Am I the only one who has been curious about this topic? I have seen histamine mentioned so many times in the lipedema community, people have asked me about it, and honestly, much of it was new to me.
What is histamine?
Histamine is a natural signalling molecule involved in immune responses, blood vessels, digestion and the nervous system. Mast cells are one important source of histamine in the body.
It is not particularly relevant to me personally. Except for white refined sugar, hormones and stress, which are my lipedema triggers, I do not have any known food intolerances or food allergies. My lipedema is not triggered by eating whole-grain bread, pasta or pizza, for example. White refined sugar is a completely different story for me.
But LipedemaScience is not only about what affects me. I want this to be an inclusive platform where we also explore things that may affect some of you, even when they do not affect me. We are different, our bodies are different, and our journeys with lipedema are different. This might be the one article that someone reads and thinks: This sounds like me. So I wanted to understand what the research actually says about histamine, mast cells and lipedema.
Why are histamine and mast cells interesting?
Histamine is a normal signalling molecule in the body. It is involved in immune responses, blood vessels, stomach acid production and the nervous system. Mast cells are immune cells that can release histamine together with many other signalling molecules.
What has been found in lipedema?
One small controlled study did not detect increased numbers of mast cells in lipedema tissue. A later study found higher histamine levels in lipedema adipose tissue compared with control tissue.
This makes mast cells interesting in lipedema research because histamine and mast-cell activity can influence vascular permeability, inflammation and nerve signalling, processes that could theoretically be relevant to pain and swelling. There is also research on mast cells in other conditions involving adipose tissue, pain and hormones. However, evidence from another disease, an animal model or a laboratory experiment cannot tell us that the same mechanism occurs in lipedema.
When we look specifically at lipedema, the evidence is still very limited. A controlled tissue study by Al-Ghadban and colleagues in 2019 examined tissue from women with and without lipedema. The researchers found several differences, including increased macrophages, but they did not detect a significant increase in mast-cell numbers in the lipedema groups. Because the study was small, this does not prove that mast-cell numbers are identical. It simply means that an increase was not demonstrated.
Then came an interesting histamine finding
In 2023, Bonetti and colleagues analysed subcutaneous adipose tissue from 44 people with lipedema and 18 controls. They reported substantially higher histamine in the lipedema tissue, with a mean concentration of 3.00 pg/mg compared with 1.38 pg/mg in control tissue. Several compounds involved in histamine metabolism were also higher. This provides a reason to investigate local histamine biology further, but it does not tell us why the difference was present.
Does this mean people with lipedema have histamine intolerance?
No. Local histamine in adipose tissue and histamine intolerance are different biological questions. There is currently no good evidence that histamine intolerance is more common in people with lipedema.
This distinction is important because mast-cell number, mast-cell activity and histamine concentration are not the same measurement. The earlier study did not detect more mast cells, while the later study found more histamine. Those findings are not necessarily contradictory. A tissue could theoretically contain a similar number of mast cells while differing in mast-cell activation, histamine release or histamine metabolism. We simply do not have enough research yet to know whether this is happening in lipedema.
The same study also included a very small experiment in which three people with lipedema received sodium cromoglycate, a mast-cell stabilising drug, for 15 days. Their tissue histamine decreased, but there was no placebo group and the study did not demonstrate improvements in clinical outcomes such as pain, swelling or quality of life. Three participants are far too few to establish that mast-cell stabilisation is an effective treatment for lipedema.
This is not evidence of histamine intolerance
This is where I think much of the online discussion goes too far. Finding more histamine in lipedema adipose tissue is not the same as demonstrating histamine intolerance. It also does not demonstrate allergy or MCAS. These are different biological and clinical questions. At present, there is no good evidence showing that histamine intolerance is more common in people with lipedema than in comparable people without it.
Histamine intolerance generally refers to symptoms thought to occur when the body cannot adequately handle a histamine load, particularly from food. The difficulty is that there is no single reliable laboratory test that confirms it. Serum DAO is sometimes marketed for this purpose, but current evidence does not support using DAO alone to diagnose histamine intolerance.
The symptoms are also very non-specific. They may include headache or migraine, facial flushing, a blocked or runny nose, itching or hives, diarrhoea, abdominal pain, bloating, nausea, palpitations and dizziness, often appearing from minutes to several hours after eating. The same symptoms can have many other explanations, including food allergy, coeliac disease, IBS and other gastrointestinal conditions.
Should people with lipedema eat a low-histamine diet?
Not based on lipedema alone. There is currently no clinical evidence that a low-histamine diet treats lipedema. If you have symptoms that repeatedly appear after eating histamine-rich foods, possible histamine intolerance can be investigated separately.
This uncertainty was illustrated in a 2023 study of 59 people who suspected they had histamine intolerance. After a single-blind, placebo-controlled histamine challenge, histamine intolerance was excluded in about 85% of them. More than 60% reacted to placebo, while only four participants developed objective symptoms after histamine but not placebo. This does not mean that histamine-related symptoms are imaginary. It shows how difficult they are to diagnose from symptoms alone.
What if you think histamine affects you?
Having lipedema alone is not a reason to follow a low-histamine diet. Nothing currently shows that reducing dietary histamine treats lipedema. But if you repeatedly experience symptoms that appear to be connected to certain foods, it may be reasonable to investigate this separately from your lipedema.
Foods with higher histamine levels are often aged, fermented or stored for longer periods. Examples include aged cheeses, cured meats, sauerkraut, kimchi, soy sauce, miso, canned or smoked fish and some alcoholic drinks. Tomatoes, spinach, aubergine and avocado are also commonly listed as relatively high-histamine foods. Histamine can also increase during storage, particularly in protein-rich foods such as meat and fish, which means freshness can matter.
You may also find very long lists online of foods described as “histamine liberators”, including strawberries, citrus fruits, nuts and chocolate. Evidence for many of these claims is poor, so there is little reason to automatically eliminate every food appearing on such a list.
If histamine intolerance is genuinely suspected, clinical guidance recommends a short and structured approach rather than a permanent restrictive diet. A histamine-reduced diet can be tried for around 10 to 14 days while symptoms are monitored. If symptoms do not clearly improve, histamine becomes a less convincing explanation. If they do improve, foods can gradually be reintroduced to identify individual tolerance. The long-term goal should be the most varied diet possible, not the longest possible list of foods to avoid.
This is particularly important in the lipedema community. Many people have already been told to remove carbohydrates, gluten, dairy, sugar, nightshades or other food groups. Adding another restrictive diet without a good reason can unnecessarily reduce both nutritional variety and quality of life.
Where does this leave us?
There is a genuine scientific reason to investigate histamine and mast cells in lipedema. One small controlled tissue study did not detect increased mast-cell numbers, while another study found substantially higher histamine and histamine-related metabolites in lipedema adipose tissue. What we do not yet know is whether mast-cell activity is altered, why local histamine was higher, whether the finding can be independently replicated, or whether any of this contributes directly to lipedema symptoms.
For now, the evidence does not show that people with lipedema generally have histamine intolerance, MCAS or allergy, and there is no evidence that a low-histamine diet, DAO supplements, antihistamines or mast-cell stabilisers treat lipedema.
But that does not mean histamine is irrelevant. It means we have an interesting research signal and many unanswered questions.
If the symptoms of histamine intolerance described here sound familiar to you, investigate your symptoms, rather than assuming they are part of lipedema. Other causes should be considered first, ideally with a doctor or registered dietitian. If a low-histamine trial is appropriate, keep it short, structured and followed by reintroduction.
The question is not whether everyone with lipedema should avoid histamine.
It is whether histamine might matter for you.
Histological and Molecular Characterization of Lipedema Adipose Tissue (DOI: 10.1155/2019/8747461)
Targeting Mast Cells: Sodium Cromoglycate as a Possible Treatment of Lipedema (DOI: 10.7417/CT.2023.2496)
Increased levels of VEGF-C and macrophage infiltration in lipedema patients without changes in lymphatic vascular morphology (DOI: 10.1038/s41598-020-67987-3)
Guideline on management of suspected adverse reactions to ingested histamine (DOI: 10.5414/ALX02269E)
Histamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: a randomised, double-blind, placebo-controlled cross-over study (DOI: 10.1111/j.1398-9995.2010.02498.x)
My histamine is off the charts. Discovered on genetic bloodwork. Says I am in danger for clotting and more. I was instructed to take methylated B complex. And I recently had to go gluten free after having horrific intestinal issues. Self diagnosed due to needing immediate relief.
Great post.
Another thing worth noting is that sometimes people react SOMETIMES.
I sometimes get a stuffy nose when drinking wine, sometimes I do not.
I also sometimes have a reaction to fire ants- full blown sneezing, watery swollen eyes- and some years I do not.
Collagen was messing with my gut for awhile. But now it does not. It is all so nuanced and definitely not one size fits all.