[ed. note: Michael Jorrin, who I dubbed “Doc Gumshoe” years ago, is a longtime medical writer (not a doctor) who writes for us a couple times a month about health issues, marketing, and trends. He does not typically focus on specific investment opportunities, but has agreed to our trading restrictions… as with all of our authors, he chooses his own topics and his words and opinions are his alone]

When I was a little kid, back in the dawn of time, I was given a daily dose of cod liver oil.   In those days, my cod liver oil dose was administered by my mother in the form of a large spoonful of a rather nasty tasting liquid.   I would then get a few swallows of orange juice to get the disagreeable taste out of my mouth.   By the time my little sister came along, the cod liver oil came in the form of pretty little gelatin pills, which went down my sister’s gullet with relative ease.

What was the cod liver oil supposed to do for us?   Currently, the best-known benefit of cod liver oil (which just about everybody referred to as CLO) is that, along with other fish oils, it is a good source of omega-3 fatty acids.   But when my sister and I were given CLO it was because it was known to be an excellent source of Vitamin D and thus prevented rickets, a disease of nutritional deficiency, which causes weak bones and frequently bow-leggedness.   Infants who are exclusively breast-fed are thought to be particularly susceptible to rickets, a disease caused by Vitamin D deficiency, and Vitamin D supplementation is currently recommended until they get switched to Vitamin D-fortified milk.   I kept getting the CLO until I was 8 years old or so, perhaps because our physician recommended it, or perhaps because my mother was extra cautious.

Why did I start out with CLO?   Because that yucky stuff precisely meets the definition of a dietary supplement.   We ourselves make Vitamin D, but we need abundant exposure to sunlight to do so, and most of us don’t get anywhere near the amount of sun exposure we need to keep our Vitamin D levels optimal.   (Exposing our skin to sufficient sunlight might mean risking skin cancer in the summer and frostbite in the winter.)   Therefore, we need or at least benefit from Vitamin D supplements.

Another dietary supplement that specifically guards against diseases is Vitamin B1 (thiamin), which protects us against beriberi.   This disease particularly affects populations whose diet is based on polished white rice, with the outer coating of the grain removed.   It can be prevented by eating unpolished rice, or supplementing the diet with rice bran, which contains thiamin – or, of course, by taking Vitamin B1 pills.   Beriberi causes a range of symptoms – neurologic, cardiac, respiratory, muscular, and digestive.

And pellagra, which was endemic in the southern part of the United States as well as many other parts of the world, is caused by a lack of Vitamin B3 (niacin) in the diets of populations whose principal food is corn.   In regions in South America where corn is traditionally treated with a strong alkali prior to being ground into grain, pellagra is much less common, because that treatment, called “nixtamalization” makes the niacin in the corn nutritionally available.    (“Nixtamalization,” by the way, is composed of two Nahuatl words meaning “ashes,” the source of the alkali used to treat the corn, and – you guessed it! – “tamal,” which, as we know, is a dough made from dried corn that has been treated to remove the tough outer skin.)   But as corn cultivation spread to other regions where this was not practiced, pellagra became a fairly common blight.   This disease also causes a number of symptoms, usually summarized as diarrhea, dermatitis, dementia, and ultimately death.   In the first half of the 20^th century, there were three million cases of pellagra in the US, and about 100,000 deaths.   Today it is very rare in the US and steeply declining elsewhere.

Vitamins are the quintessential nutritional supplements.   By definition, they are present in our food, or, more to our point, they are supposed to be present in our food.   And they are essential to our physiologic function.   Vitamin deficiencies are responsible for a great range of serious and sometimes fatal health problems, and if they are absent from our diets, we can remedy this quite directly by supplementation.   For example, folate (Vitamin B9) is necessary for red blood cell formation and is particularly important in pregnancy.   Pregnant women are counseled to make sure their diets are a good source of folate by eating abundant amounts of green leafy vegetables, plus peas, beans, nuts, and a variety of fruit.   A dire birth defect, Spina bifida, may affect their babies due to a folate shortage.  And in addition to a folate-rich diet, they may be advised to take folic acid as a supplement.

So this much is obvious: if essential vitamins are absent from our diet, we need to supplement our diet with sources of those vitamins in order to ward off those health issues.   Those nutritional supplements may be vital to our health.

But what about drugs?

At the other end of the spectrum are substances that we call “medicines” or “drugs.”   What distinguishes these from nutritional supplements?   For one thing, they aren’t meant to compensate for deficiencies in our diets, so we don’t call them “supplements.”   For another, we mostly don’t need them except when we are actually experiencing a disease or health issue of some kind.

Drugs are drugs largely by definition.   They are characterized as drugs through having complied with certain legal requirements, which may be different in different nations, but whose common characteristic is that the substance in question, in order to qualify as a drug, needs to openly demonstrate a certain degree of efficacy in treating a medical condition, and also to demonstrate that the benefits provided by treatment with this substance clearly outweigh the risks that this substance will result in harm to the person undergoing the treatment.   The data that leads to those conclusions needs to be open to public scrutiny.   What this means in the United States is that pharmaceutical companies, in applying for approval from the Food and Drug Administration, must hand over the complete documentation of all the clinical trials that they cite in support of the candidate drug.   (I have worked on New Drug Applications (NDA), and the amount of data that gets incorporated in NDAs can run to tens of thousands of pages.)   The key relevant data from the clinical trials are condensed and made public in the form of the drug’s prescribing information (PI), which is available to anyone.

… and what about the supplements that would like to be drugs?

In between the substances that are clearly nutritional supplements and those that have met the standard for drugs is a large and very poorly defined agglomeration of substances and preparations, some of which continue to go under the name “supplements,” even though they are clearly not supplements.   Another term that has been floated is “neutraceuticals.”   A huge range of stuff falls into this undefined category.   I do not have another suggestion for a name, so we’ll continue to refer to them as supplements, for want of a better term.   They fall under the category of “Complementary and Alternative Medicine,” sometimes abbreviated as CAM.

The cohort that has opted to take sides in the battle between drugs and supplements, which to my mind is utterly unnecessary, has chosen to march under various banners.   One banner characterizes drugs as entirely artificial chemicals and therefore essentially unsuited for human consumption, whereas supplements are entirely natural or at least derived from natural substances, and therefore healthful.   But the “artificial” versus “natural” dichotomy is phony, as is the notion that “artificial” means that it’s bad for you, while “natural” means that it’s good for you.   What’s more “natural” than Amanita phalloides (the death cap mushroom) or rattlesnake toxin?

A great many antibiotics originate in naturally-occurring substances, such as molds.   As a Doc Gumshoe reader pointed out, the paclitaxel class of cancer drugs originated in the Pacific Yew tree.   Since we don’t want to treat infections with molds, and there aren’t enough Pacific Yew trees to treat all the cancer patients, chemists have duplicated those molecules in the lab, and pharmaceutical companies manufacture them.   But both the originals in nature and their “artificial” duplicates are chemicals.

It is certainly the case that drugs are chemicals.   They may be simple molecules or highly complex molecules, but they are molecules just the same.   All nature consists of atoms and molecules, including every bit of our own bodies.   Nature has the capacity of constructing molecules of incredible complexity.   It is not easy to draw a clear line between the most complex molecules and the simplest forms of life.

But supplements are also inescapably molecules.   This goes for the Vitamin D in cod liver oil and for all the other vitamins, as well as for all the supplements on all the shelves of all the naturopathic shops on the planet.   That does not make them any less natural.

The frequent proclamation that supplements cannot be advertised as drugs – i.e., agents that are effective in treating medical conditions – because “natural” substances cannot be patented and therefore pharmaceutical companies will not spend the admittedly colossal amounts of money going through the clinical trials needed to gain regulatory approval, is mostly false, although that position does have a bit of validity.   I discussed that issue at considerable length in the Doc Gumshoe piece called “The Regulatory Maze: What It Means for Our Health,” which posted on December 19^th, 2017.   In a nutshell, it’s true that the original natural substance may not be patentable, but pharmaceutical companies have been isolating the active ingredients in these substances for more than a century and patenting those, as well as the methods of extracting the active ingredients.   And by doing so, they have developed hugely successful drugs.   As I have repeatedly said, the pharmas keep a sharp eye on all these natural cures and are waiting to pounce.

Looking beyond the exaggerated claims for these supplements …

The question before us is, might some of these have merit?   And in trying to answer that question, on what might base our answer?

A common, almost universal characteristic of the promotions for supplements is that they are bolstered by a great number of convincing-sounding testimonials, often accompanied by pictures and first names, but usually no last names.   These are supposed to compensate for the absence of published scientific studies.

However, many of these supplements have indeed been the subjects of scientific studies.   For example, when I was looking into curcumin for the Doc Gumshoe piece called “Somewhere Between ‘The Next Aspirin’ and ‘An Ingredient in Curry,’ ” (posted March 22, 2016) I found that PubMed lists 8695 citations that include some discussion of curcumin.   Of these, 1357 discuss the mechanism of action of curcumin.   But when it comes to human studies, the number shrinks dramatically – only 138 in toto.   And the number of randomized controlled human studies is just 21.   Of those 21, some report mildly encouraging results, including lowering LDL-cholesterol, reducing gingivitis (but not plaque), and reducing the pain from osteoarthritis.   Others were inconclusive.

The major stumbling block with curcumin is that we humans just don’t absorb enough of it, and the tiny fraction that we do absorb gets eliminated very quickly.   Various means of increasing its bioavailability have been tried, including combining it with bioperine, which is an extract of black pepper.   What can be said of curcumin is that, without any doubt, pharma is interested.

That does not mean that we should swallow the hype that it’s a cure for all 619 known diseases!

Gundry MD Vital Reds

This one has been popping onto my computer screen with increasing frequency.   It’s basically a nutritional supplement, but as presented by Dr Gundry it’s definitely a wannabe drug.   Vital Red doesn’t compensate for any specific nutritional deficiencies except to the extent that, according to the Gundry Gospel, all of us in the present-day world are eating all the wrong things and failing to eat all the right things.   The promotion for Vital Red hits all the high points of supplement promotions, including lots of testimonials, repeated assertions that Vital Red will quickly put your own physiology on the right track to heal all your ills, comparisons with the healthy diet that sustained our ancestors prior to the harmful invention of agriculture, and reference to clinical studies that supposedly support the validity of Vital Red’s claims.    But I had a look at the 16 citations in Dr Gundry’s presentation, and none of them specifically supported those claims.

Vital Red consists mostly of the extracts of 31 different fruits, although carrot juice is the lead ingredient.   These are selected because they are the richest in polyphenols and anthocyanins.   There is reasonably solid evidence that a diet that provides ample amounts of these substances, which are in the flavonoid category, may deter several diseases, including cancers, cardiovascular diseases, and diabetes, osteoporosis, and neurodegenerative diseases.   This is not the same thing as evidence that a preparation containing the extracts of these polyphenols would absolutely prevent those diseases.   What evidence there is does no more than suggest a benefit from including those foods in our diet.

Vital Red also contains ingredients that are meant to support health by boosting our metabolism.   An extract of bitter lemon supposedly increases glucose metabolism, thereby raising energy levels and leading to weight loss.   And green tea extract supposedly helps our bodies by “burning” fat – i.e., metabolizing body fat and converting it to energy.   Vital Red also contains our old friend curcumin and ginger root extract.

Finally, Vital Red contains several classes of probiotics, which are thought to contribute to the health of our intestinal flora.   Probiotics are particularly important when we are taking antibiotics, which tend to carry out a mass slaughter of those beneficial microbes that inhabit our gut.   As we have noted, probably more than once, antibiotics are a major cause of Clostridium difficile , (C. diff), a common and nasty intestinal infection that often wallops people who have been treated with an antibiotic for something else.   However, in order for probiotics to be in the least effective, the little probiotic microbes have to be alive when you swallow the stuff, and the data that I have seen on the percentage of those little creatures that survive packaging into pills is not encouraging.

Vital Red comes as a powder, which users are instructed to mix with water and  drink right down.   Ignoring the extremely exaggerated claims made by Dr Gundry, Vital Red might indeed bring some health benefits.   It’s hard to see how it could be harmful in any way, unless one happened to be allergic to one of the ingredients.

Like all the promoters of miraculous supplements, Dr Gundry has written a book in which he discusses his health secrets.   I have not looked into his book, but judging from the interminable video, Dr Gundry is not one of those paranoid health preachers who urges his faithful to stay away from regular physicians, hospitals, pharmaceuticals, etc.   He does warn his audience to shun certain foods – soy products, wheat grass, goji berries, and the like – and there Doc Gumshoe  concurs.

Here are a few more possible treatment options, some of which were suggested by the Gumshoe faithful, and some that turned up as I was sleuthing around.   We’ll fit in as many as we can for this edition.

Platelet-rich plasma for the treatment of osteoarthritis

I never considered this as a potential option for my two arthritic knees (both of which I have swapped for new-fangled titanium knees, which are working just fine), but if I had heard of this option back when my first bum knee began giving me problems I would perhaps have given it a try.

Platelet-rich plasma (PRP) consists of whole blood that has been filtered to remove white blood cells, resulting in an increase in the concentration of platelets to about three times what is normal in whole blood.   For reasons that are not entirely understood, PRP appears to encourage cell growth in some parts of the body.   It is used as a treatment for chronic degeneration of the tendons, and has been investigated with mixed results for treatment of knee osteoarthritis, where it may lead to some renewed growth of the cells in the articular surfaces of the knee joints and in the cartilage that protects the bone.   Some studies have demonstrated that, compared with injection of a placebo (saline solution), PRP injections significantly improved knee osteoarthritis symptoms, but only for a limited time – around six months.

Lots of questions remain about PRP for osteoarthritis.   It may be a safer option than intra-articular steroid injections, which are also effective for a limited time, but are associated with potential side effects, while PRP injections, being derived from the patient’s own blood, are free from side effects.   The duration of the benefit is shorter than that for hyaluronic acid injections (marketed under the name Euflexxa and others).   Neither the optimum dose nor the optimum frequency of PRP have been determined, and, of course, the long-term treatment for knee osteoarthritis is total knee replacement.

I am not sure that PRP qualifies as a “supplement,” but it is not a drug, and it is also not, at this point, established medical practice, so it fits under the CAM category.

HCG for weight loss

HCG is human chorionic gonadotropin, a hormone produced during pregnancy, mostly during the early months.    It helps maintain the production of important hormones like progesterone and estrogen, which are essential for the development of the embryo and fetus.   As a diet aid, it was first proposed by a British physician, Dr Albert Simeons, in 1954, but only in combination with a near-starvation diet – about 500 calories per day.   What the HCG was supposed to do is help people stay on the diet by suppressing hunger.   The regimen as proposed by Dr Simeons called for HCG to be delivered by injection; however, currently HCG is sold as tablets, capsules, and even sprays.

Careful controlled studies have concluded that the impressive weight-loss figures attributed to the Simeons diet have nothing to do with HCG, and are the results only of the extreme diet.   When a group of dieters that were being given HCG were compared with another group of dieters that got placebo, the weight loss was about the same in the two groups.   And the HCG group were just as hungry as the placebo group.

There’s plenty of evidence that a diet that extreme can have severe consequences, such as gallstone formation, irregular heartbeat, limited intake of vitamins and minerals, and an imbalance of electrolytes.   A number of side effects that may occur with the HCG diet include fatigue, irritability, restlessness, depression, edema, and swelling of the breasts in boys and men.   Another serious concern is the risk of blood clots forming and blocking blood vessels.

The FDA has issued an advisory against over-the-counter products claiming to contain HCG.   The likelihood that these products actually constitute a risk is small, because most of these products are labeled as being “homeopathic,” which means that they only contain trace amounts of the actual hormone.   The risk to consumers mostly comes from launching on this extreme diet.

And, by the way, as we all know, when you lose a couple of pounds a day during a period of extreme dieting, you mostly gain it back pretty quickly afterwards.

Mistletoe extracts for the treatment of cancer

This one is a bona fide drug, approved in a number of nations, primarily Germany, Austria, and Switzerland, and it may be on its way to at least seeking approval elsewhere, including the US.   Mistletoe grows on several species of trees, and, in spite of the fact that its leaves and berries are toxic to humans, it has been used as a folk treatment for a variety of ailments, as well as for encouraging informal osculatory activities among susceptible individuals when hung overhead as a Christmas decoration.

The use of mistletoe extracts as cancer drugs is based on the demonstrated in vitro effectiveness of the extract to kill cancer cells, and also to stimulate the immune system both in vitro and in vivo.   The components of mistletoe that are thought to convey these effects are viscotoxins and lectins.   Viscotoxins have cell killing capacities, not specifically targeting cancer cells, but perhaps being preferentially absorbed by those cells, thus simulating cancer chemotherapy agents.   Lectins are considered to be biological response modifiers, and may perhaps lessen the adverse side effects of other cancer drugs.   Mistletoe extracts have also been shown in vitro to have other potential anti-cancer effects, such as impeding the activity of cancer cells to induce the growth of blood vessels for the purpose of obtaining nourishment (antiangiogenesis).

Several mistletoe extracts are commercially available outside the US, marketed under such names as Iscador, Eurixor, Helixor, Isorel, and others.   Mistletoe extracts vary with the species of tree on which the mistletoe feeds, and the drug names typically identify the host tree species by adding initial suffixes to the brand name.   Thus, IscadorM is from apple trees (Malus domesticus), IscadorQu from oak trees (Quercus robur), IscadorU from elm trees (Ulmus minor) and so forth.   So far, none of the clinical trials of any of the several mistletoe extracts have been considered robust enough to warrant an NDA.   But according to the National Cancer Institute, at least two investigators have been granted approval of their Investigational New Drug applications, a required first step before they can conduct clinical drug research in the US.

I’ll summarize what I have learned about a few others.

Graviola (Annona muricata)

This is the fruit of a common tree in the Amazon rain forest, and has been promoted as “the one true cure for cancer, 3000 times stronger than adriamycin,” a common chemotherapy drug.   It is known by a number of other names besides graviola: cherimoya, guanábana, corossol, soursop, custard apple, and Brazilian paw paw.

According to Cancer Network, an online information site provided by the journal Oncology, the active ingredients in this natural product are phytochemicals called acetogenins, which may have some physiologic effects in humans, including potentially countering the Herpes simplex virus.   Extracts of this plant in vitro have demonstrated effects against some human cancer cells, including doxorubicin-resistant breast cancer cells.   Thus far, studies in human subjects are lacking.

A study of graviola in several groups of rats found that some substances in this plant did have potential beneficial effects in several classes of cancer cells, including the capacity to trigger apoptosis (cell death) in some cancer cells.   The conclusion was that extracts of graviola had the capacity to diminish the formation of these precancerous lesions in rats, as well as other potential anticancer effects, and thus had significant promise in the treatment of cancer.   That study, published in 2015, is pre-preliminary.   Graviola is years if not decades from becoming a legitimate cancer drug, but there’s some promise there.

Coptic salt (Coptis chinensis) 

This is made from the root of a plant called Chinese Goldthread, of the Ranunculacea family, which is used in folk medicine for a number of diseases and conditions.   According to the World Health Organization, these may include bacterial diarrheas, acute conjunctivitis, gastroenteritis, boils, and cutaneous and visceral leishmaniasis (“oriental sore”).   Coptis chinensis is also used in the treatment of arthritis, burns, diabetes, dysmenorrhoea, toothache, malaria, gout, and kidney disease.   WHO points out that none of these uses are in any way supported by clinical data.

The active constituent of the so-called Coptic salt is the alkaloid berberine, which does have in vitro antibacterial properties, inhibiting the growth of some common bacteria including staphylococci, streptococci, and some pathogens that cause cholera and dysentery, but not of others, including E. coli, Salmonella, and Shigella.   The specific mechanism through which berberine exerts its antidiarrheal effects is thought to be inhibition of cyclic AMP accumulation, which results in a reduction of the motility of the intestinal system.   Essentially, what berberine does is reduce stool volume.   It does not appear to combat the infection itself.

Lion’s Mane mushroom (Hericeum erinaceous) 

This has been proclaimed as a sure-fire cure for Alzheimer’s disease by the Alliance for Health.   A 2009 paper (Mori K, Phytother Res 2009;23:367-372) reported a double-blind placebo-controlled clinical trial comparing two cohorts, 15 subjects each, with mild cognitive impairment.   One group received tablets consisting of dried powder of the Yamabushitake mushroom, which is what this mushroom is called in Japanese, while the other group got placebo.   The findings were that the group that got the mushroom treatment showed improvement on a cognitive function scale starting after about 8 weeks of three-times-daily dosing.   But by about 4 weeks after the 16-week treatment period, those improvements in cognitive function had vanished.   The authors nonetheless concluded that the Lion’s Mane mushroom treatment regimen could be effective in treating mild cognitive impairment.

This, if I may make a mildly negative comment, is a far cry from curing Alzheimer’s disease.   Several drugs have been shown to improve cognitive function, at least on a short-term basis; these include drugs used in treating Parkinson’s disease – Aricept and others.

Colloidal Silver

For readers who might just be scanning this piece, I will reverse the usual order and put my conclusion right at the top: colloidal silver, in some cases, might be useful as a topical treatment only.   However – and this is a major however – it should not be taken internally.   It may be appropriate with bandages and dressings to treat some skin infections, superficial wounds, abrasions, burns, and sores.   In newborns it is sometimes used to treat conjunctivitis, which is mild inflammation of the mucus membrane in the inside of the eyelid and the front of the eyeball.   It is an antiseptic, not an antibiotic, meaning that it is completely non-selective in what microbes it kills.

Colloidal silver is currently being promoted as treatment for diseases such as cancer, diabetes, arthritis, and internal infections.   According to the National Center for Complementary and Integrative Health (part of NIH), there is no evidence whatever to support those uses.   Colloidal silver can cause a serious and permanent side effect called argyria.   What happens is that silver is deposited in the skin, turning the skin bluish-grey.   The reason this takes place is that the human body has no way of excreting silver through any of the normal physiologic pathways.   When taken internally, silver is neither excreted in the urine nor in the feces.   Instead, the particles of silver migrate to the skin, turning it an unattractive and unhealthy color, and especially susceptible to sunburn.   In this way it behaves like arsenic, which similarly cannot be excreted through normal pathways.   Colloidal silver can also interfere with the absorption of some drugs, including certain antibiotics and thyroxine, which is used to treat thyroid deficiency.

When I was a child, back in the days when I was taking my daily dose of CLO, the standard treatment when I caught cold was to get Argyrol nose drops.   They tasted horrible, but I somehow survived.   Argyrol was colloidal silver bound with a protein, and it continued to be sold legally until the mid 1990s.   It was used to treat infections in the mucous tissues of the nose and throat.   The developer of Argyrol, Dr Alfred C. Barnes, made enough money from Argyrol to acquire just about the best collection of French Impressionist paintings on the planet, now in the Barnes Foundation in Philadelphia, which you can (and should!) visit.

* * * * * * * * *

The supplements (for want of a better term) discussed above are about half the ones mentioned in comments to past Doc Gumshoe pieces.   I’ll follow up with another piece looking at some others before too long, although I’m primed just now to look at the current flu season, the effectiveness (or lack of it) of this year’s vaccine, and the prospects for vaccines in the near or perhaps distant future.   Meantime, do please keep the comments coming!   Thanks to all, Michael Jorrin (aka Doc Gumshoe)