Polysaccharides derived from plant foods are major components of the human diet, with limited contributions of related components from fungal and algal sources. In particular, starch and other ...storage carbohydrates are the major sources of energy in all diets, while cell wall polysaccharides are the major components of dietary fiber. We review the role of these components in the human diet, including their structure and distribution, their modification during food processing and effects on functional properties, their behavior in the gastrointestinal tract, and their contribution to healthy diets.
Background
Ketogenic diets (KDs) are high in fat and low in carbohydrates and have been suggested to reduce seizure frequency in people with epilepsy. Such diets may be beneficial for children with ...drug‐resistant epilepsy.
This is an update of a review first published in 2003, and last updated in 2018.
Objectives
To assess the effects of ketogenic diets for people with drug‐resistant epilepsy.
Search methods
For this update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 26 April 2019) on 29 April 2019. The Cochrane Register of Studies includes the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and randomised controlled trials (RCTs) from Embase, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We imposed no language restrictions. We checked the reference lists of retrieved studies for additional relevant studies.
Selection criteria
RCTs or quasi‐RCTs of KDs for people of any age with drug‐resistant epilepsy.
Data collection and analysis
Two review authors independently applied predefined criteria to extract data and evaluated study quality. We assessed the outcomes: seizure freedom, seizure reduction (50% or greater reduction in seizure frequency), adverse effects, cognition and behaviour, quality of life, and attrition rate. We incorporated a meta‐analysis. We utilised an intention‐to‐treat (ITT) population for all primary analyses. We presented the results as risk ratios (RRs) with 95% confidence intervals (CIs).
Main results
We identified 13 studies with 932 participants; 711 children (4 months to 18 years) and 221 adults (16 years and over).
We assessed all 13 studies to be at high risk of performance and detection bias, due to lack of blinding. Assessments varied from low to high risk of bias for all other domains. We rated the evidence for all outcomes as low to very low certainty.
Ketogenic diets versus usual care for children
Seizure freedom (RR 3.16, 95% CI 1.20 to 8.35; P = 0.02; 4 studies, 385 participants; very low‐certainty evidence) and seizure reduction (RR 5.80, 95% CI 3.48 to 9.65; P < 0.001; 4 studies, 385 participants; low‐certainty evidence) favoured KDs (including: classic KD, medium‐chain triglyceride (MCT) KD combined, MCT KD only, simplified modified Atkins diet (MAD) compared to usual care for children. We are not confident that these estimated effects are accurate. The most commonly reported adverse effects were vomiting, constipation and diarrhoea for both the intervention and usual care group, but the true effect could be substantially different (low‐certainty evidence).
Ketogenic diet versus usual care for adults
In adults, no participants experienced seizure freedom. Seizure reduction favoured KDs (MAD only) over usual care but, again, we are not confident that the effect estimated is accurate (RR 5.03, 95% CI 0.26 to 97.68; P = 0.29; 2 studies, 141 participants; very low‐certainty evidence). Adults receiving MAD most commonly reported vomiting, constipation and diarrhoea (very low‐certainty evidence). One study reported a reduction in body mass index (BMI) plus increased cholesterol in the MAD group. The other reported weight loss. The true effect could be substantially different to that reported.
Ketogenic diet versus ketogenic diet for children
Up to 55% of children achieved seizure freedom with a classical 4:1 KD after three months whilst up to 85% of children achieved seizure reduction (very low‐certainty evidence). One trial reported a greater incidence of seizure reduction with gradual‐onset KD, as opposed to fasting‐onset KD. Up to 25% of children were seizure free with MAD and up to 60% achieved seizure reduction.
Up to 25% of children became seizure free with MAD and up to 60% experienced seizure reduction. One study used a simplified MAD (sMAD) and reported that 15% of children gained seizure freedom rates and 56% achieved seizure reduction. We judged all the evidence described as very low certainty, thus we are very unsure whether the results are accurate.
The most commonly reported adverse effects were vomiting, constipation and diarrhoea (5 studies, very low‐certainty evidence). Two studies reported weight loss. One stated that weight loss and gastrointestinal disturbances were more frequent, with 4:1 versus 3:1 KD, whilst one reported no difference in weight loss with 20 mg/d versus 10 mg/d carbohydrates. In one study, there was a higher incidence of hypercalcuria amongst children receiving classic KD compared to MAD. All effects described are unlikely to be accurate.
Ketogenic diet versus ketogenic diet for adults
One study randomised 80 adults (aged 18 years and over) to either MAD plus KetoCal during the first month with MAD alone for the second month, or MAD alone for the first month followed by MAD plus KetoCal for the second month. No adults achieved seizure freedom. More adults achieved seizure reduction at one month with MAD alone (42.5%) compared to MAD plus KetoCal (32.5%), however, by three months only 10% of adults in both groups maintained seizure reduction. The evidence for both outcomes was of very low certainty; we are very uncertain whether the effects are accurate.
Constipation was more frequently reported in the MAD plus KetoCal group (17.5%) compared to the MAD only group (5%) (1 study, very low‐certainty evidence). Diarrhoea and increase/change in seizure pattern/semiology were also commonly reported (17.5% to 20% of participants). The true effects of the diets could be substantially different to that reported.
Authors' conclusions
The evidence suggests that KDs could demonstrate effectiveness in children with drug‐resistant epilepsy, however, the evidence for the use of KDs in adults remains uncertain. We identified a limited number of studies which all had small sample sizes. Due to the associated risk of bias and imprecision caused by small study populations, the evidence for the use of KDs was of low to very low certainty.
More palatable but related diets, such as the MAD, may have a similar effect on seizure control as the classical KD, but could be associated with fewer adverse effects. This assumption requires more investigation. For people who have drug‐resistant epilepsy or who are unsuitable for surgical intervention, KDs remain a valid option. Further research is required, particularly for adults with drug‐resistant epilepsy.
A direct approach to beta-iodophosphonates and beta-iodophosphine oxides from 2,3-dideoxy-3-phosphoryl carbohydrate derivatives has been achieved by using the anomeric alkoxyl radical ...1,2-fragmentation protocol. The reaction has been conducted on carbohydrate derivatives under mild conditions with (diacetoxyiodo)benzene and molecular iodine. Subsequent dehydroiodination afforded the corresponding vinylphosphonates and vinylphosphine oxides.
There has been much concern regarding the role of dietary fructose in the development of metabolic diseases. This concern arises from the continuous increase in fructose (and total added caloric ...sweeteners consumption) in recent decades, and from the increased use of high-fructose corn syrup (HFCS) as a sweetener. A large body of evidence shows that a high-fructose diet leads to the development of obesity, diabetes, and dyslipidemia in rodents. In humans, fructose has long been known to increase plasma triglyceride concentrations. In addition, when ingested in large amounts as part of a hypercaloric diet, it can cause hepatic insulin resistance, increased total and visceral fat mass, and accumulation of ectopic fat in the liver and skeletal muscle. These early effects may be instrumental in causing, in the long run, the development of the metabolic syndrome. There is however only limited evidence that fructose per se, when consumed in moderate amounts, has deleterious effects. Several effects of a high-fructose diet in humans can be observed with high-fat or high-glucose diets as well, suggesting that an excess caloric intake may be the main factor involved in the development of the metabolic syndrome. The major source of fructose in our diet is with sweetened beverages (and with other products in which caloric sweeteners have been added). The progressive replacement of sucrose by HFCS is however unlikely to be directly involved in the epidemy of metabolic disease, because HFCS appears to have basically the same metabolic effects as sucrose. Consumption of sweetened beverages is however clearly associated with excess calorie intake, and an increased risk of diabetes and cardiovascular diseases through an increase in body weight. This has led to the recommendation to limit the daily intake of sugar calories.
The carbohydrate-insulin model of obesity posits that habitual consumption of a high-carbohydrate diet sequesters fat within adipose tissue because of hyperinsulinemia and results in adaptive ...suppression of energy expenditure (EE). Therefore, isocaloric exchange of dietary carbohydrate for fat is predicted to result in increased EE, increased fat oxidation, and loss of body fat. In contrast, a more conventional view that "a calorie is a calorie" predicts that isocaloric variations in dietary carbohydrate and fat will have no physiologically important effects on EE or body fat.
We investigated whether an isocaloric low-carbohydrate ketogenic diet (KD) is associated with changes in EE, respiratory quotient (RQ), and body composition.
Seventeen overweight or obese men were admitted to metabolic wards, where they consumed a high-carbohydrate baseline diet (BD) for 4 wk followed by 4 wk of an isocaloric KD with clamped protein. Subjects spent 2 consecutive days each week residing in metabolic chambers to measure changes in EE (EEchamber), sleeping EE (SEE), and RQ. Body composition changes were measured by dual-energy X-ray absorptiometry. Average EE during the final 2 wk of the BD and KD periods was measured by doubly labeled water (EEDLW).
Subjects lost weight and body fat throughout the study corresponding to an overall negative energy balance of ∼300 kcal/d. Compared with BD, the KD coincided with increased EEchamber (57 ± 13 kcal/d, P = 0.0004) and SEE (89 ± 14 kcal/d, P < 0.0001) and decreased RQ (-0.111 ± 0.003, P < 0.0001). EEDLW increased by 151 ± 63 kcal/d (P = 0.03). Body fat loss slowed during the KD and coincided with increased protein utilization and loss of fat-free mass.
The isocaloric KD was not accompanied by increased body fat loss but was associated with relatively small increases in EE that were near the limits of detection with the use of state-of-the-art technology. This trial was registered at clinicaltrials.gov as NCT01967563.
•Dramatic glycosylation changes occur with carcinogenesis and cancer progression.•Tumor-associated carbohydrate antigens are candidates for targeting by antibodies.•Antibodies can envelop the whole ...epitope to recognize Lewis carbohydrates.•Lewis epitopes display similar and relatively rigid three-dimensional structures.•Glycan structural data may be useful for the design of new antibody therapeutics.
Monoclonal antibodies represent the most successful class of biopharmaceuticals for the treatment of cancer. Mechanisms of action of therapeutic antibodies are very diverse and reflect their ability to engage in antibody-dependent effector mechanisms, internalize to deliver cytotoxic payloads, and display direct effects on cells by lysis or by modulating the biological pathways of their target antigens. Importantly, one of the universal changes in cancer is glycosylation and carbohydrate-binding antibodies can be produced to selectively recognize tumor cells over normal tissues. A promising group of cell surface antibody targets consists of carbohydrates presented as glycolipids or glycoproteins. In this review, we outline the basic principles of antibody-based targeting of carbohydrate antigens in cancer. We also present a detailed structural view of antibody recognition and the conformational properties of a series of related tissue-blood group (Lewis) carbohydrates that are being pursued as potential targets of cancer immunotherapy.
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