Deconstructing the Herxheimer (and Lyme toxins)

It is common knowledge that many patients feel much worse for a time when they start treating Lyme disease.  This temporary worsening of symptoms is known as Herxheimer reaction or simply Herx.  Commonly the reaction is attributed to “toxins” and it is commonly held that treatment which removes toxins – detox, alleviates symptoms. 

Critics of this reasoning say it is a lot of hogwash. What toxins? There are no toxins. Bacterial endotoxins occur with gram negative bacteria not spirochetes. And detoxing? Complete mumbo-jumbo. 

Let's take a look.

There is a lot of stuff we don’t know. A great thing about science is we are always learning new stuff. 

We know that Herxheimer reactions are modulated by cytokines – the traffic cops that direct a very busy immune system hither and thither.

Its true. Lyme spirochetes do not process traditional endotoxins. Classic bacterial endotoxins are comprised of lipopolysaccharides (LPS). I have read this critique many times.  Lyme bacteria have something else: membrane derived lipoproteins. These molecules are not endotoxins but may be equally problematic.  Killed spirochetes spill these molecules into the circulation. These molecules wildly overstimulate usual immune responses leading to unbridled production of inflammatory cytokines. This is called a cytokine storm. 

A Herxheimer reaction, a well described scientific phenomenon, is caused by a cytokine storm. Unregulated cytokines cause chaos within a usually well-ordered machine.  There is a yin-yang balance within immune responses to kill germs. Some inflammation is necessary but this must be balanced against greater forces that diminish inflammation.  In a cytokine storm inflammation is unchecked.  Effector mechanisms (ways the immune system kills germs), T cell responses, B cell responses and complement activation become poorly regulated.  Germs are being killed but tissues cannot tolerate the excess inflammation. 

Inflammation is in part modulated by such molecules as histamine, leukotrienes, prostaglandins, enzymes and others, in part due to excess mast cell activation. This is something that can be limited with medical management. Cellular debris accumulates in the face of destroyed tissues, blood vessels and immune cells. Oxidative stress and mitochondrial dysfunction lead to an accumulation of intracellular toxins. Tissue damage may be associated with a build up of lactic acid. Macro toxins in excess, those eliminated by kidneys and liver may tax the system.

Let’s get to “detoxing.”  Two things are commonly recommended:  Lemon water and Alka-Seltzer Gold.  A gazillion patients have told me it works.  The first question is: what do lemon juice and Alka-Seltzer Gold have in common?  Citric acid. Citric acid has established anti-inflammatory properties. A recent study reported citric acid decreased the production of inflammatory cytokines: tumor necrosis factor, interleukins and cyclooxygenase (promotes prostaglandins) in LPS stimulated macrophages. The next question is why only Alka-Seltzer Gold? The main difference is aspirin. Regular Alka-Seltzer contains  aspirin, sodium bicarbonate and citric acid. The “Gold” version substitutes aspirin with potassium bicarbonate.  What’s wrong with aspirin? Isn’t it an anti-inflammatory? The answer is not always. Aspirin has different properties from other NSAIDS.  Peer reviewed studies have shown that in the presence of bacterial antigens aspirin has proinflammatory effects.  Sodium bicarbonate is best known as baking soda. It is also an antacid. Studies show that athletes who consume sodium bicarb  prior to intense exercise have improved performance. Our cells function best in the buffered blood pH of 7.4, slightly alkaline.  As in the case of Herxheimer responses, the athlete's tissues run out of available oxygen and Lactic acid accumulates. The blood become slightly acidic and metabolic functions suffer. Baking soda partially restores pH (acid-base) balance. Cellular metabolic dysfunction improves. 

How about those Epsom salt baths?  I have read various explanations and none make sense. It’s supposed to be about the magnesium which has healing powers. Its been scientifically shown that magnesium from Epson salts can’t get through the dermal barrier – the skin and therefore into tissues.  That’s not it.  Maybe it’s just the bath?  Hot water. Heat. Heat dilates blood vessels. Heat is well known to have healing properties. That is how saunas work. The process facilitates egress of inflammatory wastes from injured tissues. So, it’s just the water. The magnesium is for show – or is it?  When you mix molecules, they interact.  Magnesium sulfate “Epsom salts” is a salt.  Salt crystals have a particular physical characteristic. They hold on to heat.  Epsom soaks have a higher average temperature and stay warmer for longer than tap water baths.   

There are other detox strategies many of which seem helpful.  There is always a mechanism, an explanation, even if we do not yet know it.

Glutathione is the master antioxidant and help mollify oxidative stress and cellular dysfunction.  The problem is that oral forms are ineffective. Patients with IVs do great with IV GTH.  Other available forms, sublingual sprays and nasal spray (may require prescription) can be helpful. 

In my experience, and largely unknown, mast cell approaches can be very helpful for managing Herx responses -- in some patients.