B Complex Vitamins Overview
Beneficial properties of B complex Vitamins
All people need adequate quantities of the total of 13 vitamins present.
Their categorization is as follows:
- four fat-soluble vitamins (A, D, E, K) and
- nine water-soluble vitamins,
including Vitamin C and the 8 vitamins of the B complex
Thiamine (B1),
Riboflavin (B2),
Niacin (B3),
Pantothenic acid (B5),
Vitamin B6,
Folic acid (B9),
Biotin
Vitamin B12
People have generally lost their ability to compose sufficient portions of the specific vitamins during their development. This evolutionary paradox, that is, why an organism has lost the ability to synthesize compounds that are required for his survival, is resolved by the fact that during the course of development, vitamins were ubiquitous and abundant in the food chain.
An organism that can simply isolate its "vitamins" from the environment, may therefore be in an evolutionary advantage as the process of endogenous enzymatic De-Novo synthesis of these compounds would entail a disadvantageous position in terms of energy expenditure because of the needs which have cellular functions and the oxidative stress involved in metabolism.
As far as the human requirements for vitamins are concerned, the clearest example of this process is the vitamin C monosaccharide, which is endogenously produced by normal metabolism by most beings. In the case of humans, the inability to synthesize vitamin C is due to a mutation in the gene for the enzyme L-gluconolactone oxidase, an enzyme in the synthetic pathway of ascorbic acid, which was lost about 35-55 million years ago.
The same applies to B complex vitamins, one or more of the required genes expressing the enzymes required for the synthesis of vitamin B6 (pyridoxal 5'-phosphate) have been lost in several different cases in the animal kingdom, leaving it most of the animals, including all mammals, are unable to synthesize this compound endogenously. Similarly, the ability to synthesize De-Novo's vitamin B9 (folate) was lost, but the synthetic road genes needed to save and recycle folic acid from extraneous sources were retained.
B-complex vitamins act as coenzymes in a significant percentage of enzyme processes that support every aspect of cellular normal function.
In total, the abundance of functions taken up by B complex vitamins can generally be subdivided into 2 roles:
- Catabolic metabolism, leading to energy production
- Anabolic metabolism, resulting in the construction and conversion of bioactive molecules
Catabolic Energy Production:
Each of the B vitamins participates in every aspect of the absolutely necessary catabolic process to produce energy in the cells. This means that the deficiency in any vitamin B complex will have a negative effect on this process.
Particularly important here are the active forms of thiamine, riboflavin, niacin, and pantothenic acid that are essential coenzymes in mitochondrial aerobic respiration and in the production of cellular energy through their direct roles in the citric acid cycle, in the transport chain electron and the resulting formation of adenosine triphosphate (ATP), the known energy currency of the cell.
Acetyl-CoA (pantothenic acid incorporation) provides the main substrate for this cycle. In addition, thiamine and biotin and vitamin B12 play a unique, nodular, essential role in the mitochondrial metabolism of glucose and fatty acids and amino acids, respectively, thus contributing to the substrates in the citric acid cycle.
Anabolic Procedures:
The vitamin-dependent citric acid cycle provides energy, but also intermediates for the biosynthesis of numerous basic compounds, including amino acids, fatty acids and pyrimidines.
The vitamin B complex also plays an essential role in all aspects of carbon metabolism, a process by which functional compounds such as amino acids, purines, pyrimidines as well as methyl groups required by molecules to be able to participate in biochemical reactions, are created within cells by the addition of individual carbon units.
Of particular interest are many vitamin B coenzymes that are intrinsic factors for two ubiquitous interconnected cellular processes: the "folic acid cycle", whereby through various enzymatic modifications they ultimately provide the one carbon unit required for carbon metabolism, and "Methionine cycle" during which the amino acids methionine and homocysteine will interact, resulting in the synthesis of the methyl groups required for all genomic and non-genomic methylation reactions in the form of S-adenosyl methionine (SAM). These two enzymatic cycles are essential for cellular function, including interactions with other pathways.
Similarly, the trans-thiolation pathway converts homocysteine into cysteine, ultimately leading to the synthesis of the potent endogenous glutathione antioxidant and the production of substrates for the citric acid cycle, which is a direct product of the methionine cycle. While the roles of folic acid and vitamins B6 and B12 are well recognized in these important cycles, the contribution of other B vitamins is rarely recognized. In this respect, the active form of riboflavin is a coenzyme and limits the rate of methionine synthase turnover in the methionine cycle. Likewise, niacin, in the form of NAD, is a necessary cofactor for dihydrofolate reductase enzymes in the folic acid / tetrahydrobiopterin cycles and S-adenosyl monocysteine hydrolase cycle in the methionine cycle.
Consequences of Insufficiency:
One of the many consequences of deficiency in any of the B vitamins is the possible inhibition of the natural distribution and recycling of homocysteine, leading to its accumulation and a number of negative cellular consequences.
The brain is by far the most metabolically active organ of the body, representing only 2% of body weight, but it accounts for over 20% of the body's total body energy expenditure. The general metabolic functions of B vitamins, along with their roles in neurotransmitter synthesis, can therefore be considered to have a particular effect on brain function. Indeed, the importance of vitamins B for brain function is shown by the fact that each vitamin is actively transported through the blood brain barrier and / or the choroid mesh from a special transport mechanism. Once they reach the brain, specific cellular uptake mechanisms dictate distribution, and their levels are tightly regulated by multiple homeostatic mechanisms in the brain. This ensures that brain concentrations remain comparatively high. For example, folate concentration in the brain is four times more than in plasma, while biotin and pantothenic acid in the brain are at concentrations up to 50 times higher than in plasma.
The complex of vitamins B in analysis
Thiamine (vitamin B1) is a coenzyme in the pentose phosphate pathway, which is a necessary step in the synthesis of fatty acids, steroids, nucleic acids and aromatic amino acid precursors in a spectrum of neurotransmitters and other bioactive compounds necessary for the brain function. Thiamine plays a neurotrophic role in the acetylcholine neurotransmitter system and is distinguished by its actions as a cofactor during metabolic processes and contributes to the structure and function of cellular membranes, including neurons and glial cells.
Riboflavin (Vitamin B2) is essential for two co-enzymes of flavoproteins, FMN and FAD, which are critical rate-limiting agents in most cellular enzyme processes. As an example, it is vital for the synthesis, conversion and recycling of niacin, folic acid and vitamin B6 for the synthesis of all heme proteins, including hemoglobin, nitric oxide synthase, P450 enzymes, and proteins involved in electron transport and transport and storage of oxygen. Flavanoproteins are also cofactors in the metabolism of essential fatty acids in brain lipids, absorption and utilization of iron, and in the regulation of thyroid hormones. A malfunction in any of these procedures due to riboflavin deficiency is associated with adverse effects on brain function. Riboflavin co-enzyme derivatives also have antioxidant properties and increase endogenous antioxidant status as essential cofactors in the glutathione redox cycle. A wide range of processes and enzymes involved in each aspect of peripheral and cerebral cell function depend on niacin, such as nucleotides (NAD) and NADP (NADP) phosphate. In addition to energy production, they include oxidative reactions, antioxidant protection, participate in DNA metabolism and repair, in cellular signaling reactions (via intracellular calcium), and the conversion of folic acid to its tetrahydropylic derivative.
Niacin is also associated with two G protein receptors, the high-affinity niacin 1 receptor (NIACR1), responsible for the niacin uptake-associated flash, and low affinity NIACR2. Niacin receptors are distributed both peripherally in cells of the immune system and in the adipose tissue, but also throughout the brain.
Pantothenic acid (vitamin B5) is a substrate for the synthesis of ubiquitous coenzyme A (CoA). In addition to its role in oxidative metabolism, CoA contributes to the structure and function of brain cells through its involvement in the synthesis of cholesterol, amino acids, phospholipids, and fatty acids. Of particular importance is pantothenic acid, via CoA, which is also involved in the synthesis of multiple neurotransmitters and steroid hormones.
Vitamin B6, in addition to its role as a necessary cofactor in the follicle cycle and amino acid metabolism, is also a determining cofactor in the synthesis of neurotransmitters, such as dopamine, serotonin, γ-aminobutyric acid (GABA), noradrenaline and melatonin. The synthesis of these neurotransmitters is very sensitive to vitamin B6 levels, even with a mild deficiency leading to a decrease in GABA production and serotonin synthesis, resulting in the removal of inhibition of GABA neuronal activity and impaired sleep, behavior, and cardiovascular problems and a loss of control of hormone secretion from hypothalamus-hypophysea.
Vitamin B6 also has a direct effect on the function of the immune system, gene expression and plays a role in regulating glucose in the brain. More generally, levels of pyridoxal-5'-phosphate (vitamin B6) are associated with tryptophan metabolism or carbon metabolism. This role is particularly important in inflammatory processes that contribute to the etiology of many pathological conditions including dementia and cognitive impairment.
The brain is particularly sensitive to glucose delivery and metabolism. Biotin plays a key role in glucose metabolism and homeostasis, including regulation of hepatic glucose uptake, gluconeogenesis (and lipogenesis), transcription of insulin receptors and pancreatic β-cell function.
The functions of the two B vitamins, folate and B12 are inextricably linked to complementary roles in the "folic acid" and "methionine" cycles.
A deficiency of vitamin B12 creates a deficiency of folic acid because it traps functional folic acid in the form of methyltetrahydrofolate. This results in functional folate deficiencies, accompanied by a decrease in purine / pyrimidine synthesis and genomic and non-genomic methylation reactions in the brain tissue, leading to decreased DNA stability and repair and gene expression / transcription, which could prevent neuronal differentiation and repair, promoting hippocampal atrophy, demyelination and compromising the integrity of membrane phospholipids by altering the proliferation of Action-economic.
Effective function of the folate cycle is also essential for the synthesis and regeneration of tetrahydrobiopterin, which is essential cofactor for the amino acids converting the two amino acid neurotransmitters (serotonin, melatonin, dopamine, noradrenaline, adrenaline), and nitric oxide.
The importance of the vitamin B complex for the body
The importance of all vitamins B for brain function is illustrated by the neurological and psychiatric symptoms usually associated with deficiency in any of these eight vitamins.
For example, the primary symptoms of a deficiency in vitamin B6 are neurological.
Symptoms include depression, cognitive impairment, dementia, and dysfunction of the autonomic nervous system.
Still, the symptoms of vitamin B12 deficiency often manifest in the form of neurological symptoms long before the typical hematologic changes occur.
It is worth noting that, while about one-third of people suffering from lack of folic acid or vitamin B12, has anemia. A similar proportion is seen in neuropsychiatric symptoms. Indeed, more than one third of psychiatric cases have been found to suffer from deficiencies in folate or vitamin B12.
No description of the mechanisms of action of B vitamins would be complete without taking into account the predominant mechanistic theory that led to a great deal of human research in this field. The "homocysteine hypothesis" originally arose from the observation that elevated fasting plasma levels of potentially toxic amino acid homocysteine were an independent predictor of cardiovascular disease, after which observation was extended to cognitive function, Alzheimer's disease and dementia. In essence, the hypothesis yields mild to moderate increases in homocysteine levels with the causal contribution to these diseases. Deficiencies in several of the essential vitamins involved in the effective recycling of homocysteine to the methionine cycle, particularly folic acid, and vitamins B12 and B6, are then implicated as an underlying cause. The mechanisms under which homocysteine has been assumed to have these detrimental effects on cerebral function include its theoretical roles in increasing oxidative stress, inhibiting methylation reactions, increased damage to DNA and dysfunction of its repair, and direct and indirect neurotoxicity leading to cell death and apoptosis. These procedures are suggested to lead to general effects such as beta amyloid accumulation, tau hyperphosphorylation, cerebral tissue atrophy and assisted cerebrovascular circulation.
This hypothesis has been the driving force not only for the majority of observational studies investigating the epidemiological relationships between vitamins and cardiovascular or cerebral function, but also for a huge research effort that showed a plethora of clinical trials involving folic acid alone or in combination with vitamin B12 and less frequently with vitamin B6. These studies have been conducted on the basis that increasing levels of these vitamins will reliably reduce homocysteine levels. The post-data analysis of 17 studies, involving 39,107 participants and 12 trials involving 47,429 participants, found that the administration of B12 / B6 vitamins and folic acid reliably reduced homocysteine levels.
An unfortunate consequence of the "homocysteine hypothesis" is that it essentially stimulates the majority of clinical investigations in this area to clarify the effects of folic acid and to a lesser extent vitamin B12 followed by vitamin B6. The potential effects and roles of the other five vitamins B have been neglected almost entirely, despite the fact that the entire B vitamin palette is complicated. Still with the homocysteine issue, the status of folic acid and vitamin B6 and B12 depend on the levels of ribavirin-derived flavoproteins. Riboflavin (vitamin B2) is also essential for the metabolism of homocysteine as a cofactor for methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTRR) reductase. Homocysteine levels have been negatively correlated with plasma riboflavin, and riboflavin supplementation has been shown to decrease both elevated homocysteine levels and blood pressure in individuals with MTHFR polymorphism.
It is generally considered that the populations of the developed countries have adequate nutrition and therefore do not suffer from deficiencies in essential micronutrients. However, in the last four decades the shortcomings are large because there are also impressive individual differences in the absorption and excretion of vitamins as a consequence of a wide variety of factors including specific genetic polymorphisms, gender, endocrine dysfunction, thyroid function, even the usual co- consumption of drugs, drugs, alcohol and other factors such as obesity, total energy consumption, intense exercise and age, determine and intensify the necessity B complex.
Statistics also show that many people in developed countries do not consume either the minimum recommended amount of any given micronutrient. In general, there is a gap between the intake of vitamins and the requirements for a significant percentage of the population. As a result, studies evaluating blood levels of vitamins show that a significant proportion of the population of developed countries have biochemical levels of each of the B vitamins that may predispose them to deficiency-related diseases.
In addition, a large proportion of the population is "at risk" and has deficiencies in vitamin B12, predominantly in people over 60 years of age. This may be due to an age-related damage to the absorption of protein-bound vitamin B12 found in food, although it should be noted that levels of deficiency in this vitamin are high for vegetarians and vegans.
The levels of thiamine deficiency are also higher in the elderly, with a 26% -28% deficiency. It is also worth noting that although rifophilin deficiency levels are not investigated, biochemical deficiency is potentially widespread due to the high prevalence of a hereditary absorption / utilization of riboflavin that affects 10% -15% of the world's population.
This deficiency phenomenon is largely based on the fact that current dietary choices are mainly loaded on sugars and processed starches, while micronutrients are included in an infinitesimal amount, leading to vitamin and mineral deficiency.
For example, thiamine plays an important role in glucose metabolism and between 20% and 35% of obese patients examined prior to bariatric surgery in various studies have been found to be inadequate. Similarly, thiamine deficiency rates have been reported to range between 17% and 79% in patients with diabetes.
At similar frequency, type II diabetes and elevated fasting plasma glucose levels have been found to be associated with lower biotin levels.
Overall, all these data suggest that a very significant percentage of the developed country population suffers from a deficiency or marginal shortage of one or more B vitamins, which may be a predisposition for a variety of chronic diseases.
There is a plethora of epidemiological studies suggesting the relationships between the biochemical levels of certain vitamins and their benefits for cardiovascular function, cognitive function and reduced incidence of dementia.
Of course, vitamins B, as a group and separately, also function with other vitamins, minerals and micronutrients.
