The situation of increasing serum uric acid, related factors and efficacy of dietary intake in over 30 year of age subjects in rural area of thai binh province

BACKGROUND
Increased serum uric acid (hyperuricemia) is a metabolic disorder that
is closely related to a series of chronic non-infectious diseases such as
myocardial infarction, stroke, diabetes, gout This topic has attracted
authors interested but new researches just focused on big cities and in
hospitals. Currently there are no adequate studies in epidemiology increased
serum uric acid and prevention in the community. Meanwhile, scientific
evidence has shown the effectiveness of intervention programs in the
community in reducing the risk of death from diseases related to metabolic
disorders.
Thai Binh is a province in the Northern Delta where there is also a
transition of disease patterns. Therefore, early detection and control the
increase in serum uric acid without clinical manifestations are essential to
help reduce the risk of some chronic non-infectious diseases. At the same
time, the identification of factors related to the scientific basis for the
selection of appropriate and specific community interventions.As the theory
of increased serum uric acid with metabolic disorders in rural areas is
becoming a significant issue of public health and the consultancy of suitable
diet will help control the serum uric acid level, the thesis has been carried out
with 3 objectivess as follows:
1. Describing the current status of serum uric acid levels in people at
the age of 30 and older in rural community in Thai Binh.
2. Identifying factors related to the condition in serum uric acid levels
in the study area.
3 Assessing the intervention effects of dietary for people increased
serum uric acid in the community.
New contributions of the Dissertation
- Giving an abundant database in serum uric acid levels which were
analyzed in collaboration with a number of indexes of anthropometry, blood
pressure and blood lipids in people over 30 years old in rural communities in
Thai Binh. It first came up with the rate of increased serum uric acid which

was not managed or cared in community, this helped warn a number of
groups who often have a high risk of increased serum uric acid including
obese and overweight group, big waist, high WHR index, a history of heart
disease.
- Through multivarible correlation analysis, logistic regression analysis
using Bayesian methods the study helped build models to predict serum uric
acid levels by age, sex, BMI, abdominal obesity; detect factors
independently associated with age, BMI, regular use of red meat, organ
meats, bone water, alcohol in males; the independent factors associated with
age, BMI, regular use of red meat, organ meats in females.
- Proved that "Nutrition communication, counseling for subjects to perform
reasonable diet as the sample menu based on the actual diet and locally
available food sources" has been remarkably effective in reducing serum uric
acid concentration and reducing serum uric acid levels.
Layout of the thesis
The dissertation consists of 130 pages, 30 tables, 12 charts and 153
references including 106 foreign ones. Background has 2 pages, 37 page
literature review, research methodology 23 pages, 34 page research results,
discussion 31 pages, 2 page conclusions and 1 page recommendations.
CHAPTER I
LITERATURE REVIEW
1. Studies on increased serum uric acid levels
Cohort study follow-up data of Medicine for 50 years showed that if the
1954 -1958 period, the average serum uric acid levels was 5 mg / dl in males
and 3,9mg / dl in females, in the 1972 -1976 period, the average level rose
5,7mg / dl in men and 4,7mg / dl in women. Australian researches showed
that the rate of increased serum uric acid and gout accounted for high
percentage compared to some countries in the region with similar economic
conditions. The rate of increased uric acid increased quickly in 1959
compared with 1980 (17% in men aged 30-40) in the original Australian

populations. Correspondingly, the incidence of gout increased from 0% in
1965 to 9.7% in men and 2% of women in 2002. Chuang's study evaluated
trends in serum uric acid levels in Taiwan adults in two phases from 1993 to
1996 and from 2005 to 2008 showed a different trend. Period 1993-1996,
average uric acid levels were 6,77mg / dl in males and 5,33mg / dl in
females, this value was reduced to 6,59mg / dl in men and 4,97mg / dl in
women after 12 years. The increased uric acid ratio decreased from 25.3% to
22% in men and from 16.7% to 9.7% in women, respectively. This was
explained by the change in diet which reduces consumption of organs, fresh
bamboo shoots and fresh water use
In Vietnam, the investigation on the subject who were military staff at
the middle-aged in 1999, the rate of increased serum uric acid was 17.96%.
Doan Thi Tuong Vi studied the group which had a periodic health
examination at the hospital 19/8, said men aged 30-60 with hyperuricemia
was 6.2%, women 2.5%; the overall incidence was 4.9%. Related factors
were frequency of consumption of foods rich in protein and much alcohol,
weight and high BMI. The people with increased serum uric acid were at risk
for hypertension, cholesterol, serum triglycerides higher than normal. Phan
Van Hop carried out research in the elderly in Nam Dinh in 2011 showed
that the rate of increased serum uric acid was 9.5%, of which 16.3% in male,
5.5% female, group aged 60-90 was10.1%, group aged 70-79 was 9.7% and
over 80 years was 8.1%. Le Van Doan's research on subjects of middle-aged
military officers in the military zone 9 showed the percentage of increased
serum uric acid was 26.2%, and the incidence tends to increase with age.
Factors related to increased serum uric acid levels were age, high protein
diet, hypertension, dyslipidemia, overweight and obesity.
2. Factors related to serum uric acid levels
The relevant factors have been reported from domestic and foreign studies
included age, male gender, racial factors, genetics and gene mutations, diet,
physical activity, nutritional status, puppets hyperlipidemia, hypertension,

renal disease, cardiovascular disease and other chronic non-infectious
diseases. Many studies have identified the clear relationship between the
state of increased serum uric acid with a number of non-infectious chronic
diseases especially cardiovascular diseases such as heart failure, myocardial
infarction, stroke. Increased serum uric acid was found in approximately
60% of patients hospitalized with decompensated chronic heart failure.
Increased serum uric acid linked to insulin resistance status, hypoxic tissue,
increases the production of cytokines and free radicals so they could affect
the cardiovascular system and prognosis in these patients deteriorate. The
risk of hypertension also significantly higher in patients with increased
serum uric acid of above 400μmol/l compared with those with serum uric
acid below 200μmol/l. Among patients with untreated hypertension,
deterioration phenomenon of coronary artery blood flow in people with
increased serum uric acid levels was higher than people with normal serum
uric acid. A number of studies have given evidence that theere was the
combination between increased cholesterol, increased triglycerides and
serum uric acid. Up to 80% of the triglycerides increased people may
increase serum uric acid and up to 50-70% of gout patients have triglycerides
increased
3. Intervention methods to decrease serum uric acid
- Use of drugs: In the case of asymptomatic hyperuricemia, drug should be
used only when the serum uric acid level is too high, above 12mg / dl (700
μmol / l) or when there is an increase in the level of acute uric acid
production. The regularly tested cases with hyperuricemia over 10 mg / dl
which resists to dietary adjustments, or have a family history of gout, kidney
stones with increase serum uric acid, signs of kidney damage are required to
take drugs to reduce uric acid.
- Control of nutritional status: Many studies have shown that increased
serum uric acid is related to obesity, overweight, diabetes, lipid disorders,
metabolic syndrome. This relationship is in general illness of Insulin

resistance syndrome which is essentially due to the excessive accumulation
of fat cells. Therefore, to reduce the risk of chronic non-infectious diseases in
general, it is necessary to maintain a weight level with ideal body mass index
of 21-23. This is one of 8 independent recommendations of the World
Cancer Research Fund and American Institute for Cancer Research
published in 2007. A number of studies have recommended, in obese people,
if weight is well controled, it will help reduce serum uric acid similar to
implementing a low-purine diet
- Control diet: The increased serum uric acid is closely linked to diet. Most
uric acid in the body is derived from the metabolism of endogenous purine
but diets with purine foods of animal origin may cause increased serum uric
acid, because over 50% purine of ARN and 20% of ADN derived from food.
Therefore, the cases of increased serum uric acid should reduce the
consumption of alcohol, soft drinks and fructose, reduce consumption of
products of animal origin rich in purines, increase the use of vegetables,
fruits, milk and supplement vitamin C.
CHAPTER 2. METHODOLOGY
2.1 Study participants
Stage 1: First investigation among people aged 30 and older.
Stage 2: Interventional study within 6 months among people with increase in
serum uric acid. The control group was at 2 communes as Minhkhai and
Songlang; the interventional group was at Tanphong and Viethung.
2.2. Methodology
2.2.1. Study design
a. Stage 1: Cross-sectional descriptive study in order to:
- Describe mean of serum uric acid concentration and increase serum uric
acid rate in relation to age group, gender, nutritional situation, level of
physical activities.
- Identify some factors related to serum uric acid concentration and rate of
increase serum uric acid as: gender, age, overweight, obesity, waist

circumference, waist-hip ratio, hypertension, high blood glucose, blood lipid
metabolic disorders, use of alcohol drink, food consumption.
b. Stage 2: Community interventional study with control:
People with increase in serum uric acid levels were divided into two groups
of interventional and control groups, we followed up along 6 month period to
evaluate the effectiveness of dietary intervention on serum uric acid levels.
Evaluation results were taken 2 times before and after intervention.
Interventions:
Method 1: Mass media on nutrition
Training people with increased serum uric acid content includes general
knowledge about the consequences of increased serum uric acid, advice on
diet to people with increase in serum uric acid focusing on the selection and
use properly of common food sources available locally. Organize training in
CHCs one time each three months. The first time is at the start of the
intervention (M0), the second time was at 3 months after conducting
research.
Compiled communication materials "Community Guidelines for Prevention
of Gout," and each object was distributed this document after the first
training.
Method 2: Nutrition counseling
We based on dietary habits, dietary practice, based on the source of food and
nutrition habits of the local people to build and provide menus for a week, a
month participants. We developed menus for people with increase in serum
uric acid based on nutritional needs for Vietnamese recommended by gender,
age, level of physical activity, nutritional status, medical history and based
on actual portions of objects. Energy build must ensure a stable weight for
people with normal weight, creating cumulative positive energy with the thin
and energy reduction with overweight people. The menu was based on the
principle of reducing the use of protein, especially animal protein, animal
protein accounted for approximately 30%. The recommended dietary protein

level 1g / kg / day and 12-14% to meet energy needs. Demand for lipid
occupies 20-25% of total energy. We performed nutritional counseling 1
time / month for 6 months.
Control group: Applying nutritional communication approaches
Intervention group: Apply both nutrition communication approaches and
monthly nutritional counseling, as well as dietary building for participants.
2.2.2. Sampling procedure and sample size
+ Identify the percentage of increase in serum uric acid and related factors:
combining some sampling method, randomly selected 4 communes of Vuthu
District and make a list to randomly selected subjects with proper age by R
software, sample sizes was as follows:

2
2
)2/1(
)(
)1(
p
pp
Zn





(Formula 1)
The sample size for the cross-sectional survey as calculated was 1727
participants, in reality we has studied among 1910 people.
+ Intervention study: we used intentionally sampling to select all the object
with increase in serum uric acid levels. Sample size applied for an

interventional group as follows:

2
21
2
2
),(
)(
2




s
Zn

(Formula 2)
We calculated the minimum sample size of 68 subjects / 1 group. In reality
we has taken all eligible subjects included 77 subjects in intervention group
and 72 subjects in control group to participate in the study.
2.2.3. Techniques applied to the study
Assessment of nutritional status through BMI, waist circumference, waist/hip
circumference. Investigation dietary of the last 24 hours, interview to
determine the frequency of food consumption, eating habits, medical history,
physical examination, blood pressure, blood biochemistry tests.
2.2.4. Data processing
Data were analyzed using R software. We calculated average value, the ratio,
percentage, the statistical test applied in biomedical research to analyze the
results. Odds ratio OR was calculated to evaluate the factors related to the
increase in serum uric acid levels. We used multivariate linear regression and

logistic regression to identify associated factors, to exclude of confounding
factors and to identify interaction effects. The study used a Bayesian method
to select the optimal model for multivariate analysis.
2.2.5. Ethical consideration
The study complied with the Declaration of Helsinki of the World Medical
Association on ethical issues in Biomedical Research. The research proposal
was adopted Council Ethics in Biomedical Research at the National Institute
of Hygiene and Epidemiology before conducting research. Research ensured
the voluntary participation of subjects. Safety issues and benefits of the study
subjects had been assured during the research process.

Chapter III. RESULTS
3.1. Situation of increasing in serum uric acid among people aged 30 and
older at rural ThaiBinh
Table 3.1. Socio-demographic characteristics of participants
Age group

male
(n=935)
female
(n=975)
total
(n=1.910)
n
%
n
%
n
%
30-39

40-49
50-59
60-69
70-79
80 +
total
118
165
246
245
124
37
935
12.6
17.6
26.3
26.2
13.3
4.0
49.0
121
178
254
254
127
41
975
12.4
18.2
26.1

26.1
13.0
4.2
51.0
239
343
500
499
251
78
1910
12.5
18.0
26.2
26.1
13.1
4.1
100.0
Occupation
Farmer
Worker
businessman
Civil servant
Other

696
148
43
32
16

74.4
15.8
4.6
3.4
1.7

851
52
24
36
12

87.3
5.3
2.5
3.7
1.2

1547
200
67
68
28

81.0
10.5
3.5
3.6
1.4

Table 3.1 showed that in total of 1.910 participants, male was
accounted for 49.0%. Participants were distributed based on age groups were
gender equally.

30-39 40-49 50-59 60-69 70-79 80+
Age group
Uric acid (micromol/l)
0 50 150 250 350
male
female


Figure 3.2. Average serum uric acid concentration based on age group and
gender
Figure 2 showed that average serum uric acid concentrations were not
different between 2 genders between age group of 30-39 and 40-49.
However, after 50 years old, the concentration increased with age and
reached the highest at age group of 80 and more. The difference was
significant at p <0,001. Average serum uric acid concentration in male was
higher than in female at all age group with p<0,001.
Table 3.5. Average values and rate of increasing in serum uric acid based
on age group and gender
Gender
n
Average
concentration
Increasing in serum uric acid
(µmol/l)
n
% (95%CI)

Male
935
316.1±79.7
112
12.0 (10.0-14.2)
Female
975
247.1±64.1
63
6.5 (5.0-8.2)
Total
1910
280.9±79.9
175
9.2 (7.9-10.5)

p<0.001
p<0.001
Table 3.5 showed that average serum uric acid concentrations was
280,9 µmol/l, in which male was 316.1 µmol/l, female was 247.1 µmol/l.
Rate of increasing in serum uric acid was 9.2% (95%CI:7.9-10.5%), in
which male was 12% and female was 6.5%. Average serum uric acid
concentration in male was significant higher than female with p<0,001.



Figure 3.3. Increasing in serum uric acid following age group
Result from figure 3.3 showed that serum uric acid increased with age.
Female had lower rate of increasing uric acid as compared to male. However
after age of 60, there was an increasing in serum uric acid and they were

similar to those among male aged 80 and more.
3.2. Factors associated with situation of increase in serum uric acid
Table 3.12. The correlation coefficient between serum uric acid
concentration and anthropometry, blood pressure and blood biochemistry
Variables
correlation coefficient
p
Age
0.21
<0.001
BMI
0.28
<0.001
hip
0.33
<0.001
WHR
0.34
<0.001
Diastolic blood pressure
0.18
<0.001
Systolic blood pressure
0.16
<0.001
Blood glucose
0.02
>0.05
Cholesterol
0.2

<0.001
Triglycerid
0.26
<0.001
Table 3.12 showed that Waist/hips (WHR) index had a high positive
correlation coefficient with serum uric acid levels (r = 0.34), followed by
waist circumference (r = 0.33), then to BMI, triglycerides, age, blood
cholesterol, and blood pressure. The variables of age, anthropometric and
blood pressure were positively correlated with serum uric acid levels with p
<0.001. We used Bayesian method to select the optimal model to prognostic
uric acid levels according to the associated factors. Results were 2 models as
follows:
1. Uric acid (μmol / l) = 48.7 to 62.2 * gender (1: male, 2 female) + 1.17 *
age (years) + 5.9 * BMI (kg / m 2) + 161 , 8 * WHR
2. Uric acid (μmol / l) = 102.7 to 63.2 * gender (1: male, 2 female) + 1.22 *
age (years) + 4.92 * BMI (kg / m 2) + 1 , 37 * waist (cm).
Table 3.14. Association between increase in uric acid with age and gender
group
Variable
n
UA
increase
Univariate analysis
OR (95%CI)
p
Gender
Female
975
6.5
1

Male
935
12.0
1.9 (1.4-2.7)
< 0.001
Age
group
30-39
239
4.6
1

40-49
343
5.8
1,2 (0.6-2.7)
>0.05
50-59
500
9.8
2,2 (1.1-4.4)
<0.05
60-69
499
10.0
2,3 (1.2-4.5)
<0.05
70-79
251

12.4
2,9 (1.4-5.9)
<0.01
80+
78
17.9
4,5 (1.9-10.5)
< 0.001
Male was at risk of increase in uric acid 1.9 times as higher compared to
female (95% CI: 1.1 -2.7). The risk of high uric acid levels increased
gradually with age. Age group of 40-49 was at risk of increase in uric acid
1.2 times as higher than 30-39 age group, but the difference was not
statistically significant with p> 0.05. Age groups of 50-59 and 60-69 year
were at increased risk of uric acid at 2.2 and 2.3 times as higher compared to
the age group of 30-39. The difference was statistically significant with p
<0.05. This risk increased to 2.9 times and 4.5 times in the age group of 70-
79 and 80 and older.
Table 3. 15. Relation between uric acid levels with anthropometric
indicators
Variable
n
UA
increase
Univariate analysis
OR (95%CI)
p
BMI
Normal
1378
9.2

1

Overweight/obesity
183
23.0
2.9 (2.0-4.3)
< 0.001
hip
Normal
1758
7.7
1

High
152
24.1
3.8 (2.5-5.6)
< 0.001
WHR
Normal
1751
9.0
1

High
159
11.3
2.8 (2.1-3.9)
< 0.001
Results from table 3.15 showed that overweight subjects had risk of

hyperuricemia at 2.9 times higher than the normal group, the difference was
statistically significant with p <0.05. The high waist and the high waist / hips
participants were at higher risk of increasing serum uric acid levels of 3.8
and 2.8 times higher than the normal group respectively. The difference was
statistically significant with p <0.001.
Table 3.16. Relationship between hyperuricemia with hypertension
Variable
n
UA
increase
Univariate analysis
OR (95%CI)
p
Hypertension
No
1320
6.7
1

Yes
590
14.6
2.4 (1.7-3.2)
< 0.001
Hypertension
level
Normal
1503
7.9
1

Level 1
255
12.5
1.7 (1.1-2.6)
<0.05
Level 2
152
16.4
2.3 (1,5-3.7)
< 0.001
Table 16 indicated that hypertensive group showed an increased risk of
elevated serum uric acid at 2.4 times higher than the normal group. The
difference was statistically significant with p <0.001. The risk of
hyperuricemia increases with hypertension level. The risks of hypertension
in the group level 1 were 1.7 times and 2.3 times increase in group level II
respectively. The differences are statistically significant at p <0.05 and p
<0.001.
Table 3.17. Association between hyperuricemia and some biochemical
blood indices
Variable
n
UA
increase
Univariate analysis
OR (95%CI)
p
Cholesterol
increase
No

1296
5.2
1

Yes
614
17.6
3.9 (2.8-5.4)
<0.001
Triglyceride
increase
No
1362
7.3
1

Yes
548
13.9
2,1 (1.5-2.8)
<0.001
HDL-C decrease
No
1643
9.3
1

Yes
267
8.6

0.9 (0.6-1.5)
>0.05
LDL-C increase
No
1438
6.5
1

Yes
472
17.2
2.9 (2.1-4.1)
< 0.001
Dyslipidemia
No
839
4.2
1

Yes
1071
13.1
3.5 (2.4-5.1)
< 0.001
Metabolic
syndrome
No
1536
8.2
1

Yes
374
13.1
1.7 (1.2-2.4)
<0.01
Table 3.17 showed that increased cholesterol, triglycerides and LDL-C
would increased the risk of hyperuricemia at 3.9, 2.1 and 2.9 times higher
than the normal group respectively. The difference was statistically
significant with p <0.001. The level of HDL-C did not show relation to
serum uric acid levels with p> 0.05.
Participants with at least one blood lipid disorders had an increased risk of
serum uric acid at 3.5 times (95% CI: 2.4 to 5.1) as compared with a group
without any lipid disorders.
Subjects with metabolic syndrome had an increased risk of serum uric acid at
1.7 times (95% CI: 1.2 to 2.4) as compared with those not suffering from
metabolic syndrome. The difference was statistically significant with p
<0.01.
Table 3.18. Association between increased uric acid and smoking and
alcohol use
Variable
n
UA
increase
Univariate analysis
OR (95%CI)
p
Smoking
No
1449

8.2
1

Yes
461
12.1
1.5 (1.1-2.2)
<0.05
Use of
wine
Rarely
1444
7.2
1

Monthly
22
9.1
1.3 (0.3-5.6)
>0.05
Weekly
240
15.0
2.3 (1.5-3.4)
<0.001
Daily
204
16.2
2.5 (1.6-3.8)
<0.001

Use of beer
Rarely
1542
7.8
1

Monthly
71
12.7
0.7 (0.3-3.5)
>0.05
Weekly
253
13.0
1.8 (1.2-2.7)
<0.01
Daily
44
29.5
4.9 (2.5-9.7)
<0.001
Table 3.18 showed that smoking group was at risk of high uric acid levels
than the non-smokers at 1.5 times. The difference was statistically significant
with p <0.05. The risk of increasing uric acid increased with the level of
using alcohol. Group which used alcohol weekly was at increased risk of 2.3
and 1.8 times as compared with groups that did not drink or rarely drink
alcohol. This risk increased to 2.5 and 4.9 times in participants who used
alcohol at daily level respectively.

Table 3.19. Association between increase in uric acid and the frequency of

using some food groups
Usual consumption
n
UA
increase
Univariate analysis
OR (95%CI)
p
Red meat
No
1773
6.9
1

Yes
137
38.7
8.5 (5.7-12.6)
<0.001
Viscera of
animals
No
1748
6.4
1

Yes
162
39.5
9.6 (6.7-13.9)

<0.001
Fisheries
No
1371
8.5
1

Yes
539
10.9
1.3 (0.95-1.9)
>0.05
Tofu
No
1443
9.0
1

Yes
467
9.6
1.1 (0.8-1.5)
>0.05
Beans
No
1466
9.0
1

Yes

444
9.7
1.1 (0.7-1.6)
>0.05
Bone soup
No
1807
7.4
1

Yes
103
40.8
8.7 (5.6-13.3)
<0.001
Milk
No
1864
9.2
1

Yes
46
8.7
0.94 (0.3-2.7)
>0.05
Soft drink
No
1828
9.1

1

Yes
82
11.0
1.2 (0.6-2.5)
>0.05
Green tea
No
1222
10.3
1

Yes
688
7.1
0.7 (0.5-0.9)
< 0.05
Table 3.19 showed that regularly use (daily, weekly) of red meat and animal
viscera and bone soup increased the risk of hyperuricemia at roughly 9 times.
The difference was statistically significant with p <0.001.
Regularly use of seafood, tofu, beans and soft drink increased uric acid levels
compared with not regular use, but the difference was not statistically
significant with p> 0.05.
Table 3.21. Analysis of multivariate logistic regression between serum uric
acid levels and gender
Factors
Unit
Female
Male

OR (95%CI)
p
OR (95%CI)
p
Age (year)
10
2.5 (1.6-3.7)
<0.001
1.6(1.2-2.1)
<0.01
BMI (kg/m
2
)
1
2.2 (1.5-3.1)
<0.001
3.8(2.6-5.4)
<0.001

Frequently
use
Red
meat
Yes=1
2.9 (1.8-3.9)
<0.001
2.2(1.2-4.0)
<0.01
Visceral
Yes=1

13.9(4.8-40.7)
<0.001
4.2 (2.4-7.8)
<0.001
Bone
soup
Yes=1
-

3.9 (2.2-7.1)
<0.001
Alcohol
Yes=1
-

1.8(1.1-2.8)
<0.05
Table 3.21 showed that independent factors related to serum uric acid levels
in men were age, BMI, use of red meat, organ meats, bone soup and use of
soft drink regularly. In female, we eliminated 2 factors of using alcohol and
using bone soup in the analysis as less frequent use of these. For each unit of
10 years old would increase the risk of hyperuricemia at 2.5 times in female
and 1.6 times in male. Increasing one unit of BMI would increase the risk of
hyperuricemia to 2.2 times in female and 3.8 times in male.
3.3. Effectiveness of dietary to reduce serum uric acid levels
Table 3.23. Effective of dietary to reduce serum uric acid after 6 month
intervention
Indicator
Intervention
group (n=72)

Control group (n=77)
p
Average serum uric acid concentration: (µmol/l)
M
0

448.8 ± 61.7
446.7 ± 54.3
>0.05
M
6

425.9 ± 55.7
365.8 ± 63.5
<0.001
M
0
- M
6

22.9
80.9

p before-after
<0.001
<0.001

Uric acid increase : n (%)
M
0

72 (100.0)
77 (100.0)
-
M
6

63 (87.5)
34 (44.2)
<0.001
Effective
index
12.5%
55.8%

Intervention
effectiveness
43.3%

Table 3.23 showed that before the intervention, 2 groups of control and
intervention had average serum uric acid concentrations was similar. After 6
month intervention, in the intervention group, the uric acid level reduced at
80.9 μmol/l while the control group decreased less as compared with the
counterpart. The difference was statistically significant with p <0.001. More
than 50% participants in the intervention group and 12.5% in control group
showed serum uric acid returned to normal after 6 months. The difference
was statistically significant with p <0.001. Effective intervention after 6
months was 43.3%.
Table 3.24. Effectiveness of reducing serum uric acid by age group
Indicators

≤ 60 age (a)
> 60 age (b)
p
Control
group
(n=39)
Intervention
group
(n=34)
Control
group
(n=33)
Intervention
group
(n=43)
Average serum uric acid concentration: (µmol/l)
M
0

461.7
±59.8
446.2±52.1
433.5±61.4
447.1±56.7
p(a)>0.05
p(b)>0.05
M
6

436.2±54.3

369.3±70.7
413.9±55.8
363.0±57.9
p(a)<0.001
p(b)<0.001
p before-
after
< 0.001
< 0.001
< 0.001
< 0.001

Increase in serum uric acid : n (%)
M
0

39 (100.0)
34 (100.0)
33 (100.0)
43 (100.0)

M
6

35 (89.7)
17 (50.0)
28 (84.8)
17 (39.5)
p(a)<0.001
p(b)<0.001

Effective
index
10.3%
50.0%
15.2%
60.5%

Intervention
effectivenes
s
39.7%
45.3%

Evaluation of the effect of serum uric acid decreased with age, the results
showed in table 3.24 that in intervention group, two age groups of under and
over 60 reduced serum uric acid levels as compared to control group. These
difference were statistical significance with p <0.001 compared with the
control group. Group of more than 60year old had the rate of returning uric
acid to normal higher as compared to the age group of less than 60 in both
control group and the intervention group. Effective intervention after 6
months in the group of over 60 years was 45.3%, in group of 60 years and
younger had lower efficiency (39.7%).

Figure 3.10. Frequency of consumption of foods according to uric acid
group after intervention
Figure 3.10 showed that participant who did not use of alcohol, beer, red
meat, organ meats and bones soup regularly had higher rate of serum uric
acid levels returning to normal after 6 month intervention as compared to the
counterpart. The difference was statistical significance with p <0.05.
Table 3:26. Effective intervention to regular frequency of consumption
of some food groups
Food
Before intervention

After intervention
control
(n=72)
intervention
(n=77)

control
(n=72)
intervention
(n=77)
Wine
37.5
42.9
(a)


36.1
31.2
(a)

Beer
20.8
32.5
(a)

18.1
16.9
(a)
Soft drink
5.6
6.5

5.6
3.9
Red meat
31.9
28.6
(a)


34.7**
11.7**
.(a)

Visceral
43.1
33.8
(a)

37.5**
16.9**
.(a)

Seafood
34.7
35.1

38.9
32.5
Bone soup
25.0
24.7
(a)


26.4*
11.7*
.(a)

Beans
25.0
27.3

25.0
26.0
Tofu
27.8
27.3

27.8
27.3
Milk
1.4
3.9

1.4
3.9
Green tea
30.6
27.3
(a)


30.6
37.7
(a)

Coffee
1.4
3.9

1.4
3.9
Table 3.26 showed that, before the intervention, the frequency of regular
consumption of food group between control and intervention group were
similar. The difference was not statistically significant with p> 0.05. After
the intervention, the frequency of consumption of food groups in control
group was significant difference as compared to pre-intervention. In the

intervention group, the frequency of regular consumption of wine, beer, red
meat, organ meats, bone soup significantly reduced as compared to pre-
intervention (p <0.05). After intervention, the frequency of consumption of
red meat, organ meats, bone soup in intervention group was statistically
lower as compared with the control group and compared with pre-
intervention with p <0.01 and <0, 05 respectively.
Table 3.29. Compare the nutritional value of diets between the 2 groups of
before and after intervention at age group of 30-60 years old
Indicators
Before intervention
After intervention
Control
(n=39)
Intervention
(n=34)
Control
(n=39)
Intervention
(n=34)
Energy
(Kcal)
2116.6±345.0
2206.9±325.5
(a)

2085.3±228.6*
1906.0±220.5*
.(a)

Protein(g)

Total
Animal
Protein
animal/Total
(%)

91.6±29.4
47.9±27.6
49.7±13.2

91.2±19.7
(a)
44.4±19.7
(a)

47.3±14.2
(a)


96.9±19.1*
53.3±16.2*
54.6±10.4*

72.6±9.7*
.(a)

28.6±1.9*
.(a)

39.9±5.1*

.(a)

Lipid (g)
Total
Animal
Animal
Lipid /
Total(%)

50.0±24.8
32.0±18.4
65.6±18.8

55.4±18.1
(a)

36.6±17.3
(a)

65.3±20.4
(a)


56.6±19.6*
36.0±18.0*
62.2±17.3

45.4±11.5*
.(a)

26.1±10.1*
.(a)

57.9±18.6
(a)

Vitamin
A (µg)
Caroteno
C(mg)

570.0±358.5
6265±4800
140.8±100.5

742.7±591.6
(a)

6881±3837.6
(a)

133.0±72.1
(a)


666.8±370.9
6720±3335.6
130.6±79.6

577.7±310.7

(a)

7727±3374.1
(a)

120.0±71.6
(a)

Mineral (mg)



Calcium
phosphorus
Fe
514.2±260.1
1121.5±372.1
16.9±8.8
613.8±455.7
(a)

1075.8±236.4
(a)

16.0±4.4
(a)

595.6±418.2
1129.1±220.5
16.7±7.8*

467.3±184.7
(a)

893.6±136.9
(a)

14.1±4.4*
.(a)

Dietary
Fiber
6.5±2.1
7.1±2.9
6.1±1.7
5.6±1.3
Table 3.29 showed that, at the beginning of investigation there was no
significant difference in dietary energy, protein, lipids, vitamins, minerals
and fiber between the 2 groups control and intervention. After 6 month
intervention, total protein, especially animal protein, protein levels in
intervention group were significantly reduced as compared with the control
group and compared to itself before intervention.

Table 3.30. Comparing the nutritional value of diets between the 2 groups
of before and after intervention at the age of over 60 years
Indicators
Before interention
After intervention
Control
(n=33)
Intervention

(n=43)
Control
(n=33)
Intervention
(n=43)
Energy
(Kcal)
1878.3±215.9
1879.4±227.9
(a)

1888.9±99.0
1841.8±216.6
(a)

Protein(g)
Total
Animal
Protein
animal/Total
(%)

78.1±19.6
35.6±16.5
44.0±14.3

77.8 ± 19.2
(a)

36.9±17.0

(a)

46.4±13.5
(a)


77.8±9.0*
39.7±8.2*
50.9±6.6*

66.1±9.9*
.(a)

20.6±7.2*
.(a)

31.3±9.7*
.(a)

Lipid (g)
Total
Animal
Animal
Lipid/ total
(%)

46.1±15.2
28.5±12.9
62.0±21.1

43.8±13.9
(a)

28.5±13.8
(a)

64.1±20.5
(a)


46.4±9.2*
29.6±11.4*
62.5±15.9

39.4±13.6*
.(a)

21.3±9.5*
.(a)

54.8±19.9
(a)

Vitamine
A (mcg)
Caroteno
C (mg)

475.6±308.1
5535±3742.9

97.5±62.1

532.1±406.7
(a)

5935±3934.8
(a)

111.3±93.7
(a)


559.6±323.9
6813.0±4152.2*
108.6±60.7*

493.6±248.8
(a)

9593.0±4974.3*
.(a)

156.2±93.9*
.(a)

Mineral (mg)



Canxi

Phospho
Fe
403.1±142.6
911.4±197.0
13.3±3.2
471.8±223.6
934.1±228.6
(a)

13.5±4.0
597.8±459.9
936.1±131.6*
13.3±2.9
487.7±142.5
828.4±103.9*
.(a)

13.4±2.6
Fiber (g)
5.4±1.8
5.9±2.0
(a)

5.6±1.7*
6.5±1.5*
,(a)


Similar to the age group of under 60, table 3.30 showed that, at the beginning
of the investigation there was no significant difference in dietary energy,

protein, lipids, vitamins, minerals and fiber between two groups of control
and intervention among age group above 60. After 6 month intervention,
total protein, especially animal protein, lipid content were significantly
reduced in intervention group as compared with the control group and with
itself before intervention. Levels of vitamin C and fiber in intervention group
were also higher than the control group and higher than before the
intervention (p <0.05).


CHAPTER IV. DISCUSSION
4.1. The increase in serum uric acid among people 30 years and older in
rural communities in Thaibinh
This study was conducted in a rural area of northern delta region in the
context as the World Health Organization indicated that non-infectious
diseases are of serious impact on household incomes and national economies
especially in middle and low income countries. Average serum uric acid
levels of the adult in this study was 280,9μmol / l, in which male was
316,1μmol/l, higher than female (247,1μmol / l). The difference was
statistical significance at p <0.01 (table 3.5). These average values at all ages
were higher in male than in female and increased with age in both male and
female but average serum uric acid concentrations were no significant
differences between age groups of 30 and 40 (Chart 3.2). The rate of increase
in serum uric acid level in this study was 9.2% (95% CI: 7.9 to 10.5%). This
proportion among male was 12% (95% CI: 10 to 14.2%) higher than females
6.5% (95% CI: 5.0 to 8.2%). The difference was statistically significant with
p <0.001. Study about the biological values of Vietnamese adult at years of
90s of the 20th century showed that the average concentration of serum uric
acid was 293,05mol / l in male and 197.0 mol / l in female, which were
lower than the results of our research. Thus, the concentration of uric acid in
the community also has a similar increasing trend as indicated in a number of

overseas studies.
However, when compared to the results of research on the subject with the
task of health management at the Huunghi Hospital in 2006, the average
concentration of uric acid in our study was lower by 50mol / l. This also
makes sense because these objects were in the big city, where common
metabolic disorders were observed more. Author Phan Van Hop on elderly
subjects aged 60 years and over in Nam Dinh - a province in the Red River
Delta which was similar to our study area also showed the rate of increase in
serum uric acid was 9.5% which accounted for 16.3% in males and 5.5% in
female. A study in Taiwan on elderly subjects aged 65 years and older
indicated that average serum uric acid concentration in male was 437.6
μmol/ l and in female was 376 μmol / l. Increase in serum uric acid were
common among these objects. The prevalence among male was 57.3% and
among female was 40.9%; and tends to be stable with age groups. The
incidence among the elderly was much higher than among adult people in the
community which was about 20% in male and 10% in female. Many studies
in China showed that the rate of increase in serum uric acid vary according to
geographic conditions, climate and economic conditions. Yu conducted a
study among 7,403 subjects aged 20 or older at Foshan of Guangdong
Province in 2010, the rate of increasing uric acid was 15.09%, which
accounted for 19.9% in male and 10.54% in female. Nan’s research
investigated among 2438 subjects age 20-70 in Qingdao, the rate of
increasing uric acid was 25.3%, which accounted for 32.1% n male, 21.8%
in female. Author Miao performed study on 5,003 adult subjects in 5 coastal
areas of Shandong Province in China, the rate of increasing uric acid was
13.19%, in which the incidence in males was 18.3% which was 8.56% higher
than females. Increased uric acid was more common in male over 30 of age
and in female over 50 of age, the incidence was higher in urban areas than in
rural areas (14.9 and 10.1%). Liu conducted a systematic analysis of
epidemiological studies on serum uric acid levels in China, results showed

that the rate of increase in serum uric acid was 21.6% in male and in female
was 8.6%. The risk of increased serum uric acid begins at age of 30 for male
and of 50 for female.
4.2. Identify factors related to the condition of increasing serum uric
acid level
Serum uric acid levels had positively correlation with a number of variables
such as age, anthropometry, blood pressure and blood biochemistry. The
correlation coefficient was highest in the group of anthropometric (0.28 to
0.34), then the triglyceride (0.26), age (0.21), cholesterol (0.2), the
maximum blood pressure (0.18) and the minimum blood pressure (0.16)
(table 3.12). From these correlations, our research has developed two models
to predict uric acid with 3 similar factors as age, sex, and BMI, the different
factor was factor to assess abdominal obesity (one model using index waist
circumference, another model using waist / hips index). With these 4 factors,
both 2 models could explained about 30% of the differences in uric acid
levels between participants. Research conducted by Pham Ngoc Kieu in
Angiang has also identified a closely positive correlation between the
anthropometric indices, blood pressure and serum uric acid concentration.
Male had risk of increasing serum uric acid at 1.9 times higher than female
(95% CI: 1,1-2,7). The risk of high uric acid levels increased gradually with
age. Age group of 40-49 had risk of increasing serum uric acid higher than
age group of 30-39 by 1,2 times, but the difference was not statistically
significant with p> 0.05. Age group of 50-59 and 60-69 were at increased
risk of uric acid of 2.2 and 2.3 times higher than the age group of 30-39. The
difference was statistically significant with p <0.05. The risk of increasing
serum uric acid was 2.9 times in the age group of 70-79 and 4.5 times in the
age group of 80 and older as compared to the age group of 30. Our results
were consistent with epidemiological studies in Vietnam and oversea.
Assessment of the relationship between the anthropometric characteristics
showing nutritional status with rate of increasing in serum uric acid, the

results of our study showed that overweight, obesity, waist circumference
and waist /hip was risk factors of increasing serum uric acid. Obesity
subjects had risk of increasing serum uric acid at 2.9 times higher than
normal group (95% CI: 2.0-4.3), the difference was statistically significant
with p <0, 05. The larger waist people were at risk of serum uric acid levels
of 3.8 times higher than the normal group, and subject with high waist / hips
index also had risk of increasing serum uric acid of 2.8 times higher than the
normal group. The difference was statistically significant with p <0.001.
Hypertension was closely associated with increased serum uric acid. Group
with hypertension had increased serum uric acid was 2.4 times higher than
the normal group. The difference was statistically significant with p <0.001.
The risk of increasing serum uric acid was increased according to level of
hypertension. This risk in group of hypertension level I increased 1.7 times
and in group of hypertension level II increased 2.3 times as compared to the
normal group. The differences are statistically significant, p <0.05 and p
<0.001 respectively (Table 3:16). Research of Doan Thi Tuong Vi indicated
that hypertension may double uric acid level as compared to the normal
group. This result was similar to studies of Le Van Doan, Bui Duc Thang
and a number of oversea studies.
Study the relationship between dyslipidemia with increased serum uric acid,
our study showed that subjects with high cholesterol increased the risk of
increasing uric acid, LDL-C and triglycerides (3.9; 2,9 and 2.1 times
respectively higher than the normal group). The difference was statistically
significant with p <0.001. Groups with metabolic syndrome have an
increased risk of uric acid of 1.7 times higher than the normal group (no
metabolic syndrome). The difference was statistically significant with p
<0.01. These results were similar to study by Doan Thi Tuong Vi which
indicated that increased serum uric acid had closely relationship with
dyslipidemia. Subjects with increased serum uric acid had the risk of high
cholesterol at 4.5 times and increased risk of high triglyceride levels at 3.7

times as compared to those who did not increase serum uric acid. The
difference was statistically significant with p <0.001. Comparing serum uric
acid levels in relation to dyslipidemia in male age over and under 45 years, a
study in India found that male under 45 with higher uric acid levels were at
risk of increased uric acid, increased cholesterol, increased triglycerides,
decreased HDL-C, increased LDL and increased VLDL as compared with
male with normal uric acid levels. These differences were statistical
significance. However in those aged 45 years or older, only triglycerides and
VLDL were different between 2 groups of increased and not increased uric
acid levels.
To evaluate the relationship between the frequency of using some food
groups and increased uric acid, results showed that the risk of increasing uric
acid would increase following the increased level of using alcohol. The
group of using alcohol weekly had the risk of increasing uric acid of 2.3 and
1.8 times higher as compared to group without using alcohol. This risk
increased to 2.5 and 4.9 times among participants with daily use of alcohol.
The frequent use of red meat, animal viscera and bone soup would increase
the risk of increasing uric acid level at 9 times. The difference was
statistically significant with p <0.001. Group with consumption of seafood,
tofu, bean, had higher rate of increased uric acid than those who did not often
use, however the difference was not statistically significant with p> 0.05.
Regular use of green tea reduced the risk of uric acid increased at 30% as
compared to the counterparts. The difference was statistically significant
with p <0.05. Using milk has been known as a protective factor reducing
serum uric acid, but in our study, the proportion of subjects with milk use
was a very low as 82/1910 subjects (4.3%), therefore the differences found
were not statistically significant with p> 0.05. Similarly, numerous studies
have shown that consumption of soft drinks which contain fructose would
increase the level of serum uric acid, but in our study we did not find the
impact of soft drink use to condition of serum uric acid levels.

Reducing consumption of animal products which were rich in purine help
reduce the serum uric acid levels dramatically. Williams indicated that the
increased use of a serving of meat per day increased the risk to 1.45 times,
but the use of more fruits reduced the risk of increasing uric acid. The
research showed that the use of more than 2 servings of fruit per day reduced
the risk by 50% compared with using less than 0.5 serving per day.
4.3. Assessing the effectiveness of dietary interventions for people with
increase in serum uric acid
Community interventional study with control during 6 months showed that
the concentration of uric acid reduction in intervention group reduced by
80.9 μmol/l while in the control group only 22.9 μmo/l were reduced. There
were 55.8% people in the intervention group and 12.5% in the control group
with uric acid level returned to normal after 6 months. The difference was
statistically significant with p <0.001. Effective intervention was 43.3%. Age
group of over 60 years decreased the uric acid level higher than the age
group of 60 and less. Effective intervention after 6 months in the group of
over 60 year was 45.3% which was higher than the group 60 years and
younger (39.7%).
After 6 month intervention, total protein, animal protein, lipid content of the
intervention group had a statistically significant reduction as compared with
the control group and compared with pre-intervention in both groups of
below and above 60 years of age. Particularly in intervention group at aged
60 and over, levels of vitamin C and fiber were higher than the control
group and higher than that of before the intervention. The difference was
statistically significant with p <0.05. Phan Van Hop studied on the elderly
indicated that dietary energy of the group with increasing serum uric acid
was 2073.7 ± 178.1 kcal which was higher than the normal group (1997.9 ±
186, 6 kcal) (p <0.05). Provided energy from protein, animal protein, and
animal protein per total protein of group with increased serum uric acid
levels were higher than normal group (p <0.05). Ryu studied in Korea

showed that the use of meat among people with increased serum uric acid
was 93,4g /day, statistically significant higher than the control group (77,2
g). The results from many studies showed that group with increased serum
uric acid had provided dietary structure from protein higher than the normal
group. Our study also showed similar results in rural areas.
Our community intervention to reduce uric acid levels was similar to the
dietary intervention to reduce serum uric acid for Gout patients at hospital
based of author Nguyen Thi Lam. Participants in her study were people with
diagnose of Gout disease and aged from 40 to 70. The author conducted
nutritional counseling including building daily menu and food choices based
on the eating habits of each participant. After 6 month intervention, the
results showed that the frequency of alcohol consumption reduced in
intervention group. Nutritional value of diets of intervention group was
lower than those in control group in terms of energy, total protein, animal
protein, purine, cholesterol, vitamins and minerals. The amount of protein in
the diet of intervention group were reduced as compared to that at pre-
intervention and meet the recommended requirements. The purine-rich foods
has been reduced the frequency of daily consumption and 3 times per week
or more as compared with pre-intervention such as animal viscera, beans,
beer and wine. Intervention group reduced average serum uric acid of 151.1
μmol /l; the control group reduced average serum uric acid of 27.1 μmol/ l.
Comparing 2 researches together studied the influence of 6 month dietary to
serum uric acid, in our study, intervention group reduced 80,9mol/l
compared with 151 mol/l in Lam’s study. The difference may came from
the participants of our study who had increase in serum uric acid alone,
therefore average uric acid levels may lower. In Lam’s study, participants
were Gout patients with higher serum uric acid levels and had pain caused by
acute gout.
Thus, nutritional counseling for dietary intervention helped reduce the
frequency of consumption of some foods such as red meat, organ meats,

bone soup, and reduce the use of beer, wine in the intervention group, helped
reduce serum uric acid levels, helping to reduce the risk of diseases
associated with increased serum uric acid such as gout and cardiovascular
disease, kidney disease.

CONCLUSION

1. Situation of increasing in serum uric acid
- The average concentration of serum uric acid was 280.9 mol/l, in male
was 316,1mol/l, higher than women (247mol/l). The difference was
statistically significant with p <0.001. The rate of increase in serum uric acid
was 9.2% (95% CI: 7.9 to 10.5%), in which increasing in serum uric acid
was 6.5% in female and 12.0% in male.
- Serum uric acid levels increased with age in both male and female. The rate
of increase of uric acid was 4.6; 5.8; 9.8; 10.0; 12.4 and 17.9% for the age
groups 30-39, 40-49, 50-59, 60-69, 70-79 and 80+ respectively
- The rate of increase in serum uric acid were more common in overweight
group (23.0%), high waist circumference (24.1%), the high WHR (14.1%),
lower level of physical activity (14.7%), history of cardiovascular disease
(16.5%).
2. Factors related to serum uric acid level
- Two models of linear regression to explain the 30% difference in
concentration of uric acid among participants were:
AU (μmol / l) = 48.7-62.2 * gender (1: male, 2: female) + 1.17 * age (years)
+ 5.9 * BMI (kg / m
2
) + 161.8 * WHR.
AU (μmol / l) = 102.7 - 63.2 * gender (1: male, 2: female) + 1.22 * age
(years) + 4.92 * BMI (kg / m
2

) + 1.37 * waist circumference (cm).
- Associated factors independently in male was age (OR = 1.6), BMI (OR =
3.8), frequent use of red meat (OR = 2.2), frequent use viscera (OR = 4, 2),
frequent use bone soup (OR =3.9) and alcohol (OR = 1.8). Associated factors
independently in female was age (OR = 2.5), BMI (OR = 2.2), frequent use
of red meat (OR = 17.8), and frequent use of visceral (OR = 13.9).
3. Effectiveness of dietary intervention to serum uric acid level
- After 6 months, the intervention group had reduced the frequency of
consumption of red meat, organ meats, water and bones soup as compared to
that of before intervention and compared with the control group at the same
time. The difference was statistically significant with p <0.05. Intervention
group decreased consumption of processed food, meat and processed
products, fish and seafood from baseline and compared with the control
group after the intervention. Vegetable consumption increased in
intervention group as compared to before and higher than the control group.
The difference was statistically significant with p <0.05. Dietary structure of
intervention group changed towards reducing animal protein, lipid animals in
both groups over and under 60 years; increased levels of vitamins and fiber
as compared to pre-intervention in the group of over 60 years old.
- Dietary intervention helped reduce an average of 80.9 mol/l of serum
uric acid in the intervention group and 22.9 mol/l in the control group.
After 6 month intervention, 55.8% participants in the intervention group and
12.5% in the control group had serum uric acid levels return to normal.
Effectiveness of intervention was 43.3%. Effective in reducing uric acid in
those aged over 60 and female was higher than those of 60 years or younger
and male.



RECOMMENDATIONS

- Apply community media to restrict the use of alcohol, celiac foods from
animals, selecting food available locally to build a healthy diet, contributes
to reduce the rate and concentration of serum uric acid.
- Dietary built in this study may be used as guidance materials for
community especially for those who are at risk of elevated serum uric acid
levels such as male, obesity, or abdominal obesity.
- Research and analysis of a purine content of food availability and
characteristics of Vietnam.


MINISTRY OF EDUCATION
AND TRAINING
MINISTRY OF HEALTH


NATIONAL INSTITUTE OF HYGIENE AND EPIDEMIOLOGY
***************



PHAM THI DUNG

THE SITUATION OF INCREASING SERUM URIC ACID,
RELATED FACTORS AND EFFICACY OF DIETARY
INTAKE IN OVER 30 YEAR OF AGE SUBJECT IN
RURAL OF THAI BINH PROVINCE

Scientific field: Nutrition and Dietetics
Code: 62 72 73 10



SUMMARY OF MEDICAL DOCTORAL THESIS






HA NOI - 2014