1.
Role of Ketogenic Diets in Neurodegenerative Diseases (Alzheimer's Disease and Parkinson's Disease).
Włodarek, D
Nutrients. 2019;11(1)
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The ketogenic diet (KD) is characterised by a low-carbohydrate, high-fat content that induces a fasting-like state in the body. The KD has been used clinically for children with epilepsy and recent studies have shed light on potential neuro-protective effects. The aim of this systematic review was to evaluate the role of the KD in prevention of Parkinson's disease (PD) and Alzheimer's disease (AD). Among the existing literature, there is very limited data on long-term application of the KD in patients with neurodegenerative disease. The research using animal models or in-vitro models look very promising however the use of KD in elderly adults with neurodegenerative disease is very complex. Based on these results, the authors conclude there is a need for further research to evaluate the suitability of KD for patients with AD or PD.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The studies into the effectiveness of ketogenic diets in neurodegenerative diseases tend to be too small and heterogeneous to draw firm conclusions.
- Specific elements of ketogenic diets may be useful for individual cases, however healthcare practitioners are encouraged to take an individualised approach to the clinical management of neurodegenerative conditions, drawing from different approaches that suit the individual living with the disease.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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X
C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
The role of ketogenic diets for the management of a number of conditions has become a discussion subject, not only for scientists and clinicians, but also for the general public, however the evidence of their effectiveness in neurodegenerative diseases is patchy. Studies are either too small to be good enough to draw conclusions from, or the interventions are too mixed / heterogeneous to be able to attribute any potential benefit to the ketogenic dietary component alone. This highlights the need to take an individualised approach to the clinical management of neurodegenerative conditions, drawing from different approaches that suit the individual living with the disease.
Clinical practice applications:
Specific elements of ketogenic diets might be useful for individual cases. However clinicians should be encouraged to draw from a wide array of approaches and not be limited to one single method when it comes to dealing with complex conditions such as Alzheimer's and Parkinson's Disease. Patient-centred care where dietary recommendations revolve around the individual's needs - based on biochemical markers but also on subjective experience of their own quality of life / wellbeing - should be the basis upon which to tailor nutrition programmes that support those living with neurodegenerative conditions.
Considerations for future research:
Good methodological quality studies with placebo / control groups and clear outcomes are needed in order to contribute to the evidence base of the potential role of ketogenic diets in the support of patients living with neurodegenerative conditions.
Abstract
The goal of this review was to assess the effectiveness of ketogenic diets on the therapy of neurodegenerative diseases. The ketogenic diet is a low-carbohydrate and fat-rich diet. Its implementation has a fasting-like effect, which brings the body into a state of ketosis. The ketogenic diet has, for almost 100 years, been used in the therapy of drug-resistant epilepsy, but current studies indicate possible neuroprotective effects. Thus far, only a few studies have evaluated the role of the ketogenic diet in the prevention of Parkinson's disease (PD) and Alzheimer's disease (AD). Single studies with human participants have demonstrated a reduction of disease symptoms after application. The application of the ketogenic diet to elderly people, however, raises certain concerns. Persons with neurodegenerative diseases are at risk of malnutrition, while food intake reduction is associated with disease symptoms. In turn, the ketogenic diet leads to a reduced appetite; it is not attractive from an organoleptic point of view, and may be accompanied by side effects of the gastrointestinal system. All this may lead to further lowering of consumed food portions by elderly persons with neurodegenerative diseases and, in consequence, to further reduction in the supply of nutrients provided by the diet. Neither data on the long-term application of the ketogenic diet in patients with neurodegenerative disease or data on its effects on disease symptoms are available. Further research is needed to evaluate the suitability of the ketogenic diet in the therapy of AD- or PD-affected persons.
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Chronic Ketogenic Low Carbohydrate High Fat Diet Has Minimal Effects on Acid-Base Status in Elite Athletes.
Carr, AJ, Sharma, AP, Ross, ML, Welvaert, M, Slater, GJ, Burke, LM
Nutrients. 2018;10(2)
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The low-fat, high-carbohydrate ketogenic diet has recently been applied to the context of elite athletes to observe potential impact on performance and metabolism during exercise and rest. The aim to this study was to assess the effect of a long-term ketogenic diet on the acid-base status in elite athletes, particularly investigating whether sustained diet change caused alterations in overall acid production. Twenty-one athletes were assigned to a high carbohydrate diet, low carbohydrate diet and periodised carbohydrate availability diet for three sustained weeks. Acid-base balance was measured via blood samples at baseline and post-intervention. The main finding of this study was that a sustained ketogenic diet had no influence of acid-base status. Based on these results, the authors conclude that long-term manipulation of macronutrient intake is unlikely to influence acid-base status in this population. It is also noted that elite athletes may have an increased buffering capacity compared with the general population, and that further research should be done in different participant populations.
Abstract
Although short (up to 3 days) exposure to major shifts in macronutrient intake appears to alter acid-base status, the effects of sustained (>1 week) interventions in elite athletes has not been determined. Using a non-randomized, parallel design, we examined the effect of adaptations to 21 days of a ketogenic low carbohydrate high fat (LCHF) or periodized carbohydrate (PCHO) diet on pre- and post-exercise blood pH, and concentrations of bicarbonate (HCO₃-) and lactate (La-) in comparison to a high carbohydrate (HCHO) control. Twenty-four (17 male and 7 female) elite-level race walkers completed 21 days of either LCHF (n = 9), PCHO (n = 7), or HCHO (n = 8) under controlled diet and training conditions. At baseline and post-intervention, blood pH, blood [HCO₃-], and blood [La-] were measured before and after a graded exercise test. Net endogenous acid production (NEAP) over the previous 48-72 h was also calculated from monitored dietary intake. LCHF was not associated with significant differences in blood pH, [HCO₃-], or [La-], compared with the HCHO diet pre- or post-exercise, despite a significantly higher NEAP (mEq·day-1) (95% CI = [10.44; 36.04]). Our results indicate that chronic dietary interventions are unlikely to influence acid-base status in elite athletes, which may be due to pre-existing training adaptations, such as an enhanced buffering capacity, or the actions of respiratory and renal pathways, which have a greater influence on regulation of acid-base status than nutritional intake.
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Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus.
Cervenka, MC, Hocker, S, Koenig, M, Bar, B, Henry-Barron, B, Kossoff, EH, Hartman, AL, Probasco, JC, Benavides, DR, Venkatesan, A, et al
Neurology. 2017;88(10):938-943
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Superrefractory status epilepticus (SRSE) is a neurologic emergency that persists despite anti-seizure medication. The ketogenic diet (KD) has been shown to be successful for treating epilepsy and recent retrospective studies suggest KD may be effective for treating SRSE. The aim of this clinical trial was to investigate the feasibility, safety and efficacy of a ketogenic diet on SRSE in adults. After screening, this prospective multi-centre study enrolled 15 participants with SRSE. Participants received a classic ketogenic diet via gastronomy tube. Of the 14 participants whom completed KD treatment SRSE resolved in 11 participants. Five patients ultimately died. This study found KD is feasible in adults with SRSE, and further randomised controlled trials are required to establish comparative safety and efficacy.
Abstract
OBJECTIVE To investigate the feasibility, safety, and efficacy of a ketogenic diet (KD) for superrefractory status epilepticus (SRSE) in adults. METHODS We performed a prospective multicenter study of patients 18 to 80 years of age with SRSE treated with a KD treatment algorithm. The primary outcome measure was significant urine and serum ketone body production as a biomarker of feasibility. Secondary measures included resolution of SRSE, disposition at discharge, KD-related side effects, and long-term outcomes. RESULTS Twenty-four adults were screened for participation at 5 medical centers, and 15 were enrolled and treated with a classic KD via gastrostomy tube for SRSE. Median age was 47 years (interquartile range [IQR] 30 years), and 5 (33%) were male. Median number of antiseizure drugs used before KD was 8 (IQR 7), and median duration of SRSE before KD initiation was 10 days (IQR 7 days). KD treatment delays resulted from intravenous propofol use, ileus, and initial care received at a nonparticipating center. All patients achieved ketosis in a median of 2 days (IQR 1 day) on KD. Fourteen patients completed KD treatment, and SRSE resolved in 11 (79%; 73% of all patients enrolled). Side effects included metabolic acidosis, hyperlipidemia, constipation, hypoglycemia, hyponatremia, and weight loss. Five patients (33%) ultimately died. CONCLUSIONS KD is feasible in adults with SRSE and may be safe and effective. Comparative safety and efficacy must be established with randomized placebo-controlled trials. CLASSIFICATION OF EVIDENCE This study provides Class IV evidence that in adults with SRSE, a KD is effective in inducing ketosis.