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Should you tell your friends about andrographis?

Andrographis is one of the most popular herbal remedies for Lyme disease

Yet there’s reason to believe that it doesn’t effectively treat the condition.

Although Andrographis has been used in China for millenia to treat some infections, its popularity for treating Lyme derives solely from one book published in 2005 by Stephen Buhner called Healing Lyme.

Due to the popularity of that one book, Andrographis has rapidly become one of the big three herbal Lyme disease treatments, along with Japanese knotweed and cat’s claw. 

Yet besides Buhner’s book, there’s no other indication of it being effective for Lyme disease at all.

His assurance may not mean much considering he also claims to have read 30,000 books and 50,000 scientific articles, a nearly impossible amount in my view.

That’s two books and 3 ⅓ articles per day, every day, for forty‑one years.

Now that many articles is easily believable, but not even von Neuman could read two books per day, unless they were of the Dr. Seuss variety.

Yet evidence now shows that Andrographis has no inherent antibacterial effect against Borrelia spirochetes, the causative agent in Lyme disease.

In fact, Andrographis doesn’t have a direct bactericidal effect on most microbial species tested.

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This is certainly not an isolated finding and has been consistently reported by others:

“Anti-bacterial activity was not demonstrable even in a solution containing 25,000 mg per litre of crude powder.” ―Leelarasamee, 1990

The use of Andrographis in treating Lyme is likely the result of its high success against leptospirosis, a disease similar insofar as it’s also caused by a spirochete.

However, Borrelia burgdorferi and Leptospira interrogans are quite unrelated to each other, so extrapolating antibiotic susceptibility should be made with caution.  

Even though they’re both spirochetes they actually belong to two different kingdoms, the taxonomic equivalent of distant cousins.

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It’s almost as if Stephen Buhner had come across anti‑Leptospira studies and just assumed Andrographis should work against Borrelia as well, despite there being no evidence of such.

Yet we don’t have to speculate any longer about this interaction because, as recently as this year, we finally have in vitro results of Andrographis extracts being tested against Borrelia burgdorferi.

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In partial fulfillment of her B.A. degree in biochemistry, Sarah Kerns evaluated 30 anecdotal Lyme disease treatments for in vitro efficacy.

The results were not good for Andrographis.

The methanol extract was about as effective as marjoram, oregano, and milk thistle while the water extract wasn’t much better.

The most active agent was surprisingly monolaurin, a lipid found in coconut oil, and the doxycycline control came in second.

Andrographis had ranked 17th out of the 27 methanol extracts tested, and 18th out of the 26 water extracts.

The hexane extract of Andrographis was inconclusive because of fungal growth, yet its widely‑assumed to be active agent — andrographolide — would be expected in the methanol fraction anyway.

Besides this, what more blatantly contradicts Buhner’s protocol is the inefficacy of cat’s claw.

Of all thirty herbs tested, only cat’s claw promoted the growth of Borrelia with all three extract types.

“An impressive twelve out of 27 fully tested plant sources showed inhibition of B. burgdorferi growth in all three extracts, while one (Uncaria tomentosa, or cat’s claw) was consistently growth-inducing […]” ―Kerns, 2009

So if the Buhner protocol actually works it’s probably on account of Japanese knotweed and nothing else.

The common weeds dandelion and nettle actually had the most potent water extracts, with the former even exceeding the antibiotic control:

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Just as surprising was that dandelion and nettle, in particular, were tested on account of being commonly eaten by deer and not because they’re anecdotal treatments for Lyme.

Deer are actually highly resistant to Borrelia burgdorferi , with its main vector actually being the nocturnal white‑footed mouse.

“Two plant products (dandelion and nettle) were included for investigation due to their status as preferential fodder for Borrelia-resistant deer.” ―Kerns, 2009

These results are in total contrast to studies demonstrating Andrographis extracts to have potent activity against Leptospira interrogans, that other unrelated spirochete that causes leptospirosis.

In fact: Andrographis appears quite effective against the entire Leptospira genus but, unfortunately, not against anything else.

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So you may wonder, what about its in vivo effects?

Does Andrographis interact with the immune system in such a way as to destroy and/or inhibit Borrelia burgdorferi

Or does a metabolite of andrographolide induce direct bactericidal effects?

These mechanisms also appear somewhat improbable.

Although andrographolide has been shown to induce β‑defensin through the epidermal growth factor receptor, Borrelia burgdorferi is resistant to defensins in general.

Treponema denticola is another spirochete also resistant to human β‑defensins.

This spirochete is classified within the same taxonomic family as Borrelia so it’s more closely related than to Leptospira.

Besides being sensitive to the direct effects of andrographolide, Leptospira are also highly susceptible to β‑defensins.

For this reason, it’s plausible to believe that andrographolide could inhibit Leptospira in two ways.

In short, all data on Andrographis support its clinical efficacy against leptospirosis.

On the other hand, Borrelia burgdorferi is resistant to both andrographolide and the human β‑defensins it induces. 

Moreover, the tick known to transmit Lyme disease — Ixodes ricinus — is known to produce its own defensin.

Obviously, Borrelia burgdorferi cannot be inhibited by this very much if it can survive in the tick’s midgut.

It has also been shown that three other tick defensins would not affect Borrelia garinii the slightest, the only inhibitory peptide tested being human LL‑37.

So whatever separates the tick species which harbor Borrelia from those which destroy it, it’s probably not the defensins.

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Another study also indicates that LL‑37 is about 12‑fold more potent than HNP‑1, a human α‑defensin, and also that natural LL‑37 is more potent than the synthetic forms used above.

Large peptides don’t always spontaneously fold in ways achieved by living cells so their synthetic forms can have different tertiary structures.

The peptide LL‑37 is synonymous with human cathelicidin, an antibacterial compound specifically upregulated by vitamin D3

The induction of cathelicidin is the agreed‑upon mechanism for how sunlight and vitamin D3 cures tuberculosis.

So vitamin D3 would theoretically be more effective than andrographolide in reversing Lyme disease because it induces cathelicidin, but also for another reason…

Vitamin D3 also has direct effects against Borrelia burgdorferi.

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Vitamin D3 could be the reason why the white‑footed mouse, a nocturnal species, is the main vector of Borrelia spirochetes.

Other mammalian species such as deer, cattle, and rabbits get more sunlight and are completely resistant to Borrelia burgdorferi infection.

Many humans never get much sunlight, so in terms of serum vitamin D3 they could be considered semi‑nocturnal.

Yet despite its seemingly ineffective role against Lyme disease, andrographolide isn’t completely worthless and has uses beyond just leptospirosis. 

Andrographolide is undoubtedly a potent “anti‑inflammatory” agent, the effect which the majority of its studies focus on.

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Upon screening hundreds of plant extracts for the ability to inhibit NF‑κB, andrographolide was the only one identified as effective.

This says a lot, so whatever andrographolide does you can be certain that it’s unique.

“During this screening, we identified only one purified compound, called Andro, which inhibited NF‑κB activation.” ―Xia, 2004

Besides being the exclusive NF‑κB inhibitor identified among the plant kingdom, further investigations had revealed andrographolide to be extremely potent at doing so.

In cell transfection studies using vectors for NF‑κB and one of its targets, E‑selectin, transcription induced by TNF‑α was effectively inhibited by only 3 μM andrographolide.

The IC50 of andrographolide was approximately 7μM, a modest concentration which could probably be achieved upon routine supplementation.

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Besides genes such as E‑selectin, NF‑κB also transcribes for cyclooxygenase‑2 and iNOS.

For this reason, it could be about as effective as cyclooxygenase inhibitors against pain.

It could be worth noting that Andrographis has been shown effective against pain, at least in rodents. 

Andrographolide has also been shown to protect against septic shock in this study, exactly what you’d expect through inhibiting NF‑κB and iNOS.

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In humans, septic shock is thought to occur primarily through hypotension caused by excessive nitric oxide.

Since the induction of iNOS by the cytokines TNF‑α and IL1‑β is mediated through NF‑κB, you could have predicted less deaths in the andrographolide group.

“The activities of nitric oxide also afford a potential explanation for other characteristic features of septic shock, including maldistribution of the circulation, myocardial suppression and mitochondrial respiratory suppression.” ―Kilbourn, 1996

Yet on the other side of the coin, you have what could be considered immunosuppressive effects.

Although the inhibition of NF‑κB can be lifesaving when excessive, inhibiting it during times of infection could promote bacterial survival and be fatal.

The immunosuppression induced by high‑dose glucocorticoids is often considered a result of NF‑κB inhibition.

Indeed, the terms “anti‑inflammatory” and “immunosuppressive” have considerable overlap and could be used interchangeably in many instances.

Andrographolide has also inhibited the adhesion of leukocytes to epithelial cells by downregulating E‑selectin and VCAM‑1, meaning that immune cells would be less capable of finding their targets.

Immune cells have no flagella and cannot move by themselves.

They apparently get around by using the bloodstream and “planting” themselves when they sense invaders.

“These data indicate that Andro can inhibit the cytokine and bacterial endotoxin-induced overexpression of E-selectin and thus reduce the adhesion of leukocytes to the activated HUV-epithelial cells.” ―Xia, 2004

Consistent with this was the observation that ~50% less immune cells were found in areas previously injected with TNF‑α, IL1‑β, and LPS in the andrographolide group.

If leukocytes cannot home‑in on their targets, then how can they destroy them?

So it would be easy to imagine that some infections could be promoted by Andrographis if the invading microorganisms are resistant to β‑defensin and andrographolide yet susceptible to the immune effects mediated through NF‑κB.

Although clinical data is sparse, blood taken from human subjects given Andrographis at six grams per day has been shown ineffective against the five bacterial strains tested.

So besides being seemingly ineffective for Lyme disease, the anti‑inflammatory effects of Andrographis could give a person a sense of improvement.

Due to the criteria used to ascertain success by Stephen Buhner, that would no doubt be chalked‑up a success.

“[Question:] How do you know if the protocol is working?

[Answer:] You begin to feel better.” 

So in short, the evidence for Andrographis against Lyme disease is nothing like that for treating leptospirosis.

Leptospira are potentially killed by both andrographolide and the β‑defensins it induces, while Borrelia isn’t affected much by either.

Moreover, the ability of andrographolide to inhibit NF‑κB could actually facilitate Lyme disease.

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Doing it every day — and they’re almost 100 years old!

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It sounds crazy…it’s been completely ignored in the media…

But it turns out that these older Japanese men are having more sex than any other men on the planet…

Us Westerners don’t hear about all these men having so much sex.

But they are talking about it a lot in other corners of the world.

In fact, they call this the “quiet revolution” and it is crazy how much sex these older men are getting…

———-

 


Matt Cook is editor-in-chief of Daily Medical Discoveries. Matt has been a full time health researcher for 26 years. ABC News interviewed Matt on sexual health issues not long ago. Matt is widely quoted on over 1,000,000 websites. He has over 300,000 daily newsletter readers. Daily Medical Discoveries finds hidden, buried or ignored medical studies through the lens of 100 years of proven science. Matt heads up the editorial team of scientists and health researchers. Each discovery is based upon primary studies from peer reviewed science sources following the Daily Medical Discoveries 7 Step Process to ensure accuracy.

Kerns, Sarah. "Evaluating Anecdotal Lyme Disease Treatments for Borrelia-inhibitory Properties." Wellesley College (2019). https://repository.wellesley.edu/cgi/viewcontent.cgi?article=1905&context=thesiscollection

Goc, A. "In vitro evaluation of antibacterial activity of phytochemicals and micronutrients against Borrelia burgdorferi and Borrelia garinii." Journal of applied microbiology (2015) https://sfamjournals.onlinelibrary.wiley.com/doi/pdf/10.1111/jam.12970

Xia, Yi-Fengl. "Andrographolide attenuates inflammation by inhibition of NF-κB activation through covalent modification of reduced cysteine 62 of p50." The Journal of Immunology (2004) https://www.jimmunol.org/content/jimmunol/173/6/4207.full.pdf