Whether we’re juggling childcare, work, caring for the elderly, volunteering or all of the above, we women do it all! Fueling our bodies with the right nutrients to stay healthy can be especially challenging, given our hectic schedules.
What’s more, our nutritional needs change throughout the different stages of our lives. That’s why having a strategic supplement plan is a great way to complement a healthy lifestyle.
But where to start? Choosing the right supplements is tough. So, the experts at Life Extension put together a list of the top supplement recommendations you should be taking to properly nourish the warrior woman that you are!
Your body needs minerals to function optimally. And while you don’t need large amounts compared to macronutrients like carbs, proteins and fats, not getting enough can affect your overall health and lead to more serious health implications.
Most of us occasionally gravitate towards less-than-ideal dietary choices from time to time, like processed foods, which lack necessary minerals. “Getting your minerals from nutrient-rich foods is the best starting point,” explained Registered Dietitian Holli Ryan. “Then, turn to your customized supplement plan to target any nutritional gaps.”
|
Mineral |
Health benefits |
Food source |
Recommendations |
|---|---|---|---|
|
Iron |
Your red blood cells need iron to carry oxygen, supporting energy production and healthy muscle function. |
Red meats, seafoods, poultry, leafy greens, vegetables, lentils, beans, dried apricots and raisins. |
A highly absorbable iron supplement is ideal. |
|
Calcium |
Essential for sturdy bones and healthy teeth, muscle health, cell-to-cell communication and hormone balance. |
Dairy and non-dairy products like almonds, bok choy, kale, spinach, broccoli. |
Look for bone-friendly calcium supplements that are easy for your body to absorb. |
|
Magnesium |
Needed for healthy energy and protein production, and bone, muscle and nerve health. |
Dark, leafy greens, avocados, dark chocolate, cashews and brown rice. |
Adding a magnesium supplement helps ensure you meet your daily needs. |
Plus, healthy mineral levels also depend on your age and how well your body absorbs and uses the foods you eat, pointed out Life Extension's Education Specialist, Dr. Crystal M. Gossard, DCN. "Your body will require different amounts of certain minerals throughout the different stages in your life," she explained.
If you're of childbearing age, for example, you'll "need more iron than when you start menopause because the menstrual cycle depletes iron levels," added Dr. Gossard. Once you reach menopause, however, you can switch to a lower dose of iron intake and turn your attention more to calcium and magnesium.
Vitamins are crucial for your overall well-being. But the hectic demands of our daily lives make it easy to fall behind because (let's be honest), who has time to eat five to seven servings of fruits and veggies every day?
If your first thought is "take a multivitamin," you're definitely not wrong! However, in some cases, a specific vitamin supplement may be more beneficial, according to Dr. Gossard. "A multivitamin would be a foundational choice to support overall health, but choosing specific vitamin supplements helps you personalize your health needs based on your goals or for optimization," she explained.
Here are our two crucial (but often overlooked) suggestions: vitamin D and B vitamins.
Magnesium and vitamin B are good for women in their childbearing years for one other important reason: they offer support for mood and energy levels all cycle long, even during PMS. If your "time of the month" is sometimes accompanied by cramps, nausea, and/or lower back discomfort, you might consider a supplement that combines these nutrients with a clinically studied ginger, shown to reduce menstrual cramp discomfort scores by an average of 84%.
Cranberries are potent urinary health supplements, packed with powerful antioxidants, and they do wonders for your urinary tract. "Clinical research shows that cranberries support women's urinary tract health by inhibiting the adherence of certain bacteria to the urinary wall," explained Dr. Gossard.
Another reason why cranberries are considered a "superfood" is because they protect against cellular stress, which in turn promotes heart health, healthy digestion and may even encourage immune health, Ryan noted.
But before you stack your fridge with cranberry juice, keep in mind that it often has added or hidden sugars (so not ideal when you want to maintain a healthy weight). Look for a cranberry supplement instead—you'll get all the health benefits of cranberries without the added sugars.
If you ever needed a reason to eat more broccoli and cruciferous vegetables, it's to get your indole-3-carbinol (IC3s). Its role in hormone metabolism makes indole-3-carbinol a star player in women's health— it even helps promote breast tissue health! "It specifically supports healthy estrogen metabolism, which is crucial because estrogen balance affects cell growth in estrogen sensitive tissues," explained Dr. Gossard.
You'd need to eat a lot of these veggies to benefit your metabolism of estrogen, though—about two and a half cups per day, according to Ryan. Which is…a lot. Here's where finding an IC3 supplement that combines ingredients like broccoli, cabbage or cauliflower extracts will help you meet your nutritional needs—even if you skip a serving or two of broccoli.
You've heard of the "good bacteria" that support digestive health, but do you know what they are? These bacteria are part of an intricate ecosystem that make up your microbiome. It includes trillions of microorganisms (along with fungi, protozoa, viruses and bacteriophages) that live on and inside you.
Because these friendly bacteria (and the rest of your microbiome) participate in the many biological processes that regulate different aspects of your health—from digestion to brain and immune health, skin health and even your mood—they are key to a long, fulfilling life.
In addition to a well-balanced diet, which should include fermented foods and healthy sources of fiber like veggies, "taking a well-formulated probiotic strain supplement will ensure your body has access to the many health benefits probiotics offer," noted Ryan.
And while we’re talking about bacteria, did you know that there are bacteria (both healthy and not so healthy) in your vagina as well? A probiotic that supports vaginal flora balance is an important tool in a woman's overall "maintenance routine" because it helps keep the vagina comfortable and the tissue healthy.
Remember, health is about more than "feeling fine." Your wellness depends upon all the daily choices you make every day, from nourishing your body to drinking enough water, exercising regularly and getting plenty of restful sleep.
A focused dietary supplement plan, that includes longevity supplements, supports those choices so that you can live your best life—at every age.
By: Jessica Monge, Health & Wellness Writer
Scientifically Reviewed By: Michael A. Smith, MD
Source: bit.ly/4hVMbOG
Electrolytes are essential minerals like sodium, potassium, magnesium, and others that conduct electricity when dissolved in water and are found inside and outside the cells1. Essential bodily functions rely on the small electrical charge that electrolytes provide. Some of these functions include nerve impulses, muscle contractions, balancing pH and hydration maintenance. An electrolyte imbalance can be detrimental to overall health, the most common of which are imbalances of sodium and potassium. This is a particular concern for certain populations such as athletes, the elderly and those with certain medical conditions2.
Electrolyte imbalances usually occur due to dehydration and dehydration usually causes further electrolyte imbalances. Dehydration is a major concern in healthcare today and is one of the leading causes for hospitalization. Along with adequate water consumption, the use of electrolytes can help prevent dehydration. The body needs to keep the right amount of water inside and outside cells to be properly hydrated and prevent them from either shriveling up or bursting3. Electrolytes such as sodium regulate the amount of fluid in the body by telling cells in the body cells how much water to hold onto or let go of. This process is called osmosis. The body can become dehydrated and electrolyte imbalanced through exercise, weather conditions, bouts of diarrhea and vomiting or from certain medications. Incorporating electrolytes into water during consumption can bring the body back to hydration homeostasis.
But how can we incorporate more electrolytes into our daily routine? Fruits and vegetables contain electrolytes - so a balanced healthy diet can keep your electrolytes in check. However, more aggressive interventions might be needed to replenish levels in the body in certain situations that can cause more instances of dehydration. There are many mineral supplements on the market that can be found either isolated or as a blend. These can be as convenient as mixing in with water.
At Healthquest Vitamins and healthquestvitamins.com we have these key electrolytes in isolated forms from brands such as Pure Encapsulations, Bluebonnet, Natural Factors and others. For electrolyte mixture products we carry brands such as Ultima and Trace Minerals.
Multiple studies reveal magnesium’s cardio-protective effects. One found that those with the highest magnesium levels had a 44% lower risk of heart failure. More than half of all Americans have low magnesium levels.
MAGNESIUM is a hard-working mineral. It helps 300 enzymes perform vital functions throughout the body. Magnesium’s benefits range from building bone to producing energy and synthesizing proteins.1 But it doesn’t stop there. It also helps prevent an array of cardiovascular disorders. Dietary surveys have shown deficient intake of magnesium is epidemic in the United States. Data from the National Health and Nutrition Examination Survey show that 48% of Americans of all ages have intake below the estimated average requirement.1,2 Inadequate magnesium levels have been linked with an increased risk for cardiovascular disease, including stroke, coronary heart disease, heart failure, arrhythmias, and death.3,4
Higher blood levels of magnesium are associated with a lower cardiovascular disease risk.4
Magnesium is a mineral found in many foods, including leafy vegetables, whole grains, beans, nuts, yogurt, and fish. But it’s difficult to get and absorb enough from dietary sources alone. Approximately 64% of all men and 67% of women in the U.S. have inadequate dietary intake of magnesium. Among those above age 71, roughly 81% of men and 82% of women have inadequate dietary intake of magnesium.5,6 That’s a serious problem. Magnesium is involved in critical metabolic functions.7 This means that myriad bodily systems and functions depend on adequate magnesium and suffer when deficiency occurs.5 Adequate magnesium is especially important for healthy and efficient function of heart muscle and blood vessels. Recent human studies confirm a strong association between low magnesium levels and higher heart disease risk.5
People with low magnesium levels are more susceptible to developing arrhythmias, potentially fatal disorders of heart rhythm.8 Arrhythmias involve abnormal conduction of the electrical impulses that govern heartbeat, causing a beat that is irregular, too fast, or too slow.9 Atrial fibrillation, an irregular and often rapid heartbeat, is the leading cardiac cause of strokes. This happens when a fluttering atrial chamber in the heart causes a clot (thrombus) to form that travels up a carotid artery and blocks blood flow to a portion of the brain. This is called an ischemic stroke; the term “ischemia” means “no blood flow”. One large study found that people with the lowest blood magnesium levels were approximately 50% more likely to develop atrial fibrillation than those with thehighest levels. This association occurs even in people without cardiovascular disease.10 Magnesium intake has been shown to correct low-magnesium-related arrhythmias.11,12 For example, intravenous (IV) magnesium is routinely used before many heart surgeries that are known to induce postoperative arrhythmias.13-17 Oral magnesium is often recommended for those with arrhythmias and low magnesium levels.
Endothelial dysfunction occurs when the cells lining the inside walls of blood vessels (the endothelium) lose normal, healthy function.18 This promotes the formation of artery-blocking plaque, resulting in atherosclerosis, a narrowing of the arteries that restricts blood flow.19,20 In cultured human endothelial cells, magnesium deficiency activates the protein complex NF-kB (nuclear factor kappa B), a major facilitator of atherosclerosis.21 In a randomized, controlled human trial, women aged 40-65, all of whom had high blood pressure and were on diuretic therapy, took either a placebo or 600mg of magnesium daily.22 After six months, those taking magnesium had significantly improved endothelial function, which led to reductions in blood pressure and increased blood vessel dilation (widening). Systolic blood pressure fell, on average, from 144 mmHg to 134 mmHg, and diastolic blood pressure decreased from 88 mmHg to 81 mmHg. In addition, the thickness of the carotid artery—a measure of unhealthy arterial thickening—rose in placebo patients but remained unchanged in magnesium- treated patients.22 Thickening of the carotid artery indicates progression of atherosclerosis.
Heart failure occurs when the heart doesn’t pump enough blood to meet the body’s needs. Currently there are about 6.2 million adults in the U.S. with heart failure.23 In one study of 22 patients with symptomatic chronic heart failure, an 800 mg/day dose of magnesium for three months produced a significant increase in arterial compliance (a measure of how well an artery can relax and contract in response to blood flow).24 This suggests improved endothelial function and improved ability of the arteries to deliver oxygen-rich blood to target organs. Blood levels of magnesium are also strongly associated with cardiovascular risk. An epidemiological study of 3,523 men aged 60-79, with no prior history of cardiovascular disease, demonstrated that risk for heart failure declined steadily with rising magnesium levels.25
The U.S. Food and Drug Administration has advised doctors to check patients’ magnesium levels before prescribing medications known as proton-pump inhibitors or PPIs.38 Proton-pump inhibitors like Prevacid®, Prilosec®, and Nexium® are taken for the treatment of heartburn, also known as gastroesophageal reflux disease (GERD). They are also used to treat peptic ulcer disease. A scientific review of 35 studies from 2010 to 2018 suggests that, in some people, taking proton-pump inhibitors causes low magnesium levels.39 These low levels are associated with increased risk of cardiac arrhythmias, and with one often-deadly type in particular, torsade de pointes (or TdP), which can result in sudden cardiac arrest.39 Talk to a doctor about whether to check your magnesium levels before taking proton- pump inhibitors. Those with the highest magnesium blood levels had a 44% lower risk of heart failure than those with the lowest levels. Higher magnesium levels in this study were associated with reduced markers of inflammation and endothelial dysfunction.25
Excess body weight, lack of physical activity, diabetes, and normal aging increase the chances of developing high blood pressure.26,27 A link between magnesium and hypertension has been shown in several human clinical trials.28-30 These studies show that the lower the magnesium level in patients, the higher the systolic blood pressure. One meta-analysis of trials that enrolled more than 2,000 subjects, found that supplementation with magnesium reduced systolic and diastolic blood pressure in hypertensive patients.31 Those who fail to achieve optimal systolic blood pressure under 120 to 130 mm Hg should consider an anti-hypertension drug like telmisartan.
Human studies also demonstrate an association between low magnesium and increased risk of heart attack and stroke.6,32-35 In one analysis of human trials that included a whopping 241,378 participants, researchers found that every 100 mg of magnesium in the daily diet was associated with an 8% lower risk of stroke.34 A similar association was found in a later published meta-analysis.35
Coronary artery disease occurs when the arteries to the heart become narrowed due to atherosclerotic plaque. This reduces blood flow and significantly boosts the risk of a heart attack. It is the leading cause of death in men and women in the U.S.36 Magnesium intake has been shown to improve heart function and exercise tolerance in patients with coronary artery disease. In one study, scientists gave 53 men with coronary artery disease 365 mg of oral magnesium citrate twice daily. After six months, they had improved oxygen utilization during exercise and greater pumping action in their left ventricle, the heart’s main pumping chamber.37 These effects indicate that magnesium improved blood flow and oxygen delivery in these patients.
The mineral magnesium is vital for heart health. More than 80% of people over age 71 have inadequate dietary intake of magnesium, placing them at risk for serious cardiovascular events. Cardiovascular disease, including stroke, coronary heart disease, heart failure, arrhythmias, and even death, has been associated with inadequate magnesium levels. Low-cost magnesium supplements offer an easy solution to replenish this essential mineral.
Shop MAGNESIUM
By Michael Downey.
Source: bit.ly/3qVro3v
Clinical trials show that vitamin D decreases rates and severity of viral respiratory tract infections. More than 70% of Americans have either deficient or insufficient vitamin D blood levels. Vitamin D has shown promise against winter illness because it plays a critical role in supporting the immune system. Low vitamin D levels have been associated with higher rates of many chronic diseases. This includes an increased risk for acute communicable diseases, including viral infections in vitamin D deficient people. A meta-analysis of randomized, controlled clinical trials showed a protective effect against acute respiratory infections with vitamin D supplementation. More than 40% of Americans have been found to have insufficient blood levels of vitamin D (defined as levels between 20-30 ng/mL). An additional nearly 30% of Americans have lower vitamin D levels (below 20 ng/mL) that qualify as deficiency. This factor may be especially important among adults aged 60 and over. Oral intake of vitamin D to ensure healthy levels may help protect against winter-season conditions.
For the body to produce its own vitamin D, we need direct skin exposure to sunlight. But we spend most of our time indoors or covered up by clothes and sunscreen. And spending more time in the sun raises the risk of skin cancer and accelerated skin aging. The other way to get vitamin D is through diet, but most foods contain only modest amounts. As a result, a majority of people are getting too little of this crucial vitamin. Having low levels of vitamin D is associated with a greater risk for many health problems, from cognitive decline to heart disease.
Vitamin D supports immune health by helping:
When excessive levels of immune-system proteins called cytokines provoke attacks on healthy tissues, the result is called a “cytokine storm.” This is a dangerous reaction that can lead to acute respiratory distress syndrome (ARDS), an often-fatal complication in which fluid collects in the lungs.
Viral respiratory tract infections, such as the flu, are more common during winter. One of the reasons for this may be seasonal variations in our vitamin D levels. During winter, we get less sun, leading to lower vitamin D production. That puts us at increased risk for viral infection. Research shows that infections are more common and more severe in those with vitamin D deficiency. Low vitamin D is also a risk factor for more severe lung disease, including acute respiratory distress syndrome (ARDS). Research suggests that those with insufficient vitamin D are at increased risk of a cytokine storm.
This hyperproduction of inflammatory factors leads to worsening disease severity and increased risk of death. Low vitamin D levels may be associated with the dangerous inflammation that occurs in ARDS.14,15
Vitamin D contributes to many functions that help shield the body from infections and lessen their severity.
Maintaining adequate levels of vitamin D:
Many studies have evaluated whether daily oral intake of vitamin D can reduce rates of viral respiratory illness. Meta-analyses of clinical trials have shown that vitamin D has a protective effect against respiratory tract infections. The impact of vitamin D treatment is greatest in those who, to begin with, have low levels of vitamin D.
Vitamin D supports the immune system in many different ways, helping to shield the respiratory tract from viral illness. A large majority of adults have vitamin D levels below the optimal level. Trials have shown that oral vitamin D intake modestly decreases rates of viral respiratory tract infections.
There are no universal guidelines for frequency of vitamin D testing. However, given the high prevalence of vitamin D deficiency and the strong association of low vitamin D levels with several health issues, annual testing and supplementation to achieve adequate blood levels is highly recommended. Annual blood tests can let people know whether they are taking the correct dosage to ensure optimal blood levels of vitamin D.
If you do not already maintain an optimal blood level of 25-hydroxyvitamin D of 50 to 80 ng/mL, then take between 5,000 to 8,000 IU of vitamin D daily with meals.
Shop VITAMIN D
Scientifically reviewed by: Julia Dosik, MPH, on October 2020. Written By Julie Myers.
Source: bit.ly/3nhNtai
Q: MCT oil and coconut oil seem alike in my mind. I’m not sure how they differ and which one to use. Do they have the same benefits, and can they be used interchangeably?
A: No, definitely not. While both can be therapeutic for certain conditions, there are key differences between MCT and coconuts oils, and each has unique benefits and uses. It’s important to understand the pros and cons of each to determine which oil is more appropriate for you—or whether you want to use them both.
Coconut oil is a historically used fat in many tropical areas of the world, and it has become popular among many health-oriented shoppers in recent years. It is considered the richest food source of medium-chain triglycerides (MCTs), also called medium-chain fatty acids, which are primarily capric, caprylic, and lauric acids. It also contains some long-chain fatty acids, which aren’t as easy for the body to digest.
The fact that coconut oil is listed as a rich source of MCTs should have an asterisk next to it, though. The highest percentage of fatty acids in coconut oil is from lauric acid. Even though lauric acid is considered a medium-chain fatty acid by chemists, it behaves more like a long-chain fatty acid in terms of digestion and absorption. For this reason, many experts suggest that coconut oil should not be considered an MCT-rich oil. Lauric acid has notable antimicrobial effects, but it doesn’t have the easy-to-digest characteristics of MCTs that encourage the body to burn fat and provide quick energy.
MCTs, on the other hand, don’t require the enzymes or bile acids for digestion and absorption that long-chain fatty acids require. This allows MCTs to go straight to your liver where they are either used for immediate energy or turned into ketones, compounds produced when your liver breaks down a lot of fat.
MCT oil contains 100 percent MCTs, compared with about 50 percent in coconut oil. MCT oil is made by refining coconut oil or palm oil to remove other compounds and to concentrate the MCTs naturally found in the oils.
Research suggests that MCT oil may help boost weight loss, metabolic functioning, and energy production more than other oils. As mentioned, your body turns MCTs into alternative forms of energy called ketones, which provide your brain with energy, increase your metabolic rate, and burn excess fat. Mark Hyman, MD, author of Eat Fat, Get Thin, calls MCT oil “the secret fat that makes you thin.” He calls MCT oil a super fuel for your cells that increases mental clarity and boosts fat-burning.
MCTs can increase the number of calories your body burns compared with longer-chain fatty acids‚ and replacing other dietary fats with MCT oil can produce weight loss. One study found that people saw more weight loss and decreased body fat from consuming MCT oil rather than olive oil. Other studies suggest that MCT oil may help you exercise longer and improve your stamina.
Because of the rapid and simple digestion of MCTs, MCT oil also may help people who have malabsorption issues. Some holistic-oriented medical practitioners use MCTs as nutritional therapy for reducing intestinal irritation in patients with irritable bowel disease, short bowel syndrome, or celiac disease, or after gastrointestinal surgery.
Decades ago, coconut oil was avoided because it is a saturated fat that people in the Western world incorrectly associated with heart disease. History shows that coconut oil doesn’t appear to increase cardiovascular disease, and some clinical research also supports this. In parts of the world, such as the South Pacific islands and Papua New Guinea, where coconuts are a dietary staple, people have thrived eating coconut oil for generations and have very low rates of heart disease.
Lauric acid makes up about half of the fatty acids in coconut oil. When your body digests lauric acid, it forms a substance called monolaurin. Both lauric acid and monolaurin may kill harmful pathogens, such as bacteria,
viruses, and fungi. Test-tube studies show that these substances help wipe out Staphylococcus aureus, which causes staph infections, and the yeast Candida albicans, a common source of yeast infections in humans. Research also shows that lauric acid has potent inhibitory effects against Clostridium difficile, often abbreviated C. diff, a bacteria that affects the intestines and is resistant to many antibiotics.
Monolaurin and lauric acid also have the physiochemical property of being able to destroy the membrane of lipid-coated viruses, such as the virus that causes COVID-19. Clinical trials using coconut oil on COVID-19 patients in hospitals in the Philippines are underway as of this writing.
Unlike MCT oil, which should not be used in cooking, coconut oil has a high smoke point, meaning it stands up well to heat and is good for stir-frying and pan-frying. Coconut oil also is an excellent substitute for butter in baking.
Coconut oil can be used topically to improve the health and appearance of skin and hair. Research shows that when coconut oil is applied to skin, it can improve the moisture content and reduce the symptoms of eczema. When applied to hair, coconut oil may soften texture, protect against damage, and act as a weak sunscreen, blocking about 20 percent of the sun’s UV rays.
Which of these oils is best for you to use depends on the condition of your health and your personal goals. If you want to lose weight, especially if you’re following a keto-type diet, supplementing with MCT oil can ensure you’re getting enough fat to stay in ketosis—the state in which your body burns fat, rather than carbs, for fuel. But even if you’re on a different type of eating plan, MCT oil can help you feel fuller, longer; help you feel more mentally alert; and might even improve endurance during exercise.
If you have a digestive disorder or difficulty digesting and absorbing fat—which is often characterized by diarrhea, greasy stools, foul-smelling stools, bloating, and gas—consider supplementing with MCT oil to provide an easy-to-digest source of fat that might help reduce irritation in your intestines.
On the other hand, coconut oil is the one to choose if you’re looking for a versatile cooking oil that can also be used therapeutically on the skin and hair. It is an all-star in these areas. It’s also possible that because of its high lauric acid content, consuming raw coconut oil is potentially beneficial for protecting against—or combating—infections caused by numerous pathogenic bugs, including Candida albicans, bacteria, and viruses. For the best health benefits and the most nutrients, opt for organic, unrefined virgin coconut oil.
Regardless of which one you choose, be aware that taking too much MCT oil or coconut oil can lead to stomach discomfort, cramping, diarrhea, and bloating. So, it’s a good idea to start small (say, ½ Tbs. per day), see how your body reacts, and increase as tolerated to a maximum dose of 3–4 Tbs per day.
If you experience digestive distress from supplementing with MCT oil, consider trying another brand of the product. Some people who experience digestive trouble from MCT oil may react to the proprietary blend of MCTs or to the solvents used in the processing that may not be in another brand.
Finally, whether you decide to use MCT oil, coconut oil, or both in your diet, understand that MCT oil supplies no essential fatty acids (EFAs) and coconut oil supplies a negligible amount. As the name implies, EFAs are essential for our health and well-being. To avoid becoming deficient in EFAs, eat plenty of cold-water fish, grass-fed beef, omega-3-enriched eggs, hemp seeds, and flaxseeds.
*Source: https://rb.gy/p8xztj
MCT Oil from Coconut - Nature's Way
Coronavirus infection, including SARS-CoV, MERS-CoV, and SARS-CoV2, causes daunting diseases that can be fatal because of lung failure and systemic cytokine storm. The development of coronavirus-evoked pneumonia is associated with excessive inflammatory responses in the lung, known as “cytokine storms,” which results in pulmonary edema, atelectasis, and acute lung injury (ALI) or fatal acute respiratory distress syndrome (ARDS). No drugs are available to suppress overly immune response-mediated lung injury effectively. In light of the low toxicity and its antioxidant, anti-inflammatory, and antiviral activity, it is plausible to speculate that curcumin could be used as a therapeutic drug for viral pneumonia and ALI/ARDS. Therefore, in this review, we summarize the mounting evidence obtained from preclinical studies using animal models of lethal pneumonia where curcumin exerts protective effects by regulating the expression of both pro- and anti-inflammatory factors such as IL-6, IL-8, IL-10, and COX-2, promoting the apoptosis of PMN cells, and scavenging the reactive oxygen species (ROS), which exacerbates the inflammatory response. These studies provide a rationale that curcumin can be used as a therapeutic agent against pneumonia and ALI/ARDS in humans resulting from coronaviral infection.
During the Spanish influenza pandemic in 1917–1918, it was found that the deaths were not just seen in the elderly with weak immunity, but also young individuals with normal immunity. As part of a robust immune response in severe cases, the virus triggers overaction of immune systems, producing a large number of inflammatory factors, which causes severe damage to the lung and manifests acute respiratory distress syndrome (ARDS), resulting in high mortality. The same damaging effects of immune over-reaction were observed in outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV), middle east respiratory syndrome CoV (MERS-CoV), highly pathogenic avian influenza viruses (including H5N1 and H7N9), and novel coronavirus (SARS-CoV2).
Inflammation under physiological conditions is a protective mechanism that acts to eliminate exogenous agents invading to living bodies, remove necrotic tissues and cells, and promote damage repair. Being said that the inflammation initiates a protective immune response when it is confined to locally affected tissues. However, when the negative regulatory mechanism is suppressed, a persistent and extensive inflammatory reaction occurs, which can reach pathological levels causing fatally systemic damage. Such an inflammatory response, including overproduction of immune cells and pro-inflammatory cytokines, is defined as the cytokine storm that usually occurs in viral infection and causes acute lung injury (ALI) and ARDS. Resulting symptoms include congestion, atelectasis, and pulmonary edema, which affects oxygen exchange in the lung and eventually lead to death. There is no effective regime for cytokine storm and resultant lung injury. Therefore, drugs to suppress the cytokine storm are urgently needed to treat deadly virus infection that causes lung damage and ARDS.
Curcumin[(1E,6E)-1,7bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is a natural medicine mainly extracted from plants of the Curcuma longa that has a long history to be used in humans in treating diseases without overt side effects. Numerous in vitro and in vivo studies indicate that curcumin has antioxidant, anti-inflammatory, anti-cancer, and anti-diabetic activity. Several clinical investigations have reported beneficial effects in treating cardiovascular diseases, metabolic syndrome, or diabetes, and infectious diseases, especially viral infection. All of these clinical findings point to that curcumin alleviates these diseases mainly via modulation of immune responses. Indeed, some preclinical studies have suggested that curcumin could inhibit the cytokine storm induced by the viral infection. Therefore, in this review, we outline the relationship between virus infections and cytokine storm and discuss the potential use of curcumin in treating viral infection-triggered ARDS. We hope to provide useful information and references for clinicians in combating devastating severe pneumonia caused by SARS-CoV2, a current global pandemic.
Cytokine storm arises from different factors that could derive from autoimmune, inflammatory, iatrogenic, and infectious origins. It is characterized by the production of excessive amounts of inflammatory cytokines as a result of unchecked feedforward activation and amplification of immune cells. Its clinical manifestations include systemic inflammation, multi-organ failure, hyperferritinemia, which is referred to as “cytokine storm syndrome” and could be lethal if untreated.
Under physiological conditions, the steady-state cytokine levels are maintained by negative and positive feedback regulation of their expression. A large amount of virus in the body will induce over-reacted innate and adaptive immune response, triggering extravagant cytokines release and lymphocytes activation. Common to cytokine storm syndromes engendered by all insults is a loss of negative regulation of the production of inflammatory cytokines, which in turn drives a positive feedback regulation, leading to exponentially growing inflammation and multi-organ failure.
At an early stage, virus infection induces host cells to generate cytokines and chemokines, inflammatory mediators, and apoptosis of the host cells, which then attracts immune cells to the damaged areas. Macrophages, dendritic cells, and mast cells engulf antigen fragments, virus, and virus-bearing damaged cells, which triggers the production of the inflammatory mediators. Myeloid cells, including monocytes, neutrophils, and dendritic cells, contain multiple pattern recognition receptors (PRRs) on their surfaces to help them recognize and bind to viruses via Pathogen-associated molecular patterns (PAMPs) such as viral RNA/DNA, or damage-associated molecular patterns (DAMPs) from necrotic tissue and cells in aseptic inflammation. Subsequently, the immune cells are activated and produce pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (e.g., IL-1β, IL-6), and interferon-gamma (IFN-γ). The release of cytokine causes increased vascular permeability; consequently, the leukocytes increasingly migrate to damaged tissues through margination, rolling, adhesion, transmigration, and chemotaxis. Activated leukocytes simultaneously release prostaglandins and inflammatory factors, and activate the complement system, producing C3a and C5a components that kill pathogens.
An additional effect of cytokines is to activate NADPH oxidase in leukocytes, leading to the generation of reactive oxygen species (ROS) such as superoxide, hydroxyl radicals, and singlet oxygen. On the one hand, ROS helps to remove proteins, lipids, and nuclear acids of the damaged cells and activate immune cells to eliminate foreign microorganisms through extracellular mechanisms. On the other hand, ROS acts as a second messenger to regulate intracellular signaling events. For example, it activates the nuclear factor-κB (NF-κB) to promote further production of pro-inflammatory cytokines such as TNF-α, IL-6, IL-8, and other inflammatory factors. Therefore, pro-inflammatory cytokines and ROS exert forward feedback regulation of their production.
The inflammatory response can be turned off by the anti-inflammatory cytokine IL-10. The positive and negative regulatory inputs maintain normal innate immunity. However, if the balance is disturbed in some cases, for instance, inhibition of the immuo-suppressor cytokine IL-10, a cytokine storm takes place. Infections from such viruses as Ebola, avian influenza, dengue, and coronavirus, can lead to cytokine storms, producing a massive amount of pro-inflammatory cytokines. The concerted action of these inflammatory mediators causes the destruction of tissues and cells, manifested by clinical syndromes such as extensive pulmonary edema, alveolar hemorrhage, ARDS, and multiple organ failures.
Numerous in vivo and in vitro studies have been shown that curcumin and its analogs markedly inhibit the production and release of pro-inflammatory cytokines, such as IL-1, IL-6, IL-8, TNF-α. In line with this, Zhang et al. (2019) have observed that direct pulmonary delivery of solubilized curcumin dramatically diminishes pro-inflammatory cytokines IL-1β, IL-6, TNF-α in the BAL cells, the lung and serum of mice with severe pneumonia induced by Klebsiella. In addition, curcumin also decreases expression of many other inflammatory mediators, including MCP1(CCL2), MIPI1 (CCL3), GROα (CXCL1), GROβ (CXCL2), IP10 (CXCL10), SDF1 (CXCL12), MMP-2, IFN-γ, and MMP-9, which regulate the activity of immune cells and inflammatory responses and promote fibrosis in the lung after infection.
The mechanism underlying curcumin modulation of inflammation has been extensively investigated and engages diverse signaling pathways, among which NF-κB plays an essential role. It was reported that curcumin effectively regulates NF-κB signaling through multiple mechanisms. First, curcumin inhibits activation of IKKβ. In a study of patients with head and neck cancer receiving curcumin, reduced activity of IKKβ was observed in saliva samples, associated with a decrease in the expression of IL-8, TNF-α, and IFN-γ. Second, curcumin enhances the expression or stability of IκBα. Curcumin inhibits the IκBα degradation, phosphorylation of IκB serine 32 to block the cytokine-mediated NF-κB activation and thus pro-inflammatory gene expression. Third, curcumin activates AMPK. It has been documented that curcumin blocks NF-κB signaling upon infection with Influenza A virus (IAV) as a consequence of AMPK activation. Fourth, curcumin acts on p65 to disturb the NF-κB pathway. Infection with IAV led to a decrease of p65 in the cytosol of macrophages and a corresponding increase in the nucleus, where it forms a functional complex with NF-κB, ultimately upregulating transcription of pro-inflammatory cytokines. In contrast, the use of curcumin blocks the nuclear translocation of NF-κB and p65, downregulating transcription of the cytokine genes.
Other inflammatory mediators have been reported to be regulated by curcumin. One of them is cyclooxygenase 2 (COX-2), a key enzyme for the synthesis of prostaglandin. In an animal model of chronic obstructive pulmonary disease, it has been shown that curcumin treatment effectively inhibits the degradation of IκBα and disturbs the production of COX-2. In addition to disrupting the NF-κB pathway, curcumin inhibits the virus-induced expression of TLR2/4/7, MyD88, TRIF, and TRAF6 genes, and blocks IAV-induced phosphorylation of Akt, p38, JNK as well.
Many studies have documented that curcumin disrupts the viral infection process via multiple mechanisms, including directly targeting viral proteins, inhibiting particle production and gene expression, and blocking the virus entry, replication, and budding. A recently in vitro study has demonstrated that curcumin inhibits respiratory syndrome virus (RSV) by blocking attachment to host cells. In this study, curcumin was also found to prevent the replication of RSV in human nasal epithelial cells. Additional evidence suggests that curcumin inhibits Porcine reproductive and RSV (PRRSV) attachment, possibly by disrupting the fluidity of viral envelopes. Curcumin also obstructs virus infection by inhibiting PRRSV-mediated cell fusion, virus internalization, and uncoating.
For a century, different subtypes of IAV, H1N1, H2N2, H3N2, and H5N1 have been the leading cause of pandemic outbreaks in the world. It has been reported that curcumin and its derivatives have a high binding affinity to hemagglutinin (HA), a major capsid glycoprotein of influenza virus that mediates virus attachment have demonstrated that curcumin interacts with HA and disturbs the integrity of membrane structure to block virus binding to host cells and prevent IAV entry. In another study with cells infected by IAV, it was found that curcumin directly inactivates various strains of IAV, disturbs their adsorption, and inhibits their replication. Further, the study showed that curcumin inhibits IAV absorption and replication by activating the NF-E2-related factor 2 (Nrf2)-hemeoxygenase-1 (HO-1)-axis, a classical anti-inflammatory and antioxidative signaling, which possesses antiviral activity.
Furthermore, curcumin acts against SARS-CoV. Accordingly, a study on the anti-SARS-CoV activity of 221 phytocompounds revealed that 20 μM of curcumin exhibits significant inhibitory effects in a Vero E6 cell-based cytopathogenic effect (CPE) assay. The authors presented evidence for a mild effect of curcumin against SARS-CoV replication and the inhibitory effect of curcumin on SARS-CoV 3CL protease activity, which is essential for the replication of SARS-CoV. This study provides promising evidence for curcumin as a potential anti-SARS-CoV agent .
In the last two decades, coronavirus infection has gained much attention for its high mortality. The consensus from recent research is that the cytokine storm plays a crucial role in the development and progression of fatal pneumonia. Among those who experienced SARS-CoV infection in 2003, many manifested ALI and developed ARDS, and the death rate was greater than 10%. Similar syndromes are seen in the MERS-CoV, H5N1, H7N9, and SARS-CoV2 infection. The high mortality rate from fatal pneumonia is due to the over-activation of immune cells in the lung.
Targeting cytokine storm is considered as an essential strategy for CoV infections. In clinical settings, glucocorticoids have been used to treat fatal viral pneumonia and shown therapeutic benefits. In the treatment of patients with SARS in 2003, glucocorticoids were widely used to suppress the cytokine storm in severe cases. However, it has been found that large doses of glucocorticoids create many side effects such as osteoporosis and secondary infection with other pathogenic microbes, and small doses have little effect on improving lung injury. These clinical findings indicate that it is increasingly important to seek alternative agents with effectiveness and low toxicity.
Many studies on virus-induced pneumonia have highlighted the potential usage of curcumin in the improvement of lung index and survival rate. Curcumin mitigates the severity of viral pneumonia through inhibiting the production of inflammatory cytokines and NF-κB signaling in macrophages. Curcumin has also been shown to activate Nrf2 in association with reduced oxidative stress and inhibit TLR2/4, p38/JNK MAPK, and NF-κB in response to IAV infection; and as a result, pneumonia is improved.
Up to now, it has been claimed that curcumin benefits human health and prevents diseases. A recent study suggested that a low dose of curcumin (80 mg/day) produced a variety of health-promoting actions, such as direct and indirect antioxidant actions. Additionally, accumulating evidence from animal studies has shown that curcumin prevents the development of severe pneumonia. Thus, pre-treatment of curcumin (5 mg/kg/day) inhibits paraquat-induced lung inflammation and structural remodeling of the lung at an early phase of ALI have demonstrated that pre-treatment of mice with curcumin (150 mg/kg) for 15 days before Klebsiella pneumonia infection prevents the tissue from injury and reduces ALI-associated pneumonia by the anti-inflammatory action of curcumin. The similar protective role of curcumin has been found in preclinical studies of viral-induced pneumonia. Treatment with curcumin (50 mg/kg/day) beginning at 5 days prior to reovirus 1/L infection protects CBA/J mice from the development of ALI/ARDS and suppresses subsequent fibrosis have reported that pre-infection or post-infection administration of curcumin significantly improves the lung index and prolongs the survival rate. Interestingly, the fatality rate is also reduced by pre-administration with curcumin. All these studies suggest that curcumin administration could have both prophylactic and therapeutic effects on virus-induced pneumonia and mortality.
Clinical investigations have suggested that curcumin might be effective in improving inflammation and the treatment of virus infections. A clinical trial conducted by have demonstrated that curcumin nanomicelle supplement ameliorates oxidative stress, and reduces inflammatory biomarker, including TNF-α, compared to a placebo. Furthermore, a phase II randomized controlled study has reported that the topical application of curcumin and curcumin polyherbal cream has a higher HPV clearance rate than the placebo.
Currently, no data in humans on the link between curcumin and coronavirus infection have been available, but in light of and its preventative and therapeutic role in viral infection and cytokine storms common to all viral infections, curcumin could conceivably be considered as an attractive agent for the management of coronavirus infections.
Cytokine storm syndrome triggered by viral infections is the culprit of death. It is exacerbated by unchecked regulation of the production of pro-inflammatory cytokines and ROS, leading to pneumonia, ALI, multiple organs failures, and eventually death. No effective therapy is available for the cytokine storm syndrome and associated lung and other organ failures. Curcumin is a natural plant extract with high safety and low toxicity such that people take it as a diet supplement, and growing evidence from preclinical studies demonstrates that it effectively inhibits viral infection, alleviates the severity of lung injury through offsetting the cytokine storm, inhibits subsequent fibrosis, and increases survival rates. Additionally, its anti-SARS-CoV replication and 3CL protease have been reported in an in vitro study. In sum, the preclinical studies we have reviewed here motivate a call for attention to the clinical investigation of curcumin as a therapeutic agent for the cytokine storm syndrome following coronavirus infections, especially pneumonia caused by the coronavirus.
For full text and references, go to: https://doi.org/10.3389/fcell.2020.00479
Abstract
This paper presents an evidence-based strategy for improving clinical outcomes in COVID-19. Recommendations are based on the phases of the disease, because optimal interventions for one phase may not be appropriate for a different phase. The four phases addressed are: Prevention, Infection, Inflammation and Recovery. Underlying this phased approach is recognition of emerging evidence for two different components of pathophysiology, early infection and late stage severe complications. These two aspects of the disease suggest two different patterns of clinical emphasis that seem on the surface to be not entirely concordant. We describe the application of therapeutic strategies and appropriate tactics that address four main stages of disease progression for COVID-19. Emerging evidence in COVID-19 suggests that the SARS-CoV-2 virus may both evade the innate immune response and kill macrophages. Delayed innate immune response and a depleted population of macrophages can theoretically result in a blunted antigen presentation, delaying and diminishing activation of the adaptive immune response. Thus, one clinical strategy involves supporting patient innate and adaptive immune responses early in the time course of illness, with the goal of improving the timeliness, readiness, and robustness of both the innate and adaptive immune responses. At the other end of the disease pathology spectrum, risk of fatality in COVID-19 is driven by excessive and persistent upregulation of inflammatory mechanisms associated with cytokine storm. Thus, the second clinical strategy is to prevent or mitigate excessive inflammatory response to prevent the cytokine storm associated with high mortality risk. Clinical support for immune system pathogen clearance mechanisms involves obligate activation of immune response components that are inherently inflammatory. This puts the goals of the first clinical strategy (immune activation) potentially at odds with the goals of the second strategy (mitigation of proinflammatory effects). This creates a need for discernment about the time course of the illness and with that, understanding of which components of an overall strategy to apply at each phase of the time course of the illness. We review evidence from early observational studies and the existing literature on both outcomes and mechanisms of disease, to inform a phased approach to support the patient at risk for infection, with infection, with escalating inflammation during infection, and at risk of negative sequelae as they move into recovery.
Four Phases of COVID-19
Clinicians will encounter patients in one of four phases of COVID-19, each requiring its own focus.
Prevention - support is focused on immune surveillance efficiency and reduction of baseline levels of inflammation, to improve outcomes if the patient becomes infected,
Infection - support emphasizes immune activity against infection,
Escalating Inflammation - support is focused on anti-inflammatory measures, and
Recovery - support is focused on resolving inflammation, inhibiting fibrosis and other forms of tissue damage, curtailing losses of function, and restoring and reoptimizing function. Because patients have been observed to relapse into the Escalating Inflammation Phase, it is essential for clinical surveillance to continue well into what may appear to be the Recovery Phase.
1. Foundational Support
To address foundational support, clinicians can consider addressing factors that impact immunological integrity as well as factors that drive non-purposeful inflammation.
Address factors known to impact immunological integrity
Sleep - Healthy sleep is anti-inflammatory and promotes appropriate Th1 response. Disordered sleep is characterized by reduced sleep efficiency, less slow wave sleep, and more REM sleep. Disordered sleep yields increased inflammation and increases Th2 response at the expense of Th1 response.66
Sound sleep hygiene practices, reviewed elsewhere,140-143 are fundamental for promoting healthy sleep. In addition, substances such as melatonin may be added to enhance sleep promotion. Not only is melatonin a useful sleep aid, it also inhibits NLRP3 inflammasome activation,144-146 and reduces airway inflammation.147 Melatonin has also been identified as a potential therapeutic drug in an in silico model of the human interactome with SARS-C0V-2 (4).
Stress - As referenced earlier, stress chemistry is inflammatory and has been shown to shift the patient away from effective Th1 response. Many patients will have been enduring significant chronic stress by the time they become infected. Though it is not part of the main protocol, for patients with significantly elevated stress levels, it may be useful to give adaptogens like ginseng or ashwagandha.148-152
Stress chemistry can and should also be addressed by a number of other techniques that have proven useful for decreasing the stress response. Patient ability and personal preferences will guide the appropriate choices. Techniques include mindfulness-based stress reduction (MBSR)153,154 exercise,155 relaxing music, creative pursuits, biofeedback,156 and many others, reviewed elsewhere.157
Supporting levels of vitamins, minerals, and other substances with known immunological roles.
The role of nutritional agents as immune modulators has recently been reviewed.185 It's noteworthy that many of these nutrients play dual roles in immunology, supporting immune surveillance while also reducing inflammation.
Vitamin D - The potential utility of vitamin D in COVID-19 has been reviewed, with the authors recommending a multi-day loading of 10 000 iu qd and a steady dose of 5000 iu qd, with the goal of bringing lab ranges above 40-60 ng/ml.186 Many studies have shown that vitamin D deficiency not only impairs immune function but also promotes excessive inflammatory reactions. The role of vitamin D in inflammatory and autoimmune disorders has been extensively reviewed, including here.187 Deficiency has been shown in many inflammatory and autoimmune diseases such as asthma,188 various types of arthritis,189 SLE,190 Type 1 diabetes,191 Multiple Sclerosis,192 among others. Supplementation is most likely primarily effective in those deficient in vitamin D or with a VDR polymorphism impairing vitamin D absorption and metabolism.193
A meta-analysis of studies on vitamin D and acute lung injury (ALI) found that, in studies that did not use very large, rare bolus dosing, vitamin D was safe and protected against ALI. Patients who were deficient and received non-bolus dosing had the most benefit.194 Vitamin D has been shown to prevent experimental lung fibrosis and predict survival in patients with idiopathic pulmonary fibrosis, via inhibition of TGF?.138 TGF? is a central player in lung fibrosis and a central generator of the NETosis discussed above, that is associated with sepsis, thickening mucous secretions, and thrombus formation. Vitamin D has also been shown to reduce the risk of acute respiratory infection.195
Vitamin D is necessary for the formation of macrophage lysosomal enzymes, a key component of the ability of macrophages to kill pathogens, including viruses, that have been engulfed by phagocytosis.196 In many experimental models, macrophages are infected with pathogen in vitro, and the cytokine profiles the macrophages generate are measured. As described in the work of Hewison,196 healthy macrophages with adequate vitamin D status will respond more effectively to infection. This includes greater production of cytokines whose function is to stimulate chemotaxis of neutrophils and other immune elements to the site of infection. Effective neutrophil chemotaxis is induced by inflammatory cytokines, and neutrophil influx into tissue is at the center of normal anti-pathogenic inflammation. These chemical signals are normal in the context of a well-orchestrated inflammatory response, including the resolution phase. Isolating the role of vitamin D in allowing macrophages to respond normally to pathogens does not reflect the total picture of vitamin D's role in the body. Vitamin D plays a key role in both immune system antipathogenic function and anti-inflammatory functions.
Vitamin A - Vitamin A was the first fat-soluble vitamin to be identified. Early researchers found that young animals fed a diet deficient in natural fats became very unhealthy and that their eyes became severely inflamed and infected. Vitamin A was once known as the "anti-infective vitamin," and vitamin A status is a major determinant of overall immune status. Those deficient in vitamin A experience impaired antibody response, decreased levels of helper T cells, and impaired integrity of the mucosal linings of the respiratory and gastrointestinal tracts. Vitamin A-deficient individuals are more susceptible to infectious diseases, respiratory conditions like asthma and allergies, and have higher mortality rates.197
The prevalence of deficiency is difficult to determine as numbers vary widely worldwide and criteria are inconsistent. Nonetheless, deficiency is common worldwide, with epidemic prevalence in Saharan Arica (48%) and South Asia (44%).198
Unfortunately, vitamin A deficiency is also common in the US with 34% of adults consuming less than the EAR.199 Co-author Pizzorno in an unpublished study of retinol levels in 200 adult oil field workers in Canada found that 40% were deficient.
While beta-carotene is commonly considered synonymous with vitamin A, this an error with significant clinical consequences, especially for vegans. Emerging research has shown multiple, surprisingly common, genomic variations that impair conversion of beta-carotene to vitamin A by 24 to 57%. Single nucleotide polymorphisms have been identified that decrease activity of 15,15'-monoxygenase, the key enzyme converting beta-carotene to retinol. rs12934922) and rs7501331 variants have been found in 42% and 24%, respectively. Those with one copy of the less common allele have shown a 32% drop in activity, while those who are homozygous for the polymorphism experience a 57% reduction in conversion rate.200
A controlled animal study in calves found that low dietary vitamin A impaired IgG1 titers against intramuscularly inoculated inactivated bovine coronavirus vaccine.201
Vitamin A levels drop during various types of infection and multiple studies have shown that vitamin A supplementation improves resistance and recovery rate.202 Given the numbers above regarding the high prevalence of vitamin A deficiency, this is cause for concern in the current crisis.
Vitamin A, especially when in balance with vitamin D, has low toxicity except at high dosages. For adults, toxicity is typically seen after 100 000 IU/d for 6 months.203 A study that looked at the positive effects of multivitamin supplementation in women with HIV showed that Vitamin A was detrimental to outcome.204 However, in this study, vitamin A was supplemented in the absence of the other fat soluble vitamins notably D and K. Animal studies have demonstrated that vitamin A both decreases the toxicity of and increases the dietary need for vitamin D and vice versa.205 In addition, concomitant supplementation with vitamin D significantly increased the dose of vitamin A that causes toxicity.206
Multiple studies have shown that vitamin A deficiency increases inflammation and more limited research has shown supplementation decreases inflammation. This appears particularly important for the mucosal barriers. However, the research is complex as inflammation itself appears to decrease blood levels of vitamin A.207
Zinc - Zinc plays a crucial role in the function of essentially all immune cells. Deficiency of this critical element has a profound impact on immune response, increasing susceptibility to a variety of infections.208-212 One of zinc's critical roles in immune function is its role in thymulin production and activity.213
In addition, zinc has specific and well-known antiviral properties.214 Increasing intracellular zinc concentrations in cell culture impairs the replication of a variety of RNA viruses including SARS-CoV-1. Intracellular zinc has been shown to inhibit RNA synthesis by suppressing the SARS-CoV-1 replication and transcription complex.215 In vivo evidence for zinc's antiviral role comes from a Cochrane review that found zinc intake was associated with a significant reduction in the duration of the common cold. Many of the studies showing benefit when taken during the course of an infection were in the form of a zinc lozenge.216 It makes sense to utilize this mode of delivery during the acute infection phase.
Zinc has also been shown to suppress Th17 cell development.217 Interleukin-17 (IL-17) made by Th17 cells has been shown to drive an inflammatory feedback loop via IL-6 induction.218 Zinc dependent transcription factors are involved in the regulation of the gene expression of IL-6 and TNF?.219 The effect of SNPs in genes encoding zinc transporters on blood zinc levels in humans has been examined.220 Older individuals with gain of function IL-6 SNPs have been shown to have a greater need for zinc.221 Zinc supplement in older individuals with gain of function IL-6 SNPs and low zinc were shown to have lower IL-6 and MCP-1 levels upon zinc supplementation.222
Anosmia (loss of smell) and dysgeusia (distorted sense of taste) are commonly being reported in patients at every phase of COVID-19.223 These are also classic symptoms of zinc deficiency. It is too early in the discovery process to determine if this is cause or effect, nonetheless zinc deficiency greatly impairs immune function, especially resistance to viral infections. Notably, inadequate dietary consumption of zinc is found in almost half the older population.224
Vitamin C - Vitamin C is recognized as an essential nutrient in many aspects of the immune system, especially immune cell function of both the innate and adaptive immune responses.225,226 Microbial killing requires vitamin C for chemotaxis, phagocytosis and generation of ROS.227,228 Vitamin C deficiency contributes to decreased immune responsiveness and increased susceptibility to infections. Once infected, the enhanced inflammation and metabolic requirements place a further demand for additional vitamin C.229 Vitamin C supplementation has been shown to both prevent and treat respiratory and systemic infections. The utility of vitamin C and thiamine in sepsis has been reviewed.230
Optimal cell and tissue levels of vitamin C in the plasma saturation range are needed for prophylaxis, while treatment of infections requires significantly higher doses.231,232 In addition, vitamin C's role as an antioxidant is important in protecting the body against the damage from oxidative stress generated during an infection.233,234 Vitamin C also plays an critical role in endothelial stability, supporting nitric oxide generation and vasodilation. In light of the coagulopathy found in many COVID-19 patients, this role seems highly relevant.235
The CITRIS-ALI study, an RCT published in JAMA in 2019, showed a possible decrease in mortality in 167 patients with sepsis-related ARDS receiving ~15 grams/day of IV vitamin C for four days.236 Recruitment is underway at this writing for an RTC IV vitamin C trial (24g/day) in COVID-19 patients hospitalized with severe pneumonia.237 At Northwell Hospital in New York, there are multiple anecdotal reports of the use of IV vitamin C (1500 mg TID to QID) in COVID-19 patients. Those receiving the IV vitamin C appear to be doing significantly better than those not receiving it.238
A meta-analysis of six controlled trials published in March 2019 demonstrated that an average oral delivery of 2 grams of vitamin C per day shortened length of ICU stay by 8.9%. In three trials in which patients required mechanical ventilation for over 24 hours, vitamin C shortened the duration by 18.2%.239
Quercetin - As discussed above, the antiviral roles of zinc are well documented. However, protection of cells against viral appropriation of cellular metabolism to replicate viral RNA requires adequate intracellular zinc. Ionophores play a critical role in facilitating transport of zinc into cells. The commonly available flavonoid quercetin is a zinc ionophore and has been shown to facilitate transport of zinc across lipid membranes. This is particularly relevant as chloroquine is also a zinc ionophore, which has been postulated as a possible mechanism for its apparent efficacy against SARS-CoV-v2.240,241
Quercetin is also important as one of multiple flavonoids shown in vitro to block the activity of MERS-CoV 3CLpro, a critical enzyme for coronavirus replication. Animal studies are limited at this time but support efficacy.242
In a molecular docking study looking for agents that could bind to the SARS-CoV-2 Viral Spike Protein and thus have potential to inhibit its infectivity, researchers found quercetin to be the fifth most effective.243 However, quercetin has low bioavailability and therefor requires special formulations to achieve clinically effective blood levels. A trial with a phytosomal quercetin formulation has been started in Italy on 660 hospitalized COVID-19 patients (private communication with study PI).
Fish Oil - The role of fish oil in reducing inflammation is long established. However, in an acute care setting, the time scale involved in addressing acute inflammation may preclude the use of fish oil as a strategy for influencing the body's inflammatory equilibrium. Nonetheless, it is worth mentioning the potential role that specialized pro-resolving lipid mediators (SPMs) may play in influencing the biology of risk, in those for whom care is occurring in the Prevention Phase.
SPMs are downstream products of the metabolism of EPA and DHA, the primary active constituents of fish oil. EPA is the precursor for the E series resolvins, and DHA is the precursor for the D series resolvins, neuroprotectins, and maresins.244,245 These lipid mediators play a key role in the resolution phase of the inflammatory process.9
SPMs can inhibit priming and activation of macrophage NLRP3 inflammasome (in vivo and in vitro). SPMs, specifically D2,246 suppressed IL-1? production and secretion in LPS- and ATP-challenged macrophages, and reduced inflammasome assembly and caspase-1 activity. D2 also deactivated the inflammasome in a mouse peritonitis model, as shown by reduced IL-1? release and increased M2 markers of inflammation resolution.
2. Natural Killer (NK) cell support
Radix astragali (Astragalus) - One of the top prescribed botanicals in TCM preparations for SARS-CoV-1 was Radix astragali, with numerous published clinical trials demonstrating significant efficacy for both prevention and treatment. In SARS-CoV-2, astragalus continues to be the most common botanical in TCM prevention formulas prescribed in China.247
Andrographis paniculata (Andrographis) - The antiviral properties of andrographis have been proposed as leads for pharmaceuticals in the antiviral drug discovery literature.248-251 Andrographis has been shown in human randomized controlled trials to be effective in upper respiratory tract infection252,253 and pharyngotonsillitis.254 Andrographis has been shown to promote natural killer cell activity255,256 and also reduce the levels of inflammatory cytokines.257
Ganoderma lucidum (Reishi mushroom) - Ganoderma has been used in traditional Chinese medicine (TCM) for thousands of years. The antiviral properties of ganoderma have been studied in dengue,258,259 HIV,260 HPV,261 enterovirus71,262 and herpes.263 Reishi activates NK cells264-268 and Th1 cells269,270 and downregulates inflammatory cytokines in human alveolar epithelial cells.271,272
3. Th1 cell support
Berberine - containing Botanical Medicines (Hyrastis canadensis, Coptidis Chinensis) - Berberine has been shown to have activity across a broad range of viruses.273-280 Berberine has activity against RSV via upregulation of type 1 interferons.281 Type 1 interferons are key activators of NK cells and play a central role in antiviral immunity.282,283 The anti-inflammatory,284-286 cardioprotective,285,287 and antifungal effects of berberine have also been reviewed.288 One mechanism by which berberine downregulates inflammation is through activation of AMP kinase (AMPK).289 AMPK is a known activator of SIRT2,290 a known inhibitor of NLRP3 inflammasome assembly.23 Other mechanisms of berberine inhibition of NLRP3 have also been described.291-293 Berberine-induced AMPK inhibits IL-6-induced inflammation in human liver cells by inhibiting STAT3, the signal transduction factor required for Th17 cell differentiation.294 Berberine promotes the Th1 cytokines IL-12 and IFN? and inhibits the Th2 cytokine IL-4.295-297
Berberine also has potential advantages in impacting clotting. Hypoxia inducible factor 1 alpha (HIF1?) has been described as a promoter of thrombosis.298-300 As the name implies, HIF1? is upregulated by tissue hypoxia. With poor oxygenation, higher HIF1? levels will drive more thrombus formation. As described before, neutrophil NETs offer an additional base material for clot formation.60 The combination of these factors may be a driving force in the extensive pulmonary microvascular damage seen in severe manifestations of COVID-19. Berberine has been shown to downregulate HIF1?.301-305
In a human trial with 130 acute coronary syndrome subjects receiving percutaneous coronary intervention, those receiving 300 mg of berberine TID for 30 days had significant reductions in matrix metalloproteinase (MMP)-9, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, C-reactive protein, IL-6 and monocyte chemoattractant protein-1 (MCP-1), all of which are inflammatory signaling molecules.306
Goldenseal is often used because its high concentration of berberine. In a study examining the inhibition of influenza A by berberine, goldenseal at higher dosages was found to be effective at inhibiting both growth of influenza A and production of TNF? and PGE2.307
Baicalin - containing Botanical Medicines (Scutellariae baicalensis (SB) and other Scutellaria spp.) - The high infectivity rate of SARS-CoV-2 separates it from the genetically similar SARS-CoV-1. Preprint research suggests that one difference might lie in a unique furin-like cleavage site on the SARS-CoV-2 Spike protein that is absent in SARS-CoV-1.308 Dengue virus also infects human cells via furin cleavage, and could be inhibited in vitro and in vivo by application of the flavonoid luteolin.309
Evidence for antiviral, antioxidant, and anti-inflammatory effects of SB has been reviewed.310,311 The ability of SB to downregulate Th17 cell differentiation , the major source of IL-17 that induces macrophage IL-6 production , has been reviewed.312 Compounds isolated from SB have been shown to have antiviral and Nrf2-promoting antioxidant properties.313 SB has shown utility in downregulation of NLRP3 inflammasomes,314,315 antimycobacterial and anti-inflammatory effects in macrophage infection,316 and anti-H1N1 activity in vitro and in vivo through induction of IFN-? producing cells.317 Activity against H1N1 and H3N2 infected cells has been show to be associated with upregulation of type 1 interferons.318
In children with acute lymphocytic leukemia, administration of SB extract yielded increased production of IFN? in peripheral blood lymphocytes (PBLs), and reduced TNF? and IL-10 production in bone marrow cells (BMC), in all patients.319 The increase in immune surveillance (increased IFN?) and downregulation of inflammation (reduced TNF?) constitute a potentially useful dual effect. Other phytochemicals similar to SB have been identified that block the entry of SARS-CoV into host cells.320
Glycyrrhiza glabra (Licorice root) - Glycyrrhiza glabra, common name licorice root, has a long history of use in Western herbal medicine for viral infections and in traditional Chinese medicine (TCM) as a key ingredient for pandemic formulas. It was a component in TCM formulas for SARS-CoV-1 prevention and treatment. Along with astragalus, it is the most frequently used botanical in TCM formulas for SARS-CoV-2 prevention in China.321 Multiple clinical trials have demonstrated its effectiveness as a part of TCM formulas for CoV-1 and H1N1.322 Numerous in-vitro studies have shown the major active constituent of licorice, glycyrrhizin, to be effective against SARS-CoV-1.322 The Th1 promoting properties of licorice may contribute to its antiviral action and have been reviewed.323
A 2003 study published in Lancet looking at two clinical isolates of coronavirus from patients with SARS-CoV-1 identified glycyrrhizin to be the most active component of licorice in inhibiting viral replication as compared to ribavirin, 6-azauridine, pyrazofurin, and mycophenolic acid.324
A preprint molecular docking study suggests that the major active constituent, glycyrrhizin, can bind the ACE2 receptor, and therefore may have anti-SARS-CoV-2 activity.325
Licorice is considered a botanical of low toxic potential and has been safely used in Western and Eastern herbal medicin for millennia. However, excessive use can exert an aldosterone-like affect resulting in potassium wasting. Prescribing glycyrrhizin in individuals on potassium wasting medications may result in hypokalemia.326 It's also important to note that SARS-CoV-2 itself has been associated with potassium wasting,327 as is hydroxychloroquine, a drug gaining some renown as a potential COVID19 therapeutic, especially early in the disease process.328 Clinical considerations for patients with an increased risk for cardiac arrhythmias, either secondary to acquired conditions or co-morbidities or consequent to inherited syndromes, have been reviewed.329 Thus, while glycyrrhizin may be a very important COVID19 intervention, serum potassium should be monitored to avoid hypokalemia in vulnerable individuals.
Note that while DGL has substantial clinical research for such conditions as gastric ulcers, this form is not appropriate for COVID-19 as it is deglycyrrhizinated, i.e., the antiviral constituent has been removed.
Echinacea spp. - Extracts of various species of echinacea have been used traditionally in North America for many years and are currently popular for the treatment of many types of upper respiratory infections. Recent studies have supported its use by demonstrating that echinacea extracts possess potent pleomorphic antiviral activities. Direct viricidal activity has been demonstrated particularly against membrane containing viruses including coronaviruses by targeting membrane components, capsid proteins, and virus replication. In addition, reversal of the pro-inflammatory response of epithelial cells to viral infection, and reduction of excessive mucin secretion has also been observed.330,331
Of possible particular utility in COVID-19 is a species of echinacea with a long history of use in Western herbal medicine: Echinacea angustifolia. Also known as narrow-leaved purple coneflower, this medicinal herb is native to North America. A particular standardized extract of echinacea was shown to upregulate IL-2 and IL-8 and downregulate TNF? and IL-6 gene expression.332 An uncontrolled pilot study of this preparation in 36 adults with existing respiratory disorders (chronic bronchitis, respiratory insufficiency, or intrinsic asthma) found improved response to influenza vaccination and a substantial, statistically significant increase in IgG.333
Variation in extractions methods, errors in identification, and inconsistent choices in part of plant used present challenges in the clinical choice of echinacea products. Research on a particular extract cannot be reliably extrapolated to other products.
Th2 Dominance Inhibition - Understanding the complex dynamics of T cell polarization patterning has gone far beyond Mossman's original Th1/Th2 dichotomy.334 There are currently seven known maturation fates of naïve T cells, and immunologists no longer think of Th1 as inflammatory and Th2 as anti-inflammatory. In patients whose baseline function likely involves Th2 dominance, indicated by asthma, chronic sinusitis, allergies, or other known Th2-dominant disease processes, or in patients for whom there are other concerns about the prospect of a loss of adequate Th1 response early in the infection phase of illness, it may be useful to consider downregulating an overly exuberant Th2 response.
Perilla spp. - Perilla has been shown to downregulate Th2 dominance-based processes like allergic airway inflammation, seasonal allergic rhinoconjunctivitis, and asthma.335,336 Mechanistic studies suggest this effect is mediated by downregulation of Th2 effector cytokines, including most importantly (IL-4), the cytokine driving Th2-biased autocrine responses. Perilla has also been shown to inhibit platelet aggregation and thrombus formation.337,338 Dietary supplementation with perilla seed oil in patients with asthma suppressed the generation of leukotriene (LT) C4.339
Radix astragali (Astragalus) - Astragalus has substantial Th2 inhibiting properties. As with perilla, astragalus significantly decreased intensity of Th2 dominance-based disease processes like rhinorrhea.340 Mechanistic studies have shown that astragalus downregulates Th2 cytokines and lowers the ratio of GATA3 (Th2 cell transcription factor) to Tbet (Th1 cell transcription factor).341-343 Astragalus also upregulates the formation of NK cells in peripheral blood mononuclear cells (PBMCs) from SLE patients.344
4. Anti-Inflammatory Support
Inhibition of the NLRP3 inflammasome and NFkB are central to this task.
Potassium - Maintaining blood potassium levels is important, to prevent potassium cellular efflux, which upregulates inflammasome assembly.42
COVID-19 drug therapy guidance published on April 8, 2020, from the American Heart Association, the American College of Cardiology, and the Heart Rhythm Society states that hypokalemia should be corrected to >4.0 mEq/L and hypomagnesemia corrected to >2.0 mg/dL.345
Curcuma longa (Tumeric) - Curcuminoids are long used turmeric-derived compounds with well-documented pleotropic effects, including antiviral and anti-inflammatory activity.346,347
As has been discussed, the aggressive virulence of SARS-CoV-2 may be driven in part by upregulation of NLRP3 leading to production of IL-1?, IL-18 and pyroptotic cell death.348
Curcuminoids have been shown to specifically inhibit caspase-1 activation and IL-1? secretion through suppressing LPS priming and NLRP3 activation.349
Regarding activity specific to SARS-CoV-2, recent prepublication molecular docking data suggest that the curcuminoids demethyoxycurcumin and curcumin have viral replication inhibition potential against the main protease (Mpro) identified as likely involved in viral maturation and spread. Note that a number of other flavonoids demonstrated inhibition potential in the docking study, with the strongest and best potential SARS-CoV-2 Mpro inhibitors being: kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate.350
In another molecular docking study, curcumin showed effective inhibition of SARS-Cov-2 Spike viral glycoprotein binding to ACE2 receptor. While these data are clearly preliminary, the findings suggest the potential of curcumin to halt viral entry into host cells. Other effective flavonoids included hesperidin, with the highest binding affinity.351
Bromelain - Many studies have documented efficacy of bromelain in reducing inflammation and inflammatory diseases. Clinical benefit has been shown in injuries, infections, respiratory tract diseases, arthritis, inflammatory bowel disease, etc. Of particular importance here is its documented ability to decrease tissue edema and inflammation.
Several studies have shown that bromelain is effective in respiratory conditions such as asthma, bronchitis, and sinusitis that are characterized by increased mucus production and inflammation. Spirometry before and after bromelain treatment demonstrated increased FEV1 and vital capacity, which were suggested by the researchers to be a result of bromelain's mucolytic activity.352,353
Of particular interest here is the limited research showing that bromelain decreases cytokines. A placebo-controlled randomized clinical trial found that high-dose oral bromelain showed immunomodulation of both Th1- and Th2- cytokines.354
Resveratrol - Constituents of resveratrol have been shown to reduce inflammation via several mechanisms including downregulation of IL-6 and TNF? and promotion of Sirtuins.355-358 Crucial to the utility of resveratrol is its ability to inhibit the accumulation of acetylated ?-tubulin caused by mitochondrial damage in macrophages stimulated by NLRP3-inflammasome induction. Inflammasome assembly is strongly induced by acetylated ?-tubulin. Resveratrol upregulates SIRT2, a known deacetylator of ?-tubulin.359-361 The utility of resveratrol has been studied in SARS-CoV-1.362 Resveratrol has been shown to protect lung epithelia against the effects of cigarette smoke by upregulating Nrf2 to promote GSH.363
The utility of resveratrol has been studied in a wide range of diseases including cardiovascular364 and metabolic inflammatory processes.365
Quercetin - See the quercetin discussion above.
Melatonin - See the melatonin discussion above.
Boswellia serrata (Boswellia) - Via a variety of mechanisms, boswellic acid (BA), an active constituent in Boswellia serrata, exerts a number of anti-inflammatory effects. BA was shown to potently inhibit TGF? induced pulmonary fibrosis and 5-lipoxygenase in an animal model.366 BA has also been shown to significantly inhibit cyclooxygenase, NFKB signaling and TNF?.367,368
Sulforaphane - Sulforaphane is a well-studied anti-inflammatory phytochemical found in cruciferous vegetables that also inhibits NLRP3 inflammasome biology.369,370 Sulforaphane activates the antioxidant Nrf2 pathway and drives significant anti-fibrotic activity benefit in both TGF? treated cell lines, and induced fibrosis in animal models.371 Sulforaphane also upregulates GSH levels.372,373
It is noteworthy that curcumin, resveratrol, quercetin, and berberine have all been shown to promote AMPK.374 AMPK is a promoter of SIRT2, also known to inhibit NLRP3 inflammasome assembly.23
5. Anti-Oxidant Support
Patient GSH status can be supported with oral GSH (liposomal forms appear to offer better absorption), NAC, vitamin E, and selenium. In addition, GSH can be delivered by nebulizer or by IV. It may be appropriate to give both NAC and GSH, in service of supporting GSH status. When available, lab testing can support the clinician's monitoring of GSH levels.
NAC and GSH - Oral and Nebulized Delivery
Nebulized NAC and reduced GSH have a long history of clinical use by natural/ integrative/ functional/ holistic doctors for the treatment of COPD and other chronic inflammatory lung conditions. While there is substantial research support for the value of oral NAC and oral GSH in respiratory illnesses, the research to date on the nebulized delivery is limited but encouraging.
NAC-oral, IV and nebulized-has considerable research support for improving respiratory tract immunity, normalization of inflammation, helping reduce excessive mucous secretion and functioning as a mucolytic. A recent review well summarized its value in respiratory diseases:
Biological and pharmacological effects of NAC include improvement in rheological properties of mucus, reduction of excess mucin production, restoration of mucociliary clearance and production of sIgA, suppression of excess production of IgE and IgG4, destruction of biofilms and inhibition of their formation, suppression of adhesion of pathogenic bacteria to epithelial cells, antioxidant activity, regulation of the production of pro-inflammatory and profibrotic cytokines.375
While nebulized forms are likely more effective, oral NAC at 600 mg bid was shown in in a controlled study of patients with COPD to significantly improved PaO2, PaCO2, wheezing, and dyspnea and decrease the need for nasal oxygen support.376
While most studies support this intervention, a clinical study on mechanically ventilated patients showed that while NAC was more effective than saline in decreasing mean secretion density the results were not statistically significant (P = .087), likely due to a small sample size (20 patients in each arm). However, despite small sample size, NAC was significantly effective at increasing O2 saturation.377
A randomized, controlled study of IV NAC (50 mg/kg/day for three days) for 27 ICU patients with ALI/ARD demonstrated statistically significant improvement in oxygenation and decreased mortality.378
Normally, nebulized GSH would be recommended for respiratory inflammation. However, the high level of mucous secretion in COVID-19 could impair its ability to penetrate deeply enough into the lungs. Therefore, the authors recommend IV GSH, to protect both the lungs and also the heart from the damaging inflammation.
While there are a considerable number of controlled clinical studies on the various forms of NAC, there is a surprising dearth of such studies on IV GSH as an independent therapy. Virtually all existing studies examine the use of IV GSH in conjunction with drugs, especially chemotherapy agents. There are several studies showing modest benefit in Parkinson's disease, but virtually no other conditions we could find in PubMed.379
The research is clear that inhaled GSH substantially increases blood levels. A few controlled studies have shown modest benefit from inhaled GSH in cystic fibrosis and asthma.380,381
Read the entire article HERE
We’ve been hearing on the news a lot about people with “compromised immune systems” being at greater risk of contracting unwelcomed viruses. What does “compromised” actually mean except that you’re more susceptible to getting sick?
The immune system is defined as a complex network of cells, tissues, organs and the substances they make that help the body fight infections and other diseases; it includes white blood cells and organs and tissues of the lymph system, such as the thymus, spleen, tonsils, lymph nodes, lymph vessels and bone marrow.
In this article, we’ll explore what it means to have a strong immune system, how it evolves throughout life, and how to boost your immune system to promote overall health.
A strong immune system has both powerful adaptive and innate immunity; both work together to protect the self from foreign invaders. Living a healthy lifestyle boosts the immune system in many ways that we’ll explore later on in this article.
Typically people between the ages of 10 and 50 will have stronger immune systems when compared with infants and the elderly. Other factors that contribute to having a strong immune system include lower stress and getting a good night’s sleep.
In one study that tracked elderly people in Taiwan, 639 blood samples were taken to measure the levels of self-reactive antibodies, which are antibodies that are capable of fighting your own tissues. Interestingly, the researchers discovered that people with these antibodies seemed to live longer and had a 33% lower chance of dying that year. The downside is that these antibodies are the same ones implicated in autoimmune diseases, such as lupus and rheumatoid arthritis. In either case, however, it validates how important our immune response is to our overall health.
In summary, people who suffer from autoimmune disease are said to have powerful immune systems, which, in one respect appears to provide greater protection from parasites, but may make people more susceptible to other diseases.
The immune system changes over our lifetimes. The seven stages of a man’s life derived from Shakespeare’s As You Like It, paint an interesting picture of life. Each “act” offers different levels of immunity from disease.
"And one man in his time plays many parts, his acts being seven stages." -William Shakespeare
Here are the seven stages of man, as explained by Shakespeare, and how the immune system develops over time:
In some aspects, the immune system of the elderly resembles that of the newborn due to reduced antimicrobial activity by neutrophils and macrophages, and somewhat compromised adaptive lymphocyte responses. Therefore, both the very young and old immune systems are similarly compromised in coping with a typical viral infection. Also, the evolution of the immune system appears to protect the young adult by providing optimal immune responses during procreative years.
There are some conditions where an immune system can get too strong. For example, allergies, asthma or eczema can occur if an immune system is too strong. Autoimmune disease is also thought to happen due to an overactive immune system.
Healthy lifestyle habits cannot make your immune system too strong. Normally immune systems that fight themselves are due to genetic factors in the innate immune system.
An immune system might be considered “weak” due to a person’s age or if someone is health-compromised from a medical issue or if taking medication that lowers the immue response. Also, in situations that can be controlled, poor lifestyle choices, like drinking too much alcohol can result in a weakened immune system.
A blood test can determine how well an immune system is functioning by looking at levels of immunoglobulins, for example, which are proteins that fight infection. The test will also compare your levels of white blood cells and red blood cells to detect any possible weakness in your immune system.
1. Exercise
We all know that exercise is good for us. Increased overall fitness can boost the immune system, in turn, fighting off colds and infections. In a year-long study, published in the American Journal of Medicine, researchers found that walking for half an hour a day can cut your chances of getting a cold in half.
Exercising increases white blood cell count, specifically T-cells that are essential immune-boosting cells. It’s important to note that exercising is a preventative measure. It can be too taxing on your body to exercise when you have an infection. Another study showed that one hour of brisk walking a week can protect you from disability.
2. Immune System Boosting Foods
The foods that we eat impact our health immensely. To boost your immune system, try incorporating some of these ten immune system boosting foods:
3. Nutrients to Boost the Immune System
Your immune system develops over time and adapts to your environment. There are many lifestyle choices that can be made that help to boost your immune system, such as eating a diet rich in whole foods and getting enough exercise. In addition, a number of nutrients are especially good at promoting a healthy immune system, such as zinc, vitamin D, vitamin A, vitamin C and target-specific probiotics.
Source: bit.ly/2XFi6wR
The end stage of virus infections often correlates with the onset of a cytokine storm. This uncontrolled release of proinflammatory cytokines by the body’s immune system involves more than 150 known inflammatory mediators. There are many factors involved in the progression of what begins as a healthy immune response to a state of amplified cytokine production.
Cytokines signal immune cells such as T-cells and macrophages to travel to the site of infection when the immune system is fighting a pathogen. This signaling activates those cells, stimulating them to produce more cytokines. The feedback loop is normally managed efficiently by the body, but in some cases the process becomes unregulated, with too many immune cells activating in a single location.
This exaggerated immune response is not completely understood but could be attributed to the body encountering a new, highly pathogenic attacker. Cytokine storms have the potential to cause significant damage to various tissues and organs. For example, if a cytokine storm occurs in the lungs, macrophages and fluids may accumulate, eventually obstructing the airways.
A study looked at how curcumin influences cytokine release and cytokine storm. The article reported on the effects of curcumin on cytokine expression in a mouse model of virus-induced acute respiratory distress syndrome. The authors stated: “Curcumin blocks cytokine release, most importantly the key pro-inflammatory cytokines, interleukin-1, interleukin-6 and tumor necrosis factor-α. The suppression of cytokine release by curcumin correlates with clinical improvement in experimental models of disease conditions where a cytokine storm plays a significant role in mortality.” The research team concluded that curcumin may offer support to those experiencing cytokine storms.
One challenge when using curcumin is that it is poorly absorbed across the gut lining. While the study authors propose using IV curcumin preparations it may be of value to consider the use of oral curcumin that provides increased bioavailability via dual phase polar/non-polar emulsion technology, which has been shown in a human clinical trial to be 5x and 6x better absorbed than phospholipid or oil preparations respectively.
Source: bit.ly/2Kf1QuA
It seems the latest and greatest to cure all of our health woes is invented every month… But maybe the answer exists in your body already.
Enter glutathione.
Glutathione is the most abundant antioxidant in our bodies. In fact, virtually every organism on Earth has some glutathione in its cells.
And for good reason. This “master” antioxidant protects the human body like few others. Without adequate levels of glutathione, you are at risk of dangerous medical conditions, including stroke, Alzheimer’s disease, and heart disease.
But when glutathione levels are healthy, that’s when the magic happens. You can not only prevent health problems, but possibly experience amazing energy, glowing skin, a strong heart, and a sharp brain.
Sound too good to be true? Keep reading to learn about the research that backs this up.
Glutathione is a potent antioxidant found in both plants and animals. Often called the “master antioxidant,” glutathione also boosts (recycles) other antioxidants, like vitamin C and vitamin E, as well as alpha lipoic acid and CoQ10.
Glutathione is a tripeptide, which means a very small protein composed of three amino acids:
There are two different forms of glutathione:
Glutathione protects your mitochondria, ensuring your cells are able to make the energy your body needs.
Mitochondria are the “power plants” of your cells. Every one of your cells has mitochondria, which convert glucose, amino acids and fats into energy.
But mitochondria can also sense danger when cell energy levels drop, and are even involved in sending the final "death" message (apoptosis) when a cell is damaged beyond repair and needs to die.
Mitochondria need to be protected, and the “knight in shining armor” who guards our source of energy is none other than glutathione.
Glutathione makes sure that heavy metals, organic toxins, and free radicals generated during normal metabolism don’t damage the mitochondria.
Age is the most natural reducer of glutathione levels. However, there are a number of environmental factors and medical conditions that increase your risk of deficiency.
Environmental risk factors of glutathione deficiency include:
Certain illnesses are known to decrease glutathione levels. Researchers are still determining whether low glutathione causes some of these diseases, or the other way around.
The most common low glutathione-related diseases are:
The role of glutathione in your bodily function cannot be understated. Healthy levels of glutathione possess some potent health benefits, including anti-aging properties.
These health benefits largely relate to glutathione’s role in these vital bodily processes:
But the most powerful functions glutathione offers your system are its antioxidant properties. Glutathione fights free radicals and the oxidative damage they cause.
Many people know the chef’s trick of sprinkling a little lemon juice over fruit to keep it from turning brown. Antioxidants are like that lemon juice. By consistently “sprinkling” your body with antioxidants like glutathione, you can prevent your body from “browning” or “oxidizing” which causes damage and aging of cells. Antioxidants are the “anti-agers” of the nutrient world, working to protect your body from free radicals, and the oxidative damage they cause.
Every time you eat, breathe, or move, your body uses fuel created from the food you eat to produce energy. But just as a car releases harmful byproducts as exhaust, so too does your own body’s energy-producing efforts produce a dangerous byproduct: free radicals.
Free radicals are highly reactive forms of oxygen that are missing an electron. When they come into contact with normal molecules, they steal an electron, damaging the healthy cell and its DNA.
In fact, some estimates show that your DNA takes 10,000 oxidative hits daily. Antioxidants work to counteract the damage caused by free radicals.
Glutathione is the “master” antioxidant, directly binding to oxidative compounds that damage cell membranes, DNA, and energy production. It directly neutralizes a wide range of oxidants, including superoxide, nitric oxide, carbon radicals, hydroperoxides, peroxynitrites, and lipid peroxides.
Glutathione offers the all-important antioxidant defense like few others can.
The role of glutathione in your body’s detoxification system is vital. But your natural processes sometimes need a boost from increased glutathione from your diet or supplements.
Here’s how the detoxification system works, in three phases.
During Phase 1 detoxification, all sorts of toxins and xenobiotics are partially processed by specialized proteins inside mitochondria called cytochromes.
Unfortunately, Phase 1 is an incomplete processing and can turn toxins into dangerous free radicals. These are not only damaging, but they can single handedly deplete glutathione, creating an imbalance between Phase 1 and Phase 2 activity.
In Phase 2 detoxification, various enzymes act directly on the toxins partially degraded and processed in Phase 1. These enzymes use glutathione to neutralize the toxins.
Phase 3 detoxification is the elimination of toxins and xenobiotics. Toxins are removed from your body, mainly by the kidneys (urine) and liver (bile).
Without glutathione, your body would not be able to neutralize and eliminate toxins effectively.
Energy production occurs within all cells (except red blood cells) via the mitochondria. Glutathione protects mitochondria from free radicals and the oxidative damage they cause. In this way, glutathione is paramount to energy production.
If mitochondria are damaged, they slow down and start to make less energy. The affected “diseased” mitochondria leads to decreased bodily function and efficiency.
To make things worse, damaged mitochondria output more free radicals. In turn, these free radicals cause further mitochondrial damage and create a vicious cycle of less energy and more damage.
GSH binds these free radicals and relieves oxidative stress — not just on the mitochondria, but on the rest of the cell.
Whether concerned with acne, wrinkles, dryness, eczema, or puffy eyes, many are seeking flawless, youthful skin. Science says that glutathione is an effective answer.
Fortunately, you don’t have to empty your wallet to restore the youth and health of your skin. You can solve the problem from the inside out. Cells can heal and regenerate themselves, thanks to glutathione.
Glutathione not only decreases the melanin (pigmentation) in your skin, but has also been found to decrease wrinkles and increase skin elasticity.
Glutathione works on the skin pigment production by inhibiting tyrosinase, an enzyme involved in making melanin.
In one study, both GSH and GSSG achieved a skin lightening effect — though it takes a few weeks to develop. The effect on pigmentation is transient, so you would need to continue using glutathione to maintain the skin-whitening effect.
A scientific review of multiple studies confirmed that the use of glutathione results in skin lightening.
Glutathione has also been shown to decrease psoriasis. The glutathione levels in this clinical trial were increased by consumption of whey protein, which contains glutamylcysteine, a precursor to GSH.
The same studies also show that glutathione doesn’t just lighten skin, but it improves skin elasticity and decreases wrinkles.
How do low levels of glutathione affect brain and mental health? There is a clear link between low glutathione levels and decreased brain health.
As we age, it’s not uncommon to experience a bit of forgetfulness or difficulty concentrating. These are just two examples of neurodegeneration, a process by which the neurons in our brains become damaged and may even die.
This leaves us with “shrinking” brains that don’t function to their full capacity. While this process is unavoidable as we age, it can be slowed, or even reversed, and glutathione (GSH) plays an important role.
Accelerated neurodegenerative diseases, like Parkinson’s disease and Alzheimer’s diseases exhibit high levels of oxidative stress damage to the brain as well as low active glutathione (GSH) levels. GSH can ease and decrease the rate of damage to brain tissue.
While these results are promising, a 2017 study involving Alzheimer’s patients using intranasal GSH found that GSH and placebo had equally good results — after three months. Glutathione produced positive results. However, so did the placebo.
Other neurological illnesses like Lyme disease weaken when your body experiences higher levels of glutathione.
The number one health related cause of death in the United States is still a heart attack. A lesser known fact is that glutathione may prevent heart attack and other heart disease, thanks to its ability to neutralize the “lipid oxidation” (fat oxidation) process.
Virtually all heart disease starts with the accumulation of arterial plaque inside the artery walls. Bad cholesterol (LDL) is lipid oxidized and damages the lining of the blood vessels, forming a plaque (atherosclerosis).
When these plaques eventually rupture and break off, they can clog your blood vessels and block blood flow that causes heart attacks or strokes.
With the help of an enzyme called glutathione peroxidase, glutathione stops the superoxides, free radicals, hydrogen peroxides, lipid peroxides, and peroxynitrites that cause this lipid oxidation and wreak havoc on your health.
In this way, glutathione helps to prevent damage and lowers the risk of heart attacks.
In a study of 643 cardiac patients who underwent coronary angiography in Germany, those who died of heart attacks had much lower levels of glutathione peroxidase than those who survived.
If we don’t have enough glutathione to neutralize damage to our arteries, we are at increased risk of heart disease and cardiovascular events.
Does glutathione help with inflammation? As a matter of fact, glutathione is great at fighting chronic inflammation!
Inflammation has been a hot topic in the natural health world for the past decade; however, many people still don’t fully understand exactly why inflammation lies at the root of most of the health concerns plaguing Americans today.
High levels of inflammation are present in virtually every chronic illness, like diabetes, heart disease, and cancer. However, inflammation is also healthy and necessary (in short bursts) to fight infectious invaders.
Injury can also incite an inflammatory response. Whether you are talking about trauma, infection, toxins, or allergies, your immune system answers the same.
First, the blood vessels in the injured area begin to expand and open wide to allow your body’s natural healing compounds to get the injured site as quickly as possible. Because of the increased blood flow, fluid and immune cells flood the area often in overwhelming amounts.
This increase in permeability of the blood and lymph vessels is what causes the physical manifestations of acute inflammation, namely redness, pain, stiffness, and swelling. After the infection or injury is repaired the acute inflammatory response normally subsides and goes away.
The inflammatory response comes to your rescue when it’s needed and cools itself off once the healing is complete. But we don’t live in an ideal world.
In the real world, environmental toxins, your diet, stress, and other lifestyle issues have disabled the checks and balances of this system and inflammation doesn’t subside and go away as it is meant to. As a result, many people suffer from chronic, systemic inflammation.
When this happens, you’re in trouble. You need a lot of extra protection. That’s where glutathione can help.
Glutathione (GSH) controls when inflammation increases or decreases as needed, by instructing and influencing our immune white cells. This is a completely separate mechanism from its antioxidant properties.
Rebalancing glutathione levels reduces chronic inflammation and restores immune function.
Glutathione helps your immune system stay strong and ready to fight infections. While vitamin C seems to get all the accolades when it comes to immunity, glutathione is the under-recognized supporting actor who deserves the starring role.
Research shows that active glutathione (GSH) primes white cells such as natural killer (NK) and T cells, your body’s front-line infection fighters. GSH-enhanced T cells are able to produce more infection-fighting substances, controlling both bacterial and viral infections.
One clinical trial in particular found that GSH doubled NK cells’ ability to be cytotoxic (kill invaders) after just six months of use. Glutathione actually has a potent antibacterial effect as it helps the immune cells called macrophages fight the bacterium that causes tuberculosis, Mycobacterium tuberculosis.
In another study, researchers found that GSH modulates the behavior of many immune system cells, affecting adaptive immunity and protecting against microbial, viral and parasitic infections.
There are many chronic infections such as EBV, hepatitis, herpes viruses and Lyme, to name a few, which can deregulate and suppress the immune system. Glutathione can modulate and reverse this suppression.
Autoimmune diseases also appear to be hallmarked by imbalanced glutathione levels.
Glutathione can boost athletic performance when used before workouts. Best of all, you don’t have to be an ultramarathoner or a bodybuilder. Anyone from the average runner to the weekend warrior can benefit from this exercise enhancer.
In a study of eight men receiving 1,000 milligrams of glutathione before exercise, the glutathione group performed better, felt less fatigued, and had lower blood lactic acid levels than the placebo controlled group.
This is key, since increased lactic acid in the body can result in fatigue, low blood pressure, muscle aches, a drop in body temperature, and respiratory problems.
Glutathione combined with L-citrulline boosted nitric oxide production (NO) better than placebo or L-citrulline alone.
Nitric oxide is well known to dilate blood vessels improving blood flow and oxygen delivery to muscles and tissues. This improves athletic performance and exercise output.
1 in 59 children is diagnosed with autism. It’s important to do everything you can to alleviate the more harmful symptoms of autism spectrum disorder. Supplementing glutathione should prevent the oxidative stress that is common in children dealing with autism.
How does glutathione help autism?
Low levels of glutathione are a common finding in autism, among other biomarkers. Promising new research shows that liposomal and transdermal glutathione might help raise levels of GSH in plasma in children with autism. Some evidence suggests that glutathione support may improve function in autism, but double blinded large scale studies are needed to scientifically support this.
Glutathione supplementation has been linked with reduced symptoms of peripheral vascular disease (PVD). Since PVD affects 10% of Americans, glutathione offers a much needed solution to this circulatory system disease.
PVD occurs when narrowed blood vessels do not supply enough blood supply to muscles when needed — most often muscles in the legs. Fatigue and pain with walking are hallmark symptoms of PVD.
In a double blind study, 40 PVD patients were given IV infusions of either GSH glutathione or placebo, twice a day. The patients receiving GSH were able to walk pain-free much further than the patients receiving placebo injections.
IV clinics which offer glutathione injections, are gaining in popularity. However, these aren’t quite mainstream yet. The extra work of finding such a clinic may be a worthwhile pursuit for those afflicted by PVD.
Low serum glutathione seems to lead to abnormalities in the lungs. Preliminary research suggests a clear link between low glutathione and occurence of COPD.
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States. As damage from smoking or even pollution accumulates to the respiratory tract and the lungs, oxygen and carbon dioxide (CO2) exchange suffers, making it difficult to breathe.
Low glutathione levels have been linked to abnormalities in the lining of the lungs, which can lead to COPD. Having normal glutathione levels protects lung tissue from free radical damage, such as inflammation.
Additionally, animal studies found that intravenous glutathione supplementation maintained normal lung function, when exposed to otherwise toxic levels of oxygen. It also increased lung compliance, decreased swelling, and increased lung tissue.
Researchers concluded that glutathione supplementation promotes normal airflow and lung tissue, as well as lowering the risk of “oxygen-induced lung injury.”
Vitamin D3 — the most active form of vitamin D — has been a hot topic in medicine because it controls and modulates the immune system. And when glutathione levels are low, vitamin D3 doesn’t work as efficiently.
Initially thought to play a role in calcium metabolism and bone formation only, we now know that low vitamin D3 levels can increase your risk of:
What happens to vitamin D with glutathione deficiency? In fact, low vitamin D3 levels have been correlated with simultaneous glutathione deficiency.
Observing animals deficient in vitamin D3, researchers found that supplementing vitamin D3 and cysteine (a GSH precursor) restored glutathione levels, increased the bioavailability of vitamin D3, and lowered inflammation.
Researchers noted that the vitamin D supplements widely consumed by the public “are unlikely to be successful unless the GSH status is also corrected.”
In other words, simply taking vitamin D isn’t enough. You need to be sure you have adequate glutathione levels to make sure that your vitamin D3 is working as it should.
Glutathione production starts with the amino acid cysteine. Cysteine usually comes from homocysteine, a major product of the methylation cycle. Making glutathione depends on a well functioning methylation cycle.
Methylation is critical for human survival. It’s like an electrical switch that turns genes on and off. Methylation regulates neurotransmitters, brain function, mood, energy, and hormone levels.
Conversely, if the glutathione production process (or the “trans-sulfuration” pathway) is not functioning properly, the process backs up and homocysteine levels accumulate putting additional strain on the methylation cycle to remove it.
This is not ideal since high homocysteine levels have been linked to heart disease and atherosclerosis.
In many instances , people can have mutations in the enzymes that catalyze the production of glutathione from homocysteine.
One such enzyme is cystathionine beta synthase (CBS), which catalyzes the first and most important (rate limiting) step in trans-sulfuration from homocysteine to cystathionine. Individuals with CBS mutations will be slow to make glutathione.
Flipping this around, individuals who have poor-functioning methylation cycle enzymes will have lower homocysteine levels. Since it’s the first step in making glutathione, slow methylation can directly lower your levels of glutathione.
By now, you may have heard of the most famous enzymes — MTHFR and MTR — regulating the speed of the methylation cycle. For those of you who know you have MTHFR, MTRR, or CBS mutations, you are likely experiencing low glutathione levels without realizing it.
Clearly, methylation is a critical process — as well as a complicated one. The key message to remember here is that low methylation equals low glutathione and that low glutathione slows methylation. They are interdependent.
Tough stuff, right? But before you run for the hills, take comfort in the fact that there are a few simple steps you can take to restore and replenish your glutathione levels.
There are a handful of foods that naturally contain glutathione or glutathione-boosting nutrients.
A variety of factors can affect the levels of this vital nutrient, including storage and cooking. Cooking these foods can reduce their glutathione content by up to 60 percent.
Here are some easy examples of foods you can add to your diet to ensure your glutathione levels are at a healthy level.
Eating grass-fed whey protein can make it easier for your body to make GSH.
Whey protein contains gamma-glutamylcysteine, which is glutamine bound to cysteine.
Because this combination bypasses the tough first step to making glutathione in your cells, it is key in supporting higher glutathione levels through diet.
Allium is a genus of plants rich in sulfur, a precursor to glutathione synthesis. The more sulfur, the more natural glutathione production.
Plant foods belonging to the allium genus include:
Cruciferous vegetables are packed with glucosinolates, which will increase your body’s glutathione levels. These compounds give Brassica plants their distinctive sulfuric aroma.
Great cruciferous vegetables include:
Alpha lipoic acid regenerates and increases levels of glutathione within the body. Adding it to your diet should afford you all the health benefits of glutathione.
Good food sources of alpha lipoic acid include:
Selenium is a trace mineral that is part of the building blocks that make up antioxidant enzymes. It is also key in the production of glutathione.
Good dietary sources of selenium include:
While diet is the most natural way to boost glutathione levels, there are a variety of glutathione supplements available. Glutathione supplementation is a growing trend, especially in America, India, and the UK. Glutathione supplements come in many forms.
Glutathione can be taken orally in its plain powder form. However, powdered glutathione metabolism cleaves glutathione into the three amino acids it is made up of (glycine, glutamine, and cysteine).
This digestive cleaving process is so effective that nearly all of the plain glutathione you would take by mouth would never make it into circulation.
A better option for oral supplementation is to take liposomal glutathione on an empty stomach.
Liposomes are microscopic spheres with an active ingredient like glutathione contained in the center of the sphere. Randomized trials show that liposomal formulations increase GSH levels and absorption.
To use liposomal glutathione, start with 500 milligrams and increase to between 1,000 and 2,000 milligrams per day. Be sure to wait 45 minutes before eating or drinking or taking other supplements to allow for absorption of liposomal glutathione.
Glutathione can also be taken in an inhaled form called a nebulizer. A physician would need to write you a prescription for this form.
Additionally, you can use targeted nutrients to increase your body’s natural production of glutathione indirectly. These include selenium, vitamin E, alpha lipoic acid, NAC, and SAMe.
Use of glutathione as a supplement may bring about rare side effects: abdominal cramps, bloating, loose stools, gas, and possible allergic reactions. These adverse effects are uncommon.
Always consult your healthcare provider before taking dietary supplements, but especially if you are pregnant or breastfeeding.
If you’re worried about your glutathione levels, there are some common sense lifestyle changes we can all apply to our daily lives. Keeping the body healthy means glutathione is less likely to fall out of balance.
Not only can you add cruciferous veggies and selenium-rich foods to your diet, but you should cut out processed foods and processed sugars. Processed foods (such as cheese, cereal, and potato chips) can lead to heart disease, among other things.
It’s also wise to drink eight cups of water every day. That’s half a gallon.
Reducing stress makes it easier for your body to function properly, including your mitochondria.
The US government recommends half an hour of exercise five days a week — and for good reason. The exercise keeps your body healthy and your glutathione levels normalized.
Get your 7-8 hours of sleep every night. As a side note, you shouldn’t exercise within an hour of when you go to sleep.
Consult a healthcare professional before making any major lifestyle changes.
Your heart is one organ you can't live without. In times past, people actually considered the heart the seat of thought and emotion, rather than the brain. After some time, experts realized that the heart actually delivers life-giving oxygen and nutrients throughout the body.
Getting enough heart-healthy nutrients is just as vital to cardiovascular health as exercise. Vitamins, minerals, and certain herbs help your heart, blood vessels, and entire circulatory system function well. Below we list the 14 best supplements that provide the biggest bang for your buck, so you can choose what's right for you.
Eating a healthful, balanced diet is one of the most important things you can do for your heart. And whether you get them through diet or supplements, certain vitamins and minerals play a special role in supporting a healthy, happy heart.
As you grow older, your body may produce less of certain nutrients, or your body may absorb them less efficiently than when you were younger — that makes supplementation increasingly helpful with age.
These nutrients will help keep your heart healthy throughout life, and well into your golden years.
Studies have linked low levels of vitamin D to heart health risk factors. Getting more will make your heart happy.
Did you know that the sunshine vitamin plays a big role in how nerves carry messages to your heart?
Vitamin D is a fat-soluble hormone produced by your liver and kidneys, although exposure to the sun can boost its production. That's why people call it the sunshine vitamin! With age, your body makes less vitamin D, as well.
Vitamin D helps regulate levels of calcium in the blood, which plays a role in how nerves carry messages to your heart — along with other parts of your body.
This vitamin may promote normal blood sugar levels.
The daily requirement for adult men and women is 15 mcg (micrograms) or 600 IU. The Institute of Medicine Food and Nutrition Board recommends that adults over 70 get 20 mcg (800 IU) per day.
Vitamin C is a robust antioxidant that boosts collagen and repairs damaged tissues!
Found in oranges and other heart-healthy citrus fruits, vitamin C helps the body repair damaged tissue. Extra vitamin C also boosts your body's production of collagen, a protein that supports healthy blood vessels. A powerful antioxidant, this nutrient counteracts free radicals that damage cells. Vitamin C also plays a key role in the body’s production of L-carnitine, a compound critical to metabolism and heart health.
Adult women need 75 mg (milligrams) while adult men need 90 mg of vitamin C each day, but if you eat a standard American diet, you might not get enough.
Your best bet? Boost your citrus fruit intake! Eating vitamin C-rich fruits and vegetables — at least five servings a day — has been linked to a more than 15 percent reduction in heart disease risk.
Vitamin C normalizes levels of LDL (bad) cholesterol and promotes normal blood pressure. It does this by boosting production of a compound called nitric oxide that helps relax and open blood vessels, helping your blood flow smoothly and efficiently.
Vitamin K plays a role in how your blood clots. It also interacts with your body's processing of calcium, which transmits electrical impulses in the heart. Low vitamin K is linked to "vascular calcifications" or deposits on arterial walls, which leads to atherosclerosis — a leading risk factor for heart disease.
With normal levels of vitamin K, people generally have fewer calcium deposits. Higher vitamin K intake improves cardiovascular health by optimizing calcium levels in tissues. The right amount of vitamin K promotes proper blood flow.
The daily requirement for vitamin K is 90 mcg for adult women and 120 mcg for adult men; pregnant or breastfeeding women and children require different amounts.
Magnesium is the fourth most plentiful mineral in your body — but many people do not get enough. This mineral regulates muscle and nerve function, blood sugar levels, and blood pressure.
Magnesium helps the body absorb calcium, which, as mentioned, transmits the electrical impulse of your heartbeat. Magnesium helps muscles relax, while calcium helps them contract; together they help the heart muscle work properly.
Maintaining adequate magnesium levels is critical for heart health. The daily recommendation is 320 mg for adult women and 420 mg for adult men. While you can get magnesium from nuts, seeds, and legumes, you may need a supplement to ensure you get enough.
Different forms of magnesium are sold as supplements with different absorption rates; make sure you do your research on the best types for your needs.
A deficiency in potassium can lead to blood pressure issues in adults.
Potassium is an electrolyte, a mineral that acts as an electrical charge to help your body. These electrolytes help your heart, muscles, and nerves function normally and to maintain a proper blood volume. Like vitamin K, potassium also promotes normal calcium levels in blood vessels.
Many people don't get enough potassium. Too little of this mineral, along with too much sodium, can lead to blood pressure issues. The good news? Adequate potassium promotes normal blood pressure in adults.
Adults need quite a bit daily — 4,700 mg — which you can get from apricots, bananas, lentils, and brown rice, along with supplements.
Avoid processed foods like white rice and refined-flour bread, because processing grains removes much of their natural potassium.
Besides vitamins and minerals, other types of nutrients help you maintain a healthy heart. Below are the best supplements for heart health.
CoQ10, or coenzyme Q10, plays a critical role in every single cell in your body. Also called ubiquinone, CoQ10 sparks chemical reactions that help mitochondria, your cells' “power plants," convert food into energy. That's important because your heart consumes so much energy!
CoQ10 also helps keep veins open so blood can flow freely and without obstruction. It may also promote normal blood pressure.
CoQ10 promotes heart health and protects against toxins.
CoQ10 is a strong antioxidant that helps counteract oxidative stress — the damage caused to cells from toxins, illness, UV rays, or the body's natural aging processes.
You can also find CoQ10 naturally in olive oil, pistachios, sesame seeds, and cruciferous veggies like brussels sprouts, cabbage, and cauliflower.
Omega-3s are called the “essential" fatty acids because your body needs them, but it can't make them on its own; thus, you have to get them from supplements or food. Omega-3 fatty acids — including ALA (alpha-linolenic acid), EPA (eicosapentaenoic acid), and DHA (docosahexaenoic acid) — improve your chances of living a long life with a healthy heart.
Did you know that your body doesn't produce omega-3s? You have to get them from supplements or natural foods!
Omega-3 fatty acids keep chronic redness and swelling in check, and they also lower the body's production of triglycerides — fats that circulate in the blood. Studies have also found that omega-3s balance levels of high-density lipoprotein (HDL) or "good" cholesterol.
The daily requirement for ALA is 1.1 g (grams) in adult women and 1.6 g in adult men. Breastfeeding and pregnant women need more, and children need a bit less. Experts haven't set recommended amounts for the other main types, EPA and DHA, although they are still important nutrients to obtain regularly.[11] Natural plant-based sources include algae oil, flax seeds, olives, and olive oil.
You may have heard of the heart health benefits of red wine. Scientists think resveratrol, a polyphenol antioxidant, provides red wine's heart-healthy benefits. Scientists isolated this compound from the skin of grapes and have since found it also in other fruits, like mulberries, cranberries, and blueberries.
Resveratrol may protect blood vessel walls and promote healthy levels of both HDL (good) and LDL (bad) cholesterol. It also promotes normal blood pressure. Further, resveratrol mimics the positive health effects of calorie restriction and fasting. Both fasting and resveratrol spur production of adiponectin, a compound that promotes fat metabolism and blood sugar balance.
While you can get small amounts from food or red wine, you won't get enough to make a significant difference in your heart health. Supplements concentrate the nutrient in servings that can effectively support heart health.
Make sure to look for trans-resveratrol, which studies find much more effective than its isomer cis-resveratrol. Some supplements contain both, but higher-quality ones contain up to 99 percent trans-resveratrol.
Folate is the natural form of vitamin B-9; folic acid is the manufactured form of B-9 that's used in most supplements or in fortified foods (which we do not recommend because your body processes vitamins and minerals most efficiently from their natural form).
Whichever form, vitamin B-9 helps your body make red blood cells and DNA. It also helps balance your body's levels of homocysteine. Without enough folate, your homocysteine levels can get too high, which can cause swelling of the arteries and other blood vessels. Lower levels of homocysteine are linked with a healthier heart.
Folate-rich foods include nuts, leafy greens, mushrooms, and other fruits and veggies. You can supplement with folic acid. The recommended daily allowance is 400 mcg for both men and women.
Herbs and spices are more than flavor enhancers: They're powerful substances that many cultures have used to support health for centuries. Modern research has found that several can, indeed, benefit your heart.
Bergamot is a type of citrus plant. Its oil is the fragrant ingredient in Earl Grey tea. You can also get it in supplement form. Bergamot is rich in polyphenols, a disease-fighting compound found in plants.
When people took bergamot extract for six months, they not ended up with lower triglycerides, total and bad cholesterol, and atherogenic lipoproteins (molecules that tend to build up in arteries). Bergamot also increased good (HDL) cholesterol — all of which make for a healthier heart.
Traditional healers have long used the leaves, berries, and flowers of the hawthorn plant to address heart and blood vessel conditions. Hawthorn can promote normal blood pressure, LDL (bad) cholesterol, and triglycerides.
Hawthorn may also fight free radicals, expand blood vessels, and protect muscles — including the heart. Most people take it in supplement form. Interestingly, hawthorn berries are extremely hard to distinguish from other closely related species; most of the hawthorn used in supplements come from Europe.
People have used this sweet apple pie spice for centuries for its health-promoting traits. Chemicals found in cinnamon, including cinnamaldehyde and cinnamic acid, act as antioxidants — fighting off free radicals and harmful organisms.
Cinnamon also reduces systemic redness and swelling and balances blood lipid (fat) levels. A daily serving of cinnamon promotes normal blood sugar and blood pressure, both of which keep the heart healthy. You can buy cinnamon in stick form or ground in a jar — and it is an increasingly popular supplement, which concentrates the helpful compounds.
Ginger root contains several anti-inflammatory and antioxidant compounds including gingerol and zingerone that can protect the heart and soothe systemic redness and swelling in your body.
Some studies have shown these properties of ginger help normalize blood sugar, cholesterol and triglycerides, and HDL (good) cholesterol. All of these factors make for a happy heart!
Garlic was one of the earliest herbal medicines. Chemicals found in this tangy bulb soothe chronic redness and swelling. You can use it in cooking or you can take odor-free garlic capsules.
Garlic may slow plaque buildup, which encourages blood vessels to stay open. It also has a strong ability to regulate blood pressure as well as blood lipid (fat) levels — keeping your heart in top shape.
Even if you include all of these heart-healthy substances in your diet or consume them as supplements, the best way to keep your heart healthy is by living a well-rounded, healthy lifestyle. The most important things you can do for your heart include:
Gastrointestinal reflux disease (GERD) is a common digestive disorder characterized by chronic symptoms resulting from abnormal reflux of contents from the stomach into the esophagus, leading to mucosal damage. The underlying cause of GERD is multifactorial and can result from stress, poor diet, impaired digestion, dysbiosis, hiatal hernia, and esophageal sphincter dysfunction. Risk factors associated with GERD include smoking, alcohol, and NSAID use.
Previously, I had shared research demonstrating that the damage of the esophagus in GERD was shown to be cytokine-mediated due to inflammation and not caused directly by the acid in the stomach.
Pharmaceutical interventions may provide symptom management but they do not correct many of the underlying factors and often have side effects. Lifestyle changes and nutritional support are usually sufficient to address acid reflux. Patients should consider eating smaller portions at meals. In addition, they should avoid laying down after meals and avoid eating too close to bedtime. Also, alcohol and certain foods can trigger symptoms.
While proton pump inhibitors (PPIs) may help with the symptoms, they may not be the solution. Recent previous studies have linked PPIs to chronic kidney disease, cardiovascular disease and an increase risk of a heart attack. PPIs can also lead to other problems such as dysbiosis and small intestinal bacterial overgrowth (SIBO).
According to a new review published two weeks ago in Nutrients, researchers investigated the effects of probiotics in mitigating the severity and frequency of symptoms in GERD. Probiotics are associated with modulation of the immune system and accelerate gastric emptying via their action with stomach mucosal receptors; their benefits are less known on supporting upper gastrointestinal health.
This review included thirteen prospective studies published in twelve articles. Seventy-nine percent reported benefits of probiotic supplementation and symptoms of GERD and 45% reported benefits specifically associated with reflux symptoms. These included a reduction in regurgitation and improvements in heartburn or reflux. Five of the eleven positive studies demonstrated an improvement in dyspepsia symptoms and nine of the studies showed an improvement in upper gastrointestinal symptoms, including nausea, abdominal pain, belching, gurgling, and burping. As a result, this review demonstrates the potential benefits of probiotics for patients with GERD.
Other nutritional supplements to consider include deglycyrrhizinated licorice (DGL) and melatonin. DGL is a well-established anti-ulcer botanical that is soothing and protective to the gastric mucosa and mucous membranes lining the digestive tract. Melatonin is often used to support sleep or for its antioxidant properties in cancer; however, the enteroendocrine cells in the GI tract are a major source of intestinal melatonin. One of the main functions of melatonin produced by the GI tract is to protect the esophageal and gastric mucosa from stressors and irritants. Melatonin is a potent antioxidant that can influence all major functions of the GI tract, including secretion, motility, digestion and intestinal absorption. It has an inhibitory influence on gastric acid secretion resulting in an increase in gastrin release, which increases the contractile activity of the lower esophageal sphincter, helping to reduce the symptoms of GERD.
Helicobacter pylori can also contribute to gastritis. Mastic gum, zinc-carnosine, methylmethionine sulfonium and vitamin C have anti-H. pylori as well as supportive properties for the gastric mucosa.
An alternative approach is typically more effective than what is provided by PPIs and does not have side effects or other complications that can be associated with PPIs such as mineral deficiencies, bacterial infections, and dysbiosis.
By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS
