Caloric restriction

Confers protection from invasive breast cancer and particularly if it occurs prior to first birth.

It is suggested that calorie restriction may prolong lifespan in humans.

Refers to a dietary regimen that is based on low calorie intake.

A low caloric intake can be defined relative a person’s previous intake before restricting calories, or relative to an average person of similar body type.

Caloric restriction is linked to improvement in weight, blood pressure, and insulin sensitivity in humans.

Caloric restriction without malnutrition has been shown in a variety of species such as fish, rodents and dogs to decelerate the biological aging process, and an increase in both median and maximum lifespan.

No clinical trial has been performed involving humans, but two trials have been performed involving primates, have not demonstrated increases in median lifespan.

Daily calorie restriction has modest, less than 5%, mean weight loss after 12 months, and long-term maintenance of weight loss remains a challenge, in most trials.

Long-term CR has a powerful protective effect against atherosclerosis.

A 20% CR for 12 months in overweight individuals results in a significant reduction in visceral fat mass, LDL-cholesterol, triglycerides, and C-reactive protein, and improves insulin sensitivity.

Individuals practicing CR have lower levels of total and abdominal fat, circulating insulin, testosterone, estradiol and inflammatory cytokines.

Data suggest limiting food intake to an eight-to-12-hour window can improve insulin sensitivity, blood pressure, fat metabolism, gut function, and immune function. 

It can also lower inflammation and help regulate uric acid.

The long-term effects of moderate CR with adequate intake of nutrients is unknown.

Members of the calorie restriction society who follow calorie restriction with optimal nutrition have low rates of diabetes mellitus, with low levels of insulin like growth factor1, growth hormone, and markers of inflammation and oxidative stress.

Extreme CR may result in serious deleterious effects.

CR promotes hunger and slowing of the metabolic rate, and these adaptive biological responses antagonize ongoing weight loss and undermine long-term dietary adherence.

A study of lean men with restricted caloric intake of 45% for 6 months, resulted decreased body fat, blood pressure, improved lipid profile, low serum T3 concentration, and decreased resting heart rate and whole-body resting energy expenditure, anemia, lower extremity edema, muscle wasting, weakness, neurological deficits, dizziness, irritability, lethargy, and depression.

Calorie restriction associated with loss of muscle mass and strength and reduced bone mineral density. disrupts protein synthesis, amino acid uptake, and immune response.

Long-term CR associated with reduced bone mineral density.

CR diets typically lead to reduced body weight, and low body weight has been associated with increased mortality, particularly in late middle-aged or elderly subjects.

A controlled study of human CR found no increase in eating disorder symptoms or other harmful psychological effects.

Calorie restriction in those with a binge-eating disorder can precipitate binge eating.

CR not appropriate for young individuals or women seeking pregnancy, as it can impair development in the young and impair fertility and increase preterm deliveries.

CR weight loss associated with cold sensitivity, menstrual irregularities, infertility, hormonal changes, and when extreme, starvation.

Explanations for benefit of CR include reduced cellular division rate, lower metabolic rates, decreased production of free radicals, reduced DNA damage and hormesis.

Life-extending effects of CR may arise partly from a shift toward a gene expression profile more typical of females.

Prolonged CR lowers testosterone levels while increasing SHBG concentrations.

CR lowers of the concentration of insulin and substances related to insulin, such as insulin-like growth factor 1 and growth hormone: this process up-regulates autophagy, the repair mechanism of the cell.

Biological effects of CR are closely related to chromatin function.

CR associated with less free radical generation.

Lower blood glucose levels due to CR means less glycation of adjacent proteins and less fat to oxidize in the bloodstream to cause atherosclerosis.

Calorie restriction reduces production of reactive oxygen species.

Reactive oxygen species cause several types of DNA damage including 8-hydroxy-2’-deoxyguanosine, an indicator of the general level of oxidative damage in DNA.

Exercise increases health and life span and lowers the incidence of several diseases relative to sedentary and obese controls, but not to energy-restricted sedentary controls of matching body weight.

A 12% reduction in daily caloric intake for a period of two years improves many cardiovascular risk factors in non-obese patients (CALERIE).

Overweight adult asthmatics following alternate day calorie restriction (ADCR) for eight weeks show a marked improvement in oxidative stress, inflammation, and the severity of the disease.

Patients with asthma and obesity who adhere to an alternate day fasting and elevated serum level of ketone bodies on energy restriction days and lost weight over a two month period, during which asthma symptoms and airway resistance were mitigated.

Alternate day calorie restriction in the absence of weight loss prolongs life span in humans.

Intermittent fasting encompasses the spectrum of nutritional behaviors that intentionally interrupt energy consumption for extended periods of time on a regular intermittent schedule.

Time restricted eating is an intermittent fasting regimen that involves a short period of time for eating within a 24 hour period

Studies show that patients with multiple sclerosis who adhere to intermittent fasting regimens have reduce symptoms in a period in short is two months.

Intermittent fasting types are alternative day fasting and time-restricted fasting.

In alternative day fastig a subset may consist of 24 hour fast followed by a 24 hour eating: Which can be done several times a week.

Some programs interrupt  energy consumption for 16-24 hours with cessation of calorie intake and feeding during 6-8 hour blocks.

For time-restricted first programs, variations include 16 hour fast with eight hour feeding times, 20 hour fast with four hour feed times, or other similar versions.

Intermittent fasting is a dietary intervention similar to caloric restriction, in that it uses the principle of restricting food intake.

Studies comparing intermittent fasting to caloric restriction in terms of blood pressure, cholesterol levels, inflammation, and cognitive function have mixed results,  but overall not significant differences.

Intermittent fasting is linked to better glucose control.

During intermittent fasting, insulin resistance increases substantially as the body switches its energy source from glucose to Ketones and fatty acids, but insulin resistance returns to baseline on refeeding after intermittent fasting.

Repeated fasting episodes are linked to improved insulin sensitivity and reduced insulin levels, and these changes are similar to those as with caloric restriction.

The long-term adherence to caloric restriction is low, whereas adherence to intermittent fasting maybe more promising.

Intermittent fasting in type two diabetes has a risk of hypoglycemia  in patients  on anti-diabetic agents and also dehydration, hypotension.

Intermittent fasting focuses on the timing of when meals are consumed either within a day or a week.

Intermittent fasting increases the resistance of neurons in the brain to excitotoxic stress.

Intermittent fasting results in metabolic switching from liver-derived glucose to adipose cell derived ketones that occurs daily or several days each week.

Intermittent fasting results in reduced free radical production and weight loss.

Intermittent fast day causes evolutionary conservation, adaptive cellular responses integrated between and within organs that improves glucose regulation, increases stress resistance, and suppresses inflammation.

Intermittent fasting interventions ameliorate obesity, insulin resistance, dyslipidemia, hypertension, and inflammation.

Intermittent fasting in type two diabetes is associated with decreases in weight, most studies  showing  declines in hemoglobin A-1 C, most showing improve glucose, improved quality-of-life, improved blood pressure, but not improved insulin resistance.

Intermittent fasting conference health benefits to a greater extent than can be attributed just to the reduction in caloric intake.

Intermittent fasting improves physical function and memory, Global cognition and executive function.

Alternative day fasting in obese shows lower levels of inflammation such as tumor necrosis factor-alpha and brain derived neurotrophic factors as well as oxidative stress.

On the island of Okinawa intermittent fasting is associated with low rates of obesity and diabetes and is associated with extreme longevity.

Studies of daily caloric restriction or intermittent fasting reversed insulin resistance  in patients  with pre-diabetes or type two diabetes.

Two weeks of pre-operative daily energy restriction improves outcomes in patients undergoing gastric bypass surgery.

Preop and fasting reduces tissue damage and inflammation and improves the outcome of surgical procedures.

Intermittent fasting improves blood pressure, resting heart rate, levels of high density and low density lipoprotein, triglycerides, glucose, and insulin along with insulin resistance.

Intermittent fasting reduces the markers of systemic inflammation in oxidative stress that are associated with atherosclerosis.

Studies show that intermittent fasting is as effective for weight loss is standard diets.

Historically human ancestors did not consume three regularly spaced meals, plus snacks every day, nor did they live a sedentary lifestyle.

Most organ systems respond to intermittent fasting to enable the organism to tolerate or overcome the challenge and then restore homeostasis.

Alternate day fasting is effective for weight loss and cardio protection in normal weight and overweight adults.

Improvements in cardiovascular health indicators become evident within 2-4 weeks if the start of alternate fasting.

Repeated exposure to fasting results in adaptive responses that confer lasting resistance to subsequent challenges.

Cells  respond to intermittent  fasting by and adaptive stress response it leads to increased expression of antioxidant defenses, DNA repair, mitochondrial biogenesis and autophagy and down regulation of inflammation.

There is evidence that calorie restriction may increase formation of free radicals within the mitochondria, causing a secondary induction of increased antioxidant defense capacity.

Cells of animals maintained on intermittent fasting and regimen shows improve function and resistance to damaging insults and include metabolic, oxidative, ionic, traumatic, and prototoxic stress.

Intermittent fasting stimulates autophagy and mitophagy while inhibiting the mTOR protein synthesis pathway.

Responses to intermittent fasting allows cells  to remove oxidative damage proteins and mitochondria to recycle and damage molecular constituents while temporarily reducing  global protein synthesis to conserve energy and molecular resources.

The above pathways are untapped by suppressed when one over eats and is sedentary.

Studies conclude that reduce food intake increases lifespan.

Fasting allows cells to activate Pathways that enhance defenses against intrinsic defects against oxidative and metabolic stress and those that removal repair damaged molecules.

It is suggested that the periodic flipping of the metabolism provides ketones necessary to fuel cells during fasting, but also is used for cellular responses that carry over into the fed state to bolster mental and physical performance, as well as disease resistance.

Intermittent fasting affects general health and slows or reverses aging and disease processes.

The main sources of energy for cells or a glucose and fatty acids.

After eating, glucose is used for energy, and fat that is stored in adipose tissue as triglycerides.

Caloric restriction and exercise-mediated weight loss in obese individuals with type 2 diabetes are associated with reduced NLRP3 inflammasome expression in adipocytes as well as with decreased inflammation and improved insulin sensitivity.

With fasting triglycerides are broken down to fatty acids and glycerol, which are use for energy.

During feeding cells engage in tissue processes of growth and plasticity.

Because most people consume three meals a day plus snacks, intermittent fasting does not occur.

Sustained calorie deprivation leads to a decrease in basal metabolic rate and energy expenditure, negating the effect of reduced calorie intake.

Reducing daily food intake by the equivalent of around 300 calories, over 2 years leads to improvements in body composition but a range of cardiometabolic risk factors that could result in reductions in the incidence of cardiovascular disease.

The Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) trial is a phase 2 study involving more than 200 normal to slightly overweight but otherwise healthy individuals up to aged 50 years.

Study aimed at reducing energy intake by 25% in study patients, or a control group, who continued with their normal diet.

Individuals in the intervention group actually achieved an average reduction in energy intake of almost 12% over 2 years, with an average weight loss of 7.5 kg or approximately 16.5 lbs.

These findings are associated with significant improvements in lipid levels, better insulin sensitivity, metabolic syndrome scores, and C-reactive protein levels.

Severe calorie restriction has a protective effect against atherosclerotic risk factors such as carotid artery intimal-media thickening, reduced left ventricular diastolic function, and poor heart rate variability.

The CALERIE study randomized individuals from three US clinical centers who were normal weight or slightly overweight, defined as a body mass index (BMI) of 22.0-27.9 kg/m2.

Men aged 21-50 years and premenopausal women aged 21-47 years were included.

The calorie restriction intervention aimed at reducing calorie intake by 25% or to ad libitum control group.

Reults were seen for BMI, percentage body fat, fat mass, and fat-free mass, with individuals in the calorie restriction group having significant reductions over baseline at years 1 and 2. but no significant changes recorded in the control grpup.

The calorie restriction intervention was associated with significant reductions in low-density lipoprotein cholesterol (LDL-C) levels, triglycerides, and total cholesterol to high-density lipoprotein cholesterol (HDL-C) ratio at 1 and 2 years.

The intervention group also had significant increases in HDL-C levels from baseline at both year 1 and 2.

Moderate calorie restriction, can be implemented early in life to optimize cardiometabolic health and reduce the lifetime risk of developing some of the most common, disabling, and expensive chronic diseases

The modest weight gain of around 5 kg during young and middle adulthood is associated with a significantly increased risk of type 2 diabetes, cardiovascular disease, obesity-related cancer, and premature death.

Intermittent fasting is thought to impair energy metabolism in cancer cells: trials are ongoing.

Epidemiological information suggests that excessive energy intake, particularly in midlife, increases risk of stroke, Alzheimer’s disease, and Parkinson’s disease.

Intermittent fasting has the potential benefit of slowing the progression of neurodegenerative diseases like Alzheimer’s and Parkinson’s disease.

Intermittent fasting increases neuronal stress resistance bolstering mitochondrial function, stimulating autophagy, neutrotropic factor production, antioxioxidant defenses and DNA repair.

Intermittent fasting could lead to better cardiovascular outcomes as it relates to decreased oxidative stress, circadian rhythm and the ketogenic state.

Decreased energy intake causes mitochondria to produce fewer radicals and leads to lower levels of inflammatory markers such as tumor necrosis factor Alpha and brain derived neurotrophic factors as well as oxidative stress including nitrotyrosine, eight-iso prostane, protein carbonyls, and 4  hydroxynoneal adducts.

Fasting may allow optimization with organ’s  periphera clocks such as the liver, adipose and skeletal tissues.

Examples of the influence of circadian rhythm is that there are decreasing insulin levels later in the day, as late dinners are associated with higher postprandial glucose levels than daytime meals, increasing the risk of diabetes.

Circadian rhythm misalignment increases insulin resistance after only three days

Nighttime eating decreases the quality and quantity of sleep, which also leads to insulin resistance, obesity, and cardiovascular disease.

Dysregulation of the circadian rhythm system increase the risk of chronic diseases, as evidence by higher risk for chronic disease development in shift workers.

Intermittent fasting enhances GABA inhibitory neurotransmission and can prevent seizures and excitotoxicity.

On attempting an intermittent fasting regimen, many individuals experience hunger, irritability, and reduced ability to concentrate during periods of food restriction.

The above symptoms however usually disappear within one month.

Among patients with obesity time restricted eating was not more beneficial with regard to reduction in body weight, body fat, or metabolic risk factors then daily caloric restriction (Liu D).



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