Oxidative stress plays a central role in the disease and progression of AD. The brain is particularly susceptible to oxidative damage for the following reasons:
- High oxygen demand,
- High content of polyunsaturated lipids, which are particularly susceptible to lipid peroxidation and which produce free radicals, and
- Relatively low concentration of antioxidants.
In addition, the aging process causes morphological and physiological changes in the brain that lead to a higher production of reactive oxygen species (free radicals) and a decrease in antioxidative capacity. To combat the cytotoxic activities of free radicals, cells are equipped with a variety of defense mechanisms, including antioxidant enzymes such as catalase and glutathione peroxidase, and radical scavengers such as vitamin C and vitamin E. Antioxidants can work by minimizing oxidants such as free radicals and metal ions or by disrupting underlying chain reactions and by optimizing cellular antioxidant defense mechanisms.
Vitamin C and vitamin E
Vitamin E (tocopherols and tocotrienols) is the most important membrane-bound fat-soluble antioxidant, and vitamin C (ascorbic acid) is an important water-soluble antioxidant that protects low-density lipoproteins from oxidation. In vitro studies (tests with substances in the test tube) indicate that antioxidants, including vitamins C and E, may prevent the unphysiological changes in tau protein associated with AD. In addition, vitamin E has been associated with a reduced mortality rate of nerve sites in the hippocampus
However, there seems to be a synergistic connection between the effects of vitamin C and E, so that it can be assumed that the supplementation of both vitamins together is indeed effective for brain health and the positive effect in AD. However, further studies are needed to be certain.
The vitamin E contained in dietary supplements is usually synthetic and consists of only one of eight natural isoforms (alpha-tocopherol), so vitamin E from food sources should have priority: These also contain important components and phytochemicals that interact with each other, enhance their positive effects against each other, and provide various combinations of tocopherol and tocotrienol forms that can play an important role in the prevention of AD.
Studies evaluating the relationship between Se levels and cognitive degeneration suggest that a lack of Se could increase the risk of dementia.
Se is an important trace element for the body and also plays a role as an antioxidant, through selenoprotein P (SeP) and the enzymes glutathione peroxidase (GSH-Px) and thioredoxin reductase (TrxR). In in vitro studies it was observed that neuronal cells exposed to the oxidative effects of amyloid plaques were protected in the presence of SeP. GSH-Px is expressed in neurons and glial cells and its main function is the elimination of peroxides (free radicals). Some studies suggest that cognitive degeneration is associated with a decrease in GSH-Px activity.
Beef, chicken, fish, eggs and wheat are considered good sources for Se. However, the amounts of Se in such foods reflect its concentration in the soil, so the same type of food may have different Se concentrations depending on its origin. Germany is one of the areas where selenium is deficient. Brazil nuts are considered the best source of Se due to their high concentration and high bioavailability. Some studies have shown an improvement in Se status in healthy people after eating two Brazil nuts daily for 12 weeks. Brazil nut consumption may also be effective in improving Se status in patients with AD, and this improvement could be an important therapeutic goal in maintaining cognitive function in patients.
Among the vitamins of the B complex, deficiencies of niacin (B3), thiamine (B1) and vitamin B12 (cobalamin) in particular show a correlation to certain neurological diseases.
Thiamine deficiency is associated with Wernicke-Korsakoff syndrome, which leads to damage to the central and peripheral nervous system, vision and coordination problems and subsequent dementia (memory loss, confabulations and hallucinations).
Pellagra is caused by niacin deficiency and is characterized by dementia (disorientation, memory loss and confusion), diarrhea and dermatitis.
Vitamin B12 deficiency is an important cause of treatable dementia. In addition to dementia, it can cause various clinical syndromes: Myelopathy (subacute combined degeneration), optical neuropathy and peripheral polyneuropathy. Myelopathy associated with vitamin B12 is damage to the posterior and lateral spine leading to incoordination (ataxia), gait abnormalities and numbness or paresthesia. Peripheral neuropathy can lead to neuropathic pain, numbness and ascending paresthesia. General weakness can also be observed.
Vitamin B12 has another very important function: together with vitamin B6 (pyridoxine) and folic acid (B9) it can lower homocysteine levels (an important inflammatory marker). Homocysteine is an amino acid produced by protein metabolism. High blood levels of this substance (hyper-homocysteinemia) destroy cells that line the inner walls of blood vessels (endothelium), promote the formation of thromboses and increase LDL cholesterol levels – all factors that promote the occurrence of atherosclerosis and cardiovascular disease. Homocysteine also has a direct neurotoxic effect.
Prospective observational studies have shown that total plasma concentrations of homocysteine are strongly associated with the risk of dementia and AD, and an increase in homocysteine concentration by 5 μmol/L increases the risk of AD by 40% (even after adjustment for variables such as age, sex, apolipoprotein E (ApoE) genotype and serum folate, vitamin B6 and vitamin B12 concentrations)
Given its role in lowering homocysteine plasma levels, folic acid, vitamin B12 and vitamin B6 may reduce the risk of dementia, enabling healthy cerebral aging.
Omega-3 fatty acids
Omega-3 long-chain polyunsaturated fatty acids, including linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are dietary fats that are incorporated into cell membranes and play a role in anti-inflammatory processes and the viscosity of cell membranes. ALA can only be obtained from food, while DHA and EPA can be synthesized from ALA in the body, but only to a limited extent. Therefore it is crucial to take in DHA and EPA additionally through food or supplements (if you do not eat fish). DHA is the most abundant lipid in the neuronal cell membrane, and EPA is involved in synaptic plasticity and increases the number and function of synapses. DHA and EPA are found mainly in foods such as fish oils and fatty fish, including salmon, tuna and trout, while ALA is commonly found in vegetable oils such as soy, rapeseed and linseed oils, nuts and in smaller amounts in seeds, vegetables, legumes, cereals and fruits.
Studies have shown that fish consumption is associated with a lower risk of AD development. In addition, an increased intake of omega-3 fatty acids appears to have positive long-term effects on the structure and volume of certain neuron-rich regions of the brain. The results of observational studies suggest that a sufficient intake of fatty fish and the omega-3 fatty acids they contain (especially DHA) may help prevent the development of pathological, progressive tissue loss from the cerebral cortex and reduce the risk of Alzheimer’s disease. An interesting study showed that the combination of omega-3 and alpha lipoic acid slowed cognitive and functional degeneration in AD over 12 months. Alpha lipoic acid is a powerful antioxidant and can recycle other antioxidants such as vitamin C, vitamin E and glutathione.
Another study showed a correlation between DHA and B vitamins: When DHA levels were high, supplementation of V vitamins showed greater effects.
(Link zu dem Kapitel: Omega-3 Fettsäuren und Omega-6 Fettsäuren- Relation)
These results suggest that the right combination of micronutrients is also important and not one substance alone, as the different micronutrients interact with each other and therefore a certain balance between them is important. A good balance provides all the substances that neurons need to function properly and live longer.
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