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Alpha men make it occur and eventually become the wind behind the sails of everyone they meet. They do the thing and get up. They act, they measure success, modifications are made by them, until it is only perfect and then do it all over again. This is exactly what creates progress and ultimate victory.
Don't be one of those Woodland California backpage incall escorts who are squandering people's backpage escorts rear Woodland. In online dating desperate, some sites require that you pay a commission. This ensures that only the serious ones are being admitted into those dating sites.
Nice guys aren't liked by Girls. Some guys grow up that should they would like to get the woman they must be a guy that is nice. A guy that is good looking has a man image and dresses nicely. Notice that gentleman wasn't said by me, I said gentle man. There is a difference.
Exercise Think about times where your date with a girl obtained terminated at last min or a lady straight claimed no to your deal on a day. What do you assume triggered this to happen. i. e. you didn't construct enough relationship, provided her value or chose a difficult close. Compose it down in your journal.
Perhaps you have noticed how easy it is to jump to a response as soon as your partner presents something that you don't agree with? We quickly counter with the concept is bad or will not work or why our point of view is better or more" right. " All of us do this from time to time, also it causes paper cuts of pain for our partners to be closed. With some additional backpage repldcement for escorts Woodland California or thought or more information, our spouse's thoughts might be discovered by us have legitimacy than we believed. We have not heard everything we need to hear in order to respond.
Third, your overall goal in online dating is to have an enjoyable time with the procedure. You don't want a structure of disappointment. The more you invest in corresponding with the guy, the more disappointed you'll be if he ends up to be a dud. Maintain your investment's proportion to expectations in equilibrium! Prepare to be pleasantly surprised if you really like him in person and don't build up a" head of steam" or overblown fantasies over months of emailing back and forth. You don't wish to live in a dream world, although letting your imagination run wild is a natural reaction to a long email correspondence.
Just make sure that the profile contains the points that I have mentioned and ends that she sees you. Backpage escorts over 50 Pittston PA are some organisations which can write you a profile for a fee although I wouldn't really recommend it. You need to be certain as nobody understands you as well as you you write your profile. Again there are lots of tools available to help you write an interesting profile. There is simply is no excuse to come up.
MINDFULNESS EXERCISE: Attempt this mindfulness practice detect your ideas and your feelings and Take some time to do some where to get prostitutes Woodland CA breathing. Get centered and produce a feeling of loving kindness towards yourself. Remain in the moment with no expectations or Woodland briana lee fuck buddy and just ask your self ifyou're choosing this individual to be your spouse for the reason that it serves you and it feels like a fantastic match. Notice the message you get from the self. You don't need anything outside yourself to complete you, when you are in this spacious state. You make choices from alignment and love rather than fear or explanations that are outer. Listen to the guidance you diary and receive about it later.
Profiles with photos get more clicks The sense of mystery that is connected with a profile really is a thing of the past. Actually, people are more inclined if they see a question mark or a square in the space that should have been for your display photo to skip your profile.
Why a woman wouldn't realize that fact in the very first urbano fuck buddy tonight Woodland California that when a guy would be interested in romance, the man wondered. His conclusion was that all she desired was lunch and he's ready to give up online relationship.
Everything that's occurred in your mind since you were born is filed off in your mind. The level of recall differs, although it is storing the forms of information as your subconscious.
Converting your negatives is a course. Instead of pointing out that" I'm tired of playing games all of the time" , attempt to soften it by saying, " I think honesty and venetian hookers is the backpage escorts sex Woodland California of any relationship. " So that they will not cause you to come across as tried and jaded, with a backpage escorts banned Woodland California thought, some points which you have experienced in your relationships could be assessed. Remember, you need them to have an interest in you, which how many backpage escorts are police Woodland California you need to give a nice vibe right.
I usually throw a series and may pop some popcorn and put on something funny, but not wear something since it will divert from the squirt backpage escorts Woodland and interaction thatyou're building with her that you are seriously interested in watching like a serious play. The target is not to watch a show that is Woodland California backpage escorts sluts to put on something that is just on in the background while the both of you are talking and being close, although to keep her fully participated.
Aggressive: it's an clear and open manifestation of Woodland backpage reviews for escorts. To give you an example, I understand girls that, in order to" take revenge" on their spouse, have entered his home and threw away his garments, or others who have even slapped the rival girl, and so on.
This guy needs to obtain a dating site that is entirely free to use. He needs it to be free to viewfree to create a profile, and free to interact with other users of the website that is relationship. He's currently attempting to prevent having his credit card attached to a website that is dating.
Body movement always talks initially in any conversation. When you are certain your backpage escorts unwinds, comes to be much more open, you lean in, you smile, and also you end up being much more computer animated. When you are strained or otherwise at simplicity with on your own, you will certainly be kicking back, crossing your legs, maybe your arms, your mouth will barely break a smile, and also your eyes will certainly be searching somewhere else in the space. Knowing this will certainly allow you to communicate confidence with your body movement. Your verbal dating discussion skills will mostly be judged on exactly how able you are to produce a conversation that your companion delights in. Inevitably, that results in you obtaining more days. Ifyou're thinking this is apparent, yes, it is! The inquiry is HOW to develop a fascinating conversation. Your dating discussion Woodland CA collage casual sex be composed of you both asking as well as answering concerns. Your partner is going to have fun if you ask the appropriate inquiries. They are going to ditch you if you ask the wrong concerns. If you are evasive or much less than honest when addressing her inquiries, she is going to ditch you quicker.
What ever you do, don't act too eager- - only say enough to allow her understand that you did have a good time and you would love to see her again; that's all. Give her a hug or a peck on the cheek. DON'T try to provide a snog to her; she freak out! The Next Step: In the event the date didn't go well. . .
Adhering to the escorts madison backpage Prescott audio file, the conversation then improved to us meeting this weekend to get the real thing up. In addition, a couple of days later she suggested a date to talk about the weekend. Seemed like a good idea to me. The date went well by my criteria as well as our plans for the weekend have been cemented. I left feeling great.
She would like him a lot but when he screws up in any stage in this, she'll reject him. But he is not being rejected by her. She is only giving him a indication that she's not ready yet. She is not saying cease. She is saying continue doing whatyou're currently doing but give me a few more moments. I want to be a bit more familiar with you.
Seveno'clock Sunday came soon enough, and there I was knocking on the door. Was I actually going to date the beautiful blonde in the photograph? The door opened, and I instantly recognised the eyes and cheeky grin but was startled to realise that she was probably four dress sizes bigger than her profile photograph suggested. Not that this was a problem, actually as a positive incentive, Icouldn't help but notice that the front of her tee shirt was rather dramatically swollen and I kettle river sex dating Woodland fucking chest.
Backpage escorts bust Woodland CA by. . . watching it in the paper. . . for months. . . weeks, but only now. . . Could we have a look? " I let them have a look. I let them have a look. For letting them have a look and I thanked the corner of the room.
My first approach was when I was in school. I found a woman on campus attractive. I'd see her but I didn't know who she was she didn't know me. 1day I waited for my buddy outside college and she came.
Alpha males have their own source of Woodland new backpage escorts sites. They recognize no sf hookers Yazoo City is ideal, also are comfortable in their own skin. They understand themselves. They embrace their flaws, while hoping to improve upon them. They know that strength is inspired by vulnerability and are okay with being exposed.
This will not only go for striking up conversations with girls, it goes for android free dating apps Woodland like starting a company even if it contradicts what colleagues and friends may express about it. It means when everybody in your household has eaten 14, revamping your diet. It means going to better yourself and your own life.
You Woodland California escorts website instead of backpage things to work absolutely and if you are really in love, then you should feel comfortable speaking about it. Isn't it better to talk about sex with your partner rather than in forums? Then share it with your Woodland real cougar dating apps if you have got an issue hindering you from having sex. I understand that speaking about sex can make some alternatives for backpage escorts Woodland California anxious, which may lead you to prevent conversations. Do not talk about your sexual problems in the bedroom. Instead, select a venue such as the dining area. Avoid blaming and discuss your expectations your fears, and your own desires. Be daring, and don't be scared of speaking about what you believe. Below are some issues related to gender and to speak with your partner about them without feeling stressed.
However, we also understand that companies expect a readable, typed resume with info that is actual and no spelling errors, not a pack of crap scribbled on a napkin in crayon! Therefore, in the event that you want to entice a date on the internet, you must take the exact same care with your online profile.


text:
This is a
playground to test code. It runs a full
Node.js environment and already has all of
npm's 1,000,000+ packages pre-installed, including
@modngn/server with all
npm packages installed. Try it out:
require() any package directly from npm
await any promise instead of using callbacks (example)
This service is provided by RunKit and is not affiliated with npm, Inc or the package authors.
The ModNGN core server module. To learn more about the Server and other ModNGN core modules, check out the documentation.

subset: commoncrawl


text:
[UPDATE 11-18-20 @ 6:30pm CST] – uploaded fixed 'TOPPLATFORM-_TALL_WALLS_AND_ROOF – v2.st' file, thickened up top roof
This is a project I have had in the back of my mind for a very long time! Today we bring you the "Modular Bandit Watchtowers" set.
This set allows you to build watchtowers, as the name implies (and essentially generic scaffolding systems). The watchtowers are designed to be relatively haphazard/roughly construced with wood, nails, and leather/cloth. They are ~1.5×1.5″ footprint, with enough size for a mini to fit comftorably in them without being huge.
They are modular so you can make them as tall as you would like, with each section easily stacking on top of the section below. The modular scaffolding sections have a built-in ladder, and various orientations/options are included to make each tower look unique. Each scaffolding section is available as a "regular" section or with a bottom platform – so each level can have a platform you can place supplies/scatter/minis inside, or leave open.
There are 4 options for toppers – no wall, short wall, tall with roof, and tall walls with no roof, and the tops are designed with only partial walls to allow easily access/removal of minis. There's also a ramp thrown in so you can bridge between scaffolding or tower sections if you wish!
Each piece will print without supports in resin or FDM. Cheers, and happy printing and gaming!
For instructions on how to get started with OpenForge, take a look at our
Print Settings
Printer brand: Creality
Printer: Ender 3 Pro
Rafts: No
Supports: Yes
Resolution: 0.16
Infill: 25%
Filament_brand: Polymaker Polyflex
Filament_color: Black
Filament_material: TPU
I used Polyflex TPU, with tree supports with the camera mount printed on its side. Print Speed of 20mm/s.


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Vitamin D is a fat-soluble vitamin required by all living beings for bone health, calcium absorption, and brain function. This vitamin is also known as calciferol.
Most of the vitamin D is obtained naturally from sunlight. While melanin (the skin pigment) protects the skin from the harmful effects of ultraviolet rays, excess melanin can also hinder the absorption of vitamin D from the sunlight.
According to a study published in the Journal of Nutrition, healthy vitamin D levels in mother during pregnancy can positively affect the child's IQ (Intelligent Quotient). The higher the vitamin D levels, the greater the IQ scores during childhood.
The sunlight consists of two kinds of UV-rays - UVA, and UVB. UVA doesn't have much of a biological role. Only UVB helps in the synthesis of vitamin D in the skin.
Melanin has photoprotective action - It protects the skin from the harmful effect of ultraviolet radiation. However, higher melanin levels can lead to lower production of vitamin D3.
Darker skin tone is associated with higher levels of melanin.
For light-skinned people, an exposure time from 20-30 min, for two-three times a week, is enough to produce around 20,000 IU of vitamin D3, while for dark-skinned people, the exposure time needs to increase by 2-10 fold to get the same level of vitamin D3.
The baby in-utero (in the womb) receives its vitamin D supply for brain development from the pregnant mother.
The melanin production is higher in black women - so there are a higher number of cases of vitamin D deficiency among them.
According to the study, 80% of black pregnant women in the U.S. may have vitamin D deficiency.
Among the study participants, approximately 46% of the mothers were deficient in vitamin D during their pregnancy, and vitamin D levels were lower among black women compared to white women.
After controlling several other factors that influence IQ, a study examined the relationship between vitamin D levels in pregnant women and IQ in children.
It was observed that higher vitamin D levels in pregnancy were associated with higher IQ in children ages 4 to 6 years old.
The recommended daily intake of vitamin D is 600 international units (IU). However, on average, Americans consume less than 200 IU in their diet.
In most cases, vitamin D deficiency has an easy fix. Even if it is difficult to get enough sun exposure, vitamin D supplementation is an effective alternative to meet your requirements.
Carbohydrates are one of the most prominent food groups in the diet. They are present as sugars, starches, and fiber in food. Glucose molecules are linked together to form starch and fiber. When carbohydrates enter the body, the fiber goes undigested, while the sugar and starch are broken down into glucose. Glucose provides the energy required for bodily functions.
Carbohydrates are commonly associated with weight gain. However, the right kind of carbs in the right amounts can earn a rightful place in your diet.
Carbohydrates are subdivided into three categories depending on the number of sugars present and the nature of the chemical bonds between them.
Although this is the conventional way of classifying carbohydrates, a more useful approach would be to classify them as refined and whole carbohydrates.
Whole carbohydrates include vegetables, legumes, whole fruits, and grains, which are unprocessed and thus have their nutrient content intact.
The stripping of nutrients in refined carbohydrates as a part of processing makes them 'empty calories.' This removal of the nutrients results in rapid absorption and metabolism of these carbohydrates. This results in spiked sugar levels and unstable energy levels.
Previous studies on the development of the brain and other human traits suggest that the shift from plant-based to meat-based diet played a critical role. Since then, a lot of evidence has come to light that indicates the involvement of plant-based carbohydrates in meeting the demands of the growing brain.
Further, the role of cooking in improving the digestion and breakdown of carbohydrates has also been factored in.
According to Mark Thomas, an evolutionary geneticist from University College London, the brain's size started significantly increasing only around 800,000 years ago - which is speculated to be the time period where the usage of fire started.
What does this mean?
Glucose is the main source of energy for the brain. When the cooked vegetables were consumed, the body had to put in much less work to convert the carbohydrates to glucose for feeding the brain.
For example, the starch in cooked potatoes digests 20 times faster than the uncooked ones. This suggests that cooked carbs, which became the major source of energy, contributed to brain growth.
To further investigate the hypothesis, the starch digesting enzyme amylase was studied. An analysis revealed that the genes that produce amylase started evolving to higher numbers around the same time cooking was started.
This was an advantage since more amylase was required to digest the increasing amounts of starch consumed. So, with every mouthful, the brain derived more energy from the starch.
There are still uncertainties about the antiquity of cooking and the reason for the increase in the amylase enzyme gene. However, the above-mentioned correlation cannot be just dismissed as a coincidence!
The AMY1 gene encodes the enzyme amylase, which is responsible for the digestion of starch. Salivary amylase is the enzyme found in your saliva, which begins the process of digesting starch in food. It breaks the insoluble starch into smaller soluble forms. High-AMY1-gene copy number (number of copies of a gene) indicates increased secretion of amylase. This results in a faster breakdown of starch. The difference in the copy number of the AMY1 gene is reported to be the genome's largest influence on obesity. According to a recent study, each copy of AMY1 decreases the risk of obesity 1.2-fold.
rs4244372 is a Single Nucleotide Polymorphism (SNP) in the AMY1 gene. The A allele in this SNP is associated with a lower copy number of AMY1 gene, and hence poor starch metabolism. People who have the AA type may tend to put on more weight on carbohydrates when compared to the people who have the TT or the AT type.
Refined carbohydrates cause sudden spikes in sugar levels. As the sugar levels rise, the body produces insulin to regulate them. Insulin converts excess sugar into fat. A higher spike in sugar levels results in increased insulin secretion, which leaves you with excess stubborn body fat. Various studies show that refined carbohydrates are associated with type 2 diabetes and heart diseases.
Whole carbohydrates, also known as complex carbohydrates, have natural fiber components in them. This fibrous part is easy to digest and thus helps us stay full for a longer time. A balanced diet that is rich in natural fiber helps maintain the blood sugar levels in our body. These foods have a low glycemic load. Glycemic load estimates how much a person's sugar level will rise upon consuming food. A low glycemic load indicates longer digestion time and a smaller spike in blood sugar levels.
An ideal whole carb diet contains seeds (chia seeds and pumpkin seeds), grains (quinoa and oats) with fresh vegetables and fruits. Many nutritionists also advise a switch from white rice to brown rice. This is because brown rice is packed with nutrients that help us prevent heart diseases and type 2 diabetes.
Other than being an important source of energy to the body, carbohydrates also perform the following functions:
Research tells us that a fibrous diet can help maintain a healthy gut. Complex carbohydrates contain a sugar component and a fiber component. Fiber is present in two categories, soluble and insoluble. Soluble fiber helps maintain bowel movements, as well as the consistency of the stool. Insoluble fiber relieves constipation and prevents various digestive tract diseases. Studies also show that a diet rich in fiber helps maintain our blood sugar levels and also benefits our heart.
While refined carbs are not really your heart's best friend, dietary fiber can help maintain blood sugar levels and is heart-healthy. When fiber passes through the intestines, it prevents reabsorption and hence, the buildup of bad cholesterol. This reduces the risk of heart diseases.
Dr. Tamar Polonsky, MD, from the University of Chicago Medicine, said that foods that contain complex carbs "decrease inflammation and help us decrease the risk of plaque buildup in our arteries." Plaque is the deposition of certain substances in the blood vessels that block the blood flow. This buildup is caused by fat, cholesterol, and calcium that is present in the blood. This can potentially lead to a heart attack or stroke. Polonsky advises us to stick to healthier carbohydrates with less fat and cholesterol to prevent these.
Our body stores the extra glucose in the form of glycogen (another sugar), which is very important to us. When there's no available glucose from carbohydrates, the body breaks down the muscles to generate glucose for energy. To prevent muscle mass loss due to starvation, the consumption of adequate amounts of carbs is essential.
Apart from all the impacts on physical health, research suggests that carbohydrates can improve mental health as well. A study from the Archives of Internal Medicine showed that people who were on a low-carbohydrate diet for a year experienced symptoms of depression and anxiety.
The idea behind a low-carbohydrate diet (for weight loss) is that if the body does not receive the extra carbohydrate, no excess fat will be stored. Instead, the fat already present will be burnt for energy.
High-carbohydrate need not necessarily be our enemy. In fact, high carbohydrate foods with adequate fiber are extremely healthy.
All these foods are rich in fiber and help us from feeling hungry frequently. They also help us maintain good gut and heart health.
Carbohydrates are one of the major food groups. There are two types of carbohydrates - whole or complex and refined. Whole/Complex carbohydrates present in food like oats and bananas are healthy, while the refined carbohydrates are "empty calories" that spike your blood sugar levels. The starch in the carbohydrates is digested by the salivary enzyme, amylase, encoded by the AMY1 gene. A higher copy number of the AMY1 gene is considered beneficial, as it results in a faster breakdown of starch. rs4244372 is an SNP in the AMY1 gene associated with the difference in the copy number of the gene. People who have the AA type tend to have a low copy number and hence may be poor digestors of starch. These people are at an increased risk for weight gain on carbohydrate consumption and may benefit from a low-carbohydrate diet. Some low carbohydrate foods include leafy greens, nuts, and olive oil. Animal foods like lean meat and fish are low in carbohydrates. Another option can be switching to a fiber-rich carbohydrate (complex carbohydrates) diet. Fiber is digested slowly and thus keeps you full for longer. Quinoa, buckwheat, berries, and sweet potatoes are good sources of complex carbohydrates.
Alcohol has become a part of people's lives. People drink when they are happy, excited, sad, or stressed out. It is one of the oldest recreational drugs in use. While many people can handle their drink well, some have extremely unpleasant symptoms when they consume even limited quantities of alcohol.
Alcohol Flush Reaction (AFR) is a condition that causes red patches on the skin after consuming alcohol. These red patches are mostly seen on the cheeks, neck, and shoulders. Sometimes, they can also be seen all over the body.
If you have East Asian friends and go out for drinks with them, you may have noticed their faces turning red after just a couple of sips of their drinks.
About 30-50% of East Asians, including Koreans, Chinese, and Japanese experience alcohol flush regularly.
According to 100 different studies, moderate consumption of alcohol may reduce the risk of cardiovascular diseases by up to 40%.
The right levels of alcohol consumption also increases healthy High-Density Lipoprotein (HDL) levels in the body
Moderate drinkers may be at a lower risk of developing type II diabetes than non-drinkers.
However, when you consume more than four drinks a day, the risks of alcohol consumption may outweigh the benefits.
Genetically, some people can handle their alcohol better and benefit from moderate drinking. For others, even small quantities of alcohol only cause increased health risks. We will discuss this in the later sections.
Scientists believe that the alcohol flush reaction has its roots in China about 10,000 years ago. This was the same time that agriculture became a staple form of livelihood here and people's diet changed. Rice became a common food choice.
According to the experts, the change in diet and lifestyle caused changes in the gene makeup of the Chinese population.
Alcohol flush reaction is a result of such a random change in the genes (gene mutation). It spread from here to neighboring parts of the country and is now very common with East Asians.
It is very rare for non East-Asians to carry this variant (type) of gene.
When you consume alcohol, 90% of its processing happens in the liver. An enzyme called alcohol dehydrogenase converts ethanol into ethanal (acetaldehyde).
Acetaldehyde is a toxic by-product. Another enzyme called aldehyde dehydrogenase quickly converts this by-product into ethanoate (acetate).
Before the liver starts processing alcohol (in about 20 minutes after consumption), alcohol is absorbed from the stomach to the bloodstream and reaches the whole body, including the brain.
Some people experience alcohol flush and others don't because of their genes.
In people with alcohol flush, the body does not produce enough aldehyde dehydrogenase to convert acetaldehyde to acetate. This causes excess accumulation of the toxic acetaldehyde in the body. This leads to the symptoms of alcohol flush including skin blotching, nausea and general feeling of discomfort.
Alcohol reaches your brain within minutes after you have had your drink.
Your Central Nervous System (CNS) helps with processes like thinking, reasoning, understanding, and motor functions. Alcohol slows down the CNS processes. People experience a foggy mind, inability to remember things, slowed motor functions, and dull hearing after they start drinking because the alcohol affects the nerve cells and makes them slow.
How fast alcohol affects your brain's activity can depend on factors like what other drugs you have had before, your age, size, and gender and also your genes.
If you are a woman, then you are at a higher risk for developing alcohol-related disorders than a man! It sounds unfair but this is true.
Drinking the same amount of alcohol as a man seems to damage the woman's health more than it does a man's.
When it comes to alcohol disorder-based deaths, women have 50-100% more mortality rate than men.
Women have lesser water content in their body than men. So, the concentration of alcohol in the body of a woman is higher and they get intoxicated faster.
Because of the presence of estrogen, more women experience liver damage because of excess alcohol consumption than men.
The U.S. Dietary Guidelines for Americans suggest the below recommended values for moderate alcohol consumption.
Adult men - 2 drinks a day
Adult women - 1 drink a day
The recommended values are for normal adults without alcohol flush or alcohol abuse conditions.
People with alcohol flush reactions will have to limit their alcohol consumption based on how intense their symptoms are.
The Body Alcohol Content (BAC) is a measure of how much alcohol has reached your Central Nervous System (CNS). BAC is measured in terms of percentage of alcohol in 100 ml of blood. Below are the values of BAC and their corresponding symptoms.
Alcohol flush is one of the earliest symptoms of alcohol consumption.
Here are the symptoms of alcohol flushing:
Alcohol is a drug and depending on the tolerance levels and the years of alcohol use, symptoms of alcohol withdrawal may include:
People with alcohol flush reaction are not usually prone to overusing the drug as the side effects discourage them from drinking more.
Genetics play an important role in determining whether or not your body can handle alcohol.
The ALDH2 gene helps produce aldehyde dehydrogenase (ALDH) that converts the toxic acetaldehyde from alcohol into acetate. This step is very important to prevent acetaldehyde accumulation in the body that leads to alcohol flush.
Alcohol flush reaction is a condition that causes red patches in the skin, nausea, and general discomfort after a person drinks. This condition is very common in people with East Asian ancestry. As the person continues to drink, the symptoms get worse. Genetics play a very important role in causing alcohol flush reactions. Knowing your limit, choosing alcohol with lowered ABV and keeping the stomach full and the body hydrated all help bring down the intensity of the condition. Certain medications can help too.
Do you start your day with a cup of freshly brewed coffee? Does a cup of tea warm your insides and leave you feeling fresh in the evening? Do you stock up energy drinks in your fridge to help handle late nights?
All these beverages have one thing in common - caffeine.
Caffeine is an organic compound found in plant sources. Caffeine is a legally accepted and consumed psychoactive drug ( a chemical that alters nervous system functions). Caffeine alters a person's mood, behavior, and energy levels.
While some studies have praised the beneficial effects of caffeine on human health, others warn about the health risks. Why does the same substance lead to different health outcomes?
The answer to these questions is not only applicable to caffeine but also to a lot of other substances.
We are all genetically unique. While some substances produce relatively similar effects on our bodies- many substances, including caffeine, are processed differently in different individuals.
When a drug fails a clinical trial- it does not mean that every individual who took that drug failed to respond. On the other hand, there is no approved drug that works equally well on every individual.
It is common knowledge that some drugs work really well for some, but not for others. We need higher doses of certain drugs and lower doses of others. There is a dose difference for certain drugs for men, women and children.
Caffeine is no different. Unless the genetics and other factors are accounted for, it will not be easy to say whether caffeine is good or bad for you. Keep reading to find out the unique genetic aspects of caffeine metabolism (processing in the body)
There are about 60 species of plants that can produce caffeine. Few top sources are:
Did you know that about 85% of Americans consume at least one caffeinated drink a day? Coffee remains the most consumed caffeinated drink among adults.
How much caffeine is too much? Do you have to give up on caffeine to lead a healthy lifestyle? Keep reading to know more.
The history of caffeine is closely associated with the histories of its plant sources.
It was 2437 BCE. The Chinese Emperor Shen Nung was relaxing in his garden. The wind blew a couple of leaves into his cup of boiling water. He noticed that the water changed color and smelled fragrant. The leaves were later identified to be from the tea shrubs. Tea leaves are considered a stimulant (a drink to energize the body).
There are many stories on the discovery of caffeine. Some scripts say the ethnic Oromo people of Ethiopia recognized coffee beans to have energizing properties.
The more popular version is of Kaldi, an Ethiopian goat herder. He noticed his goats getting all excited after consuming coffee beans. He mentioned this in a monastery and the first cup of coffee was brewed there.
The leaves of the yaupon holly tree were brewed as early as 8000 and 1000 BC. This was then known as the black drink.
In many West African cultures, it is still a regular practice to chew on kola nuts when people feel tired.
Caffeine is very easily absorbed by the body. 99% of caffeine is absorbed in about 45 minutes.
Once you consume a caffeinated beverage, it enters the gastrointestinal tract. Caffeine is processed in the liver by an enzyme that breaks it apart into different chemicals like paraxanthine, theobromine, and theophylline.
Peak levels of caffeine are observed in the plasma between 15 minutes and 120 minutes after oral consumption.
Caffeine easily reaches the brain. Adenosine is a chemical in the brain that induces sleep. The structure of caffeine is similar to that of adenosine. Caffeine attaches itself to the adenosine receptors (a protein that responds to adenosine) and prevents people from feeling sleepy.
The more caffeinated beverages you drink, the more adenosine receptors your body will produce.
Over time, you will need more amounts of caffeine to keep you awake.
Plant sources are not the only way to get your dose of caffeine. Caffeine is artificially synthesized in industries too.
The production of caffeine in industries began during World War II. Germans were unable to obtain caffeine because of various trading bans. They hence had to create caffeine artificially.
Today, synthetic caffeine is very cheap and tastes just like natural caffeine. It would not be surprising if you cannot tell the difference between the two.
While synthetic caffeine is safe when had in small amounts, the problem is with the manufacturing process. Ammonia goes through a lot of steps and chemical interactions to turn into caffeine.
The synthetic caffeine industry is also unregulated in most countries. All this makes synthetic caffeine a slightly worrying product in the market.
Caffeine is addictive. Your body goes through withdrawal symptoms when you try to reduce your caffeine intake. Few popularly noticed symptoms of caffeine withdrawal are:
Withdrawal symptoms can start 24 hours after giving up caffeine and can last for up to 9 days.
Caffeine sensitivity refers to having an adverse reaction to consuming caffeine. For most people, consuming more than 400 mg of caffeine can cause physical and mental discomforts.
Few others can be hypersensitive to caffeine and cannot tolerate it even in small quantities. Here are some non-genetic factors causing caffeine sensitivity.
How are some people able to process caffeine better than others? Genetics is the answer.
CYP1A2 gene - The CYP1A2 gene influences how fast caffeine is processed in your body and how you react to it. One particular SNP that can increase or decrease the effects of caffeine consumption is the rs762551.
AA genotype
AC and CC genotype
ADORA2A gene - The ADORA2A gene produces the adenosine receptors in the brain. You know by now that caffeine attaches itself to the adenosine receptors and prevents the person from feeling tired or sleepy.
The ADORA2A gene is also responsible for increasing dopamine levels (the happy hormone). Variations in the ADORA2A gene are said to cause mood swings, anxiety, and irritation.
Caffeine is a legally consumed drug that can alter the mood and increase attention and focus. It is naturally present in up to 60 plant sources. It is also artificially produced in industries. Normal adults have to limit their caffeine intake by up to 400 mg. Caffeine overdose can lead to mood disorders, rapid heartbeats, and high blood pressure. Caffeine withdrawal has to be handled gently and causes symptoms like depression, anxiety, and low energy levels. Genetically, some people can show high caffeine sensitivity and need to monitor their caffeine consumption.
Gluten is a family of storage proteins found in various grains such as barley, rye, and wheat. Gluten is responsible for the soft and chewy texture of pastries and baked items. It also retains the moisture in bread, pasta, and cereal.
Gluten intolerance and gluten sensitivity are two terms used interchangeably to describe a condition where the body recognizes gluten as an 'enemy' and initiates an immune response against it.
Gluten intolerance is also known as 'non-celiac' gluten sensitivity.
Celiac disease is an exaggerated form of gluten intolerance. Upon consuming gluten, the immune system attacks the lining of the intestines. the symptoms are more severe, and the recovery is a lot harder.
Here, the body's immune system, which is meant to protect it, mistakenly acts against it. This is known as an auto-immune response, which can be due to genetic reasons.
Since intestines play a big role in the absorption of essential nutrients, attacks to it over a period of time can result in poor absorption of nutrients, putting you at risk for various deficiencies. Gluten intolerance is non-celiac - the immune responses triggered do not damage the intestines but instead contribute to milder symptoms.
Gluten sensitivity symptoms are not restricted to just the digestive system.
All the fad about gluten-free diets has portrayed gluten-containing products, mainly wheat, in a bad light. While gluten is a big no-no for the gluten-sensitive, reduced consumption of whole-grains may negatively impact your health.
Whole grains like wheat, bran, and rye are rich sources of fiber. They also contain carbohydrates, proteins, and small amounts of B vitamins and minerals.
Thus, avoiding gluten in the absence of an intolerance/sensitivity can end up being detrimental to your health.
Diana Gitig, a Ph. D. graduate from Cornell University, Massachusetts, mentions that celiac disease's first reported case dates back to 100 A.D. It was diagnosed by a Greek doctor, Aretaeus. But the cause of the disease was never understood clearly.
During the Dutch famine in the 1940s, when celiac patients received very less amounts of flour (wheat) for consumption, their symptoms started improving.
When fresh supplies of bread were reintroduced, the symptoms started worsening again. This was when wheat was isolated as the cause of the intestinal symptoms.
Until the 1950s, only 1 out of 8000 were sensitive to gluten. Today, as high as 1 in every 100 individuals are gluten sensitive .
Prof. David Sanders from the University of Sheffield takes help from the concept of evolution to answer this huge rise in cases. He claims that humans started eating wheat only recently, about 10,000 years ago. This is a very brief period considering that humans have walked on the planet for more than 2 million years.
Humans initially consumed raw food, such as plants, fruits, and meat. Processed food (wheat, rye, and other grains), are relatively new in the evolutionary timeline. Prof. David acknowledges this fact and states that our body is still in the process of adapting, especially the food that contains gluten in it. With millions of years of having a gluten-free diet, it makes sense as to why gluten is considered a foreign body by our immune system.
Although a global analysis of gluten intolerance is yet to be done, a nationwide study was conducted in the United States. Over 400,000 biopsy results were examined to understand if ethnicity played a role in gluten intolerance and celiac disease. The following results were concluded after the study :
It is also worth mentioning that gender studies showed that both men and women had equal chances of being gluten-sensitive. Hence it can be inferred that gender does not play a role in this intolerance.
The Human Leukocyte Antigen (HLA) gene system plays a role in the production of the Major Histocompatibility Complex (MHC), which are proteins present on the cell surfaces. They play a role in regulating the immune system.
Two classes of the HLA gene known as HLA-DQ2 (HLA-DQ2.2 and HLA-DQ2.5) and HLA-DQ8 are linked with gluten intolerance risk.
Four types of the HLA gene, HLA DQ, HLA DQ 2.5, HLA DQ 2.2 (has three sub-types), and HLA DQ7, have been linked to gluten intolerance.
In a study conducted to assess the genetic influence on gluten intolerance, nearly all the patients with celiac disease had the risk allele in the HLA DQ2 and the HLA DQ8 genes. The absence of the same was found in 100% of people without celiac disease.In another study conducted to analyze the HLA gene types, people with the C allele in HLA DQ8, T allele in HLA DQ 2.5, the T, C and A alleles in different subtypes of HLA DQ 2.2 (M1, M2, and M3 respectively), and A allele in HLA DQ7 were shown to have an increased risk of reacting to gluten in their diets.
Some of the non-genetic causes of gluten sensitivity are:
Not all people are born with gluten sensitivity. It is possible to acquire it during the course of life. This intolerance can be triggered after surgery, childbirth, or after a period of severe stress.
Gluten sensitivity increases the risk of an adrenal hormone imbalance.
The adrenal glands pick up on the stress levels.
Unstable sugar levels and inflammation of the digestive tract resulting from gluten intolerance cause the adrenal glands to secrete cortisol.
This leads to an increase in body fat, fatigue, and irritable mood.
Fatigue is one of the most common symptoms of celiac disease and non-celiac gluten sensitivity.
In fact, fatigue and tiredness are the symptoms that last longest, even after the individual has shifted to a gluten-free diet.
Fatigue in gluten intolerant individuals occurs due to two main reasons:
Dehydration is also a major cause of fatigue and tiredness in gluten intolerant people.
Patients suffering from celiac and non-celiac forms of gluten intolerance have reported neurological symptoms such as headaches, brain fog, anxiety, depression, and peripheral neuropathy.
Gluten can also cause other disorders like insomnia, migraines, ADHD, epilepsy, schizophrenia, bipolar disorder, and in a minute number of cases, gluten ataxia (antibodies directed at gluten attacks the brain).
Many studies have shown a correlation between gluten intolerance and depression, anxiety, and other neurological syndromes.
A study conducted by Christine Zioudrou and her colleagues at the National Institute of Mental Health in 1979 found that some gluten compounds can attach to the morphine receptors in the brain.
The morphine that is produced in the body is known as endorphins. These are released in our body for various reasons, for instance, to reduce/manage pain.
Certain compounds of gluten (exorphins) mimic the structure of endorphins and attach to the receptors.
Thus, the endorphins have no place to attach to and are not activated. This can lead to mood-related disorders like depression and anxiety.
A large majority of the people who suffer from gluten-intolerance report lack of sleep and poor sleep quality.
Due to digestive symptoms, neurological symptoms, and generalized fatigue and tiredness, most people suffer from a lack of sleep or other related conditions.
[what to do to maintain healthy levels- generally for everyone and specifically for your genotype]
A gluten-free diet seems pretty straightforward - just removing gluten from your diet. But completely avoiding gluten can be challenging as many ingredients added to food like soy sauce, mayonnaise, and roasted nuts also contain gluten.
Whole grains like wheat and barley are well-known harbourers of gluten. So wheat-based bread, pasta, or baked goods should be avoided.
Gluten intolerance or non-celiac gluten sensitivity occurs when the immune system sees gluten as an invader and attacks it. Certain types of the HLA gene family that mediate immune responses in our body play a role in putting an individual at risk of developing gluten intolerance. Gluten sensitivity has also been linked with other health conditions like hormonal imbalance and mental illnesses. Therefore, people who are sensitive to gluten are advised to switch to a gluten-free diet. However, it is important to keep in mind that a gluten-free diet is not everyone's cup of tea. Most gluten-free products available in the market today are also stripped off of other nutrients and are advantageous only to the gluten-intolerant.
Vitamin E has gained popularity recently. The association between vitamin E and skin health is a key reason for its popularity.
Vitamin E is a fat-soluble nutrient. Both plant and animal sources are available:
Animal sources: fish and oysters, dairy products like butter and cheese, Plant sources: vegetable oils, nuts and seeds, and green vegetables like broccoli and spinach.
There are 8 different chemical forms of vitamin E found.
All of these have varied effects on the body. Out of these, alpha-tocopherol (α-tocopherol) is the most active form while gamma-tocopherol (γ-tocopherol) is the most common form found in foods consumed by North Americans.
Here are some of the significant functions of vitamin E:
Vitamin E as an antioxidant
Vitamin E is a proven anti-oxidant (substances that prevent oxidation). It helps prevent cell damage from free-radicals.
Free radicals are active molecules in the body that can harm the cells in the body and prevent the cells from staying healthy.
Free-radical damage is the most common reason for skin problems including aging of the skin, development of wrinkles, fine lines, and dark spots, and skin becoming loose and saggy.
Vitamin E in both dietary forms and topical forms (external application in the form of creams, gels, and serums) is beneficial for healthy skin.
Vitamin E and immunity - Vitamin E helps improve immune response and provide protection against various infections by keeping the immune cells healthy.
Vitamin E and lifestyle risks - Lifestyle risks like smoking, drinking, and UV exposure can harm the cells in the body. Vitamin E provides protection against these.
Vitamin E and degenerative diseases - Many studies have shown that taking the recommended amounts of vitamin E reduces the risk of developing diseases like cancer, high blood pressure, and coronary heart diseases. These promising early results are being further investigated.
The early 1900s was the time when some of the initial vitamins like vitamin A, B, C, and D were discovered. Scientists and biochemists were involved in intense research identifying what else these vitamins could and couldn't do.
Herbert McLean Evans and Katherine Bishop were anatomists experimenting with rats at the University of California. They fed rats only milk and studied how the rats were progressing. While they found that the rats were growing healthier, they were not reproducing!
They tried modifying the diet and included some starch and animal fats. The female rats became pregnant but were unable to carry the pregnancy to full term.
That's when they introduced lettuce as a part of the diet. Now they found that the rats got pregnant and delivered healthy babies.
It was then recorded that healthy and natural sources of food were important for fertility. A particular nutrient was extracted from lettuce and was named vitamin E in 1922.
Since the nutrient was related to fertility in rats, it was given a Greek name 'Tocopherol'. In Greek, 'toco' meant birth, 'pher' meant carrying, and 'ol' referred to it being a chemical.
Upon consuming vitamin E rich foods or vitamin E supplements, it is absorbed in the body like any regular fat source that you eat. Vitamin E is absorbed by the small intestine and from here, it reaches the blood and is circulated around.
The liver absorbs most of the vitamin E from the blood. You should know that the liver only acts on alpha-tocopherol and converts it into a form that is usable by the cells in the body. All other types of vitamin E are sent (excreted) out.
The converted form of alpha-tocopherol is now sent out to the blood and reaches all the tissues and cells.
Excess vitamin E is stored in the adipose tissues (fat-storing tissues present in several locations in the body) just like how normal fat is stored and is used when needed.
The use of vitamin E in the cosmetics and skincare industry has become quite common. Every product in the market seems to have added vitamin E to it.
Are all of these actually beneficial?
No, says research.
Vitamin E needs to remain stable to be useful for your skin. Most generic skincare products use unstable vitamin E forms that get destroyed as soon as you expose the product to light and air.
Hence the products you religiously use may do nothing to your skin.
The next time you buy a vitamin E-enriched product, make sure the base nutrient used is an ester form of vitamin E (a type of compound produced from acids) that is more stable and is also easily absorbed by the skin.
You cannot get vitamin E toxicity by just consuming foods rich in vitamin E. You get it only when you consume excess supplements. Here is a list of maximum levels of vitamin E that your body can handle safely.
Vitamin E toxicity can lead to internal and external blood loss (hemorrhage). When you consume excess vitamin E supplements for a longer duration, the side effects get worse.
For normal healthy individuals, vitamin E deficiency is quite rare. These individuals can easily get their recommended values only from regular food that they eat.
If a person gets vitamin E deficient because of certain genetic and non-genetic reasons mentioned below, it can result in:
Genetically, few people can have higher levels of vitamin E in the body and a few others can have lower levels. You will have to plan your vitamin E intake based on your genetic design.
APOA5 gene - The APOA5 gene is responsible for producing (encoding) the Apolipoprotein A-V protein. This is important for transporting fats including vitamin E. There are two SNPs of this gene that alter the vitamin E needs in the body.
CYP4F2 gene - The CYP4F2 gene produces the CYP4F2 enzyme. This helps in breaking down vitamin E. A particular allele of the gene is known to result in higher levels of vitamin E in the body.
TTPA gene - The TTPA gene helps produce the alpha-tocopherol transfer protein. This helps in transferring vitamin E in the body. Few mutations of the TTPA gene can cause Ataxia with Vitamin E Deficiency (AVED). AVED is another very rare inherited disorder that can lead to vitamin E deficiency.
Here, the transfer protein required to process vitamin E into cell-usable forms is absent or doesn't function right. AVED results in vitamin E deficiency and individuals with these mutations are likely to require more vitamin E than recommended levels.
MTTP gene - The MTTP gene is responsible for producing a particular type of protein called microsomal triglyceride. This protein, in turn, helps produce beta lipoproteins. Beta lipoproteins carry fats in the food you eat from the intestine to the blood. These also carry fat-soluble vitamins like vitamin E.
There are about 60 different mutations of the MTTP gene that cause a condition called abetalipoproteinemia.This is a very rare inherited disease that hinders dietary fat absorption in the body.
People with abetalipoproteinemia are likely to require more vitamin E levels. They will need large doses of vitamin E supplements (5-10 grams a day) to prevent getting vitamin E deficient.
A research study on the data from Adolescent Brain Cognitive Development (ABCD) Study suggests a relationship between certain regions in the brain and weight gain among children and adolescents. The study explored the relationship between "reward region" and food processing and suggests that this region may predict obesity in children.
Childhood obesity is a serious problem in the United States, putting children and adolescents at risk for poor health. Overweight children are much more likely to become overweight adults unless they adopt and maintain healthier patterns of eating and exercise.
Previous research has identified a region in the brain associated with overeating or unhealthy eating behavior.
Almost all our actions are driven by two things: Necessity and Reward. An activity can be considered a reward when it motivates us or gives us pleasure. Neurons, the brain's fundamental working unit, communicates this "reward" using dopamine, which is popularly known as the "happy hormone."
Incidentally, food-reward is common in animal training routines. An animal is rewarded with a treat when it performs certain actions and this programming of food-reward is routinely used by animal trainers in zoos and entertainment venues and other animal training facilities.
Hedonic hunger describes eating for pleasure than hunger - to enjoy the taste rather than to meet the body's energy needs. This pleasure eating triggers the brain's reward system region, which can lead to overeating - a common cause of obesity.
"The ABCD study or the Adolescent Brain Cognitive Development Study is the largest long-term study of brain development and child health in the United States." The study was done on over 10,000 children from ages 9-10 and was followed up through early adulthood.
Using the data from this study, the researchers attempted to investigate the relationship between the reward system region in the brain (called the nucleus accumbens) and eating behavior by examining 5300 research participants.
It was observed that when 2000 participants returned for a one year follow up, the waist circumference had increased by an average of 2.76 centimeters per participant.
The cell density (number of cells for a given area) in the reward region of the brain was examined using a noninvasive MRI technique.
The MRI revealed changes in the cell density that reflected the increase observed in the waist circumference.
The study speculates that the increase in this cell density can be because of an inflammation caused due to a diet rich in high-fat foods.
The findings essentially tell us that a vicious cycle of pleasure eating leading to changes in brain, in turn leading to overeating and increasing the risk of obesity.
Not all children who carry a few extra pounds can be classified as obese. Weight fluctuations are commonly observed in the growing stage of children. Before you decide on dietary changes for your child based on any weight gain you see, it's best to consult a doctor. The doctor may use growth charts, calculate the BMI and, take a family history, and, if necessary, may order a few tests to outline the issue behind the weight gain.
Vitamin K refers to a group of fat-soluble vitamins that play a role in blood clotting. It also helps your body make proteins for healthy bones and tissues.
Vitamin K is produced in our bodies by gut bacteria.
Two natural forms of this vitamin exist - vitamin K1 and vitamin K2. Vitamin K1, also called phylloquinone, is produced in plants. It is the main type of dietary vitamin K.
Vitamin K2, which is the main form stored in animals, has a number of subtypes referred to as menaquinones.
Vitamin K3, K4, and K5 are the synthetic forms (made artificially) of vitamin K.
A Danish scientist, Henrik Dam, aimed to study the effects of low cholesterol (fat-like substance present in the body) levels in the body, in 1929. He examined chickens that were fed a diet low in cholesterol.
After a few weeks, the chickens started developing hemorrhages (bleeding inside the body). However, restoring the cholesterol in their diets did not seem to reverse this.
It was then learned that another compound had been extracted from the food along with the cholesterol. That compound was the coagulation vitamin, which was described as vitamin K because it was first reported in a German journal as "Koagulations vitamin."
It was only much later in 1974 that the exact function of vitamin K in the body was discovered.
During pregnancy, vitamin K does not cross the placenta (tissue that develops in the womb during pregnancy) to reach the developing baby, and the gut does not have any bacteria to make vitamin K before birth. After birth, vitamin K in breast milk is also not adequate enough.
Insufficient vitamin K levels can put the baby at a risk for a rare but serious disease called Haemorrhagic Disease of New-Born (HDN), also known as Vitamin K Deficiency Bleeding (VKDB)
Thus, vitamin K is administered to the baby at birth using either of the following ways:
So far, vitamin K administration to the newborns has not resulted in any noticeable side effects.
Most of the diets followed in the United States contain an adequate amount of vitamin K. Thus, reports of vitamin K deficiency in adults are very rare.
VKROC1 gene is located on the short or p-arm of chromosome 16.
The VKORC1 gene plays a vital role in the vitamin K cycle. The gene produces the enzyme (vitamin K epoxide) reductase that converts vitamin K to another form (from vitamin K epoxide to vitamin K) that is required for the blood clotting process.
Warfarin usage can interfere with this conversion. Warfarin is a blood thinner that is prescribed to treat blood clots and is advised for people with a high risk for stroke or heart diseases.
Since warfarin is a blood thinner (doing the opposite of what vitamin K does), it tends to inhibit the activity of the VKROC1 gene. This results in reduced vitamin K levels that can hamper the functioning of various blood clotting proteins.
The SNP rs9923231 can alter the activity of the enzyme vitamin K epoxide reductase. The C allele shows enhanced enzyme activity compared to the T allele, and thereby increases the availability of active vitamin K. The T allele, on the other hand, results in lower enzyme levels, and therefore less active clotting factors.
The GGCX gene is located on the p arm of chromosome 2.
It produces the enzyme Gamma-glutamyl carboxylase. This enzyme helps in the modification of several vitamin K-dependent proteins that are involved in blood clotting.
The SNP rs699664 influences the activity of the enzyme gamma-glutamyl carboxylase. The G allele produces a protein that is less active than the A allele. This results in lower levels of vitamin K which may lead to blood clotting issues.
Vitamin K deficiency can be very dangerous, as it could result in uncontrolled bleeding - which is the primary symptom.
Vitamin K toxicity is extremely rare. The natural forms of vitamin K (K1 and K2) don't cause toxicity even when consumed in large quantities.
However, a synthetic form of vitamin K - vitamin K3 - is associated with toxicity and should not be used to treat vitamin K deficiency. K3 interferes with the body's natural antioxidants which can result in cell damage. In infants, the toxicity manifests as jaundice and can result in hemolytic anemia (where the red blood cells are destroyed faster than they are produced) in adults.
Vitamin K deficiency is easily treatable using the drug phytonadione, which is essentially vitamin K1, that is given orally or subcutaneously (skin). The dosage for the drug varies based on the age, gender, and requirement of each patient. However, the best way to ensure you get the optimum recommended amount of vitamin K is through diet.
You must get your daily dose of green vegetables as they are natural sources and contain large amounts of vitamin K. These include:
Vitamin K is a fat-soluble vitamin that plays a major role in blood clotting. It is also essential for regulating blood calcium levels. Most newborns are born vitamin K deficient as this vitamin cannot cross the placenta. Hence, vitamin K needs to be administered either orally or through injection after birth. Though vitamin K deficiency in adults is pretty rare, it can potentially be life-threatening as it could lead to uncontrolled bleeding. Certain genetic types can put you at a risk for vitamin K deficiency, especially when on anticoagulants like warfarin. Vitamin K1 injections and oral supplements can bring vitamin K levels back to normal. However, in order to continually maintain adequate levels of vitamin K, dietary sources are the way to go!
Folate, also known as vitamin B9, is a water-soluble B vitamin. It is naturally found in many folate-containing foods like spinach, broccoli, avocados, and lentils.
Apart from natural sources, the synthetic form of folate, folic acid, is also sold as a supplement. This form is supposedly absorbed better by the body.
Lucy Wills, a researcher, was the first one to identify folate and its function, in 1931. She demonstrated that anemia in pregnant women could be prevented/reversed with brewer's yeast. In the late 1930s, folate was isolated from brewer's yeast.
It was first extracted from spinach in 1941 - the term "folic" is from the Latin word 'Folium', which means leaf.
Further, the crystalline form of folate was extracted in 1943, which was the basis of the synthesis of Aminopterin, a derivative of folic acid.
Aminopterin was the first-ever anticancer drug developed, and its clinical efficacy was proved in 1948.
Vitamin D and folate are linked by their disparate sensitivities to Ultra Violet Radiation (UVR). While UVR stimulates the production of Vitamin D in the skin, it degrades folate through oxidation.
The hypothesis suggests that skin pigmentation may have evolved to maintain a balance in the levels of these vitamins.
The increased pigmentation observed in high-UVR regions was attributed to the need for protecting folate levels, while the depigmentation is low-UVR regions was a result of facilitating adequate vitamin D levels.
The VDR gene provides instructions for making a protein called Vitamin D Receptor, which allows the body to take in vitamin D. The different variants of the VDR genes are present in different frequencies across populations.
For example, the common VDR variant Fok1 has a lower frequency in African populations compared to European/Asian populations, while the frequency of another variant, Cdx2, is highest in African populations and the lowest in Europeans.
The difference in the frequency of these alleles across different ethnic populations can be attributed to the different UV regimes.
Several relationships are reported between UVR and folate metabolism genes. Two main enzymes involved in folate metabolism, serine hydroxymethyltransferase (SHMT) and methylenetetrahydrofolate reductase (MTHFR), have been studied to be UVR responsive.
For example, in regions where there's a higher exposure to UVR, the frequency of a thermolabile MTHFR variant, C677T, is less.
These findings collectively provide strong molecular support to the Vitamin D-Folate hypothesis and showcase the existence of interactions between UVR, skin type, and vitamin D and folate genes.
Typically, the body has around 10-30 mg of folic acid stored in the liver, and 5-15 ng/mL in the blood.
In order to understand the recommended dosage of folic acid, the following terms are important:
It is important to note that the bioavailability of folate depends on the source. Synthetic vitamin B9 (folic acid) is readily absorbed (about 85%) into the body, compared to folate from food sources (about 50%). Dietary Folate Equivalent (DFE) was developed to reflect the total amount of bioavailable folic acid.
1 mcg DFE = 1 mcg food folate = 0.6 mcg of fortified foods/supplements taken with foods = 0.5 mcg folic acid in the form of a supplement (taken on an empty stomach).
A healthy adult needs 400mcg DFE folate daily. Pregnant women need 600 mcg of folate per day to meet the requirements of the growing fetus as well.
MTYL1 gene is located on chromosome 2.
It codes for myelin transcription factor 1, which is expressed in the neuronal tissues.
This transcription factor converts postnatal human fibroblasts into induced neuronal cells, thus playing a big role in cognitive function.
A variant in this gene is linked with serum folate levels.
This gives an initial idea of an association between folate levels and depression and schizophrenia.
A variation in this gene, with a C genotype, is reported to be linked to serum folate levels. In a GWAS study conducted, a single copy of the C allele was seen to decrease the serum folate levels by 0.169 units.
The MTHFR gene is located on chromosome 1. It codes for an enzyme called methylenetetrahydrofolate reductase, which plays a role in processing amino acids. This enzyme is involved in a chemical reaction that processes folate to its primary form (5-methyl tetrahydrofolate) found in the blood.
This compound is necessary for the multistep process that converts homocysteine to methionine.
In the normal functioning of the body, there is a balance between homocysteine and folate levels. However, when this balance is disturbed, it leads to health effects.
Mutations in the MTHFR gene have been associated with high homocysteine and low folate levels, both of which are harmful to the body.
rs1801133The most-studied variant of the MTHFR gene is 677T←C (rs1801133) in exon 5. The 677T variant has been studied to be less effective in the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate.
Thus, the serum folate concentration is lower in individuals with the 677TT genotype than in those with 677CC or 677CT genotypes.
Inherited folate deficiency, also called Hereditary folate malabsorption, is a disorder that interferes with the body's ability to absorb folates from food. Infants with this condition have normal folate levels at birth; however, they begin to show signs of folate deficiency within the first few months of life. Feeding difficulties, diarrhea, and failure to thrive are common signs observed in infants with inherited folate deficiency.
This condition is inherited in an autosomal recessive manner.
Now, for the expression of a recessive trait, both parents must pass on their recessive versions of traits.
A random process selects the gene to be passed down to the next generation.
In the case of autosomal recessive conditions, there is a 25% chance of occurrence.
If just one parent passes it on, the child will remain healthy but acts as a carrier of the gene.
Carriers could potentially pass it on to the coming generations.
Folate deficiency is usually a result of poor diet, alcoholism, and malabsorptive disorders. Hence the prevalence of isolated folate deficiency is pretty rare; other nutritional deficiencies mostly accompany it.
What Are The Signs And Symptoms Of Folate Deficiency
Causes of folate deficiency
Who's at risk for folate inadequacy
It is rare to reach a toxicity level from consuming folate via natural food sources. An arbitrary upper limit for folic acid on a daily basis is 1000mcg.
Dangers of folate toxicity
Since vitamin B9 is water-soluble, it needs to be replenished in the body on a daily basis. There are a lot of sources of vitamin B9.
Folate is also available in the form of dietary supplements. Multivitamin supplements and B-complex tablets usually contain folic acid. These supplements are advised for individuals that have a mutation in the MTHFR gene.
It is recommended to take the active form of folic acid (L-methyl folate, or 5-MTHF). It is beneficial to have folic acid supplements daily to ensure optimal nutrient health for an individual.
Folate is an important vitamin that helps in cell replication, production of RBCs, and the maintenance of healthy cells in the body.
It is a water-soluble vitamin and should be included in the daily diet for a healthy individual.
There are vast implications if an individual has folate deficiency, with symptoms ranging from mouth sores to life-threatening anemia.
Pregnant women should also be wary of the amount of folic acid in their diet, as it can heavily impact the health of the fetus.
An individual can have inadequate folic levels because of an unbalanced diet, genetic variations, or other risk factors.
Folate deficient individuals can meet their requirements by adjusting their diet or taking supplements. When it comes to supplements, the dosage is an important factor.
Excess folate consumption can lead to folate toxicity the could result in a decline in cognition.
Thus, as always, it is recommended to consult a physician before starting any supplementation.
Vitamin A plays a very important role in the overall development and maintenance of the body. This fat-soluble vitamin is stored in the liver and is available externally in two forms
Vitamin A is known to support a variety of metabolic functions. It helps with better vision and improves your immunity. Getting the right dose of vitamin A also plays a role in keeping the skin and teeth healthy. The right amounts of vitamin A protect the skeletal system and the soft tissues in the body.
In pregnant women, right vitamin A levels help with tissue repair after delivery and also keeps the risks of infections low.
It took almost 130 years for researchers to identify the existence of vitamin A and understand its effects on the human body.
Early accounts of Vitamin A Deficiency (VAD) have only been recorded in terms of night blindness amongst children, soldiers, and sailors. Back then, the only solution offered was to consume cod liver oil or eat an excess of cooked liver. Doctors knew this worked, but didn't understand why it worked.
There were innumerable studies that tried to understand the effects of nutritional deprivation on animals and human beings between the mid-1800s and 1900s.
In 1912, Sir Frederick Gowland Hopkins concluded in his clinical trial that an additional factor in milk apart from carbohydrates, fats, and proteins helped rats survive on only a dairy-based food plan. He won the Nobel Prize for this study later.
This additional factor was narrowed-down to be a fat-soluble nutrient in 1918 and was finally identified as vitamin A in 1920.
In 1931, the International Conference on Vitamin Standards was first held in London and the league set to make standards and recommended values for all identified vitamins, including vitamin A.
Though people all over the world have become conscious about their nutritional intake, WHO states that about 250 million preschool children are still diagnosed with VAD. Making the right change in food habits, identifying the effects of one's genes in his/her vitamin A requirements and taking vitamin A supplements, if needed, will all help bring down the risk of VAD.
We humans cannot produce vitamin A in our body, hence it is called an essential vitamin. We need to obtain it through diet or supplements. Vitamin A can be derived from both plant and animal sources.
Animal sources provide vitamin A in its active form, retinol, while plant sources provide vitamin A as carotene, an inactive form, which in-turn needs to be converted into the active form, retinol.
The genetics of some individuals predispose them to less efficient conversion of biologically inactive carotene to active retinol. They are usually advised to consume animal sources of vitamin A or take vitamin A supplements or consume higher amounts of plant sources to compensate for lowered conversion efficiency.
We will look into more details of specific genes that influence this predisposition in the following sections.
Everyone knows carrots are a good source of vitamin A and that they can improve general eyesight.
Did you know where this idea stemmed from?
During World War II, the British government ordered citywide blackouts to prevent German bomber flights from identifying their targets. On the other side, the British defenses were safeguarding a secret Intercept Radar System that helped their British flyers see better despite blackouts. To keep this information a secret, the British Ministry let out official information stating their flyers were able to see better in the dark because of excess consumption of carrots!
This detail has taken deep roots and is believed to date.
According to the U.S Department of Health & Human Services, here are the recommended values of vitamin A at every stage in life.
When you consume more vitamin A than recommended every day, here are some of the possible side effects recorded.
When your Daily Value Intake of vitamin A is consistently lesser than the suggested levels, you could be at a higher risk of developing the below conditions.
Insufficient dietary intake
A key source of vitamin A to the body is the food we consume. Naturally, not including enough of vitamin A rich foods is a top non-genetic reason for Vitamin A Deficiency (VAD). Not taking enough vitamin A can be a result of an unhealthy lifestyle, lack of awareness on the importance of nutrients, or poverty/unavailability of food.
People who suffer from chronic diarrhea and respiratory infections are also prone to having lower levels of vitamin A in the body.
Avoiding animal sources of vitamin A
Though vitamin A is available in both plant and animal sources, vegans have to depend exclusively on fruits and vegetables for their vit A needs. When vegans don't plan their diet well and don't consciously include enough carotenoid-rich foods, they can be prone to VAD.Veganism is hence a growing cause of concern as a non-genetic influence for VAD. If you follow a vegan lifestyle, you should be working on carefully choosing your food sources to prevent nutritional deficiencies.
Infants whose mothers show signs of VAD end up not getting enough Vitamin A in breast milk and hence are at a higher risk of developing VAD related health complications.
Mutations in both the TTR gene and the RBP4 gene can cause low levels of retinol in the body. The TTR gene produces a protein called transthyretin that transports vitamin A internally. The RBP4 gene (Retinol Binding Protein 4) produces the RBP4 transporting protein that delivers vitamin A from the liver to the tissues around.
RBP works with transthyretin in the plasma and prevents the kidneys from filtering out excess vitamin A.
Two gene variations can cause VAD.
BCMO1 gene – The BCMO1 gene helps encode enzymes that convert the carotenes from plant-based food sources into forms that can be used by the human body.
CYP26B1 gene – This gene is responsible for bringing down the active form of vitamin A called retinoic acid. The SNP rs2241057 with G variant in this gene can cause an increased breakdown of retinoic acid and hence can result in lowered vitamin A levels in the body.
Here is what you should do to maintain the right levels of vitamin A in the body.


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forming a basket or angle, and then grap¬
ple it to you with both hands. The high-
running line-breaker would, of course,
take the ball under one arm and use the
other in warding off. For runs around
the end, the ball should be carried un¬
der one arm. Just how to carry it so as
to prevent an opponent from relieving
you of the ball must be acquired by
practice. One suggestion, perhaps, will
help. Do not carry the ball too far under
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is surprising how many tacklers can be
warded off by using that arm like a pis¬
ton-rod against every man that comes up.
In line - breaking, the back should re¬
member to keep his feet and fight for the
last inch of ground. If he can only keep
his feet and give his own side a chance to
Permalink: http://pid.emory.edu/ark:/25593/n6nr2


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Sneakers (1992)
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Sneakers (1992)
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McGonagall role) - Swag Hag Potions (Prof. Snape role) - Joe Pilot Defence Against The Dark Arts (Prof. Lockhart with Lupin's brain) - Dr Henry Jekyll Charms (Prof. Flitwick role) - Minerva Care of Magical Creatures - Diana Herbology (Prof. So the magic and stuff is the same, just more crazy misadventures among the staff than fighting a noseless Dark Lord. Everyone has been cast based on fitting of their personalities, the subject/role, voice actor similarities, similarities to the Hogwarts character, humorous irony, or a combination of any of those.
|Take Me Down
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