Pangamic acid, also called pangamate, is the name given to a chemical compound discovered by Ernst T. Krebs Sr. His son,
Ernst T. Krebs Jr., promoted it as a medicinal compound for use in treatment of a wide range of diseases. They also termed this chemical "Vitamin B
15", though it is not a true
vitamin
A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an Nutrient#Essential nutrients, essential micronutrient that an organism needs in small quantities for the proper functioning of its ...
, has no nutritional value , has no known use in the treatment of any disease and has been called a "quack remedy". Although a number of compounds labelled "pangamic acid" have been studied or sold (including the 1951 ''
d-gluconodimethylamino acetic acid''), no chemical compound, including those claimed by the Krebses to be pangamic acid, has been scientifically verified to have the characteristics that defined the original description of the compound.
The Krebses derived the term "pangamic" to describe this compound which they asserted to be ubiquitous and highly concentrated in seeds (''pan'' meaning "universal" and ''gamic'' meaning "seed").
Chemistry
Pangamic acid is the name given to the chemical compound with the empirical formula C
10H
19O
8N and a molecular weight of 281 which appeared to be an
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...
derived from
d-
gluconic acid
Gluconic acid is an organic compound with molecular formula C6H12O7 and condensed structural formula HOCH2(CHOH)4COOH. It is one of the 16 stereoisomers of 2,3,4,5,6-pentahydroxyhexanoic acid.
In aqueous solution at neutral pH, gluconic acid fo ...
and
dimethylglycine
Dimethylglycine (DMG) is a derivative of the amino acid glycine with the structural formula (CH3)2NCH2COOH. It can be found in beans and liver, and has a sweet taste. It can be formed from trimethylglycine upon the loss of one of its methyl groups ...
. In 1943, the Krebses applied for a
patent
A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention."A p ...
for a process for extracting this chemical compound which they reported had been previously isolated from
apricot
An apricot (, ) is a fruit, or the tree that bears the fruit, of several species in the genus ''Prunus''.
Usually, an apricot is from the species '' P. armeniaca'', but the fruits of the other species in ''Prunus'' sect. ''Armeniaca'' are also ...
seeds, and received the patent in 1949 (US2464240). A 1951 paper by the Krebses (PMID 14840945) reported the first isolation of this compound using this patented process, but did not include enough information to confirm that this compound was actually isolated. In 1955, the Krebses received a patent for another synthesizing process for "N-substituted glycine esters of gluconic acid" (US2710876), but the patent contained no supporting data to confirm the process was able to synthesize compounds described by the patent, including pangamic acid.
[
Subsequent attempts at synthesizing this ester by other researchers found Krebs' purported methods of producing pangamic acid were not ]reproducible
Reproducibility, also known as replicability and repeatability, is a major principle underpinning the scientific method. For the findings of a study to be reproducible means that results obtained by an experiment or an observational study or in a ...
, and research into pangamic acid have focused on compounds of various chemical compositions. A review noted that of all the chemicals described in research about pangamic acid, " t a single product labeled 'pangamate' or 'B15' has been established in a scientifically verifiable manner to conform to the empiric formula" described by the Krebses.[ Analysis of a sample of a compound called "pangamic acid" which was provided by a co-worker of the Krebses in the 1950s showed only ]lactose
Lactose is a disaccharide sugar synthesized by galactose and glucose subunits and has the molecular formula C12H22O11. Lactose makes up around 2–8% of milk (by mass). The name comes from ' (gen. '), the Latin word for milk, plus the suffix '' - ...
upon further evaluation by nuclear magnetic resonance spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fiel ...
.[ Thus, "pangamic acid" is more a label used to describe one of any number of chemical compounds rather than a particular substance.][
Chemical compounds sold as "pangamic acid" for medicinal purposes have also had various chemical compositions, and suppliers of "pangamic acid" have regularly changed the chemical composition of the compounds sold under this label.] One anecdote noted that the Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) has seized lots of " calcium pangamate" sold by General Nutrition Center
GNC Holdings, LLC (abbreviated GNC; alternatively General Nutrition Centers) is a retail company based in Pittsburgh, Pennsylvania. It specializes in health and nutrition related products, including vitamins, supplements, minerals, herbs, sports ...
(GNC), which agreed to stop selling the compound in those bottles after the FDA filed suit
A suit, lounge suit, or business suit is a set of clothes comprising a suit jacket and trousers of identical textiles worn with a collared dress shirt, necktie, and dress shoes. A skirt suit is similar, but with a matching skirt instead of tr ...
to stop sales. Afterwards, it was noted that GNC was still selling something in the same bottles with the same labels, likely a different compound.[ Due to ambiguity in situations like this, the FDA considers it "not an identifiable substance".][
To summarize, substances that have been claimed to be pangamic acid include:][
* d-gluconodimethylamino acetic acid (Krebes 1951), never synthesized. Alternative Soviet synthesis of calcium salt also fails to reproduce.
* Variety of mixtures containing ]dimethylamine
Dimethylamine is an organic compound with the formula (CH3)2NH. This secondary amine is a colorless, flammable gas with an ammonia-like odor. Dimethylamine is commonly encountered commercially as a solution in water at concentrations up to aroun ...
. Result of attempts to synthesize the 1951 compound. Possibly mutagenic.
* Diisopropylamine dichloroacetate (Krebes 1955 patent "analogue"), synthesized. Readily hydrolyzes to known-toxic compounds.
* Pharamacologically inert materials, ranging from "synthesis attempts" containing calcium gluconate
Calcium gluconate is a mineral supplement and medication. As a medication it is used by injection into a vein to treat low blood calcium, high blood potassium, and magnesium toxicity. Supplementation is generally only required when there is no ...
to pure lactose.
Clinical claims and research
The Krebses' original patent claimed pangamic acid could be used for detoxification
Detoxification or detoxication (detox for short) is the physiological or medicinal removal of toxic substances from a living organism, including the human body, which is mainly carried out by the liver. Additionally, it can refer to the period of ...
as well as treatment of asthma
Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...
, skin conditions, joint pain, and nerve pain, with none of these claims supported by evidence in the patent application. Early promotion for pangamic acid included use by race horses
Race Horses were a Welsh band based in Cardiff, Wales and originally from Aberystwyth. Formed in 2005 as Radio Luxembourg, they changed their name in 2009 due to possible legal problems with the radio station of the same name. Initially the m ...
as well as humans. Although given the name "Vitamin B15" by the Krebses, there is no evidence that it meets the definition of a vitamin as there is no evidence it is a nutrient
A nutrient is a substance used by an organism to survive, grow, and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi, and protists. Nutrients can be incorporated into cells for metabolic purposes or excret ...
needed by the body.[
Much of the clinical research on pangamic acid took place in the former Soviet Union, though that research often did not describe which of the many compounds called "pangamic acid" was used in the study. This research was also of limited quality due to being overwhelmingly ]anecdotal
Anecdotal evidence is evidence based only on personal observation, collected in a casual or non-systematic manner. The term is sometimes used in a legal context to describe certain kinds of testimony which are uncorroborated by objective, independ ...
in nature (as opposed to controlled experimentation) and ignoring short and long term safety in human use.[
Although more recent claims include treatment of a wide variety of conditions including ]cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
, heart disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...
, schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...
as well as providing improvement in oxygen utilization, there is no significant evidence for any of these claims or that it is safe for human use. One review noted that it meets "the criteria that define a quack remedy".[
]
Safety
Positive results from mutagenicity
In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in ...
analysis via the Ames test of compounds commonly found in preparations labelled "pangamic acid" including diisopropylamine dichloroacetate, diisopropylamine
Diisopropylamine is a secondary amine with the chemical formula (Me2CH)2NH (Me = methyl). Diisopropylamine is a colorless liquid with an ammonia-like odor. Its lithium derivative, lithium diisopropylamide, known as LDA is a widely used reagent.
...
, dichloroacetate
Dichloroacetic acid (DCA), sometimes called bichloroacetic acid (BCA), is the chemical compound with formula . It is an acid, an analogue of acetic acid, in which 2 of the 3 hydrogen atoms of the methyl group have been replaced by chlorine at ...
, as well as dimethylglycine mixed with sodium nitrite
The nitrite polyatomic ion, ion has the chemical formula . Nitrite (mostly sodium nitrite) is widely used throughout chemical and pharmaceutical industries. The nitrite anion is a pervasive intermediate in the nitrogen cycle in nature. The name ...
suggests there may be concern for the development of cancer with the use of these substances.
Legal status
The FDA has recommended seizing any chemicals advertised as pangamic acid and restraining the importation and interstate shipment of pangamic acid on the grounds that pangamic acid and pangamic acid products are unsafe for use and have no known nutritional properties. Pangamic acid's distribution in Canada has been prohibited by the then-named Canadian Food and Drug Directorate.[
]
See also
*List of unproven and disproven cancer treatments
This is a non-exhaustive list of alternative treatments that have been promoted to treat or prevent cancer in humans but which lack scientific and medical evidence of effectiveness. In many cases, there is scientific evidence that the alleged tr ...
References
{{Authority control
Alternative medicine
Amines
Health fraud
Pseudoscience
Sugar acids