Pangamic A

What is Pangamic Acid?

Pangamic acid, sold as "vitamin B15," is not a defined chemical substance, and the FDA has said so in writing since 1976. Compliance Policy Guide 457.100 states that "there has been no identity established for a substance characterized by the name pangamic acid (or 'vitamin B-15')." It has never been withdrawn.

The name came from Ernst T. Krebs Sr., who reported pulling a substance out of apricot kernels and coined "pangamic" from pan for universal and gamic for seed. He filed on an extraction process in 1943 and received US Patent 2,464,240 in 1949. His son, Ernst T. Krebs Jr., did the promoting. The two published a preliminary report in 1951 claiming isolation of a crystalline "pangamic acid sodium," assigned it the formula C10H19NO8, and patented a synthesis route in 1955. No independent laboratory has reproduced either process, and no product sold under the name has matched the formula.

Common Names

• Vitamin B15, B-15

• Calcium pangamate, sodium pangamate

• DMG-B15 complex, a modern relabeling

Primary Active Compounds

• N,N-dimethylglycine (DMG), a real and fully characterized compound, present in most current products

• Calcium or sodium gluconate, mineral salts with no relationship to the claimed structure

• Trimethylglycine (betaine), added to newer blends

• Diisopropylamine dichloroacetate (DIPA-DCA), in some older and some non-US formulations

• d-gluconodimethylamino acetic acid, the Krebs compound, never confirmed in any product

Key Note

Three things get conflated under one name. Pangamic acid is undefined. DMG is a real metabolite of choline breakdown that you already make, sold legally at 125 mg per capsule, on a thin and mostly negative evidence base. Dichloroacetate is an investigational drug with a dose-limiting neurotoxicity. Anyone holding a "B15" bottle needs to know which is inside, and the label often will not say.

This issue treats all three, because the shelf treats them as one.

Primary Functions & Benefits

Pangamic acid has no established function because it has no established identity. The functions attributed to it belong to the compounds substituted for it. The oldest of them, improved oxygen utilization, has never been demonstrated in a human trial.

• DMG sits one step down the betaine pathway. When betaine donates a methyl group to homocysteine, the leftover is DMG. This happens whether or not you supplement.

• DMG's one positive human immune result is a 1981 double-blind study in the Journal of Infectious Diseases, 20 volunteers, reporting a roughly fourfold increase in antibody response to pneumococcal vaccine. Unreplicated since.

• Dichloroacetate does have a real function, inhibiting pyruvate dehydrogenase kinase. That is a drug action, and it is what puts the nerve damage on the table.

Who Should Take Pangamic Acid

Nobody should take a product labeled pangamic acid or B15, because the label does not tell you what is in it. That is not a hedge, it is the regulatory finding.

• People curious about DMG can buy it by name as a single ingredient, where identity and dose are knowable. The evidence is weak, but the product is at least defined.

• People wanting homocysteine lowering should look at betaine, 3 to 6 g daily, which has human data and an FDA-approved prescription form for homocystinuria. DMG is the spent product of that reaction, not the active one.

• Athletes citing Soviet training literature should know the Western replications came back flat, including a 1982 trial in Medicine and Science in Sports and Exercise that found no change in maximal treadmill performance.

Who Should AVOID or Use Caution

Contraindications

• Anyone pregnant or breastfeeding. DIPA-DCA and diisopropylamine tested positive in Ames assays, and the contents of any B15 product are unverifiable.

• Anyone with existing peripheral neuropathy. If the product contains dichloroacetate, you are adding a neurotoxin to a damaged nerve.

• Children. The 1980 federal case turned partly on the finding that N,N-dimethylglycine was an unsafe food additive lacking safety data.

Use Caution

• Chronic kidney disease. DMG accumulates in uremia, and a 2004 crossover trial in Clinical Biochemistry giving 400 mg daily for 28 days to pre-dialysis patients found no effect.

• Anyone with high nitrite intake. DMG plus sodium nitrite was mutagenic in the Ames test, per JAMA in 1980.

Critical Safety Point

A bottle marked "B15" can legitimately contain dichloroacetate, which causes peripheral neuropathy at doses used in supervised trials. You cannot dose-titrate around a compound you did not know you were taking.

Recommended Dosages

There is no recommended dose for pangamic acid, because there is no pangamic acid to dose. What follows is what is actually on the market.

Single-ingredient DMG

• 125 mg per capsule is the standard commercial unit, and trial doses ranged from about 125 mg to 400 mg daily. No dose has produced a reproducible benefit in a controlled human trial.

"B15" or "pangamic acid" blends

• A current product sells 90 capsules for $29 and lists, per capsule, calcium pangamate 100 mg, dimethylglycine 100 mg, trimethylglycine 100 mg, calcium gluconate 100 mg, and gluconic acid 100 mg. It lists calcium pangamate alongside the parts it is supposedly made of, which is a tell.

Dichloroacetate

• Not a supplement dose. Trial doses were 25 mg/kg/day, which is the dose that produced the neuropathy.

Duration

• None can be recommended for an unidentified product. For DMG, the longest controlled human exposures run about four weeks, so there is no long-term safety data.

Timing & Administration

• DMG is water soluble and taken with or without food, often sublingually in autism-focused products, though sublingual delivery has never been shown to matter here.

• For a B15 blend, timing is the wrong question. Composition comes first.

Benefits of Taking Pangamic Acid

There are no demonstrated benefits of taking pangamic acid, and the FDA position since 1976 is that it has no known nutritional properties. The benefits attached to the name belong to other molecules, most of which did not survive testing.

• Athletic performance. The largest claim with the weakest support. The literature is overwhelmingly Soviet and later Russian, and Herbert's 1979 review in the American Journal of Clinical Nutrition noted it was largely anecdotal and generally did not name the compound given. Western replication came back negative, including the 1982 treadmill trial and later work in trained runners.

• Immune function. One small positive study from 1981, unreplicated. Memorial Sloan Kettering's assessment is that the data conflict and are unconfirmed.

• Autism. Bolman and Richmond, 1999, Journal of Autism and Developmental Disorders, 8 participants, no significant effect. Kern and colleagues, 2001, Journal of Child Neurology, 37 children aged 3 to 11, no difference from placebo.

• Cancer, heart disease, schizophrenia, detoxification. The original promotional claims, none with human evidence. The cancer claim drew the FDA's drug-classification finding.

Potential Negatives & Side Effects

• The dominant negative is compositional uncertainty. There is no adverse effect profile for a product class whose contents change between manufacturers and between runs.

• DMG alone is generally tolerated in the short trials that exist, with no consistent adverse event signal at 125 to 400 mg. That reflects small brief studies, not a clean bill of health.

• DIPA-DCA and diisopropylamine were mutagenic in Ames testing, reported in Nutrition and Cancer in 1982, and dichloroacetate itself in the American Journal of Clinical Nutrition in 1980. Ames positivity is a screening signal, not a demonstration of human cancer risk.

Deficiency Symptoms

There is no deficiency state for pangamic acid, and the reason matters more than the fact. A vitamin designation requires showing that removing the substance from the diet produces a specific, reproducible deficiency syndrome that the substance corrects. No such state was ever produced in humans or in any animal model, and that failure is precisely why the B15 name never entered accepted vitamin nomenclature.

What pangamic acid addresses

• Nothing demonstrated in a controlled human trial.

• DMG is not essential either. You produce it every time homocysteine is remethylated, and it appears in beans, cereal grains, and liver.

• The only known human disorder involving DMG is an excess. In dimethylglycine dehydrogenase deficiency, characterized in 2001, the reported patient had a fish-like body odor from age 5, chronic muscular fatigue, serum DMG around 221 micromolar, roughly 100-fold above normal, and creatine kinase four to five times normal.

Bottom line

Nobody has ever been deficient in vitamin B15, because there is no vitamin B15.

Toxicity Symptoms

At high intake

• For DMG alone, no toxic threshold exists in humans, because nobody has run the dose-ranging study.

• For any product containing dichloroacetate, the toxicity is specific and documented. In a randomized, placebo-controlled crossover trial published in Neurology in 2006, 30 patients aged 10 to 60 with MELAS received DCA at 25 mg/kg/day. All 15 patients on DCA discontinued, against 4 of 15 on placebo, and 17 of the 19 discontinuations were for onset or worsening of peripheral neuropathy. The trial was terminated early for peripheral nerve toxicity.

• DCA clearance is governed by GSTZ1 genotype, and adults are markedly more susceptible than children. Two people on identical doses do not carry identical risk.

Signs to reduce or stop

• Tingling, burning, or numbness in the feet or hands, especially if progressing upward. This is the presentation of DCA neuropathy and the reason to stop and get evaluated.

• New unsteadiness on the feet, or loss of fine motor control.

General note

Peripheral neuropathy from dichloroacetate is not an idiosyncratic reaction. It is the dose-limiting toxicity of the drug, seen under supervision at a defined dose in a controlled trial. A supplement that may contain it gives you none of those protections.

How Pangamic Acid Works

There is no mechanism to describe for pangamic acid. There are mechanisms for the substitutes.

• DMG's actual role is as an intermediate, not an actor. Mitochondrial dimethylglycine dehydrogenase strips a methyl from it to form sarcosine, moving the one-carbon unit onto tetrahydrofolate. DMG is the output of a reaction, a poor starting point for a supplement built on the idea that more of it drives something forward. The "oxygen utilization" story behind the endurance claim has no identified biochemical step at all.

• Dichloroacetate inhibits pyruvate dehydrogenase kinase, pushing pyruvate into the mitochondrion rather than to lactate. That is a drug mechanism, not a nutrient one.

• Diisopropylamine dichloroacetate hydrolyzes to dichloroacetate and diisopropylamine, which is how a product sold as a vitamin delivers a neuroactive drug metabolite.

Synergistic Supplements

Since the base ingredient is undefined, synergy claims here are unusually empty. What follows is what the defined compounds pair with.

• Betaine and DMG are sold together constantly. Betaine is the one with human data, so taking both is paying twice for one pathway.

• Folate and vitamin B12 are the genuine partners of one-carbon metabolism. If methylation support is the goal, that is where the evidence is, and neither needs a B15 label.

• Products pairing "B15" with "B17" are a single red flag rather than a stack. B17 is laetrile, the other Krebs family invention, and it runs as its own issue this week.

Interactions & What NOT to Take

• Sodium nitrite and nitrite-preserved foods. DMG plus nitrite was mutagenic in Ames testing per the 1980 JAMA report. In vitro only, but it is the interaction specific to this compound.

• Digoxin, calcium channel blockers, and thiazide diuretics. Reference databases flag moderate interactions with pangamic acid products, driven by the calcium content of the gluconate and pangamate salts.

• Any drug carrying peripheral neuropathy as a known adverse effect, including metronidazole, isoniazid, and the platinum and taxane chemotherapies. If the product contains DCA, the risks stack.

Special Considerations

• Legal status is asymmetric. Canada prohibited pangamic acid outright, and in the US B15 products remain subject to CPG 457.100. But single-ingredient DMG labeled for food use only was carved out of that guidance, and after the 1994 Dietary Supplement Health and Education Act it is sold openly. That is why the shelf is full of DMG capsules while B15 branding lives on the fringe.

• Diisopropylamine dichloroacetate has been marketed as a pharmaceutical outside the United States under names including Oxypangam, Disotat, and Kalodil. The survival of "pangam" inside a drug brand links the vitamin marketing directly to the drug.

• If you already have a bottle, read the supplement facts panel, not the front. If it lists "pangamic acid," "calcium pangamate," or a proprietary blend, you do not know what you are holding.

Research Status & Evidence Quality

Strong Evidence For

• Nothing. No controlled trial has tested a chemically verified sample of the compound the Krebses described.

Moderate Evidence For

• Nothing for pangamic acid. For dichloroacetate, the evidence that it causes peripheral neuropathy in adults at 25 mg/kg/day is strong, and it is the best-established fact in this issue.

Emerging / Preliminary Evidence For

• DMG and immune response, on a single 20-person study from 1981 unreplicated for four and a half decades. Preliminary is generous.

• DCA in oncology, still investigational after 50 years, resting mostly on case reports, and approved nowhere despite being sold by clinics that say otherwise.

Research Limitations

• Most of the literature does not say what was administered. Herbert's 1979 review made this the central criticism: the Soviet reports forming the bulk of the clinical literature generally failed to name the compound used and were anecdotal rather than controlled.

• Controlled DMG trials are small and short. The autism trials enrolled 8 and 37, the renal trial 7, and four weeks is the typical exposure.

• The mutagenicity work is Ames screening from 1980 to 1982 with no human epidemiology behind it, so the cancer question is neither confirmed nor cleared.

Summary & Key Takeaways

Pangamic acid is the rare supplement where the honest description is that the product does not exist. The Krebses named a molecule, patented processes nobody could reproduce, and attached a vitamin number without demonstrating a deficiency state. Everything sold under the name since has been a substitution. Some are inert, some are mineral salts, one is a real metabolite with a poor trial record, and one is a drug that damages peripheral nerves. The label does not distinguish between them.

Bottom Line

Do not buy anything sold as pangamic acid, B15, or calcium pangamate. If you want DMG, buy it by name at a stated dose and know the human evidence is weak and mostly negative. If you want the homocysteine effect, you want betaine. If you want the endurance effect from the Soviet literature, no Western trial has found it.

Key Safety Points

• A product labeled B15 may contain dichloroacetate, whose dose-limiting toxicity is peripheral neuropathy, established in a randomized trial stopped early for that reason in 2006.

• Stop immediately and seek evaluation for new tingling, burning, or numbness in the hands or feet.

• Avoid entirely in pregnancy, breastfeeding, childhood, and existing neuropathy.

Special Note

Pangamic acid and laetrile came from the same family and share more than a surname. Both were given vitamin numbers, B15 and B17, that no nomenclature body recognized, and both used the number to borrow the credibility of nutrition for something that was never a nutrient. When a supplement's identity is a number rather than a molecule, ask who assigned the number and what deficiency it corrects. If nobody can name one, the number is branding.