Selenium Protects a Specific Type of Interneuron in the Brain
Summary: A new study reveals selenium is essential for the postnatal development of a specific type of interneuron.
Source: Helmholtz.
Exactly 200 years ago, the Swedish scientist Jöns Jacob Berzelius discovered the trace element selenium, which he named after the goddess of the moon, Selene. Besides its industrial applications (chemical industry, production of semiconductors and toners), selenium is an essential trace element and indispensable for humans, many animals and some bacteria. A team led by Dr. Marcus Conrad, research group leader at the Institute of Developmental Genetics (IDG) at Helmholtz Zentrum München, showed for the first time why selenium is a limiting factor for mammals.
Scientific ‘by-catch’ solves decades-old mystery
The scientists have been investigating for years the processes of a novel type of cell death, known as ferroptosis. In this context, the enzyme GPX4, which normally contains selenium in the form of the amino acid selenocysteine, plays an important role.
In order to better understand the role of GPX4 in this death process, we established and studied mouse models in which the enzyme was modified,” said study leader Conrad. “In one of these models, we observed that mice with a replacement of selenium to sulfur in GPX4 did not survive for longer than three weeks due to neurological complications.”
In their search for the underlying reasons, the researchers identified a distinct subpopulation of specialized neurons in the brain, which were absent when selenium-containing GPX4 was lacking. “In further studies, we were able to show that these neurons were lost during postnatal development, when sulfur- instead of selenium-containing GPX4 was present,” stated first author of the study, Irina Ingold.
Furthermore, the scientists were able to show that ferroptosis is triggered by oxidative stress, which is known to occur for instance during high metabolic activity of cells and high neuronal activity. “Our study demonstrates for the first time that selenium is an essential factor for the postnatal development of a specific type of interneurons,” said Dr. José Pedro Friedmann Angeli, a scientist at the IDG, describing the results. “Selenium-containing GPX4 protects these specialized neurons from oxidative stress and from ferroptotic cell death.”
Thus, the study explains why certain selenoenzymes are essential in some organisms, including mammals, whereas they are dispensable in other organisms, such as fungi and higher plants. In future investigations, study leader Marcus Conrad and his team aim to investigate how ferroptosis is triggered in cells. As a long-term goal, he wants to elucidate the role of ferroptosis in various disease conditions in order to be able to alleviate diseases, such as cancer or neurodegeneration, which are currently difficult to tackle.
ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE
GPX4 stands for the enzyme glutathione peroxidase 4, one of 25 selenoproteins in humans. In the enzyme, selenium is an integral part of the 21st amino acid selenocysteine. The enzyme plays a decisive role in ferroptosis. The word ferroptosis, which means a type of programmed cell death dependent on iron, is derived from the Greek ptosis: fall and Latin ferrum: iron. Ferroptosis has not yet been completely elucidated, but the importance of cellular suicide has already been impressively confirmed, for example, by apoptosis, which has been more extensively studied.
Source: Marcus Conrad – Helmholtz Publisher: Organized by NeuroscienceNews.com. Image Source: NeuroscienceNews.com image is credited to Ingold et al., Cell. Original Research:Abstract for “Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis” by Irina Ingold, Carsten Berndt, Sabine Schmitt, Sebastian Doll, Gereon Poschmann, Katalin Buday, Antonella Roveri, Xiaoxiao Peng, Florencio Porto Freitas, Tobias Seibt, Lisa Mehr, Michaela Aichler, Axel Walch, Daniel Lamp, Martin Jastroch, Sayuri Miyamoto, Wolfgang Wurst, Fulvio Ursini, Elias S.J. Arnér, Noelia Fradejas-Villar, Ulrich Schweizer, Hans Zischka, José Pedro Friedmann Angeli, and Marcus Conrad in Cell. Published online December 28 2017 doi:10.1016/j.cell.2017.11.048
Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis
Highlights
•Selenium-containing GPX4 is necessary for full viability of mice
•The GPX4-Cys variant is highly susceptible to hydroperoxide-induced inactivation
•Hydroperoxide induces ferroptosis in Gpx4cys/cys cells
•GPX4-Cys bypasses the requirement of selenoproteins for cell viability
Summary
Selenoproteins are rare proteins among all kingdoms of life containing the 21st amino acid, selenocysteine. Selenocysteine resembles cysteine, differing only by the substitution of selenium for sulfur. Yet the actual advantage of selenolate- versus thiolate-based catalysis has remained enigmatic, as most of the known selenoproteins also exist as cysteine-containing homologs. Here, we demonstrate that selenolate-based catalysis of the essential mammalian selenoprotein GPX4 is unexpectedly dispensable for normal embryogenesis. Yet the survival of a specific type of interneurons emerges to exclusively depend on selenocysteine-containing GPX4, thereby preventing fatal epileptic seizures. Mechanistically, selenocysteine utilization by GPX4 confers exquisite resistance to irreversible overoxidation as cells expressing a cysteine variant are highly sensitive toward peroxide-induced ferroptosis. Remarkably, concomitant deletion of all selenoproteins in Gpx4cys/cys cells revealed that selenoproteins are dispensable for cell viability provided partial GPX4 activity is retained. Conclusively, 200 years after its discovery, a specific and indispensable role for selenium is provided.
“Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis” by Irina Ingold, Carsten Berndt, Sabine Schmitt, Sebastian Doll, Gereon Poschmann, Katalin Buday, Antonella Roveri, Xiaoxiao Peng, Florencio Porto Freitas, Tobias Seibt, Lisa Mehr, Michaela Aichler, Axel Walch, Daniel Lamp, Martin Jastroch, Sayuri Miyamoto, Wolfgang Wurst, Fulvio Ursini, Elias S.J. Arnér, Noelia Fradejas-Villar, Ulrich Schweizer, Hans Zischka, José Pedro Friedmann Angeli, and Marcus Conrad in Cell. Published online December 28 2017 doi:10.1016/j.cell.2017.11.048
I LOVE cream of asparagus soup, it’s pure comfort in a bowl and so simple to make. This recipe is made with just 5 ingredients, not counting salt and pepper and is ready under 25 minutes!
Skinnytastes.com
My senior client loves it too and helps him with his lung cancer and constipation.
Connie of Motherhealth caregivers 408-854-1883
INGREDIENTS:
2 lbs asparagus (2 bunches), tough ends snapped off
1 tbsp unsalted butter
1 medium onion, chopped
6 cups reduced sodium chicken broth
2 tbsp low fat sour cream
kosher salt and fresh pepper, to taste
DIRECTIONS:
Melt butter over low heat in a large pot. Add onion and sauté until soft, about 2-minutes.
Cut the asparagus in half and add to the pot along with chicken broth and black pepper, to taste. Bring to a boil, cover and cook low about 20 minutes or until asparagus is very tender.
Remove from heat, add sour cream and using your hand held blender, puree until smooth (or in two batches in a large blender).
Rating: 3.5/4 – 311 reviews – 1 hr 10 min – 310 cal
Preparation. Cut tips from 12 asparagus; 1 1/2 inches from top and halve tips lengthwise if thick. Reserve for garnish. Cut stalks and all remaining asparagus into …
Directions. In a large saucepan, combine asparagus, chopped onion, and 1/2 cup chicken broth. Cover, and bring to a boil over high heat. In the same saucepan, melt the butter over medium-low heat. Stir in the flour, salt, and pepper. Put the sour cream in a small bowl, and stir in a ladleful of the hot soup.
Mar 7, 2018 – Melt butter over low heat in a large pot. Add onion and sauté until soft, about 2-minutes. Cut the asparagus in half and add to the pot along with chicken broth and black pepper, to taste. Bring to a boil, cover and cook low about 20 minutes or until asparagus is very tender.
Directions. Bring 6 cups water to a boil in a medium saucepan; season with 2 teaspoons salt. Add asparagus tips and blanch until bright green and just tender, 2 to 3 minutes. In another saucepan, heat olive oil over medium. Add sliced shallot and chopped garlic and cook until softened but not browned, about 5 minutes.
I developed this recipe myself by substituting asparagus for broccoli in cream of broccolisoup. It’s a big favorite at our house! —Westelle Griswa, Monroe …
Sep 29, 2017 – Learn how to create a flavorful Cream of Asparagus Soup with the addition of Parmesan Cheese and Garlic. Best part, it’s ready in 15 minutes.
This delicate and creamy asparagus soup tastes wonderfully luxurious, yet it’s made without heavy cream — just vegetables, broth and a hint of cheese puréed …
The use of vinegar (this particularly apple cider vinegar), has been effective in the treatment and the remission of many of these types of fungus.
Based on the stage of the condition and the general immunity system of the individual, whether the individual has the recuperative powers to recover with the assistance of the vinegar, the body can heal aided with less stress, adequate sleep and optimum nutrition.
High doses of Vitamin C, the use of lemon and other anti-oxidants (from whole foods) are primary cancer fighters that we can use.
Vinegar provides great benefit in countering most fungus types. Most cancer is a psychological condition, caused by free radicals within the system that have an effect upon the metabolism, creating a dissolving of the immunity system to allow these fungi, and other destructive elements (air pollution, metal toxins,stress,lack of sleep,poor nutrition, sugar) to grow in a destructive manner within the tissue.
Eggplant and garlic are rich in sulfur and other nutrients that can fight cancer.
Coramsine (SBP002) was an experimental cancer drug that was evaluated in preliminary … company in Vanuatu and markets it worldwide via the internet under the name Curaderm BEC5, a cream ofsolasodine rhamnosyl glycosides (BEC).
PDF | Solasodine rhamnosyl glycosides (BEC) are a new class of antineoplastics that show superior … and Cisplatin-Resistant Human Lung Cancer Cells,” Bio-.
rhamnosyl glycosides as anticancer agents … Solasodine rhamnosyl glycosides are secondary me- ….. the promise that BEC may be potent antineoplastic bio-.
Jul 20, 2011 – Solasodine rhamnosyl glycosides (BEC) are a new class of antineoplastics that ….. and Cisplatin-Resistant Human Lung Cancer Cells,” Bio-.
Jan 13, 2012 – Solasodine rhamnosyl glycosides cause apoptosis in cancer cells. Do they also prime the immune system resulting in long-term protection …
In this presentation, the development of promising novel cytotoxic solasodine rhamnosyl glycosides will be addressed that offer not only gains in specificity and …
Therapies of Solasodine Rhamnosyl Glycosides Derived from the … Solasodine rhamnosyl glycosides(SRGs) are chemotherapeutic agents for the treatment of cancer. SRGs in a ….. and Cisplatin-Resistant Human Lung Cancer Cells,” Bio-.
These glycoside compounds were named BEC. … “Solasodine rhamnosyl glycosides specifically Bind cancer cell receptors and induce apoptosis and necrosis.
Feb 27, 2012 – … present evidence that an eggplant extract can cure cancer, while a search of “solasodine glycosides” and “skin cancer” revealed only three.
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How to Prevent and Treat Kidney Problems With Food
Story at-a-glance
Poor kidney function is associated with diabetes, hypertension, and heart disease. Common signs of kidney problems include frequent urination, problems urinating, and constant thirst
Good kidney function is essential for maintaining homeostasis in your body, including your pH level and electrolyte balance; your kidneys also produce hormones that make red blood cells and regulate blood pressure
Most Americans consume three to five times more protein than they need, and two to four times more fructose than is safe. These two dietary factors places significant stress on your kidneys, promoting kidney disease and stones
By Dr. Mercola
Your kidneys — two bean-shaped organs — are located just below your rib cage one on either side of your spine. Positioned on top of each kidney are your adrenal glands. Each day, your kidneys filter up to 150 quarts of blood and flush out waste products through your urine.
One of the reasons why you need to drink enough water is to ensure healthy kidney function. In fact, chronic low-grade dehydration is one of the most common causes of kidney stones.
Poor kidney function is also associated with a number of other serious health problems, including diabetes, hypertension, and heart disease. Common signs of kidney problems include:
Frequent urination
Problems urinating
Pain or burning sensation during urination
Constant thirst
Good kidney function1 is essential for maintaining homeostasis in your body, starting with the composition of your blood. For example, your kidneys are responsible for maintaining proper pH level and electrolyte balance (the ratios of sodium, potassium and phosphates).
They also produce hormones that make red blood cells, and those that help regulate your blood pressure.
Dietary Factors That Threaten Kidney Health
Waste products removed by your kidneys and eliminated through your urine include urea and uric acid, produced from the breakdown of proteins and nucleic acids respectively.
Excessive protein intake increases urea, while uric acid is a byproduct of both protein and fructose metabolism. Fructose typically increases uric acid within minutes of ingestion.
Most Americans consume three to five times more protein than they need, and two to four times (or more) fructose than is considered safe. These two dietary factors, alone and especially in combination, places significant stress on your kidneys and promote kidney disease and kidney stones.
Kidney stones are particularly linked to a diet high in processed fructose and other sugars, as sugar upsets the mineral relationships in your body by interfering with calcium and magnesium absorption. The phosphorus acid in soda also acidifies your urine, which promotes stone formation.
Analgesic drugs are also known to damage your kidneys when taken in excess, and/or over long periods of time. This includes aspirin, anti-inflammatory drugs (NSAIDs), ibuprofen, naproxen, and acetaminophen — especially when taken in combination with alcohol, even if the amount of alcohol is small.
Research2,3 shows that combining alcohol with acetaminophen raises your risk of kidney damage by 123 percent, compared to taking either of them individually. Long term alcohol consumption and smoking also take their toll on kidney function.
3 Dietary Keys to Protect Kidney Function
To protect your kidney function, keep the following three basic factors in mind:
•Restrict protein to just what your body needs. An ideal protein intake is likely around one-half gram of protein per pound of lean body mass, which for most is 40 to 70 grams a day.
The American Kidney Fund recommends restricting protein to a maximum of 50 grams if you have kidney disease4
•Restrict fructose to 25 grams per day (about 6 teaspoons), or less (especially if you’re insulin/leptin resistant)
•Drink pure, clean water. Simply swapping out sweetened beverages like sodas and fruit juices for pure water can go a long way toward improving your kidney function and overall health.
The best way to gauge your water needs is to observe the color of your urine (it should be light pale yellow) and the frequency of your bathroom visits (ideally, this is around seven to eight times per day).
How to Calculate Your Protein Requirement
Considering the fact that the majority of Americans are overweight or obese, I recommend calculating your individual protein requirement based on lean bodyweight (your total weight minus your fat) only.
For optimal health, I believe most adults need about 1 gram of protein per kilogram of lean body mass (not total body weight), or 0.5 gram of protein per pound of lean body mass.
In this formula, you must first determine your lean body mass. To do that, subtract your percent body fat from 100. For example, if you have 30 percent body fat, then you have 70 percent lean body mass.
Then multiply that percentage (in this case, 0.7) by your current weight to get your lean body mass in pounds or kilos. As an example, if you weigh 170 pounds; 0.7 multiplied by 170 equals 119 pounds of lean body mass.
Using the “0.5 gram of protein” rule, you would need 59.5 or just under 60 grams of protein per day.
100 – % of body fat = % of lean mass X actual weight X 0.5 gm protein = total grams of protein recommended
Example: A 170 lb individual with 30% fat mass
100% total weight – 30% fat mass = 70 % lean mass
0.70 X 170 = 119 X 0.5 = 60 grams of protein recommended
Translating Ideal Protein Requirements Into Foods
To determine whether you’re getting too much protein, simply calculate your lean body mass as described above, then write down everything you’re eating for a few days, and calculate the amount of daily protein from all sources.
Again, you’re aiming for one-half gram of protein per pound of lean body mass, which would place most people in the range of 40 to 70 grams of protein per day. If you’re currently averaging a lot more than that, adjust downward accordingly.
The chart below can give you a general idea of the protein content of many foods. I personally use Cronometer.com to enter everything I eat and carefully calculate my protein requirement to the gram.
Just be sure to enter the correct foods and amounts into the program, as the results will be inaccurate if you don’t enter the correct details.
Red meat, pork, and poultry average 6 to 9 grams of protein per ounce.
An ideal amount for most people would be a 3-ounce serving of meat (not 9 or 12 ounce steaks!), which will provide about 18 to 27 grams of protein
Eggs contain about 6 to 8 grams of protein per egg.
So an omelet made from two eggs would give you about 12 to 16 grams of protein.
If you add cheese, you need to calculate that protein in as well (check the label of your cheese)
Seeds and nuts contain on average 4 to 8 grams of protein per quarter cup
Cooked beans average about 7 to 8 grams per half cup
Cooked grains average about 5 to 7 grams per cup
Most vegetables contain about 1 to 2 grams of protein per ounce
Interestingly, while fish is typically considered a good source of protein, most fish contain only HALF of the protein found in beef and chicken. The reduced protein content in fish may actually be one reason why the Mediterranean diet is linked to life extension and reduced risk for chronic disease.5In essence, those who eat more fish than red meat are automatically getting far less protein.
Other Dietary Dos and Don’ts If You Have Kidney Disease and/or Stones
If you have kidney disease, you also need to reduce consumption of foods rich in phosphorous, as they may promote the formation of kidney stones. On the other hand, if you have problems urinating but don’t yet have kidney disease, try adding more potassium-rich foods (primarily vegetables and seeds) to your diet. Depending on the type of kidney stone you have, you may also need to modify your diet in other ways:
•Struvite stones: Found more often in women, these are almost always the result of urinary tract infections
•Cystine stones: Represent a very small percentage of kidney stones. These are the result of a hereditary disorder that causes your kidneys to excrete massive amounts of certain amino acids (cystinuria)
•Uric acid stones: These are a byproduct of protein and fructose metabolism, and are commonly seen with gout. Cutting your protein and fructose consumption is essential for preventing and treating these types of stones. Taking potassium citrate (which lowers urine acidity and reduces urine excretion of calcium) may also help prevent uric acid stones6
•Calcium oxalate stones:7 These are the most common. About 80 percent of kidney stones are calcium based, and about 80 percent of those are calcium oxalate stones. Typically, they are the result of insufficient water intake and dietary factors, including excessive oxalate, protein, and processed salt consumption
Oxalate is found in some fruits and vegetables, but your liver produces most of your oxalate. If you are found to have oxalate stones, your physician may recommend avoiding oxalate-rich foods. Also, make sure you’re getting enough magnesium, as magnesium helps prevent calcium from combining with oxalate to form stones8
If you have calcium oxalate stones, rather than reducing your calcium intake you’ll want to minimize the amount of oxalates in your body. Soy and beer are two primary culprits that should be avoided. For reasons that are unclear, grapefruit juice has been shown to increase the risk of kidney stones9 and is therefore best avoided. Other foods that contain high levels of oxalate10 that you’ll want toavoid if you have calcium oxalate kidney stones include:
Potassium is a nutrient that receives a great deal of attention when you have kidney disease. On the one hand, potassium (a mineral and electrolyte) is essential for your cells, tissues, and organs to function properly. It plays a vital role in heart health, digestive, and muscular function, bone health, and more.
While potassium is found in many foods commonly consumed in the U.S. — including fruits, vegetables, dairy products, salmon, sardines, and nuts — only 2 percent of U.S. adults get the recommended daily amount of 4,700 milligrams (mg).
This can be problematic because potassium needs to be kept in proper balance with sodium in your blood. If you consume too much sodium, which is common if you eat many processed foods, you’ll have an increased need for potassium. Others who are at particular risk of low potassium (hypokalemia) are those with chronic malabsorption syndromes, such as Crohn’s disease, or those taking heart medicine (particularly loop diuretics).
However, anyone who eats a poor diet — an excess of processed foods and not enough fresh, whole foods — is potentially at risk of inadequate potassium levels.
All of that said, if you have severe kidney impairment, you typically need to restrict your intake of high-potassium foods.14 Why? Because your kidneys are responsible for maintaining the proper amount of potassium in your body, and when they’re not working well, your levels could become excessively elevated.
Potassium helps maintain a regular heart rhythm and plays a role in muscle function, and when your potassium level gets too high, it can lead to irregular heartbeat and/or a heart attack.
Recommended Potassium Intake Varies Depending on the Health of Your Kidneys
If your kidneys are working well, the recommended amount of potassium is about 4,700 mg per day,15 which also needs to be balanced with sodium. As a general rule, your potassium to sodium ratio should be around 5:1. The easiest way to achieve this ratio is to eat REAL food (lots of fresh vegetables), ideally organically and locally grown to ensure optimal nutrient content.
This type of whole food diet will naturally provide much larger amounts of potassium in relation to sodium, whereas a processed food diet is virtually guaranteed to provide you with an upside-down ratio. Juicing your vegetables is a good way to ensure you’re getting enough potassium.
If you have kidney disease, you need to pay careful attention to your potassium level and dietary intake. Most who are being treated for kidney disease will monitor their potassium level by measuring it monthly, and potassium- restricted diets typically recommend keeping potassium intake to about 2,000 mg per day.
Kidney-Friendly Superfoods
Besides monitoring your protein and sugar/fructose intake and drinking plenty of water, adding the following foods to your diet can also help promote optimal kidney function.16,17,18,19,20
Red bell peppers: low in potassium, rich in vitamins A, B6, C, folic acid and fiber
Cabbage: low in potassium, rich in vitamins C and K, and fiber, and phytochemicals that protect against free radical damage
Red and purple grapes: rich in antioxidants; the skin is particularly rich in resveratrol
Cauliflower: high in vitamin C, folate and fiber
Watermelon: rich in water, with diuretic properties, allowing you to produce more urine to flush out toxins
Garlic: antioxidant, anti-inflammatory, and anti-clotting properties
Lemon juice: helps reduce kidney stone formation
Onion: low in potassium, rich in antioxidants, particularly quercetin, which has natural antihistamine properties
Pumpkin seeds: rich in antioxidants, vitamins and minerals, especially magnesium, which helps reduce the risk of kidney stones
Apples: high in fiber, antioxidants, and anti- inflammatory compounds. Raw organic apple cider vinegar is helpful for the prevention of kidney stones
Kale: lower in potassium, good source of vitamins A and C, rich in iron — the latter of which is important for kidney health. Many with kidney disease are also iron deficient21
Berries,22 including blueberries, raspberries, and strawberries
Sweet potatoes: rich in beta-carotene, vitamins A and C, and fiber, and a good source of B6 and potassium
Herbal Kidney Cleansers
A number of herbs also have kidney-cleansing properties, including the following:
Ginger: purifies the blood and kidneys of toxins
Red clover: diuretic that stimulates waste removal from the kidneys
Turmeric: has antiseptic and anti-inflammatory properties that help prevent and treat kidney infections and inflammation
Chanca Piedra: Used in South America to break up kidney stones (its Spanish name actually means “stone breaker”)
Dandelion: a natural diuretic that helps strengthen the kidneys and soothe urinary tract problems
Hydrangea root: Native American remedy for kidney stones
Nettle: natural diuretic that helps purify blood and treat urinary tract infections; also high in iron, making it beneficial for building blood
Uva ursi root: helps treat urinary and bladder problems
Marshmallow root: natural diuretic that helps treat urinary tract infections, kidney stones, and bladder infections
Gravel root (Joe-Pye weed): Indian remedy for urinary tract and kidney health
Juniper: improves kidney function and helps treat urinary tract infections and kidney and/or bladder stones.
Avoid juniper berry if you have a kidney infection and/or are pregnant. Also don’t take continuously for more than four weeks
Goldenrod root: Native American remedy traditionally used to support urinary tract and kidney health
Yarrow root: a natural diuretic with antiseptic and anti-inflammatory properties; helpful for urinary tract infections
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Vitamin C inhibits the synthesis of a molecule essential for bacteria survival
That vitamin C, an anti-oxidant agent, boosts and strengthens immunity is well known. Its ability to speed-up recovery from tuberculosis and impede the TB causing bacteria from causing disease, and even kill the bacteria in culture at high concentration are also known. Now, a study by a team of researchers at the Indian Institute of Science (IISc), Bengaluru has found the molecular mechanism by which vitamin C impedes and even kills Mycobacterium smegmatis, a non-pathogenic bacterium that belongs to the same genus as the TB-causing mycobacteria. The results were published in the journal FEMS Microbiology Letters.
Stress response
During times of stress or hostile conditions, such as increased temperature and presence of antibiotics, bacteria tend to come together and form a biofilm to protect themselves. The stress response pathway is crucial for bacteria to survive during hostile conditions. So blocking this pathway is a sure way of killing the bacteria.
In mycobacterium, the (p)ppGpp (Guanosine pentaphospahte or Guanosine tetraphosphate) is a key molecule in the stress response pathway. The (p)ppGpp is synthesised by Rel protein, which in turn is made by the Rel gene.
The team led by Dipankar Chatterji from the Molecular Biophysics Unit at IISc looked at the effects of vitamin C on the stress response pathway. “We chose vitamin C because its structure is similar to (p)ppGpp,” says Prof. Chatterji. “So we hypothesised that vitamin C should be competing to bind to the Rel enzyme and inhibiting (p)ppGpp synthesis.”
To test their hypothesis, the researchers conducted experiments using M. smegmatis. M. smegmatis is used as a model organism for TB-causing Mycobacterium tuberculosis.
Role of vitamin C
In vitro studies showed “significant” inhibition of (p)ppGpp synthesis in the presence of vitamin C. The inhibition level was seen to increase as the vitamin C concentration increased. The more the vitamin C concentration, the greater the possibility of vitamin C binding to the Rel enzyme, thus inhibiting (p)ppGpp synthesis. At about 10 mM concentration, the synthesis of (p)ppGpp molecule was completely inhibited.
The binding of vitamin C to the Rel enzyme is weak and this explains why high concentration of vitamin C is needed to inhibit (p)ppGpp synthesis.
“Using Mycobacterial cells we found that 1 mM of vitamin C produced 50% inhibition in (p)ppGpp synthesis. Vitamin C is able to get inside cells and inhibit (p)ppGpp synthesis,” says Kirtimaan Syal from IISc, the first author of the paper.
When 2 mM of vitamin C was added, “significant” defect in biofilm formation was seen. There was more than 50% reduction in viability of cells in a matter of four days when M. smegmatis was treated with 2mM of vitamin C. The viability of cells reduced even further with time, raising the possibility of therapeutic implications.
In the early literature, vitamin C deficiency was associated with pneumonia. After its identification, a number of studies investigated the effects of vitamin C on diverse infections. A total of 148 animal studies indicated that vitamin C may alleviate or prevent infections caused by bacteria, viruses, and protozoa. The most extensively studied human infection is the common cold. Vitamin C administration does not decrease the average incidence of colds in the general population, yet it halved the number of colds in physically active people. Regularly administered vitamin C has shortened the duration of colds, indicating a biological effect. However, the role of vitamin C in common cold treatment is unclear. Two controlled trials found a statistically significant dose–response, for the duration of common cold symptoms, with up to 6–8 g/day of vitamin C. Thus, the negative findings of some therapeutic common cold studies might be explained by the low doses of 3–4 g/day of vitamin C. Three controlled trials found that vitamin C prevented pneumonia. Two controlled trials found a treatment benefit of vitamin C for pneumonia patients. One controlled trial reported treatment benefits for tetanus patients. The effects of vitamin C against infections should be investigated further.
Vitamin C Has Effects on the Immune System
Vitamin C levels in white blood cells are tens of times higher than in plasma, which may indicate functional roles of the vitamin in these immune system cells. Vitamin C has been shown to affect the functions of phagocytes, production of interferon, replication of viruses, and maturation of T-lymphocytes, etc. in laboratory studies [1,23,42,43,44]. Some of the effects of vitamin C on the immune system may be non-specific and in some cases other antioxidants had similar effects.
The Diverse Biochemical, Physiological, and Psychological Effects of Vitamin C
Biochemistry textbooks usually mention the role of vitamin C in collagen hydroxylation. However, the survival time of vitamin C deficient guinea pigs was extended by carnitine [45] and by glutathione [46], which indicates that scurvy is not solely explained by defects in collagen hydroxylation, and it is not clear whether hydroxylation is important at all in explaining scurvy [6]. Vitamin C participates in the enzymatic synthesis of dopamine, carnitine, a number of neuroendocrine peptides, etc. [6,47,48,49,50]. Vitamin C is also a powerful antioxidant, as mentioned above.
Experimentally induced vitamin C deficiency leads to depression and fatigue [11,51]. Recently, vitamin C was reported to improve the mood of acutely hospitalized patients [52,53]. Such effects cannot be explained by collagen metabolism, and vitamin C effects on the immune system are not plausible explanations either. Instead, the effects of vitamin C on the neuroendocrine system or carnitine metabolism might explain such effects. Thus, if vitamin C has beneficial effects on patients with infections, that does not unambiguously indicate that these effects are mediated by the immune system per se.
The Effects of Antioxidants against Infections May Be Heterogeneous
It is quite a common assumption that the effects of vitamins are uniform. Thus, if there is benefit, it is often assumed that the same benefit applies to all people. However, it seems much more likely that the effects of vitamins, including vitamin C, vary between people depending on biology and their lifestyle. Thus, it is possible that there are benefits (or harms) restricted to special conditions or to particular people. In the case of vitamin E, there is very strong evidence for the heterogeneity in its effects on pneumonia [54,55] and on the common cold [56]. Although the factors modifying the effects of vitamin E cannot be extrapolated to vitamin C, it seems probable that there is comparable heterogeneity in the effects of vitamin C.
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