Food Intolerance

Food intolerance is estimated to affect 10-20% of the population, though diagnosis is difficult and so the number could be lower or even higher than this. Intolerances are a non-immunological reaction or hypersensitivity to food, often associated with gastro-intestinal symptoms.

There are three potential causes of a food intolerance:

1. Pharmacology

There are a number of chemicals present in food with potential pharmacological activity including salicylates, vasoactive amines (e.g. histamine), glutamates (e.g. monosodium glutamate) and xanthines such as caffeine. These chemicals are typically not a problem, but in hypersensitive individuals they can induce gastrointestinal symptoms through poorly understood and ill defined pathways. These chemicals are widespread in the diet as you can see in the table below. Avoidance of reactive foods is the recommended course of action but we must be aware that diets avoiding food chemicals are extremely difficult to undertake and limit a wide variety of foods with the potential to lead to multiple nutrient inadequacies – so a client considering such an eliminination protocol should be referred to a registered dietician for further instruction. Furthermore, surprisingly, there is no robust clinical evidence that these diets are effective in the management of gastrointestinal symptoms.

There is a significant amount of anecdotal evidence to say that elimination is effective but this should be taken with a pinch of salt due to the potential influence of the placebo or nocebo effect and expectation bias. Finally it can be difficult to isolate particular reactive foods because unlike allergies the response may take a longer time to manifest. There are other complications, too:

All of these things (histamine, salicyate, and oxalate intolerances), are not only influenced by food intake but with the health/state of the gastrointestinal tract. Remember we have already mentioned how certain species of bacteria produce histamine – if we have a bacterial overgrowth due to a poor diet or other factors that dysregulate this and the overgrowth includes species known for their histamine production, we may develop intolerances to high histamine containing foods not because dietary histamine is a problem per se, but because intake plus endogenous synthesis totals an amount beyond that which we can tolerate. In this instance it would not be sufficient to eliminate histamine-containing foods, the underlying issue would need to be rectified.

Finally with the example of a histamine intolerance, it may not be that histamine intake/production is too high but metabolism and thus clearance may be too low. This metabolism is heavily under the influence of an enzyme called diamine oxidase. Although outside a coach’s remit, a practitioner can test for diamine oxidase activity and studies have suggested that in individuals with symptoms triggered by histamine-rich food, measuring the serum diamine oxidase activity can help identify subjects who can benefit from a histamine limitation diet and/or diamine oxidase supplementation.

This above section illustrates the danger of acting without proper medical referrals – if in doubt, refer out.

2. Non-coeliac gluten sensitivity (NCGS)

Non-coeliac gluten sensitivity is a relatively new definition to describe gastrointestinal symptoms that occur in response to including gluten in the diet but in the absence of diagnostic features of coeliac disease or wheat allergy. The mechanisms by which gluten causes symptoms are not elucidated and dietary studies using gluten in double-blind placebo controlled food challenge have been inconsistent and unreliable to confirm gluten sensitivity.

In a review released in the journal Nature it was stated

“moreover, emerging evidence suggests that NCGS can be associated with organic gastrointestinal pathologies, such as IBD, in which its presence might be a reflection of severe or stricturing disease. However, NCGS is not without its controversies and uncertainties, in particular pertaining to whether it is gluten or non-gluten components of the grain evoking symptoms; evidence suggests that fermentable carbohydrates, amylase trypsin inhibitors and wheat-germ agglutinin can also be responsible culprits.”

A randomised control trial in 2013 concluded:

“In a placebo controlled, cross-over re-challenge study, we found no evidence of specific or dose-dependent effects of gluten in patients with NCGS placed diets low in FODMAPs.”

This trial has been criticised by other researchers and more research is being completed at present, so in conclusion there is still debate as to the existence of NCGS. It is very likely from the significant amount of anecdotal reporting and self-diagnosis that some amount of NCGS does exist, but considering the above noted issues with placebo etc, it is very likely not as prevalent as many people make out.

3. Enzyme/transport defects

The third type of food intolerance is related to enzyme defects, exemplified by prpbably the most common food intolerance – that of a hypersensitivity to lactose. Lactose is a disaccharide found in mammalian milk that is broken down into its constituent monosaccharides, glucose and galactose, in the brush border of the jejunum (lining of the small intestine) by an enzyme called lactase prior to absorption.

Primary lactase deficiency occurs in approximately 65% of the adult population, globally. This is a genetically programmed decrease in the lactase enzyme production after weaning, which is in fact the norm – typically mammals lose the ability to digest milk after infancy because they no longer need to do so. In some populations such as that of Northern Europe, however, lactose consumption after weaning (from dairy) over the last 10,000 years or so has gradually created a situation of later in life lactase production. As such, while the global prevalence may be 65% this varies greatly between populations – for example it may be as high as 100% in some East Asian communities, and as low as single digit percentages in Scandinavia. Regardless of prevalence, within a given intolerant individual a decrease in the lactase enzyme comes with a decrease in the ability to digest the sugar lactose.

Secondary lactase deficiency is often the result of damage to the jejunal brush border (lining of the small intestine) and may be affected by gastrointestinal disease (e.g. coeliac disease, Crohn’s disease, acute gastroenteritis, or small intestine bacterial overgrowth). This is reversible and not due to genetics. Here is a key quote to consider when on this topic:

“Lactose intolerance depends not only on the expression of lactase but also on the dose of lactose, intestinal flora, gastrointestinal motility, small intestinal bacterial overgrowth and sensitivity of the gastrointestinal tract to the generation of gas and other fermentation products of lactose digestion.” 

Because of this, secondary lactose intolerance is reversible, when the inflammation has resolved in the small intestine, lactase production will recommence. This also means that those intolerant to lactose not necessarily being completely unable to consume it. Symptoms of lactose intolerance generally do not occur until there is less than 50% of lactase activity and indeed, most lactose intolerant people can tolerate small amounts of lactose in the diet when it is spread throughout the day and, in total, up to 12– 15 g/day.

The above visual summarises the mechanism by which lactose intolerance may cause symptoms. If lactose is not digested effectively, it enters the large intestine where our microbiome ferments the sugar, which leads to the production of excess gas, such as hydrogen, as well as organic acids (another metabolite of bacteria fermenting food). These gases and organic acids then trigger symptoms – the common symptoms of lactose intolerance are bloating, abdominal cramping, and diarrhoea.

Overall, regardless of which kind of intolerance is present the symptoms caused are much more variable than those typifying allergies, and can include fatigue, bloating, irritable bowel, joint pains, rashes, nettle rash, eczema, migraine and various other symptoms – this is partially why diagnosis is so difficult as many of these symptoms may also be psychosomatic. Chronic conditions such as Arthritis, Eczema, Irritable Bowel Syndrome, ME (Chronic Fatigue Syndrome), Rheumatoid Arthritis, Migraine and Ulcerative Colitis are sometimes linked to allergy or intolerance to foods or other substances. However, it is very rare for true allergy to be an issue in these conditions. In some people, an intolerance might be a factor; in others, it may just exacerbate their underlying condition. In many people, allergy and intolerance will play no part.

You can test for lactose, or, fructose intolerance via a hydrogen breath test.

Listen to Episode 6 of The Alex Manos Podcast (click here) to hear Functional Medicine Practitioner Robyn Puglia go in to further detail around the many difference ways we can inappropriately react to our food,  which may contribute to a higher inflammatory load and thus autoimmune disease (the topic of this episode with Robyn).


Deng (2015) Lactose Intolerance in Adults: Biological Mechanism and Dietary Management, Nutrients, 7, 8020-8035

Iziz I et al., 2015, The spectrum of non-coeliac gluten sensitivity, Nat Rev Gastroenterol Hepatol.;12(9):516-26

Lomer (2015) Review article: the aetiology, diagnosis, mechanisms and clinical evidence for food intolerance, Aliment Pharmacol Ther; 41: 262–275

Skypala et al., (2015) Sensitivity to food additives, vaso-active amines and salicylates: a review of the evidence, Clin Transl Allergy; 5:34


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