Fasting application and considerations
Justin Gregory Maguire
Table of contents
- What is fasting
- Physiological insight into shifts that occur during fasting
- Three factors to consider before fasting
- Why should you implement intermittent fasting?
- Digestion: intestinal inflammation. Pancreas. biliary tree function
- Metabolic adaptation
- When should you NOT implement intermittent fasting:
- Stage 3 adrenal fatigue (imbalanced release of ACTH and thyroid activity)
- Renal disease
- Autoimmune disease
- Type fasting diets:
- IF: intermittent fasting 12 hours
- TRF: time restricted fasting: 4 hour feeding window
- ADF: alternative day fasting
- ADMF: alternative day modified fasting
- PF: periodic fasting, one to two days fasting per week
- Supplementation to aid intermittent fasting:
- Exogenous ketones
- Adaptogenic herbs
- Bentonite clay
- Molecular hydrogen (a wonder to fasting and oxidative stress as a whole)
What is fasting?
Physiological insight into shifts that occur during fasting
Fasting is the process by which the body reduces intake of calories for a period of time in which metabolic adaptations take place. From glycogenolysis to fatty acid derived ketones, the way in which our metabolism shifts toward using fat as a primary fuel source instead of glucose is often the motivating force behind utilising fasting diets.
Not only does fasting provide opportunity to lose excessive fat but it also has multiple applications in promoting health. Both Benjamin Franklin and Mark Twain have been sited to proclaim the health benefits within a fast. Yet it is the purpose of this manual to guide when to apply or avoid application of a fasting protocol.
- Within the fasting period a metabolic switch occurs 12-36 hours into a fast, at which point bound lipids (triaglycerol and diacyclglycerol) undergo beta oxidation within the liver and thus produce ketones, namely beta hydroxybuyterate and acetoacetate.
- Once ketones have been released by the liver they enter into muscle and neuron cells and through process of mitochondrial biogenesis they are oxidised to form acetyl-Co A.
- Oxidation of ketones within mitochondria is dependent on PPAR alpha activity, which is a transcription factor used to turn on gene expression of fatty acid oxidation.
- PPAR (peroxisome proliferators activated receptor)-alpha activates the following reactions process of fuelling fatty acid oxidation:
- Fatty acid translocase CD36
- Fatty acid binding protein 3
- Mitochondrial uncoupling protein 3
- PGC 1 alpha
- Pyruvate kinase dehydrogenase 4
The metabolic switch within a fast
A fasting induce switch called SIRT1 suppresses glucose production through inhibitory CRTC2 mediated gluconeogenesis. SIRT1 serves to provide further physiology reaction within a fasted state through the following:
- Represses lipolysis and cholesterol synthesis thereby regulating activity of cholesterol in catabolic pathways. In other word you use the cholesterol in your body for energy, prevent a build up which may damage your arteries.
- Positive regulator of liver oxidation of fatty acids. Reduces build up of fat in your liver, helpful for those with impaired detoxification or transferase enzyme activity.
- Deacetylates PGC-1alpha thus increasing the rate of fatty acid oxidation, in short it aids how much fat your body is able to use for energy.
- Activates PPAR-alpha: improving mitochondrial biogenesis as a whole.
- FGF21 (fibroblast growth factor): inducing ketogenesis whilst preventing hepatic steatosis (fatty liver build up) and controlling energy expenditure.
The most notable health improvement of fasting would be that of increased insulin sensitivity along with improved glucose management, both of which transcend outcome beyond that of the weight loss associated with fasting! Not only does fasting aid in hormonal sensitivity but one would also note that fasting protocol aids the prevention of lipid build up in the liver, especially when poor fat emulsification is present due to excessive stress or oxidation throughout the body.
Essentially following a high fat dietary regime would do well to include a form of fasting, in which the liver would better contend with digesting fat; accessing nutrients found within fat for purpose of improved health.
As conventional diets high in fat often note the following symptoms:
- Increased inflammatory markers (especially if fat is poorly emulsified)
- Decrease of glucose-6-phosphate
- Depletion of glutathione
All of which can be managed through the inclusion of a ADF (alternative day fast), thus those following high fat diets and not gaining positive outcome, should possibly consider including fasting as an additional aid in their health efforts.
Three factors to consider before fasting
However, before we go ahead and throw you straight into a fast there are three major determining factors to consider:
- Metabolic flexibility: At rest or in time of stress, how efficient is your body currently producing energy? Those whom are predominantly accessing energy at rest from glucose (sympathetic dominance), often note increased volume/rate of oxidation. Re-establishing basal lipid expenditure would be the first step before implementing a fast. Simply opting to fast in a higher state of sympathetic dominance would lead to potential cortisol dominance thus further compromising metabolic flexibility. In essence look to calm down your autonomic nervous system by fuelling the body with the energy source it most uses, thus lowering the need to further mobilise glucose via cortisol induced pathways.
- Suprachiasmatic nucleus: Exactly how well is your circadian rhythm functioning? Poor eating habits, whereby one goes without food throughout the day only to binge on calories before bed, thus impairing digestion along with quality of sleep, should not implement a fast until better control of eating times has been established. Implementing a fast in those with poor circadian eating will more than likely lead to poor psychological compliance and increased fatigue. First restrict the times in which one eats, once that has been accomplished then opt to go through a fasting plan in which a metabolic switch may occur.
- Zeitgeber influence: Does your lifestyle allow for environmental influence to not disrupt the metabolic switch associated with fasting? From technological exposure to industry pollution, where you work and live play a huge role into the potential effectiveness of fasting.
Why should you implement intermittent fasting?
Fasting provides our GI (gastro intestinal) tract time to ‘recovery’, abstaining from an intake of food simply lowers the need for interaction from the stomach to the intestines. Stress is often a factor which impacts our digestion, living in the modern day world essentially leaves us gassy and bloated! Abstinence from food simply allows motility to calm down and in doing so reduce the possible inflammation and gastro-intestinal stress.
Intestinal hyper-permeability is a condition whereby the tight junctions of the intestinal wall become inflamed and lose protective function in limiting exposure of harmful pathogens to our blood stream. Over time, intestinal hyper-permeability sets off potential pathological disease ranging from auto-immune disease to excessive endotoxin accumulation, all of which reduce metabolic efficiency and overall health. Fasting simply allows our intestinal mucosa the time to HEAL, reducing inflammation and eventually aiding the repair of the intestinal tract.
Microbiome balance is essential for purpose of immunity to psychology. Given that our bodies contain a greater value of bacterial cells than human cells, our microbiome essentially controls and influences how human genome is expressed. Unwanted bacteria may issue cause ranging from bowel toxemia to immune reaction or complete suppression, thus limiting growth of unwanted bacterial species is imperative toward establishing optimal digestion and overall nutrient assimilation. Fasting provides a solution to microbiome balance due to the fortunate nature of doubling time bacterial species may exhibit. Healthy bacterial species have a far longer doubling time than that of unwanted bacterial species, thus fasting provides a scenario whereby unwanted bacteria are starved for the outcome of healthy bacterial species having the opportunity to flourish. From flatulence to stomach cramps, fasting may be the resolution within a dietary plan focused on addressing dysbiosis (bacterial imbalance).
Assimilation of nutrients is highly dependent on the release and availability of enzymes and emulsification catalysts. Fasting aids, the regeneration of the:
- Pancreas: regeneration of both the exocrine and endocrine pancreatic cells has been noted throughout intermittent fasting periods ranging from 8-24 weeks in duration. Thus not only would one improve glucose modulation but also nutrient assimilation, all derived through the outcome of a revived pancreas.
- Liver: The liver is a powerhouse whereby detoxification and conversion of metabolites, amino acids and hormones take place. Bile is also produced in the liver, given the essential nature bile plays within fat emulsification, the state of hepatocyte (liver cells) health plays a big role in assimilating essential fatty acids and associated nutrients found in fat. Fasting aids in contending with liver steatosis (fatty liver build up) thereby reducing oxidative load the liver may need to contend with, whilst also promoting bile production and subsequent release.
- Gall bladder: With a reduce need to release bile through the bile duct during nutrient assimilation and overall digestion, the Gall bladder has time to regenerate its stores of bile and contend with healthy release. Fasting reduces excessive glucose load within our blood, this in turn improved bile release from the gall bladder, thus improving overall efficiency within fat emulsification.
From the liver to the kidneys and everything in between, detoxification happens regularly throughout our bodies, the capacity one has to detoxify determines the quality of life and overall energy cells may access. In a world whereby pollution is on the rise, one is confounded by increasing levels of toxins to contend with. Fasting not only provides a solution to our toxin problems but also aids in revival of essential organs which aid the detoxification process as a whole.
The liver goes through ongoing modification and conjugation processes which neutralise toxins to be released from our bodies. Poor metabolic flexibility increases the use and need of glucose at rest, which unfortunately also increases glucose exposure to hepatocytes. An increase of glucose exposure to the liver increases the build up of fat within hepatocytes, this in tern reduces detoxification capacity the liver may have in contending with environmental and endotoxin variables. Fasting provides resolution to fatty liver build up in the release of FGF 21 (fibroblast growth factor) which is expressed through translational gene expression of noted during heighten SIRT 1 activity (discussed in physiological impact of fasting). FGF 21 induces ketosis and thus also prevents hepatic steatosis, thus reducing the build up of fat in the liver. Thus fasting improves the capacity our body may have through initial and ongoing detoxification process by means of a leaner liver.
Previously within the topic of digestion, discussion of microbiome balance was mentioned within the role fasting may play toward establishing a healthy state of bacterial balance. In context of detoxification microbiomes play a huge role, in that each bacterial species exhibits its own metabolic cycle, thus proliferation of unwanted bacterial species increases the rate of endotoxin (toxins produced within the body) exposure. Fasting provides solution to not only crowding unwanted bacterial species but also reducing the toxin load such ‘bad’ bacteria may release within our body.
Oxidative stress can be either beneficial or detrimental all depending on the volume and type of free radicals produced through oxidation. Ketones supply neuron with 4x the energy per molecule to that of glucose, thus ketones are an effective fuel source in sustaining metabolic energy needs. Not only does fasting exhibit the increase release of ketones, but notable the release of B-OHB (beta hydroxybuyterate).
B-OHB is a powerful ketone that supplies neurons with energy reaction to release BDNF (brain derived neurotropic factor) which in turn stimulates the biogenesis and formation of new synapses.
Attaining a ketone shift releases:
- Fibroblast growth factor 2
- Heme oxygenase 1
- Glucose regulation protein 78
*all of which increase DNA methylation, which sustains expression/responsivity of genes involved in adaptive neuroplasticity and cognition. Fasting thus not only improves the biogenesis of new synapses but may also increase plasticity within neuron cell bodies, thus preventing age-related decline of cognitive capacity.
During fasting SIRT 1 switch initiates a whole host of beneficial physiological reactions, interestingly SIRT 1 is also a catalyst for the following gene expression:
- PGC-1 alpha
- Uncoupling protein 3
*all of which are also stimulated through muscle contraction, thus fasting may improve the adaptation of endurance through the same metabolic/genetic pathways in which endurance-based training exhibits.
Through the adaptive shift of fasting one notices increase of:
- Mitochondrial biogenesis.
- Autophagy and cellular stress resistance.
- Metabolic flexibility within the ANS (autonomic nervous system) tone.
- Less proteolysis in comparison to simple calorie restricted diets alone.
Thus fasting improves how:
- Mitochondria use energy.
- We are able to get rid of unwanted (useless) cells and thus increased regeneration of healthy tissue.
- Digestion and reaction through modulation of the autonomic tone.
- Preserve muscle tissue in the process of aging.
When should you NOT implement intermittent fasting?
Stage three adrenal fatigue
Adrenal fatigue is the result of constant demand on the motor peripheral nervous system to fuel excitation, resulting in the overuse of the adrenal glands. As reaction of our bodily systems in large is controlled by the central nervous system, adrenal fatigue is the outcome of over-excitation in both the CNS (central nervous system) and PNS (peripheral nervous system). Dependent on the stage of adrenal fatigue the body may or may not be receptive to the positive changes fasting may exhibit on physiology.
However, in the case of stage (final) adrenal fatigue, fasting would prove to be counterproductive due to the following reasons:
- Stage 3 adrenal fatigue is characterized by the poor release of cortisol, thus low glucose availability would not be addressed efficiently if the body is unable to release energy modulating hormone catalyst, potentially resulting in immune compromise and increased renal stress.
- In the event of poor cortisol production and release the central nervous system tries to contend with the imbalance through the increased release of ACTH (adrenocorticotropic hormone) which aggravates the brain into a state of further anxiety and increased stress perception. An increase of stress not only plays havoc on psychology but also wreaks havoc to the renal system as a further release of mineralocorticoids is amplified during the heightened state of ACTH profiles. As such fasting in a state of poor stress hormone release and overall modulation will only further impact renal health and associated immunity.
- Parathyroid activity is often impacted in cases of stage 3 adrenal fatigue, issuing a state of metabolic acidosis. Given the nature fasting has on mineral profile release, further compounding stress to Cation’s: 1. Sodium and 2. Potassium would only further exacerbate metabolic acidosis and in turn further compromise renal health and overall immunity.
Due to the nature fasting has on the release of mineralocorticoids those with renal disease would do well to not include fasting as a dietary management process. As renal disease decreases the kidneys’ ability to filter toxins and protein metabolites (both of which are notably increased during detoxification noted through fasting), abstaining from fasting practice would slow down the detoxification and proteolysis metabolite load the kidneys have to contend with.
Increased renal stress, issues an increase of oxidative stress within the liver. Given the conversion reaction noted through fasting; of bound fats into their free fatty acid form, an increase of oxidative stress would limit bilirubin activity and thus impair bile metabolism and subsequent red blood cell formation. Thus fasting in states of renal disease may actually lower concentration of available oxygen noted in hemoglobin formation.
Lastly, in cases of renal disease concentration of calcium and phosphorous are both contentious issues to deal with. Given the nature fasting has in the release of calcium and potassium during metabolic shifting, an increasing disparity of mineral concentration and release would only further compromise renal health resulting in potential nephron damage.
Cases of hypothyroidism are expressed through poor activity of the thyroid gland to readily convert and release Triiodothyronine. Primary or secondary cases all associate hypothyroidism as an impaired physiological reaction noted in both the periphery and central nervous system.
Although secondary hypothyroidism is often associated with stress, both major types of hypothyroidism influence and effect the immune system. Fasting may seem like the way to go in order to address thyroid imbalance, however as mentioned in previous chapters the state of one’s metabolic flexibility needs to be considered before administering a fasting protocol. In the case of hypothyroidism metabolic flexibility is often stunted and poor, giving precedence over glycolytic priority at basal rest (burning more carbs than fat at rest).
Not only is there a lack of autonomic tone within metabolic flexibility, cases of hypothyroidism one may also note there is an apparent lack in control of an energy switch from parasympathetic to sympathetic reaction. Given the nature fasting has on a metabolic switch, cases of hypothyroidism may not do too well in contending with the gene expression instigating autophagy in process of cellular renewal and overall stress resistance adaptation. An increase of autophagy increases peripheral tissue activity within metabolic turnover, heighten autophagy results in eventual increase of rT3 (reverse T3) thus inhibiting the little available T3 within cases of hypothyroidism.
Those whom are suffering from hypothyroidism would do best to first re-establish healthy circadian eating, inevitably improving on metabolic flexibility through modification of Suprachiasmatic nucleus and Zeitgeber influence prior to partaking within a fasting protocol.
Fasting accelerates autophagy, which under ‘normal’ circumstances issues regeneration of new healthy tissue. However, an increase of autophagy in cases of autoimmune disease may heighten subsequent immune response, thus increasing the probability of autoimmune reaction(s).
An increased rate of detoxification increased the rate of endotoxin removal from bacterial species. In those with an autoimmune disease increased endotoxin detoxification may prove to issue immune response reactive complication setting off an autoimmune ‘episode’.
Persons suffering from an autoimmune disease would do best to avoid dietary schedule which may accelerate detoxification past ‘normal’ values. Instead, cases of autoimmune disease would do well to follow a balanced routine in which food sensitivities and reactive factors are excluded, along with implementing positive lifestyle changes to improve on stress management.
Types of fasting diets
Intermittent fasting has multiple variants in dietary application. Before we go into subsequent fasting diet variations let’s first identify what constitutes as an intermittent fast:
Intermittent fasting is when caloric intake is nullified whilst consumption of almost zero-calorie beverages are consumed (coffee, water with lemon etc…) for a period of no less than 12 hours. This subsequently activates SIRT-1 activity through mediated fasting ‘switch’, issuing metabolic shift adaptation of mitochondrial biogenesis. Often fasting protocols would have the participant use amino acids to aid the fast, however note that amino acids such as
- Branched Chain amino acids
*will induce an insulin response and thus push the participant out of the fasting switch SIRT-1. Thus during a fast it is imperative to keep consumption of ‘aids’ to a minimal with the exception of a few supplements listed at the end of this guide.
TRF (time restrictive fasting)
Within this form of fasting one is only able to eat for a 4-hour window within a 24-hour period. Following intake of During the 4-hour window only 50% of regular caloric intake is allotted, additionally meal timing is of the highest importance as one of the limiting factors in this type of fast may be induced insomnia or sleep deprivation. Ensuring that meal intake occurs 3 hours prior to sleep will improve the longevity and effectiveness of this type of protocol.
ADF (alternate day fasting)
Alternate day fasting is by far reported as the most effective and yet manageable of all the fasting protocols. With most studies having utilised the parameters associated with ADF, one would do well to consider the application of ADF in your fasting efforts. Essentially alternative day fasting would have a participant not consume any calories for 36 hours whilst allowing a feeding opportunity for 12 hours in the following day after the fast.
ADMF (alternate day modified fasting)
This version of fasting would have the participant only consume 25% of their regular dietary intake on said fasting day. Although this is supposed to be a form of intermittent fasting one would do well to note that even a slight calorie intake during times of proposed SIRT-1 activity will NOT issue dominant gene expression or reaction noted with fasting protocol. An ADMF fast would best serve as a slow introduction toward eventual ADF protocol. One could rather consider this form of ‘fasting’ calorie restriction, which has its benefits but not to the extent in which fasting may express physiological change/adaptation.
PF (periodic fasting)
Periodic fasting entails following a 24-hour period of fasting for one or two days within a seven-day period. This is arguably the easiest form of fasting to implement, however irregular application may prove psychologically limiting in maintaining consistency of protocol. In this form of fast you may either interject the fast throughout the week or have two days follow succession in application, essentially you could do 5 on 2 off or 3-4 on 1 off.
Supplementation to aid intermittent fasting
Aids energy (neurological) during transition into mitochondrial biogenesis. Ketones also do not push one out of SIRT-1 activity thus the use of ketones serves to provide support whilst still encouraging the benefits of the metabolic shift associated with fasting.
I would recommend approx. 12gr of beta hydroxybuyterate twice throughout a fasting day to aid your fasting efforts.
Metagenics provide a full spectrum product which I highly recommend
Stress is an issue to contend with during fasting, notably through increased detoxification and mitochondrial gene expression. During the initial transition one may experience unwanted ‘stress’ symptoms in which case the use of adaptogenic herbs such as:
- Holy basil
- Rhodiola Rosea
*may serve to aid in effective cortisol modulation. Note however the assimilation of adaptogens during times of fasting is relatively poor due to the lack of gastric parasympathetic activity. As such I would not highly recommend their use, preferably one would be in a positive ‘stress’ state prior to participating in a fasting protocol thus not to need added cortisol modulation support.
- Used to aid cellular response of ATP production, especially in cases whereby available glucose is low.
- Chelated forms of magnesium serve superior as they do not require carriers (often attached through co-factors derived in process of digestion) to enter into the blood stream.
- As fasting may often cause constipation due to its influence on endotoxin removal derived from bacterial metabolism, one would do well to include magnesium to aid bowel movements.
Fasting increases, the release of sodium thereby influencing Cation balance. In order to not issue parathyroid stress, the use of electrolytes will go a long way in establishing a healthy metabolic pH. Thus using electrolytes proves to control exacerbated adrenal activity through modulating parathyroid response in controlling the anion gap.
This is an interesting supplement that may do well to be utilised beyond the realms of fasting. During fasting (and most other metabolic detoxification processes) an increase of unstable electrons is noted, molecular hydrogen provides an electron donor which stabilises reckless oxidative damage brought on through free radicals.
Most notably molecular hydrogen serves to quench activity of:
- Hydroxyl radicals
- Peroxy nitrates
Those suffering with oxidative stress or simply poor oxygen turnover during exercise would benefit from including molecular hydrogen into either daily drinking water or pre-workout formulae.
Connect with Justin Gregory Maguire
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