Orthomolecular veterinary medicine

…a trip to the twilight zone (ll)

There is no question that nutritional intake is a foundational pillar of any animals’ health and well being. Along with reproduction, adequate food intake is likely key to the supreme goal of survival- at least long enough to “get the job done’’. Animals and humans are living longer healthier lives today in part due to improvements in nutrient intake and significant research is under way to explore any potential advantages different foods and food profiles (i.e.; Mediterranean diet) might have.

Animal Veterinary Nutritionists and Certified Nutritionists among other qualified professionals continue to delve into the intricacies of nutrient actions. With such disciplines as biochemistry, genomics, physiology, and medicine the effort goes on towards expanding this nutritional knowledge.

There are an increasing number of novel avenues of study that are shedding new light on the meaning of “optimum” nutrition and whatever this really means. The evolutionary dietary histories of many species offer insight into how flexible or not their nutrient profiles might be and may add to our understanding of ideal nutritional parameters. For example, in humans, the evolutionary tale seems to suggest that we posses an incredibly wide and flexible nutrient range where nutritional needs can be met in many different ways depending on the conditions- “optimum” nutrition may not even really exist as we might imagine!

Enough is known to realize the importance of maintaining nutrient intake during times of stress and disease. It’s a no brainer that it significantly impacts therapeutic outcomes. That nutritional consideration in medicine has been somewhat under the radar and given less importance than it deserves is a problem that is being remedied with increasing urgency. The coming deluge of retiring baby boomers, for example, demands increasing attention to a host of health and social issues including nutritional considerations.

However, as mentioned in other posts, there is still much to be gleaned, a huge tangle of complex data needs sifting, and in some cases more studies need to be completed before some promising ideas can be implemented.

So, it was with some interest that a glossy promotional mailing caught my eye highlighting an upcoming veterinary nutritional seminar. Unfortunately the title “Nutritional Integrative Therapeutics” immediately sent up red flags as “integrative” and “nutritional therapeutics” are often utilized to dress up alternative or less mainstream practices. A further perusal of this promotion revealed a familiar pattern- learned during a brief naïve experience of my own- of classic descriptors for a pseudo-scientific nutritional supplement support program.

The lecturer states “From cancer, heart disease and allergies, to arthritis, anxiety, and nervous conditions, some level of nutritional deficiencies can be traced to every disease condition in the world today” This is only a slightly more nuanced yet typical non sequitor of fallacious causality that is often prostetlyzed- usually to a ready audience.

The reasoning behind believing, as implied here, that disease is a product of nutritional deficiencies is based on a long history of claims- albeit unsubstantiated- and has allowed some in the supplement industry the opportunity to capitalize on an eager and credulous consumer.

In this particular promotional program, there are two topics of interest worth mentioning. They illustrate some of the dissonant thinking commonly encountered in the world of pseudo-scientific discussion. First, the seminar starts with a lecture titled “Whole food nutritional vitamin complexes…and how they differ from synthetic vitamins”- they really don’t as discussed in a previous post.

Second, a large portion of the seminar is dedicated to something I had not seen before- at least under this title “Orthomolecular Nutritional Medicine” with the following descriptor: “Using nutritional components to augment your current medical protocols and gain greater patient response in disease…improving immune function….”

This particular section, it seems, is especially laden with significant pseudo-science. “Orthomolecular” and “augmentation” seem to be interchangeable terms often used to describe the concept of treating disease with nutrient supplements as therapeutic compounds- as in mega-vitamin therapy- a fairly common and unproven alternative nutritional modality.

A simple data search on “orthomolecular medicine” opened the doors to a strange world of peculiar medical claims and a strange cast of characters including the great novel prize winner Linus Pauling and his infamous and bizarre vitamin C obsession. Though his well known antics deserve consideration, its the other weirdness that is of interest today.

The Orthomolecular Medicine Online site notes that “Orthomolecular medicine describes the practice of preventing and treating disease by providing the body with optimal amounts of substances which are natural to the body...The key idea in orthomolecular medicine is that genetic factors affect not only the physical characteristics of individuals, but also the biochemical milieu. ”

This introduction sounds reasonable at first glance- until you read further. Another page on this site describes the principles that define orthomolecular medicine (OM)¹. It is a rambling essay that bounces between holistic and conventional descriptions of OM in an attempt to have your cake and eat it too.

For example the author notes “On the one hand we are confused with Holistic Medicine; on the other we are seen only as the avant garde of orthodox medicine. In hopes of defining our true identity let me update the concept of OM as a new medical specialty.” Later he continues “First of all, the orthomolecular data base rests strongly on the following areas of scientific knowledge: 1.nutrition 2. biochemistry 3.cell biology…10. toxicology…12. parasitology…19. climatology 20. medical politics.” He then goes on to say “The following therapeutic modalities fit the definition of orthomolecular: 1. vitamins 2. minerals…6.enzymes… 9. cell therapy, 10. chelation therapy…17air ion therapy…20. acupuncture…23. biofeedback. 24. hypnotherapy…” This seems to be an attempt to cover all the bases, make everyone happy, and essentially not say a thing!

Essentially it seems that with OM you can treat disease with nutrients, enzymes, hormones, among other things. Finding the right amount to give of these substances for “optimal” dosage is difficult because laboratory tests don’t really reflect the patients’ nutrient status and you really can not rely on statistical models because of “biochemical individuality”; therefore “therapeutic trial and dose titration is often the most practical test.” Folded within these claims is an outright rejection of evidence based medicine and research. Another page attempts to minimize scientific methodology and the lack of evidence for OM stating that “Although double-blind studies are an important part of the scientific endeavor to find the truth, so to, are observations...Then, too, in a broad sense science incorporates philosophy. Some point out that science, too, must recognize that experiments once observed by a observer, become changed by the act of observation. The character of scientific procedures places restriction on the relevance of results.” This is classic complementary and alternative medicine (CAM) cognitive dissonance at its best.

This is also evident in some of the interesting discussions of other diagnostic tools such as chromatography, electrophoresis, and mass spectrometry where the science of “metabolomics” might produce an effective means of obtaining a rich and unique “cellular metabolic fingerprint.”

This forms part of the nascent science of nutrigenomics where “New types of functional foods with proven health claims could be developed, and perhaps personalized diets created…” So far, this is conjecture and may or may not provide some helpful information in the future. The problem is that OM and OVM seem to have created a world of clinical maladies and treatments with minimal solid and durable evidence.

The story of nutritional supplement companies making assumptions and hijacking ideas (some of which may prove to be sound at some level) has a long and convoluted history and parallels, to a degree the “snake oil” trade of other centuries.

Refocusing on the veterinary side, a search for veterinary related sites or information regarding OVM presented several complementary and alternative veterinary medicine (CAVM) sites that mention OVM in conjunction with a variety of other modalities (i.e.; acupuncture, homeopathy, herbal therapy) and mirror the above discussion on OM.

According to one web site, the advent of orthomolecular veterinary medicine was initiated by a Dr Belfield in the 1960s’ via the administration of injectable sodium ascorbate (vitamin C) to a dog infected with Canine Distemper. His bio page “There is a tendency by many, in and out of the healing sciences, to trivialize vitamins and minerals beyond the treatment and prevention of deficiency diseases. Dr. Belfield has made a giant step beyond this archaic perception by administering nutrients in gram amounts that will treat, prevent, and control conditions other than deficiency diseases.” The page goes on to critique “conventional” nutritional concepts and prop up OVM. This is basically the same old OM discussion regarding nutritional therapeutics. That is, basing theory and treatment more on the promise of an idea rather than -to name a few- reliable amassed data, controlled studies, and a well honed scientific consensus.

The Veterinary Institute of Integrative Medicine and the American Holistic veterinary Medical Association both have similar descriptions of OVM on their sites. The VIIM site mentions environmental and individual deficiencies adding “Orthomolecular medicine becomes necessary because of variability in food quality due to soil depletion or contamination and because individual patients have unique nutritional needs depending on heredity, health status, and lifestyle.”

Additionally, this site promulgates a publication titled “Veterinarians Desk Reference of Natural Medicines” that combines different conditions and diseases with recommended nutrient products. Similar booklets and publications exist for a variety of supplement companies and their specific products creating an impossible quagmire of different treatments and protocols and “a fast and loose with the facts” approach- partly due to lax regulations and intense industry competition.

Coming back to the little veterinary seminar that started this whole adventure, it seems one successful method for making CAVM modalities more mainstream is to provide educational seminars analogous to regular continuing education courses given throughout the country and layer them with a veneer of legitimacy. This particular seminar for example, allows for certain credit hours that may count towards veterinary practitioners’ continuing education hours per year- an obligation in the states.

With very little probing, the wording and make up of this veterinary informational seminar- while superficially innocuous- quickly takes on familiar CAVM overtones and directly associates it with some very serious pseudo- science. Whatever sound information this seminar may have is drowned and diluted by the insidious nature of integrating incompatible non-science with science. You inevitbly end up with a pile of garbage.

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1) Among the mentioned areas of established sciences that OM claims to depend on, in part for its “data base” are the veterinary sciences- so we can probably safely describe this area as orthomolecular veterinary medicine or OVM

The Clone frontier

ANDi (inserted DNA spelled backwards) is the first rhesus monkey cloned by embryo splitting

Dawn of a new age

A new press release from the US Federal Food and Drug Administration published yesterday is a big sign that the world of genetic research with all of its potential is not going away. On the contrary, this is likely an important salvo across the bow of public consciousness that this topic- along with all the issues it brings- can not be ignored or set aside for another time.

Whether we like it or not, the exploration of the gene continues to move forward with increasing significance and real world impact. According to the press release “after years of detailed study and analysis, the Food and Drug Administration has concluded that meat and milk from clones of cattle, swine, and goats, and the offspring of clones from any species traditionally consumed as food, are as safe to eat as food from conventionally bred animals.” This is probably only the beginning of a whole new category of evaluations and recommendations as the FDA struggles to keep up with the plethora of scientific advances and how they should be assimilated into the tapestry of everyday industry, consumption, and safety.

These findings agree with the National Academy of Sciences 2002 conclusions and were also examined by a peered reviewed group of independent scientific experts in cloning and animal health. In addition, this decision opens the doors for lifting the 2001 voluntary moratorium by US producers and the US Department of Agriculture is already convening meetings with the industry to “discuss efforts to provide a smooth and orderly market transition…”

If the related world of genetically modified agricultural produce is any indication, this news will prove a hot bed for public debate, discussion, and more. It’s an area of human endeavor that deserves major discussion as it forces us to face a whole spectrum of ethical, philosophical, and scientific considerations we can no longer ignore or set aside for later.

Like it or not, the future is here. If life is a series of changes- and this may prove seismic- then human civilization is on a threshold of a whole new era. Though, this technology is still pretty much in its pre-infancy, enough is known to make it very hard to step back and reverse its course. Having an informed idea of where science is with respect to cloning technology may serve to lessen some of the concern and provide ground for reasoned discussion as we attempt to navigate a world that is familiar and alien at the same time.

In a way, cloning is familiar because humans have been manipulating the genetic code of animals and plants for centuries attempting to mold nature towards more human friendly and accessible forms. The manipulation and creation of organisms through genetic engineering and cloning is a true extension of agriculture and engineering and reflects primordial human qualities.

Sam Harris wrote an interesting article “Mother Nature is Not Our friend” where he discussed the fact that there is no obvious special favor given to humans or any species for that matter regarding the “bounty” of nature and there is really no special meaning in our present status as Homo sapiens. He writes “Life is a continuous flux. Our nonhuman ancestors bred, generation after generation, and incrementally begat what we now deem to be the species homo sapiens- ourselves. There is nothing about our ancestral line or about our current biology that dictates how we will evolve in the future. Nothing in the natural order demands that our descendants resemble us in any particular way. Very likely, they will not resemble us. We will almost certainly transform ourselves, likely beyond recognition, in the generations to come.” This is pretty heady stuff, but if you think about it, very true.

Thirty years ago Apple and Microsoft were nascent concepts in the minds of some teenagers working out of a garage in a world where the dial telephone, radio, and three channels on the television served as bastions of human communication. Today, other teenagers have belt sized communication devices that provide instant access to hundreds of informational inputs and outputs the flow of which they deftly handle with a precision that would have seemed alien those 30 years ago. If you take a step back, one can almost see the fusion of man and machine already in the making.

The manipulation of genetic codes and whole organisms that is the frontier of genetic science seems to be a part of this type of expansion; where change paradoxically provides a foundation in some way for the survival of life- whatever the form. As Harris notes “Considering humanity as a whole, there is nothing about natural selection that suggests our optimal design…we are acquiring the tools that will enable us to attempt our own optimization. Many people think this project is fraught with risk. But is it riskier thanm doing nothing? There may be current threats to civilization that we cannot even perceive, much less resolve at our current level of intelligence. Could any rational strategy be more dangerous than following the whims of nature? This is not to say that our growing capacity to meddle with the human genome couldn’t present some moments of Faustian over-reach. But our fears on this front must be tempered by a sober understanding of how we got here.”

The machinations of humanities probing mind are now taking us beyond the constraints of our own biological evolution. Though fraught with risk and danger, a new world of genetic science with its potential for change, may open the doors to something wondrous.

Complexity, connectivity, and rising consciousness

Patterns of evolution

When trying to understand how consciousness emerges, it is important to take into account that we, as humans are just a complex conglomeration of interacting microscopic cells. These multitudes act together in a grand orchestral scheme that are our bodies and what many presume is but a vehicle ruled ultimately by the master molecule- the gene.

The most successful lineage of “vehicles” by far for these genes are the innumerable unicellular organisms dispersed throughout the globe- easily outstripping anything we colonized masses of cells could offer in terms of ubiquity and reproductive success- yet here we are. There occurred, in the midst of the myriad of evolutionary possibilities, a successful and intimate arrangement that gave rise to the dawn of our multi-cellular family.

Though, tiny in comparison to the rest of the living biomass, these cellular colonies successfully made a run at survival- for the moment. Though the combinations of these cellular colonies seem infinite in variety, there seem to be patterns and rhythms that reflect something fundamental that arise from some primary point- maybe the gene or an even more foundational structure.

It is crucial to note that colonization in no way represents a new paradigm in cellular evolution. It is better described as a random path-a milestone to be sure- among many others that an already complex organism- the cell itself- could have followed all inextricably linked to the demands of evolutionary pressures. Indeed, the cell is itself a part of that previously mentioned conglomeration; an evolutionary thread and a product of cooperative effort.

Richard Dawkins¹ notes “Perhaps two billion years ago, an ancient single-celled organism, some kind of proto-protozoan, entered into a strange relation ship with a bacterium: a relationship similar to that between Mixotricha and its bacteria. As with Mixotricha, the same thing happened more than once, with different bacteria, the events possibly separated by hundreds of millions of years. All our cells are like individual Mixotrichs, stuffed with bacteria which have become so transformed by generations of co-operation with the host cell that their bacterial origins are almost lost to sight.”

The seeds of what we call human consciousness likely have evolutionary roots that, in part, germinate from these cooperative interactive beginnings. One would think that this is some part of a beautifully sublime evolutionary process meant to lead somewhere- not so.

Evolution has been a rather messy and jumbled proposition and care should be taken when discussing the patterns we find in its nature. The likely truth is that this evolutionary process managed to rather haphazardly propagate and expand "life" from deep within the structure of genes to, for example, the incredibly complex and interconnected nature of our neurons. That these little structures in turn create swirling patterns of information that cumulatively seem to reflect an “us” is but another seemingly "accidental"event among many that may or may not happen again.

Patterns of consciousness

It is this complexity and interconnectivity that seem to be critical elements in allowing for this level of information processing. Neurons, for example, are far more than just a bag of ionized atoms producing triggered action potentials when stimulated. In and of themselves, they have the ability to sift and prioritize signals discriminating between reliable inputs and background ‘noise”.

In turn, as neurons cooperate and function under ever higher systems of neurons, a layered functionality begins to appear. For example, only when a certain number- a threshold- of sensory sight neurons are stimulated for a specific amount of time will this information be consciously registered- yet the trigger could have been initiated by one cell.

In essence, consciousness can be considered a form of processing and discriminating information that depends on the amount of information received and how this information is ordered. In fact, the brain processes the incoming flow of information in a median range between extreme regularity and total randomness. Basically, we are children of chaos.

Chaotic systems are not random, though might seem to be. They are extremely sensitive to initial conditions and tiny inputs can have dramatic effects on larger outcomes. As David Liley² notes “Hence, in the brain, it is possible that a single firing of one neuron (among billions) at a critical moment, could cause a shift in the entire system, producing a brain state (and behavior) that seems entirely unpredictable. Any one seeing the results of such a shift from the outside world would reasonably conclude that it happened spontaneously or randomly- so it would seem to be free from the sort of rigid determinism that is seen in non-chaotic systems, like computers.”

This phenomenon produces, over time, semi-stable states called “strange attractors” and form patterns of rhythm or harmony with the surrounding activity- in this case neural electrical activity. This recalls to some extent the coalescing nature of cellular evolution.

These neural rythms can grow and take on other dimensions. Chaotic systems create patterns- fractals- that are a spectrum of structures all having an overall identical shape at every size scale and can grow. According to Liley “Brains have a fractal composition in that its major processing “modules” (visual, auditory, etc.) are made up of hundreds of even more finely specialized mini-modules, which in turn are made up of yet more specialized neurons. The neurons are now known to be “mini-brains...”

In the future, computer/brain interfaces and genomic science may exponentially expand the connectivity and complexity of neural chaotic phenomenon towards heretofore unimagined levels breaking out of the constraints of our cellular ancestors- but not out of what seems to be a universal evolutionary constant. Like a “grand unifying theory” as Dawkins put it “evolution rhymes, patterns recur”

These breathtaking concepts form a full and powerful organic arch that reaches back to our most primordial beginnings and stretches forward toward an incredible and mysterious future. It’s likely we will not keep stride with this process and fall into the abyss of extinction. But maybe, one way or another, humanity will contribute something somehow….

Ref:

1) Dawkins, R. The Ancestors Tale. Houghton Mifflin Company. New York, NY.

2005

2) Carter, R. Exploring Consciousness. Univ. of California Press. Berkely and Los Angeles, California. . 122-124 (David Liley, et al. Chaos) 2002.

The Placebo

...a world of kindred spirits
The persisting question of whether a placebo or a placebo “effect” somehow has the power to effectively change the state of a disease- even today- continues to challenge and confront practicing clinicians of all stripes. For example, this recent article in Reuters discusses a questioner done at three Chicago academic medical centers and illustrates just how ingrained placebo use and its associated problems may be among health professionals.

Although a simple and superficial survey, it does shed some light on how medical practitioners view the concept of the placebo beyond a research setting. According to the authors 45 percent of 231 internists admitted to using a placebo during clinical practice. A positive aspect to this is it suggests these practitioners are aware of the body’s natural healing potential. On the other hand according to the survey, some level of deception was used on patients when implementing placebo use. The survey also supports the familiar mantra that the placebo effects- at least in clinical settings- require "belief" on the part of the patient in order to work.

The authors correctly note that this opens the doors to serious ethical dilemmas regarding the all important doctor/patient relationship. Interestingly, a possible solution mentioned by them is to develop consent forms, thus obviating any ethical issues.

On the surface, placebo consent forms sound comical- basically asking for permission to lie to your patient. They could open the doors all kinds of other unanticipated issues and problems. Consider, for example the fact that there exist “nocebo” effects- the anti-placebo if you will- and one can only imagine the hopelessly tangled web of legal and regulatory hell just waiting to really complicate things. Even an imaginary effect from a sugar pill might conceivably require professional advice and a warning label before ingesting!

At any rate, this does bring us to an age old problem concerning placebos, their study, and their use in a clinical setting. Thomas Jefferson in 1807 described the placebo in terms of being a “pious fraud” noting “one of the most successful physicians I have ever known has assured me that he has used more bread pills, drops of colored water, and powders of hickory ashes, than all of the other medicines put together”.*

Many today support this sentiment- that it is legitimate to deceptively use a clinical placebo- as did this fine 19th century doctor. The implication might be, at best, that this deception gives the body time to spontaneously heal while occupying the patients mind on something besides their suffering. However, though there is some merit to the essence of this concept, this is not the 19th century. The placebo effect should no longer be confused and connected with mythical mind/body powers or other mysterious magical influences.

In and of itself, the placebo might occasionally have mild physiological effects but it does not significantly impact the natural history of an organic disease. Its influence lies in the fog of the mind- human and, to a degree, otherwise. A plethora of socio-cultural and psychological conditions- not to mention the often naturally waxing and waning nature of disease- can now be teased away from the placebo phenomenon and focused on much more effectively. These complex interactions between doctors, patients, disease, and emotions to name but a few describe the ever so nuanced “human condition”. In this context, it seems we can do better than just giving a clinical placebo. Maybe the perceived need for deception -for a "white lie"- can be better turned towards more honest and open client/doctor interactions.

On a related note, there has recently appeared an intriguing and rather refreshing site on the web that claims to sell homeopathic products. They openly admit to selling items that have no therapeutic effects beyond the placebo, recommend medical care at the drop of a hat if one is actually sick, and note that belief is required for the placebo to have any effect. Spoof or not, this site certainly illustrates a possible solution to these difficult issues.

It wouldn’t surprise me that part of a solution to much of alternative medicine- heavily laden with placebo- might not be to follow this lead and create a whole new genre. An open and honest approach that moves away from deceptive therapeutic claims offering instead differing versions of belief based services that may make you feel better- if you want them to.

Imagine that.


* De Craen AJ, Kaphthuk. TJ, et al Placebos and placebo effects in medicine: historical overview. JR Soc Med. 1999 Oct, 92 (10): 511-515

Failure to launch

Another disappointing veterinary acupuncture study

A recent study published in the September 2007 issue of the Journal of Veterinary Medicine discusses the potential positive effects of electroacupuncture for treating varying degrees of intervertebral disk disease (IVDD). The authors describe the putative effects of utilizing this modality as an adjunct along with oral medications, particularly steroids, as a possible alternative therapy before surgical intervention.

This prospective controlled study titled “Evaluation of electroacupuncture treatment for thoracolumbar intervertebral disk disease in dogs” starts off routinely enough but quickly begins to unravel in the methods and materials section and finally leaks like a rusty bucket in the discussion.

The authors compared two groups of dogs suffering varying degrees of compressive spinal disease based on clinical, neurological, and radiographic signs. Both groups received some form of standard oral medical treatment during the study (some seem to have been started before the study) and one group also received electroacupuncture using an electroacupuncture a devise (model DS 100 CB) and acupuncture needles (0.25x 25mm).

The animals were evaluated with respect to the clinical degree of disease using a “functional numeric scale” or FNS and distributed into 5 subgroups (Table 1) in an attempt to standardize a base line to better determine any subsequent changes during the study. The goal was to minimize the necessarily subjective nature of the evaluators and owners. The authors also used statistical measures to account for discrepancies between groups.

Table 1

Grade 1-2

No neurological signs to some back pain and weakness- but walking

Grade 3-4

Can not walk, but can feel limbs- with or with out urinary incontinence

Grade 5

Paralyzed- with or with out urinary incontinence

According to the study, “Selection and determination of the site of the acupuncture points were based on the authors’ clinical experience and the veterinary literature. Acupuncture points were previously selected by the theory of traditional Chinese medicine…” The electroacupuncture consisted of using three paired points or “sets” at several areas of the animals’ body and simultaneously passing alternating currents of frequencies of 3Hz and 100Hz for three seconds. Other acupuncture points were utilized as well at the same time with no electrical stimulation. The average totals treatments consisted of at least three applications with more severely affected animals receiving more (twice weekly for two weeks, then weekly for at least two weeks).

The studies results basically reveal that, on average, the groups undergoing electroacupuncture- especially in the three to four FNS group- improved in neurological deficits faster than the other group, although both groups eventually finished (after several weeks) with similar FNS scores.

The authors go on to conclude that electroacupuncture can serve as an important option before surgical intervention and then, unfortunately go on a meaningless ramble discussing questionable acupuncture theories and other related acupuncture use in IVDD.

Though, this just one small study among many it is meant to contribute some modicum of meaningful information. Unfortunately it doesn’t. In addition, a variety of concerns immediately come to mind as to this studies ultimate value. The overall trial design brings significant concerns that decrease its potential for adding meaningful data to add to further larger systematic reviews (garbage in/ garbage out sequence). This is especially true when evaluating any claimed effects of alternative modalities often rife with implausible theoretical concepts that have scant scientific support. The results of this study are blunted by several problems that may alter the observations and increase the likelihood of bias and equivocal conclusions.

For example, it is not blinded with regards to the patient owners and researchers. Additionally the same researchers who apply the acupuncture treatment also interpreted the results of this treatment. The authors do partly acknowledge this problem stating “A variety of neurological signs were observed in the study, which can result in difficulties for comparison among treatment groups” but consider the FNS and recovery of ambulation in those dogs that could not walk a mitigating factor. This is not enough to cover for the lack of blinding.

Blinding in and of itself can dramatically alter any meaningful results in a study- often giving completely different results than a non-blinded study. Granted, blinding is difficult to accomplish in acupuncture, but it is not impossible to minimize many of these issues to improve the “fidelity” of the data

The blinding issue also diminishes the effort made by the authors initially at randomizing as well as accounting for differences between the two compared groups of dogs. A lack of proper randomization can overestimate any putative treatment effect by as much as 41%.

Additionally, the small size of this study decreases its impact as larger studies are much better at reducing random effects related to possible treatment results. In fact, the significance of treatment can be over estimated in these cases by as much as 30%. For example larger and better quality acupuncture studies in humans are consistently negative as are systematic reviews that utilize high quality smaller studies as a back bone.

Though the authors made an attempt at ascertaining that the dogs in the study indeed suffered from IVDD and categorizing them according to severity, using clinical, radiographic, and neurological findings gets you only so far in differentiating this from a constellation of similar maladies from cancerous lesions to muscular traumas. Three dogs in the non electroacupuncture three- four groups ended up going to surgery before they recovered. Though not mentioned, a myelogram at the least was likely performed in order to localize the lesion or lesions in these cases. This brings to mind that further attempts at better defining the parameters of an often difficult to diagnose disease by using myelograms, MRI, and spinal fluid analysis on all the dogs (not mentioned as having been done) could have added more significance to the study.

Perhaps among the most critical errors within this study is the existence of an important confounding factor, also noted in many if not most other animal acupuncture studies. The authors combine the concept of acupuncture and electrical stimulation¹- two different things and call it the same. It remains to be seen if the electrical component of these acupuncture studies has anything to do with any effects. But if they do, then many animal acupuncture studies have a big problem.

Another big problem is that the authors used traditional Chinese medicine and clinician experience to determine the acupuncture points used- neither of which is conducive to objective analysis. Traditional Chinese medicine is a historical quagmire of non science and no matter how proficient a clinician might be, their individual opinion falls into the notoriously self aggrandizing testimonial category.

This study reflects a large amount of the “same old” issues that has hampered so many other acupuncture studies. Another familiar “a failure to launch” attempt for acupuncture efficacy has been added to the books.

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1) The use of electricity to treat a variety of maladies without the needles is another modality that has been around for some time. Known as Transcutaneous Electrical Nerve Stimulation (TENS) it is often utilized for pain management. With regards to efficacy, this modality has problems of its own.

Natural versus Synthetic Vitamins

Whole food based vitamin supplements: neither here nor there….

The amazingly complex and varied tapestry of health claims skillfully weaved by the supplement industry seems to defy reason. This is because the majority of the implied health benefits have actually not been validated. At best, the sum of these assertions can only be described as either a hopelessly tangled web of deceptive claims or a meaningless morass of well meaning and unfettered propaganda.

Scattered amongst this maelstrom of mostly vacuous assumptions (because of insufficient scientific support), are points of interest that might reflect, albeit in a hopelessly twisted and contorted way, glimpses of what the real world of scientific inquiry has discovered. For example, nutritional researchers are opening new horizons into the world of functional foods- those foods that impact health in certain ways as compared to others.

The research is literally buzzing with studies evaluating everything from whole food matrices to individual food related components poring over innumerable potential biological actions, effects, or physiological events these substances might produce in human or animal health. They include a broad category of substances such as vitamins and other bioactive compounds that seem to have actions at genetic, epigenetic, and biochemical levels and promise possible new therapeutic modalities.

However, there is still much to be resolved and elucidated and precious little hard dependable data from which to make the monumental claims often heard from supplement advocates. One of the interesting and reliable threads of observational information is the anticlimactic fact that regular food- whole food- has generally beneficial effects on people. In other words; it seems that the best way to maintain ourselves; this “bag” of chemicals we call our body is to have access to a variety of chemicals from the “outside”. To date and to our knowledge, this is best represented as good old food, preferably of the wholesome variety type.

In essence, there remains a large fog of undetermined effects from food related compounds; some may provide exciting new therapeutic or nutritional avenues many others will not. That the sum total of these elements- the food matrix- appears to be beneficial is a definite no brainer. The relationship between health and nutrition is real and there is much yet to be learned towards optimizing any benefits of nutrients with respect to possible targets such as health and age.

Unfortunately, many alternative practitioners take the leap from there to asserting that all disease is a result of some kind of "nutritional deficiency". Here is where so many supporters of supplement support tend to begin to fill in the blanks, so to speak, and literally create an incredibly muddled litany of food based products for these “conditions”. Some of the more intriguing health related claims come from those in the industry that “specialize” and promote the concept of natural whole food supplements. From here, comes a steady and persistent drum beat of support for the concept of whole food substances that are processed and packaged, often in mysterious proprietary ways, into tablets, capsules, powders, power bars, and liquids.

The obvious claim is that if wholesome food is good for you, then whole food based supplements are also good for you. There is a fuzzy undulating thread of reason that leads from this basic assumption, dips into the above mentioned incomplete and equivocal research, then leads back again to the creation of a cornucopia of whole food based products that are linked to an endless stew of nutritional recommendations built on falsehoods, half-truths, and even solid facts- though slightly tinted to favor the theme at hand (i.e.; sub-clinical nutritional deficiencies exist; therefore every body has some form of sub-clinical deficiency and needs “something”).

Among the more common nutritional recommendations and claims of whole food supplement advocates has to do with their clear and assured statements regarding vitamin supplementation. In particular food based vitamins or natural vitamins as opposed to synthetic vitamins implying that these are two different things and that the natural vitamin is inherently superior to synthetic vitamins. This claim has become increasingly loud with the growing number of negative studies regarding vitamin supplementation and benefit.

Some whole food supplement claims include:

A) Whole food vitamins claim special status because they come from wholesome and nutritious foods. For example, vegetables are dehydrated at low temperature and undergo a “process” such that the “vital” vitamin substance is extracted in it entirety. Because these vitamins are natural they have the correct three dimensional (sterio) isomeric configurations to fit the bodies’ physiological machinery.

Synthetic vitamins, on the other hand, contain all the possible isomers mixed in equal amounts¹. Non identical synthetic isomers often differ in their biological effect and in many cases are non-functional or partially functional. Sometimes they are actually antagonistic to the naturally occurring isomer.

B) Whole vitamins are powdered food substances that contain an unknown number of additional co-factors, other vitamins, enzymes, fiber, minerals, and synergistic factors, compounds that synthetic vitamins do not have. These substances enhance the bioactive function of the supplement.

Synthetic vitamins are chemically created and form an isolated or incomplete vitamin product. They do not contain the complex of organic chemicals found in natural products. People can not absorb vitamins that are synthesized into “analogues” of vitamins extracted from food. Additionally, they can not absorb non- chelated minerals.

What some of the facts tell us:

A) The actual chemical structures of most vitamins are identical whether they are natural or synthetic in origin. Additionally, most synthetic vitamins are synthesized having the correct sterio-isomer. An exception is vitamin E where the synthetic (dl) version has various isomers all of which have some effects².

For example, biotin and panthothenate are the correct d forms, ascorbate is the correct L, and vitamin B12 is not synthesized- it is made by bacteria utilized from that source by the supplement industry. Interestingly, many vitamins such as folate, niacin, B6, and beta-carotene do not even have sterio-isomers.

B) The idea of a “natural” source of vitamins does not really exist as all chemicals are natural and derive from natural chemical precursors. Even “natural” vitamins claimed to be extracted from food- undergo a process that necessarily changes their original place in that food. As such, they are not the same as the sum of compounds found in food.

The amount of vitamins found in many of these whole food supplement tablets, capsules, or whatever are often miniscual (same for other important elements such as fiber) and often far from accepted RDAs or other accepted dietary intake parameters. These groups claim that this is a good thing and the therapuetic effects are due to the additive synergies of ingredients

However, there are no broad independent studies corroborating the claim that “hundreds” of co-factors, enzymes…and other synergistic factors are actually in the capsule or tablet and that they potentiate the core vitamin. Even if they are, there is no evidence that these supplements are effective- even necessary in the general population beyond well known caveats. Additionally, the evidence is clear that the positive effects of vitamins, factors, and synergistic substance actually describe real food- not food extracts. A tiny dribble of dehydrated food extracts being linked to positively benefiting and "promoting" (code for treating) health is unconvincing. Also, there are no obvious generalized critical deficiencies in the general food supply even with the significant issues and problems regarding food production and distribution.

The absorption of vitamins can vary depending upon whether they are ingested as food or not. Otherwise, in general, a chemical is a chemical. For example, most minerals from the ground are absorbed quite well without the need to be chelated (more expensive). Some vitamins and related substance actually need to be metabolically changed by the body before they can be utilized. For example, synthesized folate is more active than the "natural" forms found in food as these configurations need to undergo biochemical changes before the body can take advantage of them.

The bottom line seems to be that food, in and of itself, is the key and vehicle through which vitamins and other substances should be ideally “administered”. The question and thrust of optimizing health from a micronutrient and macronutrient stand point needs to focus more on food distribution, safety, and quality rather than on non food supplementation.

On the other hand, there is a critical need to understand the effects of substances found in food and identify those substances that could very well benefit the general population as well as target groups of populations (i.e.; gerontology, nutrition in chronic diseases, metabolic disorders). As always, advancing scientific knowledge will continue to shed light on many of today’s tentative assumptions regarding the continuum of food, health, and function and shed light on truly effective possibilities.

Zempleni and Rucker in “Handbook of Vitamins” note that in the case of vitamins “Recent advances in molecular and cellular biology, analytical chemistry, and nanotechnology have dramatically improved the understanding of vitamin biomechanics and the requirements for human function. Vitamin-dependant signaling cascades, alterations in gene expression due to variations in vitamin supply, and DNA stability and packaging are just a few of the new roles for vitamins that these sciences reveal”. There is yet much to be learned- the right way.

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1) A classical mantra is that these isomers can be compared to a pair of gloves identical in size, shape, and composition, but their 3-D configuration is different. Only one glove fits- they are not interchangeable.

2) As for vitamin E, products that contain dl-tocopherols have 8 isomers one of which is natural. Other products contain d-alpha tocopherols that are semi-synthetically derived where the isomer is in the ‘natural’ configuration. The question of whether the dl version of vitamin E is less efficacious is a good one and the varying effects of these variable isomers may have an impact. It may be that more of this form needs to be ingested to get similar result than for the d form of vitamin E. That said, the recent accumulating evidence does not support the use of tocopherols beyond what is found in food anyway.

Critics of these studies claim that only synthetic vitamin E was used. Though this is worth another post, a couple of points on this are that this may be, in part, a “the poison is in the dose” issue along with a possible vitamin E effect between opposing pro-inflammatory/anti-inflammatory actions.

Ref:

Zempleni J, Rucker R, et al. Handbook of vitamins. Taylor and Francis Group, Fla. 2007

Of Monkeys, Men, and Herpes simplex virus

A possible new herpes danger

When thinking of infectious disease, it’s usually the simpler things we need to be vigilante of such as Influenza virus, Streptococcus (i.e.; respiratory disease), Giardia and E. coli (i.e.; intestinal disease) to Staphylococcus (i.e.; “flesh” diseases) to name a few. The advent of national health campaigns, hygiene and prevention practices, food supply monitoring, vaccines, and antibiotics have all to one degree or another made huge impacts towards ensuring improved human and animal health in this respect. In fact, the rapidly changing global environment makes all these tools ever more critical and important. Among the more relevant up and coming global issues in disease vigilance is the increasingly more urgent need to monitor for the risk of zoonotic disease (those diseases that can potentially jump from one species to another).

With the advent in the human and animal medical world of the concept of ONE medicine, this particular branch of infectious disease- this crossover through species barriers- can be more effectively brought front and center. It is becoming increasingly apparent that the dangers are real.

As our knowledge continues to expand into the genomic, biochemical, and evolutionary aspects of infectious elements from prions to parasites researchers, medical doctors, and veterinarians are beginning to realize the extent to which things might go bad.

The geographic porosity of an increasingly smaller world is opening up niches for these organisms giving them an opportunity to adapt and capitalize on new horizons. The plasticity and ability for organisms such as bacteria and viruses to adapt to new situations is simply astounding. The risk for a more dangerous zoonotic event to occur can- in spite of the better known cross over media favorites like bird influenza H1N5- also involve those infectious diseases that work under the rubric of similar species. For example, virus’s acting within the umbrella of the primate genera. This particular case report entails just such a condition that unfortunately, in this case has potentially deadly consequences for its non-host primates- including humans.

Titled “Naturally transmitted herpesvirus papio-2 infection in a black and white colobus monkey”, this case involves the transmission of herpesvirus papio-2 virus to a colobus monkey that originated from a nearby baboon zoo colony. Though, this study may be somewhat tangential to any immediate risk to the general public, it illustrates how factors can serve as either facilitators or key prerequisites for how animal to human infections of potentially deadly diseases could occur.

The authors describe the death of a colobus monkey at the Hanes Veterinary Medical Center at the North Carolina Zoological Park and their subsequent investigation that eventually led to the recommendation of adding herpesvirus papio-2 to the differential diagnosis for any human or animal suffering from an acute neurological disease.

The herpesvirus papio-2 (HVP-2) is a simian virus that is endemic in wild and captive baboons. This virus affects over 90 percent of wild –caught baboons and over 80 percent of captive baboons are seropositive for this virus. The HVP-2 shares genome composition, organization, and has a close sequence homology to other primate simplexviruses. (i.e.; SA8, Bvirus, HSV 1 and 2). These viruses are so similar serologic anti-body testing can not offer a positive identification between them.

When simplexviruses infect their normal primate hosts the resulting disease is usually mild or even absent. For example, HSV infection in humans are mild primarily affecting the oral or genital mucosa forming vesicles and papules that eventually form ulcerative lesions – similar pathophysiology occurs in other primates affected by their particular “brand” of simplexvirus.

However the story changes if a primate alphaherpsvirus infects a non-host animal where the virulence of the virus can vary dramatically. For example HVP-2 thought only to infect baboons and African green monkeys has been isolated as causing fatal encephalomyelitis in humans and other primates. The commonly benign human HSV-1 has caused fatal disease in several monkey species, shrews, lemurs, and rabbits.

The capacity for these viruses to cause such severe neuro virulence seems related to their capacity to replicate in there hosts- facilitated replication equated to higher virulence. Scientists have been able to phylogenically separate the HVP-2 virus into two distinct clades related to this neuropathic or non- neuropathic quality. That is their ability- or not- to cause severe central nervous system signs in non-host animals. Interestingly, this virulent HVP-2 caused similar signs to their non-hosts as another virus; the previously mentioned and related B virus effected on humans- a very crucial detail.

The authors in this study were able to isolate this particular virus that killed the colobus monkey to the neuropathic phylogenic strains calling it HVP-2 C1490. Most importantly, they found that this particular strain causes very similar clinical signs and histological lesions that another HVP-2 – the HVP-2nv- as those created in mice.

They were able to deduce that the most likely source of the HVP-2 C1490 infect ion came from a large baboon colony located in the zoological park, possibly through fomite contamination. That is, certain toys- even though they were disinfected- were shared by the colobus and baboon groups and it is possible some virus survived the decontamination process.

The authors note “As highlighted by the infection of the colobus monkey of this report, HVP-2nv can be transmitted naturally from baboons to a non-host species and result in development of fatal encephalitis. Given the extreme neurovirulence of HVP-2nv in non-host species, HVP-2 should be considered a potential zoonotic risk”.

In addition to the more obvious considerations of modifying zoo animal practices these findings suggest larger, more ominous possibilities. Because of the similarities between the virulent HVP-2nv, HVP-2, and the B virus that kills humans, the authors have discovered a new potential zoonotic link that needs to be added to the data base of human virulent viruses- originating from the common mostly benign herpes simplexvirus genus no less.

This small case study illustrates the need for constant vigilance in the search for emerging disease, especially in an increasingly complex global community. Very interesting news indeed.

NOTE:

Aetiology has an excellent zoonosis series that starts in 2006. For some reason the link does not go through right now- but search 2006 emerging disease and zoonosis at the sight-should get you to the series page.