THE HYPOPHOSPHITE FALLACY
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report and authorized its publication.
W. A. Puckner, Secretary.
The introduction of hypophosphites into medicine was due to an erroneous and now discarded theory as to the cause of tuberculosis of which one Dr. J. F. Churchill of London, and later of Paris, was the promulgator and propagandist.[92] This theory was that the so-called “tuberculosis diathesis” was due to a deficiency of phosphorus in the blood. Believing that the hypophosphites, while nontoxic, were capable of further oxidation in the organism, Churchill recommended them as the best means of supplying the supposedly lacking phosphorus. It is now known that tuberculosis is not due to a deficiency of phosphorus. Of more importance is the fact, now known, that little phosphorus, if any, is assimilated from the hypophosphites—far less than from phosphorus compounds of ordinary food.[93] There is no justification for giving hypophosphites for the sake of their phosphorus content. For various reasons, however—partly from force of habit and partly because of the power of advertising—many physicians still prescribe hypophosphite preparations, and consequently, they are still included in the Pharmacopeia and in textbooks on materia medica and therapeutics. They are put out in the form of “specialties” and of proprietary preparations, and are lauded extravagantly by the manufacturers of the latter.
Although the overwhelming weight of evidence was against the probability that the hypophosphite preparations are of value as therapeutic agents, the Council thought it well to investigate the subject. Dr. W. McKim Marriott of Baltimore was therefore requested to review the evidence for and against the therapeutic usefulness of the hypophosphites and to conduct such experiments as seemed necessary. His report has already appeared in The Journal.[94]
Dr. Marriott found that nine observers (Paquelin and Joly, Vermeulen, Boddaert, Massol and Gamel, Panzer, Delaini and Berg), who endeavored to test the alleged utilization of the hypophosphites in the organism, reported that there is complete, or practically complete, elimination of hypophosphites in the urine, with little or no effect on the body. Only one experimenter (Patta) claimed that a considerable amount of ingested hypophosphite was retained in the body; however, he used a method now known to be inaccurate and made obvious errors in calculation, so that his conclusions were unwarranted.
Since the evidence was even to this extent contradictory, Marriott performed a series of experiments. The methods of this study and details of results are described in his paper, in which he also discusses the experiments of some other observers. Marriott writes:
“None of the subjects of the experiment [Marriott’s] experienced any effect whatsoever from the administration of the drug.... Almost all of the ingested hypophosphite is promptly eliminated unchanged....
“These experiments [Forbes’] demonstrate conclusively that the hypophosphites possess no specific value as a source of phosphorus for the body. This is not to be wondered at in view of the fact that 85 per cent. of the phosphorus ingested in the form of hypophosphite is excreted unchanged, and there is no proof that even the remaining 15 per cent. is available to the organism. It is doubtful if there are any conditions in which the body suffers from lack of phosphorus. Even should such conditions exist, phosphorus, in the form that it occurs in the ordinary foods, or as phosphates, is more efficient in supplying the deficit than hypophosphites that must be oxidized before utilization and which are only about 15 per cent. oxidized, if at all. For example, half a glass of milk contains more available phosphorus than three large doses of hypophosphites of 15 grains each, as great a dosage as is usually given.
“What, then, is the therapeutic value of hypophosphites? There is no reliable evidence that they exert a physiologic effect; it has not been demonstrated that they influence any pathologic process; they are not ‘foods.’ If they are of any use, that use has never been discovered.”
In view of the foregoing, it seemed to the Council advisable to examine the claims under which a few of the proprietary hypophosphite preparations are marketed. The following are representative:
FELLOWS’ SYRUP OF HYPOPHOSPHITES
No very exact information concerning the composition is furnished by the manufacturers (Fellows Medical Mfg. Co., New York). They say that the product
“... contains the chemically pure hypophosphites of iron, quinin, strychnin, calcium, manganese and potassium, agreeably blended in the form of a bland, stable syrup with a slightly alkaline reaction....
“Each fluid drachm contains the equivalent of 1-64th of a grain of pure strychnin.”
The Fellows’ Hypophosphites advertising furnishes something like a barometer of the popular status of hypophosphites. In one circular (undated, but, from certain references contained in it, presumably issued ten or fifteen years ago) we read:
“It is an indubitable fact that the hypophosphites have earned the distinction of having their therapeutic value more completely established than have any other remedial agents.... it is only by accepting the current view, which was originally advanced by Mr. Fellows, that we can satisfactorily account for the incontestable fact that the hypophosphites are of supreme importance in the treatment of a very extensive variety of affections.... the hypophosphites increase the consumption of oxygen and the elimination of carbon dioxide. In this manner, they stimulate nutrition and promote constructive metamorphosis.... It is now universally conceded that the widespread utility of the hypophosphites is due to the fact that they substantially improve metabolic processes, thus increasing the disease-resisting capacity of all the tissues.”
The circular, continuing, emphasizes the “incomparable phosphorus-contributing properties” of Fellows’ Syrup, its “extraordinary reconstructive properties” and “the magnificent results which invariably attend its employment in the treatment of anemia, chronic bronchitis, chlorosis, neurasthenia, mollities ossium, delayed union of fractures, rickets, convalescence,” etc.
A circular bearing the copyright date 1914, on the other hand, admits that:
“The theories for the favorable action of Fellows Syrup of Hypophosphites have undergone several changes.”
The same circular further maintains, however, that:
“... the fact has never been challenged that in Fellows Syrup of Hypophosphites we have one of the most efficient, most complete, most all-around tonics and roborants in the materia medica.”
No attempt is made to base this assertion on the therapeutic action of the constituents. In other words, the old theory, which formed the basis for the popularity of Fellows’ Syrup, has been thrown overboard, but no substitute is deemed necessary; the momentum already acquired is apparently regarded as sufficient to insure its continued sale.
Fellows’ Syrup of Hypophosphites is a semisecret, unscientific preparation—an affront to sound therapy—exploited by means of extravagant and misleading statements.
SYRUPUS ROBORANS (SYRUP HYPOPHOSPHITES COMP. WITH QUININ,
STRYCHNIN AND MANGANESE)
Little information concerning this preparation seems to be furnished at present by the manufacturers, Arthur Peter & Co., Louisville, Ky. According to an old circular, it contains, in each fluidounce,
| Grains | |
“Hypophos. Potass. | 11⁄2 |
Hypophos. Manganese | 1 |
Hypophos. Lime | 1 |
Hypophos. Iron | 11⁄2 |
Hypophos. Quinin | 6⁄16 |
Hypophos. Strichnin | 1⁄16 |
| “1⁄128 grain Strychnia to Teaspoonful.” | |
Further, according to the same circular:
“The Hypophosphites are especially useful in all diseases where there is a lack of nutrition.... They are the best of all remedies in Rachitis, non-union of fractures, Osteomalacia and Syphilitic Periostitis.”
As for Syrupus Roborans itself:
“This elegant preparation is ... the best general tonic and reconstructive known.”
The unwarranted therapeutic claims formerly made for it seem to be no longer circulated. Syrupus Roborans is an unscientific, shotgun mixture.
SCHLOTTERBECK’S SOLUTION HYPOPHOSPHITES OF LIME AND SODA
(LIQ. HYPOPHOSPHITUM, SCHLOTTERBECK’S)
The Schlotterbeck & Foss Co., Portland, Maine, the manufacturers, say of their preparation:
“This solution contains 30 grains of the combined Hypophosphites of Lime and Soda to the ounce. It contains No Sugar, No Acid and it is Perfectly Neutral.”
“Indications for use.—Galactostasis, Imperfect Metabolism, Neurasthenia, Nervous Dyspepsia, Insomnia, Convalescence, Acetonuria, Cyclic Vomiting in Infants, Diabetes, Starvation, Deficiency of Lime, Mother’s Teeth during Pregnancy, Dentition of Infants, Rachitis, Furunculosis, Vomiting of Pregnancy, Obesity.”
“Migraine is often caused by conditions for which this Solution is one of the most satisfactory remedies:”
“In Insomnia due to advancing age, it will often act as a hypnotic....”
Of the hypophosphites the Schlotterbeck & Foss Company say:
“If ‘damning it with faint praise’ on the part of some of the leading medical authorities, or utterly condemning it as useless, on the part of others, would kill a medicine, the Hypophosphites would long since have disappeared as medicinal agents. Negative testimony in regard to the value of a drug does not settle anything.”
Of their own preparation they say:
“When we get the results that ought to follow the administration of Hypophosphites, we have proved that Schlotterbeck’s Solution enters the system unchanged.”
“This Solution is primarily a blood and nerve tonic and chemical food.”
Schlotterbeck’s Solution of Hypophosphites of Lime and Soda is a semisecret preparation marketed under claims that are both unwarranted and misleading.
ROBINSON’S HYPOPHOSPHITES
According to the manufacturers, the Robinson-Pettet Company, Louisville, Ky., each fluidounce of this preparation contains:
| “Hypophosphites Soda | 2 | gr. |
| Hypophosphites Lime | 11⁄2 | gr. |
| Hypophosphites Iron | 11⁄2 | gr. |
| Hypophosphites Quinin | 3⁄4 | gr. |
| Hypophosphites Strychnine | 1⁄16 | gr.” |
It is claimed to be
“Nutritive, Tonic Alterative. A Standard Remedy in the treatment of Pulmonary Phthisis, Bronchitis, Scrofulous Taint, General Debility, etc. Stimulates Digestion, promotes Assimilation.”
The declared composition of the preparation is unscientific, and the therapeutic claims are unwarranted.
EUPEPTIC HYPOPHOSPHITES
Nelson, Baker & Co., Detroit, Mich., who market Eupeptic Hypophosphites, call this preparation:
“A superior combination containing the Hypophosphites of Potassium, Calcium, Iron and Manganese, and the bitter tonics, Quinin and Strychnin, agreeably associated with natural digestive ferments of the pancreatic secretion. It is thus a general reconstructive tonic.... The remedy is of especial value in the treatment of mental and nervous affections.... It is indicated in pulmonary tuberculosis, in all wasting diseases, in debilitated conditions generally and in all exhaustion from over work.”
On the basis of the manufacturer’s statement, Eupeptic Hypophosphites must be regarded as a semisecret, unscientific, shotgun preparation, exploited through unwarranted therapeutic claims.
MCARTHUR’S SYRUP OF THE HYPOPHOSPHITES COMP. (LIME AND SODA)
So far as the recent literature and trade package are concerned, no information as to the composition of this product is furnished beyond what is conveyed in the name. The advertising for McArthur’s Syrup, like that for Fellows’ Syrup and Peters’ Syrupus Roborans, has been modified as time has passed. A few years ago it was advertised under such claims as the following:
“... Has Stood the Test during many years for unequaled efficacy in the treatment of Tuberculosis.... Indicated also as a Tonic and Tissue Builder in convalescence from Fevers, in Nervous Diseases, Rickets, Senile Debility and Bronchitis.”
“Its use is indicated in ... diseases of the chest, chronic cough, throat affections, general debility, brain exhaustion, cholera infantum and wasting diseases of children.”
At present no definite claims seem to be made for it; the manufacturers evidently find the magic name of hypophosphites sufficient to evoke the spell for which the advertisement writer’s aid was once sought. A testimonial contained in a circular which seems to be still used illustrates both the kind of aura which surrounds hypophosphites in the minds of physicians who are still living in the past, and the kind of logic which has made the reputation of this and many other equally worthless preparations.
“Just about six years ago I had a severe attack of La Grippe which almost killed me. Left me with Asthma (Catarrh) and a severe cough. Did not get out of the house for three months. Took over a dozen bottles McArthur’s Hypophos.—came out all right and since then worked hard, but last Fall took another cold, but worked on, used McArthur’s Hypophos., am using it now, am on my 12th bottle.
“I have five or six patients whom I have put on McArthur’s Hypophos., but I do not prescribe the single bottle, but wholesale no less than half dozen bottles. One patient is on his 24th bottle with orders to get another half dozen and keep it up all winter. I have given the same order to all (keep it up all winter) and I myself intend to do the same, for with its use I have lost no time—rain or shine I am doing my work. I know what it has done for me and what it is doing for my patients.”
It would be hard to find a more characteristic example of the naïve mental processes of the simple folk who in all good faith write testimonials for worthless medicines. This well-meaning practitioner (a homeopath, by the way), because he “came out all right” after an attack of grip, returns all praise to McArthur’s Hypophosphites, which he has taken “wholesale.” Not the faintest doubt of the validity of his post hoc ergo propter hoc argument seems to glimmer across his consciousness.
McArthur’s Syrup of the Hypophosphites is an irrational preparation. While its faults are fewer and less glaring than those of some other proprietaries, the circulation of such a testimonial as the one just quoted is sufficient of itself to cast suspicion on the product.
BORCHERDT’S MALT OLIVE WITH HYPOPHOSPHITES, MALTZYME WITH HYPOPHOSPHITES AND MALTINE WITH OLIVE OIL AND HYPOPHOSPHITES
These preparations are now described in the appendix to New and Nonofficial Remedies. Borcherdt’s Malt Olive with Hypophosphites (Borcherdt Malt Extract Company, Chicago) is said to contain in each 100 c.c., 0.64 gm. each of calcium and sodium hypophosphites, with malt extract, olive oil and glycerine. Maltzyme with Hypophosphites (Malt-Diastase Company, New York) is said to contain, in each 100 c.c., 0.4 gm. each of calcium, sodium and potassium hypophosphites and 0.005 gm. each of iron and manganese hypophosphites, with maltzyme. Maltine with Hypophosphites (Maltine Company, Brooklyn, N. Y.) is said to contain in each 100 c.c., 0.64 gm. each of calcium and sodium hypophosphites and 0.42 gm. of iron hypophosphite, with maltine. Maltine with Olive Oil and Hypophosphites (Maltine Company, Brooklyn, N. Y.) is said to contain, in each 100 c.c., 0.6 gm. each of calcium and sodium hypophosphites, with maltine and olive oil. In general, no therapeutic claims are made for these mixtures so far as the hypophosphites are concerned. The addition of hypophosphites to such mixtures is irrational and, since it tends to perpetuate the hypophosphite fallacy, detrimental to sound therapeutics.
THE COUNCIL’S ACTION
The Council endorsed the conclusions of the work of Dr. Marriott referred to above, and noted: (1) that the therapeutic use of hypophosphites (except possibly in some cases as a convenient means of administering the positive element in the salt, as ammonium in ammonium hypophosphite or calcium in calcium hypophosphite) is irrational; (2) that the merits of each hypophosphite salt submitted for consideration under the foregoing exception must be judged individually, and (3) that Fellows’ Syrup of Hypophosphites, Peters’ Syrupus Roborans, Schlotterbeck’s Solution Hypophosphites of Lime and Soda, Robinson’s Hypophosphites, the Eupeptic Hypophosphites of Nelson, Baker & Co., and McArthur’s Syrup of the Hypophosphites are ineligible for inclusion in New and Nonofficial Remedies, and that Borcherdt’s Malt Olive with Hypophosphites, Maltzyme with Hypophosphites, Maltine with Hypophosphites, and Maltine with Olive Oil and Hypophosphites be deleted from the appendix of N. N. R. Of these preparations, all are in conflict with Rule 10; Fellows’ Syrup, Schlotterbeck’s Solution, Robinson’s Hypophosphites and Nelson, Baker & Co.’s Eupeptic Hypophosphites are in conflict with Rule 6; the Fellows, Schlotterbeck, and Nelson, Baker preparations are also in conflict with Rule 1.—(From The Journal A. M. A., Sept. 2, 1916.)