Acupuncture of the Five Shu Acupoints in spleen meridian to lower blood uric acid level

The primary hyperuricemia is an unexplained hyperuricemia caused by a variety of factors including genetic background, age, and environment. Causes of hyperuricemia can be classified into three functional types: increased production of uric acid (overproduction type), decreased excretion of uric acid (underexcretion type), and mixed type. Clinically it may manifest as increased blood uric acid level, but may remain asymptomatic in some patients. It is often detected when the patients are presented due to gout attacks, metabolic diseases, and/or cardiovascular and cerebrovascular diseases. High blood uric acid level is closely correlated with metabolic syndrome and cardiovascular diseases (1-4), which has aroused great attention in recent years. The mainstream treatment for this disease remains the drugs capable of promoting uric acid excretion and inhibiting uric acid synthesis. Typically long-term medication is required (5,6). Acupuncture has found to be an effective treatment for acute gout (7), while its role in lowering blood uric acid remains unclear. Metabolic disorder of uric acid is a manifestation of the body’s poor absorption and excretion of substances. Based on the principle of “spleen governing transportation and transformation”, hyperuricemia is a manifestation of the dysfunction of spleen in transportation, which results in the poor functioning of the meridians and Qi. A proper adjustment of the meridians and Qi will facilitate the recovery of the spleen’s function in governing transportation and transformation. According to the Nine Needles and Twelve Source in Ling Shu, the meridians and Qi originate from the limb extremities and spread along the Five Shu Acupoints (Jing, Xing, Shu, Jing, and He) towards heart, during which their activities gradually increase. Thus, we found that acupuncture of the Five Shu Acupoints in spleen meridian can dredge the spleen meridians and Qi and thus lower the blood uric acid level, without being affected by the patients’ inherent lifestyles.

In our current study, all the patients signed the informed consents, and the study was approved by the Institutional Review Board of the First Affiliated Hospital of Sun Yat-sen University.

Subjects and methods

General data

A total of 32 eligible patients were obtained in our cohort. These patients were inpatients in our department from January 2013 to October 2013. There were 20 men and 12 women, aged (64.35±12.35) years, with a body weight of (68.33±12.41) kg and disease course of (10.87±8.66) years. Table 1 summarizes the concomitant diseases.

Table 1 The concomitant diseases
Full table

Methods

Inclusion and exclusion criteria

Inclusion criteria: (I) Met the diagnostic criteria for hyperuricemia (8): when fed with normal-purine diets, the patients had a fasting serum uric acid level of >420 µmol/L 
(7 mg/dL) (for men) or >357 µmol/L (6 mg/dL) (for women) on two separate days; (II) Aged 18-80 years; and (III) Signed the informed consents.

Exclusion criteria: (I) Secondary hyperuricemia; (II) With a bleeding tendency: prothrombin time (PT) >17 s, platelet 9/L, and/or hemophilia; (III) Pregnant or lactating women; accompanied with severe diseases in cardiovascular system, liver, kidney, or hematopoietic system; with psychopath/psychosis; and/or with malignant tumors; (IV) While taking or have taken within the past two weeks uric acid-lowering drugs, azathioprine, 6-mercaptopurine, or drugs containing aspirin (>325 mg), or salicylates; (V) With serum creatinine >1.5 mg/dL and ALT exceeding two times of the upper limit of the normal value; (VI) With suspected or confirmed history of alcohol/drug abuse; or, upon the investigator’s scrutiny, the enrollment of such a patient may lower the credibility or make the grouping more complex (e.g., highly possible to drop out due to the frequent change of working environment).

Interventions

The fundamental treatment for all the enrolled patients (e.g., patients with type 2 diabetes, hypercholesterolemia, or hypertriglyceridemia) remained unchanged (no drug was added for those who had not used drugs). In the acupuncture group, the Yinbai, Dudu, Taibai, Shangqiu, and Yinlingquan were sticked, and the encountering of Qi (aching and tingling sensation at the sticking site) was regarded as a proper stick. Retain the needle for 30 min. The acupuncture was performed once daily for ten consecutive days. The included patients adhered to their usual diets and lifestyles. The observation was formally initiated at 8:00 am on day 1. Acupuncture was not performed within the 48 hours, and only the 24-hour urine volume was recorded. The urine uric acid concentration and urinary creatinine concentration were detected from 25 to 48 hours. On the 46th hour, venous blood samples were collected to detect serum uric acid, creatinine, and triglycerides concentrations. After the 48th hour, the patients received acupuncture of the Five Shu Acupoints in spleen meridian each morning. Once Qi was encountered, retain the needle for 30 min. The acupuncture was performed once daily for ten consecutive days. Record the 24-hour urine daily, and, on the morning of the 11th day, the fasting levels of blood uric acid, blood creatinine, blood urine creatinine, urine uric acid, and urine triglyceride concentrations were recorded.

Tests

Blood uric acid, blood creatinine, urine creatinine, urine uric acid, and urine triglycerides were determined using instrument. Rate of decline of serum uric acid = (Pre-treatment blood uric acid - Pre-treatment blood uric acid)/pre-treatment blood uric acid ×100; 24-hour urine volume change rate = (Post-treatment 24-hour urine volume – pre-treatment 24-hour urine volume)/post-treatment 24-hour urine volume ×100 [note: analysis of the change in urine volume is based on the 24-hour urine volume only since the habits (e.g., drinking water) differ remarkably many individual patients], the fraction excretion of uric acid (FEUA) = Urine uric acid × blood creatinine/(blood uric acid x urine creatinine) ×100.

Type-specific evaluation (9)

An FEUA of <7% is defined as the underexcretion type, 7-12% as mixed type, and ≥12% as overproduction type.

Statistical analysis

Data are processed and analyzed using SPSS 17.0 software package. The normally distributed measurement data before and after treatment are presented using (Mean ± SD) and analyzed using paired t-test and ANOVA. Chi square test was applied for the analysis of the ranked data and non-normal measurement data. A P value <0.05 was considered to be statistically significant.

Results

Enrolment

A total of 35 patients were enrolled in this study. Among them one patient was excluded due to the self-medication of benzbromarone, one patient withdrew from the study because he could not tolerate the acupuncture pain, and one patient quit the study due to a private matter. The remaining 32 patients signed the informed consents and entered the final analysis.

Changes in urine pH, urine uric acid, blood uric acid, triglycerides, creatinine, and urine creatinine (Table 2)

Table 2 Changes in urine pH value, urine uric acid, blood uric acid, 24-hoururine volume, blood creatinine, urine creatinine, and blood lipid profile (mean ± SD)
Full table

(I) In our cohort, the underexcretion type, mixed type, and overproduction type accounted for 40.63%, 25.00%, and 34.38%, respectively (χ²=1.781, P=0.410); (II) the blood uric acid level significantly decreased in all three group after the acupuncture (P<0.01); (III) before the acupuncture, the urine uric acid level was significantly lower in the underexcretion type than in the mixed type and overproduction type (P<0.01). After the treatment, the urine uric acid level became similar (P>0.05). In the underexcretion type, the urine uric acid concentration significantly increased after the treatment (P<0.01); (IV) before the treatment, the urine creatinine concentration was significantly lower in the overproduction type than in the mixed type (P<0.05); however, it became comparable after treatment (P>0.05). After the treatment, the blood creatinine concentration slightly decreased in the overproduction type (P<0.05); (V) the urine pH value and triglycerides showed no significant change before and after treatment (P>0.05).

Fractional excretion of uric acid and the rate of decline of serum uric acid (Table 3)

Table 3 Fractional excretion of uric acid and the rate of decline of serum uric acid
Full table

(I) FEUA before treatment: underexcretion type < mixed type < overproduction type (P<0.01); (II) the post-treatment FEUA significantly increased in both underexcretion type and mixed type (P<0.01) but decreased in the overproduction type (P<0.01); (III) the decrease of blood uric acid was comparable among these types (F=0.057, P=0.944). Also, the changes in the 24-hour urine volume were also comparable (F=0.191, P=0.827); (IV) the pooled FEUA significantly increased after treatment (P<0.01); (V) after the acupuncture, the blood uric acid level decreased by 16.32-18.29%, while the urine volume increased by 24.22-29.32%.

Adverse effects

The major adverse effect during the study was the acupuncture pain sensation. No obvious hematoma, ulceration, or other injury was found at the sticking site. No patient experienced fainting during acupuncture in the supine position. The acupuncture did not cause obvious damage to the local functions.

Discussion

As shown in our current study, the acupuncture of the Five Shu Acupoints in spleen meridian can remarkably decrease the blood uric acid level in patients with primary hyperuricemia; during the acupuncture, both the 24-hour urine volume and the FEUA increases, whereas the blood creatinine and triglycerides show no significant changes. For patients with the Underexcretion type and mixed type of hyperuricemia, acupuncture of the Five Shu Acupoints in spleen meridian can increase the FEUA; for patients with overproduction type, however, it increases the uric acid excretion mainly by increasing the urine volume. Thus, acupuncture of the Five Shu Acupoints in spleen meridian can decrease the blood uric acid level by promoting the excretion of uric acid and by increasing the urine volume.

Current research on uric acid metabolism indicates that two thirds of the blood uric acid in human body is excreted via kidney in the form of urate. The degree of excretion mainly depends on the status of glomerular filtration, renal proximal tubule reabsorption, and excretion of the distal convoluted tubule. The urates are actively transported by urate transporters (10,11). Interventions (e.g., use of thiazide diuretics) on these links often lead to the decreased excretion of uric acid and increased reabsorption (12), while some drugs [e.g., benzbromarone (13)] may suppress the renal tubules’ reabsorption of uric acid and thus promote the excretion of uric acid. The acupuncture of the Five Shu Acupoints in spleen meridian can remarkably reduce the blood uric acid level but has no obvious effect on blood creatinine and urine creatinine levels, which may be explained by the increased urine volume and uric acid excretion. Therefore, its activity in lowing uric acid is closely correlated with the regulation of glomerular filtration, renal proximal tubule reabsorption, and excretion of the distal convoluted tubule. By stimulating the acupuncture points on the body, the acupuncture can cause the responses of the neuroendocrine network; however, the corresponding changes in the specific molecular signaling pathways remain unknown.

From the perspective of TCM, the main function of the spleen is to regulate the transportation and distribution of nutrients and body fluids throughout the body. The dysfunction of spleen often results in the imbalance of nutrients and humoral metabolic disorders. Uric acid is an important nutrient that is dissolved in a body fluid. The accumulation of uric acid in the body often prompts dysfunction of spleen in transportation. Thus, regulating the spleen’s functions in regulating transportation and transformation facilitates the maintenance of the normal levels of serum uric acid. The Five Shu Acupoints in meridians regulate the flow and movement of Qi from meridians towards the heart. The Five Shu Acupoints including Jing, Xing, Shu, Jing, and He reflect the occurrence and development of the Qi in meridians (Qm). The Jing acupoint reflects the occurence of Qm, the Xing acupoint reflects the enhancement of Qm, the Shu acupoint reflects the transportation of the enhanced Qm, the Jing acupoint reflects that the Qm has merged and then further enhanced, and the He acupoint reflects that the Qm has merged into a “lake”, which is also the source of Qm that steadily nourish the whole body (14,15). The Five Shu Acupoints reflect the progress and status via which the splenic function occurs and grows. Acupuncture of the Five Shu Acupoints in spleen meridian can regulate the occurrence, growth, transportation, enhancement, and aggregation of the Qi in spleen meridian, thus regulating the role of spleen in regulating the transportation and transformation of Qi, which will favorably adjust the transportation and distribution of nutrients and body fluids in human body. This may explain the efficacy of acupuncture of the Five Shu Acupoints in spleen meridian in lowing blood uric acid from the TCM perspective.

Our study had some limitations: only the efficacy after ten days of treatment was observed, and the long-term effectiveness and its mechanism still require further investigation. Nevertheless, the effectiveness of the acupuncture of the Five Shu Acupoints in spleen meridian in lowing blood uric acid in patients with primary hyperuricemia is clinically meaningful. Unlike benzbromarone (which only promotes the excretion of uric acid) or diuretics (which may suppress the excretion of uric acid while promoting the production of urine), acupuncture of the Five Shu Acupoints in spleen meridian can not only promote uric acid excretion but also increase urine volume. This may also enlighten the future development of drugs with similar efficacies.

Acknowledgements

We would like to express our gratitude to the Department of Traditional Chinese Medicine of the First Affiliated Hospital of Sun Yat-sen University and the Institutional Review Board of our hospital.

Disclosure: The authors declare no conflict of interest.

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