Part Two: Why We Use Cyanocobalamin — The Science and Philosophy Behind Formula 3
In part one, we explored the paradox of Vitamin B12 — a nutrient that can both heal and harm, depending on context. We saw how methylated forms of B12, while the most bioactive, may also amplify mercury's toxicity when introduced into the wrong biochemical environment.
Part two is the logical extension, discussing in greater detail the different forms of vitamin B12 and comparing each. Ultimately, it provides our rationale for using cyanocobalamin as the form of vitamin B12 in our supplement, Formula 3.
The Form Defines the Function
Vitamin B12 exists in several molecular configurations, each defined by the ligand attached to its cobalt core. These structural differences profoundly shape how each form behaves within the human body.
1. Methylcobalamin
Origin / Source:
Naturally produced by bacteria, methylcobalamin is found in animal-derived foods such as meat, fish, eggs, and dairy. Supplemental forms are typically biosynthesised through bacterial fermentation and purified for human use.
Mechanism / How It Works:
Methylcobalamin is one of the two biologically active coenzyme forms of Vitamin B12 used directly by the body. It donates a methyl group (–CH₃) to homocysteine via the enzyme methionine synthase, converting it to methionine. Methionine then forms S-adenosylmethionine (SAMe) — the body's primary methyl donor — critical for DNA methylation, neurotransmitter synthesis, and detoxification reactions.
Summary:
The most neurologically active form of B12 is key to methylation pathways. However, its strong methyl-donating capacity can methylate inorganic mercury into methylmercury, a highly neurotoxic form. Best suited for individuals with proven methylation deficiencies and minimal toxic load.
2. Adenosylcobalamin (Cobamamide)
Origin / Source:
Like methylcobalamin, adenosylcobalamin is naturally synthesised by bacteria and archaea, then accumulated in animal tissues — particularly the liver. Supplemental forms are derived from bacterial fermentation but are chemically unstable and degrade easily when exposed to light, heat, or oxygen.
Mechanism / How It Works:
Adenosylcobalamin is the mitochondrial coenzyme form of Vitamin B12. It serves as a cofactor for methylmalonyl-CoA mutase, facilitating the conversion of methylmalonyl-CoA to succinyl-CoA, an essential step in the Krebs cycle — the core process of cellular energy (ATP) production. This reaction links the metabolism of amino acids and fatty acids directly to mitochondrial function.
Summary:
Essential for mitochondrial energy metabolism and neurological health. However, due to poor oral stability and the need for cold-chain storage, it is less practical for general supplementation. Often used in specialised formulations or injectable forms for mitochondrial support.
3. Hydroxocobalamin
Origin / Source:
Produced naturally by bacteria and present in certain animal foods, hydroxocobalamin is also generated during the purification of bacterial B12 cultures. Pharmaceutical-grade hydroxocobalamin is purified and stabilised for use in injectable formulations.
Mechanism / How It Works:
Hydroxocobalamin is a natural, intermediary form of B12 that the body can readily convert into either methylcobalamin or adenosylcobalamin as needed. It has a high affinity for binding cyanide and nitric oxide, making it valuable in clinical toxicology (cyanide antidote) and for regulating nitric oxide metabolism. Its slower release and longer half-life make it effective for sustained B12 delivery.
Summary:
Highly versatile and well-tolerated, hydroxocobalamin is the preferred injectable form of B12 used in medical settings due to its long-lasting effect and low reactivity. However, it is unstable in oral supplements and difficult to preserve, limiting its suitability for mass production or shelf-stable products.
4. Cyanocobalamin
Origin / Source:
Synthesised from bacterial fermentation, cyanocobalamin is created by reacting hydroxocobalamin with cyanide under controlled laboratory conditions. It was the first commercially available form of B12, developed for pharmaceutical stability and mass production.
Mechanism / How It Works:
Cyanocobalamin is the synthesised form of Vitamin B12. It is produced by attaching a cyanide (–CN) molecule to the cobalt centre of the cobalamin structure to stabilise it. Once ingested, the body converts it into active forms (methylcobalamin and adenosylcobalamin) as required. The trace cyanide — about 20 micrograms per 1,000 mcg dose — is detoxified by the enzyme rhodanese, which converts it to thiocyanate for safe excretion.
Summary:
The most stable and widely used form of B12, cyanocobalamin, offers predictable absorption, excellent shelf life, and safety when used correctly. It does not donate methyl groups, thus avoiding the risk of mercury methylation or overstimulation. Ideal for oral supplementation and clinical use where consistency, safety, and controlled dosing are critical.
The Rise and Risk of the Methylation Movement
Over the past decade, methylated B vitamins, particularly methylcobalamin, have become synonymous with "advanced nutrition." Their popularity has been fuelled by genetic testing, especially MTHFR polymorphism screening, and the promise of "personalised supplementation" — the idea that by bypassing metabolic bottlenecks, one can optimise energy, mood, and detoxification.
Practitioners and consumers alike have embraced the narrative that "active" forms of nutrients are inherently superior — that methylcobalamin, because it is already in a bioactive state, ensures better utilisation and faster results. In theory, this logic holds: methyl donors drive methylation, and methylation underpins vital processes such as DNA repair, neurotransmitter balance, and cellular detoxification.
But in practice, the story is far more complex. Methylation is not a switch to be flipped — it is a network to be balanced.
When methyl donors are added to a body burdened by toxins, oxidative stress, or mineral imbalance, the system can be pushed into biochemical overdrive. We see this clinically all too often. Clients arrive overstimulated, anxious, or hypersensitive — symptoms not of deficiency, but of disordered regulation.
This is often due to excess methyl donors accelerating the turnover of key neurotransmitters (mainly dopamine, norepinephrine, and serotonin) while simultaneously mobilising stored toxins, such as mercury, faster than the body can neutralise or excrete them. The result is a state of neurochemical excitation and oxidative stress — energy without balance, toxin mobilisation without clearance.
The Methylation Craze: A Lesson in Misplaced Reductionism
Methylation should never be the starting point; it is the final refinement of a well-prepared system. Before introducing methyl donors, five biochemical foundations must first be in place:
- Glutathione sufficiency — to bind and safely excrete toxins.
- Mineral balance — particularly zinc, copper, magnesium, and potassium, which stabilise enzymatic reactions.
- Liver and kidney function — to handle the increased metabolic waste load.
- Redox equilibrium — to prevent oxidative damage.
- Mercury and heavy metal management — to avoid re-mobilisation of stored toxins.
Only when these systems are restored and resilient can methylation truly enhance health rather than destabilise it. So, you can see how mindlessly pursuing methylaiton is counterintuitive to health.
When Methylation Meets Mercury: The Case Against Methylcobalamin
Methylcobalamin's therapeutic appeal lies in its ability to donate methyl groups that drive DNA synthesis, neurotransmitter balance, and detoxification. Yet, this same capacity becomes a liability in those with mercury exposure.
When methyl groups encounter inorganic mercury (Hg²⁺), they can convert it into methylmercury (CH₃Hg⁺) — a compound exponentially more neurotoxic, bioaccumulative, and capable of crossing the blood–brain barrier.
For individuals undergoing Total Dental Revision (in conjunction with Eric Davis Dental), or those with amalgam fillings, seafood-derived mercury, or other toxic burdens, methylcobalamin can act as a catalyst in the wrong reaction — transforming a relatively inert compound into one of biology's most insidious poisons.
The issue with methylcobalamin is that it overemphasises methylation.
Why Not the "Natural" Alternatives?
Now that we've ruled out methylcobalamin, what about the other natural forms? If cyanocobalamin is synthesised, why not choose one of the non-methylated natural alternatives — hydroxocobalamin or adenosylcobalamin? The answer is as much practical as it is biochemical.
- Hydroxocobalamin: Though excellent in injectable form, it is unstable when taken orally and difficult to preserve at scale.
- Adenosylcobalamin: Essential for mitochondrial metabolism, it also degrades easily and requires cold-chain storage.
A Record of Clinical Reliability
Cyanocobalamin, by contrast, is stable, safe, and clinically consistent. Its reliability allows clinicians to control dosage, anticipate outcomes, and minimise the biochemical variability that complicates client recovery.
Unlike methylated forms, cyanocobalamin does not donate methyl groups. It delivers all the benefits of B12 — supporting neurological integrity, red blood cell formation, and metabolic balance — without the risk of mercury methylation or biochemical overstimulation.
It may not be the trendiest choice — but it is the tested one.
Hormesis and the Truth About Cyanide
Cyanocobalamin's critics often point to the trace amount of cyanide used in its synthesis — roughly 20 micrograms per 1,000 mcg dose. But toxicology, like nutrition, is a matter of context and dose. This amount is biologically negligible, rapidly neutralised by the enzyme rhodanese, which converts cyanide into thiocyanate for safe excretion. Humans routinely consume more cyanide equivalents through foods like almonds, cassava, or even cruciferous vegetables (such as broccoli).
In toxicology, there is a principle called hormesis, where a low dose of a toxin may actually trigger beneficial adaptive responses. Trace exposure to cyanide through cyanocobalamin may mildly up-regulate antioxidant defences like rhodanese and glutathione systems. While this isn’t the reason we use cyanocobalamin, it shows that nature is complex — and the dose determines whether a compound is therapeutic or harmful.
In short, the dose makes the poison, and cyanocobalamin's dose makes the medicine.
Cyanocobalamin and Porphyrin Metabolism
Cyanocobalamin’s critics also often claim that the cyanide component can disrupt porphyrin metabolism — the biochemical pathway responsible for producing heme, the iron-containing molecule central to oxygen transport (via hemoglobin) and energy production (via cytochromes).
The argument suggests that cyanide interferes with heme synthesis, thereby impairing red blood cell function or mitochondrial energy production. However, this interpretation misunderstands both the pathway and cyanide’s mechanism of action.
Where Cyanide Actually Acts
Cyanide does not inhibit the enzymes responsible for porphyrin or heme synthesis. Instead, it acts after heme is already produced. Specifically, cyanide binds to the ferric (Fe³⁺) iron within cytochrome oxidase (Complex IV) — the terminal enzyme of the mitochondrial electron transport chain. When this occurs, it temporarily halts electron transfer and oxygen utilisation at the cellular level.
Cyanide’s effect occurs downstream of porphyrin synthesis, at the mitochondrial stage of heme utilisation rather than production. By transiently binding to cytochrome oxidase (Complex IV), it can momentarily slow the use of heme in cellular respiration — but it does not inhibit porphyrin synthesis itself, nor does it produce cumulative toxicity at supplemental doses. This brief, reversible interaction is rapidly neutralised by the enzyme rhodanese, ensuring normal mitochondrial function is restored.
It is for this reason that cyanocobalamin remains both clinically safe and metabolically stable, delivering reliable B12 support without compromising heme metabolism or cellular energy production.
Comparative Effects of Heavy Metals on Porphyrin Metabolism
By contrast, other toxins interfere directly with the porphyrin synthesis pathway, blocking specific enzymatic steps essential for heme formation. The table below outlines where these disruptions occur. Particular attention should be given to mercury, as similar patterns of interference can arise when methylcobalamin — the methylated form of B12 — is used in individuals with existing mercury exposure.
| Toxin | Enzyme/Process Affected | Effect on Heme Synthesis |
|---|---|---|
| Lead (Pb) | Inhibits ALA dehydratase and ferrochelatase | Prevents formation of porphobilinogen and the final conversion of protoporphyrin IX to heme |
| Arsenic (As) | Disrupts conversion between uroporphyrinogen and coproporphyrinogen | Causes accumulation of uroporphyrin and heptacarboxylporphyrin intermediates |
| Mercury (Hg) | Interferes with coproporphyrinogen oxidase | Impairs conversion of coproporphyrinogen to protoporphyrinogen and ultimately protoporphyrin IX |
Summary: The Right Form, The Right Context
Cyanocobalamin endures because it embodies three qualities that matter most in clinical nutrition: safety, stability, and system alignment.
- Safe: It avoids mercury methylation and provides B12 without neurotoxic risk.
- Stable: It resists degradation, ensuring potency and consistency.
- Systemic: It supports, rather than disrupts, the body's biochemical equilibrium.
Supplements should not chase trends; they should restore balance. In choosing cyanocobalamin, we choose prudence over popularity — a form that aligns with both toxicology and the art of clinical practice.
That's why Formula 3 continues to use cyanocobalamin as its form of vitamin B12: because when used within a balanced, tested system, it does precisely what it should do — support what heals, and avoid what harms.
The Bigger Picture: Holistic Function
Ultimately, the lesson extends beyond Vitamin B12. It underscores the importance of evaluating all nutrients within a broader biochemical and physiological context. The form matters — but only insofar as it serves the system.
The purpose of Formula 3, particularly when used alongside Formula 2, is to optimise red blood cell formation and function. Together, they enhance oxygen transport, support efficient metabolism, and establish the foundation for detoxification and recovery.
Across more than four decades of analysing blood chemistry, we’ve observed that when clients avoid these formulas due to misconceptions about “synthethised” ingredients or MTHFR polymorphisms, progress frequently stalls. This is often reflected in persistently low or declining iron levels — a sign of impaired oxygen delivery and increased toxin retention through competitive binding in the gut.
In summary, the efficacy of a supplement cannot be judged by a single ingredient or pathway in isolation. Supplementation must be viewed through a holistic, functional lens — one that recognises the interdependence of nutrients, metabolism, and detoxification.
