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When Histamine is the Missing Link

What do frequent muscle cramps, headaches, dribbling saliva, a longer second toe, easy orgasm, a type A driven personality, sneezing in bright sunlight, a preference for opiates and alcohol, and reactions to certain foods have in common? High levels of histamine.

And, what do canker sores, plentiful body hair, a pear-shaped figure, low libido, voices or ringing in the head, dry mouth, lots of dental fillings, a tendency to paranoia, and a need for lots of sleep have in common? Low levels of histamine.

For those of us concerned with addiction prevention and recovery, histamine is an important hidden reason for failure in treatment.

Histamine is a biochemical produced inside our body as part of our immune force, but it’s also a hormone and an important neurotransmitter when levels are healthy. In excess it becomes a potent initiator of itching, swelling, flushing, pain, difficulty breathing, and other distressing and even life threatening reactions.

Using histamine as a clinical sign is attributed to the late Carl Pfeiffer, MD, PhD, the brilliant and lovable pioneer in clinical nutrition whose Brain Bio Center in Princeton, New Jersey, was a haven of comfort and treatment for those with mental and physical ailments given up on by other physicians. According to Pfeiffer, normal blood histamine is 35 to 65 ng/ml. Above 70 ng per ml is abnormally high, a condition he called histadelia.

It was one of our Alliance founders, the late Joan Mathews Larson, PhD, who applied Pfeiffer’s work to addiction treatment with clients at her Health Recovery Center in Minneapolis, MN.

As she explains in her book Depression-Free, Naturally, p. 214, Larson was at first distressed by compulsive, impulsive, obsessive go-getters who cried easily and plummeted just as easily into deep depression, walking into the treatment program high with enthusiasm then abandoning the program before the first week was over. Larson soon learned that they fit the high histamine model and needed immediate intervention to thwart their impulsivity, an impulsivity that can, in the extreme, lead to suicide.

Joe Eisele, CACIII, is Clinical Director at InnerBalance Health Center in Loveland, Colorado and has experience with young histadelia sufferers, too. He points out in his book Leaving Drug and Alcohol Addiction for Good, that histadelia symptoms of night terrors, difficulty falling asleep, trouble concentrating, and difficulty in school are sometimes mistakenly diagnosed as Attention Deficit Disorder when the child really has too much histamine in the brain.

It’s also common for people to mistake histadelia for food or environmental allergies if symptoms include runny nose, gastrointestinal distress, erratic heartbeat, hives, asthma, or migraine headaches. These are the mystery patients whose skin prick tests are negative and only after careful detailing in a diet diary do the foods and drugs that release histamine reveal themselves as the culprits.

Pfeiffer identified problems triggered by low histamine as well, a condition he called histapenia. It is usually linked to excessively high copper in the body. High copper is associated with autism, violence, depression, and anxiety. According to Pfeiffer, blood histamine levels of 27 to 28 ng per ml for women and around 20 ng per ml for men is a sign of histapenia.

The Methylation Question

There is one curious conflict among experts related to histadelia and histapenia that must be mentioned. William Walsh, PhD, though his doctorate was in chemical engineering, became fascinated with the link between nutrition and violence.

Over multiple decades he has researched how biochemical treatments can influence mental health issues, autism, schizophrenia, criminal behavior, and other conditions. He worked with Pfeiffer for several years and after Pfeiffer’s death created the nonprofit Walsh Research Institute in Naperville, Illinois to continue the work.

In his book Nutrient Power: Heal Your Biochemistry, Heal Your Brain, Walsh describes a negative correlation between histamine and methylation meaning when histamine is high methylation is low, and vice versa.

Methylation, says Walsh, “is a biochemical process of extraordinary importance in human functioning” as it influences how DNA expresses itself, among other critical consequences. Walsh claims his own database of 30,000 persons shows that about 70% of the population exhibit normal methylation, 22% have too little methylation going on inside them and 8% have too much methylation occuring. Yet, he insists in his book, “more than two-thirds of persons diagnosed with a behavior or mental disorder exhibit a methylation imbalance.”

It’s basically to do with a complicated choreography of chemicals changing partners. How each body dances this biochemical dance is set, he says, when we are developing before birth though food choices and supplements can correct abnormalities.

The reason this issue is important is the link Walsh claims exists between histamine and methylation.

In contrast, Tappan Audya, PhD, also worked with Pfeiffer for years, and yet has the opposite perspective on the histamine/methylation relationship. Audya received his graduate degree in biochemistry and chemistry of natural products and worked in basic research in the pharmaceutical industry. He has been a professor of biochemistry and endocrinology in New York University Medical School, and is currently the Director at Health Diagnostics Research Institute in South Amboy, New Jersey.

According to Audya, “We have been doing histamine testing for almost 30 years and I’ve never seen that over-methylating people have low histamine. If there has been any, it hasn’t been more than 1 or 2% of the time.”

This doesn’t mean that methylation issues are unimportant. As Academy for Addiction and Mental Health Nutrition founder Christina Veselak, LMFT, CN notes, plenty of people with addiction problems have a genetic abnormality that doesn’t allow their body to process the B vitamin supplement folic acid unless it has been “methylated”.

The problem, according to Veselak, lies in sections of their DNA code abbreviated by the letters MTHFR. It is too complicated a condition to go into here, but it is a good idea to look it up as it is one more often unrecognized barrier that can be eliminated to assure successful long-term recovery.

Raising if Low

What Audya learned from Pfeiffer, among all else, is that low histamine indicates a problem digesting protein. There is yet another interesting aspect to low histamine: by raising histamine with the drug betahistine (often used to treat dizziness and ringing in the ears) some researchers improved human subjects’ long term memory! As mentioned before, low histamine is related to high copper. Excessive copper is reduced by taking zinc, vitamin C, and niacin.

Lowering if High

The protocol to lower overly high histamine includes amino acids L-tryptophan and L-methionine, vitamins A, B-6, and C, and minerals calcium and magnesium. It is also useful to stop eating histamine-rich foods like wine and other alcohol, bone broth, cheese, chocolate, egg whites, tea, soybeans, peanuts, mushrooms, spinach, shellfish, vinegar, bacon, sauerkraut, kimchi, and yogurt, eggplant, and nuts. On the other hand, tomatoes, strawberries, citrus fruits, bananas, and avocados are low in histamine but can trigger the release of histamine and cause similar problems.

In an email, Joe Eisele commented, “Two years ago I ran across an article that stated that codeine lowers histamines more than anything. Maybe that's why so many people love opioids.”

The Questionnaires

All of us can easily discover if our own symptoms are due to histadelia or histapenia by using the questionnaires based on the work of Pfeiffer and Larson and adapted by Julia Ross, MA, for her treatment program in Mill Valley, CA. Appropriate responses to the discovery of these often undiagnosed conditions includes consulting a nutritionist familiar with histamine, researching on the Internet (see Resources, below, for a start), and reading Larson’s book Depression-Free, Naturally.

_High Histamine Questions
Download DOC • 25KB
_Low Histamine Questionnaire -4-06
Download DOC • 25KB

Lab Testing

Walsh suggests laboratory testing as well, including whole blood histamine.

Why bother?

Recognizing and treating histadelia and histapenia relieves years of frustrating persistent symptoms, making full recovery from addiction all the more likely.


Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories

Hiroshi Nomura, Hiroto Mizuta, et al

Biological Psychiatry

Archival Report, Vol 86, Issue 3, p. 230-239, August 1, 2019

Histamine and histamine intolerance

Laura Maintz, Natalija Novak

The American Journal of Clinical Nutrition, Volume 85, Issue 5, May 2007, Pages 1185–1196,

Victoria Groce, Updated on January 25, 2021

Good Night and Good Luck: Norepinephrine in Sleep Pharmacology. Antihistamines block the wake-promoting effects of histamine, which shares reciprocal signaling with NE.

Re norepinephrine and sleep: Biochem Pharmacol. 2010 Mar 15;79(6):801-9. Epub 2009 Oct 13.

Leaving Drug and Alcohol Addictions For Good: How biochemical restoration radically improves your chances of recovery

by Joseph Eisele, CACIII in conversation with Sharon R. Montgomery

Paradise Lane Publishing, 2020

Depression-Free, Naturally: 7 Weeks to Eliminating Anxiety, Despair, Fatigue, and Anger from Your Life

by Joan Mathews Larson, PhD

Random House Publishing, paperback, 2001


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