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the uric acid levels of chinese people are rising rapidly.

a study involving more than 2 million people showed that from 2001 to 2017, the prevalence of hyperuricemia (hua) in people over 15 years old in mainland china more than doubled from 8.5% to 18.4%.south china is the hardest hit area。

for a long time, people only knew that long-term high uric acid levels would increase the risk of gout and kidney stones. however, as medical research continues to deepen, the relationship between elevated uric acid and other chronic diseases has begun to emerge.

this is an important public health issue.why are chinese people's uric acid levels getting higher and higher? what causes the regional differences?we try to shed some light on this issue.

china high uric acid map

most patients with hyperuricemia have no symptoms, and they often learn that their uric acid level is elevated from a physical examination report. in people's vague impression, more and more people have been found to have elevated uric acid levels in recent years.

this is not an illusion. in a study published in 2021, researchers analyzed data from 177 studies and more than 2 million people and found that in 2001, the prevalence of hyperuricemia in people over 15 years old in mainland china was still 8.5%. by 2017, the figure had climbed to 18.4%.in less than 20 years, it has more than doubled。

another national survey released in 2022 also yielded surprising results. using the china nutrition and health monitoring data and including 52,627 subjects, the survey found that the estimated overall prevalence of hyperuricemia in adults aged 18 to 59 in my country was 15.1%.this means that nearly 3 out of every 20 adults have abnormal uric acid levels.。

this is the general trend. if we analyze it more carefully, we will find that the increase in uric acid levels varies in different regions.

china is the world's largest developing country, with 1.4 billion people spread across a vast land. in the above study involving more than 2 million people, the researchers further divided mainland china into seven regions: east, north, central, south, southwest, northwest and northeast (see the figure below).the prevalence of hyperuricemia in the southern china, represented by guangdong and guangxi, and the southwestern china, represented by yunnan, guizhou, sichuan and tibet, leads the country., 25.5% and 21.2% respectively.

in south china and southwest china, the prevalence of hyperuricemia among people over 15 years old leads the country. original image: reference 1

the highest value appeared in guangdong province, the prevalence rate among people over 15 years old reached 42.2%. in another survey of 2,940 people undergoing health checkups in qingxi, dongguan city, guangdong province, the abnormal detection rate of uric acid in male blood was as high as 51.89%. the researchers directly stated that "elevated uric acid threatens the health of people in qingxi area."

the data reveals the reality of high uric acid in chinese people. according to the "chinese multidisciplinary expert consensus on diagnosis and treatment of hyperuricemia-related diseases (2023)", in china,hyperuricemia has become the second largest metabolic disease after diabetes.。

when the balance is broken

uric acid in the human body mainly starts from an organic substance called "purine".

purines come from two sources. one is "self-contained" and exists in the body since birth, and is an important component of genetic materials dna and rna. the other is exogenous, when people eat foods containing purines, they enter the body.

in a healthy human body, the liver processes excess purines, producing uric acid in the process. uric acid, as a metabolic waste, is soluble in the blood, with about 2/3 of it excreted through the kidneys and the remaining 1/3 through the digestive tract.

under normal circumstances, the production and excretion of uric acid in the human body maintain a dynamic balance.however, many factors can disrupt this balance, causing excessive production of uric acid or reduced excretion, thereby increasing the uric acid level in the human body.

under normal purine diet, the fasting blood uric acid level of adults measured on two different days exceeded420μmol/L（7mg/dL）, it can be diagnosed as hyperuricemia.

among physiological factors, the effects of age and gender on uric acid levels are clear.

as we age, the structure and function of the kidneys change, and their filtering capacity physiologically decreases.starting from the age of 30 to 40, the glomerular filtration rate decreases by about 1 ml/min/m per year.²。this natural change will increase the body's uric acid level.

men are generally more likely to have high uric acid levels than women.starting from puberty, men's uric acid levels generally begin to be higher than women's; before the age of 50, the prevalence of hyperuricemia in men is about 2 to 4 times that of women. after the age of 50, the gap between the sexes begins to narrow.

adult males are generally more likely to have high uric acid levels than females (blue line for males, red line for females)丨original image: reference 1

estrogen is considered to be the main cause of gender differences.estrogen can affect the kidney's clearance and reabsorption functions, and its level is negatively correlated with uric acid levels. due to the development of secondary sexual characteristics and hormone differences, uric acid levels begin to show gender differences during puberty. this is why adult males generally have higher uric acid levels than females of the same age, but the gap between females and males gradually narrows after menopause.

society is changing. my country's population life expectancy is increasing and aging is intensifying. in addition, health examinations are becoming more popular, such as employee examinations with higher coverage and welfare examinations for special groups. the proportion of people diagnosed with elevated uric acid levels will naturally increase.

but this is not enough to explain the rapid increase in uric acid levels among chinese people, and it cannot explain the regional differences. there are more factors at work behind this.

the double whammy of genetics and lifestyle

family and twin studies are two commonly used genetic research methods. the former observes family members with blood relations, and the latter compares identical or fraternal twins to find the relationship between diseases or symptoms and genetics. through these two methods, researchers have found that25% to 60% of the differences in blood uric acid levels among the population are determined by genetic factors.。

genome-wide association study (gwas) is a method that studies the genomes of a large number of individuals to identify genetic variants associated with a specific disease or trait.several genes related to hyperuricemia and gout have been discoveredsome researchers have even discovered unique susceptibility genes rfx3 and kcnq1 in the han chinese population, which may directly or indirectly cause hyperuricemia and gout.

it can be seen that from a genetic point of view, chinese people do not have specific genetic advantages to be "immune" to hyperuricemia and gout.

comparison of susceptibility loci in different populations, among which rfx3 and kcnq1 (which are also diabetes susceptibility genes) are unique to china | reference 7

elevated uric acid is a global health problem. since the 1970s and 1980s, developed countries such as the united states and japan have experienced a general increase in uric acid levels, and the prevalence of hyperuricemia in the population once exceeded 20%. however, thanks to the early discovery and attention paid to this phenomenon, the prevalence of hyperuricemia in these countries has begun to stabilize in recent years.

in contrast, the disease situation in the chinese population presents unique characteristics.first, the prevalence began to rise relatively late, but it grew rapidly; second, there is a clear trend of younger age. in a summary study of 54,580 children and adolescents, the prevalence of hyperuricemia among children and adolescents aged 3 to 19 in my country increased from 16.7% between 2009 and 2015 to 24.8% between 2016 and 2019, even higher than the prevalence among children and adolescents in the united states and south korea during the same period.

such rapid development is closely related to changes in lifestyle.in addition to genetic factors, the medical community generally recognizes that lifestyle can affect uric acid levels, such as eating habits.

some foods are natural "uric acid raisers". they are either rich in purines or can make the body produce more uric acid through other pathways. representative foods include some fish and shellfish in seafood (anchovies, sardines, cod, lobster, mussels, scallops, etc.), some common meats (beef, lamb, offal, etc.), alcoholic beverages (especially beer), and fructose.

with the improvement of living standards and the development of logistics, the amount of food we eat is increasing.

in the past decade, my country's consumption of animal aquatic products has increased significantly, with per capita consumption of edible aquatic products increasing by 33%. the prevalence of drinking among adults has also increased from 35.7% in 2007 to 41.3% in 2015. other studies have found that compared with 2002, the average intake of red meat by chinese residents in 2018 increased by 134.3%, and sugary drinks (one of the main applications of industrial fructose) increased by 16.1%. the average intake of both is higher than the recommended level of dietary guidelines.

the more you eat, the higher your risk.researchers from peking union medical college hospital systematically analyzed 19 studies and found that hyperuricemia was positively correlated with the intake of red meat, seafood, alcohol, and fructose. specifically, the consumption of red meat, seafood, alcohol, and fructose increased the risk of hyperuricemia in the study subjects by 24%, 47%, 106%, and 86%, respectively.

just as there are lifestyle habits that increase risk, there are also habits that reduce risk, but the reality is that we don’t do very well with the latter.

drinking water properly can promote uric acid excretion. people who do light physical activities are recommended to drink 1500-1700 ml of water every day, and people with hyperuricemia and gout with normal heart and kidney function should drink 2000-3000 ml of water every day.but not drinking enough water is commonfor example, a study sampled the summer water drinking volume of adult residents in four cities, namely beijing, chengdu, shanghai and guangzhou, and found that one-third of the people drank less than 1,200 ml of water per day.

regular and moderate exercise is also beneficial to the metabolism of uric acid. whether it is to prevent or improve hyperuricemia, current domestic and international guidelines encourage exercise as an important part of non-drug therapy, such as at least 150 minutes of moderate-intensity aerobic exercise per week, which is also the "minimum standard for adequate physical activity" considered by the world health organization.

however, research shows that from 2010 to 2018,the proportion of chinese adults who are not physically active has increased from 17.9% to 22.3%, with the most significant increase in the 18-34 age group.it can be said that at present, at least more than one-fifth of chinese adults do not meet the above minimum standards for physical activity. in contrast, according to a large study published by the lancet global health, in 28 high-income western countries such as australia, the united kingdom, and the united states, the lack of physical activity among adults has been on a downward trend from 2000 to 2022.

when we do more things that increase risks and fewer things that reduce risks, the phenomenon of increased uric acid in the entire group may be difficult to avoid.

regional differences: why are some provinces so high?

in a family, eating habits are similar; in a specific region, eating habits are also similar, forming a unique regional eating pattern. therefore, when further exploring the reasons for the regional differences in hyperuricemia in china, researchers also linked it to the local food culture.

a fairly general correspondence is that if a regionthe consumption of seafood is abundant, the drinking culture is prevalent, red meat and offal are common, and high-fructose foods are popular., then that area may be facing a higher uric acid crisis.

take seafood as an example. in china's aquatic product consumption market, guangdong province leads the way in consumption. according to estimates, the three provinces with the largest total consumption of aquatic products by residents in my country are guangdong, zhejiang, and jiangsu. in 2022, the total fresh weight of animal aquatic products consumed nationwide was about 48.37 million tons.guangdong province consumed 7.612 million tons, accounting for 15.7%; 60.15 kg per person, exceeding the upper limit of intake recommended by the balanced diet pyramid (50.23 kg/year).

guangdong province is the leader in china's aquatic product consumption market | reference 13

the chinese center for disease control and prevention published a study that used a representative survey of 189,198 adults in 31 provincial-level administrative regions.it was found that the drinking rate in southern china is also the highest, in the past 12 months, the prevalence of drinking was 69.1% for males and 28.4% for females.

age-standardized prevalence of drinking in the past 12 months among men in various provinces in china in 2015 | reference 14

of course, regional differences in diseases and symptoms are a very complex issue, and unique dietary habits may explain part of the reasons, but they cannot describe the whole picture.

in fact, people's preference for certain foods is also influenced by genetic factors to a certain extent.scientists have discovered some specific gene variants that affect whether we like certain foods, such as drinking habits, and the influence of genetic factors may be between 43% and 53%. it can be seen that the formation of a region's eating pattern is not just about living by the mountains and living by the water, but also a complex picture of genetics and environment intertwined.

specific diseases that are prevalent in a region may also be associated with hyperuricemia.a study analyzed data from more than 9 million people and found that chronic kidney disease (ckd) is highly prevalent in southern and southwestern china.guangxi and sichuan are the most severely affected provinces, followed by guizhouthe researchers speculate that genetic differences plus dietary habits are the reasons for the high incidence of chronic kidney disease in these places. for example, the high consumption of high-sodium smoked meats in the southwest may increase the risk of kidney disease.

chronic kidney disease and hyperuricemia are closely related.on the one hand, hyperuricemia is a risk factor for chronic kidney disease; on the other hand, if you have chronic kidney disease, impaired kidney function will also affect the metabolism of uric acid. the high prevalence of hyperuricemia in guangxi, sichuan, guizhou and other places may also be related to the special spectrum of diseases.

the sweet trap of fructose

among the many foods that can increase uric acid, fructose deserves special mention. it does not contain purine and is easily overlooked. the popularity of fructose is inseparable from the joint promotion of industrialization and commercialization.

fructose originally existed mainly in fruits and honey, but most of the fructose we eat is not from this natural source. in 1957, american biochemist richard marshall and his colleagues discovered an enzyme that can convert glucose in corn syrup into fructose through structural rearrangement; about ten years later, yoshiyuki takasaki's team at the japan industrial technology research institute achieved mass production of this enzyme.

from then on, the sweetness is high, the production cost is low,highly concentrated industrial fructose products enter the historical stage, and it has become the main way for people to consume fructose.

fructose syrup is a syrup product with fructose as the main ingredient. this ingredient can be found everywhere in ultra-processed foods such as sugary drinks, desserts, and sauces. in 2019, the sugar company czapp conducted an analysis that, as a sweetener, fructose syrup has a significant price advantage over table sugar (white sugar, rock sugar, etc.). analysts believe that this will stimulate the industry to continue to increase the use of fructose syrup, and more fructose syrup may replace table sugar in the beverage field.

in 2019, the price difference between sugar and fructose syrup (equal to sugar price) remained at 1,724 yuan/ton丨czapp.com

according to an industry report released by zhiyan consulting, fructose is also on the rise in the chinese market in terms of market size, output and demand, with demand increasing from 3.003 million tons in 2016 to about 3.8393 million tons in 2023. however, in almost the same period, the production of high-fructose sweeteners in other countries or regions around the world was stagnant or declining.

surrounded by delicious food and a promising market, fructose is a "sweet trap" when it comes to raising uric acid levels.

the main component of table sugar is sucrose, which is composed of one fructose molecule and one glucose molecule. fructose and glucose are the two most common monosaccharides, and their structures are almost the same except for some differences in chemical bonds.but the tiny differences make their sweetness and metabolic pathways in the human body completely different.

we usually use the indicator of "relative sweetness" to measure the sweetness of sweet substances, where sucrose is set as the benchmark and the sweetness value is 100. compared with sucrose, the relative sweetness of glucose is 70~80,the relative sweetness of fructose is as high as 150~170, with a smaller dosage, it can achieve the same sweetness as sucrose and glucose. at the same time, the sweetness advantage of fructose will be more significant in low temperature environments. for example, in an environment of 0~10℃, the sweetness of fructose solution can be more than twice that of glucose solution of the same concentration.

the sweetness advantage of fructose is more significant in low temperature environments, so it is more "favored" by ultra-processed foods that require or can be refrigerated. original image: reference 22

after glucose is absorbed into the blood, it is mainly used for energy. the excess will be stored in the form of glycogen in the muscles and liver, or enter fat cells for emergency use. after fructose enters the human body, it will be transported to the liver for metabolism. in the liver, the enzyme that breaks down fructose begins to work.in a complex series of processes, a substance called adenosine monophosphate (amp) is formed, which is the substrate for the production of uric acid.。

fructose metabolism in the liver | original image: intechopen.com

therefore, the more fructose you consume, the more uric acid is synthesized.ultra-processed foods with large amounts of fructose usually have poor satiety and obvious hedonic effects. this can lead to us easily overeating even if we don’t need energy physiologically, and we may even want to eat more the more we eat, increasing the risk of elevated uric acid levels.

dietary sugar intake has been linked to a range of metabolic diseases, including ectopic fat accumulation, obesity, and cardiovascular disease, which researchers believe can be largely attributed to excessive fructose intake.and excessive uric acid synthesis may be one of the important intermediate mechanismsthis also makes the connection between uric acid and more chronic diseases begin to emerge.

the relationship between uric acid and diseases goes far beyond gout

as mentioned earlier, the clinical diagnostic threshold for hyperuricemia is 420 μmol/l (7 mg/dl). this is a rather ambiguous value. the saturated concentration of uric acid in human blood is about 420 μmol/l. when this value is exceeded, the uric acid originally dissolved in the blood will precipitate in the form of monosodium urate crystals.

as these crystals continue to be produced and accumulate, they can be deposited in the joints and surrounding soft tissues.this is the physiological basis of gout。

as early as the end of the 18th century, the medical community had discovered the connection between uric acid and gout. as one of the most common diseases in modern society, gout causes sudden severe pain, swelling, and redness in one or more joints of the patient. the pain it brings has been described as "so painful that even the weight of the sheets is unbearable."

in traditional thinking, the risk of elevated uric acid levels is directly related to gout and kidney stones (caused by crystals deposited in the kidneys). in medical terms, "asymptomatic hyperuricemia" also refers to the absence of symptoms related to gout and kidney stones. however, with the continuous deepening of medical research, this traditional perception has been broken.more and more studies are beginning to reveal the relationship between high uric acid and other chronic diseases, such as hypertension, diabetes, obesity, metabolic syndrome, etc.

a meta-analysis of 18 prospective cohort studies with 55,667 participants found thathyperuricemia is associated with increased risk of hypertension, every 1mg/dl increase in uric acid levels increases the risk of hypertension by 13%. and hypertension is a risk factor for a series of cardiovascular diseases, such as stroke and coronary heart disease.

other researchers tracked 9,471 people, with an average follow-up time of 2.9 years.it was found that people with higher uric acid levels have a relatively higher risk of developing type 2 diabetes later in life, every 1 mg/dl increase in uric acid levels increases the risk of type 2 diabetes by 9% after adjusting for other variables. the study even found that if a person's blood uric acid level increases by more than 30% in a year, the risk of diabetes will increase by 30%; conversely, if the uric acid level drops by more than 10%, the risk of diabetes will decrease by 21%.

many studies have shown thatobesity and high uric acid are also closely relatedthere may be a bidirectional association. the metabolic characteristics and eating habits of obese patients may lead to increased uric acid in the body; and hyperuricemia can also affect blood lipid metabolism through a series of mechanisms, increasing the risk of obesity.

a series of mechanisms that may be involved between uric acid and chronic diseases | original image: reference 27

some researchers analyzed data from 10,000 participants in the taiwan biobank and found that uric acid may increase the risk of metabolic syndrome by increasing blood pressure, increasing triglyceride (a component of fat) levels, and lowering high-density lipoprotein cholesterol (hdl-c) values.

in addition, various medical studies have also found potential links between hyperuricemia and non-alcoholic fatty liver disease, chronic inflammation, and even alzheimer's disease.although it will take more time and research to fully elucidate the causal relationship and mechanism, there is a basic consensus that uric acid should receive more attention.。

ancestral traces, modern life

in many mammals, there is a substance called "urate oxidase" that can break down uric acid and convert it into allantoin, which is more water-soluble and can therefore be more easily excreted from the body by the kidneys.but in humans and some higher primates, this enzyme is missing.

scholars studying biological evolution speculate that the lack of urate oxidase-related genes may be beneficial to the survival of human ancestors. in ancient times, the environment was harsh, and those human ancestors who could endure energy shortages for a long time had a better chance of survival. the lack of this enzyme can increase uric acid, and then increase survival advantages by increasing blood pressure and fat storage. the entire evolutionary process of "survival of the fittest" is long and has lasted for millions of years.

but the changes in the human living environment are coming too fast.in just a few decades or hundreds of years, the food industry has developed rapidly, material resources have become extremely abundant, and the lifestyles of modern residents have changed dramatically. however, the speed of environmental change does not match the speed of human natural evolution, and people living today have not evolved the ability to deal with large amounts of uric acid.

the evolution of urate oxidase restored by researchers | original image: reference 29

according to the consensus of chinese experts, in the management of hyperuricemia patients, they should be given health guidance in diet, exercise, etc., develop personalized lifestyle interventions, and start drug treatment when the effect is not good. especially for young hyperuricemia patients, to reduce the subsequent risks, it is best to change their lifestyle from now on, such as eating more whole grains and fresh vegetables, doing at least 150 minutes of moderate-intensity aerobic exercise per week, and quitting smoking and limiting alcohol.

but in reality, this is not easy.there are two main motivations for people to eat: fighting hunger and seeking pleasure. in this era full of uncertainty and stress, the pleasure brought by food seems to play a greater role and even become a way for many people to seek comfort. and many foods that are likely to cause elevated uric acid are the so-called "sources of happiness."

maintaining a healthy diet, exercising regularly, and seeking and responding to medical advice in a timely manner also requires investment of money, time, energy, or a suitable place. however, many people may not have these conditions due to busy work, fast pace of life, limited living environment, or insufficient financial ability.

moreover, even if individuals can make their body indicators healthier by changing their lifestyle,but collective health problems have long gone beyond the individual level and are also social issues.the general increase in uric acid levels, and even the collective changes in more concerned health indicators such as blood sugar, blood pressure, and weight, are not only a reflection of individual behavior, but also a microcosm of the characteristics of the times. to solve them, it naturally requires more efforts and support from the society.

but everyone knows that this is a long and difficult process.

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