Citric Acid Allergies: the basics

What is Citric Acid? Where is Citric Acid found? Wait… can you really react to Citric Acid? Allergy, sensitivity, or intolerance?

What is Citric Acid?

Citric acid is an organic acid that looks like this:

It’s not even that cute.

Citric acid is found naturally in many foods, but can also be manufactured by the fermentation of Aspergillus niger.  As the name implies, it tastes “citrusy” or acidic.

The conjugate base of citric acid, citrate, is an important intermediate in the metabolic (energy-making) cycle of nearly all living things; this cycle takes place in our cells’ mitochondria and is appropriately named the Citric Acid Cycle.

Where is Citric Acid found?

Citric acid comes in two flavors: natural and synthetic. Natural citric acid can be found in ALL fruits, ALL vegetables, ALL legumes, garlic, onion, ginger, and lots of other stuff. Synthetic citric acid is made by fermenting the mold Aspergillus niger, typically by feeding it some sort of corn sugar; it can also lurk about in its citrate form (potassium citrate, calcium citrate, etc.).  Both forms can be found as a preservative in almost any food, body product, medication, or horror movie. Some people who are sensitive to mold and/or corn may react to synthetic citric acid only.  Generally, people who react to natural citric acid will also react to synthetic citric acid.

Wait… can you really react to Citric Acid?

Why yes, yes you can.

“But it’s part of the Citric Acid Cycle!  You’ll die without it!”

This argument is incorrect.  Take a look at the schematic below: the white part is outside the cell, the tan part is inside the cell, and the purple part is the mitochondrion — where the Citric Acid Cycle occurs.

If you look at what’s going into the cell, you’ll see not citric acid, but glucose!  Glucose (sugar) is the one thing our cells need from an external source (food) in order to make energy; the citrate in the Citric Acid Cycle is made from this glucose in the mitochondria.  Even someone on a 100% citric acid-free diet can make energy, because dietary citric acid is not used as part of Citric Acid Cycle.

“But there’s Citric Acid in your body!  Even if you don’t need to eat it, it’s still there in the Citric Acid Cycle. You can’t be allergic to yourself, you’ll die!”

Wrong again, masked stranger.  Take a look again at the schematic: the Citric Acid Cycle occurs inside the mitochondria, which is inside the cell. Reactions to foods and chemicals take place in extracellular spaces; the reaction mediators are outside our cells and never “see” the citrate that is formed in our mitochondria, therefore they cannot react to it.  Location, location, location!

“But there’s NO WAY there is absolutely zero citric acid in your body.  WHY AREN’T YOU DEAD?!!”

Well, okay… despite your inexplicably vehement desire to see me dead, I will give you  credit for that one.  There is, in fact, citric acid in everyone’s blood and urine, not to mention saliva, sweat, tears, and yes- even breast milk and semen.  My immune system can “see” all of that inside my body (uhm… well, most of it), so why am I not dead? The first–and most obvious–reason is that I’m a ninja.  However, there’s a more boring reason, which has to do with things like severity and tolerance; I shall explain it using two more pedestrian immune conditions: peanut allergies and lupus.

Well, sometimes it is lupus.  To grossly oversimplify, when someone has systemic lupus erythematosus, their immune system forms antibodies against the person’s own tissues (e.g. heart, lung, and kidney), so the immune system attacks the body.  If severe enough it can be fatal, but 80-90% of patients with lupus will survive as long as a healthy person.  Lupus is a type III hypersensitivity and, along with hundreds of other autoimmune conditions, exists for the sole purpose of proving my point: depending on the severity of the attack, one can survive one’s own immune system attacking things native to their bodies.

In addition to people’s remarkable ability to survive declaring war on themselves, people’s immune systems also have different thresholds at which these wars–and wars on foreign offenders–begin.  For example, both my brother and my college roommate have the classic type 1 hypersensitivity known as peanut allergies.  My brother is able to eat peanut butter toast, as long as he only has it once a week on a full stomach.  If he goes beyond his tolerance and has it a couple of days in a row, he will begin to suffer unpleasant GI symptoms.  My roommate’s tolerance is much lower: when we went on an adventure to see RENT in California, we had to book on a peanut-free airline, lest being trapped thousands of feet in the air with peanut dust lead her to take the show’s “live each moment as your last” theme a bit too literally.

People who react to citric acid also have different tolerance levels.  One food pretty much guaranteed to make a ninja flee the scene is lemons, which contain anywhere from 40,000-80,000ppm (parts per million) citric acid.  Some ninjas can eat blackberries (4,000ppm), some can only tolerate as high as pears (2,000ppm), and a few can’t even consume peas (200ppm).  Compare that to the 15ppm in blood, 4-25ppm in saliva, or 1-2ppm in sweat1, and we’re talking orders of magnitude of difference: even those who react to the un-citrusy-est of vegetables are safe from the tears they’ll cry when they must choose between life and that blackberry pie they’re craving.

That ice cream is probably lethal, but at least her tears won’t burn her face off.

But what about things like urine (100-700ppm), breast milk (500-1250ppm) and semen (2000-4000ppm)?  It is here that we return to one of our earlier arguments: location, location, location!  Not all areas of our bodies are equally responsive to evil things, thanks to differences in their reaction mediator inhabitants.  As long as low-tolerance ninjas don’t put these things (this is life-or-death ninja science here, no laughing!) in their mouths or other sensitive areas, they’re probably going to stay not dead.  It’s worth mentioning that most ninjas with extremely low tolerance were born with a much higher, or even normal tolerance, and they were inducted to ninjahood later in life thanks to medications or illness.  However, some babies do react to breast milk for any number of reasons; perhaps infant ninjahood is one of those reasons.  Also worth mentioning: there are people who have allergic-like conditions involving the bladder, and semen allergy is an actual thing that has been medically documented in women.  These ninjas can get by thanks to their reaction severity, as we discussed earlier.

In sum: if there exists a human whose tolerance for citric acid is lower than the small amount circulating in the responsive areas of their body, and who has life-threateningly violent reactions to citric acid, that person is probably not alive, and probably not me. (I say probably because, although it is unlikely I can type from the beyond, you never know. I am a ninja, after all.)

tumblr_inline_mrtiklouCt1qz4rgp Is this an allergy, sensitivity, or intolerance?

This is a very complicated question with no certain answer.  Let’s first take a look at the definitions (provided by my fantastic allergist!):

Allergy: a Type I, IgE-mediated “classical” allergic reaction.  An anaphylactic reaction is an IgE-mediated systemic reaction.
Examples: Milk ingestion –> hives.  If the person is IgE-positive for milk protein, this person is allergic to milk protein. Bee sting –> systemic reaction.  If the person is IgE positive to bee venom, this is anaphylaxis.

Sensitivity: an immunological reaction of non-IgE, undefined source. Type II, III and IV reactions are all considered sensitivities.  An anaphylactoid reaction is a non-IgE mediated systemic reaction.
Example: Patient is exposed to radiocontrast dye –> systemic reaction.  There is no IgE antibody for radiocontrast dye; this is an anaphylactoid reaction.

Intolerance: a reaction that may not be immunological in nature, and may be metabolic, neurogenic, etc.
Examples: Milk ingestion–>GI upset. If relieved with lactaid tablets, this is lactose intolerance (a lack of lactase enzyme in the intestines to break down the lactose milk sugar). MSG reaction is probably a neurogenic reaction (we don’t know!).

So where does this put us with citric acid?  Possibly a sensitivity with anaphylactoid properties, but we can’t be sure because the mechanism of reaction is unknown.

But wait, Lemon Ninja!  If it’s a sensitivity, why do you call it an allergy everywhere on this site?

(1) Try saying “citric acid sensitivity” 5 times fast. Yeah, it hurts my brain too.

(2) People are more likely to Google “citric acid allergy,” and the Google Overlords tell me using that phrase repeatedly on this site will make it easier to find.

(3) I don’t have a third reason, but I can’t make a list of only two things.

The four types of hypersensitivity (The following info is taken directly from this website, check it out if you’re nerdy like me and want more details):

Type 1: Type I hypersensitivity is also known as immediate or anaphylactic hypersensitivity. The reaction may involve skin, eyes, nose, lungs, and gastrointestinal tract. The reaction may cause a range of symptoms from minor inconvenience to death. The reaction usually takes 15 – 30 minutes from the time of exposure to the antigen, although sometimes it may have a delayed onset (10 – 12 hours).  Immediate hypersensitivity is mediated by IgE.

Type 2: Type II hypersensitivity is also known as cytotoxic hypersensitivity and may affect a variety of organs and tissues. The antigens are normally from inside the body, although external chemicals which can attach to cell membranes can also lead to type II hypersensitivity. The reaction time is minutes to hours. Type II hypersensitivity is primarily mediated by IgM or IgG.

Type 3: Type III hypersensitivity is also known as immune complex hypersensitivity. The reaction may be general or may involve individual organs including skin, kidneys, lungs, blood vessels, joints or other organs. The reaction may take 3 – 10 hours after exposure to the antigen. It is mediated by mostly by IgG, although IgM may also be involved. The antigen may be from inside or outside the body.

Type 4: Type IV hypersensitivity is also known as cell mediated or delayed type hypersensitivity. Type IV hypersensitivity is involved in many autoimmune and infectious diseases. Another form of delayed hypersensitivity is contact dermatitis (like with poison ivy, chemicals, heavy metals, etc.). Mechanisms of damage in delayed hypersensitivity include T lymphocytes and monocytes and/or macrophages.

Unlinked References: (1) ‘‘Citric Acid’’ in ECT 1st ed., Vol. 4, pp. 8–23, by G. B. Stone, Chas. Pfizer & Co., Inc.; in ECT 2nd ed., Vol. 5, pp. 524–540, by L. B. Lockwood and W. E. Irwin, Miles Chemical Co.; in ECT 3rd ed., Vol. 6, pp. 150–179, by E. F. Bouchard and E. G. Merritt, Pfizer Inc.; in ECT 4th ed., Vol. 6, pp. 354–380, by G. Blair and P. Staal, Haarman & Reimer Corpora- tion; ‘‘Citric Acid’’ in ECT (online), posting date: December 4, 2000, by G. Blair and P. Staal, Haarmann & Reimer Corporation.