Increase in low ejection fraction of heart failure patients by using fresh betel leaves and capsule of dry betel leaves – A randomized clinical trial

STUDY

RATIONALE

Background and Purpose of the study:

Heart failure (HF) is a global public health problem that affects more than 26 million people worldwide. The global burden of heart failure is growing and is expected to increase substantially with the ageing of the population. Heart failure with reduced ejection fraction accounts for approximately 50% of all cases of heart failure in the United States and is associated with significant morbidity and reduced quality of life. Diseases like myocardial infarction, certain infectious diseases and endocrine disorders, can initiate a primary pathophysiological process that can lead to reduced ventricular function and to heart failure (Bloom, et al. 2017). The management of HF with reduced ejection fraction has seen significant scientific breakthrough in recent decades, and the ability to alter the natural history of the disease has never been better. Disease morbidity and mortality remain high, with a 5-year survival rate of 25% after hospitalization for HF with reduced ejection fraction (Murphy, S. P., Ibrahim, N. E., & Januzzi, J. L. (2020). Heart failure is a progressive condition. Approximately one-half of HF patients have heart failure with reduced ejection fraction (HFrEF). In the real-world setting, 1 in 6 patients with HFrEF develop worsening HF within 18 months of HF diagnosis. These patients have a high risk for 2-year mortality and recurrent HF hospitalizations. The use of standard-of-care therapies both before and after the onset of worsening HF is low. With high unmet medical need, patients with worsening HF require novel treatment strategies as well as greater optimization of existing guideline-directed therapy.

 Importance of Nutrition in Heart Failure: Implementation of evidence-based nutrition strategies which have shown benefit in carefully controlled clinical trials may positively impact HF outcomes in a cross section of the HF population. Use of the DASH (Dietary Approach to Stop Hypertension) diet in diagnosed HF patients has not yet become standard of care in HF management as it has not been evaluated in pragmatic clinical trials. Many research studies evaluating the effectiveness and implementation of the DASH diet for outpatient HF management are acceptable and have the potential to influence the future health care approaches in CVD prevention, treatment, and management (Wickman, et al. 2021).  The gut microbiota plays a critical role in the pathogenesis of heart failure through complex signaling pathways and interactions. A healthy diet is able to reduce inflammation and promote healthy gut microbiota biodiversity that promotes cardio protective effects and also limits the progression of metabolic, cardiovascular and neurological diseases. Dietary interventions are promising non-pharmacologic therapeutic approaches that patients could benefit from and should be at the core of interventional studies. Future studies need to focus on the clinical application of several therapeutic interventions that have proved to be beneficial so far in order to reduce the prevalence of cardiovascular diseases (Masenga, et al. 2023)

 Betel leaves:

The fresh leaves of betel vine are popularly known as ‘Paan’ in India, which are consumed by about 15-20 million people in the country (Guha, P. (2006). Piper betle L., belonging to Piperaceae family, known as a traditional herbal medicinal plant, which are consumed by about 15-20 million people in the country. It is cultivated following the traditional methods in India on about 55,000 ha with an annual production worth about Rs 9000 million and used for several health benefits in Asian countries. Currently, demand for its products such as herbal drugs, medicines, and natural herbal formulations have increased. The beneficial effects of betel leaves and its products have traditionally exploited for the treatment of several diseases like bad breath, cuts, injuries, inflammations, cold cough, indigestion, etc. Till now, a broad range of bioactive compounds including polyphenols, terpenes, etc., has been identified from the extracts and essential oil of betel leaves (Guha, P. (2006), (Madhumita, M., Guha, P., & Nag, A. (2020).

Medicinal uses of betel leaves: Betel leaves have a tremendous potential as a potent source for novel therapeutic usage and has anti-fertility activities, anti-allergic activities, antiulcer property, antioxidant property, anticancer activity and many beneficial properties, these wide pharmacological profile reveals it to be fit for its future usage as a promising source for treating various conditions. Therefore, in the near future the standardization and stabilization studies on the leaf extract can be carried out which can help in improving its usage for varied medicinal usage (Rekha, V. et al. 2014)

Ayurveda Significance:

Piper betel is a Vedic plant and its Vedic name is Saptasira and in sankrit it known as Tambool, Nagvelleri, Nagani were used as remedy against various diseases. In most of these texts were various medicinal properties has been highlighted.  In Ayurveda betel leaf extract is frequently used as an adjuvant and mixed with different medicines possibly for better effects beside its independent use as medicine. In addition to these, the aphrodisiac effect of betel chewing has been indicated in ancient texts. Leaf also believed to provide strength to heart and regulate blood. Its utility as anti-inflammatory and anti-microbial is emphasized at several place. In Ayurveda it acts as vata and kapha suppressant. It also helps in expelling out the mucus from the respiratory tract because of its hot potency. The chewing of betel leaf results cardio-tonic action by accelerating catecholamine from adrenal cortex contributing to increase the stamina of the cardiac muscles, heart rate, blood pressure and sympathetic neural activity. It has also the platelet inhibition activity leads vasorelaxation effect mediated through endothelium dependent and nitric oxide pathways. Hence, betel leaf is beneficial for different cardiovascular disorders like Congestive heart failure, Coronary artery disease, acute myocardial infarction, atherosclerosis etc.  Leaf is considered to provide strength to the heart (cardio tonic) and regulates irregular heart beat and blood pressure (Pradhan, D., et al. (2013).

  

**Nutritive Values of 100
gms Betel leaves***

|Protein

2.5 gms

|Fibre

2 gms

|Energy

45 Kcal

|Vit K1

210 microgram

|Beta-Carotene

4.5 mg

|Lutein

5 mg

|Potassium

650 mg

|Calcium

210 mg

|Iron

3 mg

|Omega 3 fatty acids

150 mg

|Clorogenic acid

6.8 mg

|* Indian Food Composition tables-2017

                                   Thus we have seen that heart failure patients with low ejection fraction can be beneficial from lifestyle modification by dietary changes and exercise, as per Ayurveda betel leaves are useful in improve for cardiac health, so we will be conducted a nutrition intervention by including betel leaves in low ejection fraction cardiac patients to see any improvement in ejection fraction,  as betel leaves are available all over the India throughout the year.