Study on Vitamin B12 Deficiency in the Elderly

The importance of vitamin B12 is increasingly recognized, especially in the elderly. Clinically, the view that persistent or severe vitamin B12 deficiency causes megaloblastic anemia, atrophic glossitis, and subacute combined degeneration of the spinal cord is increasingly accepted. In recent years, it has been found that the incidence of vitamin B12 deficiency in the elderly is increasing, and it has been found that vitamin B12 deficiency is also closely related to cardiovascular system diseases, reproductive system, and other nervous system diseases.

Figure 1. Diagnosis, treatment, and long-term management of vitamin B12 deficiency. (Sources: Kufe DW., 2009)

Biochemical Properties of Vitamin B12

Vitamin B12 is a coenzyme of N5-CH3-FH4 methyltransferase (methionine synthetase), catalyzing the methylation of homocysteine to produce methionine. It is also a coenzyme of L-methylmalonyl CoA, catalyzing succinyl CoA and generation, which is necessary for cell growth at all stages of life. When B12 is deficient, the effects are as follows:

1. The methyl group on N5-CH3-FH4 cannot be transferred out, which affects the synthesis of methionine, reduces the regeneration of tetrahydrofolate, hinders the metabolism of one-carbon units, and reduces the synthesis of deoxynucleotides;

2. Homocysteine metabolism is impaired, causing its accumulation, which damages cardiovascular function and cognitive function;

3. L-methylmalonyl accumulates in large quantities, affecting the normal synthesis of fatty acids and leading to obesity.

Causes of Vitamin B12 Deficiency

1. Insufficient intake, such as long-term vegetarianism or partial eating;

2. Acquired absorption disorders, such as pancreatic, gastric, and intestinal diseases, which interrupt a certain process of B12 absorption;

3. Increased demand for vitamin B12, such as pregnancy;

4. Drug-induced: Studies have found that oral metformin can lead to lower serum vitamin B12 levels;

5. Food, such as CathaEdulis, which can reduce human serum iron, ferritin, and vitamin B12, and increase homocysteine.

Vitamin B12 Deficiency and Related Diseases

In addition to causing megaloblastic anemia, atrophic glossitis, and combined degeneration of the spinal cord, vitamin B12 deficiency is also closely related to the cardiovascular system, other nervous systems, and skeletal systems.

• Relationship Between Vitamin B12 Deficiency and Cardiovascular Disease

Vegetarianism has a certain effect on reducing the incidence and mortality of ischemic heart disease and stroke, but eating too much can lead to vitamin B12 deficiency, which is not good for cardiovascular health. Vitamin B12 deficiency can lead to homocysteineemia. Hyperhomocysteinemia can lead to abnormal function of vascular endothelial cells, increase the production of oxygen free radicals, and enhance NO inactivation, causing vascular inflammation, oxidative stress, etc., which affect the elastic function structure of arteries. Studies have shown that vitamin B12 deficiency can lead to damage to arterial endothelial function and increase the thickness of the carotid intima, that is, vitamin B12 is closely related to the thickness of the carotid intima and the endothelium-dependent vasodilation mediated by blood flow. In patients with vitamin B12 deficiency, vitamin B12 supplementation increases serum vitamin B12 levels, decreases serum homocysteine levels, and improves carotid intima-media thickness and flow-mediated endothelium-dependent vasodilation. It has also been shown that vitamin B12 supplementation decreases systolic and diastolic blood pressure, and improves the stiffness level of vascular stiffness. However, there is limited evidence to support that vitamin B12 deficiency is a high-risk factor for the incidence and mortality of cardiovascular disease and type 2 diabetes. The combined use of folic acid, vitamin B6, and vitamin B12 can reduce homocysteine levels in cardiovascular patients or high-risk patients, but cannot reduce the risk of cardiovascular disease. The combined use of folic acid, vitamin B6, and vitamin B12 is not recommended for secondary prevention of cardiovascular disease.

• Relationship Between Vitamin B12 and the Nervous System

Vitamin B12 is an essential substance for the methylation of myelin, neurotransmitters, and membrane phospholipids, and it plays an important role in the integration of peripheral and central nervous systems. Vitamin B12 deficiency can cause hyperhomocysteinemia and high bMMA and uMMA. Hyperhomocysteinemia is associated with depression, cognitive impairment, and dementia in the elderly. MMA is also toxic to the nervous system. uMMA and bMMA are associated with diabetic neuropathy, and the superficial peroneal nerve sensory and motor conduction velocity and ulnar complex artery potential amplitude uMMA are closely related. Studies have shown that in the vitamin B12-deficient group, the maximum optic nerve fiber thickness was significantly less than that in the control group, and the average and maximum optic nerve fiber thickness were closely related to the vitamin B12 level. However, for patients with moderate vitamin B12 deficiency who have not developed anemia and have no neurological and cognitive symptoms and signs, correcting vitamin B12 deficiency has no proven beneficial effects on neurology and cognition.

• Vitamin B12 and the Reproductive System

Vitamin B12 can promote the synthesis of proteins and deoxynucleotides. Studies have shown that supplementing vitamin B12 can improve semen quality. During pregnancy and lactation, vitamin B12 deficiency may cause damage to spermatocytes and germ cells.

• Vitamin B12 and Obesity

Vitamin B12 is a coenzyme for the conversion of methylmalonyl CoA to succinyl CoA. Vitamin B12 deficiency will lead to the accumulation of methylmalonyl CoA, which can inhibit the rate-limiting enzyme of fatty acid oxidase, leading to fatty acid synthesis. Vitamin B12 deficiency is very common in patients with type 2 diabetes and is related to the formation of hyperlipidemia. In non-diabetic British pregnant women, low vitamin B12emia was found to be closely related to obesity and insulin resistance. There is currently no evidence to support the relationship between vitamin B12 deficiency and diabetes.

In summary, there are many factors that cause vitamin B12 deficiency in the elderly, so vitamin B12 deficiency is more common in the elderly. Vitamin B12 deficiency is closely related to cardiovascular function, nervous system diseases, and reproductive system diseases. Therefore, serum vitamin B12 in the elderly must be monitored, and more research is needed to prove that the time and dosage of vitamin B12 supplementation in specific diseases and the relationship between vitamin B12 and other systemic diseases need to be further proved.

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