Curious Cook: Allergic reaction


Nearly a quarter of the British population has a severe reaction to shellfish. — MICHELLE TSANG/Unsplash

An old schoolmate asked recently about the safety protocol for eating raw fish during the Chinese New Year season. The answer is simple. Eat only raw fish that had been super-frozen for at least one to two days at temperatures of -35°C to -40°C. Or frozen at -20°C for a week. If one intends to prepare raw fish at home, then note that house freezers seldom get colder than -18°C. Therefore, it is recommended to store raw fish in home freezers for around 3 weeks at -18°C before use in raw fish dishes.

Without freezing at the appropriate temperature and duration, raw fish can contain viable bacteria such as salmonella, listeria, and Group B streptococcus, which has caused several outbreaks in Singapore over the last decade. Perhaps even worse outcomes might be parasitic infections from tapeworms and the very common Anisakis worms, resulting in a condition called “anisakiasis”.

In terms of risk, fish tapeworms (aka Diphyllobothrium spp) are found only in fish that live at least part of their lives in freshwater, while Anisakis worms (aka Anisakis simplex ss) are found in over 75% of wild salmon (and present in 100% of wild Pacific salmon in one study). Worryingly, they have also been detected in very small numbers in farmed salmon from Norway some years ago.

The symptoms of anisakiasis are curious. Apart from gastrointestinal disorders, anisakiasis also induces allergic reactions such as urticaria, dermatitis, asthma, and potentially even anaphylaxis, which is the most dangerous and life-threatening allergic reaction for humans. Anisakis worms cannot survive or reproduce in humans, eventually dying in the small intestine, but not before provoking often severe allergies in infected humans.

The rise and rise of allergies

At this point, it should be understood that every allergy is caused by some defect in the immune system. An allergy is not the normal response to an external event such as the local skin swelling due to an insect bite; an allergy would be a non-local response to the insect bite, which may include severe reactions such as rashes, nausea, vomiting, breathing difficulties, loss of consciousness, etc.

A higher intake of beef and lamb has likely accelerated the increase in allergies since the 1970s. — JON TYSON/UnsplashA higher intake of beef and lamb has likely accelerated the increase in allergies since the 1970s. — JON TYSON/Unsplash

The incidence of human allergies has grown at an uphill trajectory over the last 200 years, but it accelerated markedly since 1970 or so. In the early 19th century, a scientist called John Bostock searched all over Britain and could only find 28 people suffering from hay fever in a population of around 12 million. Today, the UK NHS estimates that 20% (over 13.4 million) of the entire population of over 67 million suffers from hay fever, an allergy triggered mostly by plant pollen.

Adding in other allergies makes the statistics even more sobering. A staggering 44% of UK adults suffer from at least one allergy, with 23% of the population allergic to one or more kinds of fruits, 22% reacting badly to shellfish, 16% cannot tolerate various kinds of nuts, etc. Other common allergens include air pollution, dust, insects (particularly house mites), plants, etc.

The UK stats are more or less consistent with allergy statistics in other modern countries, with much of the rise in allergies increasing exponentially around 1970. Additionally, the fastest-growing demographic developing allergies is children, where rates are shooting up 50% every dozen years or so. As an example, pediatric asthma was a rare condition until around 1970. Making things worse is the fact that people are becoming allergic to more and more different kinds of food.

Important clue?

Explaining the surge in allergies since 1970 would be difficult as there are lots of factors that have applied since then. However, an important clue may have been uncovered recently in a research paper released just last month by the Tokyo University of Science called ‘Butyrate, Valerate, and Niacin Ameliorate Anaphylaxis by Suppressing IgE-Dependent Mast Cell Activation: Roles of GPR109A, PGE, and Epigenetic Regulation’.

The catchy title of the paper partly obscures an important finding. For many years, it has been known that the Human Gut Microbiome (HGM) plays an important role in augmenting the immune system, but it has been unclear how the HGM affects allergies, which are faults in the immune system.

Many allergies seem to be triggered by the actions of specialised white blood cells called mast cells (MC). These MCs contain sacs called “granules,” which are packed with enzymes and potent signaling molecules like histamine. An MC activates when it encounters an allergen (or what it perceives to be foreign organic material), and undergoes a process called “degranulation” whereby it releases the contents of its granules into nearby tissue.

The highly inflammatory contents of the MC sacs then aggravate the affected tissue cells which in turn causes a cascade of larger immune system responses in an attempt to counter what the body regards as an attack on its tissues by foreign pathogens or toxins. In reality, the immune system is actually launching an attack on itself as it is responding to flawed activations of MCs.

The Tokyo study was done on rodents and the results provided strong evidence of how a properly functioning HGM can mediate the activations of MCs. This mediation happens in two ways.

The first way is when Short-Chain Fatty Acids (SCFAs) produced by the HGM bind with special receptors called GPR109A. Upon binding with SCFAs, a chemical cascade is induced in GPR109A receptors which results in the creation and secretion of hormone-like compounds called prostaglandins. These prostaglandins interact with receptors called EP3 on MCs and this interaction prevents degranulation.

The second way SCFAs mediate MCs is via temporary modification of the functions of specific genes (a process called epigenetics), in particular, the genes which modulate a body function called “histone deacetylase inhibitory activity”. How this works is too complex to explain here but a beneficial side effect is that SCFA epigenetics also inhibits the growth of tumours. The end outcome is that SCFA-induced epigenetics modifies receptors called IgE on MCs, which also inhibits degranulation.

People can develop allergies at any time and any age, and diets can contribute to this. — RON LACH/PexelsPeople can develop allergies at any time and any age, and diets can contribute to this. — RON LACH/Pexels

The SCFAs tested on the rodents were butyric acid and valeric acid, both known to be produced by healthy HGM bacteria. Butyric acid is produced by bacterial families such as Lactobacillus, Coprococcus, Eubacterium, Roseburia, etc, while valeric acid comes mainly from families such as Clostridia and Megasphaera.

So we now have evidence that a combination of two specific SCFAs (butyric acid and valeric acid) from the HGM can mitigate allergic reactions. It is probably not a coincidence that a combination of these SCFAs has earlier been tested on poultry farms where they improved the health of chickens.

Research into SCFAs is still relatively new, and there are four other important SCFAs (formic acid, acetic acid, propionic acid, and caproic acid) that have not been investigated in detail, especially the effects of various combinations of SCFAs.

Why the increase in allergies?

If it is established that most allergies are caused by the lack of certain SCFAs, then it is a plausible assertion that an unbalanced HGM which is unable to produce these SCFAs is very probably a root cause of many allergies.

The dramatic increases in the number of allergies in many populations since 1970 suggests that major dietary changes happened around that time. This period is marked by the markedly enhanced use of sweeteners such as high-fructose corn syrup, more use of vegetable cooking oils and trans-fats, much higher consumption of baked goods made from refined white flour, greater use of food additives, and sharply higher intake of animal proteins.

The common factor in all the above changes in dietary consumption patterns is the reduction of soluble and insoluble plant fibres in diets, combined with foods that actively damage or unbalance the HGM, such as sweeteners, trans-fats, refined flours, food additives, etc.

SCFAs are optimally produced when the HGM is supplied with a healthy diet of various fibres and natural nutrients. Allergies therefore are probably simply a symptom of poor nutrition.

Modern foods do not help

Much of the food supplied by major food producers would generally not help reduce the current pandemic of allergies. In many cases, ultra-processed foods (UPFs) are more likely to induce the development of allergies in any population where UPFs are marketed.

Children especially tend to be targeted by food companies as they (or their parents) can develop brand loyalty to various food products for many years. Therefore, it is probably not a coincidence that the fastest-growing demographic developing allergies are children. That may be because most convenient foods sold as children’s meals and treats are invariably UPFs.

The next fastest growing demographic affected by allergies are people of working age and under the age of 35, probably constrained by their lifestyles to eating too much fast food and other UPFs.

Note that anyone can develop an allergy at any time and any age, especially with a damaged HGM. However, bad diets alone may not account for some of the sudden new allergies as they may arise due to persistent exposure to environmental factors such as industrial wastes and contamination. However, the Tokyo paper suggests that SCFAs produced by a healthy HGM can potentially mitigate and alleviate to some degree allergies caused by earlier poor dietary habits and possibly other causes. Many allergies may also be avoided if the health of the HGM is maintained from an early age.

The views expressed here are entirely the writer’s own.

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