Glycative Stress Research
Online edition : ISSN 2188-3610
Print edition : ISSN 2188-3602
Received : July 3, 2018
Accepted : November 25, 2018
Published online : December 31, 2018
doi:10.24659/gsr.5.4_181

Original article: Case report

Fasting therapy, a medicine for human rescue:
Live a life with fasting, yoga and brown rice.
Eiichi Sekizuka 1, 2), Daisuke Sekizuka 3), Tian Zheng 4, 5)
1) Secom Medical System Co., Ltd., Tokyo, Japan2) (Social Welfare Corporation) Wako Fukushi-kai, Wako, Saitama, Japan
3) Fasting Yoga Medical Laboratory, Saitama, Japan4) Seishin-dou, Xi'an, Shaanxi Province, China
5) Anti-Aging Medical Research Center and Glycative Stress Research Center, Faculty of Life and Medical Sciences,
Doshisha University, Kyoto, Japan

Abstract

Fasting therapy is an old folk therapy that has been used since ancient times. In this research, We, first, showed the seriesof changes of physical information before and after fasting therapy and second, classified the fasting therapies into calorie
restriction, intermittent fasting and long-term fasting and explained them based upon the fundamental changes caused by
fasting therapies and recent medical viewpoints.
In the seven-day fasting therapy, decreases of body weight and visceral fat, increases of values of hemoglobin and uricacid associated with dehydration, and increases of ketone bodies such as β-hydroxybutyric acid and acetoacetic acid wereobserved, and in relation to bone metabolism, the acceleration of bone absorption (the increase of bone-type tartrate-resistantacid phosphatase-5b and type -1 collagen cross-linked N-telopeptide) were observed. In relation to the glycation stressindex, the increasing tendencies of 3-deoxyglucosone, acetaldehyde, glyoxal and methylglyoxal were observed; however,the fluorescence intensity of skin advanced glycation end products (AGEs) decreased by 13%. In the genetic analysis ofgastric mucosa conducted in the past, the enhanced expression of von Hippel-Lindau tumor suppressor protein (VHL) was
recognized, which suggested the possibility that it is related to the control of cancer growth.
Long-term fasting is fundamentally different from intermittent fasting and calorie restriction. Due to the long-term
existence of extremely low blood glucose and hypoinsulinemia and ketosis, senescent and weakened cells and lesioned(genetic mutation and cancerous transformation) tissues are broken down, which makes it possible for them to self-replicate byrecycling the broken-down parts. It can be said that fasting is the most appropriate simultaneous and multiple micro-surgery
without using a scalpel.

KEY WORDS: fasting therapy, genetic analysis, advanced glycation end products (AGEs), oxidative stress,		von Hippel-Lindau tumor suppressor protein (VHL)

Introduction

Japan is a low birthrate and super-aging society. The
most frequent cause of death of the elderly is malignant
tumor (45%), followed by cardiac disease (13%), vascularbrain disease (8%) and pneumonia (6%), and these diseases
are caused by immune deficiency, arterial sclerosis, highblood pressure, diabetes and inflammation. It has been
proven that fasting therapy and a calorie restriction diet

improves on these causes and leads to healthy life expectancy
based on the research with humans and animals thus far.
However, these therapies are not considered as important
as taking medication and surgery. I am carrying out fasting
therapy for seven days twice a year. In this report, I reported
the changes of physical information at the time of fasting
therapy and the measured results centering on glycolipid
metabolism index relating to glycation stress, in particular, inthe form of a case report, along with some literature reviews.

Contact Address: Eiichi Sekizuka MD, PhD
Secom Medical System Co., Ltd.
1-5 -1Jingumae, Shibuya-ku, Tokyo, 150 - 0001 Japan

TEL: 03-5775-8150 FAX: 03 -5775 - 8903
Mail: e-sekizuka@healthcarenet.jp
Co-authors: Sekizuka D, sekizuka0 424@gmail.com ;Zheng T, tomtomtom1990@hotmail.com_ 181 _

Glycative Stress Research 2018; 5 (4): 181-191(c) Society for Glycative Stress ResearchFasting Therapy

Case

60 years old (as of 2011), male (born in 1951)

Back Groundrice

20 years old: My encounter with fasting, yoga and brown

After entering university, I lived in the house of my uncle
in Kawaguchi, Saitama, Japan. This area was called “cupola(foundry) town” and there were many small and medium
scale foundries. Affected by heavy smoke emission fromthese foundries, he developed bronchial asthma, and received
pharmacotherapy and desensitization therapy; however, his
symptoms did not improve. He tried various folk therapies
but nothing went right. Finally, he tried raw food therapy,
brown rice diet, fasting therapy as well as Yoga, and finally,
he was able to recover from bronchial asthma without taking
drugs.
There were many books including a complete collectionof Indian philosophy and those of yoga and fasting therapy in
his uncle’s study. I read these books at random and I was very
interested in yoga, in particular. As a result of yoga training,
I acquired the yoga technique of Nauri (dent belly and movethe muscles of both sides) in the course of a week, that ofSirsiasana (cross legs in the posture of handstand) in thecourse of a month and those of all Asanas of the instructional
book 1) in the course of a year. When I was 20 years old (inthe summer of my first year of university), I experienced
fasting for the first time for two weeks in a fastinghall in
Kofu, Yamanashi, Japan. I was relatively energetic during
the first week and I had enough physical strength to takea walk with other participants. However, from the second
week, suddenly my physical strength declined and I had aterrible experience where I could not sit still. Although I was
reading a book to distract my mind, I could not concentrate
in reading and various thoughts came to my mind one after
another. My body weight decreased to 51 kg from 61 kg, 10
kg in 14 days (no change in my body height of 175 cm). Next
year, I went to the National Kaivalyadhama Health and Yoga
Research Center in Lonavla, Maharashtra, India for training
with the assistance of my uncle. Since then, I have continued
yoga and a brown rice diet.

Changes of Property of Stool: Actual Condition ofBlack Stool Impaction

Since 1980, I had studied abroad as an intern andresident. Because I was very busy during that time, I did
not practice fasting therapy. I returned to Saitama National
Hospital in 1988 and was assigned to the position of directorof the hospital from 2010 to 2017. Since then, I haveconducted fasting for one week during New Year holidays
and summer vacation until now.
The change of property of stool caused by fasting
therapy was as follows: 2-3 days after fasting, coal-black andsticky stool was excreted. This is called “stool impaction”
and it had been said to be the mixture of sludge fastened tothe intestinal wall and mucosa which peeled off becauseof fasting. However, looking at it carefully, I found that thecolor of stool impaction was deep green, which means that
it was mainly the color of concentrated bile. During fasting,the gallbladder expands and concentrated bile is stored init. Because the gallbladder shrinks due to the stimulus of
returning to diet, concentrated bile is excreted, so that thestool becomes dark green in color.
In the Saitama National Hospital, fasting (very low calorie,
100 to 200 Kcal/day) therapy which is acknowledged by theJapan Fasting Therapy Society was conducted with patients
interested in the therapy out of those with type 2 diabetes,
obesity, high-blood pressure and metabolic syndrome. The
achievements of fasting therapy were presented under thetitle of “Current Status of Fasting Therapy in Japan and
Genetic Study of Gastrointestinal Mucosa” at the 48th
Japan Digestive Disease Week (JDDW) Panel Discussion of“Merits and Demerits of Fasting (no eating and drinking)
Therapy for the Patients with Digestive Diseases,” held on
October 13, 2006. A paper was presented concerning fasting(no eating and drinking) therapy and nutrition administration
for patients with digestive diseases, which was published ina special edition “Gastrointestinal Medicine” 2). Even now,
fasting therapy (very low calorie) is conducted with patients
who desire it in the Saitama National Hospital.

Current Status of Fasting Therapy

In the relevant literature shown in the journals of theWest and America, the fasting therapies are classified into
intermittent fasting, alternate-day fasting and long-term
fasting based on fasting periods, with the patients with type2 diabetes who are taking medicine and the sustained longterm effect into consideration. In Japan also, petit fasting,half-day fasting, one-day fasting, week-end fasting andthree-days-or-more fasting are conducted. There are cases
when water or low-calorie juice (300 to 400 Kcal/day) is
given during fasting. Japanese words of zesshoku and danjiki,both expressing fasting, are often confused. Danjiki therapy
or danjiki training places emphasis on the spirit more thanthe body, and zesshoku therapy places emphasis on the bodymore than the spirit. Both danjiki and zesshoku are translated
as “fasting” in English.
In order to distinguish between the fasting as folk
therapy and the one with religious aspects, the two relatedsocieties in Japan changed the names of the societies to theJapan Fasting Therapy Society and the Japan Fasting Study
Group, respectively. It is truly regretful that Dr. Mitsuo Koda
has passed away, who was leading the study group famousfor “light eating fasting therapy” (died in 2008) 3). Many great
religious persons such as Buddha, Christ and Muhammad
practiced fasting as a religious ascetic practice. In Japanalso, thousand-day circumambulation and eating none of
the five grains are practiced in Mt. Koyasan. The history offasting therapy, which had so far been a religious practiceand a folk therapy, started in 1930 as the medicine in Japan
from the study by Hideo Takahira et al. of Department of
Physiology, Keio University (Tokyo, Japan). After that, theJapan Fasting Therapy Society and the Japan Fasting Study
Group were established. “Tohoku University method offasting therapy” is covered by insurance as a psychosomatictherapy 3).
In the early days, fasting therapy was conducted forthe purpose of conquering chronic and incurable diseases.
However, recently, it is broadly applied for various purposes,
such as improvements of metabolic syndrome including
obesity, therapies for anti-aging, beauty, anti-cancer andspiritual exercise (Table 1) 4). The period of fasting is often
around a week as the typical, basic method. The period offasting should be determined based on individuals’ mental
endurance and the purpose of fasting.

_ 18 2 _Glycative Stress Research

Table 1. The practical purpose of Fasting therapy (Rebuilding of body and mind).

Prevention and improvement of metabolic syndrome and weight reduction(obesity, diabetes, hypertension, dyslipidemia)

Overcome and treatment of chronic diseases, incurable disease and cancer
Health care and promotion
Constitutional improvement, rejuvenation, longevity and beauty (improvement of skin conditions)
Slow aging (no an anti - aging therapy)

Relieve of constipation and fecal impaction

Temperance (stop drinking) and off cigarettes (stop smoking)Stress elimination and autonomous neural training
Religious training, spiritual exercises and comprehension
Enhancement in memory
Treatment and prevention of physical and mental diseases
Detoxication
Reflection of dietary behavior, improvement of unbalanced diet and promotion of appetite
Forced molting in chicken (restoration of egg production ability)
Table is quoted and modified from the reference “Fasting therapy for psychosomatic diseases” 4).

There are various periods of fasting therapies from very
short- term fasting therapies of one day a week and one or
two days a month to long-term fasting therapies of several
weeks. Recently, long term fasting tends not to be conducted
due to taking accidents and complications into consideration.
Fasting therapy is contraindicated for the following
diseases: tuberculosis, non-obese diabetes, high emaciation,
weakness, gastrointestinal ulcer, digestive tract stenosis andadhesion and more than moderate chronic kidney failure(blood urea nitrogen [BUN] is 4 0 mg/dL or more). Before
you take fasting therapy for three days or more, you should
receive a detailed doctor’s examination.
In order to prevent accidents during this rigorous fasting
therapy, a therapy that should be called “very low-calorie
therapy” is devised by experts, and micro-diets, low-carbdiets and ketogenic diets are incorporated into it.

Examination of Visceral Fat, Liver Stiffness andVarious Blood Parameters Before and After Fasting
Therapy
PurposeBased upon the findings on fasting therapy until
recently, and based upon the genetic study of gastrointestinal
mucosa (2006) 2) and the experiment of this time (2017)
including oxidative stress and glycation stress as acceleratorsof arteriosclerosis, malignant transformation and aging, we
attempted to clarify the fundamental reaction of a living
body to fasting therapy, including new aspects.

MethodA fasting therapy for seven days was conducted.
Although at a previous time, fluid replenishment byintravenous drip by Tohoku University Method wasapplied, this time more than two liters of water were orally
administered. Blood parameters on the starting day offasting therapy, the 4th day, the 8th day and the 14th day
were measured. As the indicators of glycation stress, theconcentrations of 3-deoxyglucosone (3DG), acetaldehyde(AA), glyoxal (GO) and methylglyoxal (MGO) in plasma,
and the fluorescence intensity of skin AGEs were measured.
The fluorescence intensity of skin advanced glycation endproducts (AGEs) was measured by RQ-1201J-SET (Sharp
Life Science, Kobe, Hyogo, Japan) placed on the tip of theleft middle finger 5). 3DG, AA, GO, MGO are the substanceswith aldehyde group as functional group, and they were
measured by HPLC-FL method using 2, 3-diaminonaphtalen(DAN) indicator 6, 7).
Visceral fat was measured using 320 columns CT(Toshiba; Minato-ku, Tokyo, Japan), liver fat content andliver stiffness were measured using liver stiffness measuring
equipment (Fibro Scan 502; Echosens, Paris, France) on thestarting day of fasting therapy and the 8th day. The gastricmucosa and large intestine mucosa of the previous therapy
were biopsied and the results were histologically discussed
and at the same time the results of the analysis of their gene
expression analysis were discussed_ 18 3 _Fasting Therapy

Resultsincreased from 7.0 mg/dL to 16.1 mg/dL. No gout attack
was observed, so it was considered to be the variations
due to dehydration. In glucose metabolism examination,
fasting blood glucose shifted between 72 mg/dL and 82 mg/
dL and HbA1c between 5.6% and 5.7%, which showed nolarge variations (Fig. 1). In lipid metabolism examination,
low-density lipoprotein cholesterol (LDL-C), triglyceride(TG) and lipoprotein (a) (LP (a)) increased 1.4-1.8 times.
In endocrine examination, insulin decreased by almost halffrom 13.1 μU/mL to 5.9 μU/mL (− 45 %), glucagon increased
1.8 times, growth hormone increased 1.5 times and insulinlike growth factor- I (IGF- I) remained almost unchanged.

Body weight decreased by 8.0 kg and the rate of decrease
was 8.4%. Body mass index (BMI) was 8.5% and abdominal
girth decreased by 4.1%.
As a result of the measurement of visceral fat using CT,
visceral fat area decreased to 85.9% and the ratio of visceralfat/subcutaneous fat area decreased to 83.5% ( Table 2).
The time lapse of blood test is shown in Table 3. In
general biochemical examination of blood, deviation
enzymes including AST (GOT), ALT (GPT) and creatine
phosphokinase (CPK) increased by 20-30%, hemoglobin
increased from 14.4 g/dL to 17.3 g/dL (20%), and uric acid

Table 2. hanges of anthropometry.
Hight

Body weightcm

kg

Before fasting（12/27）

175.0

89.2

Right after fasting
（1/3）

175.0

81.7

BMI

Total
Waist
circumference fat square

Visceral
fat square

Subcutaneous
fat square

cm

cm 2

cm 2

cm 2

29.1

96.7

385.7

236.3

149.3

1.58

26.7

92.9

356.8

202.9

153.7

1.32

10,0005,000
Ketone bodies (μmol/L)
1,000
500

TC (mg/dL)
TG (mg/dL)

100
50

Glucose (mg/dL)

10
0day

Visceral ／Subcutaneoussquare ratio

3day

7day

Fasting

14day

ConvalescentFig. 1. Glucose/lipid metabolism and fasting.
TC, total cholesterol; TG, triglyceride.

_ 18 4 _Glycative Stress Research

Table 3. Blood biochemical examination.

【Blood chemistry】
TP
Albumin
AST (GOT)
ALT (GPT)
ALP
γ-GTP
CPK
UA
BUN
Cre
Cystatin C
Na
K
Ca
CRP
【Peripheral blood examination】
WBC
Lymphocyte %Lymphocyte count
RBC
Hb
Plt
【Lipid profile】
TC
TG
LDL-C
Lipoprotein (a)RLP-C【Glucose metabolisim】
Glucose
HbA1c【Endocrinology】
Insurin (IRI)
Glucagon (IRG)
Growth hormone
IGF-I【Ketone bodies】
Total ketone bodies
Acetoacetic acid
β-Hydroxybutyric acid【Liver fibrosis marker】
Hyaluronic acidType 4 collagen【Bone metabolisim】
TRCP-5bSerum NTX
【Tumor markers】
Pro-GRP
Anti-p53 Ab

g/dL
g/dL
U/L
U/L
U/L
U/L
U/L
mg/dL
mg/dL
mg/dL
mg/L
mmol/L
mmol/L
mg/dL
mg/dL
/μL
%
/μL
x104 /μL
g/dL
x104 /μL
mg/dL
mg/dL
mg/dL
mg/dL
mg/dL
mg/dL
%
μU/mL
pg/mL
ng/mL
ng/mL
μmol/Lμmol/Lμmol/L
ng/mL
ng/mL
mU/ｄL
nMBCE/L
pg/mL
U/mL

Before fasting

During fasting

Right after fasting

12 / 27

12 / 30

1/3

One week
after fasting
1/10

8.9
5.1
65
81
161
59
308
10.9
16.0
1.21
1.1
14 0
4.3
9.7
0.07

8.7
5.2
72
80
162
52
371
16.1
26.7
1.55
1. 3
136
4.7
9.9
0.09

7. 9
4.6
49
64
147
37
291
9. 3
18. 4
1.06
NE
14 2
4.7
8.8
0. 34

3,240
55.2
1,788
528
16.7
23.2

3,840
50.5
1,939
537
17.3
25.3

4,220
57.1
2,410
430
13.5
20.6

270
88
174
28.9
3.5

303
122
217
36.8
6.0

199
217
108
9.6
12.4

96
5.6

1 01
5.6

111
5.7

12. 2
312
0.38
14 5

5.9
381
0.96
13 9

NE
NE
NE
NE

1,066
143
923

2,418
388
2,030

16 3
47
116

166. 4
105

183.4
83

172. 5
16 4

3 07
17. 3

319
20. 2

322
15. 7

38.8
< 0.6953. 7< 0.6978.2< 0.69

7. 7
4. 5
56
60
142
53
279
7.0
17. 4
0.91
0. 9
141
4.6
8.8
0. 31
2,810
51.6
1,45 0
4 56
14.4
18.4
213
71
123
12. 2
2.8
11 6
5. 7
13.1
209
0.65
129
66
7
59
115. 9
14 3
226
14.1
NE
< 0.69NE, not examined; TP, total protein; AST (GOT), aspartate aminotransferase (glutamic oxaloacetic transaminase); ALT (GPT), alanine aminotransferase(glutamic pyruvate transaminase); ALP, alkaline phosphatase; γ-GTP, γ-glutamyl transpeptidase; CPK, creatine phosphokinase; UA, uric acid; BUN, bloodurea nitrogen; Cre, creatinine; CRP, C-reactive protein; WBC, white blood cell; RBC, red blood cell; Hb, hemoglobin; Plt, platelet; TC, total cholesterol; TG,
triglyceride; LDL-C, low-density lipoprotein cholesterol; RLP-C, remnant-like lipoprotein particles-cholesterol; IRI, immunoreactive insulin; IRG,
immunoreactive glucagon; IGF-I, Insulin-like growth factor-I; TRCP-5b, tartrate-resistant acid phosphatase 5b; NTX, type I collagen cross-linked
N-telopeptide; Pro-GRP, pro-gastrin-releasing peptide; Ab, antibody.

_ 18 5 _Fasting Therapyof skin AGEs decreased. 3DG, AA, GO and MGO are theindicators of early and interim periods in glycation stress
reaction and skin AGEs is that of last period. It is certainthat glycation stress indicators change in one fasting therapy:
however, it is quite unknown about the variations in the
periods from three to four months after fasting. How thesevariations affect living bodies is the task for the future.
In the previous observation, gene expression state wasobserved using biopsy specimens of gastric mucosa andlarge intestinal mucosa. As a result, enhanced expression ofvon Hippel-Lindau tumor suppressor protein (VHL) was
recognized in gastric mucosa. VHL controls the sensing ofoxygen concentration of peripheral tissues, and has the actionof specifically combining with Hypoxia-inducible factor
1α (HIF-1α), a transcription factor important for hypoxia
response, and collapsing it HIF has the function of promoting
blood supply to cancer tissue, encouraging its growth 8-10),
therefore, it can be expected that the collapse of HIF by VHLleads to controlling the growth of cancer tissue.
Gene expressions of various antioxidants including
glutathione peroxidase, β2-microglobulin and ferritin andribosomal protein having various functions were enforced in
the large intestine.

Due to the effects of starvation, ketone bodies increased
37 times, β-hydroxybutyric acid increased 34 times andacetoacetic acid increased 55 times, hyaluronic acid, which
is a liver fibrosis marker, increased 1.6 times and type IV
collagen decreased 40%.
Regarding bone metabolism, bone-type tartrateresistant acid phosphatase-5b (TRACP-5b), which is abone resorption marker, and type I collagen cross-linked
N-telopeptide (NTx) increased 1. 4 times. TRACP-5b isan enzyme existing in osteoclasts and leaks into the blood
along with the acceleration of bone resorption. NTx is adegradation product of bone type I collagen and is excreted
into urine, reflecting on bone resorption. As these findings
indicate the acceleration of bone resorption, calcium wasorally administered.
Regarding the intermediate aldehyde compounds,
which are indicators of glycation stress measured a new inthis research, 3-DG, AA and GO slightly increased 10%
and MGO only increased nearly three times. In skin AGEs
fluorescence intensity measurement, AGEs fluorescenceintensity decreased 13% from 0.62 to 0.54 ( Table 4 ).
Changes were observed in the property of stool. The
stool two days after fasting was sticky and deep-green
colored, almost black. This is the color of concentrated bile,as above mentioned. The stool excreted on the second day
after the completion of fasting was noteworthy.

Biochemical Characteristics of Fasting Therapy

The following are the fundamental aspects of thebiochemistry of fasting therapy. The changes in living bodies
by fasting therapy start from the dissolution of body fat andearly dissolution of protein caused by stopping the energy
supply. According to Voet’s Biochemistry 11), because thestorage of carbohydrates is used up in a day, after fastingfor several days, oxaloacetic acid in liver is used up for
gluconeogenesis, so that the metabolic capacity of acetylCoA by citric acid cycle has an extreme decrease. The
secretion of insulin decreases and fatty acid is mobilized
from fat tissue. Therefore, the liver converts acetyl-CoA toketone body and releases it. The brain synthesizes necessary
enzymes and gradually adapts to ketone body. After thethree-day fasting, ketone bodies fill only a third of the energy
demand of the brain; however, after around 4 0 days, they canDiscussion
Comparison with Previous Fasting Therapy

The results of the fasting therapy of this time and aprevious one were discussed from the fundamental viewpointof fasting therapy and the recent viewpoint of medicine,
Glycation stress indicators were measured in theprevious report, too. As a result of previous therapy,
pentosidine was nearly unchanged (Fig. 2). As a result of
therapy of this research, 3-DG, AA and GO only slightly
changed, MGO increased and the fluorescence intensity

Table 4. Changes of intermediate aldehydes.
Intermediate aldehydes in serum (ng/mL)
3-DG

Acetaldehyde

GO

MG O

Before fasting

12/27

97.5

37.3

6.2

8.8

During fasting

12/30

85.4

41.3

5.9

15.2

Right after fasting

1/ 3

111.8

45.8

6.7

22.6

One week after fasting

1 /10

102.8

45.7

7.4

8. 5

3-DG, 3-deoxyglucosone; GO, glyoxal; MGO, methylglyoxal.

_ 18 6 _Glycative Stress Research

100％

AGEs

103％

Pentosidine

92％

3 -DG

115％

Acetaldehyde

123％

GO

108％

MGO

257％

Lipid peroxide

49％

MD-LDL93％

8 -Isoprostane

121％

Urine 8 -isoprostane

44％

Urine creatol

51％

Paraoxonase

73％

GPx

76％

0％

30％
Anti-glycation

60％

90％

Peroxides

120％

150％

Anti-oxidation activity

Fig. 2. Previous results of fasting therapy showing percent change of data.

AGEs, advanced glycation end products; 3-DG, 3-deoxyglucosone; GO, glyoxal; MGO, methylglyoxal; LDL, low-density lipoprotein;
MD-LDL, malondialdehyde-modified LDL; GPx, glutathione peroxidase.

fill 75% of energy demand. The main constituents of ketone
body are β-hydroxybutyric acid and acetoacetic acid, andtheir levels increase more than 70 times during fasting. The
muscle break-down rate after long-term fasting is about 25%of that after fasting for several days.
In association with the decrease of blood glucose, thedecrease of insulin and the increases of glucagon, ketone
bodies, cortisol and norepinephrine are observed. The
rise of the level of norepinephrine (adrenalin) prevents thelowering of metabolic rate. A moderate decrease in bloodpressure is observed. Rapid increase of free fatty acid (FFA)
and increases of TC, LDL-C and TG are recognized, whichmeans that body fats are mobilized. Water dissolving vitamin
B and C are led to a light-level deficiency condition due tofasting longer than a week. As vitamin A is stored in the liver
for use for 5 to 10 months, it does not vary in a short period.
Regarding organs and systems of the body, theinduction of AST and ALT in the liver, and the lowering ofintestinal peristalsis and atrophy of the intestinal mucosa
are recognized. A moderate decrease in high-sensitivity
C-reactive protein (CRP) was observed. The increases ofsex hormone binding globulin, IGF -I and IGF- II wereobserved. The markers of oxidative stress and inflammation
also decreased. The symptom relating to asthma also
decreased and improvements were found in some indicatorsof quality of life (QOL). AGEs causing glycation stress are
said to worsen degenerative diseases including diabetes,

atherosclerosis, chronic renal failure and Alzheimer
dementia 12). AGEs are also said to be the cause of diabetic
vascular complications and accelerate cell damage causedby active oxygen and change the function of cells. AGEs
derived from glyceraldehyde are the most poisonous 13).
Depending upon the recent medical findings, fasting
therapies were classified into caloric restriction (CR),intermittent fasting (IF) and long-term fasting (LF) andcompared ( Table 5 ) 14,15). The decreasing rates of fasting
insulin and insulin resistance of both groups of LF and IF
were moderate, and the decreasing amounts of LF and IF
were larger than that of CR. The decreasing rate of bodyweight of LF was rapid in proportion to calorie restriction
amount, and those of I F and CR were moderate. In thecase of fasting for 24 hours, the growth hormone of female
subjects increased 13 times and that of male subjects
increased 20 times. The secretion of growth hormone
increased more than twice during fasting for five days. A
high level of growth hormone maintains muscle mass, leantissue mass and bone density. The muscle degradation rate
after a long-term fasting is about 25% of that of fasting forseveral days. Sirtuin gene, which is said to be a longevity
gene and anti-aging gene, increases 2-4 times by fasting for
48 hours, and it increases from several times to 10 times
by CR for seven weeks. Obese patients with asthma lose
8% weight and reduced oxidative stress and inflammatory
markers by IF for eight weeks (20% calories at fasting time).

_ 18 7 _Fasting Therapy

Table 5. Summary of recent medical finding of fasting therapy.
LF

IF

CR

Body weight↓(right after↓↓)↓↓

Visceral fat

↓

↓

↓

Lean body mass

〜

〜

↓

Energy metabolism

↓↓

↓↓

↓

Fasting plasma glucose

50 〜7090 〜 14090 〜 140

Ketone bodies

40 times

Slight elevation〜

Uric acid

↑↑↑

↑

〜

Insulin↓↓↓↓↓

Glucagon↑↑〜

Growth hormone

↑

↑

〜

Noradrenaline

↑

↑

〜

Cortisol↑〜〜

Ghrelin↓〜↑

Sirtuin gene expression

2 〜 4 timesNI

4 〜 10 times

Skin gross and elasticity

↑↑↑

↑

〜

High-sensitivity CRP

↓↓

↓

↓

B/T cell acute lymphoblastic leukemia

Inhibition

NI〜

Apoptosis

Elevation

NI

NI

LF, long-term fasting; IF, intermittent fasting; CR, caloric restriction; NI. No information; C-reactive protein.

Effect on Endoplasmic Reticulum

Endoplasmic reticulum (ER) is an important subcellular organelle controlling secretion within cells andquality control of membrane protein. The denatured protein
formed by starvation, ischemia, infection and inflammation
becomes abnormal protein with incomplete folding and isaccumulated in ER and causes ER stress, and as a result,it becomes the cause of apoptosis (cell death). ER stress isconfirmed in brain neuron cells of degenerative diseases
such as Alzheimer’s disease 16-18).
Oxidative stress and glycation stress cause abnormal
holding of protein in ER and accelerate ER stress. If ER stressis enhanced, the generation of active oxygen by mitochondria
increases and oxidative stress is further enhanced. Meanwhile,
GRP78, which is one of the molecular chaperones as anindicator of the response to ER stress, which develops andadvances in glucose starvation conditions 19, 20).
According to Professor Valter Long of the Longevity
Institute of Southern California University (Los Angeles,USA), LF and IF decrease the enzyme inhibiting activation ofstem cells (PKA) and decrease IGF- I increasing the risks ofaging and cancer growth. Fasting can regenerate and protect
the immune system damaged by aging and side effects ofchemotherapy and promote its neogenesis by enhancing theregenerative powers of stem cells and hematopoietic stem
cells. Seventy-two hours of fasting before chemotherapy
can protect the immune system and increase the effect ofchemotherapy up to 20 times. Hematopoietic stem cells
associated with the generations of blood and immune systemis activated by fasting, and as a result, new white blood cells
are generated and the immune system is regenerated 21).

Effect on Cancer Cells

Fasting therapy is considered to exert some influence incancer risk, too. Cancer cells metabolize glucose and aminoacids, but not fatty acids or ketone 22). In order to starvecancer cells, it is indispensable to restrict glucose and aminoacid (glutamine). Ketogenic diet 23) was effective when it was
combined with the period of intermittent diet, in particular.
Ideal blood glucose concentration to weaken cancer cells is
60 -70 mg/dL, and ketone level of 4 -7 mM is recommended(Table 6 ). LF enhances Keap-Nr f 2 system, decreases the
production of heme oxygenase and activates cytotoxic T
cells. It shows that fasting increased the expression of Nr f 2
target gene via Nr f 2- and SIRT1-dependent mechanisms.
Fasting induces Nr f 2 target gene by at least 1. 5 - 5 times in
the mouse liver.
GRP78 of ER stress response indicator is expressed andadvanced in glucose starvation environment even in cancer
cells 20). The balance between ER stress response in normal
cells and that in cancer cells at the time fasting should
be considered; however, it has been clinically confirmedthat cancer tissue shrinks by fasting 24-27). It is simply the_ 18 8 _Glycative Stress Research

Table 6. Comparison of energy use between normal cells and cancers cells.
Normal food intake (non-fasting)
GlucoseKetone bodies

Fasting
GlucoseKetone bodies

Normal cells
Cancer cells

sophistication of the living body.
An enhanced expression of VHL in gastric mucosa
was recognized in the previous experiment. VHL inhibits
angiogenesis and cell growth by working as a ubiquitin ligaseof HIF, specifically combining with HIF and disrupting it(Fig. 3 ).
Phospholipase C, which gene expression is inhibited in
the large intestine, specifically acts on phosphatidylinositol
diphosphate, lipids of the membrane, generates watersoluble inositol trisphosphate and increases the concentrationof calcium in cell 28). The inhibition of the expression of
the phospholipase C gene is also possibly involved in
the inactivation of protein kinase C having an effect on
carcinogenesis.

Effect on Intestinal FloraThe number of genes of the whole intestinal flora ismore than 1,000 times that of all human genes, so that
intestinal flora is said to be a new organ and that it functions
as a control tower of health maintenance. Due to thewesternization of the diet (high-protein, high-lipid and lowfiber diet), the balance of the structure of intestinal flora,
which is a very important partner for human beings, is being
lost (dysbiosis). Even though the number of good bacteria
is decreasing by aging, even the elderly can dramaticallyincrease it by 24-hours of fasting 29). Recently, it is said that
intestinal flora is deeply involved in the working of brain
and nerve system and it has effects on sleep, stress reaction,
memory and cognitive ability 30-34). There have been very
few studies on fasting therapy affecting intestinal flora 35, 36),
so that additional research in this respect is expected in the
future. Finally, what we should not forget is the changesin psychological and spiritual aspects during fasting. The
feelings of exhilaration and vitality and the awareness ofchanges in cognitive ability are deepened, which arise fromthe last part of the fasting period to the early part of fastbreaking period and are different from those which arethought to come from the increase of endogenous opioid.

Conclusion

We discussed the results of previous research and thatof this current research, based on the fundamental changes
caused by fasting therapy and recent medical viewpoint.
The fundamental difference of long-term fasting fromintermittent fasting and calorie restriction is considered tobe caused by extremely low blood glucose, hypoinsulinemia

and ketosis remaining for a long-term period. It is theprocess that long-term fasting causes the self-destructionof the cells aged and weakened with low blood glucose,hypoinsulinemia and ketosis and the tissues lesioned (bygene mutation and cancerous transformation), and makethem regenerate by recycling broken-down parts, so that it
can be said that “ it is the most appropriate simultaneous andmultiple micro-surgery without using a scalpel.”
The cancers which age-adjusted death rate is increasingare pancreatic cancer for males and pancreatic cancer andbreast cancer for females. Metastatic pancreatic cancer,
having approximately 61 cancer-related mutations, wasexamined using the technique of molecular clock ofevolutionary biology. It was found out that in order for an
original cancer to generate in the pancreas, it takes morethan 10 years after the first mutation and original cancer
takes five years to have metastatic nature and it takes two
additional years to lead to death. Fasting has the ability tomake micro cancer disappear, reduce cancer and inhibit the
migration and transplantation of cancer while metastasizing,by the induction of apoptosis and activation of hematopoietic
stem cells, as well as conquer the immune depression caused
by cancer chemotherapy 37).
For the longevity and cancer inhibition as the greatest
purposes of anti-aging, the restriction of calorie intake isbeing positioned as an essential and fundamental therapy
rather than indiscriminant replacement therapy. Calorie
restriction optimizes the adaptation mechanism like this,and eventually it optimizes individual existence. Regarding
the fasting therapy existing in the extreme position ofcalorie restriction, we would like to diffuse fasting therapy
while continuing the research of the cases of fasting therapy,
comparing with the results of animal experiments based
upon the results of this research and clarifying the realmechanisms of inhibition of cancer, anti-atherogenic action,
anti-inflammation action, immune improving action andspiritual trance condition.
The atrophy of intestinal tract caused by long-term
fasting is observed and the breakdown of aged cells andcancerous tissues can be expected. Therefore, the directabsorption of nourishment through intestinal tract wall is
not desirable because it stimulates the cells of the intestinal
tract wall. Dehydration should be avoided in the elderlywith advanced arterial sclerosis for the prevention of brain
infarction, cardiac infarction and arrhythmia, so that thedrip infusion of 500 -1,000 mL/d including electrolytes
recommended by fasting therapy society is necessary. In
order to write this paper, I did fasting with water only fora week. Probably due to this, I excreted a beautiful straightstool 35 cm in length that I took a picture with a mobile_ 18 9 _Fasting Therapy

Fig. 3. VHL/HIF pathway and cell proliferation.

VHL, von Hippel-Lindau tumor suppressor protein; HIF, hypoxia-inducible factor; VEGF, vascular endothelial growth factor;
GLUT, glucose transporter; NOS, nitric oxide synthase; PO 2, partial pressure of oxygen.

phone, because it was the first time in my life of 66 years.
Long-term fasting (for around a week) is the best duration
for me, not only from a physical aspect, but to look backat my life. As the fasting was proceeding, feelings ofexhilaration and euphoria appeared. Various ideas were
floating probably because of ketosis. It is dangerous to carryout the ideas immediately after returning to diet.
I wonder if I was reincarnated as a man with physicallyhigh efficiency. Because I gain weight consuming two
meals a day, I am maintaining a diet of one meal a day. In
short, “long-term fasting and daily calorie restriction” arenecessary. When I do not have lunch with my colleagues,
I take a walk in Meiji Shrine for an hour. I recommend
everyday walking, a brown rice meal a day, yoga, bodily
exercise, recitation of Heart Sutra (mantra in particular) andlong fasting twice a year.

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Acknowledgement

The authors are indebted to the cooperation of Mr.
Misato Kon Professor, Yoshikazu Yonei of Doshisha
University Faculty of Life and Medical Science (Kyoto,
Japan) in the measurement of aldehyde in plasma andfluorescence intensity of skin AGEs. I appreciate my uncle,
Tadahira Yamaguchi, and my aunt, Yoko Yamaguchi, who
made the opportunity for me to encounter fasting, yoga andbrown rice 50 years ago, and my wife, Nobue, who cooks
delicious brown rice for me every day.

Conflict of Interest Statement
The authors claim no conflict of interest in this study.

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