Herxheimer reaction, die-off and toxins

Healthy state

When antibiotics kill certain bacteria very quickly, components of the bacteria are released. The immune system responds with a brief burst of inflammation: chills, fever, headache and muscle pain, sometimes a stronger skin rash. This is the Jarisch-Herxheimer reaction.

It typically begins within 24 hours of the first dose and fades after a few hours. It is triggered mainly by lipoproteins from spirochaetes, and messengers such as TNF, IL-6 and IL-8 mediate it. Spirochaetes are spiral-shaped bacteria, which include the causes of syphilis, Lyme disease, leptospirosis and relapsing fever. In syphilis, it occurred in just under a third (31.5 %) of 355 people treated in one study, most often in the early stage. That it occurs with fungi, gut parasites or gut bacteria during a cure has not been shown.

Similar reactions to dying pathogens also exist beyond spirochaetes, but where the pathogens sit in tissue. In river blindness (onchocerciasis), worm larvae live in the skin and eyes. When treatment kills them, the immune system responds with itching, rash, eye inflammation and sometimes a drop in blood pressure: the Mazzotti reaction. It is stronger the more larvae were present beforehand. With tapeworm cysts in the brain (neurocysticercosis), treatment can increase the inflammation around the dying cysts and trigger seizures, which is why the guideline recommends starting corticosteroids beforehand. What these cases share is that the immune system is in direct contact with the pathogens. Microbes inside the gut are largely kept apart from it by the mucus layer Mucus layer A gel layer of mucins on the gut wall that keeps bacteria at a distance. In the colon, the inner layer is almost free of microbes. More in the chapter “The mucus layer and additives” and the gut wall; such a reaction has not been shown for them.

How the body really detoxifies: no product does this, but a team of organs. The liver converts fat-soluble substances in two steps so that they become water-soluble. The kidney excretes the water-soluble part in urine, the liver sends the rest with bile into the gut, and the gut carries it out with the stool. Some of it is split off again by gut bacteria and reabsorbed (enterohepatic circulation), which is why fibre and regular digestion help. Skin and lungs excrete substances too. This system works constantly and without a cure; it works as long as the organs are healthy.

Toxins from the gut do exist, just differently from how they are often described. Some bacteria make poisons, such as C. difficile Clostridioides difficile A bacterium that can spread after antibiotics and cause severe diarrhoea with its toxins. More in the chapter “After antibiotics: C. difficile and faecal transplants”. And endotoxin Endotoxin (LPS) A component of the outer coat of certain bacteria. When it reaches the blood, it triggers inflammatory responses. More in the chapter “The gut barrier” (lipopolysaccharide, LPS) from the envelope of certain bacteria constantly reaches the blood in small amounts. In mice, a high-fat diet raised this level two- to threefold and promoted inflammation and insulin resistance. What helps against this is a tight gut barrier and a healthy liver, not detox cures. There are exceptions in which “binding” is a real treatment, such as bile acid Bile acids Substances made by the liver that make fat digestible. About 95 percent are reabsorbed in the last part of the small intestine; gut bacteria transform the rest. More in the chapter “Bile acids: when bile causes diarrhoea” binders for bile acid diarrhoea, but that is a medicine prescribed by a doctor for a proven cause.

Disrupted state: causes and effects

On the internet almost every worsening during a cure is called “Herx” or “die-off”: with anti-Candida diets, herbal cures for small-intestine overgrowth or parasites, probiotics Probiotics Live microorganisms that are meant to provide a benefit in sufficient amounts. The effect depends on the individual strain. More in the chapter “Using fermented foods well” or “detoxes”. There is no evidence for this. The interpretation is the dangerous part: anyone who understands worsening as a sign of healing carries on, even though a side effect, an intolerance or another illness may be behind it.

What can actually get worse during such cures usually has ordinary reasons. New fibre, prebiotics Prebiotics Food components, usually certain fibres, that specifically feed beneficial gut bacteria, such as inulin or GOS. More in the chapter “Prebiotics that build up gently” or probiotics increase fermentation and with it gas, bloating and cramps, especially at the start. Herbal products such as essential oils irritate the stomach and gut. Antifungals and antibiotics have side effects of their own such as nausea, diarrhoea or headache. Anyone who suddenly drops sugar, caffeine, alcohol or carbohydrates can get withdrawal headache, tiredness and irritability. Then there is the nocebo effect: if you expect a worsening, you notice symptoms more. That is real, but not a sign that pathogens are dying.

The word “die-off” comes up especially often with strong probiotics and ferments, such as milk kefir made from grains. Grain kefir is something different from most shop-bought kefir: a laboratory analysis found a completely different community in it, led by Lactobacillus kefiranofaciens, while Lactococcus lactis dominated in commercial products. Various yeasts add to this, and which microbes end up in the glass, and how many, depends on the grains, the fermentation time and the temperature. Anyone who starts drinking it suddenly takes in many unknown live microbes, plus residual lactose, acid, carbon dioxide, a little alcohol and, depending on the fermentation, biogenic amines such as histamine Histamine A messenger substance of the body that is also found in aged and fermented foods. Too much can cause headache, flushing or diarrhoea. More in the chapter “Histamine intolerance: much searched, little proven”. Bloating, cramps, loose stools, headache or flushing in the first days can be explained by this without anything “dying off”. With small intestinal bacterial overgrowth Small intestinal bacterial overgrowth (SIBO) Too many bacteria in the small intestine, where normally few live. Bloating and diarrhoea are typical; it is usually diagnosed with a breath test. More in the chapter “When the small intestine is too densely colonised” there may be more to it: in a small study without a proper control group, all 30 people with brain fog and bloating had been taking probiotics, many had D-lactic acid in their urine, and after stopping the probiotics and taking an antibiotic the fog improved in most of them. No study has tested reactions to kefir as a sign that it is working.

Some people also feel worse at first after a faecal microbiota transplant. In a review of 50 publications, 28.5 % of those treated had side effects, most often abdominal complaints such as cramps, bloating and more frequent stools, followed by brief fever (in around 3 %). This resembles a Herxheimer reaction, but counts as a side effect of the procedure and should be reported to the treating practice. The same applies to herbal cures with oregano oil or berberine and to antifungal drugs: whatever gets worse afterwards is first of all a possible side effect of the remedy.

One example of the harm: people diagnosed with “chronic Lyme disease” were sometimes given intravenous antibiotics for months. The US Centers for Disease Control (CDC) described blood poisoning, bone infections, abscesses and C. difficile infections as a result. A long-term benefit of such treatments has not been shown.

Detox programmes as a whole do not deliver what they promise. A review found not a single controlled study showing a detoxifying effect of commercial programmes in humans; the few small studies have major methodological weaknesses. According to a systematic review, colonic cleansing for general health is not supported, whereas there are numerous reports of harm. Coffee enemas have led to inflammation of the colon and rectum, and there are also injuries and electrolyte disturbances. In inflammatory bowel disease Inflammatory bowel disease Umbrella term for Crohn’s disease and ulcerative colitis: long-term, relapsing inflammation of the gut that needs medical treatment. More in the chapter “Immune system and inflammation”, enemas are dangerous.

“Binders” are not harmless either. Activated charcoal is an emergency measure in acute poisoning shortly after ingestion, but it also binds medicines and nutrients, and there is no evidence for long-term use. In 2016 the US Food and Drug Administration (FDA) warned against edible clay because products contained raised lead levels.

A true Jarisch-Herxheimer reaction can rarely become dangerous: with a fall in blood pressure, liver or kidney problems and, in pregnancy, contractions. It should therefore be medically supervised.