PHYSIOLOGICAL

EFFECTS OF FASTING,
NUTRITION &DIETEICS
GEETHA B SHETTY
I Year MD Naturopathy (Clinical)

Definition
Fasting is defined as abstinence from all food
and drink except water for a specific period of
time, usually for a therapeutic or religious
purpose1.

1. Mosby's Medical & Nursing Dictionary. St Louis, MO: CV Mosby. 1983: P417
2

Definition
Nutrition

is the science of food, the

nutrients and other substances therein,
their action and interaction and balance in
relation to health and disease and the
process by which the organism ingest,
digest, absorbs, transport, and finally
excretes food substances2.
Dietetics is the science of applying
nutritional principles to the planning and
preparation of foods and regulation of the
3
diet
inBiochemistry,
relation23to
both
health
and
2. Lange
edition,
Section
VI, Special
Topicsdisease
, Chapter
rd

43. Nutrition
3. Mosby's Medical Dictionary, 8th edition. 2009, Elsevier

In a physiological context, fasting may refer to

(1) the metabolic status of a person who has
not eaten overnight, and
(2) to the metabolic state achieved after
complete digestion and absorption of a meal.

The feed/fast cycle

The feed/fast cycle refers to the chain of

events that occur after the ingestion of a meal
0 - 4 hrs (Absorptive state)
4 - 24 hrs
1 - 2 day
2 days - several weeks

4. Lippincotts illustrated reviews, Biochemistry 4th Edition, Page 321-325

5

0 - 4 hrs (Absorptive state)

I. Overview of the absorptive state

After ingestion of a normal meal
Transient increase in plasma glucose, amino acids &
TAG
Increased secretion of insulin & drop in the glucagon
All tissues in the body use glucose as a fuel
Increased synthesis of TAG, Glycogen to replenish
fuel stores & enhanced synthesis of protein

0 - 4 hrs (Absorptive state)

II. Liver nutrient distribution

center
After the absorption all the nutrients are

enters into liver through hepatic portal

vein
These nutrients are then metabolized,
stored or routed out to other tissues
Carbohydrate metabolism
Fat metabolism
Amino acid metabolism

Carbohydrate metabolism:
Increased glycogen synthesis
Increased rate of HMP Shunt pathway
Increased glycolysis
Decreased gluconeogesis

Fat metabolism:
Increased fatty acid synthesis
Increased TAG synthesis

Amino acid metabolism

Increased amino acid degradation
Increased protein synthesis

10

0 - 4 hrs (Absorptive state)

III. Adipose tissue : Energy

storagetissue
depotis 2nd only to the liver in its
Adipose
ability to distribute fuel molecules
These nutrients are then metabolized,
stored or routed out to other tissues
Carbohydrate metabolism
Increased glucose transport
Increased glycolysis
Increased HMP Shunt pathway

Fat metabolism
Increased synthesis of fatty acids
Increased TAG synthesis
Decreased TAG degradation

11

12

4 - 24 hrs
Insulin levels have dropped because the
glucose from the meal is gone. Most cells are
using fat as their main energy source; glucose
is being reserved primarily for the brain. Now
blood glucose is maintained by the liver,
through the breakdown of glycogen stores.
These stores are normally depleted within 24
hrs

13

1 - 2 day
After the glycogen stores are gone, the liver
maintains blood glucose levels through
gluconeogenesis. Thus, the liver makes
glucose from either fat or proteins. Making
glucose from protein means the body is
breaking down muscle tissue and other
essential proteins because the body does not
store any protein as an intended energy
reserve.
14

15

The study of the physiology of fasting reveals

a highly ordered series of events, which
conserve body energy reserves while
maintaining the basal metabolic rate ,the BMR
decreases by about 1%/day during fasting,
until it stabilizes at about 75% of normal5

5. Goodhart RS, Shils ME. Modern nutrition in health and disease. 6th edn.
Philadelphia, PA: Lea & Febiger. 1980: p 738, 826, 983-986, 1086

16

The body's response to the lack of energy

input can be divided into three stages:

early fasting,
fasting, and
starvation

17

Early fasting
The initial physiological response to the

lack of food is the increased synthesis of

the glucose by the liver, from glycogen
through glycogenolysis for release into the
bloodstream. Glucose is especially needed
by the brain, which consumes about 65%
of the total circulating glucose (400-600
kcal/day), and the red blood cells.6
6. Goodhart RS, Shils ME. Modern nutrition in health and disease.
6th edn. Philadelphia, PA: Lea & Febiger. 1980: p 738, 826, 983986, 1086

18

Liver glycogen stores can only supply enough

glucose for a few hours, and glucose

production starts from gluconeogenesis
Gluconeogenesis from amino acids, glycerol
and other non carbohydrate sources

19

Fasting -2

nd

stage

Fat
Lipolysis( Hormone sensitive Lipase)
Free fatty acids
Beta Oxidation

Acetyl Co A

Ketone Bodies

Citric acid cycle

Energy

20

Starvation
Starvation occurs when the body's fat

reserves are depleted and significant protein

catabolism becomes necessary for energy
production.7
Research has determined that an average 70
kg male has the fat stores to maintain basic
caloric requirements for 2-3 months of
fasting.8

7 . Lehninger A. Biochemistry. New York, NY: Worth Publishing. 1964: p

841-845
8. Saudek C, Felig P. The metabolic events of starvation. Am J Med 1976; 60: 117126

21

Starvation
2 days - several weeks
As the fat cells release more fat into the
blood, the liver starts to release ketone
bodies. The brain begins to use ketone bodies
for energy and thus, requires less glucose.

22

23

 After the fat reserves are depleted (timeline

depends on individual body fat), the sole

method of blood glucose maintenance is
through the breakdown of proteins.
The body basically cannabilises itself. People

that die from starvation do not die because

they run out of protein; they die because they
eat away essential proteins like the heart.

24

Research in fasting
The earliest research was primarily observational;

physiologic and metabolic changes were recorded

while an individual fasted.
These included: Tanner, 40 days (1880), Jacques,

30 days (1887) and 40 days (1888), Penny, 30

days (1905) and Levanzin, 31 days
The earliest record of therapeutic fasting in the

medical literature occurred in 1910.

not available)

( abstract

9.Morgulis S. Fasting and under nutrition. New York, NY: EP Dutton. 1923

25

Physical changes during fasting

Physical changes during the fast generally

include a decrease in weight, pulse, and

10
blood pressure
EKG

changes
may
include
sinus
bradycardia, decreased QRS complex and
T-wave amplitude, elongation of the QT
interval, and shifts to the right of the QRS
and T-wave axes. These changes return to
10. Consolazio CF, Nelson RA, Johnson HL.
10Metabolic aspects of acute starvation in
normal
after
fasting.
normal humans: performance and cardiovascular evaluation. Am J Clin Nutr 1967; 20:
684-693
26

Electrolyte balance during Fasting

Serum electrolyte levels usually do not change

significantly during fasting and are not good indicators

of tissue stores but are considered the most important
blood values during fasting.
During early fasting the body loses 150-250 mEq (3.55.8 g) of sodium and 40-45 mEq (1.6-1.8 g) of
potassium a day. Later, these drop to 1-15 mEq (0.020.35 g) and 10-15 mEq (0.4-0.6 g), respectively.
The total body stores of sodium are 83-97 g (of which
65% is exchangeable) and of potassium are 115-131 g
(of which 98% is exchangeable). The typical daily
dietary intake of sodium is 3-7 g and of potassium is 35 g. 11
11. Nutrition Reviews. Present knowledge in nutrition. 5th edn. Washington,
DC: Nutrition Foundation. 1984: p 439-453

27

Serum potassium usually decreases but

may be elevated. Results below 3 mEq/L or
above 6 mEq/L may necessitate breaking
the fast. Total calcium is usually stable, but
ionic calcium often decreases, especially if
vomiting is present.12

12. Kernt PR, Naughton JL, Driscoll CE, Loxterkamp DA. Fasting: the
history, pathophysiology and complications. West J Med 1982; 137:
379-399
28

Laboratory changes during fasting

Serum protein usually declines with fasting.

Pancreatic lipase and amylase usually decline

with fasting.
Liver enzymes may increase considerably if
liver disease is present and may rise even
when liver disease is not present.
Triglyceride, cholesterol, and uric acid levels
usually rise during fasting indicating
mobilization of tissue stores13
13. Valenta LJ, Elias AN. Modified fasting in the treatment of obesity.
Postgrad Med J 1986; 79: 263-267
29

Laboratory changes during

fasting
Blood glucose drops in most patients, possibly

below 30 mg/dl. If blood glucose is low prior to

fasting, it may rise post-fasting.14
Complete blood counts usually show no significant

change
Hematocrit, hemoglobin, and RBC count may be

increased, but this usually indicates inadequate

hydration. 15
14. Fuhrman J. Fasting and eating for health. New York, NY: St. Martin's Press.
1995
15. Cinque R. Hematological changes during fasting. IAHP Newsletter 1993; 7: 1:
6-8

30

Urine analysis
Urinalyses may be difficult to interpret during fasting,

since the body discards considerable waste via the

kidneys.

It is not uncommon to see various types of casts,

RBCs, WBCs, bilirubin (+1 to +2), protein (trace, +2),
and ketones (+4), and, if liver disease is present,
urobilinogen elevation.

Specific gravity is commonly elevated (possibly to

1.035), which may reflect inadequate hydration.

31

Hormonal changes during fasting

Hormonal changes during fasting typically include

decreases of insulin and thyroid hormones. Increased

levels of growth hormone cortisol, glucagon, plasma nor
epinephrine,
serum
melatonin,
and
certain
prostaglandins (in animals) usually occur. By contrast,
a decrease in growth hormone is usually found in obese
individuals16
In one study conducted on 10 postmenopausal women

who underwent short-term fasts, no significant changes

in adrenal hormones, androgens, serum and urinary
estrogens, plasma epinephrine, or dopamine were
recorded.

16. Beitins IZ, Barkan A, Kiblanski A et al. Hormonal responses to short

term fasting in post menopausal women. J Clin Metab 1985; 60: 11201126

32

Effects of fasting on immune function

The immune system undergoes very important changes

during the fast, and an increase in various aspects of

immune function has been observed. The first evidence
of this came from the study in which found increased
resistance to infection during the post-fast period. 17
Changes in the immune system during fasting include
increased macrophage activity
increased cell-mediated immunity (T-lymphocytes and lymphokines)
decreased complement factors
decreased antigen-antibody complexes
increased immunoglobulin levels
increased neutrophil bactericidal activity
heightened monocyte killing and bactericidal function
enhanced natural killer cell activity in animals and humans.

17. Miller JD. Life extension. N Eng J Med 1985; 313: 760

33

Quantity of water
The optimal quantity of water to ingest during fasting is best

determined by thirst, but patients should drink at least a few

glasses a day. During fasting the need for water decreases,
since obligatory water excretion is reduced (due to lower
excretion of urea, the major osmotic solute) and water is
released from catabolized fat. [18]
One liter of water each day is actually sufficient to maintain

adequate hydration for most people

Although

researchers
recommend 3 L/day.[19]

fasting

[18]

obese

individuals

often

18. Young VR, Scrimshaw NS. The physiology of starvation. Sci Am 1971; 225: 4: 14-21
19. Goodhart RS, Shils ME. Modern nutrition in health and disease. 6th edn. Philadelphia, PA:
Lea & Febiger. 1980: p 738, 826, 983-986, 1086

34

SUPPLEMENTS
Loss of minerals or vitamins is usually not a

concern, and deficiencies while fasting are

rare. In fact, problems, such as nausea and
indigestion, have been reported when these
were supplemented during the fast20
It
is
known
that
nicotinic
acid
supplementation inhibits the release of free
fatty acids from adipose tissue21
20. Rapoport GL, From A, Hudson H. Metabolic studies in prolonged fasting:
inorganic metabolism and kidney function. Metabolism 1965; 14: 1: 30-47
21. Goodhart RS, Shils ME. Modern nutrition in health and disease. 6th edn.
35
Philadelphia, PA: Lea & Febiger. 1980: p 738, 826, 983-986, 1086

Exercise
Exercise is discouraged while fasting. Fuel

conservation is necessary to allow maximal

healing and the avoidance of unnecessary
gluconeogenesis.
The body utilizes certain muscle proteins
early in a fast, thus initiating the natural
restriction of activity. Short walks or light
stretching is permissible, but intense
exercise
will
inhibit
repair
and
23. Shelton HM. The science and fine art of fasting. Chicago, IL: Natural Hygiene
23
Press.
1978
elimination.
36

Sunlight

Sunlight is important for general health

during fasting, and patients should try to

obtain 10-20 minutes/day.
An increase in heart rate of 10-15
beats/minute would indicate excessive
exposure.

37

Enemas
Enemas are not usually necessary and

may not offer any added benefit. Some

authors have found that they cause
discomfort for the patients.
To help prevent constipation, a pre-fast

meal of fresh fruit or vegetables will assist

in elimination23
23. Shelton HM. The science and fine art of fasting. Chicago, IL: Natural
Hygiene Press. 1978
38

Effects of Fasting on different

systems/diseases
Yang YG; Makita T : Morphometry of fine structural alterations of

hepatocytes of Japanese monkeys under fasting. J Vet Med Sci 1998

Jul;60(7):849-52.

The fine structural alterations of hepatocytes of Japanese

monkeys under 4 days of fasting were analyzed
morphometrically. One of the conspicuous alterations was the
enlargement of mitochondria. The average diameter of
mitochondria in fasting group increased to approximately 1.89fold of that in control group, though their number did not
change. The number of peroxisomes was 1.36-fold of that in
control, though their area did not change. The appearance of
bundle of actin-like stress fiber also increased in the fasting
animals. The glycogen area as well as liver weight decreased in
fasting group.
39

Fasting & GIT Diseases

Iannello

S, Cavaleri A, Milazzo P, Cantarella S,

Belfiore F;Low fasting serum triglyceride level as a
precocious
marker
of
autoimmune
disorders.
MedGenMed. 2003 Aug 7;5(3):20.
Data in this study seem to indicate that low TG value may
be a precocious marker of autoimmunity or immune system
hyperreactivity
Savendahl L, Underwood LE, Haldeman KM, Ulshen
MH, Lund PK ; Fasting prevents experimental murine
colitis produced by dextran sulfate sodium and
decreases interleukin-1 beta and insulin-like growth
factor I messenger ribonucleic acid. Endocrinology.
1997
Feb;138(2):734-40
This study concludes that fasting has a protective

effect on the progression of

colitis. This is
40
associated with decreased _expression of IL-1 beta

Fasting & Asthma

Avenell A, Brown TJ, McGee MA, Campbell MK, Grant AM,

Broom J, Jung RT, Smith WC. What are the long-term

benefits of weight reducing diets in adults? A systematic
review of randomized controlled trialsJ Hum Nutr Diet. 2004
Aug;17(4):317-35..
In patients with preasthma and bronchial asthma, short-term
courses of fasting dietotherapy (FDT) with a 7-day fasting period
proved to be effective, as evidenced by clinical-and-functional and
laboratory investigations. The incidence rate of viral infections was
much lower with short-term courses compared to long-term
courses. Too low an effect, if any, with FDT short-term courses can
be explained by excess of the patient's body weight. Short-term
FDT courses with a 3-day fasting period have been found out to
result in a significant decrease in the level of anxiety, as measured
by Spilberger Anxiety Inventory.
41

Tovt-Korshyns'ka MI, Spivak MIa, Chopei IV. Lik

Sprava ; Effectiveness of short courses of

fasting in pre-asthma and asthma patients ,
2002 Apr-Jun;(3-4):79-81
In patients with preasthma and bronchial asthma,
short-term courses of fasting dietotherapy (FDT) with
a 7-day fasting period proved to be effective, as
evidenced by clinical-and-functional and laboratory
investigations. The incidence rate of viral infections
was much lower with short-term courses compared
to long-term courses. Too low an effect, if any, with
FDT short-term courses can be explained by excess
of the patient's body weight. Short-term FDT courses
with a 3-day fasting period have been found out to
result in a significant decrease in the level of anxiety,
as measured by Spilberger Anxiety Inventory.
42

Fasting & Hypertension

Goldhamer AC, Lisle DJ, Sultana P, Anderson

SV, Parpia B, Hughes B, Campbell TC:

Medically supervised water-only fasting in
the treatment of borderline hypertension.
Altern Complement Med 2002 Oct;8(5):64350
Medically supervised water-only fasting appears to be a

safe and effective means of normalizing BP and may

assist in motivating health-promoting diet and lifestyle
changes

43

 Nakano Y, Oshima T, Sasaki S, Higashi Y, Ozono R,

Takenaka S, Miura F, Hirao H, Matsuura H, Chayama

K, Kambe M: Calorie restriction reduced blood
pressure in obesity hypertensives by improvement of
autonomic nerve activity and insulin sensitivity. J
Cardiovasc Pharmacol. 2001 Oct;38 Suppl 1:S69-74

The purpose of this study is to examine the

relationship of insulin sensitivity and autonomic

nervous activity with reduction of blood pressure
by the calorie restriction.
They evaluated the heart rate variability,
nocturnal change of blood pressure and insulin
resistance before and after a short-term lowcalorie diet in 12 overweight essential
hypertensives.
44

 After a week of standard diet (2000 kcal), 2 weeks

of low-calorie diet (800 kcal) with normal sodium

content induced a significant reduction in
triglyceride, fasting immunoreactive protein,
insulin resistance, and urinary excretion of sodium
and potassium
Systolic blood pressure was significantly reduced
both in daytime and night-time after the lowcalorie diet.
In daytime, diastolic blood pressure was also
reduced (90.3+/-2.1 to 88.1+/-4.8 mmHg).
In conclusion, weight loss by low-calorie diet with
a constant intake of sodium, reduced blood
pressure in obese hypertensive's by improvement
of vagal nervous activity and insulin resistance
45

 Koletsky

S, Puterman DI.: Effect of low calorie diet

on the hyperlipidemia, hypertension, and life span
of genetically obese rats. Proc Soc Exp Biol Med
1976 Feb;151(2):368-71

A new strain of genetically obese rat recently obtained in our

laboratory exhibits endogenous hyperlipidemia (marked hyper
triglyceridemia and moderate hypercholesterolemia) and
spontaneous hypertension.
The animals die prematurely from kidney failure or from the
complications of atherosclerosis. A low calorie diet proved to be
highly beneficial to these rats
.
Body weight declined, obesity diminished, the hyper
triglyceridemia
was
almost
eliminated,
and
the
hypercholesterolemia was reduced. However, the hypertensive
state was not alleviated.
Since the life span of the rats was greatly prolonged by a low calorie
diet, the latter undoubtedly served to prevent or arrest the
development of renal and vascular disease in these obese animals .
46

 Pekkarinen T; Takala I; Mustajoki : Weight

loss with very-low-calorie diet and

cardiovascular risk factors in moderately
obese women: one-year follow-up study
including ambulatory blood pressure
monitoring. Int J Obes Relat Metab Disord
1998 Jul;22(7):661-6
In the above study, they studied the longer-

term effects of weight loss on 24h ambulatory

blood pressure (ABP), lipids, glucose and insulin
This weight loss programme with a very-lowcalorie diet enabled obese subjects to lose
weight and decrease cardiovascular risks.
Despite some regain in weight during follow-up,
the beneficial effects were overall maintained 47

 Smith JV, Heilbronn LK, Ravussin E; Energy restriction

and aging.
Curr Opin Clin Nutr Metab Care. 2004 Nov;7(6):615-22.
Pennington Biomedical Research Center, Baton Rouge,
Louisiana, USA.
PURPOSE : To study the long-term calorie restriction and the
resulting changes observed in possible biomarkers of aging
RECENT FINDINGS: Prolonged calorie restriction has been shown
to extend both the median and maximal lifespan in a variety of
lower species such as yeast, worms, fish, rats, and mice.
Mechanisms of this lifespan extension via calorie restriction are
not fully elucidated, but possibly involve significant alterations
in energy metabolism, oxidative damage, insulin sensitivity, and
functional changes in both the Neuro-endocrine and
sympathetic nervous systems. Ongoing studies of prolonged
energy restriction in humans are now making it possible to
analyze changes in these aging biomarkers to unravel some of
the mechanisms of its anti-aging phenomenon
48