[ed note: Michael Jorrin is longtime medical writer who has been sharing his thoughts with our readers as “Doc Gumshoe” for several years (he’s not a doctor, I gave him the name). He generally covers medical and health news and sometimes health promotions and hype, but he rarely opines about investments or specific stocks. All of his past commentaries can be seen here]
It never fails that when I write about drugs, a certain tribe out there in Gumshoe Nation patiently informs me about such matters as the inherent capacity of the human body to heal itself, if only we took the trouble to nourish it with the necessary healthful natural nutrients, and also, of course, about the inherent danger of ingesting the chemicals that drugs consist of, which, although they may convey some benefits, pose severe and indeed life-threatening risks that can be avoided simply by following the course of natural health.
That’s a mild and reasonable way of putting it, and many of the comments are couched in mild and reasonable language. But within that tribe there are those who go a wee bit further, and unmask the evil plot that links the pharmaceutical industry, the medical community, and the FDA – NIH axis, to suppress information about the near-miraculous benefits of natural supplements, in order to squeeze trillions of dollars, Euros, Yuan, bitcoin, Electrum, &c., from the duped and deluded masses who have not yet twigged to the truth revealed in my first paragraph.
(For the sake of simplicity, I’ll use the term “supplements” to cover the whole territory, including not only nutritional supplements but also those non-drug preparations that are meant to “support health,” whether heart-health, digestive health, or any other.)
They have certain arguments in their favor. It is certainly true that the pharmaceutical industry at least in part supports the FDA, in the form of fees paid to the FDA when drugs are submitted for approval. It is certainly true that the pharmaceutical industry pays large amounts to many physicians for their work as investigators in clinical trials and for participation in forums and presentations in connection with specific drugs. And it is also true that pharmaceutical companies are focused on the development of drugs that they anticipate will make money for them, which means that they spend their money working on molecules on which they have a patent, and which potentially treat diseases or conditions that affect large numbers of people. That means that they steer away from commonplace substances that they cannot patent, and also that they may need inducement to develop drugs for really rare diseases.
But this is far from amounting to a conspiracy to keep the lid on the supposedly life-saving benefits of supplements. Does the FDA attempt to suppress information about drug adverse effects? On the contrary: the FDA requires pharmaceutical companies to reveal all potential drug adverse effects in overwhelming detail, such that there is a strong view among many medical practitioners that direct-to-consumer advertising, with its litany of side effects, may discourage more people from using a drug rather than encourage them to use it.
And do pharmaceutical companies, or the FDA – NIH, or the medical community, attempt to suppress information or advertising about nutritional supplements or neutraceuticals? Even if they wanted to, there’s no way that they would be able to achieve this squirrely objective. Advertising and hyping of supplements and health cures of all types floods all media – internet, television, print, direct mail – it’s all over the place.
Before going much further down this path, I need to re-emphasize a point that I have made several times. I will resist the temptation to put this next statement in 96 point type all caps bold, but do please focus your keen minds on this: the assertion that drugs are chemicals and therefore artificial, whereas supplements are not chemicals but natural substances, is a distinction without any real difference. Yes, drugs are chemicals. But supplements are also chemicals. In fact, all the food we eat, and indeed all of nature – plants, animals, soil, rocks, air, water – all of nature consists of chemicals. It is the chemicals in the food we eat that nourish us. We convert carbohydrates into glucose, a simple chemical, and glucose provides us with the fuel that we require for all our bodily functions. When we consume protein-containing comestibles, we break down the protein into amino acids, also simple chemicals. And the same thing goes for fats. Vitamins are chemicals. The healthful components of everything we eat and drink are chemicals. And, by the same token, the harmful components of what we eat and drink, as well as the harmful components of drugs – and of supplements! – are chemicals as well.
Drugs as well as supplements are meant to affect our physiologic functioning. These effects are due to chemicals. There is no difference between the way aspirin relieves pain and the effect produced by consuming an infusion of willow bark. In both cases, the chemical responsible for the effect is a salicylate (salix is Latin for willow). A key difference – pointing it out is no doubt superfluous in this case, but it applies to the drugs vs. supplements issue in general – is that with aspirin you know exactly what you’re getting and, just as important, exactly how much.
A colossal difference between drugs and supplements is that while developing a drug and getting it to market is a long and exceedingly costly process, doing the same for a supplement is pretty easy.
For a supplement, the process frequently starts with information, whether reliable or not, that a particular food or plant extract or spice is being used by a group of people somewhere, and it has a valuable and beneficial effect.
Cancer, apricot seeds, and laetrile
Here’s a story which some Gumshoe denizens may remember. About 90 years ago, an isolated group called the Hunza people, living in a long, narrow valley in northern Pakistan, were visited by an eminent English physician named Sir Robert McCarrison. Conditions in the Hunza valley are harsh in the extreme. It is very elevated, exceedingly cold in winter, about as isolated as any region on the planet (the pass between Hunza territory and Pakistan is at more than 13,000 feet), food is the opposite of plentiful, and they did not have even the most essential “modern conveniences,” such as cook stoves or wheeled vehicles. Yet they appeared to be healthy, fit, and long-lived. McCarrison attributed this to their diet, and pointed to the consumption of apricot seeds as a key factor.
Another visitor to the Hunza valley, Renée Taylor, was similarly impressed, in particular by the assertion on the part of the Hunza leader that Hunza people routinely lived to the age of 140 year or older. She also singled out apricot seeds as the key to this magic, and wrote a book entitled Hunza Health Secrets for Long Life and Happiness in 1964.
What is it about apricot seeds that might conceivably convey a health benefit? Like some other seeds and nuts, apricot seeds contain a substance called amygdalin, which, when it interacts with some enzymes that are normally present in the human body, releases cyanide (HCN, prussic acid). This cyanide, so goes the theory, is preferentially taken up by cancer cells, which are thereby poisoned and killed.
This mechanism is precisely the one on which conventional cancer chemotherapy is based. Cancer cells are greedier than normal cells, therefore they absorb whatever is in our bloodstream more avidly than do normal cells, and therefore whatever harmful chemical the chemotherapy agent consists of will kill the cancer cells before it will do serious harm to the human host.
Cyanide, however, in the words of Dorothy Sayers, is Strong Poison.
The apricot seeds/amygdalin (also sometimes called, in my opinion fraudulently, “Vitamin B 17”) cancer-cure theory led to the development of a widely publicized cancer cure called laetrile, which had its moment of glory in the 1970s. Laetrile is a man-made form of amygdalin, and I am sorry to say that its efficacy in curing cancer is without any basis in fact. This has not prevented true believers from seeking out laetrile treatment centers outside the US, e.g., Steve McQueen, who was diagnosed with mesothelioma, a really tough from of lung cancer, went to Mexico to be treated with laetrile in 1980, proclaimed that he was cured, and died shortly thereafter.
This was shortly before a 1982 study in 175 cancer patients treated with laetrile. Only one patient in that group showed any evidence of a tumor shrinking.
Apricot seeds themselves have been demonstrated to be far from harmless. In Turkey, where eating apricot seeds is popular, there were 260 cases in one year of children hospitalized from cyanide poisoning due to eating apricot seeds. One of the children died from eating just ten apricot seeds. The European Food Safety Authority has issued a warning that apricot seeds are dangerous, and the FDA served an injunction against an apricot-seeds salesman named Jason Vale, prohibiting him from promoting apricot seeds as a cancer cure. Vale ignored the injunction and served three years in jail, during which he had a kidney removed likely due to cyanide toxicity
Nevertheless, as you can quickly learn by clicking around on the internet, the apricot-seed cancer cure is still alive and well, despite all evidence to the contrary, and despite legitimate efforts by the FDA to prevent the promoters to advertise apricot seeds as a cancer cure.
Does this constitute a conspiracy to conceal a “natural cure” from the public? Or is the FDA simply trying to protect the public from false and dangerous claims?
But do the Hunza people really have health advantages that we should know about?
The stuff about Hunza people living to a 140 years plus is pure guff. They don’t keep accurate track of their own ages. If a person is old and wise, they tag that person with an elevated year count as a way of describing that person’s wisdom. But there may be other characteristics worth noting. They do appear to be very physically active, and they subsist on an extremely limited diet, which does not include most of the harmful things that we routinely gobble. For example, sugar and sweet drinks have been virtually unknown, carbohydrates are very scarce, the animal proteins they consume are low in fat, and nothing is processed. And the water they drink is uncontaminated and high in minerals.
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There may also be a genetic component. The Hunza appear to be genetically distinct from any of their neighbors on either side of their long narrow valley, which is about 100 miles long and no wider than about one mile. They are much lighter complexioned than the Pakistanis to their south, and distinctly different from their northern neighbors. There is a local legend that they are descended from a group of soldiers from Macedonia who penetrated that far in the days of Alexander the Great. That’s likely just a legend, but because of the extreme isolation of their valley, they appear to have remained genetically distinct, and if indeed there were genetic advantages, these may have been preserved.
Another factor of interest is that there appears to be a cultural characteristic among the Hunza that disregards the treatment of the sick. For example, when that English physician observed that many Hunza suffered from incapacitating vision problems, resulting from excessive smoke exposure (remember, no cookstoves, therefore open fires inside their dwellings) and proposed a clinic to treat these severely handicapped persons, the local rajah suggested that it was better to let them die, since they provided no economic advantage to the community. There have been those who, at various times, opposed treating severely sick people on the grounds that keeping them alive would damage the gene pool. Perhaps this kind of legislated racial purity in some way benefited the Hunza. Fortunately, I don’t see it being advocated these days.
The Hunza may indeed be an example of the health benefits of the non-Western life-style. This does not mean that we should eat apricot seeds. And I also need to point out that in the promotion of many supplements, which are touted as beneficial because they are part of the traditional healing practices of various groups of people here and there around the globe, the promoters fail to point out that the life expectancy in many of those populations is far, far lower than the life expectancy of people in developed countries.
Similarities and differences between drug and supplement development pathways
Yes, there were similarities between the course of events that led to the establishment of apricot seeds and laetrile as health supplements and conventional drug development. Both supplements and drugs are based on the discovery of associations. In the case of apricot seeds, the supposed link was between a group of people who lived to an extraordinary age and the consumption of these seeds. When this supposed association was discovered, the post hoc ergo propter hoc fallacy immediately came into play: since these people ate apricot seeds and then lived to the age of 140 (or older), it must have been because of the apricot seeds that they lived so long. Well, Dr Carrington (and many others), do please remember what you learned in school: correlation does not prove causality.
Of course, in this case, even the association part was fallacious. The Hunza people do not live to those extraordinary ages; they merely don’t keep track of birthdays and make extraordinary claims.
(I hope Gumshoe citizens will indulge me as I go on a bit about the post hoc fallacy. Let’s go back to the 18th century, when empiricists were maintaining that all knowledge derived from observation. David Hume demonstrated convincingly that causation could not be directly observed, and proposed that when we observed two events in proximity, our minds inserted the causal link, whether or not it was present in reality. Immanuel Kant, taking up the argument where Hume left off, then proposed that causation was one of the categories of perception, along with continuity, contiguity, and a few others. In other words, we are born with the tendency to make that causal connection between observed events. We observe separate events; our brains are hard-wired to link them as cause-and-effect. We flick the light switch and the doorbell rings. Our instantaneous reaction is that the light switch made the doorbell ring, somehow. We dismiss that notion pretty quickly – unless, of course, every time we flicked that light switch the doorbell rang. The correlation has to be scrupulously verified. Hard-wired or not, the post hoc fallacy has to be assiduously avoided in seeking effective drugs or health-giving supplements.)
Returning to the main subject: beyond that, there was another factor about the proposed apricot seed/cancer cure link, namely, that there was a putative mechanism of action that was at least, on the surface, entirely rational. It was known that cyanide was released by the apricot seeds when the amygdalin interacted with glucosidase in our digestive tract. The cyanide would then selectively kill cancer cells, leaving healthy cells unharmed. This mechanism had been proposed as far back as the middle of the 19th century – amygdalin was tried as a drug in Russia in 1845. It didn’t work then and it doesn’t work now.
Drug development proceeds in much the same way, frequently starting out with a correlation. Researchers working on drug development are not constitutionally immune from the notorious post hoc fallacy, so correlations, as between a specific pathogen and a specific set of symptoms, are subjected to rigorous standards. Statistical significance, stated as a P value, supports the premise that the correlation has a degree of causality. If in 100 children with a particular kind of throat infection, 95 are colonized with large populations of Streptococcus pneumoniae, the inference that the bug causes the symptom is robust. But even a correlation as obvious as that is necessarily subject to scrutiny. What if we turn the investigation around, and find that in 100 children colonized with S. pneumonia, fully half are symptom free? Do we scrap the inference that the cause of the throat infection is the pathogen? Or do we ascribe the freedom from symptoms in those lucky children to some other factor, such as that the disease is lurking and has not yet manifested, or that the kids have some innate form of immunity that permits them to live with the pathogens and not get sick?
Failure to demonstrate causality doesn’t stop the process. Researchers look for other ways to nail down the cause-effect link. What if we kill the S. pneumoniae – will the sick kids get better? How can we go about killing the germ without harming the child? Well, we can swab their throats with silver nitrate, or give them Argyrol nose drops, which is what we did in the olden times before antibiotics. And, nasty as that was, it worked pretty well – well enough, anyway, to bolster the proposition that it was the germ that caused the infection that produced the symptoms that sickened the child. When the putative cause was removed, the effect disappeared.
The larger the number of individuals in whom the correlation is observed, the more robust is the premise that causation is present. For example, many millions of people have seriously elevated blood pressure. These persons are also affected by higher incidence of cardiovascular diseases – stroke, heart attack, heart failure – and the higher the blood pressure, the higher the incidence of these diseases. This observed correlation is reinforced by another correlation: in those persons in whom the elevated blood pressure is treated, by whatever means, the incidence of those diseases diminishes. The numbers of individuals in whom these correlations have been reliably observed is huge. These large numbers are stated as being statistically significant, meaning that the likelihood that the correlation came about through chance is small. Generally, for the purposes of demonstrating medical “truths,” the expectation is that the odds of a correlation occurring due to chance should be 1 in 20 or less. Such odds are stated as a P value of 0.05 or less.
But in addition to statistical significance, correlations, especially between an intervention and an outcome, should be clinically meaningful. For example, returning to S. pneumoniae infections, supposing a drug were discovered that quite effectively eradicated this pathogen from the upper airways of infected children, but the children’s symptoms persisted? The drug’s effectiveness might be statistically significant, but not clinically meaningful. Back to the lab.
This kind of thing does happen, although not, fortunately, with S. pneumoniae. But it happened to a highly frustrating degree in the development of drugs to treat heart disease that was correlated with elevated cholesterol. The presumption that the essential cause of myocardial infarctions was the deposition of cholesterol in coronary arteries goes back now for a bit over a hundred years. This was based initially on anatomy; cholesterol was found in the walls of arteries, and the narrowing of these arteries due to deposition of this cholesterol-laden plaque was thought to be a factor in the trapping of blood clots that would obstruct the coronary arteries, blocking blood flow to the heart and causing heart attacks. (Note, this presumed mechanism has been refined over the past century. Currently, there is a focus on so-called “vulnerable plaque” and also on the role of inflammation, but the correlation between elevated cholesterol and MIs is real.)
For about three-quarters of a century after the cholesterol- MI correlation was established as statistically significant, researchers tried to find a clinically meaningful intervention with no success. Diets did not work. Finally, in 1994, the Scandinavian Simvastatin Survival Study (4S) was published. The 4S study treated 4,444 patients with established coronary heart disease and elevated serum cholesterol with either simvastatin or placebo for about five and a half years. The results were both highly statistically significant and highly clinically meaningful. For the first time, lowering serum cholesterol reduced all-cause deaths, coronary deaths, and coronary revascularization. The P values for these reductions were 0.0003, 0.00001, and 0.00001 respectively. (Lancet 1994 Nov 19;344:1383-9) That’s the kind of P values that drug researchers lust for. P = 0.00001 means that the odds that the results were due to chance were about 1 in 100,000. And as for clinically meaningful, what could be more clinically meaningful that a reduction in deaths?
This demonstrates that it can take a long, long time for a correlation to be translated into an effective clinical intervention. Most of the time in drug development, that demonstration is the last step before the drug seeks regulatory approval from the FDA or the European Medicines Agency (EMA). The sequence, which we’ve discussed in these pieces before, is:
- first determine a likely mechanism of action, usually in the laboratory;
- then demonstrate safety in animals and humans;
- then demonstrate benefit of some kind in small populations;
- and then, finally, demonstrate efficacy and safety in a human population large enough to establish statistical significance.
This simply does not happen with supplements. The entire world is full of confident assertions regarding the effectiveness of supplements (please remember that I am using the term “supplements” to refer to the entire range of pills, tablets, elixirs, what have you, that are supposed to have healthful benefits). Recently, a helpful, intelligent person recommended a supplement called SierraSil to my wife. It was supposed definitively to treat her plantar fasciitis, which has been a vexation. SierraSil is a mixture of several types of clay, and it is presumed to lubricate the joints in some way. Beyond the assertions that SierraSil will provide pain relief in two weeks, there is no evidence whatever that it works, or that it doesn’t also result in adverse effects.
I have no doubt that the person who recommended SierraSil to my wife had herself experienced pain relief after taking this supplement, and perhaps many others have also experienced pain relief. Their hard-wired assumption is that their pain relief is the result of taking SierraSil. This is precisely the post hoc fallacy that we humans are prone to fall into. In order to bolster the premise of causation, there would have to be a large number of individuals who took this supplement and experienced pain relief, and this number would have to be significantly larger than the number who took the supplement and did not experience pain relief. Such evidence is absent in the case of this particular supplement, and with supplements in general. They rely on what is called anecdotal evidence.
That term is frequently brandished as a cudgel against the whole supplements category. I do not think it should be such a despective term. After all, the first person who made a cup of willow-bark tea and proclaimed that he/she felt better was stating anecdotal evidence. I don’t doubt that some individuals who ate apricot seeds or took laetrile experienced cancer remissions. That’s the first step in the investigation of an intervention that might potentially be valuable, but only the first step. No further investigations of apricot seeds or laetrile demonstrated any legitimate clinical benefit; the 1982 trial mentioned above showed that only one in 175 cancer patients experienced any tumor shrinkage after taking laetrile. Research into the interactions between amygdalin and our cells continues, although with a high level of caution due to the toxicity of the released cyanide.
But is there anything behind the conspiracy theory?
The supplements industry has a couple of beefs that have at least a bit of substance. The major beef is that supplements are not permitted to state in their advertising or promotional material that they actually treat any disease or medical condition. The most they can do is state that taking a supplement “supports” a particular area of health, such as heart, bone, digestive, etc, unless – as happens very seldom indeed – there are acceptable clinical studies substantiating specific claims.
But this restriction is easy to get around. All the supplement marketer needs to do is find a compliant physician and a few patients who have used the supplement and experienced benefits, and the personal testimonials regarding the supplement’s effectiveness as a cure for any and all ailments can be propagated far and wide with no restrictions. We see this every day.
The FDA has tried, with little success, to regulate vitamins as well as other supplements. The Dietary Supplement Health and Education Act (DSHEA) of 1994, among other things, drastically revised previous provisions that would have labeled some supplements as being adulterated. Senator Orrin Hatch of Utah was instrumental in getting DSHEA passed, and his objective was to get the supplements industry “out from under the heavy hand of the FDA.” Supplements were to be regulated as food, and not as drugs. Therefore, there was no requirement that supplement marketers provide information regarding specific health benefits. The ingredients need to be listed. But, by the way, in my previous piece about the drugs vs. supplements feud, I referred to the Canadian study that found that of the supplements from 12 marketers, only 2 were exactly as represented on their labels. Two were totally bogus, and the other 8 were significantly adulterated, sometimes with potentially harmful ingredients.
As for safety, the NIH language makes it clear that it’s the responsibility of the manufacturer to have evidence that the product is safe, but that they do not have to provide that evidence to the FDA before the product is marketed.
Another charge leveled by the partisans of supplements is that the mainstream pharmaceutical industry is in cahoots with the FDA regarding the need to conduct extremely expensive clinical trials in order to get approval to market a drug. But, they observe, perhaps with a certain degree of justification, that if the particular agent in question is a natural substance it cannot be patented, and therefore it would be beyond foolish to spend a billion or two going through the clinical trial protocols. Even supposing the specific molecule that conveys the health benefit in a natural substance could be identified, patented, determined to be safe and effective in clinical trials, and approved by the FDA, Big Pharma would be reluctant to spend the time and the money, because folks could just go out and buy the original natural substance and cut Big Pharma out. It’s possible that some patients who are prescribed monoamine oxidase inhibitors (MAOIs) would prefer to take St John’s Wort, which some people claim has the same effect, although the claim is disputed.
But there are thousands of drugs essentially derived from natural substances, and Big Pharma is always on the lookout for something that has a desirable therapeutic effect. The public is not being deprived of miraculous natural cures because Big Pharma looks the other way. Big Pharma is ready to pounce on any lead.
Finally, the supplements partisans accuse the pharmaceutical industry and mainstream medicine of being greedy, out for the big bucks, and eager to cover up miracle drugs that would end disease and, in consequence, eliminate the need for their own less effective drugs. Yes, along comes the miraculous healer who waves his magic wand and renders all humanity immune from diseases, thus putting the entire medical and pharmaceutical community out of business. Would it not make sense to find this threatening personage and lock him up in the deepest dungeon before he can ruin us? Perhaps it might, but to go along with that particular conspiracy theory, first you have to believe in miracles. I wish I did.
What is possibly the biggest risk
Unquestionably, drugs have adverse effects, and in some cases the adverse effects are truly nasty. A risk that doesn’t get much discussion is the risk that patients may be more afraid of the possible adverse effects than of the much more likely and in some cases certain consequences of letting the disease progress untreated. Statins have a bad reputation, and some people genuinely have difficulty tolerating statins. But an MI can kill you, and certainly one of the reasons that we have seen such a large decline in the incidence of cardiovascular disease in developed countries is that so many people are being treated with statins, as well as with other agents that reduce cardiovascular risk, such as blood pressure drugs. Avoiding drugs with demonstrated clinically meaningful benefits and attempting to manage potentially fatal diseases with supplements is one of the biggest risks that anyone can take. As Doc Gumshoe has said before, do whatever you need to do to stay healthy, but if you have a disease, heed the commandments of your physician.
Best to all and thanks in advance for comments, including the ones that skewer me for being a toady for Big Pharma! I’m girding for battle! (Do I need to add that I’m just kidding?) Michael Jorrin, aka Doc Gumshoe