Fact or Fiction – Biogenic Amines in Beer

A recent topic that recently has become of some concern among wild brewers is the potential risk presented by biogenic amines. But what are biogenic amines, why are they toxic, are they really a risk, and can we limit their production in beer?

Note: this article is a part of my Fact or Fiction series on microbial risks in brewing.

Note: Dave Janssen and I have prepared complementary posts on this topic. Follow this link to view his article which focuses on the timing and production of biogenic amines during spontaneous fermentation.

What Are Biogenic Amines?

Biogenic amines (abbreviated as “BAs” from now on) are a large class of chemicals produced by all living things. They are generally made by decarboxylation of amino acids – i.e. the removal of acid groups from the building blocks of proteins. They can also be formed by amination (addition of nitrogen) of other simple chemicals. Regardless of how they are synthesised, these chemicals share a few features – they are relatively small, volatile, and contain one or more amine (nitrogen-containing) chemical groups.

BAs can be waste products, metabolic intermediaries (chemicals synthesised as part of a larger biological process), or can be functional molecules. Histamine is an example of the latter – it is produced by our bodies as regulator of our immune system and of blood pressure. Cadaverine is an example of a waste product – as its name suggests, this is a compound produced during the decomposition of cadavers (and other dead animals), and is not normally made by the human body.

Intro to Toxicity

The concept of toxicity isn’t completely straight forward. Clinically, we tend to define a toxic dose as a dose which causes a measurable, negative effect on a biological parameter. For example, one of the first measurable toxic effects of the biogenic amine histamine is a drop in blood pressure, which occurs after you consume more than 10 mg per kg of body weight (e.g. for the average 82kg/180lb man, you would need to eat >800 mg (0.03 oz) of histamine). This is much lower than the acutely lethal dose of 220 mg/kg.

A second thing to consider is the possibility of cumulative damage. This occurs via two possible routes. Firstly, some compounds will accumulate in tissues, allowing their concentration to build to toxic levels over time – assuming that there are repeat exposures. Secondly, some compounds may be cleared quickly, but cause irreversible (or slow to repair) damage, allowing damage to accumulate over successive exposures. Of course, those are not mutually exclusive phenomenon, with some of the most toxic compounds engaging in both of those activities. But good news brewers – BAs are not known to have cumulative effects, and are rapidly cleared from the body, so we need to only worry ourselves about acute effects.

Thirdly, there can be additive or synergistic effects between multiple BAs. In other words, the presence of one BA can enhance the toxic effect of another BA. Meaning that in foods with multiple BAs, the actual toxic risk may be higher than the levels of individual BAs suggest. While these effects are known to occur, they are thankfully small effects, meaning that so long as no single BA approaches the maximum safe dose,the food should be safe.

All that said the maximum safe dose of a BA is not a good maximum limit for foods. This is because other undesired effects can occur below this limit. Histamine is a great example – at concentrations well below its maximum safe dose it can induce migraines and headaches, plus has an unpleasant aroma/flavour. So the maximum acceptable dose in a food is likely going to be below the maximum safe dose.

There is one final consideration that needs to be made when discussing BA toxicity – that being the interactions between BAs and monoamine oxidase inhibitors (MAOI’s, commonly used to treat depression). Many BAs are broken down by monoamine oxidases, meaning patients on MAOIs have an impaired ability to process BAs. This has resulted in a few cases of hypertensive crises (extreme high blood pressure) following consumption of BA-rich foods such as cheese. Patients on MAOI’s are supposed to avoid alcoholic beverages, so the risk to this patient population is (in theory) minimal.

Biogenic Amines in Foods and Beer

Because biogenic amines are a large class of chemicals, there is not a singular manner in which they are toxic. Likewise, each BA has its own safe versus toxic dose and toxic effect. Given that all organisms produce them, it is not surprising that we can tolerate fairly high doses of many BAs, and that some can even be used as a source of nutrition. In some foods – especially fermented foods such as cheese and yoghurt – BAs are often key flavour and aroma compounds critical to the character of these foods. They may also contribute to the unique character of spontaneously fermented beers, although this remains somewhat controversial.

That said, hard limits on some BAs have been established for certain foods. For example, histamine is often found in spoiled sea foods, leading to several countries to place limits on histamine in these foods. Depending on the country, allowable histamine levels vary between 50-100 PPM, with some countries also set a max of 300 – 500 PPM of total BAs. Given that these are food safety standards, they represent a 10-fold (or more) lower dose than where actual toxicity would be observed. However, these limits are not the same across all foods – for example, in the EU cheeses can be sold with BAs above 4000 PPM; this is still considered safe as the amount of cheese you would have to consume to hit a toxic dose is well beyond what any person could physically consume.

This brings up a critical issue when discussing toxicity – the concentration in the food is only one factor; the quantity of food you can expect you/your customer to consume also matters. Beer is (sometimes) consumed in fairly large amounts, so lower BA concentrations may impart a toxic effect relative to an equivalent concentration in a food like cheese. Below, I’m going to do a deeper dive into BAs doses in beer, and you will see that you need to consider not just the concentration of BAs, but also the volume of beer being consumed and the weight of the person consuming the beer.

Risk in Brewing

Because all living organisms produce biogenic amines, their presence is both normal and expected in beer. There is no conceivable mechanism in which we could produce a beer free of BAs, given that these will be provided to the wort from our malt, hops and yeast/bugs. So the presence of them is normal – the question is whether we ever see them at doses which would be toxic following consumption of a normal amount of beer – with all of the other complexities discussed above factored in.

As an example, a beer that delivered 5 mg of histamine per kilogram of customer body weight could be considered “safe”, as you’d be below the 10 mg/kg maximum safe dose. But from a brewers perspective this would be far too high to be acceptable. Firstly, because there is likely to be other BAs in the beer, there is a risk that additive effects between BAs could cause a toxic effect. In addition, this dose is well within the range that causes other unpleasant effects – headache or migraine – in some people. Finally, this would also be a beer with histamine well above its flavour threshold, meaning your beer would have the flavour and aroma of spoiled fish. So a food-safe (and customer-acceptable) dose would be much lower than a toxic dose – generally 1/10th to 1/100th the maximum safe dose.

A number of studies have looked into BA concentrations in beer (examples: Paper 1, Paper 2), with a lot more work conducted in wine. Dave Jansses is preparing a parallel article on BAs (link coming soon), and was kind enough to share a table of BA concentrations in several styles of beer, which he assembled from a variety of sources (see table, below). Looking at the table, it is obvious that BAs are not of concern in clean beers – a person would have to drink hundreds of litres of beer in a sitting to get anywhere near a toxic dose of BAs, and the concentrations also are well below the aroma/flavour threshold for these compounds.

Lambics (and presumably other wild beers) are a different story, having much higher levels of BAs due to the activity of bacteria during fermentation. The highest single risk is histamine in 2-year old lambic (16-18 mg/L versus 10 mg/kg maximum safe dose). Meaning that your average 82 kg man would need to consume ~45 L of lambic in one sitting to hit the maximum safe dose. In other words, you’d be dead of alcohol poisoning long before the BA’s would get you. But that is no reason to be complacent – keep in mind that while 45 L avoids medically visible signs of BA toxicity, other effects can occur well below that volume of beer. This includes unwanted flavour/aroma, and the potential to induce migraines, headache, or other unpleasant sensations in you/your consumer. Again, we typically want to have less than 1/10th the maximum safe dose in a food item – using that standard, your 82 kg man would be safe to drink 4.5L in one sitting – again, more than most people would consume…but getting uncomfortably close to that limit.

But also consider that there are additive effects between BAs; especially between vasoactive BAs. Tyramine is another vasoacive BA found in lambic, at relatively high concentrations. Tyramine and histamine are known to engage in additive effects, and while there is not good data on how potent this effect is, we should assume that in beers containing both that we’d want to limit ourselves to half the maximum safe dose of each – equivalent to ~25 L of lambic (in terms of staying below the maximum safe dose) or 2.5 L of lambic (in terms of avoiding other unwanted effects) in one sitting…and less than that for a smaller person. As little as 0.5 L of lambic may contain enough BAs to trigger a migraine in a highly susceptible individual.

In other words, lambic and other spontaneous beers, when prepared using traditional methods, do not contain enough BAs to have an acutely toxic effect on drinkers. But they can contain enough BAs to have other unwanted effects – both in terms of the character of the beer, but also in terms of potentially inducing unpleasant sensations in you or your consumer.

Where Are BAs Coming From & What Can We Do About Them?

As you may have predicted, it is the bacteria present in mixed fermentations which generate the “extra” biogenic amines found in these beers. Both Gram negative (e.g. the enterobacteria often present early in wild ferments) and Gram positives (Lactobacillus/Pediococcus) produce BAs, with about half of the total BAs produced by the Gram negatives, and the remainder by the Gram positives.

As you may expect, pre-acidifying the wort to suppress Gram negatives has a beneficial effect in terms of total BAs present in the finished beer. One study predicted an ~50% decrease in total BAs following acidification, a nice margin in terms of reducing the unwanted flavours and potential negative effects on the drinker imparted by BAs. The benefit of pre-acidification is understated if you consider only total BAs, as Gram negatives tend to produce more of the vasoactive (e.g. bad – histamine and tyramine) BAs than do Gram positives.

What This Means in the Brewery

At the end of the day, the only question that really matters is what does this mean to me/my customers?

If all you brew are clean beers, than this means that biogenic amines are not something that you have to concern yourself with…so long as you don’t suffer infections in your beer.

But for sour/wild brewers (including, in all likelihood, people engaging in quick-souring), BAs are something to be aware of. It is highly unlikely that you will reach toxic levels in your beers – indeed, at those doses these compounds impart flavours and aromas that would make a beer unpalatable. But it is well within the realm of possibility that spontaneous/mixed/wild fermentations may produce sufficient BAs to impart unwanted flavours and aromas, and even to induce non-toxic but unpleasant effects in drinkers. Commercial brewers may also need to consider the possibility that BA levels may one day be regulated in their products, meaning that addressing them now may act to either stave off regulation or ensure that their brewery is compliant when/if regulation occurs.

For spontaneous/mixed culture brewers, it will not be possible to reduce BAs to the levels observed in clean beers. Indeed, ranges more typical of yoghurt and younger cheeses will be more typical. But there are some things we can do to limit their production:

1. Checking for BAs prior to blending or packaging. This can be done almost entirely by aroma – unpleasant/sharp scents (vomit, faeces, decomposition, cheesy, ammonia, fishy) indicate that biogenic amines are present at levels which should be avoided. Dedicated testing equipment should not be necessary, unless you are subject to strict legal limits.
2. Pre-acidify your wort to below a pH of 4.5 if you are spontaneously fermenting (coolshipping) or using unpurified wild cultures.
3. Use established (commercially available) mixed cultures in place of truly wild cultures.
4. Create “domesticated” cultures by mixing purified yeast and bacteria from previous wild ferments.
5. Extended ageing.

A Final Note

Often times these “Fact or Fiction” posts generate a lot of concern among some of my readers. So I thought it may be worth stating that it is extremely unlikely – almost to the point of impossibility – that you could brew a beer that contained concentrations of biogenic amines high enough to cause physical harm. Moreover, the conventional methods we use to produce mixed culture/wild/spontaneous beers should be more than sufficient to reduce this risk to an acceptable level, and there are easy-to-employ methods we can use to further control this risk.

As is almost always the case in these discussions, the alcohol in our beers is many hundreds (if not thousands) of times a greater risk to our health than are BAs or other trace chemicals. Alcohol is present in large amounts in beer (a 5% ABV beer has 50,000 PPM ethanol), causes cumulative damage, and is directly responsible for nearly 3 million deaths world-wide each year.

In other words, drink in moderation – it’ll keep you safe from alcohol and from lesser risks such as BAs.