Nice study, the DIRECT study, found a better weight loss and longer maintenance of weight loss in low carbohydrate diet compared to low fat diet and mediterranean diet.
In this study, a high carbohydrate diet was replaced with a diet higher in monosaturated fats. The result was: a lower carb diet with resultant increase in monosaturated fats resulted in a reduction in triglycerides, reduction in systolic B/P, increase in HDL, and resultant decrease in CVD risk
Five branched chain and aromatic amino acids (isoleucine, leucine, valine, tyrosine, and phenylalanine) showed significant associations with future diabetes
there is increasing evidence that longer term high-protein intake may have detrimental effects on insulin resistance [68, 117–123], diabetes risk [69], and the risk of developing cardiovascular disease
high-protein and the high GI diets significantly increased markers of low-grade inflammation
significant and clinically relevant worsening of insulin sensitivity with an isoenergetic plant-based high-protein diet
healthy humans that are exposed to amino acid infusions rapidly develop insulin resistance
longer term high-protein intake has been shown to result in whole-body insulin resistance [68, 118], associated with upregulation of factors involved in the mammalian target of rapamycin (mTOR)/S6K1 signalling pathway [68], increased stimulation of glucagon and insulin within the endocrine pancreas, high glycogen turnover [118] and stimulation of gluconeogenesis [68, 118].
it was recently shown in a large prospective cohort with 10 years followup that consuming 5% of energy from both animal and total protein at the expense of carbohydrates or fat increases diabetes risk by as much as 30% [69]. This reinforces the theory that high-protein diets can have adverse effects on glucose metabolism.
Another recent study showed that low-carbohydrate high-protein diets, used on a regular basis and without consideration of the nature of carbohydrates or the source of proteins, are also associated with increased risk of cardiovascular disease [70], thereby indicating a potential link between high-protein Western diets, T2DM, and cardiovascular risk.
small study shows that low carb results in greater calories burned in weight loss. The least calories burned goes to low fat diet. Many, many studies have show the negative benefits of a low fat diet.
low carb diet found to benefit atherosclerosis and lipid abnormalities (Triglycerides, HDL, and LDL particle size). Interesting enough, no significant weight loss was seen.
For thousands
of years humans consumed fructose amounting to 16–20 grams per day
daily consumptions amounting to 85–100 grams of fructose per day
Of key importance is the ability of fructose to by-pass the main regulatory
step of glycolysis, the conversion of glucose-6-phosphate to fructose 1,6-bisphosphate,
controlled by phosphofructokinase
Thus, while glucose metabolism is negatively regulated by phosphofructokinase, fructose can continuously enter the glycolytic pathway. Therefore, fructose can uncontrollably produce glucose,
glycogen, lactate, and pyruvate, providing both the glycerol and acyl portions of
acyl-glycerol molecules. These particular substrates, and the resultant excess energy
flux due to unregulated fructose metabolism, will promote the over-production of TG
(reviewed in [53]).
Glycemic excursions and insulin responses were reduced by 66% and 65%, respectively, in the fructose-consuming
subjects
reduction in circulating leptin both in the short
and long-term as well as a 30% reduction in ghrelin (an orexigenic gastroenteric hormone)
in the fructose group compared to the glucose group.
A prolonged elevation of TG was
also seen in the high fructose subjects
Both fat and fructose consumption usually results in low leptin concentrations which,
in turn, leads to overeating in populations consuming energy from these particular
macronutrients
Chronic fructose consumption reduces adiponectin responses, contributing to insulin
resistance
A definite relationship has also been found between metabolic syndrome and hyperhomocysteinemia
the liver takes up dietary fructose rapidly where it can be converted to
glycerol-3-phosphate. This substrate favours esterification of unbound FFA to form
the TG
Fructose stimulates
TG production, but impairs removal, creating the known dyslipidemic profile
the effects of fructose in promoting TG synthesis are independent
of insulinemia
Although fructose does not appear to acutely increase insulin levels, chronic exposure
seems to indirectly cause hyperinsulinemia and obesity through other mechanisms. One
proposed mechanism involves GLUT5
If FFA are not removed from tissues, as occurs in fructose fed insulin
resistant models, there is an increased energy and FFA flux that leads to the increased
secretion of TG
In these scenarios, where there is excess hepatic fatty acid uptake, synthesis and
secretion, 'input' of fats in the liver exceed 'outputs', and hepatic steatosis occurs
Carbohydrate induced hypertriglycerolemia results from a combination of both TG
overproduction, and inadequate TG clearance
fructose-induced metabolic dyslipidemia is usually accompanied
by whole body insulin resistance [100] and reduced hepatic insulin sensitivity
Excess VLDL secretion has been shown to deliver increased fatty acids and
TG to muscle and other tissues, further inducing insulin resistance
the metabolic effects of fructose occur through rapid utilization
in the liver due to the bypassing of the regulatory phosphofructokinase step in glycolysis.
This in turn causes activation of pyruvate dehydrogenase, and subsequent modifications
favoring esterification of fatty acids, again leading to increased VLDL secretion
High fructose diets can have a hypertriglyceridemic and pro-oxidant
effect
Oxidative stress has often been implicated in the pathology of insulin resistance
induced by fructose feeding
Administration of alpha-lipoic acid (LA) has been shown to prevent
these changes, and improve insulin sensitivity
LA treatment also prevents several deleterious effects of fructose feeding: the
increases in cholesterol, TG, activity of lipogenic enzymes, and VLDL secretion
Fructose has also been implicated in
reducing PPARα levels
PPARα is a ligand activated nuclear hormone
receptor that is responsible for inducing mitochondrial and peroxisomal β-oxidation
decreased PPARα expression can result in reduced oxidation, leading to cellular lipid
accumulation
fructose diets altered the structure and function of VLDL particles
causing and increase in the TG: protein ratio
LDL particle size has been found to be inversely related to TG concentration
therefore the higher TG results in a smaller, denser, more atherogenic LDL particle,
which contributes to the morbidity of the metabolic disorders associated with insulin
resistance
High fructose, which stimulates VLDL secretion, may initiate the cycle that results
in metabolic syndrome long before type 2 diabetes and obesity develop
A high flux of fructose to the liver, the main organ capable of metabolizing this
simple carbohydrate, disturbs normal hepatic carbohydrate metabolism leading to two
major consequences (Figure 2): perturbations in glucose metabolism and glucose uptake pathways, and a significantly
enhanced rate of de novo lipogenesis and TG synthesis, driven by the high flux of glycerol and acyl portions
of TG molecules coming from fructose catabolism
Fructose and metabolic syndrome. Good discussion of the impact of high fructose intake and metabolic dysfunction. This study also does a great job of highlighting the historical change of fructose intake.
low-glycemic index diet aids in mobilization of adipose tissue in exercise. In this study, exercise after a low-glycemic meal resulted in a greater mobilization of adipose tissue for energy production than a high glycemic meal. This will help in weight loss
Only abstract available here. Article looked at the evidence of daily carb intake for levels of training: low training-3-5 g/kg; moderate training (1h)-5-7 g/kg; endurance training (1-3h)-6-10 g/kg; extreme endurance (>4-5h)-8-12 g/kg
Extra-adrenal cortisol production is increased by 11-Beta-HSD1 via low Carb diet. This is counter to that seen in mice studies. The fat content of the diet could explain this. This study looked at men.
Diet higher in fats and lower in carbs associated with a reduction in weight, fat mass, improved insulin sensitivity, lowered fasting glucose, and a reduction in TNF-alpha
Mechanistic studies further showed that such metabolic inflammation is related to the induction of various intracellular stresses such as mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, and autophagy defect under prolonged nutritional excess
intracellular stress-inflammation process for metabolic syndrome has been established in the central nervous system (CNS) and particularly in the hypothalamus
the CNS and the comprised hypothalamus are known to govern various metabolic activities of the body including appetite control, energy expenditure, carbohydrate and lipid metabolism, and blood pressure homeostasis
Reactive oxygen species (ROS) refer to a class of radical or non-radical oxygen-containing molecules that have high oxidative reactivity with lipids, proteins, and nucleic acids
a large measure of intracellular ROS comes from the leakage of mitochondrial electron transport chain (ETC)
Another major source of intracellular ROS is the intentional generation of superoxides by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
there are other ROS-producing enzymes such as cyclooxygenases, lipoxygenases, xanthine oxidase, and cytochrome p450 enzymes, which are involved with specific metabolic processes
To counteract the toxic effects of molecular oxidation by ROS, cells are equipped with a battery of antioxidant enzymes such as superoxide dismutases, catalase, peroxiredoxins, sulfiredoxin, and aldehyde dehydrogenases
intracellular oxidative stress has been indicated to contribute to metabolic syndrome and related diseases, including T2D [72; 73], CVDs [74-76], neurodegenerative diseases [69; 77-80], and cancers
intracellular oxidative stress is highly associated with the development of neurodegenerative diseases [69] and brain aging
dietary obesity was found to induce NADPH oxidase-associated oxidative stress in rat brain
mitochondrial dysfunction in hypothalamic proopiomelanocortin (POMC) neurons causes central glucose sensing impairment
Endoplasmic reticulum (ER) is the cellular organelle responsible for protein synthesis, maturation, and trafficking to secretory pathways
unfolded protein response (UPR) machinery
ER stress has been associated to obesity, insulin resistance, T2D, CVDs, cancers, and neurodegenerative diseases
brain ER stress underlies neurodegenerative diseases
under environmental stress such as nutrient deprivation or hypoxia, autophagy is strongly induced to breakdown macromolecules into reusable amino acids and fatty acids for survival
intact autophagy function is required for the hypothalamus to properly control metabolic and energy homeostasis, while hypothalamic autophagy defect leads to the development of metabolic syndrome such as obesity and insulin resistance
prolonged oxidative stress or ER stress has been shown to impair autophagy function in disease milieu of cancer or aging
TLRs are an important class of membrane-bound pattern recognition receptors in classical innate immune defense
Most hypothalamic cell types including neurons and glia cells express TLRs
overnutrition constitutes an environmental stimulus that can activate TLR pathways to mediate the development of metabolic syndrome related disorders such as obesity, insulin resistance, T2D, and atherosclerotic CVDs
Isoforms TLR1, 2, 4, and 6 may be particularly pertinent to pathogenic signaling induced by lipid overnutrition
hypothalamic TLR4 and downstream inflammatory signaling are activated in response to central lipid excess via direct intra-brain lipid administration or HFD-feeding
overnutrition-induced metabolic derangements such as central leptin resistance, systemic insulin resistance, and weight gain
these evidences based on brain TLR signaling further support the notion that CNS is the primary site for overnutrition to cause the development of metabolic syndrome.
circulating cytokines can limitedly travel to the hypothalamus through the leaky blood-brain barrier around the mediobasal hypothalamus to activate hypothalamic cytokine receptors
significant evidences have been recently documented demonstrating the role of cytokine receptor pathways in the development of metabolic syndrome components
entral administration of TNF-α at low doses faithfully replicated the effects of central metabolic inflammation in enhancing eating, decreasing energy expenditure [158;159], and causing obesity-related hypertension
Resistin, an adipocyte-derived proinflammatory cytokine, has been found to promote hepatic insulin resistance through its central actions
both TLR pathways and cytokine receptor pathways are involved in central inflammatory mechanism of metabolic syndrome and related diseases.
In quiescent state, NF-κB resides in the cytoplasm in an inactive form due to inhibitory binding by IκBα protein
IKKβ activation via receptor-mediated pathway, leading to IκBα phosphorylation and degradation and subsequent release of NF-κB activity
Research in the past decade has found that activation of IKKβ/NF-κB proinflammatory pathway in metabolic tissues is a prominent feature of various metabolic disorders related to overnutrition
it happens in metabolic tissues, it is mainly associated with overnutrition-induced metabolic derangements, and most importantly, it is relatively low-grade and chronic
this paradigm of IKKβ/NF-κB-mediated metabolic inflammation has been identified in the CNS – particularly the comprised hypothalamus, which primarily accounts for to the development of overnutrition-induced metabolic syndrome and related disorders such as obesity, insulin resistance, T2D, and obesity-related hypertension
evidences have pointed to intracellular oxidative stress and mitochondrial dysfunction as upstream events that mediate hypothalamic NF-κB activation in a receptor-independent manner under overnutrition
In the context of metabolic syndrome, oxidative stress-related NF-κB activation in metabolic tissues or vascular systems has been implicated in a broad range of metabolic syndrome-related diseases, such as diabetes, atherosclerosis, cardiac infarct, stroke, cancer, and aging
intracellular oxidative stress seems to be a likely pathogenic link that bridges overnutrition with NF-κB activation leading to central metabolic dysregulation
overnutrition is an environmental inducer for intracellular oxidative stress regardless of tissues involved
excessive nutrients, when transported into cells, directly increase mitochondrial oxidative workload, which causes increased production of ROS by mitochondrial ETC
oxidative stress has been shown to activate NF-κB pathway in neurons or glial cells in several types of metabolic syndrome-related neural diseases, such as stroke [185], neurodegenerative diseases [186-188], and brain aging
central nutrient excess (e.g., glucose or lipids) has been shown to activate NF-κB in the hypothalamus [34-37] to account for overnutrition-induced central metabolic dysregulations
overnutrition can present the cell with a metabolic overload that exceeds the physiological adaptive range of UPR, resulting in the development of ER stress and systemic metabolic disorders
chronic ER stress in peripheral metabolic tissues such as adipocytes, liver, muscle, and pancreatic cells is a salient feature of overnutrition-related diseases
recent literature supports a model that brain ER stress and NF-κB activation reciprocally promote each other in the development of central metabolic dysregulations
when intracellular stresses remain unresolved, prolonged autophagy upregulation progresses into autophagy defect
autophagy defect can induce NF-κB-mediated inflammation in association with the development of cancer or inflammatory diseases (e.g., Crohn's disease)
The connection between autophagy defect and proinflammatory activation of NF-κB pathway can also be inferred in metabolic syndrome, since both autophagy defect [126-133;200] and NF-κB activation [20-33] are implicated in the development of overnutrition-related metabolic diseases
Both TLR pathway and cytokine receptor pathways are closely related to IKKβ/NF-κB signaling in the central pathogenesis of metabolic syndrome
Overnutrition, especially in the form of HFD feeding, was shown to activate TLR4 signaling and downstream IKKβ/NF-κB pathway
TLR4 activation leads to MyD88-dependent NF-κB activation in early phase and MyD88-indepdnent MAPK/JNK pathway in late phase
these studies point to NF-κB as an immediate signaling effector for TLR4 activation in central inflammatory response
TLR4 activation has been shown to induce intracellular ER stress to indirectly cause metabolic inflammation in the hypothalamus
central TLR4-NF-κB pathway may represent one of the early receptor-mediated events in overnutrition-induced central inflammation.
cytokines and their receptors are both upstream activating components and downstream transcriptional targets of NF-κB activation
central administration of TNF-α at low dose can mimic the effect of obesity-related inflammatory milieu to activate IKKβ/NF-κB proinflammatory pathways, furthering the development of overeating, energy expenditure decrease, and weight gain
the physiological effects of IKKβ/NF-κB activation seem to be cell type-dependent, i.e., IKKβ/NF-κB activation in hypothalamic agouti-related protein (AGRP) neurons primarily leads to the development of energy imbalance and obesity [34]; while in hypothalamic POMC neurons, it primarily results in the development of hypertension and glucose intolerance
the hypothalamus, is the central regulator of energy and body weight balance [
The ketogenic diet (KD) is a high-fat, low-protein, low-carbohydrate diet that has been employed as a treatment for medically refractory epilepsy for 86 years
The hallmark feature of KD treatment is the production of ketone bodies by the liver
almost any diet that produces ketonemia and/or diminished blood glucose levels can induce an anticonvulsant effect.
For endurance athletes, low carb and high fat diet utilizes the high fat oxidation in these athletes compared to a high carb diet. Glycogen stores did not differ between the two groups.