Is It True That Antioxidants Cause Headaches?

While it seems to be mentioned somewhat less frequently these days, there is a persistent claim that antioxidants contained in wine—specifically additives called sulfites or sulfurous acid—are the cause of headaches that occur when drinking wine. This theory has been whispered about as if it were fact, and many people probably still believe it. But is it really correct?

This article will examine the causes of headaches that occur when drinking wine, while also investigating the relationship between these causes and antioxidants.

What Are Antioxidants, Anyway?

Let's start with a review. The antioxidants added to wine are generally chemical substances called sulfur dioxide, represented by the chemical symbol SO2. On the other hand, "sulfurous acid," which is commonly seen on wine labels, refers to a substance expressed by the chemical symbol H2SO3.

As you can see from the chemical symbols, sulfurous acid is composed of sulfur dioxide combined with water. "Sulfites" are substances formed when sulfurous acid combines with certain other molecules. Representative substances include potassium sulfite (K2SO3) and sodium hydrogen sulfite (Na2SO3).

You'll notice that all of these substances contain the SO3 component. While we'll set aside detailed chemical explanations, you can understand that all of these substances are basically the same as sulfur dioxide because they contain this SO3 component.

Previously, I wrote an article titled "Quality Control Basics | How to Use Sulfur Dioxide" about this sulfur dioxide (SO2), explaining the role this substance plays and the amounts needed to fulfill that role. In that article, I also explained something called "free SO2."

Later in this article, the concept of "free SO2" will become extremely important. If you're uncertain about what this was, I encourage you to review that article before continuing with this one.

Does Sulfur Dioxide Cause Headaches?

To conclude first: "The possibility is extremely low."

When sulfur dioxide is absorbed into the human body through the stomach, it is basically rendered harmless. Even if this weren't the case, the amount of free SO2 contained in wine decreases over time through combination with oxygen contained in the bottle. Therefore, drinking roughly one bottle of wine doesn't result in consuming significant amounts. If this caused headaches, eating dried fruits would be catastrophic.

For information about the amounts of sulfur dioxide contained in foods other than wine, please refer to the article "Do You Really Understand Sulfur Dioxide? Part 4," which provides several examples with numerical values.

It Is True That Sulfur Dioxide Is Harmful to the Human Body

As I've written repeatedly in other articles, it is a fact that sulfur dioxide itself is harmful to the human body. Therefore, consuming extremely large amounts at once could cause health problems at levels far beyond headaches.

There are also people who are quite sensitive to sulfur dioxide, even if not to the point of having allergies.

I am actually one of those people—I'm so sensitive to sulfur dioxide content that I could be called hypersensitive. When working in the cellar, my colleagues don't perceive anything at all, but I'm the only one shouting "It smells like sulfur!"

Since there's also a lot of work in the cellar that involves handling sulfur dioxide directly, I'm constantly tearing up and coughing during these tasks.

People with this kind of hypersensitivity may indeed experience headaches due to their constitution, and even if not, they may develop secondary headaches due to psychological factors because they can sense its presence. However, these can also be classified as special cases affecting only some people.

What Causes Headaches?

First, the biological cause of headaches is said to be the expansion and contraction of blood vessels. Since I'm not a medical professional, I cannot provide answers if pressed for detailed mechanisms in this area. Please understand this limitation in advance.

There are actually several possible causes of headaches. Regarding causes involving chemical substances, all have effects on blood vessel expansion or contraction, supporting the theory that "blood vessel expansion and contraction" causes headaches.

The possible causes are as follows:

• Drinking too much
• Acetaldehyde
• Biogenic amines
• Psychological factors (preconceptions)

Let's examine each in order.

Possibility of Overconsumption Due to Alcohol Content Rather Than Volume

This is a cause commonly assumed for people who don't usually drink much alcohol.

Generally, people who don't drink much alcohol regularly tend to consume drinks with low alcohol content. Even when the alcohol itself has high alcohol content, it's often diluted with water, hot water, or tea, resulting in lower actual alcohol consumption.

Wine, on the other hand, is basically never diluted with anything. Moreover, wines commonly imported to Japan tend to have relatively high alcohol content. Therefore, even if the volume consumed isn't particularly large, when converted to actual alcohol intake, it represents a considerable amount, potentially exceeding the body's ability to metabolize it and causing headaches or hangovers.

While people probably don't calculate their alcohol metabolic capacity while enjoying drinks, it would be good to keep in mind that wine basically has high alcohol content.

For information about alcohol metabolism in the body and hangover prevention, please refer to the article "To Avoid Hangovers: Understanding Alcohol Metabolism!"

As mentioned in that article, Haichiol C, which contains high amounts of L-cysteine, is actually highly effective for preventing hangovers. People who tend to get hangovers despite being careful, not just with wine but with any alcohol, might want to try it.

Highly Toxic Acetaldehyde

I wrote in a previous article about how alcohol absorbed into the human body is broken down from ethanol to acetaldehyde through the action of an enzyme called alcohol dehydrogenase.

This substance called acetaldehyde, also known as ethanal, is said to have approximately 10 times the toxicity of ethanol.

This acetaldehyde is actually also a fermentation byproduct generated during wine fermentation.

It's known to be produced in large quantities particularly when damaged grape clusters are mixed in, and lower-priced wines focused mainly on quantity production have a higher possibility of relatively high acetaldehyde content.

Production tends to increase with wild yeast fermentation as well.

Biogenic Amines Represented by Histamine

There's also a lesser-known group of substances called biogenic amines.

Histamine, one of the biogenic amines, is probably a well-known substance, but when consumed in large quantities, both histamine and tyramine exhibit strong toxicity and can cause allergies, blood pressure drops, and blood vessel expansion or contraction. In other words, they can cause headaches.

Biogenic amines are mainly caused by microbial (bacterial) activity, generated when decarboxylase enzymes affect amino acids.

While biogenic amines are said to vary in content mainly depending on the condition of grape clusters, they are also generated during malolactic fermentation commonly performed in red wines—that is, during lactic acid fermentation—when arginine, an amino acid, is broken down by a type of lactic acid bacteria called Pediococcus damnosus.

In other words, regarding this "generation during malolactic fermentation," red wines have a higher possibility of containing more biogenic amines than white wines.

For people who don't get headaches from white wine but do get headaches from red wine, they may be affected by biogenic amines caused by this lactic acid fermentation.

The Most Likely Possibility? Psychologically Induced Headaches

This becomes an extremely unscientific discussion, but there are cases where "preconceptions" are the cause.

When someone has the preconception that drinking wine gives them headaches, that preconception alone may actually cause headaches. It's the same principle as the placebo effect with fake medicine.

The Relationship Between Each Cause and Sulfur Dioxide

Except for the last case of preconceptions, all cases actually have connections to sulfur dioxide.

This "connection" may have worked in a negative direction, resulting in something that supports the wine truism mentioned at the beginning: "antioxidants are the cause of headaches."

What does "having a relationship" actually mean? The more acetaldehyde present, or the higher the content of biogenic amines, the more sulfur dioxide tends to be added to that wine.

Acetaldehyde is Sulfur Dioxide's Best Partner

I wrote in a previous article that managing the amount of free SO2 is important when adding sulfur dioxide.

The amount of this free SO2 can be expressed by the following simple formula:

Total SO2 Added - Bound SO2 = Free SO2

In essence, free SO2 is the remaining amount of the total SO2 added to wine that hasn't yet bound to anything.

When you want to increase the amount of this remaining free SO2 in wine, two approaches are possible:

1. Increase the total amount of sulfur dioxide added
2. Reduce the content of substances that bind with sulfur dioxide

The first approach is straightforward: regardless of how much binds, add enough SO2 to ensure saturation while securing the desired amount of free SO2. The second approach is essential for controlling total SO2 additions: reduce the demand for SO2 by decreasing the substances that consume it through binding.

Acetaldehyde is probably one of the substances in wine that consumes the most SO2.

How much does it consume? One milligram of acetaldehyde binds with as much as 1.45 mg of SO2.

Therefore, when wine originally contains high levels of acetaldehyde, the total amount of SO2 added must inevitably be increased to secure free SO2. Since acetaldehyde content is basically invisible from the outside, even when headaches are caused by acetaldehyde, only the sulfur dioxide content stands out, potentially leading to the conclusion that the headache was caused by the large amount of added sulfur dioxide.

The Relationship Between Biogenic Amine Generation and Sulfur Dioxide

Biogenic amines like histamine and tyramine are basically not expected to be binding partners for sulfur dioxide.

However, as mentioned above, bacteria are involved in biogenic amine generation.

The key point in this case is that sulfur dioxide is used to inactivate these bacteria.

While the situation is somewhat different for malolactic fermentation, in terms of grape health, conditions where bacterial development is a concern mean situations where grape berries or clusters are damaged or rotting. In such situations, considerable amounts of sulfur dioxide are inevitably added to suppress the activity of these bacterial populations.

The specific health condition of grapes used in wine is not something that can be easily determined from the outside.

Therefore, in this case too, only the large amount of added sulfur dioxide stands out from the outside, making it impossible to determine whether the real cause of headaches was sulfur dioxide or biogenic amines.

If Large Amounts Are Added, Isn't Sulfur Dioxide Still the Cause of Headaches?

I've explained that wines with high content of either acetaldehyde or biogenic amines inevitably tend to have increased SO2 additions.

Reading this raises the question: if SO2 additions are ultimately high, isn't SO2 still the cause of headaches?

This question could certainly be correct in some sense. If SO2 additions could be increased without limit, this tendency would indeed become more pronounced.

However, in reality, the total amount of SO2 that can be added to wine is legally regulated in many countries. No matter how low the amount of free SO2 in wine, it's impossible to add SO2 exceeding these regulated amounts. This means that in such wines, while biogenic amines aside, high amounts of acetaldehyde likely remain.

Conversely, regarding biogenic amines, as mentioned earlier, when generated through lactic acid fermentation, their content can increase regardless of free SO2 levels.

Given this reality, it's impossible to definitively conclude that SO2 alone causes headaches.

The Relationship Between Drinking Large Quantities and Sulfur Dioxide

When people who aren't strong drinkers consume more alcohol than they can tolerate, this can be interpreted as consuming excessive alcohol when acetaldehyde dehydrogenase activity is low, so the effect on the human body can be considered damage from unmetabolized acetaldehyde.

However, the damage in this case comes not from acetaldehyde originally contained in the wine, but from acetaldehyde generated during alcohol metabolism, so the content is completely different from the acetaldehyde-containing cases mentioned above.

Nevertheless, when drinking wine that originally contains high amounts of acetaldehyde, there's a double impact from both consumed acetaldehyde and acetaldehyde generated during alcohol metabolism, so the severity is naturally expected to be worse.

Summary

It's difficult to definitively summarize the causes of headaches, and there's no single cause that can be identified as absolute. However, except for some exceptional constitutional cases, it's unreasonable to think that antioxidants—sulfur dioxide—which are basically rendered harmless in the body, cause headaches.

Rather than forcing the conclusion that sulfur dioxide causes headaches, wouldn't it be more natural to say that acetaldehyde and biogenic amines, which have high toxicity to humans, are the causes?

Understanding that wines containing these substances also likely contain high amounts of sulfur dioxide may help explain why this wine truism—that antioxidants cause headaches—came to exist.

The amounts of acetaldehyde and biogenic amines usually cannot be determined from the outside. Moreover, since these substances can be contained in any wine, it's impossible to avoid them when drinking wine.

In this sense, there are no clear methods to avoid headaches caused by drinking wine.

When enjoying wine, be careful not to raise blood alcohol concentration by drinking water in parallel, and if you feel "I might not like this wine" when taking the first sip, it's important to stop drinking decisively, regardless of what kind of wine it is.

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