How blood sugar affects histamine release

There is a link between histamine and blood sugar, with blood sugar imbalances increasing histamine levels. Histamine intolerance and mast cell activation syndrome (MCAS) can contribute to metabolic issues such as insulin resistance and diabetes.

If you’re struggling with histamine intolerance that is contributing to vagina or urinary tract issues, managing blood sugar is extra important.

Dysregulated blood sugar increases histamine release from mast cells, which in turn causes inflammation. Over time, blood sugar dysregulation can reduce overall immunity, resulting in more frequent infections​1​.

Understanding blood sugar

Glucose is a form of sugar, transported in the blood after eating, travelling around to cells. Cells then use glucose as a form of energy.

When you eat, sugars from the meal are absorbed into the bloodstream, triggering the release of insulin from the pancreas. Insulin is the key that unlocks the cell door to allow the glucose safely inside. Without insulin, the sugar can’t get into the cell and remains in the blood where it is dangerous.

Understanding metabolic issues like diabetes and insulin resistance

Insulin resistance

Insulin resistance is the first step to prediabetes and diabetes.

Insulin resistance means your cells won’t ‘open the door’ when insulin comes a-knockin’, so your pancreas sends out more and more.

Insulin can have a problematic impact on other tissue, for example, stimulating the ovaries to produce testosterone and other androgens.


Diabetes is a condition whereby blood sugar levels become excessive. Type I diabetes means your body can’t make insulin, while type 2 diabetes means your body isn’t making enough insulin or isn’t making the most of it.


In prediabetes, blood sugar levels are too high, but not high enough to be considered diabetes.


Hypoglycaemia is a low blood sugar condition where blood sugar drops and symptoms are felt such as shaking, anxiety, sweating, dizziness, irritability and tiredness. Diabetics may experience hypoglycaemia.

You can get hypoglycaemia a few hours after eating (‘reactive’) or when you haven’t eaten for a while (‘fasting’). Some medication or underlying health conditions can contribute to or cause hypoglycaemia.

If you don’t eat for long spells or eat high sugar foods, you may experience hypoglycaemia.

Blood sugar changes can impact your histamine levels.

Understanding histamine

Histamine, produced by mast cells (white blood cells), has a great many tasks in our bodies, from the release of stomach acid to relieving your tissue of allergens.

Histamine is being released regularly for various functions and would build up if not for the action of diamine oxidase (DAO).

DAO degrades histamine, but it can only go so fast, and some people don’t produce enough DAO naturally to keep up with demand.

Histamine intolerance (or excess) can be a contributing factor driving insulin resistance, prediabetes and diabetes.

Blood sugar and histamine are closely connected. You don’t have to have diabetes for this connection to be playing out every day in your body – many of us are walking around with blood sugar issues without them being as noticeable as diabetes.

Balancing blood sugar can help manage histamine intolerance, so eating the right kinds of food regularly slows the release of glucose into the blood and keep it steady, rather than highs and lows. Blood sugar fluctuations can stimulate the release of histamine, with each of us with varying levels of sensitivity.

What the research tells us

  • Diabetics have elevated histamine levels​2​
  • Diabetic rats have lower levels of DAO​3​
  • H1 and H2 histamine receptors may have an impact on blood sugar regulation and fat metabolism​4​
  • Tweaking the H3 histamine receptors in diabetic mice reduces blood sugar​5​
  • Targeting and inhibiting H4 histamine receptors may be useful in the treatment of diabetes and diabetic neuropathy​6​
  • Mast cells should be taken into consideration when treating metabolic disease, inflammation and immune system conditions​7​
  • Advanced glycation end products (AGEs) accumulated in those with diabetes, cardiovascular diseases, cancer, neurodegenerative disease can activate mast cells and lead to histamine release​8​
  • Mast cell stabilising drugs including antihistamines may help reduce complications in diabetics

Balancing blood sugar

Measuring blood sugar

To balance your blood sugar, you’ll need a starting point, which is a relatively inexpensive gadget.

Do a search for a ‘blood sugar measuring device’ and compare products or ask your local diabetes organisation for a recommendation. This device will allow you to measure your progress in real-time and tweak your actions according to results.

The low-histamine diet

Just eating like a diabetic isn’t going to be the only change you’ll need – the low-histamine diet is an important method of reducing your overall histamine load.

The low glycaemic index (GI) diet

Eating foods that are digested slowly – low GI – to allow steady flows of glucose, is the goal. This may mean a dramatic diet change, to eating like a diabetic.

Searchable GI foods list

Taking histamine-degrading herbs and nutrients

Vitamin C, quercetin, nettle and fresh ginger are all examples of nutrients and herbs that degrade histamine in the body.

Taking DAO enzymes with food

There are specific products that contain DAO, the enzyme that breaks down histamine in the digestive tract. These products can help when taken before eating high histamine foods.


  1. 1.
    Alves C, Casqueiro J, Casqueiro J. Infections in patients with diabetes mellitus: A review of pathogenesis. Indian J Endocr Metab. Published online 2012:27. doi:10.4103/2230-8210.94253
  2. 2.
    Gill D, Barradas M, Fonseca V, Dandona P. Plasma histamine concentrations are elevated in patients with diabetes mellitus and peripheral vascular disease. Metabolism. 1989;38(3):243-247. doi:10.1016/0026-0495(89)90082-6
  3. 3.
    Fogel WA, Chmielecki C, Grałek M, Maslinski C. Histamine metabolism in diabetic rats. Agents and Actions. Published online April 1990:243-246. doi:10.1007/bf01969050
  4. 4.
    Wang K, Tanimoto A, Yamada S, et al. Histamine regulation in glucose and lipid metabolism via histamine receptors: model for nonalcoholic steatohepatitis in mice. Am J Pathol. 2010;177(2):713-723. doi:10.2353/ajpath.2010.091198
  5. 5.
    Henry M, Zheng S, Duan C, et al. Antidiabetic properties of the histamine H3 receptor protean agonist proxyfan. Endocrinology. 2011;152(3):828-835. doi:10.1210/en.2010-0757
  6. 6.
    Rao AU, Shao N, Aslanian RG, et al. Discovery of a Potent Thiadiazole Class of Histamine H3Receptor Antagonist for the Treatment of Diabetes. ACS Med Chem Lett. Published online November 22, 2011:198-202. doi:10.1021/ml200250t
  7. 7.
    Kempuraj D, Caraffa A, Ronconi G, Lessiani G, Conti P. Are mast cells important in diabetes? Pol J Pathol. 2016;67(3):199-206. doi:10.5114/pjp.2016.63770
  8. 8.
    Sick E, Brehin S, André P, et al. Advanced glycation end products (AGEs) activate mast cells. Br J Pharmacol. 2010;161(2):442-455. doi:10.1111/j.1476-5381.2010.00905.x

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Jessica Lloyd - Vulvovaginal Specialist Naturopathic Practitioner, BHSc(N)

Jessica is a degree-qualified naturopath (BHSc) specialising in vulvovaginal health and disease, based in Melbourne, Australia.

Jessica is the owner and lead naturopath of My Vagina, and is a member of the:

  • International Society for the Study of Vulvovaginal Disease (ISSVD)
  • International Society for the Study of Women's Sexual Health (ISSWSH)
  • National Vulvodynia Association (NVA) Australia
  • New Zealand Vulvovaginal Society (ANZVS)
  • Australian Traditional Medicine Society (ATMS)