepsy. In this review, we summarize the recent advances and current perspectives in the use of KD in refractory epilepsy.
... Additional adverse events noted during the ICU stay are listed in Table 2, but were considered to be unlikely caused by KD according to NIH Common Terminology Criteria for Adverse Events [20]. One patient developed nephrolithiasis 6 weeks after KD initiation in the setting of concurrent topiramate use which was felt to be the likely causative agent, rather than KD-associated nephrolithiasis, which is a long-term complication [21]. similar at 1 and 2 week timepoints (61 % vs. 60 %, p = 0.317), and while most responders were seen by 2 weeks, there were 5 additional responders between 2 weeks and 1 month timepoints. ...
Article
Purpose The ketogenic diet (KD) is initiated emergently in the intensive care unit (ICU) for patients with super refractory status epilepticus (SRSE) and epileptic encephalopathies (EE). However, few data are available regarding safety, effectiveness, and long-term outcomes. Methods We performed a retrospective cohort study of consecutive patients with KD initiated in the ICU from 2010 to 2018 for SRSE and EE. We characterized time to ketosis, adverse effects, and seizure outcomes. Responders were defined as having ≥50 % reduction in seizure frequency compared to prior to KD initiation. Results We identified 29 patients. KD was initiated for SRSE in 12 patients, EE in 8 patients, and EE with SRSE in 9 patients. KD was initiated after a median of 9 days. Ketosis was achieved 2 days faster in fasted patients (p < 0.0001). All patients had at least 1 KD-related adverse effect, most often hypoglycemia, constipation, or acidosis. There was ≥50 % reduction in seizure frequency compared to prior to KD initiation by 1 week in 17/28 patients, seizure-freedom by 2 weeks in 7/28 patients, and weaned off anesthetics in 11/17 patients. All KD-responders at 1 month had continued response at 6 months. Mortality at 1 year was 24 %. There was no difference in KD response or mortality between KD indication groups. Conclusion Emergent KD initiation in the ICU is feasible, safe, and often effective for SRSE and EE. Expected adverse effects were common but treatable. Morbidity and mortality in this group was high. A ≥ 50 % reduction in seizure is achieved in most responders by 1–2 weeks.
... The cKD has been associated with a 3.1%-6.7% incidence of renal calculi [93,94]. In Freeman et al.'s prospective cohort, 3 of 150 children were found to have uric acid stones and 3 with calcium oxalate or calcium phosphate stones [95]. ...
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Epilepsy in the pediatric and adolescent populations is a devastating condition where individuals are prone to recurrent epileptic seizures or changes in behavior or movement that is the direct result of a primary change in the electrical activity in the brain. Although many children with epilepsy will have seizures controlled with antiseizure medications (ASMs), a large percentage of patients are refractory to drug therapy and may consider initiating a ketogenic diet. The term Ketogenic Diet or Ketogenic Diet Therapy (KDT) refers to any diet therapy in which dietary composition results in a ketogenic state of human metabolism. Currently, there are 4 major Ketogenic diet therapies—the classic ketogenic diet (cKD), the modified Atkins diet (MAD), the medium chain triglyceride ketogenic diet (MCTKD) and the low glycemic index treatment (LGIT). The compositions of the 4 main KDTs differ and limited evidence to distinguish the efficacy among different diets currently exists. Although it is apparent that more randomized controlled trials (RCTs) and long-term studies are needed to evaluate efficacy, side effects and individual response to the diet, it is imperative to study and understand the metabolic profiles of patients with epilepsy in order to isolate which dietary restrictions are necessary to maximize clinical benefit.
... Long-term ketogenic diets increase the risk of bone fractures (despite the use of calcium supplements) [109] and the formation of kidney stones, which suggests that bone metabolism is effected [110]. An earlier study by Hahn et al. [111] observed that mineral metabolism was affected by ketogenic diets, with osteomalacia developing and vitamin D levels decreasing. ...
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Two trials separately measured the bioavailability and impact on inflammation of a supplement taken daily containing 510 mg Docosahexaenoic acid (DHA), 344 mg Eicosapentaenoic acid (EPA), and 1000 IU of vitamin D (25-hydroxyvitamin D; 25(OH)D), for healthy and Crohn’s disease (CD) populations. Both trials were double blinded, randomized, placebo-controlled with cross-over. Participants were randomly allocated to groups A (placebo then supplement) or B (supplement then placebo). Both included a washout. Fatty acid (N-3 PUFAs) and vitamin D serum levels, plasma C-reactive protein (CRP), and stool calprotectin were measured before and after each treatment period. Outcome measures were analyzed using generalized linear mixed models, including terms for treatment, period, and a treatment-by-period interaction. The supplement significantly increased serum levels in healthy and CD groups for EPA (p < 0.001 and p < 0.001, respectively), Docosapentaenoic acid (p < 0.001 and 0.005), DHA (p < 0.001 and 0.006), the omega-3 index (p < 0.001 and 0.001), and (vitamin D (p < 0.001 and 0.027). CRP and calprotectin measures showed no evidence of a treatment effect on inflammation; however, model estimation was imprecise for both outcomes, hence further research is required to elucidate potential inflammation effects. The nutrient supplement increased serum levels of key N-3 PUFAs and vitamin D in both populations, showing the preparation was readily bioavailable.
... [154,155] Adverse effects of the KD include GI problems (which typically are worst in the first weeks of the diet and gradually diminish over time), hyperlipidemia, [156] and renal calculi. [157] Cardiovascular adverse effects are recognized as well, in that QT-interval prolongation on an electrocardiography (ECG) has been reported in up to 15% of pediatric patients on the KD and is potentially arrhythmogenic. [158] The role of macronutrients in heart health remains controversial. ...
... This diet is also harmful to patients with metabolic disorders encompassing impaired gluconeogenesis (Goswami & Sharma, 2019). Studies have also shown deleterious effects of this diet on the gastrointestinal (Kossoff et al., 2018;Lin et al., 2017), skeletal (Bergqvist et al., 2008Simm et al., 2017), cardiovascular (Bank et al., 2008), and renal systems (Choi et al., 2010;Sampath et al., 2007). Moreover, growth impairments are reported in children exposed to this diet long-term (Ferraris et al., 2019;Groleau et al., 2014). ...
Article
Epilepsy is one of the oldest known neurological disorders and is characterized by recurrent seizure activity. It has a high incidence rate, affecting a broad demographic in both developed and developing countries. Comorbid conditions are frequent in patients with epilepsy and have detrimental effects on their quality of life. Current management options for epilepsy include the use of anti‐epileptic drugs, surgery, or a ketogenic diet. However, more than 30% of patients diagnosed with epilepsy exhibit drug resistance to anti‐epileptic drugs. Further, surgery and ketogenic diets do little to alleviate the symptoms of patients with pharmacoresistant epilepsy. Thus, there is an urgent need to understand the underlying mechanisms of pharmacoresistant epilepsy to design newer and more effective anti‐epileptic drugs. Several theories of pharmacoresistant epilepsy have been suggested over the years, the most common being the gene variant hypothesis, network hypothesis, multidrug transporter hypothesis, and target hypothesis. In our review, we discuss the main theories of pharmacoresistant epilepsy and highlight a possible interconnection between their mechanisms that could lead to the development of novel therapies for pharmacoresistant epilepsy.
... Decreases in bone mineral content and bone loss have been documented [135,136]. In addition, the concern of kidney stones exists in approximately 6% of children with intractable epilepsy on the KD, which may be reduced with administration of potassium citrate [137,138]. Interestingly, recent studies have identified significant reductions in the hormone ghrelin, which may be responsible for low growth rates in epileptic children [139,140]. Future investigations should focus on the characterization of hormonal changes that may occur with KD consumption in adults. ...
Article
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The ketogenic diet (KD) has gained a resurgence in popularity due to its purported reputation for fighting obesity. The KD has also acquired attention as an alternative and/or supplemental method for producing energy in the form of ketone bodies. Recent scientific evidence highlights the KD as a promising strategy to treat obesity, diabetes, and cardiac dysfunction. In addition, studies support ketone body supplements as a potential method to induce ketosis and supply sustainable fuel sources to promote exercise performance. Despite the acceptance in the mainstream media, the KD remains controversial in the medical and scientific communities. Research suggests that the KD or ketone body supplementation may result in unexpected side effects, including altered blood lipid profiles, abnormal glucose homeostasis, increased adiposity, fatigue, and gastrointestinal distress. The purpose of this review article is to provide an overview of ketone body metabolism and a background on the KD and ketone body supplements in the context of obesity and exercise performance. The effectiveness of these dietary or supplementation strategies as a therapy for weight loss or as an ergogenic aid will be discussed. In addition, the recent evidence that indicates ketone body metabolism is a potential target for cardiac dysfunction will be reviewed.
... This progressive bone demineralization was associated with hypercalciuria, where 40% of children had an elevated fasting urinary calcium:creatinine ratio prior to starting the diet and this increased to 75% within 6 months (7). This hypercalciuria is a risk factor for development of nephrolithiasis in children on this diet (7,10), with 3% to 10% of children developing this complication (11). The disturbed mineral homeostasis in children on the ketogenic diet appears to be the result of a state of low bone remodeling in which the rate of bone resorption exceeds the rate of bone formation, with more calcium exiting the skeleton than entering it. ...
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Context The ketogenic diet is associated with progressive skeletal demineralization, hypercalciuria and nephrolithiasis. Acute hypercalcemia has been described as a newly recognized complication of this treatment. Objective To describe the clinical characteristics of acute hypercalcemia in children on the ketogenic diet through analysis of the presentation, response to treatment, and natural history in a large cohort of patients. Design A multicenter case series was performed including children who developed acute hypercalcemia while treated with the ketogenic diet. Information on clinical presentation, treatment and course of this complication was collated centrally. Results There were 14 patients (median (range) age 6.3 (0.9 to 18) years) who developed hypercalcemia 2.1 (range 0.2 to 12) years after starting the ketogenic diet. All had low levels of parathyroid hormone and levels of 1,25-dihydroxyvitamin D were low in all except one. Seven (50%) had impaired renal function at presentation. All except the two oldest had low alkaline phosphatase levels for age. Once normocalcemia was achieved, hypercalcemia recurred in only two of these patients over observation of up to 9.8 years. One patient discontinued the ketogenic diet prior to achieving normocalcemia while four more stopped the diet during follow-up after resolution of hypercalcemia. Conclusions Ketotic hypercalcemia can occur years after starting the ketogenic diet, especially in the setting of renal impairment. The mechanism is unknown, but appears to be due to reduced osteoblast activity and impaired bone formation. We recommend close attention to optimizing bone health in these children, and screening for the development of ketotic hypercalcemia.
... Wortsman et al. (2000) were the first to provide strong evidence that VD may become sequestered within adipose tissue. Chronic ketoacidosis results in increased demand for bone minerals for buffering capacity and decreased renal conversion of 25 OH vitamin D to 1, 25 (OH)2 vitamin D (Sampath et al., 2007). There is only one published report that explored the effect of KD on the developing skeleton and demonstrated reduced bone mineral content in patients on KD when followed up for 15 months (Bergqvist et al., 2008). ...
Article
Ketogenic (KD) and high-fat (HFD) diets and vitamin D (VD) produce variable effects on insulin secretion and body weight (BW), but mechanisms remain unclear. We investigated the effects of normal fat diets (NFD), KD, and HFD with and without VD on BW and serum glucose, insulin, VD, insulin resistance, C-reactive protein, interleukin-6, and tumor necrosis factor-alpha in rats. Three isocaloric NFD, KD, and HFD containing respectively protein-carbohydrate-fat (NFD: 14.8%-75.7%-9.5%; KD:20.2%-10.3%-69.5%; HFD:15.2%-42.7-42.0%) and three other similar diets but with (1000 IU/kg) VD were used. Forty-five adult male Sprague-Dawley rats were used, 5 rats were sacrificed at the start, remainders were randomly divided into NFD (n=15) and HFD (n=25), and fed for 8 weeks, then 5 rats from each were sacrificed. NFD remainders were divided into 2 subgroups (n=5) and fed NFD and NFD-VD, and HFD remainders were divided into 4 subgroups (n=5) and fed HFD, HFD-VD, KD, and KD-VD for further 8 weeks, then all rats were sacrificed. BW and food intake were measured, food conversion ratio (FCR) was calculated, and biological variables were determined following standard protocols. BW change and FCR (-15.6±-10.13g; 0.033±0.350 respectively) of rats fed KD-VD were the lowest (P<0.05) among those fed KD (144.8±1.47g; 0.189±0.050), HFD-VD (143.0±8.49g; 0.187±0.100), HFD (155.8±0.3g; 0.203±0.010), NFD-VD (142.8±6.34g; 0.183±0.009), and NFD (51.0±1.02g; 0.074±0.110) respectively. BW change correlated (P<0.01) with food intake (r=0.752), % carbohydrate (r=0.292), and % fat (r=0.341). None of the diets affected other biomarkers. Results clearly show BW-reducing effects for KD-VD that may be mediated by changes in food intake and dietary fat and carbohydrate proportion. .
... The classic KD consists of a 4:1 ratio of fats to protein and carbohydrates that physiologically mimics the fasting state (29). Although the classic KD is safe and generally well-tolerated, barriers to long-term adherence such as palatability issues, its restrictive nature, and side effect profile (30)(31)(32) has led to the exploration of dietary variations [e.g. modified Atkins diet; MAD (33,34)] and the supplementation of exogenous ketogenic agents such as medium-chain triglycerides (MCTs) to promote the elevation of ketone bodies in the blood (12). ...
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Ketone bodies have potential disease-modifying activity that represent a novel therapeutic approach for neurodegenerative diseases (NDD). The aim of this systematic review was to summarize and evaluate the evidence for the application of ketogenic therapies (dietary or exogenous ketogenic agents) for NDD and provide recommendations for future research. Eight databases were electronically searched for articles reporting on controlled trials (≥4 wk duration) that induced ketosis or elevated serum ketone concentrations in people with NDD. Of 4498 records identified, 17 articles met the inclusion criteria with a total of 979 participants including studies on mild cognitive impairment (MCI; n = 6), multiple sclerosis (n = 4), Alzheimer's disease (n = 5), Parkinson's disease (n = 1), and MCI secondary to Parkinson's disease (n = 1). Of 17 studies, 7 were randomized double-blind placebo-controlled trials. Most studies used dietary interventions (n = 9), followed by medium-chain triglycerides (n = 7) and a fasting protocol (n = 1). Generally, trials were 6 wk in duration and assessed cognition as the primary outcome. Studies were heterogeneous in type and severity of NDD, interventions used, and outcomes assessed. Overall, 3/17 studies carried a low risk of bias. Based on available evidence, exogenous ketogenic agents may be more feasible than dietary interventions in NDD from a compliance and adherence perspective; more research is required to confirm this. Recommendations for future research include improving exogenous formulations to reduce adverse effects, exploring interindividual factors affecting response-to-treatment, and establishing a "minimum required dose"for clinically meaningful improvements in disease-specific symptoms, such as cognition or motor function. Adv Nutr 2021;00:1-23.
... High fat intake of KD-fed mice led to induce hepatic inflammation and development of nonalcoholic fatty liver disease [73,97]. There are also reports in the literature on the development of nephrolithiasis in people (mainly children) following a ketogenic diet [98][99][100]. KD is also associated with impaired bone health [101,102]. ...
Article
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3-hydroxybutyrate (3-HB) as a very important metabolite occurs in animals, bacteria and plants. It is well known that in animals, 3-HB is formed as a product of the normal metabolism of fatty acid oxidation and can therefore be used as an energy source in the absence of sufficient blood glucose. In microorganisms, 3-HB mainly serves as a substrate for the synthesis of polyhydroxybutyrate, which is a reserve material. Recent studies show that in plants, 3-HB acts as a regulatory molecule that most likely influences the expression of genes involved in DNA methylation, thereby altering DNA methylation levels. Additionally, in animals, 3-HB is not only an intermediate metabolite, but also an important regulatory molecule that can influence gene expression, lipid metabolism, neuronal function, and overall metabolic rate. Some of these effects are the direct effects of 3-HB itself, while others are indirect effects, regulated by the metabolites into which 3-HB is converted. One of the most important regulatory functions of 3-HB is the inhibition of the activity of histone deacetylases and thus the epigenetic regulation of many genes. Due to the number of functions of this compound, it also shows promising therapeutic properties.
... Wortsman et al. (2000) were the first to provide strong evidence that VD may become sequestered within adipose tissue. Chronic ketoacidosis results in increased demand for bone minerals for buffering capacity and decreased renal conversion of 25 OH vitamin D to 1, 25 (OH)2 vitamin D (Sampath et al., 2007). There is only one published report that explored the effect of KD on the developing skeleton and demonstrated reduced bone mineral content in patients on KD when followed up for 15 months (Bergqvist et al., 2008). ...
Article
Full-text available
Ketogenic (KD) and high-fat (HFD) diets and vitamin D (VD) produce variable effects on insulin secretion and body weight (BW), but mechanisms remain unclear. We investigated the effects of normal fat diets (NFD), KD, and HFD with and without VD on BW and serum glucose, insulin, VD, insulin resistance, C-reactive protein, interleukin-6, and tumor necrosis factor-alpha in rats. Three isocaloric NFD, KD, and HFD containing respectively protein-carbohydrate-fat (NFD: 14.8%-75.7%-9.5%; KD:20.2%-10.3%-69.5%; HFD:15.2%-42.7-42.0%) and three other similar diets but with (1000 IU/kg) VD were used. Forty-five adult male Sprague-Dawley rats were used, 5 rats were sacrificed at the start, remainders were randomly divided into NFD (n=15) and HFD (n=25), and fed for 8 weeks, then 5 rats from each were sacrificed. NFD remainders were divided into 2 subgroups (n=5) and fed NFD and NFD-VD, and HFD remainders were divided into 4 subgroups (n=5) and fed HFD, HFD-VD, KD, and KD-VD for further 8 weeks, then all rats were sacrificed. BW and food intake were measured, food conversion ratio (FCR) was calculated, and biological variables were determined following standard protocols. BW change and FCR (-15.6±-10.13g; 0.033±0.350 respectively) of rats fed KD-VD were the lowest (P<0.05) among those fed KD (144.8±1.47g; 0.189±0.050), HFD-VD (143.0±8.49g; 0.187±0.100), HFD (155.8±0.3g; 0.203±0.010), NFD-VD (142.8±6.34g; 0.183±0.009), and NFD (51.0±1.02g; 0.074±0.110) respectively. BW change correlated (P<0.01) with food intake (r=0.752), % carbohydrate (r=0.292), and % fat (r=0.341). None of the diets affected other biomarkers. Results clearly show BW-reducing effects for KD-VD that may be mediated by changes in food intake and dietary fat and carbohydrate proportion. .
... Hyperlipidemia has been seen in a majority of children treated with the traditional ketogenic diet, although this can be avoided by adjusting the types of fats consumed [76,77]. Kidney stones are seen in approximately 10% of children on the ketogenic diet [78,79]. There is concern that a strict ketogenic diet may affect growth rates, possibly due to protein or overall calorie restrictions [80,81]. ...
Article
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The high-fat, low-carbohydrate (ketogenic) diet has grown in popularity in the last decade as a weight loss tool. Research into the diet’s effects on the body have revealed a variety of other health benefits. The use of exogenous ketone supplements to confer the benefits of the diet without strict adherence to it represents an exciting new area of focus. Synthetic ketogenic compounds are of particular interest that has received very little emphasis and is an untapped area of focus for chemical synthesis. In this review, we summarize the chemical basis for ketogenicity and opportunities for further advancement of the field.
... Long-term ketogenic diets increase the risk of bone fractures (despite the use of calcium supplements) [109] and the formation of kidney stones, which suggests that bone metabolism is effected [110]. An earlier study by Hahn et al. [111] observed that mineral metabolism was affected by ketogenic diets, with osteomalacia developing and vitamin D levels decreasing. ...
... This can partly be explained by persistent acidosis and dehydration which can together lead to increased risk of renal stones. 8,24,26 A recent systematic review of prospective studies on the safety and tolerability of KD by Cai et al 27 reported the incidence of hyperuricemia to be only about 5 percent which was much less than our study. The explanation for this could be that in our study the available uric acid results were only from those who were already detected with hyperuricemia and the number was rather small. ...
Article
Background and objectives: Ketogenic diet (KD), a well-known nonpharmacologic treatment of intractable epilepsy, could adversely affect growth and nutritional status; however, such data are limited in Thailand. This study aimed to assess growth and nutritional status of Thai children treated with KD together with dietary adherence and its related factors. Methods and study design: The records of children treated with KD for more than 1 month between January 2009 to September 2020 were reviewed. Weight, height, and biochemical indices were retrieved at baseline, 1, 3, 6, 12, 18, and 24 months. Type of KDs, compliance and adverse effects were extracted. Results: Forty-eight patients (21 male) were enrolled. Median age was 3.5 years (IQR 0.9, 10.1). There was no significant decrease in weight-for-age z-score (WAZ) despite a trend toward minimal reduction in WAZ at 3 months. Median follow-up time was 13 months (IQR 7, 29.5). Height-for-age z-score (HAZ) significantly decreased at 12 months [median -1.55 (IQR -3.35, -0.43) vs baseline median -0.6 (IQR -2.07, 0.29)]. Adherence of KD in tube feeding patients was better than oral feeding. Thirty seven percent (18/48) of the patients continued the diet beyond 2 years. Early discontinuation before 6 months was mostly due to poor compliance from patients and families (6/11, 55%). Common adverse effects were GI problems (77%), dyslipidemia (64%) and hypercalciuria (29%). Conclusions: Under close monitoring, KD can be administered in Thai children with minimal adverse effects on growth and nutritional status. Adherence depends on route of feeding, clinical response, and cooperation of the families.
... Overall, they responded to dietary adjustments and medication, and therefore this did not lead to discontinuation of the dietary treatment [133]. Up to 7% of children on KD therapy may develop kidney stones [142]. QT interval prolongation and cardiomyopathy have been found during prolonged KD, with unclear causal mechanisms [143]. ...
Article
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Obesity is defined as a condition characterized by an excessive fat accumulation that has negative health consequences. Pediatric obesity is associated with an increased risk for many diseases, including impaired glycemic and lipidic control that may lead to the development of chronic, and potentially disabling, pathologies, such as type 2 diabetes mellitus (T2DM) and cardiovascular events, in adult life. The therapeutic strategy initially starts with interventions that are aimed at changing lifestyle and eating behavior, to prevent, manage, and potentially reverse metabolic disorders. Recently, the ketogenic diet (KD) has been proposed as a promising dietary intervention for the treatment of metabolic and cardiovascular risk factors related to obesity in adults, and a possible beneficial role has also been proposed in children. KD is very low in carbohydrate, high in fat, and moderate to high in protein that may have the potential to promote weight loss and improve lipidic derangement, glycemic control, and insulin sensitivity. In this review, we present metabolic disorders on glycemic and lipidic control in children and adolescents with obesity and indication of KD in pediatrics, discussing the role of KD as a therapeutic tool for metabolic derangement. The results of this review may suggest the validity of KD and the need to further research its potential to address metabolic risk factors in pediatric obesity.
... Böbrek taşı riskinin değerlendirilmesi için KD alan tüm çocuklarda ayda bir kez evde idrar "dipstick" ile hematüri varlığı değerlendirilmeli ve her 3 ayda bir idrar kalsiyum/kreatinin oranı hesaplanmalıdır. Ardışık üç ayrı idrar analizinde hematüri saptanan hastalarda ileri değerlendirme için mutlaka böbrek ultrasonografisi yapılmalıdır (2,96). ...
... citrates. 63,64 On the other hand, more serious complications may be observed in patients with disorders of fatty acid transport or metabolism, in whom the KD should be avoided because it could precipitate a severe metabolic crisis leading to coma or death. 27,63 HFD and brain function: improvement or impairment? ...
Article
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The prevalence of obesity tripled worldwide between 1975 and 2016, and it is projected that half of the US population will be overweight by 2030. The obesity pandemic is attributed, in part, to the increasing consumption of the high-fat, high-carbohydrate Western diet, which predisposes to the development of the metabolic syndrome and correlates with decreased cognitive performance. In contrast, the high-fat, low-carbohydrate ketogenic diet has potential therapeutic roles and has been used to manage intractable seizures since the early 1920s. The brain accounts for 25% of total body glucose metabolism and, as a result, is especially susceptible to changes in the types of nutrients consumed. Here, we discuss the principles of brain metabolism with a focus on the distinct effects of the Western and ketogenic diets on the progression of neurological diseases such as epilepsy, Parkinson’s disease, Alzheimer’s disease, and traumatic brain injury, highlighting the need to further explore the potential therapeutic effects of the ketogenic diet and the importance of standardizing dietary formulations to assure the reproducibility of clinical trials.
... citrates. 63,64 On the other hand, more serious complications may be observed in patients with disorders of fatty acid transport or metabolism, in whom the KD should be avoided because it could precipitate a severe metabolic crisis leading to coma or death. 27,63 HFD and brain function: improvement or impairment? ...
Article
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The prevalence of obesity tripled worldwide between 1975 and 2016, and it is projected that half of the US population will be overweight by 2030. The obesity pandemic is attributed, in part, to the increasing consumption of the high-fat, high-carbohydrate Western diet, which predisposes to the development of the metabolic syndrome and correlates with decreased cognitive performance. In contrast, the high-fat, low-carbohydrate ketogenic diet has potential therapeutic roles and has been used to manage intractable seizures since the early 1920s. The brain accounts for 25% of total body glucose metabolism and, as a result, is especially susceptible to changes in the types of nutrients consumed. Here, we discuss the principles of brain metabolism with a focus on the distinct effects of the Western and ketogenic diets on the progression of neurological diseases such as epilepsy, Parkinson's disease , Alzheimer's disease, and traumatic brain injury, highlighting the need to further explore the potential therapeutic effects of the ketogenic diet and the importance of standardizing dietary formulations to assure the reproducibility of clinical trials.
... La prevención con el uso de citratos durante la DC reduce el riesgo de formación de cálculos [34], como así la monitorización de la litiasis renal (análisis de orina, calcio/creatinina urinarios y ecografía abdominal) y el mantenimiento de una hidratación adecuada. ...
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IntroducciónEfectos adversos agudosHipoglucemiaAcidosis metabólicaEfectos gastrointestinalesEfectos adversos crónicosHiperlipidemia y enfermedad cardiovascularAlteración del crecimientoMetabolismo mineral-óseoHiperuricemia y nefrolitiasisDéficit de vitaminas, micronutrientes y oligoelementosDéficit de carnitinaInfecciones recurrentesConclusionesVea nuestros másteresAbierta la Preinscripción Máster en Trastornos del Espectro Autista 11ª Edición Abierta la Preinscripción Máster en Psicobiología y Neurociencia Cognitiva 15ª Edición [REV NEUROL 2018;66:193-200]PMID: 29537059DOI: https://doi.org/10.33588/rn.6606.2017280 Introducción. La dieta cetogénica es una terapia no farmacológica que se ha usado como alternativa para el tratamiento de la epilepsia refractaria desde 1921. Es una dieta alta en grasas y baja en hidratos de carbono, que se utiliza en el tratamiento de la epilepsia refractaria pediátrica, efectiva en alrededor del 50% de los pacientes que la inician. Se trata de un plan alimentario desequilibrado tanto en macro como en micronutrientes, que puede causar déficits nutricionales en energía, proteínas, minerales y vitaminas, y exceso de lípidos, con riesgo de ocasionar efectos secundarios no deseados tanto en el inicio del tratamiento como de forma tardía. Desarrollo. Se describen los efectos adversos más frecuentes que se presentan en forma aguda o tardíamente, y se brindan herramientas para su manejo y prevención durante el tratamiento para pediatras y equipos de dieta cetogénica. Conclusiones. Algunos efectos adversos son de difícil interpretación, y pueden ser manifestación por afectación a diferentes niveles del organismo, poniendo en duda si son secundarios a la dieta, a la medicación antiepiléptica o a intercurrencias del propio paciente. Es importante seguir el protocolo de frecuencia de estudios y evaluaciones para detectar y prevenir estos efectos, y consultar a centros de referencia evaluando el coste-beneficio de continuar o no el tratamiento.
... Furthermore, previous studies have reported that chronic ketoacidosis led to an increase in bone minerals to maintain the buffering capacity and decrease renal conversion of 25-(OH)-VD to 1,25-(OH) 2 -VD 3 (30). Low 25-(OH)-VD levels, particularly those <20 ng/ml, were associated with an elevated fracture risk in women aged ≥50 years during a 15-year follow-up period (31). ...
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A ketogenic diet (KD) is composed of low-carbohydrate, high-fat and adequate levels of protein. It has been used for decades as a method to treat pediatric refractory epilepsy. However, recently, its side effects on the bones have received increasing attention. In order to comprehensively evaluate the effect of KD on the microstructures and mechanical properties of the skeleton, 14 male Sprague-Dawley rats were equally divided into two groups and fed with a KD (ratio of fat to carbohydrate and protein, 3:1) or a standard diet for 12 weeks. Body weight, as well as blood ketone and glucose levels, were monitored during the experiment. Bone morphometric analyses via micro-computerized tomography were performed on cortical and trabecular bone at the middle L4 vertebral body, the proximal humerus and tibia. The compressive stiffness and strength of scanned skeletal areas were calculated using micro-finite element analysis. The KD led to higher ketone levels and lower glucose levels, with reduced body weight and total bone mineral density (TBMD). After 12 weeks, the diet reduced the bone volume fraction, the trabecular number of cancellous bone, cortical thickness, total cross-sectional area inside the periosteal envelope and the bone area of cortical bone in the tibia and humerus, while increasing trabecular separation. However, KD may not affect the L4 vertebral body. The serum calcium or phosphate concentrations in the blood remained unchanged. In addition, bone stiffness and strength were clearly decreased by the KD, and significantly correlated with the BMD and bone area at all scanned sites. In conclusion, KD led to significant bone loss and reduced biomechanical function in appendicular bones, with a lesser impact on axial bones.
... Amongst the urinary symptoms, hypercalciuria was observed in almost one fourth of the children. There was only one case in which the child suffered nephrocalcinosis (3.8%), which corresponded to the same frequency shown in literature that indicates 3%-7% [46][47][48]. The singular case was diagnosed 12 months after the KD was implemented and was probably associated to a mutation in the sodium channels. ...
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Background: The ketogenic diet (KD) is an effective treatment against drug-resistant epilepsy in children. The KD is a diet rich in fats that produces anticonvulsant and neuroprotective effects that reduces seizures and improves the cognitive state. Nevertheless, it can produce side effects that sometimes can be serious. Further, the effect on growth is quite controversial when used for an extended period of time. The aim of this paper was to assess the effectiveness, side effects, and repercussions in the development of children who have been treated with a KD for more than 2 years. Methods: Observational descriptive study of 26 pediatric patients on a KD, with data collection at baseline, at 3, 6, and 12 months, and then once a year. Number of seizures, type of seizures, anti-seizure drugs, anthropometry, side effects, and alterations in laboratory assessment were monitored. Results: In every assessment, about 60%-75% of the patients experienced a reduction in number of seizures of over 90%, and at least 50% experienced side effects, of which digestive issues, alteration in the lipid metabolism, and hypercalciuria were the most common. The KD significantly affected height after 2 years of treatment. Conclusions: The KD is an effective treatment for drug-resistant epilepsy. Its side effects, although common, are very mild; therefore, this constitutes a very safe treatment for children of all ages. More studies are needed to identify and prevent potential causes of growth retardation in children on the KD.
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Drug-induced nephrolithiasis is a rare condition in children. The involved drugs may be divided into two different categories according to the mechanism involved in calculi formation. The first one includes poorly soluble drugs that favor the crystallization and calculi formation. The second category includes drugs that enhance calculi formation through their metabolic effects. The diagnosis of these specific calculi depends on a detailed medical history, associated comorbidities and the patient’s history of drug consumption. There are several risk factors associated with drug-induced stones, such as high dose of consumed drugs and long duration of treatment. Moreover, there are some specific risk factors, including urinary pH and the amount of fluid consumed by children. There are limited data regarding pediatric lithogenic drugs, and hence, our aim was to perform a comprehensive review of the literature to summarize these drugs and identify the possible mechanisms involved in calculi formation and discuss the management and preventive measures for these calculi.
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Objective: Obesity has become one of the world's biggest issues. This condition has a great impact on several metabolic and chronic diseases. For example, obesity is often accompanied by hyperuricemia or gout. However, few drugs are available for the treatment of obesity. The present study is to evaluate the antiobesity effect of Lactobacillus plantarum GKM3 in high-fat-diet-induced obese rats and whether taking L plantarum GKM3 can effectively reduce uric acid accumulation caused by obesity and ameliorate other harmful factors. Method: Sixty male Wistar rats were divided into five groups as follows: ( 1 ) ND group, fed normal diet; ( 2 ) HFC group, fed AIN93G-based high-fat diet containing 65% solids, 7% soybean oil, and 25% lard; ( 3 ) HFL group, fed AIN93G-based high-fat diet supplemented with 102.7 mg/kg/d L plantarum GKM3; ( 4 ) HFM group, fed AIN93G-based high-fat diet supplemented with 205.4 mg/kg/d L plantarum GKM3; and ( 5 ) HFH group, fed AIN93G-based high-fat diet supplemented with 513.5 mg/kg/d L plantarum GKM3. After 6 weeks, the body, organ, and fat weights; food intake; blood serum levels; and adipocyte size were measured. Results: Results showed that rats fed on the high-fat diet showed more body weight, increased feed efficiency, higher fat deposition, higher total liver weight, elevated serum lipid levels, and increased adipocyte size compared with those on the normal diet. All these effects were reversed by supplementation of L plantarum GKM3. Conclusions: In conclusion, we suggest that the L plantarum GKM3 supplement may have beneficial antiobesity and uric acid-lowering effects.
Article
Aim Ketogenic dietary therapies (KDT) produce anticonvulsant and neuroprotective effects, reduce seizures and improve the cognitive state in patients with epilepsy. Our purpose was to evaluate the effects of KDT in children with refractory epilepsy (effectiveness, side effects, impact on nutritional status and growth). Methods A retrospective and prospective observational descriptive study was conducted in a Spanish tertiary hospital (January 2000 to December 2018). One hundred sixty pediatric patients with epilepsy were treated with KDT (82 males; mean age 5 years 9 months). Seizures, anti-epileptic drugs, anthropometric measures, side effects, and laboratory assessment were monitored baseline and at 3, 6, 12 and 24 months after the onset of KDT. Results In these time intervals, the seizure-free patients were: 13.7, 12.5, 14.4 and 10.6%, respectively, and a reduction of seizures ≥ 50% was achieved in 41.9, 37.5, 28.7 and 16.2%. Side effects were frequent, especially digestive disorders, hypercalciuria, hypoglycemia, hepatic dysfunction and dyslipidemia. Prealbumin, retinol binding protein, vitamin A and magnesium decreased significantly. Height was affected, especially in children below 2 years. Conclusions KDT are effective for refractory epilepsy in children. However, adverse effects are frequent, and it may affect nutritional status and growth.
Article
Urolithiasis is a most common health problem seen amongst most of the population suffering from the recurrence of kidney stones composed of calcium and oxalate crystals. Although the various conventional therapies are available for the urothialisis, the recurrence of kidney stones and the side effects of the drugs cannot be avoided. Increasing incidence of the stone formation associated with inflammation and severe pain, the demand of polyherbal formulations have gained more attention in preventing a suffering from lithiasis. The various herbal plants extract consist of active phytoconstituents like flavonoids, alkaloids, saponins, strerols possesses an bioactivity like diuretic, ant-inflammatory, analgesic and anti-oxidant property. The current review emphasizes the understanding pathology of the stone formation and traditional used medicinal plants as an alternative complementary therapy with less side effects. In addition, the review has also put an effort to summarize mechanisms of various herbal plants in the management of urolithiasis and providing a future investments and direction in developing plant based formulations for urolithiasis.
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Although kidney stones are less common in children than in adults, incidence in children is rising. Kidney stones may lead to significant morbidity in addition to escalating medical costs. Clinical presentation is variable. Bilateral kidney stones in a younger child should prompt work-up for primary hyperoxaluria. Metabolic abnormalities are more frequent in children and can result in frequent stone recurrence. Whole exome sequencing data shows genetic defects in about 30% of stone formers. 24 h urine collection should be conducted when patient receives his usual diet and fluid intake with normal activity. Infrared spectroscopy and X-ray diffraction are used for stone analysis. Urine studies should be delayed by 4–6 wk after stone fragmentation or treatment of any stone related complications. The goal of evaluation is to identify modifiable risk factors for which targeted therapy may be instituted. Primary indications for surgical intervention include pain, infection and obstruction. Extracorporeal shockwave lithotripsy (ESWL), ureteroscopy, and percutaneous nephrolithotomy (PCNL) are most commonly used, and selection is based on stone size, anatomy, composition and anatomy. Advances in technology have allowed a shift to minimally invasive surgeries. Comprehensive management requires multidisciplinary team. Children with kidney stones require long term follow-up with periodic assessment of stone forming activity and ascertaining stone burden. High index of suspicion should be there to diagnose diseases like primary hyperoxaluria, Dent’s disease, renal tubular acidosis (RTA) etc. as these diseases have ramifications on kidney function and growth.
Article
Cancer is the second most prevalent disease worldwide and it presents characteristic hallmarks common to all its types. Within these, it has been described a reprogramming of its energy metabolism, characterized by the preferential use of glucose as energy source in an aerobic glycolysis process. Although this feature may provide adaptive advantages to tumoral cells, it has been described as a weakness that could make them more vulnerable. The ketogenic diet, characterized by high fat and very low carbohydrate intake, aims to eliminate glucose, the main fuel used by cancer cells. Animal studies have described promising results in terms of survival and regression of tumor size; nonetheless, these have failed to replicate in human studies. Furthermore, the ketogenic diet presents possible adverse effects when used in the long term, which should be considered in a vulnerable population such as cancer patients. To date, there is no solid evidence to demonstrate the effectiveness of the ketogenic diet in tumor progression or in overall survival of cancer patients, since most of the studies are observational, uncontrolled, and of short duration. At the moment, we only have limited data to guide us, and at the same time, to promote further study of this approach as a therapeutic opportunity.
Article
Dietary restriction of carbohydrate has been demonstrated to be beneficial for nervous system dysfunction in animal models and may be beneficial for human chronic pain. The purpose of this review is to assess the impact of a low-carbohydrate/ketogenic diet on the adult nervous system function and inflammatory biomarkers to inform nutritional research for chronic pain. An electronic data base search was carried out in May 2021. Publications were screened for prospective research with dietary carbohydrate intake <130g/day and duration of ≥2 weeks. Studies were categorised into those reporting adult neurological outcomes to be extracted for analysis and those reporting other adult research outcomes Both groups were screened again for reported inflammatory biomarkers. From 1548 studies there were 847 studies included. Sixty-four reported neurological outcomes with 83% showing improvement. Five hundred and twenty-three studies had a different research focus (metabolic n=394, sport/performance n=51, cancer n=33, general n=30, neurological with non-neuro outcomes n=12, or gastrointestinal n=4). The second screen identified 63 studies reporting on inflammatory biomarkers with 71% reporting a reduction in inflammation. The overall results suggest a favourable outcome on the nervous system and inflammatory biomarkers from a reduction in dietary carbohydrates. Both nervous system sensitisation and inflammation occur in chronic pain and the results from this review indicate it may be improved by low-carbohydrate nutritional therapy. More clinical trials within this population are required to build on the few human trials that have been done.
Chapter
Urolithiasis is a relatively common problem around the world. In neurologically impaired children and those with cerebral palsy, kidney stones represent an understudied and unique challenge. Children with cerebral palsy are at increased risk of kidney stones due to their limited mobility, associated hypercalciuria, and inability in some to self-regulate their water intake. Some children are exposed to antiepileptic medications that have lithogenic potential, while other children may be receiving a ketogenic diet to help control their epilepsy. Children with cerebral palsy presenting with kidney stones mayCerebral palsywith kidney stonesKidney stones be unable to verbalize their discomfort and do not have a typical clinical presentation of renal colic, which can cause a delay in the diagnosis and treatment. Conservative management includes analgesia, hydration, and medical expulsive therapy. Surgical treatment of kidney stones is considered for larger stones, patients with persistent pain, and presence of urinary tract infection or urinary tract obstruction. The prevention strategies for recurrence of kidney stones include dietary modification and ample fluid administration. In some cases, alkali therapy and administration of thiazide diuretics may also be helpful.
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Very-low-carbohydrate diets or ketogenic diets are frequently used for weight loss in adults and as a therapy for epilepsy in children. The incidence and characteristics of kidney stones in patients on ketogenic diets are not well studied. Methods: A systematic literature search was performed, using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from the databases’ inception through April 2020. Observational studies or clinical trials that provide data on the incidence and/or types of kidney stones in patients on ketogenic diets were included. We applied a random-effects model to estimate the incidence of kidney stones. Results: A total of 36 studies with 2795 patients on ketogenic diets were enrolled. The estimated pooled incidence of kidney stones was 5.9% (95% CI, 4.6–7.6%, I2 = 47%) in patients on ketogenic diets at a mean follow-up time of 3.7 +/− 2.9 years. Subgroup analyses demonstrated the estimated pooled incidence of kidney stones of 5.8% (95% CI, 4.4–7.5%, I2 = 49%) in children and 7.9% (95% CI, 2.8–20.1%, I2 = 29%) in adults, respectively. Within reported studies, 48.7% (95% CI, 33.2–64.6%) of kidney stones were uric stones, 36.5% (95% CI, 10.6–73.6%) were calcium-based (CaOx/CaP) stones, and 27.8% (95% CI, 12.1–51.9%) were mixed uric acid and calcium-based stones, respectively. Conclusions: The estimated incidence of kidney stones in patients on ketogenic diets is 5.9%. Its incidence is approximately 5.8% in children and 7.9% in adults. Uric acid stones are the most prevalent kidney stones in patients on ketogenic diets followed by calcium-based stones. These findings may impact the prevention and clinical management of kidney stones in patients on ketogenic diets.
Article
Resumen Introducción Las terapias dietéticas cetogénicas (TDC) tienen efecto neuroprotector y anticonvulsivante, reducen las crisis epilépticas y mejoran el estado cognitivo en pacientes epilépticos. Nuestro propósito fue evaluar los efectos de las TDC en niños con epilepsia refractaria (eficacia, efectos secundarios, impacto en el estado nutricional y crecimiento). Métodos Se realizó un estudio observacional descriptivo retrospectivo y prospectivo en un hospital terciario español (enero de 2000-diciembre de 2018). Ciento sesenta pacientes pediátricos con epilepsia fueron tratados con TDC (82 varones; edad media 5 años 9 meses). Las convulsiones, los fármacos antiepilépticos, la antropometría, los efectos secundarios y los parámetros analíticos se controlaron al inicio del tratamiento y a los 3, 6, 12 y 24 meses. Resultados En estos intervalos los pacientes libres de crisis fueron: 13,7%, 12,5%, 14,4% y 10,6%, respectivamente, lográndose una reducción de las convulsiones ≥ 50% en el 41,9%, 37,5%, 28,7% y 16,2%. Los efectos secundarios fueron frecuentes, especialmente trastornos digestivos, hipercalciuria, hipoglucemia, disfunción hepática y dislipidemia. La prealbúmina, la proteína de unión al retinol, la vitamina A y el magnesio disminuyeron significativamente. La talla se vio afectada, especialmente en niños menores de 2 años. Conclusiones Las TDC son efectivas para la epilepsia refractaria infantil. Sin embargo, los efectos adversos son frecuentes y pueden afectar al estado nutricional y al crecimiento.
Chapter
Although many medications are currently available in the prevention and treatment of migraines, lifestyle modifications are still recommended to modify symptoms. The role of dietary and nutritional factors in causing as well as treating headache disorders has been widely studied. In this chapter, we review research related to common food triggers and IgG food sensitivity testing to prescribe an elimination diet. Prospective studies on various types of comprehensive diets such as the ketogenic diet, the modified Atkins diet, low glycemic index diet, and low-fat diet will also be summarized. Comprehensive diets do not require the exclusion of food triggers but the quantitative adjustment of micronutrients, protein, carbohydrates, and fats. Comorbid conditions such as obesity, irritable bowel syndrome, and celiac disease will be also examined in the context of migraines and studies on condition-specific dietary modifications evaluated. Finally, brain energy metabolism in migraineurs and its relationship to nutrient deficiencies will also be discussed in conjunction with the use of nutraceuticals and phytomedicine to improve migraine symptoms.
Article
Ketogenic diet (KD) is widely used for drug-resistant epilepsy (DRE). The study was designed to evaluate one of the risk factors for development of renal calculi with KD. Twenty patients with DRE on Modified Atkins diet (MAD) were subjected to full history and laboratory investigations, including microscopic urine analysis, urinary calcium after overnight fasting, and calcium/creatinine ratio, as well as pelviabdominal ultrasound. Frequency and severity of seizures assessed by Chalfont severity score were recorded. All assessment measures were repeated after 3 and 6 months of KD therapy. There were significant reductions in both frequency and severity of seizures, yet 2 patients (10%) developed renal stones after 6 months on KD. Gross hematuria was reported in 1 of those 2 patients (50%), but microscopic hematuria was detected in both patients. The urine calcium and the urine calcium/creatinine ratio were elevated in both patients having renal calculi after 6 months. KD increases the risk of renal stones with hypercalciuria among the causes. We recommend initiation of prophylactic measures once KD is commenced by maximizing fluid intake and urine alkalinization with regular urinary studies including calcium/creatinine ratio and renal ultrasound for patients with symptoms. KD has been increasingly used in epilepsy management and beyond. The potential side effects of such diet should be highlighted while valuing the merits. KD increases the risk of renal stones because of hypercalciuria among other causes. We recommend initiation of prophylactic measures once KD is commenced by maximizing fluid intake and urine alkalinization with estimation of urinary calcium/creatinine ratio and renal ultrasound in patients with relevant symptoms.
Article
Previously, medical diets, including the ketogenic and gluten-free diets, were rare outside of their target population. Subspecialists more familiar with risks and benefits often managed nutrition and any associated shortcomings. With more patients electively following a gluten-free or ketogenic diet for nonmedical needs, as well as the increasing prevalence of vegetarian diets, general pediatricians are seeing more followers of restrictive diets with general well-child care. Increasingly, general pediatricians can be the first provider to witness presenting signs or symptoms of associated nutritional deficiencies. This article reviews signs and symptoms of possible nutrient deficiencies seen with the vegetarian, ketogenic, and gluten-free diets.
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Several studies have demonstrated the effectiveness of ketogenic diet (KD) on refractory epilepsies, especially in children. In this category of patients, a strong collaboration between the healthcare providers and the full engagement of parents is required. The regimen is significantly effective for different types of epilepsy that are resistant to medical treatment. It can also be used as a first-line treatment, given its well tolerance. Treatment has been rolled out for children but research into its use in adults is promising. There is no international or national protocol, the implementation of this diet follows a rigor being specific to every ketogenic center. The understanding of the underlying mechanisms is not well elucidated, it would make it possible to optimize the clinical use of the ketogenic diet, but also to develop novel antiepileptic treatments. This article aims to review the different variants of KD and their prescription terms in children with intractable epilepsy. Keywords: drug-resistant epilepsy, ketogenic diet, children, Modified Atkins Diet.
Article
Full-text available
Several studies have demonstrated the effectiveness of ketogenic diet (KD) on refractory epilepsies, especially in children. In this category of patients, a strong collaboration between the healthcare providers and the full engagement of parents is required. The regimen is significantly effective for different types of epilepsy that are resistant to medical treatment. It can also be used as a first-line treatment, given its well tolerance. Treatment has been rolled out for children but research into its use in adults is promising. There is no international or national protocol, the implementation of this diet follows a rigor being specific to every ketogenic center. The understanding of the underlying mechanisms is not well elucidated, it would make it possible to optimize the clinical use of the ketogenic diet, but also to develop novel antiepileptic treatments. This article aims to review the different variants of KD and their prescription terms in children with intractable epilepsy.
Article
Full-text available
To provide a review of the mechanism of action, clinical efficacy, adverse effects, drug interactions, and therapeutic considerations associated with the use of a ketogenic diet to manage patients with intractable seizures. A MEDLINE search from January 1966 to the present and relevant articles from journals were reviewed. The ketogenic diet has been used as a treatment modality since the early 1920s to control intractable seizures. The exact mechanism of action is unknown. Overall, uncontrolled clinical studies have reported that approximately one-third of patients with intractable seizures have become seizure-free on the ketogenic diet. Common adverse events attributed to the diet include dehydration, gastrointestinal symptoms, hypoglycemia, as well as carnitine and vitamin deficiencies. Cognitive effects, hyperlipidemia, impaired neutrophil function, urolithiasis, optic neuropathy, osteoporosis, and protein deficiency may also occur in some patients. Carbohydrate content and drug formulation in the selection of medications while on the diet are important. Acetazolamide, phenobarbital, and valproic acid have been reported to interact with the ketogenic diet. Medications that cause carnitine deficiency or influence carbohydrate metabolism should also be used with caution. The carbohydrate content of drugs in various therapeutic classes is presented to aid in the selection of the most appropriate drug and formulation for patients on the ketogenic diet. The success of the diet in controlling intractable seizures is related to the patient's close adherence to the diet. Minimizing carbohydrate ingestion from medications along with a multidisciplinary team approach to the selection and monitoring of the diet are important to the success of the ketogenic diet in controlling seizures. The ketogenic diet has shown promising results in controlling intractable seizures; however, carefully controlled clinical trials are needed to better assess the efficacy of the diet during its use and after discontinuation.
Article
Long-term outcomes of the ketogenic diet in the treatment of epilepsy have not previously been reported. A retrospective chart review of children treated with the ketogenic diet for more than 6 years at the Johns Hopkins Hospital was performed. The response was documented at clinic visits and by telephone contacts; laboratory studies were obtained approximately every 6 to 12 months. Satisfaction and tolerability were assessed by means of a brief parental telephone questionnaire. In all, 28 patients (15 males, 13 females), currently aged 7 to 23 years, were identified. The median baseline seizure frequency per week at diet onset was 630 (range 1–1400). Diet duration ranged from 6 to 12 years; 19 remain on the diet currently. After 6 years or more, 24 children experienced a more than 90% decrease in seizures, and 22 parents reported satisfaction with the diet's efficacy. Ten children were at less than the 10th centile for height at diet initiation; this number increased to 23 at the most recent follow-up (p=0.001). Kidney stones occurred in seven children and skeletal fractures in six. After 6 years or more the mean cholesterol level was 201mg/dl, high-density lipoprotein was 54mg/dl, low-density lipoprotein was 129mg/dl, and triglycerides were 97mg/dl. Efficacy and overall tolerability for children are maintained after prolonged use of the ketogenic diet. However, side effects, such as slowed growth, kidney stones, and fractures, should be monitored closely.
Medicine is both an art and a science. This volume is a compendium of 35 years experience with over 20,000 seizure patients. It is our good fortune that the senior author has been a student of epilepsy over this long period; his vast experience has been carefully documented, analyzed, and interpreted in this book. He recapitulates and updates those portions which have appeared in earlier publications including extensive discussions of petit mal, grand mal, and psychomotor epilepsy. Experience with febrile convulsions, now extending over 25 years, gives the reader a lucid perspective and rationale for management. Three studies are summarized, one based on 622 patients. An equally impressive discussion of breath-holding spells draws upon experience with 384 cases. Dr. Livingston has long been identified with efforts to treat the "whole patient." This book is an important contribution to "physicians, nurses, psychologists, social workers, school teachers, vocational rehabilitation counselors, employers and
Article
The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of children with difficult to control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. This prospective study sought to determine the ketogenic diet's effectiveness and tolerability in children refractory to today's medications. One hundred fifty consecutive children, ages 1 to 16 years, virtually all of whom continued to have more than two seizures per week despite adequate therapy with at least two anticonvulsant medications, were prospectively enrolled in this study, treated with the ketogenic diet, and followed for a minimum of 1 year. Seizure frequency was tabulated from patients' daily seizure calendars and seizure reduction calculated as percentage of baseline frequency. Adverse events and reasons for diet discontinuation were recorded. The children (mean age, 5.3 years), averaged 410 seizures per month before the diet, despite an exposure to a mean of 6.2 antiepileptic medications. Three months after diet initiation, 83% of those starting remained on the diet and 34% had >90% decrease in seizures. At 6 months, 71% still remained on the diet and 32% had a >90% decrease in seizures. At 1 year, 55% remained on the diet and 27% had a >90% decrease in seizure frequency. Most of those discontinuing the diet did so because it was either insufficiently effective or too restrictive. Seven percent stopped because of intercurrent illness. The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.
Article
The ketogenic diet has been used for treating seizure disorders for more than 70 years. Nephrolithiasis is a known complication of this diet with a reported stone rate as high as 10% but there is sparse literature detailing the nature and treatment of these stones. We report on 4 children with nephrolithiasis on this diet. We describe stone treatment and analysis as well as metabolic and urine abnormalities in 4 children with nephrolithiasis on the ketogenic diet who presented to our institution. All patients were treated with shock wave lithotripsy, fluid liberalization and oral citrate. One child was ultimately withdrawn from the diet due to persistent stone formation. Analysis revealed 3 calcium and 1 ammonium urate stones. Three patients had hypercalciuria, 2 elevated urinary uric acid and 1 hypocitruria. Serum studies revealed acidosis in 3 cases. The ketogenic diet induces several metabolic abnormalities that increase the propensity for stone formation. Urologists should be aware of this potential complication. Fluid liberalization and bicitrate are recommended as prophylaxis.
Article
Kidney stones have been associated with use of the ketogenic diet in children with refractory seizure disorders. We performed a case-control study examining risk factors for the development of stones on the ketogenic diet, and prospectively followed children initiating the ketogenic diet to evaluate the incidence of urolithiasis. Clinical characteristics of 18 children presenting with stones (8 uric acid stones, 6 mixed calcium/uric acid stones, 1 calcium oxalate/phosphate stone, 3 stones not evaluated) were compared with characteristics of non-stone-forming children initiating the ketogenic diet at Johns Hopkins since July 1996. Since July 1996, 112 children initiating the ketogenic diet have been followed for development of stones. Follow-up times on the diet range from 2 months to 2.5 years. Of 112 children, 6 have developed stones (3 uric acid, 3 mixed calcium/uric acid stones) (0.8 children developing stones/ 100 patient-months at risk). Comparisons of children presenting with stones on the ketogenic diet with characteristics of the entire cohort initiating the ketogenic diet suggest younger age at diet initiation and hypercalciuria are risk factors for the development of stones. Prospective evaluation of children initiating the ketogenic diet revealed that almost 40% of patients had elevated fasting urine calcium: creatinine ratios at baseline; this increased to 75% after 6 months on the diet. Median urine pH was 5.5 at diet initiation, and remained at 6.0 thereafter. In a subset of patients tested, urinary citrate excretion fell from a mean of 252 mg/24 h pre diet initiation to 52 mg/24 h while on the diet. Uric acid excretion remained normal. Patients maintained on the ketogenic diet often have evidence of hypercalciuria, acid urine, and low urinary citrate excretion. In conjunction with low fluid intake, these patients are at high risk for both uric acid and calcium stone formation.
Article
Because carbonic anhydrase inhibitors and the ketogenic diet are each known risk factors for kidney stones, simultaneous use of these therapies has been discouraged. The objective of this study was to establish the prevalence of nephrolithiasis in children in this combination-therapy population. Since 1996, 301 children have been started on the ketogenic diet at our institution. A retrospective cohort study of renal calculi in ketogenic diet patients was performed to evaluate the increased risk with combined use of a carbonic anhydrase inhibitor. In 15 (6.7%) of 221 children on the ketogenic diet without the use of carbonic anhydrase inhibitors, stones developed. In five (6.3%) of the 80 children on the diet in combination with topiramate or zonisamide, stones developed. There was no difference between these two groups (p = 0.82). No child was treated with either acetazolamide or more than one carbonic anhydrase inhibitor simultaneously. Prior ketogenic diet duration was shorter (10.4 vs. 22.4 months; p = 0.03), and more children had either a family history of renal stones or significant urologic abnormalities (80 vs. 27%; p = 0.04) in the combination-therapy group. The combined use of carbonic anhydrase inhibitors and the ketogenic diet does not increase the risk of kidney stones. We recommend that all patients treated with combination therapy should be treated with increased hydration. Urine alkalinization should be considered for children with previous renal abnormalities, family histories of kidney stones, hematuria, or elevated urine calcium-to-creatinine ratios. If renal stones are found, we advocate discontinuation of the carbonic anhydrase inhibitor.
Article
This study was undertaken to evaluate the exact limitations of the ketogenic diet (KD) and to collect data on the prevention and management of its risks. Patients (129) who were on the KD from July 1995 to October 2001 at our epilepsy center were assessed in the study. Early-onset (within 4 weeks of the commencement of the KD until stabilization) and late-onset complications (occurring after 4 weeks) were reviewed. The most common early-onset complication was dehydration, especially in patients who started the KD with initial fasting. Gastrointestinal (GI) disturbances, such as nausea/vomiting, diarrhea, and constipation, also were frequently noted, sometimes associated with gastritis and fat intolerance. Other early-onset complications, in order of frequency, were hypertriglyceridemia, transient hyperuricemia, hypercholesterolemia, various infectious diseases, symptomatic hypoglycemia, hypoproteinemia, hypomagnesemia, repetitive hyponatremia, low concentrations of high-density lipoprotein, lipoid pneumonia due to aspiration, hepatitis, acute pancreatitis, and persistent metabolic acidosis. Late-onset complications also included osteopenia, renal stones, cardiomyopathy, secondary hypocarnitinemia, and iron-deficiency anemia. Most early- and late-onset complications were transient and successfully managed by careful follow-up and conservative strategies. However, 22 (17.1%) patients ceased the KD because of various kinds of serious complications, and four (3.1%) patients died during the KD, two of sepsis, one of cardiomyopathy, and one of lipoid pneumonia. Most complications of the KD are transient and can be managed easily with various conservative treatments. However, life-threatening complications should be monitored closely during follow-up.
Article
Although the ketogenic diet has been used for more than 80 years, the optimal methods of initiating the diet and its maintenance have not been clearly defined. This retrospective study was performed to review our experience with initiation of the ketogenic diet in the outpatient and inpatient settings and maintenance of the diet without fluid or caloric restriction. We analyzed 54 patients who had medically intractable epilepsy of whom 44% manifested some degree of mental retardation, 80% had multiple seizure types, and failed on average 4.8 antiepileptic drugs. Forty-four patients underwent induction of the ketogenic diet on an outpatient basis and 21 as inpatients. Three patients in each group were fasted at the initiation of the diet. No significant differences were observed with regard to seizure control in that 62% and 71% had greater than 50% improvement in the outpatient and inpatient groups, respectively. Both groups manifested improvement in alertness and social interaction. The efficacy of a ketogenic diet in the symptomatic epilepsies was confirmed, and benefit for medically refractory childhood absence epilepsy was documented. We conclude that a prospective, randomized trial is necessary to compare outpatient vs inpatient initiation of the ketogenic diet and the utility of fluid and caloric restriction.
Article
The ketogenic diet is a low-carbohydrate, adequate-protein, and high-fat diet with a long history of use for the treatment of intractable seizures in children. This dietary therapy has been enjoying increasing popularity in recent years, despite the availability of increasing numbers of new antiepileptic drugs and surgical treatments. The authors review the history of the ketogenic diet, the traditional protocol in initiating it, possible mechanisms of its action, evidence for efficacy, and side effects. In addition, they highlight some of the areas of active research in this field as well as future directions and unanswered questions. The ketogenic diet is an efficacious and relatively safe treatment of intractable seizures. Despite its long history, however, much remains unknown about the diet, including its mechanisms of action, the optimal protocol, and the full range of its applicability. Investigations of the diet are providing new insight into the mechanisms behind seizures and epilepsy itself, as well as possible new therapies.
Article
The Atkins diet may induce ketosis as does the ketogenic diet, without restrictions on calories, fluids, protein, or need for an inpatient fast and admission. Our objective was to evaluate the efficacy and tolerability of a modified Atkins diet for intractable childhood epilepsy. Twenty children were treated prospectively in a hospital-based ambulatory clinic from September 2003 to May 2005. Children aged 3-18 years, with at least three seizures per week, who had been treated with at least two anticonvulsants, were enrolled and received the diet over a 6-month period. Carbohydrates were initially limited to 10 g/day, and fats were encouraged. Parents measured urinary ketones semiweekly and recorded seizures daily. All children received vitamin and calcium supplementation. In all children, at least moderate urinary ketosis developed within 4 days (mean, 1.9). Sixteen (80%) completed the 6-month study; 14 chose to remain on the diet afterward. At 6 months, 13 (65%) had >50% improvement, and seven (35%) had >90% improvement (four were seizure free). Mean seizure frequency after 6 months was 40 per week (p = 0.005). Over a 6-month period, mean serum blood urea nitrogen increased from 12 to 17 mg/dl (p = 0.01); creatinine was unchanged. Cholesterol increased from 192 to 221 mg/dl, (p = 0.06). Weight did not change significantly (34.0-33.7 kg); only six children lost weight. A stable body mass index over time correlated with >90% improvement (p = 0.004). A modified Atkins diet is an effective and well-tolerated therapy for intractable pediatric epilepsy.
A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy All rights reserved. Not for commercial use or unauthorized distribution
  • Eh Kossoff
  • Jr Mcgrogan
  • Rm Bluml
  • Dj Pillas
  • Je Rubenstein
  • Vining
Kossoff EH, McGrogan JR, Bluml RM, Pillas DJ, Rubenstein JE, Vining EP. A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy. Epilepsia. 2006;47: 421-424. 378 Journal of Child Neurology / Vol. 22, No. 4, April 2007 © 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at WELCH MEDICAL LIBRARY on July 2, 2007 http://jcn.sagepub.com Downloaded from
  • Da Bushinsky
  • Nephrolithiasis
Bushinsky DA. Nephrolithiasis. J Am Soc Nephrol. 1998;9:917-924.