In a first of its kind study, higher levels of vitamin D in brain tissue were associated with lower rates of dementia and mild cognitive impairment.
Dietary and nutritional factors have long been linked to thinking or reasoning ability in older adults. But previous studies of vitamin D only looked at dietary intake or measurements of it in the blood, said the study’s lead author, Kyla Shea, PhD, an associate professor at Tufts University.
“We wanted to know if vitamin D is even present in the brain, and if it is, how those concentrations are linked to cognitive decline,” Shea said in a news release.
Researchers examined brain tissue samples from 290 people whose cognitive function had been tracked long-term and prior to any known cognitive decline. The average age of the subjects at time of death was 92 years old.
The researchers found that vitamin D was present in brain tissue and that people with higher concentrations of vitamin D in the brain also reported higher cognitive function prior to death. The findings were published this week in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
“This research reinforces the importance of studying how food and nutrients create resilience to protect the aging brain against diseases such as Alzheimer’s disease and other related dementias,” said co-author Sarah Booth, PhD, director of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University.
Vitamin D levels were examined in four regions of the brain as part of the study: two regions associated with Alzheimer’s disease, one region linked to blood-flow related dementia, and a fourth region not associated with cognitive decline.
Further study is needed, the researchers said, particularly because they could not link vitamin D levels with physiological markers associated with Alzheimer’s disease in the brain. Also, vitamin D levels are known to vary by race and ethnicity, and their study was limited by the majority of subjects being white.
Vitamin D is used by the body to build and maintain bones, and is also known to have anti-inflammatory, antioxidant and neuroprotective properties, the Mayo Clinic says. It’s found in a small number of foods, and our skin can convert sunlight into vitamin D. Recommended supplement levels of vitamin D are 400 international units (IU) for children up to age 12 months, 600 IU for people ages 1 to 70 years, and 800 IU for people over 70 years. Taking too much vitamin D in the form of supplements can be harmful, the organization warned.
People who died of severe COVID-19 had brain tissue similar to that of people who were at least 71 years old, prompting Harvard Medical School researchers to recommend that recovered COVID-19 patients seek neurological follow-up care.
The new study adds molecular-level findings to the growing body of evidence that severe and long COVID add to thinking problems sometimes referred to as “brain fog.”
“Ours is the first study to show that COVID-19 is associated with the molecular signatures of brain aging,” author Maria Mavrikaki, PhD, an instructor of pathology at Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School, said in a news release. “We found striking similarities between the brains of patients with COVID-19 and aged individuals.”
Researchers looked at 54 brain tissue samples from people ages 22 to 85. Samples from people who died of severe COVID-19 were compared to brain tissue of people of the same age and gender who did not have a history of neurological or psychiatric disease. Another comparison was made of a person who had both severe COVID and Alzheimer’s disease to a patient who had Alzheimer’s but not COVID-19. A third evaluation set was of samples from people with and without COVID-19 who had a history of intensive care or ventilator treatment.
“While we did not find evidence that the SARS-CoV-2 virus was present in the brain tissue at the time of death, we discovered inflammatory patterns associated with COVID-19,” said co-author Jonathan Lee, PhD, a postdoctoral research fellow at BIDMC and Harvard Medical School. “This suggests that this inflammation may contribute to the aging-like effects observed in the brains of patients with COVID-19 and long COVID.”
The study was published in the journal Nature Aging this month.
“Given our findings, we advocate for neurological follow-up of individuals who recovered from COVID-19 and suggest potential clinical value in modifying risk factors to reduce the risk or delay the development of aging-related neurological pathologies and cognitive decline,” the researchers wrote.
The FDA is reviewing comments on a draft policy that could alter the way Americans see LASIK surgery to improve their vision.
The FDA proposal pushes for warnings about double vision, dry eyes, ongoing pain, and other issues. It even says people might still need eyeglasses after the surgery.
About 500,000 adults opt for the procedure each year. Many people view the procedure as safe and commonplace, The New York Times reported, and that could change if the FDA adopts the advisories.
LASIK, which stands for laser in-situ keratomileusis, is a popular surgery that can correct vision in people who are nearsighted or farsighted or who have astigmatism.
It’s one of many vision correction surgeries that work by reshaping your cornea, the clear front part of the eye, so that light focuses on the retina in the back of your eye.
It takes about 15 minutes per eye and has been performed for about 25 years. It can cost thousands of dollars, and most insurance plans don’t cover it.
Most people report satisfaction with LASIK results.
The Times reported that many ophthalmologists insist it is safe with only rare long-term complications.
“All we’re asking for is balance,” said Vance Thompson, MD, incoming vice president of the American Society of Cataract and Refractive Surgery. “This document mainly emphasizes the dangers and complications of Lasik, with no mention of the advantages, and the tone is negative enough that it will scare patients.”
The FDA draft says some patients become depressed, even considering suicide. Chronic conditions such as diabetes and some prescriptions can put people at risk.
Warnings would benefit consumers, said Paula Cofer, a Florida woman who claims LASIK ruined her vision and caused chronic pain. “Right now, even if patients do research on the internet and see warnings, they think it’s just one or two unhappy people. Now they see it’s the F.D.A. saying this.”
Alzheimer’s disease is the most common form of dementia. About a third of people 85 and older show signs of the disease. The genes you get from your parents play a part at this age, but so do things like diet, exercise, your social life, and other illnesses. Dementia isn’t a normal part of getting older.
Heart Disease
2/15
It could lead to a heart attack or stroke, which makes dementia more likely. Heart disease is usually caused by plaque buildup in arteries around your heart (atherosclerosis). That can slow blood flow to your brain and put you at risk for stroke, making it harder to think well or remember things. And many things that cause heart disease — tobacco use, diabetes, high blood pressure, and high cholesterol — also can lead to dementia.
Air Pollution
3/15
An English study found older adults who lived in areas with the highest yearly concentration of air pollution were 1.4 times more likely to get dementia than people who lived in places with cleaner air. Nitrogen dioxide (NO2) and particulate matter (micro-particles in the air you might not see but can inhale) caused the most harm.
Diabetes
4/15
Doctors aren’t sure exactly why people with diabetes get dementia more often. But they do know that people with diabetes are more likely to have damaged blood vessels. This can slow or block blood flow to the brain and damage areas of the brain, leading to what’s called vascular dementia. Some people may be able to slow brain decline if they keep diabetes under control with medicine, exercise, and a healthy diet.
Poor Sense of Smell
5/15
Older people who have trouble identifying odors are more than twice as likely to have dementia as those with a sharp sense of smell. Almost half of people in an American study who’d been diagnosed with dementia had had olfactory dysfunction 5 years before. A simple smell test can flag a need for early treatment.
High Cholesterol
6/15
High levels, especially in middle age, are linked to obesity, high blood pressure, and diabetes. All of these raise your risk of dementia, but it’s not yet clear if the cholesterol by itself adds to the problem. Some research shows that high cholesterol in midlife could raise your chances of Alzheimer’s disease later in life, but the exact link isn’t clear.
Herpes
7/15
vHerpes simplex virus 1 (HSV1), or oral herpes, usually appears as blisters or sores on or around your mouth. But the virus can also get into and infect your brain. A recent study linked HSV1 with a decline in some mental functions, but not to dementia. However, lab studies on a realistic brain model showed HSV1 triggered major Alzheimer’s signs, including swelling and clumps of protein in the brain tissue.
Depression
8/15
If you have depression, or have had it in the past, you may be more likely to get dementia. Scientists aren’t yet sure that it’s a cause. It may simply be an early symptom or a sign of other causes like Parkinson’s disease or Huntington’s disease. Talk to your doctor or a therapist if you feel down for more than 2 weeks, and right away if you think of harming yourself. Therapy and medication can help with depression.
Eating Patterns
9/15
Super-starchy and processed foods never make the “healthy” list. But did you know eating the two together can up your chances of having dementia? French researchers found people who developed dementia often paired processed meats – i.e. ham, pepperoni, and deli meats – with high carbs like potatoes, alcohol, and baked sweets. Meanwhile, people who stayed healthy ate their share of meat – but enjoyed it with fruits and veggies.
Head Injury
10/15
A single, mild traumatic brain injury may not make you more likely to get dementia later in life. But more severe or repeated hits or falls could double or quadruple your chances, even years after the first injury. Get to the hospital if you’ve hit your head and you pass out or have blurry vision, or feel dizzy, confused, nauseated, or become sensitive to light.
Loneliness
11/15
Feeling lonely over time can increase your chances of having dementia, even when your overall risk of getting the disease – such as with genetics or age – is low, a 10-year study found. People under age 80 who reported feeling alone were twice as likely to have dementia as those who didn’t feel that way. Time is key, though. People who recovered from their loneliness didn’t have the same risk.
Obesity
12/15
If you have a lot of extra weight in middle age, you may be more likely to get dementia later in life. Extra pounds raise your risk for heart disease and diabetes, which are also linked to dementia. You can check your BMI (body mass index) online to see if it’s in the “obese” range. Your doctor can help you set a weight loss goal that’s right for you. A healthy diet and regular exercise could help you turn things around.
Genes
13/15
Dementia doesn’t have to run in your family for you to get it, but genes make a difference. A parent or sibling with Alzheimer’s raises your odds. Genes seem to matter more in some types of dementia than others. But even risky genes don’t mean you’ll get dementia. If you’re thinking about genetic testing for Alzheimer’s, ask your doctor about the pros and cons — and genetic counseling. Doctors don’t routinely recommend those tests.
Sleep
14/15
Many people have a bad night of sleep now and then. But if it happens often — you wake up a lot or don’t sleep enough — you could be more likely to get dementia, including Alzheimer’s disease, or make it worse. It may help to try and keep a healthy sleep routine: Avoid alcohol, caffeine, and electronics in evening, and set up a soothing bedtime ritual with regular bedtime hours.
Smoking
15/15
It seems to put you at risk of getting dementia, possibly because it’s bad for your blood vessels. And it definitely makes you more likely to have a stroke, which can and often does damage the brain and cause vascular dementia. That might lead to problems with thinking or remembering. Talk to your doctor or a mental health professional if you smoke and want support to quit.
Our health landscape is changing rapidly and we find ourselves in a new era. An era of degrading food supply, systemic inflammation, and overuse of drugs, including antibiotics. Living in our modern world takes its toll and we see it in our practices every day. Antibiotics are failing, superbugs are on the rise, and digestive health is compromised by food and lifestyle choices. Society is at a new crossroads. On one side, antibiotic-resistant bacteria are currently killing approximately 23,000 people every year and the number of antibiotic-resistant superbugs is climbing. On the contrary, long-standing and pervasive over-prescribing of antibiotics is at an all-time high. Additionally, we are exposed to antibiotic effects by eating many types of meat and using antibacterial soaps. Never before in history have we had to overcome the effects of man-made drugs in the quantities we are seeing today. By having a well-stocked toolbox and the ability to talk about TCM with Western medicine-friendly language, we may be able to lead a worldwide resurgence of healthy modalities to combat superbugs and promote long-term digestive health. I strongly believe we have tremendous healing opportunities in this new era.
Chinese medicine has always been a deeply holistic healing approach. We know acupuncture and herbs have far-reaching effects to heal even the most difficult pathologies. But the focus here is the importance of digestion. Whole schools of thought were developed in the 12th century stressing “the importance of Preserving Stomach-Qi” as the most important treatment method. Digestion is a cornerstone of traditional Chinese medicine with a full range of modalities including, healing cuisine, herbs, acupuncture, and Qi Nei Tang, to name a few. Zhang Jie Bin, one of the four great masters from the Ming Dynasty and one of the most important doctors in the history of TCM wrote, “The doctor who wants to nourish life has to tonify stomach and spleen.”
Could simply treating the spleen and stomach with acupuncture along with treating the chief complaint be enough? Although this is an easy approach to include into just about every treatment protocol, I believe there is much more we can do that already falls within our scope of practice. Our place is at the forefront of the “healthy gut” movement. What Western science is “discovering,” we have known for thousands of years and what Western science is giving us are tools which help convince our patients of the critical importance of their digestive health.
Emerging science is proving our gut is acting as our “second brain”. Its ability to constantly transform us is being unraveled by trail-blazing scientists studying human bacteria worldwide. The project, known as the Human Microbiome Project may have something to teach us about the way we practice TCM and Eastern/Integrative medicine today. The Microbiome Project is confirming microscopic bacterial colonies living in our digestive tract have important jobs for both our physical and mental well being. They are confirming what we have always known: If we nourish them, we simultaneously nourish ourselves. Because “for hundreds of thousands of years bacterial and human cells have existed in a peaceful symbiosis that is responsible for the health and equilibrium of our body. Now, this invisible Eden is being irrevocably damaged by some of our most revered medical advances—antibiotics—threatening the extinction of our irreplaceable microbes with terrible health consequences.”
Trillions of tiny microbes living on our skin, mucosal membranes, and in our intestines are helping us extract nutrients from our food. Others are exerting enormous influence over our metabolism, hormones, cravings, and even our genes. The Microbiome Project is proving healthy gut bacteria is the secret to dramatic weight loss, significant improvements in overall health, mood, energy, and mental function. The dysbiosis of our guts is contributing to systemic inflammation, leading to the rise of obesity, asthma, diabetes, autoimmune diseases, and certain forms of cancer. In addition, The Human Microbiome Research Project is also inadvertently proving what Chinese medicine has understood and has practiced for centuries: maintain the health of the spleen and stomach and lower jiao, and you have the basis for good health.
When we nourish the spleen/stomach we indirectly tonify all the other organs.
The good news is that unlike our inherited genes, which are more or less fixed, we can exert a huge influence over our gut bacteria genetics. “We can repair some of the damage to your gut bacteria simply by changing your dietary habits,” remarked Oluf Pedersen who co-headed the Danish portion of theMetagenomics of the Human Intestinal project. When we counsel our patients on their dietary habits, we can be successful at preventing and reversing the top three pathologies of our time. These three include:
1. Obesity—Gut bacteria appear to help food processing functions by producing signaling chemicals that regulate our appetite, satiety, and digestion. People with low bacterial richness are significantly more likely to be obese.
2. Insulin Resistant / Diabetes—Those with fewer bacteria diversity are more likely to be insulin resistant and at greater risk for diabetes or heart disease.
3. Cancer—The Microbiome Project is providing insights into new ways in which our bacteria, viruses, and fungi interact with our bodies and increase cancer risks.
Help Your Patients Restore and Repair Gut Flora by Integrating New Tools into Your Practice
Research has shown that we can reshape, repopulate, and even cultivate beneficial bacteria. As health practitioners, we are the gardeners able to help change the landscape for our patients. So, where do we start? In regards to acupuncture treatments, Giovanni says “The stomach and spleen could be tonified at the end of each season, particularly at the end of winter, to regenerate the energy.”
In addition to acupuncture, we can prescribe dietary supplements such as probiotics. However, I do not believe probiotics supplements (alone) are the answer. Consuming higher and higher dosages of probiotics with one, two, or ten probiotic Colony Forming Units (CFU’s) can cause dysbiosis. Research shows no single probiotic is specific for every individual’s microorganism makeup. Although there may be a benefit to taking a certain strain(s), we have no current tools to decipher which strain is most beneficial for which patient. Long-term benefits are also unproven. Failure to change dietary habits or prescription drug use will prevent healthy bacterial colonies from thriving and will disable them from becoming long-term beneficial communities.
As a health practitioner, I believe the answers for our patients can be found within a variety of modalities including acupuncture, patient education, dietary changes, practitioner tools and herbs to cultivate healthy bacteria. We have a huge opportunity to alter our patients gut flora with these tools.
Acupuncture
Support the spleen and stomach in all your treatments. At the very least, add Zusanli St 36 to every treatment protocol or a variety of Sp/St tonifying points. Miriam Lee, the first Licensed Acupuncturist in the state of California, used St 36 in every treatment with every patient.
Patient Education
Ask patients to keep a food diary and go over it with them. For example, have them write about a two- day food “cleanse” where they remove sugar. Instruct patients to observe how their body reacts when they revert back to their normal diet and get patients to commit to a plan.
Give each patient a calendar that includes times of the year to get an acupuncture tune-up. Tell them you will send them an email to remind them. Give them a list of results they will see and feel as they heal. Get them involved in the project. Celebrate the good results
Limit processed foods and supplements containing emulsifiers. Ingredients commonly called lecithin derived from soy (likely GMO), Datem, (found in commercial bread) Calcium propionate, CMC and polysorbate 80 are creating a host of new absorption problems in our digestive tracts.
Explain to your patients why avoiding antibacterial hand sanitizing products is recommended and recognizing bacterial diversity is good. Use safe natural cleaning products in your office. (A small sign next to the bathroom hand soap container can easily do this for you.)
Encourage “playing in the dirt” (i.e. gardening) and playing with your animals (dogs, cats, horses etc.). Our pets spread healthy bacteria which have proven benefits.
Get patients back to real foods! The perfect diet is a lofty goal for many. Make the goal the 80/20 rule. 80% REAL food, 20% less than perfect/real food. This will still improve the balance of healthy gut flora.
Avoid prescription antibiotics as much as possible.
(NatalyaBond/Shutterstock)
Dietary Changes
Don’t eat meat fed antibiotics.
Eat Pre-biotics every day. Prebiotics enhance the growth of beneficial bacteria and can be found in fermented foods such as kimichi, sauerkraut, pickles, kombucha, miso, and other fermented foods. Add these to your diet to provide a variety of healthy bacteria. A daily sampling of new live bacteria from fermented foods makes your gut community more adaptable.
Try Coconut Milk Yogurt. Not all yogurts are created equal. Some yogurts, although fortified with probiotics, often contain a lot of sugar and not all micro-organisms survive and thrive during processing.
Add Extra Virgin Coconut Oil – 4 tablespoons per day, after meals. This heals the GI tract and kills Candida Albicans and other pathogenic fungi, bacteria, and viruses.13
Use the art Qi Nei Tang and teach it to your patients.
Practitioner Tools
Ask every patient if they have ever had severe food poisoning as this could upset the microbiome balance even 20 years later. The more knowledge you have about your patient’s gut health, the better equipped you will be to recommend treatment protocols.
Be mindful of the tongue coating or lack thereof. We are the only health practitioners trained to look at the tongue coating at every visit and derive our diagnosis partly from the information we attain. Because the stomach function is closely tied to the tongue coating, consider the coating or lack thereof, with utmost seriousness in every visit.
Check Vitamin D levels – Vitamin D3 plays a crucial factor. Low levels can weaken the barrier of the small intestine which contributes to gut irritation and exaggerates the systemic effects of food sensitivities/allergies.
Huang Qi (Astragalus) is an extremely powerful herb used alone or in formulas. Huang Qi’s high polysaccharides content is fantastic for improving overall immune health and the growth of healthy bacteria.14 “The safest way to increase your microbial biodiversity is to eat a variety of polysaccharides,”15 (Other single herbs with substantial Sp/St benefits are codonopsis (dangshen), atractylodes (baizhu), Chinese angelica (dang gui) dioscorea (shanyao), lotus seed (lianzi), roasted ginger (paojiang), longan (long yan rou), and baked licorice (zhi gan cao). 16 Encourage patients to use these herbs in everyday foods such as soups or teas.
Herbs
Use herbal formulas to support the digestive tract when your diagnosis fits. This is a short list (for brevity) of a few important formulas.
Si Jun Zi Tang (Four Gentleman Decoction)
Liu Jun Zi Tang (Six Gentlemen Decoction)
Bu Zhong Yi Qi Tang (Center-Supplementing Qi-Boosting Decoction)
Chai Hu Shu Gan San (Bupleurum Liver- Coursing Powder)
Bao He Wan (Harmony-Preserving Pill)
Gui Pi Tang (Restore the Spleen Decoction)
Xiang Sha Liu Jun Zi Tang (Saussurea and Cardamon Six Gentlemen Pill)
Final Thoughts
Cutting edge Western research can give us a new perspective on our ancient wisdom. We know the origins of many diseases are in the gut and in today’s world we can no longer ignore the effects of superbugs, toxic foods, and toxic lifestyles. As we help patients fortify their digestive tracts, disease resistance and long-term health improve. By starting small with each patient, you create a ripple effect which will grow and scale and revitalize an entire community. Encourage active participation from every patient and watch the seeds you plant, grow in time. Imagine the implications as you help society heal one individual at a time.
A surgeon team uses a Loop-X live medical imagery system to secure the work on the spine of a patient affected by a metastatic breast cancer at the University-affiliated hospital (CHU) in Angers, France, on June 10, 2021. (AFP via Getty Images/Loic Venance)
A simple drug regimen to diminish stress and inflammation reduced the risk of developing metastases after surgery to remove cancerous tumors, according to a recent study.
The study found that 5 years after surgery, nine of the 18 patients who received a placebo (50 percent) developed metastatic cancer, compared with only two of the 16 patients (12.5 percent) who received the drug regimen.
This first-of-its-kind clinical study was led by Shamgar Ben-Eliyahu, professor at Sagol School of Neuroscience and School of Psychological Sciences at Tel-Aviv University, and Oded Zmora, MD, a colorectal surgeon and a professor at Tel-Aviv University’s Sackler Faculty of Medicine.
The two professors have been researching this subject together for 15 years.
The research was published in the European Journal of Surgical Oncology. An overview of the theory and principles underlying the research was published in Nature Reviews Clinical Oncology in 2020.
‘The Decisive Treatment’
When a tumor without known distant metastases is detected in an organ, the standard treatment is surgery to remove the segment of the intestine that includes the tumor, Zmora told The Epoch Times.
He said it is the most important treatment, calling it “the decisive treatment that gives the highest chance of curing the disease.”
In some cases, after the patients recover, additional oncology treatments are given, such as chemotherapy.
At the time of surgery, when the primary tumor is removed, it carries the risk of recurrence. In the follow-up period, the tumor may recur either in the target organ itself or more commonly as metastases in other organs such as the liver or the lungs.
The risk of metastases after tumor removal is estimated at 30–40 percent among colon cancer patients, and about 90 percent among pancreas cancer patients, according to Zmora.
He said that while the surgery is the cornerstone in the treatment of the disease, “it also places a very heavy burden on the body, [in the form of] stress.”
Most deaths related to cancer result from metastatic recurrence after surgery. So the goal of the study was to try to reduce the recurrence rate of metastases.
The Peri-Operative Period Is Critical
“We and others have found that the short period around the surgery, a week before and a week or two after are very critical in their effect on metastatic processes of cancer,” Ben-Eliyahu told The Epoch Times.
Various interventions during this period have a much greater effectiveness than in other periods that are less critical.
Paradoxically, most of the anti-metastatic treatments such as radiotherapy, chemotherapy, and immunotherapy, are not given during this period because they interfere with the surgery, he said. Most of the treatments are not given during the peri-operative period—they end a month before it or start a month after it.
And so “one of the special things about our intervention is that we actually use this period of the surgery itself,” he said.
‘A Watershed Point in Life’
The second point is that the researchers looked for how surgery in this short peri-operative period affects metastatic processes.
They found that, during the peri-operative period, stress and inflammatory reactions each separately and together affect cancerous processes, through several mechanisms.
Being diagnosed with a tumorous disease “is a watershed point in life” said Zmora. “It is a period of time when one has to mobilize his mental resources to undergo the surgery and go through the treatments.”
The patients experience a lot of stress while waiting for surgery. Then stress and inflammation reactions occur in the body during the operation itself as well as during the physical recovery. And there is the constant anxiety at every visit for checkups, with the question of whether the cancer has come back or not.
In earlier studies with animals, Ben-Eliyahu found that the magnitude of the effect of psychological stress was no smaller than the effect of the surgery itself.
“Its weight can be more significant than we estimate,” he said.
All these mental and physiological conditions create stress responses that cause the release of stress hormones called catecholamines, such as adrenaline and noradrenaline, and inflammatory responses which cause the release of prostaglandins.
“We assume that those patients in whom the disease returns, tumor cells were implanted, seeded, back in the period when there was an original tumor before the operation and something in the body caused them to be dormant, inactive,” said Zmora.
Exposure to stress-inflammatory hormones directly affects these remaining cancer cells to become more aggressive and metastatic, said Ben-Eliyahu.
These hormones also indirectly encourage the development of metastases by suppressing anti-metastatic immune activity.
“They suppress the immune elements that the immune system uses to fight cancer metastases,” he said.
So all these stress-inflammatory mechanisms taking place during the peri-operative period increase the risk of metastatic outbreak in patients, in some cases this becomes evident only years after the operation.
Once the mechanisms were understood by the researchers, it was possible to think about which type of treatment could be used to influence them.
The treatment given in the study was designed to prevent metastatic development, which may be accelerated around the time of surgery.
The Medication Treatment
The treatment included two known, inexpensive drugs that were in long-standing use in medicine for other indications, and they are available in local pharmacies.
One drug was Deralin, or propranolol, which is usually given to patients with hypertension to reduce blood pressure and to reduce anxiety.
The second drug was Etopan, or etodolac, which is used to prevent inflammation and pain.
Both drugs, which are given orally, have “a high profile safety” according to the researchers and both need to be taken at the same time.
Since both the inflammatory response and the stress response each can cause a variety of problems that ultimately converge to the same mechanisms, according to Ben-Eliyahu, blocking only one axis is not enough.
“You need to simultaneously block both the inflammatory response and the stress response when both are happening at the same time around the time of surgery,” he said.
They found in animal studies “that each of the drugs does a little bit, and both do much more than the sum of them,” he said. “This is called synergism; they have synergies between their effects.”
The 16 randomly chosen patients in the treatment group took the medication for 20 days—five days before the surgery to two weeks after the operation with minimal-to-no adverse effects.
This drug regimen showed promising results of reduced markers of metastasis in the excised tumor tissues, according to Ben-Eliyahu. Five years later, only 12.5 percent of the patients that had received the treatment developed cancer metastases, compared with 50 percent of the patients who received the placebo.
Similar results were found in a previous study with 38 breast cancer patients. The same drug regimen that was given prior to and after surgery significantly reduced markers of risk of cancer recurrence after surgery.
However, even though the results of these two studies were found to be statistically significant, a large-scale clinical study is needed to establish the beneficial effects of this treatment and to advance toward potential clinical implementation.
This Research Falls in the Gap
The next step is to repeat the study on a large scale, said Ben-Eliyahu.
“We see something very promising here.”
However, he said his concern is that it is research on a treatment protocol that pharmaceutical companies will not support.
There are many, much less-promising treatments that pharmaceutical companies will push, he added, because they present very large financial profits.
“The drugs in question are unpatented; they are generic,” said Zmora. “There is no company that has an interest in pushing such research, and it is difficult to raise funds.”
When they approach a pharmaceutical company and say there are a lot of cancer patients in the world but the treatment will only be given for 3 weeks or a month, the company is less interested because they usually want to invest in long-term therapies.
Nevertheless, the researchers have begun a large-scale study, but still don’t have the funds they need. It is already on its way in at least 4 hospitals in Israel and a few more hospitals are planning to join in.
The researchers are aiming to recruit over 300 patients but they face big financial challenges.
“There is really some scientific excitement here,” said Zmora. “At the same time, it is very, very difficult to raise funding for such research.”
“The bottleneck for us is money,” said Ben-Eliyahu. “It’s not [medical] centers that want to cooperate with us, but money to pay the hospitals … for the cost of the research.”
The researchers said they receive funding from the Israeli Ministry of Health, the Israel Ministry of Science, the Israel Cancer Research Fund, and SPARK, an innovation center at Tel Aviv University.
But the amount of money is a small fraction of what is needed.
“We need between $2–4 million to conduct research on 300 colon cancer patients,” he said. “And these bodies each give us $50,000–200,000.
“So we live from hand-to-mouth and we try to look for donors.”
Major science foundations in Israel (e.g., Israel Science Foundation) do not fund clinical trials on drugs since they are usually funded by pharmaceutical companies, Ben-Eliyahu said.
“We do it entirely on a nonprofit basis,” he said. “There is no economic profit here and, therefore, pharmaceutical companies will not push it.”
“I don’t say this as a grudge against the drug companies, I also work with them and I appreciate what they do,” said Zmora. “But that’s the way it is.”
In Western medicine, acne is considered a skin condition where the pores of the skin become blocked by hair, sebum, bacteria, and dead skin cells.
Traditional Chinese medicine looks deeper at the root cause of the skin condition: an experienced Chinese traditional medicine practitioner can identify the underlying internal organ issues by looking at the location of the acne.
Acne on the Forehead: Heart Needs Cooling
If you get acne on your forehead, in traditional Chinese medicine, it could be a sign of the heart “having too much heat,” which is due to stress or lack of sleep. Usually, when someone is stressed and can’t sleep at night, acne could show up on their forehead.
Therefore, from the traditional Chinese medicine’s point of view, one would focus on “cooling the heart” to remove acne on the forehead. Relieving stress, adjusting sleep schedule, and staying hydrated are highly recommended.
Lotus seed and lily bulb soup: Place a handful of lotus seeds, lily bulbs, and dried jujubes in enough water to cover the ingredients, bring the water to boil, then simmer for 40 minutes.
The soup can cool the heart, strengthen the yin in the heart, and eliminate the acne on the forehead.
There are two acupuncture points that can be helpful in getting rid of acne on the forehead: the Shen Men point on the wrist and Tai Chong point on the foot. Massaging these points can calm the heart and unblock the liver.
Acne Between Eyebrows
If the acne appears in between the eyebrows, it might have something to do with the heart and lungs. Other symptoms such as heart palpitations and chest tightness might accompany this, or one may find breathing difficult when running. This could be caused by a sedentary lifestyle.
If one does not exercise much, one should not eat salty or heavily seasoned preserved foods, to prevent the body from bloating and to lighten the burden of the heart.
Massaging the Da Ling point and Nei Guan point on the wrist can have a calming effect.
Foods that help people sleep, help nourish the heart and lungs can target the root problem and eliminate the acne between the eyebrows. These include ophiopogon root tuber (maimendong), Chinese asparagus roots (tianmendong), American ginseng, and lotus seeds.
Turnip and two roots soup: First prepare a thick broth with 3 grams of ophiopogon root tuber, 3 grams of Chinese asparagus roots, 5 grams of American ginseng, and boiling water.
Then add your favorite stock, white turnip, 15 dried jujubes, 10 lotus seeds, and the broth into the pot. Put the pot lid on and simmer. Add a little salt before serving.
Acne on and Beneath the Nose: Spleen and Stomach Need Tonification
Traditional Chinese medicine believes that the tip of the nose corresponds to the spleen, while the sides of the nose correspond to the stomach. So if blackheads and pimples show up on the nose, it might be because of the excessive consumption of nuts, fried or BBQ’d foods, and/or spicy foods. These foods put a heavy burden on the spleen and stomach and can cause acne on the nose.
Those with acne on the nose could also suffer from bloating, sour regurgitation, and difficulty with bowel movements. All of these symptoms are caused by the digestive tract having excessive “dampness and heat.”
Massaging the Zu San Li point and Feng Long point on the leg can help rebalance one’s appetite: if someone’s appetite is too strong, massaging these points can decrease their appetite; when someone does not want to eat, massaging these points can increase their appetite. In addition, diarrhea can be treated by warming these two points.
A traditional recipe called “four spirit soup” can nourish the digestive tract. Parents commonly use it to increase a child’s appetite and improve digestion.
Four spirit soup: Prepare equal amounts of Gordon Euryale Seeds (qianshi), lotus seeds, Chinese yams, Poria (fuling), and Job’s tears, boil and simmer them with pork ribs. Add a small amount of Chinese Angelica root (danggui) and rice wine to taste.
Acne on the Left Cheek: Liver Needs Tonification
When looking at the cheeks, there is a saying in traditional Chinese medicine: “Left liver; right lung.” So acne on the left cheek might be related to the liver.
Staying up late at night and alcohol intake can cause liver malfunction, and the symptoms can show up on the left cheek.
According to traditional Chinese medicine, to treat acne on the left cheek, one can massage Gong Sun point and Tai Chong point.
Foods that can cool the liver are mung beans, small cucumbers, and winter melons.
Wolfberry chrysanthemum tea is also very effective. Wolfberries (goji berries) can nourish the liver and moisten the lungs. Chrysanthemum flowers can cleanse the liver, brighten the eyes, and strengthen the gallbladder.
Acne on Right Cheek: the Lungs Need Tonification
Many people with allergic rhinitis have acne on their right cheek. This is because their lungs have too much “heat” or other imbalance.
Massaging the Lie Que point and Chi Ze point can help cool down and moisten the lungs, so as to remove acne on the right cheek.
Foods that are beneficial to the lungs are Job’s tears, wood ear mushrooms, almonds, and pears. They can thus improve the acne.
Honeysuckle flowers can reduce heat and inhibit the action of germs. American ginseng can replenish the energy in the lungs. This tea can moisten the lungs and is also very tasty.
Acne Around the Temples
The temples are related to the gallbladder. If one has acne around their temples, maybe this person has an irregular meal schedule, and they often skip meals, or just have one larger meal per day.
Massaging Tai Chong point, San Yin Jiao point, and Dan Nang point might help with the situation.
A fixed meal schedule also helps. Furthermore, bitter melon juice and winter melon soup can help alleviate the burden of the digestive tract.
Acne Around the Mouth
Acne around the mouth might occur if someone eats too much spicy food, too much meat, and an insufficient amount of vegetables. These people should eat more foods that are high in fiber.
Massaging Zu San Li point and Qu Chi point can help.
People with acne around their mouth can drink a type of tea called Yin Qiao, which consists of honeysuckle flowers, fructus forsythiae (lianqiao), mint, cassia seeds, and jujubes.
The cassia seeds must be fried before consumption. They can help reduce the edema caused by eating heavy and salty/spicy foods. Honeysuckle flowers and fructus forsythiae can clear fever and heat. Mint can regulate digestive functions.
Acne on the Chin: Endocrine System Needs Regulation
In traditional Chinese medicine, the chin corresponds to the genitourinary system. So acne on the chin might indicate an unbalanced endocrine system. Women might experience issues with their ovaries and uterus during monthly menstrual periods. Men might suffer discomfort in the genitourinary system. Resolving these issues first will clear up the acne.
Speaking from his clinical experience, Dr. Dawei Guo, president of the Fu Yuan Chinese Medicine Clinic in Taiwan, said that 80 percent of those who have acne on the chin enjoy eating overly spicy food.
He recommends they eat water spinach and bamboo shoots to encourage intestinal motility and clear the residual feces in the intestines. Men can also eat a lot of tomatoes, which are beneficial for their lower urinary tract.
Massaging the Xue Hai point and Shen Guan point can also help.
They can also drink tea made from honeysuckle flowers, fructus forsythiae, mint, cassia seeds, and jujubes.
EGFR-TKI targeted therapy is one of the most effective treatments for lung cancer patients harboring EGFR activating mutations. However, inhibition response is easily attenuated by drug resistance, which is mainly due to bypass activation or downstream activation. Herein, we established osimertinib-resistant cells by stepwise dose-escalation in vitro and an osimertinib-resistant patient-derived xenograft model through persistent treatment in vivo. Phosphorylated proteomics identified that MEK1 and AKT1/2 were abnormally activated in resistant cells compared with parental cells. Likewise, EGFR inhibition by osimertinib induced activation of MEK1 and AKT1/2, which weakened osimertinib sensitivity in NSCLC cells. Consequently, this study aimed to identify a novel inhibitor which could suppress resistant cell growth by dual targeting of MEK1 and AKT1/2. Based on computational screening, we identified that costunolide could interact with MEK1 and AKT1/2. Further exploration using in vitro kinase assays validated that costunolide inhibited the kinase activity of MEK1 and AKT1/2, which restrained downstream ERK-RSK2 and GSK3β signal transduction and significantly induced cell apoptosis. Remarkably, the combination of osimertinib and costunolide showed synergistic or additive inhibitory effects on tumor growth in osimertinib-resistant cell lines and PDX model. Hence, this study highlights a potential therapeutic strategy for osimertinib-resistant patients through targeting of MEK1 and AKT1/2 by costunolide.
Background
Based on the Global Cancer Statistics of 2020, lung cancer ranks the second most frequently diagnosed cancer (11.4% of total cases) and is the leading cause of cancer-related death (18% of total cancer deaths)[1]. At present, therapeutic regimens for lung cancer include surgery, chemotherapy, immunotherapy, and targeted therapy[2]. Despite the continuous refinement of treatment options, the 5-year survival rate still remains below 20%[3]. Therefore, further investigation is needed to optimize therapeutic strategies.
Of the diverse therapeutic schemes, targeted therapy showed significant preponderance with lower side effects, stronger pertinence, and more convenience for patients[4]. Epidermal Growth Factor Receptor (EGFR)-focused targeted therapy is one of the most widely used treatments for non-small cell lung cancer (NSCLC) patients that harbor EGFR mutations, with more than 60% object response rate[5]. Osimertinib is a third generation EGFR- tyrosine kinase inhibitor (TKI) that has been approved by the FDA as a second-line treatment of EGFR acquired mutant(T790M) NSCLC patient, a first-line treatment for EGFR activating mutant (L858R or exon 19 deletion) NSCLC patients, and as a postoperative adjuvant therapy approved by National Medical Products Administration in China[6]. However, drug resistance is an inevitable issue. Due to tumor heterogeneity, mechanisms of drug resistance vary among different populations and are mainly caused by acquired EGFR mutations, activation or tetraploidization of bypass signal molecules, or phenotypic transformation[5]. Bypass activation, such as Erb-B2 receptor tyrosine kinase 2 (HER2) activation could abnormally activate the mitogen-activated protein kinase (MAPK) or protein-serine-threonine kinase- glycogen synthase kinase 3 beta (AKT-GSK3β) pathways, leading to increased cell proliferation and drug resistance[7]. Currently, EGFR-TKI combined with other drugs are popular regimens for managing drug resistance.
To further explore strategies that could overcome osimertinib resistance, we established osimertinib-resistant cells through a stepwise dose-escalation method and performed phosphorylated proteomics analysis to identify the aberrant activated pathways in resistant cells. In the present study, we identified that mitogen-activated protein kinase kinase 1 (MEK1) and AKT1/2 were abnormally activated in resistant cells. Knockdown of MEK1 and AKT1/2 inhibited the growth of osimertinib-resistant cells and partially restored osimertinib sensitivity. Moreover, we found that costunolide functions as a dual inhibitor of MEK1 and AKT1/2 that significantly induces cell apoptosis in the osimertinib-resistant cell pool. Combination of costunolide with osimertinib showed synergistic or additive inhibitory effect on osimertinib-resistant cells and a resistant patient-derived xenograft (PDX) model. These data demonstrated that costunolide may be considered as a promising strategy for osimertinib-resistant patients with activated MEK1 and AKT1/2.
Discussion
EGFR targeted therapy has achieved prominent performance for NSCLC treatment; however, acquired drug resistance inevitably limits long-term effects[7]. An appropriate drug resistant model is rather important for preclinical studies. Consequently, we generated osmertinib-resistance in cell lines harboring EFGR mutations through a step-wise dose escalation method, which showed a remarkably higher IC50 of osimertinib compared with parental cells. The lower drug susceptibility was further confirmed by foci formation and cell apoptosis assays in the resistant cells. To establish a more comprehensive resistance mechanism in vivo, we also generated an osimertinib-resistant PDX model through continuous induction using lung cancer tissue harboring an EGFR mutation. These long-term inducted resistant models are effective tools to realistically simulate the process of drug resistance in a laboratory setting.
Due to tumor heterogeneity, the reported mechanisms of osimertinib resistance may vary depending on the terms of different regimens. Acquired EGFR mutation, c-MET amplification, HER2 amplification or mutation, PIK3CA mutation, BRAF and KRAS mutation have been reported as the dominant factors contributing to osimertinib resistance in response to first-line treatment. Acquired EGFR mutation, c-MET amplification, cell cycle gene alteration, HER2 amplification, PIK3CA amplification or mutation have been reported as contributors to osimertinib resistance in response to second-line treatment. Obviously, most of the dysregulated proteins highlighted above can activate PI3K/AKT and MAPK-ERK pathways. As reported, AKT is a key modulator in regulating multi-drug resistance[12]. One mechanism occurs through AKT-triggered activation of NFκB, which can inhibit cell apoptosis and promote tumor growth. Furthermore, activated AKT also modulates cell proliferation through the phosphorylation of GSK3β, which can facilitate resistance by promoting the evasion of EGFR-targeted therapy. Besides, MEK also plays a profound role in regulating drug resistance. The paradoxical activation of MEK stimulates ERK to promote cell proliferation and drug resistance[13]. Most often, activation of MEK or AKT also play crucial roles during the drug resistance process. As reported, combination of gefitinib with MEK1/2 inhibitor synergistically inhibited gefitinib-resistant NSCLC cell growth[14]. Dual blockade of PI3K/AKT and MEK/ERK pathways potentiated gefitinib sensitivity in gefitinib resistant NSCLC and breast cancer cells. Accordingly, AKT/GSK and MEK/ERK are the most frequently dysregulated signaling pathways in acquired drug resistance. However, individually targeting AKT or MEK may facilitate active bypass or downstream signaling which will limit the success of therapies. Thus, the rational to inhibit PI3K/AKT and MAPK pathways simultaneously seems logical to produce a more robust inhibitory response that may prevent further resistance. In present study, we identified that costunolide is an effective inhibitor capable of suppressing the kinase activity of MEK1 and AKT1/2, thereby inducing significant cell apoptosis and inhibition of cell growth. Costunolide is a natural bioactive sesquiterpene lactone with antioxidant, anti-inflammatory and anticancer effects that is extracted from the roots of Saussurea lappa. Recent studies have shown that costunolide can inhibit the proliferation of various cancer cells. In ovarian cancer cells, costunolide promotes the expression of apoptosis signals, such as caspase 3, caspase 8 and caspase 9 by enhancing the production of ROS, thereby inhibiting the growth of cisplatin-resistant cells[15]. In addition, costunolide can inhibit the growth of colorectal cancer and melanoma cells by inhibiting the kinase activity of AKT[10]. Costunolide also showed a similar inhibitory effect compared with the combination of AKTi and MEKi, but at a higher dose. Our data suggested that, costunolide could act as a safe and effective inhibitor to suppress osimertinib-resistant cell growth.
Another critical finding of our study is that costunolide reversed osimertinib resistance in vivo. Due to the stable biological characteristics of patient derived tissues, we used an EGFR mutant PDX model to further evaluate the combination effects of costunolide and osimertinib. Based on the data, costunolide inhibited tumor growth and a significant synergistic effect was observed in the model. Moreover, downstream signaling effectors of MEK and AKT were markedly inhibited in the combination treatment group. Additionally, we did not observe obvious changes in total body weight, ALT or AST level between the different groups, indicating a well-tolerated dose of costunolide plus osimertinib. However, it should be noted that costunolide did not show a growth inhibitory effect in the HLG57-DMSO model. This observation is mainly because p-MEK and p-AKT protein expression levels are lower in the HLG57 relative to other lung tumor tissues. Based on this in vivo study, we concluded that the efficiency of costunolide is dependent on the levels of activated MEK1 and AKT1/2. Additional studies are required to further characterize suitable strategies for managing osimertinib-resistant cell populations deficient in active MEK and AKT.
Conclusion
Our study demonstrated that MEK1 and AKT1/2 are critical for the development of osimertinib resistance. Moreover, costunolide reversed osimertinib resistance through direct targeting of MEK1 and AKT1/2. A synergistic or additive effect was observed with the combination treatment of costunolide and osimertinb both in vitro and in vivo, which might offer a candidate strategy in the clinic.
Lung cancer ranks as the No.1 killer of all cancers globally.
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Lung cancer ranks as the No.1 killer of all cancers globally. The main treatment method of Western medicine for non-small cell lung cancer, the most common type of lung cancer, is targeted therapy.
However, a thorny problem with targeted therapy is the development of drug resistance in patients.
Lee Mi-hyun, a pre-Korean medicine professor at Dongshin University in South Korea, announced on Nov. 14 that the extract of a herb “costustoot” could solve the problem of patients’ resistance to the targeted drug Osimertinib.
Lung cancer can be pathologically divided into small lung cancer and non-small cell lung cancer (NSCLC). More than 80 percent of lung cancer patients have non-small cell lung cancer, and about 50 percent of non-small cell lung cancers have mutations in the epidermal growth factor receptor (EGFR).
In treating the gene mutation, if the patient is injected with the targeted anti-cancer agent Osimertinib for a long period of time, the body will develop resistance to the drug, reducing the effectiveness of the treatment.
Osimertinib is a third-generation epidermal growth factor receptor inhibitor (EGFR-tyrosine kinase inhibitors, EGFR-TKIs), a targeted drug.
It was approved by the Food and Drug Administration and the European Union in 2017 for the treatment of non-small cell lung cancer and by the China Food and Drug Administration in 2018 for the treatment of advanced or metastatic non-small cell lung cancer.
A study shows that the extract of the herb “costustoot” could solve the problem of patients’ resistance to the targeted drug Osimertinib.
Lee found that this resistance is due to the over presence of MEK and AKT proteins that affect cancer cell proliferation and survival.
Based on this, Lee confirmed that costunolide, extracted from the roots of costustoot, was able to target MEK and AKT proteins, effectively blocking cancer appreciation and inducing death in oxitinib-resistant cells and animal models.
From the perspective of Korean medicine (traditional Chinese medicine), costustoot is mainly used to treat thoracic or epigastric abdominal distension, jaundice, lack of appetite, diarrhea, tenesmus, and food stagnation.
Modern pharmacological studies have shown that costustoot has the functions of protecting gastric mucosa, anti-inflammatory, analgesic, regulating gastrointestinal motility, improving gallbladder, inhibiting pathogenic microorganisms, and anti-tumor.
“We are conducting various studies to solve the problem of drug resistance in the treatment of lung cancer by Western medicine, and we will try to make these studies an opportunity for the development of Korean medicine,” Lee said.
Melatonin can reduce the rate of severe COVID outcomes, help regulate sleep, promote genomic stability, and protect against neurodegeneration
Melatonin’s multiple actions as an antiinflammatory, antioxidant, and antiviral (against other viruses) make it a reasonable choice for use.
Two key studies have identified the role that melatonin plays in reducing the risk of a positive test for COVID-19 and lowering the incidence of severe symptoms.
That new finding adds to a list of benefits linked to melatonin since it was first discovered in 1958 by Dr. Aaron Lerner, a dermatologist who was able to isolate it from the pineal gland in a cow.
Scientists began studying melatonin in the 1980s, and by the 1990s, it received more attention. Research data showed that melatonin influences a number of bodily processes, including calcium-dependent metabolism, immune modulation, and tumor growth—which it can restrain.
Although melatonin is produced in a variety of tissues, the major source is the pineal gland, a tiny endocrine gland found in the center of the brain. One of melatonin’s initial functions is likely as a free radical scavenger. Interestingly, melatonin also functions in plants to reduce oxidative stress and promote seed germination and growth. The necessary precursor in plants and animals is tryptophan.
Your body controls the release of melatonin through a master circadian clock, located in an area of the brain called the suprachiasmatic nuclei.
This area synchronizes the secretion of melatonin through a complex pathway in the nervous system affected by the light input through the eyes. Since melatonin helps control the sleep-wake cycles, it became popular to use it to help control jet lag or support sleep.
Now data demonstrates that melatonin may be beneficial in preventing complications in people with COVID-19.
Lower Incidence of Severe COVID-19
A study published in the International Journal of Infectious Diseases in October was initiated to look at the effect melatonin may have on adult patients with severe COVID-19 infection. They engaged 158 patients with severe disease in a single center, prospective, randomized clinical trial conducted in Mosul, Iraq, from Dec. 1, 2020, to June 1, 2021.
The patients were split into two groups. In the control group, there were 76 who were given standard therapeutic care only. There were 82 in the intervention group who received standard therapeutic care plus 10 milligrams (mg) of melatonin per day. Physicians then evaluated the incidence of sepsis, thrombosis, and mortality in patients on days 5, 11, and 17.
When the researchers compared the data in the control group to the intervention group, they found there was a significant reduction during the second week in thrombosis and sepsis in those that took melatonin. They also found that mortality was significantly higher in those that didn’t take melatonin.
Men made up 72.2 percent of the patients and the mean age was 56.3 years with a range of 32 to 78 years. Researchers split the intervention and control group with no significant difference in relationship to comorbidities that increase the risk of COVID-19, such as high blood pressure, asthma, diabetes, and heart disease.
When measuring the individual endpoints, the researchers found that there was a significantly greater number of patients with thrombosis in the control group on day 17 than there were in the group taking melatonin. No patient developed sepsis in the first five days in either group. However, by day 11, two patients in the group taking melatonin developed sepsis and eight patients in the control group developed sepsis.
At the end of the study, the researchers found there was a significantly higher mortality rate in the control group of 17.1 percent than in the melatonin group of 1.2 percent. Melatonin was administered orally.
The researchers declared that the results of their study signal a need to look closer.
“Improved thrombosis, sepsis, and mortality rates support the adjuvant melatonin’s efficacy in mitigating this infectious disease,” they wrote.
“Given melatonin’s superior performance as a cheap, highly safe, and readily available medication, it is strongly recommended to be addressed in future studies.”
From this data, they identified conditions that were similar and that had approved drugs for treatment. Using this information, the researchers identified 34 FDA-approved drugs used to treat similar conditions that may be considered for repurposing in the treatment of COVID-19.
After identifying these drugs, the researchers used the information alongside data from nearly 27,000 inpatients at Cleveland Clinic. They adjusted for confounding factors such as age, smoking history, race, and a variety of disease comorbidities when they found melatonin use reduced the likelihood of a positive COVID-19 test by 28 percent.
Interestingly, when these same adjustments were made to a population of black Americans in the registry, the reduction rose to 52 percent. The study’s lead scientist, Feixiong Cheng, talked about the results in a statement from Cleveland Clinic:
“It’s important to note that this doesn’t mean people should start taking melatonin without first consulting with their health care provider. We’re excited about these results and to study that connection more, but large-scale observational studies and randomized controlled trials are essential to confirm what we’ve found here.”
“Although the adoption of MATH+ has been considerable, it largely occurred only after the treatment efficacy of the majority of the protocol components (corticosteroids, ascorbic acid, heparin, statins, Vitamin D, melatonin) were either validated in subsequent randomized controlled trials or more strongly supported with large observational data sets in COVID-19.”
“Despite the plethora of supportive evidence, the MATH+ protocol for hospitalized patients has not yet become widespread.”
The team developed an algorithm to help physicians identify the type of treatment based on the patient’s symptoms. However, all patients are advised to use vitamin C, omega-3 fatty acids, vitamin D3, and melatonin.
While there are likely benefits to supplementing with oral melatonin, it also helps to optimize your body’s own production. It’s relatively simple and inexpensive, and at the same time, you will help to optimize your vitamin D levels. Optimizing melatonin production begins with getting enough bright sunlight during the day, since this helps to set your circadian clock.
As the evening approaches and the sun sets, you’ll want to avoid artificial lighting. Blue light from electronic screens and LED lights is particularly problematic and inhibits the production of melatonin. If you do need lighting, use incandescent light bulbs, candles, or salt lamps. The blue light from electronic screens can be counteracted by using blue-blocking software or wearing blue-blocking glasses.
My decision to personally use melatonin supplementation makes even more sense now that we understand that melatonin is not only produced in the pineal gland (which would benefit from circadian optimization), but also in our mitochondria. So, it appears that additional melatonin could serve as a useful adjunct in modulating your immune response.
Dr. Joseph Mercola is the founder of Mercola.com. An osteopathic physician, best-selling author, and recipient of multiple awards in the field of natural health, his primary vision is to change the modern health paradigm by providing people with a valuable resource to help them take control of their health.
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