Can Traditional Chinese Medicine Help You Live Longer?

I have just returned from three months in Beijing as a visiting scholar at the National Institute for Biological Sciences.  My host was Meng-Qiu Dong, who heads a lab studying aging in worms.  At the end of my stay, I took a look at longevity from the perspective of Traditional Chinese Medicine.  There is no doubt that TCM has some gems to offer longevity science, but the overall effectiveness of TCM resists quantification by the usual scientific standards meaning not that it is ineffective, but that it is extraordinarily difficult to define suitable tests.  But the contrast between TCM and modern Western approaches offers us a valuable perspective on our own practices.


[Disclaimer: No one in my institute thinks much about Traditional Chinese Medicine.  They are all trained in Western scientific methodology, many with PhDs from American universities, and they tend to be more conservative, more Western than Western scientists, because they are seeking recognition from American and European bio-medical journals.  They can’t afford to have their reputations tainted by anything that might be labeled as unscientific.]

Personal note

I first became interested in China in the 1970s.  I was a Berkeley grad student, auditing Chinese I every morning at 8 before my physics classes.  I knew that I was viewing the world through lenses shaped by my own education and the culture around me; and I wondered what that world might look like from a very different perspective.

The same idea applies to Chinese medicine.  Its approach and its basis of validity, its range of effects and benefits are different from Western medical science in ways that help me question assumptions that I didn’t know I was making.  I am tempted to scour the English language literature for credible clinical trials of single ingredients isolated from traditional Chinese herbs.  I am more than “tempted” – this is all I really know how to do.  And yet I know that this is an unfair and very limited snapshot of Chinese medicine – see below.  US NIH has a page devoted to TCM, and concludes “For most conditions, there is not enough rigorous scientific evidence to know whether TCM methods work for the conditions for which they are used.”

Headliners

Berberine is derived from goldenseal=小檗碱 and is a promising anti-diabetic drug, comparing favorably to metformin, though, of course there is much less data available.  Berberine increased lifespan in one fruitfly experiment, but has not been tested in rodents.

I wrote two years ago about Ginseng (人参), the Chinese longevity tonic with the longest pedigree.  Multiple benefits have been documented, including modest effect on lifespan.

The best-documented benefits of royal jelly (蜂王浆), harvested from beehives, are for retaining insulin sensitivity.  There are credible reports of anti-inflammatory activity and promotion of wound healing.  Benefits are claimed for blood lipid profile.  There is one mouse longevity study which showed a promising 25% increase in mean LS without increase in max LS, but the control LS was suspiciously short.  Dosage was 0.05% of dry diet, equivalent to ~2 g/day for humans.

LEF’s “AMPK Activator” =Gynostemma pentaphyllum= jiaogulan= 绞股蓝 is another traditional longevity herb, found in one trial to lower blood sugar.  AMPK is a sigal molecule in the insulin metabolism.  Jiaogulan promotes AMPK, which can reasonably be expected to preserve insulin sensitivity.  To my knowledge, there have been no trials of jiaogulan for rodent life span, and just one 30-year-old study in which it was found to prolong lifespan in flies.

Huperzine-A is derived from club moss=Huperzia serrata= 石杉, and is used for cognitive enhancement and neuroprotection.

Wolfberry (Goji berry= Lycium barbarum = 宁夏枸杞 = ning xia gou qi) has been studied in connection with glycation of proteins in the skin, which contributes to skin aging.

One-liners

Acupuncture is effective for relieving pain and inflammation of arthritis [review].  Surgery patients anesthetized with acupuncture have shorter recovery times and better outcomes than patients under chemical anesthesia.  (Western science doesn’t have a clue how acupuncture works.)  Chinese herbs are effective in treating irritable bowel syndrome, and even more effective when the treatment is individualized by a TCM practitioner [ref].  Ginger in the diet is linked to lower levels of inflammation [ref]. Tree ear fungus (木耳=Aricularia) reduces risk of stroke and heart attacks from blood clots [ref], and oyster mushroom (蚝蘑) has anti-inflammatory effect and benefit for blood lipid profile [ref, ref].  Elders who practice Tai chi (slowest and gentlest of the Chinese martial arts) are less likely to fall and less likely to suffer fractures if they do fall (ref).  Meditation lowers morbidity and mortality, improves measures of mental and physical health, lengthens telomeres [my review].

Chinese and Western Medicine A general comparison

Traditional Chinese MedicineWestern Biomedical Science
Legtimacy comes from thousands of years of collective experience, in oral and written traditions.Legitimacy based on statistical analysis of objectively measurable responses, averaged over large populations in the last decade or two.
Individualized treatment different for each patient.Standardized treatment; same for everyone diagnosed with a given condition.
Qualitative, multi-dimensional diagnosis.Binary diagnosis the patient has the condition or he doesn’t.
Treatment aimed at restoring long-term health.Treatment aimed at relieving acute condition.
Combination of many herbs with dietary recommendations, acupuncture, and some prescribed behaviors that seem to us random and irrelevant.One drug for one condition.
Integrated diagnosis and treatment of body and mind.Treatment of each body part or system as a separate entity.
Doctor-patient relationship is integrated into the treatment plan.Doctor-patient relationship is treated as an artifact, the “placebo effect”, noise that interferes with evaluation of the core treatment.

Those few Western scientists who pay attention to ancient medical traditions treat them as a trove of ideas for suggesting single chemicals that can be isolated and tested for efficacy, in animals and people the same way we might test any new drug.  It is hard to find funding for these tests, promising as they are, because the chemicals are not patentable.  

And when such studies are funded, they don’t do justice to the Gestalt of TCM.  If we find that individual molecules isolated from TCM herbs are potent healers, how much more benefit should we expect from synergy of the traditional combinations of herbs and the personalized diagnoses by healer with training and experience?

For all the reasons above, TCM doesn’t fit with the standard mode of scientific evaluation.  If each patient is treated differently, how can you make statistical inference?  If the doctor-patient relationship is part of the treatment plan, how can you subject the plan to a double-blind comparison?  If we test one chemical at a time, we may miss important synergies.  And if we look just at short-term outcomes, we are blind to what is most important to the patient over the course of his life.

Fictions of Western Medical Science

What can we learn about our habits of thought by immersing ourselves in another culture and looking back?  Our first reflex may be to subject TCM to standard evaluations from evidence-based medicine.  But equally important is the perspective we gain from criticizing  Western medicine fromt he vantage of TCM.  

We (Western, scientific types) know that different people’s reactions to disease and responses to treatments are highly idiosyncratic; yet we treat all differences as though they were random scatter in the data, and look for one-size-fits-all treatments.

We know that drugs interact with one another, including both synergies antagonisms, and that these .   All of life depends on homeostatic balance among thousands of active chemical agents, catalytic enzymes, and signal molecules.  Yet our research is based on testing one drug at a time. Building knowledge from the ground up is the only way we know how to do science.   Less than one experiment in 100 looks for pair-wise interactions, and almost none explore the effects of a dozen or more treatments in combination.  

We value predictability and reproducibility, sometimes to the neglect of miraculous effectiveness.  We imagine that the world is a predictable clockwork, of which our task is to learn the mechanism, and we are suspicious of any intervention that works only some of the time.  We disdain anecdotal evidence.  Thousands of credible stories of one-off cancer cures are discarded in the dustbin of quackery; we refuse to learn from them because other people given the same treatment were not cured.

We have moved toward standardization of medical practice.  American caselaw in medical malpractice sets a disastrous incentive structure, defining malpractice as doing anything different from what the majority of other doctors are doing.  A good doctor’s experience and subjective intuitions can potentially provide a treasurechest of treatment options, but in America there is a powerful legal and cultural discouragement from trying anything that is not “the standard of care”.

As medical knowledge has multiplied, Western medicine has moved toward specialization.  We rely on experts who know one field, even a single disease, or even a single treatment for a single disease in great depth.  With specialization, we have lost the generalist’s knowledge of interacting body systems and organs, and the art of gathering diverse symptoms and observations to infer a diagnosis has been replaced with algorithmic medicine.

Background Western and Eastern Thought

Western science doesn’t have life completely figured out yet this is no surprise.  “Too complex” is the common refrain, but I think the problem may be deeper.  Since the 19th Century, biology has been committed to a reductionist approach.  Modern biologists are committed to a program of building an understanding of life from the bottom up, beginning with molecules.

It’s commonplace to say that Eastern thought is more holistic, Western more reductionist.  Many of the principles of Chinese medicine are conceived in terms that make a Western scientist snicker, and many are tempted to dismiss the whole field based on its theory.  But the other side of Chinese medicine is that it incorporates thousands of years of experience, and the treatments that have survived the centuries are the ones that work.  For example, the whole field of acupuncture was once dismissed as superstition, but now is accepted as a set of techniques that work for pain relief and sometimes for healing, but Western medicine has no way to think about its mechanism.

There are MDs here who practice both TCM and Western medicine, and they have the experience and the wisdom to know which patients will respond best to one or the other approach.  There are drug stores here that carry Traditional Chinese Medicine alongside their prescription drugs, in a separate department.  

A typical Chinese prescription consists of a bag full of a dozen or so herbs and roots that are boiled, and the broth imbibed once or more per day.  It’s safe to assume that tradition has combined these herbs in these combinations for a reason, but the Western analytic approach is yet quite far from a predictive science of how they interact.  The moral is that when we encounter evidence for the effectiveness of TCM, we should resist the temptation to look for the Active Ingredient, lest we risk killing the goose that lays the golden egg.  

I would like to see a study of people who have used TCM over several decades, not just to treat a particular malady but as a tonic for general health.  Compare specific health outcomes as well as morbidity and mortality for a cohort of such people with a matched cohort that has comparable diet, income and lifestyle, but does not use TCM.

Optimizing the Placebo Effect

Don’t look down on what Western medicine calls the placebo effect.  While its power is universally acknowledged, Western institutions do nothing to try to get the most out of the doctor/patient relationship, and in fact the Balkanization of medicine and the economic pressures that have progressively curtailed doctor/patient interactions speak loudly of disdain for the power of “bedside manner” in the healing process.  The mind/body connection may not be understood, but it is of paramount import, probably as powerful as all of Western medicine combined.  It is only common sense that some practitioners will be much more effective than others, and that time to foster a human relationship has potential both to restore meaning and satisfaction to the work-life of physicians, and also to turn them into more effective healers.  In contrast to Western medicine, a personal connection with the doctor is well-integrated into the culture of TCM.

Random observations on Chinese health and longevity

China is westernizing at a pace and TCM is declining in popularity, especially with the younger generation.  At the same time, TCM and acupuncture in particular are gaining adherents and practictioners in the US and Europe.

Life expectancy in China is 75 years, compared to 79 years in Taiwan (tied with USA), 85 years in Japan.  The amount that Americans spend per capita on health care is about $9,000, compared to $1,800 in Taiwan and $500 in China.  In fact, Chinese expenditure on everything put together (per capita GDP) is only $8,000.

Two thirds of Chinese men smoke (compared to <20% in the USA), but the smoking rate for women is actually lower than the US.  Only recently, the Chinese government has begun measures to reduce smoking, beginning with a ban in public buildings in 2010.

I have seen people in China eat liberal quantities of rice with each meal, and yet the obesity rate among Chinese men is 0.6% compared to >30% in America.  The weight difference is something you might readily notice while walking around any Chinese city.  The traditional Chinese diet includes small bites of meat as a condiment, but with recent prosperity has come increasing meat consumption.  The “sweet tooth” as an addictive affliction is less prevalent in China than the West.  “Gym rats” can be found in China, but much more rarely than in the US.  People have more exercise built into their day, less time set aside for exercise as a Thing To Do.  Chinese cities have undergone explosive growth in recent decades.  Pollution in Chinese cities (Beijing is worst) is bad enough to be a major factor in mortality statistics.  

…and a glimpse of the modern side of Chinese medicine

This week, oncologists at Sichuan University Hospital in Chengdu announced that they had used CRISPR technology for the first time in a human medical application.  Immune cells were harvested from a lung cancer patient, and the cells were treated with CRISPR-Cas9 to remove the gene for a protein called PD-1.  The function of PD-1 is to help killer T-cells identify the body’s own healthy cells and make sure that the immune system does not attack them; but some cancers have learned to evade immune attack by displaying a PD-1 target.  The Sichuan team cultured the modified T-cells and returned them to the patient, on the theory that they might renew the body’s failed immune response to the cancer.  Results of the trial are not yet reported.  Principal Investigator Lu You emphasized that this is a small trial focused on safety, and ten patients will be closely monitored to look for indications that the modified immune cells have attacked the patient himself.

The Bottom Line

The Western, scientific approach to medicine is my paradigm and (I presume) yours; but it is not the perfect paradigm or the only paradigm.  People who dismiss the 2500-year-old wisdom of TCM as superstitious nonsense are missing a potential influx of new ideas and an opportunity for self-reflection.  It is only by getting outside our paradigm that we can see its limitations, realize that our thinking has been within a box.  

Research scientists in America and Europe have to compete for grants and have to get their work accepted into one or another elite journal.  This creates incentives to stick to the kinds of biological questions that can be addressed through standard methodology, that will yield definitive answers within a few years at a cost the lab can afford.  We can hardly expect  researchers to behave otherwise.  But we might, at least, recognize that the system steers researchers to ignore approaches that involve multiple coordinated interventions, that rely on experience or expert judgment to be tailored to individuals, or that work via pathways that we do not understand.  We ought to recognize that some promising treatments for life extension and health have been excluded from investigation “in the name of Science”.

In an Age of Epigenetics, Does Antagonistic Pleiotropy Still Make Sense?

The dominant theory of aging today was conceived at a time when genes were thought to be biological destiny.  Handiwork of George Williams, it is called Antagonistic Pleiotropy.  Pleiotropy is the idea that one gene can have multiple effects, and the core of the AP theory is that there are genes that give us strength and fertility in youth, but they cause havoc later in life, ultimately destroying the body.  Fifty years after Williams, we now know that genes are routinely turned on when and where they are needed, and turned off most of the time.  More than 97% of our genome is devoted not to genes but to epigenetics, which is the regulation of gene expression, and a mainstay of 21st century molecular biology.  Why should the body ever be stuck with a gene that is doing it harm?   Can antagonistic pleiotropy be re-cast to make sense in this age of epigenetics?  


In 1957, George Williams proposed an evolutionary theory of aging that later became known as Antagonistic Pleiotropy, and under than name has been the most influential theory of aging to this day.  It has formed the basis for interpreting a huge variety of phenomena in aging labs around the world.  Pleiotropy is routinely invoked to explain results in genetics, and “evolutionary medicine” is guiding (or misguiding) research priorities for the future of anti-aging science.

Williams began with the idea (still dominant today) that rapid and copious reproductive output is the ticket for evolutionary success.  A mathematical measure of time-weighted reproduction is the Malthusian Parameter r, which Williams assumed (many today agree) is as good a mathematical translation as we have for Darwin’s concept of “fitness”.

I have argued that there is more to fitness than reproducing as fast as possible. The very word “fit” came from the notion of traits appropriate to a particular environment, a particular ecosystem.  Ecological consequences can’t be separated from individual fitness.  Any individual that achieves a growth rate (r) that is higher than species further down the food chain has only a very short-term fitness advantage, because its grandchildren risk starvation.  I’ve written about fitness in an ecological context here and in my new book.

Genes “your way”!  Tucked away when you don’t need ’em

Today, I am offering another reason to discredit antagonistic pleiotropy.  Williams’s theory is rooted in the idea that if a gene is selected in evolution for its advantage early in life, then the bearer of that gene is stuck with it late in life as well.  Now that we know how routinely genes are turned on and off in particular tissues, at particular times, for just a few minutes or for years on end, it is no longer credible to imagine that the individual is stuck with a gene at a time when it has become a liability.  Can we find a way to make sense of antagonistic pleiotropy in the context of complex and robust epigenetic adaptation?

I’ll say this much for pleiotropy: some of the genes most detrimental to the body do indeed have “legitimate” functions (good for the individual or her reproduction).  I have come to see the proximate cause of aging as a re-balancing of hormones, some turned up and some turned down, with detrimental effect.  Inflammation is turned up too high.  Apoptosis is turned up generally, causing loss of perfectly good muscle and nerve cells, but the strong apoptosis signals that kill cancer cells before they can become tumors becomes less effective with age.  Melatonin (for the circadian clock) and glutathione (antioxidant) and CoQ10 (cellular energy) are all in progressively shorter supply as we age.

It is common to call this rebalancing “dysregulation” and ask what went wrong [example, another, a third].  But I don’t think evolution makes such big mistakes.  I see not dysregulation but  re-regulation or even re-purposing of a system that protects the body, toward the end of self-destruction.

Mikhail Blagosklonny has written often about a theory in which aging comes from the body’s inability to turn off the genetic program that led to development and growth early in life.  He knows his stuff, and writes convincingly about particular genes (notably mTOR) and the evidence that they are being kept on later in life, when their main consequence is to increase inflammation, promote disease and shorten lifespan.  I question only the part of Blagosklonny’s theory that says this is an accident.  I see it as one of the many instances in which genetic machinery is repurposed.  How does Blagosklonny explain this mistake?  “A potential switch that would turn off the developmental program cannot be selected, because most animals die from accidental death before they have a chance to die from senescence. A program for development cannot be switched off, simply because there is no selective pressure against aging.”  This idea has a venerable past, but no future.  Indeed, there is selective pressure against aging, and the cost of aging in the wild can be as high as 70% of fitness, though it is typically about 20-30% [ref].  This idea that aging comes about because no animals in the wild live long enough to die of old age was a brilliant insight due to a Nobel immunologist sixty years ago; but today it is no longer tenable.

Oft-cited Example of Antagonistic Pleiotropy

A classic example used to illustrate pleiotropy is Huntington’s Disease.  This is a congenital syndrome caused by a gene variant that actually increases fertility early in life, but typically around age 40, neurological symptoms begin, affecting coordination and causing mood swings.   Brain cells die, and Huntington’s is eventually fatal.  Huntington’s is not normal aging, of course, but the idea is that there are other genetic variants that are so common we don’t think of them as diseases but they are also promoting fertility early in life and degeneration later on.

In this case, it is not the timing of the gene but the version of the gene (allele) that is caused.  Is Huntington’s Disease truly an example of antagonistic pleiotropy?  Yes, in the sense that the allele causing Huntington’s Disease has both a benefit and a cost, and the cost is connected to disease and death later in life.  But no, in the sense that natural selection has actually rejected the Huntington’s gene time and again.  The Huntington’s mutation is one that occurs spontaneously in one child, and then is transmitted to children and grandchildren.  It lasts for several generations, but would disappear from the population were it not for the fact that it is constantly being re-introduced by fresh mutations.  Here is an allele with early benefits and late costs that is being rejected by natural selection on an ongoing basis.  So should Huntington’s be considered a counter-example to the AP theory?

Grade inflation for (some) scientific theories

Nowhere in science are theories given a pass when contradicted so frequently and so flagrantly as in evolutionary theory of the selfish gene.  Manuscripts describing evidence against the selfish gene, or theories based on group selection are routinely rejected for publication.  (This situation isn’t nearly as bad as it was 15 years ago.)  But Antagonistic Pleiotropy continues to get by with a “gentleman’s C”, because (like the Ivy League preppies), the theory has a pedigree.

“Direct experimental evidence for age-specific effects of mutations comes from only a handful of reports” [Scott Pletcher and Jim Curtsinger]  These geneticists actually mutated fruitflies at random and went looking for gene variations that could cause benefits at one stage of life and costs at another.  And they found them!  Except, curiously, they were all at early stages of life, and none affecting old age [ref].  “The main evolutionaty models of senescence are antagonistic pleiotropy and mutation accumulation, neither of which has substantial experimental support.” [1995]  Yes, that was written move than 20 years ago.  The difference today is that we now have a huge body of evidence contradicting each of these theories.

May we live to see the day when scientists look back at the theory of Antagonistic Pleiotropy, scratch their heads and say, “I wonder why people would have believed that!”