Vitamin B12 deficiency and its effects on wellbeing

Vitamin B12 is a molecule which is synthesised by bacteria which thrive in the intestines of animals. It is involved in the production of neurotransmitters which are essential in neural function, sleep, digestion, focus, memory, movement, energy, perception, feeling, sensation and many more through their essential role in cellular communication. It is also involved with the maintenance and repair of cellular tissues such as myelin sheathing which protects and insulates our nerve cells. It is vital in processes which maintain the acid/base balance surrounding our cells and nerves. As previously spoken of, it is essential in the production of blood cells and therefore cellular respiration (Allen, L.H. 2012).

The most common symptoms of vitamin B12 deficiency include; decreased sensation in limbs (pins and needles, peripheral neuropathy), impaired reflexes, confusion, low energy, depression, anxiety, weakness, impaired focus and numbness. The reason these symptoms are seen is because there is an increase in neural degeneration. This can lead to peripheral and spinal nerve degeneration and eventually dementia.

But why is vitamin B12 deficiency such a problem in a country which eats a lot if not too much meat? The answer in my opinion as I stated in my previous article, commonly starts with stomach acid and stress (if not genetic abnormalities, medications or vegetarianism).

Considering that humans only require 2.5mg of stored B12, that the RDI is only 2.4mcg/day and that many of us consume meat in a glutinous manner it is difficult to imagine that deficiency is common in Australia. In fact it is quite common in adults and causes many symptoms which can easily be misdiagnosed as conditions requiring medications (Allen, L.H. 2012). An Australian study published in 2006 found 22.9% of participants to be b12 deficient and urged that Appropriate public health action be considered to reduce health concerns in older Australians (Flood VM, Smith WT, Webb KL, et.al. 2006). Instead, Australia lowered the level of which it considers serum b12 to be deficient. A few years after this reduction a study on a random elderly sample published in 2012 showed that 14% of subjects were confirmed deficient and a further 36% had levels which were considered abnormal (Mirkazemi C, Peterson GM, Tenni PC, et.al. 2012).

So what constitutes a deficiency?

It would make logical sense that being deficient in a nutrient would require you to not have enough of that nutrient in circulation to conduct essential biochemical reactions efficiently. This is in fact not the definition. We classify our levels of deficiency depending on the average in our population. So if the population begins to become malnourished in a certain nutrient, the ranges for adequate levels are reduced. This is scary when you consider the evidence linking b12 deficiency to mental health disorders and dementia. A study in 2006 showed a direct correlation between low levels of B12, high levels of homocysteine and increased risk of dementia (Haan MN, Miller JW, Aiello AE, et.al. 2006).

A study in 2001 came to a result which indicated that deficiency of vitamin b12 can double your risk of developing Alzheimer’s disease. They found that the risk began increasing consistently when vitamin levels were defined as being lower than 250 pmol/L for B12 and lower than 12 nmol/L of folate (Wang, HX., Wahlin, A., Basun, H., et.al. 2001).

Last year the department of dementia research Australia said this after analysing their studies:
“In Australia, dementia is now the second leading cause of death. Over 320,000 Australians are living with dementia, including one in four Australians over the age of 85. Deaths due to dementia have increased approximately 137% over the last 10 years, with nearly 11,000 deaths recorded in 2013. The increasing prevalence is placing a growing emotional and financial burden on patients, their families, and friends. By 2050, it is estimated that nearly one million Australians will have dementia, and 7500 Australians will be diagnosed each week, with a far greater number living with this progressive disabling condition.” (Bush, A.I., Fink, G. & Lei, P. J. 2016)

This is scary in itself but when you consider that in 2007 their predictions were that “prevalence will increase from 172 000 in the year 2000 to 588 000 by 2050. Over the same period, the incidence of dementia is estimated to increase from 43 000 to 143 000 new cases a year” (Jorm, AF., Dear, KBG. Burgess, NM. 2005). This shows that in fact prevalence of dementia is accelerating at a rate of which has almost doubled previous estimations.

There are many factors involved here although I consider the integrity of our nervous system to be a high priority. With studies showing a benefit of B12 supplementation for symptoms of cognitive decline even at blood levels of 250pmol/L (Moore, E.M, Watters D.A.K, Ames, D., et.al. 2015). I believe we not only need to change the level of what constitutes a B12 deficiency, I believe we need to change our current definition of deficiency.

It is important to note that B12 deficiency can cause a functional folate deficiency (folate trap). This is because it is essential in the conversion of n-5 methyl tetrahydrofolate into tetrahyrofloate. Furthermore, folate deficiency and MTHFR gene defects have been linked to conditions such as Depression, schizophrenia, mental retardation, dementia, bipolar disorder. (E.S. Mitchell, N. Conus, J. Kaput. 2014)

Why it is so easy to become deficient in B12

What is relevant to know about the absorption of B12 is that it is complicated and easily disrupted. Understanding the prerequisite factors needed for absorption is more important than going over the biochemistry involved.

Firstly we need to have a healthy and functioning gastric glands; the chief and parietal cells in particular need to be in great condition. The problem with this is the vast number of ways these cells can become damaged. Gastritis, infection and inflammatory diet and lifestyle are among the most common causes.
Secondly the health of our intestinal cells needs to be in good shape to absorb and transport b12 into the blood and around the body.
Thirdly our pancreas needs to in healthy shape to produce the enzymes needed for breaking down b12’s co-factors.
Finally, in order to get B12 to where we need it (inside the cell) we need transcobalamin (the B12 transport protein) to be functioning and in adequate levels.

With low digestion, inflammatory diet and lifestyle, gastrointestinal infections and high stress so prevalent today, it is easy to see why deficiency is so common.

What does it mean that B12 is a water soluble vitamin

Water soluble vitamins are excreted readily through urination. Their ability to be stored is very low and so they need to be consumed constantly in order to maintain healthy levels. When a person is chronically low in vitamin B12, they can have a B12 injection at the GP. What most people don’t understand though is that this needs to be as often as twice a week for 6 weeks to correct deficiency states (Allen, L.H. 2012). Most people tend to go once a month or a few times a year. There are two fundamental reasons that this is not sufficient in itself. Firstly being water soluble, any B12 which your body doesn’t utilise straight away will be excreted into the urine. The secondly, the reason the deficient person was not able to absorb B12 before is still relevant and a few days after the injection, it is likely they will be at a similar level of deficiency to what they were before. For these reasons it is important to combine once off booster injections with daily supplementation. The tablets are sublingually (under the tongue) absorbed and therefore bypass the complicated processes of gastrointestinal absorption.

Biochemically, how does B12 function in the body

Unless you are familiar with Biochemistry, you may want to skip this part. There are two active forms of B12 in the body and each plays a seperate role and function. Deoxyadenosylcobalamin (Adeno-B12) is needed for the conversion of methylmalonyl‐CoA into succinyl-coA using the enzyme methylmalonyl‐CoA mutase. Adeno-B12 deficiency will ultimately lead to acidosis due to accumulation of methylmelonic acid and therefore methylmelonate. This shows as methylmelonic acidemia and methylmelonicacidurea. This will ultimately lead to the breakdown of tissues such as myelin sheathing which protects and insulates neurons. (Takahashi-Iñiguez T., García-Hernandez E., Arreguín-Espinosa R., et.al. 2012)

Methylcobalamine (methyl-B12) is used in the conversion of homocysteine into methionine using methionine synthase. Methionine is then converted into polypeptides (e.g neurotransmitters and proteins) and/or S‐adenosyl methionine (SAMe) to participate in methylation and/or myelination (synthesis of myelin sheathing). SAMe is converted into s-adenosylhomocysteine (SAH) and then homocysteine or adenosine. Deficiency will cause elevation in homocysteine (due to inhibition of methylation), a decrease in methionine and therefore a decrease in myelination and tissue repair (leaving nerve tissues vulnerable to toxins and acids). It will also cause a decrease in purine synthesis which disrupts erythrocytes in bone marrow formation (Ragsdale SW. 2008)

Conditions which commonly cause B12 deficiency

Pernicious anaemia

Pernicious anaemia is caused by an inability to produce intrinsic factor in the stomach. It is thought to be often caused by autoimmune attack of the parietal cells of the stomach. This causes B12 deficiency and has been linked to the development of Hashimoto’s Thyroiditis. If left untreated, people die of pernicious anaemia. Historically it was treated by ingestion of large amounts of raw liver. Nowadays injections and supplements are used.

Vegetarianism

B12 is only found in animal foods and so is an essential nutrient to be supplemented by vegans and vegetarians.

Atrophic gastritis

Helicobacter pylori infection is quite common in Australia and is a common cause of atrophic gastritis. This infection can lead to the destruction of the parietal cells in the stomach and therefore lead to malabsorption of B12. Gluten and glyphosate, alcoholism and consumption of other inflammatory toxins can cause damage to the parietals cells and have all been linked to atrophic gastritis (Centre for digestive diseases, 2009)

Intestinal malabsorption

Anything which causes gastrointestinal inflammation will reduce intestinal absorption of all nutrients including B12. This includes toxins, intolerant/allergenic foods, inflammatory foods such as grains and chillies or drugs and alcohol. Phytates and foods which compete for or block uptake of nutrients will reduce absorption.

Bacterial overgrowth, parasitic infection and SIBO

Pathogenic bacteria can both cause harm to the gastrointestinal tract reducing absorption and can compete for nutrient uptake. Parasitic infection can both cause intestinal bleeding leading directly to anaemia and can compete for nutrient uptake. Small intestinal bacterial overgrowth will both cause damage to the intestines and compete for nutrient uptake (Dukowicz AC, Lacy BE, Levine GM. 2007)

Gastrectomy and surgeries

Causing damage to the stomach obviously will reduce the efficiency of all stomach cells and therefore lead to malabsorption of most of what we consume daily.

Transcobalamin deficiency

Transcobalamin is the molecule which transports B12 throughout the body and across cell membranes to get b12 into the cell so it can do work. It is essential for the function of B12 across the board and transcobalamin defects can cause functional deficiencies. When transcobalamin is low, serum B12 levels will be high although the patient will suffer symptoms of deficiency. Commonly this is missed and the person is prescribed anti-depressants and anti-psychotic drugs. An example of this is bi-polar disorder. One of the key metabolic defects common in bi-polar patients is transcobalamin defects. This is one of the reasons lithium is useful in bipolar as it is has been shown to assist transportation of vitamin B12 and folate (Marshall T.M. 2014). Lithium has also been shown to increase NaK-ATPase Activity which has shown to be a major factor in bipolar disorder (Hokin-Neaverson M., Jefferson J.W. 1989). Deficiencies of folate and B12 have also been implicated in the development of Bipolar disorder (Ozbek Z., Kucukali CI, Ozkok E., et.al. 2008). Lithium is not just a pharmaceutical, it is an essential trace mineral and in certain cases could be considered to be nutritionally deficiency. It plays many roles in the body and is involved in many neurotrophic functions (Machado-Vieira R, Manji HK, Zarate CA Jr. 2009). There are various reasons why transcobalamin levels and function may be low. Two other important considerations are vitamin C status and glutathione synthesis.

Medications

Consumption of proton pump inhibitors is a common cause of B12, zinc, iron, calcium, magnesium and protein deficiencies.
Inhalation of nitrous oxide such as in surgery, causes the inactivation of methylcobalamin leading to functional deficiency.
Asprin has been found to cause damage to parietal cells of the stomach (Konturek, SJ., Konturek, PC., Konturek, JW., et.al. 2006).
Methotrexate is a folic acid antagonist and has been found to cause deficiency of folate (Strober, BE, Menon, K. 2005).
Antibiotics such as; isoniazid, tetracycline, and trimethoprim-sulfamethoxazole can cause deficiencies of B vitamins and vitamin K.
Anticonvulsants such as; phenytoin and phenobarbital can cause deficiencies of B vitamins and vitamin K.

Tests

The markers which will be effected by B12 and folate deficiency include:

  • Serum cobalamin estimation
  • Serum intrinsic factor antibodies
  • Serum parietal cell antibodies
  • Homocysteine estimation
  • Methylmelonicacid estimation
  • Serum and RBC folate estimation
  • Folate estimation
  • Complete blood count
  • Mean corpuscular volume
  • White blood cell count, platelet count and blood smears can also show abnormalities in size and shape of blood cells and neutrophils.

Article by Dean Gainsford N.D

References

Allen, L.H. (2012). Vitamin B12. Retrieved on 28/9/17 from: http://advances.nutrition.org/content/3/1/54.full.pdf+html
Bush, A.I., Fink, G. & Lei, P. J. (2016). Dementia Research Australia: the Australian Dementia Research Development Fellowship Program. Retrieved on 23/9/17 from: https://link.springer.com/article/10.1007/s12031-016-0842-4
Centre for digestive diseases, 2009. Helicobacter pylori. Retrieved on 21/9/17 from: http://www.cdd.com.au/pages/disease_info/heliobacter_pylori.html
Dukowicz AC, Lacy BE, Levine GM. 2007. Small intestinal bacterial overgrowth: a comprehensive review. Retrieved on 21/9/17 from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099351/
E.S. Mitchell, N. Conus, J. Kaput. 2014. B vitamin polymorphisms and behavior: Evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline. retrieved on 21/9/17 from: http://ac.els-cdn.com/S0149763414002048/1-s2.0-S0149763414002048-main.pdf?_tid=7da6e9ac-9e81-11e7-92ae-00000aacb35d&acdnat=1505966645_ef26cd3906b579fd98eeb3651c7c865f
Flood VM, Smith WT, Webb KL, Rochtchina E, Anderson VE, Mitchell P (2006). Prevalence of low serum folate and vitamin B12 in an older Australian population. Retrieved on 23/9/17 from: http://onlinelibrary.wiley.com/doi/10.1111/j.1467-842X.2006.tb00084.x/full
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DM, Allen LH, Green R. (2006). Homocysteine, B vitamins, and the incidence
of dementia and cognitive impairment. Retrieved on 28/9/17 from: http://ajcn.nutrition.org/content/85/2/511.full.pdf+html
Hokin-Neaverson M., Jefferson J.W. 1989. Deficient Erythrocyte NaK-ATPase Activity in Different Affective States in Bipolar Affective Disorder and Normalization by Lithium Therapy. retrieved on 21/9/17 from: https://www.karger.com/Article/Abstract/118587
Jorm, AF., Dear, KBG. Burgess, NM. 2005. Projections of future numbers of dementia cases in Australia with and without prevention. Retrieved on 23/9/17 from: http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1614.2005.01713.x/full
Konturek, SJ., Konturek, PC., Konturek, JW., et.al. 2006. Journal of Physiology – HELICOBACTER PYLORI AND ITS INVOLVEMENT IN GASTRITIS AND PEPTIC ULCER FORMATION. Retrieved on 21/9/17 from: http://www.jpp.krakow.pl/journal/archive/09_06_s3/articles/03_article.html
Marshall T.M. 2014. Lithium as a Nutrient. Journal of American Physicians and Surgeons; Volume 20, Number 4, Winter 2015. Retrieved on 21/9/17 from: http://www.jpands.org/vol20no4/marshall.pdf
Machado-Vieira R, Manji HK, Zarate CA Jr (2009) The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar Disord 11(Suppl 2):92–109. Retrieved on 21/9/17 from: https://link.springer.com/chapter/10.1007%2F978-3-319-45923-3_9
Mirkazemi C, Peterson GM, Tenni PC, Jackson SL. 2012 Vitamin B12 deficiency in Australian residential aged care facilities. J Nutr Health Aging. Retrieved on 23/9/17 from: https://www.ncbi.nlm.nih.gov/pubmed/22456786
Ozbek Z., Kucukali CI, Ozkok E., et.al. 2008. Effect of the methylenetetrahydrofolate reductase gene polymorphisms on homocysteine, folate and vitamin B12 in patients with bipolar disorder and relatives. retrieved on 21/9/17 from: www.sciencedirect.com/science/article/pii/S0278584608001322
Ragsdale SW. (2008). Catalysis of Methyl Group Transfers Involving Tetrahydrofolate and B12. Retrieved on 23/9/17 from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037834/
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Strober, BE, Menon, K. 2005. Folate supplementation during methotrexate therapy for patients with psoriasis. Retrieved on 21/9/17 from: https://www.ncbi.nlm.nih.gov/pubmed/16198787
Takahashi-Iñiguez T., García-Hernandez E., Arreguín-Espinosa R. & Flores M. E. Role of vitamin B12 on methylmalonyl-CoA mutase activity. J. Zhejiang Univ. Sci. B 13, 423–37 (2012).  Retrieved on 23/9/17 from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370288/
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Author Info

Dean Gainsford

Comments ( 3 )

  • Keith Page

    Gee, Dean, so very interesting and also shows just how extremely COMPLEX things are, certainly to a layman such as myself. (Quite mind boggling) or perhaps I’m low on B12. (hahahaha). By the by, have you ever read any papers by Dr D.A. Gilbert. (RIP Don) ? He’d been a lecturer in the biochemistry department at WITS for quite a few years before retiring and returning to his native U.K. (Ilford, London).

    • Hi, thanks Keith I appreciate your feedback. It’s a subject I think is relevant for many Australians.
      No I haven’t heard of him but I will look him up, any you found particularly interesting?

    • Well I just watched a great Ted talk by Him. I get what you’re saying there. Yes beauty and happiness is in the eye of the beholder and perspective is everything.
      How do you though take an unhappy/ uncontent person and help them to be happy? As D.A. Gilbert would probably have put it, that’s totally up to their ability to see
      the beauty and magnificence that surrounds them and he would be totally correct. Its also very interesting though when you conduct a double blind placebo controlled clinical
      trial and find that with the use of an intervention such as B12 supplementation a significant improvement is noted in a large percentage of the sample group. Are they happy and
      fully content with life? Maybe not… Are they happier and less uncomfortable than before? Yes. Does this make their ability to change their paradigm easier? I like to think
      so.

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