B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review
Abstract
:1. Background
What Are Vitamins?
Vitamin | Generally Known as | Good Dietary Sources | RDA 1 (mg) | UL 2 | Principal Bioactive Coenzymes (and Principal Coenzyme Role [8]) | Symptoms of Deficiency | Brain Specific Symptoms of Deficiency | Specific Risk Factors for Deficiency |
---|---|---|---|---|---|---|---|---|
B1 | Thiamin(e) | Cereals (esp. whole grain), brown rice, green vegetables, potatoes, pasta, liver, pork, eggs | 1.2/1.1 | - | Thiamine pyrophosphate (Generation of leaving group potential) | Mild deficiency: general fatigue/weakness gastro-intestinal symptoms [9]. Deficiency: “Beri-beri”— Peripheral nerve damage and cardiovascular dysfunction leading to: pain, impaired sensory perception; swelling, weakness and pain in the limbs; shortness of breath, irregular heart rate, heart failure [10] | Mild deficiency: irritability, emotional disturbances, confusion, disturbed sleep, memory loss [9]. Deficiency: Wernicke-Korsakoff syndrome (neurodegeneration, within the medial thalamus and cerebellum). Ataxia, abnormal motor function and eye movement, amnesia, apathy, confabulation [10] | Alcohol abuse, obesity [9] |
B2 | Riboflavin | Dairy products, leafy vegetables, legumes, liver, kidneys, yeast, mushrooms | 1.3/1.1 | - | Flavoproteins: flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN) (redox reactions) | Weakness, oral pain/tenderness, burning/itching of the eyes, dermatitis, anaemia [11] | Fatigue, personality change, brain dysfunction [11] | inherited riboflavin malabsorption/utilisation (10%–15% prevalence) [12] |
B3 | Niacin | Meat, fish, whole grain cereal, legumes, mushrooms, nuts | 16/14 | 35 mg | Nicotinamide adenine dinucleotide (NAD) and its phosphate (NADP) (redox reactions) | Pellagra: dermatitis/photo dermatitis, alopecia, muscle weakness, twitching/burning in the extremities, altered gait, diarrhoea [13] | Depression, anxiety, progressing to vertigo, memory loss, paranoia, psychotic symptoms, aggression (Pellagrous insanity) [13] | Alcohol abuse |
B5 | Pantothenic acid | Meat, whole grain cereals, broccoli | 5 | - | Co-enzyme A (CoA) (acyl activation and transfer) | Numbness/burning sensations in extremities, dermatitis, diarrhoea [14] | Encephalopathy, behaviour change, demyelination [14] | |
B6 | Vitamin B6 (referring to: pyridoxal, pyridoxamine, pyridoxine) | Meat, fish, legumes, nuts, bananas, potatoes | 1.3/1.3 (1.7/1.5 >50 year) | 100 mg | pyridoxal-5′-phosphate (PLP) and pyridoxamine-5′-phosphate (PMP) (Generation of leaving group potential) | Anaemia | Irritability, impaired alertness, depression, cognitive decline, dementia, autonomic dysfunction, convulsions [15] | Alcohol abuse, age-related malabsorption, contraceptive medications [16] |
B7 | Biotin | Eggs, liver, pork, leafy vegetables | 30 (µg) | - | biotin (carboxylation reactions) | Seborrheic eczematous rash, tingling/burning of the extremities [17] | Depression, lethargy, hallucinations, seizures [17] | Type II diabetes, poor gluco-regulation [18] |
B9 | Folic acid/folate | Leafy vegetables, legumes, citrus fruits | 400 (µg) | 1000 µg | tetrahydrofolates inc. methyltetrahydrofolate (One carbon transfer) | megaloblastic anaemia, peripheral neuropathy 3, spinal cord lesions, metabolic abnormalities [19,20] | Affective disorders 4, behaviour changes, psychosis, cognitive impairment/decline, dementia (inc Alzheimer’s disease and vascular dementia) [19] | Common genetic polymorphisms (inc. MTHFR C667T) [21] Low Riboflavin and B12 [22] |
B12 | Vitamin B12 (referring to: the cobalamins) | Meat, fish and other animal products | 2.4 (µg) | - | Methylcobalamin, adenosylcobalamin (vicinal rearrangements) | age-related malabsorption [23], vegetarians, vegans [24] Genetic polymorphisms [21] |
2. Mechanisms of Action and Functions of B Vitamins
2.1. Brain Specific Roles of B Vitamins
2.1.1. Thiamine (Vitamin B1)
2.1.2. Riboflavin (Vitamin B2)
2.1.3. Niacin (Vitamin B3)
2.1.4. Pantothenic Acid (Vitamin B5)
2.1.5. Vitamin B6 (Pyridoxine, Pyridoxal, Pyridoxamine)
2.1.6. Biotin (Vitamin B7)
2.1.7. Folate (Vitamin B9) and Vitamin B12 (Cobolamin)
3. The Homocysteine Hypothesis
4. B Vitamin Deficiencies in Developed Societies
5. How Much Is Enough?
6. Do B Vitamins Have an Impact on Brain Function?
6.1. Observational Studies
6.2. Controlled Intervention Trials
6.2.1. Folate, Vitamin B12 and Vitamin B6
6.2.2. Thiamine, Riboflavin, Biotin, Pantothenic Acid, Niacin
6.2.3. Multivitamins and Brain Function
6.2.4. Acute Effects of Multivitamins
6.2.5. Chronic Effects of Multi-Vitamins in Children
6.2.6. Chronic Effects of Multi-Vitamins in Adults
7. Summary and Conclusions
Acknowledgments
Conflicts of Interest
Abbreviations
AADC, aromatic l-amino acid decarboxylase |
AAAH, aromatic amino acid hydroxylases |
ATP, adenosine triphosphate |
BCKDC, branched-chain α-ketoacid dehydrogenase complex |
BH2, dihydrobiopterin |
BH4, tetrahydrobiopterin |
CBS, cystathionine beta synthase |
CGL, cystathionine gamma-lyase |
CoA, coenzyme A |
CS, citrate synthase |
DHFR, dihydrofolate reductase |
dTMP, thymidine monophosphate |
dUMP, deoxyuridine monophosphate |
EEG, electroencephalography |
EGRAC, erythrocyte glutathione reductase activation test |
FAD/FADH2, flavin adenine dinucleotide (oxidised/reduced) |
fMRI, functional magnetic resonance imaging |
GABA, gamma-aminobutyric acid |
GSSG, glutathione disulphide |
IDH, isocitrate dehydrogenase |
MAT, methionine adenosyltransferase |
MDH, malate dehydrogenase |
MCM, methylmalonyl-CoA mutase |
MMSE, Mini Mental State Exam |
MS, methionine synthase |
MTHFR, methyltetrahydrofolate reductase |
MTRR, methionine synthase reductase |
NAD, nicotinamide adenine dinucleotide (+/H = oxidised/reduced) |
NIACR, Niacin receptor |
NOS, nitric oxide synthase |
OGDH, α-ketoglutarate dehydrogenase |
PCC, propionyl-CoA Carboxylase |
PC, pyruvate carboxylase |
PD, pyruvate dehydrogenase |
RDA, Recommended Daily Allowance |
RDI, Recommended Daily Intake |
SAH, S-adenosylhomocysteine |
SAHH, S-adenosylhomocysteine hydrolase |
SAM, S-adenosyl methionine |
SCS, succinyl-CoA synthetase |
SH, serine hydroxymethyltransferase |
SQR, succinate-coenzyme Q reductase |
THF, tetrahydrofolate |
TS, thymidylate synthase |
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Kennedy, D.O. B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review. Nutrients 2016, 8, 68. https://doi.org/10.3390/nu8020068
Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review. Nutrients. 2016; 8(2):68. https://doi.org/10.3390/nu8020068
Chicago/Turabian StyleKennedy, David O. 2016. "B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review" Nutrients 8, no. 2: 68. https://doi.org/10.3390/nu8020068