FAHF-2 Chinese herbal formula for peanut allergies

Never has such a small, modest legume been so feared as the peanut for the allergic person. It's notorious for creating significant anaphylaxis reaction in those susceptible.

Food allergies such as this one are caused by an excessive immune response mediated by IgE. Symptoms typically appear within several minutes and can include abdominal pain, diarrhea, vomiting or an anaphylaxis reaction involving throat swelling and rash.

Treatments that have been explored include extended courses of injecting minute amounts of peanut protein, or administering small amounts of peanut protein orally to desensitize the immune system. These approaches have been met with overwhelming indifference. In the case of the injected proteins, a subject was killed instantly by a miscalculated dose that put an end to that investigation. In the case of oral desensitization, it's a long and slow process, but has made its way into regular clinical application For many it's too time consuming or too expensive. It requires going into the doctor weekly for more than 40 weeks. 

Our understanding of how these allergies occur within a Chinese Medical paradigm would be an interesting discussion. But, an article in the Journal of Allergy and Clinical Immunology might help answer that question for me.  

Some serious rockstars (Srivastava, Dr. Li and friends) at Mount Sanai School of Medicine have tested an herbal formula that was able to entirely eliminate the anaphylaxis reaction in mice with peanut allergies. The formula, called "Food Allergy Herbal Formula" (FAHF for short), and it's successor FAHF-2 are modified versions of Wu Mei San. The initial formulation included xi xin and fu zi, FAHF-2 did not, but was still effective. Other researchers in other facilities took this and ran with it, and there have been and are several studies all over examining this effect and trying to understand it. (here's the study: http://www.ncbi.nlm.nih.gov/pubmed/15637565 not sure if there is a full text version out there, but if someone finds one could you post a link to it in the comments? I have the full text version so I'll try to summarize all the important details :) 

There are actually a lot of really interesting things to learn from these papers. Not the least of which being that they could get rid of a food allergy! But also, how exactly did they get mice to be allergic to peanuts in the first place? And what does that tell us about the allergic process in general? Not only that, but in the study we are examining they also did some tinkering with the murine immune system prior to the study, depleting the CD4 T cells in some mice and the CD8 T cells in other mice, and neutralizing the interferon gamma in a third set. This makes it possible to identify which aspects of the immune function the herbal formula acted through.

So I know it's the first thing you want to know, so I'll tell you now here are the ingredients, it's a modified Wu Mei San:

Prunus Mume

Zanthoxylum schinifolium

Angelica sinensis

Zingiber officinalis

Cinnamomum cassiae

Phellodendrom chinense

Coptis chinensis

Panax ginseng

and Ganoderma lucidum

and the Chinese:

Wu Mei

Cang Er Zi

Dang Gui

Sheng Jiang

Gui Zhi

Huang Bai

Huang Lian

Ren Shen

and Ling Zhi.

Here are the juicy tidbits:

First an immune hypersensitivity to peanuts was established. The specifics about how that happened is interesting. Here's a previous study that looked at how this is done: http://www.ncbi.nlm.nih.gov/pubmed/21762973. The authors found that in order for an antigen to result in an allergic response it needed to be administered with an adjuvant (read "toxic ingredient") to completely freak out the immune system. In the absence of a wickedly toxic tag-along these antigens could not create an allergic reaction. In these mice they mixed cholera toxin with pureed peanuts and fed it to the mice over a 5 week period. When they fed these mice plain old peanuts at week 14 they had increased histamine response, lower temperature, and peanut specific IgE and IgG indicating indeed they now had a peanut allergy. (did we need more reasons to avoid toxins in children and breastfeeding mothers, anyway?)

They administered 64 mg of the herbal mixture twice daily for 7 weeks (from week 8 through week 15). The ratio of each herb in the final formula isn't available in this paper, but is published in "phytotherapy research." I've requested a full text from the author...fingers crossed. I'll let you know if I find out. 

So in the FAHF-2 treated mice the peanut allergy was completely abolished for 40 weeks and even at up to 90 weeks they had only a very mild reaction. The sham group had significant reaction to the peanut challenge at every testing (done 7 times over 50 weeks) with "near fatal reactions." (In fact one mouse did die from the peanut allergy challenge at week 40. Our hats go off to him in gratitude as he joins a long list of mice suffering for the sake of our health going all the way back to the tortured specimens of Hans Selye.) 

The discussion section suggested the benefits are a result of a relative increase in the TH1 division of the immune system (demonstrated by the attenuation of the FAHF-2 effect with neutralization of interferon gamma, and with the depletion of CD8 cells.)

There is currently a human trial going on using FAHF-2 in peanut allergies with promising preliminary results. The ability to rebalance an imbalanced Th1/Th2 immune system is a significant accomplishment with far reaching implications. It is also a useful piece of information as we consider which herbal formulas fit our patient's presentations. It is disturbing that this information isn't spreading quickly across our professional circles. A repurposing of our medicine with this sort of clinically validity is big news for us, and we should be the first to know, not the last. It's an exciting and valuable opportunity to gain a more nuanced understanding of how our herbs influence the immune system in general. It also has repercussions in how we approach clinical problem solving. It echos teachings from Heiner Fruehauf that urge us to reframe our idea of parasite, or Gu patterns as encompassing a wider range of conditions involving systemic immune dysfunction and chronic illness. 

For more information on Gu syndrome look at Heiner's stuff here: 

http://www.prodseminars.net/product/gu-syndrome-unique-strategies-treatment-chronic-fatigue-syndrome-fibromyalgia-lyme-disease-p

and here: http://www.classicalchinesemedicine.org/wp-content/uploads/2010/04/fruehauf_guinterview.pdf

For a great blog on food allergies and the experience of a human subject in the FAHF-2 human trial:

http://foodallergybitch.blogspot.com/

And here's a link to the an article by Jake Fratkin on Dr. Li's work on allergic conditions including this formula:

http://www.acupuncturetoday.com/archives2005/dec/12fratkin.html

Gu Sui Bu, Mender of Shattered Bones

Glad to be back writing blog articles again.  I've been busy getting a new practice running and all the necessary hoop jumping done.  But I'm back, and my new working situation will allow me a lot more time to dig through studies and write this blog.

This is an entry for the herbalists, any patients out there, and the general public may want to tune out, because this is gonna be rich with biology mumbo jumbo and herbalist jargon.

The herb gu sui bu, some may recall, has the action of speeding the mending of broken bones. It translates to literally "bone medicine mender." Interesting stuff.  Every once in a while I'll tell a patient something that is apparently completely ludicrous.  Like, "this root can really speed the healing of your bones."  Or better yet, "did you know that there is a type of cockroach used in chinese medicine that can help to knit fractures and tears back together?"  The incredulous stares have qi and blood dispersing functions on their own.  I'm often forced to go find a study in order to create any real belief that this stuff has a foundation in reality.  Well, I dug up one such study regarding Gu Sui Bu, because I was trying to get a recent fracture patient to use it.  The study was fascinating so I thought I'd pass on what I learned.

"The Effect of Gu-Sui-Bu (Drynaria fortunei J. Sm) on bone cell activities." Biomaterials Journal 2002.

Previous efforts to identify the mechanism by which Gu Sui Bu might increase bone mineralization have demonstrated actions, but were insufficient to fully explain the benefits.  The authors of this study utilized bone cultures that included osteoblasts and osteoclasts, and used an alcohol extraction of gu sui bu, and did find multiple mechanisms.

When I hear about an herb increasing bone density I think that perhaps there is some impact on calcitonin and/or parathyroid hormone synthesis, metabolism, or signaling.  Perhaps this was the target of previous studies, and explains why they didn't find any effect. If you look into the traditional use of this herb, however, you would save yourself the time, because in addition to increasing bone mineralization when taken internally, Gu Sui Bu is also used to harden the teeth used topically.  (non-toxic alternative to fluoride?)  This action would be absent if Gu Sui Bu's actions were mediated through hormonal activity.

The authors of this study found that adding gu sui bu extraction to a bone culture indeed did yield increased mineralization.  They measured the effect of gu sui bu on a number of things: osteoblast concentration, mixed bone cell concentration, alkaline phosphatase (dephosphorylates) (ALP), acid phosphatase (phosphorylates) (ACP), and Prostaglandin E2 (mediates osteoclast binding and bone reabsorption)(PGE2).  They also measured the Osetonectin and Osteopontin mRNA in the cultures. These are two extracellular matrix proteins that are involved in the spreading of osteoclasts through bone tissue, and the mineralization of new bone.

Previous studies had found that Gu Sui Bu have anti-oxidant activities for osteoblasts specifically.  This study also found that Gu Sui Bu affected the cell numbers in a culture, ALP and ACP, and PGE2 as well as the expression of osteonectin and osteopontin.

They found that initially, many markers indicated slower bone formation when gu sui bu was added.  ALP decreased, as did cell concentration.  However by day 3 the effects had reversed considerably, and by day 7 the gu sui bu cultures were indicating significant increased bone formation over the control.

ALP increased, as did ACP in the cultures.  The formation of osteopontin decreased, and with the increased presence of ACP in the matrix, the osteopontin that did present was dephosphorylated faster.  When dephosphorylated, osteopontin's action of assisting the adhesion of osteoclasts is decreased, and bone breakdown slows.  The PGE2 present in the gu sui bu culture also increased significantly (over 25 times that of the control).  PGE2 among other things, inhibits the formation of osteoclasts into multi-nucleated super osteoclasts that break down bone rapidly, further slowing breakdown.

So, interestingly, most of the actions Gu Sui Bu has on improving bone mineralization are due to restricting the actions of osteoclasts, rather than enhancing the actions of osteoblasts. The effects are contrary initially, but pronounced after a week, so administration should continue for several weeks at least. While topical application is appropriate for teeth, the jury is still out whether or not it can be applied to the skin over a fracture and have beneficial actions. (although the pain relieving actions are fantastic!)

The Synergy of Chinese Herbs

Herbal prescription in Chinese Medicine follows advanced and sophisticated dosage and combining protocols. For example an herb may have a specific action like raising prolapsed organs (for instance the herb sheng ma), however that action may only come out when that herb is prescribed with other herbs with similar actions. An herb might treat a particular symptom, but when prescribed with a guiding herb is capable of treating a related but different symptom in a different part of the body. In short, herbal medicine combining, or Dui Yao is not a additive, cumulative science, but a complicated science of synergy and complex interaction.

(entirely off topic, here's a really great video for any adrenalin junkies out there, if you haven't seen this nut, you should.)

Anyway, this is a pretty fascinating topic. We have a sense of how these things operate from a Chinese Medical Paradigm. Within our strange and interesting Chinese Medicine brains, acupuncturists really get these relationships, they make sense and are intuitive, because we have taken the time to build the rules and thought processes for how this world operates. Within the framework of western sciences these relationships are much more difficult to identify. In truth, like a lot of what happens in Chinese Medicine, western science just hasn't caught up yet. But there are some promising approaches developing out there, and I found one particularly interesting study.

"Synergistic therapeutic actions of herbal ingredients and their mechanisms from molecular interaction and network perspectives." (sorry no full text, but I'll try to give you all the juicy details.)

What this paper sought to do, was to elucidate the mechanisms by which herbs interact. (one example of this is Jiao Tai Wan. Huang lian and rou gui interact synergistically to improve symptoms of xin shen bu jiao (noninteraction of heart and kidney)). Chinese Medicine is rife with these sorts of combinations: nu zhen zi and han lian cao; gan cao, sheng jiang and da zao; sheng ma and huang qi; huang lian, huang bai, and huang qin; ma huang and gui zhi; bao shao and gan cao...and so on. We identify each of these combinations as embodying powers beyond the contributions of each individual herb. In some cases entirely new functions are created that are not found, even in lesser power, in the constituent ingredients.

Often one herb alters the ADME (absorption, distribution, metabolism and excretion) of the other. This is suspected to be the case in Jiao Tai Wan, and particularly with regard to absorption. As this study shows, the specific ratio of huang lian to rou gui enhances the absorption of huang lian across the intestinal membrane, thereby increasing the activity of huang lian without increasing its dose.

Constituents also act as teams to influence change in the body. This sounds oddly reminiscent of our understanding of how to build a formula with chief, deputy, assistant, and envoy.

a. Anti-Counteractive: reduce a network's counteractive activities against a constituent's effect. 

b. Complementary: actions positively regulate a target or negatively regulate a competing target. 

c. Facilitating: secondary actions of one constituent in enhancing the activity level of another. 

d. Potentiative modulation: affecting things like cell transports, permeability, delaying or reducing first pass excretion, or metabolism, all of which enhance the activity of the first constituent. 

 The paper gave some examples of studies that have been done into single herb synergism (multiple constituents in one herb act together to have effects larger than the effects of the individual constituents added together), as well as synergism from multiple ingredients.

Berberis:  Plants of this family contain the two key ingredients berberine and 5' methyoyhydnocarpin (5 MHC). What's interesting about these two ingredients is that while berberine has pretty good antibacterial actions, it is much more potent when in the presence of 5 MHC. In order to see why think about a bacteria. Bacterial cell walls have special little pumps on them that work to pump out synthetic and natural antibacterial agents, and keep them from killing the bacteria. These pumps are called multi drug resistant pumps. 5MHC inhibits the activity of these pumps allowing berberine to accumulate inside the bacteria and result in much more effective treatment. I'm not sure whether our big berberine herbs (huang lian, and huang bai) contain 5MHC. A quick glance at Chen didn't answer that question. If anybody out there knows let me know. (here's a link to the full text of this interaction.)

Onions and Garlic: Ancient food pairing. Goes together like acupuncture and flutes, especially in the presence of rich or fatty foods. Conveniently enough when together onions and garlic act in a synergistic manner to inhibit the peroxidation of lipids. You heard me right, go big on the onions and garlic to keep those newly absorbed triglycerides and free fatty acids from turning into little artery cloggers. This one is pretty tangled and complicated...what they found is that they could feed someone 100 grams of butter (sounds like a dare I responded to as a teenager), and onions and garlic limited the increase in serum cholesterol and plasma fibrinogen, and increased fibrinogen activity and clotting time.    Onions contain quercitin, myricetin, and kaempferol all of which inhibit various enzymes involved in splitting fats (lipoxygenase 5, 16, and phospholipase A2). Garlic contains sulfurous substances (diallyl disulfide, diallyl disulfide, allicin, alliin, ajoene, N-acetyl cysteine, S-allyl cysteine, S-ethyl cysteine, S-methyl cysteine, S-propyl cysteine) all of which inhibit the mechanisms that the body uses to upregulate those now-downregulated lipase enzymes, allowing the onions to have a stronger effect than they would otherwise. This is an example of an anti-counteractive effect.

Gou Teng and Tian Ma: These two herbs are found in the formula Tian Ma Gou Teng Yin, used for wind due to rising liver yang. This study looked at these two herbs and their actions on decreasing convulsions. Gou teng contains Hirsuteine, which decreases the incidence of seizures by blocking nicotinic receptor ion channel complexes. Tian Ma contains vanilline which inhibits acetylcholinesterase and butyrlcholinesterase, which results in decreased seizures caused by acetylcholine. But unfortunately this decreases acetylcholine degradation, which increases the activity of nicotinic acetylcholine receptor, which would lead to more seizures, if it wasn't for the actions of Gou Teng and that Hirsuteine, blocking nicotinic receptor channels. An example of what the study called an "anti-negatie effect."

Ren Shen and Zhi Gan Cao: The formula ban xia xie xin tang, among others, utilizes this combination. This combination was investigated in ulcerative colitis.  The authors used the entire formula, as well as individual isolates and those isolates in combination. The combination of ginsenoside saponins (GS) and glycyrrhizin (GZ) was effective beyond the effect of both used alone. GS is effective in decreasing the activation of defective Th1 response, while GZ is effective in suppressing defective Th2 response. Together they cover both divisions of aberrant immune response, resulting in benefit beyond either alone. I wasn't aware before reading this paper that this division existed in between these two herbs. That makes these two herbs a handy herb pair that I am likely to employ in my auto-immune formulas in the future, as long as the pattern fits.

It's nice to have western science backing us up for a change, but I'm not convinced of the power of these sorts of methods to really offer a whole lot to our understanding of Dui Yao at the moment. I for one will continue to trust the time honored classics in my herb pairing over the pages of "Bioinformatics and Drug Design." I think that most herbalists out there feel the same way. Studies can provide us with the nitty gritty molecular interaction details about why what we've been doing for thousands of years works so well, but at this point the main things they are likely to add are improvements on delivery methods and small tweaks on use. But the real gems are still to be found in the pages of the Shang Han Lun, Jin Gui and, for me the Pi Wei Lun. It doesn't mean that the information about absorption, distribution, metabolism and excretion isn't important. We are likely to need to know more and more of this in order to stay current in this field. Now excuse me while I go get some onions and garlic chopped for dinner.