A question from Ms.
Josephine Wong was posted to me on a video claim that frequent eating with
short intervals between meals is more health-protective and contributes towards
longevity than those who eat less and less often.
Thank you for your
question.
Caloric Restriction
and Longevity:
First of all I want to
quote a very famous study by Clive McCay of Cornell University as far back as
in 1935 that when rats were put on a caloric restriction diet, it considerably prolongs
their life span.
This study was
repeated many times on other animals showing the same result. Even before all
these well-established studies, Hippocrates of Kos, circa 460 – c. 370 BC, now considered the Father of Medicine
and Nutrition, and later Galen have all advocated eating less.
Avicenna c. 980 –1037) a Persian physician, astronomer, thinker
and writer of the Islamic Golden Age also taught the same advice that we should eat less for longevity and
freedom from disease.
Let me now elaborate
on their thinking as well as giving probable explanations what modern scientists
found when we eat little, and less often. We will begin by seeing what happens
when food is consumed
However, we will not
go into the physiology of food consumption, its digestion, absorption,
transportation and distribution as discussion on these are very lengthy, unnecessary,
and irrelevant within the scope of answering your enquiry.
We will instead go
straight away into metabolism of food using simple biochemistry and the role of the liver and kidneys as these
are the only two organs that have to deal with the nutrients absorbed (the
liver), and the chemical fate of the nutrients (metabolism), and the kidneys
that has to deal with the metabolic wastes like urea.
Metabolism:
Once food has been
digested, absorbed and transported to the liver by the portal vein, the nutrients
are either metabolized or stored. The body is continuously undertaking a series
of complicated chemical reactions called metabolism to empower the body to
continue to exist, provide the energy the body needs, and the cells to divide
and grow.
Metabolic reactions
are divided into catabolism by obtaining energy derived from the nutrients, and
anabolism for the development of new cells that necessitates energy from the
catabolism.
There are hundreds of
thousands of chemical reactions going on and their pathways in the body at any
moment in time, but we shall not deal with biochemistry here.
In order to keep this
answer short and neat and within the scope of the question, we shall only give
some examples of major sources of energy the body derives from the metabolism
of nutrients. These are:
1.
Glycolysis
which is the oxidation of glucose that empowers the synthesis of energy-rich ATP
2.
Krebs'
cycle or citric acid cycle (CAC), sometimes also called the tricarboxylic acid
cycle (TCA) is a chain of chemical reactions used by the body to release stored
energy through the oxidation of acetyl-CoA acquired from carbohydrates, fats,
and proteins.
Acetyl-CoA
is a molecule that participates in many biochemical reactions involving
protein, carbohydrate and lipid metabolism. Its main function is to deliver the
acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy
production.
They
then give off carbon dioxide and the release of chemical energy and other
intermediary products. The Kreb’s Cycles requires the B group of vitamins to
proceed.
The oxidative
phosphorylation encompasses the disposal of the electrons released by
glycolysis and citric acid cycle. Much of the energy released in this activity is
subsequently stored as adenosine triphosphate (ATP), an energy-rich phosphate
bond.
The discharge
of electrons in a metabolic or in any chemical reactions generates destructive
free radicals to the cells, tissues and body systems, and more crucially to the
DNA. We shall deal with this later.
3.
The
pentose phosphate pathway is the synthesis of pentose, and the release of
reducing energy needed for anabolic reactions
4.
The urea
cycle comprises of the disposal of NH4+ in less toxic forms
5.
Fatty acid
beta-oxidation activates fatty acids breakdown into acetyl-CoA. This then
enters into the Krebs' cycle once again.
6.
Gluconeogenesis
that involves in glucose synthesis is used by the brain for energy.
The Liver:
One of the major
functions of the liver is the maintenance a fairly balanced concentration of
glucose in the blood. This is accomplished through gluconeogenesis and glycogen
synthesis and degradation. It synthesizes ketone bodies when acetyl-CoA is adequate.
It is also the site of
urea synthesis. There are hundreds if not thousands of chemical reactions and various
pathways taking place in the liver. But we shall not go into all the liver
chemistry
It is estimated the
liver has to deal with over 500 – 700 functions. Many of these include
assimilating and storing fat-soluble vitamins, producing bile, filtering blood,
metabolizing fats, proteins, and carbohydrates, and endogenous hormones, dealing
with wastes, and detoxifying alien
chemicals, toxins and drugs, changing ammonia
into urea through the urea or ornithine
cycle.
The liver also syntheses
blood proteins, depositing nutrients like glucose into glycogen, as well as
storing fat soluble vitamins, and minerals.
The Liver and Free
Radicals:
Since the liver is the
site of most of the synthesis and metabolic breakdown, and since these
biochemical reactions involve the transfer of elections; either to lose or to
capture them, it generates free radicals. Any atoms, molecules or molecular fragments
that lose an election become a highly destructive free radical.
The simplest free
radical is an electron. A hydrogen atom is also the simplest free radical
A hydrogen molecule
has an electron pair, and hence, it is not a free radical. But when hydrogen is
irritated with UV light without oxygen, a hydrogen molecule (H-H) may be
fragmented evenly (homolytic cleavage) it produces two hydrogen atoms or two
free radicals:
H2 → 2H•
A very good example of
a free radical production in chemical reactions in the liver, or elsewhere in
the body, and in the environment outside the body, is production of the
hydroxyl radical (HO•)
Since free radicals are
highly unstable chemically they can only exist for just a fraction of a second in
the presence of an electron recipient
However even their
very short existence is long enough to cause untold damage to the DNA, cells,
tissues, organs and systems of the body. We shall go more into free radicals a
little later, and how they can damage the DNA in the body.
Unfortunately, the
more food we eat, the more toxic wastes and metabolites we produce, and the more
destructive free radicals are generated in the process of anabolism and catabolism.
After the liver have broken down the toxic waste of metabolism, most of them
are handed over to the kidneys for excretion
The Kidneys:
The kidneys besides being
an excretory organ can also carry out gluconeogenesis to release glucose into
the bloodstream. But its main role is
the excretion of urea, electrolytes, and other excretory metabolites.
There is a condition
called metabolic acidosis that occurs when the body produces excessive amounts of
acid or when the kidneys are not clearing sufficient acid from the body.
However, metabolic
acidosis may be increased during the ornithine (urea) cycle, since urea
synthesis executed in the liver uses HCO3-, and in so doing further lowers the
blood pH. Under these conditions, nitrogen may be removed by the combined action
of kidney and liver.
Any surplus nitrogen
is first integrated in glutamine by glutamine synthetase. The renal enzyme glutaminase
then splits glutamine in glutamate NH3, which the kidneys directly excrete.
This procedure permits nitrogen excretion without affecting blood bicarbonate
levels.
This process involves
lots of excretory products of metabolism from the food consumed giving neither
the liver nor the kidneys physiological or biochemical rest
Hormone Regulator:
Hormone regulations are
principally performed through the action of two hormones synthesized by the
pancreas via its insulin and glucagon.
Insulin is released by
the beta cells in the pancreas when blood glucose levels are elevated primarily
after food. Insulin stimulates glucose
uptake by the muscle, glycogen synthesis, and triglyceride production by the
adipose tissue.
Insulin blocks gluconeogenesis
and glycogen degradation. Glucagon is then released by the pancreas when blood
glucose levels drops significantly.
This biochemical event
is the reversal of the action of insulin.
In the liver, glucagon excites glycogen breakdown, and the absorption of
amino acids. It inhibits glycogen synthesis and stimulates the release of fatty
acids by adipose tissue.
All these biochemical
events snowballed when more and more food are consumed at libitum. More and
more excess nutrients are stored, old cells including cancer cells and tissues
cannot be disposed of until the excess sugars, triglycerides (fats) and amino
acids (proteins) from over eating are metabolized (burnt) first.
Once again keep in
mind free radicals are produced in all these above metabolic process.
However, if the body
is put on a caloric restricted diet, or on a prolonged and frequent fasting, it will
start to break down its stored sugars (glycogen) first, than the body stored fats, and lastly its own body tissues and muscle to supply it with
energy. That is where a biological event called autophagy kicks in by digesting
its own old and unwanted cells first.
Autophagy:
Autophagy is a normal
physiological function the body performs in the destruction of old and
degenerated cells in the body. Its function is to maintain a homeostatic check
and balance for normal cellular functioning by inducing protein degradation for
the birth of new healthy cells.
During cellular stress
and trauma such as attacked by free radicals released in metabolic pathways,
and in their breakdown, the rate of autophagy is increased. Autography is also increased in prolonged
fasting
Autophagy hence can be
achievable through intermittent fasting or by longer fasts. This biological
event is initiated when liver glycogen is depleted. This takes place around
12-16 hours into a fast. Studies showed the rate of autophagy peaks during this
period, and then fall off after about 2 days.
This also takes place
when cells in a healthy human body are continuously being damaged as a normal
part of metabolic processes.
However, as we age, or
endure any kind of physiological, psychological or chemical stress such as from
the food and medicine we take, we have to deal with more and more free radical damage, resulting
in more and more cellular damage at an
increased rate.
Autophagy also comes
in by clearing damaged and senescent cells that serve no more functional role
in the body. The reason why it is so important to remove senescent and damaged
cells is because they can trigger damaging inflammatory pathways that
contribute to various diseases including cancers.
Autophagy and
Longevity:
It is only in very
recent animal studies that researchers have shown how autophagy can promote
longevity by conferring benefit to the nervous and immune systems, as well as
the cardiovascular system.
Naturopathic (Natural)
Medicine:
While scientific research
only over the last two decades has demonstrated the medical and health benefits
of autophagy or autophagocytosis induced during fasting, this piece of evidence
is not new.
Doctors of
naturopathic medicine have already known this, and have put this principle into
their clinical practice or the science of clinical autophagy through
physiological fast on fruit juice. They have already practiced this on their
patients for almost 10 decades already.
Prize in Medicine or
Physiology:
It was only in 2016
that a Japanese medical researcher Dr. Yoshinori Ohsumi won the prestigious
Nobel Prize in Medicine or Physiology for his work on the mechanism of
autophagy when doctors of naturopathic medicine have already put that mechanism
into their practice almost 100 years earlier.
Autophagy is a non-specific
term for the degradation of cytoplasmic components within lysosomes as shown by
several workers (Cuervo 2004; Levine and Klionsky 2004; Shintani and Klionsky
2004; Klionsky 2005, 2007; Mizushima and Klionsky 2007).
This process is quite separate
from endocytosis-mediated lysosomal degradation of extracellular and plasma
membrane proteins.
There are actually three
types of autophagy (macroautophagy, microautophagy, and chaperone-mediated
autophagy). We shall not go into all of them. However, “autophagy” usually signifies
macroautophagy.
Autophagy is mediated by
a unique organelle called the autophagosome. Organelles are specialized
cellular parts such as lysosome, mitochondrion, chloroplast, or nucleus inside
a cell.
As autophagosomes swamp
around a portion of cytoplasm, autophagy becomes part of a nonselective
degradation system.
Its role can be beneficial
or bad. For instance it can switch on tumor suppressors to prevent the onset of
cancer, but it can also promote cancer cell survival among many other
pathophysiological functions.
Recent Studies:
However, recent
studies have clearly demonstrated that autophagy has a greater function other than
its pathophysiological roles of destroying old, damaged and non-functional
cells. They are also mediated during starvation
adaptation, intracellular protein and organelle clearance, development of new
healthy cells, anti-aging function, the destruction of pathogens and microorganisms, promotes cell death, cancer suppression, and
antigen production among others (Mizushima 2005).
Nonetheless, its
mechanisms can be very complex such as its role in cancer suppression or
promotion or in cell death. Autophagocytosis is thus a double-edged sword
much like the double personalities of Dr. Jekyll and Mr. Hyde.
Autophagocytosis Fasting:
The best and easiest way to induce autophagy or
sometimes called autophagocytosis (meaning
"self-devouring") is through intermittent
fasting using plain drinking water with
added minerals, or on fruit juice to maintain fluid and electrolyte balance.
This is recently termed as autophagocytosis fasting or physiological fasting has
already been put into clinical practice as one of the therapeutic modalities by
doctors of naturopathic medicine.
Free Radicals and
Cellular Damage:
The human body is
mainly made up of 65 % oxygen, 18 % carbon and about 10 %hydrogen. The presence
of carbon with other elements made up the organic compounds. Hence the body consists mainly of organic
compounds. Most of the biochemical reactions
in the body involve organic molecules such as sugars, amino acids, fatty acids,
enzymes and hormones
In almost all chemical
reactions, free radicals are generated during the transfer and exchange of
electrons from one atom to the other among the donor and recipient molecules.
These are free radical reactions. This type of reactions occurs very often in
organic reactions.
Free radicals are
highly reactive when molecules lose their electrons. They become highly
unstable, and in order to stabilize themselves, they snatch an electron from
the next molecule or molecular fragment such as a DNA, damaging it and causing
it to be unstable.
The amount of damage
done to the body by free radicals by excessive eating is horrendous. This has already
being earlier explained in our brief discussions of metabolisms and the role of
the liver and kidney.
Even at rest and on
fasting, free radicals are also continuously being generated by untold number
of chemical reactions of metabolism throughout the body. The more we eat, or
the more frequent we eat in between meals, the more free radical reactions
occur to process the excess nutrients. This event causes a lot of damage to the
cells which the body tries to repair or replace. In doing so we do not even
allow a chance for the body to have bowel, physiological and biochemical rest. We
treat it like whipping a tired horse.
Cellular Repairs:
‘
Normally cells will
try to repair themselves. But when a cell cannot be repaired, the body will substitute
it with stromal connective tissue to maintain tissue and organ function
Metabolic activities and
environmental factors such as radiation resulting in free radicals can also cause
DNA damage, and there may be about as many as 1 million individual molecular
lesions per cell per day.
Many of these lesions initiate
structural damage to the DNA molecule and can alter or eliminate the cell's
ability to transcribe the gene that the affected DNA encodes.
Other lesions generate
potentially unsafe mutations in the cell's genome. This affects the survival of
its daughter cells after it undergoes mitosis. As an after-effect, the DNA
repair process is continuously active as it responds to damage in the DNA
structure.
The rate of DNA repair
is dependent on various factors, including the cell type, the age of the cell,
and the extracellular environment.
A cell that has amassed
a large degree of DNA damage, or one that can no longer effectively repair the
damage to its DNA, it then enters into one of four possible events:
1.
Go into senescence
which is an irreversible state of dormancy
2.
Induce autophagocytosis
3.
Commit
apoptosis or programmed cell death which is cellular suicide
4.
Uncontrollable
cellular dissection which may lead to the formation of a cancerous tumor
Number of Cells in the
Body:
Scientists are not
very sure how many cells are there in the human body, because this depends on
the age, the body weight, growth rates,
aging, degenerations of old cells, etc.
Our current estimate
is at 37 to 38 trillion. This number fluctuates over time and varies from individual
to individual, but about 37.5 trillion cells should be a close estimate for an
average adult.
Cellular Molecular Damage:
Within the structure
of each cell, untold numbers of molecular lesions occurs at any point in time
each day, and as already estimated, it could be as many as 1 million individual
molecular lesions per cell per day.
Even if we put the
number of cells of a small child at just ten million, million (1013)
the child would have been bombarded with tens of thousands of DNA lesions per
day
Scientists estimate
the human body is injured by no less than 1 million individual molecular
lesions per cell per day even during physiological and metabolic rest.
Many of these lesions cause
structural damage to the DNA and can change or eliminate the cell's ability to
transcribe the gene that the affected DNA encodes.
Other lesions induce
potentially injurious mutations in the cell's genome, which affect the survival
of its daughter cells after it undergoes mitosis.
All these destructive
factors affect human health, the onset of degenerative diseases and cut short
life span
All these destructive biochemical
events cause a lot of stress to the liver and other organs brought about by free
radicals generated during the exchange of free elections in their chemical
reactions, causing uncountable damage to all the cells involved. All these
events are the result of over eating or eating too often.
We estimate there are
about 37 thousand billion, billion chemical reactions per second taking
place in the human body at any moment in time, and this biochemical scenarios
occurs throughout 24 hours even when we are at rest or sleeping.
This is chemically a
disaster by shortening our programmed longevity drastically through damaging lifestyle
and over nutrition that promote these destructive chemical events.
Summary:
In summary we can see
the benefits of intermittent fasting to allow autophagocytosis to take its
course through bowel rest and metabolic clearance via the liver and kidneys
This would be contrary
to a video claim you sent to me for comment that frequent eating is more health protective than a longer delay
between small feeds. I do not know where that American lady in her U-tube video
claim got that belief from?
Best of all to my
understanding, to ensure a disease-free life and longevity go on regular physiological
fasts on low-sugar fruit or vegetable juice, or go on a caloric restricted diet as demonstrated in
countless studies, subsequent to the famous and classical study of Clive McCay of Cornell University in 1935
Thank you once again Ms.
Josephine Wong for your question. I hope my brief and easy to understand
explanation helps
Lim ju boo
