In severe or prolonged cases, damage to the nerve cells may occur. In this case, symptoms may develop, such as sense loss, difficulty in proprioception, unsteady walking (ataxia), poor balance, loss of sensation in the feet, muscle weakness, blurred vision (either due to retinopathy or optic neuropathy), fertility problems, Impaired sense of taste and smell, decreased level of consciousness, depression, Irritability, confusion, memory loss, changes in reflexes, anxiety, clumsiness, cognitive impairment, psychosis, and, in severe cases, dementia. In some, less common, cases,<unk>  deficiency can occur without anemia. Tissue deficiencies may negatively affect nerve cells, bone marrow, and the skin. A further complication of severe deficiency is the neurological complex known as subacute combined degeneration of spinal cord. also myelosis funicularis, or funicular myelosis. This complex consists of the following symptoms: # Impaired perception of deep touch, pressure and vibration, loss of sense of touch, very annoying and persistent paresthesias # Ataxia of dorsal column type # Decrease or loss of deep muscle-tendon reflexes # Pathological reflexesBabinski, Rossolimo and others, also severe paresis Pernicious anemia The main cause of<unk>  is pernicious anemia, caused by insufficient absorption. It is characterized by a triad of symptoms: # Anemia with bone marrow promegaloblastosis (megaloblastic anemia). This is due to the inhibition of DNA synthesis (specifically purines and thymidine). # Gastrointestinal symptoms: alteration in bowel motility, such as mild diarrhea or constipation, and loss of bladder or bowel control. These are thought to be due to defective DNA synthesis inhibiting replication in a site with a high turnover of cells. This may also be due to the autoimmune attack on the parietal cells of the stomach in pernicious anemia. There is an association with watermelon stomach (GAVE) and pernicious anemia. # Neurological symptoms: Sensory or motor deficiencies (absent reflexes, diminished vibration or soft touch sensation), subacute combined degeneration of spinal cord, or seizures. Deficiency symptoms in children include developmental delay, regression, irritability, involuntary movements and hypotonia. The presence of peripheral sensory-motor symptoms or subacute combined degeneration of spinal cord strongly suggests the presence of a<unk>  deficiency instead of folate deficiency. Methylmalonic acid, if not properly handled by<unk> , remains in the myelin sheath, causing fragility. Dementia and depression have been associated with this deficiency as well, possibly from the under-production of methionine because of the inability to convert homocysteine into this product. Methionine is a necessary cofactor in the production of several neurotransmitters. Each of those symptoms can occur either alone or along with others.<unk> <unk>  is essential for the development of the brain. Its deficiency can cause neurodevelopmental problems which can be partly reversible with early treatment. In babies, a number of neurological symptoms can be evident due to malnutrition or pernicious anemia in the mother. These include poor growth, apathy, having no desire for food, and developmental regression. While most symptoms resolve with supplementation some developmental and cognitive problems may persist.<unk>  may accompany certain eating disorders or restrictive diets. Only a small subset of dementia cases have been found to be reversible with<unk> <unk>  therapy. Tinnitus may be associated with<unk> . Metabolic risk in offspring<unk> <unk>  is a critical micronutrient essential for supporting the increasing metabolic demands of the foetus during pregnancy.<unk>  deficiency in pregnant women is increasingly common and has been shown to be associated with major maternal health implications, including increased obesity, higher body mass index (BMI), insulin resistance, gestational diabetes, and type 2 diabetes (T2D) in later life. A study in a pregnant white non-diabetic population in England, found that for every 1% increase in BMI, there was 0.6% decrease in circulating<unk> . Furthermore, an animal study in ewes demonstrated that a<unk> , folate and methionine restricted diet around conception, resulted in offspring with higher adiposity, blood pressure and insulin resistance which could be accounted for altered DNA methylation patterns. Both<unk> <unk>  and folate are involved in the one-carbon metabolism cycle. In this cycle,<unk> <unk>  is a necessary cofactor for methionine synthase, an enzyme involved in the methylation of homocysteine to methionine. DNA methylation is involved in the functioning of genes and is an essential epigenetic control mechanism in mammals. This methylation is dependent on methyl donors such as<unk> <unk>  from the diet.<unk>  has the potential to influence methylation patterns in DNA, besides other epigenetic modulators such as micro (RNAs), leading to the altered expression of genes. Consequently, an altered gene expression can possibly mediate impaired foetal growth and the programming of non-communicable diseases.<unk> <unk>  and folate status during pregnancy is associated with the increasing risk of low birth weight, preterm birth, insulin resistance and obesity in the offspring. In addition it has been associated with adverse foetal and neonatal outcomes including neural tube defects (NTDs) and delayed myelination or demyelination. The mother’s<unk>  status can be important in determining the later health of the child, as shown in the Pune maternal Nutrition Study, conducted in India. In this study mothers with high folate concentrations and low<unk> <unk>  concentrations, led to babies having a higher adiposity and insulin resistance at age 6. In the same study, over 60% of pregnant women were deficient in<unk> <unk>  and this was considered to increase the risk of gestational and later diabetes in the mothers. Increased longitudinal cohort studies or randomised controlled trials are required to understand the mechanisms between<unk> <unk>  and metabolic outcomes, and to potentially offer interventions to improve maternal and offspring health. Cardiometabolic disease outcomes Multiple studies have explored the association between<unk> <unk>  and metabolic disease outcomes, such as obesity, insulin resistance and the development of cardiovascular disease. A long-term study where<unk> <unk>  was supplemented across a period of 10 years, led to lower levels of weight gain in overweight or obese individuals (p 12 deficiency is one of the main causes of anemia. In countries where<unk>  deficiency is common, it is generally assumed that there is a greater risk of developing anemia. However, the overall contribution of<unk>  to the global incidence of anemia may not be significant, except in elderly individuals, vegetarians, cases of malabsorption and genetic disorders.<unk>  is also a major risk factor for megaloblastic anemia; a condition in which the body doesn't have enough healthy red blood cells, so tissues and organs don't get enough oxygen, causing feelings of weakness and tiredness, breathlessness, headaches, looking pale, feeling faint, rapid heartbeat, and dizziness. There are relatively few studies which have assessed the impact of haematological measures in response to<unk>  supplementation. One study in 184 premature infants, reported that individuals given monthly<unk> <unk>  injections (100 µg) or taking supplements of<unk> <unk>  and folic acid (100 µg/day), had higher haemoglobin concentrations after 10–12 weeks, compared to those only taking folic acid or those taking no<unk> <unk>  injections. In deficient Mexican adult women and pre-schoolers, it was found that<unk> <unk>  supplementation did not affect any haematologic parameters. Ageing In the elderly,<unk>  has been associated with the development of macular degeneration, and the risk of frailty. Macular degeneration is the leading cause of severe, irreversible vision loss in older adults. Several risk factors have been linked to macular degeneration, including family history, genetics, hypercholesterolemia, hypertension, sunlight exposure and lifestyle (smoking and diet). It has been shown that daily supplementation of<unk> <unk> , B6 and folate over a period of seven years can reduce the risk of age-related macular degeneration by 34% in women with increased risk of vascular disease (n=5,204). However, another study failed to find an association between age-related macular degeneration and<unk> <unk>  status in a sample of 3,828 individuals representative of the non-institutionalized US population. Frailty is a geriatric condition which is characterized by diminished endurance, strength, and reduced physiological function that increases an individual’s risk of mortality and impairs an individual from fulfilling an independent lifestyle. Frailty is associated with an increased vulnerability to fractures, falls from heights, reduced cognitive function and more frequent hospitalisation. The worldwide prevalence of frailty within the geriatric population is 13.9%, therefore there is an urgent need to eliminate any risk factors associated with frailty. Poor<unk>  B status has been shown to be associated with an increased risk of frailty. Two cross sectional studies have reported that deficiencies of<unk> <unk>  were associated with the length of hospital stay, as observed by serum<unk> <unk>  concentrations and methylmalonic acid (MMA) concentrations 139, 140. Furthermore, another study looking at elderly women (n=326), found that certain genetic variants associated with<unk> <unk>  status (Transcobalamin 2) may contribute to reduced energy metabolism, consequently contributing to frailty. In contrast, a recent study by Dokuzlar et al., found that there was no association between<unk> <unk>  levels and frailty in the geriatric population (n=335). Given that there are limited studies, which have assessed the relationship between<unk> <unk>  and frailty status, more longitudinal studies are needed to clarify the relationship. Neurological decline Severe<unk>  is
Vitamin B12 deficiency
Vitamin A deficiency
Copper deficiency
Biotin deficiency
Megavitamin-B6 syndrome
Vitamin E deficiency
Fluorine deficiency
Zinc deficiency