# Pangamic acid

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{{Short description|Hypothetical chemical compound}}
{{Chembox
| Name = <small>d</small>-gluconodimethylamino acetic acid
| ImageFile = Pangamic acid Structure V.1.svg
| ImageSize = 200px
| ImageCaption = <br>Chemical structure of <small>d</small>-gluconodimethylamino acetic acid, a structure of "pangamic acid" proposed in 1951
| IUPACName = 6-''O''-(''N'',''N''-dimethylglycinyl)-<small>D</small>-gluconic acid
| SystematicName = (2''R'',3''S'',4''R'',5''R'')-6-[(Dimethylamino)acetyl]-2,3,4,5-tetrahydroxyhexanoic acid
| OtherNames = dimethylglycine d-gluconic acid ester 
| Section1 = {{Chembox Identifiers
| CASNo = 20858-86-0
| CASNo_Ref = {{cascite|correct|CAS}}
| ChEMBL = 3707449
| ChemSpiderID = 32700433
| EC_number = 236-087-9
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = MPQ53A9F5C
| PubChem = 45934203
| SMILES = CN(C)CC(=O)OC[C@H]([C@H]([C@@H]([C@H](C(=O)O)O)O)O)O
| StdInChI = 1S/C10H19NO8/c1-11(2)3-6(13)19-4-5(12)7(14)8(15)9(16)10(17)18/h5,7-9,12,14-16H,3-4H2,1-2H3,(H,17,18)/t5-,7-,8+,9-/m1/s1
| StdInChIKey = ZQTHOIGMSJMBLM-BUJSFMDZSA-N
  }}
| Section2 = {{Chembox Properties
| C=10 | H=19 | N=1 | O=8
  }}
}}
'''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.](/source/Ernst_T._Krebs), promoted it as a medicinal compound for use in treatment of a wide range of diseases.  They also termed this chemical "vitamin B<sub>15</sub>", though it is not a true [vitamin](/source/vitamin), has no nutritional value,<ref name=Check/> 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 ''<small>d</small>-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").<ref name=Herbertbook>{{Citation | last1 = Herbert | first1 = Victor | last2 = Herbert | first2 = Robert | title = Controversies in nutrition | place = New York | publisher = Churchill Livinstone | year = 1981 | chapter = Pangamate ("Vitamin B<sub>15</sub>") | pages = 159–170] | isbn = 978-0-443-08127-9 | chapter-url-access = registration | chapter-url = https://archive.org/details/controversiesinn0000unse/page/159 }}</ref>

==Chemistry==
Pangamic acid is the name given to the chemical compound with the empirical formula {{chem|C|10|H|19|O|8|N}} and a molecular weight of 281 which appeared to be an [ester](/source/ester) derived from <small>d</small>-[gluconic acid](/source/gluconic_acid) and [dimethylglycine](/source/dimethylglycine). In 1943, the Krebses applied for a [patent](/source/patent) for a process for extracting this chemical compound which they reported had been previously isolated from [apricot](/source/apricot) seeds, and received the patent in 1949.<ref>{{Cite patent | country = US | number = 2464240 | title = Therapeutic material and method of obtaining the same}}</ref>  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.<ref>{{Cite journal | pmid = 14840945 | date = 1951 | author1 = KREBS ET Sr | author2 = KREBS ET Jr | author3 = BEARD HH | author4 = MALIN R | author5 = HARRIS AT | author6 = BARTLETT CL | title = Pangamic acid sodium: A newly isolated crystalline water-soluble factor; a preliminary report | journal = International Record of Medicine and General Practice Clinics | volume = 164 | issue = 1 | pages = 18–23 }}</ref>  In 1955, the Krebses received a patent for another synthesizing process for "N-substituted glycine esters of gluconic acid",<ref name=US2710876>{{Cite patent | country = US | number = 2710876 | title = N-substituted glycine esters of gluconic acid | }}</ref> but the patent contained no supporting data to confirm the process was able to synthesize compounds described by the patent, including pangamic acid.<ref name=Herbertbook/>

Subsequent attempts at synthesizing this ester by other researchers found Krebs' purported methods of producing pangamic acid were not [reproducible](/source/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 'B<sub>15</sub>' has been established in a scientifically verifiable manner to conform to the empiric formula" described by the Krebses.<ref name=Herbertbook/> 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](/source/lactose) upon further evaluation by [nuclear magnetic resonance spectroscopy](/source/nuclear_magnetic_resonance_spectroscopy).<ref name=Check/> Thus, "pangamic acid" is more a label used to describe one of any number of chemical compounds rather than a particular substance.<ref name=Herbertbook/>

Chemical compounds sold as "pangamic acid" for medicinal purposes have also had various chemical compositions, and suppliers of "pangamic acid" have regularly changed the identity of the chemical compounds sold under this label.<ref name=Herbert>{{cite journal |author=Herbert V |title=Pangamic acid ("vitamin B15") |journal=Am. J. Clin. Nutr. |volume=32 |issue=7 |pages=1534–40 |date=July 1979 |pmid=377937 |doi= 10.1093/ajcn/32.7.1534}}</ref> One anecdote noted that the [Food and Drug Administration](/source/Food_and_Drug_Administration) (FDA) has seized lots of "[calcium pangamate](/source/calcium_pangamate)" sold by [General Nutrition Center](/source/General_Nutrition_Center) (GNC), which agreed to stop selling the compound in those bottles after the FDA filed [suit](/source/lawsuit) 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.<ref name=Check/> Due to ambiguity in situations like this, the FDA considers it "not an identifiable substance".<ref name=Herbert/>

To summarize, substances that have been claimed to be pangamic acid include:<ref name=Herbertbook/>
* d-gluconodimethylamino acetic acid (Krebes 1951), never synthesized. Alternative Soviet synthesis of calcium salt also fails to reproduce.
* Variety of mixtures containing [dimethylamine](/source/dimethylamine). Result of attempts to synthesize the 1951 compound. Possibly mutagenic.
* [Diisopropylamine dichloroacetate](/source/Diisopropylamine_dichloroacetate) (Krebes 1955 patent "analogue"), synthesized. Readily hydrolyzes to known-toxic compounds.
* Pharmacologically inert materials, ranging from "synthesis attempts" containing [calcium gluconate](/source/calcium_gluconate) to pure lactose.

==Clinical claims and research==

The Krebses' original patent claimed pangamic acid could be used for [detoxification](/source/Detoxification_(alternative_medicine)) as well as treatment of [asthma](/source/asthma), 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](/source/race_horses) as well as humans. Although given the name "Vitamin B<sub>15</sub>" by the Krebses, there is no evidence that it meets the definition of a vitamin as there is no evidence it is a [nutrient](/source/nutrient) needed by the body.<ref name=Herbert/>

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](/source/anecdotal) in nature (as opposed to [controlled experimentation](/source/control_experiment)) and ignoring short and long term safety in human use.<ref name=Herbert/>

Although more recent{{when|date=October 2021}} claims include treatment of a wide variety of conditions including [cancer](/source/cancer), [heart disease](/source/heart_disease), [schizophrenia](/source/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".<ref name=Herbert/>

==Safety==

Positive results from [mutagenicity](/source/mutagenicity) analysis via the [Ames test](/source/Ames_test) of compounds commonly found in preparations labelled "pangamic acid" including [diisopropylamine dichloroacetate](/source/diisopropylamine_dichloroacetate), [diisopropylamine](/source/diisopropylamine),<ref>{{cite journal |vauthors=Gelernt MD, Herbert V |title=Mutagenicity of diisopropylamine dichloroacetate, the "active constituent" of vitamin B15 (pangamic acid) |journal=Nutr Cancer |volume=3 |issue=3 |pages=129–33 |year=1982 |pmid=6752894 |doi=10.1080/01635588109513714}}</ref> [dichloroacetate](/source/dichloroacetate),<ref>{{cite journal |vauthors=Herbert V, Gardner A, Colman N |title=Mutagenicity of dichloroacetate, an ingredient of some formulations of pangamic acid (trade-named "vitamin B15") |journal=Am. J. Clin. Nutr. |volume=33 |issue=6 |pages=1179–82 |date=June 1980 |pmid=6992558 |doi=10.1093/ajcn/33.6.1179 }}</ref> as well as dimethylglycine mixed with sodium [nitrite](/source/nitrite)<ref name=Check>{{cite journal |author=Check WA |title=Vitamin B15--whatever it is, it won't help |journal=JAMA |volume=243 |issue=24 |pages=2473, 2480 |date=June 1980 |pmid=7382025 |doi= 10.1001/jama.1980.03300500005002 }}</ref> 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.<ref>{{Cite web | title = CPG Sec. 457.100 Pangamic Acid and Pangamic Acid Products Unsafe for Food and Drug Use  | publisher = Food and Drug Administration | date = March 1995 | url = https://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074396.htm  | archive-url = https://web.archive.org/web/20090710083451/http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074396.htm  | url-status = dead  | archive-date = July 10, 2009  | access-date = 25 October 2010}}</ref>  Pangamic acid's distribution in Canada has been prohibited by the then-named Canadian Food and Drug Directorate.<ref name=Herbert/>

==See also==
*[List of unproven and disproven cancer treatments](/source/List_of_unproven_and_disproven_cancer_treatments)

==References==
{{Reflist}}

{{Unproven and disproven cancer treatments}}
{{Authority control}}

Category:Alternative cancer treatments
Category:Alternative medicine
Category:Dimethylamino compounds
Category:Health fraud
Category:Pseudoscience
Category:Sugar acids
Category:Alpha hydroxycarboxylic acids
Category:Esters
Category:Tetrols

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Adapted from the Wikipedia article [Pangamic acid](https://en.wikipedia.org/wiki/Pangamic_acid) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Pangamic_acid?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.