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How Vitamin B12 Deficiency Symptoms Might Worsen With Supplementation

How Vitamin B12 Deficiency Symptoms Might Worsen With Supplementation

  • Does B12 supplementation have a negative effect on you? If so, you are not alone!

Vitamin B12 is at the heart of many vital processes in human health. A deficiency can go unnoticed for years, resulting in a cascade of negative outcomes. I’ve read several reports of b12 supplementation causing very negative reactions that are oddly similar to symptoms of b12 deficiency.

Symptoms of b12 deficiency are usually easily addressed with a dietary change or the use of supplements. I’ve found several case studies and read dozens of personal accounts that detail accounts of b12 supplements making symptoms associated with b12 deficiency worse. This article details what is, at best, a working personal theory to explain this phenomenon.


Vitamin B12 helps generate new blood cells, supports detoxification, and is essential to childhood brain development. Lack of b12 can cause any number of unfavorable health issues to pop up. Common symptoms of b12 deficiency include low red-blood-cell counts, high MCV counts, fatigue, cognitive dysfunction, insomnia, digestive issues, and nervous system issues.

B12 Deficiency

A B12 deficiency can wreak all kinds of havoc. There are many potential causes of such deficiency including restricted diets, digestive disorders, and even unfavorable bacterial balances. Regardless of the cause, the symptoms can become life-altering. B12 is deeply involved in the healthy functioning of the nervous system. One set of symptoms associated with low-b12 levels includes numbness, tingling, burning, and hypertension. These are the issues that have piqued my interest.

Symptoms of B12 Deficiency

I’ve struggled with digestive issues for years that have required a prolonged restriction in my diet. Before, during, and after these dramatic dietary restrictions, I’ve tested with “sub-optimal” b12 levels. That is; low enough to keep an eye on but not low enough to be considered the “cause” of anything particular.

Among many symptoms attributable to low B12, I have experienced the following over the years:

  • Tongue Burning
  • Numbness of Limbs
  • Tingling of Limbs
  • Insomnia
  • Burning Sensation Throughout Body
  • Strange Skin Discomfort
  • Brain Fog

The list could go on, but these are the symptoms I’d like to discuss with the greatest focus. I have taken B12 supplements and shots in the past without issue. More recently, I experience very dramatic adverse reactions given relatively low doses (50mcg compared to 5000mcg years prior.)

Types of B12 Supplementation

There are several scientifically-supported approaches for correcting b12 deficiency. Among them are dietary increases, b12 shots, and b12 supplementation. Dietary changes are ideal but subject to the most unknown variables. B12 shots are likely the most effective at correcting acute deficiency but also the least convenient. Personally, I don’t like the idea of daily—or even weekly—shots.

Dietary B12 Sources

Vegan and vegetarian diets are particularly at high-risk for b12 deficiency. There is no plant-based b12 source with sufficient concentration to meet daily requirements. Most of the case reports I’ve read describing acute b12 deficiency involve some degree of Veganism, often forced on a dependant on their primary caregiver. Most cases resolve quickly on supplementation but some observe negative reactions initially.

Vitamin B12 Shots

For acute cases of B12 deficiency, cyanocobalamin shots are commonly administered. These are can be given intramuscularly or subcutaneously and are fairly commonplace—common enough one can pick them up through a local pharmacy anyway. Vitamin B12 shots are also administered as B-Complex shots sometimes and may include other compounds such as folate.

Vitamin B12 Supplements

Methylcobalamin is the go-to for deficiency-corrective supplementation in most cases. This form is water-soluble and well-absorbed via sublingual dosage. This form is considered ideal for those with genetic variants that may contribute to disrupted methylation processes. Other forms include Hydroxycobalamin, adenosylcobalamin, and cyanocobalmin. It’s worth noting that research suggests cyanocobalamin may not be as bioavailable as other forms (R). That’s concerning, considering it’s a common form recommended for injections.

Symptoms of B12 Deficiency Worsen on Supplementation

In many case reports, as well as dozens of individual accounts, I’ve read of the symptoms of b12 deficiency getting profoundly worse upon supplementation. I have experienced this myself and can attest to how strange it truly is. I’ve found some interesting research that I’d like to share, with the hopes of starting a conversation that might help get to the bottom of this issue.

Current Working Theory

B12 is essential in nervous system health—that much is clear from available research. This is particularly true for brain cells and low b12 is known to cause memory impairment and issues with reasoning skills. B12 is also essential throughout the central nervous system in preserving nerve health and function.

Low b12 can cause a sensation of burning, muscle spasms, numbness, and tingling (neuropathy). These symptoms are usually noted as being resolved quickly with supplementation. I have personally experienced a worsening of symptoms with supplementation and have seen enough similar accounts to believe I’m not alone.

Chronically-low levels of b12 have caused an increase in receptor density. If symptoms of burning and/or spasming are present, and increased availability of b12 (and the resultant neurotransmitters) might cause an increase in signaling capability within the nervous system—resulting in an increased perception of those symptoms.

Below are some related articles I’ve found to help support this theory, even if only indirectly.

Effects of perinatal vitamin B6 deficiency on dopaminergic neurochemistry.

TL;DR: Mixed support from B6 testing on animals 

The administration of vitamin B6 to deprived animals did not raise the level of D-2 receptor binding during the period of observation. Scatchard plots indicated that the differences in binding were due to changes in receptor number and not in KD

Iron Receptor Protein Density Decreases Following Deficient Levels

TL;DR: Neurotransmitter receptors may be particularly subject to nutritional state

These results support the concept that D2 receptor gene expression is not significantly changed by iron deficiency, whereas dopamine receptor trafficking is affected and is likely related to known dopamine system alterations in iron deficiency.

Iron deficiency decreases dopamine D1 and D2 receptors in rat brain.

TL;DR: Iron deficiency decreases dopamine D-1 and D-2 receptors in rat brain

The loss of iron in the striatum due to dietary ID was significantly correlated with the decrease in D(2) receptor density; however, this relationship was not apparent in other brain regions

These experiments thus demonstrate abnormal dopamine receptor density and functioning in several brain regions that are related to brain regional iron loss. Importantly, the impact of ID on dopamine was more pronounced in males than females, demonstrating sex-related different sensitivities to nutrient deprivation.

Behavioral alterations are associated with vitamin B12 deficiency in the transcobalamin receptor/CD320 KO mouse

TL;DR: B12 insufficiency affects postsynaptic—but maybe not presynaptic—physiology.

Unchanged PPF ratios suggest no impairment in presynaptic neurotransmitter release in the KO mouse. However, reduced tetanus envelope in the KO mouse suggests deficient depolarization to induce LTP. Moreover, impaired initiation of LTP suggests a failure in the recruitment of post-synaptic mechanisms involved in the early expression of LTP.

The peripheral neuropathy of vitamin B12 deficiency

TL;DR: Effects of B12 seen directly on nerve structure but not protective covering. Also, some effects of long-term b12 insufficiency may be irreversible.

Nerve conduction studies and sural nerve biopsy were performed on three patients with vitamin B12 deficiency and symptoms of peripheral neuropathy. The pathological findings were those of axonal degeneration; there was no evidence of demyelination … progression of the neuropathy had been arrested by treatment, but in all cases, residual neurological abnormalities persisted.

Vitamin B12 deficiency neuropathy; a rare diagnosis in young adults: a case report

TL;DR: B12 Therapy effective but may take weeks or months

A 28-year-old female Cameroonian presented with progressive burning painful sensations on the upper trunk, paraesthesia, and numbness of the upper and lower limbs for a period of 5 years. She was placed on oral vitamin B12 supplements at 2 mg daily for 3 months. Follow up was marked by good clinical recovery after 1 month of therapy.

The Many Faces of Cobalmin (Vitamin B12) Deficiency

TL;DR: B12 Deficiency can be hard to diagnose and treatment make take several months to fully address issues

treated with hydroxocobalamin, 1000-μg injections twice weekly, with a beneficial effect on her symptoms (Below Table). As can be appraised from her symptom list, many improved considerably or resolved completely.

Symptom Before Treatment 1 Mo. Followup 6 Mo. Followup
Numbness in hands 5 4 1
Difficulties focusing 5 4 3
Not being able to find the right words 6 4 0
Mood changes 7 6 0
Pain in mouth and tongue 6 6 4
Fatigue, weakness 9 9 0
Nausea, reduced appetite 8 6 0
Menstrual pains 9 9 8
Pain in joints 6 6 3
Dyspnea on exertion 6 8 1
Dizzy spells 7 5 0
Pale skin 5 5 4
Feeling cold 8 8 0
Muscle cramps 6 6 4
Stomach complaints, acidity 6 4 0

Update: Another Anecdotal Theory

After having slowly built up a b12 supplementation regimen, I was able to go from barely tolerating 1 drop of B12 as hydroxocobalamin/Adenosylcobalamin every three days to tolerating 1000mcg daily. It was slow and I definitely hit some speedbumps along the way. However, as my body got used to it, symptoms associated with Burning Mouth Syndrome slowly began to disappear.

To be clear; I have health with many other nutritional issues as well. One theory that I have begun developing through my personal experience is related to secondary nutritional deficiencies. Think of B12 as a supercharger for metabolism—when you take b12 supplements it signals the body to build new muscle, make repairs, and digest food.

I can imagine that a deficiency in any other nutrient essential to normal metabolism might have a magnified effect in the presence of excessive B12 supplementation. Kind of like driving a car without the tires—it’ll move but it won’t feel pleasant. Research suggests that the most common nutritional deficiencies associated with BMS are the following (R):

  • Vitamin D3
  • Vitamin B2
  • Vitamin B6
  • Zinc
  • Vitamin B1 (thiamin)
  • Thyrotropin (TSH)
  • Vitamin B12
  • Folic Acid

Addressing these types of nutritional issues alongside B12 might help reduce the negative symptoms associated with b12 supplementation in some cases. Again, this is purely guesswork taken from my personal experience. You should always work with a licensed professional when trying to develop a plan of action for addressing nutritional issues.

Note: The deficiencies listed above are from a decades+ reporting from the Mayo Clinic. However, the Mayo Clinic will not accept patients reporting burning mouth syndrome (personal experience) among their symptoms.


Vitamin B12 deficiency is a serious concern of mine and, from the research and statistics I’ve seen, it’s a potential issue for millions. It can be incredibly hard to diagnose and it seems also that treatment can be somewhat paradoxical.

I hesitate to publish an article with such a haphazard structure. My goal here is to hopefully start some conversations and help shed light on the underlying mechanisms that might cause symptoms of b12 deficiency to worsen upon treatment.

Vitamin B6 has shown paradoxical reactions in some cases. I don’t think that’s the same type of concern here as the b12 issues seems, at least in my experience, to be agnostic of type.

Please reach out If you have experienced this, have a patient that’s experienced this or know someone who has experienced this. I would love insight for my own selfish reasons but also would love to help others dealing with similar issues have a better resource than what currently exists.