Acetylcholine in foods: 9 Foods High in Choline and Why You Need It

02.02.197922.11.2021 by alexxlab

Содержание

Know Your Neurotransmitters: Acetylcholine – UNC NRI

June 1, 2017 – It’s high time we covered acetylcholine — the most plentiful neurotransmitter in the body. And our Know Your Neurotransmitters series continues with the best guest possible to talk to us about acetylcholine: Dr. Steven Zeisel, MD, PhD.
Dr. Zeisel, UNC Nutrition Research Institute Director, was involved in the first study of the effects of choline — the nutrient precursor to acetylcholine — on humans.

What’s the Big Deal About Choline?

In Dr. Zeisel’s first experiment with humans, he fed men and women a diet deficient in choline. Most men and postmenopausal women became ill when deprived of choline.
Their bodies weren’t able to produce their own choline and they began to experience liver problems: fatty liver accumulation and liver cell death. These problems reversed within a few days of reintroducing choline to their diet.
For younger women, however, 55% did not experience any negative effects from choline deprivation. The difference? Estrogen.
There’s a gene in our livers, PEMT, that can produce choline but it’s only turned on by estrogen. Neither men nor postmenopausal women produce enough choline to switch on the gene. And those 45% of women who did get sick? They have a gene “misspelling” that makes their PEMT gene unresponsive to estrogen.

Why We Need Choline

For adults, choline deficiency can have two serious consequences. For most people, lack of choline means that your liver is unable to properly process fat, and you get fatty liver. A fatty liver puts you at risk of prediabetes and liver cancer. For 10% of adults, choline deficiency leads to muscle breakdown.
But for fetuses and infants, insufficient choline has even more devastating consequences.

Choline is absolutely essential in developing a normal brain. The development of the hippocampus, the memory center of the brain, requires choline. The development of the frontal cortex, responsible for high-level thinking, requires choline.
And lack of choline in the earliest stages of development impairs a child’s mental function for years to come. A high intake of choline during pregnancy results in higher cognitive performance in children at 7 years old.

Choline & Acetylcholine

Choline is a precursor to the neurotransmitter acetylcholine. Nerves use choline to make acetylcholine, which acts as a messenger between nerves — a huge variety of nerves.
Acetylcholine tells muscles to twitch and more, but it also tells your hippocampus to store a memory. It plays an essential role in alertness, attention, learning, and memory. It’s so essential to memory, in fact, that acetylcholine deficits are associated with Alzheimer’s disease.

Getting Enough Choline

Clearly, it’s important to get enough choline in your body. Foods that are high in fat and cholesterol are also generally high in choline. That means eggs and meat, particularly beef (418mg of choline per 100g) and chicken liver (290mg/100g), are the best dietary sources of choline.
Don’t despair vegans, as wheat germ (152mg/100g) is also a good source of choline. You can also take a choline supplement, like CDP Choline.
As for how much choline you should aim for a day, women need 400mg, 450mg if pregnant. Men should aim for 500mg of choline a day.

There can be too much of a good thing, however. Don’t get more than 3g of choline per day. That much choline will cause low blood pressure, and potentially increase your risk of heart disease.
This post was originally published on smartdrugsmarts.com and compliments a podcast on acetylcholine featuring NRI Director Dr. Steven Zeisel.

How to Get Choline on a Vegan and Vegetarian Diet

Choline may not be on your radar, but it should be. This essential nutrient has been highlighted recently because Americans aren’t getting enough of it. According to a recent study, only about 11% meet their daily needs, and 65% don’t even know what it is! Yet, this nutrient is critical for your health, particularly in maintaining a healthy liver system and brain. While everyone needs choline, it seems to be even more important early in life while the brain is developing, and later in life to prevent cognitive decline. That’s why the FDA recently established a RDI (Reference Dietary Intake) of 550 milligrams (mg) for choline for adults and children 4 and above, and a Daily Value (DV, the daily requirement abased on 2,000 calories per day), which you will soon see listed on the Nutrition Facts labels of foods—indicating what percentage of the Daily Value a portion of food provides.

Here are the Adequate Intakes established for choline.

Adequate Intakes for Choline

Table 1: Adequate Intakes (AIs) for Choline
Age	Male	Female	Pregnancy	Lactation
Birth to 6 months	125 mg/day	125 mg/day
7–12 months	150 mg/day	150 mg/day
1–3 years	200 mg/day	200 mg/day
4–8 years	250 mg/day	250 mg/day
9–13 years	375 mg/day	375 mg/day
14–18 years	550 mg/day	400 mg/day	450 mg/day	550 mg/day
19+ years	550 mg/day	425 mg/day	450 mg/day	550 mg/day

Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998.

This Instant Pot Banana Brown Rice Pudding provides choline, compliments of the bananas and brown rice.

So, where can you get choline in your diet? The top sources include beef liver, eggs, beef, scallops, salmon, chicken, and cod. But where are you going to get choline if you’re a vegetarian or vegan? Vegetarians can get some choline in eggs and milk products. And there are several plant-based sources of choline (see chart below), including legumes, tofu, green vegetables, potatoes, nuts, seeds, grains, and fruit—all of which contain some amounts of choline. However, plant sources are fairly low in choline, making it even more difficult to reach that RDI of 550 mg/day if you’re vegan. Keep in mind that the average intake for choline in the U.S. is 402 mg in men and 278 mg in women.

This recipe for Peanut Butter Chocolate Chickpea Bars is rich in choline, compliments of chickpeas and peanuts.

We don’t have a great deal of data on choline intakes among plant-based eaters. But here’s a sample menu for a vegetarian eating pattern providing 2000 calories per day:

Breakfast: Avocado Toast with Hard Boiled Egg
AM Snack: Apple & Cheddar Cheese Stick
Lunch: Loaded Sweet Potato with Brown Rice, Black Beans, Guacamole, Cotija Cheese & Sour Cream
PM Snack: Non-Fat Latte and Dried Dates
Dinner: Asian Tempeh Bowl

The estimated daily choline intake of this sample menu is 187 mg (37% DV).

However, keep in mind that I analyzed my version of a recommended healthy, well-planned vegan diet, as follows:

Breakfast
1 cup oats
1 banana
2 tablespoons wheat germ
2 tablespoons flax seeds
8 ounces soy milk

Lunch
Salad:
3 ounces extra firm tofu
2 cups kale
1/4 cup almonds
1/2 cup broccoli florets
1/2 cup cherry tomatoes
2 tablespoons tahini
1 slice whole grain bread + 1/2 avocado

Dinner
1 cup chickpeas
1 cup masala sauce
1 cup cooked quinoa
1 cup cooked brussels sprouts
1 apple

The estimated choline intake from this vegan menu (2452 calories) is 255 mg choline.

This recipe for Asparagus Dill Tofu Quiche is a good source of choline, compliments tofu, tomatoes, and flax seeds.

So, what should you do? First off, my recommendation for all vegans and vegetarians is to eat a diet rich in whole, minimally processed plant foods, including portions from all the major food groups at each meal: pulses (beans, lentils, peas) or soyfoods, nuts or seeds, whole grains, fruits, and vegetables (green vegetables daily). This will help supply a source of important essential vitamins and minerals to your diet, including calcium, iron, zinc, and choline. If you aim for a diet filled with whole plant foods, you may come pretty close to meeting your choline needs, as evidenced in my sample meal plan. Adult women should aim for 425 mg per day, and men for 550 mg per day.

Orangesicle Popsicles contain choline, compliments of oranges, bananas, and soymilk.

My second recommendation for plant-based eaters (particularly for vegans) is to supplement smartly. It is important to supplement a few key nutrients. One is vitamin B12, which is found primarily in animal foods. In addition, I recommend that you consume fortified sources of calcium and vitamin D (for example, in plant-based milk) and evaluate whether you need to take an additional supplement to meet your needs. Other nutrients that may be worth supplementing include long chain omega-3s (algae DHA and EPA) and iodine. And, considering the recent news on choline, it seems that you might want to take a closer look at this nutrient in your diet.

If you eat a diet filled with whole plant foods, you may come pretty close to meeting your needs. However, if your intake is lower than 2000 calories per day for women, or 3000 calories per day for men, you may fall short of choline. So, you may want to supplement your diet a few times per week with choline. However, keep in mind that new research has linked high choline intake and blood levels with increased mortality. That’s because high choline intake has been linked with increased production of TMAO, which has been associated with significantly higher risk of heart attacks and strokes compared with lower levels. So, it may not be a good ideas to over supplement with choline. As with all dietary supplements, you should discuss them with your health care professional before taking them. It may be beneficial to take small doses of choline (about 250 mg) a few times per week to balance out low intake, but it’s not a case of more is better! Here is a really good article on this topic of choline intake and heart risks written by one of my colleagues, Carrie Dennett.

This recipe for Gado Gado is a good source of choline, due to broccoli, tempeh, peanut butter, and potatoes.

I prefer to approach supplementation from the perspective that you should supplement your diet with the nutrients you fall short on, not the whole kitchen sink in one pill. For example, plant-based eaters typically get higher levels of vitamins E, A and C, thiamin, riboflavin, and folate than omnivores. So, why supplement all of these nutrients, which may come along for the ride in a multi? And multivitamins may not contain those nutrients you are looking for, such as calcium and choline. A supplement should be just that—a supplement to your diet, covering the shortfall. You may need to only take half the recommended level to meet your diet half way. And remember that overdoing supplements is never a good thing. I recommend sticking as close to the recommended daily level as possible, factoring in that you gain some of these nutrients in your diet, too.

Please note that it is important to discuss any dietary supplement regimen with your healthcare practitioner. In addition, you should discuss your own personalized diet plan and nutrient needs with a trained, plant-based health care practitioner, such as a registered dietitian or physician knowledgable in this area.

Boost choline in your diet with chickpeas in this recipe for Chickpea Curry with Sorghum.

Vegan and Vegetarian Food Sources of Choline

The following plant foods offer sources of choline.

Vegan	Serving	Choline (mg)
Almonds, dry roasted	1 ounce	7
Apples, raw, with skin	1 large	8
Bananas, raw	1 medium	12
Bread, whole wheat	1 slice	15
Broccoli, cooked	1 cup, chopped	63
Brussels sprouts, cooked	1 cup	63
Brown rice, cooked	1 cup	18
Chickpeas, cooked	1 cup	70
Dates, medjool	1	10
Flaxseed, ground	2 tablespoons	11
Lentils, cooked	1 cup	65
Oats, instant, fortified, plain	1 cup	17
Oranges, raw	1 large	16
Peanut butter, smooth	2 tablespoons	20
Peanuts	1 ounce	15
Potatoes, boiled, in skin	½ cup	11
Quinoa, uncooked	¼ cup	30
Soymilk, original and vanilla, unfortified	1 cup	57
Sunflower seeds, dried	1 ounce	15
Spaghetti, cooked, enriched	1 cup	13
Squash, summer, cooked	1 cup	9
Tofu, firm	½ cup	35
Tomato sauce	1 cup	15
Wheat germ, toasted	2 tablespoons	25
Vegetarian
Egg	1 large	147
Milk, skim	1 cup	38
Yogurt, low-fat, plain	1 cup	37

Source: USDA

Brussels sprouts are a good source of choline. Try this recipe for Maple Balsamic Roasted Brussels Sprouts.

Image: This Harvest Grain Bowl, which is rich in choline, is featured in my new book California Vegan, coming out in 2021.

Written by Sharon Palmer, MSFS, RDN on January 30, 2017; updated on August 6, 2020.

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The dietary sources of acetylcholine.

Context 1

… humans, ACh serves as a NT at the neuromuscular junctions, ganglionic synapses, and at diverse sites within the central nervous system. Its presence (Figure 1) is documented in more than 50 plant species belonging to all the major systematic groups, comprising the most economically important plant families: Gramineae, Leguminosae, and Solanaceae [11]. In particular, extracts from Cucurbita pepo L. (that is, squash), Solanum melongena L. (that is, aubergine), and Spinacia oleracea L. (that is, spinach) were reported to contain a considerable amount of ACh [12]. Besides its presence in plants that could suggest its role in the regulation of membrane permeability or specific metabolic pathways [13], ACh was found in the seeds of Pisum sativum L. (that is, pea), Phaseolus radiatus L. (that is, mung beans), and Phaseolus vulgaris L. (that is, common bean), thus, indicating a possible role during germination [11]. The fruits of Citrus aurantium L. (that is, bitter orange), Fragaria vesca L. (that is, wild strawberry) [14], and the edible root vegetable of Raphanus raphanistrum subspecies sativus L. (that is, radish) [15] were indicated to contain Ach. The highest concentrations of ACh was found in the nettle species of Urtica dioica L. (for example, about 0.5 μmol/g dry weight of roots) [14] and of Urtica ureus L. [16], whose folium and herba are traditionally used as adjuvants in minor urinary problems and articular pain. Other plants, such as Viscum album L. (that is, mistletoe) and Digitalis purpurea L. (that is, foxglove), contain significant amounts of ACh [11]. In particular, mistletoe had a traditional use in the treatment of patients with high blood pressure, arteriosclerosis, hypertensive headache, epilepsy, chorea, hysteria, and other neurological diseases [17]. The cardiac-depressant and sedative properties of mistletoe were attributed to various biologically active constituents, such as ACh itself, but also to histamine and GABA [18]. …

Choline – an overview | ScienceDirect Topics

7.1 Choline

Choline is a water-soluble organic compound with a molecular weight of 104.17 g/mol. It is classified as an essential nutrient by the Food and Nutrition Board of the Institute of Medicine [85]. It is involved in the synthesis of phospholipids and other structural components of cell membranes, and as a precursor for the important neurotransmitter acetylcholine [86]. Humans can synthesize choline in small amounts by converting the phospholipid, phosphatidylethanolamine, to phosphatidylcholine via de novo synthesis. However, humans cannot synthesize enough choline to meet metabolic needs. Sufficient amount of choline can be obtained through the diet.

In a study of 7074 healthy subjects, plasma choline was found to be associated with a number of cardiovascular risk factors [87], including a positive correlation between choline and serum triglycerides, glucose, body mass index, body fat, and waist circumference. High choline concentrations were associated with an unfavorable cardiovascular risk factor profile. Choline in blood has recently been recognized as a potentially useful biomarker for diagnosis and risk stratification of ischemic heart disease, especially in those with negative initial troponins [88]. In a prospective study of 327 troponin-negative patients suspected of ACS, whole-blood choline was a predictor of cardiac death and nonfatal cardiac arrest, life-threatening arrhythmias, and heart failure [89]. Elevated choline concentration at hospital admission was a predictor of adverse cardiac events in patients with suspected ACS, and it might consequently be useful for early risk stratification of these patients. Danne et al. demonstrated that both whole-blood choline and plasma choline were significant and independent predictors of major cardiac events in ACS patients with initial negative troponin [90]. Both were associated with events related to tissue ischemia as choline was firstly released from injured ischemic tissues into plasma with a secondary uptake into blood cells, whereas only whole-blood choline could predict risks related to coronary plaque instability as activation of phospholipase D in blood cells leading to an intracellular increase in choline concentration that was not detectable in plasma. Serum choline has also been demonstrated as a useful biomarker for prediction of 30-day cardiovascular outcomes in patients with ACS [91].

Further studies are required to investigate its clinical significance in patients with suspected ACS. Also, choline is currently determined by using a high-performance liquid chromatography-mass spectrometry, which complicates its adoption into routine clinical use. Development of a rapid and simple assay is necessary to evaluate whether choline can identify high-risk patients in clinical practice.

Ethanolamine Produced from Oleoylethanolamide Degradation Contributes to Acetylcholine/Dopamine Balance Modulating Eating Behavior | The Journal of Nutrition

Abstract

Oleoylethanolamide is a well-recognized anorectic compound which also has noteworthy effects on food-reward, influencing the acetylcholine (ACh)/dopamine (DA) balance in the cholinergic system. After its administration, oleoylethanolamide is quickly degraded into oleic acid and ethanolamine. The effect of oleic acid on the gut–brain axis has been extensively investigated, whereas ethanolamine has received scarce attention. However, there is scattered evidence from old and recent research that has underlined the influence of ethanolamine on the cholinergic system. In the present article, we propose a model by which the released ethanolamine contributes to the overall balance between DA and ACh after oleoylethanolamide administration.

Oleoylethanolamide (OEA) is a well-recognized anorectic compound (1). Investigations have pointed out that, when administrated at a dose of 10 mg/kg, it affects food reward by influencing the acetylcholine (ACh)/dopamine (DA) balance in the cholinergic system (1). Published data support the effect of OEA on both the homeostatic and nonhomeostatic regulation of food intake through the activation of peroxisome proliferator–activated receptor-α (PPAR-α) in the small intestine, which mediates satiety signals to the brain via the afferent vagal fibers (2).

Mammals have the enzymes to synthesize and degrade N-acetylethanolamines (NAEs), including OEA. NAEs are biosynthesized “on-demand” from their precursors N-acylated ethanolamine phospholipids through 3 different enzymatic pathways (3). The absolute concentration of NAEs in tissues is very low, in the order of a few nanomoles per gram of tissue, the highest concentration being present in the brain and intestine (3).

NAEs, including OEA, can also be provided by certain foods, oatmeal, nuts, and cocoa powder being the major food sources, but the amount per gram of OEA found in these foods is very low (<2 μg/g) (4) compared with the amount used in clinical trials. OEA can also be synthesized upon ingestion of precursor-containing foods, such as olive oil. For example, the intake of a meal containing a high amount of oleic acid increased the plasma concentration of OEA in rats and humans (5, 6), reducing the following energy intakes in humans (6; for a summary of human studies addressing the role of OEA on eating behavior see Supplemental Table 1).

Hydrolysis of NAEs is catalyzed by the fatty acid amide hydrolase, which has a strong activity in the intestine, liver, brain, and at the blood–brain barrier level (7), resulting in the production of fatty acids and ethanolamine (EA). After OEA is orally or intragastrically administrated in relatively abundant doses, i.e., 10 mg/kg, it is likely that after its degradation, a peak in oleate and EA occurs in several organs. The effect of oleic acid on the gut–brain axis has been extensively investigated, whereas EA has received scarce attention. One study (8) tested the effect of oral EA (1.88 mg/kg, equivalent to the amount released by 10 mg/kg of OEA) and found no effect on food intake compared to a control group, in rats. However, in this study only food intake and no other aspects of eating behavior, such as food preferences for high-sugar or -fat foods that may also be influenced by the activation of brain areas related to food reward, were investigated. On the contrary, there is scattered evidence from old and more recent research which underlines the influence of EA on the cholinergic system.

Here, we briefly describe effects of OEA and EA on the cholinergic system, suggesting that EA contributes to the overall balance between DA and ACh after OEA administration (9, 10).

The Cholinergic System Regulates Food Reward by Interacting with the Dopaminergic System

The cholinergic system modulates various brain functions through the release of ACh (11). This occurs as a result of depolarization of the axonal termination that induces a rise in the cytosolic Ca²⁺ concentration and fusion between the axoplasmic membrane and the vesicles containing ACh. Projection neurons constitute the main brain structure of the cholinergic system, which originates mainly in subcortical regions, such as the basal forebrain, and extends into many brain regions, including cortical areas and the hippocampus. Interneurons with cholinergic activity were also identified in specific target areas of the mesolimbic system, such as the nucleus accumbens (NAc) (11), which are involved in pleasure and motivation, contributing to the hedonic dimension of eating.

In the regulation of eating behavior, the cholinergic system constantly interacts with, and regulates the activity of, one of the main neurotransmitters involved in reward, DA (12). DA is synthesized by dopaminergic neurons in the midbrain (i.e., ventral tegmental area and substantia nigra). The dopaminergic mesolimbic pathway is a neuronal circuit that is activated in order to translate motivation into action in a variety of behaviors, including eating (12).

In human lean subjects, food cues stimulate DA release in the dorsal striatum (12) and during eating, DA response is positively correlated with the pleasantness of the food. This evidence indicates that, in lean subjects, DA may be considered as a biomarker of the hedonic value of foods. Conversely, in obese subjects, responses to food cues and food ingestion stimuli are blunted (12).

The dopaminergic and cholinergic systems have a similar anatomical connectivity with numerous functional neuronal endings, such as in the NAc. Here, cholinergic interneurons, together with dopaminergic projections of the ventral tegmental area, modulate the activity of γ-aminobutyric acid (GABA) projection neurons (12). In the NAc, ACh/DA fluctuations modulate eating behavior. For example, when rats are exposed to an adverse conditioned stimulus, there is a concomitant ACh increase and DA decrease. In addition, mice deprived of food in a free feeding state stop eating when the ACh:DA ratio begins to increase (12).

OEA Influences Cholinergic-Mediated Food-Reward Regulation

Some investigations have also suggested that OEA influences the food-reward system by modulating DA release. High-fat diet chronic consumption in mice produces a significant reduction in intestinal OEA synthesis, but not in other tissues, which is concomitant with a reduction of DA in the brain. In high-fat diet–fed mice, infusion of 10 mg/kg OEA solution 25 min before intragastric lipid emulsion infusion restored DA release. No difference was found in DA increase in response to the calorific content of the emulsion. In low-fat diet–fed mice, OEA influenced the release of DA when stimulated by intragastric infusion of a low-calorie emulsion. In addition, in low-fat diet–fed mice, the infusion of OEA decreased the intake of both low-calorie and high-calorie emulsions. Finally, the authors demonstrated that these effects were abolished in subdiaphragmatic bilaterally vagotomised and in PPAR-α knockout mice (1). This evidence indicates that OEA interacts with the mesolimbic system, probably via activation of PPAR-α on the vagal afferent nerves. In contrast, another investigation provided evidence that OEA can regulate DA release through central mechanisms as well. In rats, when injected in the lateral hypothalamus, OEA increased extracellular DA concentrations in the NAc (9). The molecular mechanisms of OEA–DA interaction have not been fully clarified yet.

Ethanolamine, a Downstream Metabolite of OEA, May Serve as a Neuromodulator Stimulating Acetylcholine Release in the Brain

The quantitative degradation of 10 mg of OEA may produce 1.88 mg of EA and this is particularly interesting because it is a small molecule with a rather good ability to pass the blood–brain barrier and influence the activity of diverse brain areas (13). Several pioneering studies demonstrated that EA can be released from different brain regions after electrical or chemical depolarization (14). A more recent in vitro study demonstrated that, when synaptosomes and synaptoneurosomes were incubated with EA, this was stored in intracellular compartments, and released by classical exocytosis after depolarization (15). The authors pointed out that the concentration of EA released was low compared to a classical neurotransmitter, but they did not exclude the possibility that a discrete receptor exists postsynaptically for EA (15). Although EA cannot be considered as a pure neurotransmitter, all in all, these studies support the role of EA as a neuromodulator, a molecule that is not directly excitatory or inhibitory, but that can sustain both activities depending on the site and the time frame of its release. Therefore, it is convincing that the EA released from the degradation of NAEs in the intestine or at the blood–brain barrier level may play a role in the brain. In fact, it is known that EA can modulate neurotransmitters. It was shown that EA stimulates the release of aspartic and glutamic acids in the anterior hippocampus of rabbits (16), and it is also known to inhibit the enzyme GABA aminotransferase with the consequence of reducing GABA breakdown and increasing its concentration in the brain (17).

Some investigations demonstrated that, similarly to OEA, EA could influence the cholinergic system. A first suggestion came from the neuronal cells’ ability to use EA as a precursor of ACh. In chicken neuronal cultures, it was proved that EA is rapidly phosphorylated to phosphoethanolamine and converted to phosphatidylethanolamine that may also be methylated to phosphocholine (18). In vivo, intraventricular injections of ³H-EA showed that the rat brain has the capacity to synthesize free choline de novo by stepwise methylation of EA, phosphoethanolamine, and phosphatidylethanolamine (19). In the human cell line neuroblastoma LA-N-2, it was demonstrated that the same pathway exists and that the choline thus produced is a source of de novo synthesis of ACh (20). In contrast, Ansell and Spanner (21) described that after injection of labeled EA in the ventricle side of the rat brain, labeled phosphatidylethanolamine was formed, but no labeled phosphatidylcholine was found. Similar results were obtained by Browning and Schulman (22) in slices of cerebral cortex of rats. They showed that labeled ACh was formed in the presence of labeled choline, whereas ACh was not labeled if choline was substituted with labeled EA, serine, or methionine. Therefore it is accepted that, although the conversion of EA into ACh is possible, in vivo and in the presence of normal plasma choline concentrations, EA is not used for choline and ACh synthesis.

However, other investigations found that EA can increase ACh extracellular concentrations in the brain by indirect mechanisms. In cultured explants of the medial septal nucleus from rat brains, EA enhances the ability to develop cholinergic neurons to utilize choline for the production of ACh (23). EA has been shown to increase extracellular concentrations of ACh in rat hippocampus slices during continuous infusion in a depolarizing KCl buffer. This increase was not mediated by a greater synthesis of ACh, but by a higher cellular release that would be stimulated by amino-alcohols such as EA (24). In a subsequent study, they suggested that the mechanism through which amino-alcohols facilitate ACh release in the hippocampus may involve the activation of calcium channels (25). Interestingly, this effect appears to be specific to cholinergic endings, because other neurotransmitters, such as norepinephrine and DA, were not affected. A similar result was obtained by Khairy et al. (10), who showed that the application of EA on dorsal root ganglion neuron cells, with a threshold of 10 nM, increases the amplitude and duration of the transport of KCl-stimulated Ca²⁺ release. Furthermore, EA stimulated voltage-activated K⁺ currents independently of the activation of Ca²⁺ channels. In another study, Liao and Nicholson (17), in accordance with Bostwick, also found that EA increased neurotransmitter release from brain synaptosomes, but they proposed different mechanisms of release. They demonstrated that synaptosomes incubated with EA, at a concentration from 0.31 mM to 5 mM, increased their capability to release neurotransmitters, i.e., [³H]-D-aspartic acid. They suggested that EA permeated into synaptic vesicles, increasing their filling capability. The enhanced capability of synaptic vesicles to load neurotransmitters explains how EA influence may regulate synaptic transmission. The concentrations used in the study were within physiological levels of EA in the brain, i.e., between 197 and 870 nmol/g (17).

Therefore, even if the mechanisms are still not clear, there is strong evidence to support that EA influences neurotransmitter release in the brain. This is of great interest especially when the source of EA is OEA, because this NAE has itself an action on the cholinergic/dopaminergic system. It is also possible that there are differences in the overall effect on the brain between the administration of pure EA, as investigated by Nielsen et al. (8), and EA released after OEA degradation, because this EA can keep acting on neurotransmitters previously stimulated by OEA.

In conclusion, this evidence supports the hypothesis that OEA and its metabolite, EA, can interact in the regulation of the overall ACh/DA balance influencing brain areas involved in food reward (Figure 1). Taking into account this perspective, further studies should investigate the kinetics of EA release after OEA administration and whether it can affect the cholinergic regulation of dopamine.

FIGURE 1

Schematic representation of OEA and EA effects on ACh/DA balance. From the intestine, OEA communicates via vagal afferent fibers with brain areas regulating DA release. OEA is then degraded by the enzyme fatty acid amide hydrolase into oleic acid and EA, which pass into the bloodstream and can in part penetrate the blood–brain barrier. In the brain, EA acts as a neuromodulator, being able to stimulate ACh release from cholinergic neurons. ACh/DA fluctuations modulate eating behavior. ACh, acetylcholine; DA, dopamine; EA, ethanolamine; FAAH, fatty acid amide hydrolase; OEA, oleoylethanolamide.

FIGURE 1

Acknowledgments

The authors’ contributions were as follows—IM designed the research and has primary responsibility for the final content; and all authors: wrote the article and have read and approved the final manuscript.

Notes

Supported by the AgreenSkills+ fellowship programme which has received funding from the EU’s Seventh Framework Programme under grant agreement N°FP7- 609398 (099/2017).

Author disclosures: GB and DV-L, no conflicts of interest. IM reports grants from Brittany Region (SAD program, Stratégie d’Attractivité Durable), University Bretagne Loire, and AgreenSkills+ during the conduct of the study.

The funding source had no involvement in decisions related to the research and publication of results.

Supplemental Table 1 is available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/jn/.

Abbreviations used:

GABA

PPAR-α
peroxisome proliferator–activated receptor-α

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Frontiers | In silico Gene Set and Pathway Enrichment Analyses Highlight Involvement of Ion Transport in Cholinergic Pathways in Autism: Rationale for Nutritional Intervention

Introduction

Sensory processing dysfunction, which is commonly experienced by persons diagnosed with autism spectrum disorder, extends across auditory, visual, pressure, temperature, pain, vestibulary, and interoceptive processing domains (Craig, 2002; Ashburner et al., 2008; Case-Smith et al., 2015; Boterberg and Warreyn, 2016; Crasta et al., 2016). Some features of sensory processing, including heightened sensitivity to sound (hyperacusis), appear to be prevalent in the majority of the autistic population (Wilson et al., 2017; Williams et al., 2020). All types of sensory processing rely on sensory gating—the ligand-activated, ion-channel mediated pathways built upon cholinergic neurotransmission signals. Acetylcholine, a primary neurotransmitter ligand in these pathways, plays a key role in cognitive function, memory, learning, and sensory processing signal transduction. Acetylcholine is made in an enzymatic reaction between acetyl-CoA and choline, which is facilitated by the choline acetyltransferase (Oda, 1999). Neuronal molecules associated with acetylcholinergic signal transmission, including the nicotinic receptor family, are heavily implicated in propagation of auditory signals through respective transmission pathways (Simmons et al., 2011; Bertrand et al., 2015; Deutsch et al., 2015; Dineley et al., 2015; Sinkus et al., 2015; Gillentine et al., 2017). Research of cholinergic function in autism has led to clinical trials examining efficacy of cholinergic enhancement and/or acetylcholinesterase inhibitors—more commonly used in Alzheimer’s disease—to address social and cognitive aspects of autistic behaviors (Bentley et al., 2003; Hertzman, 2003; Nicolson et al., 2006; Ghaleiha et al., 2014; Karvat and Kimchi, 2014; Rossignol and Frye, 2014; Eissa et al., 2018). However, cholinergic support to sensory processing in autism remains less examined. Recent developments in autism genome-wide association studies (GWAS) have provided estimates of an overlap of autism-related gene sets with those involved in sensory processing and in cholinergic signal transmission.

While humans can make small amounts of choline endogenously, the replenishment of the pool of acetylcholine available in the human body depends heavily upon dietary choline intake (Gibellini and Smith, 2010). In the United States, nearly nine in 10 Americans over 2 years of age do not meet recommended daily consumption levels of dietary choline. Moreover, an estimated 60–93% of children on the autism spectrum are not meeting their adequate intake (AI) level for choline either, even as experts in choline metabolism continue to emphasize its criticality for nutrition across the lifespan, particularly at critical stages of neurodevelopment (Caudill, 2010; Hamlin et al., 2013; Wallace and Fulgoni, 2016; Blusztajn et al., 2017; Ganz et al., 2017; Wallace et al., 2018, 2019; Zeisel, 2019). In rodents, choline-deficient diets are associated with decreased levels of brain acetylcholine (Cohen and Wurtman, 1976). In both rodents and humans, choline deficiency is associated with impaired sensory gating function (Wu et al., 1993; Fendt and Koch, 1999; Stevens et al., 2008; Knott et al., 2014; Swerdlow et al., 2016). Given possible risk of choline underconsumption and/or its deficiency in humans, and the known impact of choline deficiency upon brain acetylcholine and sensory function in rodents, further investigations into the potential impact of choline underconsumption upon sensory processing are warranted, particularly with respect to those on the autism spectrum. Such research may eventually open an avenue for modulation of sensory processing through nutritional interventions.

To explore the potential relationship between autism spectrum disorders (ASDs) and choline intake, we conducted an enrichment analysis of gene sets associated with ASD and cholinergic pathways, and constructed the model reflecting this relationship. Results of our study highlight the potential impact of dietary choline deficiency upon cholinergic signaling within the genetic context of autism.

Materials and Methods

Overview of Workflow

This study has focused on gene ontologies cataloged in the Gene Ontology (GO) database for enrichment analysis of an overlap between two gene sets, one for cholinergic pathways and one for autism-associated genes. Gene ontological enrichment analysis was conducted within the Pathway Studio environment (Elsevier, Inc.) between December 2019 and March 2020. The Pathway Studio database contains functional relationships and pathways of mammalian proteins, including human, mouse, and rat genes. It contains over 1.4 million entities of 14 well-defined categories, including cells, proteins, disease, and small molecules, and more than 13.4 million relationships among these entities. The database includes over 24 million PubMed abstracts and 3.5 million Elsevier and third party full-text papers. Using the natural language processing (NLP) functionality of Pathway Studio, intersections of these gene sets’ pathways were rendered graphically, with connections indicating directional relationships being supported by the current scientific literature. This exploratory analysis and figure development which employed in part some of Pathway Studio’s graphical capabilities took place between March 2020 and November 2020. Since many of the autism-associated genes in the GWAS study have been recently identified as autism-associated only within the past 2 years, this gene/pathway modeling effort was supported by secondary analyses, including use of predictive tools in splice site identification.

Identification of Ontologies Associated With Each Gene Set, and Shared Ontologies

To identify GO database pathways shared between cholinergic pathways and autism-associated genes, gene set enrichment analysis was conducted. Molecular Signatures Database v7.1 (MSigDB)—one of the most widely used repositories of thoroughly annotated gene sets, used in research on both neurological conditions and on cholinergic pathways, specifically—was chosen as a precurated resource for gene sets connected with cholinergic activity (Tan et al., 2010; Turcan et al., 2010; Liberzon et al., 2011; Koker et al., 2018; Schijven et al., 2018; Zhang et al., 2019). A key word search for “cholin^∗,” identifying any word beginning with cholin- (choline, cholinergic, cholinesterase, etc.), was used to identify cholinergic-relevant gene sets encompassing a total of 345 genes, which constituted the cholinergic activity gene set for this ontological enrichment analysis. An autism gene set containing 47 genes from a recent cross-trait genome-wide meta-analysis (Wu et al., 2020) was used because it identified more risk genes for ASD compared with another GWAS study for ASD, thus providing enhanced statistical power for the present study (Grove et al., 2019).

Gene ontology association analysis was conducted with each respective set of genes within Pathway Studio. The lists of ontologies assigned to each of these gene sets were trimmed at approximately the lowest 100 p-values (p < 0.01). A shift in the magnitude of p-values, nearest the lowest 100 p-values, served as the final determinant of cut-off for each respective gene sets’ ontology lists. The overlaps were identified using the Venn diagram web tool, Venny 2.1 (Oliveros, 2007–2015).

Genes from the autism gene set were then examined for their potential upstream or downstream relationships with acetylcholine, with additional attention paid to potential roles related to the identified shared ontologies, as they were related to sensory processing and cholinergic sensory signal transmission. The identification of upstream and downstream elements and related pathways was conducted using Pathway Studio’s natural language processing tools within its menu architecture, which generate indices of related entities (genes, proteins, physiological conditions, etc.) per tool sorting specifications. The main two tool specifications used in this exploratory analysis were the Pathway Studio options to view first degree connections (known in Pathway Studio as Direct Interactions) and to view the shortest path between entities within the literature (known in Pathway Studio as Shortest Path). Both of these tool specifications were the primary means of building a broader understanding and figure illustration of literature-supported cholinergic networks related to both genes within the autism gene set and to theoretical cholinergic signal disruption related to dietary choline deficiency.

Gene Set Pathway Intersection Analysis of Shared Ontologies

Shared ontologies and associated pathways were rendered graphically using Pathway Studio’s NLP-driven platform. Additionally, certain elements of interest from the ontological overlap and the intersection between pathways involving genes from these sets were inserted.

Graphical models were developed to examine specific pathways or networks with key autism-associated genes, and respective genetic variants which may alter choline and/or acetylcholine levels available for neuronal sensory signal transport. Each instance of a relationship identified by NLP-based word triplet identification was graded by Pathway Studio in terms of confidence levels of 1–3, with a maximum confidence level of 3 being defined as an entity-to-entity relationship supported by at least three peer reviewed publications reflected by the graphical rendering. For this study and related models, the confidence threshold for including elements in graphical representation was set at 3.

Supplemental Analyses for Model Refinement

Splice site identification algorithm Alternative Splice Site Predictor (ASSP) (Wang and Marín, 2006) was used to examine potential changes in the splicing expression which may arise from intronic variants located within autism-associated genes.

Results

Shared Gene Ontologies

Two ontologies were shared between the cholinergic pathway and the autism GWAS gene sets (p < 0.05), namely, those for ion transport regulation and positive ion transport regulation (Figure 1). These ion-transport-related pathways are associated with sensory processing functionality across broad spectrums of the relevant domains, including nociception, tactile response, vestibular reflex, startle response, pupillary light reflex, and sensory gating in general.

Figure 1. Gene ontology overlap between autism and cholinergic metabolism gene sets. Overlap between an autism-associated genome-wide associated studies gene set (Wu et al., 2020) and cholinergic pathways gene set (MSigDB v7.1) was identified using Venny 2.1. The two shared ontologies were (1) regulation of ion transport and (2) positive regulation of ion transport, identifying ion transport functionality as a critical area of enrichment for further analysis.

Within these two ion transport regulation ontologies, two common genes were identified as implicated in neuronal signal transmission: the gene GABBR1, which encodes the gamma aminobutyric acid membrane receptor GABA_B₁, also known as “GABA receptor” elsewhere in the literature, and the gene KCNN2, which encodes potassium intermediate/small conductance calcium-activated channels of SK2 type. The latter channels are often co-located with cholinergic receptors and are capable of modulating cholinergic signaling through membrane repolarization.

Analysis of the Intersection of Autism-Related Cholinergic Gene Sets

Analysis with Pathway Studio’s graphical pathway rendering platform identified regulatory and functional relationships between acetylcholine, ion transport/ion levels, GABBR1 and KCNN2 activity, and aspects of sensory processing. All depicted relationships are supported by experimental evidence extracted from the scientific literature (Figure 2).

Figure 2. Sensory processing is associated with autism functionally, in the context of ion transport and cholinergic signaling. Acetylcholine regulates both the ion transport and the GABA signaling. A deficiency in its precursor, dietary choline, may impact ion transport, GABA⇒GABBR1 signaling, and KCNN2/SK2 channel function, either or all of which may result in altered sensory processing function.

Choline and acetylcholine were linked to ion transport function across several pathways, with the most direct implication being the neuronal influx of membrane depolarizing calcium resulting from the binding of acetylcholine to cholinergic receptors, such as the alpha-7 nicotinic receptor. This transition from chemical signal transduction (release of acetylcholine into the synapse which binds with the nicotinic receptor on the dendrite of the signal recipient neuron) to ionic signal transduction down the axon is a core aspect of sensory signal pathway functionality (Figure 3).

Figure 3. Overview of acetylcholinergic signaling. Acetylcholine (ACh), sourced from precursors choline and acetyl-CoA, leaves the presynaptic neuron’s axon terminal through vesicle-mediated exocytosis. Acetylcholine molecules diffuse through the synapse, until binding with cholinergic receptors (CR) in the membrane of the postsynaptic signal-recipient neuron’s dendrite. This binding event permits influx of calcium ions into the dendrite. Ionic membrane depolarization activates an action potential, causing an electrical signal to be propagated down the length of the axon in a series of ion transport events, until the signal reaches the axon terminal and is translated again into neurotransmitter signals destined to reach the next neuron’s dendrite.

Binding of acetylcholinergic receptors is modulated through multiple means, both preemptive and ex post facto. The enzyme acetylcholinesterase functions by cleaving acetylcholine in the synapse, including either acetylcholine recently made available for signal transduction, or acetylcholine released from membrane-bound acetylcholinergic receptors in the signal recipient neuron (Figure 4).

Figure 4. Clearance of acetylcholine from the synapse by acetylcholinesterase. Acetylcholine (ACh) is delivered to the synapse as a result of vesicle exocytosis from pre-synaptic neuronal signaling and a release of the recycled acetylcholine from the postsynaptic neuron’s cholinergic receptors. In the synaptic cleft, acetylcholinesterase (ACHE) then degrades acetylcholine. Resulting choline is then taken back by the presynaptic neuron to be recycled in order to make more acetylcholine for future signaling. This figure was extracted from Pathway Studio’s curated pathways and was edited according to the needs of this study.

The regulatory role of GABA-ergic binding in acetylcholinergic activity is nuanced. Typically, GABA is released from the signal-transmitting neuron synchronously with acetylcholine through separate GABA-specific vesicles, which serve as an immediate signal modulator. The subsequent cascade that arises from GABA binding to the GABA_B₁ receptor suppresses further upregulation of acetylcholinesterase (ACHE) and preserves acetylcholine in the synaptic cleft from destruction. The signal propagated through the GABA_B₁ receptor is, therefore, hypothesized to modulate an availability of acetylcholinesterase within the cleft. In other words, GABA-ergic suppression of ACHE upregulation may lead to decrease of synaptic acetylcholine degradation, leaving more acetylcholine available for cholinergic signal transmission. This cascade’s impact upon synaptic acetylcholine levels is depicted in Figure 5. A hypothetical impact of genetically determined differences in GABA–GABA_B₁ binding activity upon cholinergic sensory signal modulation is depicted in Figure 6A.

Figure 5. GABBR1 may influence acetylcholinesterase regulation. GABBR1 is an autism-associated gene that codes for a membrane-bound protein (GABA_B₁) (Wu et al., 2020). The binding of the neurotransmitter GABA to GABA_B₁ has several implications for cholinergic signaling, sensory signal transduction, and ion transport, across multiple cascades. As depicted here, a typical GABA/GABBR1 binding cascade inhibits adenylyl cyclases (ADCY), thereby preventing positive upregulation of acetylcholinesterase (ACHE). This figure was extracted from Pathway Studio’s curated pathways and was edited according to the needs of this study.

Figure 6. GABBR1/ACHE regulation. (A) In the presence of GABBR1 variant. The autism-associated GABBR1 variant may affect levels of acetylcholinesterase (ACHE) in the synaptic cleft by decreasing either total levels of GABBR1 expression and/or function of its gene product, the GABA_B₁ receptor. Under this condition, the cascade that normally downregulates acetylcholinesterase expression may be suppressed. Because of that, larger amounts of the enzyme are produced, and the acetylcholine degrades at an elevated rate, resulting in less acetylcholine in the synaptic cleft and less signaling through the cholinergic receptor. (B) In the presence of GABBR1 variant and a dietary choline deficiency. When choline levels are deficient, less acetylcholine (ACh) is available in the neurons for signaling, and a decrease in cholinergic binding/signaling attributed to GABBR1 variant would be exacerbated.

Other modulators of acetylcholinergic signal transmission include SK2 ion channels, which counter the membrane depolarization in the signal recipient neuron (Figure 7A). These types of membrane repolarizing ion channels prepare the signal recipient neuron to receive other action potential-activated sensory signals immediately after processing the preceding signal.

Figure 7. KCNN2/SK2 impact on cholinergic signal modulation. (A) SK2 channel operation. SK2 channels operate in tandem with a propagation of cholinergic signal as they counter the membrane depolarization brought about by calcium influx through cholinergic receptors. The calcium influx activates the calmodulin domains on SK2 channels, permitting passage of potassium back into the synapse to restore membrane hyperpolarization. Thus, SK2 channels serve a critical role in helping a neuron to recover and re-hyperpolarize before receiving the next cholinergic signal. (B) In the presence of KCNN2/SK2 variant. When SK2 channel binding activity and/or functionality is altered, the sensory signaling modulation could either be too efficient—that is, the membrane repolarizes too soon due to overflow of K + ions back into the synapse, or not efficient enough, with membrane taking too long to repolarize, leaving the neuron less ready to process any subsequent signals transmitted from the presynaptic neuron. In either of these two conditions, the neuron’s capacity to modulate sensory signaling through membrane repolarization may be diminished. (C) In the presence of KCNN2/SK2 variant and a dietary choline deficiency. When choline levels are deficient, less acetylcholine (ACh) is available in the neurons for signaling, and a post-signal repolarization may be less amenable to modulation by SK2 channels. When these channels are working in a suboptimal regimen due to the presence of KCNN2 variant, modulation leeway may be curtailed even further.

In part, the magnitude of the sensory signal depends upon SK2 channels’ ability to effectively counter membrane depolarization in the wake of a cholinergic signal, thus, serving as an ex post facto modulator of cholinergic activity. The autism-associated KCNN2 variant may either change the level of the baseline SK2 channel expression or lead to the alteration of the splicing, and the shift of the open reading frame. In either case, sensory signal stands to be impacted. These hypothetical impacts of a KCNN2 genetic variant upon cholinergic sensory signal can be seen in Figure 7B.

The final modeling stage sought to evaluate and depict these hypothesized sensory signaling outcomes in light of a deficiency sufficient to reduce available acetylcholine. The intersection of dietary choline deficiency with GABBR1-related pathways can be seen in Figure 6B, and the intersection of dietary choline deficiency with KCNN2-related pathways can be seen in Figure 7C.

Supportive Evidence for KCNN2 Variant as a Modifier of Splicing

To examine a possible change in splicing patterns attributable to autism-associated variants in GABBR1 and KCNN2, both the wildtype loci and the variant loci representing each of these two genes were compared using the Alternative Splice Site Predictor (ASSP) tool. While the (rs740883) SNP-related differences in predicted splicing patterns of GABBR1 were minimal, the KCNN2 variant rs13188074 yielded a high confidence prediction of a lowered strength within the splice site between the seventh and eighth exons (Table 1), indicating the possibility of a lower rate of splicing than may occur in the wildtype version of this site.

Table 1. The Alternative Splice Site Predictor (ASSP) tool (Wang and Marín, 2006) determined short windows containing the loci for each of the GABBR1 and KCNN2 autism-associated genes.

Discussion

This paper presents the results of a gene set enrichment analysis focusing on shared gene ontologies between an autism-associated gene set obtained through meta-analysis of GWAS and a gene set centering on cholinergic function, which has been collated using a combination of curated gene sets in the Molecular Signatures Database (MSigDB) (Liberzon et al., 2011; Liu et al., 2020). Our study identified two shared gene ontologies, an ion transport regulation and a positive ion transport regulation. Within these ontologies, two genes were further identified as being involved with cholinergic neuronal signal transmission, GABBR1 and KCNN2. The role of ion transport in neurological signaling is complex, as it features a series of ion transport enablers, which boost ion transport and depolarize membranes, as well as counter-transporters, which work to maintain membrane hyperpolarization. These ion transport players in cholinergic and GABA-ergic pathways amplify or inhibit transmission of synaptic signals, respectively. As a result of these interactions, a carefully tuned balance emerges. Potential implications of the presence of GABBR1 and KCNN2 variants in the context of autism and sensory processing are discussed below. Further consideration is given to how operation of these pathways may be altered during acetylcholine deficiency resulting from an inadequate supply of dietary choline.

GABBR1/GABA_B₁ Implications

The GABBR1 gene encodes for the membrane protein known as GABA_B₁ (or sometimes GABA_B). This membrane protein, which constitutes the metabotropic class of GABA-binding membrane-bound receptors, functions at a slow, steady level, in partnership with another membrane-bound GABA-binding protein, GABA_B₂. Through activation of potassium ion channels that release potassium (K⁺) out of the neuron and inhibition of calcium ion (Ca²⁺) channels which permit passage of Ca²⁺ ions into the neuron, this set of proteins brings about membrane hyperpolarization. In this circuit, GABA–GABA_B₁ binding activity serves an inhibitory function, which counters the possibility of excitation of membrane depolarized neurons. This functionality helps to modulate a magnitude of incoming stimulation by inhibiting sensory signals transmitted by cholinergic membrane depolarization. Thus, activation of neuronal action potentials and a subsequent, consistent state of neuronal overexcitation are prevented (Figure 5).

Additionally, GABA_B₁ receptor binding initiates a cascade which eventually results in the inhibition of acetylcholinesterase—the enzyme that degrades acetylcholine in the synapse. This indicates a possibility that GABA_B₁ receptor binding activity may at least in part regulate the size of the acetylcholine pool available for cholinergic signaling.

The GABBR1 variant associated with autism—variant rs740883—is an intronic variant in which a thymine replaces an adenine (Liu et al., 2020). This single-nucleotide polymorphism (SNP) occurs in approximately 9–10% of individual human genomes, and is located within a 3 prime untranslated region, commonly associated with a stability of a transcript. GABBR1-encoded GABA_B₁ receptors are expressed at lower levels in autistic brains, in both the superior frontal and parietal cortices, and in the cerebellum (Fatemi et al., 2009, 2010). Levels of related GABA-ergic biomarkers also differ in the brains of people with an autism diagnosis, when compared to levels of GABA-ergic biomarkers in control brains (Blatt and Fatemi, 2011). While the autism-associated GABBR1 intron variant discussed here is discovered too recently to be analyzed for its relation to these epigenetic differences, examining the possibility that this variant may explain the observed autism-specific differences in GABA-ergic transcriptomic regulation described in the scientific literature is warranted.

Impact of GABA/GABA

_B₁ Binding on the Synaptic Supply of Acetylcholine

GABA is a common neuromediator which often functions in tandem with acetylcholine, in either inhibitory or excitatory roles that span learning, memory, sensory signal transmission, neuromuscular function, and cardiac function. In the hippocampus/somatosensory cortex, the mammalian central nervous system, and elsewhere in the body, GABA and acetylcholine may be co-released, in a relationship which is not yet fully understood (Bianchi et al., 1982; Kusunoki et al., 1984; Granger et al., 2016; Takács et al., 2018). Both of these mediators rely upon vesicle-based exocytosis to be released into the synapse, with GABA and acetylcholine transporting vesicles within the same presynaptic vesicle pools being filled independently of each other (Takács et al., 2018).

Notably, the binding of GABA_B₁ to its ligand impacts available interneuronal acetylcholine supply (Figures 5, 6A). More specifically, GABA–GABA_B₁ binding inhibits a cascade in which the transcription factor CREB1 boosts expression of acetylcholinesterase (ACHE), an enzyme that degrades acetylcholine in the interneuronal junction, thereby lessening the magnitude of cholinergic signal. If GABA–GABA_B₁ binding activity were to decrease as a result of a presence of a genetic variant in a GABBR1 gene—for example, rs740883, which is strongly associated with autism—an increase in acetylcholinesterase production would ensue after being prompted by an increase in the binding of CREB1 ACHE promoter. In this scenario, the increased supply of acetylcholinesterase would degrade acetylcholine in the interneuronal junction faster, thus suppressing cholinergic signaling to a greater extent than in the brain with wildtype GABBR1. Figure 6A systematically depicts hypothesized impact of GABBR1’s autism-associated intronic variant on GABA-ergic and cholinergic signaling.

Impact of Acetylcholine Deficiency on Cholinergic Output, and Hypothesized Interplay With

GABBR1 Genetics

Both our modeling and limited experimental evidence suggest that insufficient dietary intake of a choline may contribute to a reduced acetylcholine supply in the brain (Cohen and Wurtman, 1976). The combination of a dietary choline deficiency with a GABBR1 variant may result in cholinergic signaling being lowered further, or even markedly impaired. Moreover, given that GABA sometimes co-transmits with acetylcholine, reduced acetylcholinergic signaling may also be tied to the temporal restriction on the GABA-driven neuronal inhibition as a secondary event. Sensory processing depends upon function of both of these neurotransmitters, so it is reasonable to extrapolate that the combination of dysregulated ion transport due to the presence of GABBR1/GABA_B₁ variants and dietary-driven acetylcholine deficiency may result in altered sensory processing for the individual in question.

KCNN2/SK2 Channel Implications

The gene KCNN2 encodes for the membrane-bound SK2 calcium-activated potassium ion channel, which modulates the excitability of neurons and neuromuscular activity. After being activated through co-located acetylcholine nicotinic receptors, SK2 channel modulates cholinergic signals through neuronal membrane repolarization (Figure 7A). SK2 channels are abundant throughout the body, including the brain and the cardiorespiratory system (Gu et al., 2018). The SK2 channel encoded by KCNN2 is associated with sensory processing in a variety of contexts, with much research focusing on auditory processing with respect to cholinergic nicotinic receptors in the cochlear hair (Elgoyhen et al., 2001, 2009; Kong et al., 2008; Murthy et al., 2009),vestibular awareness (Wangemann, 2002), and nociception (Bahia et al., 2005; Mongan et al., 2005; Pagadala et al., 2013; Hipólito et al., 2015; Thompson et al., 2015).

Impact of Acetylcholine Supply on the Function of

KCNN2/SK2 Channel

As discussed above in relation to the GABA_B₁ receptor, dietary choline deficiency may markedly reduce the pool of acetylcholine in the brain (Cohen and Wurtman, 1976). It follows that diminished binding of the acetylcholine to cholinergic receptors may reduce activation of co-located SK2 channels. In turn, reduced acetylcholine supply in the brain may require increased sensory input, which, in practical terms, translates into sensory hyposensitivity, or sensory underresponsiveness. Reduced signaling may alter the closely-tied counterfeedback of SK2 ion transport signal modulation.

Impact of Acetylcholine Deficiency on Cholinergic Output, and Its Possible Interplay With

KCNN2 Genetics

Similar to the autism-associated epigenetic regulation of GABBR1 observed in the literature, an autism-specific epigenetic regulation of SK2 ion transport activity was noted. In the brains of people with an autism diagnosis, cholinergic nicotinic receptors are expressed at lower levels when compared to that in neurotypical brains (Lee et al., 2002; Andersen et al., 2013). A lower level of available cholinergic receptors may translate to fewer opportunities for acetylcholine binding, and, as collateral, the normally colocalized SK2 channels may also fire less frequently, cumulatively altering the degree of membrane repolarization, and therefore, the timing of subsequent cholinergic sensory signaling.

Because SK2 signaling depends upon the signals from co-located cholinergic nicotinic receptors, diminished or altered SK2 activity arising from the presence of autism-associated KCNN2 coding variant(s) may be compounded by the synaptic acetylcholine deficiency. Thus, dietary choline deficiency may ultimately exacerbate genetic weakness in the SK2 activity, resulting in altered sensory processing, possibly resulting in sensory over-responsiveness, under-responsiveness, or a combination of both, for a given autistic person.

rs13188074 Variant May Influence

KCNN2 Splicing Pattern

Currently, there is a little evidence of direct impact of intronic variants in GABBR1 and KCNN2 on the function of the respective proteins. ASSP analysis hints that, in case of KCNN2, the change in a strength of a splice site may influence an amount of functional mRNA encoding for full-size KCNN2. Experimental gauging of the impact of KCNN2 variant upon sensory processing is warranted.

Targeting Cholinergic and GABA-ergic Signaling Pathways May Modulate Sensory Processing in Autism

The models indicated in Figures 2, 3 are consistent with extant literature examining the possibility of cholinergic pharmacotherapy of autism, as increasing the pool of available interneuronal acetylcholine may improve function in several domains related to cholinergic signaling activity and related ion transport dynamics. For example, acetylcholinesterase inhibitors galantamine and memantine, which are typically prescribed for Alzheimer’s disease patients, are also actively explored in autism (Maire and Wurtman, 1984; Hertzman, 2003; Nicolson et al., 2006; Ghaleiha et al., 2014; Rossignol and Frye, 2014; Rahman et al., 2018). A systematic review examining the impact of these drugs in individuals with autism identified an improvement across several domains, including communication and social interaction, and a decrease in disruptive behavior, hyperactivity, inattention, and irritability (Rossignol and Frye, 2014). Many of these domains are linked to sensory processing difficulties (Ashburner et al., 2008; Sanz-Cervera et al., 2015). In the present study, we posit that variant function of GABBR1 may lead to a smaller pool of available acetylcholine (Figure 5). For patients with GABBR1 variants, including individuals with autism, prescription of acetylcholinesterase inhibitors such as galantamine or memantine may counter the disturbance in GABA/GABBR1/acetylcholinesterase cascade, by boosting the synaptic acetylcholine levels to match these seen in neurotypical brains.

In the context of addiction, the literature supports a relationship between acetylcholinergic transmission and genetic variation of GABBR1. Individuals with genetics variants of the GABBR1 locus are more likely to develop dependency upon a major cholinergic nicotinic receptor agonist, nicotine. This observation highlights the complexity of the influence of genetic GABBR1 variation upon acetylcholinergic function (Li et al., 2009; Li, 2018). Notably, nicotinic receptors have been of particular interest as a therapeutic target in autism, as their stimulation affects both working memory and executive functions. In a placebo-controlled trial, nicotine patches have been investigated as a mean to improve sleep and to address aggressive behavior in autistic adults (Deutsch et al., 2015; Olincy et al., 2016; Lewis et al., 2018; Deutsch and Burket, 2020).

The evidence for pharmacological intervention on GABA_B₁ upon autism-related sensory domains is equivocal. GABA_B₁ receptor agonists such as arbaclofen have been investigated through evaluation of their efficiency across measurable features of irritability, lethargy, and social responsiveness (Veenstra-VanderWeele et al., 2017). When examining a specific sensory subdomain—auditory processing—a subset of teenagers with autism taking arboclofen were found to exhibit improved magnetoencephalographic (MEG) measures of their auditory response (Roberts et al., 2019).

It is of certain importance that in addition to pharmacological means, cholinergic transmission may also be influenced by change in the dietary intake of the choline, one of the common nutrients abundant in milk, liver, eggs, and peanuts. As discussed, many Americans do not consume the daily AI level of choline, and indeed, recent surveys indicate that a majority of a sample of autistic children (60–93%) do not meet their choline AI level recommended respective of age (Hamlin et al., 2013; Wallace and Fulgoni, 2016). A number of autism-associated traits such as preference for routine, aversion to particular foods, as well as sensory aversions to particular smells, textures, or temperatures are known to profoundly shape the diets of people on the autism spectrum (Dunn, 1997; Baranek et al., 2006; Cermak et al., 2010; Nadon et al., 2011; Kral et al., 2013; Hubbard et al., 2014; Sanz-Cervera et al., 2015; Bogdashina and Casanova, 2016; Boterberg and Warreyn, 2016; Crasta et al., 2016; Bitsika and Sharpley, 2018; Weeden, 2019). Because of that, the availability of an adequate pool of acetylcholine for cholinergic signaling may be a legitimate concern, particularly in light of the potentially exacerbated need for proper function of sensory signaling pathways discussed above.

Dietary Choline: A Low-Risk Intervention to Support Acetylcholine Supply, Cholinergic Signaling, and Sensory Processing in Autism

The recommended dietary consumption levels for choline are set by the Food and Nutrition Board of the National Academies as assessed by measuring serum alanine aminotransferase levels reflecting overall liver function. Whether or not the choline at AI level would be sufficient to modulate sensory processing symptoms is not known. It is notable, though, that most Americans do not achieve even this level of the choline intake (Wallace and Fulgoni, 2016). For autistic individuals, who experience particular difficulty in meeting dietary guidelines for choline through diet alone, choline supplementation may provide an alternate effective means of ameliorating daily choline intake levels. As opposed to pharmacological interventions, using the dietary modifications or choline supplements is considered low risk, because neither dietary nor supplementary forms of choline are known to interact with medications. Additionally, overconsuming choline through diet or supplementation to the point of excess—which is defined by the tolerable upper limit of 3,500 mg/day—would require Americans to consume more than seven times their recently estimated mean intake levels of choline, which is currently at less than 500 mg/day for all age groups (Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline, 1988; Wallace and Fulgoni, 2016; Wallace et al., 2018).

To call dietary intervention for choline status “low risk” does not negate the challenges specific to supporting the increased consumption of choline in autistic children and adults. The research and development which is required to determine targeted, effective ways for elevating choline consumption and identifying personalized intake baselines sufficient for fulfilling physiological need for choline in this population is considerable. As with any autism research, investigations should purposefully include representatives and researchers with an autism diagnosis who can help to shape such interventions optimally for autistic children and adults (Chown et al., 2017; Hoekstra et al., 2018; Lebenhagen, 2019; Cascio et al., 2020; Hogan et al., 2020).

Future Research Directions

The autism-associated GABBR1 and KCNN2 genetic variants have been highlighted as such only recently, and therefore there is an opportunity to collect more definitive experimental data, which can inform the modeling of sensory processing dynamics as they relate to these variants. Studies of GABBR1 and KCNN2 in autism should examine possibilities such as structure/function differences in the autism-associated variant version of these membrane proteins, as well as measurement of GABBR1 and KCNN2 expression levels in those presenting with the respective autism-associated variants.

Because of the relative likelihood that autism-associated intron variants such as those found in GABBR1 and KCNN2 would result in transcriptomic changes, transcriptomics should be a primary focus of future research on these genetic variants’ impact. Because of the measured difference in GABA_B₁ protein expression in autism, examining a potential link between the autism-associated GABBR1 variant and these expression differences should be a priority. Similarly, SK2 channel expression levels in autism should be examined with respect to this SK2 channel variant. Any transcriptomic differences which would be found to be associated with these genetic variants would set the foundation for more refined examination of impact upon cholinergic signal transmission and modulation.

In terms of further examination of potential alterations to autism-related variant versions of GABA_B₁ and SK2 channel structure and/or function, there are several tools and methods available, which vary in scope and performance. For example, if it can be determined that a reading frame shift has occurred as a consequence of an altered splice site, basic computational homology modeling may be helpful. Without the context of a frame shift, if structural differences are still suspected for the variant version of either of these proteins, validated structural assessment through means of electron microscopy, NMR spectroscopy, and X-ray crystallography remains as resource-intensive possibilities. Additionally, new structure prediction AI presented by AlphaFold, exhibiting unprecedented accuracy in structural prediction, could be considered as a potential future tool (DeepMind, 2020). Additionally, if structural differences were uncovered, molecular dynamics modeling may provide insights into the relative binding frequencies and strength in wildtype vs. variant versions of GABA_B₁ receptors and SK2 channels. If these models provide actionable information, they may merit further development in terms of broadening molecular dynamics model scope to include various elements from the cholinergic sensory signal pathways and cascades discussed in this study. Computational modeling and pathway exploration may continue to provide support and context as researchers continue to explore potential impact of these genetic variants upon sensory processing in autism.

In terms of clinical interventions, while available evidence on dietary interventions for autism remains limited, this work provides mechanistic support for further exploration of exogenous choline—through diet or supplementation—as a potential low-risk sensory processing support intervention. Future clinical interventions in humans will de facto require the input of multidisciplinary teams of researchers and stakeholders—including those with autism diagnoses—to effectively develop and test autism-tailored clinical interventions that carefully measure inputs through diligent nutritional assessment, and outcomes such as standardized sensory processing scores, and choline activity measured through functional magnetic resonance imaging (fMRI). Such teams may include researchers from a broad range of fields including nutrition, neuroscience, occupational therapy, bioinformatics, and computational biology. Additionally, choline-related biomarkers such as serum alanine aminotransferase may provide useful outcome measurements, particularly in cases where nutritional assessment indicates risk of deficiency.

Conclusion

In connecting dietary choline intake as a mediator of acetylcholinergic pathways, especially for sensory signal ion transport in the context of two autism-associated genes, GABBR1 and KCNN2, this study is consistent with the growing evidence base concerning the role of choline in pre- and postnatal nutrition and neurodevelopment. In our opinion, clinical evaluation of choline intake interventions with respect to validated sensory processing scores is warranted in future studies whose age ranges include children, teens, and adults.

Because of the physically, mentally, and logistically demanding requirements involved in collection of experimental data through clinical trials, particularly from participant individuals with autism and their families, it is incumbent upon researchers to ensure that clinical trials examining dietary status, genetic variants, and sensory processing are effective, efficient, and respectful of their participants. Advance planning and implementation for these clinical trials is therefore at a premium. Accordingly, in preparation for clinical trials, research employing computational biology, bioinformatics, and predictive modeling should also be considered as essential precursor elements in examining the intersection of dietary choline status with sensory processing in the context of autism-associated genes.

Data Availability Statement

The autism GWAS dataset is available as a supplementary file for the original article (Wu et al., 2020).

Author Contributions

AO, AB, and MS were responsible for the conception of the project and editing the final manuscript. AO carried out analyses and interpretation with input from all other authors and drafted the manuscript with feedback from all other authors. All authors contributed to the design.

Funding

Funding to conduct this research was received from the American Egg Board/Egg Nutrition Center. The funder was not involved in the conducting of research or generation of the manuscript. Article processing fees were partially covered by George Mason University’s Open Access Publishing Fund (OAPF).

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Footnotes

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Health Benefits, Side Effects, Uses, Dose & Precautions

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Thiamin (Vitamin B1)

THIAMINE – VITAMIN B1

Vitamin B1 (thiamine, the old name is aneurin) was discovered in 1926. It is a colorless crystals with a yeast odor, readily soluble in water, poorly soluble in organic solvents, and completely insoluble in alcohol. In an alkaline medium in the ultraviolet region of the spectrum, vitamin B1 exhibits fluorescent properties.This property is the basis of the method for the determination of thiamine in biological objects.

Vitamin B1 is thermostable – it can withstand heating up to 140 ° C in an acidic environment, but in an alkaline and neutral environment, resistance to high temperatures decreases.

Vitamin B1 is synthesized in nature by plants and many microorganisms. Animals and humans cannot synthesize thiamine and get it from food. All animals need thiamine, with the exception of ruminants, since the bacteria in their intestines synthesize a sufficient amount of it.

Chemical formula of vitamin B1 – C ₁₂ H ₁₇ N ₄ OS

Being absorbed from the intestines, thiamine in the presence of magnesium is converted into its active form, thiamine pyrophosphate. Other derivatives of thiamine are: thiamine triphosphate, adenosine thiamine diphosphate, adenosine thiamine triphosphate.

ROLE OF VITAMIN B1 IN THE BODY

All B vitamins work in “close cooperation” and vitamin B1 is no exception. Thiamine plays a huge role in the human body, exerting a regulatory effect on its most important functions:

Necessary for the transmission of nerve impulses (due to participation in the synthesis of acetylcholine). Thus, it improves the functioning of the nervous system. Helps improve mental health. Vitamin B1 is sometimes called the vitamin of optimism.
Plays a particularly important role in carbohydrate metabolism and associated energy, fat, protein and water-salt metabolism.
Promotes the processes of hematopoiesis and improves blood circulation through the vessels.
Reduces the level of homocysteine, an amino acid, high levels of which are associated with the risk of heart attacks and strokes.
Prevents brain cells from aging, allows you to maintain a good memory to a ripe old age, optimizes cognitive activity and brain function.
Improves the functioning of the gastrointestinal tract, normalizing the acidity of gastric juice, helps digestion, especially the absorption of carbohydrates, is necessary for muscle tone in the digestive tract.
Has analgesic properties, relieves toothache postoperative pain.
Thiamine in combination with other B vitamins and ascorbic acid helps the body resist infectious and viral diseases.
Supports the treatment of shingles.
Interferes with the destruction of cells due to age and the effects of smoking and alcohol, i.e. manifests itself as an antioxidant.
Thiamine, actively interacting with vitamin B12 and folic acid, participates in the synthesis of methionine, an amino acid necessary for the neutralization of toxic products.
Reduces blood cholesterol levels.
Promotes wound healing by actively participating in cellular metabolism.
Helps with motion sickness and motion sickness.
Drives away insects, especially mosquitoes.

VITAMIN B1 CONTENT IN FOOD

Vitamin B1 is found in many products of both plant origin (especially nuts and cereals) and animals (pork, liver, kidneys). In small quantities, it is synthesized by bacteria that live in the human intestine.A table showing the level of thiamine content in various foods will help you to build your diet correctly.

Products with a thiamine content of 0.09 – 0.06 mg per 100 grams: eggs, white cabbage, beets, onions, cucumbers, radishes, bell peppers, tomatoes, pineapple, figs, raspberries, oranges, tangerines.

Products with a thiamine content of 0.05 – 0.01 mg per 100 grams: dairy products (milk, cottage cheese, sour cream, cheese), herring, turnips, eggplant, pumpkin, parsley, sauerkraut, grapes, currants, cherries, plums , apricots, lemons, grapefruit, apples, pears, watermelon, melon, peach, pomegranate, bananas, fresh mushrooms.

The data are rather arbitrary, the content of vitamin B1 strongly depends on the soil where the product grew. Long-term (for example, 12 months) storage of food in the cold can also lead to significant losses. Green beans, for example, lose over 90% of their original thiamine content in one year of frozen storage. Its loss for other products varies in the range of 20-60%.

EFFECT OF VITAMIN B1 IN THE BODY

In the body, thiamine becomes active when magnesium is present.Along with foods containing thiamine, include in your diet and foods rich in magnesium: oat and wheat bran, nuts and seaweed, cocoa, dried apricots, sesame seeds, soybeans, spinach and shrimp.

The main cause of low thiamine levels is high alcohol consumption. Tea and coffee in large quantities also remove thiamine from the body, so it is better to drink less of these drinks, and take vitamin preparations, if you have been prescribed them, with clean water. Certain foods, such as raw fish, break down thiamine very quickly.

In the composition of food, all vitamins and minerals usually perfectly complement each other’s action, but in the case of injections, an undesirable interaction of thiamine with vitamin B6 and vitamin B12 is possible if they are administered simultaneously. In this case, if a person has an allergic reaction to thiamine, vitamin B6 and vitamin B12 can increase it several times.

Thiamine is also incompatible with penicillin, streptomycin or nicotinic acid. Sulfonamides, as well as alcohol-containing drugs, disrupt the normal absorption of vitamin B1.The antagonist of thiamine is choline. Antibiotics, drugs containing sulfur, oral contraceptives, antacids can reduce the level of thiamine in the body.

DAILY NEED FOR VITAMIN B1

Physiological requirements for vitamin B1 according to Methodological recommendations MR 2.3.1.2432-08 on the norms of physiological needs for energy and nutrients for various groups of the population of the Russian Federation:

The upper acceptable level has not been set.
The specified physiological requirement for adults is 1.5 mg / day.
Physiological requirement for children – from 0.3 to 1.5 mg / day.

Table 1. Recommended daily intake of thiamine (vitamin B1) depending on age (mg):

	Age	Daily requirement for vitamin B1, (mg)
Babies	0 – 3 months	0.3
	4 – 6 months	0.4
	7 – 12 months	0.5
Children from 1 year to 11 years	1 – 3	0.8
	3 – 7	0.9
	7 – 11	1.1
Men (boys, youths)	11 – 14	1.3
	14 – 18	1.5
	> 18	1.5
Women (girls, girls)	11 – 14	1.3
	14 – 18	1.3
	> 18	1.5
	Pregnant	1.7
	Nursing	1.8

The vast majority of people need vitamin B1 supplementation.For example, more thiamine is needed if the majority of the diet is cooked food or refined flour and grain products. People who drink alcohol and tea also need higher doses. In cold climates, the need for thiamine increases to 30-50%.

LACK OF VITAMIN B1 IN THE BODY

Vitamin B1 hypovitaminosis can develop if its intake from food is insufficient or if for some reason it is not absorbed.In this case, not only is the normal course of the processes regulated by it disrupted, but also toxic products of carbohydrate metabolism (lactic and pyruvic acids) accumulate.

The main enemy of vitamin B1 is alcoholism. People who consume large amounts of coffee, especially instant coffee, tea and refined sugar may also have an increased risk of thiamine deficiency, since these drinks, on the one hand, actively destroy B vitamins, and on the other hand, act as diuretics (diuretic) and remove fluids with water-soluble vitamins from the body.

Early symptoms of vitamin B1 deficiency are: increased irritability, constant fatigue, lack of appetite and memory loss. Then appear: worsening sleep, lethargy, muscle weakness, itching and tingling in the legs, depression.

With a more acute and prolonged thiamine deficiency, a number of pathological symptoms arise:
From the nervous system: headache, peripheral polyneuritis – inflammation of the nerves, paresis – weakening of motor functions, in severe cases, paralysis.
From the side of the cardiovascular system: tachycardia – increased heart rate, pain in the heart, expansion of the heart, weakening of cardiac activity, shortness of breath, edema.
From the digestive organs: a significant decrease in appetite and intestinal tone, constipation, abdominal pain, nausea.

The severity of these symptoms depends on the degree of vitamin B1 deficiency in the body.

VITAMIN B1 – TREATMENT OF DISEASES

One of the diseases associated with vitamin B1 (thiamine) deficiency is alimentary polyneuritis (or Beri-beri ; in Sinhalese (Ceylon) “extreme weakness”, from beri weakness).The development of this disease is caused by both a lack of vitamin B1 (thiamine) in the diet, and a violation of its (thiamine) absorption in the body. Beriberi is characterized by amyotrophy, cardiovascular disorders, and polyneuritis.

Vitamin B1 is used in the treatment of organic brain dysfunctions, such as “ organic brain damage syndrome “, helps to improve brain function in healthy people, increasing the ability to learn. Thiamine supplementation can help treat depression and other mental health conditions.Thiamine improves the functions of the nervous system and reduces pain in a variety of neurological diseases.

It is used for: neuritis , polyneuritis , peripheral paralysis , asthenovegetative syndrome , etc.

Vitamin B1 is prescribed for diseases of the cardiovascular system, such as: circulatory failure , myocarditis , endarteritis . An additional intake of thiamine is needed during the use of diuretic drugs for hypertension, congestive heart failure, i.e.because they increase its excretion from the body.

In dermatological practice, vitamin B1 is used for dermatoses of neurogenic origin , itching of the skin of various etiologies , pyoderma , eczema , psoriasis .

The use of vitamin B1 is indicated for the treatment of diseases of the digestive system:

Peptic ulcer of the stomach and duodenum.
Chronic gastritis, accompanied by impaired motor and secretory functions of the stomach.
Chronic enteritis with malabsorption syndrome (celiac disease, Whipple’s disease, Crohn’s disease, radiation enteritis).
Chronic pancreatitis with secretory insufficiency.
Hepatitis.
Enterocolitis.
Diseases of the operated stomach.
Cirrhosis of the liver.
Diabetes mellitus.
Obesity.
Thyrotoxicosis.

For the prevention and complex treatment of these diseases, as well as other diseases associated with thiamine deficiency, incl.in case of disorders of absorption of vitamin B1 in the intestine, we recommend taking probiotics and (or) functional food products based on ferments of probiotic microorganisms: bifido- and propionic acid bacteria.

Be healthy!

REFERENCES TO SECTION ABOUT PROBIOTIC DRUGS

PROBIOTICS
PROBIOTICS AND PREBIOTICS
SYNBIOTICS
HOMEMADE SQUARE
CONCENTRATE OF BIFIDOBACTERIA LIQUID
PROPIONIX
IODPROPIONIX
SELENEPROPIONIX
BIFICARDIO
PROBIOTICS WITH PUFA
MICROELEMENTS COMPOSITION
BIFIDOBACTERIA
PROPIONIC BACTERIA
HUMAN MICROBIOME
GIT MICROFLORA
INTESTINAL DYSBIOSIS
MICROBIOM and IBD
MICROBIOMES AND CANCER
MICROBIOM, HEART AND VESSELS
MICROBIOM AND LIVER
MICROBIOM AND KIDNEY
MICROBIOM AND LUNGS
MICROBIOME AND PANCREAS
MICROBIOME AND THYROID
MICROBIOMA AND SKIN DISEASES
MICROBIOMES AND BONES
MICROBIOMES AND OBESITY
MICROBIOMES AND DIABETES MELLITUS
MICROBIOME AND BRAIN FUNCTIONS
ANTIOXIDANT PROPERTIES
ANTIOXIDANT ENZYMES
ANTIMUTAGENIC ACTIVITY
MICROBIOM and IMMUNITY
MICROBIOMES AND AUTOIMMUNE DISEASES
PROBIOTICS and BABIES
PROBIOTICS, PREGNANCY, LABOR
VITAMIN SYNTHESIS
AMINO ACID SYNTHESIS
ANTIMICROBIAL PROPERTIES
SHORT-CHAIN FATTY ACIDS
SYNTHESIS OF BACTERIOCINS
ALIMENTARY DISEASES
MICROBIOM AND PRECISION FOOD
FUNCTIONAL POWER SUPPLY
PROBIOTICS FOR ATHLETES
PROBIOTIC PRODUCTION
STEADERS FOR THE FOOD INDUSTRY
NEWS

What foods improve memory and mental performance / Reviews / Shopping cart

According to the WHO, there are more than 50 million people worldwide with dementia or senile marasmus.This is a syndrome in which a person’s cognitive activity decreases over time, early acquired knowledge and skills are lost, while acquiring new ones becomes quite problematic. The development of this disease is often influenced by lifestyle, including the food that a person consumes. Experts told Korzinka which substances improve brain function and which foods contain them.

Effect of stress

Before you start enriching your diet with foods useful for the brain, nutritionist and detox coach Ekaterina Wunder advises to improve the functioning of the nervous system, because this structure is inextricably linked with brain activity:

Food for the mind: foods that improve brain function

“There is a special substance in the central nervous system – acetylcholine.It performs two mirror functions – exciting and depressing. This neurotransmitter makes the brain awake when we need to perform energetic actions, and, accordingly, slows down the transmission of signals when our activities require focus and attention. ”

Also, acetylcholine neutralizes the harmful effects of stress on the human body. At this time, the substance is actively released and consumed. It’s not so easy to restore this neurotransmitter, – says the nutritionist.

“Even if you provide your brain with adequate nutrition, but you are nervous, your psychophone will be unstable – all the benefits of food will go nowhere,” Ekaterina warns.

In order to stabilize the nervous system, the expert does not recommend that you independently resort to “hard” drugs, such as antidepressants or tranquilizers. To begin with, the expert advises trying herbs – chamomile, motherwort or griffonia – a natural product that does not cause addiction, drowsiness, lethargy and decreased concentration.

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In addition, foods containing choline – egg yolk, cruciferous vegetables, organ meats, fish, whole grains and legumes, and hard cheeses – can help support the production of acetylcholine in the body.

“Quality products are rich in nutrients. For example, the more yellow and richer the yolk, the more beneficial it is. Therefore, it is worth giving preference to natural products – farm products, not store-bought products, ”the expert notes.

Foods harmful to the brain

Before you start actively including healthy foods in your menu, Ekaterina Wunder recommends removing foods that are harmful to the brain:

“If the blood vessels are clogged with cholesterol plaques, and you continue to eat foods that aggravate this phenomenon, then there will be no point in adding healthy food to the diet.”

To improve brain function, nutritionist Tatyana Maralova advises first of all to exclude sweets from your menu:

“Sweets, including sugary drinks, slow down the division of hemoglobin, and it is this substance that carries all the nutrients and oxygen to our brain.In addition, sugar neutralizes the effects of omega-3 fatty acids, which improve brain function. ”

Ekaterina Wunder also advises to give up foods rich in fast carbohydrates, fatty meats, as well as foods containing trans fats, including fast food.

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“The consumption of alcoholic beverages, weak or strong, leads to the adhesion of red blood cells, as a result of which they cannot reach the capillaries, the diameter of which corresponds to the size of blood cells in a normal state, they simply do not pass.Let these not be immediate, but delayed consequences, but sooner or later they will make themselves felt in the form of impairment of memory and reaction and problems with the assimilation of information. Ultimately, this can lead to Alzheimer’s disease or Parkinson’s syndrome, ”explains Ekaterina.

Beneficial substances for the brain and their sources

First of all, it is worth noting omega-3 unsaturated fatty acids, which are found in abundance in sea fish. But often, for one reason or another, people cannot use this product regularly.In this case, fish oil can help.

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“Children who regularly received fish oil in kindergarten had no problem memorizing information at school. Moreover, nowadays a product that is not the most pleasant in smell, taste and consistency can be replaced with a food additive in the form of capsules, ”the expert adds.

Another important food for the brain is foods containing lecithin: sprouted grains, legumes, oatmeal and barley, white cabbage and freshly squeezed orange juice.

“Lecithin is a source of phospholipids, which serve as building blocks for the membranes of our nerve cells. This substance is responsible for the speed of reactions in the brain, has a beneficial effect on thinking, memory and intellectual work, ”notes Ekaterina.

Lecithin can be obtained from food, but this is quite problematic, given the quality of store goods. But there is a way out – lecithin, like omega-3, is sold as supplements.

“Alternate between these supplements: it will be unnecessary to take them at the same time.For example, take a lecithin supplement one day and an omega-3 supplement the next, ”the nutritionist recommends.

The brain also needs magnesium to function well. This element reduces tension, irritability and anxiety, increases concentration and improves memory.

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Tatyana Maralova notes the following products, which contain magnesium and other substances useful for brain activity: nuts, pumpkin seeds and avocados.

Taurine is a substance that is responsible for maintaining blood vessels in good shape and saturating the brain with oxygen. It is found in turkey and chicken meats.

Another element that is useful for brain activity is chlorophyll. This pigment makes plants green, so it is not difficult to determine where it is found.

“During the season, actively add green foods to your diet – parsley, dill, lettuce, broccoli, spinach, and more. In winter, chlorophyll can be produced artificially – it is produced as an additive in liquid form. “

Ekaterina Wunder also recommends paying attention to such superfood as chlorella as a source of chlorophyll. As a whole, this algae contains many useful vitamins and useful microelements.

DMAE DMAE Dimethylaminoethanol 250 mg. 100 capsules.

Description

Dimethylaminoethanol
Healthy Brain Function
Supports the production of neurotransmitters
Non-GMO
Food additive
Vegetarian / Vegan
Supports general health
Family company since 1968
GMP quality standard

DMAE (dimethylaminoethanol) is a natural amino alcohol that is present in small amounts in the brain.It is considered a precursor to the essential nutrient choline, which is required for the production of acetylcholine in the brain, a neurotransmitter involved in nerve signaling and healthy brain function.

Application Note

Take 1 capsule daily, 3 times a day, preferably between meals. Do not exceed the recommended dosage unless advised by your doctor.

DMAE DMAE (dimethylaminoethanol)

How does DMAE help?

DMAE increases the levels of those chemicals in the central nervous system that help us think clearly.Millions of people take DMAE capsules simply to enhance cognition. Buy

Despite the fact that DMAE is considered to be very effective protection against the aging process, few people consider this substance as an antioxidant. Nevertheless, moving away from the formulaic thinking, DMAE acts precisely as an antioxidant, since it helps to stabilize cell membranes: it protects them from damage caused by free radicals, by helping cells to get rid of waste products and retain valuable nutrients.When applied externally, this not too common nutritional complex, it not only acts quickly (within a few minutes after application), but also strengthens the skin for a long time. Besides, there is nothing safer.

Dimethylaminoethanol (DMAE) is one of the most effective and safe drugs of natural origin.

Despite this extravagant name, DMAE is a natural nootropic found in food and in the body.Nootropics are drugs that improve brain function and, in part, rejuvenate it.

Of all life-prolonging agents, nootropics are arguably the most important to us. Some of the nootropics prolong life by 30-50 %%.

In addition, nootropics, firstly, improve the quality of life. Secondly, and this is worth mentioning especially, they can significantly increase mental abilities. Perhaps this property is even more important than their ability to prolong life. After all, in order to prolong life and succeed in it, you need to act wisely!

Why do nootropics prolong life so pronouncedly ?!

It is the brain that is responsible for regulating all processes in the body.If its regulatory role falls, then a more rapid disintegration of the body occurs – otherwise, a faster aging. And, conversely, with the best work of the brain, you can “squeeze” the maximum of its resources from the body.

Nootropics enhance the supply of blood to the brain, which means glucose, oxygen, etc. Nootropics improve the “communication” between individual cells of the brain and its individual parts and hemispheres. As a result, memory, concentration, intelligence, etc. improve.

An important feature of nootropics is their ability to improve the activity of the hypothalamus, which is called the conductor of the entire hormonal system.

The body contains one of the most important substances – acetylcholine . It is a neurotransmitter or neurohormone that is responsible for transmitting and regulating signals from one nerve cell to another, both in the brain and throughout the central nervous system. That is, it is acetylcholine that makes our body a single whole. The lack of acetylcholine impairs the regulation and functioning of the whole organism – in fact, the body disintegrates faster than usual.
Note that up to 75% of the population may be deficient in acetylcholine .That is, many do not have enough of it even to satisfy a physiological need. To prolong the life of acetylcholine, several times more are required.
From a lack of acetylcholine, there are: lethargy, fatigue, depression, delayed reaction, difficulty thinking, poor memory, irritability, etc.
DMAE, when ingested, is converted to acetylcholine.
It is extremely important to note: in order to prolong life, we need to abandon the surplus of animal products and switch mainly to plant products.However, such a diet can worsen acetylcholine deficiency. Therefore, from the point of view of prolonging life, we must choose the following strategy: predominantly plant-based nutrition and use of DMAE !
DMAE has a pronounced antioxidant effect. Protects cells from damage by their most dangerous types of free radicals. Also prevents cross-linking of molecules.
With age, in the cells of the brain, central nervous system, heart, skin, etc.accumulates toxic pigment lipofuscin . Previously, it was thought that lipofuscin was just garbage, the pigment of aging. Now we know that lipofuscin poisons cells! In old age, each cell can be clogged by 30% with lipofuscin. DMAE removes up to half or more of this waste within a period of several months to 2 years. Obviously, if we take DMAE from a young age, we will be able to prevent a significant accumulation of lipofuscin in cells at all.
DMAE significantly improves the properties of blood, – the capture and transfer of oxygen to the tissues.It has also been shown that the addition of DMAE to canned blood doubles its shelf life.

All these effects cause a pronounced prolongation of life, but in addition DMAE : like all nootropics, it clearly stimulates brain function: enhances memory, concentration, cognitive abilities;

improves mood, in the right dosages, improves sleep, inducing vivid realistic dreams;
increases the energy status of the body, therefore it is used by athletes;
improves skin elasticity, tone, appearance.

DMAE prevents aging!

Aging skin is characterized by many changes, including wrinkling, discoloration, staining, ruptured blood vessels, and loss of shine. However, the face betrays age not only because of the changes that occur on the surface of the skin. On the chin, on the nose and along the jaw line, the skin itself begins to sag.

Why do muscles sag?

When you tense a muscle in your arm or make the muscles of your face smile, a signal is sent along the nerves (the process is very similar to the functioning of an electrical wire) to exactly the muscle tissue that should work.At the very tip of the nerve, there is a thickening where, like in a reservoir, chemicals accumulate. Among them is acetylcholine. Whenever a certain amount of acetylcholine enters the muscle tissue, it responds with increased tone or movement. Like all other systems in the body, the nervous system is also aging due to the incessant harmful effects of free radicals and insufficient optimal nutrition. As aging begins, both the amount of acetylcholine produced and the extent of its effect on the muscles decrease.The only way to reverse this process (which means getting a stronger muscle response and tighter skin) is to increase the level of active acetylcholine in the body, which can be achieved by better nutrition and application of DMAE both externally and internally. As a result, both general well-being and the nutritional environment of the skin will improve.

However, the most dramatic changes are observed when the effects of DMAE on the neck and jaw lines are monitored. The skin tone of the neck increases markedly, after a few weeks the jaw line becomes definite.Yet the most amazing effect of DMAE is in the natural lifting of the eyelids. All participants in the experiment reported that after a few weeks, the skin around the eyes began to look firmer and tighter. DMAE, when combined with antioxidants, can help alleviate another beauty problem: thin or aging skin around the lips. In the right combination, DMAE can even make overly thin lips fuller or remove fine lines and wrinkles from them. Clinical study confirms that DMAE does indeed help increase blood circulation and tone the lips, making them look fuller and firmer.

DMAE is considered an integral part of food, so you can take it without any harm. After long-term use of the product, some of the patients even noticed that their tip of the nose was slightly raised, due to the fact that DMAE improved the tone of the forehead muscle tissue. Nothing gives a face a more youthful appearance than pulling up a saggy nose.

Side effects and contraindications.

Since DMAE is a substance of natural origin and is present in some foods and in the body, then side effects are possible only in cases of extreme overdose.This is overexcitation, headaches, insomnia, muscle twitching, etc. In this case, you need to reduce the dosage or temporarily stop taking it.

90,000 Vitamin B1: benefits, properties and features

Vitamin B1, that is, thiamine, is found in various plant and animal foods, so it is not difficult to ensure its adequate intake in the daily diet.
Vitamin B1 is essential for the proper metabolism and conversion of carbohydrates, as well as for the formation of nucleotides that make up DNA.Its deficiency can cause serious problems with the health of the nervous and cardiovascular systems. B vitamins are usually found in foods, so vitamin B1 deficiency is extremely rare.

Discovery of vitamin B1

Thiamin was discovered in 1897 by the Dutch physician Christian Eikmann in 1897. While working on methods of treating vitamin deficiency, Eikman discovered that there is a compound in rice bran, the absence of which causes the development of this disease. In 1929, the doctor received the Nobel Prize for his discovery.Polish biochemist Kazimierz Funk made other discoveries as well. In 1911 he was able to isolate vitamin B1 from rice bran. Funk proposed to call compounds with the structure of amines as vitamins. The final chemical formula for vitamin B1 and the method for its synthesis were developed by Robert Runnels Williams in 1933-1936.
In the 19th century, beriberi was widespread among the poorest segments of the population in Asia. After the invention of methods for cleaning rice grains from bran, husked rice became the basis of their nutrition.As it turned out, the deprivation of rice from the valuable shell (bran), rich in thiamine, led to a deficiency of vitamin B1 in the diet of the poor and caused massive beriberi disease. Nowadays, beriberi symptoms are quite rare since a varied diet is available to most people. Diet supplements containing thiamine can be obtained as needed.

What is vitamin B1 and what are its functions in the body

Vitamin B1 is a water-soluble substance that occurs in the body in the form of monophosphate, diphosphate or thiamine triphosphate (TTF).Diforsoran is a coenzyme of many enzymes that are involved in the conversion of carbohydrates and nucleotides (molecules that make up the genetic material of DNA). Thiamine triphosphate is a form that plays a role in neurophysiological processes and also supports the functioning of the heart and blood vessels.
Thiamine is essential for the proper course of metabolic processes, especially the metabolism of carbohydrates and branched-chain amino acids: valine, leucine and isoleucine. Vitamin B1 is used by the cells of many organs because it is required in the process of intercellular respiration.It is involved in the synthesis of neurotransmitters (acetylcholine) and accelerates wound healing. Vitamin B1 also has antioxidant properties.
Vitamin B1 is also involved in nerve conduction and can affect the functioning of the immune system and kidney function, especially in people with type 2 diabetes. B1 causes a decrease in the amount of protein excreted in the urine (a symptom of kidney damage).

Vitamin B1: dosage

The daily requirement for vitamin B1 varies with age, gender and physiological condition.According to the recommendations of the Food and Nutrition Institute, this is:
• 0.3 mg for infants under 1 year old,
• 0.5 mg for children 1-3 years old,
• 0.6 mg for children 4-6 years old,
• 0.9 mg for children 7-9 years old,
• 1.0 mg for boys and girls 10-12 years old
• 1.2 mg for boys 13-18 years old
• 1.1 mg for girls 13-18 years old, for women> 19 years old and
• 1.3 mg for men> 19 years old,
• 1.4 mg for pregnant women
• 1.5 mg for breastfeeding women.

Vitamin B1: in food

Vitamin B1 is ubiquitous in food, therefore its deficiency is very difficult. It is found in both plant and animal foods. The best sources of vitamin B1 are yeast, various nuts and legumes, and bran.
Foods rich in B1 (content indicated per 100 g of product):
• baker’s yeast (dried) 2.7-6.6 mg,
• 2.75 mg rice bran,
• 2.1 mg wheat germ,
• sunflower seeds 1.3 mg,
• 1.1 mg pork tenderloin,
• lentils 0.87 mg,
• soy 0.85 mg,
• millet 0.73 mg,
• white beans 0.6 mg
• whole grain wheat flour 0.55 mg,
• walnuts 0.39 mg,
• green peas 0.32 mg,
• whole grain rye flour 0.3 mg,
• beef liver 0.3 mg.
• brown rice 0.29 mg,
• pumpkin seeds 0.21 mg,
• salmon 0.17 mg,
• wholemeal rye bread 0.14 mg,
• eggs 0.12 mg,
• cauliflower 0.11 mg,
• orange 0.08 mg.

Vitamin B1 deficiency: causes and consequences

Vitamin B1 deficiency is most often caused by poor diet or chronic medication. Thus, the risk group for vitamin B1 deficiency includes:
• patients with anorexia because they restrict food intake,
• drinking excessive amounts of alcohol (alcoholics),
• people with diabetes,
• seniors,
• patients after major surgery,
• pregnant and lactating women,
• chronic diuretics, such as furosemide,
• tobacco smokers,
• preferring a high-carbohydrate diet based on simple sugars.
People whose diet is based on foods that are low in vitamins and minerals are at a high risk of vitamin B1 deficiency. These include fast food, toast, frozen pizzas and casseroles, sweet and savory snacks, takeaways, and sugary sodas. Therefore, there are no fresh vegetables and fruits, whole grains, pods, or high quality meats in everyday meals. Vitamin B1 deficiency can also result from thiamine malabsorption. In such cases, despite the abundance of food consumed, it reaches a state of deficiency.
Vitamin B1 deficiency suppresses chemical reactions in which thiamine plays an important role as an enzyme activator. The first symptoms of insufficient intake of thiamine in food appear in the nervous system. Thiamine deficiency decreases the production of acetylcholine, a neurotransmitter that acts in the nervous system. Acetylcholine is responsible for memory processes, the work of the heart muscle, skeletal muscles and muscles that form the digestive tract.
With vitamin B1 deficiency, toxic lactate accumulates in the body, which does not convert to pyruvate due to the limited activity of the pyruvate dehydrogenase complex.This leads to an increased influx of sodium ions into the cells, and with them water, which causes edema.
Symptoms of vitamin B1 deficiency resulting from the above disorders are:
• fatigue and weakness,
• impaired concentration,
• short-term memory loss,
• dizziness,
• nystagmus,
• edema,
• emotional imbalance,
• accelerated rhythm and enlargement of the heart
• arrhythmia, i.e.e. cardiac arrhythmias,
• digestive disorders: nausea, vomiting, loss of appetite and diarrhea,
• polyneuritis, or polyneuropathy,
• muscle atrophy of the limbs (atrophy)
• muscle tremor.
Long-term vitamin B1 deficiency can cause beriberi disease, which manifests itself in muscle disorders and cardiovascular failure, and can lead to death. Vernitsky encephalopathy and Korsakov psychosis (Vernitsky-Korsakov syndrome) can develop in people whose vitamin B1 deficiency is caused by alcohol abuse.
Thiamine is a common ingredient in supplements containing B vitamins and multivitamins. Also, in the pharmacy you can buy only vitamin B1 tablets (without adding other vitamins). Vitamin B1 is most commonly found in dietary supplements in the form of thiamine mononitrate or hydrochloride. Fat-soluble synthetic thiamine BTMP is used to treat vitamin B1 deficiency (especially nervous system symptoms). With proper nutrition, thiamine supplementation is not necessary.

Excess vitamin B1: causes and effects

Thiamine is soluble in water, so excess vitamin B1 is excreted in the urine.The second defense mechanism, when consumed in an amount of more than 5 mg per day, is a decrease in its absorption in the gastrointestinal tract. Therefore, an overdose of vitamin B1 is almost impossible. Possible hypervitaminosis (excess) of vitamin B1 can cause dizziness and allergic reactions.

Sources:

Lindboe CF, Loberg EM .. Wernicke’s encephalopathy in non-alcoholics. An autopsy study. J Neurol Sci 1989; 90: 125-9.

Kerns JC, Arundel C, Chawla LS .. Thiamin deficiency in people with obesity.Adv Nutr 2015; 6: 147-53.

Donnino M … Gastrointestinal beriberi: a previously unrecognized syndrome. Ann Intern Med 2004; 141: 898-9

Institute of Medicine [Internet]. Thiamin. In: Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Vol. 2016. Washington (DC): The National Academies Press; 1998. p. 58–86. [cited 2016 Oct 10].

Luong KV, Nguyen LT .. The impact of thiamine treatment in the diabetes mellitus.J Clin Med Res 2012; 4: 153-160.

Gibson GE, Hirsch JA, Fonzetti P, Jordan BD, Cirio RT, Elder J .. Vitamin B1 (thiamine) and dementia. Ann N Y Acad Sci 2016; 1367: 21-30.

Leite HP, de Lima LF .. Metabolic resuscitation in sepsis: a necessary step beyond the hemodynamic? J Thorac Dis 2016; 8: E552-7.

90,000 Information about Alzheimer’s disease (for patients and their loved ones)

Many people can at least once in their life encounter a situation when their memory and attention are not in such good condition as they would like.The condition is often transient and usually accompanies stress, anxiety, depression, or sleep disturbances.

With age, people are more likely to encounter memory problems. This can be both a natural manifestation of aging and a sign of illness. In most cases, age-related changes do not cause serious problems in daily life. If constant forgetting begins to interfere with a person’s daily life, and he cannot cope with previously performed actions, this may be a manifestation of dementia.

Dementia is a progressive deterioration in memory, mental ability and ability to cope with daily activities, which leads to a state where a person cannot cope without assistance.
There are several causes of dementia, and the most common cause is Alzheimer’s disease.

Disease Alzheimer’s is a chronic disease of the nervous system that was first described by Dr. Alois Alzheimer in 1906.The disease got its name from his name. The disease causes slow neuronal damage and brain tissue death. Due to the disease, memory, mental abilities gradually deteriorate, and the ability to cope with daily activities decreases.

Other causes of dementia include, for example, recurrent cerebrovascular disorder (vascular dementia), degeneration of the frontal and temporal lobes (frontotemporal dementia) and long-standing Parkinson’s disease.

Severe renal or hepatic impairment, thyroid insufficiency, tumors or brain injury sometimes result in decreased mental performance. If a doctor suspects that a person with memory impairments has the aforementioned diseases, he or she may conduct the necessary tests and examinations to rule out these diseases.

The diagnosis of Alzheimer’s disease cannot be confirmed by a blood test. Decreased brain volume can be seen on examination of the brain.

Due to the aging of the population, the incidence of Alzheimer’s disease is also increasing.Therefore, it is very important to raise public awareness of this disease. Treatment for Alzheimer’s disease can help slow the progression of the disease, so it is very important to see your doctor as early as possible.

The Patient Manual in your hand is intended for Alzheimer’s patients and their loved ones, as well as all other interested parties. The aim of the guide is to help people with Alzheimer’s and their loved ones understand the nature of the disease, diagnose it and find suitable solutions if problems arise.A holistic knowledge of the disease helps to recognize the disease as early as possible, and thanks to this we can better understand the patient’s problems and provide him with effective assistance.

Acetylcholine is a transport substance through which communication occurs between brain cells. Alzheimer’s disease causes a lack of acetylcholine in the brain.

Dementia is an aggravating impairment of memory, mental ability and ability to cope with daily activities, which leads to a condition that a person needs assistance.

Guardianship – legal relations in which the court appoints a guardian to a person with limited legal capacity (ward) to protect his personal and property rights of a person and to carry out specific actions prescribed by law and provided by the court for the protection and well-being of persons.

G lutamate is a transport substance through which communication occurs between brain cells. Alzheimer’s disease is caused by excessive release of glutamate in the brain.

Primary caregiver ( eng. primary caregiver ) – a person close to the patient or someone else responsible for the well-being of the patient.

Legal capacity – the ability of a person to independently make existing transactions. The presence of legal capacity implies that a person can adequately understand the meaning of his actions.

Brief Examination Mental Status is a screening test used to diagnose dementia and assess the severity of the disease.

If your memory and skills are impaired, contact your family doctor. If you notice these changes in a loved one, help him go to the family doctor’s appointment. Stay with him at your doctor’s appointment to help describe the changes, if needed.
Call your family doctor immediately if problems occur suddenly and progress over days, weeks, or months.If necessary, the family doctor will cooperate with a neurologist and / or psychiatrist and / or geriatrician.
Tests and blood tests, as well as computed tomography and magnetic resonance imaging, are performed to determine the causes of memory problems.
Alzheimer’s diagnosis begins with treatment that helps maintain the ability to cope with daily activities and slows down the development of memory impairment. Treatment of the disease with drugs is not possible.
If you experience hallucinations (eg, seeing ghosts), mood swings, anxiety attacks, aggressive behavior, seek the help of your family doctor or psychiatrist.Mental and behavioral disorders are common in patients with Alzheimer’s disease. They can be associated with a medical condition, but they can also be caused by insufficient treatment for other comorbid conditions. Conduct disorders substantially impair the ability to cope with daily activities.
Memory and behavioral problems make it difficult to relate to family members and loved ones and complicate daily life. People with memory impairments should have a loved one who can help them in their daily work, as well as in solving legal issues.Financial, property and property issues must be resolved even when the person with Alzheimer’s is still capable of working.
Alzheimer’s disease affects memory, orientation in space, speed of thinking and reaction. Therefore, driving a car becomes difficult, and to ensure traffic safety, it is necessary to restrict driving rights.
A person with Alzheimer’s disease may be impaired in their ability to critically assess their actions. Track the ability of people with Alzheimer’s to drive and operate household appliances.If he cannot perform these types of activities at the proper safe level, then they must be abandoned.
Alzheimer’s is a serious and progressive disease and caring for such patients is physically and emotionally exhausting for those close to them. Understanding the nature of the disease and learning how to care in a new environment will help to avoid burnout. It is recommended that you seek help from a clinical psychologist or psychotherapist.
You can find helpful reading materials at the end of this manual on this topic.

The triggering mechanisms for Alzheimer’s are not yet fully understood. Early-onset Alzheimer’s disease may first appear before age 65 and may be hereditary. If you have relatives with Alzheimer’s and have questions about the inheritance of the disease, it is recommended that you consult with a geneticist.

Late-onset Alzheimer’s is much more common than early-onset Alzheimer’s.It is not known why some people develop Alzheimer’s disease, while others remain clear-cut for the rest of their lives. The factors of heredity and the environment, as well as the way of life, probably play a role. The most well-defined risk factor is age. Smoking and depression in middle age are also cited as contributing risk factors. Moderate physical activity, healthy eating and communication are known to have good effects on both mental and physical health, but they do not protect against the development of Alzheimer’s disease.

Changes characteristic of Alzheimer’s disease occur in the brain tissue already decades before the onset of symptoms of the disease. Abnormal proteins (amyloid and tau proteins) deposited in the brain tissue disrupt the functioning of nerve cells, which ultimately leads to the death of the nervous tissue (atrophy).

Memory impairment is the most common symptom of Alzheimer’s disease. At first, it can be difficult to distinguish from normal age-related ones (for example, difficulty remembering names and faces).In case of illness, small details begin to be forgotten: keys and documents are lost, when leaving the house they forget to close it, when cooking, dishes with food are forgotten on the stove or the gas tap remains open, for a long time the recipes used for dishes begin to get confused during cooking and the taste of food becomes narrower not the same as before, the actions associated with putting the house in order are no longer successful, etc. (see Figure 1).

People with a high level of education and those involved in mental work may have the first signs of the disease later, because their brain is better able to cope with changes in it.The manifestation of the disease is individual for each person. Some early stage people may find it difficult to find words, recognize faces and objects, find the right path in a familiar place, understand and make decisions, and memory impairment can occur later.

Figure 1. Changes associated with Alzheimer’s disease

Depending on the severity of the disease, its course can be divided into periods: at the beginning of the disease, mild dementia develops, then moderate memory impairment develops, and in the later period of the disease it is already severe dementia (see.Annex 1).

At the onset of the disease, people often notice their own problems. During this period, a person can understand his condition, he can independently seek help and cope with most of his daily activities. This period should be the best time to diagnose the disease.

When memory impairment and forgetfulness worsen, a person may repeat the same story, ask the same questions, forget the answers, forget dates, promises and obligations (such as paying bills).When you go to the store, you forget to buy the necessary things.
It can happen that a person starts to be careless with money and buys unnecessary things instead of necessary ones.
Household skills are forgotten and take longer to complete (for example, it is more and more difficult to cope with cooking, cleaning, repair and construction, laundry, the quality of the actions performed deteriorates and the result becomes more and more simplified each time).
The patient can no longer learn new activities (for example, using a new telephone, opening a new door lock, etc.).
Indifference and loss of interests often arise, the desire to clean the house and visit friends is lost.
Self-care is deteriorating – previously always well-groomed hairstyles and tastefully chosen clothes are becoming more and more casual.

It may happen that a person initially tries to hide his problems from others.

As the disease progresses, critical judgment and attention are further reduced, and memory impairment becomes more pronounced. People with Alzheimer’s disease forget the date, day of the week and year, their address, and where they are currently. In most cases, patients do not notice changes around and in themselves, although sometimes there may be moments of clarification when the understanding is clearer.

Difficulties appear in recognizing familiar, objects and places.They are often confused in familiar places.
It becomes more and more difficult to act in new situations, anxiety arises.
The time estimate can decrease / disappear.
It becomes more difficult for the patient to cope with daily activities, it takes more and more time (for example, paying bills and transactions with money, preparing food, dressing, eating, going to the toilet).
Mental and behavioral disorders (suspicion, hiding things, aggression, screaming) may also occur.
The ability to recognize your loved ones gradually decreases. The daily rhythm is disturbed, sleep disorders are formed. Often a person is more active in the evenings and at night, when he calls and wanders.

In the later stages of the disease , the ability of people to speak and understand speech is so impaired that they cannot express themselves or understand the meaning of others. The more important is non-verbal communication with loved ones – tone of voice, facial expression, gestures. All previous skills of the person disappear, and he can no longer get out of bed, dress, walk, go to the toilet or eat.

In case of memory and mental impairment, as well as impairment of usually well-performed skills, it is recommended to first consult a family doctor (see Figure 2). If possible, the patient needs to come to the doctor with a loved one who will help describe the changes as an outside observer, this will help confirm the diagnosis. The patient himself may underestimate some of the problems or forget to share them with the doctor. The doctor may ask a loved one to fill out a questionnaire about the patient’s behavior and daily activity over the past six months.

Tell your family doctor:

What is the main problem that causes you to see a doctor?
How long does it take for these problems to appear?
What was the first sign that something was wrong?
How has human behavior changed?
How much does he need outside help in everyday life?
Does he have any mood swings, thoughts of suicide, joy, aggressive behavior?
Are there any comorbidities and what medications, including dietary supplements, are they taking?
How and at what age did family members develop dementia?

The family doctor assesses the memory disorder using a test (for example, using a brief mental health examination).Mini Mental State Examination, MMSE). The test assesses the ability to navigate in space and time, attention and memory, as well as the ability to plan the activities necessary for the task. The maximum number of points in the test is 30; a result of 24 or less will indicate dementia. To analyze the results, the doctor takes into account the patient’s educational level, language proficiency and other possible factors affecting the level of task performance (for example, hearing and visual impairments).The test can determine the severity of dementia (mild, moderate, severe) (see Appendix 1).

Testing is not enough to diagnose Alzheimer’s disease. The test also does not provide information on the causes of memory impairment. This will require additional surveys.

A blood test can be used to investigate whether memory problems are caused by any other medical conditions, such as decreased thyroid function, anemia (anemia), vitamin deficiencies, infectious diseases (such as borreliosis, syphilis, AIDS) and dr.With proper treatment of the above diseases, memory impairments can recede to one degree or another.

If necessary, the family doctor will refer the patient to an appointment with a specialist dealing with memory impairments (neurologist, psychiatrist, geriatrician).

A patient with suspected Alzheimer’s disease undergoes a general examination of the head (computed tomography or magnetic resonance imaging) to exclude other brain diseases (eg, brain tumor, chronic hemorrhage, hydrocephalus).

If the diagnosis remains unclear, the doctor may refer the patient for a neuropsychological examination, which is carried out by a clinical psychologist. Tests carried out during the examination will help determine exactly which type of memory impairment is present in the patient. Neuropsychological evaluation is only beneficial for patients with mild dementia syndrome and patients with early onset of the disease. For patients in advanced stages of the disease, the tests can be overwhelming and tedious.

Figure 2. Patient collaboration with specialists from different fields

Treatment of Alzheimer’s disease slows its progression. The sooner the disease is detected and treatment is started, the longer the patient’s ability to cope with daily activities remains. This allows loved ones and caregivers more time to adapt to the changing lifestyle and think through the most important issues that inevitably arise at the end of life.

Alzheimer’s disease progresses slowly.The late stage of the disease is formed over an average of five to ten years. This condition is considered an end-of-life stage that cannot be cured and life prolongation by various medical procedures is not considered ethically acceptable.

Since the cause of the disease is unclear, it cannot be prevented. A good, varied diet, moderate physical activity, social activity, mental work and hobbies (for example, theater, solving crosswords, dancing, fishing, hiking, traveling, mushroom picking, etc.)) are good for mental and physical health and help reduce the risk of Alzheimer’s disease. Research has not proven that taking vitamins and supplements helps prevent disease.

Patients are encouraged to eat a variety of wholesome foods (see Figure 3). They don’t have to adhere to any special diet. In the food pyramid, you can see which foods and in what quantity are recommended to be eaten.

Figure 3. Food pyramid (for more details visit http://toitumine.ee/ru/kak-pravilno-pitatsya/rekomendatsii-v-oblasti-pitaniya-i-piramida-%20pitaniya)

Patients with Alzheimer’s disease often have a risk of weight loss. They may forget about eating and not notice the feeling of hunger. Reduced appetite can be reduced by decreased physical activity, certain medications, and decreased sense of smell and taste. The reason for this may be poorly installed prostheses, as well as the fact that patients do not recognize food, etc.Thus, patients can lose too much weight and lose muscle mass, which, in turn, increases the risk of falling and other diseases. Therefore, it is recommended to eat protein-rich foods and prevent weight loss. Protein supplements (protein powders or drinks) sold in pharmacies and eating smaller meals more often can help with decreased appetite. Adequate fluid intake is also important.

On the other hand, there are cases of excessive appetite due to loss / decrease in the feeling of satiety.Some people with Alzheimer’s eat too much sweets. Patients should try to eat wholesome and varied, and have small snacks between meals. At the same time, excessive restriction of food can cause anxiety and irritation in the patient.

As Alzheimer’s disease progresses, sufferers are no longer able to use kitchen utensils and prepare food on their own due to the gradual fading away of skills. Pre-cooked meals and meal reminders can help here.It is best to have a joint meal. In case of swallowing disorders, food can be pre-crushed or divided into small pieces, it is better to thicken drinks.

There are two types of treatment options for patients with memory impairments: supportive therapies and medication (see Figure 4). In both cases, the goal is to improve the quality of life of the patient and his loved ones, to maintain the existing level of skills and to maintain the ability to cope with everyday affairs for as long as possible.

Figure 4. Treatment of Alzheimer’s disease

Supportive therapies

Among the possible treatments for Alzheimer’s disease, the importance of different types of creative activity is especially noted. Constant communication and activity slows down the worsening of speech, attention and behavior disorders. A person with Alzheimer’s thinks more slowly and may not understand more complex speech. During the conversation, you need to be patient, not to be irritated by the patient’s repetitive questions, or his inappropriate or “childish” statements.It is advisable to speak slowly and in simple phrases, to avoid command, heightened or irritated tone of speech.

Patients with moderate to moderate memory impairment are advised to play games, take care of the garden or pets, music, art or aroma therapy, food preparation, and other stimulating activities. Versatile physical activity improves gait speed, body strength, muscle strength, balance, state of mind, and promotes better ability to cope with daily activities.

Listening to your favorite familiar music can evoke positive emotions and memories and thus have a good effect on your mood and quality of life. It doesn’t matter what kind of music you listen to – the most important thing is that a person liked it!

It is important to continue pursuing the hobbies you already have. If a person has played any musical instrument before, you need to continue playing it. This is a good way to stimulate your brain and keep you in a good mood. The above activities are simple and suitable for both patients and their loved ones.

Medicines

Medicines can help preserve memory and slow down the disappearance of existing skills. The process of the death of nerve cells that occurs as a result of the disease cannot be influenced by drugs.

In the process of memory functioning, acetylcholine plays an important role, which is responsible for communication between nerve cells. Alzheimer’s disease is caused by a lack of acetylcholine in the brain. In the initial stage of the disease, treatment is usually started with donepezil, which stops the breakdown of acetylcholine.At the beginning of treatment, side effects can sometimes appear – a feeling of nausea, vomiting, diarrhea, dizziness, weight loss, slowing of the heart rate and short-term loss of consciousness. To reduce side effects, treatment is started with small doses and usually the side effects disappear within the first month. After that, the dose of the medicine can be increased.

For patients with severe Alzheimer’s disease, the first choice is memantine , which can be combined with donepezil.Exactly how memantine helps maintain acquired skills is not known exactly. However, it was found that in the case of Alzheimer’s disease in patients in the brain there is an excessive release of the transport substance glutamate, which destroys nerve cells. Memantine balances the action of glutamate and possibly thus slows down the destruction of nerve cells. The most common side effect of memantine is a drowsy, inhibited state. Less commonly, illusions or aggressive behavior may appear.All side effects must be reported to the doctor and then decide on the further use of the medication.

Donepezil and / or memantine are not effective in all cases. As the disease progresses, the effectiveness of drugs decreases. Therefore, the doctor should regularly assess the course of the disease, the effect of drugs and their side effects.

Donepezil and memantine are the names of the active ingredients of the preparations. Medicines containing these active ingredients are sold under different brand names, but their effectiveness is the same.

Mental and behavioral disorders are common in patients with Alzheimer’s disease. They can be as follows:

irritability
aggressiveness
Mood Swings
apathy
unreasonable, excessive feeling of fear
Anxiety
Suspiciousness (suspicion that someone wishes the patient ill, and intentionally harms in any way)
Sleep disorders (difficulty falling asleep, violation of the daily regimen, night walks)

The above problems may indicate some other medical condition or that the patient feels insecure in some circumstances.Mental and behavioral disorders can be part of Alzheimer’s disease and their incidence can increase as the disease progresses.

It is important to understand that a person with Alzheimer’s is not behaving so deliberately, but it is caused by their disease!

A person with Alzheimer’s disease does not always know how to talk about their problems, so it is important to understand what exactly bothers or annoys him. Sometimes it can be a fever or a feeling of pain. Other times, the path to the toilet is forgotten or the skill of eating a sandwich or using a fork is lost.Failure can cause too many people around or other people’s expectations of the patient. With the progression of the disease, it is more and more difficult to explain their desires and feelings to other people, the right words are not found, and the patient cannot find solutions to his problems. All of these can act as annoying and depressing factors.

At calm the patient down and speak with him in a friendly tone, rather slowly and in short phrases . Give him time to respond, as illness usually slows down the thinking process.Irritability towards the patient can piss him off, and it can take some time to re-establish the relationship of trust.

If you experience mental and behavioral disorders, contact your family doctor to try to find out the causes of the problems. Not all disorders require the use of medications, sometimes it is enough to change the behavior of loved ones or a caregiver (you can calm the patient down, divert thoughts to another area, engage in a feasible type of activity, etc.)

Sometimes the cause of behavior change can be unmet basic needs – inadequate nutrition and water intake: too little or too much communication with loved ones, fatigue and / or sleep disturbances, noise and other environmental factors, pain or other feeling of discomfort in the body.

Sometimes the patient can be aggressive, present a danger to himself and others. In some cases, depression may occur, due to which everyday affairs may remain unfulfilled, a person becomes apathetic, speaks of the meaninglessness of life, and loses hope.In such cases, be sure to consult a psychiatrist. Living with people with Alzheimer’s can be exhausting and cumbersome. Some days can be harder than others. Caring for the sick should not fall on the shoulders of just one family member.

To support the caregiver:

Be in touch with him, ask him how he copes with leaving and how to help him. For example, if you are planning to go to a mall, ask if you need to buy something for it.Ask if you can help him with housekeeping (cooking, gardening).
Give him the opportunity to continue pursuing his hobbies and interests. Sometimes a few hours are enough for him to be able to do his own business or just relax.
Be a sympathetic and sympathetic listener. You don’t always have to give advice, but give people the opportunity to talk about their problems or everyday work.
Read as much as you can about Alzheimer’s.This way you can better help and support both the patient and his family members.

Alzheimer’s disease worsens the treatment of underlying chronic conditions and vice versa. At the beginning of the disease, the patient is shown treatment procedures that improve the quality of life, for example, cataract surgery, surgical treatment of fractured ribs, dental treatment, oral care, purchasing a hearing aid or glasses.

Regular monitoring and treatment of other chronic diseases is important, since cardiovascular insufficiency or fluctuations in blood sugar levels impair the normal nutrition of nerve cells.In the treatment of chronic diseases, it is necessary to monitor the safe use of drugs to prevent overdose and reduce the dosage of drugs due to memory impairment.

The question of stopping treatment with pills to maintain existing skills and quality of life is decided individually, taking into account the wishes of the patient. If the patient himself can no longer decide, then the wishes of his loved ones are taken into account, while the patient’s well-being must be taken into account. For example, if a patient refuses to take a drug or it cannot be guaranteed that it will be used safely, then it would be wise to stop that treatment.If the patient has another serious illness in addition to Alzheimer’s disease, then taking medications can cause additional inconvenience, since it does not improve the quality of life and does not prolong life.

Also, treatment is completed if the disease progresses to such a level when the patient needs outside help in all actions, he himself cannot get out of bed, cannot walk and refuses to eat and drink.

As the disease progresses, it becomes increasingly important to treat that alleviate suffering (palliative care).Its goal is to make the patient feel as comfortable as possible and free him from suffering. The goal of patient care is her well-being. Well-being is ensured, among other things, by taking care of hygiene. If a person is constantly in bed and cannot change his position on his own, you need to help him do this every three hours – this way you can prevent the occurrence of bedsores. Make sure that no part of your body is pressed against a hard surface – this will interfere with the blood supply and contribute to the formation of pressure ulcers.Dry skin requires creams; dry mouth requires moisturizing. Pain relievers may be needed. If a person can no longer swallow on their own, then there is no need to prolong his suffering and switch to feeding through a vein or tube. The body at this stage dies out and no longer absorbs nutrients and does not produce energy.

Memory and mental impairment, as well as communication problems, cause problems with daily activities.Over time, the problems worsen, this process occurs in different ways in different patients. It is influenced by the type of activity that the patient was engaged in before, the level of his education, personality traits, previous lifestyle and the course of the disease.

It is important for close ones or guardians to introduce themselves as early as possible with the necessary business issues, his legal and monetary obligations. If the patient is still independent, then you can monitor whether he is paying bills correctly or help him with a trip to the store.It is important to maintain a friendly and trusting relationship.

For people with memory impairment, attention and the ability to critically assess their activities gradually fade away. At some point, he can no longer correctly assess the risks, so important things remain unfulfilled (unpaid bills, uncleaned house) or dangerous situations arise (the gas valve is forgotten open, working tools are inaccurately used, carelessness when crossing the street).

Progressive disorders of the patient’s memory and behavior can cause severe stress for caregivers and family members, especially in a state when the patient himself is no longer able to understand the problem.With this in mind, loved ones need to organize help and care for the patient. If family members are unable to care for the sick on their own, then help should be sought from available social services: home care, day care centers, nursing homes, or other support systems. For more information, contact your local government social worker.

If family members are caring for the sick at home, assistive devices (such as diapers, function beds, wheelchairs, or walking frames) can be used to simplify day-to-day procedures.Assistive products can be purchased or rented from stores selling goods for the disabled. For rental or discount purchases, the attending physician or family doctor must issue a certificate of receipt of a personal accessory card and notification of the need for the specific accessory. More information can be obtained from family doctors, social workers and companies selling aids.

If a person with Alzheimer’s can no longer cope on their own and relatives cannot care for them, then it is possible to find a safe place to live for the person in a care facility.You can ask your social worker for information about care facilities. If the patient is outside his home, you can try to make the environment similar to his home, so that he recognizes familiar objects, for example, photographs of his adolescence are suitable for this, etc. An adapted environment can reduce the anxiety of patients with dementia and improve their behavior.

Restricted legal capacity

The ideal option is a situation when a person with Alzheimer’s disease, even before the disease or at its initial stage, takes the necessary measures and signs powers of attorney to manage their concluded contracts, finances and property.As the disease progresses, he can no longer make clear decisions and fulfill his obligations. Thus, abuse of the patient’s financial resources can also occur – for example, when neighbors, relatives or strangers, towards whom the patient suddenly becomes very trusting, lure the patient out of money, housing or other property. Sometimes the patient may have contracts that need to be monitored and followed. Relatives have the opportunity through the court to limit the legal capacity of a person suffering from Alzheimer’s disease, and / or to appoint a certain guardian to carry out legal transactions, as well as to protect their interests, rights and property.You can request information from a local government social worker or court clerks. Local self-government bodies deal with the issues of guardianship of people who have no relatives.

Driving a motor vehicle

Alzheimer’s dementia syndrome is a severe mental disorder that limits the right to drive.

People with memory impairments do not believe and often do not notice that their ability to drive and other acquired skills are beginning to decline.People with mild memory impairments usually cope with driving in familiar territory, but their loved ones should regularly assess the situation and restrict access to the car if necessary. The family doctor must issue a health certificate to obtain a driving license for a person with memory impairments for a shorter than usual period of time (for example, 3-6 months or a year). Each time the certificate needs to be renewed, the applicant’s condition is assessed again and, if necessary, he is referred for a neuropsychological examination.Sometimes test drives may be conducted to assess driving skills and ability to drive a vehicle.

The right to drive of people with Alzheimer’s is restricted by the road traffic law.

Weapon proficiency

Possession of a weapon requires a weapons permit, which is regulated in Estonia by the Arms Act. A medical certificate is required to issue a weapon permit. Alzheimer’s dementia syndrome is a severe mental disorder that is a contraindication to obtaining and renewing a gun license.Loved ones should restrict access to weapons for people with Alzheimer’s, as they can be dangerous to themselves and to others.

Agree with family members about who will be the primary caregiver and how the burden of care will be shared.
It is necessary to try to maintain a trusting relationship with the patient and regularly monitor his condition and behavior.
Go with the patient to the doctor, if necessary, and in other places.
Pay attention to changes in the patient’s condition, regularly remove objects that have become dangerous for him from his environment, and create a favorable environment for him around the ward.
Track your medication intake. Medicine boxes can be a good help, in which you can put pills according to the order of taking for each day. Some pharmacies offer the option of repackaging medicines. This way the patient and caregiver will have a clearer picture of the medication they are taking.Sometimes it can help to recount the tablets available in the package of the medicine.
Remind the patient to eat. Patients often forget to find and take food from the refrigerator on their own. Eat together if possible and make sure the person is able to cope with rewarming food or using kitchen appliances. For safety reasons, check if household appliances are turned off after use.
Try to create a clear plan of the day for the patient and help him to form from it the adhered regimen, routine.Post the day plan in a prominent place in your home, such as on the refrigerator door. When providing the necessary physical, mental and social activity, diet, personal care and collective activities (this can be a joint viewing of photographs and recalling events captured on them, joint meals, reading books, etc.), always take into account the patient’s real capabilities and wishes …
Track who a person with Alzheimer’s is in contact with. A person with Alzheimer’s can be easily suggestible and gullible towards strangers, so it can be easily used.His trust can also be abused by acquaintances.
Try to avoid conflicts. The patient can use his own behavior for his own purposes, relatives, mistreat them, manipulate. In case of problems, consult a social worker.
Do not bring alcohol into your home or share with someone who is sick. Drinking alcohol causes conflicts and behavioral disorders, as well as misunderstandings with relatives and friends.
If someone close to the sick person feels that they need professional help in mental health issues, then it is better to find an opportunity to consult on this topic.Detailed information can be obtained from your doctor or go to thematic sites on the Internet.
People with Alzheimer’s are better off calling more often, reminding them of things from the day plan, and checking to see if they have done them. Daily activities can be facilitated by placing labels on the doors. Emphasize the need for self-care, the importance of connecting with friends and family, and, if necessary, how to get help.

Additional information on the Internet in Estonian:

Other materials and publications:

“Käsiraamat dementsete haigete hooldajale”, Ülla Linnamägi, Mark Braschinsky, Kai Saks, Eve Võrk, Terje Lääts.Iloprint, 2008.
Eesti toitumis- ja liikumissoovitused, 2015, kättesaadav: www.tai.ee.
Juhtimisõiguse ja relvalubade alane seadusandlus, kättesaadav: www.riigiteataja.ee.
“Elu dementsusega”, Angela Caughey. Petrone Print, 2017.
“Siiski veel Alice”, Lisa Genova. Kunst, 2016
“Loomulik vananemine ja dementsus”, Anna Follestad. TEA Kirjastus, 2016
„Mul on Alzheimer. Minu isa lugu “, Stella Braam.Tammerraamat, 2008.

Additional information on the Internet in English:

Alzheimer’s Disease Association, website: www.alz.org.
Alzheimer’s Disease Association of Great Britain, website: www.alzheimers.org.uk.

Additional information on the Internet in Russian:

Further information on the Internet in German:

Points	Severity	Need for further tests	Legal capacity
25-30	Questionable clinical importance	If clinical signs are found, new tests may be helpful.	Normal / Clinical decline may be present
20-24	Light	May be useful for assessing the magnitude of the deficit and its severity	Significant decline, may require assistance and monitoring
10-19	Moderate	May be useful	Clear reduction, may require assistance around the clock
0-9	Heavy	Most likely testing is not possible	Severe violations, needs constant round-the-clock assistance

Prince, M., Anders, W., Guerchet, M., Ali, G., Wu, Y., Prina, M. World Alzheimer Report 2015. The Global Impact of Dementia [Internet]. Alzheimer’s Disease International; 2015. Available from: http://www.worldalzreport2015.org
Tanna, S. Alzheimer Disease and other Dementias Background Paper 6.11 [Internet]. 2013. Available from: http: //www.who. int / medicines / areas / priority_medicines / BP6_11Alzheimer.pdf
Hort, J., O’Brien, J. T., Gainotti, G., Pirttila, T., Popescu, B.O., Rektorova, I., et al. EFNS guidelines for the diagnosis and management of Alzheimer’s disease. Eur J Neurol. 2010 Oct; 17 (10): 1236–48.
Bruni, A. C., Conidi, M. E., Bernardi, L. Genetics in degenerative dementia: current status and applicability. Alzheimer Dis Assoc Disord. 2014 Sep; 28 (3): 199–205.
Linnamägi, Ü. Alzheimeri tõve riskiteguritest. Eesti Arst. 2014; 93 (2): 90-4.
Alzheimer’s Disease Fact Sheet [Internet].National Institute on Aging. [cited 2017 Sep 1]. Available from: https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet
Kryscio, R. J., Abner, E. L., Caban-Holt, A., Lovell, M., Goodman, P., Darke, A. K., et al . Association of Antioxidant Supplement Use and Dementia in the Prevention of Alzheimer’s Disease by Vitamin E and Selenium Trial (PREADViSE). JAMA Neurol. 2017 May 1; 74 (5): 567–73.
Charemboon, T., Jaisin, K. Ginkgo biloba for prevention of dementia: a systematic review and meta-analysis.J Med Assoc Thail Chotmaihet Thangphaet. 2015 May; 98 (5): 508-13.
Olazarán, J., Reisberg, B., Clare, L., Cruz, I., Peña-Casanova, J., Del Ser, T., et al. Nonpharmacological therapies in Alzheimer’s disease: a systematic review of efficacy. Dement Geriatr Cogn Disord. 2010; 30 (2): 161–78.
APA Work Group on Alzheimer’s Disease and other Dementias. Rabins, P. V., Blacker, D., Rovner, B. W., Rummans, T., Schneider, L. S., et al . American Psychiatric Association practice guideline for the treatment of patients with Alzheimer’s disease and other dementias.Second edition. Am J Psychiatry. 2007 Dec; 164 (12 Suppl): 5-56.
Segal-Gidan, F., Cherry, D., Jones, R., Williams, B., Hewett, L., Chodosh, J., et al . Alzheimer’s disease management guideline: update 2008. Alzheimers Dement J Alzheimers Assoc. 2011 May; 7 (3): e51-9.
Liiklusseadus. Riigi Teataja (internet). Kättesaadav: https://www.riigiteataja.ee/akt/117032011021?leiaKehtiv
“Soetamisloa ja relvaloa taotleja tervisekontrolli kord, loa andmist välistavate tervisehäirete loetelu ning tervisetõendi sisu ja vormi nõuded”.Riigi Teataja (internet). Kättesaadav: https://www.riigiteataja.ee/akt/126032015012?leiaKehtiv
Alzheimeri assotsiatsiooni koduleht. Kättesaadav: https://www.alz.org/care/alzheimers-food-eating.asp
Eesti toitumis- ja liikumissoovitused. Kättesaadav: https://intra.tai.ee//images/prints/documents/14
33869_eesti%20toitumis-%20ja%20liikumissoovitused.pdf
Linnamägi, Ü., et al. Dementsuse Estonian ravi- tegevus- ja diagnostikajuhend.2006. Kättesaadav: http://www.enns.ee/Ravijuhendid/Dementsuse_ravijuhend.pdf
Tahlhauser, C. J., et al . Alzheimer’s disease: rapid and slow progression. J R Soc Interface. 2012. Jan 7; 9 (66): 119-126.
Toidupüramiid. Kättesaadav: http://tervisliktoitumine.ee/toidupuramiid-on-tervisliku-toitumise-alus/; http://toitumine.ee/ru/kak-pravilno-pitatsya/rekomendatsii-v-%20oblasti-pitaniya-i-piramida-pitaniya
Folstein, M.F. et al .“Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research. 1975: 189-198.

90,000 Antidepressant Products or Foods to Improve Mood

Our
mood and emotions depend not only on external circumstances and health, but also
from the function of the endocrine glands – the hypothalamus and pineal gland. Hormones that
produced by them, regulate our sleep, the state of the immune system,
emotional mood and the degree of protection of the body in stressful situations.

Special
place is taken by neurotransmitters – chemicals in the brain,
transmitting information from one neuron to another. They are synthesized by amino acids
and their formation requires a constant supply of certain nutrients
substances. The most famous neurotransmitters that affect
neuropsychiatric state of a person, are serotonin, norepinephrine,
dopamine (dopamine), acetylcholine, and GABA (gamma-aminobutyric acid).

What substances regulate our
mood?

From
of these substances dopamine has the most significant effect on our mood
(dopamine) and serotonin.

Dopamine
creates a sense of pleasure when we do what we like (for example, eat,
listening to music, doing sports). Thanks to him, we can show
being active, motivated and satisfied. By the way,
drugs such as cocaine, nicotine, opiates, heroin and alcohol
increase dopamine levels. Therefore, many researchers believe that
the tendency of some people to smoke, use drugs and alcohol,
addiction to gambling and overeating is a dopamine deficiency in the head
brain.Decreased dopamine levels lead to impaired memory and concentration
attention, a decrease in vital energy (the so-called “vital activity”),
a person ceases to enjoy life and becomes susceptible to bad habits and
obsessive states. a lack of
dopamine in the corresponding parts of the brain leads to a loss of initiative (to “sitting
and dreaming “), a more serious deficit is the complete impossibility of making an active
action.

However
it must be remembered that excess
of this substance promotes pleasure seeking behavior
(hedonistic behavior).

Serotonin in our body is synthesized from
the amino acid tryptophan, which is ingested with food. It participates in the regulation of mood, suppresses feelings of anxiety,
affects libido and appetite. With its deficiency, social disorders can be observed,
phobias, sleep and memory disorders, as well as cardiovascular and
endocrine functions. Low serotonin levels can lead to depression
mood, anxiety, decreased energy, migraines, sleep disorders,
obsessive or manic states, feelings of tension and irritation,
there is a craving for sweets or, conversely, loss of appetite, memory impairment and
concentration of attention, angry and aggressive behavior, delayed
muscle movements and delayed speech.By the way, serotonin deficiency contributes to alcoholism (alcohol is temporarily
increases serotonin levels, but lowers them in the long term).

How bad autumn
mood with a lack of serotonin?

The role of the brain serotonin system in such pathological conditions has been studied
like seasonal depression and premenstrual syndrome. In both cases, to symptoms
diseases include depression, anxiety, often some degree of relaxation
control over behavior.In seasonal disorders, these phenomena occur in
autumn-winter period, accompanied by prolonged sleep and depressed mood.
PMS occurs in the last days of the menstrual cycle, and the change in hormonal
background during this period also affects the level of serotonin in the brain.

If the amount of serotonin
off scale? ..

It is necessary
note that an excessive amount of serotonin causes sedation, a decrease in
sexual arousal, a sense of well-being, bliss.However, if the level
serotonin becomes too high, this can lead to the development
serotonin syndrome.

Serotonin syndrome: excess
worse than a disadvantage?

Extreme
high serotonin levels can be toxic, but reaching such levels
thanks to food is impossible. This condition can only occur
with the abuse of antidepressants. Serotonin syndrome causes severe
tremors, profuse sweating, insomnia, nausea, toothache, chills,
shivering from cold, aggressiveness, self-confidence, agitation and increased
body temperature.

How to increase the level with the help of nutrition
mood-regulating substances?

Increasing serotonin levels naturally comes from a diet rich in
tryptophan, vitamins, zinc and poor “empty” carbohydrates. And of course it is
the misconception that ready-made serotonin is already found in foods. Serotonin is produced in the brain from the essential amino acid tryptophan.

Research
Oxford University’s Department of Psychiatry shows that when
patients with depression in remission are deprived of tryptophan, their depression
returns.Women who once had depression were divided into two groups and
fed some with food containing tryptophan, others with food not containing it. V
at the end of the experiment, ten out of fourteen women who did not receive
tryptophan, were mildly depressed, while none of
women who received tryptophan did not have
mood problems.

Tryptophan, which is used in the synthesis
serotonin, found in meat, eggs, cheese, bananas, milk, yogurt. but
without enough vitamins B ₃, B ₆, omega-3 fatty
tryptophan acids can be processed according to a different chemical formula and
turn into a substance that does not affect mood.Therefore, it is important to consume
source products and these essential substances.

For
increasing the amount of dopamine in the body, which affects mood and motivation,
the content of the preceding amino acids tyrosine should be increased in the diet and
phenylalanine. These amino acids are converted to dopamine by vitamins
co-factors such as vitamin B ₆ and folic acid. Big
the amount of dopamine precursors found in beets, soy, meat, almonds,
cereals and eggs.

Folic
acid and iron are also important for participating in the production of substances that regulate
mood. Study
at King’s College Hospital in London found that 33% of patients with
mental disorders, including depression, were deficient in folate
acid and iron.

What, apart from products, affects
the content of serotonin in the body?

On
the amount of serotonin in our body affects the level of female sex hormones
(estrogen).In this regard, in some women in the premenstrual period, and
also in menopause there are mood problems. In addition, one must remember
that stress decreases the amount of serotonin as the body uses it
stocks for calming.

Physical
exercise and good lighting help stimulate the synthesis of serotonin and
increase its amount. Antidepressants also help the brain
restore serotonin stores.

Foods that improve mood

It should be noted that the recommended antidepressant foods do not contain
of these neurotransmitters.Both serotonin and dopamine are only produced
by the human body when eating food rich in already known to you
precursor substances (carbohydrates, tryptophan, tyrosine, etc.),
from which they are synthesized.

Fish

Fat
fish (herring, sardines, mackerel, salmon, cod, salmon) are rich in omega-3 fatty
acids that regulate the level
serotonin. To foods rich in fatty acids
Omega-3s, in addition to fish, include nuts, seeds, avocados, unrefined
vegetable oil.Including fatty fish in meals twice a week in
an amount of at least 200 g (per week), you will provide your body
the required amount of omega-3 fatty acids. Held in Kyoto (Japan)
studies have shown that students who have taken
daily from 1.5 to 1.8 g of fish oil (as part of oily fish), not
showed an increase in social aggression during the examination period,
characterized by significant mental stress.

Chicken,
turkey, lean pork and beef, egg white, low-fat dairy
products

Listed
foods are the leading sources of the amino acids tyrosine and tryptophan and
B vitamins, necessary for the synthesis of “pleasure hormones”.V
in particular, meat contains pantothenic acid, which is involved in
the production of the amino acid phenylalanine, which is a precursor to dopamine –
a hormone that improves mood and prevents the development of depression.

Cabbage
marine

Marine
cabbage is rich in B vitamins, which regulate the adrenal glands and,
accordingly, the production of the hormone adrenaline, the lack of which is capable of
cause chronic fatigue.It is also a leading source of
organic iodine and other trace elements that normalize work
the thyroid gland, on the activity of which our mood depends.

Marine
it is better to buy dried cabbage not pickled, and then at home
cook or grind on a coffee grinder and use as a seasoning and
as a substitute for table salt.

Fruit,
especially bananas

V
bananas, in addition to tryptophan, contain vitamin B ₆, which, as already
it was said to be essential for the synthesis of serotonin – the main regulator
mood.In addition, bananas are rich in the alkaloid harman, the base
which is the “drug of happiness” – mescaline, which can cause a feeling of euphoria. To maintain strength, it is recommended to eat 1 banana, mashed and
drenched in boiling water (in the form of mashed potatoes).

Gorky
chocolate

Cocoa beans,
from which chocolate is obtained contain phenylethylamine, which contributes to
the production of endorphins in the body – substances that increase mood. Besides,
Cocoa beans contain magnesium, which can relieve stress.

Oatmeal and buckwheat dishes

Same as
meat, oatmeal and buckwheat contain the precursor of serotonin –
the amino acid tryptophan. Also, these foods contain complex carbohydrates, which,
slowly absorbed, normalize blood sugar levels. Hence,
regulate the concentration of insulin. And insulin, in turn, performs the function
transporting tryptophan to the brain, where it is already processed into serotonin.

Vegetables (green leafy, tomatoes, chili peppers, beets, garlic, broccoli,
celery and cauliflower)

All of these are sources of essential micronutrients (vitamins A, C, E, B ₁,
B ₂, B ₉, PP, minerals: potassium, calcium, iron, sodium,
phosphorus, magnesium, copper, manganese, iodine, chromium, boron), which are necessary for
formation of the main neurotransmitters.

Tomatoes also contain the compound lycopene, which is a powerful
an antioxidant that regulates metabolic processes in the brain, which helps
cope with depression.Also tomatoes
contain other “mood enhancers” such as folic acid and magnesium, and
also iron and vitamin B ₆, which are important for the brain’s production of mood regulating agents
neurotransmitters such as serotonin, dopamine, and norepinephrine.

Beetroot
contains another active substance – betaine. Vitamin-like compound,
which affects the hormonal status of a woman, thereby contributing to
normalization of mood in the premenstrual and climacteric periods.

Thanks
chili capsaicin, dishes become not only spicy, but also
healthful for our mood. The fact is that in response to the use of this
an irritating substance, our brain produces endorphins – natural compounds
which have a calming effect.

Well
concerns garlic, it contains a large amount of chromium, which affects
to regulate the production of serotonin, a “lucky” chemical.

Honey

B
unlike useless refined sugar, honey contains B vitamins,
folic acid, iron, manganese, chromium plus about 180 biologically active
compounds such as quercetin and caffeic acid that increase production
“Mood hormones” and energy in the brain.

Menu
anti-stress diet

Breakfast

2 tsp.
sprouted and washed grains with sprouts 1.5–3 mm long, oat muesli with
dried apricots, raisins and nuts, a cup of cocoa, 2 pieces toasted
rye bread, banana.

Second
breakfast

Orange,
2-3 cubes of dark chocolate and a cup of green tea, rye or oat bread.

Lunch

Vegetable
soup, a side dish of brown rice or buckwheat, a slice of chicken or fish, a salad of
tomatoes and sweet peppers with vegetable oil and chili, rye bread,
green tea or mineral water.

Afternoon snack

Yogurt
and chocolate chip cookies, raisins, dates, nuts.

Dinner

Vegetable
stew (stewed asparagus, pepper, kohlrabi, celery root and greens, tomatoes), cheese
or feta cheese. Juice or biokefir.

Before
sleep

Hot
milk or a cup of cocoa with milk and honey or infusion of phyto-collection-regulator
mood + brewer’s yeast pill.

Herbal teas that regulate mood

From
medicinal herbs that have a sedative effect will help reduce
emotional stress during stress valerian root and leaves, oregano,
lemon balm, St. John’s wort and hops.

At
stress, depression, apathy, it is useful to brew tea from St. John’s wort, rose hips,
raspberry or strawberry leaves, oregano and mint. Better to use a thermos: a handful
rose hips, 1 tbsp. l. pour herbs with a liter of boiling water and leave for at least 2 hours.You can not filter, but add boiling water during the day. Prepare a new one in the morning
infusion. This soothing tea can be drunk for 5-7 days.

Also
an infusion of St. John’s wort and valerian root will be effective: 1 tbsp. l.
St. John’s wort, 1 tsp valerian root. Cook and take the same as
previous collection.

Try
for a week, instead of regular or green tea, brew this
a soothing herbal tea. You will feel an improvement in your
emotional state.

Infusion
from hop cones and mint acts similarly to synthetic tranquilizers, but
has no side effects and is safe for health. The infusion is prepared as follows:
1 tsp hop cones and mint steamer with a glass of boiling water. Insist 30 minutes
strain and drink in 2 doses, adding a slice of lemon and a teaspoon of honey.

For
in order to normalize sleep and ease the neuropsychic stress of the body
you can make a sachet from a collection of herbs: hop cones, lavender, oregano, lemon balm.With such a collection, it is necessary to fill a small pillow sewn from
cotton or linen and place under the headboard pillow.

Except
In addition, aromatic essential oils will help improve mood: lavender
soothe, ylang-ylang will relax and relieve tension, cedar will help to cope
with anxiety and fears. During the day, other aromatic oils will help: orange oil
tones, reduces mental fatigue, spruce and pine oil tones and stimulates the physical and
mental performance.

Natalia Batsukova,

candidate
Medical Sciences, Associate Professor, Head of the Department of General Hygiene of the Belarusian
State Medical University

Vitamin B5 (pantothenic acid)

Vitamin B ₅ (pantothenic acid) is a water-soluble vitamin necessary for the construction and development of cells both in the central nervous system and in the body as a whole.

Synonyms Russian

Pantothenic acid, anti-dermatitis factor.

English synonyms

B ₅ (pantothenic acid), B ₅ -FORWARD.

Research method

High performance liquid chromatography-mass spectrometry (HPLC-MS).

Units

Nmol / L (nanomole per liter).

What kind of biomaterial can be used for research?

Venous blood.

How to properly prepare for the study?

Do not eat for 2-3 hours before the test (you can drink clean non-carbonated water).
Do not smoke within 30 minutes prior to examination.

General information about the study

Vitamin B ₅ (pantothenic acid) is a water-soluble vitamin widely distributed in food. Its main sources for humans are liver, kidneys, egg yolk and bran bread. In addition, it is produced in significant quantities by the intestinal flora.

Pantothenic acid is absorbed in the small and large intestine, turning into pantethine, which is a part of coenzyme A, without which the exchange of proteins, fats and carbohydrates in the body is impossible.He participates in processes such as:

oxidation and biosynthesis of fatty acids,
oxidative decarboxylation of keto acids (pyruvic, alpha-ketoglutaric, etc.),
citric acid synthesis (when tricarboxylic acids are included in the cycle),
synthesis of corticosteroids, acetylcholine, etc.,
in general, the vitamin is an acceptor and carrier of acid residues.

Thus, the lack of this vitamin affects the work of all body systems, especially the nervous, muscular, gastrointestinal tract, excretory system and skin.

The daily intake of pantothenic acid for adults is 5-10 mg. Given its widespread prevalence in food, hypovitaminosis can occur only in exceptional cases: in case of impaired absorption in the intestine (malabsorption syndrome), destruction of the vitamin in the gastrointestinal tract (more often in children with an excess of digestive enzymes, hypoacid gastritis), with prolonged use of antibiotics , sulfa drugs (again typical for children).

As for the excess of B ₅: in rare cases, during therapy with vitamin B ₅, hypervitaminosis may develop, manifested by dyspepsia and diarrhea.

What is the research used for?

The study allows you to determine if there is a lack of vitamin B in the body ₅. More often, this analysis is carried out as part of a comprehensive diagnosis of hypovitaminosis or as a control of vitamin doses during vitamin therapy.

When is the study scheduled?

With the following symptoms of hypo- and avitaminosis.

In children in the first half of life: diaper rash, dry skin, maceration and pustular diseases.In addition, the deficiency of B ₅ is often accompanied by rickets, especially in the midst of the disease. The level of pantothenic acid decreases in children with diabetes due to the fact that the loss of vitamin in the urine increases significantly.
Subclinical vitamin B deficiency ₅. Its signs are not very specific: increased fatigue, sleep disturbance, head and muscle pain, dizziness, weakness, paresthesia, nausea, vomiting, flatulence, decreased function of the gonads, dermatitis and glossitis.
Severe vitamin deficiency is accompanied by depression, burning sensation in the feet, tingling and numbness of the toes, burning, excruciating pain in the lower extremities (mainly at night). The skin of the feet turns red. With pantothenic insufficiency, the body’s resistance to infection decreases, and acute respiratory diseases often occur.

What do the results mean?

Reference values: 54.5 – 604.4 nmol / L.

Reasons for the increase in B level ₅

Long-term vitamin B therapy _5.
Uncontrolled intake of multivitamin complexes with high B content _5.

Reasons for lowering the level B ₅

Effects of caffeine, alcohol, barbiturates.

Acetylcholine in foods: 9 Foods High in Choline and Why You Need It

Know Your Neurotransmitters: Acetylcholine – UNC NRI

What’s the Big Deal About Choline?

Why We Need Choline

Choline & Acetylcholine

Getting Enough Choline

How to Get Choline on a Vegan and Vegetarian Diet

The dietary sources of acetylcholine.

Choline – an overview | ScienceDirect Topics

7.1 Choline

Ethanolamine Produced from Oleoylethanolamide Degradation Contributes to Acetylcholine/Dopamine Balance Modulating Eating Behavior | The Journal of Nutrition

Abstract

The Cholinergic System Regulates Food Reward by Interacting with the Dopaminergic System

OEA Influences Cholinergic-Mediated Food-Reward Regulation

Ethanolamine, a Downstream Metabolite of OEA, May Serve as a Neuromodulator Stimulating Acetylcholine Release in the Brain

Acknowledgments

Notes

References

Frontiers | In silico Gene Set and Pathway Enrichment Analyses Highlight Involvement of Ion Transport in Cholinergic Pathways in Autism: Rationale for Nutritional Intervention

Introduction

Materials and Methods

Overview of Workflow

Identification of Ontologies Associated With Each Gene Set, and Shared Ontologies

Gene Set Pathway Intersection Analysis of Shared Ontologies

Supplemental Analyses for Model Refinement

Results

Shared Gene Ontologies

Analysis of the Intersection of Autism-Related Cholinergic Gene Sets

Supportive Evidence for KCNN2 Variant as a Modifier of Splicing

Discussion

Impact of GABA/GABA

Impact of Acetylcholine Deficiency on Cholinergic Output, and Hypothesized Interplay With

Impact of Acetylcholine Supply on the Function of

Impact of Acetylcholine Deficiency on Cholinergic Output, and Its Possible Interplay With

rs13188074 Variant May Influence

Targeting Cholinergic and GABA-ergic Signaling Pathways May Modulate Sensory Processing in Autism

Dietary Choline: A Low-Risk Intervention to Support Acetylcholine Supply, Cholinergic Signaling, and Sensory Processing in Autism

Future Research Directions

Conclusion

Data Availability Statement

Author Contributions

Funding

Conflict of Interest

Footnotes

References

Health Benefits, Side Effects, Uses, Dose & Precautions

Thiamin (Vitamin B1)

THIAMINE – VITAMIN B1

What foods improve memory and mental performance / Reviews / Shopping cart

Effect of stress

Foods harmful to the brain

Beneficial substances for the brain and their sources

DMAE DMAE Dimethylaminoethanol 250 mg. 100 capsules.

Description

Application Note

DMAE DMAE (dimethylaminoethanol)

Discovery of vitamin B1

What is vitamin B1 and what are its functions in the body

Vitamin B1: dosage

Vitamin B1: in food

Vitamin B1 deficiency: causes and consequences

Excess vitamin B1: causes and effects

Supportive therapies

Medicines

It is important to understand that a person with Alzheimer’s is not behaving so deliberately, but it is caused by their disease!

Restricted legal capacity

Driving a motor vehicle

Weapon proficiency

Vitamin B5 (pantothenic acid)

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