Food Chemical Elimination Diets and Symptoms of Food Intolerance

—Reviewers found evidence for low histamine diets for chronic urticaria and salicylate elimination diets for respiratory symptoms and recommended improving the study design of dietary intolerance investigations.

By Alexandra McPherron, PhD

According to a new systematic review of food chemical component studies, low or elimination diets may improve reported symptoms for chronic urticaria, aspirin-exacerbated respiratory disease, chronic rhinosinusitis, and asthma, but the field needs to improve study design to generate higher-quality evidence to guide management of food intolerance.¹

Food intolerance to specific food chemical components may induce adverse responses that are mechanistically different from allergic responses.² Intolerance reactions vary, but among the most common are urticaria, headache, and gastrointestinal symptoms.

The food chemical component causing an adverse reaction is identified by eliminating potential chemical components from the diet after excluding other causes and, when symptoms are relieved, challenging with the component to see if the reaction reoccurs. This trial-and-error approach is time-consuming and challenging, and few studies have robust designs that can provide clear guidance for diagnosis and symptom management.²

According to the authors of the new study, who are based at Swinburne University in Hawthorn, Victoria, Australia, “To better inform future studies and determine the current evidence base for low food chemical diets, there is a need to synthesise currently available data.”¹

To do this, they conducted a systematic review of studies of naturally occurring food chemical components and intolerance symptoms and summarized the strength of evidence for the efficacy of elimination diets.¹

Study inclusion

The studies evaluated were published from 1980 through September 27, 2023. Only participants aged 17 years and older were included. In addition, those with IgE-mediated food allergies were excluded.¹

Included studies tested elimination and/or low chemical diets, challenges with food chemical components, or associations with symptoms. The naturally occurring food chemicals evaluated were salicylates, vaso-active amines, and glutamate. Studies of monosodium glutamate (MSG) challenge after low glutamate diets and low pseudo-allergen diets for chronic atopic dermatitis were also included.¹

Twenty-one out of 1373 articles screened were eligible for inclusion. Of the studies with elimination diets, 8 were RCTs, 4 were non-randomized CTs, 4 were cohort studies with placebo-controlled challenge, and 1 was a prospective cohort study. The duration of the elimination diet before challenge varied by study, ranging from a single day to 1.5 months.¹

An additional 4 studies were observational and included self-reports of dietary triggers, symptoms, and severity.¹

The level of evidence was evaluated according to the Australian National Health and Medical Research Council (NHMRC) standards.³

Vaso-active amines

Pruritus and the number of hives were improved with histamine elimination or low-histamine diets in some participants with chronic urticaria in 3 of 4 studies and an additional study using a histamine-free low pseudo allergen diet. One study that challenged with histamine worsened symptoms.¹

Few studies examined symptoms other than chronic urticaria. One study examined dermatitis symptoms in participants with atopic dermatitis and found that symptom severity was reduced after histamine elimination and increased after the histamine challenge. In 2 other studies, most participants with irritable bowel syndrome reported that amine-rich foods increased their symptoms. Finally, participants in 1 study reported more severe headaches after both high- and low-amine feeding.¹

The authors concluded, “There is consistent NHMRC-I [National Health and Medical Research Council] evidence to support the role of a low-histamine diet for the management of symptoms in chronic urticaria, while the effect of a low-histamine diet for other conditions remains inconclusive.”¹

Salicylates

Most studies of dietary salicylates analyzed respiratory symptoms. In 3 studies, participants with aspirin-exacerbated respiratory disease, chronic rhinosinusitis, or hypersensitivity to non-steroidal anti-inflammatory medications had improved sino-nasal symptoms after low-salicylate diets.¹

In an epidemiology study, self-reported sensitivity to salicylates was more common among individuals with chronic rhinosinusitis compared with controls.¹

The findings for an association between salicylates and asthma were not all in agreement. Asthma severity improved in 1 study with low-salicylate diet, but not in another. In a third study, participants with hypersensitivity to non-steroidal anti-inflammatory medications had improvements in asthma control and pruritus symptoms with a low-salicylate diet.¹

Gastrointestinal symptoms were analyzed in 2 studies. In participants with irritable bowel syndrome, 1 study found no significant differences in symptoms while on diets of different salicylate levels. Another study found that participants in remission for ulcerative colitis had a higher dietary intake of salicylates than participants with high disease activity did.¹

“Elimination of dietary salicylates were found to reduce sino-nasal symptoms of aspirin-exacerbated respiratory disease and chronic rhinosinusitis and/or asthma in NHMRC-I studies, but more evidence is needed to elucidate the effect of salicylates on gastrointestinal symptoms,” the authors concluded.¹

Glutamate

In a double-blind RCT, 40 participants with Gulf War Illness on a 1.5-month low-glutamate diet had improvement in measures of pain sensitivity, myalgia, and fatigue. They also had lower overall mean symptom scores compared with wait-listed controls. Pain sensitivity after the low-glutamate diet worsened upon MSG challenge compared with placebo.¹

In another study, participants with fibromyalgia and concurrent irritable bowel syndrome had improved overall mean symptom scores after a 4-week diet that excluded MSG and aspartame. Gastrointestinal and fibromyalgia symptoms worsened after MSG challenge.¹

In an observational study, nearly half of participants with unstable asthma reported flushing and sweating after MSG challenge.¹

The authors wrote, “In summary, while this data provides some evidence for the role of MSG in gastrointestinal symptoms in fibromyalgia with concurrent irritable bowel syndrome and pain symptoms in Gulf-War illness, it is limited, and additional research among these specific populations is needed to verify these findings.”¹

Pseudo allergens

Two studies evaluated the effects of a pseudo-allergen elimination diet. In one, almost half of participants with atopic dermatitis had improved symptoms after 6 weeks on the diet. Of those who responded, 79% had worse skin symptoms after 2 days on a pseudo allergen–rich diet.¹

As described above for low histamine diets, 46% of participants with chronic urticaria had improved symptoms after a histamine-free low–pseudo allergen diet, with symptom recurrence in some responders who were challenged with oral histamine.¹

The authors wrote that the contribution of pseudo allergens to skin symptoms is hard to determine because low–pseudo allergen diets are also low in histamines, glutamate, antioxidants, and preservatives.¹

Overcoming study design issues

While the authors concluded that evidence existed for a role for low histamine diets in chronic urticaria and for salicylate elimination diets in certain respiratory conditions, more studies are needed to ascertain the efficacy of these diets in managing other symptoms. More data are also needed to support the efficacy of low-glutamate and low–pseudo allergen diets for reducing the severity or frequency of a variety of symptoms.¹

Future studies are also needed on the efficacy of diets used in clinical practice that eliminate multiple food chemical components.¹

“A lack of robust, consistent elimination diet protocols and objective symptom measures limit intolerance studies,” the authors wrote.¹

The researchers offered suggestions for overcoming methodological limitations in future studies. For example, many study limitations could be addressed by protocol standardization. In the studies reviewed in the paper, diets varied, as did the challenge protocols, doses, and delivery modes. Larger sample sizes are also needed.¹

Also suggested was that future studies could provide meals and use validated measures of symptoms. Few studies included any assessment of diet adherence. Studies also mainly used self-reports for outcome measures, and expectations for diets or challenges could have influenced participants’ reports of their symptoms. Double-blind RCTs would help remove bias, although these studies are difficult to carry out for diet interventions. Future studies should also use dose levels for food chemical component challenges comparable to those found in real-world diets.¹

Published: December 27, 2024

Alexandra McPherron, PhD, is a freelance medical writer based in Washington, DC, with research experience in molecular biology and metabolism in academia and startup companies.

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