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The Effect of Ketogenic Diet on Shared Risk Factors of Cardiovascular Disease and Cancer.
Mohammadifard, N, Haghighatdoost, F, Rahimlou, M, Rodrigues, APS, Gaskarei, MK, Okhovat, P, de Oliveira, C, Silveira, EA, Sarrafzadegan, N
Nutrients. 2022;14(17)
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Cardiovascular disease and cancer are major causes of mortality worldwide and share common pathophysiological mechanisms and risk factors. The ketogenic diet, a low-carbohydrate and high-fat diet, may alter metabolic pathways, potentially lowering the risk of developing these diseases. Specifically, the ketogenic diet improves energy metabolism by promoting the use of body ketones for energy production. This review examines the protective effects of the ketogenic diet in reducing cardiovascular disease and cancer risk and explores the underlying mechanisms. The ketogenic diet may suppress oxidative stress and inflammation while improving common risk factors such as obesity, hypertension, diabetes, and dyslipidaemia. It is important to conduct further rigorous studies to assess the long-term effects of the ketogenic diet. However, healthcare professionals can use these findings to understand the short-term benefits of the diet in managing metabolic abnormalities and reducing the risk of developing cardiovascular disease and cancer.
Abstract
Cardiovascular disease (CVD) and cancer are the first and second leading causes of death worldwide, respectively. Epidemiological evidence has demonstrated that the incidence of cancer is elevated in patients with CVD and vice versa. However, these conditions are usually regarded as separate events despite the presence of shared risk factors between both conditions, such as metabolic abnormalities and lifestyle. Cohort studies suggested that controlling for CVD risk factors may have an impact on cancer incidence. Therefore, it could be concluded that interventions that improve CVD and cancer shared risk factors may potentially be effective in preventing and treating both diseases. The ketogenic diet (KD), a low-carbohydrate and high-fat diet, has been widely prescribed in weight loss programs for metabolic abnormalities. Furthermore, recent research has investigated the effects of KD on the treatment of numerous diseases, including CVD and cancer, due to its role in promoting ketolysis, ketogenesis, and modifying many other metabolic pathways with potential favorable health effects. However, there is still great debate regarding prescribing KD in patients either with CVD or cancer. Considering the number of studies on this topic, there is a clear need to summarize potential mechanisms through which KD can improve cardiovascular health and control cell proliferation. In this review, we explained the history of KD, its types, and physiological effects and discussed how it could play a role in CVD and cancer treatment and prevention.
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The effect of periodic ketogenic diet on newly diagnosed overweight or obese patients with type 2 diabetes.
Li, S, Lin, G, Chen, J, Chen, Z, Xu, F, Zhu, F, Zhang, J, Yuan, S
BMC endocrine disorders. 2022;22(1):34
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Currently, the ketogenic diet is gaining popularity in managing Type 2 diabetes (T2D). Ketogenic diets replace carbohydrates with fat and include limited carbohydrates and adequate protein. This randomised controlled trial evaluated the effects of the 12-week ketogenic diet on sixty overweight or obese T2D patients. Both the ketogenic and control diabetes diet groups achieved significant reductions in weight, body mass index, waist circumference, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, fasting blood glucose, fasting insulin, and HbA1c. However, the ketogenic group showed significantly greater reductions in body mass, blood lipids, and blood glucose than the control group. In the ketogenic diet group, serum uric acid levels were higher than those in the control diet group. It was found that the control diet group adhered to the diet for a longer period than the ketogenic diet group, whose willingness to adhere to the diet long-term was weaker. More robust long-term studies are needed to evaluate the long-term effects of a ketogenic diet. In this study, more patients who followed the ketogenic diet experienced hypoglycaemic events during the first four weeks. Healthcare providers should exercise caution when recommending a short term therapeutic ketogenic diet.
Abstract
BACKGROUND The ketogenic diet (KD) is characterized by fat as a substitute of carbohydrates for the primary energy source. There is a large number of overweight or obese people with type 2 diabetes mellitus (T2DM), while this study aims to observe periodic ketogenic diet for effect on overweight or obese patients newly diagnosed as T2DM. METHODS A total of 60 overweight or obese patients newly diagnosed as T2DM were randomized into two groups: KD group, which was given ketogenic diet, and control group, which was given routine diet for diabetes, 30 cases in each group. Both dietary patterns lasted 12 weeks, and during the period, the blood glucose, blood lipid, body weight, insulin, and uric acid before and after intervention, as well as the significance for relevant changes, were observed. RESULTS For both groups, the weight, BMI(body mass index), Waist, TG (triglyceride), TC(cholesterol), LDL (low-density lipoprotein cholesterol), HDL (high-density lipoprotein cholesterol), FBG (fasting glucose), FINS (fasting insulin), HbA1c (glycosylated hemoglobin) were decreased after intervention (P < 0.05), while the decrease rates in the KD group was more significant than the control group. However, UA(serum uric acid) in the KD group showed an upward trend, while in the control group was not changed significantly (P > 0.05).The willingness to adhere to the ketogenic diet over the long term was weaker than to the routine diet for diabetes. CONCLUSION Among the overweight or obese patients newly diagnosed as type 2 diabetes mellitus, periodic ketogenic diet can not only control the body weight, but also control blood glucose and lipid, but long-term persistence is difficult.
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The Effect of a Ketogenic Low-Carbohydrate, High-Fat Diet on Aerobic Capacity and Exercise Performance in Endurance Athletes: A Systematic Review and Meta-Analysis.
Cao, J, Lei, S, Wang, X, Cheng, S
Nutrients. 2021;13(8)
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A low-carbohydrate diet has been shown at the cellular level to be of benefit to endurance athletes, however how this effects performance remains controversial. Ketogenic diets have recently become popular and is a special type of low-carbohydrate, high-fat diet with 5% or less energy from carbohydrates. This systematic review and meta-analysis aimed to determine the effects of a ketogenic low-carbohydrate, high-fat diet (K-LCHF) on aerobic capacity and exercise performance in endurance athletes. The results showed that 10 studies were found and that K-LCHF diets had no effect on aerobic capacity and exercise performance of endurance athletes. It was concluded that K-LCHF diet is unlikely to be of benefit to endurance athletes. This study could be used by healthcare professionals to understand that modifying fat and carbohydrate ratios may have little effect on endurance and that alternative dietary modifications should be researched.
Abstract
A low-carbohydrate, high-fat (LCHF) diet has been proposed to enhance the fat utilization of muscle and the aerobic capacity of endurance athletes, thereby improving their exercise performance. However, it remains uncertain how the macronutrient intake shift from carbohydrate to fat affects endurance exercise training and performance. This study performed a systematic review and meta-analysis to explore the effects of a ketogenic low-carbohydrate, high-fat (K-LCHF) diet on aerobic capacity and exercise performance among endurance athletes. Searches were carried out in five electronic databases, and we followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. The search included studies using an LCHF diet as an intervention protocol and compared data on factors such as maximum oxygen uptake (VO2max) and rating of perceived exertion (RPE) from the graded exercise test. In this case, 10 studies met the criteria and were included in the meta-analysis. We did not find a significant effect of K-LCHF diet interventions on VO2max, time to exhaustion, HRmax or RPE. However, a significant overall effect in the substrate oxidation response to respiratory exchange rate was observed. The meta-analysis showed that K-LCHF diets did not affect aerobic capacity and exercise performance. Therefore, high-quality interventions of a K-LCHF diet are needed to illustrate its effect on various endurance training programs.
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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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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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Satiating Effect of a Ketogenic Diet and Its Impact on Muscle Improvement and Oxidation State in Multiple Sclerosis Patients.
Benlloch, M, López-Rodríguez, MM, Cuerda-Ballester, M, Drehmer, E, Carrera, S, Ceron, JJ, Tvarijonaviciute, A, Chirivella, J, Fernández-García, D, de la Rubia Ortí, JE
Nutrients. 2019;11(5)
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Multiple sclerosis (MS) is an auto-immune condition that affects the brain and spinal cord. In MS, the coating that protects the nerves (myelin) is damaged, and this can lead to muscle wasting. The aim of this pilot study was to establish whether a low carbohydrate (‘ketogenic’) diet would lead to improvements in muscle mass in patients with MS. 27 MS patients were given instructions to follow a Mediterranean-style ketogenic diet that consisted of 20% total calories from protein, 40% of calories from carbohydrate and 40% of calories from fat, including 60ml of coconut oil per day. After four months on the diet, participants had gained muscle mass and lost fat. They also felt less hungry, and blood tests showed lower levels of inflammation and oxidation. The researchers concluded that a ketogenic diet has the potential to provide an additional therapy for patients with MS.
Abstract
BACKGROUND It was previously established that Multiple sclerosis (MS) generates energy alterations at the mitochondrial level related to the loss of muscle mass. Ketone bodies, mainly beta-hydroxybutyrate (BHB), re-establish this energy alteration causing satiety, changes in body composition and a decrease in hormone-dependant hunger, such as ghrelin. The aim of this study was to establish possible improvements in body composition and the level of oxidation in patients with MS, by means of the satiating effect of a ketogenic diet. METHODS A pilot study was carried out with 27 MS patients who were given a Mediterranean isocaloric and ketogenic diet for 4 months. Anthropometric measurements, as well as satiety and hunger perception (VAS scale), were taken. In addition, BHB and paraoxonase 1 (PON1), as an oxidation marker, were measured by spectrophotometric automated assays, and ghrelin was determined by an enzyme immunoassay in the serum. All measurements were taken before and after the intervention. RESULTS A significant increase in satiety perception at lunch and dinner and of BHB in the blood was obtained. Hunger perception decreased significantly at lunch and dinner with similar levels of ghrelin. In addition, an important increase in lean mass and PON1 was observed. To our knowledge, this is the first study addressing improvements in body composition, oxidation state and metabolism in MS patients, based on the satiating effect of a Mediterranean isocaloric diet. CONCLUSION A ketogenic diet increases lean mass and decreases inflammation and oxidation possibly as a consequence of an increase in satiety and decrease in hunger in MS patients.
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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.
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The effects of a ketogenic diet on exercise metabolism and physical performance in off-road cyclists.
Zajac, A, Poprzecki, S, Maszczyk, A, Czuba, M, Michalczyk, M, Zydek, G
Nutrients. 2014;6(7):2493-508
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While it is well-known that nutrient availability affects numerous aspects of exercise metabolism, new concepts of improving endurance performance are being explored. Sports nutrition has historically focused on a high carbohydrate diet to increase glycogen stores, however there is increasing evidence that a low carbohydrate, high fat diet may benefit endurance athletes. The aim of this crossover study was to determine the effects of a long-term keteogenic diet on aerobic performance and exercise metabolism in eight male cyclists. The participants were assigned to either a mixed or ketogenic diet for one month with a one-week recovery period and performed an exercise protocol consisting of moderate and high intensities. The findings indicated that consuming a low carbohydrate diet promotes fat oxidation during moderate-intensity and reduces post-exercise muscle damage. Based on these results, the authors conclude that long-term, high fat diets may be favourable for aerobic endurance athletes during the preparatory season.
Abstract
The main objective of this research was to determine the effects of a long-term ketogenic diet, rich in polyunsaturated fatty acids, on aerobic performance and exercise metabolism in off-road cyclists. Additionally, the effects of this diet on body mass and body composition were evaluated, as well as those that occurred in the lipid and lipoprotein profiles due to the dietary intervention. The research material included eight male subjects, aged 28.3 ± 3.9 years, with at least five years of training experience that competed in off-road cycling. Each cyclist performed a continuous exercise protocol on a cycloergometer with varied intensity, after a mixed and ketogenic diet in a crossover design. The ketogenic diet stimulated favorable changes in body mass and body composition, as well as in the lipid and lipoprotein profiles. Important findings of the present study include a significant increase in the relative values of maximal oxygen uptake (VO2max) and oxygen uptake at lactate threshold (VO2 LT) after the ketogenic diet, which can be explained by reductions in body mass and fat mass and/or the greater oxygen uptake necessary to obtain the same energy yield as on a mixed diet, due to increased fat oxidation or by enhanced sympathetic activation. The max work load and the work load at lactate threshold were significantly higher after the mixed diet. The values of the respiratory exchange ratio (RER) were significantly lower at rest and during particular stages of the exercise protocol following the ketogenic diet. The heart rate (HR) and oxygen uptake were significantly higher at rest and during the first three stages of exercise after the ketogenic diet, while the reverse was true during the last stage of the exercise protocol conducted with maximal intensity. Creatine kinase (CK) and lactate dehydrogenase (LDH) activity were significantly lower at rest and during particular stages of the 105-min exercise protocol following the low carbohydrate ketogenic diet. The alterations in insulin and cortisol concentrations due to the dietary intervention confirm the concept that the glucostatic mechanism controls the hormonal and metabolic responses to exercise.
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Comparison of short- versus long-term ketogenic diet for intractable infantile spasms.
Kang, HC, Lee, YJ, Lee, JS, Lee, EJ, Eom, S, You, SJ, Kim, HD
Epilepsia. 2011;52(4):781-7
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Ketogenic diets (KD) have shown favourable effects on childhood epilepsy. However, these is reluctance to use these as a form of treatment because of the possible adverse impact on the growing child. This study compared short (8 months) and long term (24 months) KD on infantile spasms. 40 children aged between 6 and 60 months who had achieved seizure free outcomes within 6 months of a KD were randomly assigned to to short (16 patients) and long term (19 patients) trial groups. The children completed a KD with a 3:1 ratio of fat to non-fat and also took multivitamins, calcium, vitamin D2 and L-carnitine. The study measured seizure relapse and frequency after the KD. Adverse effects most commonly experienced by the children during the KD included gastrointestinal disturbances (nausea, vomiting, diarrhoea, constipation), and elevated lipids. Growth failure only occurred in the group who maintained the KD long term (7 out of 19). The authors concluded that a KD for 8 months in children with infantile spasms appears justified; it has the benefit of less growth disturbances but similar spasm-free outcomes compared to longer term durations.
Abstract
PURPOSE To compare the prognoses between short-term (8 months) and conventional long-term (> 2 years) trials involving patients with refractory infantile spasms who successfully completed the ketogenic diet (KD). METHODS Of 40 patients who achieved seizure-free outcomes and showed improvement in hypsarrhythmic patterns within 6 months of the KD, with a 3:1 fat to nonfat ratio as an add-on treatment, 16 patients were randomized into the short-term trial group and the diet was tapered throughout two additional months. Twenty-four patients were randomized into a long-term trial group, and 19 patients could successfully discontinue the diet after 2 years. Primary outcome measures included seizure relapse and frequency of 35 patients for > 12 months after successful completion of the KD. KEY FINDINGS Of 16 patients in the short-term trial group, two patients relapsed with clusters of spasms, and one patient had recurrence of occasional focal seizures. Of 19 patients in the long-term trial group, two patients progressed to Lennox-Gastaut syndrome and one patient experienced recurrence of occasional focal seizures with secondary generalization. An early response to the KD, evidenced by short latency before seizure freedom and disappearance of hypsarrythmia and cryptogenic etiology, may indicate a successful early discontinuation of the KD. Significant growth failure was complicated only in conventional long-term trial group. SIGNIFICANCE Use of the KD for only 8 months in children who become spasm-free appears to be justified, with similar outcomes, recurrence rate, and less growth disturbance than a longer-term, traditional use.