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What Is Hypertension?

Just like how water exerts pressure on the walls of the pipes when flowing, blood too exerts pressure on the surface blood vessels. The pressure exerted must be constant and of a particular value. A drop or hike in this pressure may likely be a warning of an abnormality.
When the pressure exerted by blood on the walls increases beyond a certain level, it is known as hypertension or high blood pressure. Hypertension is a pretty common health condition, with nearly half the American population expected to be diagnosed with it.

Symptoms Of Hypertension

Most people don't experience any particular symptom until the condition becomes severe. That is why hypertension is rightly known as the "silent killer." Even when people do experience the symptoms, they are almost always associated with other issues.
Some of these warning signals for hypertension include:
- Severe headaches
- Nose bleed
- Difficulty in breathing
- Chest pain
- Extreme tiredness and fatigue
- Sweating and anxiety

What Causes Hypertension?

The causes of hypertension or high blood pressure are still being studied. Some of the well-accepted and scientifically proven causes are smoking, obesity or being overweight, diabetes, having a sedentary lifestyle (one involving very minimal physical activities), and unhealthy eating habits.

What is Riboflavin?

Riboflavin, or vitamin B2, is a water-soluble vitamin. B vitamins are important for making sure the body's cells are functioning properly.
In addition to energy production, riboflavin also acts as an antioxidant and prevents damages by particles called free-radicals. It is involved in the production of folate (vitamin B9), which is crucial for red blood cell formation.
People need to consume vitamin B2 every day because the body can only store small amounts, and supplies go down rapidly.

How Does Riboflavin Affect Blood Pressure Response?

A study published by the American Journal of Clinical Nutrition revealed that one in ten people could significantly lower their blood pressure and, in turn, their risk of heart disease and stroke by increasing their vitamin B2 intake.

Previous studies have found an association between the 677C-->T polymorphism in MTHFR and hypertension. This transition from C to T results in increased homocysteine levels. About 30 to 40 percent of the American population may have a mutation at gene position C677T.

The relationship between riboflavin and hypertension was examined because riboflavin is known to have an important modulating effect on elevated homocysteine.

A study demonstrated that increasing riboflavin status reduced systolic blood pressure by 13 mmHg and diastolic blood pressure by almost 8 mmHg, specifically in patients with the TT genotype.

Another study showed that riboflavin (1.6 mg per day) lowers homocysteine levels in healthy adults with the TT genotype but not in those with CT or CC genotypes.

rs1801133

rs1801133 is an SNP in the MTHFR gene that is commonly studied. It is also known as C677T, Ala222Val, and A222V.
People with the TT type have a lower blood pressure upon riboflavin/vitamin B2 administration than those with the CT or CC type.

Dietary Recommendations

People whose blood pressure responds better to vitamin B2 should consider increasing their riboflavin intake. Vitamin B2 supplements can be taken after consulting with a qualified medical practitioner.

Another way to get vitamin B2 is through dietary sources.

Animal Sources of Vitamin B2

  1. Salmon
  2. Lean beef and pork
  3. Chicken breast
  4. Eggs
  5. Cheese

Plant Sources of Vitamin B2

  1. Fortified tofu
  2. Mushrooms
  3. Spinach
  4. Almonds
  5. Avocados
  6. Grains such as wheat

Summary

  1. Many research studies have clearly outlined the role of the MTHFR gene in regulating blood pressure. A common mutation, C677T, is associated with increased blood pressure or hypertension. C677T also results in increased homocysteine levels.
  2. Observational studies have indicated an inverse relationship between vitamin B2 and homocysteine - the higher the levels of vitamin B2, the lower the homocysteine levels.
  3. The observed relationship between vitamin B2 and homocysteine led researchers to explore the role of riboflavin in regulating blood pressure.
  4. People who have the TT type in rs1801133 of MTHFR gene respond better to vitamin B2 supplementation - riboflavin seemed to have a blood pressure-lowering effect on people with the TT genotype. The same effect was not seen in those with the CC type.
  5. The TT type people can benefit more from vitamin B2 consumption. Some dietary sources of vitamin B2 include salmon, lean meat, eggs, tofu, avocados, and almonds.

Reference

https://www.medicalnewstoday.com/articles/219561
https://www.tandfonline.com/doi/abs/10.1081/CEH-120020391?journalCode=iceh20
https://pubmed.ncbi.nlm.nih.gov/19952781/
https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.105.580332

Antioxidants Overview

Antioxidants are any compounds that help prevent cell damage in the body. One of the common reasons for cell damage is oxidation, where an atom or a molecule loses electrons.

While oxidation is useful for a few processes, excess oxidation leads to cell damage. The use of antioxidants is to regulate the level of oxidation in the body.

Depending on whether the antioxidants are soluble in water or fat (lipids), they are classified into two broad categories:

Antioxidants At The Molecular Level - Getting Technical

There are four basic levels of defense that all antioxidants have:

  1. Neutralizing free radicals by donating their own electrons
  2. Proactively searching and removing free radicals before they cause damage
  3. Self-repair and regulation of the internally produced antioxidants
  4. Adapting themselves to the body’s changes

Inside the body, the following factors determine antioxidant absorption and utilization:

The effectiveness of antioxidants depends on the internal environment they survive in.

Generally, larger molecules of antioxidants are broken down by the gut bacteria to help them enter the cell membranes.

The liver produces a few very important antioxidants. The cell membranes absorb some, while a large part is excreted out through urine.

Did You Know?

Have you heard of the famous egg or chicken question? The debate over whether the egg or the chicken came first to the world is never-ending. Until recently, scientists debated whether antioxidants were produced before or after the earth received oxygen through photosynthesis.

One may assume that microbes developed the ability to produce oxygen through photosynthesis first. This caused oxidative stress, and their bodies adapted themselves to produce antioxidants.

This is not the case, though!

According to this 2017 article, an anaerobic bacterium (oxygen-free bacterium) started producing an antioxidant called ergothioneine before it started the process of photosynthesis.

If not for neutralizing the effects of oxidation, what was the use of this antioxidant? Researchers are still trying to find out the answer to this question.

Why Do Humans Need Antioxidants?

Free radicals are unstable molecules that contain an unpaired electron. Because of this, they are highly reactive. Free radicals start taking electrons from the cells in your body and damages them in this process.

Free radicals are found in the air you breathe in, in the water you drink, in the foods you eat, and even in certain medications!

Antioxidants help by sacrificing/giving up their own electrons to the free radicals, thereby neutralizing them. Instead of damaging your cells, the free radicals damage the antioxidants, keeping you safe.

When your body does not have antioxidants, your cells are damaged faster because of free radicals, and this causes a variety of physical issues, including:

Genetic Association

GPX1 and Antioxidant Needs

Selenium is an important antioxidant that is needed for the healthy functioning of the body. Many enzymes in the body that fight free radicals are affected by how much selenium you get in your food.

Certain variations in the proteins GPX1 because of inadequate selenium intake are associated with increased cancer risk. In the rs1050450 SNP of the GPX1 gene, a minor allele ‘A’ increases your risk of developing cancer when your dietary selenium levels are low.

PON1 and Antioxidant Needs

Lycopene is a type of carotenoid that gives the red color to fruits and vegetables. This is also a very important antioxidant.
The PON1 gene helps produce the PON1 enzyme to protect against the oxidation of Low-Density Lipoprotein (LDL). LDL oxidation results in risks of atherosclerosis, heart attacks, and strokes.

The Q192R (denoted by rs662) is a polymorphism in the PON1 gene. The presence of the TT allele can imply lower or decreased levels of PON1 enzyme activity. The higher the PON1 enzyme activity, the lower is the risk for heart disease.

Non-genetic Factors Affecting Antioxidant levels

Unhealthy food habits - Most of the antioxidants required by your body can be obtained by including various fruits, vegetables, and other plant-based ingredients regularly. If you depend on restaurant takeaways or packaged and frozen foods for your meals, you may be at a higher risk for developing antioxidants deficiency.
Harvesting and handling of fruits and vegetables - Certain methods of harvesting and handling fresh fruits and vegetables can cause a reduction in the antioxidant levels in these produces. Consuming these fruits and vegetables will not give you your recommended values of antioxidants.
Cooking methods - According to a study boiling and pressure cooking the vegetable bring down the antioxidant levels. Opt for gentler cooking methods like steaming and quick frying instead.

Symptoms Of Excess Antioxidants

It is difficult to get an overdose of antioxidants with just food sources. However, it is possible to overdose when you are using antioxidant supplements. Here are some of the symptoms of excess antioxidant consumption:

  1. High doses of beta carotene are associated with an increased risk of lung cancer in those who smoke.
  2. High doses of vitamin E supplements can cause prostate cancer and bleed in the brain.
  3. High doses of vitamin A can lead to liver damages.
  4. Some studies suggest consuming excess antioxidants can make existing symptoms in cancer patients worse.
  5. Selenium overdose leads to nausea, bad breath, and various kidney and heart problems.
  6. Excess antioxidants can interact with certain medications that you take. Talk to your healthcare provider about recommended levels.

Symptoms Of Antioxidant Deficiency

A 2018 study analyzed the intake of 10 antioxidants. The antioxidants under consideration were beta carotene, alpha-carotene, beta-cryptoxanthin, lutein, lycopene, zeaxanthin, selenium, zinc, and vitamins C and E.

The study concluded that those deficient in these ten antioxidants had lowered anti-inflammatory activities and lowered HRQOL - Health-Related Quality Of Life. It includes factors needed for physical, mental, social, and emotional quality of life.

Oxidative stress, over time, can damage healthy cells in the body. This can result in increased risks of:

## Recommendations To Get The Right Amounts Of Antioxidants
**Include a variety of vegetables and fruits** - Vegetables and fruits are very rich sources of different antioxidants. One of the best ways to prevent antioxidant deficiency is to include colorful fruits and vegetables in your diet. Studies show that fresh fruits and vegetables bring down your risk for developing several diseases apart from keeping you fit.
**Prefer food-based antioxidants over supplements** - Unless you have been advised specifically, stay away from supplements and change your food habits to increase your antioxidant intake.
**Know how your genes affect you** - If you are genetically prone to requiring more antioxidants than normal individuals or at a higher risk for developing certain diseases because of antioxidant deficiency, plan your food choices right.
**Supplement antioxidants with caution** - While supplements can easily cause an overdose, supplements can also interact unpleasantly with certain medications you consume.
**Change your cooking methods** - Your cooking methods matter a lot. Choose healthier cooking options like broiling, steaming, and quick frying on a flat pan instead of boiling and pressure cooking.

## Summary
1. Antioxidants are compounds that help prevent cell damage. There are 1000s of individual antioxidants available in nature.
2. While most antioxidants are obtained from food sources, few very vital ones are produced in the body.
3. Antioxidants bring down the risks of several diseases and keep you younger for a longer time.
4. Antioxidant overdose is rare and occurs only upon consuming supplements. Antioxidant deficiency can lead to a lowered Health-Related Quality Of Life (HRQOL).
5. Some people can be genetically inclined to absorb lesser quantities of antioxidants than others. Such individuals may need to compensate with supplements.
6. For healthier individuals, it is recommended to get the dose of antioxidants from food rather than from supplements.

References

https://www.hsph.harvard.edu/nutritionsource/antioxidants/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249911/
https://www.nccih.nih.gov/health/antioxidants-in-depth
https://pubmed.ncbi.nlm.nih.gov/18630141/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614697/
https://www.ahajournals.org/doi/10.1161/circ.136.suppl_1.12351
https://www.nccih.nih.gov/health/antioxidants-in-depth
https://pubmed.ncbi.nlm.nih.gov/24915343/
https://www.sciencedaily.com/releases/2009/04/090415163730.htm
https://www.health.harvard.edu/staying-healthy/understanding-antioxidants
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249911/
https://www.cbc.ca/news/health/antioxidant-supplement-overload-can-be-hazardous-1.1412993

Phosphorus is a mineral that makes up 1% of a person's total body weight. It is also the second most abundant mineral in the body that is important for filtering out waste and building healthy bones and teeth. It is commonly found in many foods, like beer and cheese. Phosphate is a form of phosphorus that can be taken as supplements when you can’t get the required amounts through diet.

Importance Of Phosphate

Our body uses phosphorus for
- Movement of muscles
- Strong bones and teeth
- Providing energy
- Lowering post-exercise muscle pain
- Filtering waste from the kidney
- Formation of DNA
- Nerve conduction
- Maintaining a regular heartbeat

Phosphate is also known to treat urinary tract infections and prevent the development of calcium stones in the kidney.

When Was Phosphate Discovered?

In the quest to create the “philosophers’ stone” like every other alchemist, Henning Brandt, a German scientist, collected and boiled around 1200 gallons of urine. He then mixed the tar-like residue obtained with sand and charcoal and maintained the mixture at the highest temperature the furnace could reach. After several hours of heating the residue, a white vapor was formed, which was then condensed into white drops. These drops had the “glow in the dark” property and hence the substance was named phosphorus.
The discovery of phosphorus made Brandt the first-ever scientist to discover a chemical element. Due to financial constraints, he ended up selling the discovery process to other scientists. Within 50 years of its discovery, phosphorus was being produced and sold to apothecaries, natural philosophers, and showmen. Further down the line, this element was making its way into matches, fertilizer, and bombs.

What Is The RDA Of Phosphate?

The recommended dietary allowance (RDA) of phosphate varies between 100mg and 1250 mg. Infants need about 200mg, while children between the ages of 9 and 18 need 1250 mg. Adults need 700mg.

How Genes Influence Phosphate Requirements?

CASR Gene and Phosphate Needs

The CASR gene encodes the calcium-sensing receptor (CASR). It is found in the plasma membranes of the parathyroid gland and renal tubule cells (in the kidneys). Calcium molecules bind to the calcium-sensing receptors. This receptor also regulates the release of the parathyroid hormone, which is responsible for phosphorus reabsorption in the kidney.

rs17251221 of CASR Gene And Phosphate Deficiency Risk
rs17251221 is an SNP in the CASR gene. The G allele of rs17251221 was also associated with higher serum magnesium levels and lower serum phosphate levels. Each copy of the G allele was also associated with a lower bone mineral density at the lumbar spine.

Non-genetic Factors Influencing Serum Phosphate Levels

  1. Vitamin D3 levels: A deficiency in vitamin D levels could result in poor absorption of phosphate
  2. Alcoholism: Alcoholism is treated with refeeding, which depletes phosphate levels
  3. Dietary intake: Severe malnutrition, such as from anorexia or starvation, can result in phosphate deficiency
  4. Kidney disease: Affects the renal reabsorption of phosphate
  5. Diarrhea: Diarrhea has been shown to increase phosphate losses through the intestines

What Happens When Phosphate Levels Are Too Low?

  1. Low phosphorus levels can result in
  2. Anxiety
  3. Appetite loss
  4. Joint pain
  5. Irritability
  6. Tiredness or fatigue

Children with phosphorus deficiency may also show poor bone development.

What Happens When Phosphorus Levels Are Too High?

Hyperphosphatemia is a rare condition characterized by high levels of phosphorus in the blood. It occurs mainly due to kidney problems or issues in calcium homeostasis (maintenance of calcium levels). The presence of higher levels of calcium in the blood can result in:
1. Diarrhea
2. High vitamin D levels
3. Damage to kidneys
4. Serious infections

"## What Is The Test To Identify Phosphorus Levels?
Phosphorus levels can be determined using a serum phosphorus test. This test is usually carried out to check phosphate levels as an indicator of kidney or bone disease. It also aids in assessing the functioning of parathyroid glands.
"

Dietary Sources Of Phosphorus

Plant Sources Of Phosphorus

Animal Sources Of Phosphorus

Summary

  1. Phosphorus plays an important role in the health of bones, muscles, and kidneys. It works with calcium to regulate bone health.
  2. Most people get enough phosphorus through their diets; however, several factors can affect its absorption in the body.
  3. A region rs17251221 in the CASR gene influences the intestinal absorption of phosphorus; the G allele has been associated with decreased absorption and, thus, decreased phosphate levels in the body.
  4. Low vitamin D3 levels, diarrhea, and alcoholism are also risk factors for phosphate deficiency - it can lead to anxiety, joint pain, and fatigue.
  5. Some dietary sources of phosphorus are dairy, nuts, chicken, and seafood.

Reference

https://medlineplus.gov/genetics/gene/casr/
https://academic.oup.com/hmg/article/19/21/4296/665947
https://www.mayoclinic.org/diseases-conditions/rickets/symptoms-causes/syc-20351943

Iron is an essential mineral that is a major component of hemoglobin - a protein in blood that transports oxygen in the body. It also binds to myoglobin, a protein present in muscle tissues, and provides oxygen.

This mineral is naturally present in many foods as well as added to some food products - iron-fortified foods. It is also available as a dietary supplement.

Dietary iron has two main forms: heme and nonheme. Heme iron (present as hemoglobin/myoglobin) is found only in animal flesh like meat, poultry, and seafood. Non-heme iron is found in plant foods like whole grains, nuts, seeds, legumes, and leafy greens. Heme iron is more well-absorbed than non-heme iron.

Importance of Iron

History of Iron in Human Health

Studies suggest that an estimated 2 billion in the population suffer from the most common outcome of iron deficiency - Iron Deficiency Anemia (IDA).

Human skeletal remains from prehistoric times show small holes in the outer layers of the skull. This condition, called Porotic Hyperostosis (PH), was put forth by Stuart-MacAdam in 1992, who said that these findings in the remains of prehistoric times became more evident as mankind moved from being hunters to an agricultural society. One of the prominent crops that he holds responsible for iron deficiency in prehistoric humans is maize, as it is a poor source of absorbable iron. It has also been suggested that iron-deficiency causing PH usually occurs in infancy.

Chalybeate waters
Early in the 17th century, Chalybeate water (named after the Chalybes, skilled ironworkers in Roman Asia Minor) was identified. These waters were found to be rich in salts of iron. It has been suggested that the chalybeate waters have contributed to the healing properties since prehistoric times and were considered to be beneficial to cure conditions like anemia. Many British spa towns are famous for their chalybeate springs. Despite the importance of chalybeate waters for healing, the role of iron in hemoglobin formation and red cell function took centuries to be recognized.

Identifying iron deficiency
It was only in 1902 Bunge, a professor of physiology in Basle, identified the possibility of iron-deficiency and admitted that 'the habitual consumption of foods poor in iron may lead to anemia.' However, he contradicted this by stating that ‘it is difficult to imagine a diet that would not contain the small amounts of the metal required daily.’
He also conducted studies to show that human breast milk was very low on iron but recognized that foods like spinach, egg yolk, lentils, beef, and apples were iron-rich. He said that newborn infants had much higher concentrations of iron in their liver and kidneys compared to older infants, children, or adults.
Bunge considered iron deficiency ‘unimaginable’; despite that, he also stated that iron supply through just food sources is not sufficient to treat iron deficiency.

RDA of Iron

The recommended amount of dietary iron intake is slightly higher for adult women than men. For men over 18 years, the RDA is 8.7mg a day, while it is 14.8mg a day for women aged 19 to 50. Women need more iron than men to make up for the amount of iron they lose in their menstrual period.

The RDA for vegetarians is 1.8 times higher than for people who eat meat - this is because the iron from animal sources is more easily absorbed than iron from plant sources.

Genetics of Iron Requirements

TMPRSS6 gene is associated with the synthesis of a protein TransMembrane PRotease Serine 6 (also known as matriptase-2). This protein regulates the levels of another protein, hepcidin, which controls the iron balance in the body.
Whenever there are low iron levels in the body, hepcidin production is reduced, allowing more amounts of iron to be absorbed from the diet.
There are two Single Nucleotide Polymorphisms (SNPs) in this gene, rs855791 and rs4820268 that influence the serum iron levels.

rs4820268 of TMPRSS6 Gene and Iron Deficiency Risk

In a study conducted on children aged 6-17 months, G allele in rs4820268 was identified as the “Iron-Lowering Allele” (ILA) - it led to the overexpression of hepcidin, thereby reducing the serum iron levels.

rs855791 of TMPRSS6 Gene and Iron Deficiency Risk

In a study conducted on 2100 elderly women, people with the T allele in rs855791 had lower serum iron and hemoglobin levels.
Another study on 14,100 Danish men also revealed the T allele to be associated with lower iron levels in the body.

Some other genes that play a role in iron levels in the body are TF (transferrin) and TFR2 (transferrin receptor 2).

Non-genetic Factors That Influence Iron Requirements

Some groups of people are at an increased risk for iron deficiency:
1. Pregnant women: Iron needs increase during pregnancy to meet the needs of the growing fetus and placenta.
2. People with cancer: Many cancers like colon cancer are associated with chronic blood loss - so they may require more iron. Sometimes the requirements may increase due to the risk of chemotherapy-induced anemia.
3. People who donate blood frequently: According to a study, 25-35% of frequent blood donors develop iron deficiency.
4. People with heart failure: Poor nutrition, absorption, and use of aspirin or oral anticoagulants are the common causes of iron deficiency in people with heart failure.
5. Infants and children: Iron deficiency is more commonly seen in preterm births or infants with low birth weight.
Even full-term infants can develop an iron deficiency if they do not obtain enough iron from solid foods.

Effects of Iron Deficiency

Effects of Excess Iron

The Tolerable Upper Limit - TUL (highest level of daily intake that is likely to pose no adverse health effects) for iron in healthy adults over 19 years of age is 45 mg.
Acute intakes of more than 20 mg/kg iron from supplements can lead to iron toxicity. It can also reduce zinc absorption and plasma zinc concentrations.
Some signs of excess iron consumption include:
- Nausea
- Constipation
- Gastric upset
- Abdominal pain
- Vomiting

Dietary Sources Of Iron

Iron is an essential nutrient, which means that you need to get your iron from food sources/supplements.

Animal Sources

  1. Liver and organ meats
  2. Red meat
  3. Shellfish
  4. Turkey
  5. Fish

Plant Sources

  1. Spinach
  2. Broccoli
  3. Legumes
  4. Tofu
  5. Dark chocolate
  6. Quinoa

Summary

Reference

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2141.2003.04529.x
https://en.wikipedia.org/wiki/TMPRSS6
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521251/
https://www.ncbi.nlm.nih.gov/pubmed/22323359
https://www.ncbi.nlm.nih.gov/pubmed/26597663
https://en.wikipedia.org/wiki/Transferrin
https://en.wikipedia.org/wiki/Transferrin_receptor
https://pubmed.ncbi.nlm.nih.gov/25668261/

Calcium is the most abundant material in the body. The body stores over 99% of the calcium in bones and teeth. The rest is found in nerve cells, body tissues, blood, and other body fluids. The body uses bones as a reservoir for (and sometimes source of) calcium. A proper level of calcium in the body over a lifetime can help prevent osteoporosis.
When you don’t get enough calcium, you also increase your risk of developing other conditions like:
- Osteopenia
- Calcium deficiency disease (hypocalcemia)

Importance of Calcium

Other than its vital role in the formation and strengthening of bones and teeth, calcium also helps with the following:
- Muscle contractions
- Normal enzyme functioning
- Clotting blood
- Sending and receiving nerve signals
- Squeezing and relaxing muscles
- Releasing hormones and other chemicals
- Maintaining a normal heart rhythm

The Evolutionary Perspective of Calcium

The present nutritional requirements of calcium is a result of a 200 million year evolution. The evidence indicates that this evolution occurred in a high-calcium nutritional environment.

Humans who lived during the Stone Age period consumed a lot more calcium (1500mg/day or even more) than we do today. The higher calcium consumption can be attributed to the requirement for higher physical exertion. Examination of bony remains from that period revealed a higher bone mass and lesser age-related bone loss.

While the Americans today get the majority of calcium through dairy foods, the stone age people had to rely on plant sources as domestication hadn’t begun by then. Their diet was also high in protein, fiber, and other micronutrients, and at the same time, low in sodium and fats. Archaeological evidence suggests that the Stone Age diet helped prevent diseases like heart disease, stroke, osteoporosis, and other chronic diseases.

Evolution has programmed our genes to adapt to a certain kind of nutritional pattern- which has many positive implications on our health. Changing our diet to match this ‘designated’ nutritional pattern can be a big challenge but can help achieve major improvements in our health.

RDA of Calcium

The RDA of calcium for adults 19-50 years of age is 1000 mg for both men and women. Women who are 51 and older (post-menopausal) and men who are 71 and older require about 1200 mg of calcium.
However, the WHO states that adults require only 500 mg of calcium per day.

How Genes Influence Calcium Requirements?

CASR Gene and Calcium Needs

The Calcium sensing receptor (CASR) gene encodes a calcium-sensing receptor, which binds to calcium present in the blood. The [CASR protein}(https://medlineplus.gov/genetics/gene/casr/) is present on the cells of the parathyroid glands and is associated with the secretion of the parathyroid hormone. This hormone transfers calcium from the bone into the blood, with bones acting as storage centers for calcium.
When calcium levels are high, the levels of parathyroid hormone are low. This facilitates increased binding of calcium to CASR receptors in the kidney. This ultimately leads to more removal of calcium via kidneys.

rs1801725 of CASR Gene And Calcium Deficiency Risk
rs1801725 is an SNP in the CASR gene associated with serum calcium levels. This SNP is also called A986S. It contributes to 1.26% of the variance in serum calcium levels. The T allele of rs1801725 was associated with higher serum calcium.

rs17251221 of CASR Gene And Calcium Deficiency Risk
Previous studies have indicated that rs17251221 in the CASR gene is associated with total serum calcium levels. People with the GG + GA genotypes have higher calcium levels than those with the AA genotype.

GATA3 Gene and Calcium Needs

GATA3, or GATA binding protein 3, is a gene that is located on chromosome 10 and belongs to the GATA family of transcription factors.
Defects in this gene have been associated with hypoparathyroidism.
Hypothyroidism causes a reduction in the calcium levels in the blood, i.e., hypocalcemia.

rs10491003 of GATA3 Gene And Calcium Deficiency Risk
rs10491003 is an SNP in the GATA3 gene. It is implicated in disorders of calcium imbalance. The T allele has been associated with a 0.027 unit increase in calcium levels.

CYP24A1 Gene and Calcium Needs

The CYP24A1 gene is located on chromosome 20 and encodes the enzyme 24-hydroxylase.
This enzyme is responsible for controlling the amount of active vitamin D available in the body.
Vitamin D is absolutely essential for the proper absorption of calcium from the intestines and is also involved in various processes required for bone and tooth formation.
Many mutations in this gene are found to be associated with idiopathic infantile hypercalcemia 1.

rs1570669 of CYP24A1 Gene And Calcium Deficiency Risk
rs1570669 is an SNP in the CYP24A1 gene. The A allele in this SNP is associated with a 0.012-0.024 decrease in the serum calcium levels. People with the AA genotype are at a higher risk for calcium deficiency.

Other genes like CARS, DGKD, DGKH, GGCKR, TTC39B, and WDR81 also influence calcium levels in the body.

Non-genetic Factors That Influence Calcium Requirements

Factors That Lower Calcium Levels

Causes Of Increased Calcium Levels

Overactivation of parathyroid hormone: Also called hyperparathyroidism, this condition results in excess parathyroid hormone. This results in a calcium imbalance.
Medications: Diuretics release a lot of water from the body, which results in the underexcretion of calcium. Lithium causes excess secretion of the parathyroid hormone.
Lung diseases: Certain lung diseases like sarcoidosis result in high vitamin levels, which increases the level of calcium.
Cancer: Some cancers, especially lung, blood, and breast, increases your risk for calcium buildup.
Dehydration: This, coupled with poor kidney function, can increase your calcium levels.

Symptoms of Calcium Deficiency

Also called hypocalcemia, calcium deficiency is a condition where there are low calcium levels in the body. Women are more prone to calcium deficiency, especially those who are going through menopause. This is because of the decrease in the female hormone estrogen, which plays a vital role in calcium metabolism.
Some symptoms of hypocalcemia include:
-Muscle problems such as aches, spasms, cramps
-Increased numbness and tingling in the arms, legs, hands, and feet
-Severe fatigue, lack of energy
-Dry skin
-Weak and brittle nails
-Osteoporosis, that increases the chances of breaking or brittle bones
-Dental problems like poor oral health, week roots of teeth, brittle teeth, gum irritation, increased cavities
-Depression
-Hallucinations

Symptoms of Excess Calcium

Hypercalcemia/excess calcium describes a condition where there are high concentrations of calcium in the blood. This can be harmful to your bones and organs, especially to your kidneys.
The parathyroid hormone controls the levels of calcium in the body. Hypercalcemia is usually the effect of overactive parathyroid glands that result in an increase in the blood calcium levels.
Hypercalcemia affects different organs differently:
Kidneys: Kidneys need to overwork to filter all the extra calcium. This causes increased thirst and frequent urination
Bones: The calcium in the bone is leached out into the blood - thus, it gets weakened, which results in bone pain
Abdomen: Symptoms related to the abdomen include nausea, constipation, vomiting, and abdominal pain
Heart: High calcium levels can result in abnormal heart rhythms
Muscles: Hypercalcaemia can cause muscle weakness and spasms
Brain: Symptoms like lethargy, confusion, fatigue, and even depression

Dietary Recommendation for Calcium

One of the best ways to ensure healthy and optimum calcium levels is by sufficient dietary intake of the mineral.

Animal Sources of Calcium

Plant Sources of Calcium

Summary

  1. Calcium is a mineral that is vital for the health of bones and teeth. Adequate calcium levels are very important to prevent osteoporosis, a condition where the bones become brittle and weak.
  2. Women require more calcium than men. The requirements also increase with age. Older people require more calcium in order to maintain their bone health.
  3. Certain genes regulate serum calcium levels. They do so by modifying the calcium receptors, vitamin D, and parathyroid hormone levels. Some examples of genes influencing calcium levels include CASR, GATA3, and CYP24A1. SNPs in these genes can increase or decrease the calcium levels in your body.
  4. Both excess (hypercalcemia) and low (hypocalcemia) levels of calcium are harmful. Hypocalcemia can result in muscle pain, fatigue, dry skin, depression, and brittle bones, while hypercalcemia can affect various organs like the kidney, brain, and heart.
  5. Sufficient dietary intake can help prevent calcium deficiency. Dairy products, sardines, chicken, seeds, and leafy greens are some good sources of calcium.

Reference

https://www.health.harvard.edu/staying-healthy/how-much-calcium-do-you-really-need
https://medlineplus.gov/genetics/gene/casr/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2908705/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778004/
https://medlineplus.gov/genetics/gene/cyp24a1/#conditions
https://en.wikipedia.org/wiki/Parathyroid_hormone

Choline Overview

Choline is one of the nutrients that has risen in ranks very quickly. The Institute of Medicine declares choline as an ‘essential nutrient’. There are many complex roles performed by this nutrient in the body.

While humans do produce choline in their bodies, the quantities are mostly insufficient. It is hence important to also obtain choline from the foods you eat. Choline acts like amino acids and facilitates various processes to function seamlessly.

It is not easy to decide on the global recommended values for choline intake. Certain genetic changes increase or decrease a person’s choline needs. We will discuss more of this in the genetic section.

Why Do You Need Choline?

Here are some of the important functions of choline in the body.
Helps in making fats that holds together cell membranes
Choline is useful in producing acetylcholine. This is a basic neurotransmitter (messengers that transmit signals from one cell to another)
Helps with DNA synthesis (the production/creation of DNA molecules)

The History Behind Choline

In the middle of the 19th century, a large number of researchers were analyzing the chemical composition of tissues of living organisms.

During the 1850s and 1860s, several scientists were working on a new molecule at the same time in different parts of the world.

In 1850, Theodore Gobley, a pharmacist in Paris extracted this new molecule from the tissues of the brain and named it ‘Lecithin’. The word meant egg yolk in Greek.

In 1862, Adolph Strecker, a German scientist extracted lecithin from bile and then heated it. The result was a new chemical named Choline.

In 1865, another expert named Oscar Liebreich identified a new chemical found in the brain and named it neurine.

It was later proven that choline and neurine were the same substances.

It was only in the 1930s that scientists proved fatty liver could be cured with choline supplemented food.

In 1998, choline was added to the list of essential nutrients needed for human survival.

Choline At The Molecular Level - Getting Technical

De Novo Synthesis - De Novo synthesis of choline is the production of choline inside the body. The phosphatidylethanolamine N-methyltransferase (PEMT) is an enzyme that helps convert certain kinds of lipids called phospholipids into phosphatidylcholine.

An enzyme called Phospholipase D converts phosphatidylcholine into phosphatidic acid. In this process, choline is released, which then enters circulation.

Absorption from food - Once you eat choline-rich foods, different forms of choline enter the small intestine and then choline gets stored in the liver. The liver then passes on the choline to the bloodstream and this reaches all the cell membranes.

While this would be enough to match bare requirements, you will need to match up with the right foods to get your complete recommended levels of choline.

How Genes Influence Calcium Needs

PEMT gene

The PEMT gene is responsible for making phosphatidylcholine in the body. Phosphatidylcholine is eventually converted into choline. Extreme cases of choline deficiency can lead to liver damage. For some individuals, variations in the PEMT gene can result in an increased risk of liver damage, obesity, and abdominal fat build-up.

rs12325817
The G allele of the rs12325817 SNP causes increased risk of liver problems when you consume inadequate amounts of choline.

rs7946
The C allele of the rs7946 SNP increases PEMT activity in the body. This leads to excess choline production and increased risks of obesity. The T allele however results in normal PEMT activity and normal choline levels. The risk of obesity is also low.

MTHFD1 gene

The MTHFD1 gene helps in activating folic acid into forms usable by the body. Certain variations in the MTHFD1 gene affects the choline levels in the body too.

*rs2236225 *
The A allele of the rs2236335 SNP causes folate deficiencies. When your choline intake is also low, you can develop serious signs of choline deficiency like fatty liver. The G allele however does not cause folate deficiencies. The body is able to handle a low-choline diet better without resulting in extreme symptoms.

Non-genetic Factors Affecting Choline Levels

Pregnancy and lactation - About 95% of pregnant and lactating women consume less choline than what’s needed. Women who do not consume folic acid supplements during pregnancy are at a greater risk for choline deficiency. Talk to your gynecologist to know if you should change your diet pattern during pregnancy.

Menopause - Estrogen is an important hormone that helps produce choline internally in the body. During menopause, estrogen levels come down and so do choline levels.

Alcoholics - Alcoholics have higher needs for choline. When they do not have a healthy diet regime, the chances of them developing choline deficiency is very high.

Athletes and high endurance trainers - If you are physically very active, regular workouts and training sessions can cause a fall in the choline levels. Supplements can help stabilize the levels

Symptoms Of Choline Deficiency

Since choline is also produced internally in the body, choline deficiency is rare. However, it does happen in the below categories of individuals.
- Pregnant women
- People with genetic polymorphisms that prevent absorption of choline
- Individuals who are intravenously fed

People with choline deficiency develop Nonalcoholic Fatty Liver Disease (NAFLD). This condition usually resolves when the person is supplemented with choline. Here are some of the conditions associated with NAFLD.
- Obesity
- Hypertension
- Insulin resistance
- Increased risks of liver damage, liver cancer and liver cirrhosis

Recommendations For Healthy Choline Levels

  1. For healthy adults, it is better to meet your nutritional requirements with only food sources. Make sure you include unprocessed meat, grains, egg yolk, and dairy products adequately to maintain your choline levels.
  2. Get your genetic testing done to see if you will need excess choline to stay healthy.
  3. If you are at a risk for choline deficiency because of genetic or non-genetic reasons, then do consider supplements and choline fortified foods.
  4. If you are pregnant or lactating, talk to your doctor about matching your increased needs for choline.

Summary

  1. Choline is an essential nutrient that is not given the importance it deserves.
  2. Though choline deficiency is considered rare, a lot of people don’t get enough choline from the foods they eat.
  3. Changes in certain genes can make few people require more choline than others.
  4. Unless you have extreme choline deficiency or require more choline than recommended amounts, you do not have to worry about choline supplements. Including choline-rich foods is enough.
  5. For people struggling with extreme side effects of choline, supplements can help.

Reference

https://www.hsph.harvard.edu/nutritionsource/choline/
https://ods.od.nih.gov/factsheets/Choline-HealthProfessional/
https://lpi.oregonstate.edu/mic/other-nutrients/choline
https://www.researchgate.net/publication/233773350_A_Brief_History_of_Choline
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422379/
https://www.foodnavigator-usa.com/Article/2014/10/17/Time-for-the-DGAC-to-look-again-at-choline#
https://ods.od.nih.gov/factsheets/Choline-HealthProfessional/
https://lpi.oregonstate.edu/mic/other-nutrients/choline#deficiency-symptoms

Copper is an essential mineral for the body. Along with iron, it plays a vital role in the formation of Red Blood Cells (RBCs). It is a cofactor for several enzymes (cofactors are substances required for enzyme activation). Copper is a trace element - which means our body requires it only in small quantities. It is also crucial for organ functioning and a healthy metabolism. Meeting your copper requirements is important for the prevention of osteoporosis and cardiovascular diseases. The body cannot synthesize copper on its own - therefore, it must be consumed through diet or supplements.

Copper Metabolism and Absorption - Getting Technical

Hepatocytes - cells of the liver - are the primary sites for copper metabolism.
When copper enters the body through dietary sources, it is first absorbed by the intestines.
It is then transported to the hepatocytes by a tube-like structure called the portal vein.
The copper then enters the hepatocytes - this is mediated by a protein called copper transporter (CTR1). After it enters the hepatocytes, either of the two things happens:
1. With the help of another transporter protein ATP7B, it reaches the ‘Golgi apparatus’ (packages protein to transport it to the destination) where it binds to another protein, ‘apoceruloplasmin.’ Once copper binds to this protein, it becomes ceruloplasmin. Subsequently, this ceruloplasmin exits the hepatocytes and is transported to other organs.
Sometimes, the copper is loosely bound to another protein called albumin and is circulated in the blood. This is called free serum copper.
Free serum copper + ceruloplasmin = Total serum copper
These three parameters are very important for blood diagnostics of copper metabolism.
2. If the body doesn’t require copper, it is transported to the bile ducts. From there, it is excreted into the bile.

If the ATP7B protein doesn’t function well, the copper gets accumulated in the cells leading to Wilson’s disease.

Importance of Copper

Copper is found in the cells of almost all organs. It plays an important role in blood vessel formation, maintenance of the nervous and the immune system.
Our body needs copper for several activities. These include:
1. Formation and functioning of RBCs
2. Immune functioning - by forming white blood cells
3. Fetal and postnatal brain growth and development
4. Collagen formation
5. Turning sugar into energy
6. Protection from cell damage
7. Absorption of iron
8. Maintenance of healthy skin and connective tissue

Copper and Cardiovascular Health

Copper deficiency is associated with changes in lipid levels. According to animal studies, low copper levels can lead to cardiac abnormalities.
Some researchers believe that people with heart failure can benefit from copper supplementation.

Copper and Arthritis

Some studies have shown that copper may help delay or prevent arthritis. That’s why wearing a copper bracelet as a remedy for arthritis is popular.

RDA of Copper

For adolescents and adults, the RDA is about 900 mcg per day.

The upper limit for adults aged 19 years and above is 10,000 mcg, or 10 milligrams (mg) a day. An intake above this level could be toxic.

The copper requirement changes with age, gender, and events like pregnancy.

How Genes Influence Copper Intake?

SELENBP1 and Copper Requirements

The SELENBP1 is located on chromosome 1 and encodes selenium-binding protein.
Selenium is an essential mineral and is known for its anticarcinogenic properties, and a deficiency of it can result in neurologic diseases.
While selenium-binding protein has majorly been studied only for its tumor suppressant activities, a 2013 study found a significant association between this protein and erythrocyte (red blood cells) copper levels.

rs2769264 of SELENBP1 and Copper Deficiency Risk
rs2769264 is an SNP in the SELENBP1 gene. It is located on chromosome 1. This SNP has been associated with serum copper levels. According to a study, the presence of the G allele increases the copper levels by 0.25-0.38 units.

SMIM1 and Copper Requirements

The SMIM1 gene is located on chromosome 1 and encodes Small Integral Member Protein 1. This protein plays a vital role in the formation of red blood cells.

rs1175550 of SMIM1 and Copper Deficiency Risk
rs117550 is an SNP in the SMIM1 gene. This SNP has been associated with serum copper levels. People who have an A allele in this SNP are at a greater risk for copper deficiency - the presence of A allele decreases copper levels by 0.14-0.26 units.

Non-genetic Factors That Influence Copper Requirements

Breastfeeding
Infants fed on formula milk had lower copper levels than those on breast milk.
Excess zinc
Consuming excess zinc can lead to an inefficient absorption of copper.
Gastrointestinal (GI) diseases
GI conditions like celiac diseases, short-gut syndrome, and irritable bowel syndrome can impair copper absorption.
Certain health conditions
Some conditions, such as central nervous system demyelination, polyneuropathy, myelopathy, and inflammation of the optic nerve, can increase the risk of copper deficiency.

Symptoms of Copper Deficiency

Clinical symptoms of copper deficiency include:
- Premature hair greying
- Fatigue and weakness
- Sensitivity to cold
- Easy bruising
- Weak and brittle bones
- Learning and memory problems
- Pale skin
- Unexplained muscle soreness
- Loss of vision

Symptoms of Excess Copper

Copper toxicity means you have more than 140 mcg/dL of copper in your blood. It can be caused due to excess copper in drinking water, eating meals cooked in uncoated copper cookware, and IUDs (Intrauterine devices like copper-T).
Some symptoms of copper poisoning include:
- Fever
- Headaches
- Vomiting
- Diarrhea
- Yellow skin (jaundice)
- Dark stools
- Abdominals cramps
- Anxiety
- Mood changes
If left untreated, copper toxicity can lead to liver damage, heart failure, and in some cases, death.

Dietary Sources of Copper

Animal Sources of Copper

  1. Shellfish
  2. Oysters
  3. Organ meat
  4. Salmon
  5. Liver
  6. Lobster

Plant Sources of Copper

  1. Shiitake mushrooms
  2. Nuts and seeds
  3. Sweet potatoes
  4. Chickpeas
  5. Leafy greens
  6. Dark chocolate

Summary

  1. Copper is an essential mineral which is required for the formation of Red Blood Cells (RBCs) and healthy immune functioning. Studies have also indicated that adequate copper consumption can help prevent or delay cardiovascular diseases and arthritis.
  2. Liver is the primary site of copper metabolization with the involvement of 2 important transporter proteins - CTR1 and ATP7B. It is then circulated in a bound form as ceruloplasmin or as a loosely-bound form (free form) with albumin.
  3. Two genes, namely SELENBP1 and SMIM1, are involved in regulating copper levels in the body. The A allele in an SNP present in SMIM1 has been associated with reduced serum copper levels. People who carry the AA type may be at a greater risk of copper deficiency.
  4. Copper deficiency is recognized through symptoms like premature greying of hair, loss of vision, sensitivity to cold, easy bruising, and brittle bones. While lower levels of copper are dangerous, too much of it also can harm the body. Copper toxicity is characterized by anemia, mood swings, fever, headache, and vomiting.
  5. Copper requirements can easily be met through diet. Some dietary sources of copper include shellfish, oysters, Shiitake mushrooms, nuts, and dark chocolate.

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034109/
https://pubmed.ncbi.nlm.nih.gov/10721936/
https://academic.oup.com/eurheartj/article/27/1/117/608121
https://en.wikipedia.org/wiki/Wilson%27s_disease
https://academic.oup.com/hmg/article/22/19/3998/571929
https://www.snpedia.com/index.php/Rs2769264
https://www.snpedia.com/index.php/Rs1175550
https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-015-0474-9%20

Zinc is an essential nutrient that plays many important roles in the body. It is ‘essential’ because the body cannot produce zinc on its own, and thus, it should be obtained through food sources.  

After iron, zinc is the most abundant trace mineral (minerals required in small quantities) in the body.

Zinc boosts the immune system and is important for metabolic function. 

It is well known for its role in wound healing and the sense of taste and smell. 

It is a part of many enzymes that are required for sending messages across cells in the body. 

An Interesting Note About Zinc Consumption

Zinc absorption from the diet depends on the total amount of zinc present in the food.  

It has been found that the more the amount of zinc present in food, the lower the amount absorbed. 

This means that zinc is better absorbed when taken in small doses.  

Why Is Zinc Important For Us?

Zinc plays an important role in the functioning of immune cells. So a deficiency in this nutrient can lead to a weakened immune response. 

Zinc is present in the part of the cell where the formation of DNA and proteins occur. Protein production from DNA is a multi-step process, where zinc plays an important role in each step.

Gene expression is the process where the information in the gene is used to produce proteins and other gene products. Zinc plays a role in regulating how much protein or product is produced by the genes. 

Zinc plays a role in the activity of more than 300 enzymes. The ‘zinc-binding’ sites help one compound attach to another in chemical reactions.

Zinc supports normal growth and development during pregnancy, infancy, and adolescence. According to a study, infants with low birth weight saw significant weight gain improvements when supplemented with zinc.

Zinc has anti-inflammatory properties - the ability to reduce inflammation or swelling. So, it can help with skin problems like acne and rashes.

What Are The Different Forms Of Zinc?

Zinc is available as supplements in various forms, each of which impacts health in different ways. 

Zinc sulfate is the least expensive form available; however, it is also the least absorbed by the body. This form is used for acne treatment.

Other forms of zinc include:

  1. Zinc Gluconate: It is a commonly available form and is used in many cold medications and nasal sprays
  2. Zinc Picolinate: It is easily absorbed and dissolved - more readily than the other forms - in the body to release zinc
  3. Zinc Citrate: This form of zinc supposedly tastes better than the other forms
  4. Zinc Acetate: Like gluconate, this is also commonly used in cold and flu medications 

The Story Behind Zinc Requirements

Though the importance of zinc in humans was established only in the 1960s, its impact on agricultural production was identified in 1869 itself, when zinc was reported as an important nutrient for the growth of a fungus, Aspergillus niger. In 1914, it was discovered that maize, a common crop, also required zinc for normal growth. By the 1920s, it was established that zinc is needed for the growth of all higher plants.

The years from 1920 to 1950 witnessed the essentiality of zinc in mice, poultry, and swine. However, researchers were still skeptical about the possibility of zinc deficiency in humans. This ended when the first case of zinc-deficiency-induced dwarfism that resulted in delayed sexual maturation was reported in the United States. Subsequent zinc supplementation resulted in improved growth and development. 

In 1974, the National Research Council of the National Academy of Sciences declared zinc as an essential element for humans, and in 1978, FDA mandated the inclusion of zinc in prenatal supplements.

In the developing world, nearly 2 billion people may be affected by zinc deficiency. Consumption of cereal proteins high in phytate was identified as the major culprit for this. Phytate/phytic acid is a natural substance found in plant seeds. It is known for impairing the absorption of various minerals like iron and zinc. 

What Is The Recommended Daily Intake Of Zinc?

The recommended daily intake (RDI) for adults varies between 8 to 11mg. The maximum tolerable amount is 40mg per day.

Genetics of Zinc Requirements

Several proteins, called the zinc transporters are responsible for the circulation and absorption of zinc in the body. Zinc homeostasis (ability to maintain stable levels of zinc) is managed by zinc intake and output transporters that are coded by SLC30A and SLC39A gene families. 

SLC39A4 

SLC39A4 codes for zinc transporter ZIP4, which is responsible for the absorption of zinc in the intestines. Differences in the SLC39A4 can alter the structure of the ZIP4 protein and hence affect zinc absorption. Certain types of SLC39A4 gene are associated with lower zinc levels.

SLC30A2

SLC30A2 codes for zinc transporter 2 or the ZNT2 protein. This gene plays a role in neonatal (newborn) zinc deficiency. A type of this gene produces an ‘incomplete’ ZNT2 protein that results in the poor secretion of zinc into the breast milk. Infants that feed on this zinc-deficient breast milk go on to develop zinc deficiency in their later years. Two SNPs of SLC30A2, rs35235055 - also known as c.68T>C - and rs35623192 - also known as c.1018C>T - play a role in lower zinc secretion in breast milk.

SLC30A8

SLC30A8 codes for zinc transporter 8 or the ZNT8 protein. This protein is responsible for transporting zinc inside insulin cells, thereby promoting insulin release. Differences in the SLC30A8 can affect zinc transport. A certain type of this gene plays a role in increasing the risk of diabetes by reducing zinc transport and decreasing insulin secretion. A study on this gene also concluded that zinc supplementation could fix the error in glucose breakdown (by promoting insulin secretion), thereby treating diabetes.

SLC30A8 SNP rs13266634 is associated with the risk of type 2 diabetes. The CC type was found to have the lowest concentrations of zinc. Further, it was noted that zinc supplementation in people having the C type reduced the blood sugar levels.

The same study claimed that “Zinc intake has a stronger inverse association with fasting glucose concentration in individuals carrying the glucose-raising A allele of another SNP rs11558471 (in SLC30A8 gene.)” This meant that as zinc intake increased, a reduction in blood glucose levels was seen.

SLC30A3SLC30A3 codes for zinc transporter 3 or the ZNT3 protein. This protein is required for the transport of zinc into synapses, which are the site of electronic signalling between two nerve cells.

rs11126936 is an SNP in the SLC30A3 gene. A study found that individuals having TT and TG types had higher levels of zinc levels than those with GG.Previously, another SNP rs73924411 in the same gene was found to play a role in regulating zinc levels in people with cognitive impairment.

IL6

White blood cells express cytokines. Cytokines are a group of proteins that are expressed by the immune system. They play an important role in cellular communication, especially during immune responses. 

Some of these cytokines are termed as interleukins - abbreviated as IL. IL6 or interleukin 6 is a cytokine that is produced at the site of inflammation. The IL6 gene encodes IL6 protein. This is mainly responsible for the acute phase response (a response that is raised immediately after an injury/infection). 

It also has an anti-inflammatory myokine role. Myokine responses are essentially cytokine responses that occur due to muscle contraction. 

Evidence suggests that IL6 can be used as an 'inflammatory marker' for COVID-19 prognosis -meaning, higher levels of IL6 are linked to a high fatality rate of COVID-19. 

The levels of IL6 are related to the zinc levels in our bodies. 

The relationship between the IL6 gene and zinc levels is reciprocal.

When there’s a zinc deficiency, it affects the IL6 gene, increasing IL6 cytokine production, which lowers zinc levels even further. 

rs1800795

Also known as 174 G/C, rs1800795 affects the zinc levels upon dietary consumption of zinc. A study on the European population revealed that people having the GG type of rs1800975 had higher levels of IL6 (and hence, lower levels of zinc) than those with CC type.

What Are The Symptoms Of Zinc Deficiency?

According to the World Health Organization (WHO), about one-third of the world’s population suffers from zinc deficiency. 

The symptoms of zinc deficiency include:

What Are The Symptoms Of Having Excess Zinc In The System?

The tolerable upper intake level (UL) - the maximum amount of nutrient intake that is likely to be not risky for health - for zinc is 40 mg per day for healthy adults. Excessive intake of zinc can lead to zinc toxicity.

Although there are no reported zinc toxicity cases from food sources, some zinc supplementation at incorrect doses could cause a problem. 

 Zinc toxicity can result in the following symptoms:

How You Can Test Your Zinc Levels

Zinc levels can be determined using a simple blood plasma test or a urine and hair analysis, since zinc is distributed throughout the body. 

However, it is difficult to identify zinc levels using laboratory tests alone. 

Doctors may assess other risk factors, including genetics and dietary intake, along with blood test results to identify your zinc requirements.

What Are The Health Benefits Of Zinc?

Zinc Helps Boost Immunity

Zinc is important for the growth and development of immune cells, namely the T-cells and B-cells. It also plays a role in immune responses that require antibody production.

Zinc ions exhibit antimicrobial activity and are necessary for the functioning of natural killer cells (another type of immune cells)

Acrodermatitis enteropathica, a rare disease, is associated with zinc deficiency. This condition increases the risk of viral, fungal, and bacterial infections.

The zinc requirements for women increase during pregnancy. Its deficiency can be harmful to the growing fetus.

A study conducted on mice showed that gestational (during pregnancy) zinc deficiency affected the offsprings' immune function, which persisted for three generations.

Zinc Can Help Preserve Bone Health

Zinc helps the formation of cells that are required for bone building. It also slows down the excessive degradation of bones. 

Zinc forms a part of many enzymes that are necessary to hold the structure of bones in place.

According to a study, excess zinc excretion plays a role in the development of osteoporosis.

Zinc Aids The Maintenance Of Healthy Hair And Skin

Hair loss in patches is often seen in people with zinc deficiency. This is because zinc plays an important role in a process that leads to the formation of hair follicles. 

Collagen is an important protein that gives structure to the skin and protects it against different strains. Zinc is a crucial component of collagenases, the enzymes that form collagen. According to a study, zinc supplementation can help slow down the degradation of collagen.

Zinc Can Reduce The Risk Of Certain Diseases

The progression of age-related diseases like macular degeneration can be prevented/delayed using zinc supplements.

Since zinc boosts immune function, it also helps prevent infection in older people. In fact, according to a study, people with adequate zinc levels had a 50% lesser risk of developing pneumonia compared to those who had lower levels. 

Non-Genetic Factors Influencing Zinc Levels

Zinc deficiency could also occur in people with the following conditions:

  1. Crohn’s disease or similar gastrointestinal diseases
  2. Sickle cell anemia
  3. Chronic kidney disease
  4. Pregnant and breastfeeding women
  5. Vegetarians and vegans
  6. Alcohol addictions
  7. Poor absorption of protein-energy
  8. Intestinal parasites or protozoal infection
  9. Pancreatic insufficiency - leads to poor absorption in intestines

What Are The Dietary Sources of Zinc?

Zinc is not stored in the body, so it must be included in the diet to ensure sufficient amounts are available. A healthy and balanced diet, which includes zinc-rich foods, will ensure sufficient vitamin and nutrient intake.

Animal Sources

  1. Oysters: Shellfish, in general, are healthy, low-calorie sources of zinc. Per 100 grams, oysters provide 61 mg of zinc. 
  2. Red meat: 100g of red meat contains around 4.8 mg of zinc, which is around 44% of the RDA.
  3. Eggs: With one big egg, you can meet 5% of the RDA for zinc.

Plant Sources

  1. Soy products: Food sources derived from soy like tofu, legumes can help you meet 12-15% of the RDA for zinc.
  2. Seeds: Although most seeds are packed with nutrients, some are better sources of zinc than the other. Hemp seeds, in particular, contain 3 mg of zinc per ounce.
  3. Nuts: Cashews, almonds, peanuts, and pine nuts don’t just boost zinc levels but are also rich in healthy fats and fiber.

Summary

Zinc is a trace mineral that is important for its role in immune function, growth and development, and protein production. The role of zinc in human health was only identified in the 1960s, and since then, the FDA has made it mandatory to include it in all prenatal products. The SLC gene family codes for proteins that are responsible for zinc transport and absorption in the body. Studies have shown that rs13266634 in the SLC30A8 gene plays a role in zinc transport into insulin cells. Individuals who have the CC type have decreased transport of zinc to the insulin cells. This results in lowered secretion of insulin, and hence a higher risk  for type 2 diabetes. rs35235055 and rs35623192 are two SNPs in SLC30A2 gene that are important for transport of zinc to the breast milk. Lower levels of zinc in breast milk can increase the risk for neonatal zinc deficiency. The recommended daily intake (RDI) for adults varies between 8 to 11mg, with maximum tolerable amount being 40mg per day. Oysters are an excellent source of zinc with one serving providing over 600% of the RDI. Some plant based food sources rich in zinc are tofu, legumes, hemp seeds, and nuts. 

References

  1. https://www.hsph.harvard.edu/nutritionsource/zinc/
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877790/
  3. https://pubmed.ncbi.nlm.nih.gov/29193602/
  4. https://academic.oup.com/advances/article/3/6/783/4557955
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649098/
  6. https://www.nature.com/articles/pr2016108?proof=t
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896616/
  8. https://www.mdpi.com/2072-6643/9/2/148/htm
  9. https://www.sciencedirect.com/science/article/abs/pii/S1344622317303565
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896616/
  11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7129451/
  12. https://pubmed.ncbi.nlm.nih.gov/28218639/
  13. https://www.who.int/whr/2002/chapter4/en/index3.html

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 Story Behind Vitamin E

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. 

Molecular Role Of Vitamin E- Getting Technical

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. 

Did You Know?

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.

What Happens When You Take Excess Of Vitamin E

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. 

What Happens When You Have Vitamin E Deficiency

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:

Non-Genetic Factors Affecting Vitamin E Levels

Genetic Factors Affecting Vitamin E Levels

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.

Recommendations For Healthy Vitamin E Levels

Summary

  1. Vitamin E is a fat-soluble vitamin that is especially known to maintain healthy skin.
  2. Vitamin E is available naturally in eight forms. The alpha-tocopherol form is the major kind used by the body.
  3. This nutrient is an excellent antioxidant and prevents free radical damage to the cells in the body.
  4. While vitamin E deficiency in healthy individuals is rare, vitamin E toxicity can happen when you consume excess supplements.
  5. There are many health conditions that can prevent the normal absorption of vitamin E from the intestine and hence leads to a possible deficiency.
  6. Genetically, few people can be prone to requiring more vitamin E levels than normally recommended doses. Get your genetic testing done to know your recommended vitamin E values.

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266234/

https://academic.oup.com/jn/article/135/3/363/4663706

http://www.vivo.colostate.edu/hbooks/pathphys/topics/vitamine.html

https://pubmed.ncbi.nlm.nih.gov/23183290/

https://www.healthline.com/health/food-nutrition/vitamin-e-deficiency

https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/

 https://www.healthline.com/health/all-about-vitamin-e

https://www.hsph.harvard.edu/nutritionsource/vitamin-e/

https://lpi.oregonstate.edu/mic/health-disease/skin-health/vitamin-E

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.

The Story Behind 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.

The Significance of Vitamin K

Vitamin K Requirements For Newborns

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:

  1. Vitamin K injection: In multiple scientific studies, the vitamin K shot has proved effective in preventing both early and late forms of bleeding.
  2. Oral vitamin K: Oral supplements are not absorbed by the babies effectively, and thus are not as effective as an injection. Hence, 3 doses of vitamin K supplements are required. 

So far, vitamin K administration to the newborns has not resulted in any noticeable side effects. 

The Recommended Dietary Allowance (RDA) for Vitamin K

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.

Genetic Influence On Vitamin K Status

VKROC1 Gene

VKROC1 gene is located on the short or p-arm of chromosome 16.

Chromosomal location of VKORC1 gene.
Chromosomal location of VKORC1 gene.

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. 

rs9923231

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.

GGCX Gene

The GGCX gene is located on the p arm of chromosome 2. 

Chromosomal location of GGCX gene vitamin K gene
Chromosomal location of GGCX gene

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. 

rs699664

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. 

Non-Genetic Factors That Influence Vitamin K Requirements

What Happens When You Have Vitamin K Deficiency

Vitamin K deficiency can be very dangerous, as it could result in uncontrolled bleeding - which is the primary symptom.

Other symptoms include:

What Happens When You Take Excess Vitamin K?

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.

What Are The Foods Rich In Vitamin K?

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:

Other sources of vitamin K include

Summary

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!

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040265/

https://pubmed.ncbi.nlm.nih.gov/9076586/

https://pubmed.ncbi.nlm.nih.gov/23850343/

https://medlineplus.gov/genetics/gene/vkorc1/

https://www.snpedia.com/index.php/Rs9923231

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761647/

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