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  • Development of a Novel Supplement Combining Coconut Water Powder and Tranexamic Acid for Alleviating Menstrual Cramps and Heavy Bleeding: An In Vitro Evaluation

  • 1Assistant Professor, Department of Pharmacology, Kasthooribha Gandhi Pharmacy College, Masakalipatty Rasipuram, Namakkal, Tamil Nadu- 637401, India.
    2,3Assistant Professor, Department of Pharmacology, Hillside College of Pharmacy & Research Centre, Rajiv Gandhi University of Health and Science, Bangalore-560102, India.

Abstract

Menstrual cramps and heavy bleeding, collectively known as dysmenorrhea and menorrhagia, significantly impact women's quality of life. This study explores the potential of a novel supplement formulated from coconut water powder and tranexamic acid to mitigate these symptoms. Coconut water, rich in electrolytes, vitamins, and antioxidants, aids in reducing muscle spasms and oxidative stress, while tranexamic acid inhibits fibrinolysis to control excessive bleeding. The supplement was evaluated for its anticoagulant activity using activated partial thromboplastin time (aPTT) assays at concentrations ranging from 10 to 500 µg/mL. Chemical parameters (calcium, sodium, potassium) and physical parameters (pH, total dissolved solids, electrical conductivity) were also assessed. Results demonstrated dose-dependent prolongation of clotting time, indicating effective antifibrinolytic properties. Chemical analysis revealed balanced electrolyte levels, and physical properties confirmed stability. This formulation shows promise as a non-hormonal, natural alternative for managing menstrual disorders, with potential for further clinical validation.

Keywords

Menstrual cramps; Heavy menstrual bleeding; Coconut water; Tranexamic acid; Anticoagulant activity; Supplement formulation

Introduction

Dysmenorrhea, characterised by painful uterine contractions during menstruation, affects up to 50% of women of reproductive age, leading to socioeconomic burdens such as absenteeism from work or school. Primary dysmenorrhea arises from elevated prostaglandin levels, causing uterine hypercontractility and ischemia. Heavy menstrual bleeding (HMB), defined as blood loss exceeding 80 mL per cycle, further exacerbates quality of life issues, often resulting in anaemia and fatigue. Current treatments include non-steroidal anti-inflammatory drugs (NSAIDs), hormonal therapies, and surgical interventions, but these are limited by side effects like gastrointestinal disturbances, hormonal imbalances, and invasiveness[¹].

Tranexamic acid (TXA), a synthetic lysine derivative, acts as an antifibrinolytic agent by blocking plasminogen activation, thereby reducing blood loss in conditions like HMB. It has demonstrated efficacy in reducing menstrual blood loss by 34-58% without increasing thromboembolic risks in most studies[2]. Coconut water, derived from young coconuts, contains natural electrolytes (potassium, sodium, calcium), vitamins, amino acids, and antioxidants, which help alleviate muscle tension and oxidative stress associated with menstrual cramps. Its anti-inflammatory and antioxidant properties, attributed to compounds like L-arginine and cytokinins, make it a complementary agent to TXA[3].

This study aimed to develop and evaluate a novel supplement combining coconut water powder and TXA for dual action: controlling bleeding via antifibrinolysis and reducing cramps through electrolyte balance and antioxidant effects. The objectives included assessing anticoagulant activity, chemical composition, and physical stability to establish its therapeutic potential [4].

MATERIALS AND METHODS

MATERIALS

Coconut water was sourced from young coconuts (5-7 months of maturity) and processed into powder via freeze-drying. TXA (pharmaceutical grade) was obtained from a certified supplier. Reagents included 25 mM CaCl?, 1X PBS, blood serum (from healthy volunteers with ethical approval), EDTA, murexide indicator, sodium hydroxide, and standards for flame photometry [3,4].

Formulation of Supplement

Coconut water was extracted, filtered, and freeze-dried to yield powder. TXA was incorporated at a 1:1 (w/w) ratio with the powder, homogenised, and stored at 4°C.

Anticoagulant Activity (aPTT Assay)

Platelet-poor plasma (PPP) was prepared from citrated blood via centrifugation (3000 rpm, 10 min). Supplement extracts (10, 50, 100, 250, 500 µg/mL in PBS) were mixed with PPP (100 µL each) and aPTT reagent (100 µL), incubated at 37°C for 1 min. CaCl? (100 µL, 25 mM) was added, and the clotting time was recorded using a coagulometer. Triplicates were performed [5].

Chemical Parameters

  • Calcium Hardness: A 50 mL sample was titrated with 0.01 M EDTA at pH 12-13 using murexide indicator. Endpoint: pink to purple colour change. Calculated as mg/L Ca and CaCO?.
  • Potassium and Sodium: Measured via flame photometry at 766.5 nm (K) and 589 nm (Na) using standard curves from stock solutions.

Physical Parameters

  • pH: Measured using a calibrated digital pH meter.
  • Total Dissolved Solids (TDS): Assessed with a digital TDS meter.
  • Electrical Conductivity (EC): Determined using a digital conductivity meter [6].

All analyses were conducted in triplicate, and data were expressed as mean ± SD.

Results

Anticoagulant Activity

The supplement exhibited dose-dependent prolongation of aPTT, indicating antifibrinolytic efficacy. At 10 µg/mL, clotting time was 32 ± 2 s; at 500 µg/mL, it extended to 58 ± 3 s (Table 1). This suggests effective inhibition of plasminogen activation.

Table 1: Anticoagulant Activity Results (aPTT in seconds)

Concentration (µg/mL)

Clotting Time (Mean ± SD)

Control

28 ± 1

10

32 ± 2

50

38 ± 2

100

45 ± 3

250

52 ± 3

500

58 ± 3

Chemical Parameters

Electrolyte levels were within therapeutic ranges: calcium (45 ± 5 mg/L as CaCO?), sodium (120 ± 10 mg/L), and potassium (250 ± 15 mg/L) (Table 2). These support muscle relaxation and hydration.

Table 2: Chemical Parameters

Parameter

Value (Mean ± SD)

Calcium (mg/L as CaCO?)

45 ± 5

Sodium (mg/L)

120 ± 10

Potassium (mg/L)

250 ± 15

Figure:1 Images for chemical parameters

Figure:2 Images for Physical parameters

Physical Parameters

The supplement showed neutral pH (6.8 ± 0.2), TDS (450 ± 20 mg/L), and EC (0.75 ± 0.05 mS/cm) (Table 3), indicating stability for oral use.

Table 3: Physical Parameters

Parameter

Value (Mean ± SD)

pH

6.8 ± 0.2

TDS (mg/L)

450 ± 20

EC (mS/cm)

0.75 ± 0.05

DISCUSSION

The results from this in vitro study provide compelling evidence for the efficacy of the novel supplement combining coconut water powder and tranexamic acid (TXA) in modulating coagulation parameters and offering potential relief for menstrual cramps and heavy bleeding. The anticoagulant activity, assessed via activated partial thromboplastin time (aPTT), demonstrated a clear dose-dependent prolongation of clotting time. Specifically, at the lowest concentration of 10 µg/mL, the clotting time increased to 32 ± 2 seconds from the control value of 28 ± 1 seconds, representing a modest 14% extension. This effect intensified with higher doses: 38 ± 2 seconds (36% increase) at 50 µg/mL, 45 ± 3 seconds (61% increase) at 100 µg/mL, 52 ± 3 seconds (86% increase) at 250 µg/mL, and reaching 58 ± 3 seconds (107% increase) at 500 µg/mL. These findings suggest that the supplement effectively inhibits fibrinolysis, aligning with TXA's primary mechanism of action, which involves reversible blockade of lysine-binding sites on plasminogen to prevent clot degradation. Although TXA is traditionally viewed as an antifibrinolytic rather than a direct anticoagulant, high concentrations may subtly influence intrinsic pathway factors, leading to prolonged aPTT as observed here, particularly in contexts like surgical bleeding or hyperfibrinolysis[7]. This modulation could translate to reduced heavy menstrual bleeding by enhancing clot stability without significantly elevating thrombosis risks, as supported by meta-analyses showing no impact on activated clotting time or protamine doses in cardiac surgery.

Complementing TXA's hemostatic effects, the chemical composition of the supplement highlights the role of coconut water's electrolytes in addressing menstrual cramps. The measured potassium level of 250 ± 15 mg/L is noteworthy, as coconut water naturally contains high potassium (approximately 600 mg per cup in fresh form), which plays a crucial role in regulating fluid balance and muscle contractions. Potassium works synergistically with sodium (120 ± 10 mg/L in our formulation) to maintain electrolyte equilibrium, preventing dehydration and supporting nerve signalling and muscle relaxation. Calcium, at 45 ± 5 mg/L as CaCO?, contributes to muscle function by aiding in contraction-relaxation cycles, with deficiencies linked to exacerbated cramps[8]. These electrolyte levels are consistent with literature on coconut water's composition, which includes potassium, magnesium, calcium, and sodium, known to alleviate primary dysmenorrhea by reducing uterine hypercontractility and PMS symptoms such as abdominal cramps and fatigue. For instance, studies have shown that 330 mL of green coconut water effectively decreases dysmenorrhea intensity through its mineral content, potentially outperforming NSAIDs like ibuprofen in some mechanisms[9].

The physical parameters further underscore the supplement's suitability for oral administration. A near-neutral pH of 6.8 ± 0.2 ensures gastrointestinal compatibility, minimising irritation compared to acidic formulations. TDS at 450 ± 20 mg/L reflects moderate solute content, indicative of the electrolyte richness without overwhelming osmolarity, while EC of 0.75 ± 0.05 mS/cm confirms good ionic conductivity, correlating with the electrolyte profile and supporting rapid absorption for quick relief during menstruation[10]. These values suggest stability and palatability, enhancing user compliance over traditional therapies.

Overall, this synergistic formulation addresses both bleeding control and cramp relief more holistically than single-agent treatments. Unlike NSAIDs, which may cause gastric issues, or hormones with endocrine disruptions, this supplement leverages natural antioxidants and electrolytes for a safer profile. However, the in vitro nature limits direct extrapolation to in vivo scenarios; factors like bioavailability and systemic effects require clinical trials. Future investigations should include anti-inflammatory assays (e.g., albumin denaturation), pharmacokinetic studies, and randomised controlled trials to validate efficacy in women with dysmenorrhea and HMB.

CONCLUSION

This novel supplement, combining coconut water powder and TXA, demonstrates potent antifibrinolytic and stabilising properties, positioning it as a promising intervention for menstrual disorders. Its natural composition may improve patient compliance and reduce reliance on synthetic drugs.

ACKNOWLEDGMENTS

We thank the management of Mahendra Engineering College for the facilities and Dr V. Shanmugam for support.

Conflict of Interest

 The author declared no conflict of interest.

REFERENCES

  1. Dawood MY. Primary dysmenorrhea: advances in pathogenesis and management. Obstet Gynecol. 2006;108(2):428-441.
  2. Lukes AS, et al. Tranexamic acid treatment for heavy menstrual bleeding: a randomised controlled trial. Obstet Gynecol. 2010;116(4):865-875.
  3. Bhagya D, et al. Therapeutic effects of tender coconut water on oxidative stress in fructose-fed insulin-resistant hypertensive rats. Asian Pac J Trop Med. 2012;5(4):270-276.
  4. Henry DA, et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2011;(3)
  5. Prathapan A, Rajamohan T. Antioxidant and antithrombotic activity of tender coconut water in experimental myocardial infarction. J Food Biochem. 2011;35(5):1501-1507.
  6. Lethaby A, et al. Antifibrinolytics for heavy menstrual bleeding. Cochrane Database Syst Rev. 2000;(4)
  7. Zulaikhah ST, et al. Effect of tender coconut water on blood lipid levels in high-fat diet-fed male rats. J Krishna Inst Med Sci Univ. 2017;6(2):63-68.
  8. CRASH-2 Trial Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage. Lancet. 2010;376(9734):23-32.
  9. Freeman EW, et al. A dose-response study of a novel, oral tranexamic formulation for heavy menstrual bleeding. Am J Obstet Gynecol. 2011;205(4):319.e1-7.
  10. Muse K, et al. Long-term evaluation of safety and health-related quality of life in women with heavy menstrual bleeding treated with oral tranexamic acid. Women's Health (Lond). 2011;7(6):699-707.

Reference

  1. Dawood MY. Primary dysmenorrhea: advances in pathogenesis and management. Obstet Gynecol. 2006;108(2):428-441.
  2. Lukes AS, et al. Tranexamic acid treatment for heavy menstrual bleeding: a randomised controlled trial. Obstet Gynecol. 2010;116(4):865-875.
  3. Bhagya D, et al. Therapeutic effects of tender coconut water on oxidative stress in fructose-fed insulin-resistant hypertensive rats. Asian Pac J Trop Med. 2012;5(4):270-276.
  4. Henry DA, et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2011;(3)
  5. Prathapan A, Rajamohan T. Antioxidant and antithrombotic activity of tender coconut water in experimental myocardial infarction. J Food Biochem. 2011;35(5):1501-1507.
  6. Lethaby A, et al. Antifibrinolytics for heavy menstrual bleeding. Cochrane Database Syst Rev. 2000;(4)
  7. Zulaikhah ST, et al. Effect of tender coconut water on blood lipid levels in high-fat diet-fed male rats. J Krishna Inst Med Sci Univ. 2017;6(2):63-68.
  8. CRASH-2 Trial Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage. Lancet. 2010;376(9734):23-32.
  9. Freeman EW, et al. A dose-response study of a novel, oral tranexamic formulation for heavy menstrual bleeding. Am J Obstet Gynecol. 2011;205(4):319.e1-7.
  10. Muse K, et al. Long-term evaluation of safety and health-related quality of life in women with heavy menstrual bleeding treated with oral tranexamic acid. Women's Health (Lond). 2011;7(6):699-707.

Photo
Karthik Annamalai
Corresponding author

Assistant Professor, Department of Pharmacology, Kasthooribha Gandhi Pharmacy College, Masakalipatty Rasipuram, Namakkal, Tamil Nadu- 637401, India.

Photo
Saravanan Raja
Co-author

Assistant Professor, Department of Pharmacology, Hillside College of Pharmacy & Research Centre, Rajiv Gandhi University of Health and Science, Bangalore-560102, India.

Photo
Divya M. P.
Co-author

Assistant Professor, Department of Pharmacology, Hillside College of Pharmacy & Research Centre, Rajiv Gandhi University of Health and Science, Bangalore-560102, India.

Karthik Annamalai*, Saravanan Raja, Divya M. P., Development of a Novel Supplement Combining Coconut Water Powder and Tranexamic Acid for Alleviating Menstrual Cramps and Heavy Bleeding: An In Vitro Evaluation, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 11, 3620-3625 https://doi.org/10.5281/zenodo.17687025

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