Betaine, Vit B6, B12 and folate have a pivotal role for the regulation of hyperhomocysteinemia

Betaine pharmacological properties

• Important methyl donor
• Acts a cofactor in the chemical reaction catalyzed by betaine-homocysteine-methyltransferase (BHMT) enzyme
• Essential for the remethylation of homocysteine to methionine
• One of the main regulators of plasma homocysteine levels

Importance of folate administration

• For all the reactions involving DNA synthesis, repair, and methylation;
• For homocysteine metabolism (remethylation);
• In other important biochemical reactions, especially during intense periods of cell division and in the case of a rapid growth;
• The elderly people frequently have chronic folate deficiency due to poor diet, malabsorption, and drug interactions.

Folic acid

Folic acid, or pteroyl(mono)glutamic acid or folacin, is derived from the Latin: folium (leaf).
It is a water-soluble B group vitamin.
Folic acid as such is not active, but it is the active form precursor: it is considered a prodrug.

Stages to obtain bioactive forms of folate

5-MTHF

• 5-Methyltetrahydrofolate (5-MTHF) is the metabolically active form of folate i.e., it represents:
• 95-98% of serum folate and red blood cells,
• the essential form in which folates are stored in the body,
• An immediately and fully bioavailable source of folate,
• The only source of folate that can cross the blood-brain barrier.

It is also ideal:

• in cases of MTHFR genetic defect since the folate cycle continues to function,
• When the accumulation of unmetabolized folic acid has to be avoided with chronic therapies.

Vitamin B12

• Protein found exclusively in foods of animal origin, not synthesizable by the body.
• The intrinsic factor, a glycoprotein secreted by the parietal cells of the stomach, is essential for its absorption.
• vitamin B12 bounded-intrinsic factor is absorbed by the distal part of the ileum.
• That produced by the intestinal flora, since it cannot bind to intrinsic factor, is not absorbable.

Importance of Vit B12 administration

• Vitamin B12 is necessary for the correct metabolism of nerve tissue and it is involved in protein, fat, and carbohydrate metabolism.
• It also contributes to improve iron function in the body and it is useful for vitamin A attachment in body tissues, enhancing carotene absorption or conversion to vitamin A.
• Ten percent of the elderly people have vitamin B12 deficiency showing up with neuropsychiatric disorders.
• The deficiency is generally due to an assimilation problem caused by the intrinsic factor deficiency.
• Its deficiency can be cause by a defect in the molecules able to transport B12 from the blood to the tissues, even when there is a good vitamin B12 level in the serum.
• It can also be the result of intestinal parasitosis, a high bacterial load in the stomach or intestines.

THE METHYL FOLATE TRAP

• Under Vit B12 deficiency conditions, homocysteine cannot be converted into methionine, even if there is adequate folate availability.
• Therefore, folates remain “trapped” without being able to be used
• Importance of folate + B12 administration

Vitamin B6

• Transamination or decarboxylation of amino acids,
• Oxidative deamination of amines,
• Tryptophan metabolism,
• lipid metabolism, with transformation of linoleic acid to arachidonic acid and formation of sphingolipids (an important event for the production of myelin sheaths),
• Glycogenolysis, as a coenzyme of glycogen phosphorylase,
• Synthesis of various neurotransmitters,
• converts homocysteine to cystathionine and subsequently to cysteine.

Vitamin D and neuroprotection

• Counteracts age-related inflammatory changes
• Limits B-amyloid accumulation and facilitates its elimination
• Protects against glutamate neurotoxicity
• Antioxidant activity
• Hypovitaminosis D is linked to the reduction of gray matter and brain atrophy and a reduced cortical activity

Vit D deficiency

• Values below 20 ng/mL (50 nmol/L) are defined as vit D deficiency, but between 21-29 ng/mL (52.5-72.5 nmol/L) there is already deficiency
• Based on these definitions, about one billion people suffer from vit D deficiency worldwide
• The elderly people frequently need Vit D supplementation, due to reduced sun exposure and renal metabolism.

VIT D and dementia

• Subjects with AD have reduced levels
• Not only advanced AD stage but also MCI subjects have reduced Vit D levels
• Hypovitaminosis D is linked to the onset of cognitive deficits and may play a role in the disease progression

Rational of Vit D administration in patients with MCI

• Preclinical and clinical studies show an association between reduced Vit D levels and cognitive deficits.
• Non-randomized studies have shown improvement in cognitive performance after Vit D intake in elderly people