The role of diet in multiple sclerosis: A review

Multiple sclerosis (MS) is a multifactorial, inflammatory, and neurodegenerative disease of the central nervous system, where environmental factors interact with genetic susceptibility. The role of diet on MS has not been comprehensively elucidated; therefore, through an extensive search of relevant literature, this review reports the most significant evidence regarding nutrition as a possible co-factor influencing the inflammatory cascade by acting on both its molecular pathways and gut microbiota. Since nutritional status and dietary habits in MS patients have not been extensively reported, the lack of a scientific-based consensus on dietary recommendation in MS could encourage many patients to experiment alternative dietetic regimens, increasing the risk of malnutrition. This work investigates the health implications of an unbalanced diet in MS, and collects recent findings on nutrients of great interest among MS patients and physicians. The aim of this review is to elucidate the role of an accurate nutritional counseling in MS to move toward a multidisciplinary management of the disease and to encourage future studies demonstrating the role of a healthy diet on the onset and course of MS.     

The Role of Ketogenic Diet in the Treatment of Neurological Diseases

Over a hundred years of study on the favourable effect of ketogenic diets in the treatment of epilepsy have contributed to a long-lasting discussion on its potential influence on other neurological diseases. A significant increase in the number of scientific studies in that field has been currently observed. The aim of this paper is a widespread, thorough analysis of the available scientific evidence in respect of the role of the ketogenic diet in the therapy of neurological diseases such as: epilepsy, Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS) and migraine. A wide range of the mechanisms of action of the ketogenic diet has been demonstrated in neurological diseases, including, among other effects, its influence on the reduction in inflammatory conditions and the amount of reactive oxygen species (ROS), the restoration of the myelin sheath of the neurons, the formation and regeneration of mitochondria, neuronal metabolism, the provision of an alternative source of energy for neurons (ketone bodies), the reduction in glucose and insulin concentrations, the reduction in amyloid plaques, the induction of autophagy, the alleviation of microglia activation, the reduction in excessive neuronal activation, the modulation of intestinal microbiota, the expression of genes, dopamine production and the increase in glutamine conversion into GABA. The studies discussed (including randomised controlled studies), conducted in neurological patients, have stressed the effectiveness of the ketogenic diet in the treatment of epilepsy and have demonstrated its promising therapeutic potential in Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS) and migraine. A frequent advantage of the diet was demonstrated over non-ketogenic diets (in the control groups) in the therapy of neurological diseases, with simultaneous safety and feasibility when conducting the nutritional model.     

Effects of Calorie Restriction on Health Span and Insulin Resistance: Classic Calorie Restriction Diet vs. Ketosis-Inducing Diet

As the incidence of Chronic Non-Communicable Diseases (CNCDs) increases, preventive approaches become more crucial. In this review, calorie restriction (CR) effects on human beings were evaluated, comparing the benefits and risks of different CR diets: classic CR vs. ketosis-inducing diets, including intermittent fasting (IF), classic ketogenic diet (CKD), fasting mimicking diet (FMD), very-low-calorie ketogenic Diet (VLCKD) and Spanish ketogenic Mediterranean diet (SKMD). Special emphasis on insulin resistance (IR) was placed, as it mediates metabolic syndrome (MS), a known risk factor for CNCD, and is predictive of MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.     

Ketogenic Diet Decreases Alcohol Intake in Adult Male Mice

The classic ketogenic diet is a diet high in fat, low in carbohydrates, and well-adjusted proteins. The reduction in glucose levels induces changes in the body’s metabolism, since the main energy source happens to be ketone bodies. Recent studies have suggested that nutritional interventions may modulate drug addiction. The present work aimed to study the potential effects of a classic ketogenic diet in modulating alcohol consumption and its rewarding effects. Two groups of adult male mice were employed in this study, one exposed to a standard diet (SD, n = 15) and the other to a ketogenic diet (KD, n = 16). When a ketotic state was stable for 7 days, animals were exposed to the oral self-administration paradigm to evaluate the reinforcing and motivating effects of ethanol. Rt-PCR analyses were performed evaluating dopamine, adenosine, CB1, and Oprm gene expression. Our results showed that animals in a ketotic state displayed an overall decrease in ethanol consumption without changes in their motivation to drink. Gene expression analyses point to several alterations in the dopamine, adenosine, and cannabinoid systems. Our results suggest that nutritional interventions may be a useful complementary tool in treating alcohol-use disorders.     

Ketogenesis and SIRT1 as a tool in managing obesity

Obesity is a serious chronic disease and a public health concern in both developing and developed countries. Managing obesity has been a great challenge for both health care professionals and patients alike. Among the various diet programs aimed at promoting weight loss, the ketogenic diet, a diet high in fat and low in carbohydrates, has been at the forefront recently and its mechanism in weight loss is much debated. Activation of Sirtuin 1 or SIRT1 is able to circumvent various diseases, including metabolic syndrome and obesity and is thought to be a potentially reliable treatment target for both of them. Augmentation of SIRT1 may be carried out using dietary means such as nicotinamide adenine dinucleotide (NAD) supplementation and/or ketogenic diet. Although ketogenic diet may augment SIRT1 activation in people affected by obesity, recent studies have indicated that the relationship between SIRT1 and ketogenesis is unpredictable. The exact circumstances and mechanisms of SIRT1, NAD and ketogenesis in the clinical setting as an intervention tool in managing obesity remained uncertain. Although several recent literatures have documented significant weight-loss following ketogenic diet interventions, there were limitations with regards to duration of trial, choice and the number of trial subjects. Studies investigating the safety of ketogenic diet in the long term, beyond 46 weeks and related mechanism and pathways are still lacking and the sustainability of this diet remains to be determined. This review explores the recent progress on ketogenic diet and its relationships with SIRT1 as a tool in managing obesity and relevant clinical implications.     

Vitamin D and autoimmune disease--implications for practice from the multiple sclerosis literature

Recent studies and commentaries link vitamin D with several autoimmune diseases, including multiple sclerosis (MS). Adequate vitamin D intake reduces inflammatory cytokines through control of gene expression, thus inadequate vitamin D intake is suggested as a mechanism that could contribute to inflammation and, consequently, development of MS. Poor vitamin D status has been associated with increased risk for development of MS, and patients with MS may suffer consequences of vitamin D deficiency, such as bone loss. Animal studies and very limited human data suggest possible benefit from vitamin D supplementation in patients with MS. Based on the current state of research, a key principle for practicing dietetics professionals is to include vitamin D status in nutritional assessment. For those at risk for poor vitamin D status, intake can be enhanced by food-based advice and, when indicated, vitamin D supplementation.     

Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers

The ApoE4 allele is the most well-studied genetic risk factor for Alzheimer’s disease, a condition that is increasing in prevalence and remains without a cure. Precision nutrition targeting metabolic pathways altered by ApoE4 provides a tool for the potential prevention of disease. However, no long-term human studies have been conducted to determine effective nutritional protocols for the prevention of Alzheimer’s disease in ApoE4 carriers. This may be because relatively little is yet known about the precise mechanisms by which the genetic variant confers an increased risk of dementia. Fortunately, recent research is beginning to shine a spotlight on these mechanisms. These new data open up the opportunity for speculation as to how carriers might ameliorate risk through lifestyle and nutrition. Herein, we review recent discoveries about how ApoE4 differentially impacts microglia and inflammatory pathways, astrocytes and lipid metabolism, pericytes and blood–brain barrier integrity, and insulin resistance and glucose metabolism. We use these data as a basis to speculate a precision nutrition approach for ApoE4 carriers, including a low-glycemic index diet with a ketogenic option, specific Mediterranean-style food choices, and a panel of seven nutritional supplements. Where possible, we integrate basic scientific mechanisms with human observational studies to create a more complete and convincing rationale for this precision nutrition approach. Until recent research discoveries can be translated into long-term human studies, a mechanism-informed practical clinical approach may be useful for clinicians and patients with ApoE4 to adopt a lifestyle and nutrition plan geared towards Alzheimer’s risk reduction.     

Implementing A Ketogenic Diet Based on Medium-chain Triglyceride Oil in Pediatric Patients with Cancer

Traditionally, a ketogenic diet is given to drug-resistant children with epilepsy to improve seizure control. Inducing a ketogenic state in patients with cancer may be a useful adjunct to cancer treatment by affecting tumor glucose metabolism and growth while maintaining the patient's nutritional status. A ketogenic diet consisting of 60% medium-chain triglyceride (MCT) oil, 20% protein, 10% carbohydrate, and 10% other dietary fats was provided to a select group of pediatric patients with advanced-stage cancer to test the effects of dietary-induced ketosis on tumor glucose metabolism. Issues of tolerance and compliance for patients consuming an oral diet (consisting of normal table foods and daily MCT oil “shakes”) and for patients receiving an enteral formula are reviewed. Preliminary use of the MCT oil-based diet suggests a potential in pediatric patients with cancer. J Am Diet Assoc. 1995; 95:693-697.     

Medical costs are reduced when children with intractable epilepsy are successfully treated with the ketogenic diet

The ketogenic diet is used for children with drug refractory epilepsies. Although this diet was developed early in the 20th century, its use was infrequent until recently. One of the concerns about the ketogenic diet is the cost of initiating the diet. The process generally involves an inpatient visit that can last several days. In this study, the health care costs for 15 children with drug refractory epilepsy who received their care at Vanderbilt University Medical Center were compared for the period of time 6 to 12 months before they began the ketogenic diet and 6 to 12 months after they began the ketogenic diet. All comparisons within each child were done on the same amount of time before and after initiation of the diet. Total costs affiliated with care for the 15 children were: $352,820.20 for the prediet period, $41,221.91 for the diet initiation, and $149,436.86 for the postdiet-initiation period. We conclude that successful maintenance on the ketogenic diet provides a substantial financial benefit.     

Molecular Mechanisms Underlying the Bioactive Properties of a Ketogenic Diet

The consumption of a high-fat, low-carbohydrate diet (ketogenic diet) has diverse effects on health and is expected to have therapeutic value in neurological disorders, metabolic syndrome, and cancer. Recent studies have shown that a ketogenic diet not only pronouncedly shifts the cellular metabolism to pseudo-starvation, but also exerts a variety of physiological functions on various organs through metabolites that act as energy substrates, signaling molecules, and epigenetic modifiers. In this review, we highlight the latest findings on the molecular mechanisms of a ketogenic diet and speculate on the significance of these functions in the context of the epigenome and microbiome. Unraveling the molecular basis of the bioactive effects of a ketogenic diet should provide solid evidence for its clinical application in a variety of diseases including cancer.     

Consumption of a low-carbohydrate and high-fat diet (the ketogenic diet) exaggerates biotin deficiency in mice

ObjectiveBiotin is a water-soluble vitamin that acts as a cofactor for several carboxylases. The ketogenic diet, a low-carbohydrate, high-fat diet, is used to treat drug-resistant epilepsy and promote weight loss. In Japan, the infant version of the ketogenic diet is known as the “ketone formula.” However, as the special infant formulas used in Japan, including the ketone formula, do not contain sufficient amounts of biotin, biotin deficiency can develop in infants who consume the ketone formula. Therefore, the aim of this study was to evaluate the effects of the ketogenic diet on biotin status in mice.MethodsMale mice (N = 32) were divided into the following groups: control diet group, biotin-deficient (BD) diet group, ketogenic control diet group, and ketogenic biotin-deficient (KBD) diet group. Eight mice were used in each group.ResultsAt 9 wk, the typical symptoms of biotin deficiency such as hair loss and dermatitis had only developed in the KBD diet group. The total protein expression level of biotin-dependent carboxylases and the total tissue biotin content were significantly decreased in the KBD and BD diet groups. However, these changes were more severe in the KBD diet group.ConclusionThese findings demonstrated that the ketogenic diet increases biotin bioavailability and consumption, and hence, promotes energy production by gluconeogenesis and branched-chain amino acid metabolism, which results in exaggerated biotin deficiency in biotin-deficient mice. Therefore, biotin supplementation is important for mice that consume the ketogenic diet. It is suggested that individuals that consume the ketogenic diet have an increased biotin requirement.     

The Role of the Gut Microbiota on the Beneficial Effects of Ketogenic Diets

The ketogenic diet is a dietary regime focused on strongly reducing carbohydrate intake and increasing fat intake; leading to a state of ketosis. The ketogenic diet has gained much popularity over the years due to its effects on promoting weight loss, increasing insulin sensitivity and reducing dyslipidaemia. All these factors play a crucial role in the development of cardio-metabolic diseases; one of the greatest health challenges of the time. Moreover, the ketogenic diet has been known to reduce (epileptic) seizure activity. It is still poorly understood how following a ketogenic diet can lead to these beneficial metabolic effects. However, in recent years it has become clear that diet and the gut microbiota interact with one another and thus influence host health. The goal of this review is to summarize the current state of knowledge regarding the beneficial metabolic effects of the ketogenic diet and the role of gut microbiota in these effects.     

Ketogenic Effects of Multiple Doses of a Medium Chain Triglycerides Enriched Ketogenic Formula in Healthy Men under the Ketogenic Diet: A Randomized,Double-Blinded,Placebo-Controlled Study

Ketogenic diets, which are carbohydrate-restricted high-fat diets, may have therapeutic effects on various diseases, including cancer. However, ketogenic diets are often not standardized and, therefore, results are difficult to interpret. We previously investigated the usefulness of ketogenic diets in cancer therapy, where ketogenic formulas (KF) were used as supplements to enhance blood ketone bodies; however, the amount of KF was determined empirically with reference to blood ketone bodies levels. Here, to determine a standardized optimal amount of KF, we investigated temporal changes in blood ketone bodies (acetoacetic acid (AcAc), β-hydroxybutyrate (BHB)) and safety in 20 healthy individuals when KF was taken repeatedly under the conditions of a ketogenic diet (UMIN000034216). The diurnal variation in total ketone bodies, and AcAc and BHB levels significantly increased after lunch and after dinner, on the 4th day of KF administration. There were no significant safety issues related to KF in the context of anthropometric, metabolic, nutritional, urological and gastrointestinal parameters. In addition, ketogenic diets lead to changes in gut microbiota. KF showed a decrease in phylum Firmicutes. Our study provides baseline data of the usefulness of KF in a ketogenic diet.     

Quelle alimentation proposer aux patients présentant une stéatohépatite non-alcoolique ?

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects a quarter of the world's population, some of whom will progress to a more severe form called non-alcoholic steatohepatitis (NASH). The main factor leading to this condition is an unbalanced diet. No drug treatment is approved to date and only dietary management can improve the histological lesions of NASH through weight loss. However, the efficacy of standard diets, patient compliance and the ability to maintain weight loss over the long term are common difficulties. In this review, we analyze recent scientific data on different types of diet (Mediterranean diet, intermittent fasting, ketogenic diet), which can bring benefits on general and liver health. Drawbacks or limitations are also listed. The possible benefit of other nutritional strategies (coffee consumption, omega-3, polyphenols…) is discussed. The value of dietary change could be tailored to the patient's needs without necessarily imposing an intense weight loss.     

Evaluation of E-Health Applications for Paediatric Patients with Refractory Epilepsy and Maintained on Ketogenic Diet

E-health technologies improve healthcare quality and disease management. The aim of this study was to develop a ketogenic diet management app as well as a website about this dietary treatment and to evaluate the benefits of giving caregivers access to various web materials designed for paediatric patients with refractory epilepsy. Forty families participated in the questionnaire survey, from January 2016 to March 2016. All caregivers were exposed to paper-based materials about the ketogenic diet, whereas only 22 received the app, called KetApp, and videos produced by dieticians. Caregivers with free access to web materials were more satisfied than the others with the informative material provided by the centre (p ≤ 0.001, Mann–Whitney test). Indeed, they showed a better attitude towards treatment, and they became more aware of dietary management in comparison to the control group (p ≤ 0.001). Moreover, caregivers provided with web materials were stimulated to pursue the treatment (p = 0.002) and to introduce it to their children and other people (p = 0.001). Additionally, caregivers supplied with web materials were more willing to help other families in choosing the ketogenic diet (p = 0.004). Overall, these findings indicate that web materials are beneficial for caregivers of paediatric patients with refractory epilepsy in our centres. Thus, the use of e-health applications could be a promising tool in the daily aspects of ketogenic diet management, and it is especially of value in the attempt to start or maintain the diet during the ongoing COVID-19 pandemic crisis.     

Italian Ketogenic Mediterranean Diet in Overweight and Obese Patients with Prediabetes or Type 2 Diabetes

Obesity is a multifactorial disease strongly associated with insulin resistance and/or type 2 diabetes mellitus. Correct nutrition represents a valid strategy to fight these dysmetabolic pathologies responsible for numerous diseases, including inflammatory and cardiovascular ones. Medical nutrition therapy, including a Mediterranean diet (MD) and a very low-calorie ketogenic diet (VLKCD), is the first-line treatment for prediabetes/diabetes and overweight/obesity. Eighty patients (forty women and forty men) affected by overweight/obesity and type 2 diabetes mellitus or impaired glucose tolerance or impaired fasting glucose (51 (ys) ± 1.75; BMI (kg/m²) 33.08 ± 1.93; HA1c (%): 6.8% ± 0.25) were enrolled at the University Service of Diet Therapy, Diabetology and Metabolic Diseases, Policlinico Riuniti Hospital of Foggia, and subjected to a very-low-calorie Mediterranean diet and a very-low-calorie ketogenic Mediterranean diet for thirty days. Both diets result in a marked decrease in body weight (kg) and BMI (kg/m²). At the same time, only the very-low-calories ketogenic Mediterranean diet reduced waist and hip circumferences. Both diets helped reduce fat mass, but a major loss was achieved in a very low-calorie ketogenic Mediterranean diet. Among gluco-metabolic parameters, only the very-low-calorie ketogenic Mediterranean diet group showed a significant decrease in fasting blood glucose and HbA1c, insulin, C-peptide total cholesterol, LDL, and triglycerides. The results of our study seem to show that the very-low-calorie ketogenic Mediterranean diet is a good strategy to improve rapidly metabolic, anthropometric, and body composition parameters in patients with prediabetes or diabetes and overweight/obesity.     

The Effects of a Ketogenic Diet on Exercise Metabolism and Physical Performance in Off-Road Cyclists

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 (VO_2max) 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.     

Breath acetone predicts plasma ketone bodies in children with epilepsy on a ketogenic diet

OBJECTIVE: The high-fat ketogenic diet has long been used to treat refractory childhood seizures, but whether there is a relation between the degree of ketosis and effectiveness of seizure control remains unclear. Frequent measurements of plasma ketones are difficult in children so the goal was to determine the utility of breath acetone as a marker of systemic ketosis and seizure control in children given the ketogenic diet because of seizures refractory to medication. METHODS: In experiment I, breath acetone and plasma ketones were assessed every 2 h during an 8-h test day in seven children. In experiment II, a preliminary assessment of the possible relation between breath acetone and seizure frequency was made over 14 d in five children and one adolescent on the ketogenic diet. RESULTS: Breath acetone was positively and curvilinearly related to plasma acetone (r2 = 0.99, P < 0.0001), plasma acetoacetate (r2 = 0.89, P < 0.0001), and plasma beta-hydroxybutyrate (r2 = 0.94, P < 0.0001). No significant relation was found between breath acetone and seizure frequency or change in seizure frequency. CONCLUSIONS: Breath acetone is indicative of systemic ketosis while on the ketogenic diet. However, owing to the wide range of seizure types and plasma acetone, more subjects will be needed to determine whether there is a clear link between breath acetone and seizure frequency or decreased seizure frequency while on the high-fat ketogenic diet.     

Use of the ketogenic diet and dietary practices in the UK

Background: In 2000, a survey showed that use of the ketogenic diet as a treatment for intractable epilepsy in the UK was low. Subsequently, the number of medical publications supporting its efficacy has increased and demand from parents for this treatment has also increased. This survey was undertaken to determine whether there had been an increase in the use of the ketogenic diet and the necessary resources to provide it. Methods: A survey of paediatric dietitians in the UK was undertaken. Data were collected on their experience of implementing a ketogenic diet, the type of diet used, patient caseloads, other members of the care team, the process for initiation of the diet and funding. Results: Twenty‐eight hospitals offered the ketogenic diet treatment with a total of 152 patients. The caseload per dietitian ranged from 1–36 patients. The classical diet was prescribed for 74% cases. The majority of patients began the diet as outpatients. Six dietitians were specifically funded to provide the treatment. Fifty more dietitians had experience of implementing the diet but currently had no patients. The reasons given for this were no referrals, no funding or not working with patients with epilepsy. Conclusions: The number of patients on the ketogenic diet had increased since 2000. However, numbers remained low and the main reasons given were the lack of referrals and a lack of funding. Recommendations are made to improve the dietetic and funding resources available so that an efficacious treatment for intractable epilepsy of childhood can be made more widely available.     

A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men

Very low-carbohydrate (ketogenic) diets are popular yet little is known regarding the effects on serum biomarkers for cardiovascular disease (CVD). This study examined the effects of a 6-wk ketogenic diet on fasting and postprandial serum biomarkers in 20 normal-weight, normolipidemic men. Twelve men switched from their habitual diet (17% protein, 47% carbohydrate and 32% fat) to a ketogenic diet (30% protein, 8% carbohydrate and 61% fat) and eight control subjects consumed their habitual diet for 6 wk. Fasting blood lipids, insulin, LDL particle size, oxidized LDL and postprandial triacylglycerol (TAG) and insulin responses to a fat-rich meal were determined before and after treatment. There were significant decreases in fasting serum TAG (-33%), postprandial lipemia after a fat-rich meal (-29%), and fasting serum insulin concentrations (-34%) after men consumed the ketogenic diet. Fasting serum total and LDL cholesterol and oxidized LDL were unaffected and HDL cholesterol tended to increase with the ketogenic diet (+11.5%; P = 0.066). In subjects with a predominance of small LDL particles pattern B, there were significant increases in mean and peak LDL particle diameter and the percentage of LDL-1 after the ketogenic diet. There were no significant changes in blood lipids in the control group. To our knowledge this is the first study to document the effects of a ketogenic diet on fasting and postprandial CVD biomarkers independent of weight loss. The results suggest that a short-term ketogenic diet does not have a deleterious effect on CVD risk profile and may improve the lipid disorders characteristic of atherogenic dyslipidemia.