Many of you may be familiar with names like histamine, tyramine, or dopamine. These substances are called "biogenic amines." Recently, discussions about biogenic amines (BA) in relation to wine have become increasingly common.
Biogenic amines occupy a somewhat different position from wine defects such as off-flavors. Due to their potential harm to human health, biogenic amines themselves have been studied for a long time from a food safety perspective. Research on wine has also existed for some time, but the number of studies has particularly increased around the year 2000.
Previously, sulfur dioxide added to wine was believed to be the cause of post-drinking headaches. However, the involvement of biogenic amines has now been pointed out. This can be seen as a result of deepened understanding of biogenic amines through verification studies.
While we increasingly hear and use the term "biogenic amines," explaining what they actually are is not simple when asked. The terminology is still somewhat ahead of actual understanding. This article explains what biogenic amines are.
Biogenic Amines as Organic Nitrogen Compounds
In simple terms, biogenic amines are organic nitrogen compounds synthesized within living organisms. Let's examine this in more detail.
First, biogenic amines are amines synthesized within living organisms. "Living organisms" here refers to all living things in general, including animals, plants, humans, and microorganisms. Next, "amines" are, chemically speaking, the general term for compounds in which hydrogen atoms of ammonia (NH₃) are replaced by hydrocarbon groups or aromatic groups. They can also be described as compounds having amine groups in their structure. Ammonia itself is also classified as an amine.
You probably often detect ammonia odors in daily life. However, no one directly drinks or eats ammonia. This is proof that humans synthesize ammonia within their bodies. In other words, amines and biogenic amines are not special substances—they are that commonplace.
What is important is that, as can be understood from ammonia being a compound of nitrogen and hydrogen, the raw material for amines is nitrogen. This is why biogenic amines are described as organic nitrogen compounds synthesized within living organisms.
Necessary Substances or Harmful Substances?
When biogenic amines are discussed, the focus is often on their toxicity to the human body. Indeed, much of the impetus for research on biogenic amines comes from attention to their toxicity.
Are you familiar with substances like adrenaline, dopamine, and serotonin? Recently, terms like adrenaline have become almost everyday vocabulary, with increasing opportunities to hear them. We don't often hear negative things about these substances. However, these are also biogenic amines.
Many biogenic amines play important physiological roles as hormones and neurotransmitters. They are said to play particularly important roles within cells exposed to strong stress. The reason adrenaline and dopamine do not generally cause major problems is that these biogenic amines are physiologically inactivated and detoxified by oxidative enzymes present in the intestinal tract.
Conversely, even biogenic amines that are not usually problematic can exhibit direct or indirect toxicity when their concentration in the body increases beyond the capacity for detoxification. The physiological action of biogenic amines is, in a sense, fighting poison with poison. Therefore, when the amount increases beyond control, they simply become poisonous.
Various symptoms caused by the toxicity of biogenic amines include headaches, breathing difficulties, palpitations, low or high blood pressure, intestinal histaminosis, and several allergic diseases. In the worst cases, the possibility of causing anaphylactic shock leading to death has also been pointed out.
Biogenic Amines Created by Enzymes
Biogenic amines, particularly those related to wine, are broadly classified by their chemical structure into aromatic amines, heterocyclic amines, and aliphatic amines. Basically, all three types are produced through the action of enzymes.
There are said to be four types of reaction pathways for enzyme action. It has been found that tyramine (TYR), classified as an aromatic amine and considered particularly harmful to humans, and histamine (HIM), classified as a heterocyclic amine, are generated through the decarboxylation reaction of amino acids by enzymes called decarboxylases.
Most biogenic amines are nitrogen compounds, meaning amino acids are their raw materials (nitrogen is a major constituent element of amino acids). However, some aliphatic amines are synthesized from non-nitrogen-containing compounds such as ketones and aldehydes through reactions called amination or transamination. These reactions are also mediated by enzymes within living organisms.
Additionally, among aliphatic amines, compounds called aliphatic volatile amines have no harmful effects on human health, but they are known to negatively affect sensory evaluation when present in wine.
The Relationship Between Biogenic Amines and Wine
So far, we have examined what biogenic amines are and what causes their formation. The important points are these three:
- Living organisms and the enzymes they produce are involved
- Amino acids are the raw materials
- They exhibit toxicity when they cannot be detoxified
By firmly understanding these three points, you can clearly understand the relationship with wine.
Living Organisms in Winemaking
The living organisms involved in winemaking are mainly grapes as plants, and yeasts and bacteria as microorganisms. Furthermore, this includes microorganisms attached to the grape skin surface, even if not directly related to winemaking. All of these have the potential to synthesize biogenic amines.
Biogenic amines already exist in harvested grapes. They are also generated through yeast metabolism during alcoholic fermentation. The stage when the largest amount of biogenic amines is said to be generated during the wine production process is malolactic fermentation (MLF), when lactic acid bacteria, a type of bacteria, actively metabolize.
Because the amount of biogenic amines in wine increases through MLF, it is known that biogenic amine content tends to be higher in red wines than in white wines.
Organism Types, Grape Varieties, Climate, and Soil
Various microorganisms are included among the living organisms that produce biogenic amines in wine. This creates relationships between grape varieties, the year's climate, the soil of the vineyard where grapes are grown, and the biogenic amines contained in wine.
It is said that changes in grape variety produce changes in the microbial flora present on the fruit skin surface. This condition also varies greatly depending on the health status of the grapes. Furthermore, it is known that differences in soil type also create differences in the types and quantities of microorganisms inhabiting that soil.
Even with the same grape variety, it is not uncommon for grapes cultivated in vineyards with different soil types to have completely different microbial flora on their skin surfaces. Moreover, the living conditions of these microorganisms are strongly influenced by climate.
Changes in these microbial flora, which are likely to enter grape juice during the winemaking process, lead to differences in the types and amounts of enzymes that these microorganisms produce during metabolism. This ultimately affects the types and amounts of biogenic amines that may be contained in wine.
Amino Acid Content, Grapes, Vineyards, and Weather
Even if wine contains large amounts of enzymes that produce biogenic amines, biogenic amines will not be produced if the amino acids that are their raw materials are absent. Conversely, when the amount of amino acids contained in wine is high, the potential biogenic amine content increases.
Amino acids enter wine through multiple pathways.
The first is grapes. Since grapes also contain proteins, these become amino acids when decomposed. The types and content ratios of amino acids contained in grapes differ not only by grape variety. Weather conditions during the growth stage, the ripeness of harvested grapes, and even cultivation methods and the types and composition of soil are said to have an influence.
Also, since most proteins are contained in the skins and stems, performing long skin extraction during the winemaking process leads to an increase in the amount of protein contained in grape juice or wine.
Another major factor that increases amino acid content in wine is the decomposition of yeast.
After alcoholic fermentation ends, lees accumulate at the bottom of the container. Much of the material composing those lees consists of dead yeast cells. The dead yeast cells contained in the lees slowly decompose, releasing large amounts of amino acids into the wine during this process. These amino acids supplied to the wine become raw materials, and biogenic amine synthesis occurs.
Multiple verification studies have also reported that long-term lees aging increases the amount of biogenic amines including histamine and tyramine contained in wine.
Winemaking Conditions and Biogenic Amine Levels
When grape juice or wine contains many amino acids, and furthermore when living organisms capable of synthesizing them into biogenic amines are present, the amount of biogenic amines contained in that wine does not necessarily increase. What ultimately becomes important are the environmental conditions for the living organisms and enzymes.
Even if microorganisms and enzymes are present in wine, if they can be inactivated or removed through the addition of sulfur dioxide or clarifying agents, the probability of biogenic amines actually being generated decreases significantly. Also, since the generation factors for biogenic amines are fundamentally a response to cells being exposed to strong stress, preparing a winemaking environment where yeasts and lactic acid bacteria are less stressed also leads to lowering the probability of biogenic amine generation.
Conversely, when lees aging is performed without appropriate SO₂ addition and without inactivating microorganisms, the probability increases that released amino acids will be metabolized directly into biogenic amines. Also, when wine pH is high, in addition to the effectiveness of SO₂ decreasing, microorganism activity increases, so biogenic amine generation tends to increase.
For both alcoholic fermentation and subsequent MLF, it is known that conducting spontaneous fermentation without using starters increases biogenic amine production.
Why Are the Effects of Biogenic Amines Greater in Wine?
Biogenic amines are not special substances and are quite commonly contained in foods and beverages. Content is particularly high in so-called fermented foods, and among these, there is a tendency for higher amounts in those using lactic acid bacteria.
In cheese and dried fish, there are many examples where biogenic amines are detected in amounts far exceeding those in wine. In particular, almost no cases have been reported where the amount of histamine contained in wine exceeds the amount contained in cheese.
Despite this, the reason biogenic amines frequently become problematic in wine is strongly related to the presence of alcohol and amines called polyamines.
Biogenic amines exhibit toxicity to the human body when they exceed the tolerance that can be detoxified by amine oxidase enzymes in the intestinal tract. It is known that the amount of this amine oxidase enzyme varies greatly among individuals. Furthermore, it has been found that the activity of this enzyme is inhibited by alcohol and acetaldehyde, and also by types called aliphatic polyamines among biogenic amines.
In other words, even if the histamine content itself is low, the presence of alcohol and polyamines enhances potential toxicity, leading to more severe symptoms.
Several biogenic amines are classified as aliphatic polyamines. Among these, putrescine (PUT) and agmatine (AGM) use arginine and ornithine as raw materials among amino acids. Furthermore, ornithine is generated by the decomposition of arginine. And that arginine is one of the amino acids abundant in grapes.
In other words, wine made from grapes potentially contains many polyamines, and the possibility of amine oxidase enzyme inhibition by them is also potentially high.
Summary | Approaches to Reducing Biogenic Amines in Wine
The structure of biogenic amine content in wine is very complex when pursuing the details. However, on the other hand, the fundamental factors are actually very simple.
For biogenic amines to be contained in wine, there are three absolute conditions:
- The presence of precursors (amino acids) that serve as raw materials
- The presence of microorganisms that produce decarboxylase enzymes
- The absence of environmental factors that inhibit microorganism proliferation or the activity of produced enzymes
If even one of these three conditions is missing, the amount of biogenic amines contained in wine becomes almost zero, or at least the risk of content is greatly reduced. In other words, to prevent biogenic amines from being contained in wine, you only need to thoroughly manage at least one of these three.
That said, no matter how much you try to reduce amino acids, yeast becomes a supply source, so complete elimination is impossible. It is known that decarboxylase enzymes are produced by all except some selected yeasts and lactic acid bacteria. Therefore, in winemaking where complete prevention of microorganism contamination through grape skins and other means is impossible, complete removal is still not easy.
What becomes important here is the inhibition of microorganisms and enzymes through appropriate addition of sulfur dioxide and implementation of clarification and filtration.
Recently, natural wines claiming to be sulfur dioxide-free have become trendy. However, on the other hand, it has been reported through verification results that these wines tend to have relatively higher amounts of biogenic amines.
Just because biogenic amine content has increased does not mean that harm to the human body is immediately confirmed. However, there is great individual variation in tolerance for biogenic amines, and there are also cases of so-called intolerance, where people constitutionally cannot accept them at all. When there is a possibility that biogenic amine content has increased, the fact that the person who made the wine was fine does not mean it is a wine that everyone can drink safely.
Currently, there are no global restrictions on the amount of biogenic amines contained in foods including wine, and only some countries have voluntarily established regulatory values. Even those regulatory values vary greatly, for example, from 2 mg/L in Germany to 10 mg/L in Switzerland when looking at histamine amounts. The International Organisation of Vine and Wine (OIV) does not establish clear regulatory values but instead has defined and recommends guidelines for reducing biogenic amine content.
As long as wine is a food that enters people's mouths, it is the obligation of producers to reduce known toxicity as much as possible. There should originally be no room for producers' own preferences or philosophies to intervene there. By having many people know what biogenic amines are, what increases them, and how they can be reduced, it is important to enhance the safety of wine as a food product.
