Quinine, Tonic Water, Cinchona Bark, Quinidine 

Summary:

Quinine is a compound found in the bark of the cinchona tree. Historically, quinine/cinchona bark was used to prevent and treat the disease malaria.  Purified quinine and/or cinchona bark is used to flavor tonic water, many bitter liqueurs, and other beverages.  The US government limits the amount of quinine (and related compounds) that may be used in beverages, because they can cause serious health complications. 

Some bartenders are making homemade tonic syrups from cinchona bark with unknown and possibly unsafe quantities of quinine. People consuming quinine in a cocktail setting have suffered from cinchonism, a series of health conditions related to ingesting too much quinine. One example of a quinine reaction is mentioned in this story [link]. Larger-than-allowed amounts of cinchona bark may cause extremely serious health effects in a small percentage of the population. 

Key Safety Issues:

• Quinine, Quinidine and other compounds found in cinchona bark can be hazardous to your health. The quantity of quinine and other cinchona alkaloids allowed in food and drink is regulated in many countries.
• Cinchonism: Quinine and other cinchona alkaloids can cause a condition called cinchonism. Often (but not always) reversible, cinchonism can cause vertigo, muscle weakness and incurable tinnitus.
• Prolonged QTc Syndrome: Small amounts of quinidine in cinchona bark can cause significant problems for people with Prolonged QTc Syndrome, an often undiagnosed heart condition. 
• Allergies: Though very uncommon, a percentage of the population is allergic to quinine.

COVID-19 Update:

This page has seen an increase in visitors since it was announced that two antimalarial drugs were under consideration for treatment of the coronavirus. 

Chloroquinine and Hydroxychloroquine are synthetic antimalarial drugs that were suggested as treatments for the coronavirus [info], but overdoses of these drugs have already lead to poisonings [link]. 

In cinchona tree bark beyond quinine we find other natural alkaloids quinidine, cinchonine, and cinchonidine. As discussed below, these can have impacts on a person's heart called Prolonged QTc Syndrome. Synthetic chloroquinine has also been associated with Prolonged QTc. 

Malaria is caused by  a plasmodium parasite. Coronavirus disease 2019 (COVID-19) is caused by a virus.

We are not medical professionals but in any case it is clear that one should Not attempt to treat or prevent malaria, COVID-19, or any other illness with cinchona tree bark. Follow your doctor's recommendations. 

Background:

In the 1600s, cinchona tree bark was discovered to be an effective treatment for the symptoms of the disease malaria. The bark is extremely bitter and was therefore consumed in beverages, typically sweetened ones. Some beverages today that contain cinchona bark or purified quinine (though not enough to cure malaria) include tonic water, Dubonnet, Lillet, Amaro Nonino, and Fernet-Branca. 

Quinine is an alkaloid (a category of organic compounds that have pronounced physiological actions on humans) found in cinchona bark. The bark also contains other alkaloids including quinidine, cinchonine, and cinchonidine. Too much quinine and/or the other cinchona alkaloids can cause health issues. Quinidine is of additional concern for health issues, please see below. 

Different varieties of cinchona contain varying amounts of quinine and other cinchona alkaloids. Companies that sell cinchona bark rarely list the analysis of the bark - the percentage of alkaloids contained- making it impossible without professional laboratory testing to know the final amount of cinchona alkaloids in a homemade product. We have seen the total quantities of cinchona alkaloids in scientific publications ranging from three to sixteen percent of the total weight of the bark. 

Cinchona bark is available for sale in solid pieces or in a fine powder. (Purified quinine is typically not available to consumers and only sold to licensed beverage producers.)  The powdered form of the bark is challenging to filter out of syrups after the flavor has been extracted, leaving more quinine in the finished product than with larger bark pieces. If the goal is to reduce the amount of cinchona alkaloids that make it into the final syrup, bark pieces would be a better choice than powdered cinchona.

Purified quinine (quinine sulfate or quinine hydrochloride) is usually only sold to licensed beverage manufacturers. It is very concentrated and only tiny amounts of it are used. Extreme caution must be used when working with purified quinine. 

Legal/Regulatory Issues:

United States:

Quinine is on the United States TTB's list of "Flavoring Substances and Adjuvants Subject to Limitation or Restriction" [link]. Purified quinine such as is used in tonic water ("Quinine, as the hydrochloride salt or sulfate salt") is limited to 83ppm "in carbonated beverages as a flavor." 

Cinchona bark, as is used in bitter liqueurs and tonic syrups ("Cinchona, Red & Yellow Bark") is limited to [link] use "in beverages only: not more than 83 ppm total cinchona alkaloids in finished beverage."

This means that it's not just the quinine in cinchona bark that's limited; it's the total quantity of quinine plus the other alkaloids including quinidine, cinchonine, and cinchonidine. 

The TTB also states [link] on their "Pre-Import Supplemental Information" form that "Cinchona Bark may not contribute more than 83ppm of total alkaloids (Equivalent to 58ppm of quinine) to the finished alcoholic beverage." This seems to  indicate that quinine is about 70% of total cinchona alkaloids. 

Canada:

According to a representative from Health Canada (email communication):

Quinine can be used as a flavouring agent in certain carbonated soft drinks such as tonic water. Health Canada does not set regulatory limits for food ingredients used as flavouring agents. However, any food product or beverage using a flavouring agent would be subject to general food safety provisions according to the Food and Drugs Act, which prohibits the sale of foods that contain a harmful substance.

The Joint Food and Agriculture Organization of the United Nations and World Health Organization Expert Committee on Food Additives (JECFA) evaluated quinine in 1993. It concluded that the use of levels of up to 100 mg/L or ppm, in soft drinks (e.g., tonic water) did not represent a safety concern. If an adverse reaction were reported, the Canadian Food Inspection Agency would conduct a food safety investigation and request a risk assessment from Health Canada. If Health Canada identified a risk from a product with a level greater than the JECFA level, Health Canada would recommend a product recall.

European Union

Quinine hydrochloride [link]: Allowed in beverages, alcoholic and non-alcoholic: Restrictions of use ML = 100 mg/kg , In spirit drinks as defined in Regulation (EC) No 110/2008 - not more than 250 mg/kg

Quinine sulphate [link]: ML = 250 mg/kg , In spirit drinks as defined in Regulation (EC) No 110/2008 - not more than 250 mg/kg

Quinine monohydrochloride dihydrate [link]: ML = 250 mg/kg , In spirit drinks as defined in Regulation (EC) No 110/2008 - not more than 250 mg/kg

Each of the above quinine forms states these levels are maximums "individually or in combination" with each other. 

Homemade Tonic Syrup

Many bartenders have been making tonic syrup in recent years. Tonic syrup is a concentrate with cinchona bark, a sweetener, and water, and often other ingredients; meant to be diluted with carbonated water to make tonic water. 

Small quantities of cinchona bark available for sale are not usually labelled with their cinchona alkaloid content. Though most tonic syrups are filtered, it is impossible to know how much quinine passes from the bark into the resulting syrup (even if we know the initial quinine amounts) without professional laboratory testing. 

By one estimate [link], the amount of quinine in a popular online recipe for tonic syrup would contain more than double the legal limit (when diluted with water to make tonic), and that estimation was based on bark 5% quinine (not taking into account other cinchona alkaloids). Some barks may have up to sixteen percent cinchona alkaloids, so this one example recipe could potentially (but not necessarily) have much higher than allowed quantities of cinchona alkaloids. 

As quinine powders and barks do not commonly list their cinchona alkaloid content, We tried to estimate how much bark could be used in a homemade quinine product to comply with the 83ppm legal limits in the United States. By our calculations if the bark contained 16 percent cinchona alkaloids (and the full bark was left in the final product or the cinchona alkaloids were fully extracted into it), then the quantity of bark allowed to be used per 1 liter bottle would only be .5 grams by weight. 

If the bark contained a lower amount of cinchona alkaloids, three percent by weight of the bark, by our calculations the total weight of bark used per liter would be 2.8 grams. That's less than the weight of three paperclips. (Note that these calculations are for reference only and do not denote a "safe" quantity of bark to be used.) These amounts would be for a finished product, as if you sweetened and carbonated the liter of liquid with the bark in it to make tonic water (rather than syrup). 

A tonic syrup may be considered a concentrate, however (the FDA describes the amount "in finished beverage"), so that if a tonic syrup gives instructions that it must be diluted to a certain amount, then it could be compliant with FDA guidance. For example, if the tonic syrup says to dilute it with three parts soda water to bring it under the FDA allowance. 

Most recipes for homemade tonic syrup starting from cinchona tree bark call for much more bark to be used than the legal limit, often ten times as much.  As described in the section on Health Concerns, it is possible at higher than permitted levels of cinchona alkaloids in beverages to not only to give oneself or one's customers the uncomfortable symptoms of cinchonism, but for a certain percentage (greater than 1 out of 100 customers) of the population the effects could be far more severe. 

Because of the severe medical complications that quinidine can have with more than 1% of the human population, we cannot in good faith recommend the use of raw cinchona bark or powder at bars, and encourage purchasers of quinine syrups to ensure that the products have been tested to meet FDA guidelines and labelled as such. 

Health Concerns:

An overdose of quinine, quinidine, or cinchona bark is called cinchonism. It describes multiple conditions rather than a single one. [link] Many bartenders and customers, particularly those experimenting with homemade tonic syrup recipes, have suffered the effects of cinchonism in recent years. Cinchonism can have short-lasting effects from tinnitus and muscle soreness, to life-threatening heart conditions, particularly in people with preexisting heart issues. 

Mid-20th Century cocktail books, including The Gentleman's Companion and The Fine Art of Mixing Drinks, warned of drinking too much tonic water to avoid cinchonism. (Modern levels of quinine in tonic are regulated.) In a medical setting, cinchonism can occur at even the therapeutic dose levels of quinine taken against malaria [link], but note that the therapeutic dose is much higher than is now allowed in beverages.

While most commercial tonic water uses purified quinine salts, home/bar recipes call for cinchona bark. The bark includes the other cinchona alkaloids that are regulated by the United States FDA. Quinidine, one of those other alkaloids, is of particular concern to people prone to cardiac arrhythmia. For a technical analysis of quinidine dangers by a medical doctor, please download the following PDF file: [ Quinidine by Matthew Powell]. From this analysis we learn:

• Quinidine can have serious impacts on heart rhythm, particularly those with "prolonged QTc."
•  Most people will not know if they have this condition, which can be exacerbated by medications including antibiotics and psychiatric medications. The number of people with prolonged QTc can be greater than 1%, or more than 1 out of every 100 customers. 
• Though products with cinchona alkaloids below the legal US limit should not impact this condition, the amounts of quinidine used in homemade tonic recipes could very well impact the hearth rhythms of people with this condition. Potentially this could have life-threatening impacts.
• Even in heart-healthy people, excessive consumption of very high-quinidine products could cause problems. 

Leg Cramps:

In addition to its use against malaria, quinine/cinchona tree bark has also been used to treat nighttime leg cramps or restless leg syndrome. However, the US FDA issued a warning [link] against this use: "Quinine is FDA-approved for the treatment of uncomplicated Plasmodium falciparum malaria. It is not considered safe and effective for the treatment or prevention of leg cramps-- an "off-label" (non-FDA-approved) use. Quinine is associated with serious and life-threatening adverse events, including thrombocytopenia, hypersensitivity reactions, and QT prolongation."

Symptoms: 

In response to "unapproved quinine products," the FDA described dangers associated with quinine [link]

Serious safety concerns, including fatalities, associated with drug products containing quinine are well-documented in the literature and in adverse drug events reported to the agency. One of these adverse events is quinine toxicity, a cluster of symptoms that includes tinnitus, dizziness, disorientation, nausea, visual changes, and auditory deficits. There is also evidence that quinine causes serious cardiac arrhythmias including torsades de pointes. People taking quinine are at risk of developing hypersensitivity to the drug and experiencing a serious, life-threatening, or fatal reaction as a consequence. Serious adverse reactions associated with quinine use also include severe skin reactions, thrombocytopenia (a decrease in blood platelets that can cause hemorrhage or clotting problems) and other serious hematological events, permanent visual and hearing disturbances, hypoglycemia, renal failure and generalized anaphylaxis. Overall, from 1969 through September 11, 2006, FDA received 665 reports of adverse events with serious outcomes associated with quinine use, including, 93 deaths. Many of the adverse events associated with quinine are dose-related, and because of age related differences in the rate at which quinine is eliminated from the body, the frequency and severity of adverse effects associated with quinine drug products may be greater in the elderly.

A very small number of people can have severe allergic reactions to quinine, as in this case profiled in the New York Times [link].

Additional Reading:

"Stop taking Quinine for night-time leg cramps," Consumer Reports, 2014 [link]

"Dangerous Drinks and How to Spot Them," Imbibe Magazine, 2017 [link]

"Cinchonism: too much of a good thing" High Desert Botanicals [link]