[ed. note: Michael Jorrin, who I call Doc Gumshoe, is a longtime medical writer (not a doctor) who writes for us about medicine and health a couple times a month. He has agreed to our trading and disclosure restrictions, but does not generally write directly about investment ideas. His ideas, thoughts and words are his own, and you can see all his past pieces here.]
Mostly the comments that Gumshoe Nation sends my way make a pretty simple point: Doc Gumshoe, that was fine! (Or else, Doc Gumshoe, that was lousy!) Or, Doc Gumshoe, did you know about this or that?
But sometimes the comments raise a genuinely philosophical issue. A couple of these appeared in response to my recent piece, “Here We Go Again! Another Plot to Suppress Life-Saving Cures,” which posted June 1. One of them leads off with this:
“I noticed the sound of a little religiosity from this article. Theists have guiding literature and beliefs. AntiTheists aka atheists tend to replace that same need for truth with belief in discovery and theory. It is in the single center mindset that men of all ages have believed they are at the pinnacle of knowledge and have all truth exposed bare to them. It is both the source of ignorance to believe all who have gone before ignorant and a source arrogance to believe that truth can be revealed to them. It is also this religiosity that drives all debunkers to take time to critically refute any and all knowledge that they do not have or does not originate with their same source of knowledge. This seems much more evident almost anywhere you look today. I think that it is the misconception that a single tome is equal to an author’s compendium….”
Initially, I was baffled. I scanned my blog for religiosity and couldn’t find the least hint. According to Webster’s New International Dictionary, Unabridged, Second Edition (which is one of our prized possessions), religiosity is “religiousness, esp. when intense, excessive, or affected.” (My OED agrees.) Then as I read the above passage, I gathered that the author seems to think that religiosity is a sort of atheism. Why would that person think that I am an atheist? Does trust in science, belief in evolution, acceptance of the geological record, mean that I am an atheist? No, I do not believe that the World was created in 4004 BC in seven days at the conclusion of which all the plants and animals came into existence exactly as they are now. But that does not make me an atheist. I believe in the divinity of existence. About that I will say no more.
But then, reading further in the comment, there was this:
“This is my fifth year without pharmaceuticals using hibiscus, willow bark, and organic whole milk to survive terminal 4th stage kidney failure.
I was first diagnosed with extreme high blood pressure and prescribed pit viper venom ( lisynapril ) and sea cucumber venom ( norvase ) in very high dose over a 6 year Doctor’s treatment that almost killed me. I hunt rattle snake and make a great stew I informed doctors of the fact that I had anti-venom and antibodies to snake venom. The cause of the High Blood Pressure was a bullet fragment impinging on a nerve at l4 l5 not what AMA pushers sell drugs for.”
I sincerely hope that everything works out for the best for the writer of that comment, and I confess that I do not know where “nerve 14 15” might be. Cranial nerves are numbered with Roman numerals; other nerves have names. But I don’t think that rattlesnake stew is likely to be an efficacious treatment for “extreme high blood pressure,” nor yet hibiscus, willow bark, and organic whole milk for terminal kidney failure.
The writer is a tiny bit correct when he links lisinopril with pit viper venom. Lisinopril is a widely prescribed ACE inhibitor (ACE being the acronym for “angiotensin converting enzyme,” angiotensin being a hormone that promotes constriction of blood vessels leading to hypertension) which is quiet effective and has, usually, mild side effects. The link is as follows: people who have the misfortune to be bitten by pit vipers experience rapid and catastrophic drops in blood pressure, often sufficient to kill them quickly. Researchers figured out which component of the pit viper venom brought about this drop in blood pressure, and engineered a drug that would lower blood pressure, based on that mechanism, but nowhere near as drastically. You definitely don’t want to use daily doses of pit viper venom to control your blood pressure.
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The other drug he mentions is Norvasc, aka amlodipine, a calcium-channel blocker. Drugs in that category work by blocking the action of calcium, the electrolyte that triggers the contraction of arteries. Blocking the calcium channel thus lowers blood pressure. I am not aware that amlodipine has a connection with sea cucumber venom. In fact, I am not aware that sea cucumbers are particularly venomous. You’re supposed to wash your hands after you touch a sea cucumber, and not rub your eyes, since they’re coated with nasty stuff that can cause blindness. I have eaten sea cucumber in Chinese restaurants, and here I am, alive and kicking.
Why does this good fellow equate trust in the so-called “natural” remedies – pit viper venom, hibiscus, willow bark – with theism, and the drugs that have painstakingly been developed, sometimes originating in a naturally-occurring substance, with anti-theism? Are we not supposed to use the sense God gave us? The willow bark this chap uses to somehow treat his kidney failure (I have no idea how!) does contain the molecule that became aspirin. But does taking aspirin instead of willow-bark tea make you an atheist?
And here’s another one with a somewhat similar take. He leads off with:
“Sorry your misinformed! A well known scientist for a well known pharm company lost his job and has been black balled from the science community for having the natural cure for cancer sitting on a shelf in front of him….”
Then he goes on as follows:
“I have an Aunt that was sent home back in the 50’s to die with cancer. My grandfather met a man at a livestock auction who said God have given him the cure for cancer and diabetes. He gave my grandfather (not sold) a quart jar with a clear liquid and told him how to give to her. On the 3rd jar my aunt was already back to eating, working in the garden etc. Tha man handed the 3rd jar to my grandfather, he said “2 men in suits showed up at my door and told me to discontinue making the elixir or he would disappear.) That same year the FDA OUTLAWED bitter almonds whitch has the second largest amount of a certain vitamin that our bodies are depleted of. Apricot seeds has the highest!
So if the FDA is looking for natural cures, than why are we told that certain fruit seeds are poisonous? When the BIBLE tells us to eat the fruits and the seeds there in. Why can a pharmacist be punished by the law if this vitamin is spoken of by them? Why will grocery stores be shut down if they put any information out about this. All of the FDA directors are former CEOs of Monsanto. The largest pharm and research company in the world.”
I am quite sure that nowhere in the Bible is there a commandment to eat apricot seeds. But eating apricot seeds was indeed thought by some to be a way of curing cancer, and it gave rise to the laetrile enthusiasm, which I wrote about in some detail in a Doc Gumshoe piece entitled “Supplements and Drugs: The Feud Redux,” posted on October, 2016. Here’s an excerpt:
“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.”
The Jason Vale story is likely the basis for the comment about the “2 men in suits showed up at my door and told me to stop making the elixir or he would disappear.” Disregarding the muddled grammar – who is the “he” who would disappear? – this is another repetition of the usual stuff about the collusion between our government and the all-powerful pharmaceutical-medical complex. God and the Bible are in one camp, instructing us that whatever is natural will somehow heal us, and all the scientists and physicians are lined up against nature. Believe that if you wish.
Frequently, however, comments from Doc Gumshoe’s readers send me sleuthing in interesting and valuable directions.
A helpful hint from a reader
A recent comment from a citizen of Gumshoe Nation who goes by the moniker SoGiAm turned me on to recent data suggesting that a diet that includes a goodly amount of olive oil may be helpful in preventing Alzheimer’s disease (AD). Possible effects of diet on AD have been a matter of speculation for decades. Long before AD was characterized and identified, dementia was sometimes attributed to hardening of the arteries, or arteriosclerosis, in the brain, and arteriosclerosis (as it was commonly termed) was associated with cholesterol in the diet. Note that I’m referring now to a time when there was not a whole lot known about the progression of what we now call atherosclerosis and its putative causes, which are still, at least in some quarters, the subject of debate. In any case, when AD was found to be at least strongly associated with the presence of a certain protein in the brain, amyloid beta (Aβ), it was entirely reasonable to try to link the formation of this protein with diet.
A short primer on amyloid beta. The identification of Aβ is relatively recent; for a long time researchers just thought the amyloid deposits themselves – the whitish deposits identified a century ago by Dr Alzheimer – were the culprits, but they have learned since that the real culprit is only a subset of the basic amyloid which occurs throughout the body. In Aβ the amino acids that make up amyloid are folded in a certain way, which is labelled amyloid beta. And another twist – it now appears that the particularly toxic version of Aβ consists of sections that are cut into snippets that are just two amino acids longer than the usual beta amyloid sections, which are 40 amino acids long. The 42 amino acid amyloid beta sections are the ones that are thought to be damaging to brain function.
So does this have something to do with diet? Maybe so. One of the first things that researchers looked at, back in the 1990s, was the effect of antioxidants in the diet on cognition, and the results were on the whole ambiguous, but mildly positive, which is to say that foods rich in Vitamin E did appear to slow cognitive decline in laboratory animals, although Vitamin E supplements did little or nothing, perhaps because the supplements were composed of a form of Vitamin E that had little effect in the brain.
But reducing dietary fat did have at least somewhat clearer results. Laboratory animals fed high-fat and high-cholesterol diets did worse on learning and memory tests compared with animals on control diets. They also had more Aβ deposition in the brain, greater loss of neurons, and other AD-related pathologies. A study in 444 men in Finland ages 70 – 89 reported that an elevated cholesterol level over 250 mg/dL in midlife was associated with three times the risk of developing AD later in life. (Notkola IL. Neuroepidemiology 1998)
A study in Rotterdam in more than 5,000 normal volunteers (i.e., no signs of dementia) found that, after two years, about twice as many of those who reported a high-fat diet showed signs of dementia, compared with the ones who reported a normal diet. However, after six years of follow-up, those differences seemed to disappear. (Kalmijn S. Ann Neurol 1997) Another study, in New York, in 815 normal individuals found that after about four years, the group in the highest fifth regarding consumption of saturated fats had about double the risk of developing AD as those in the lowest fifth. The increase in risk in the group consuming the highest amount of transfats was even higher – about 2.4 times that in the lowest fifth. (Morris, Arch Neurol 2003)
But that’s all old stuff. Moreover, none of these studies used rigorous criteria for the definition of AD. Signs of dementia certainly do not equate with AD, and the New York study, mentioned in the preceding paragraph, talks about risk of developing AD, and not necessarily frank AD. Currently, the best method of detecting AD is an analysis of spinal fluid for the particles of Aβ and the neurofibrillary tangles that are present in patients with AD.
That’s where the helpful comment from one of your fellow readers comes in. This chap pointed me to a recent study in triple-transgenic mice, which have been developed specifically for the study of AD. These mice develop the Aβ and neurofibrillary tangles characteristic of AD and also demonstrate cognitive deficits.
Researchers at Temple University who were exploring the benefits of the Mediterranean diet, found that these mice, when fed a diet rich in extra-virgin olive oil, demonstrated reduced formation of Aβ plaques and tau tangles in the brain. The olive-oil diet also appeared to protect memory and learning ability. The senior investigator, Dr Domenico Praticò, commented that olive oil reduces brain inflammation, and, what may be more important, reinforces autophagy, a process by which cells break down and clear out intracellular debris and toxins, such as the ones thought to lead to AD. (Lauretti E, Ann Clin Translational Neurol, 2017).
One could say that the olive oil/mouse study goes a certain way towards confirming the previously mentioned studies. That an olive-oil based diet instead of a diet of saturated fats or transfats should prove beneficial in those ways makes sense. It does not by any means entirely explain the benefits of the Mediterranean diet, which has other components and also results on health benefits other than the ones involved in AD. It’s also the kind of study that prompts people to say, “We knew that already!” My response to that is two-fold: A, we did not know that already, and B, we still don’t know that for absolutely sure! But we’re getting closer.
One of the key parts of the Mediterranean diet, along with olive oil, vegetables, and fish, is wine. A few years back, a theory was surging that what was especially beneficial in red wine was a flavonoid called resveratrol. This theory was gleefully taken up by the faction, not so small, that resisted any suggestion that what was good for us in wine was the alcohol. Studies in mice (those handy little creatures!) seemed to confirm the resveratrol theory, but only up to a point. But then the theory took a huge hit when it was disclosed that for humans to get the dose of resveratrol from wine equivalent to the dose that produced those nice benefits in mice, we would have to drink quite a lot of wine. I seem to remember that the equivalent amount would be about 900 liters. I don’t think I could drink that much in a year.
So it clearly was not the resveratrol that accounted for whatever benefits wine brought.
Now, a huge study to try to confirm the benefits of consuming alcohol…
… in moderate quantities, of course. The NY Times saw fit to devote nearly a full page on the Fourth of July to this projected study. It will enroll 8,000 volunteers at medical centers in the US, Europe, Africa, and South America and run for six years. It’s officially an NIH trial, estimated to cost about $100 million. The trial will be overseen by Global Alcohol Research Program at the National Institute on Alcohol Abuse and Alcoholism. The Harvard School of Public Health is described as the “hub” of the study, and Dr Kenneth J. Mukamal of the Harvard Medical School is the principal investigator, although there are other principal investigators in a number of other sites.
The chief subject of the NYTimes article is that $67.7 million so far have been pledged to support the planned study by a consortium of alcoholic beverage manufacturers. The concern is that the fact that the study is largely supported by a group that has a major financial interest in the outcome will inevitably influence that outcome. That’s certainly possible, although nearly all clinical studies in prospective new drugs are paid for by the drug’s manufacturer, and quite a few of those studies report negative results. I was involved, as a writer, in the development of a new drug that was optimistically seen as a nearly miraculous new departure in the treatment of seizure disorders. The results of a large, expensive, Phase III clinical trial were eagerly anticipated. Everything was ready for a major marketing campaign. Then the trial results were announced, and the drug never made it to market. The trial, funded by the pharmaceutical company, was the drug’s death sentence. It happens all the time.
My concern – and it’s not that I’m worried or anything like that – is that the way the study is planned, the results will certainly be open to question and may be totally inconclusive. The 8,000 study subjects will be randomly assigned either to abstain entirely from alcohol during the entire six years of the study, or to partake moderately, which is defined as one drink per day. And a drink is either a 12 ounce beer, a 5 ounce glass of wine, or 1½ ounces of distilled spirits. That’s it, no more. Teetotalers are excluded, as are “problem” drinkers. All study subjects will be 50 years of age or older, and all will either have established cardiovascular disease or be at risk for developing cardiovascular disease. The outcome measures are signal cardiovascular events – heart attacks, strokes, cardiac deaths.
Why is moderate alcohol consumption defined as one drink per day? The common definition is two drinks per day for men and one drink per day for women, but since this study expects to enroll roughly equal numbers of men and women, it made for easier comparison between groups to have every subject follow the same rule. The difference in the definition of moderate drinking between men and women is more a matter of tradition than fact-based. True, women tend to be smaller, so equal amounts of alcohol would result in higher concentrations in women than in men.
Why does the entire study population consist of individuals who are already at elevated cardiovascular risk? Clearly, because the study needs enough “signal events” in order to reach a clear conclusion. The results would then be assumed to apply to the population at large. A leap, if you ask me.
And why are the teetotalers excluded? Obviously, because you can’t randomly assign teetotalers to the cohort that is supposed to consume one alcoholic drink per day. I suspect the same with the “problem” drinkers, not because it wouldn’t be interesting to observe the effects of alcohol on their cardiac health, but because they likely couldn’t be trusted to stick with the “one drink per day” rule.
My deeper question is, can any of the study subjects be trusted to stick with the protocol for their cohort? Will the abstainers – who, you will remember, were not abstainers to start with – really go six years without a drink? Remember, they’re not getting paid for this. And will the “moderate” drinkers really pass up that second beer or second glass of wine? I’m reminded of the study comparing outcomes in men who had tests for PSA (prostate-specific antigen) with outcomes in men who supposedly did not have PSA tests. The difference in prostate cancer survival between the two cohorts was minimal. But it turned out that more than half of the men in the cohort that was not supposed to have PSA tests went ahead and had those tests anyway, so there wasn’t much difference between the cohorts.
My prediction is that the results of that alcohol benefits study will be similarly tainted. A large percentage of the abstainers will have violated the protocol. They may or may not admit to having done so, but the doubts created by the study design itself will seriously cloud the study. We can be quite sure that the alcoholic beverage manufacturers are hoping that the study will confirm the widely-held view that moderate tippling is good for us, but we can’t be sure that those results will be widely accepted.
That view, that moderate alcohol consumption is beneficial, has a long history. More than two hundred years ago, a Scottish physician noticed that among his own patients, the moderate drinkers generally outlived both the teetotalers and the drunks. He recommended a nip before dinner and wine or beer with dinner. But was it the alcohol itself, or the lifestyles connected either with abstention or dissolution? Nobody knew then, and even today nobody knows for absolutely sure. However, the evidence that a bit of alcohol confers a benefit relating to cardiovascular health is quite robust. There began to be studies in peer-reviewed medical journals in the 1970s, and in 1996 there was a big review in the British Medical Journal that more or less clinched the case for moderate alcohol consumption (Grønbaek M, Sørensen TI, BMJ 1996). Overall, the studies this review cited concluded that drinking alcoholic beverages, mostly wine, lowered heart disease risk by about 30%.
The mechanisms through which alcohol protects against cardiovascular disease are well-understood. Alcohol (always in moderate amounts) raises high-density lipoprotein (HDL), which is the mode of transport for cholesterol leaving the circulation. Alcohol also improves insulin sensitivity and improves factors that affect blood clotting, helping to prevent the formation of blood clots that cause many heart attacks and ischemic strokes.
One would think that the matter was pretty well settled – we have the data, and we understand the mechanism. But the alcohol opponents have some data on their side as well. Obviously, excessive alcohol consumption leads to serious harms. But even moderate alcohol consumption can lead to harms, particularly in women. For example, it is linked to a slightly higher incidence of breast cancer. Depending on the amount, the increase in risk can run from a couple of percentage points to almost a 50% increase over the lifetime risk for developing breast cancer, currently a shade under 12%. In women who regularly consume two or more alcoholic drinks per day, that 50% increase raises the lifetime risk to about 17%. But, according to the Nurses’ Health Study, that increase was more than offset by the 30% decrease in cardiovascular risk in the subjects who reported moderate alcohol consumption. We should note, by the way, that cardiovascular events are much more deadly than breast cancer. Survival rates in breast cancer depend on the location of the cancer and how early it is diagnosed, but more than 60% of breast cancers are confined to the breast, and the five-year survival rate for these cancers is more than 95%.
So, when all is said and done, the NIH study will go forward and results will be announced in a few years. Likely, the results will be consistent with the other data that have emerged up to now – a reduction in the risk of sustaining an acute coronary syndrome among the moderate drinkers compared with the abstainers. Of course, there may be surprises. As I suggested above, the abstainers might go off the wagon and experience much the same benefits as the moderate tipplers. Or the moderate tipplers might greatly exceed their drink-a-day limit and experience some significant harms.
The real question is, how will those results be interpreted? I do not expect the anti-alcohol faction to sound the retreat. Regarding past studies, the opponents of alcohol could point to certain other factors to explain the benefits that were seen in the moderate drinkers. E.g., they (perhaps) avoided sugary soft drinks and/or ate a healthier diet. One not unlikely outcome is that, at least in a certain proportion of the pro-alcohol faction, the reaction will be that if one glass of wine or one beer is good, why then three or four would be even better – and since the proposed study limits the subjects to that skimpy allotment, there will be no evidence either way about what happens when we exceed the drink-a-day limit.
Considering those prospects, I revert to the J-curve data, which I discussed in a post about the resveratrol bust way back in 2013. The J-curve is a curve that descends to a low point and then slopes up again. If we plot cardiovascular events starting at its incidence in teetotalers, and then go on to measure its incidence in moderate drinkers, we find that this incidence is quite a bit lower in those moderate drinkers. But as consumption rises beyond the optimal two drinks per day point, the curve starts going up again, and by the time we get to about four drinks per day, it’s right back up to the rate for teetotalers, and it goes up from there. So the people who warn about the dangers of excessive alcohol consumption are right, of course, but it doesn’t become really excessive – i.e., more dangerous than being a teetotaler – until we get to that four drinks a day mark. Those data are likely based on a predominantly male cohort, so some tweaking needs to be made for women. And, we should remember, the data are based on daily consumption of alcoholic drinks. Four drinks once in a while probably won‘t do any harm.
And then there’s the comment of a good friend, who noted that people who have a glass of wine or so with their meals are probably happier, and that goes a long way towards maintaining good health.
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Sorry, but I’ve come nowhere near discussing all the interesting comments that are directed to Doc Gumshoe. I’ll try again before too long, but meantime there are lots of developments in the health-care field that deserve a look. Thanks again for any and all comments, best to all, Michael Jorrin (aka Doc Gumshoe).