Guarana (Paullinia cupana)

To evaluate the effectiveness of guaraná in fatigue and depression in 36 patients with breast cancer undergoing adjuvant radiotherapy.

Patients were randomized to 75 mg guaraná daily or placebo for two weeks, and then switched to the opposite treatment for the last two weeks of radiotherapy. Randomization was centralized by a pharmacist.

• The final sample size was 36 patients.
• Mean age was 59 years for the experimental group and 57 years for the control group.
• All participants were women.
• Patients were diagnosed with early stage breast cancer for which adjuvant radiotherapy was indicated.

Patients were recruited at Faculdade de Medicina da Fundação do ABC.

The study was a randomized, controlled crossover trial.

• Patients completed the Chalder Fatigue Scale, the Brief Fatigue Inventory (BFI), and the Beck Depression Inventory (BDI) Scale II.
• These assessments were conducted immediately before first radiotherapy, at switching, and right before the start of the last radiotherapy treatment.

No significant differences existed between the two groups on any of the scales. In addition, no side effects were reported from the guaraná.

This study showed no effect from guaraná on fatigue for this population.

The study used patients who reported no fatigue at the beginning of the study.

A currently fatigued population may be worth exploring with guaraná. Patients using guaraná for fatigue should be educated about the research findings.

To determine whether the average decrease in fatigue from days 1 (baseline) to 21 and from days 21 to 49 was greater in patients who received guarana versus placebo, as measured by Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) scores.

Patients received baseline evaluations with questionnaires, then 50 mg of guarana or placebo twice daily, study questionnaires 21 days later, and a seven-day washout of the drug. Patients were then crossed over to the opposite group for 21 days of the drug, followed by questionnaire completion and toxicity assessment.

• The study included 60 women with breast cancer.
• Mean age was 50.2 years in the placebo-guarana group and 51.76 years in the guarana-placebo group.
• All patients had worsening fatigue on the Brief Fatigue Inventory (BFI) for eligibility and were entered prior to their second cycle of initial chemotherapy.
• Those with severe fatigue were excluded.
   

The study took place in two public and academic hospitals in São Paulo, Brazil.
 

Patients were undergoing the active treatment phase of care.

This was a double-blind, placebo-controlled, randomized, crossover trial.

• General demographic questionnaire    
• FACIT-F
• FACIT-Endocrine Symptoms (FACIT-ES)
• Hospital Anxiety and Depression Scale (HADS)
• Pittsburgh Sleep Quality Index (PSQI)
• Chalder Fatigue Scale

More patients showed improvement in FACIT-F in the guarana group at day 21 (p = 0.01) and day 49 (p = 0.02). Chalder Fatigue Scale scores decreased by 4.6 points on day 21 (p < 0.01), with no significance for day 49 compared to placebo. Sleep improvement was seen at day 49 (p = 0.05). Four patients discontinued guarana use because of tachycardia. Analysis was conducted between groups on specific days of the study, rather than analyzing the intervention condition and control condition as a whole between groups.

Guarana showed a superior effect to placebo in improving fatigue in patients with breast cancer undergoing treatment.

• The study had a small sample size, with less than 100 patients.
• Only one tumor type was used, and common comorbidities were excluded. 
• The statistical analysis was conducted to compare results between groups at days 21 and 49, rather than at a specific time point in the study and analyzing the findings between the experimental and control condition. This is not a meaningful comparison study.
   

Guarana may be an option to treat fatigue in this population, but additional research is needed to provide support for its clinical use. Patients should be cautioned on its use if they have angina, other cardiovascular disease, uncontrolled hypertension, or neurologic disorders.

To evaluate the effect of dry extract guarana (PC-18) on cancer-related fatigue (CRF) in patients with solid tumors and to evaluate the effect of maintenance doses on CRF in patients who initially improve

PC-18 37.5 mg orally twice daily for 21 days. Those with improved or stable BFI scores were randomized to 37.5 mg BID dosing of PC-18 or placebo for an additional 21 days.

• N = 40 in the induction phase and 33 in the randomization phase
• MEAN AGE = 55.9 years in the induction phase, 52.17 years in the placebo group, and 58 years in the PC-18 group
• MALES: 42.5% induction, 39.4% randomization; FEMALES: 57.5% induction, 60.6% randomization
• KEY DISEASE CHARACTERISTICS: Breast: 25% induction, 30.3% randomization; colorectal: 22.5% induction, 21.2% randomization; lung: 10% induction, 9% randomization; head and neck: 12.5% induction, 9% randomization; other: 30% induction, 30% randomization.
• OTHER KEY SAMPLE CHARACTERISTICS: Cisplatin-based chemotherapy: 25% induction, 24% randomization; doxorubicin-based: 17.5% induction, 15% randomization. All participants receiving FLOX/Xelox/FOLFOX received PC-18 after randomization (15% of randomized participants). All receiving Folfiri also received placebo after randomization (15% of randomized participants).

• SITE: Multi-site  
• SETTING TYPE: Not specified  
• LOCATION: Sao Paulo, Brazil

• PHASE OF CARE: Active anti-tumor treatment

• Stage I, uncontrolled, open study
• Patient showing improvement or stabilized BFI scores were then randomized to continue study drug or placebo.

• Brief Fatigue Inventory
• FACIT-F
• Chalder
• HADS
• PSQI

Mean BFI score decreased by 2.503 points (p = .0002). No significant difference was noted between PC-18 and placebo groups after randomization in BFI (p = .8499), Chalder (p = .6321), FACIT-F (p = .7452), HADS-A (p = .7521), HADS-D (p = .9425), or PSQI (p = .807). There was one instance of grade III depression and one instance of grade III dizziness experienced in PC-18 that was not experienced in placebo. Grade II dizziness and tremors (one instance of each) also reported in PC-18 group, but not in placebo group.

BFI improvement was seen in the induction phase with no significant difference once patients were randomized. It is difficult to make any positive conclusions on guarana as all patients initially had the drug with no washout period before randomization. Potential side effects of guarana may be undesirable.

• Small sample (< 100)
• Risk of bias (no control group)

The study is limited by its sample size and study design. Use of guarana for CRF is not supported by this study.

To determine if the use of guarana extract affects fatigue or quality of life in patients with head and neck cancer undergoing chemoradiotherapy

Patients were randomized to receive either guarana or placebo, with both given twice daily before meals for six weeks while they were undergoing chemoradiotherapy. The patients receiving guarana took 50 mg twice daily. The patients were assessed three times throughout treatment at day 1, day 21, and day 42, and once three weeks after the completion of treatment on day 63. The three assessments during treatment corresponded with cisplatin administration. Each assessment included fatigue and quality of life questionnaires, evaluation for guarana toxicity according to the World Health Organization scale, as well as weight and renal function.

• N = 52   
• AGE = Not specified
• MALES (%): Not specified, FEMALES (%): Not specified
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Stage I–IV head and neck cancer, mainly squamous cell carcinoma. Patients underwent 30 sessions of radiotherapy and three cycles of cisplatin.

• SITE: Not stated/unknown   
• SETTING TYPE: Not specified    
• LOCATION: Brazil

PHASE OF CARE: Active antitumor treatment

Phase II, placebo-controlled, double-blind, randomized study

• General questionnaire
• Guarana Toxicity Assessment 
• Functional Assessment of Cancer Therapy-Fatigue (FACT-F)
• Functional Assessment of Cancer Therapy-Head and Neck (FACIT-HN), version 4.0
• European Organization of Research and Treatment of Cancer Core Quality of Life (EORTC QLQ-30) questionnaire
• EORTC QLQ-H&N-35 questionnaire

No statistically significant reduction in fatigue or improvement in quality of life was identified in either group using any questionnaire. Some initial or transient improvements were noted but were not statistically significant or did not last the length of treatment. The authors do not recommend the use of guarana in this patient population.

This intervention was not successful for this patient population. Although the authors reported some positive benefits, based upon the description of the results, it is unclear if this is related to the guarana or other factors that could influence quality of life in the patient population.

• Small sample (< 100)
• Measurement/methods not well described
• Subject withdrawals ≥ 10%

In terms of nursing practice, this study highlights the significance of malnutrition, weight loss, and mucositis in this patient population, and addressing these complications of chemotherapy and radiation in this patient population seems like a promising area for nursing attention and research.