Protective Role The B-vitamins, particularly vitamin B6 , folate and vitamin B12, are widely believed to be protective against Alzheimer’s disease and age-related cognitive decline.

VITAMIN B-6

Introduction Vitamin B6 is actually a collective term for three naturally occurring pyridines that are functionally and metabolically related: Pyridoxine Pyridoxal Pyridoxamine Discovered during Nutritional studies on rats in 1930

2 Methyl.3 hydroxy,4,5 dihydroxymethyl pyridine Chemical structure Pyridoxal Pyridoxine or Pyridoxol 2 Methyl.3 hydroxy,4,5 dihydroxymethyl pyridine Pyridoxamine

Active forms are: Pyridoxal Phosphat Aldehyde group at position 4 can reversibly attach with PO4.

Food sources Found in wide varieties of foods. Eggs,Meats ( beef,chicken breast) Fish (Trout,Salmon, tuna) Beans and Legumes Bread and cereals Spinach and tomato Banana and nuts

Functions Vitamin B6 is involved in variety of metabolic processes. Plays a major role in amino acid metabolism Trasamination Decarboxylation Transulfuration

Functions Needed for conversion of Tryptophan to niacin Formation of melanin Breakdown of glycogen to glucose Inter conversion of glycine and serine where it functions along with Folic Acid.

Absorption and Metabolism Readily absorbed from intestine. In cytoplasm it is converted into Pyridoxal phosphate and pyradoxalamine Phosphate by pyridoxal Kinase and ATP. These are the active forms of the vitamin. Mainly found in extra-cellular fluid

Concentration is relatively high in Leukocytes Nerve tissues and Liver As water soluble, very little is stored and Any excess, is excreted in urine in the form of pyridoxic acid.

Recommended Daily Allowances The daily requirements of Vitamin B6 Directly related to protein intake RDA 2.2 mg for men and 2 mg for women.

Effects of Deficiency Epileptic convulsions Commonly seen in pregnant women and infants after prolong deficiency Dermatitis Glossitis Blood disorders Epileptic convulsions

Dermatitis

Seborrheic dermatitis

Cheilosis Angular stomatitis Peripheral neuropathy

Toxic Effects Very limited toxicity in humans

Role of Folate in brain health

The last several years have seen a number of new drug formulations that include the B-vitamins, along with increased prescribing of these products to lower homocysteine levels and to preserve brain function.

Vitamin B 9 (folate) Is needed for one-carbon metabolism and thus required for the synthesis of: Serotonin Norepinephrine Dopamine DNA and Phospholipids production. Low maternal folate status increases the risk of neural tube defects in newborns.

Prevention of Neural Tube Defect leading to spina bifida at the very early stage of pregnancy

Folate Deficiency Common among patients with mood disorders and correlate with illness severity. It is reported that those in the lowest one-third of folate consumption had a 67% increased relative risk of depression.

Folate deficiency and insufficiency Low folate levels had a significant risk of depression. Patients without deficiency but with folate levels near the low end of the normal range also report low mood. Compared with controls, patients experiencing a first episode of psychosis have lower levels of folate and B12.

Use in Brain Dietary folate must be converted to L-methylfolate for use in the brain. Patients with a tetrahydrofolate reductase (THFR) polymorphism produce a less active form of the enzyme which is associated with major depression and bipolar disorder.

Clinical point Clinical trials have shown that several forms of folate can enhance antidepressant treatment. Augmentation with L-methylfolate , which bypasses the THFR enzyme, can be an effective strategy for treating depression in these patients.

Food Sources The richest sources of folacin include Liver Spinach Wheat Yeast and Dry beans Almost all deep green leafy vegetables are also good sources of this vitamin

Role of Vit. B12 in Brain Health

Vitamin B12 (cobalamin) An essential cofactor in one-carbon metabolism. B12 is needed to produce monoamine neurotransmitters and maintain myelin. Deficiency is found in up to one-third of depressed patients and compromises antidepressant response, Higher vitamin B12 levels are associated with better treatment outcomes.

Vitamin B12 B12 deficiency has a well-recognized neurologic syndrome that is characterized by cognitive and psychiatric disturbances, as well as by sub-acute combined degeneration of the spinal cord, and peripheral neuropathy. Exclusion of vitamin B12 deficiency as an explanation of dementia is a standard procedure in the diagnosis of Alzheimer’s disease. In addition, high-dose vitamin B12 therapy can resolve symptoms of the neurologic syndrome, including cognitive disturbances .

There is a strong clinical understanding that vitamin B12 deficiency syndrome is irreversible if left untreated. Vitamin B12 deficiency is common with older age, occurring in more than 20% of persons 65 years and older as the result of increased prevalence of gastritis and other digestive conditions that interfere with absorption.

B12 Deficiency It can cause Depression Irritability Agitation Psychosis, and Obsessive symptoms.

Low Level of B12 Low B12 levels and elevated homocysteine increase the risk of CVD , Cognitive decline and Alzheimer’s disease and are linked to a 5-fold increase in the rate of brain atrophy.

Who are at risk B12 deficiencies may be seen in patients with gastrointestinal problems, older adults with achlorhydria, and vegans and vegetarians, in whom B12 intake can be low. Proton pump inhibitors such as omeprazole interfere with B12 absorption from food.

Psychiatrist should remember Psychiatric symptoms of B12 deficiency may develop before hematologic findings. Folic acid supplementation may mask a B12 deficiency by delaying anemia but will not delay psychiatric symptoms.

Risk of low level Ten percent of patients with an insufficiency (low normal levels of 200 to 400 pg/mL) have elevated homocysteine, which increases the risk of psychiatric disorders as well as co-morbid illnesses such as cardiovascular disease.

Dietary sources Fish, Meat, and Dairy products.

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