Following repeated exposure to nitrous oxide during mid 2017, I woke up from a short nap to discover that both my ankles had become severely swollen. I drove to the Emergency Room where I was reassured that this was in no way related to nitrous oxide exposure and sent home with many unanswered questions after declining an inpatient stay.
As I waited for an appointment with my primary care provider, my symptoms worsened. As the swelling in my ankles subsided, I lost all sensation from head to toe and my body ceased to exist with eyes closed. I could no longer balance my weight on the soles of my feet or feel the ground beneath me while barefoot. I lacked the strength or dexterity to grip a writing utensil effectively enough to sign my name on paperwork that required it and I had to borrow my grandmother’s walker to get around my house. I hobbled into the appointment as a twenty four year old student with full coverage insurance and no known allergies or pre-existing conditions. I was told that I would likely never walk normally again because there was “nothing” that could be done and that my condition would most likely be “permanent”; and reluctantly handed a referral to a local neurologist.
With no future in sight and nothing left to lose, I apprehensively began to pay out of pocket for intramuscular injections and intravenous infusions from a wellness clinic in my area upon the advice of my chiropractor. My routine consisted of intramuscular injections of vitamin B12 and intravenous infusions of vitamin C, vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B12, magnesium, calcium, and saline three times a week for several months. After an examination from the neurologist and multiple MRIs, I was diagnosed with a subacute combined spinal cord injury and advised to continue vitamin B12 supplementation. I steadily improved and made a full recovery.
My primary care provider subsequently refused to prescribe any form of supplemental vitamin B12 despite my noticeable progress, the recommendation from the neurologist, and zero risk for any long-term adverse effects. Had I not taken matters into my own hands, I would still be severely disabled. I have compiled some key points from my research into the harms of nitrous oxide, the benefits of vitamin B12, and the concept of remyelination.
Health Hazards and Nitrous Oxide: A Time for Reappraisal
1991 | PMID: 1809046
“Although N2O was for many years believed to have no toxicity other than that associated with its anesthetic action, bone marrow depression in patients administered N2O for extended periods of time and neurological abnormalities in health care workers who inhaled N2O recreationally have disproved this notion. Retrospective surveys of dental and medical personnel have also linked occupational exposure to N2O with a number of health problems and reproductive derangements. Nitrous Oxide reacts with the reduced form of vitamin B12, thereby inhibiting the action of methionine synthase, an enzyme that indirectly supports methylation reactions and nucleic acid synthesis. Many, if not all, of the nonancsthetic-related adverse effects of N2O may be ascribed to this action. Animal and human studies indicate that the toxic effects of N2O are concentration- and time-dependent.”
General Anesthesia May Impair Kids’ Language Learning
“The present findings suggest that general anesthesia for a surgical procedure in early childhood may be associated with long-term diminution of language abilities and cognition, as well as regional volumetric alterations in brain structure,” the authors wrote.
“A 2013 study published in Pediatric Anesthesia found that the “odds of a formal diagnosis of learning disability by age 12 years in apparently healthy children exposed to general anesthesia for minor surgery during infancy were 4.5 times greater than their peers who had never been exposed to anesthesia.”
THE ALTERNATIVE: REGIONAL ANESTHESIA
“Previous studies have shown no cognitive impairment following regional anesthesia. A 2014 study published in Anesthesia & Analgesia found no link between duration of surgery in an infant under spinal anesthesia and scores on academic achievement tests in elementary school. “We also found no relationship between infant [spinal anesthesia] and surgery with [very poor academic achievement] on elementary school testing,” the authors wrote.”
Using General Anaesthetic on Infants Could Harm Their Memory for Life – Study
“General anaesthesia before the age of one may impair memory later in childhood, possibly life-long, a study has suggested. This was the conclusion of scientists who compared the recollection skills of two groups of children — some who had undergone anaesthesia in infancy and others who had not. The children, aged six to 11 and divided into two groups of 28 each, were tested over a period of 10 months for their ability to recollect specific drawings and details therein. The children who had been anaesthetised as babies had about 28 percent less recollection on average than their peers, and scored 20 percent lower in tests that assessed how much detail they could remember about the drawings. “The children did not differ in tests measuring intelligence or behaviour, but those who had received anaesthesia had significantly lower recollection scores,” said a media summary provided by the journal Neuropsychopharmacology, which published the results. Recollection plays a role in autobiographical memory, classroom learning and reading comprehension. “Thus, even subtle recollection deficits may have immediate consequences and reduce the child’s potential to learn over time, which future studies should examine more closely,” wrote the University of California team.”
Anesthesia-Induced Developmental Neurotoxicity in Children: Past, Present, and Future
2019 | PMID: 31369429 | DOI: 10.1097/CM9.0000000000000377
“Since 1999, a large body of evidence from various animal models indicates a link between anesthesia exposure in early stage of life and subsequent neurodevelopmental impairments; namely, almost all commonly used intravenous and inhalational anesthetics, including gamma aminobutyric acid agonists and N-methyl-D-aspartate antagonists, can induce dose and age dependent neuronal apoptosis and death in vitro.”
”Alarmingly, these neurotoxic effects by neonatal exposure to anesthesia may result in the long-term detrimental functional outcomes in later childhood or adulthood, such as deficits in memory, learning, attention, and motor function.”
“It is both a responsibility and an opportunity for specialties such as anesthesiology, surgery, and neurology to work together to address this critical public health issue closely related to clinical anesthesia of pediatric and pregnant patients until a clear solution about the source of this potential harm to the developing brain is obtained.”
Pediatric Anesthesia Neurotoxicity: An Overview of the 2011 SmartTots Panel
2011 | PMID: 22021791 | DOI: 10.1213/ANE.0b013e3182326622
“Through the years, care of millions of premature infants and young children has resulted in numerous exposures to a variety of anesthetic and sedative agents. These agents, designed to achieve the substantial depth of neuronal inhibition required for complete loss of consciousness and insensitivity to pain, are often a necessary component of successful treatment. However, data collected in animal models over the past decade suggest that general anesthetics damage developing neurons. Emerging animal and human data also suggest an association between early exposure to general anesthesia and long-term impairment of cognitive development. Consequently, the prudence of administering anesthesia to this population is now being scrutinized. Because general anesthesia cannot often be avoided when young children are diagnosed with conditions requiring surgery, or undergo time in intensive care units, the scientific community is focused on gaining a thorough understanding of the mechanisms of action so that we may take full advantage of the beneficial effects of anesthetics and sedatives without potentially devastating neurotoxic outcomes.”
2019 | PMID: 31192102 | DOI: 10.1177/2192568218758633
ON THE BASIS OF PREOPERATIVE PLANNING:
“N2O irreversibly oxides the cobalt ion at the center of B12, and impedes its crucial cofactor function for methionine synthetase. This enzyme is required for the formation of tetrahydrofolate (THF) and methionine. THF is involved in thymidine synthesis and DNA production, while methionine is required for the methylation of myelin sheath phospholipids. Consequently, patients with already low levels of B12 or methylene-tetrahydrofolate-reductase deficiency are particularly at risk for perioperative myelopathy due to N2O administration. Given that N2O can be used during spine surgery, this points to the necessity of routinely monitoring B12 levels in patients with DCM to optimize surgical outcomes and prevent perioperative or postoperative neurological deficit development. Recognition of this phenomenon is important, as intramuscular injection of B12 has been shown to rapidly reverse SACD symptoms.”
RESULTS:
“Vitamin B12 deficiency can result in subacute combined degeneration of the spinal cord (SACD), and several case reports have pointed to patients with both DCM and SACD. Both SACD and reversible compressive injury due to DCM necessitate remyelination in the spinal cord, a process that requires adequate vitamin B12 levels. Basic science research on nerve crush injuries have shown that vitamin B12 levels are altered after nerve injury and that vitamin B12 along with dexamethasone or nonsteroidal anti-inflammatory drugs can reduce Wallerian degeneration. Furthermore, it has been suggested that a combination of B-vitamins can reduce glutamate-induced neurotoxicity.”
CONCLUSIONS:
“Given the high prevalence of clinical and subclinical vitamin B12 deficiency in the elderly, the role of vitamin B12 in myelination, and vitamin B12 deficiency as a differential diagnosis of DCM, it is important to investigate what role vitamin B12 levels play in patients with DCM in terms of baseline neurological function and whether optimization of vitamin B12 levels can improve surgical outcome.”
Treatment with High Dose Vitamin B12 Been Shown to be Safe for More Than 50 Years
A DECENNIA LONG HISTORY OF SAFE TREATMENT:
“In 1926 it was discovered that patients with pernicious anaemia could be saved from a certain death by eating a pound of raw liver a day. More than 20 years later the substance that was responsible for that was isolated from liver extract: vitamin B12 or cobalamin. Since then, numerous patients have been treated with high dose vitamin B12 worldwide. Usually per injection and often lifelong, as a deficiency is mostly caused by an irreversible absorption disorder. In all that time harmful effects have never been shown from overdose. No single case has been found in medical literature in the past 60 years.”
NO MAXIMUM DOSE:
“The Dutch National Health Council therefore decided not to determine a safe upper intake level for vitamin B12. In their report from 2003 “Voedingsnormen: vitamine B6, foliumzuur en vitamine B12” the council joined expert commissions from the American Institute of Medicine and the Scientific Committee for Human Food from the European Union, who had already reported 3 years earlier that toxicity from high dose vitamin B12 poses no real danger. Of course, like with any medical treatment, side effects can occur. Acne, eczema and itching seldom occur and very rarely anaphylactic shock. Changing brands of vitamin B12, forms of B12 (cyanocobalamin vs hydroxocobalamin), or switching from injections to tablets can be a solution in those (rare) cases.”
MISUNDERSTANDINGS ABOUT BLOOD AND REFERENCE VALUES:
“Yet often physicians reduce injections or even stop treatment altogether out of fear of overdosing B12. The result is that many patients are left with recurring or lasting symptoms, which could be relieved by more frequent injections. After an injection the serum B12 value rises quickly, well above the upper reference value (on average 150-700 pmol/L), followed by a slow decrease. Apparently the underlying thought is that it is necessary to keep the value between the (upper and lower) reference values. However the blood level of serum B12 rises regardless of therapeutic effectiveness. A high serum B12 value does not mean that symptoms are treated sufficiently.”
TREATMENT BASED ON SYMPTOMS INSTEAD OF BLOOD VALUES:
“The recommended treatment in the Netherlands consists of a hydroxocobalamin injection of 1mg every two months, after an initial loading dose of 10 injections in 5 to 10 weeks. No reference is made to the serum value or a danger of overdosing, unlike for instance in case of a vitamin D or A deficiency. The lack of danger of an overdose is further underlined by the advice to treat patients with neurological involvement with two injections a week for up to two years, if necessary. This also emphasizes that symptoms and not blood values should be used as a guideline. If serum values were decisive, even patients with neurological involvement could suffice with the maintenance dose of one injection every two months after the initial loading dose.”
ELEVATED SERUM B12 VALUES IN SERIOUS CONDITIONS:
“Maybe the concern for a possible overdose is caused by the knowledge that some life-threatening diseases can be accompanied by a strong increase in the B12 blood value, in some cases to even 30 times the upper reference value. In blood diseases like leukemia, polycythemia vera and hypereosinophylic syndrome, the cause is often an enhanced production of the transport protein haptocorrin, to which most of the circulating B12 in blood is bound. In liver diseases such as acute hepatitis, live cirrhosis, and liver cancer, elevated B12 values are often found because the liver is no longer capable of storing vitamin B12.”
SCIENTIFIC RESEARCH:
- “Scientific literature offers numerous examples from which it can be concluded that treatment with high dose B12 up to very high serum values is no cause for concern.”
- “In the treatment of children with an inborn error in the production of transcobalamin II, the binding protein that transports B12 to the cells, serum values are kept at levels of 10,000 pg/ml (about 7,400 pmol/L) without any side-effects.”
- “Japanese research from 1994 into the effects of B12 therapy in patients with multiple sclerosis shows that a daily tablet with 60 mg methylcobalamin during six months is non-toxic. Half of the patients even started with two weeks of daily 5 mg B12 injections straight into the blood.”
- “In the fifties, when chemotherapy wasn’t available yet, children with neuroblastoma (a tumour of the autonomous nervous system) received 1 mg B12 injections every other day during 2 to 3 years in a London children’s hospital. From 1957 the dose was adjusted to 1 mg per 7 kilograms of body weight. In the majority of patients the tumour disappeared wholly or partially and the chance of survival was considerably increased.”
- “In 1999 in Japan, kidney dialysis patients with polyneuropathy, received 0.5 mg methylcobalamin 3 times a week intravenously for 6 months. Because of lack of renal clearance, serum values rose to more than a hundredfold from 422 pmol/L on average to 54,000 pmol/L, with 67,000 pmol/L as highest value, without side-effects.”
- “Also in Japan, in 2007, patients with the incurable neurodegenerative disease ALS (Lou Gehrig’s disease) received daily injections with 25 mg methylcobalamin for 4 weeks, followed by daily injections of 50 mg intravenously, followed by 50 mg a week. In the long term, treated patients survived for longer because of this, than did untreated patients.”
MEGADOSES B12 AS LIFESAVING ANTIDOTE:
“The safety of vitamin B12 treatment is further illustrated by the decennia long use of hydroxocobalamin as an antidote for cyanide poisoning, often caused by smoke inhalation. In the Netherlands ambulances, fire departments, and emergency rooms have the Cyanokit at their disposal. In life threatening situations 5 g hydroxocobalamin is given intravenously within 15 minutes, an amount that corresponds with 5,000 injections of 1 mg B12. Hydroxocobalamin reacts in the body with cyanide, and forms cyanocobalamin, which is excreted in urine. The serum value of B12 can rise to an average of 560,000,000 pmol/L within 50 minutes. If necessary, this treatment is repeated within several hours, making the total dose 10 grams. The side effects that occur, like reddening of the skin and urine and changes in heart rate and blood pressure, are temporary and harmless. In short: 10,000 injections a day are still not enough for an overdose of vitamin B12.”
CONCLUSION:
“A vitamin B12 deficiency can cause many different symptoms, among which are serious neurological problems. The treatment with high dose B12 injections is not only completely safe but fortunately also very effective. With the right treatment patients can recover completely. Starting straight away with treatment is essential, as is the continuing treatment in order to give the body enough B12 to fully recover.”
B Vitamins and the Brain: Mechanisms, Dose and Efficacy — A Review
2016 | PMID: 26828517 | DOI: 10.3390/nu8020068
ABSTRACT:
“The B-vitamins comprise a group of eight water soluble vitamins that perform essential, closely inter-related roles in cellular functioning, acting as co-enzymes in a vast array of catabolic and anabolic enzymatic reactions. Their collective effects are particularly prevalent to numerous aspects of brain function, including energy production, DNA/RNA synthesis/repair, genomic and non-genomic methylation, and the synthesis of numerous neurochemicals and signaling molecules. However, human epidemiological and controlled trial investigations, and the resultant scientific commentary, have focused almost exclusively on the small sub-set of vitamins (B9/B12/B6) that are the most prominent (but not the exclusive) B-vitamins involved in homocysteine metabolism. Scant regard has been paid to the other B vitamins. This review describes the closely inter-related functions of the eight B-vitamins and marshals evidence suggesting that adequate levels of all members of this group of micronutrients are essential for optimal physiological and neurological functioning. Furthermore, evidence from human research clearly shows both that a significant proportion of the populations of developed countries suffer from deficiencies or insufficiencies in one or more of this group of vitamins, and that, in the absence of an optimal diet, administration of the entire B-vitamin group, rather than a small sub-set, at doses greatly in excess of the current governmental recommendations, would be a rational approach for preserving brain health.”
Vitamin B12 Deficiency as a Worldwide Problem
2004 | PMID: 15189123 | DOI: 10.1146/annurev.nutr.24.012003.132440
ABSTRACT:
“Dietary deficiency of vitamin B12 due to vegetarianism is increasing and causes hyperhomocysteinemia. The breast-fed infant of a vitamin B12–deficient mother is at risk for severe developmental abnormalities, growth failure, and anemia. Elevated methylmalonic acid and/or total homocysteine are sensitive indicators of vitamin B12–deficient diets and correlate with clinical abnormalities. Dietary vitamin B12 deficiency is a severe problem in the Indian subcontinent, Mexico, Central and South America, and selected areas in Africa. Dietary vitamin B12 deficiency is not prevalent in Asia, except in vegetarians. Areas for research include intermittent vitamin B12 supplement dosing and better measurements of the bioavailability of B12 in fermented vegetarian foods and algae.”
Vitamin B12 Intake From Animal Foods, Biomarkers, and Health Aspects
2019 | PMID: 31316992 | DOI: 10.3389/fnut.2019.00093
“Vitamin B12 deficiency is common worldwide, especially in populations with low consumption of animal foods because of low socioeconomic status, ethical reasons, or because of their lifestyle (i.e., vegans).”
“Diagnosis of vitamin B12 deficiency is hampered by low specificity of available biomarkers, and there is no consensus yet regarding the optimal definition of low vitamin B12 status.”
OVERALL SUMMARY:
“a major concern of diets low or without animal products is the risk of vitamin B12 deficiency. This review showed that a total intake of vitamin B12 from the diet between 4 and 7 μg/d is associated with normal plasma vitamin B12 and MMA and thus appears to be adequate to maintain body vitamin B12 status in adults. However, this intake might not be sufficient if people have difficulties in chewing foods, releasing the vitamin from its food binding, and/or absorbing it due to intrinsic factor antibodies or medications.”
“nutritional composition of different dairy (milk, yogurt, cheese, curd cheese), meat (chicken, pork, veal), and fish (lean vs. fatty) differs considerably, and bioavailability of vitamin B12 from these different animal food products together with potential interactions between vitamin B12 and other nutrients from these nutrient-dense animal products are unclear. Therefore, nutrient-density or well-known interactions between nutrients, such as folate and vitamin B12, should also be considered when studying the relations of intake on status or health.”
Vitamin B12: The Forgotten Micronutrient for Critical Care
2010 | PMID: 20717016 | DOI: 10.1097/MCO.0b013e32833dfaec
RECENT FINDINGS:
“Cobalamins could potentially be useful agents for inhibiting nitric oxide synthase and nitric oxide production, controlling nuclear factor-kappa B activation, and restoring optimal bacteriostasis and phagocytosis in which transcobalamins play a proven role. The antioxidant properties of vitamin B12, with a glutathione-sparing effect, are secondary to stimulation of methionine synthase activity and reaction with free oxygen or nitrogen radicals. Large parenteral doses are routinely administered for cyanide poisoning, with only mild, reversible side-effects. Current evidence suggests that high-dose parenteral vitamin B12 may prove an innovative approach to treat critically ill systemic inflammatory response syndrome patients, especially those with severe sepsis/septic shock. In this setting, vitamin B12 and transcobalamins could modulate systemic inflammation contributing to the anti-inflammatory cascade and potentially improve outcome.”
Vitamin B12 Deficiency in Children and Adolescents
2001 | PMID: 11148506 | DOI:10.1067/mpd.2001.112160
“Vitamin B12 (cobalamin) deficiency has been previously thought to be rare in children; however, recent studies suggest that the condition is more common than previously recognized. Vitamin B12 deficiency in children often presents with nonspecific manifestations, such as developmental delay, irritability, weakness, and failure to thrive.”
Vitamins for Chronic Disease Prevention in Adults: Scientific Review
2002 | PMID: 12069675 | DOI: 10.1001/jama.287.23.3116
CONCLUSION:
“Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation, particularly for fat-soluble vitamins. Inadequate intake of several vitamins has been linked to chronic diseases, including coronary heart disease, cancer, and osteoporosis.”
Interrelationships of Undernutrition and Neurotoxicity: Food for Thought and Research Attention
2012 | PMID: 22394483 | DOI: 10.1016/j.neuro.2012.02.015
ABSTRACT:
“The neurotoxic actions of chemical agents on humans and animals are usually studied with little consideration of the subject’s nutritional status. States of protein-calorie, vitamin and mineral undernutrition are associated with a range of neurodevelopmental, neurological and psychiatric disorders, commonly with involvement of both the central and peripheral nervous system. Undernutrition can modify risk for certain chemical-induced neurologic diseases, and in some cases undernutrition may be a prerequisite for neurotoxicity to surface. In addition, neurologic disease associated with undernutrition or neurotoxicity may show similarities in clinical and neuropathological expression, especially in the peripheral nervous system. The combined effects of undernutrition and chemical neurotoxicity are most relevant to people of low-income who experience chronic hunger, parasitism and infectious disease, monotonous diets of plants with neurotoxic potential (notably cassava), environmental pollution from rapid industrial development, chronic alcohol abuse, and prolonged treatment with certain therapeutic drugs. Undernutrition alone or in combination with chemical exposure is also important in high-income societies in the setting of drug and alcohol abuse, old age, food faddism, post-bariatric surgery, and drug treatment for certain medical conditions, including cancer and tuberculosis. The nutritional demands of pregnancy and lactation increases the risk of fetal and infant undernutrition and chemical interactions therewith.”
The Many Faces of Cobalamin (Vitamin B12) Deficiency
2019 | PMID: 31193945 | DOI: 10.1016/j.mayocpiqo.2019.03.002
CONCLUSION:
“Patients with low serum vitamin B12 levels may have no symptoms (yet). Nevertheless, they are at high risk for development of symptoms. There is a tendency among physicians to consider a serum vitamin B12 level higher than 140 pmol/L as normal, but many symptomatic patients may present with such levels, for instance because of taking oral vitamin supplementation. This does not mean that their tissue vitamin B12 levels are normal as well. Methylmalonic acid and homocysteine are not very sensitive biomarkers, but there is currently no good alternative, although systematic evaluation of more advanced metabolic factors may lead to the application of better biomarkers. When serum total vitamin B12 levels are low or questionable, the combination of total vitamin B12, active vitamin B12, MMA, and homocysteine may be the best strategy, but the validity of this combined biomarker approach needs to be validated in larger prospective studies and especially validated against objective markers of treatment response. In case of doubt, when results of biomarker measurements are equivocal, a trial with parenteral hydroxocobalamin injections may be considered, as was done in patients B and D. Because symptom improvement in long-standing (subclinical) vitamin B12 deficiency may take some time, we usually advise a treatment regimen of twice weekly hydroxocobalamin injections for 3 months, after which a thorough reevaluation is performed with systematic evaluation of symptom score as demonstrated in patient B (Table 2). There is no proof in large prospective, double-blind studies that oral supplementation is as effective in reducing symptoms associated with vitamin B12 deficiency as parenteral treatment.”
Neurologic Aspects of Cobalamin Deficiency
1991 | PMID: 1648656 | DOI: 10.1097/00005792-199107000-00001
ABSTRACT:
“Neurologic complaints, most commonly paresthesias or ataxia, were the first symptoms of Cbl deficiency in most episodes. The median duration of symptoms before diagnosis and treatment with vitamin B12 was 4 months, although long delays in diagnosis occurred in some patients. Diminished vibratory sensation and proprioception in the lower extremities were the most common objective findings. A wide variety of neurologic symptoms and signs were encountered, however, including ataxia, loss of cutaneous sensation, muscle weakness, diminished or hyperactive reflexes, spasticity, urinary or fecal incontinence, orthostatic hypotension, loss of vision, dementia, psychoses, and disturbances of mood. Multiple neurologic syndromes were often seen in a single patient.”
“In nonanemic patients in whom diagnosis was delayed, neurologic progression frequently occurred although the hematocrit remained normal. In 27 episodes, the serum cobalamin concentration was only moderately decreased (in the range of 100-200 pg/ml) and in 2 the serum level was normal. Neurologic impairment, as assessed by a quantitative severity score, was judged to be mild in 99 episodes, moderate in 39 and severe in 15. Severity of neurologic dysfunction before treatment was clearly related to the duration of symptoms prior to diagnosis. In addition, the hematocrit correlated significantly with severity, independent of the longer duration of symptoms in nonanemic patients. Four patients experienced transient neurologic exacerbations soon after beginning treatment with cyanocobalamin, with subsequent recovery.”
“All patients responded, and in 57 (47.1%), recovery was complete, with no remaining symptoms or findings on examination. The severity score was reduced by 50% or greater after treatment in 91% of the episodes. Residual long-term moderate or severe neurologic disability was noted following only 7 (6.3%) episodes. The extent of neurologic involvement after treatment was strongly related to that before therapy as well as to the duration of symptoms. The percent improvement over baseline neurologic status after treatment was inversely related to duration of symptoms and hematocrit. Some evidence of response was always seen during the first 3 months of treatment.”
B12 Deficiency with Neurological Manifestations in the Absence of Anaemia
2015 | PMID: 26385097 | DOI: 10.1186/s13104-015-1437-9
BACKGROUND:
“Vitamin B12 deficiency is often diagnosed with hematological manifestations of megaloblastic macrocytic anemia, which is usually the initial presentation. Neurological symptoms are often considered to be late manifestations and usually occur after the onset of anemia. Subacute combined cord degeneration, which is a rare cause of myelopathy, is however the commonest neurological manifestation of vitamin B12 deficiency.”
CASE PRESENTATION:
“We present a case of a 66 year old Sinhalese Sri Lankan female, who is a strict vegetarian, presenting with one month’s history suggestive of subacute combined cord degeneration in the absence of haematological manifestations of anaemia. Her serum B12 levels were significantly low, after which she was treated with hydroxycobalamine supplementation, showing marked clinical improvement of symptoms, with normalization of serum B12 levels. Hence, the diagnosis of vitamin B12 deficiency was confirmed retrospectively.”
CONCLUSION:
“Vitamin B12 deficiency could rarely present with neurological manifestations in the absence of anaemia. Therefore a high index of suspicion is necessary for the early diagnosis and prompt treatment in order to reverse neurological manifestations, as the response to treatment is inversely proportionate to the severity and duration of the disease.”
2019 | PMID: 30761552 | DOI: 10.1002/jimd.12012
ABSTRACT:
“This review gives an overview of clinical characteristics, treatment and outcome of nutritional and acquired cobalamin (Cbl; synonym: vitamin B12) deficiencies, inborn errors of Cbl absorption and intracellular trafficking, as well as methylenetetrahydrofolate dehydrogenase (MTHFD1) and methylene tetrahydrofolate reductase (MTHFR) deficiencies, which impair Cbl-dependent remethylation. Acquired and inborn Cbl-related disorders and MTHFR deficiency cause multisystem, often severe disease. Failure to thrive, neurocognitive or psychiatric symptoms, eye disease, bone marrow alterations, microangiopathy and thromboembolic events are characteristic. The recently identified MTHFD1 defect additionally presents with severe immune deficiency. Deficient Cbl-dependent enzymes cause reduced methylation capacity and metabolite toxicity. Further net-effects of perturbed Cbl function or reduced Cbl supply causing oxidative stress, altered cytokine regulation or immune functions are discussed.”
Vitamin B12 in Relation to Oxidative Stress: A Systematic Review
2019 | PMID: 30823595 | DOI: 10.3390/nu11020482
ABSTRACT:
“The triage theory posits that modest micronutrient deficiencies may induce reallocation of nutrients to processes necessary for immediate survival at the expense of long-term health. Neglected processes could in time contribute to the onset of age-related diseases, in which oxidative stress is believed to be a major factor. Vitamin B12 appears to possess antioxidant properties. This review aims to summarise the potential antioxidant mechanisms of B12 and investigate B12 status in relation to oxidative stress markers.”
CONCLUSIONS:
“Evidence from studies on B12 status in relation to oxidative stress consistently suggests that lower B12 status is related to increased pro-oxidants and decreased antioxidants, both overall and for subclinical B12 deficiency compared to normal B12 status. However, due to a lack of prospective research, consensus on appropriate biomarkers, and interventions focusing specifically on B12, causality cannot be established. It is therefore imperative that, in the future, agreed-upon gold standard assessments for B12 status and oxidative stress are established. In addition, prospective cohort studies and RCTs in healthy individuals with specific focus on B12 and oxidative stress are warranted to establish causality. If the triage theory proves true, the incidence of age-related diseases could potentially be lowered significantly by adequate B12 intake.”
2018 | PMID: 29037851 | DOI: 10.1016/j.ajpath.2017.08.032
ABSTRACT:
“Chronic deficiency of vitamin B12 is the only nutritional deficiency definitively proved to cause optic neuropathy and loss of vision. The mechanism by which this occurs is unknown. Optic neuropathies are associated with death of retinal ganglion cells (RGCs), neurons that project their axons along the optic nerve to the brain. Injury to RGC axons causes a burst of intracellular superoxide, which then signals RGC apoptosis. Vitamin B12 (cobalamin) was recently shown to be a superoxide scavenger, with a rate constant similar to superoxide dismutase. Given that vitamin B12 deficiency causes an optic neuropathy through unknown mechanisms and that it is a potent superoxide scavenger, we tested whether cobalamin, a vitamin B12 vitamer, would be neuroprotective in vitro and in vivo. We found that cobalamin scavenged superoxide in neuronal cells in vitro treated with the reduction-oxidation cycling agent menadione. In vivo confocal scanning laser ophthalmoscopy demonstrated that optic nerve transection in Long-Evans rats increased superoxide levels in RGCs. The RGC superoxide burst was significantly reduced by intravitreal cobalamin and resulted in increased RGC survival. These data demonstrate that cobalamin may function as an endogenous neuroprotectant for RGCs through a superoxide-associated mechanism.”
B Vitamins for Neuropathy and Neuropathic Pain
2014 | DOI: 10.4172/2376-1318.1000161
B VITAMINS, NEUROPATHY AND NEUROPATHIC PAIN:
“The proposed mechanisms for a role of vitamin B12 in pain relief have included the promotion of nerve regeneration and/or remyelination by accumulation of exogenous B12. Because vitamin B12 may act as a methyl donor in DNA metabolism, high concentrations upregulate gene transcription, increasing protein synthesis for nerve regeneration. Vitamin B12 may also be involved in selective blockade of sensory nerve conduction as a mechanism of action for vitamin B12 in painful conditions.”
Methylcobalamin: A Potential Vitamin of Pain Killer
2013 | PMID: 24455309 | DOI: 10.1155/2013/424651
ABSTRACT:
“Methylcobalamin (MeCbl), the activated form of vitamin B12, has been used to treat some nutritional diseases and other diseases in clinic, such as Alzheimer’s disease and rheumatoid arthritis. As an auxiliary agent, it exerts neuronal protection by promoting regeneration of injured nerves and antagonizing glutamate-induced neurotoxicity. Recently several lines of evidence demonstrated that MeCbl may have potential analgesic effects in experimental and clinical studies. For example, MeCbl alleviated pain behaviors in diabetic neuropathy, low back pain and neuralgia. MeCbl improved nerve conduction, promoted the regeneration of injured nerves, and inhibited ectopic spontaneous discharges of injured primary sensory neurons. This review aims to summarize the analgesic effect and mechanisms of MeCbl at the present.”
CONCLUSIONS:
“MeCbl or its combined use with other agents has the potential analgesic effect in specific patients and animal models, for example, nonspecific low back pain; neck pain; diabetic neuropathic pain, subacute herpetic neuralgia, glossopharyngeal neuralgia, and trigeminal neuralgia. However, its mechanisms underlying the analgesic effect were poorly understood. On the basis of recent work, the possible mechanisms can be considered as follows. (1) MeCbl improved nerve conduction velocity; (2) MeCbl promoted injured nerve regeneration, recovering the neuromuscular functions in peripheral hyperalgesia and allodynia; and (3) MeCbl inhibited the ectopic spontaneous discharges from peripheral primary sensory neurons in neuropathic pain states. As a vitamin, MeCbl may be a potential candidate for treating peripheral neuropathy with good safety.”
2018 | PMID: 29305340 | DOI: 10.2196/jmir.8667
CONCLUSION:
“Our data suggest that meat alone is not sufficient to prevent B12 deficiency and that the source of meat should also be considered. Our data also suggests that B12 intake inversely correlates with neurological symptoms, implying a role for B12 among a seemingly unaware population. Physicians should be aware of the possible role of B12 in any patient with neurological complaints or unexplained pain.”
Interrelations of Vitamin B12 and Folic Acid Metabolism: Folic Acid Clearance Studies
1962 | PMID: 13906634 | DOI: 10.1172/JCI104589
“The vast majority of patients with megaloblastic anemia have been found to have deficiency of vitamin B12, of folic acid, or of both vitamins. For this reason, the possible interrelations of these two vitamins have long piqued the curiosity of investigators (1, 2).”
“’The purpose of the present investigation was to determine whether the rapid disappearance of folic acid activity for S. faecalis from the serum of subjects with pernicious anemia reflects tissue depletion of folic acid, as believed by prior investigators, or instead indicates inadequate utilization of folic acid due to vitamin B12 deficiency. Prior results of part of these studies (7-10) suggest the latter is the case.”
“The studies here presented elaborate on our preliminary reports (7-10), indicating that folic acid activity “piles up” in human serum in the presence of vitamin B12 deficiency. The accumulation of this folic acid activity (probably N5-methyl-tetrahydrofolic acid) provides direct evidence of deranged folic acid metabolism due to vitamin B12 deficiency. This folic acid-vitamin B12 interrelationship may explain much of the confusion in therapy of pernicious anemia, as well as the fact that the anemias of vitamin B12 and folic acid deficiencies are hematologically identical.”
Vitamin B12 and the Risk of Neural Tube Defects in a Folic-Acid-Fortified Population
2007 | PMID: 17474166 | DOI: 10.1097/01.ede.0000257063.77411.e9
CONCLUSION:
“There was almost a tripling in the risk for NTD in the presence of low maternal B12 status, measured by holoTC. The benefits of adding synthetic B12 to current recommendations for periconceptional folic acid tablet supplements or folic-acid-fortified foods need to be considered. It remains to be determined what fraction of NTD cases in a universally folate-fortified environment might be prevented by higher periconceptional intake of B12.”
Folic Acid Fortification: Why Not Vitamin B12 Also?
2011 | PMID: 21674649 | DOI: 10.1002/biof.173
ABSTRACT:
“Folic acid fortification of cereal grains was introduced in many countries to prevent neural tube defect occurrence. The metabolism of folic acid and vitamin B12 intersect during the transfer of the methyl group from 5-methyltetrahydrofolate to homocysteine catalyzed by B12-dependent methioine synthase. Regeneration of tetrahydrofolate via this reaction makes it available for synthesis of nucleotide precursors. Thus either folate or vitamin B12 deficiency can result in impaired cell division and anemia. Exposure to extra folic acid through fortification may be detrimental to those with vitamin B12 deficiency. Among participants of National Health And Nutrition Examination Survey with low vitamin B12 status, high serum folate (>59 nmol/L) was associated with higher prevalence of anemia and cognitive impairment when compared with normal serum folate. We also observed an increase in the plasma concentrations of total homocysteine and methylmalonic acid (MMA), two functional indicators of vitamin B12 status, with increase in plasma folate under low vitamin B12 status. These data strongly imply that high plasma folate is associated with the exacerbation of both the biochemical and clinical status of vitamin B12 deficiency. Hence any food fortification policy that includes folic acid should also include vitamin B12.”
2013 | PMID: 11018684 | DOI: 10.1016/s0009-9120(00)00083-7
BACKGROUND:
“In November 1998, Canada began its mandatory fortification of all flour, and some corn and rice products, with folic acid. We evaluated the status of folate and vitamin B12 in Ontario since this fortification program began, and also studied the role of plasma homocysteine in the assessment of vitamin B12 deficiency since that time.”
CONCLUSION:
“In a large select group of Ontarians, serum and red cell folate concentrations appear to be higher than expected, possibly due to a recent national folate fortification programme; cobalamin levels are no higher than expected. Given our inability to detect mild B12 deficiency using such indicators as plasma homocysteine, and considering the substantial growth in the elderly segment of the Canadian population, occult cobalamin deficiency could become a common disorder. Accordingly, we recommend either consideration of the addition of vitamin B12 to the current folate fortification programme, and/or the development of better methods for the detection of cobalamin deficiency.”
5 Reasons Why Vitamin B12 Deficiency Harms Fertility
1. FEMALE INFERTILITY: “If you did not already know, vitamin B12 is a vital component for methylation and vitamin B12 deficiency can lead to high homocysteine levels. Studies show that vitamin B12 deficiency creates an imbalance in one carbon metabolism — a process involving folate, MTHFR, and homocysteine — that decreases female fertility and compromises the ability for fertilized embryos to implant themselves in the uterus. High homocysteine levels are associated with a variety of fertility and health problems. We are written about homocysteine levels at length in articles you can find here and more about MTHFR in preconception and pregnancy here.”
2. INCREASED RISK OF MISCARRIAGE: “Miscarriage is common among people who are deficient in vitamin B12, due to associated high homocysteine levels and methylation problems. Elevated homocysteine levels drastically increase the risk of developing blood clots during pregnancy, and in many cases, clots that occur during pregnancy are what leads to miscarriage.”
3. IRREGULAR OVULATION: “A regular ovulatory cycle is important for fertility because if gives you a greater chance at accurately predicting when you are most fertile. If vitamin B12 deficiencies are chronic, women seeking to become pregnancy will also experiences inconsistent ovulatory cycles, changes to the development of the ovum, and experience chronic implantation issues.”
4. INCREASED RISK OF NEURAL TUBE DEFECTS: “Neural tube defects are more prevalent in women with vitamin B12 deficiencies due to how closely vitamin B12 relates to the folate cycle. Vitamin B12 and the active form of folate is needed to convert homocysteine to methionine. Without enough vitamin B12 homocysteine begins to rise leading to previously mentioned fertility problems, but also methylation issues arise due to low methionine levels. A growing fetus requires a lot of methylation to coordinate its growth effectively, especially its nervous system, and without adequate folate and vitamin B12 levels there is an increased risk of developing neural tube defects.”
5. MALE INFERTILITY: “Women are not the only ones who need to worry about the effect vitamin B12 deficiency can have on their fertility. Men with low vitamin B12 levels are likely to be one of the causes of idiopathic male infertility, especially within men who have the MTHFR C667T genetic mutation.”
2016 | PMID: 27076577 | DOI: 10.3945/ajcn.115.123083
BACKGROUND:
“Vitamin B-12 and folate are micronutrients essential for normal embryogenesis. Vitamin B-12 insufficiency in pregnancy is high in certain parts of the world, such as India, and although this has been linked to low birth weight (LBW) in these populations, the relation between vitamin B-12 and birth weight (BW) elsewhere is unknown.”
CONCLUSIONS:
“Our review indicates that vitamin B-12 insufficiency during pregnancy is common even in nonvegetarian populations and that concentrations of vitamin B-12 decrease from the first to the third trimester. There is no consistent association between vitamin B-12 insufficiency and LBW. However, given the long-term risks of LBW, this observation warrants further cohort studies and randomized controlled trials.”
2013 | PMID: 23781950 | DOI: 10.1111/jpc.12292
RESULTS:
“Almost all of the children had been fed with breast milk and a poor nutritional state was found in all of the mothers. Non-specific findings such as growth retardation (78%), hyperpigmentation of the skin (78%), diarrhoea (63.4%), convulsion (14.6%), weakness, reluctance to eat, vomiting, irritability and tremor were found in all the patients, in addition to hypotonia, motor retardation and pallor. Treatment with vitamin B12 provided recovery in all the patients.”
1997 | PMID: 8990052 | DOI: 10.1002/mds.870120108
ABSTRACT:
“Developmental regression is the presenting symptom of most infants with cobalamin (Vitamin B12) deficiency. We present a report of three infants with cobalamin deficiency in which the infants also developed a movement disorder. In each case the mother was a vegetarian and the infant was exclusively breast-fed.”
“The presence of a movement disorder in cobalamin deficiency has received less attention than other features, but in a mild form is probably common. It may offer an early clue to the diagnosis before the onset of profound neurological deterioration.”
Brief Report: Childhood Disintegrative Disorder as a Likely Manifestation of Vitamin B12 Deficiency
2013 | PMID: 23334842 | DOI: 10.1007/s10803-013-1762-6
ABSTRACT:
“Childhood disintegrative disorder is a rare disorder, characterized by regression of acquired skills after a period of normal development. The case of childhood disintegrative disorder presented here was found to have vitamin B12 deficiency and hyperhomocysteinemia on extensive evaluation to find a probable cause for regression. This case illustrates the need for a thorough evaluation of all cases of childhood disintegrative disorder so that treatable causes of regression, like vitamin B12 deficiency, are not missed.”
Vitamin B12 Deficiency in Children: A Treatable Cause of Neurodevelopmental Delay
2015 | PMID: 24453156 | DOI: 10.1177/0883073813516194
ABSTRACT:
“Vitamin B12 deficiency in children can rarely cause neurologic manifestations. In this series, 14 pediatric cases (median age 11 months) have been described in whom association of vitamin B12 deficiency with developmental delay or regression was observed. Severe to profound delay was present in 8 (57%) patients. All the patients were exclusively or predominantly breast-fed and 10 of 12 mothers had low serum vitamin B12 levels. Three to 6 months after treatment, a mean gain of development quotient of 38.8 points was seen in 7 follow-ups. In settings with a high prevalence of vitamin B12 deficiency, this association should be actively searched for.”
Pediatric Vitamin B12 Deficiency: When Autism Isn’t Autism
“Learning and behavioral disabilities and autism spectrum disorders have multiple causes, and B12 deficiency is only 1 piece of the puzzle. Yet it is often overlooked. In fact, it is easily treated and certainly preventable. Given the epidemic of these disorders and the devastating social and financial costs, it is crucial that we explore the B12 link. As a health care provider involved with children, remember the ABCs—Autism B12 Connection—because an early diagnosis can save a child and his or her family from a lifetime of disability and hardship.”
Neuropsychiatric Disorders Caused by Cobalamin Deficiency in the Absence of Anemia or Macrocytosis
1988 | PMID: 3374544 | DOI: 10.1056/NEJM198806303182604
ABSTRACT:
“Among 141 consecutive patients with neuropsychiatric abnormalities due to cobalamin deficiency, we found that 40 (28 percent) had no anemia or macrocytosis. The hematocrit was normal in 34, the mean cell volume was normal in 25, and both tests were normal in 19. Characteristic features in such patients included paresthesia, sensory loss, ataxia, dementia, and psychiatric disorders; long-standing neurologic symptoms without anemia; normal white-cell and platelet counts and serum bilirubin and lactate dehydrogenase levels; and markedly elevated serum concentrations of methylmalonic acid and total homocysteine.”
“We conclude that neuropsychiatric disorders due to cobalamin deficiency occur commonly in the absence of anemia or an elevated mean cell volume and that measurements of serum methylmalonic acid and total homocysteine both before and after treatment are useful in the diagnosis of these patients.”
Vitamin B12 Deficiency: A Rare Cause of Excessive Daytime Sleepiness
2019 | PMID: 31538608 | DOI: 10.5664/jcsm.7936
ABSTRACT:
“Excessive daytime sleepiness (EDS) is one of the leading reasons that patients present to sleep clinics. Approximately 10% to 14% of the adults report that excessive sleepiness interferes with their daily lives. Common causes of EDS include obstructive sleep apnea, sleep deprivation, circadian rhythm disorders, medication effects, psychiatric conditions especially depression, and primary hypersomnia such as narcolepsy or central idiopathic hypersomnia. Vitamin B12 deficiency is a rare cause of EDS. We are presenting a case of severe vitamin B12 deficiency as an unusual and rare cause of hypersomnia.”
Treatment of Depression: Time to Consider Folic Acid and Vitamin B12
2005 | PMID: 15671130 | DOI: 10.1177/0269881105048899
ABSTRACT:
“We review the findings in major depression of a low plasma and particularly red cell folate, but also of low vitamin B12 status. Both low folate and low vitamin B12 status have been found in studies of depressive patients, and an association between depression and low levels of the two vitamins is found in studies of the general population. Low plasma or serum folate has also been found in patients with recurrent mood disorders treated by lithium. A link between depression and low folate has similarly been found in patients with alcoholism. It is interesting to note that Hong Kong and Taiwan populations with traditional Chinese diets (rich in folate), including patients with major depression, have high serum folate concentrations. However, these countries have very low lifetime rates of major depression. Low folate levels are furthermore linked to a poor response to antidepressants, and treatment with folic acid is shown to improve response to antidepressants. A recent study also suggests that high vitamin B12 status may be associated with better treatment outcome. Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional marker of both folate and vitamin B12 deficiency. Increased homocysteine levels are found in depressive patients. In a large population study from Norway increased plasma homocysteine was associated with increased risk of depression but not anxiety. There is now substantial evidence of a common decrease in serum/red blood cell folate, serum vitamin B12 and an increase in plasma homocysteine in depression. Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is shown to be overrepresented among depressive patients, which strengthens the association. On the basis of current data, we suggest that oral doses of both folic acid (800 µg daily) and vitamin B12 (1 mg daily) should be tried to improve treatment outcome in depression.”
Vitamin Supplementation in the Treatment of Schizophrenia
2014 | PMID: 24846474 | DOI: 10.1007/s40263-014-0172-4:
ABSTRACT:
“This article reviews the current literature addressing the treatment of schizophrenia with vitamin supplementation. It describes the important roles that vitamins play in normal metabolism, and reviews the evidence pertaining to vitamin deficiency and supplementation in patients with schizophrenia. There is mounting evidence suggesting that vitamin supplementation, in particular with folic acid, vitamin B12 and vitamin D, may be important in treatment within certain subgroups of patients.”
Massive Doses of Vitamin B12 in Treatment of Schizophrenia
1955 | PMID: 14349437 | DOI: 10.1001/archneurpsyc.1955.02330090091012
ABSTRACT:
“During the past few years vitamin B12 has been used successfully in the treatment of various disorders of the nervous system, especially various painful neuropathies. When solutions of greater potency became available, it was found that doses of 1000γ daily would relieve the pain in many cases of trigeminal neuralgia. The exact mode of action is obscure, but it does not appear to be on a simple replacement basis. An effect on the “deranged intrinsic nerve metabolism” has been suggested. Because of these encouraging reports, it was decided to try massive doses of vitamin B12 in treatment of schizophrenic patients, who might also be said to have an obscure disorder of the nervous system.”
Vitamin B12 and Folate Depletion in Cognition: A Review
2004 | PMID: 15472418
“In cross-sectional studies, low levels of folate and B12 have been shown to be associated with cognitive decline and dementia. Evidence for the putative role of folate, vitamin B12 in neurocognitive and other neurological functions comes from reported cases of severe vitamin deficiencies, particularly pernicious anemia, and homozygous defects in genes that encode for enzymes of one-carbon metabolism. The neurological alterations seen in these cases allow for a biological role of vitamins in neurophysiology. Results are quite controversial and there is an open debate in literature, considering that the potential and differential role of folate and B12 vitamin in memory acquisition and cognitive development is not completely understood or accepted. What is not clear is the fact that vitamin B12 and folate deficiency deteriorate a pre-existing not overt pathological situation or can be dangerous even in normal subjects.“
Cognitive Impairment and Vitamin B12: A Review
2012 | PMID: 22221769 | DOI: 10.1017/S1041610211002511
CONCLUSION:
“Low serum vitamin B12 levels are associated with neurodegenerative disease and cognitive impairment. There is a small subset of dementias that are reversible with vitamin B12 therapy and this treatment is inexpensive and safe.”
2004 | PMID: 15065230 | DOI: 10.1002/gps.1092
CONCLUSION:
“The observed negative correlations between levels of vitamin B12 and folate and cognitive impairment in both AD and FTD patients, raise the possibility of a non-specific etiological role. Although levels of vitamin B12 and folate did not correlate with BPSD in AD patients, negative correlations between serum vitamin B12 levels and BPSD in FTD patients were revealed. Decreased serum vitamin B12 levels may predispose FTD patients to develop hallucinations and diurnal rhythm disturbances.”
Metabolic Vitamin B12 Deficiency: A Missed Opportunity to Prevent Dementia and Stroke
2016 | PMID: 26597770 | DOI: 10.1016/j.nutres.2015.10.003
ABSTRACT:
“The purpose of this narrative review is to highlight insights into the importance and frequency of metabolic vitamin B12 (B12) deficiency, reasons why it is commonly missed, and reasons for the widespread but mistaken belief that treatment of B12 deficiency does not prevent stroke or improve cognitive function. Metabolic B12 deficiency is common, being present in 10%-40% of the population; is frequently missed; is easily treated; and contributes importantly to cognitive decline and stroke in older people. Measuring serum B12 alone is not sufficient for diagnosis; it is necessary to measure holotranscobalamin or functional markers of B12 adequacy such as methylmalonic acid or plasma total homocysteine. B-vitamin therapy with cyanocobalamin reduces the risk of stroke in patients with normal renal function but is harmful (perhaps because of thiocyanate accumulation from cyanide in cyanocobalamin) in patients with renal impairment. Methylcobalamin may be preferable in renal impairment. B12 therapy slowed gray matter atrophy and cognitive decline in the Homocysteine and B Vitamins in Cognitive Impairment Trial. Undiagnosed metabolic B12 deficiency may be an important missed opportunity for prevention of dementia and stroke”
2010 | PMID: 20838622 | DOI: 10.1371/journal.pone.0012244
CONCLUSION:
“The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer’s disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer’s disease, trials are needed to see if the same treatment will delay the development of Alzheimer’s disease.”
Homocysteine and Dementia: An International Consensus Statement
2018 | PMID: 29480200 | DOI: 10.3233/JAD-171042
ABSTRACT:
“Identification of modifiable risk factors provides a crucial approach to the prevention of dementia. Nutritional or nutrient-dependent risk factors are especially important because dietary modifications or use of dietary supplements may lower the risk factor level. One such risk factor is a raised concentration of the biomarker plasma total homocysteine, which reflects the functional status of three B vitamins (folate, vitamins B12, B6). A group of experts reviewed literature evidence from the last 20 years. We here present a Consensus Statement, based on the Bradford Hill criteria, and conclude that elevated plasma total homocysteine is a modifiable risk factor for development of cognitive decline, dementia, and Alzheimer’s disease in older persons. In a variety of clinical studies, the relative risk of dementia in elderly people for moderately raised homocysteine (within the normal range) ranges from 1.15 to 2.5, and the Population Attributable risk ranges from 4.3 to 31%. Intervention trials in elderly with cognitive impairment show that homocysteine-lowering treatment with B vitamins markedly slows the rate of whole and regional brain atrophy and also slows cognitive decline. The findings are consistent with moderately raised plasma total homocysteine (>11 mol/L), which is common in the elderly, being one of the causes of age-related cognitive decline and dementia. Thus, the public health significance of raised tHcy in the elderly should not be underestimated, since it is easy, inexpensive, and safe to treat with B vitamins. Further trials are needed to see whether B vitamin treatment will slow, or prevent, conversion to dementia in people at risk of cognitive decline or dementia.”
Reversible Vitamin B12 Deficiency Presenting with Acute Dementia, Paraparesis, and Normal Hemoglobin
2016 | PMID: 28070432 | DOI: 10.1155/2016/4301769
DISCUSSION:
“We present the case of a middle-aged man, with no previous history of psychiatric illness, who presented with acute dementia and paraparesis since two months with normal hemoglobin levels. He visited many physicians during this time and was diagnosed with organic mood disorder. The patient was prescribed antipsychotic medication but showed no improvement. The patient’s acute presentation of delirium and profound neuropsychosis was the main obstacle for early diagnosis. Further diagnostic workup indicated vitamin B12 deficiency with evidence of ineffective erythropoiesis. The patient had a remarkable response to vitamin B12 replacement, and all antipsychotic medications were stopped.”
“There are multiple factors that lead to misdiagnosis of vitamin B12 deficiency. Most physicians are not aware that psychiatric symptoms may sometimes be the only presenting symptoms of vitamin B12 deficiency. Most doctors depend on MCV and MCH values to diagnose vitamin B12 deficiency. However, perturbations in MCV and MCH are late signs of vitamin B12 deficiency. In addition, the serum vitamin B12 test is not very sensitive or specific. At the same time, serum vitamin B12 levels need not to be very low in order to produce psychiatric symptoms. It has been shown that vitamin B12 levels become deficient in neuronal tissue before deficiency is evident in the serum. In such cases, homocysteine and methylmalonic acid assays increase the specificity of the diagnosis of B12 deficiency. However, since these lab tests are not available in our hospital, we confirmed our diagnosis using the treatment response. The patient had dramatic clinical improvement and MCV dropped to 79 fL.”
”Although vitamin B12 deficiency is common, it may sometimes be overlooked. The most common known manifestation of vitamin B12 deficiency is megaloblastic anemia. The purpose of this case report is to show that if vitamin B12 deficiency remains undiagnosed, serious sequelae may occur. Assessment of B12 levels should be included as a standard evaluation in patients presenting with new onset of depressive disorders, acute delirium, dementia, or psychosis. Therefore, prevention, early detection, and management of this reversible state are of profound importance.”
The Master Key Effect of Vitamin B12 in Treatment of Malignancy–A Potential Therapy?
2008 | PMID: 17640826 | DOI: 10.1016/j.mehy.2007.05.029
SUMMARY:
“Vitamin B12 plays a functional role in a variety of organs and body systems and the list of these organs and body systems is growing. According to our working hypothesis (“Master Key Effect”) vitamin B12 has some unique functions, which are still not accepted; vitamin B12 functions to keep body systems in balance, even under the stress of severe pathology. What is the explanation for elevation of cobalamin level in oncological patients?
1. It is well known that there is a high level of vitamin B12 in different kinds of malignancy.
2. There is a positive correlation between level of vitamin B12 and the severity of the disease, the more severe the disease the higher the level of B12.
3. A number of the experimental laboratory studies indicate an inhibition in the growth of malignant cells upon use of vitamin B12.
4. There are no experimental results indicating the opposite, that vitamin B12 stimulates growth of malignant cells.
5. There is no data about toxic effect of vitamin B12 in the treatment of various diseases.
As yet I have not been able to find another explanation for high level of vitamin B12 in oncology patients other than that it is a compensatory mechanism. Perhaps following this body’s “warning sign”, we should start treatment with high doses of vitamin B12 to try to help the stabilization of normal function of the organs and systems. Laboratory researches should be continued to substantiate introduction of cobalamin as preliminary treatment of particular diseases.”
New Derivatives of Vitamin B12 Show Preferential Targeting of Tumors
2008 | PMID: 18413759 | DOI: 10.1158/0008-5472.CAN-07-6771
ABSTRACT:
“Rapidly growing cells show an increased demand for nutrients and vitamins. The objective of our work is to exploit the supply route of vitamin B12 to deliver new derivatives of this vital vitamin to hyperproliferative cells. To date, radiolabeled (Co and In) vitamin B12 derivatives showed labeling of tumor tissue but also undesired high accumulation of radioactivity in normal tissue. By abolishing the interaction of a tailored vitamin B12 derivative to its transport protein transcobalamin II and therefore interrupting transcobalamin II receptor and megalin mediated uptake in normal tissue, preferential accumulation of a radiolabeled vitamin in cancer tissue could be accomplished. We identified transcobalamin I on tumors as a possible new receptor for this preferential accumulation of vitamin-mediated targeting. The low systemic distribution of radioactivity and the high tumor to blood ratio opens the possibility of a more successful clinical application of vitamin B12 for imaging or therapy.”
Relationship Between Malignant Brain Tumors and Values of Homocysteine, Folic Acid and Vitamin B12
2018 | DOI: 10.2478/sjecr-2018-0045
ABSTRACT:
“Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Homocysteine (Hcy) has a detrimental influence on human neurons, considering that human GBM cells undergo cell death already at D,L-Hcy concentrations in culture medium of 50 μM. This data demonstrate that Hcy is a potent gliotoxic agent capable of inducing the death of human glial cells already at concentrations reached in brain during hyperhomocysteinemia. The one retrospective study found that the serum vitamin B12 level can be used to predict survival time in metastatic cancer patients including neurological cancer.”
Vitamin B12 Deficiency Mimicking Acute Leukemia in a Child
2014 | DOI: 10.4172/2165-7920.1000430
ABSTRACT:
“Deficiency of vitamin B12 is an important cause of megaloblastic anemia and bone marrow depression. Morphological and functional changes in bone marrow are observed related with vitamin B12 deficiency. Most importantly dysplastic changes can be mistaken as myelodysplastic syndrome or acute leukemia. In adult cases of vitamin B12 deficiencies mimicking acute leukemia were reported. Our case is an alerting example of vitamin B12 deficiency in children mimicking acute leukemia with dysplastic findings.”
1963 | PMID: 14085892 | DOI: 10.1136/adc.38.202.606
EXPERIMENTAL STUDIES:
“Biological studies showed that the mouse tumour, in contrast to the rat tumour, showed considerable uptake of vitamin B12, comparable to the liver (the main storage organ), and similar results were obtained when radioactive Co vitamin B12 was used. Thus it seems that uptake of vitamin B12 by the tumour is associated with its regression.”
Old or New Medicine? Vitamin B12 and Peripheral Nerve Neuropathy
2013 | PMID: 24018744
ABSTRACT:
“Methylcobalamin participates in nervous system maintenance through several mechanisms. Methylcobalamin is an active form of vitamin B12, and a coenzyme of methionine synthase, which is required for DNA and protein methylation. In addition, methylcobalamin facilitates neurite outgrowth and inhibits neural apoptosis through the Erk1/2 and Akt signaling pathways. Treatment with high doses of methylcobalamin ameliorates symptoms and negative electrophysiological findings in animal models of peripheral nerve neuropathy and in patients with carpal tunnel syndrome and amyotrophic lateral sclerosis. Thus, high-dose methylcobalamin has great potential for treating nervous system disorders.”
2014 | PMID: 25175124 | DOI: 10.2169/internalmedicine.53.1951
OBJECTIVE:
“Several experimental studies in vitro and in vivo have shown that a high dose of methylcobalamin (MeCbl), an analogue of vitamin B12, promotes axonal growth in peripheral nerve injury. We herein assessed the safety and efficacy of an ultra-high dose MeCbl treatment for patients with peripheral neuropathy and chronic axonal degeneration.”
CONCLUSION:
“Intravenous ultra-high dose MeCbl treatment is a safe and potentially efficacious therapy for patients with peripheral neuropathy and chronic axonal degeneration.”
“Scientists have found evidence suggesting that the severity of spinal muscular atrophy (SMA) may be ameliorated by common vitamins. The findings by researchers at the University of Pennsylvania School of Medicine, which are to be published Thursday in the journal Molecular Cell, suggest that folic acid and Vitamins B12 may limit the severity of symptoms that afflict SMA patients.”
“SMA afflicts one of every 6,000-to-10,000 people and is the leading genetic killer of children under the age of two. But its symptoms-muscle weakness and wasting-differ in severity from person to person across a range of debilitation that scientists still cannot explain fully. Most SMA patients die in their infancy, but some SMA patients do not become wheelchair bound before the age of 20, and still others can live relatively normally until late in life. Until now, this variability has been attributed to “genetic modifiers” but the present study raises the possibility that it is influenced, perhaps to a significant extent, by nutritional factors.”
“In addition to unraveling the function of the methylation of arginines in proteins — a common modification process that was first reported more than 30 years ago whose function remained unknown until now — the findings may have important implications for neurodegenerative disease. The methyl group tags are supplied by a “methyl donor” called SAM (for S-adensylmethionine), and SAM receives this methyl group from folic acid (also known as folate) through a pathway that requires vitamin B12. This, the Penn researchers believe, raises the possibility that deficiency in folate (many vegetables, grains and fruits are especially rich in folate) or the B vitamins could be particularly detrimental to SMA patients — because it could result in under-methylated proteins, which are exactly the kind of proteins SMN needs to find to function properly. Since SMA patients are already compromised in their levels of SMN, they might be expected to be more severely afflicted by such nutritional deficiencies.”
1948 | PMID: 18877711 | DOI: 10.1056/NEJM194808262390903
“It is well known that in patients with pernicious anemia, adequate therapy with desiccated stomach, whole liver and liver extracts for oral use, or with crude or refined liver extracts given by injection, will arrest the progress of combined system disease and may bring about a variable amount of recovery of nervous function, depending on the duration and severity of the process.”
2013 | PMID: 23566267 | DOI: 10.1111/pme.12081
CONCLUSIONS:
“Local methylcobalamin injection was not only efficacious in relieving pain, but also appears to be tolerable and a potential choice of treatment for subacute herpetic neuralgia.”
Ultra-High Dose Methylcobalamin Promotes Nerve Regeneration in Experimental Acrylamide Neuropathy
1994 | PMID: 8021696 | DOI: 10.1016/0022-510x(94)90290-9
ABSTRACT:
“After intoxication with acrylamide, all the rats showed equally decreased CMAP amplitudes. The animals were then divided into 3 groups; rats treated with ultra-high (500 μg/kg body weight, intraperitoneally) and low (50 μg/kg) doses of methyl-B12, and saline-treated control rats. Those treated with ultra-high dose showed significantly faster CMAP recovery than saline-treated control rats, whereas the low-dose group showed no difference from the control. Morphometric analysis revealed a similar difference in fiber density between these groups. Ultra-high doses of methyl-B12 may be of clinical use for patients with peripheral neuropathies.”
2014 | PMID: 24342621 | DOI: 10.1016/j.bbrc.2013.12.056
ABSTRACT:
“Our results suggest that MeCbl has beneficial effects on the muscle in vitro. MeCbl administration may provide a novel therapeutic approach for muscle injury or degenerating muscle after denervation.”
2015 | PMID: 26300733 | DOI: 10.3389/fncel.2015.00298
DISCUSSION:
“These findings led us to conclude that MeCbl may be effective in the treatment of LPC-induced neuropathic pain. Thus, the administration of MeCbl may be one of the treatments for peripheral nerve injury, neuropathic pain, and demyelinating diseases.”
Is There a Link Between Vitamin B and Multiple Sclerosis?
2018 | PMID: 28875857 | DOI: 10.2174/1573406413666170906123857
BACKGROUND:
“Damage to the myelin sheath (demyelination) is one of the main manifestations of multiple sclerosis (MS). Interestingly, both MS and vitamin B deficiency results in severe myelin degeneration that leads to loss in neuronal signal transmission.”
OBJECTIVE:
“Deficiency in vitamin B complex vary, although common symptoms include fatigue, increased oxidative stress, inflammation and demyelination. In particular, vitamin B12 (cobalamin) has had increased attention for its role in the methylation process, involvement in myelination and re-myelination, and reversal of MS symptoms.”
RESULTS:
“The anti-inflammatory and re-myelinating attributes of vitamin B complex members are promising”
Vitamin B12, Demyelination, Remyelination and Repair in Multiple Sclerosis
2005 | PMID: 15896807 | DOI: 10.1016/j.jns.2005.03.009
ABSTRACT:
“Multiple Sclerosis (MS) and vitamin B12 deficiency share common inflammatory and neurodegenerative pathophysiological characteristics. Due to similarities in the clinical presentations and MRI findings, the differential diagnosis between vitamin B12 deficiency and MS may be difficult. Additionally, low or decreased levels of vitamin B12 have been demonstrated in MS patients. Moreover, recent studies suggest that vitamin B12, in addition to its known role as a co-factor in myelin formation, has important immunomodulatory and neurotrophic effects. These observations raise the questions of possible causal relationship between the two disorders, and suggest further studies of the need to close monitoring of vitamin B12 levels as well as the potential requirement for supplementation of vitamin B12 alone or in combination with the immunotherapies for MS patients.”
MULTIPLE SCLEROSIS THERAPY AND VITAMIN B12:
“if confirmed, these findings emphasize the need for meticulous follow-up of vitamin B12 levels prior to and during immuno-therapy and for evaluation of the necessity of vitamin B12 supplementation for MS patients. This latter issue has received further support recently in a study of Mastronardi et al. who demonstrate dramatic improvements of clinical, histological, and laboratory parameters in in-vivo experimental models of demyelinating disease, through combination therapy with IFN-h plus vitamin B12.”
2015 | PMID: 25982504 | DOI: 10.1016/j.jns.2015.04.052
BACKGROUND:
“High-dose of methylcobalamin promotes nerve regeneration in rats with acrylamide neuropathy. A double-blind controlled trial suggested that high-dose methylcobalamin could increase compound muscle action potentials in patients with amyotrophic lateral sclerosis (ALS).”
RESULTS:
“In comparison with vehicle, mice treated with ultra-high dose (30 mg/kg) of methylcobalamin significantly inhibited muscle weakness and contracture in the forelimb, and increased the weight of the bicep muscles and the number of musculocutaneous nerves. Methylcobalamin-treated mice significantly elevated vitamin B12 concentrations of the serum, the bicep muscle and the spinal cord compared to vehicle.”
CONCLUSION:
“Our results suggest that treatment with methylcobalamin could delay progression of motor symptoms and neuropathological changes in wobbler mouse motor neuron disease if very high doses are used.”
2015 | NCT: 00444613
CONCLUSION:
“The present study demonstrated for the first time that ultra-high dose methylcobalamin can significantly prolong survival and retard progression in ALS if administered early.”
2018 | PMID: 30578206 | DOI: 10.2196/12046
DISCUSSION:
“JETALS is a study that aims to verify the superiority of high-dose E0302 (methylcobalamin, 50 mg) intramuscular administration over placebo and to examine its safety in patients with ALS using the Japanese version of the ALSFRS-R as an indicator.”
“Currently, only riluzole and edaravone have been approved as treatment drugs for ALS worldwide, but their effects are limited. As with the results of the subpopulation analysis, E0302 prolonged event-free survival more than 600 days and slowed the advance of the ALSFRS-R total score by 3.3 during 16 weeks; its safety and tolerability was well-established in the previous study [10]. Therefore, E0302 is highly anticipated as a new drug for treating ALS. E0302 can be used not only for monotherapy, but for multitherapy with riluzole and edaravone, which could change the strategy of ALS treatment.”
1998 | PMID: 9843082 | DOI: 10.1002/(sici)1097-4598(199812)21:12<1775::aid-mus22>3.0.co;2-v
ABSTRACT:
“To develop a symptomatic treatment for amyotrophic lateral sclerosis, we compared the effects of ultrahigh-dose and low-dose (25 and 0.5 mg/day, intramuscularly, for 14 days) methylcobalamin on averaged compound muscle action potential amplitudes (CMAPs) in a double-blind trial. No significant changes in CMAP amplitude were found in 12 patients who had the low-dose treatment at either 2 or 4 weeks after start of treatment. By contrast, 12 patients assigned to the ultrahigh-dose group demonstrated a significant increase at 4 weeks. This method may provide a clinically useful measure to improve or retard muscle wasting”
Intractable Epilepsy as the Presentation of Vitamin B Deficiency in the Absence of Macrocytic Anemia
2005 | PMID: 16026570 | DOI: 10.1111/j.1528-1167.2005.66204.x
“The diagnosis of vitamin B12 deficiency can be difficult when the typical macrocytic anemia is absent. A few cases with seizures as the manifestation of vitamin B12 deficiency have been reported, and macrocytic anemia also was noted in these patients. We report a patient with vitamin B12 deficiency presenting as intractable epilepsy in the absence of macrocytic anemia. The seizure attacks and all other symptoms/signs of vitamin B12 deficiency resolved after an intramuscular administration of cobalamin.”
Correlation Between Serum Vitamin B12 Level and Peripheral Neuropathy in Atrophic Gastritis
2018 | PMID: 29599609 | DOI: 10.3748/wjg.v24.i12.1343
CORE TIP:
“The general situation and peripheral nerve conduction velocity of 593 patients with chronic gastritis were compared. We found that serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. Vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. The occurrence of peripheral neuropathy associated with vitamin B12 deficiency may be considered in patients with chronic atrophic gastritis. Timely supplementation of vitamin B12 during the clinical treatment of chronic atrophic gastritis can reduce or prevent peripheral nervous system lesions.”
Vitamin B12 Deficiency in Chronic Gastritis
1964 | PMID: 14127505 | DOI: 10.1136/gut.5.1.27
EDITORIAL SYNOPSIS:
“This study covers a group of elderly persons who suffer from chronic atrophic gastritis and resulting vitamin B12 deficiency. Increasing weakness, loss of memory, and mental depression were common symptoms and flatulent dyspepsia was sometimes a troublesome recurring complaint. These symptoms were improved by treatment with vitamin B12. Even if untreated, persons in this group rarely develop severe pernicious anaemia.”
2013 | PMID: 23651730 | DOI: 10.1186/2251-6581-12-17
ABSTRACT:
“Vitamin B12 is an essential micronutrient required for optimal hemopoetic, neurocognitive and cardiovascular function. Biochemical and clinical vitamin B12 deficiency has been demonstrated to be highly prevalent among patients with type 1 and type 2 diabetes mellitus. It presents with diverse clinical manifestations ranging from impaired memory, dementia, delirium, peripheral neuropathy, subacute combined degeneration of the spinal cord, megaloblastic anemia and pancytopenia. This review article offers a current perspective on the physiological roles of vitamin B12, proposed pathophysiological mechanisms of vitamin B12 deficiency, screening for vitamin B12 deficiency and vitamin B12 supplementation among patients with diabetes mellitus.”
CONCLUSIONS:
“Clinical and biochemical vitamin B12 deficiency is highly prevalent among patients with both types 1 and 2 DM [diabetes mellitus].“
Risk Factors of Vitamin B12 Deficiency in Patients Receiving Metformin
2006 | PMID: 17030830 | DOI: 10.1001/archinte.166.18.1975
COMMENT:
“In conclusion, this nested case-control study in a Chinese population showed that the risk of vitamin B12 deficiency is magnified in patients who have received both a higher dose and longer course of metformin treatment, independent of other clinical variables.”
Therapeutic Role of Vitamin B12 in Patients of Chronic Tinnitus: A Pilot Study
2016 | PMID: 26960786 | DOI: 10.4103/1463-1741.178485
DISCUSSION:
“Multiple theories have been put forward to account for tinnitus related to disturbances of the peripheral auditory system, the auditory nerve, and cochlea. One of the mechanisms believed to be at play in Vitamin B12 deficiency neuropathy is hypomethylation in the central nervous system. Inhibition of the B12-dependent enzyme methionine synthase results in a fall in the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine; the resultant deficiency in SAM impairs methylation reactions in the myelin sheath. The methylation of homocysteine to methionine requires both methylcobalamin (an active form of Vitamin B12) and the active form of folic acid (5-methyltetrahydrofolate). Deficiency of Vitamin B12 leads to accumulation of homocysteine which is a neurotoxin and vascular toxin. Cochlear function is dependent on adequate vascular supply and the normal functioning of nerve tissue. B12 deficiency is associated with axonal degeneration, demyelination, and subsequent apoptotic neuronal death. Hcy has been implicated as a risk factor for vascular disease as well as brain atrophy. Concentrations of Hcy above 11.9 μmol/L were associated with approximately 3-fold higher risk for white matter damage when compared to concentrations below 8.6 μmol/L. Vitamin B12 deficiency may cause the demyelination of neurons in the cochlear nerve, resulting in hearing loss and tinnitus. In addition, low levels of Vitamin B12 and folate are associated with the destruction of the microvasculature of the stria vascularis, which might result in decreased endocochlear potential and in hearing loss and tinnitus. Martνnez-Vega et al. in their study, demonstrated, for the first time, that the relationship between hyperhomocysteinemia induced by folate deficiency and premature hearing loss involves impairment of cochlear homocysteine metabolism and associated oxidative stress.”
Vitamin B12 Supplementation in End Stage Renal Diseases: A Systematic Review
2015 | PMID: 26000261
RESULTS:
“The findings of this study revealed that, overall, the greatest effect of B12 supplementation on decreasing homocysteine levels in patients with ESRDs occurred when it was combined with folate supplementation. It was also demonstrated that injection treatments might be more beneficial than oral intake treatments.”
2017 | PMID: 29182708 | DOI: 10.14283/jpad.2017.15
CONCLUSIONS:
“High-dose B-vitamin supplementation provided modest cognitive benefit for kidney transplant recipients with elevated baseline tHcy.”
2019 | PMID: 31105562 | DOI: 10.3389/fphar.2019.00406
DISCUSSION:
“Myelin has a significant role in the progression of white matter pathology after TBI and in the potential for plasticity and subsequent recovery (Armstrong et al., 2016). Besides, myelin is an active form of vitamin B12, and the MeCbl plays an essential role in the synthesis and maintenance of myelin (Gröber et al., 2013). Vitamin B12 accelerates Schwann cells differentiation by suppressing Erk1/2 activities (Nishimoto et al., 2015). In addition, vitamin B12 has been reported to promote the remyelination in focal demyelination rat (Nishimoto et al., 2015). Thus, we evaluated the effect of vitamin B12 on remyelination after TBI. These data suggested that vitamin B12 increased the level of MBP, which plays vital roles in the myelination process and the appropriate formation of myelin thickness and compactness. Meanwhile, LFB staining showed that vitamin B12 restored myelin by reducing the vacuolar changes in the myelin sheath after TBI. We also used the ER stress inhibitor 4-PBA to assess the role of ER stress in remyelination. The results showed that ER stress was involved in the treatment of TBI induced myelin damage by vitamin B12. Therefore, we can conclude that the vitamin B12 enhance the survival of the nerve cell in the TBI mouse by inhibiting ER stress.”
Myelin Plasticity and Behaviour – Connecting the Dots
2017 | PMID: 29054040 | DOI: 10.1016/j.conb.2017.09.014
ABSTRACT:
“Myelin sheaths in the vertebrate nervous system enable faster impulse propagation, while myelinating glia provide vital support to axons. Once considered a static insulator, converging evidence now suggests that myelin in the central nervous system can be dynamically regulated by neuronal activity and continues to participate in nervous system plasticity beyond development. While the link between experience and myelination gains increased recognition, it is still unclear what role such adaptive myelination plays in facilitating and shaping behaviour.”
“In this review, we will discuss new insights into the link between myelin plasticity and behaviour, as well as mechanistic aspects of myelin remodeling that may help to elucidate this intriguing process.”
Evidence for Myelin Sheath Remodeling Revealed by In Vivo Imaging
2018 | PMID: 29429620 | DOI: 10.1016/j.cub.2018.01.017
Emerging Cellular and Molecular Strategies for Enhancing Central Nervous System (CNS) Remyelination
2018 | PMID: 29914096 | DOI: 10.3390/brainsci8060111
ABSTRACT:
“Myelination is critical for the normal functioning of the central nervous system (CNS) in vertebrates. Conditions in which the development of myelin is perturbed result in severely compromised individuals often with shorter lifespans, while loss of myelin in the adult results in a variety of functional deficits.”
“Several lines of evidence suggest it is feasible to develop strategies that enhance the capacity of the CNS to undergo remyelination and potentially reverse functional deficits. Such strategies include cellular therapies using either neural or mesenchymal stem cells as well as molecular regulators of oligodendrocyte development and differentiation. Given the prevalence of demyelinating diseases and their effects on the quality of life for affected individuals it is imperative that effective therapies are developed. Here we discuss some of the new approaches to CNS myelin repair that hold promise for reducing the burden of diseases characterized by myelin loss.”
Thin Myelin Sheaths as the Hallmark of Remyelination Persist Over Time and Preserve Axon Function
2017 | PMID: 29078396 | DOI: 10.1073/pnas.1714183114
Extensive Remyelination of the CNS Leads to Functional Recovery
2009 | PMID: 19342494 | DOI: 10.1073/pnas.0812500106
“Remyelination of the CNS in multiple sclerosis is thought to be important to restore conduction and protect axons against degeneration. Yet the role that remyelination plays in clinical recovery of function remains unproven. Here, we show that cats fed an irradiated diet during gestation developed a severe neurologic disease resulting from extensive myelin vacuolation and subsequent demyelination. Despite the severe myelin degeneration, axons remained essentially intact. There was a prompt endogenous response by cells of the oligodendrocyte lineage to the demyelination, with remyelination occurring simultaneously. Cats that were returned to a normal diet recovered slowly so that by 3–4 months they were neurologically normal. Histological examination of the CNS at this point showed extensive remyelination that was especially notable in the optic nerve where almost the entire nerve was remyelinated. Biochemical analysis of the diet and tissues from affected cats showed no dietary deficiencies or toxic accumulations. Thus, although the etiology of this remarkable disease remains unknown, it shows unequivocally that where axons are preserved remyelination is the default pathway in the CNS in nonimmune-mediated demyelinating disease. Most importantly, it confirms the clinical relevance of remyelination and its ability to restore function.”