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Relationship between food polyamines and gross domestic product in association with longevity in Asian countries

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The relationship between gross domestic pro-duct (GDP) and dietary profile, with a focus on polyamine intake, was investigated in 35 Asian countries. Data on food supply, GDP, and health condition were collected from databases of the United Nations, the International Monetary Fund, and the World Health Organization, respectively. The amount of polyamine intake from food was estimated using polyamine concentrations listed in published sources. The amounts of putrescine, spermidine, spermine, and total polyamines in 1000 kcal of food in Asian countries were 39.07 ± 17.98, 33.74 ± 14.35, 14.05 ± 6.60 and 86.85 ± 33.96 μmol/1000 kcal, respectively. Putrescine, spermidine, and spermine constituted 44, 39, and 17% of total polyamine, respectively. Vege-tables contributed the largest amount of both putrescine and spermidine and the second larg-est amount of spermine (45.5%, 62.2% and 27.2% of total putrescine, spermidine, and spermine, respectively). Meat was the richest source of spermine and contributed the greatest amount (50%) of this polyamine. We showed a signifi-cant positive association between GDP and the amount of polyamine per 1000 kcal of food. Li-fespan was associated with both GDP and the amount of polyamine per energy quotient of food. As several basic research studies have shown that polyamines help prolong longevity, it follows that polyamines may have a role in determining the lifespan of humans.
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Vol.2, No.12, 1390-1396 (2010) Health
doi:10.4236/health.2010.212206
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Relationship between food polyamines and gross
domestic product in association with longevity in Asian
countries
Phan Nguyen Thanh Binh1,2, Kuniyasu Soda3*, Chizuko Maruyama2, Masanobu Kawakami4
1Department of Community Nutrition, HCMC Nutrition Center, Ho Chi Minh City, Vietnam;
2Department of Food and Nutrition, Japan Women’s University, Tokyo, Japan;
3Department of Cardiovascular Research Institute, Saitama Medical Center, Jichi Medical University, Saitama, Japan;
*Corresponding Author: soda@jichi.ac.jp;
4Department of Internal Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
Received 15 October 2010; revised 1 November 2010; accepted 5 November 2010
ABSTRACT
The relationship between gross domestic pro-
duct (GDP) and dietary profile, with a focus on
polyamine intake, was investigated in 35 Asian
countries. Data on food supply, GDP, and health
condition were collected from databases of the
United Nations, the International Monetary Fund,
and the World Health Organization, respectively.
The amount of polyamine intake from food was
estimated using polyamine concentrations listed
in published sources. The amounts of putrescine,
spermidine, spermine, and total polyamines in
1000 kcal of food in Asian countries were 39.07
± 17.98, 33.74 ± 14.35, 14.05 ± 6.60 and 86.85 ±
33.96 μmol/1000 kcal, respectively. Putrescine,
spermidine, and spermine constituted 44, 39,
and 17% of total polyamine, respectively. Vege-
tables contributed the largest amount of both
putrescine and spermidine and the second larg-
est amount of spermine (45.5%, 62.2% and 27.2%
of total putrescine, spermidine, and spermine,
respectively). Meat was the richest source of
spermine and contributed the greatest amount
(50%) of this polyamine. We showed a signifi-
cant positive association between GDP and the
amount of polyamine per 1000 kcal of food. Li-
fespan was associated with both GDP and the
amount of polyamine per energy quotient of
food. As several basic research studies have
shown that polyamines help prolong longevity,
it follows that polyamines may have a role in
determining the lifespan of humans.
Keywords: Polyamine; GDP; Longevity;
Cardiovascular Diseases; Food
1. INTRODUCTION
The polyamines putrescine, spermidine, and spermine,
not only play an essential role in the proliferation and
differentiation of mammalian cells but also have impor-
tant physiological roles on cellular function. In addition,
very recent studies have shown that exogenous polya-
mine suppresses the progression of age-associated pa-
thologies and increases the life span of cells and several
living organisms including mice [1,2]. On the other hand,
there is evidence that increased polyamine concentra-
tions are associated with several deteriorations in health
[3-6].
Food is one of the important sources of body polya-
mines which are absorbed by the intestinal lumen and
then distributed to all organs and tissues [7]. In fact, dif-
ferences in polyamine intake have been shown to influ-
ence blood polyamine concentration in both mice and
humans [8]. As most foods originate from plants or ani-
mals, almost all foods contain polyamines, but in widely
varying concentrations [9-12]. It is therefore very im-
portant to delineate the factors that may influence po-
lyamine intake.
Socioeconomic status is closely associated with fa-
vorable health status and prolonged lifespan [13-18].
Gross domestic product (GDP) is one of the representa-
tive indicators of socioeconomic status of countries, and
we have shown using an open database that individuals
living in European and Western countries with a high
GDP prefer foods containing abundant polyamines
compared to individuals living in countries with a lower
GDP [19]. This study aimed to examine the relationship
between the amount of food polyamine and GDP in
Asian countries. In addition, as polyamines have been
shown to have several roles on health status in experi-
mental models, we also examined the relationship be-
tween health status and polyamine intake in association
P. N. T. Binh et al. / Health 2 (2010) 1390-1396
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
1391
with GDP.
2. METHODS AND MATERIALS
2.1. Database
Data on food supply in 2002 were obtained from the
online database of the Statistics Division of the Food and
Agriculture Organization of the United Nations (FAOS-
TAT). The target populations were 35 Asian countries
that included Bangladesh, Brunei Darussalam, Cambo-
dia, China, Democratic People’s Republic of Korea, Fiji,
India, Indonesia, Islamic Republic of Iran, Japan, Jordan,
Kiribati, Kuwait, Kyrgyzstan, Lao People’s Democratic
Republic, Lebanon, Malaysia, Maldives, Mongolia, Myanmar,
Nepal, Pakistan, Philippines, Republic of Korea, Samoa,
Saudi Arabia, Solomon Islands, Sri Lanka, Syrian Arab
Republic, Thailand, Timor-Leste, United Arab Emirates,
Vanuatu, Viet Nam, and Yemen. The concentrations of
spermine, spermidine, and putrescine in foods were ob-
tained from published reports of concentrations meas-
ured in Japanese foods [9,10]. When these reports did
not show the polyamine content of certain foods, we
used additional data obtained from European studies
[11,12] (Table 1). All the food items were categorized
Table 1. Polyamine contents in Asian foods (nmol/g or
nmol/mL)
Food items Putrescine Spermidine Spermine
Cereals
Barley 17 16 20
Maize 576 144 8
Millet 19 63 48
Oats 41 133 148
Rice (milled
equivalent) 8 7.5 1.5
Rye 41 133 148
Sorghum 14 12 0
Wheat 19 29.5 0.5
Other cereals 31.7 90 23.7
Vegetables
Cassava 0 0 0
Cloves 0 0 0
Onions 29.5 86.5 4.5
Potatoes 89 68 15.5
Pulses1 26 144 74
Roots & tuber
dry equiv2 118 109.3 19.8
Sweet pota-
toes 29 25.2 16.5
Tomatoes 146.3 22.5 2.5
Vegetables3 113.5 170.2 17.4
Yams 73 89.5 2
Aquatic plants 118 109.3 19.8
Fruits
Apples 10 14 0.5
Bananas 160 50 1.5
Grapefruit 436 19.5 1.5
Grapes 106 87 0
Lemons, limes 390.5 19 4.5
Oranges,
mandarins 432 15.5 0
Pineapples 46 30 0
Citrus, other4 460.2 26.5 0
Fruits, other5 74.5 55.4 4
Beans and
Nuts
Beans6 147 644.8 299.7
Groundnuts7 18 110 88
Peas8 367 341 32
Sesame seed 29 126 22
Soybean 297 909 235.5
Sunflower
seed 34 383 89
Tree nuts9 104.5 108.9 111.6
Seafoods
Cephalopods10 3.3 9.3 93.3
Crustaceans11 26.5 0 0
Fish12 27.2 37.1 53.1
Fish, oil 0 0 0
Molluscs13 19.7 143.5 383.5
Aquatic ani-
mals and
others14
26.3 55.1 87.2
Meat
Bovine meat 18.5 17.5 149
Mutton & goat
meat 8.2 39.7 131.3
Pig meat 4.5 9.5 165
Poultry meat15 13.3 48.5 3.5
Meat, other 11.5 26.7 194.2
Offal, edible16 63.8 188 825.8
Dairy prod-
ucts
Butter, ghee,
whey & milk 0 0 0
Cheese 0 15 3.5
Cream 0.3 0 0
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1392
Eggs 6.5 2.5 2.5
Vegetable oil and animal fat
Vegetable oil 0 0 0
Animal fat 0 0 0
Sugar &
Sweeteners
Sugar &
Sweeteners 3 0 0
Beverages and
stimulants
Beer 153.3 1 0
Wine 49 1.5 0
Tea leaf 49.5 96.3 72.8
Coffee 0 0 0
Other beve-
rages17 0 0 0
Pepper 621 80 45
Pimento &
Spices 0 0 0
† The average content of spermine, spermidine, and putres-
cine in each food item expressed as nmol/g or nmol/mL was
calculated using data for foods available in Japan reported
by K. Nishimura, et al., (Decrease in polyamines with aging
and their ingestion from food and drink. J Biochem 2006;
139: 81-90) and N. Nishibori, et al., (Amounts of
poly-amines in foods in Japan and intake by Japanese. Food
Chem 2007; 100: 433-872). 1Field pies; 2Burdock root and
lotus root; 3Asparagus, bean sprouts, beet, beetroot, brocco-
li, Brussel sprouts, butterbur, cabbage, carrot, cauliflower,
celery, Chinese cabbage, green cabbage, red cabbage, cher-
vil, chicory, cucumber, eggplant, escarole, green leek, leek,
lettuce, mushrooms, parsley, pumpkin, spinach, radish, sal-
sify, sorrel, watercress; 4Oranges, mandarins, and tangerines;
5Pear, strawberry, persimmon, fig, pomegranate, peach,
blueberry, melon, watermelon, cherry, prune, durian, pa-
paya, dragon fruit, kiwifruit, mango, and avocado; 6Adzuki
bean, cow pea, and soybean; 7Peanut; 8Green peas;
9Almond, cashew, and pistachio nuts; 10Squid and octopus;
11Shrimp and crab; 12Horse mackerel, Japanese needlefish,
mackerel, salmon, sardine, tuna, conger, angler, sweetfish,
alfonsino, saury, shark, scabbard fish, yellowtail, swordfish,
bonito, codfish, eel, and whitefish; 13Oyster, white scallop,
coral scallop, and clam; 14Fish and shellfish; 15Chicken and
duck; 16Beef liver, beef intestine, pork liver, chicken liver,
chicken gizzard, and chicken heart; 17Soft drink and cocoa.
the following 12 groups for further analysies; including
1) Cereals, 2) Vegetables and starchy roots, 3) Fruits, 4)
Beans, 5) Seafoods, 6) Meat, 7) Dairy products, 8) Eggs,
9) Vegetable oil and animal fat, 11) Sugar and sweeten-
ers, and 12) Beverages and stimulants. As the data on
food supply from the WHO does not necessarily indicate
the absolute amount consumed by each nation, and in
order to ascertain the features of dietary patterns, we
used a relative measure of the amount of various foods,
such as food consumption per energy quotient. GDP per
capita in 2002 was obtained from the International Mon-
etary Fund (IMF), and age-standardized mortality rates
(per 100,000 population) due to cardiovascular diseases
(CVD) and cancer in 2002 and life expectancy at birth in
2006 were derived from the World Health Organization
Statistical Information System (WHOSIS).
2.2. Statistics
The data were analyzed using the statistical package SPSS
for Windows (SPSS Inc., Chicago, IL, USA). Pearson’s
correlation coefficients were calculated to examine the
association between the relative amount of polyamine in
foods, GDP per capita, and life expectancy. A P-value <
0.05 was considered statistically significant.
3. RESULTS
3.1. Polyamine Contents in Asian Foods
The average content of the three polyamines, putrescine,
spermidine, and spermine in each food item is shown in
Table 1. Polyamine content ranged widely among the
foods, with several foods having increased polyamine
concentrations. The highest putrescine levels were found
in maize, citrus fruits, grapefruit, peas, soybeans, and
other beans. Spermidine concentrations were high in
soybeans, other beans, and vegetables, while spermine
concentrations were high in edible offal, molluscs, meats,
soybeans, and other beans. Generally, foods of plant ori-
gin tended to have higher contents of spermidine com-
pared to spermine, whereas foods of animal origin had
the opposite composition. The levels of all polyamines
were very low or undetectable in vegetable oil, animal fat,
sugar and sweeteners, eggs, and dairy products including
butter, cream, whey, cow milk and infant milk formulas.
3.2. Daily Amounts per capita and Amounts
per 1000 kcal of Polyamines
Table 2 shows the daily amounts per capita and Table 3
shows the daily amounts per 1000 kcal of the three po-
lyamines in Asian countries. The average estimated daily
intake of putrescine, spermidine, spermine, and total
polyamines in Asian countries were 106 μmol, 91 μmol,
38 μmol and 235 μmol, respectively. Putrescine, spermi-
dine, and spermine accounted for 44%, 39%, and 17% of
total polyamine intake, respectively. The amounts of
putrescine, spermidine, spermine, and the sum of the
three polyamines per 1000 kcal energy were 39, 34, 14,
and 87 μmol/day.
3.3. Sources of Polyamines
The proportions of the three polyamines provided by
each food group are shown in Figure 1. Overall, vegeta-
bles provided the largest amount of putrescine and sper-
P. N. T. Binh et al. / Health 2 (2010) 1390-1396
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
1393
Table 2. The daily amounts of polyamines in each food group.
c Amount Putrescine Spermidine Spermine
(g/day) (µmol/day) (µmol/day) (µmol/day)
Cereals 417.4 ± 101.2 26.04 ± 35.19 12.28 ± 8.63 0.92 ± 1.17
Vegetables and roots 497.6 ± 290.0 48.40 ± 30.81 59.70 ± 35.20 8.68 ± 4.90
Fruits 172.0 ± 116.3 23.85 ± 19.19 6.72 ± 5.06 0.32 ± 0.25
Beans 28.6 ± 30.9 2.24 ± 2.87 6.03 ± 9.24 2.33 ± 3.14
Seafoods 75.4 ± 97.4 1.86 ± 2.60 2.80 ± 3.65 4.64 ± 5.80
Meat 89.7 ± 67.5 1.30 ± 1.09 3.64 ± 3.34 21.34 ± 16.73
Dairy products 138.8 ± 136.5 0 0.04 ± 0.09 0.01 ± 0.02
Eggs 14.2 ± 13.8 0.09 ± 0.09 0.04 ± 0.03 0.01 ± 0.01
Vegetable oil 21.7 ± 14.3 0 0 0
Animal fat 5.1 ± 6.5 0 0 0
Sugar and sweeteners 63.2 ± 36.1 0.19 ± 0.11 0 0
Beverages and stimulants 34.6 ± 42.1 1.87 ± 2.84 0.11 ± 0.17 0.04 ± 0.01
Total 1558.2 ± 480.9 105.85 ± 52.48 91.36 ± 41.61 38.29 ± 19.61
Per-capita daily availability of amount of food and the amount of putrescine, spermidine, and spermine from each food group are expressed as the
mean ± standard deviation (SD). Values < 0.001 are expressed as 0.
Table 3. The daily amounts per 1000 kcal of polyamines in each food group.
Food groups Amount Putrescine Spermidine Spermine
(g/1000kcal) (µmol/1000kcal) (µmol/1000kcal) mol/1000kcal)
Cereals 158.7 ± 41.4 9.99 ± 13.26 4.64 ± 3.25 0.35 ± 0.42
Vegetables and roots 183.3 ± 104.3 17.68 ± 10.49 21.89 ± 12.01 3.22 ± 1.82
Fruits 62.7 ± 38.2 8.59 ± 6.24 2.46 ± 1.73 0.12 ± 0.09
Beans 10.2 ± 10.4 0.84 ± 1.17 2.32 ± 3.93 0.89 ±1.35
Seafoods 28.2 ± 36.8 0.70 ± 0.98 1.04 ± 1.37 1.72 ± 2.14
Meat 32.7 ± 24.9 0.47 ± 0.42 1.32 ± 1.26 7.74 ± 6.07
Dairy products 50.4 ± 47.7 0.0 ± 0.0 0.01 ± 0.03 0.003 ± 0.007
Eggs 5.1 ± 4.8 0.03 ± 0.03 0.01 ± 0.01 0.003 ± 0.002
Vegetable oil 7.9 ± 4.7 0 0 0
Animal fat 1.8 ± 2.3 0 0 0
Sugar and sweeteners 23.2 ± 12.5 0.07 ± 0.04 0 0
Beverages and stimulants 12.6 ± 14.6 0.69 ± 1.01 0.04 ± 0.06 0.01 ± 0.03
Total 576.8 ± 128.7 39.07 ± 17.98 33.74 ± 14.35 14.05 ± 6.60
Per-capita availability of the amount of food and the amount of putrescine, spermidine, and spermine per person are listed by food category.
The daily amounts per 1000 kcal are expressed as the mean ± SD. Values < 0.001 are expressed as 0
Figure 1. The contribution of each food group to the amount of putrescine (A), spermidine (B) and spermine (C).
P. N. T. Binh et al. / Health 2 (2010) 1390-1396
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1394
midine, and also provided the second largest amount of
spermine (45.5% of putrescine, 62.2% of spermidine,
and 27.2% of spermine). Other important sources of
putrescine were cereals and fruits, which provided
24.0% and 22.3% of total putrescine, respectively. Cere-
als, fruits, and beans supplied 15.5%, 7.7%, and 6.6% of
total spermidine, respectively. Animal meats were the
biggest source of spermine, and provided 50% of total
spermine.
3.4. Associations between the Amounts of
Putrescine, Spermidine, and Spermine
per Total Energy and GDP per capita
The GDPs of the Democratic People’s Republic of Korea
and Timor-Leste could not be obtained. These two coun-
tries were therefore excluded from the analyses which
subsequently included 33 countries. The GDP data were
transformed to natural logarithms to approximate a nor-
mal distribution. Pearson’s correlation coefficients were
calculated to investigate the relationship between po-
lyamine amount per food energy (1000 kcal) and GDP.
As shown in Table 4, GDP per capita correlated posi-
tively with all three polyamines, with different levels of
correlation being observed. Although the correlation
coefficients between GDP and spermidine and putresine
per energy quotient were < 0.4 with p values < 0.05,
spermine per energy quotient showed a strong positive
correlation with GDP.
3.5. Correlation among the Amount of
Polyamine, GDP, and Health Status
GDP was associated positively with life expectancy (r =
0.890, p < 0.001) and negatively with mortality due to
cardiovascular diseases (r = –0.640, p < 0.001). Life
expectancy was associated negatively with CVD mortal-
ity (r = –0.674, p < 0.001). Although no significance
associations were found, the correlation coefficients be-
tween CVD mortality and spermine/energy, spermidine/
energy, putrescine/energy, spermine plus spermidine/
energy, and total amount of all three polyamines/energy
all had negative values (r = –0.276, –0.057, –0.035,
–0.154, and –0.103, respectively). No significant associ-
ation was found between life expectancy and cancer
mortality. As shown in Table 4, GDP and life expectancy
were associated positively with the total amount of food
polyamine per energy, with various levels of correlation
being observed.
4. DISCUSSION
Reference to our previous report on European foods [19]
showed that although there were many similarities in the
Table 4. Correlation between polyamine/energy and GDP and
life expectancy.
GDP Life expectancies
r P r P
Putrescine / energy 0.366 0.036 0.232 0.181
Spermidine / energy 0.386 0.026 0.308 0.072
Sermine / energy 0.607 <0.001 0.585 < 0.001
Spermine plus
spermidine / energy 0.532 0.001 0.453 0.006
Polyamine / energy 0.480 0.004 0.367 0.030
The correlation between each polyamine / energy and GDP (natural
logarithm) was examined in 33 countries, as the GDP of the Demo-
cratic People's Republic of Korea and Timor-Leste could not be
obtained. r indicates the correlation coefficient of the linear regres-
sion between polyamine/energy and GDP or life expectancy.
proportions of supplied foods, there were striking dif-
ferences in the higher amounts of dairy products and
animal-derived products consumed in European coun-
tries, whereas consumption of cereals was higher in
Asian countries. Similarly, polyamine concentrations in
Japanese foods [9,10] were similar to those in European
foods [11,12], whereas in some foods, especially cheese,
the concentrations were markedly different. These va-
ria-tions in polyamine content could be explained by the
effects of food processing and storage changes, and one
of the weaknesses of the present study was the inability
to comprehend these changes. However, the estimated
daily amount of food polyamines in Asian countries was
similar to those contained in a previous report on Japa-
nese foods [9] in which the daily amount of supplied
putrescine, spermidine, and spermine per person were
113, 82, and 39 μmol, respectively. In that study, putres-
cine, spermidine, and spermine accounted for 45%, 37%
and 18% of total daily polyamine supply in Japanese
diets, respectively. The daily amount of polyamine
availability from foods in Asian countries was consider-
ably lower than that reported in European countries, es-
pecially countries with a higher GDP (350-500 μmol/
day/person) [20,21]. However, the proportions of each of
the three polyamines relative to total polyamines were
similar to those in European countries [20,21]. The low-
er amount of total polyamine availability appeared to be
due to the lower amount of total food supply in Asian
countries, as the amounts of spermine and spermidine
per food energy in Asian countries were higher than
those in European countries, while the sum of the total
amount of the three polyamines per energy was similar
to European and Western countries with a lower GDP
[19].
The results of the present study using databases for
Asian countries were relatively similar to those reported
in earlier studies in European and Western countries in
which socio-economic status showed a close positive
association with longevity and a close negative associa-
P. N. T. Binh et al. / Health 2 (2010) 1390-1396
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
1395
tion with CVD mortality [13-18]. The results of the
present study also indicated that reducing the incidence
of CVD is very important for improving health status
and prolonging lifespan, even in Asian countries. Studies
using personal databases have shown decreases in CVD
incidence and increases in life span are often associated
with socioeconomic status [13-18]. Although the factors
affecting health condition according to socioeconomic
status are not fully understood, the present study showed
that the amount of polyamine in foods was associated
closely with GDP per capita. A very interesting finding
in our study was that the amount of food polyamine per
energy quotient was associated not only positively with
GDP but also negatively with CVD incidence. As the
current study was an ecological investigation, it would
therefore be expected there were potential confounding
factors in these associations. However, recent basic re-
search studies have shown that increased polyamine in-
take prolongs the longevity of some small organisms and
rodents [1,2], and therefore increased polyamine intake
may theoretically help maintain vascular health by in-
creasing the amount of arginine available for nitric oxide
(NO) synthesis [22-25]. These findings and those of the
present study suggest a possible role of food polyamines
on human health.
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... 7 Spermidine, a naturally occurring polyamine, is widely found in vegetables, cereals, legumes, cheese, mushrooms, and other foods and particularly enriched in Mediterranean and Asian diets. 8,9 In epidemiological Liu et al Spermidine Suppresses Experimental AAAs studies, higher intake of polyamines in Mediterranean and Asian diets increases longevity and lowers mortality. 8,10 Spermidine is rapidly resorbed from the intestine and distributed in the body without degradation, 11 resulting in its subsequent increased concentration in the blood. ...
... 8,9 In epidemiological Liu et al Spermidine Suppresses Experimental AAAs studies, higher intake of polyamines in Mediterranean and Asian diets increases longevity and lowers mortality. 8,10 Spermidine is rapidly resorbed from the intestine and distributed in the body without degradation, 11 resulting in its subsequent increased concentration in the blood. 12 Spermidine, as a histone acetyl transferase inhibitor, induces protein deacetylation and autophagy, and is involved in an array of biological events including autophagy induction, DNA stability, transcription, translation, and apoptosis. ...
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Background The protective effects of polyamines on cardiovascular disease have been demonstrated in many studies. However, the roles of spermidine, a natural polyamine, in abdominal aortic aneurysm ( AAA ) disease have not been studied. In this study, we investigated the influence and potential mechanisms of spermidine treatment on experimental AAA disease. Methods and Results Experimental AAA s were induced in 8‐ to 10‐week‐old male C57 BL /6J mice by transient intra‐aortic infusion of porcine pancreatic elastase. Spermidine was administered via drinking water at a concentration of 3 mmol/L. Spermidine treatment prevented experimental AAA formation with preservation of medial elastin and smooth muscle cells. In immunostaining, macrophages, T cells, neutrophils, and neovessels were significantly reduced in aorta of spermidine‐treated, as compared with vehicle‐treated elastase‐infused mice. Additionally, flow cytometric analysis showed that spermidine treatment reduced aortic leukocyte infiltration and circulating inflammatory cells. Furthermore, we demonstrated that spermidine treatment promoted autophagy‐related proteins in experimental AAA s using Western blot analysis, immunostaining, and transmission electron microscopic examination. Autophagic function was evaluated for human abdominal aneurysmal and nonaneurysmal adjacent aortae from AAA patients using Western blot analysis and immunohistochemistry. Dysregulated autophagic function, as evidenced by increased SQSTM 1/p62 protein and phosphorylated mTOR , was found in aneurysmal, as compared with nonaneurysmal, aortic segments. Conclusions Our results suggest that spermidine supplementation limits experimental AAA formation associated with preserved aortic structural integrity, attenuated aortic inflammatory infiltration, reduced circulating inflammatory monocytes, and increased autophagy‐related proteins. These findings suggest that spermidine may be a promising treatment for AAA disease.
... In humans, spermidine has been shown to preserve female fertility [332], restore skin structure and barrier function [333] and improve mnemonic discrimination performance [334]. In humans, spermidine has been shown to preserve female fertility [335]. ...
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Recently, there has been an increase in the incidence of malignant tumors among the older population. Moreover, there is an association between aging and cancer. During the process of senescence, the human body suffers from a series of imbalances, which have been shown to further accelerate aging, trigger tumorigenesis, and facilitate cancer progression. Therefore, exploring the junctions of aging and cancer and searching for novel methods to restore the junctions is of great importance to intervene against aging-related cancers. In this review, we have identified the underlying pathogenetic mechanisms of aging-related cancers by comparing alterations in the human body caused by aging and the factors that trigger cancers. We found that the common mechanisms of aging and cancer include cellular senescence, alterations in proteostasis, microbiota disorders (decreased probiotics and increased pernicious bacteria), persistent chronic inflammation, extensive immunosenescence, inordinate energy metabolism, altered material metabolism, endocrine disorders, altered genetic expression, and epigenetic modification. Furthermore, we have proposed that aging and cancer have common means of intervention, including novel uses of common medicine (metformin, resveratrol, and rapamycin), dietary restriction, and artificial microbiota intervention or selectively replenishing scarce metabolites. In addition, we have summarized the research progress of each intervention and revealed their bidirectional effects on cancer progression to compare their reliability and feasibility. Therefore, the study findings provide vital information for advanced research studies on age-related cancers. However, there is a need for further optimization of the described methods and more suitable methods for complicated clinical practices. In conclusion, targeting aging may have potential therapeutic effects on aging-related cancers.
... The remarkable differences in the spermidine content of various foods, as well as the regional and cultural variances in human nutrition, have resulted in country-specific estimates of spermidine intake. A positive association between gross domestic product and the total PA per energy content of food for 33 Asian countries was reported (15). Gross domestic product is a representative indicator of socioeconomic status and correlates with health span and life span (15 and references therein), arguing for a potential positive association of PAs in food with healthy diet. ...
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Natural polyamines (spermidine and spermine) are small, positively charged molecules that are ubiquitously found within organisms and cells. They exert numerous (intra)cellular functions and have been implicated to protect against several age-related diseases. Although polyamine levels decline in a complex age-dependent, tissue-, and cell type–specific manner, they are maintained in healthy nonagenarians and centenarians. Increased polyamine levels, including through enhanced dietary intake, have been consistently linked to improved health and reduced overall mortality. In preclinical models, dietary supplementation with spermidine prolongs life span and health span. In this review, we highlight salient aspects of nutritional polyamine intake and summarize the current knowledge of organismal and cellular uptake and distribution of dietary (and gastrointestinal) polyamines and their impact on human health. We further summarize clinical and epidemiological studies of dietary polyamines. Please see http://www.annualreviews.org/page/journal/pubdates for expected final online publication date for the Annual Review of Nutrition, Volume 40. 2020
... Enzymatic decarboxylation of free amino acids and other metabolic processes by S. aureus, E. coli and K. pneumoniae leads to production of biogenic amines which can be serve as a quality indicator in food in terms of degree of spoilage, use of non-hygienic raw material and poor manufacturing environment. Although, intake of exogenous polyamines are beneficial in the treatment of some geriatric diseases and prolonging human life through consumption of food polyamines that are abundant in the Mediterranean diet (Binh et al., 2010) and utilization of polyamine pathway as a rational target for chemoprevention and chemotherapeutics (Nowotarski et al., 2013). Thus, effect of biogenic amines obtained in this research would be determined by individual toxicological threshold which can be extremely variable from few mg/kg in sensitive person to several hundred mg/kg in healthy person (Hungerford, 2010). ...
... Indeed, bone loss induced by ovariectomy in mice, a model of postmenopausal osteoporosis, is prevented with oral spermidine supplementation via inhibition of the formation of (bone-resorbing) osteoclasts (53). The total amount of food polyamines significantly correlates with human life expectancies across distinct Asian countries (54), although this epidemiological study did not adjust for confounding factors typically associated with longevity. Future well-controlled epidemiological studies are warranted to explore the effects of dietary spermidine on human health span and life span. ...
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Having your longevity and eating too Although caloric restriction has clear benefits for maximizing health span and life span, it is sufficiently unpleasant that few humans stick to it. Madeo et al. review evidence that increased intake of the polyamine spermidine appears to reproduce many of the healthful effects of caloric restriction, and they explain its cellular actions, which include enhancement of autophagy and protein deacetylation. Spermidine is found in foods such as wheat germ, soybeans, nuts, and some fruits and vegetables and produced by the microbiota. Increased uptake of spermidine has protective effects against cancer, metabolic disease, heart disease, and neurodegeneration. Science , this issue p. eaan2788
... Therefore, intake of exogenous polyamines was shown to be beneficial in the treatment of some geriatric diseases [8,9]. In the meantime, Binh reported a possible role for the food polyamines that are abundant in the Mediterranean diet in prolonging human life [10]. However, limited information about the polyamine content of food is available to assess dietary polyamine intake and subsequently have dieticians design proper menus. ...
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Putrescine, spermidine and spermine are the most abundant polycationic natural amines found in nearly all organisms. They are involved in regulation of gene expression, translation, cell proliferation and differentiation. They can be supplied by the endogenous synthesis inside the cell or by the intake from exogenous sources. There is a growing body of literature associated with the effects of bioactive amines on health and diseases, but limited information about polyamine content in foods is available. In the present study, the polyamine content of frequently consumed foods in a typical Turkish diet was estimated for adults, including tea, bread and yoghurt. The estimation of daily intake was defined as 93,057 nmol/day putrescine, 33,122 nmol/day spermidine, 13,685 nmol/day spermine. The contribution of foods to daily intake was: dairy products (47.32%), vegetables and grains (21.09%) and wheat products (12.75%).
... Food rich in SPD includes soya and other beans, green tea and mushrooms (302,303) . SPD rich diets are consumed traditionally in Asian (304) and Mediterranean (305) regions. ...
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Energy restriction (ER; also known as caloric restriction) is the only nutritional intervention that has repeatedly been shown to increase lifespan in model organisms and may delay ageing in humans. In the present review we discuss current scientific literature on ER and its molecular, metabolic and hormonal effects. Moreover, criteria for the classification of substances that might induce positive ER-like changes without having to reduce energy intake are summarised. Additionally, the putative ER mimetics (ERM) 2-deoxy- d -glucose, metformin, rapamycin, resveratrol, spermidine and lipoic acid and their suggested molecular targets are discussed. While there are reports on these ERM candidates that describe lifespan extension in model organisms, data on longevity-inducing effects in higher organisms such as mice remain controversial or are missing. Furthermore, some of these candidates produce detrimental side effects such as immunosuppression or lactic acidosis, or have not been tested for safety in long-term studies. Up to now, there are no known ERM that could be recommended without limitations for use in humans.
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The aim of this paper is to offer an introduction to arterial inflammation, autophagy, and senescence, and their relationship with aging and cardiovascular disease. Methods of preventing and reducing arterial inflammation, enhancing autophagy, and avoiding premature senescence will be discussed.
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Healthy foods such as beans, mushrooms, vegetables, and seafood and healthy dietary patterns such as the Mediterranean diet and Japanese food have higher concentrations of polyamines (spermine and spermidine). The continuous intake of high-polyamine foods has been shown to increase whole blood polyamine levels in mice and humans. In addition, high-polyamine chow inhibited aging-associated pathological changes in Jc1:ICR male mice and extended their lifespan. Aging is accompanied by decreased DNA methyltransferase activities, increased proinflammatory status, and enhanced abnormal gene methylation status, which is considered to be part of the pathogenesis of aging-associated diseases. In vitro and in vivo experiments have shown that polyamine supplementation reversed such changes induced by aging and polyamine-deficiency. In addition, polyamines have many biological activities that may contribute to the inhibition of lifestyle-related diseases such as diabetes, hyperlipemia, and arteriosclerosis. The possible role of dietary polyamines in human health is discussed.
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Considerable differences were found in the incidence of age-associated diseases and the mean lifespan between countries of similar social background. Previously, the inhibition of age-associated disease progression was considered to be attributable to anti-oxidants in foods, such as isoflavones and resveratrol. However, the results of recent studies do not support the role of anti-oxidants in the inhibition of age-associated diseases and senescence. We have reported that healthy foods such as beans, mushrooms, seafoods and vegetables, and healthy dietary traditions such as the Mediterranean diet and Japanese foods are rich in polyamines (spermine and spermidine). Polyamines are synthesized in rapidly growing cells; however, this ability decreases with aging. In addition to de novo synthesis, cells can take up polyamines from their surroundings. An important source of whole body polyamines originates in the intestinal lumen, e.g., food-derived polyamines. Polyamines in the intestinal lumen are absorbed quickly, and continuously increased polyamine intake elevates blood polyamine levels in humans and mice. In addition to the many biological activities that help protect cells and tissues from harmful stimuli, we have shown that polyamines suppress pro-inflammatory status, characterized by the suppression of leukocyte function associate antigen 1 (LFA-1) expression and pro-inflammatory cytokine production. Moreover, increased intracellular spermine from extra-cellular sources enhanced the activities of DNA methyltransferases (DNMT) and suppressed polyamine deficiency-induced genome-wide demethylation/methylation in vitro. Long-term increased polyamine intake inhibited age-associated pathological changes and suppressed abnormal genome-wide demethylation/methylation in Jc1 : ICR male mice. In addition, increased polyamine intake was associated with a decreased incidence of colon tumors in BALB/c mice after 1,2-demethylhydrazine administration. Aging is associated with decreased polyamine synthesis, enhanced pro-inflammatory status (e.g., increased LFA-1 expression), decreased DNMT activities, and enhanced genome-wide demethylation/methylation; therefore, dietary polyamine represents a valuable food element to suppress age-associated pathologies and extend the lifespan of humans.
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The polyamines putrescine, spermidine and spermine are essential for cell renewal and, therefore, are needed to keep the body healthy. It was previously believed that polyamines are synthesized by every cell in the body when required. However, in the present paper evidence is provided to show that, as in the case of the essential amino acids, the diet can supply sufficient amounts of polyamines to support cell renewal and growth. Systematic analysis of different foods was carried out and from the data obtained, the average daily polyamine consumption of British adults was calculated to be in the range 350–500 μmol/person per d. The major sources of putrescine were fruit, cheese and non-green vegetables. All foods contributed similar amounts of spermidine to the diet, although levels were generally higher in green vegetables. Meat was the richest source of spermine. However, only a part of the polyamines supplied by the diet is available for use by the body. Based on experiments with rats it was established that polyamines were readily taken up from the gut lumen, probably by passive diffusion, and were partly metabolized during the process of absorption. More than 80% of the putrescine was converted to other polyamines and non-polyamine metabolites, mostly to amino acids. The enzyme responsible for controlling the bioavailability of putrescine was diamine oxidase (EC 1.4.3.6). For spermidine and spermine, however, about 70–80% of the intragastrically intubated dose remained in the original form. Considering the limitations on bioavailability (metabolism and conversion), the amounts of polyamines supplied by the average daily diet in Britain should satisfy metabolic requirements.
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Socioeconomic status is known to affect dietary profile, and differences in food habits and choice may affect polyamine intake due to significant variations in the concentrations of the poly-amines spermine, spermidine, and putrescine present in different foods. The relationship be-tween gross domestic product (GDP) and die-tary profile, with a focus on polyamine intake, was investigated for 49 different European and other Western countries. The data for food sup-ply and GDP were collected from the database of the United Nations and the International Mo-netary Fund, respectively, and the amount of polyamine intake from food was estimated us-ing polyamine concentrations listed in published sources. Countries were divided equally accor-ding to GDP values into two categories, higher and lower, and the amount and composition of food polyamines as well as dietary profile were compared. Higher GDP countries supply animal products and seafood in greater amounts than lower GDP countries; however, whole milk sup-ply per calorie was higher in lower GDP than higher GDP countries. While crops supply was relatively higher in lower GDP countries, fruit supply was greater in higher GDP countries. Higher GDP was associated with increased amount of spermine and putrescine per total calorie, although spermidine amount per calorie was similar between higher and lower GDP countries. GDP, as an indicator of countries' socioeconomic status, is associated with the amount and the composition of polyamines as well as dietary pattern.
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Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, spermidine administration potently inhibited oxidative stress in ageing mice. In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis. Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan. The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells. Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.
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Although the intracellular de novo synthesis of the polyamines decreases with age, there is no similar trend in blood polyamine levels, but rather there is wide individual variability. We hypothesized that dietary polyamines attenuate a decrease in blood polyamine levels with age and augment the previously observed individual variability. The effect of a polyamine rich diet, in both mice and humans, on blood polyamine concentrations was examined in this study. Jc1:ICR male mice were fed test diets containing 3 different polyamine concentrations. Healthy human male volunteers added 50 to 100 g of the polyamine-rich fermented soybean product, natto, to their daily intake. After 26 wk, the mean blood spermine concentration in mice receiving the test diet with high polyamine concentrations was 10.1+/-2.4 micromol/L, while the mean concentrations found in mice fed with a diet with normal or low polyamine concentrations were 5.2+/-0.9 and 4.7+/-0.5 micromol/L, respectively (p<0.05). A mean daily intake of 66.4+/-3.7 g (range=46.4-89.3 g) of natto for 2 mo by human volunteers increased the mean blood spermine concentration by a factor of 1.39 (n=10) (p<0.01), while in control volunteers (n=7), asked to exclude polyamine-rich foods from their diet, blood spermine concentration remained unchanged. The individual variability of blood polyamine levels was enhanced after polyamine intake in mice and, to a lesser extent, in humans. The long-term oral intake of enhanced polyamine diets increases blood polyamine levels in both mice and humans.
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The purpose of this study was to determine if chronic administration of L-arginine, the precursor of endothelium-derived relaxing factor (EDRF), normalizes endothelium-dependent relaxation and decreases atherosclerosis in hypercholesterolemic animals. Male rabbits were fed (a) normal rabbit chow; (b) 1% cholesterol diet; or (c) 1% cholesterol diet supplemented by 2.25% L-arginine HCl in drinking water. Arginine supplementation doubled plasma arginine levels without affecting serum cholesterol values. After 10 wk, the thoracic aorta was harvested for studies of vascular reactivity and histomorphometry. Endothelium-dependent relaxations (to acetylcholine and calcium ionophore A23187) were significantly impaired in thoracic aortae from animals fed a 1% cholesterol diet. By contrast, vessels from hypercholesterolemic animals receiving L-arginine supplementation exhibited significantly improved endothelium-dependent relaxations. Responses to norepinephrine or nitroglycerin were not affected by either dietary intervention. Histomorphometric analysis revealed a reduction in lesion surface area and intimal thickness in thoracic aortae from arginine-supplemented animals compared to those from untreated hypercholesterolemic rabbits. This is the first study to demonstrate that supplementation of dietary L-arginine, the EDRF precursor, improves endothelium-dependent vasorelaxation. More importantly, we have shown that this improvement in EDRF activity is associated with a reduction in atherogenesis.
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The amounts of polyamines (putrescine, spermidine and spermine) in foods available in Japan were analyzed by HPLC. Though the polyamine concentrations varied in individual foods and food groups, significant differences in polyamine concentrations and distribution patterns were observed between food groups. Beans showed high concentrations of spermidine and spermine, vegetables had higher levels of putrescine and spermidine, fruit and seasonings had high levels of putrescine, fish and shellfish, meat and nuts had high levels spermine. Using the average polyamine concentrations and the amount of each food group consumed, the polyamine intake from foods by the Japanese was estimated to be 200μmol/day/person, and about half of the polyamine intake was putrescine. This value is significantly lower than those reported for European countries.
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Different types of food (fruits, vegetables, meat, and milk products) were analyzed by high pressure liquid chromatography to determine their polyamine (putrescine, spermidine, and spermine) contents. All foods contained some polyamines, although the concentrations in different individual food components were variable, As was established earlier using C-14-labeled putrescine, spermidine, and spermine, polyamines are readily taken up by the gut and enter the systemic circulation. Food appears to constitute a major source of polyamines for humans and animals. The distribution of polyamines in the body, as determined by measuring the accumulation of C-14-spermidine in different tissues of the rat, was correlated with the metabolic activity and growth of particular organs. Thus, phytohemagglutinin induced both extensive hyperplastic growth and the preferential accumulation of labeled spermidine in the gut. Correspondingly, when skeletal muscle growth was promoted by the beta-antagonist, clenbuterol, C-14-spermidine was sequestered by the hind leg gastrocnemius muscle. It is concluded that food polyamines are not only necessary for normal body metabolism, but are also used and directed preferentially to tissues and organs that have been stimulated to grow by metabolic signals.
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In addition to general lifestyle, a number of foods and dietary patterns, such as the Mediterranean diet (MD), are associated with lower incidences of chronic, age-related diseases, and mortality. We have shown that increased polyamine intake decreases age-associated pathology and increases longevity in mice. Several foods in the MD, such as fruits and legumes, are foods containing high amount of polyamines. Among age-associated conditions, cardiovascular diseases (CVD) are the leading cause of mortality worldwide, and individuals who adhere to a MD have a lower incidence of CVD. The possible contribution of increased polyamine intake to CVD prevention is discussed in this manuscript. Polyamines from food are distributed to all organs and tissues, and long-term intake increases polyamine concentration in blood. Because most polyamines are associated with red and white blood cells, they act to suppress synthesis of pro-inflammatory cytokines and of leukocyte function-associated antigen-1. Foods with anti-inflammatory properties such as n-3 polyunsaturated fatty acids are known to help prevent CVD. Additionally, suppression of de novo polyamine synthesis results from increased polyamines intake, normally synthesized from arginine. This in turn increases availability of arginine for synthesis of nitric oxide, which plays an important role in preserving normal vascular physiology.
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The purpose of this study was to test whether oral intake of foods rich in polyamines (spermine and spermidine) suppresses age-associated pathology in aged mice. Synthetic polyamines were mixed into experimental chows, and 24-week-old Jc1:ICR male mice were fed one of three chows containing differing polyamine concentrations. The spermine and spermidine concentrations in the low, normal, and high polyamine chows were 143 and 224 nmol/g, 160 and 434 nmol/g, and 374 and 1540 nmol/g, respectively. An increase in concentration of polyamine in the blood was found only in mice fed the high polyamine chow at 50 weeks of age. While the body weights of mice in all three groups were similar, the survival rate of mice fed high polyamine chow was significantly higher than those in the other two groups (p=0.011). Mice fed the high polyamine chow analyzed at 88 weeks of age, corresponding to the end of the study, demonstrated lower incidence of glomerulosclerosis and increased expression of senescence marker protein-30 in both kidney and liver compared to those fed the low polyamine chow. As these pathological changes are associated with senescence, oral polyamine appears to inhibit the progression of age-associated pathologies.
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The ecological association of infant mortality rate (IM) with per capita income (PI) and prevalence of adult illiteracy (AI) has been studied using countries as the unit of analysis. A negative association between IM and PI in 1960 and 1982 has been observed (sample correlation coefficient [r] = -.625 and r = -.729, respectively; P less than .05). A correlation between IM and AI has been found for both men and women (r = .827 and r = .855, respectively; P less than .05). The ecological relative risks were 7.43 for men and 5.82 for women (95% confidence intervals: 5.16-10.71 and 4.36-7.75, respectively). The association of IM and PI shows a slight but not significant improvement between 1960 and 1982. AI can be considered a good predictor of IM in countries.