Vitamin B12 is one among the B vitamins and is also known as Cobalamin, since it contains the mineral called cobalt. This water-soluble vitamin cannot be made in the body and needs to be obtained from the food we eat.
Vitamin B12 helps with the below functions in the body:
Vitamin B12 deficiency can cause irreversible damage to the body and is, unfortunately, an increasing problem in the countries around the world. There are several reasons why your body might be receiving less vitamin B12 than the recommended daily intake. We will talk about that in the coming sections.
The story behind vitamin B12 goes as far back as the 1850s and includes the efforts of many renowned pathologists, physicists, and scientists.
Thomas Addison was an English physicist working in the famous Guy’s Hospital in London. Addison was working on the different causes and effects of diseases and identified a condition called Pernicious anemia.
Pernicious anemia is characterized by abnormal and insufficient Red Blood Cells. This disease was considered fatal between the 1800s and early 1900s.
It took almost 40 years to find a cure for pernicious anemia. George Hoyt Whipple, an American pathologist, had intensely analyzed the effects of food on the disease and concluded that a liver-based diet in dogs helped increase RBC count in the blood. This led to the identification of liver as a food-based treatment option for treating Pernicious anemia.
While doctors knew this diet helped reverse the condition, they didn’t fully understand why.
It took another 30 years for scientists to successfully identify and remove a water-soluble compound from liver samples and confirm that this was what actually treated the anemia. This compound’s structure was defined in 1956 and was named ‘vitamin B12’.
There were a total of five Nobel Prizes awarded to scientists around the world for the studies related to vitamin B12. We have these great minds to thank for bringing to the world’s notice one of the most important B vitamins.
Once you consume foods rich in Vitamin B12, gastric juices in the intestine help release the vitamin from the food. Once the vitamin is free, a particular protein called R-binder attaches itself to B12 and prevents the acids in the stomach from destroying the vitamin B12 molecule.
Now, the R-binder protein takes B12 to its next destination, the intrinsic factor (IF). This is also a kind of protein produced in the stomach.
From here, the B12 reaches an important carrier protein called Transcobalamin II. This helps circulate B12 to different parts of the body.
For the proper absorption and circulation of vitamin B12, the gastrointestinal tract and its help are vital. This is why people with gastric issues may have problems absorbing B12.
Did you know that your body stores enough quantities of vitamin B12 for future use? If you have been getting enough or more than the daily recommended values of vitamin B12, a certain amount keeps getting stored in the liver. This reserve can last for anywhere between 3 and 5 years!
The body knows the importance of vitamin B12 and hence keeps a stock of it for your benefit.
If you have been consistently getting lesser vitamin B12 than what’s needed, your excess reserve is continuously used and you start getting signs of vitamin B12 deficiency only after a couple of years.
The rate at which the stored levels are depleted (turnover rate) depends on your body’s ability to get and absorb vitamin B12. Healthy individuals with normal absorption rates may have a lesser turnover rate than those with gastrointestinal issues or pernicious anemia.
The Dietary Reference Intake (DRI) is a reference for assessing the general needs of vitamin B12 levels in children and adults on an everyday basis.
Excess of vitamin B12 does not cause toxicity in the body as fat-soluble vitamins do.
Vitamin B12 that is ingested is used for everyday functioning and a part of it keeps getting stored in the liver as a reserve. The remaining doses are easily excreted out through urine. Hence it is not very easy to get an overdose when it comes to B12.
However, if you are on vitamin B12 shots, supplements, and a diet rich in red meat, poultry, and dairy products simultaneously, excess quantities of the vitamin may cause dizziness, nausea, and headaches in some individuals.
When you are consuming lesser vitamin B12 than the DRI values, you are at risk of developing the below conditions.
The FUT2 gene encodes a protein that helps a harmful bacteria called Helicobacter pylori attach itself to the digestive tract. This bacteria can inhibit the absorption of vitamin B12 in the body. Here is a list of FUT2 gene variants that can result in increased/ decreased levels of vitamin B12 in the body.
The TCN2 gene encodes a protein that helps in the final transportation of vitamin B12 from the blood to the cells in the body. A certain variant of the TCN2 gene in the Caucasian population is known to cause increased/decreased levels of B12 in the body.
Maintaining healthy vitamin B12 levels in the body is beneficial for overall health maintenance. It keeps you energetic, strong, and healthy. Here are expert recommendations on getting your daily dose of vitamin B12 right.
http://www.animalresearch.info/en/medical-advances/timeline/pernicious-anaemia/
https://ods.od.nih.gov/factsheets/VitaminB12-Consumer/
https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/
https://www.ncbi.nlm.nih.gov/books/NBK114329/ https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/vitamin-b12
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.
https://www.unicef.org/publications/files/Vitamin_A_Supplementation.pdf
http://ocw.jhsph.edu/courses/InternationalNutrition/PDFs/Lecture3.pdf
https://www.who.int/publications/cra/chapters/volume1/0211-0256.pdf
https://ods.od.nih.gov/factsheets/VitaminA-Consumer/
https://www.nhs.uk/conditions/vitamins-and-minerals/vitamin-a/
There are many different types of genetic tests that are used for a range of applications, from ancestry analysis to diagnosing clinical conditions like Alzheimer’s. The type of genetic test to be performed is based on your reason for testing. Each type of test differs in the information it can provide, the amount of data obtained from it, its cost, accuracy, and even the sample used for the test (saliva, blood, hair, etc.).
Genetic testing is used to identify the changes in your DNA sequences, also known as mutations or variations.
As a simple example- if the word “APPLE” were a gene sequence, it will be spelled correctly in the majority of people; however, you may carry a “variation” of this gene that is spelled as “APBLE.”
Biologically speaking, many of these changes are harmless, meaning small spelling variations do not alter the individual’s health. However, some variations are harmful or advantageous to varying degrees.
The analysis of your DNA data reveals what variations are present in your DNA and their effects on your health.
The genotyping test is one of the most inexpensive tests available in the market. This test is also very popular among consumers since it is widely marketed by many direct to consumer (DTC) genetic companies like 23andme and AncestryDNA to perform ancestry and health analysis.
Genotyping reveals the differences in a sample DNA sequence by comparing it with the reference DNA sequence.
As a simple example, if A-P-P-L-E is the reference gene sequence, and the sample sequence is A-P-B-L-E, genotyping tests will be able to detect the P→ B change. This kind of change in a single letter is called a single nucleotide polymorphism (SNP). Your genome contains around 4-5 million SNPs that may be unique to you.
Most SNPs do not have any significant health implications; however, some of these differences may be indicative of the development of certain health conditions or certain unique traits related to your health and wellness. They can be advantageous or disadvantageous to various degrees. These DNA variants or genotypes may act alone or in concert with a few to several hundred other DNA variants to create a health impact.
Genotyping has a broad range of applications, including ancestry, pharmacogenomics (ADME), fingerprinting, clinical and health conditions, and lifestyle and wellness traits. Though generally, genotyping is not the test of choice for health or clinical applications.
A note on genotyping:
Genetic tests based on the genotyping chip method have an accuracy of more than 99% when performed using standardized protocols in certified labs. However, even the less than 1% inaccuracy amounts to a few hundred variants, some of which can be important. Typically, genotyping tests are not used for clinical or diagnostic purposes.
The full human genome is 3 GB in size. You can imagine a book with chapters, pages, paras, and sentences which is 3 GB in size. Your clinician may only be interested in para two on page 100 in chapter 3 because it is relevant to the condition he/she is treating you for. He will order a test for your known as targeted sequencing, which is designed to read specific segments of the DNA. This test is much cheaper than reading the whole genome and has a significantly shorter turnaround time.
Targeted sequencing is typically used for:
Though the genome is 3 GB in size, much of it is filled with pages that scientists don’t yet understand the meaning of. Approximately 98% of the genome is not yet understood. The 2% that scientists do understand is known as the exome. Many people prefer to go for a test that reveals the information in their entire exome- this is known as Whole-Exome Sequencing (WES).
Exome sequencing is typically used for:
If you prefer to have your whole genome analyzed, a Whole-Genome Sequencing (WGS) test is what would be performed for this purpose.
Whole-genome sequencing is typically used for:
The accuracy of sequencing tests depends on what is known as ‘Coverage.’ Coverage, also termed as ‘sequencing depth,’ refers to the number of times the DNA sample gets sequenced. Essentially, the higher the number, the higher the accuracy.
| Technique | Cost | Site | Coverage | Data Size(depends on coverage) |
| Targeted sequencing | $300-$1000 | The specific region of interest | 200-1000x | 100 MB–5 GB |
| WES | $500 - $2000 | Exome | 150-200x | 5 GB–20 GB |
| WGS | $1000 - $3000 | Genome | 30-60x | 60 GB–350 GB |
Before choosing a genetic test, it’s important to keep in mind a few points:
Besides ancestry, 23andme also provides Health and wellness reports and traits. You can find a list of Health and wellness traits here. The term “reports” is sometimes interchangeably used with DNA raw data or data.
But first, read the disclaimer. All non-clinical DNA tests and reports, whether from 23andme or other companies, come with strong disclaimers.
“23andMe does not offer diagnostic testing. For testing related to a personal or family history of a particular genetic disease, please consult a healthcare provider in order to ensure that you are pursuing the most appropriate test for your personal situation.”
Topics not included in 23andme reports:
23andme uses genotyping, which is the simple method of identifying single (mostly) character changes in your genetic data. These single character changes are known as variants or Single Nucleotide Polymorphisms (SNPs). But, your genome has several other types of variations that are not detected by this technology.
“23andMe is not designed to analyze for repeated, inserted, inverted, translocated or deleted segments of DNA”
One important type of genomic variation is Copy Number Variations (CNVs). In copy number variations, certain genetic features are repeated again and again as in multiple copies are present. The 23andMe test is not designed to detect these and does not report data on most CNVs.
There are 23 pairs of chromosomes in most people. The 23rd pair is known as sex chromosome, written as X and Y chromosomes. X carries female features and Y carries male features. In some instances, instead of XX (for females) and XY (for males), an individual may inherit an extra chromosome leading to a condition called Trisomy. Examples of trisomies include Down syndrome (trisomy 21), and Klinefelter syndrome (XXY). These conditions are not detected and reported by 23andMe
Certain segments of the genome repeat over and over again. A group of three genomic characters such as CAG can repeat several terms. This type of repeating can lead to diseases such as Huntington's Disease and Fragile X syndrome.
The 23andMe genotyping platform is not capable of detecting trinucleotide repeats and therefore 23andMe reports do not include any condition on trinucleotide repeat disorders. Nor is there relevant data related to trinucleotide repeat disorders in the raw data.
In some cases, genomic features may be deleted or new features inserted (in comparison to reference genomes). Such disorders include DiGeorge syndrome (aka 22q11.2 deletion syndrome) and Cri du Chat syndrome (5p- where part of chromosome 5 is missing).
In addition, the majority of Spinal Muscular Atrophy (SMA) and Duchenne Muscular Dystrophy (DMD) cases are due to loss of genetic material (in each case just part of the gene is missing).
23andme’s technology is not designed to analyze repeated, inserted, inverted, translocated, or deleted segments of DNA, in most cases 23andme cannot provide information about copy number or other genetic features that are related to the number or order of base pairs present.
Recently, DTC genetic tests have become very popular due to a combination of reasons:
The cost of genetic testing in general has been decreasing primarily due to technological advancements and increasing consumer demand.
Over the last few years, the self-testing trend has gained popularity due to an increase in self-awareness and self-monitoring.
This trend is facilitated by self-learning over the internet and other media and the availability of low cost internet-connected wearable devices enabling us to understand our bodies better.
Personalization in various aspects of health and well-being. We are at the end of the one-size-fits-all era.
We understand that carbohydrates are not equally bad for everybody, fat does not always cause high cholesterol levels, and COVID-19 does not affect everyone the same way.
Genetics enables us to understand our uniqueness in several aspects of life.
Ancestry testing is the largest segment in DTC genetic testing. People love understanding where their ancestors came from- their genetic genealogy.
Not only that, The DNA data also allows people to discover their biological parents, siblings and other relatives through a variety of online services!
If you have received DTC genetic reports from one of many sources available, you may have come across the following:
There could be several reasons for this:
Some examples of mismatch between self-observation and your genetic results:
> You have been drinking milk all your life without complaints, but your genetic test results indicate that you are lactose intolerant.
> Your genetic results indicate that your are NOT gluten intolerant, however, you have issues consuming gluten.
The above are but a few examples of how there might be a mismatch between your genetic results and your own observations about yourself.
Regardless of the reasons below, please remember that your observations or your physicians/healthcare professional’s assessment of your health overrules the findings of the genetic test report.
In other words, your consumer genetic test report is always secondary to other assessments.
Genetics is about probability. Having a variant only increases the likelihood that the association may be true for you, but it's not certain. It’s very much possible that other genetic and non-genetic factors overcome the association.
The World Health Organization (WHO) declared the outbreak of this novel Coronavirus as a Global pandemic on 12th March 2020.
Caused by a virus named SARS-CoV-2 (formerly known as 2019-nCoV), this is the deadliest pandemic the world has seen since the Spanish influenza of 1918.
As of July 2020, COVID-19 is still continuing its fateful march around the globe.
In most cases, COVID-19 starts out as flu-like symptoms, and a little over 70% of the people recover on their own.
But occasionally, (if you have to put a number on it, around 1 in 6) breathing difficulty and other respiratory issues occur.
In extreme cases, COVID-19 positive individuals can be asymptomatic.
Initial research that explored the broader spectrum of things suggests that age, gender, geographic location, and underlying health conditions may all influence the severity and susceptibility to COVID-19.
To gain more clarity, GWAS studies, and other small sample size research studies were conducted on the genetic contribution to the varying symptoms.
Here’s what we know so far:
Research studies have shown that genetic variants associated with host cell entry, production of cytokines, and immune response have a link to the severity of the infection.
The study confirmed the importance of ACE gene expression and the HLA region in the host response to viral infection.
ACE2, an enzyme created by the ACE2 protein, usually plays a role in the maintenance of blood pressure.
However, it has allied with the SARS-CoV 2 by functioning as a door to the cells.
In comparison to the SARS-CoV virus, the SARS-CoV-2 virus binds with a higher affinity to the ACE2 cell receptor, making it highly infectious.
An analysis of over 300,000 individuals variant data from across the world found variants in this gene that alters the receptor making it less friendly for the virus to bind to the host cell.
Individuals carrying such variants may thus be less susceptible to COVID-19.
A diverse set of human genes in the major histocompatibility complex encodes the human leukocyte antigens (HLAs).
Most people carry between three and six different HLA alleles that show geographic-specific distributions.
These proteins are important for how the immune system recognizes and mounts immune defenses against infection.
It is thus safe to say that HLA variations could affect your immune response to the virus.
A study found that HLA-B*46:01 variant had the fewest predicted binding sites, and therefore, reduced immune responses to SARS-CoV-2.
According to CDC, the number of men who died from COVID-19 is 2.4 times that of women.
So, what puts men at a higher risk for COVID-19 infection when compared to women?
A study hypothesizes the involvement of TLR gene in this.
TLRs or Toll-Like Receptors are a class of proteins that play an important role in immune functioning.
Humans have ten classes of TLRs (TLR1 to TLR10).
TLR7 is a pattern recognition receptor present in several immune cells and can detect single-stranded RNA viruses, including coronaviruses.
The X chromosome encodes the TLR7 and TLR8 tandem.
Women carry 2 X chromosomes, whereas men carry an X and a Y chromosome.
Though one of the X chromosomes is inactivated in women, the TLR7 and TLR8 tandem seems to have escaped this silencing resulting in higher expression levels of TLR7 in females in comparison to males.
A research study involving 1610 COVID-19 positive patients with respiratory failure established that blood type may play a key role in determining who contracts COVID-19 and how severe the illness becomes.
According to the study, blood group O is associated with a lower risk of acquiring COVID-19, whereas blood group A was associated with a higher risk.
The researchers are still a bit hazy on the exact science behind it, but some authors suggest that variations in biological mechanisms in ABO blood groups may play a role, specifically in their immune response.
Pharmacogenomics, the study of how genes affect your body’s response to drugs, is a rapidly growing field that is in the process of unlocking the key to preventing adverse drug effects.
The bolus of drug and genomics research occurring during the pandemic has lead to assessing the role of genetics in personalizing COVID-19 treatment.
Hydroxychloroquine, used to treat malaria, rheumatoid arthritis, and lupus, had an approval initially by the FDA for clinical trials to treat COVID-19.
However, the clinical trials recorded a significant number of arrhythmias, especially in patients with existing cardiovascular disease.
Evaluating the genetic variants that contribute to the effectiveness of the drug metabolism can help alter the dosage accordingly to avoid such adverse side effects.
Based on the key findings from the latest genetic research on COVID-19, we have curated a comprehensive report to enable you to understand your body better and align your care, diet, and therapy to your genetic type for the best support.
The report we have built consists of 4 sections:
1. Genetic risk for severe COVID-19
2. Genetic association with nutritional traits that may affect COVID-19 severity
3. Genetic influence on drug therapy
4. Genetics of the gut microbiome
Please note that the COVID-19 genetic report is based on preliminary studies and is meant only for educational purposes.
This report should be interpreted only by a medical practitioner.
Any lifestyle modifications based on this report should be done only after consulting with a qualified medical practitioner.
The immune system is always active, carrying out surveillance, but there is an enhancement in its activity if an individual encounters an infection.
Several vitamins (A, C, D, and E) and trace elements (zinc, selenium) have been demonstrated to have key roles in supporting the human immune system and reducing the risk of infections.
It would seem prudent for individuals to consume sufficient amounts of essential nutrients to support their immune system.
While one can ensure nutritional sufficiency through diet, other factors may hinder your body from absorbing these nutrients well, making you prone to deficiencies.
For example, some genetic variants interfere with the proper metabolization and utilization of certain nutrients, ultimately leading to its deficiency.
Carriers of such variants may require additional supplementation.
The nutrition section of the report profiles the genetic variants associated with this process.
It also includes specific dietary recommendations to ensure that you are meeting your optimal nutritional needs.
Your genetic makeup has a big role in drug metabolization, and consequently the effect of the drugs on your body.
The same genetic variants also influence how well your body allows the drug to treat viral infections.
This section of the report focuses on analyzing these genetic variants.
The outcomes throw some light on which combination of drugs your body type may respond better to, ensuring little to no side effects.
One of the serious clinical manifestations of COVID-19 is pneumonia and progression to acute respiratory distress syndrome (ARDS), especially in elderly, immune-compromised patients.
Numerous experimental and clinical observations have suggested that the gut microbiota plays a key role in the pathogenesis of sepsis and ARDS.
Loss of gut bacteria diversity can lead to dysbiosis, which may then be associated with many diseases.
Thus, the speculation of gut-lung connection influencing the clinical manifestation of COVID19 seems highly plausible.
In fact, according to research, nearly 60% of patients with COVID-19 show symptoms of gastrointestinal disturbance like diarrhea, vomiting, and nausea.
Some genetic variants aid a better growth of beneficial gut microbiome, thereby curbing all unwanted GI disturbances.
You can order your COVID-19 Genetic Report here.
