Fresh concerns over ‘killer’ herbal bitters

NAFDAC raises public alert on Galant brand after lab investigation found product contaminated with poisonous methanol
They are much sought after for their health benefits. They have become common medicines in many Nigerian homes. They promise to among other things boost libido and strength, and mental alertness. But recent researches have raised concerns that indiscriminate use of packaged herbal bitters may have a toxic effect on the spleen, pancreas and heart, and lead to sudden death. It has also been discovered by the National Agency for Food Drug Administration Control (NAFDAC) that some of the products are laden or rather adulterated with ‘poisonous’ methanol and could cause neurological problems and death. CHUKWUMA MUANYA reports.

THIRTY FIVE year-old Chukwudi Okoye died after bleeding through the mouth and nose. Chukwudi who got married in April 2015 died after gulping two cans of an alcoholic herbal bitters.
The consumption of this brand of bitters has led to several other deaths, which were reported to The Guardian Newspapers.
The Guardian took a sample of the product and lodged a formal complaint with the National Agency for Food and Drug Administration and Control (NAFDAC).

Director General of NAFDAC, Dr. Paul Orhii, told The Guardian, on Monday, in a telephone chat that NAFDAC has identified ‘killer’ bitters in the Nigeria market and has sent public alert even as it has placed the products on hold.
The Guardian had, last month, made an official complaint to the Agency after reports that the drink has led to the deaths of at least three Nigerians.

Orhii explained: “We did laboratory test and found that the bitters drink contains high levels of methanol. We are mopping up the drink from the market and we want Nigerians to stay away from the bitters. The bitters were registered as imported product but it looks like somebody is adulterating and faking it somewhere here. We have sent out a public alert.”
The public alert notes: “NAFDAC hereby alerts the general public on the circulation of a possible fake and adulterated drink Galant Bitters found to be contaminated with high levels of methanol.
“The Galant bitters registered by the agency is manufactured by Rita Food and Drink Limited, 30 Street, 4 Singapore Industrial Park, Thijan An District, Bing Doing Province, Vietnam.

Methanol poisoning causes neurological problems, including visual disturbances, blurred vision, blindness, nerve damage and insomnia. Ingestion of high levels of methanol often causes death.
“NAFDAC has placed all Galant bitters on hold nationwide and currently conducting an investigation to determine the source of the contamination. Any useful information should be forwarded to the nearest NAFDAC office.

The general public is hereby advised to desist from the consumption of Galant Bitters pending the outcome of the investigation.”
According to Wikipedia, a bitter is traditionally an alcoholic preparation flavored with botanical matter such that the end result is characterized by a bitter, sour, or bittersweet flavor. Numerous longstanding brands of bitters were originally developed as patent medicines, but are now sold as digestives and cocktail flavourings.

The botanical ingredients used in preparing bitters have historically consisted of aromatic herbs, bark, roots, and/or fruit for their flavour and medicinal properties. Some of the more common ingredients are cascarilla, cassia, gentian, orange peel, and cinchona bark.

Most bitters contain water and alcohol, the latter of which functions as a solvent for botanical extracts as well as a preservative. The alcoholic strength of bitters varies widely across different brands and styles.
Indeed, plant extracts, now popularised as ‘herbal medicines’, have been shown to prevent, treat, manage and cure several diseases from cough to cancer.

This proven efficacy has resulted in great patronage for any product that comes with the name ‘herbal’. Most companies are capitalising on this window to rip in more profits. From toothpaste to creams, health drinks to bread, the story is same.
The latest craze is herbal bitters. The manufacturers in an aggressive marketing drive claim they are recipes for indigestion, weight loss, youthfulness, strength among others.

Medicinal, herbal bitters contain blended ingredients in a water or alcohol (tincture) base. Originally sold as a digestive aids because of their ability to increase the production of saliva and digestive juices, bitters became popular in Europe in the 1600s. This was due in part to the opening of trade routes with China, where the origin of bitters can be traced back more than 5,000 years.
Today, herbal bitters are used primarily as digestive stimulants, detoxifiers and antibacterial agents and can be taken either internally or externally, depending on the manufacturer and treatment.

Phytochemical analysis shows that bitters contain complex carbohydrates, alkaloids, vitamins and minerals that have antioxidant, antiviral and antispasmodic properties. It has been shown that these ingredients work together to reduce inflammation, control pain, relax muscles and improve digestion and elimination. Bitters can also be effective as appetite stimulants in some people.
Nigerian researchers from the Department of Clinical Pharmacy and Pharmacy Administration, Faculty of Pharmacy, University of Ibadan, Ibadan, Oyo State, have evaluated the extent and pattern of use of herbal bitters among students in tertiary institutions.
Showande S. J. and Amokeodo O.S conducted the study, published in October 2014 edition of Tropical Journal of Pharmaceutical Research.

This was a cross sectional study where pre-tested structured questionnaires were administered to 1000 students. The questionnaire elicited information on the extent and pattern of use, self-reported indications, side effects experienced and possible drugs that were concomitantly co-administered with herbal bitters. Pearson Chi square, Fisher exact test and Relative risk ratio were used to detect association between gender and self-reported indications and side effects experienced with herbal bitters at a level of significance of p < 0.05.

The response rate and extent of use were 96 per cent and 40.9 per cent respectively. Herbal bitters were used for claims such as cleansers 88 (40.2 per cent), anti-infectives 48 (21.1 per cent), for rejuvenation 32 (14.0 per cent), and for weight loss 14 (6.1 per cent).

Self-reported side effects included dizziness 49 (22.0 per cent), loss of taste 46 (20.6 per cent) and nausea and vomiting 22 (9.7 per cent). Herbal bitters were also co-administered with anti-malarial 22 (6.3 per cent); analgesics 16 (4.5 per cent) and herbal supplements 13 (3.7 per cent). Reports of students using two different types of herbal bitter concurrently 15 (3.9 per cent) were also garnered. Male students experienced more side effects than females (p < 0.05).

The researchers concluded: “The co-administration of herbal bitters with allopathic medicines and the use of more than one herbal bitter at a time reported in this study can be addressed by the appropriate health authorities through proper educational programme.”

They further explained: “Majority of participants in our study used HB for indications such as vigour, indigestion, stomach ache, constipation, rejuvenation and as appetite stimulants. This responsible self-treating is sometimes not without attendant risks; even over the counter (OTC) self-medication has been found to cause severe form of adverse drug reactions (ADRs). The use of HB for wrong indications such as weight loss remedy causes diarrhoea and diuresis as reported by participants; these could cause severe consequences such as dehydration or hypovolemic shock.

A Label tag such as ‘These claims have not been evaluated by NAFDAC’ is a mandatory statement on every pack of HB to dissuade people from irresponsible use of these products. Not only are HB sometimes used for wrong indications, they are also administered via wrong routes such as the ophthalmic application. About one-tenth of the students applied various HB products to the eye/ear/nose. The phytochemicals and excipients in HB may be corrosive to mucus membrane; thus, great caution should be exercised in administering these products via these routes until studies are available to support its use in order to avoid permanent damage to the mucus membrane, cornea or the eardrum. Ophthalmic preparations are sterile but this cannot be said for HB, which are mostly unstandardized and may contain unquantifiable microbial load, posing danger to the eye/ear/nose when applied.

Scanty evidence exists of the beneficial effect of traditional medicine in the treatment of eye conditions yet harmful effects have been reported. Herbal bitters advertisements on print and electronic media also influenced about a quarter of the students into using these products. In Nigeria, the regulation of DTC advertisement of HB is not strict. Peripatetic hawking of these products in commuter buses and market places is common in the country.

The preponderance of these products and the unchecked advertisements have led to the use of HB for indications that are conjecture of the user or group of users resulting in inappropriate use. Mainly, these products are indicated for indigestion, appetite stimulation and as carminatives but users tend to administer them for various reasons like weight loss, as anti-infectives, to cure chronic diseases, stress relief and for rejuvenation. These are unsubstantiated indications. The general belief is that these products are capable of multiple indications because of their poly-herbal nature. They are commonly referred to in the western part of the country in the local parlance as ‘gbogbo nise’ literarily meaning ‘effective for all ailments’.

Inappropriate use of HB includes its administration to children, concomitant administration with other medicines and taking two or more HB simultaneously. Less than one-twentieth of the students use combination of bitters simultaneously with the notion that it will work better and faster. The reason was that herbal medicines such as herbal bitters contain multiple components and when two similar products are used together, there could be a potentiation of pharmacological effects resulting in increased activity.
“The use of HB with other allopathic medicines was also noticed in this study. Africans often supplement hospital prescriptions with recommendations from family members and traditional health practitioners in the hope of hastening recovery, which may sometimes result in ADR and cause emergency admissions leading to increase morbidity and mortality.

Bitters were co-administered with antimalarial, anti-infectives, analgesics and herbal supplements. Herbs contain secondary metabolites such as flavonoids, tannins, saponins and coumarins that are inhibitors of important cytochrome P450 isoforms responsible for the metabolism of most drugs. This interaction may potentiate the activity of the co-administered allopathic medicines and lead to toxic level of such drugs.

None of the side effects experienced by the study participants is listed on the product pack or the product inserts of the HB. Since there is no prior warning to the user, experiencing any of these side effects could make the user discontinue the use of the HB and thus aborting the supposed therapeutic benefit. Sometimes, users may tolerate some of the side effects that may be a warning signal for more troublesome ADR.

According to a Professor of Phytomedicine at the University of Benin, Edo State, MacDonald Idu, “If you are suffering wound infections and rashes, foods containing bitter principles are the best antidotes, while bitters are also indicated for treating skin disorders, fever, jaundice and loss of appetite.”

Idu said that several bitter components were bactericidal, germicidal and anti viral in their nature, as well anti inflammatory in effect. “Bitter foods are known to elevate the air mass element in your body and reduce the excess amount of ills in other elements.

Oriental herbal texts indicate that herbal bitters are very light and cold in their nature and the typical taste is due to the presence of various components like caffeine, alkaloids and a bitter principle called berberine. The extreme dryness of bitters assists your body to get rid of excessive mucus, watery storage particles and help remove pus from the wounds,” he said.
According to Oriental medicine, herbal bitters are beneficial as a slimming agent and this unique action helps people reduce their weight and increase bone weight.

Bitter foods are also expectorants in removing mucus from your air passage, as well as improve circulation,” Idu added.
Indeed, fresh herbal bitters from plants like Vernonia amygdalina (Bitter leaf), Ocimum gratissimum (scent leaf), Telfairia occidentalis (ugu), Citrus medica (lemon), Citrus aurantium (lime), Gongronema latifolium (utazi in Ibo, arokeke in Yoruba), among others have been shown to be effective and safe in relieving disease conditions. But fresh concerns have been raised over the safety of packaged ones.

Until now, most Nigerians believe that herbal medicines are natural and that medications of natural origin are not toxic or dangerous. There have been reports of acute and chronic intoxication resulting from the use of herbal remedies. Several researchers also reported that most herbal remedies exhibit organ specific toxicity, hence the delay in manifestation of toxic effects.
Lack of standardisation is a major concern regarding use of medicinal herbal medicines. Herbal medicines are complex mixtures in which the active ingredient may not be known or may be only a small percent of the total product. Some are believed to achieve their beneficial effects through the combined actions of several ingredients.

However, little is known about chronic toxicities that might be associated with their prolonged use. There has been minimal research to assess possible systemic toxicity that might be associated with high doses or due to chronic administration of products.
Most herbal medicines are not registered with NAFDAC. What NAFDAC does is to list the products after doing only toxicity tests.
So far, efforts made by regulatory authorities in ensuring safety of registered pharmaceutical products in Nigeria seem to concentrate on effects of these pharmaceuticals on renal and liver function test.

Researchers at the Toxicology Unit, Department of Pharmacology, College of Health Sciences, Nnamdi Azikiwe University, Nnewi, NAFDAC, Lagos Laboratory and Department of Biochemistry, College of Medical Sciences, Abia State University, Uturu, have alerted on the possibility of heavy metal toxicity from herbal products in Nigeria.

The researchers in a study titled “Heavy metal hazards of Nigerian herbal remedies” published in the Nigerian Journal of Pharmacology said that the result showed that 100 per cent of the samples tested contained elevated amounts of heavy metals. They added that the public health hazards from ingestion of herbal medicines should be identified and disclosed by in-depth risk assessment studies.

The study characterised the content of cadmium, copper, iron, nickel, selenium, zinc, lead and mercury in a random sample of Nigerian traditional products.
Ready-to-use herbal products were purchased from the open market and digested. The heavy metal content of the digested filtrate was determined.

Researchers have also demonstrated multiple organ toxicity of a Nigerian herbal supplement, U & D Sweet Bitter, in male albino rats. The study published in Pakistan Journal of Pharmaceutical Science suggests U & D Sweet Bitter may have toxic effect on the spleen, pancreas, and heart of male albino rat.
U & D Sweet Bitter is a registered herbal supplement prepared from roots, leaves, flowers and fruits of different herbs. It is very widely used and can be available in Eastern Nigeria. The marketing label acclaimed therapeutic indications in typhoid, malaria, and stomachache.

The researchers from Abia State University, College of Health Sciences, Uturu, Abia State, Toxicology Unit, Department of Pharmacology, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Anambra State and Department of Biochemistry, Federal University of Technology, Minna, Niger State, wrote: “In the three month study, three groups of albino rats (150-200g), 539, 1077 and 1616mg/kg aqueous extract of U & Dee Sweet Bitter, were administered orally while deionized water was given to the control group. Animals had access to deionized water and were fed ad libitum with rat chow for 90 days.

The feed and fluid consumption of the animals were measured on daily basis while the body weight was measured weekly. Animals were anaesthetised with ether after 90 days, bled sacrificed, heart, spleen and pancreas were excised and weighed. The following parameters were measured namely food and fluid intake, body weight, absolute and relative weights of the, spleen, pancreas, heart.

Serum glucose, low-density lipoproteins LDL (bad cholesterol), high-density lipoprotein HDL (good cholesterol) were also determined.
“Food and fluid consumption were not significantly affected. A significant increase in absolute and relative weights was observed while the weekly body weight did not show any significant difference between the control and U & Dee Sweet Bitter treated groups. A significant decrease in total serum cholesterol, low -density lipoprotein (LDL), and high-density lipoprotein (HDL) were seen in U & Dee Sweet Bitter treated groups. This study suggests that U & Dee Sweet Bitter may have toxic effect on the spleen, pancreas, and heart of male albino rat.”

However, Idu urged for caution on the use of packaged herbal bitters. He recommended home-made bitters, a combination of scent leaf, bitter leaf, Telfairia occidentalis leaf (ugu), Gongronema latifolium leaf (utazi in Igbo)) and lime peels blended into a juice and taken first thing in the morning and last thing at night.

“Avoid herbal bitters if you are pregnant or nursing and do not treat children with bitters. You should also avoid or stop taking bitters if you have been diagnosed with the following conditions: kidney disease, Irritable Bowel Syndrome (IBS), Crohn’s disease and chronic gall bladder issues,” Idu said.

He said that bitters could also cause adverse reactions if taken in combination with other drugs like sedatives, antidepressants and tetracycline antibiotics.
“Read the instructions and recommendations on the bottle carefully before you begin treatment and do not exceed the recommended dosage for bitters or any other herbal medication. You should always consult a physician before beginning treatment,” he said.