4. Health benefits conferred by the constituents of Areca nut. Part-I (Procyanidins)

 

Areca nut contains a large number of phenolic compounds in substantial quantity. Depending on the stage of maturity they are harvested, and the method of processing, the concentration of phenolic content and type of phenolic compounds can vary. In general, total phenolic content are found to be highest in the areca nuts of 4-5 months maturity and keeps decreasing as it reaches maturity. Flavonoids (flavones, flavanones, flavanols, flavonols), phenolic acids and polyphenols (procyanidins, areca tannins etc.) are some of the important classes of phenolic compounds found in areca nuts. These compounds are responsible for the dark brownish colour in the boiled nuts (Red supari). They impart astringent taste to the nut. They turn red in the presence of lime. Most of the perceived therapeutic properties of areca nut are attributed to these flavonoids, phenolic acids and polyphenols. Almost all of them are highly potent antioxidants.

B-type procyanidins are found to be one of the most abundant phenolic compounds found in Areca nuts. B-type procyanidins can be categorized by their degree of polymerization: monomers form linkages leading to oligomers. The most common monomeric unit is (–)-epicatechin. B-type procyanidins containing 2–7 monomeric units are defined as oligoprocyanidins. They are abundantly available in Red supari (kempadike), produced out of areca nuts of  6-7 months maturity and Bing lang. These procyanidins are also present in abundance in Cocoa, apples, grape seeds, and red wine.

Various conclusive evidence suggests that the intake of foods rich in B-type procyanidins is linked to reduced risk for cardiovascular disease including coronary heart disease, myocardial infarction, and stroke. Randomized controlled trials and subsequent meta-analyses have confirmed that the dark chocolate containing large amounts of B-type procyanidins can mitigate states related to the metabolic syndrome, including hypertension, dyslipidemia (abnormally high levels of fats in the blood) and glucose intolerance. In addition, the latest largescale study found a 27% reduction in cardiovascular death by ingestion of cocoa flavanol fraction, which is rich in B-type procyanidin monomer and oligomers, for 3.6 years. Recent studies have focused on the benefit of B-type procyanidin ingestion for the central nervous system (CNS).

Almost all B-type procyanidins ingested in food move into the colon, and some are degraded by the beneficial bacteria residing in the small intestine. Further it is broken down into low molecular weight phenolic acids in the large intestine (colon). Because of their smaller size, monomeric procyanidins are more absorbable than dimeric procyanidins.

References

1.  Osakabe et al., (2023) Hormetic response to B-type procyanidin ingestion involves stress-related neuromodulation via the gut-brain axis: Preclinical and clinical observations, Frontier in Nutrition, DOI 10.3389/fnut.2022.969823.

2.   Dasiman et al., (2022) A Review of Procyanidin: Updates on Current Bioactivities and Potential Health Benefits, Biointerface Research in Applied Chemistry, Vol. 2 (5), pp. 5918 - 5940

3. Health benefits of Arecoline and Areca extracts as per contemporary research

 

Arecoline is a naturally occurring psychoactive alkaloid found in the pericarp (seeds) of Areca nuts of the areca palm (Areca catechu). Arecoline, arecaidine, guvacine, and guvacoline are the most important and prominent alkaloids found in the areca nut. Nicotine, dichroine, acatechu A, acatechu B, homoarecoline, N-ethyl-1,2,5,6-tetrahydro-1-methyl-3-pyridine carboxamide and arecatemines are some of the minor alkaloids found in areca nuts. Arecoline is found to be the most important alkaloid among all, due to its role in modulating many physiological functions upon human consumption. It is found to enhance alertness and learnability, enhance the mood, gives a feeling of great pleasure, causes awakening, stimulates the sexual desire, reduces anxiety and promote calmness.

Arecoline has a wide spectrum of pharmacological effects beyond Central Nervous System modulating cardiovascular, digestive and endocrine systems as well.  Like nicotine, arecoline also evokes addiction and withdrawal symptoms (upon discontinuation). Withdrawal symptoms could be mood swings, anxiety, irritability and insomnia. Due to its addictive nature and activity on central nervous system, it has become the fourth most commonly used human psychoactive substance after alcohol, nicotine, and caffeine. How arecoline is converted to other forms, and disposed in the human body is complex and poorly understood.

Liu & Chang have listed the therapeutic values of arecoline in their review article “The Controversial Roles of Areca Nut: Medicine or Toxin?” published in International Journal of Molecular Sciences. They concluded that arecoline and areca nut extracts can be used for developing alternate therapy for gastroesophageal reflux disease & can be used to stop the progression of hepatocellular carcinoma cells (liver cancer) and the progression of Alzheimer’s disease, eliminate the negative symptoms of psychosis, can be used as various types of worms (take worm, liver fluke, pin worms etc.). They observed that arecoline possesses anxiolytic-like activity.

Volgin and coworkers have concluded that arecoline and related compounds have a considerable potential in medicine with multiple positive neural effects, in their scientific review published in “ACS Chemical Neuroscience” (An American Chemical Society Journal). They went on to propose that Arecoline can be used effectively in neurology and psychiatry. They opined that further translational research is needed to focus on molecular mechanisms of arecoline pharmacology in both clinical and animal models, and to develop low-risk analogues of this drug for future clinical uses.

References:

Liu & Chang (2023). The Controversial Roles of Areca Nut: Medicine or Toxin?, International Journal of Molecular Science, Vol. 24, 8996.

Volgin et al. (2019). DARK Classics in Chemical Neuroscience: Arecoline, ACS Chemical  Neuroscience, Vol. 10 (5) 2176–2185.

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2. Health benefits of areca nut and its products as per Traditional Chinese Medicine system

 

Traditional Chinese medicine (TCM) has evolved over thousands of years. TCM practitioners use various psychological and/or physical approaches (such as acupuncture and tai chi) as well as herbal products to address health problems. Areca nut is an important ingredient in Traditional Chinese medicine. Traditional Chinese medicine system believes that areca nut has the effects of "killing parasites, breaking accumulation, reducing qi and stagnation, and promoting hydration". Areca nut has been used to treat tapeworms, hookworms, roundworms, worms, ginger worms and other parasitic infections.

"Compendium of Materia Medica" records that areca nut has many effects such as "down edema, joint joints, spleen tone, and heartache accumulation". Areca nut also has the functions of treating glaucoma, increasing blood pressure, stopping diarrhea and treating diarrhea, reducing inflammation and swelling, removing phlegm and asthma, purging qi and water, and killing parasites.

Binglong (areca nut ) Pill is frequently used for reinforcing vital energy. The combination of pumpkin seed and areca is most widely used, which comes from the prescription of ‘Qu Tao Tang’ (Cestode-expelling Decoction). The constituents of ‘Qu Tao Tang’ (Cestode-expelling Decoction) are very simple, 60–120 g fresh pumpkin seeds and 30–60 g areca. Areca is ground with a pestle, soaked for a few hours in 400 ml of water, decocted to 100 ml, and filtered, and the debris of the decoction are discarded. The treatment procedure consists of two steps: first, chewing up fresh pumpkin seeds or taking the powder form of it ground in advance and then drinking the decoction of areca 2 h later. Anhydrous sodium sulphate is used as laxative along with this. The worm was quickly paralyzed from head to tail with a mixture of betel nut and pumpkin seed water extract. Worm bodies would be discharged along with diarrhoea 4–5 h later.

More than 31 different formulations are being used for treating dysentery, abdominal distension, dyspepsia, parasitic diseases and constipation etc. The raw areca and charred areca nuts are the most common clinically used forms. The Charred areca nut is commonly prepared by stir-baking to a yellowish colour, stir-baking to dark brown, or carbonizing by stir-frying.

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1. Health benefits of areca nut / Tambula as per ancient Indian treatises

 

One of the earliest references describing the good qualities of Tambula is found in charter 77 of the Brhatsamhita of Varāhamihira believed to be written in 500 CE in Sanskrit. It says, “Tambula stimulates love, sets off the physical charm, creates popularity, gives good smell to the mouth, strengthens the body and dispels diseases arising from the phlegm”.

Areca nut has been mentioned in several ancient treatises such as Charaka Samhita, Susruta Samhita, Astanga Hridayam, Bhavaprakasa, Harivamsa, and Varahapurana. These classical texts consider areca nut as astringent and slightly sweet (kasaya), cold in potency (hima), helps taste (rucya), Removes moisture and dirt of the mouth (asyakleda malapaha) and bad taste (vaktravairsaya), creates dryness (ruksa), heavy for digestion (guru), stimulates digestion (dipana), it is purgative (bhedi) and intoxicant (mohana). Choorna of areca nut has been prescribed with several other medicinal ingredients for treating liver ailments as per Charakasamhita, which was believed to be written during 100 BCE to 200 CE.

As per Vatsayana’s Kamasutra, a noble person (nāgaraka) cleans his/her teeth and perfumes himself/herself in the morning, uses mouthwash, and chew some Tambula (Mixture of areca nut with slacked lime smeared betel leaf) to make himself / herself presentable. The Tambula chewing is considered as an integral part of an elaborate sexual act as per the Kamasutra. In the Kāmasūtra, it is suggested that a lover should use Tambula both as a precursor to sexual relations, at various points during the sexual act, and as a post-coital activity marking a ritualistic finish and freshening of the breath.

Jyotirnibandha written by Shivraj in AD 1524, prescribes that three parts nut, two parts betel leaf, one-part catechu and lime make an ideal Tambula. Apparently, the composition prescribed is based on weight. As per this treatise, the Tambula prepared as per this formula, shall produce pungency, bitterness, heat, sweetness, saltiness, power to remove Vata, possess antiseptic character, remove phlegm, excite passion, beautify the mouth, purify the mouth, and remove all bad odour from the mouth. The work also indicates that different numbers of areca nuts confer differing outcomes: one produces happiness; two bears fruit; three brings loss; four causes pain of misery; five brings long life; six causes death.

References

1.     P. K. Gode (1950). Studies in the history of tāmbūla — history of the verse about the thirteen qualities of tāmbūla — between A.D 1200 and 1900, Annals of the Bhandarkar Oriental Research Institute, Vol. 31, No. ¼, pp. 138-142.

2.     Andrea Gutierrez (2015). Modes of betel consumption in early India, Religion and Food, Scripta Instituti Donneriani Aboensis, Vol 26, pp. 114–34

3.      Ahuja & Ahuja (2011). Betel Leaf and Betel Nut in lndia: History and Uses, Asian Agri-History Vol. 15, No. l, pp. 13-35.

4.      Kosambi D.D (1964). The Culture and Civilisation of Ancient India in Historical Outline. First edition. Taylor & Francis. Landon.

11. Some of the most criticized IARC reports: Alcoholic beverages, Part-III

 

IARC released a monograph on alcohol consumption in 2010 (Vol 96). This monograph was prepared by a working group comprising 27 members drawn from reputed labs of 16 different countries. The monograph focused on beer, wine and spirits (whiskey, brandy, rum, vodka, Scotch and Gin etc..). Working Group concluded that acetaldehyde, the primary metabolite of ethanol, is the carcinogen that leads to the formation of various type of cancer. Working Group concluded that a large body of evidence from epidemiological studies of different design and conducted in different populations consistently shows that consumption of alcoholic beverages is associated with a higher risk for both oral and pharyngeal cancer, and that the risk increases with increasing amounts of alcohol consumed. Compared with non-drinkers, regular consumption of about 50 g alcohol (ethanol) per day (equivalent to about 150 ml of distilled spirits) is associated with an approximately threefold increase in risk oral and pharyngeal cancer cancers, two-fold increase in laryngeal & esophagus cancer. These studies provide firm evidence that the consumption of alcoholic beverages are an independent risk factor for primary liver cancer. The working group found sufficient evidence in experimental animals for the carcinogenicity of ethanol and acetaldehyde (the ethanol metabolite).  

The working group gave an overall evaluation as follows, 

 ·       Alcoholic beverages are carcinogenic to humans (Group 1).

·        Ethanol in alcoholic beverages is carcinogenic to humans (Group 1).

As per the data presented in the same IARC monograph, in Eastern European block countries (Belarus, Estonia, Hungary, Kazakhstan, Latvia, Lithuania, Republic of Moldova, Russian Federation, Ukraine), 63.7 % men consume more than 40 g of pure alcohol (in the form of alcoholic beverages) per day. Incidence of cancer in that bloc is supposed to be substantially higher compared to other regions. However, the data presented in the same monograph doesn’t provide the evidence for the same. This appears to be a serious anomaly.