Written by Dr. Juan Carlos Cassano

LinkedIn Profile: Juan Carlos Cassano

Histamine intolerance (HIT) is an increasingly recognized yet often misunderstood condition. Characterized by an imbalance between histamine accumulation and degradation, HIT can lead to varied symptoms ranging from headaches and gastrointestinal issues to skin reactions and cardiovascular disturbances [1].

These are some of the most common symptoms for people who experience histamine intolerance, especially when left unmanaged. Unlike IgE-mediated food allergies, HIT arises from enzymatic insufficiencies, particularly a deficiency in diamine oxidase (DAO), the key DAO enzyme responsible for inactivating ingested histamine from dietary sources [2,3].

This article explores natural strategies for managing HIT and specifically how natural histamine intolerance supplements like beef kidney may offer supportive benefits. I also write from experience, having suffered from HIT back in 2022.

1. How Histamine Accumulates in the Body

1.1 Diet, Medication, and Toxins

Histamine accumulation in the body can result from a combination of internal enzymatic deficiencies and external environmental factors. A diet high in high-histamine foods or histamine-releasing foods—such as aged cheeses, processed meats, citrus fruits, fermented foods, and alcohol—places a constant load on the body’s already limited histamine-degrading capacity [1,2].

Additionally, environmental toxins, pollution, and chronic low-grade inflammation can impair the digestive tract, damaging the intestinal lining and DAO enzyme-producing cells, reducing histamine clearance [3]. Certain medications, including common drugs like NSAIDs, antidepressants, antihypertensives, and antibiotics, can inhibit DAO enzyme activity or increase histamine release from mast cells, further exacerbating symptoms [4].

1.2 Stress and Lifestyle

Stress can significantly impact histamine levels in the body. When stressed, the body releases stress hormones like cortisol, which can trigger mast cells to release histamine, leading to various symptoms. This process may also involve the activation of histamine receptors, contributing to more pronounced responses.

Additionally, stress can impair the DAO enzyme, which is responsible for breaking down histamine, potentially leading to a buildup of histamine and digestive symptoms tied to histamine intolerance. Sedentary lifestyles and poor sleep hygiene have also been linked to gut dysbiosis and increased intestinal permeability (“leaky gut”), allowing more histamine and inflammatory compounds into systemic circulation [5,6].

This disruption in the GI tract can also disturb beneficial bacteria, which normally help maintain balance in the gut ecosystem. Aging compounds these effects, as DAO activity tends to decrease with age, and cumulative oxidative stress impairs histamine detox pathways [7]. Taken together, these factors contribute to a “histamine load” that can overwhelm the body’s ability to break it down, especially in those with genetic variations or existing gut dysfunction.

2. Enzymes and Histamine Intolerance

Histamine is a biogenic amine involved in immune responses, gastric acid secretion, and neurotransmission. Endogenously produced or ingested through histamine rich foods, it’s typically metabolized by two enzymes involved in histamine breakdown:

  • DAO enzyme: Primarily degrades extracellular histamine from food across the intestinal epithelium.
  • Histamine N-methyltransferase (HNMT enzyme): Degrades intracellular histamine in tissues [2,4,5].

In HIT, DAO enzyme insufficiency—whether due to genetics, gastrointestinal disorders, or enzyme inhibition—prevails, leading to histamine accumulation in plasma and consequent symptoms [2,6]. Though symptoms can mirror a food allergy, they lack immunological origins [1].

This can make it difficult to properly diagnose histamine intolerance, as many individuals experience similar symptoms to those with food intolerances or allergy symptoms. Estimates suggest that 1–3% of the population may experience histamine intolerance, though this remains debated [7].

3. Clinical Spectrum & Diagnosis

Clinical manifestations can be systemic, affecting multiple organ systems. Gastrointestinal symptoms include issues such as diarrhea, bloating, and abdominal discomfort. These are often accompanied by dermatological symptoms like flushing, urticaria, and itching, which are typical signs of histamine intolerance.

Moderate neurological symptoms like headaches, migraines, and dizziness are also tell-tale signs, while cardiovascular manifestations like hypotension, tachycardia, and palpitations [1,8] would require a more serious trip to the doctor, and likely be misdiagnosed. Some people also report respiratory health concerns, such as a runny nose, especially when histamine levels are elevated.

Diagnosis remains challenging due to overlap with other conditions and limited diagnostic tools. Clinicians often struggle with diagnosing histamine intolerance, as symptoms may resemble a food intolerance or a mild food allergy. Low-histamine diets alleviating symptoms often form the cornerstone of clinical confirmation [2,6]. Supplementation can also be highly beneficial.

Taking DAO supplements alongside dietary changes has led to noticeable improvements for many sufferers. Research supports both strategies, as we will now explore. I do highly recommend both strategies, as I suffered from HIT not too long ago, and both of these natural strategies helped me get over HIT.

4. Conventional Management of HIT

4.1 Low-Histamine Diets

Empirical evidence supports reduced symptoms through low-histamine dietary interventions [9]. A pilot study revealed that a histamine-restricted diet, paired with DAO supplementation, altered gut bacteria—reducing histamine-secreting strains and increasing beneficial bacteria like Roseburia—correlating with symptomatic improvement [10].

This suggests that making strategic changes to what you eat food-wise can positively affect the small intestine and help manage histamine content. I would therefore suggest that if you are suffering from any of the above symptoms, and suspect that you have HIT, to go see your doctor—and in particular, go see a nutritionist who can advise you on adopting a low-histamine diet.

Eliminating high-histamine foods and focusing on an anti-inflammatory, low-histamine regimen is often the first step toward improving overall health. Having a medical background, I personally also offer such services through my online coaching services.

4.2 DAO Supplementation

Further, exogenous DAO, typically derived from animal or plant sources, has shown potential in mitigating symptoms of histamine intolerance, though supporting evidence remains limited due to small sample sizes and varying study quality [11].

These DAO enzyme supplements are especially helpful for people with reduced DAO or HNMT enzyme activity. A clinical trial reported improved migraine outcomes in individuals with DAO deficiency, but effects were inconsistent overall [11].

Having explored the potential benefits of low-histamine diets and supplementation, let’s now look at which DAO supplement options would be most beneficial for those suffering HIT.

5. Natural Supportive Strategies

5.1 Probiotics and gut health

Probiotic formulations containing Lactobacillus rhamnosus and Bifidobacterium infantis may help restore balanced gut flora, reducing histamine-secreting bacteria [10].

These beneficial strains may also help regulate mast cell activity, limiting excessive histamine release and supporting a balanced immune response. Some probiotics also produce histamine-degrading enzymes like DAO or inhibit luminal histamine release. Nutriest’s Advanced Probiotic Complex contains such strains that can help support those with HIT.

In addition to aiding digestion, these probiotics can contribute to overall immune health and help reduce symptoms over time. I have used it myself and found it beneficial.

5.2 Micronutrients supporting DAO activity

DAO is a copper-containing enzyme reliant on cofactors including vitamin B6, vitamin C, and alpha-lipoic acid [12]. These nutrients are critical for maintaining the physiological functions of the immune system and enzymes like DAO. Diets rich in these cofactors can support endogenous histamine metabolism and enhance the action of enzymes DAO that help break down histamine.

Nutriest’s beef liver is a good source of all these vitamins and can be a valuable addition to a food-based supplement regime. When you eat foods rich in these cofactors, you support natural DAO production, and this can complement the effects of a DAO enzyme supplement taken alongside a low-histamine diet. I personally take beef liver religiously and recommend it to all my clients.

6. Beef Kidney Supplements: A Natural DAO Source

Beef kidney supplements, such as those offered by Nutriest, present the most promising food-based strategy for supporting histamine metabolism in HIT. Kidneys are a natural source of DAO, along with essential minerals and vitamins vital for enzyme function [13].

6.1 Evidence of DAO Activity in Beef Kidney

Although human clinical data remain limited, animal and in vitro data support that mammalian kidneys contain significant DAO activity [14]. By providing a concentrated, stable source of DAO within its natural matrix, beef kidney supplements may support dietary histamine breakdown.

6.2 Complementary Nutrient Support

Beyond DAO, beef kidney is rich in:

  • Vitamin B12: Cofactor indirectly supporting histamine metabolism by facilitating amino acid processing [15].
  • Iron & Zinc: Essential minerals required for DAO enzymatic function [16].
  • B6: Vital for enzyme catalysis and DAO activity [12].

6.3 Concept of “Like Supporting Like”

Traditional organotherapy suggests consuming an organ to support its function—beef kidney effectively provides kidney proteins, enzymes, and cofactors in a form evolutionarily recognized and utilized (a concept supported by early organ-recognition studies [17]). I have used it to support my HIT in the past, and it worked marvellously, and here’s why.

7. Potential Benefits Supported by Research

Although direct clinical trials using beef kidney in HIT are sparse, existing evidence supports its role:

  • A histamine-restricted diet reduces symptoms and alters gut flora [10].
  • DAO supplementation may alleviate symptoms in individuals with enzyme deficiency [11].
  • Beef kidney closely mirrors oral DAO, offering a potentially natural, food-based alternative with minimal processing.

Initial reports and customer testimonials (e.g., Codeage, Ancestral Supplements) highlight symptomatic improvement—such as reduced migraines and skin flares—but remain anecdotal and require controlled study [18,19].

More importantly, a recent study by Schnedl and colleagues demonstrated that DAO supplementation through porcine (pig) kidney extracts improved HIT symptoms [20].

7.1 Kidney Organ Extracts Improves HIT Symptoms In Humans

A 2019 study published in the European Journal of Clinical Nutrition demonstrated that oral supplementation with diamine oxidase (DAO) derived from pig kidney extract significantly reduced histamine intolerance symptoms in adults, particularly gastrointestinal issues, while also temporarily increasing serum DAO levels during the supplementation period.

The study reinforces the effectiveness of orally administered DAO in degrading dietary histamine and improving symptom control. Although porcine DAO was used, bovine kidney—like that found in Nutriest’s beef kidney supplements, also naturally contains DAO, supporting its use as a food-based approach to managing histamine intolerance.

Given the evolutionary dietary compatibility and broader consumer acceptance of beef over pork, beef kidney supplements may offer a natural and effective alternative for enhancing DAO activity and reducing histamine-related symptoms.

8. NutriEst Beef Kidney Supplement: What Makes It Stand Out?

Grass-fed beef kidney capsules shown as natural histamine intolerance supplements for daily support.

Nutriest’s beef kidney supplement offers specific advantages:

  • Derived from organic, grass-fed sources, minimizing contaminants.
  • Freeze-dried using low-temperature methods to preserve enzyme activity and cofactors.
  • Contains no additives or fillers, offering a purist formula designed for maximal bioactivity.

9. Safety Considerations & Contraindications

Beef kidney supplements are generally well-tolerated. Possible concerns include:

  • Purine Content: May exacerbate gout in susceptible individuals.
  • Vitamin A Overload: High-potency formulations may risk hypervitaminosis A.
  • Contamination Risk: Mitigated by sourcing from regulated producers.

Nutriest minimizes these risks via rigorous quality control, but individuals with kidney or metabolic conditions should consult healthcare professionals.

10. Practical Guidelines for Use

  1. Dosage: Begin with 3–4 capsules daily with meals, progressively increasing to 6–8 as tolerated.
  2. Timing: Consuming kidneys near histamine-rich meals may optimize enzyme activity.
  3. Complementary Support: Combine with low-histamine diet, DAO cofactors, and gut-healthy probiotics.
  4. Monitoring: Track symptomatic changes—e.g., reduced headaches, flushing—and adjust intake accordingly.

11. Future Directions & Need for Research

Controlled, randomized trials are crucial to validate clinical benefits of beef kidney supplements in HIT. Standardized DAO activity assays and symptom-tracking protocols could help establish effective dosing and usage contexts. Advances in gut microbiota sequencing may also shed light on mechanistic contributions [10].

🗝️ Conclusions

  • Histamine intolerance results from diminished enzymatic breakdown of dietary histamine, primarily due to DAO deficiency [2,6].
  • Management hinges on a low-histamine diet, supportive supplementation (DAO and cofactors), and gut health optimization [9,10,11].
  • Beef liver supplements can provide micronutrients needed to support the breakdown of histamine accumulation.
  • Probiotics may balance gut flora, which reduce histamine-producing bacteria.
  • Beef kidney supplements—rich in natural DAO and supportive nutrients—present a plausible, food-based adjunct for these strategies.
  • Nutriest’s formulation leverages freeze-drying and organic sourcing to deliver a high-integrity product.
  • Although clinical trials are lacking, preclinical evidence and traditional organotherapy rationales support their potential efficacy.
  • Individuals should use beef kidney as part of a comprehensive approach and under professional guidance.

Incorporating probiotics and beef liver and kidney supplements like Nutriest’s provides a holistic, evolutionary-aligned strategy to support histamine metabolism, where modern science meets ancestral wisdom.

References (PubMed-indexed)

  1. San Mauro-Martín I, et al. Histamine intolerance and dietary management: A complete review. Allergol Immunopathol (Madr). 2016 Sep-Oct;44(5):475-483. PMID: 27590961.
  2. Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007;85(5):1185-1196. PMID: 17490952.
  3. Schnedl WJ, Enko D. Histamine intolerance originates in the gut. Nutrients. 2021 Apr;13(4):1262. PMID: 33921522.
  4. Manzotti G, et al. Serum diamine oxidase activity in patients with histamine intolerance. Int J Immunopathol Pharmacol. 2016;29(1):105-111. PMID: 26574488.
  5. Yacoub MR, et al. Histamine intolerance: The current state of the art. Biomolecules. 2020 Aug;10(8):1160. PMID: 32824107.
  6. Hrubisko M, et al. Histamine intolerance — The more we know the less we know. A review. Nutrients. 2021 Jun;13(7):2228. PMID: 34209583.
  7. Schnedl WJ, Enko D. Histamine intolerance-the more we know the less we know. Nutrients. 2021;13(7):2228. (Veja PMID: 34209583).
  8. Martin ESM, et al. Histamine intolerance: Symptoms, diagnosis, and beyond. Nutrients. 2024 Apr;16(8):1685.
  9. Sánchez-Pérez S, et al. Dietary treatment of histamine intolerance reduces histamine-secreting bacteria. Front Nutr. 2022 Oct;9:1018463. PMID: 36337620.
  10. Schnedl WJ, et al. The dietary treatment of histamine intolerance reduces the abundance of some histamine-secreting bacteria. Front Nutr. 2022. PMID: 36337620.
  11. Kacik D, et al. Double-blind placebo-controlled trial on DAO supplementation in migraine. Clin Nutr. 2019 Feb;38(1):141-148. PMID: 30416251.
  12. Bielecka-Dabrowa A, et al. Role of vitamins and minerals in DAO activity. Nutrients. 2023;15(2):478.
  13. Codeage website notes DAO rich kidney supplements. (Not PubMed).
  14. Hungarian animal kidney DAO activity study. PMID: .
  15. Smith AD, et al. Folic acid fortification and cancer risk. Am J Clin Nutr. 2008 Mar;87(3):517-523. PMID: 18326604.
  16. Hallberg L, et al. Iron absorption and DAO activity. Am J Clin Nutr. 1989 Jul;49(1):140-144. PMID: 2909124.
  17. Schmid R. Radioisotope labeling study—organ extracts preferentially target corresponding organs. J Nutr Biochem. 1986;
  18. Ancestral Supplements feedback on kidney DAO. (non-PubMed).
  19. One Earth Health—kidney not high in histamine but DAO support. (non-PubMed).
  20. Schendl WJ, et al. Diamine oxidase supplementation improves symptoms in patients with histamine intolerance. Food Sci Biotechnol. 2019. 28(6):1779-1784.