inflammation & autoimmunity
headaches & migraines
mental health
HNMT

Are You Genetically Vulnerable to High Brain Histamine, Migraines, or ADHD? (HNMT)

Written by Jasmine Foster, BSc, BEd on August 19th, 2019
Sign Up to Unlock Personalized Results

Do you struggle with the symptoms of ADHD? Do you frequently have migraines? Poorly functioning histamine-degrading enzymes may cause either or both. Let’s dive into your HNMT gene and find out if you’re vulnerable.

Histamine in the Brain

Histamine is vitally important for brain function: it wakes you up, suppresses appetite, and lets you know when you’re thirsty. Brain histamine may also make you feel more curious and motivated. It keeps you alert, helps you prepare for stressful situations, and promotes the formation of memories [R, R, R].

However, too much brain histamine can cause serious problems. In this post, we’ll explore histamine-N-methyltransferase (HNMT), which breaks down histamine in the brain, and how low HNMT activity can impact your health.

How Does the HNMT Gene Cause Problems?

HNMT codes for histamine-N-methyltransferase, the second major enzyme (after DAO) that breaks down histamine. HNMT is found throughout the body and (perhaps most importantly) in the brain. It deactivates histamine by adding a methyl group [R, R].

Variations in the HNMT gene have been associated with chronic hives and eczema as well as neurological symptoms [R, R].

It’s plausible that the HNMT enzyme may be decreased in these conditions, and increasing it may help.

HNMT is the major histamine-degrading enzyme in the brain and much of the body.

 

Histamine and Migraines

Migraine is a condition that causes excruciating headaches, nausea, intense fatigue, sensitivity to light and sound, and inability to move without pain [R, R].

One possible villain behind these often disabling events is excess brain histamine. In fact, researchers have known for decades that they can induce a headache just by giving a person enough histamine by mouth; we also know that people who get migraines are more susceptible to histamine headaches than people who don’t [R, R, R].

Furthermore, some antihistamines are currently under investigation as future migraine medications. Drugs that activate the H3 histamine receptor may have the most potential [R].

The ‘T’ allele at rs11558538 is associated with decreased HNMT activity and increased risk of migraines [R].

Excess brain histamine may cause migraines; people who tend to get migraines are also more sensitive to the effects of histamine in the brain.

Histamine and ADHD

HNMT, as the primary histamine-degrading enzyme in the brain, appears to be linked to ADHD symptoms, but researchers aren’t sure exactly how [R].

In one interesting study, increased brain histamine worsened behavioral symptoms in children with ADHD. The children with the AA genotype at rs1050891 were more likely to have worse symptoms when they were exposed to artificial food colorings and additives (sunset yellow, carmoisine, tartrazine, ponceau 4R, quinoline yellow, Allura red AC, and sodium benzoate) that raise brain histamine [R].

The ‘T’ allele at rs11558538 is associated with decreased HNMT activity, but the link between this variant and ADHD is not clear [R].

Therefore, cases where brain histamine levels are higher, increasing HNMT may help ADHD.

Certain variations in the HNMT gene make children with ADHD more sensitive to the effects of high brain histamine and a variety of food additives.

Your Histamine Gene Results for Brain Histamine

Important SNPs

HNMT rs1050891:

  • ‘G’ = Normal breakdown of histamine
  • ‘A’ = Reduced breakdown of histamine, higher brain histamine

HNMT rs11558538:

  • ‘C’ = Normal breakdown of histamine
  • ‘T’ = Reduced breakdown of histamine, higher brain histamine

SNP Table

variant genotype frequency risk allele
rs1050891
rs11558538

 

 

Recommendations

To Increase HNMT Activity

S-adenosyl-L-methionine, also known as SAM-e, occurs naturally in your body and donates methyl groups during the methylation processes. Histamine N-methyltransferase (HMNT) inactivates histamine by methylating it; therefore, SAM-e might help HMNT work more efficiently [R, R, R, R].

To Prevent Histamine Release

People who are susceptible to migraine may benefit the most from a diet low in histamine and histamine-releasing agents. For a complete explanation of how the low histamine diet works and whether you should try it, check out this post [R, R].

If you’re looking for a supplement that targets histamine in the brain, you might want to try theanine, an amino acid found in green and black tea. Theanine crosses the blood-brain barrier (BBB), which means that it may be more effective at targeting brain histamine than other natural antihistamines [R, R, R, R].

Most of the strategies for managing histamine intolerance prevent histamine from being either produced (histidine decarboxylase inhibitors) or released (mast cell stabilizers). Over on SelfHacked, we’ve compiled a comprehensive list of supplements and lifestyle options that can help; check out this post to see them all.

It’s also a good idea to reduce the amount of histamine you consume in your food. This post explains how to make the most of a low-histamine diet. For a dive into which foods are high and low in histamine, check out this post. Also, remember to speak with your physician before starting on any new supplement regimen. 

Author photo
Jasmine Foster
BSc, BEd

Jasmine received her BS from McGill University and her BEd from Vancouver Island University.

Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

More inflammation & autoimmunity blogs

More headaches & migraines blogs

More mental health blogs

Unlock Personalized Results And So Much More!

Shipping Worldwide

30-Days Money-Back Guarantee*

HSA/FSA Eligible

Essential Bundle

  • 24/7 AI Health Coach
  • 1250+ Comprehensive DNA Health Reports
  • Personalized Diet, Supplement, & Lifestyle Recommendations
  • Lifestyle Risk Assessments
  • Unlimited access to Labs Analyzer
$418
$376

Men's Health Month 10% Off

Essential

Bundle

  • Everything in essential
  • SelfDecode DNA Kit
  • Methylation Pathway
  • +130 Medical Reports
  • 25+ Longevity Screener Risk Assessments
  • Odds ratios to evaluate your risk for 25+ medical conditions
  • 10-year risk scores to prioritize health conditions
  • Lifetime risk scores to plan for long-term health
$667
$566

Men's Health Month 15% Off

Men's Health Month 30% Off

Ultimate Bundle

  • Everything in essential+
  • SelfDecode DNA Kit
  • Medication Check (PGx testing) for 50+ medications
  • 40+ Family Planning (Carrier Status) Reports
  • Ancestry Percentages
  • Mitochondrial Ancestry
$894
$625

* SelfDecode DNA kits are non-refundable. If you choose to cancel your plan within 30 days you will not be refunded the cost of the kit.

We will never share your data

We follow HIPAA and GDPR policies

We have World-Class Encryption & Security

People Love Us

Rated 4.7/5 from 750+ reviews

People Trust Us

200,000+ users, 2,000+ doctors & 80+ businesses

SelfDecode is a personalized health report service, which enables users to obtain detailed information and reports based on their genome. SelfDecode strongly encourages those who use our service to consult and work with an experienced healthcare provider as our services are not to replace the relationship with a licensed doctor or regular medical screenings.

SelfDecode © 2025. All rights reserved.

Health reports

High Blood Sugar
Anxiety
Gluten Sensitivity
Gut Inflammation
Blood Pressure
IBS
Mood
Insomnia
PTSD
Mood Swings
Overweight
Memory Performance
Sexual Dysfunction
PCOS
Psoriasis
Joint Pain
Attention/ADHD
Chronic Fatigue / Tiredness
Allergies
Asthma
Acne
Tinnitus
Eczema
Food Allergy
Vitamin B6
Vitamin E
Restless Leg Syndrome
Grinding Teeth
Vitamin A
Magnesium
Zinc
Heart Health
Migraines
(High) Cholesterol
Headache
Chronic Pain
Back pain
Shoulder & Neck Pain
Stress
Inflammation
Omega-3 needs
Salt Sensitivity
Endurance
Power performance
Strength
Exercise recovery
Brain Fog
Female Fertility
Longevity
Addiction
Erectile Dysfunction
Male Infertility
MTHFR
Joint Inflammation
GERD
Ulcers
Sleep Apnea
Periodontitis
Varicose Veins
H. pylori
Liver Health
Canker Sores
Gallstones
Kidney Health
Gout
Hair Loss (Male-Pattern Baldness)
Riboflavin
Urticaria
Rosacea
Carpal Tunnel Syndrome
Sinus Congestion
Cavities
Artery Hardening
Vertigo
Vitiligo
Myopia
Indigestion
Excessive Sweating
Testosterone – Males
Yeast infection (Candida)
Endometriosis
Tobacco addiction
Alcohol addiction
Uterine fibroids
Length of menstrual cycle
UTI
OCD
Kidney Stones
Vitamin B12
Vitamin C
Vitamin D
Folate
Iron
Eating Disorders
Bone Health
Hypothyroidism
Hyperthyroidism
Sugar Cravings
Hearing/difficulty problem /Hearing loss
Painful Periods
Palpitations
Hemorrhoids
Hypotension
Bladder Control
Constipation
Appendicitis
Low Blood Sugar
Irregular Periods
Metabolic rate
Visceral fat
Lung Health
Anemia
Calcium
Cognition
Cognitive Decline
Seasonal Low Mood
Vitamin K
Phosphate
HRV
Cluster headaches
Knee Pain
Hip Pain
Selenium
Low back injury
Dyslexia
Cannabis addiction
Histamine Intolerance
Carnitine
Pesticide Sensitivity
Organophosphate Sensitivity
Cadmium
Lead
Melatonin
FSH
T4
T3
High PTH
Potassium
Coenzyme Q10 (CoQ10)
Chromium
Oxalate Sensitivity
Salicylate Sensitivity
Facial Wrinkles
Age Spots
Ligament Rupture (ACL Injury)
Tendon Injury (Tendinopathy)
Omega 6
Omega 6:Omega 3 Ratio
Arachidonic Acid
Oleic Acid
Alpha-Linolenic Acid
EPA
GLA
Linoleic Acid
DHA
Insulin Resistance
Sperm Motility
Homocysteine
C difficile
Pneumonia
EBV Infection
Gastrointestinal Infection
Chronic Bronchitis
Copper
Skin Elasticity
Skin Hydration
Egg allergy
ApoB
GGT
TIBC
Bioavailable Testosterone (Male)
MPV
Chloride
Free T4
Processing Speed
Short-term memory
TMAO
Air pollution sensitivity
Heart Rate
VO2 Max
Flu
Hair graying
Caffeine-Related Sleep Problems
Groin Hernia
Stretch marks
Droopy Eyelids
Strep infection
Dry eyes
Carbohydrate Consumption
Peanut allergy
Heart rate recovery
Muscle recovery
Jaw Disorders
HPV Infection
Acute Bronchitis
Chlamydia
Genital Herpes
Pancreas inflammation
Executive Function
Pyroglutamic acid
Raynaud’s
Liver Scarring
Dandruff
Bioavailable Testosterone (Female)
Shrimp allergy
Haptoglobin
Milk allergy
Beta-Alanine
Taurine
LDL Particle Size
Diarrhea
Snoring
Uric acid
Phenylalanine
Leucine
Glutamine
Valine
Glycine
Alanine
Lysine
Arginine
Histidine
Tyrosine
Cortisol
DHEAS
Insulin
Prolactin
TSH
Lactate
Ketone Bodies
IL-17A (Th17 Dominance)
Creatine Kinase
Neutrophils
Basophils
Eosinophils
Ferritin
ALT
AST
MCV
Hematocrit
RDW
SHBG
Total Protein
Albumin
MCH
Sodium
MCHC
Alkaline Phosphatase
Monocytes
Ghrelin
IL10 (Th2)
IL-6 (Th2 and Th17)
Iodine
Chili Pepper sensitivity
COMT
DRD2 (Dopamine)
Lectin Sensitivity
Thiamine
Biotin
Mold Sensitivity (Foodborne)
Chronic Lyme
BDNF
Glyphosate sensitivity
BPA Sensitivity
Pregnenolone
Luteinizing Hormone (LH)
Growth Hormone
IgA
Molybdenum
Sensitivity to Dairy (IgG Casein)
Telomere Length
Serotonin (5HIAA)
Non-Celiac Gluten Sensitivity (IgG Gliadin)
Manganese
Klotho
Mold Sensitivity (Airborne)
Amylase
Lipase
Low Sperm Count
Tryptophan
Methionine
Glutamate
Proline
Blood Calcium
Hypertriglyceridemia
HDL Cholesterol
HbA1c
Hemoglobin
Total Cholesterol
LDL Cholesterol
IGF1
Fasting Glucose
Bilirubin (total)
White blood cell count
Red blood cell count
Platelets
eGFR
Creatinine
Estradiol
Neuroticism
Sleep Quality
Lactose Intolerance
Saturated fat
Optimal diet
Unsaturated fat
Achilles tendon injury
Deep sleep
Fat
Response to Stress
Leadership
Ankle injury
Creativity
Hoarding
Protein
Optimal Exercise
Knee Injury
Rotator cuff injury
Extraversion
Risk-Taking
Happiness
Daytime Sleepiness
Morningness
Time spent watching TV
Disliking cilantro
Alcohol Sensitivity
Response to Caffeine
Snacking
Weight Regain
Sleep movement
Wearing glasses or contacts
Educational Attainment
Bitter Taste Sensitivity
Agreeableness
Aggression
Conscientiousness
Openness to experience
Physical activity
Caffeine-Related Anxiety
Naps