Document Type: Review Article

Authors

1 Assistant Professor of Toxicology & Pharmacology, Medicinal plants Department, Imam Khomeini Higher Education Center, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.

2 Laboratory Sciences Expert, Farabi Hospital Laboratory, Tehran University of Medical Sciences, Tehran, Iran

10.22038/apjmt.2020.16319

Abstract

Background: Psyllium seeds, produced from Plantago ovata Forsk, are an herbal treatment generally used as a laxative. They also reportedly have lowering effects on some metabolic parameters such as blood glucose, lipids and uric acid. In this paper, we report the effect of this herbal medicine in reducing serum uric acid levels, without major adverse effects, in a hyperuricemic patient.
Case report: A 51-year-old patient with a history of hyperuricemia (10.5 mg/dL in a recent measurement) gave consent to undergo a 40-day treatment using psyllium seeds with dosage of 83.3 mg/kg. Treatment was given in two 20-day courses: During the first course, the seeds were given daily and during the second course, the same dosage was given every other day. Serum uric acid levels decreased to 8.1 mg/dL and 6.8 mg/dL on the 20th and 40th days, respectively. No major adverse effects were observed, such as skin rashes, digestive disorders, muscular pain, allergic manifestations, abnormalities in liver and kidney function tests, and abnormalities in blood parameters.
Conclusion: Psyllium seeds may be effective in reducing serum uric acid levels in hyperuricemia patients,  and major adverse effects are not expected to occur. These data can be used for further research and designing clinical trials.

Keywords

INTRODUCTION

Uric acid is the final product of purine catabolism, and xanthine oxidase has an important role in its production. The increase of this important metabolite in serum levels is associated with many health consequences such as gout, hypertension, cardiovascular and kidney diseases (1). Hyperuricemia, which is diagnosed by an abnormal increase in serum levels of uric acid, is an important risk factor for gout and oxidative stress disorders. Hyperuricemia develops as a result of disturbances in the pathway of purine metabolism. Therefore, the most important therapeutic measure is to control uric acid production (1, 2).

 

The conventional medicines for hyperuricemia and many other chronic diseases are sometimes associated with long term side effects. Due to this, there has been an exploration for medicinal plants with potential therapeutic benefits and lack of major side effects (3-7). Psyllium is a medicinal plant which belongs to the Plantaginaceae family. It is used in traditional medicine for treating skin injuries, gastric disturbances, and inflammatory ureterorenal diseases (8). Two species of Plantago psyllium and Plantago ovata Forsk in Iran are called as "Esparzeh" in the Persian language (9). Anti-hyperglycemic and anti-hyperlipidemic effects of this plant have been ascertained in experimental and clinical studies (10, 11). Plants in the Plantaginaceae also have strong antioxidant and anti-inflammatory properties, due to the high content of phenolic compounds (12).

 

Psyllium products also have a high fiber content, which may help absorb uric acid in the bloodstream and facilitate its elimination through the kidneys (13). These features would be of interest for patients with hyperuricemia. Here, we report the solitary use of this product in a hyperuricemic patient, with promising outcomes and lack of any major adverse effects.


 

CASE PRESENTATION

A 51-year-old man with a three year history of hyperuricemia (recent measurement of > 10.5 mg/dL serum uric acid level) and no other significant health problems gave written informed consent, in accordance with the ethical principles of Helsinki declarations for human studies (14), to undergo a specific treatment plan. The patient’s past medical history showed use of the anti-gout drug Allopurinol for a couple of years and use of anti-hyperlipidemic drugs, namely Gemfibrozil. The patient was not using any medication when this protocol was initiated.

Treatment protocol& laboratory assays

Psyllium seeds were purchased from a valid herbal shop. The amount of psyllium used for this treatment was based on traditional medicine and scientific papers (15).  Treatment with psyllium was done in 2 courses. The first course of treatment lasted for 20 days and included daily intake of 5g psyllium seeds in 150 ml of water (3.33 g/dL equivalent to 83.3 mg psyllium per kg of body weight). During the second course, also lasting 20 days, the drug was continued with the same dosage but was taken every other day. No other drug was taken during this 40 day period.

Before treatment, serum uric acid levels and some other blood parameters were measured in a fasting state using a calorimetric assay kit (Pars Azmoon Co., Tehran, Iran). Experiments were carried out in the department of pathobiology laboratory in Farabi hospital in Tehran, Iran.

Therapeutic response and adverse effects

As mentioned, the serum uric acid level was 10.5 mg/dL before starting the treatment plan. The serum uric acid level was 8.1 mg/dL and 6.8 mg/dL 20 days and 40 days after treatment was initiated, respectively. Following the treatment, no remarkable adverse effects were noted, including skin rashes, digestive disorders, muscular pain, allergic manifestations, abnormalities in liver and kidney function tests, and abnormalities in blood parameters (Table 1). 

DISCUSSION

Psyllium seeds are generally made from Plantago ovata husks. They have important medicinal uses and are high in fiber content (>70% fiber). Fiber-rich plant-based foods have lowering effects on serum levels of glucose, lipids and uric acid. They either bind to food and prevent their complete digestion in the intestinal lumen, or adsorb metabolites in the blood circulation, which facilitates their excretion (13, 16-18). In this paper, we reported that the use of a psyllium product for 40 days in a patient with hyperuricemia resulted in a 3.7 unit decrease in serum uric acid level.

Psyllium seeds and their supplements are also rich in flavonoids. Flavonoids with a phenolic structure have several hydroxyl (OH) groups, which are able to neutralize oxygen free radicals and prevent oxidative damage in vitro and in vivo (19-21). Flavonoids are shown to have protective effects against cardiovascular diseases and cancer, attributable to their antioxidant properties and inhibition of certain enzymes including xanthine oxidase (22). Due to their structural similarity to the substrates of xanthine oxidase, they can attach to the active site of the enzyme and inhibit its activity (23). Accordingly, the flavonoid compounds in the psyllium plant, such as luteolin, can inhibit the xanthine oxidase either in the pathway of hypoxanthine to xanthine conversion, or the pathway of xanthine to uric acid conversion. This leads to effectively reducing the level of uric acid in the blood (Figure 1).

Our previous study showed that a psyllium supplement along with a specific dose of allopurinol were able to synergistically inhibit xanthine oxidase, thus reducing the serum uric acid levels in a patient with hyperuricemia (18). In the present report, we showed that solitary use of this product is also useful and has uric acid reducing effects. This reduction is of importance, as it could maintain uric acid at normal levels. Moreover, the use of psyllium seeds with the mentioned dosage was not associated with major adverse effects. On the other hand, allopurinol, the standard of care for hyperuricemia, may cause allergic reactions, skin rashes, and kidney and liver function abnormalities (24). In addition, xanthine oxidase inhibitors are reported to result in side effects such as increased plasma concentrations of pyrazinoic acid, hypocalcemia, metabolic acidosis, and digestive disorders (25-27). Hence, psyllium seeds might be favorable alternatives to these treatments.

 

 

CONCLUSION

Psyllium may be effective in reducing serum levels of uric acid in hyperuricemia patients, and their use lacks major adverse effects. Considering this evidence, further experimental studies and a phase I clinical study can be designed using psyllium seeds with the dose of 83.33 mg/kg of body weight/day for hyperuricemia patients.

 

 


 

ACKNOWLEDGEMENT

Authors are obliged to the staff of the‌ Farabi hospital laboratory and also appreciate the cooperation of the patient.

 

Conflict of interest: None to be declared.

 

Funding and support: None.

 

  1. Strazzullo P, Puig JG. Uric acid and oxidative stress: relative impact on cardiovascular risk. Nutr Metab Cardiovasc Dis2007;17: 409- 14.
  2. Liote F. Hyperuricemia and gout. Curr Rheumatol Rep 2003;5: 227-34.
  3. Kunle OF, Egharevba HO, Ahmadu PO. Standardization of herbal medicines- A review. IntJ Biodvers Conserv 2012;4: 101-12. 
  4. Ebadollahinatanzi A, Sabzevari O, Ghahremani MH. The effect of watercress on hepatic glutathione of intoxicated rats with acetaminophen. Toxicol Lett 2012;211S: 166.  
  5. Ebadollahinatanzi A, Arabrahmatipor G. The protective effects resulting from a combination of three medicinal plants on liver injury due to carbamazepine drug: A case report. Toxicol Lett 2016; 258S:105-6.
  6. Ebadollahi - Natanzi A. Toxicity comparison of four Cruciferous plant extracts and evaluation of their cytotoxicity - radical scavenging correlations. Jundishapur J Nat Pharm Prod 2018;13: e13866.
  7.  Arabrahmatipour G, Ebadollahinatanzi A. The accelerated removal of kidney stones by concomitant use of camel thorn distillate and Rowatinex drug: A case report. Toxicol Lett 2018;295S: 265.
  8. Zargari A. Medicinal plants. Volume4,6th ed.Iran: Tehran University Publication; 1997.

9.       -Naghdi Badi H, Dastpak A, Ziai S. A review of Psyllium plant (Plantago ovata Forsk. and Plantago psyllium L.). J Med Plants2004;1:1-14.

  1. Hannan JMA, Ali L, Khaleque J, Akhter M,Flatt PR, Abdel-Wahab YHA. Aqueous extractsof husks of Plantago ovata reduce hyperglycaemiain type 1 and type 2 diabetes by inhibition ofintestinal glucose absorption. Br J Nutr 2006;96:131 –7.
  2. -Ziai SA, Larijani B, Akhoondzadeh S, Fakhrzadeh H, Dastpak A, Bandarian F,  et al. Psyllium decreasedserum glucose and glycosylated hemoglobinsignificantly indiabetic outpatients. JEthnopharmacol 2005;102: 202 – 7.

12.    Ruiz-Ruiz JC, Matus-Basto AJ, Acereto-Escoffié P, Segura-Campos MR. Antioxidant and anti-inflammatory activities of phenolic compounds isolated from Melipona beecheii honey. Food Agr Immunol 2017;28: 1424-37.

13.    Fang CH, Tsai CC, Shyong YJ, Yang CT, Li KY, LIn YW, et al. Effects of Highly oxygenated water in a hyperuricemia rat model. J Healthc Eng 2020;2020: 1323270.

14.    World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Bull. World Health Organ 2001; 79:373-4.Available from: https://apps.who.int/iris/handle/10665/268312.

15.  Fallah Huseini H, Fakhrzadeh H, Dastpak  A, Azarabadi  M, Mohtashami TokabnyR.Review of antihyperlipedemic herbal medicine.J Med Plants 2005;3: 9-20.

16.    Diez R, Garcia JJ, Diez MJ, Sierra M, Sahagun AM, Calle AP, et al. Hypoglycemic and hypolipidemic potential of a high fiber diet in healthy versus diabetic rabbits. Biomed Res Int 2013;2013: 960568.

17.    Prasad C, Iqbal U, Westfall S, Prakash S. Management of hyperuricemia and gout by prebiotics and probiotics: potentials and limitations. Int J Probiotics Prebiotics 2017;12: 5-16.

  1. Ebadollahi-Natanzi A, Arab-Rahmatipour G. Psyllium together with allopurinol can efficiently reduce the increased serum level of uric acid, creatinine and urea: A case report. Iran J Toxicol 2017;11: 51-6.
  2. Potapovich AI, Kostyuk VA. Comparativestudy of antioxidant properties andcytoprotective activity of flavonoids.Biochemistry (Mosc) 2003;68: 514-19.
  3. Kinoshita T, Lepp Z, Kawai Y, Terao J,Chuman H. An integrated database offlavonoids. Biofactors 2006;26: 179-88.
  4. Ebadollahi Natanzi AR, Mahmoudian S, Minaeie B, Sabzevari O. Hepatoprotective activity of phloretin and hydroxychalcones against Acetaminophen induced hepatotoxicity in mice. Iran J Pharm Sci 2011;7: 89-97.
  5. Scalbert A, Manach C, Morand C, Remesy C, Jimenez L. Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr 2005;45: 287-306.
  6. Mo SF, Zhou F, Lv YZ, Hu QH, ZhangD, Kong LD. Hypouricemic action ofselected flavonoids in mice: structure–activityrelationships. Biol Pharm Bull 2007;30: 1551-6.

24.  Day RO, Graham GG, Hicks M, McLachlan AJ, Stocker SL, Williams KM. Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Clin Pharmacokinet 2007;46: 623–644.

  1. Pacher P, Nivorozhkin A, Szabó C. Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Res 2006;58: 87–114.
  2. Gerdan V, Akkoc N, Ucan ES, Bulac Kir S. Paradoxical increase in uric acid level with allopurinol use in pyrazinamide-induced hyperuricemia. Singapore Med J 2013;54: e125-6.
  3. Salem CB, Slim R, Fathallah N, Hmouda H. Drug-induced hyperuricaemia and gout. Rheumatology 2017;56: 679-88.

 

 

  1. Strazzullo P, Puig JG. Uric acid and oxidative stress: relative impact on cardiovascular risk. Nutr Metab Cardiovasc Dis2007;17: 409- 14.
  2. Liote F. Hyperuricemia and gout. Curr Rheumatol Rep 2003;5: 227-34.
  3. Kunle OF, Egharevba HO, Ahmadu PO. Standardization of herbal medicines- A review. IntJ Biodvers Conserv 2012;4: 101-12. 
  4. Ebadollahinatanzi A, Sabzevari O, Ghahremani MH. The effect of watercress on hepatic glutathione of intoxicated rats with acetaminophen. Toxicol Lett 2012;211S: 166.  
  5. Ebadollahinatanzi A, Arabrahmatipor G. The protective effects resulting from a combination of three medicinal plants on liver injury due to carbamazepine drug: A case report. Toxicol Lett 2016; 258S:105-6.
  6. Ebadollahi - Natanzi A. Toxicity comparison of four Cruciferous plant extracts and evaluation of their cytotoxicity - radical scavenging correlations. Jundishapur J Nat Pharm Prod 2018;13: e13866.
  7.  Arabrahmatipour G, Ebadollahinatanzi A. The accelerated removal of kidney stones by concomitant use of camel thorn distillate and Rowatinex drug: A case report. Toxicol Lett 2018;295S: 265.
  8. Zargari A. Medicinal plants. Volume 4, 6th ed. Iran: Tehran University Publication; 1997.
  1. -Naghdi Badi H, Dastpak A, Ziai S. A review of Psyllium plant (Plantago ovata Forsk. and Plantago psyllium L.). J Med Plants 2004;1:1-14.
  2. Ruiz-Ruiz JC, Matus-Basto AJ, Acereto-Escoffié P, Segura-Campos MR. Antioxidant and anti-inflammatory activities of phenolic compounds isolated from Melipona beecheii honey. Food Agr Immunol 2017;28: 1424-37.
  3. Fang CH, Tsai CC, Shyong YJ, Yang CT, Li KY, LIn YW, et al. Effects of Highly oxygenated water in a hyperuricemia rat model. J Healthc Eng 2020;2020: 1323270.
  4. World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Bull. World Health Organ 2001; 79:373-4. Available from: https://apps.who.int/iris/handle/10665/268312.
  5. Fallah Huseini H, Fakhrzadeh H, Dastpak  A, Azarabadi  M, Mohtashami Tokabny R. Review of antihyperlipedemic herbal medicine. J Med Plants 2005;3: 9-20.
    1. Diez R, Garcia JJ, Diez MJ, Sierra M, Sahagun AM, Calle AP, et al. Hypoglycemic and hypolipidemic potential of a high fiber diet in healthy versus diabetic rabbits. Biomed Res Int 2013;2013: 960568.
  6. Prasad C, Iqbal U, Westfall S, Prakash S. Management of hyperuricemia and gout by prebiotics and probiotics: potentials and limitations. Int J Probiotics Prebiotics 2017;12: 5-16.
  7. Day RO, Graham GG, Hicks M, McLachlan AJ, Stocker SL, Williams KM. Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Clin Pharmacokinet 2007;46: 623–644.
  1. Hannan JMA, Ali L, Khaleque J, Akhter M, Flatt PR, Abdel-Wahab YHA. Aqueous extracts of husks of Plantago ovata reduce hyperglycaemia in type 1 and type 2 diabetes by inhibition of intestinal glucose absorption. Br J Nutr 2006;96: 131 –7.
  2. -Ziai SA, Larijani B, Akhoondzadeh S, Fakhrzadeh H, Dastpak A, Bandarian F,  et al. Psyllium decreased serum glucose and glycosylated hemoglobin significantly in diabetic outpatients. JEthnopharmacol 2005;102: 202 – 7.
  1. Ebadollahi-Natanzi A, Arab-Rahmatipour G. Psyllium together with allopurinol can efficiently reduce the increased serum level of uric acid, creatinine and urea: A case report. Iran J Toxicol 2017;11: 51-6.
  2. Potapovich AI, Kostyuk VA. Comparative study of antioxidant properties and cytoprotective activity of flavonoids. Biochemistry (Mosc) 2003;68: 514-19.
  3. Kinoshita T, Lepp Z, Kawai Y, Terao J, Chuman H. An integrated database of flavonoids. Biofactors 2006;26: 179-88.
  4. Ebadollahi Natanzi AR, Mahmoudian S, Minaeie B, Sabzevari O. Hepatoprotective activity of phloretin and hydroxychalcones against Acetaminophen induced hepatotoxicity in mice. Iran J Pharm Sci 2011;7: 89-97.
  5. Scalbert A, Manach C, Morand C, Remesy C, Jimenez L. Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr 2005;45: 287-306.
  6. Mo SF, Zhou F, Lv YZ, Hu QH, Zhang D, Kong LD. Hypouricemic action of selected flavonoids in mice: structure–activity relationships. Biol Pharm Bull 2007;30: 1551-6.
  1. Pacher P, Nivorozhkin A, Szabó C. Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Res 2006;58: 87–114.
  2. Gerdan V, Akkoc N, Ucan ES, Bulac Kir S. Paradoxical increase in uric acid level with allopurinol use in pyrazinamide-induced hyperuricemia. Singapore Med J 2013;54: e125-6.
  3. Salem CB, Slim R, Fathallah N, Hmouda H. Drug-induced hyperuricaemia and gout. Rheumatology 2017;56: 679-88.