Up until quite recently, very little, however the evidence base has been growing throughout the last decade. Despite that, there are still huge gaps in our knowledge, and the quality of the data is often low, largely due to the discrepancy between the low histamine food lists used in each study.1 Public interest in this area is growing, partially due to the suggestion of a link between HIT and covid, yet we still don’t have any conclusive biomarkers that can confirm the condition or a ‘gold standard’ low histamine food list.2 In this article, I’ll discuss the things we do know about HIT, some of the potential causes and, how we as dietitian’s can help to treat this condition.
To really get to grips with the many symptoms that histamine intolerance can cause, we need to fully understand the role of histamine in the body. Histamine acts as a chemical messenger and is involved in numerous physical processes.3-6 There are histamine receptors throughout the body and, therefore, histamine has a number of roles including mediating our response to inflammation, gastric acid secretion and muscle contraction.3
It is not a primary IgE mediated allergy, however as it can share some of the symptoms of an allergy it is important that this is ruled out before a diagnosis of HIT is made.7 According to Maintz and Novak,5 it is ‘a disequilibrium of accumulated histamine and the capacity for histamine degradation’. This has been estimated to effect approximately 1% of the population, however the true number is likely to be a lot higher due to underdiagnosis as a result of a lack of clear diagnostic tools. In view of this, it is really important that we as dietitians’ are aware of the condition and the symptoms that those with HIT may present with.
In my experience, absolutely anything! HIT symptoms can vary so much between patients, and it can present very differently. In addition to this, symptoms can vary day to day for each individual. It is a whole body condition and some of the common symptoms we see are as follows:
It has also been suggested in a case report that HIT may be a cause of laryngopharyngeal reflux in a small number of patients.8 Many patients that we see have presented to a variety of specialists and have often struggled to find any resolution for their multiple symptoms, as their symptoms haven’t necessarily been assessed holistically.
Some of us who work within this field, have found that women are presenting with symptoms of HIT around the menopause, and it is certainly something that is talked about through online channels. At present the evidence base around this is extremely limited, however the effect that hormones can have on the sensitivity to histamine has been documented.5,15 It has been observed that there may be an increased sensitivity to histamine in the premenstrual phase, and this is certainly something that I’ve seen in practice.5 Many of my female clients who experience HIT, also experience dysmenorrhoea, and it has been suggested that this may be associated with this increased sensitivity to histamine.7
Another example of the role hormones may play in HIT, is the influence pregnancy has on DAO activity. During pregnancy there appears to be a higher activity and concentration of DAO.13, 16 This is thought to explain why we often see a decrease or complete regression of HIT symptoms during pregnancy.
Over the last few years there has been a growing interest in gut health and its effect on many aspects of our health. It has been proposed that histamine intolerance may originate in the gut and is primarily a gastrointestinal disorder.17 A recent study showed that those with histamine intolerance have dysbiosis and particularly lower bacterial diversity, higher proteobacteria and lower levels of bifidobacteria18. It is possible that this dysbiosis contributes to histamine intolerance as certain bacteria can produce histamine19,20 and certain bacteria may help with histamine breakdown.21
In addition to this dysbiosis, lower levels of DAO has been observed in certain gastrointestinal conditions. In Inflammatory Bowel Disease (IBD) reduced DAO activity is thought to be related to the severity of mucosal damage and level of colonic inflammation.22,23 A small study by Schnedl et al,24 also found that HIT may play a role in those with non-responsive Coeliac Disease.
As previously stated, there are currently no conclusive biomarkers for HIT at present. Diagnosis relies on us, as dietitian’s, guiding someone through an elimination of high histamine foods for 2-4 weeks, followed by a gradual re-introduction to identify individual tolerance to histamine.7 This should be considered when someone presents with more than 2 symptoms of HIT.9 As HIT symptoms can overlap with primary IgE allergy symptoms, a primary allergy should be ruled out first through an allergy focused history and any other relevant tests.7
Some consultant’s may test a patient’s serum DAO levels. Although this may add to evidence that someone has HIT, serum DAO hasn’t been found to always correlate with the activity of the enzyme in the gut and is, therefore, not a definitive diagnostic test.17
Systematic re-introduction of histamine containing foods following the elimination phase is really important as the low histamine diet can be very nutritionally and socially restrictive. Currently there is no widely agreed guidance on how best to re-introduce these foods and this process can vary widely based on individual practice and patient choice.
Re-introduction can be challenging as it isn’t just food that can increase a person’s histamine levels, and, therefore, tolerance of a certain food may change. For example, if someone has a tree pollen allergy, they may find that they are more sensitive to histamine containing foods during tree pollen season than at other times of year, as they are already producing more histamine in response to the allergy.
The bucket theory is often used in relation to HIT, and other factors that may ‘fill up the bucket’ include:
The re-introduction phase often needs a lot of dietetic support to try and help widen the diet, whilst minimising symptoms.
As discussed at the beginning of this article, there is no globally agreed list on which foods are high in histamine. Even foods that are generally accepted as low histamine can vary greatly in their histamine content depending on how fresh they are and how they’ve been stored.27 This lack of a consensus makes it very difficult for clinicians and patient’s when choosing the most appropriate list to follow. Those patients who have found the diet online may be using multiple lists and this may make the diet even more restrictive than it needs to be. The diet, and the condition, can lead to isolation, frustration, and low mood. Many social occasions involve high histamine food and drinks and there is a general lack of awareness of the condition, which can make it a very challenging condition to live with, without adequate support.
There have been no high quality trials that look at the nutritional adequacy of the low histamine diet, however the diet can result in nutritional deficiencies unless well planned. Some lists restrict beans, pulses, nuts and seeds and a range of fruit and vegetables which can result in a lower fibre intake. In addition to this, if someone is following a plant based diet this could make it more challenging to ensure that they are getting enough protein.
In conclusion, low histamine diets can vary widely depending on the list that is being used, and should be assessed on an individual basis by a dietitian with experience in this area. Support for those with HIT is vital to ensure that symptoms are minimised, nutritional deficiencies are avoided and social activities are maintained.
Chloe is a Dietitian with over 10 years experience working in the NHS and has launched her own business 'the calm gut dietitian', alongside this, which specialises in gut health, and specifically histamine intolerance and Mast Cell Activation Syndrome (MCAS). Chloe became interested in the area following her husband's experience with these conditions and is passionate about raising awareness of these lesser known conditions. Chloe has been a media spokesperson for the British Dietetic Association for a number of years and been featured in a number of written publications. In addition to this, she is an advisor for The IBS Network, the national charity for IBS.
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