Pangamic acid
Encyclopedia
Pangamic acid, also called pangamate, is the name given to the chemical compound described as d-gluconodimethylamino acetic acid, initially promoted by Ernst T. Krebs, Sr. and his son Ernst T. Krebs, Jr.
as a medicinal compound for use in treatment of a wide range of diseases. They also termed this chemical "Vitamin B15", though it is not a true vitamin
, 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, 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").
derived from d-gluconic acid
and dimethylglycine
. In 1943, the Krebses applied for a patent
for a process for extracting this chemical compound which they reported had been previously isolated from apricot
seeds, and received the patent in 1949. A 1951 paper by the Krebses 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," 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, 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, "[n]ot 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
upon further evaluation by nuclear magnetic resonance spectroscopy. 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 FDA has seized lots of calcium pangamate sold by General Nutrition Center (GNC), which agreed to to stop selling the compound in those bottles after the FDA filed suit
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 Food and Drug Administration
(FDA) considers it "not an identifiable substance."
, 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 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
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 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
, heart disease
, schizophrenia
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."
of compounds commonly found in preparations labelled "pangamic acid" including diisopropylamine dichloroacetate, diisopropylamine
, dichloroacetate, as well as dimethylglycine mixed with sodium nitrite
suggests there may be concern for the development of cancer with the use of these substances.
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.
Ernst T. Krebs
Ernst T. Krebs, Jr. was an American biochemist. He is known for promoting various substances as alternative cures for cancer, including pangamic acid and amygdalin. He also co-patented the semi-synthetic chemical compound closely related to amygdalin named Laetrile, which was also promoted as a...
as a medicinal compound for use in treatment of a wide range of diseases. They also termed this chemical "Vitamin B15", though it is not a true vitamin
Vitamin
A vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...
, 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, 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 C10H19O8N and a molecular weight of 281 which appeared to be an esterEster
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
derived from d-gluconic acid
Gluconic acid
Gluconic acid is an organic compound with molecular formula C6H12O7 and condensed structural formula HOCH24COOH. It is one of the 16 stereoisomers of 2,3,4,5,6-pentahydroxyhexanoic acid....
and dimethylglycine
Dimethylglycine
Dimethylglycine is a derivative of the amino acid glycine with the structural formula 2NCH2COOH. It can be found in beans and liver. It can be formed from trimethylglycine upon the loss of one of its methyl groups...
. In 1943, the Krebses applied for a patent
Patent
A patent is a form of intellectual property. It consists of a set of exclusive rights granted by a sovereign state to an inventor or their assignee for a limited period of time in exchange for the public disclosure of an invention....
for a process for extracting this chemical compound which they reported had been previously isolated from apricot
Apricot
The apricot, Prunus armeniaca, is a species of Prunus, classified with the plum in the subgenus Prunus. The native range is somewhat uncertain due to its extensive prehistoric cultivation.- Description :...
seeds, and received the patent in 1949. A 1951 paper by the Krebses 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," 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, 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, "[n]ot 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
Lactose is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose. Lactose makes up around 2~8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey. The name comes from or , the Latin word for milk,...
upon further evaluation by nuclear magnetic resonance spectroscopy. 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 FDA has seized lots of calcium pangamate sold by General Nutrition Center (GNC), which agreed to to stop selling the compound in those bottles after the FDA filed suit
Lawsuit
A lawsuit or "suit in law" is a civil action brought in a court of law in which a plaintiff, a party who claims to have incurred loss as a result of a defendant's actions, demands a legal or equitable remedy. The defendant is required to respond to the plaintiff's complaint...
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 Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) considers it "not an identifiable substance."
Clinical claims and research
The Krebses' original patent claimed pangamic acid could be used for detoxification as well as treatment of asthmaAsthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, 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 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
Nutrient
A nutrient is a chemical that an organism needs to live and grow or a substance used in an organism's metabolism which must be taken in from its environment. They are used to build and repair tissues, regulate body processes and are converted to and used as energy...
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 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
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, heart disease
Heart disease
Heart disease, cardiac disease or cardiopathy is an umbrella term for a variety of diseases affecting the heart. , it is the leading cause of death in the United States, England, Canada and Wales, accounting for 25.4% of the total deaths in the United States.-Types:-Coronary heart disease:Coronary...
, schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
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 analysis via the Ames testAmes test
The Ames test is a biological assay to assess the mutagenic potential of chemical compounds. A positive test indicates that the chemical is mutagenic and therefore may act as a carcinogen, since cancer is often linked to mutation. However, a number of false-positives and false-negatives are known...
of compounds commonly found in preparations labelled "pangamic acid" including diisopropylamine dichloroacetate, diisopropylamine
Diisopropylamine
Diisopropylamine is a secondary amine with the chemical formula 2HC-NH-CH2. It is best known as its lithium salt, lithium diisopropylamide, known as "LDA"...
, dichloroacetate, as well as dimethylglycine mixed with sodium nitrite
Nitrite
The nitrite ion has the chemical formula NO2−. The anion is symmetric with equal N-O bond lengths and a O-N-O bond angle of ca. 120°. On protonation the unstable weak acid nitrous acid is produced. Nitrite can be oxidised or reduced, with product somewhat dependent on the oxidizing/reducing agent...
suggests there may be concern for the development of cancer with the use of these substances.
Legal status
The United States Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
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.