Traditional Chinese Medicine, Western Science, and the Fight Against Allergic Disease

Xiu-Min Li, Henry Ehrlich

• Editore: WSPC
• Anno: 2016
• ISBN:
  9789814733717
• Argomento: Medicine
• Categoria: Alternative & Complementary Medicine

This book represents a new and hopeful paradigm for treatment of diseases that are spreading globally as countries adopt Western lifestyles and standards of living. It describes the phenomenal science and clinical efficacy of the work of Dr Xiu-Min Li across a broad array of immune and inflammatory diseases. These include food allergies, asthma, eczema, "new" diseases such as mast cell disorders, obesity, and mental health problems that are part of a worldwide "epidemic of progress".The most allergic people are caught in a cycle of medication, steroid dependency, emergency hospitalization, and curtailing their activities and diets to avoid triggers. Children are "losing their childhoods." They are fighting a battle against diet, climate change, and environmental degradation. Dr Li offers them hope by healing the entire immune system, not just address symptoms. In her practice Dr Li treats complex combinations of allergic diseases for all ages, from infancy through adulthood, bringing relief to people who have suffered terribly from oozing, bleeding skin, desperate breathing disorders, and life-threatening food allergies. She uses her vast knowledge of biochemistry to improve on the traditional decoctions to create refined versions suitable for modern tastes and lifestyles. In contrast with Western pharmaceuticals, which are the study of "one molecule's effects on one other molecule" Dr Li's work shows the effects of multiple molecules on multiple other molecules. Increasing numbers of scientists are beginning to see the possibilities for their own research, with the prospects for more collaborations with prestigious institutions around the world.

Chapter

1

FOOD ALLERGY

Some chimpanzees, when infected with intestinal parasites, eat bitter, foul-tasting plants, which they otherwise avoid and which contain biologically active compounds that kill intestinal parasites (Joseph Narby, The Cosmic Serpent: DNA and the Origins of Knowledge, 1998).

I like this passage for a couple of reasons. One is that it shows how basic the impulse to use vegetation as medicine is. TCM has thousands of years of recorded history, and clearly it did not begin with the beginnings of civilization, and it did not even start with humanity. The other is that it shows how fundamental the battle is between animals and parasites, nature’s extortionists. Chimps knew these little things were bad for them even if they could not see them or imagine them. They knew they were sick and they tried to do something about it. Readers of my other book about Dr. Li, Food Allergies: Traditional Chinese Medicine, Western Science, and the Search for a Cure know that her explorations for a food allergy treatment began with something called Wu Mei Wan, an old remedy for these worms that feed off people, weakening them without killing them, except for children who may not have time to develop their own defenses. In a body battling parasites, IgE and eosinophils are powerful defenses, but in our more hygienic society, they pick on the wrong targets and become our enemies.

It is a case of mistaken identity. Certain peanut proteins are very similar to those found in helminths, commonly known as parasitic worms. Likewise proteins found in dust mites and cockroaches, which are potent environmental allergens, are similar to some found in shrimp and lobster — major food allergens. The great moment of revelation came when Dr. Li was studying food allergy reactions and it dawned on her that it sounded like parasites so she dipped into the TCM trove Classic Formulas and Strategies and came up with Wu Mei Wan. As readers will also recall, in trying to decide how to deliver this medicine to patients, Dr. Li’s colleagues tasted it in the form of brewed tea, as it would be taken in China. They unanimously agreed that they could not stand the taste.

When I finished writing the other book, the Phase II trial of Food Allergy Herbal Formula-2 (FAHF-2), the successor to Wu Mei Wan, was still in a state of equipoise. That is, the work was done but the data had not been compiled or interpreted or published.

To recap, this double-blind, randomized, placebo-controlled study enrolled 68 subjects, 12–45 years of age, with allergies to peanut, tree nut, sesame, fish, and/or shellfish. Food allergies for all study participants were confirmed at the outset by a stringent double-blind, placebo controlled food challenge (DBPCFC). Forty-six received FAHF-2 and 22 placebo. After six months of therapy, subjects underwent another DBPCFC. For those who demonstrated increases in eliciting dose, a repeat challenge was performed three months after stopping therapy.¹

The results were disappointing to hopeful food allergy parents. There was no clinical breakthrough from this study. However, the laboratory results do suggest positive immune modulation is possible with FAHF-2. Immunological studies of the subjects’ PBMCs (peripheral blood mononu-clear cells) drawn at baseline and incubated with FAHF-2 and food allergen produced significantly less IL-5, greater IL-10 and increased numbers of Tregs than untreated cells — a shift away from the allergic Th2-dominant cytokines.

While the subjects’ cells tested in the lab outside of their bodies showed benefit with FAHF-2 treatment, what happened with the subjects themselves? It turns out that 44% had trouble sticking with the protocol. The real numbers of non-compliant subjects may have been higher, but the count was taken according to how many pills were returned at the conclusion of the study period. Even more pills may still be sitting in medicine cabinets in subjects’ homes.

As with most studies, in retrospect, there seem to have been holes in the design. This do not mean that FAHF-2 cannot work in humans. It was asking a great deal for nearly 70 individuals ranging in age from 12, where they would have at least been subject to some element of maternal supervision, through college age and into middle age to swallow 10 pills at each of three meals during the day, i.e., 30 pills per day. They had to remember to pack their noon dose to be taken at lunch. Strict medication regimens are best practiced under the watchful eye of mothers. Moreover, six months is a very short period of time to effect a wholesale renovation of the immune system. In her clinical practice, Dr. Li projects 2–4 years duration for treatment, so six months is a drop in the bucket. According to Dr. Li,

There are still a lot of things to learn from this trial. We think the product itself needs to be improved — if we can reduce the number of pills we can increase compliance and optimize the product.

We have identified a number of bio-active compounds and are able to detect the concentrations of the compounds in blood and urine. This method will be an important means of assessing adherence. We began to generate preliminary data using this technology. We need to test more work before drawing definitive conclusions. The preliminary data showed that the compliance rate is lower than 50%, but we have to figure out if it is a true compliance issue or the GI absorption or metabolism issues.

Interestingly, the preliminary data showed that if the individuals showed high enough blood concentration of the bioactive compound marker, this individual showed good clinical outcomes. This supports our in vitro study data, which shows when human immune cells are directly exposed to FAHF-2 extract there are beneficial immune modulatory effects. There are gaps of knowledge between TCM human use experience, in vivo animal model study, human in vitro study, and then finally to human in vivo study trials. Our continued work will help us fill in the gaps.

In the earlier book, I described the creation of a refined form of FAHF-2, which employs butanol (B-FAHF-2) to separate the active ingredients from the inert ones. The FDA has approved use of B-FAHF-2 for further experiments without having to go back to square one with murine models and early-phase human trials.

The test tube indicators are encouraging. Dr. Li says,

For several years we have been looking at which herb compounds affect IgE. We have demonstrated that human memory B-cell lines that produce IgE could remain very high, even if they are not stimulated. You put them in a good nutrition medium and they will grow and produce IgE. In a 2014 study we compared effects of FAHF-2 and B-FAHF-2 on IgE production. Both significantly reduced IgE, but B-FAHF-2 requires nearly nine times less concentration.

We also screened the nine herbs from B-FAHF-2 and found three of them directly suppressed IgE. Other herbs have no direct effect on IgE, but some of them suppress inflammation and histamine release while others enhance protective immune responses such as IgG. But this study only focused on identifying the constituents in vitro that we focused on one of the IgE inhibitory herbs and identified the active compounds in vitro.

B-FAHF-2 More Potently Inhibited IgE
Production than FAHF-2 in vitro

One of the things that make this avenue of research so exciting is that it holds out the possibility of making long-term changes in the underlying immune mechanisms. Allergic responses are “amnestic” — remembered. A patient can go years with no exposure to an allergen and then respond violently. It is this tendency that makes “avoidance” a dirty word in the food allergy community.

As Dr. Li says,

Memory cells do not need a strong stimulus, sometimes none at all. Most of the time they settle in the bone marrow where they wait until they are ready to produce IgE. We discovered the compound that regulates IgE through the modulation of one of the critical transcription factors that control IgE synthesis from memory cells.

That is the key — antibody production — that is where you use the term ‘switch’. The antibody-producing B-cells can be switched in a different direction. The same cells that can produce IgG or IgE are controlled by these transcription factors. They tell this cell what to produce. And so you do not have to kill the cells; you just have to initiate the signals to control what they produce.

This is one of the few subjects that lead her to employ military metaphors. She likens it to field commanders who are getting bad orders — good soldiers implementing wrong tactics.

Lack of cytotoxicity is a crucial element. In addition, there is no suppression of innate immunity, as there is with steroids, which have the side effect of leaving patients more vulnerable to bacterial or viral infection.

This is unique finding for a natural product. They are not killing the cells. The cells can still be there, but just not produce the IgE. Also, sometimes with immunomodulation, the IgE levels are still there, only they are dormant. Then when the body needs them, they can reactivate, when you encounter an intestinal parasite, for example.

The parasite connection is fundamental.

Normally the immune system can distinguish between the different proteins — food protein is very different from bacteria. Bacteria pathogens are very different from other microbes. The cells can tell. So therefore when you get a bacterial infection, your B-cells automatically start to produce IgG. Most of the time probiotics stimulate your immune system to produce IgG. Once your immune system encounters this type of stimulus, it has the capability to produce IgG to protect the individual. But with allergies, the allergen stimulates production of IgE by B cells.

Dr. Li listens to her patients, no matter how young.

Some kids have asked me “why do we need allergy?” We are not absolutely certain yet. But you can summarize it as several things — perhaps it is a single factor or combination but it has to do with microbials. There is a short window when the fetus is in the mom’s uterus when the immune system is skewed toward Th2 — but then after birth they need to gain quickly and switch to Th1 dominance through exposure to the microbials. So a type of microbial exposure is a major factor. Another theory holds that the mother or the post-natal infant is exposed to food too early or too late. This was the prevailing theory for 10–15 years, but has been recently rejected. We avoided the peanut early and the prevalence of peanut allergy (PA) has doubled. So the problem was not direct peanut exposure. Now there is no peanut restriction on mothers but the peanut prevalence allergy has tripled. We still have no consensus.

A new study is planned for B-FAHF-2 to be administered over 26 months using six pills per day instead of the 30 pills over six months. This one will be evenly divided, 17 each of medicine and placebo. While smaller, the study should produce robust data with easier compliance. This is just one of several studies using the refined food allergy formula planned over the next several years in support of the eventual aim of having a medicine that can be prescribed without accompanying knowledge of TCM. B-FAHF-2 is an FDA-registered investigational new drug (IND).

Many mothers ask if the goal of Dr. Li’s food allergy treatment is to “bite proof” patients, i.e., give them protection against small inadvertent ingestion of their allergens, desensitize them to their allergens, or to cure their allergies. The goal has always been to “reeducate” the immune system to fight the things that need fighting and ignore the ones that do not with enough capacity to fight natural enemies like parasites — a cure.

Since I started working on food allergy research, we have tested many novel therapies that we thought would be effective but when we started herbal treatment the first time we saw the mice were protected. They were all protected. It was beautiful.

Of course those mice were all fed through a tube.

If you reach the dose and duration of the mice (100%) with people, we have a good chance. But persuading our participants to use a full dose and for a long time is a big job. This product we hope will make their efforts easier. In the new blinded trial and my practice-based biomarker study we are going to use the refined product, which I hope will point the way for the pursuit of the IND.

What will the biochemistry show?

Then you’ll get protection even though your IgE may not be at a normal level. That is my prediction. Reactions don’t only involve IgE, but additional types of cells such as mast cells and basophils. The protection is not only due to reduction of IgE, but also induction of other antibodies such as IgA and IgG.

When we did the animal study, before treatment, the mice had a similar IgE level as post treatment. But in the middle, before treatment commenced, we gave a boosting dose to drive their IgE levels very high. Then after treatment the IgE got lower, but never low like the level was normal or to the level before we boosted them.

In mice, we don’t do “greater than 100” which is how it’s reported by laboratories for patients. For mice, we do a real level — for example 4,000 or 5,000, high enough to ensure that when we challenge them they have a reaction. And then after we boost them, their IgE level could reach 5,000. Then after treatment the 5,000 level can drop 2,000 or 2,500 or a little bit more than that, but at that time when you challenge… they don’t have any reactions. Even with people we know that it’s not the level of serum IgE that causes a reaction, it’s the number of antibodies that are attached to effector cells via high affinity receptors.

With very high IgE levels, if you are able to drop it to a certain level, I think you do not need it to be normal. After treatment, you may build up a new level of tolerance. In Chinese medicine, they talk about balance so I think in terms of the treatment just bringing a new level o...

Indice dei contenuti

• Cover
• Halftitle
• Title
• Copyright
• Contents
• About the Author
• Acknowledgements
• Notes on the Text
• Foreword
• Introduction
• Chapter 1. Food Allergy
• Chapter 2. Asthma
• Chapter 3. Atopic Dermatitis
• Chapter 4. Inflammatory Bowel Disease
• Chapter 5. Mast Cell Activation Syndrome
• Chapter 6. Obesity
• Chapter 7. Future Research
• Appendix Information about Dr. Li’s Practice
• Index