Tatiana M . Zilberter - Academia.edu (original) (raw)

Papers by Tatiana M . Zilberter

Despite decades of intensive research, effective treatment and prevention strategies for neurodeg... more Despite decades of intensive research, effective treatment and prevention strategies for neurodegenerative diseases (NDDs) remain elusive. This review focuses on Alzheimer’s and Parkinson’s diseases and acquired epilepsy suggesting that in their early phase, these progressive pathologies share common or interacting molecular pathways. Indeed, oxidative stress associated with disrupted glucose metabolism is the expected end state of most, if not all, risk factors preceding the onset of major NDDs. This review proposes that the initial oxidative stress in the brain resulting specifically from the hyperactivation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) causes a decline in glucose utilization and is the primary initiating factor of major NDDs. The existing clinical and experimental evidence points to NOX as the primary initiating mechanism shared within the major NDDs. During early oxidative stress, NOX activation is triggered in variable brain cells via multiple pathways, from beta-amyloid to alpha-synuclein, fibrin to glutamate and seizures. Therefore, the treatment strategy should have targeted the activation of NOX, wouldn’t there be a lack of clinically approved selective NOX antagonists? On the other hand, there are promising metabolism-altering approaches via dietary means able to switch energy intake from glucose to ketones, which influences both oxidative stress and glucose utilization and could ameliorate disease progression. The regimen of time-restricted eating appears to be the most feasible, nutritious, and palatable one providing the essential benefits of a ketogenic diet without adverse effects.

Exploration of Neuroscience, Apr 21, 2023

Despite decades of intensive research, effective treatment and prevention strategies for neurodeg... more Despite decades of intensive research, effective treatment and prevention strategies for neurodegenerative
diseases (NDDs) remain elusive. This review focuses on Alzheimer’s and Parkinson’s diseases and acquired
epilepsy suggesting that in their early phase, these progressive pathologies share common or interacting
molecular pathways. Indeed, oxidative stress associated with disrupted glucose metabolism is the expected
end state of most, if not all, risk factors preceding the onset of major NDDs. This review proposes that the
initial oxidative stress in the brain resulting specifically from the hyperactivation of nicotinamide adenine
dinucleotide phosphate (NADPH) oxidase (NOX) causes a decline in glucose utilization and is the primary
initiating factor of major NDDs. The existing clinical and experimental evidence points to NOX as the primary initiating mechanism shared within the major NDDs. During early oxidative stress, NOX activation
is triggered in variable brain cells via multiple pathways, from beta-amyloid to alpha-synuclein, fibrin to
glutamate and seizures. Therefore, the treatment strategy should have targeted the activation of NOX,
wouldn’t there be a lack of clinically approved selective NOX antagonists? On the other hand, there are
promising metabolism-altering approaches via dietary means able to switch energy intake from glucose
to ketones, which influences both oxidative stress and glucose utilization and could ameliorate disease
progression. The regimen of time-restricted eating appears to be the most feasible, nutritious, and palatable
one providing the essential benefits of a ketogenic diet without adverse effects.

Neurobiology of Disease, 2017

Metabolic intervention strategy of epilepsy treatment has been gaining broader attention due to a... more Metabolic intervention strategy of epilepsy treatment has been gaining broader attention due to accumulated evidence that hypometabolism, manifested in humans as reduced brain glucose consumption, is a principal factor in acquired epilepsy. Therefore, targeting deficient energy metabolism may be an effective approach for treating epilepsy. To confront this pathology we utilized pyruvate, which besides being an anaplerotic mitochondrial fuel possesses a unique set of neuroprotective properties as it: (i) is a potent reactive oxygen species scavenger; (ii) abates overactivation of Poly [ADP-ribose] polymerase 1 (PARP-1); (iii) facilitates glutamate efflux from the brain; (iv) augments brain glycogen stores; (v) is anti-inflammatory; (vi) prevents neuronal hyperexcitability; and (vii) normalizes the cytosolic redox state. In vivo, chronic oral pyruvate administration completely abolished established epileptic phenotypes in three accepted and fundamentally different rodent acquired epilepsy models. Our study reports metabolic correction by pyruvate as a potentially highly effective treatment of acquired epilepsies.

Glucose-Sparing Action of Ketones Boosts Functions Exclusive to Glucose in the Brain, 2020

The ketogenic diet (KD) has been successfully used for a century for treating refractory epilepsy... more The ketogenic diet (KD) has been successfully used for a century for treating refractory epilepsy and is currently seen as one of the few viable approaches to the treatment of a plethora of metabolic and neurodegenerative diseases. Empirical evidence notwithstanding, there is still no universal understanding of KD mechanism (s). An important fact is that the brain is capable of using ketone bodies for fuel. Another critical point is that glucose's functions span beyond its role as an energy substrate, and in most of these functions, glucose is irreplaceable. By acting as a supplementary fuel, ketone bodies may free up glucose for its other crucial and exclusive function. We propose that this glucose-sparing effect of ketone bodies may underlie the effectiveness of KD in epilepsy and major neurodegenerative diseases, which are all characterized by brain glucose hypometabolism.

and functional connectivity in the brain network for appetite: connecting the dots. Front. Psycho... more and functional connectivity in the brain network for appetite: connecting the dots. Front. Psychol. 6:547. doi: 10.3389/fpsyg.2015.00547 Meal replacement and functional connectivity in the brain network for appetite: connecting the dots

The ratio of carbs plus protein to fat: how it works 44 The Ketogenic Diet 45 Metabolic Changes C... more The ratio of carbs plus protein to fat: how it works 44 The Ketogenic Diet 45 Metabolic Changes Caused by a Ketogenic Diet 45 B Vitamins 46 Antioxidants 46 Vitamin D 47 Nutrients To Support Ketosis 47 Carnitine. 47 Chromium. 47 The Ketogenic Diet Plan 48 Typical Ketogenic Diet Menu. 49 Ketogenic Diet Testimonials 50 References 52 Atkins Diet Lessons 64 Atkins diet pyramid. 64 Allowed and prohibited foods 64 Diet details 65 Samples meals 70 Compare with FDA Food pyramid 71 Atkins Diet Testimonials 73 The benefits beyond weight loss 73 A few reports on negative effects of the diet 74 Comments on energy increase 74 Improvements in cholesterol levels 76 Two dieters reported increases in cholesterol numbers 77 Atkins diet statistics 77 A water loss? 78 Long term results 79 Atkins diet and calorie intake 80

Ketosis, ketogenic diet and food intake control: a complex

Carbohydrate-biased control of energy metabolism: the darker side of the selfish brain

Frontiers in neuroenergetics, 2011

Frontiers in human neuroscience, 2013

Frontiers in Public Health, 2014

There is a consensus regarding the uni-versal significance of breakfast (BF) for health, wellbein... more There is a consensus regarding the uni-versal significance of breakfast (BF) for health, wellbeing, and cognition. The suc-cess of free school BF programs (e.g., Hasz and Lamport, 2012), which reportedly improve academic performance, fortifies this belief. However, studies showing cog-nitive effects of BF vs. skipping BF in large mixed cohorts of children (e.g., Wesnes et al., 2012) are often lack-ing metabolic and nutritional specifics. This creates uncertainty regarding the metabolic consequences of BF. Another uncertainty exists regarding skipping BF, which has been argued to have univer-

Frontiers in Nutrition, 2020

From the teleological standpoint, metabolic shifting evolved due to the periodic nature of the en... more From the teleological standpoint, metabolic shifting evolved due to the periodic nature of the environment, circadian cycles being one of the conditions the life on Earth confronts. Metabolic shifting occurs on a regular basis due to the demand-availability interplay of energy resources, expenditure, and depots, all of which have periodic nature due to the environment’s circadian rhythmicity. In modern societies, however, there are discrepancies between the evolutionary acquired metabolic setup and our current dysrhythmic, artificial environment. Thus, the so-called “diseases of civilization” are thought to be due to the changes in the environment that are too fast to cause adequate adaptations in our genome. On the other hand, an inherent fundamental feature of metabolism at large is flexibility. Out of themany diversemanifestations ofmetabolic flexibility, this Research Topic addresses the triad: “Timing, Nutrition, and Exercise” for the apparent reason—they are areas where they d...

A medical device to deliver skin stimulation was developed in Russia in the early 1980s and sever... more A medical device to deliver skin stimulation was developed in Russia in the early 1980s and several studies were done on the device. These studies indicated a high degree of success in the treatment of a variety of disorders. The device and method of use were based loosely on the practice of acupuncture. These, however, does not help to explain the phenomenon within Western scientific paradigm. Aside from metaphysical explanations about energy flow through the channels-meridians, there have been few theories proposed. The present paper reviews the development and the early Russian studies, as well as results of the pilot research program conducted in the Community Wholistic Health Center, Carrboro, NC. The paper then discusses two of the theories applicable to the results.

F1000Research, 2017

Prolonging the overnight fast habitually happens on a daily basis during the time-restricted feed... more Prolonging the overnight fast habitually happens on a daily basis during the time-restricted feeding regimen (TRF). In animal studies, TRF protocols restrict food availability to 4–8 hours every circadian cycle (e.g. during the dark phase in rodents). Animal studies have shown that metabolic consequences of TRF are metabolically favorable independently of caloric intakes. Even a short-term TRF intervention in adult rats slowed down age-associated cognitive decline and improved cognitive functions (Singh et al., 2012). The effects on glucose tolerance and insulin sensitivity were more pronounced compared to caloric restriction.
In humans, TRF is achieved by consistently reducing daily meal count. Similarly, TRF has been shown to be as metabolically favorable in humans showing long-term neuroprotective effects, e.g., in the prevention of neurodegenerative diseases (Jadiya et al., 2011; Srivastava & Haigis, 2011), supposedly via improving synaptic plasticity and cognitive function (Fontán-Lozano et al., 2008; Liu et al., 2013). TRF is one of the forms of Intermittent fasting, the one with superior adherence. A recent Japanese long-term study of a very large cohort extracted from 4-year long insurance records showed that BF skippers had a lower incidence of metabolic diseases, which constitute risk factors for diseases of aging. A recent Japanese long-term study of a very large cohort extracted from 4-year long insurance records showed that BF skippers had a lower incidence of metabolic diseases, which constitute risk factors for diseases of aging. Reducing these risk factors can provide protection against early onset of aging and prolong healthy, active and happy aging (Okamoto et al., 2013)

eneuro

The ketogenic diet (KD) has been successfully used for a century for treating refractory epilepsy... more The ketogenic diet (KD) has been successfully used for a century for treating refractory epilepsy and is currently seen as one of the few viable approaches to the treatment of a plethora of metabolic and neurodegenerative diseases. Empirical evidence notwithstanding, there is still no universal understanding of KD mechanism (s). An important fact is that the brain is capable of using ketone bodies for fuel. Another critical point is that glucose's functions span beyond its role as an energy substrate, and in most of these functions, glucose is irreplaceable. By acting as a supplementary fuel, ketone bodies may free up glucose for its other crucial and exclusive function. We propose that this glucose-sparing effect of ketone bodies may underlie the effectiveness of KD in epilepsy and major neurodegenerative diseases, which are all characterized by brain glucose hypometabolism.

Despite decades of intensive research, effective treatment and prevention strategies for neurodeg... more Despite decades of intensive research, effective treatment and prevention strategies for neurodegenerative diseases (NDDs) remain elusive. This review focuses on Alzheimer’s and Parkinson’s diseases and acquired epilepsy suggesting that in their early phase, these progressive pathologies share common or interacting molecular pathways. Indeed, oxidative stress associated with disrupted glucose metabolism is the expected end state of most, if not all, risk factors preceding the onset of major NDDs. This review proposes that the initial oxidative stress in the brain resulting specifically from the hyperactivation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) causes a decline in glucose utilization and is the primary initiating factor of major NDDs. The existing clinical and experimental evidence points to NOX as the primary initiating mechanism shared within the major NDDs. During early oxidative stress, NOX activation is triggered in variable brain cells via multiple pathways, from beta-amyloid to alpha-synuclein, fibrin to glutamate and seizures. Therefore, the treatment strategy should have targeted the activation of NOX, wouldn’t there be a lack of clinically approved selective NOX antagonists? On the other hand, there are promising metabolism-altering approaches via dietary means able to switch energy intake from glucose to ketones, which influences both oxidative stress and glucose utilization and could ameliorate disease progression. The regimen of time-restricted eating appears to be the most feasible, nutritious, and palatable one providing the essential benefits of a ketogenic diet without adverse effects.

Exploration of Neuroscience, Apr 21, 2023

Despite decades of intensive research, effective treatment and prevention strategies for neurodeg... more Despite decades of intensive research, effective treatment and prevention strategies for neurodegenerative
diseases (NDDs) remain elusive. This review focuses on Alzheimer’s and Parkinson’s diseases and acquired
epilepsy suggesting that in their early phase, these progressive pathologies share common or interacting
molecular pathways. Indeed, oxidative stress associated with disrupted glucose metabolism is the expected
end state of most, if not all, risk factors preceding the onset of major NDDs. This review proposes that the
initial oxidative stress in the brain resulting specifically from the hyperactivation of nicotinamide adenine
dinucleotide phosphate (NADPH) oxidase (NOX) causes a decline in glucose utilization and is the primary
initiating factor of major NDDs. The existing clinical and experimental evidence points to NOX as the primary initiating mechanism shared within the major NDDs. During early oxidative stress, NOX activation
is triggered in variable brain cells via multiple pathways, from beta-amyloid to alpha-synuclein, fibrin to
glutamate and seizures. Therefore, the treatment strategy should have targeted the activation of NOX,
wouldn’t there be a lack of clinically approved selective NOX antagonists? On the other hand, there are
promising metabolism-altering approaches via dietary means able to switch energy intake from glucose
to ketones, which influences both oxidative stress and glucose utilization and could ameliorate disease
progression. The regimen of time-restricted eating appears to be the most feasible, nutritious, and palatable
one providing the essential benefits of a ketogenic diet without adverse effects.

Neurobiology of Disease, 2017

Metabolic intervention strategy of epilepsy treatment has been gaining broader attention due to a... more Metabolic intervention strategy of epilepsy treatment has been gaining broader attention due to accumulated evidence that hypometabolism, manifested in humans as reduced brain glucose consumption, is a principal factor in acquired epilepsy. Therefore, targeting deficient energy metabolism may be an effective approach for treating epilepsy. To confront this pathology we utilized pyruvate, which besides being an anaplerotic mitochondrial fuel possesses a unique set of neuroprotective properties as it: (i) is a potent reactive oxygen species scavenger; (ii) abates overactivation of Poly [ADP-ribose] polymerase 1 (PARP-1); (iii) facilitates glutamate efflux from the brain; (iv) augments brain glycogen stores; (v) is anti-inflammatory; (vi) prevents neuronal hyperexcitability; and (vii) normalizes the cytosolic redox state. In vivo, chronic oral pyruvate administration completely abolished established epileptic phenotypes in three accepted and fundamentally different rodent acquired epilepsy models. Our study reports metabolic correction by pyruvate as a potentially highly effective treatment of acquired epilepsies.

Glucose-Sparing Action of Ketones Boosts Functions Exclusive to Glucose in the Brain, 2020

The ketogenic diet (KD) has been successfully used for a century for treating refractory epilepsy... more The ketogenic diet (KD) has been successfully used for a century for treating refractory epilepsy and is currently seen as one of the few viable approaches to the treatment of a plethora of metabolic and neurodegenerative diseases. Empirical evidence notwithstanding, there is still no universal understanding of KD mechanism (s). An important fact is that the brain is capable of using ketone bodies for fuel. Another critical point is that glucose's functions span beyond its role as an energy substrate, and in most of these functions, glucose is irreplaceable. By acting as a supplementary fuel, ketone bodies may free up glucose for its other crucial and exclusive function. We propose that this glucose-sparing effect of ketone bodies may underlie the effectiveness of KD in epilepsy and major neurodegenerative diseases, which are all characterized by brain glucose hypometabolism.

and functional connectivity in the brain network for appetite: connecting the dots. Front. Psycho... more and functional connectivity in the brain network for appetite: connecting the dots. Front. Psychol. 6:547. doi: 10.3389/fpsyg.2015.00547 Meal replacement and functional connectivity in the brain network for appetite: connecting the dots

The ratio of carbs plus protein to fat: how it works 44 The Ketogenic Diet 45 Metabolic Changes C... more The ratio of carbs plus protein to fat: how it works 44 The Ketogenic Diet 45 Metabolic Changes Caused by a Ketogenic Diet 45 B Vitamins 46 Antioxidants 46 Vitamin D 47 Nutrients To Support Ketosis 47 Carnitine. 47 Chromium. 47 The Ketogenic Diet Plan 48 Typical Ketogenic Diet Menu. 49 Ketogenic Diet Testimonials 50 References 52 Atkins Diet Lessons 64 Atkins diet pyramid. 64 Allowed and prohibited foods 64 Diet details 65 Samples meals 70 Compare with FDA Food pyramid 71 Atkins Diet Testimonials 73 The benefits beyond weight loss 73 A few reports on negative effects of the diet 74 Comments on energy increase 74 Improvements in cholesterol levels 76 Two dieters reported increases in cholesterol numbers 77 Atkins diet statistics 77 A water loss? 78 Long term results 79 Atkins diet and calorie intake 80

Ketosis, ketogenic diet and food intake control: a complex

Carbohydrate-biased control of energy metabolism: the darker side of the selfish brain

Frontiers in neuroenergetics, 2011

Frontiers in human neuroscience, 2013

Frontiers in Public Health, 2014

There is a consensus regarding the uni-versal significance of breakfast (BF) for health, wellbein... more There is a consensus regarding the uni-versal significance of breakfast (BF) for health, wellbeing, and cognition. The suc-cess of free school BF programs (e.g., Hasz and Lamport, 2012), which reportedly improve academic performance, fortifies this belief. However, studies showing cog-nitive effects of BF vs. skipping BF in large mixed cohorts of children (e.g., Wesnes et al., 2012) are often lack-ing metabolic and nutritional specifics. This creates uncertainty regarding the metabolic consequences of BF. Another uncertainty exists regarding skipping BF, which has been argued to have univer-

Frontiers in Nutrition, 2020

From the teleological standpoint, metabolic shifting evolved due to the periodic nature of the en... more From the teleological standpoint, metabolic shifting evolved due to the periodic nature of the environment, circadian cycles being one of the conditions the life on Earth confronts. Metabolic shifting occurs on a regular basis due to the demand-availability interplay of energy resources, expenditure, and depots, all of which have periodic nature due to the environment’s circadian rhythmicity. In modern societies, however, there are discrepancies between the evolutionary acquired metabolic setup and our current dysrhythmic, artificial environment. Thus, the so-called “diseases of civilization” are thought to be due to the changes in the environment that are too fast to cause adequate adaptations in our genome. On the other hand, an inherent fundamental feature of metabolism at large is flexibility. Out of themany diversemanifestations ofmetabolic flexibility, this Research Topic addresses the triad: “Timing, Nutrition, and Exercise” for the apparent reason—they are areas where they d...

A medical device to deliver skin stimulation was developed in Russia in the early 1980s and sever... more A medical device to deliver skin stimulation was developed in Russia in the early 1980s and several studies were done on the device. These studies indicated a high degree of success in the treatment of a variety of disorders. The device and method of use were based loosely on the practice of acupuncture. These, however, does not help to explain the phenomenon within Western scientific paradigm. Aside from metaphysical explanations about energy flow through the channels-meridians, there have been few theories proposed. The present paper reviews the development and the early Russian studies, as well as results of the pilot research program conducted in the Community Wholistic Health Center, Carrboro, NC. The paper then discusses two of the theories applicable to the results.

F1000Research, 2017

Prolonging the overnight fast habitually happens on a daily basis during the time-restricted feed... more Prolonging the overnight fast habitually happens on a daily basis during the time-restricted feeding regimen (TRF). In animal studies, TRF protocols restrict food availability to 4–8 hours every circadian cycle (e.g. during the dark phase in rodents). Animal studies have shown that metabolic consequences of TRF are metabolically favorable independently of caloric intakes. Even a short-term TRF intervention in adult rats slowed down age-associated cognitive decline and improved cognitive functions (Singh et al., 2012). The effects on glucose tolerance and insulin sensitivity were more pronounced compared to caloric restriction.
In humans, TRF is achieved by consistently reducing daily meal count. Similarly, TRF has been shown to be as metabolically favorable in humans showing long-term neuroprotective effects, e.g., in the prevention of neurodegenerative diseases (Jadiya et al., 2011; Srivastava & Haigis, 2011), supposedly via improving synaptic plasticity and cognitive function (Fontán-Lozano et al., 2008; Liu et al., 2013). TRF is one of the forms of Intermittent fasting, the one with superior adherence. A recent Japanese long-term study of a very large cohort extracted from 4-year long insurance records showed that BF skippers had a lower incidence of metabolic diseases, which constitute risk factors for diseases of aging. A recent Japanese long-term study of a very large cohort extracted from 4-year long insurance records showed that BF skippers had a lower incidence of metabolic diseases, which constitute risk factors for diseases of aging. Reducing these risk factors can provide protection against early onset of aging and prolong healthy, active and happy aging (Okamoto et al., 2013)

eneuro

The ketogenic diet (KD) has been successfully used for a century for treating refractory epilepsy... more The ketogenic diet (KD) has been successfully used for a century for treating refractory epilepsy and is currently seen as one of the few viable approaches to the treatment of a plethora of metabolic and neurodegenerative diseases. Empirical evidence notwithstanding, there is still no universal understanding of KD mechanism (s). An important fact is that the brain is capable of using ketone bodies for fuel. Another critical point is that glucose's functions span beyond its role as an energy substrate, and in most of these functions, glucose is irreplaceable. By acting as a supplementary fuel, ketone bodies may free up glucose for its other crucial and exclusive function. We propose that this glucose-sparing effect of ketone bodies may underlie the effectiveness of KD in epilepsy and major neurodegenerative diseases, which are all characterized by brain glucose hypometabolism.