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.
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.
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 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.
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.
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.
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.
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.
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.
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
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.
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
Weight gain is an increase in body weight which can occur due to increase in muscle mass, fatty acids accumulation or even buildup of excess water.
Weight gain has been linked to many health conditions like obesity, diabetes, heart disease, and hypothyroidism.
According to the WHO, world wide obesity has tripled since 1975, and around 39% of the adults in the world are overweight.
A person is considered overweight if the Body Mass Index (BMI) is greater than 25.
There are two globally seen reasons for weight gain:
1. You consume more energy (calories) than you expend
2. A sedentary lifestyle with very little to no physical activities
Other leading causes for weight regain include:
Foods that are sugar and fat-filled tend to stimulate the reward center in your brain (regions in the brain that give rise to feelings of pleasure and reward). Prolonged junk food consumption can thus cause addiction. Food addiction is often compared with addiction to alcohol and drugs.
Insulin regulates blood sugar levels by moving the sugar into cells. It also promotes fat storage in the body. Insulin resistance leads to increased production of insulin. This leads to increased hunger and appetite.
Leptin is a satiety hormone that reduces appetite. With leptin resistance, the hormone fails to signal to the brain how high the fat storage is in your body. This is one of the main causes of obesity in adults.
Muscles are an efficient calorie burner. As you age, your muscle mass decreases, and as a result, you tend to burn fewer calories. If the diet is not adjusted accordingly, it may result in weight gain.
Steroids are usually used to treat conditions like arthritis and asthma. Steroids affect your metabolism and the way your body stores fats. It also increases your appetite leading to weight gain, especially in the abdominal area.
Different people respond in different ways to stress - while for some people, stress may result in weight loss, in most others, it leads to weight gain. When the stress hormone cortisol levels increase, your appetite also increases, which can lead to overeating and weight gain.
In the evolutionary history of humankind, body fat seems to have been nature’s way of storing its own food reserves. During the times of famine, people who had these “thrifty” genes that could store the greatest amount of food as fat had a better survival advantage than the others. In fact, this ability to produce more fat from less food intake may have been the difference between life and death for the species.
Fast-forwarding to this era of surplus food availability, these genes are no longer “advantageous.” In fact, it is those very same genes that have been implicated in obesity and weight gain. The easy availability of high-calorie foods and reduced physical activities seem to be the two main players that account for obesity.
More than 400 genes have been studied in association with overweight and obesity - however, only a few of them have shown a strong influence on weight gain. These genes play a role in:
- How your body stores and burns off the fat
- Your appetite
- The levels of hunger and satiety hormones
- How your body responds to stress.
The influence that genes exert over all these variables differ from person to person. Knowing the extent to which your genes influence weight gain can come in handy for weight management and weight loss measures.
FTO gene is located in chromosome 16 and encodes the enzyme alpha-ketoglutarate dependent dioxygenase FTO. FTO gene is highly active in the hypothalamus region of your brain, which controls appetite. This was the first gene to be linked to obesity. Even though the association was observed only in Europeans at first, many studies since then have confirmed the same effect on other populations. Even now, many scientists suggest that the FTO gene has the largest known effect on body weight.
rs9939609 of FTO Gene and Tendency to Gain Weight
rs9939609 is a well-researched SNP in the FTO gene. The A allele in this gene is associated with an increased expression of the FTO gene. People with the AA and AG types have an increased appetite and tend to gain more weight than those with the GG type.
Several other genes, like BDNF, LEP, ADIPOQ, ADRB1, UCP, PCSK, etc., also influence your tendency to gain weight.
An underactive thyroid leads to a decreased production of thyroid hormones - a condition known as hypothyroidism. This results in slowed-down metabolism, which may contribute to weight gain.
Cushing syndrome is a condition characterized by increased production of the cortisol hormone. Elevated levels of cortisol interfere with your metabolism and may put you at risk for weight gain. It also results in deposits of fatty tissues at the midsection, face, and lower back.
Insomnia is another condition that results in elevated levels of cortisol as well as another hormone, insulin. These hormones can interfere with the secretion of hunger and satiety hormones, making you crave sugary and fatty foods.
This condition is commonly observed in women of early reproductive ages. PCOS occurs due to a buildup of the male hormone, androgen. Elevated androgen levels lead to insensitivity to insulin. As a result, blood sugar builds up, leading to weight gain.
Congestive heart failure occurs when your heart cannot pump out enough blood to meet your body’s needs. As a result, blood and other fluids can build up in your ankles and feet, resulting in swelling and rapid weight gain.
Your calorie requirement is based on your gender, body weight, age, and level of physical activity. After you calculate your calorie needs, estimate your calorie intake, and match them to your needs. If you are looking to lose weight, consume fewer calories.
Cane sugar is essentially sucrose, which is harmful to the body when consumed in higher quantities. This type of sugar is often added to sweets and foods and can cause weight gain.
Muscle building powers up your metabolism and minimizes naturally occurring muscle loss. This way, if you choose your calories wisely, you can consume more of them without the threat of gaining weight.
Stress, as we know by now, leads to weight gain. People who are stressed out tend to overeat and go for high-calorie comfort foods. Stress can be identified with some warning signs like irritability, anxiety, and muscle tension. Meditation, a healthy sleep cycle, yoga, and mindful eating are excellent ways to combat unwanted stress.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2235907/
https://www.healthline.com/nutrition/leptin-101/
https://www.mayoclinic.org/healthy-lifestyle/weight-loss/in-depth/metabolism/art-20046508/
https://www.healthline.com/health/steroids-and-weight-gain
https://www.medicinenet.com/does_stress_make_you_fat/ask.htm
https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/fto-gene
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077364/
Differences in circadian rhythm influence chronotype, which refers to the fundamental 24-hour physiological cycle essential for various molecular and behavioral processes.
It helps regulate sleep patterns.
The timing of circadian rhythms varies across individuals and is influenced by both environmental and genetic factors.
People with earlier rhythms tend to rise early in the morning and feel sleepy earlier at night.
If your body sides with the “morning clock,” you are a “morning person.”
The other end of this spectrum has people with delayed rhythms.
They tend to sleep and wake up late and are often referred to as an “evening person” or a “night owl.”
Research has shown that morning people are more focused, persistent, agreeable, plan their future better, and are less likely to smoke, drink, or get depressed.
They may exhibit characteristics like:
Similarly, night owls enjoy a burst of strength during the night and may exhibit characteristics like:
A GWAS study of self-reported chronotype (morning/evening person) of UK Biobank data identified 22 regions in the circadian rhythm and photo-reception genes associated with morningness.
One of the strongest associations was seen in the rs516134 SNP located near the RGS16 gene.
The RGS16 gene contains instructions for producing a protein that belongs to the regulator of G protein signaling.
This protein is responsible for turning off certain signal communications between cells in the body.
Microarray studies and gene expression analysis have demonstrated that the RGS16 gene exhibits circadian variations.
According to a study, mice lacking this gene have a longer circadian period.
The rs516134 is a C>T polymorphism located in the RGS16 gene. The C allele is found to be strongly associated with morningness.
A study found that morningness is significantly associated with gender, with a prevalence of 39.7% in males and 48.4% in females.
People over 60 were more likely to prefer mornings than people under 30 - meaning people’s sleep preferences may change over time.
https://pubmed.ncbi.nlm.nih.gov/27494321/
https://pubmed.ncbi.nlm.nih.gov/26835600/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428740/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018537/
Sleep is a critical component of optimal health. A healthy sleep comprises various aspects, including adequate duration, good quality, and the absence of sleep disorders. Inadequate sleep at night is generally associated with:
- Daytime sleepiness
- Daytime fatigue
- Depressed mood
- Poor functioning
- Other health issues
Sleep duration refers to the total amount of sleep obtained either during the nighttime sleep event or across the 24-hr period.
Importance of An Adequate Sleep
Getting enough sleep at night is very important for several reasons. Sleep is linked to your mental and physical health and quality of life. When you get adequate sleep at night, you can be more productive and concentrate better during the day. It reduces your risk of heart disease and prevents depression. Your immune system becomes stronger as sleep helps the body to repair and recover. Your athletic performance can also be improved because of a good night’s sleep. Not getting enough sleep can make you gain weight faster.
RDA: What Is The “Ideal” Sleep Duration?
National Sleep Foundation guidelines recommend 7-9 hours of sleep per night for healthy adults. Babies, young children, and teens need even more sleep to enable their growth and development. People over 65 should also get 7 to 8 hours of sleep per night.
How Does Genetics Affect Sleep Duration?
Studies have shown that certain genetic variants influence habitual sleep duration, which explains why some individuals need more sleep than others.
Twin studies have shown that the heritability estimation of sleep duration is around 10 - 40%.
A GWAS study of self-reported chronotype and sleep duration of UK Biobank data identified several genetic regions associated with sleep duration. This study documented that people with genetic variants for longer sleep duration reported an average of 22 minutes more sleep.
The PAX8 gene encodes a member of the paired box (PAX) family of transcription factors involved in thyroid follicular cell development and the expression of thyroid-specific genes.
Variations in the PAX8 gene may affect different functions, including DNA binding, gene activation, and protein stability.
Research studies have found that the sleep-wake cycle may be influenced by regulating thyroid hormone levels. Individuals with hypothyroidism (a condition in which the thyroid gland does not produce enough thyroid hormones) are prone to excessive sleepiness. People with hyperthyroidism (in which the thyroid makes too much of the hormone), on the other hand, may have insomnia.
The rs62158211 is a G>T polymorphism located in the PAX8 gene. The T allele is associated with longer sleep duration.
A study documented that the rs62158211 was associated with an average 2.6-minute per-allele change in sleep duration.
Non-genetic Influences On Sleep Duration
Some risk factors that lead to shorter sleep duration include alcohol consumption, smoking, and physical inactivity.
Effects of Sleep Duration on Health
Few epidemiological and genetic studies have demonstrated a strong biological link between abnormal sleep duration, risk of schizophrenia, type 2 diabetes, fetal growth, and Crohn's disease.
Sleep duration is also associated with cardiovascular diseases, type 2 diabetes, depression, automobile and workplace accidents, learning and memory problems, and prospective mortality.
TipsTo Become An Early Riser
Summary
References:
https://www.sleepfoundation.org/articles/how-much-sleep-do-we-really-need
https://pubmed.ncbi.nlm.nih.gov/27992416/
https://pubmed.ncbi.nlm.nih.gov/27494321/
https://pubmed.ncbi.nlm.nih.gov/25469926/
Caffeine is a central nervous system stimulant, which is widely used for its psychoactive effects. It is commonly used to alleviate behavioral, cognitive, and emotional deficits caused by sleep deprivation.
Regardless of its beneficial effects, caffeine may have adverse sleep-related consequences that might lead to sleep disruption and insomnia symptoms. This is because caffeine consumption is associated with lower levels of 6-sulfatoxymelatonin. 6-sulfatoxymelatonin is a substance produced during the metabolism of melatonin. It is involved in the regulation of circadian rhythm. Lower levels of 6-sulfatoxymelatonin can result in increased alertness (wakefulness).
CYP1A2 encodes cytochrome P-450 group of enzymes. These enzymes influence the absorption and metabolization of caffeine. Caffeine is absorbed rapidly and completely from the gastrointestinal tract. After absorption, the P-450 enzymes help with the metabolization. Variation in the CYP1A2 activity represents a major source of variability in the pharmacokinetics (drug absorption, distribution, metabolism, and excretion) of caffeine.
While the CYP1A2 gene is responsible for caffeine metabolism, another gene, ADORA2A, influences how your sleep is affected by caffeine intake. This gene encodes the adenosine receptor. When an adenosine molecule binds to this receptor, it inhibits all the processes that are associated with wakefulness. Caffeine acts as an adenosine receptor antagonist - it mimics adenosine and goes and binds to the adenosine receptor. This results in increased levels of free adenosine, leading to a boost in neuronal activity and wakefulness.
The adenosine A2A receptor (ADORA2A receptor) plays a role in the effects of caffeine on arousal. Mice lacking functional A2A receptors do not show increased wakefulness in response to caffeine administration, indicating that the A2A receptor mediates the arousal response.
The rs5751876 is a T>C polymorphism located in the ADORA2A gene, which modulates the sleep-wake cycle, and contributes to individual sensitivity to caffeine effects on sleep.
Studies have documented that in caffeine consumers (less than 300mg), rs5751876 - T allele is associated with a decreased risk of sleep complaints and insomnia as compared to the C allele.
If caffeine consumption is not wisely regulated, it could lead to delayed sleep and sleep deprivation. Sleep deprivation is associated with lapses in attention, lowered alertness, and reduction in cognitive function. Scientific studies have shown that a reduction in sleep time of 90 minutes could reduce objective alertness during the day time by one-third.
https://pubmed.ncbi.nlm.nih.gov/31817803/
https://pubmed.ncbi.nlm.nih.gov/15965471/
