Csilla Ari | University of South Florida (original) (raw)
Papers by Csilla Ari
Global metabolomics analysis was performed on blood plasma from treated and untreated animals. Ad... more Global metabolomics analysis was performed on blood plasma from treated and untreated animals. Additionally, the time to paralysis of TDP-43 ALS C. elegans treated with and without the individual and combination DP supplements was measured. Results 30 and 49 biochemicals were significantly altered in the plasma of LOW and HIGH groups, respectively. Metabolites associated with mitochondrial energy metabolism , arginine metabolism, as well as long-and medium-chain fatty acids, GABA and related intermediates were elevated in response to DP. Elements of DP, arginine and alpha-ketoglutarate, GABA, and MCTs prolonged the rate of final paralysis of C. elegans TDP-43 disease models. Conclusion Targeting energy metabolism with the DP supplement as a metabolic therapy produces a change in the global metabolic profile of ALS mice that support the role of the DP for enhanced mitochondrial energy metabolism and prolongs time to paralysis of ALS C. elegans.
Journal of Ethology, 2016
Journal of Ethology, 2016
The Faseb Journal, Apr 1, 2013
The Faseb Journal, Apr 1, 2014
The Faseb Journal, Apr 1, 2014
The Open Anatomy Journal, 2011
In the present study the brain mass to body mass ratio and external morphological features of the... more In the present study the brain mass to body mass ratio and external morphological features of the brain of Mobula japanica, Mobula thurstoni and Manta birostris (devilrays) are described. The Mobulids extended the upper boundary of the minimum convex polygon described earlier by other authors for batoids, which is plotted on a double logarithmic scale of brain to body mass, causing some change in the allometric coefficient. The encephalization quotient of Mobulas was higher than unity, therefore it can be concluded that the actual brain mass is greater than expected by the given body mass. M. japanica had the highest percentage (61%) of telencephalic mass from all batoids, while the brain mass of M. birostris was the highest of all fish studied so far. The gross morphology of the enlarged Mobulid telencephalon and cerebellum prominently resembled to that of Sphyrna mokarran (great hammerhead shark). A structural dimorphism of the highly foliated cerebellum was detected between genders of the M. japanica, albeit with a small sample size. No such gender-related dimorphism was detected in brain mass/body mass ratio. Other brain parts were similar to those of other elasmobranch species. The data are discussed in terms of their ecological and evolutionary significance.
Biological Journal of the Linnean Society, 2014
ABSTRACT Changes of body coloration have not been described in manta rays (genus Manta) so far; t... more ABSTRACT Changes of body coloration have not been described in manta rays (genus Manta) so far; therefore, their natural body coloration is used to distinguish species and their ventral spot markings are used to identify individuals worldwide to estimate their population size or seasonal migration. The present study describes the first evidence of rapid coloration changes of manta rays based on observations of captive individuals. Body coloration changes were observed most intensely on the dorsal surface and on the head, which occurred within minutes prior to feeding and during intense social interactions. The coloration intensity drastically changed for the white markings of the shoulder bars, the chevron-shaped marking on the back, the dorsal side of fin tips, the area around the eyes, the upper margin of mouth, and the inner side of cephalic fins. Three out of five of the captive specimens have been identified as a putative third manta ray species, and detailed description about their rapid coloration changes is provided. The present observational study confirms the ability of manta rays to rapidly change body coloration during exposure to certain environmental stimuli. Understanding the dynamics of these rapid coloration changes is essential for accurate species identification and to perhaps gain insight into more advanced forms of communication. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, ●●, ●●–●●.
Biological Journal of the Linnean Society, 2014
ABSTRACT Manta rays (genus Manta) are listed as vulnerable on the IUCN Red List based partly on p... more ABSTRACT Manta rays (genus Manta) are listed as vulnerable on the IUCN Red List based partly on population studies that use body coloration and ventral spot patterns to identify and count individuals, as a result of such patterns being considered unique and permanent during their lifetime. The present study reports the first evidence of long-term coloration changes of manta rays based on observations of one captive individual. Darkening skin pigmentation was documented on the side of the head, the inner side of the cephalic lobes and the pectoral fin margin of the ventral side, and spot markings appeared on the gill slits within 9 months. These changes were most likely ontogenetic or were connected to maturation. The described specimen's coloration did not fulfill the taxonomic classification criteria of either manta ray species and rather resembled two different manta ray species at the beginning and end of the study. These results show that coloration patterns of manta rays are not as stable as has been assumed previously. Further studies are needed to identify the extent of such changes for accurate identification and classification of manta rays. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, ●●, ●●–●●.
Zoo Biology, 2008
This study reports on the first experimental research designed specifically for Manta birostris b... more This study reports on the first experimental research designed specifically for Manta birostris behavior. The authors attempted to learn about the feeding behavior and environmental cues influencing this behavior, as well as general cognitive ability. The preconditioned Manta's ability to identify food, on the basis of a fraction of the ordinary food signal complex, was tested. The opening of cephalic fins was considered a good indicator of feeding motivation level. The study subject animal used its biological clock to predict time and also associated a specific location with food, suggesting an ability to build up a cognitive map of its environment. Both underwater visual stimuli and olfactory stimuli had a very intense effect on food searching behavior over a 30 m distance, in contrast to visual signs from above the water surface. In addition, although an underwater visual signal resulted in a more intense response than from an olfactory signal, the specimen did not discriminate between different objects tested on the basis of visual sensation. It could therefore be suggested that food searching behavior of Mantas are governed by triggering stimuli, including smell or visual recognition, and modulated by the cognitive spatial map stored in their long-term memory. These findings will hopefully prove useful while devising protecting policies in the natural environment and/or while keeping these animals in captivity.
Nutrition & metabolism, 2016
Nutritional ketosis induced by the ketogenic diet (KD) has therapeutic applications for many dise... more Nutritional ketosis induced by the ketogenic diet (KD) has therapeutic applications for many disease states. We hypothesized that oral administration of exogenous ketone supplements could produce sustained nutritional ketosis (>0.5 mM) without carbohydrate restriction. We tested the effects of 28-day administration of five ketone supplements on blood glucose, ketones, and lipids in male Sprague-Dawley rats. The supplements included: 1,3-butanediol (BD), a sodium/potassium β-hydroxybutyrate (βHB) mineral salt (BMS), medium chain triglyceride oil (MCT), BMS + MCT 1:1 mixture, and 1,3 butanediol acetoacetate diester (KE). Rats received a daily 5-10 g/kg dose of their respective ketone supplement via intragastric gavage during treatment. Weekly whole blood samples were taken for analysis of glucose and βHB at baseline and, 0.5, 1, 4, 8, and 12 h post-gavage, or until βHB returned to baseline. At 28 days, triglycerides, total cholesterol and high-density lipoprotein (HDL) were measure...
The Faseb Journal, Apr 1, 2012
The Faseb Journal, Apr 1, 2013
Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease, 2015
Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative d... more Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survival in a mouse model of ALS (SOD1-G93A). ALS mice were fed standard rodent diet (SD), KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score, accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5% (p = 0.001) and 4.2% (p = 0.006), respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which may prolong survival and quality of life in ALS patients.
Cancer cells express an abnormal metabolism characterized by increased glucose consumption owing ... more Cancer cells express an abnormal metabolism characterized by increased glucose consumption owing to genetic mutations and mitochondrial dysfunction. Previous studies indicate that unlike healthy tissues, cancer cells are unable to effectively use ketone bodies for energy. Furthermore, ketones inhibit the proliferation and viability of cultured tumor cells. As the Warburg effect is especially prominent in metastatic cells, we hypothesized that dietary ketone supplementation would inhibit metastatic cancer progression in vivo. Proliferation and viability were measured in the highly metastatic VM-M3 cells cultured in the presence and absence of b-hydroxybutyrate (bHB). Adult male inbred VM mice were implanted subcutaneously with firefly luciferase-tagged syngeneic VM-M3 cells. Mice were fed a standard diet supplemented with either 1,3-butanediol (BD) or a ketone ester (KE), which are metabolized to the ketone bodies bHB and acetoacetate. Tumor growth was monitored by in vivo bioluminescent imaging. Survival time, tumor growth rate, blood glucose, blood bHB and body weight were measured throughout the survival study. Ketone supplementation decreased proliferation and viability of the VM-M3 cells grown in vitro, even in the presence of high glucose. Dietary ketone supplementation with BD and KE prolonged survival in VM-M3 mice with systemic metastatic cancer by 51 and 69%, respectively (p < 0.05). Ketone administration elicited anticancer effects in vitro and in vivo independent of glucose levels or calorie restriction. The use of supplemental ketone precursors as a cancer treatment should be further investigated in animal models to determine potential for future clinical use.
Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a neurodegenerative d... more Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a neurodegenerative disorder of motor neurons
causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or
effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which
is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a
metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that
alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main
ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survival in a mouse model of ALS
(SOD1-G93A). ALS mice were fed standard rodent diet (SD), KD, or either diets containing a metabolic therapy of the primary
ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in
caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score,
accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and
body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days
compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks
of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5%
(p = 0.001) and 4.2% (p = 0.006), respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived
past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic
therapy produces a therapeutic effect in ALS mice which may prolong survival and quality of life in ALS patients.
Alzheimer's & Dementia, 2014
PLoS ONE, 2013
Introduction: Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited b... more Introduction: Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD) is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO 2 T) saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease.
Neurobiology of Aging, 2014
Global metabolomics analysis was performed on blood plasma from treated and untreated animals. Ad... more Global metabolomics analysis was performed on blood plasma from treated and untreated animals. Additionally, the time to paralysis of TDP-43 ALS C. elegans treated with and without the individual and combination DP supplements was measured. Results 30 and 49 biochemicals were significantly altered in the plasma of LOW and HIGH groups, respectively. Metabolites associated with mitochondrial energy metabolism , arginine metabolism, as well as long-and medium-chain fatty acids, GABA and related intermediates were elevated in response to DP. Elements of DP, arginine and alpha-ketoglutarate, GABA, and MCTs prolonged the rate of final paralysis of C. elegans TDP-43 disease models. Conclusion Targeting energy metabolism with the DP supplement as a metabolic therapy produces a change in the global metabolic profile of ALS mice that support the role of the DP for enhanced mitochondrial energy metabolism and prolongs time to paralysis of ALS C. elegans.
Journal of Ethology, 2016
Journal of Ethology, 2016
The Faseb Journal, Apr 1, 2013
The Faseb Journal, Apr 1, 2014
The Faseb Journal, Apr 1, 2014
The Open Anatomy Journal, 2011
In the present study the brain mass to body mass ratio and external morphological features of the... more In the present study the brain mass to body mass ratio and external morphological features of the brain of Mobula japanica, Mobula thurstoni and Manta birostris (devilrays) are described. The Mobulids extended the upper boundary of the minimum convex polygon described earlier by other authors for batoids, which is plotted on a double logarithmic scale of brain to body mass, causing some change in the allometric coefficient. The encephalization quotient of Mobulas was higher than unity, therefore it can be concluded that the actual brain mass is greater than expected by the given body mass. M. japanica had the highest percentage (61%) of telencephalic mass from all batoids, while the brain mass of M. birostris was the highest of all fish studied so far. The gross morphology of the enlarged Mobulid telencephalon and cerebellum prominently resembled to that of Sphyrna mokarran (great hammerhead shark). A structural dimorphism of the highly foliated cerebellum was detected between genders of the M. japanica, albeit with a small sample size. No such gender-related dimorphism was detected in brain mass/body mass ratio. Other brain parts were similar to those of other elasmobranch species. The data are discussed in terms of their ecological and evolutionary significance.
Biological Journal of the Linnean Society, 2014
ABSTRACT Changes of body coloration have not been described in manta rays (genus Manta) so far; t... more ABSTRACT Changes of body coloration have not been described in manta rays (genus Manta) so far; therefore, their natural body coloration is used to distinguish species and their ventral spot markings are used to identify individuals worldwide to estimate their population size or seasonal migration. The present study describes the first evidence of rapid coloration changes of manta rays based on observations of captive individuals. Body coloration changes were observed most intensely on the dorsal surface and on the head, which occurred within minutes prior to feeding and during intense social interactions. The coloration intensity drastically changed for the white markings of the shoulder bars, the chevron-shaped marking on the back, the dorsal side of fin tips, the area around the eyes, the upper margin of mouth, and the inner side of cephalic fins. Three out of five of the captive specimens have been identified as a putative third manta ray species, and detailed description about their rapid coloration changes is provided. The present observational study confirms the ability of manta rays to rapidly change body coloration during exposure to certain environmental stimuli. Understanding the dynamics of these rapid coloration changes is essential for accurate species identification and to perhaps gain insight into more advanced forms of communication. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, ●●, ●●–●●.
Biological Journal of the Linnean Society, 2014
ABSTRACT Manta rays (genus Manta) are listed as vulnerable on the IUCN Red List based partly on p... more ABSTRACT Manta rays (genus Manta) are listed as vulnerable on the IUCN Red List based partly on population studies that use body coloration and ventral spot patterns to identify and count individuals, as a result of such patterns being considered unique and permanent during their lifetime. The present study reports the first evidence of long-term coloration changes of manta rays based on observations of one captive individual. Darkening skin pigmentation was documented on the side of the head, the inner side of the cephalic lobes and the pectoral fin margin of the ventral side, and spot markings appeared on the gill slits within 9 months. These changes were most likely ontogenetic or were connected to maturation. The described specimen's coloration did not fulfill the taxonomic classification criteria of either manta ray species and rather resembled two different manta ray species at the beginning and end of the study. These results show that coloration patterns of manta rays are not as stable as has been assumed previously. Further studies are needed to identify the extent of such changes for accurate identification and classification of manta rays. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, ●●, ●●–●●.
Zoo Biology, 2008
This study reports on the first experimental research designed specifically for Manta birostris b... more This study reports on the first experimental research designed specifically for Manta birostris behavior. The authors attempted to learn about the feeding behavior and environmental cues influencing this behavior, as well as general cognitive ability. The preconditioned Manta's ability to identify food, on the basis of a fraction of the ordinary food signal complex, was tested. The opening of cephalic fins was considered a good indicator of feeding motivation level. The study subject animal used its biological clock to predict time and also associated a specific location with food, suggesting an ability to build up a cognitive map of its environment. Both underwater visual stimuli and olfactory stimuli had a very intense effect on food searching behavior over a 30 m distance, in contrast to visual signs from above the water surface. In addition, although an underwater visual signal resulted in a more intense response than from an olfactory signal, the specimen did not discriminate between different objects tested on the basis of visual sensation. It could therefore be suggested that food searching behavior of Mantas are governed by triggering stimuli, including smell or visual recognition, and modulated by the cognitive spatial map stored in their long-term memory. These findings will hopefully prove useful while devising protecting policies in the natural environment and/or while keeping these animals in captivity.
Nutrition & metabolism, 2016
Nutritional ketosis induced by the ketogenic diet (KD) has therapeutic applications for many dise... more Nutritional ketosis induced by the ketogenic diet (KD) has therapeutic applications for many disease states. We hypothesized that oral administration of exogenous ketone supplements could produce sustained nutritional ketosis (>0.5 mM) without carbohydrate restriction. We tested the effects of 28-day administration of five ketone supplements on blood glucose, ketones, and lipids in male Sprague-Dawley rats. The supplements included: 1,3-butanediol (BD), a sodium/potassium β-hydroxybutyrate (βHB) mineral salt (BMS), medium chain triglyceride oil (MCT), BMS + MCT 1:1 mixture, and 1,3 butanediol acetoacetate diester (KE). Rats received a daily 5-10 g/kg dose of their respective ketone supplement via intragastric gavage during treatment. Weekly whole blood samples were taken for analysis of glucose and βHB at baseline and, 0.5, 1, 4, 8, and 12 h post-gavage, or until βHB returned to baseline. At 28 days, triglycerides, total cholesterol and high-density lipoprotein (HDL) were measure...
The Faseb Journal, Apr 1, 2012
The Faseb Journal, Apr 1, 2013
Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease, 2015
Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative d... more Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survival in a mouse model of ALS (SOD1-G93A). ALS mice were fed standard rodent diet (SD), KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score, accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5% (p = 0.001) and 4.2% (p = 0.006), respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which may prolong survival and quality of life in ALS patients.
Cancer cells express an abnormal metabolism characterized by increased glucose consumption owing ... more Cancer cells express an abnormal metabolism characterized by increased glucose consumption owing to genetic mutations and mitochondrial dysfunction. Previous studies indicate that unlike healthy tissues, cancer cells are unable to effectively use ketone bodies for energy. Furthermore, ketones inhibit the proliferation and viability of cultured tumor cells. As the Warburg effect is especially prominent in metastatic cells, we hypothesized that dietary ketone supplementation would inhibit metastatic cancer progression in vivo. Proliferation and viability were measured in the highly metastatic VM-M3 cells cultured in the presence and absence of b-hydroxybutyrate (bHB). Adult male inbred VM mice were implanted subcutaneously with firefly luciferase-tagged syngeneic VM-M3 cells. Mice were fed a standard diet supplemented with either 1,3-butanediol (BD) or a ketone ester (KE), which are metabolized to the ketone bodies bHB and acetoacetate. Tumor growth was monitored by in vivo bioluminescent imaging. Survival time, tumor growth rate, blood glucose, blood bHB and body weight were measured throughout the survival study. Ketone supplementation decreased proliferation and viability of the VM-M3 cells grown in vitro, even in the presence of high glucose. Dietary ketone supplementation with BD and KE prolonged survival in VM-M3 mice with systemic metastatic cancer by 51 and 69%, respectively (p < 0.05). Ketone administration elicited anticancer effects in vitro and in vivo independent of glucose levels or calorie restriction. The use of supplemental ketone precursors as a cancer treatment should be further investigated in animal models to determine potential for future clinical use.
Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a neurodegenerative d... more Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a neurodegenerative disorder of motor neurons
causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or
effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which
is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a
metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that
alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main
ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survival in a mouse model of ALS
(SOD1-G93A). ALS mice were fed standard rodent diet (SD), KD, or either diets containing a metabolic therapy of the primary
ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in
caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score,
accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and
body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days
compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks
of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5%
(p = 0.001) and 4.2% (p = 0.006), respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived
past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic
therapy produces a therapeutic effect in ALS mice which may prolong survival and quality of life in ALS patients.
Alzheimer's & Dementia, 2014
PLoS ONE, 2013
Introduction: Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited b... more Introduction: Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD) is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO 2 T) saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease.
Neurobiology of Aging, 2014