The B vitamins comprise a group of 8 water-soluble vitamins that are involved in numerous processes of cellular metabolism. Although each of them performs a specific function, in general they act as enzymatic cofactors in metabolic pathways that produce energy from carbohydrates, proteins and fats. In addition, the B complex plays a key role in the maintenance of brain and nervous system functions, including DNA and RNA synthesis and repair, DNA methylation reactions, and the synthesis of neurochemicals and signalling molecules. (1) Furthermore, the B vitamins have recently been investigated for their possible involvement in cardiovascular and bone health. (2)
Although the scientific community has been particularly interested in the subgroup (B6/B9/B12) for their involvement in homocysteine metabolism, maintaining adequate levels of the other B vitamins is essential for maintaining optimal physiological and neurological functioning. (1)
In an increasingly aging society and in the absence of an optimal diet rich in these nutrients, the administration of a supplement that encompasses the entire group of B vitamins in adequate doses could be a good approach to preserve brain and neurological health and boost our immune system.
Our body is not always able to convert B vitamins into their active form effectively. If digestion is not adequate or if you have a sensitive metabolism, it is possible that we do not take advantage of their full potential. Therefore, when choosing a good supplement, it is advisable to pay attention to those that offer the B vitamins in their active form (methylated and/or coenzymated) since they do not require conversion in the liver and are used directly by the body, improving their absorption and bioavailability.
THIAMINE (VITAMIN B1)
Thiamine pyrophosphate (TPP) is the active form of vitamin B1. It acts as a cofactor for enzymes involved in the metabolism of carbohydrates, lipids and amino acids, as well as in the synthesis of neurotransmitters and other bioactive compounds essential for brain function. (3) In recent years its participation in the maintenance of neurological function has been increasingly recognized, acting as a neuromodulator in the synthesis of acetylcholine and contributing to the structure and function of cell membranes, including neurons. (4) A deficiency of this vitamin could increase the risk of diseases such as Alzheimer’s disease and heart failure (5).
In older people, thiamine deficiency can become a problem due to reduced appetite and difficulty in ingesting food. Age, malnutrition, alcoholism, hepatic and cardiac dysfunction, bariatric surgery, oxidative stress (lactic acidosis), refeeding syndrome, renal failure and critically ill patients may be some risk factors associated with thiamine deficiency. (6)
The recommended daily dose is 1.1 mg for healthy adults. In case of children and pregnant women the recommended daily intake is 0.3 mg and 1.5 mg, respectively. (7) As for the foods that contain it, we have whole grains, wheat germ, yeast, soy flour and pork meat. It is a water-soluble vitamin that when ingested in small amounts is actively absorbed through transporter proteins, while if ingested in high concentrations it is passively absorbed in the small intestine. The storage of thiamine in skeletal muscle, liver, heart and kidneys is scarce, so it is necessary to guarantee a continuous supply, since its half-life is 10-20 days.
RIBOFLAVIN (VITAMIN B2)
Vitamin B2 is the main component of the cofactors flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). These coenzymes participate in the oxidation-reduction reactions of metabolic pathways involved in energy production. (8) In addition, they act as crucial cofactors for the synthesis and conversion of other vitamins such as niacin, vitamin B6 and folic acid and participate in the synthesis of haemoglobin and other proteins involved in electron transfer, oxygen transport and storage. (9) On the other hand, riboflavin contributes to promote optimal iron absorption and utilization (10) and has antioxidant properties by participating in the glutathione redox cycle. (11)
Riboflavin is found naturally in certain foods such as cereals, green leafy vegetables, some meats and fatty fish. In addition, in Western countries, milk and some dairy products are usually fortified with this vitamin. Its recommended intake is 1.4 mg for adults. It is important to note that this vitamin is not stored in the body and the excess that the body does not need is eliminated through the urinary tract. Sometimes if the amount excreted is too much, the urine may turn bright yellow. Elderly people are more prone to B2 deficiency because aging causes a reduction in the efficiency of B2 absorption. In addition, because it is continuously eliminated in the urine, deficiency is relatively common when dietary intake is insufficient. Riboflavin deficiency can cause eye, mouth and skin disorders, as well as increased tiredness and fatigue. In addition, riboflavin deficiency has been linked to preeclampsia in pregnant women.
(12) Other studies indicate that riboflavin supplementation is effective as a treatment for migraine due to its participation as a flavoprotein precursor in the mitochondrial electron transport chain. (13)
Diets poor in this nutrient, diabetes, alcoholism, hyperthyroidism and stress are some conditions that can cause riboflavin deficiency.
NIACIN (VITAMIN B3)
Vitamin B3, also known as niacin, nicotinic acid or nicotinamide, is a water-soluble vitamin that is part of the two most important coenzymes used by the body for energy: nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). These coenzymes are involved in almost all oxidation-reduction reactions at the cellular level. Their derivatives, NADH and NAD+, and NADPH and NADP+, are essential in the energy metabolism of carbohydrates, proteins and fats and are also very important for cell differentiation, DNA repair and cellular mobilization of calcium. (14) In addition to these functions, vitamin B3 contributes to the normal functioning of the nervous system, normal psychological function, maintenance of normal skin and mucous membranes and reduces tiredness and fatigue. (15)
The biosynthesis of vitamin B3 takes place in the liver from the essential amino acid tryptophan, which is converted into nicotinic acid and subsequently into nicotinamide. This synthesis is not entirely efficient (60 mg of tryptophan are required to synthesize 1 mg of niacin) so it is essential to incorporate B3 in the diet or through supplementation. Nicotinamide has the advantage of not causing the undesired flush effect of B3 like nicotinic acid, a fact to take into account when choosing a supplement of this vitamin. In food, vitamin B3 can be obtained from yeast, liver, poultry, legumes, green leafy vegetables and nuts. The recommended daily amount of niacin for adults is 16 mg per day. (16)
PANTOTHENIC ACID (VITAMIN B5)
Pantothenic acid is a water-soluble vitamin necessary for the synthesis of coenzyme A (CoA). This molecule acts as a cofactor in reactions involving the transfer of acetyl groups in the form of acetyl-CoA. It is essential for cellular respiration and contributes to the metabolism and synthesis of carbohydrates, lipids and proteins. It participates in the biosynthesis of many compounds important for the structure and function of brain cells such as fatty acids, cholesterol and acetyl choline. Moreover, vitamin B5 contributes to the synthesis and normal metabolism of steroid hormones, vitamin D and some neurotransmitters, as well as to the maintenance of normal intellectual performance. (17)
As the name “panthos” suggests, it is found everywhere, as small amounts of this vitamin are present in almost all foods. Hence, its deficiency is rare. Its main sources include liver, wheat bran, legumes, eggs and cheese. In food supplements, calcium pantothenate is usually used as it is the most thermostable form of B5. The recommended daily amount in adults is 6 mg/day. (16)
Given the importance of B5 as a component of CoA in the metabolism of fatty acids and steroid hormones, some scientists have shown its application in the treatment of skin lesions caused by acne with very good results. (18) On the other hand, the efficacy of supplementation with vitamin B5 for the treatment of intestinal ileus after surgery has also been demonstrated. (19)
VITAMIN B6 (PYRIDOXINE)
The biologically active form of vitamin B6 is pyridoxal phosphate, which acts as a cofactor for various enzymes involved in multiple chemical processes in our body such as: glycogen, phospholipid and amino acid metabolism and the synthesis of neurotransmitters (serotonin, norepinephrine, adrenaline, γ-aminobutyric acid (GABA), etc.). Vitamin B6 also plays a key role in homocysteine metabolism, haemoglobin synthesis and the normal functioning of the immune system. (20) Several animal and human studies have found that low vitamin B6 intake is associated with a number of immune disorders. This may be because interleukin production and lymphocyte proliferation are decreased in people deficient in this vitamin. (21) Moreover, studies have shown its role in brain glucose regulation (22) and pyridoxal phosphate levels have also been associated as biomarkers of inflammation. (23)
Although B6 deficiency is not very frequent, excessive alcohol consumption and malnutrition in elderly people can cause B6 deficiency caused by lack of appetite and malabsorption. The recommended daily intake depends on age, sex and other factors, but in general terms the NRV for adults is 1.4 mg. Foods containing the highest amounts include meats, whole grains, certain vegetables, bananas and nuts. Maintaining good levels of vitamin B6 is essential for cardiovascular health because, together with folic acid and vitamin B12, it helps to lower homocysteine levels. It also contributes to normal psychological function and helps regulate hormonal activity. People with depression, stress and sleep disturbances often take B6 supplements because of its participation in the synthesis of serotonin and melatonin. Finally, it is a vitamin widely consumed by athletes as it is involved in energy metabolism, reducing tiredness and fatigue and increasing muscle performance. It promotes the release of glycogen stored in the liver and muscles.
BIOTIN (VITAMIN B7)
Biotin, also known as vitamin B7 or vitamin H, is a key nutrient for energy metabolism and its presence is vital for the correct metabolization of carbohydrates, proteins and lipids. It participates as an enzymatic cofactor in the transfer of carbon dioxide from numerous carboxylases and decarboxylases essential in the processes of cellular duplication. It is also directly involved in the correct functioning of the nervous system, as well as in glucose metabolism, which makes it a very important substance in maintaining correct blood sugar levels. (24)
Biotin deficiency is not very frequent since it is present in many foods such as meat, fish, eggs and milk. In addition, it can also be synthesized by bacteria present in the intestinal flora. However, deficiencies can occur when the body requires an extra supply, for example during pregnancy, in people fed parenterally for a long period of time, and in alcoholics or people with liver disease. Interaction with anticonvulsant drugs may produce disorders in its metabolism and absorption. The recommended daily amount in adults is only 50 micrograms, but supplementation with high doses of biotin (10-15 mg/day) is becoming more and more frequent due to its benefits in the maintenance of hair and skin in normal conditions, since it favours the growth of rapidly reproducing tissues. On the other hand, there are studies that report that biotin supplementation can have beneficial effects in the treatment of neuropathies, diabetes or multiple sclerosis.
(25)
FOLIC ACID (VITAMIN B9)
Vitamin B9, also known as folic acid, is one of the most important vitamins of the B complex. Its active form is 5-methyl tetrahydrofolate. It acts as a one-carbon acceptor and donor, e.g. of a methyl group (-CH3), thus participating in the synthesis of amino acids and nucleotides. It plays a vital role in the methylation of DNA, RNA, proteins and phospholipids. (26) Methylation is a process that could be of great importance in cancer prevention, so ensuring good methylation appears to be key to this disease.
Folic acid participates as a coenzyme in the synthesis of methionine from homocysteine. Methionine is necessary for the addition of methyl groups involved in a multitude of biological reactions. A deficiency of B9 correlates with insufficient methionine synthesis and homocysteine accumulation. High levels of homocysteine in the blood are associated with serious cardiovascular and neurological diseases. The amount of homocysteine is not only regulated by vitamin B9, but vitamin B6 and B12 are also involved. (27)
In addition to all these functions, folic acid contributes to the normal formation of blood cells, to the normal functioning of the immune system, to the reduction of tiredness and fatigue, to the maintenance of normal psychological functions, to the process of cell division and to the normal growth of maternal tissue during pregnancy. It is found mainly in green leafy vegetables, legumes, liver and some citrus fruits. It has become popular to fortify cereals, flours and grains with folic acid to reduce the risk of neural tube defects (NTDs). The NRV for adults is 200 µg, but it is recommended to increase daily intake to 600 µg during pregnancy. Folic acid supplementation during pregnancy has been shown to contribute to a reduced risk of NTDs.
(28) NTDs are severe congenital malformations of the central nervous system caused by a failed closure of the neural tube. They occur early in gestation and are relatively common (between 1-8 cases per 10,000 live births). The most common conditions are spina bifida and anencephaly, the latter of which is fatal within days of birth.
VITAMIN B12 (COBALAMIN)
Vitamin B12, also known as cobalamin, is an essential vitamin for normal brain and nervous system function (initial myelination, development and maintenance of myelin). It contributes to energy metabolism, normal functioning of the immune system, DNA synthesis and normal red blood cell formation. In fact, vitamin B12 supplementation became known in the 19th century as the only effective treatment for pernicious anaemia and demyelinating lesions of the central nervous system. (29)
The main food sources are meats, eggs and dairy products and it can also be found in large amounts in liver and clams. The NRV for adults is 2.5 µg per day. The absence of B12 in vegetables means that vegans must resort to supplementation to meet their daily needs. Similarly, elderly people may have to resort to B12 supplementation because the incidence of malabsorption due to gastrointestinal problems increases with age. A B12 deficiency can cause certain disorders such as weakness, fatigue, megaloblastic anaemia, hyperhomocysteinemia, severe neurological problems, dementia, depression, etc. (30). Vitamin B12 is linked to the action of two very important enzymes: methylmalonyl-coenzyme A (CoA) mutase and methionine synthase, participating in the conversion of methylmalonic acid-CoA to succinyl-CoA and homocysteine to methionine. Once it reaches the blood, cobalamin binds to transport proteins (transcobalamins) to reach the liver, where it is stored and transformed into its two active forms that will be distributed to the rest of the body: methylcobalamin and adenosylcobalamin. There are many mutations that can produce a deficit of B12, even if its dietary intake is correct.
(31) Therefore, it is advisable to resort to those supplements that offer this vitamin in its active form.
BETAINE
Betaine, also known as trimethylglycine, is a non-essential nutrient that comes from the metabolism of choline. It can be found naturally in plant sources such as beets, spinach, cereal germ and bran, and in animal products such as seafood. It is involved in a multitude of cellular and biochemical processes as an osmoregulator, antioxidant and regulator of lipid and protein metabolism. Betaine is also a source of hydrochloric acid. In this sense, betaine supplementation supports digestion and ensures that our stomach maintains an acid pH so that some vitamins, in particular B12, can be optimally absorbed.
Its most important role is in the liver as a methyl group donor converting homocysteine to methionine through a methylation reaction. Several studies have shown that high concentrations of homocysteine in the blood (hyperhomocysteinemia) are associated with the risk of cardiovascular and cerebrovascular accidents, Alzheimer’s disease and chronic kidney disease. As mentioned above, a deficiency of B9 or B12 can lead to increased homocysteine levels, which can be decreased by increasing betaine intake. (32)
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