Health & Fitness

09/02/20

N-acetylcysteine (NAC) has a long history of use as a first-aid remedy for acetaminophen poisoning. Emergency room physicians will administer it in cases when you've taken an overdose of Tylenol or other acetaminophen products. The way it neutralizes the toxic effects of the drug is by recharging glutathione, thereby preventing liver damage.

Interestingly, NAC may also be useful against COVID-19, as explained by pulmonologist Dr. Roger Seheult in the MedCram lecture above. By raising glutathione, it helps combat oxidative stress, which is a main factor in the cytokine storm associated with COVID-19.

A recent literature analysis¹ linked glutathione deficiency to COVID-19 disease severity, leading the author to conclude that NAC may be useful both for prevention and treatment. NAC may also combat the abnormal blood clotting seen in many cases, and helps loosen thick mucus in the lungs.

FDA Cracks Down on NAC

Interestingly, with COVID-19 treatment as a new indication, the U.S. Food and Drug Administration is now suddenly cracking down on NAC, claiming it is excluded from the definition of a dietary supplement, as it was approved as a new drug in 1985.² As such, NAC cannot be marketed as a supplement.

You certainly would not suspect this looking at the supplement market. As reported by Natural Products Insider,³ there are no fewer than 1,170 NAC-containing products in the National Institutes of Health's Dietary Supplement Label Database.

Be that as it may, July 29, 2020, FDA announced⁴ it has issued warning letters to seven companies that market NAC as a remedy for hangovers. According to the FDA:

"A hangover can occur after alcohol intoxication. Alcohol intoxication, like all poisonings, causes dose-related dysfunction and damage, ranging from mild impairments to death … The products outlined in these letters, which are labeled as dietary supplements, are unapproved new drugs and have not been evaluated by the FDA to be safe and effective for their intended use."

Members of the Council for Responsible Nutrition have expressed concern that the warning letters may indicate the FDA is considering targeting NAC more widely.

While the FDA makes no mention of COVID-19 in its warning letter, the timing of its crackdown on NAC marketed for hangovers is interesting, seeing how news of its potential benefits against the viral infection have come into circulation, and research is now underway to assess whether it might be used in the treatment of COVID-19.

At present, seven studies involving NAC for COVID-19 are listed on Clinicaltrials.gov.⁵ Time will tell whether the FDA ends up trying to block access to NAC supplements, similarly to the way hydroxychloroquine access has been stifled.

NAC Inhibits Viral Replication

The idea that NAC can be helpful against viral infections is not new. Previous studies have found it reduces viral replication of certain viruses, including the influenza virus. As reported by board-certified nutritionist Joseph Debé:⁶

"NAC was tested in a 6-month human study⁷ of influenza. It was a randomized, double-blind, placebo controlled trial involving 262 people. Half of the subjects received 600 mg of NAC, the other half received placebo, twice daily for 6 months.

NAC was found to improve immune function and reduce the severity of influenza infections. Both groups had similar infection rates with A/H1N1 virus influenza. However, whereas 79% of placebo-treated people had symptomatic infections, only 25% of subjects treated with NAC were symptomatic!

There were a total of 99 flu-like episodes (symptomatic periods) that occurred in 62 people in the placebo group over the 6 month study. 48% of these were classified as mild, 47% were moderate, and 6% were severe.

In the NAC group, 46 flu-like episodes occurred in 37 subjects. 72% of these were mild, 26% were moderate and only 2% severe. There were many fewer days of being bedridden in the NAC group."

It's worth noting that the number needed to treat (NNT) in the study⁸ cited by Debé is 0.5, which means for every two people treated with NAC, one will be protected against symptomatic influenza.

That's significantly better than influenza vaccines, which have an NNV (number needed to vaccinate) of 71,⁹ meaning 71 people must be vaccinated to prevent a single case of confirmed influenza. It's even better than vitamin D, which has an NNT of 33.¹⁰ Even among those with severe vitamin D deficiency at baseline, taking vitamin D still had an NNT of 4.

NAC Inhibits Proinflammatory Cytokines

NAC has also been shown to inhibit the expression of pro-inflammatory cytokines in cells infected with highly pathogenic H5N1 influenza virus. According to the authors of such a study:¹¹

"The antiviral and anti-inflammatory mechanisms of NAC included inhibition of activation of oxidant sensitive pathways including transcription factor NF-kappaB and mitogen activated protein kinase p38 ...

NAC inhibits H5N1 replication and H5N1-induced production of pro-inflammatory molecules. Therefore, antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic."

Proinflammatory cytokines play a crucial role in COVID-19 severity. Researchers have confirmed that in severe cases, cytokines such as interleukin-6 (IL6), interleukin-10 (IL10) and TNF-ɑ are all elevated.¹² Once they reach excessive levels, a so-called cytokine storm develops, causing significant tissue damage. NAC may be able to inhibit this damaging cascade.

NAC — Potential Therapeutic Agent for SARS-CoV-2

A paper¹³ published in the October 2020 issue of Medical Hypotheses reviews the potential therapeutic benefits of NAC in the battle against COVID-19 specifically. According to the authors:

"COVID-19 … continues to spread across the globe. Predisposing factors such as age, diabetes, cardiovascular disease, and lowered immune function increase the risk of disease severity.

T cell exhaustion, high viral load, and high levels of TNF-ɑ, IL1β, IL6, IL10 have been associated with severe SARS-CoV-2. Cytokine and antigen overstimulation are potentially responsible for poor humoral response to the virus.

Lower cellular redox status, which leads to pro-inflammatory states mediated by TNF-ɑ is also potentially implicated. In vivo, in vitro, and human clinical trials have demonstrated N-acetylcysteine (NAC) as an effective method of improving redox status, especially when under oxidative stress.

In human clinical trials, NAC has been used to replenish glutathione stores and increase the proliferative response of T cells. NAC has also been shown to inhibit the NLRP3 inflammasome pathway (IL1β and IL18) in vitro, and decrease plasma TNF-ɑ in human clinical trials.

Mediation of the viral load could occur through NAC's ability to increase cellular redox status via maximizing the rate limiting step of glutathione synthesis, and thereby potentially decreasing the effects of virally induced oxidative stress and cell death.

We hypothesize that NAC could act as a potential therapeutic agent in the treatment of COVID-19 through a variety of potential mechanisms, including increasing glutathione, improving T cell response, and modulating inflammation."

A second report¹⁴ reviewing the evidence for using NAC in the treatment of COVID-19 was published April 14, 2020, by The Centre for Evidence-Based Medicine at the University of Oxford.

How NAC May Protect Against COVID-19

To fully understand how NAC might protect against COVID-19, a short lesson in biochemistry is useful. Following is a summary of Seheult's presentation, featured in the video above.

When you add an electron to an oxygen (O₂) molecule, you get superoxide (O₂), a reactive oxygen species (ROS). When you add another electron (for a total of two electrons), you get hydrogen peroxide (H₂O₂). An oxygen molecule with three electrons added becomes hydroxyl (O₃), and oxygen with four electrons added becomes harmless water (H₂O).

Not only does superoxide play a crucial role in the oxidative stress associated with the comorbidities for COVID-19, such as obesity, heart disease and diabetes, but superoxide-driven oxidative stress is also at the heart of serious COVID-19 infection. Now, your body has built-in defenses against oxidative stress. These defenses include:

• Superoxide dismutase (SOD), which converts damaging superoxide into hydrogen peroxide¹⁵

• Catalase, which converts hydrogen peroxide into oxygen and water

• Glutathione peroxidase (GSHPX), which does two things simultaneously: While reducing hydrogen peroxide into water, it also converts the reduced form of glutathione (GSH) into glutathione disulfide (GSSG), the oxidized form of glutathione.

In other words, as GSHPX turns hydrogen peroxide into harmless water, glutathione becomes oxidized. The oxidized GSSG is then "recharged" or regenerated by NADPH (the reduced form of NADP+), turning it back into GSH (the reduced form of glutathione). NADPH is also converted into NADP+ through an enzyme called GSH reductase

As noted by Seheult, serious COVID-19 infection triggers a perfect storm of superoxide-driven oxidative stress, as SARS-CoV-2 attaches to the ACE2 receptor, triggering angiotensin 2 (AT-2), which stimulates superoxide. Simultaneously, there's a deficiency of AT-1,7, which inhibits superoxide. This deficiency allows superoxide to accumulate further.

SARS-CoV-2 also attracts polymorphonuclear leukocytes (PMNs), a type of white blood cell, which also produces superoxide in its efforts to destroy pathogens. All of that superoxide is then converted into other ROS that destroy endothelial cells.

This down-spiral can be inhibited by NAC, as it boosts GSSG. As illustrated in Seheult's graphic below, when you add two GSH molecules and hydrogen peroxide together, you end up with oxidized glutathione and harmless water, thereby alleviating the oxidative stress.

NAC Reduces Lung Injury

Previous studies have also shown NAC helps improve a variety of lung-related problems, including pneumonia and acute respiratory distress syndrome (ARDS),¹⁶ both of which are common characteristics of COVID-19. It's also been shown to speed recovery, reduce intensive care unit (ICU) stays and reduce the need for mechanical ventilation among those with respiratory problems. Such studies include:

A 2017 meta-analysis,¹⁷ which found a significant reduction in ICU stays among ARDS patients treated with NAC, even though there was no significant difference in short-term mortality risk.
A 2007 study,¹⁸ which concluded that NAC improves ARDS by "increasing intracellular glutathione and extracellular thiol molecules" along with general antioxidant effects.
Research¹⁹ published in 2018 found NAC reduces oxidative and inflammatory damage in patients with community-acquired pneumonia.
Another 2018 study²⁰ found NAC improves post-operative lung function in patients undergoing liver transplantation.
A 1994 study²¹ found NAC enhances recovery from acute lung injury, significantly regressing patients' lung injury score during the first 10 days of treatment, and significantly reducing the need for ventilation. After three days of treatment, only 17% of those receiving NAC needed ventilation, compared to 48% in the placebo group.

NAC Protects Against Blood Clots Too

In this MedCram video, Seheult reviews the abnormal blood clotting aspects of COVID-19. Interestingly, NAC addresses this problem too, as several studies^22,^23,^24,²⁵ have confirmed it counteracts hypercoagulation and reduces the risk of blood clots and stroke.

As noted in one of these studies,²⁶ "NAC has anticoagulant and platelet-inhibiting properties." It also has potent thrombolytic effects, meaning it breaks down blood clots that have already formed.²⁷ According to another study,²⁸ NAC protects against stroke in part by enhancing GSH and correcting antioxidant levels.

Seheult's hypothesis for why NAC may be useful against COVID-19 can be summarized as follows: SARS-CoV-2 attaches to and reduces the ACE2 receptor, which causes AT-2 to increase and AT-1,7 to decrease. This in turn increases damaging superoxide that causes oxidative stress and endothelial cell dysfunction.

It is important to note that COVID-19 is not just a respiratory disorder, but also a vascular disorder that causes blood clots, which impair the ability to exchange oxygen in the lungs.

Fortunately, the sulfur in NAC (from cysteine) also reduces the intrachain disulfide bonds by von Willebrand factors that have polymerized by dissociating the sulfur bonds holding them together thus contributing to the clot. Once von Willebrand factor sulfur bonds are broken, the clots starts to dissolve and the blood vessels open up again allowing for exchange of oxygen and carbon dioxide.

Interestingly, NAC's mechanism of action does not appear to increase bleeding disorders like heparin or coumadin would, and appears to provide a safer alternative to these agents. This suggests that the "H" of heparin in the MATH+ protocol could simply be replaced with NAC.

Overall, the more we learn about COVID-19, the more we come to find there may be simple and inexpensive ways to treat this perplexing illness. NAC in particular looks like a good candidate for consideration. An added boon is NAC's excellent safety profile. As noted by Seheult, many studies have shown there are no serious adverse effects associated with its use.

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Calming Herb Can Ease Tension Headaches, May Promote Sleep

Tension headaches, also called stress headaches, are the most common type of headache.¹ And, with reports that people are feeling more stressed than ever, largely due to COVID-19,² I only expect the number of people with tension headaches to rise. Fortunately, there are natural solutions, like valerian, that can help.

Previous studies have looked at whether or not valerian could help alleviate migraines, but a 2020 study published in the Avicenna Journal of Phytomedicine wanted to see how it fared against tension headaches specifically.³

In the double-blind study, researchers used questionnaires to measure headache severity and how much headaches impacted daily life in 88 participants with tension headaches.

When the questionnaires were complete, participants were randomly assigned to one of two groups — an intervention group and a control group. For one month, the intervention group was given 530 mg of valerian root extract daily, while the control group was given 500 mg of breadcrumbs.

After the study period, researchers used the same questionnaires to remeasure headache severity. The participants in the intervention group reported significant reductions in headache severity and headache disability — or how much the headache interfered with regular daily life.

What Causes Tension Headaches?

As the name implies, tension headaches develop when the muscles in your neck and scalp become tense or stay contracted. Different things can trigger a tension headache, but they're typically brought on by stress. Lack of sleep and poor posture can make tension headaches worse.⁴

Researchers from a 2015 study in Cephalagia also connected tension headaches with decreased neck and shoulder strength. They compared 60 patients with frequent or chronic tension headaches to 30 healthy controls.

They found that the patients who experienced regular tension headaches had decreased strength in the exterior neck muscles, which cause a reduced cervical/flexion ratio when compared to the healthy subjects. The tension headache group also had decreased muscle strength in the shoulders.⁵ Other things that can contribute to tension headaches include:⁶

• Looking down at a computer or cell phone for extended periods of time

• Long drives without breaks

• Clenching your jaw

• Sleeping on your stomach

• Playing video games for an extended period of time

Unlike migraines, which cause a throbbing pain, tension headache pain is usually constant and aching.⁷ Typically, the pain associated with a tension headache is classified as mild to moderate. Many people describe tension headaches as feeling like they have a tight band or clamp around their head. Other symptoms of tension headaches include:⁸

Tense neck and shoulder muscles that are sore to the touch
Trouble concentrating
Difficulty sleeping

How Valerian Root Can Ease Tension Headaches

Valerian is classified as a sedative herb and an anxiolytic, or compound that helps reduce anxiety. The therapeutic effects of valerian are linked to volatile oils, monoterpenes, valepotriates and sesquiterpenes, specifically valerenic acid.⁹

In animal studies, valerenic acid has been found to act on gamma-aminobutyric acid, or GABA, receptors by binding to them and producing a GABA-like effect.¹⁰ GABA is an inhibitory neurotransmitter that helps keep a balance between nerve excitation and inhibition.¹¹ When you're stressed, GABA levels tend to drop.

When GABA levels rise, or when something like valerian binds to GABA receptors and makes your brain and body think GABA levels are increasing, it can help reduce stress and anxiety, alleviating tension headaches that come with it as well.

Other animal studies have found that valerian has a relaxing effect on the skeletal muscle. In a 2018 study in the Journal of Traditional and Complementary Medicine, researchers gave two groups of mice either a dose of valerian extract or a dose of tetrazepam, a muscle relaxing drug often prescribed for tension headaches and/or back pain.¹²

Thirty minutes later, they measured muscle strength and muscle function. They found that, when compared to the muscle-relaxing drug, valerian produced a more pronounced decrease in muscle strength without any negative effects on muscle function. In other words, the mice were able to relax their muscles without losing the ability to use them.

Valerian May Help Improve Sleep Too

Valerian is also a natural sleep aid and one of the most commonly used herbal remedies for insomnia, which makes it even more beneficial if your tension headaches keep you up at night.

Studies have shown valerian can help you fall asleep faster, get into a deep sleep faster and improve your overall sleep quality.¹³ A 2011 study that focused on postmenopausal women found 30% of participants experienced improved sleep quality after taking 530 mg of valerian twice a day for four weeks.¹⁴

An earlier study, published in 2001, also found that people who are regularly kept awake at night, plagued by thoughts of work deadlines, relationship problems or other stressful life events might find relief from either valerian or kava.¹⁵

In that study, adults who had suffered from stress-induced insomnia for over 15 years first received 120 mg daily of kava for six weeks. Then, after two weeks off treatment, they received 600 mg of valerian daily for another six weeks.

Overall, participants reported that both herbs significantly relieved their symptoms of stress and insomnia. While the majority, 58%, reported no side effects from either treatment, 16% reported vivid dreams after taking valerian and 12% experienced dizziness with kava.

Side Effects and Contraindications

There have been very few adverse effects reported from taking valerian. The most commonly reported side effects are headaches, dizziness, digestive troubles and itchy skin, although it's important to note that similar side effects were reported by people taking a placebo in clinical studies.¹⁶

Valerian does have the potential to interact with other medications and supplements though. Contraindications include the concomitant use of:¹⁷

Benzodiazepines	Barbiturates
Central nervous system depressants (morphine)	St. John's wort
Kava	Melatonin

Also, do not take it with alcohol, and do not drive or use machinery within several hours of taking valerian. Valerian may also be contraindicated if you are pregnant or nursing or have liver problems. Valerian should not be given to children under the age of 3 because the potential risks have not been studied in children this young.

Other Things You Can Do to Relieve Tension Headaches

While valerian can be an effective remedy for tension headaches, other strategies that can help relax your muscles and alleviate stress that contributes to them include:

• Strength training — Because tension headaches may be connected to weak neck and shoulder muscles, strengthening those areas through weightlifting, stretching and/or working with a physical therapist may help. In addition to focusing on the neck and shoulder muscles, you'll also want to correct imbalances in other areas, like your back, and work on strengthening your core and improving your posture.¹⁸

• Relaxation techniques and deep breathing exercises — All types of tension headaches can be relieved by finding effective ways to manage your stress and practicing different relaxation techniques,¹⁹ like deep breathing exercises, regularly. Cleveland Clinic offers other types of relaxation techniques, including progressive muscle relaxation, mental imagery relaxation and listening to relaxing music.

• Biofeedback — Biofeedback is another way to help you manage your stress levels. During a biofeedback session with a trained therapist, electrodes are connected to different areas of your body. These sensors measure things like muscle tension, heart rate and blood pressure and then display the measurements on a screen.

These measurements help you and your therapist recognize when your body is tense and why. When you have this background information, you can work on figuring out effective ways to relax your muscles and release your tension over the course of several sessions.²⁰

• Taking regular breaks — If you work on the computer all day or you have to go for a long car ride, take breaks and stretch. Avoid looking down at your phone for too long.

• Yoga — In addition to relieving stress and helping you focus on your breathing, yoga also helps you stretch your muscles. In a 2019 review in the Journal of General Internal Medicine, researchers reported that yoga could improve headache frequency, headache duration and pain intensity in people with tension headaches.²¹

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Low Vitamin K in Elderly Linked to Increased Risk of Death

Vitamin K is a fat-soluble vitamin that can be found in some foods. The body uses it for certain functions, such as those required for bone metabolism, blood clotting and a variety of other cellular functions.¹

Your body has a limited ability to store vitamin K, so it must be absorbed from your food or a supplement on a daily basis. It’s also recycled within your system, optimizing its benefits.² Several different medications, such as antibiotics, weight loss drugs, cholesterol medications and the blood thinner warfarin, may interfere with its absorption, and therefore affect blood clotting.

Vitamin K is distributed throughout the body, including in your brain, heart, bones and liver.³ Since it’s broken down and excreted quickly it rarely reaches toxic levels in a way that happens with other fat-soluble vitamins.

Since the vitamin is crucial to several bodily functions, it’s not surprising to learn that if you don’t get enough every day, on a daily basis, you could be at risk for an earlier death.

Vitamin K Lowers Risk of Death in Older Adults

Recently, a paper was published in the American Journal of Clinical Nutrition by a team that investigated the vitamin K-dependent proteins that may affect atherosclerosis, which is the stiffness and calcification of the arterial vessels.⁴

The aim of the investigation was to determine if there was an association between circulating vitamin K, cardiovascular disease and all-cause mortality. The study was carried out at Tufts University and led by Kyla Shea, who commented:⁵

“The possibility that vitamin K is linked to heart disease and mortality is based on our knowledge about proteins in vascular tissue that require vitamin K to function. These proteins help prevent calcium from building up in artery walls, and without enough vitamin K, they are less functional.”

The researchers gathered data from three science databases, including the Framingham Offspring Study. The participants had circulating vitamin K1 (phylloquinone) measured, and each person either had some type of heart event or they died. There were 3,891 men and women with 858 heart events and 1,209 deaths over 13 years.

Interestingly, although vitamin K is associated with vascular health, the data did not show an association between low vitamin K and cardiovascular disease (CVD). However, there was a link between low levels and all-cause mortality. They found a 19% increased risk of all-cause mortality in those with the lowest serum levels of vitamin K.⁶

Since the study was observational, the scientists could not establish a causal link, yet the data fit with what we know about the function of vitamin K in the body. One-third of the participants in the study were not white, which allowed the researchers to theorize that the association is multi-ethnic.⁷ Dr. Daniel Weiner, nephrologist from Tufts Medical center, explained the association between stiff arteries and CVD:⁸

“Similar to when a rubber band dries out and loses its elasticity, when veins and arteries are calcified, blood pumps less efficiently, causing a variety of complications. That is why measuring risk of death, in a study such as this, may better capture the spectrum of events associated with worsening vascular health.”

Vitamin K: The Basics

There are two basic types of vitamin K.⁹ Vitamin K1 is found in green leafy vegetables and works through the liver to help maintain a healthy clotting system. This is the type researchers measured in the study. Vitamin K1 also helps reduce calcification in the blood vessels and assists your bones in retaining calcium.

Vitamin K2 (menaquinone) is produced by bacteria in your gut and can be found in some animal products and fermented foods, particularly cheese and natto. This is the one that helps activate vitamin D and move calcium out of the arterial system and into your bones and teeth.¹⁰

There are also several different forms of vitamin K2. They are named for the length of the chemical chain, beginning with the letter M for menaquinone. The two most important types are found in animal products and fermented foods. Most Western diets are deficient in both forms of vitamin K2.¹¹

In one study, researchers sought to compare the effectiveness of giving supplements of these two types, MK-4 and MK-7, to healthy women. They “demonstrated that a nutritional dose of MK-7 is well absorbed in humans, and significantly increases serum MK-7 levels, whereas MK-4 had no effect on serum MK-4 levels.”¹²

More Benefits of Vitamin K

Vitamin K is integral to the body's ability to coagulate, or clot, blood. These clotting factors are involved in a cascade of events that stop bleeding and are produced in the liver. Therefore, individuals with severe liver disease can have difficulty with vitamin K-dependent clotting and are at an increased risk for hemorrhage.¹³

As discussed previously, Vitamin K is also integral to moving calcium out of the arterial system and to preventing soft tissue calcification. This function is central to preventing osteoporosis and maintaining strong bone health.

Another benefit is a vitamin K-dependent protein, growth arrest specific gene 6 protein (Gas6), which was identified in 1993 and is found in the heart, kidneys, lungs and cartilage. It contributes to many cellular functions that may play a role in protecting an aging nervous system, and it appears to regulate vascular homeostasis.

Separate studies using vitamin K2 on cancer cells in the lab have demonstrated an apoptotic effect. In one study, researchers found vitamin K2 induced apoptosis in bladder cancer cells and in another, against triple negative breast cancer.^14,¹⁵

Vitamin K2 and Magnesium Optimize Vitamin D Supplementation

The evidence that your serum vitamin D level is protective against COVID-19 and reduces the severity of the disease continues to grow. While your body produces vitamin D from the reaction to sunlight, many don’t get enough sun to raise their vitamin D levels above 30 ng/mL.

To reach this minimal goal, you may need a supplement. Yet, taking vitamin D3 supplements without magnesium and vitamin K2 may offer little effective protection and could increase your risk of atherosclerosis. Before you can determine how much supplementation is needed, you’ll want to test your current level. You can do this using a home kit through GrassrootsHealth.¹⁶

The kit is delivered to your home where you use a finger stick and send the kit back to the lab. Only you get the results of the test, which you can then input into the GrassrootsHealth calculator to determine the amount of supplement you’ll need to achieve your desired result.¹⁷

Vitamin D is important in the absorption and utilization of vitamin K2. In fact, a vitamin K deficiency may contribute to symptoms of “vitamin D toxicity.” In my interview with Dr. Kate Rheaume-Bleue, natural health physician and author of Vitamin K2 and the Calcium Paradox, she talked about this challenge:¹⁸

“We don't see symptoms of D toxicity very often but when we do those symptoms are inappropriate calcification. That's a symptom of D toxicity and that is actually a lack of vitamin K2 that will cause that. K2 protects you against that toxicity quite simply.”

Added to this, I’ve written about the importance of vitamin K2 when you’re taking supplemental vitamin D3 to avoid excessive calcification in your arteries. Magnesium is also a crucial part of raising your vitamin D level as it is necessary for the activation of the vitamin.

Without sufficient amounts your body can’t properly use the vitamin you’re taking. Mohammed Razzaque is a professor of pathology at Lake Erie College of Osteopathic Medicine in Pennsylvania. He notes that without magnesium, vitamin D supplements may not be useful.¹⁹

To lower the risk of vitamin D deficiency it’s necessary to have optimal amounts of magnesium.²⁰ According to one scientific review, as many as 50% of Americans who are taking vitamin D supplementation may not benefit, as it’s stored in the inactive form without sufficient levels of magnesium.^21,²²

The relationship is a two-way street. While vitamin D improves the absorption of magnesium, large doses of vitamin D may deplete magnesium.^23,²⁴ This is because large doses of vitamin D will require large doses of magnesium to convert it to the active form.

GrassrootsHealth published research that was based on data from nearly 3,000 people showing you must take 244% more vitamin D if you aren’t also taking a magnesium and vitamin K2 supplement.²⁵ Practically speaking, this means when you take all three in combination you’ll need far less vitamin D to achieve a healthy level.

According to researchers, “those taking both supplemental magnesium and vitamin K2 have a higher vitamin D level for any given vitamin D intake amount than those taking either supplemental magnesium or vitamin K2 or neither.”²⁶

Consider Supplementing With Magnesium and Vitamin K2

There are several forms of magnesium. In each form, the magnesium is bound to another molecule. Some forms have compounds that serve other functions in the body, as you’ll find in “NYC Doctor Highlights Importance of Vitamin D Optimization”:

Magnesium glycinate,²⁷ a powder with low solubility. Glycine is an important amino acid and precursor for glutathione.
Ionic magnesium found in molecular hydrogen tablets. Each water-soluble tablet has about 80 mg of highly bioavailable unbound magnesium ions, which is about 20% of the recommended daily allowance.
Magnesium threonate²⁸ is another excellent choice as it seems it can efficiently penetrate the blood-brain barrier.
Magnesium malate,²⁹ which dissolves well in water. Malate is an intermediary in the Krebs cycle, so it likely contributes to ATP production.
Magnesium citrate³⁰ also dissolves well and has a pleasant citric acid taste.

Since most people eating a Western diet are deficient in vitamin K2 and the vitamin is quickly used and excreted, it’s important to either change the foods you eat, or consider supplementation. As noted in the featured study, those with higher levels of vitamin K have a lower risk of death.

It can be difficult to tell if you’re getting enough vitamin K, as there’s no easy way to screen or test for vitamin K2 sufficiency. For more information about getting enough vitamin K, see “Spinach, Eggs and Gouda Cheese to Combat COVID?”

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Oleander Is a Deadly Plant, Not a COVID-19 Cure

While there’s evidence to support the use of several nutrients and supplements in the fight against COVID-19, oleandrin, a compound from the oleander plant, is not one of them.

Rumors about the possibility of an oleandrin remedy have been swirling in recent weeks following the posting of a study¹ on the preprint server bioRxiv, in which oleandrin was found to inhibit the replication of SARS-CoV-2 in vitro. According to the authors:²

“Typically, the fastest route to identifying and licensing a safe and effective antiviral drug is to test those already shown safe in early clinical trials for other infections or diseases. Here, we tested in vitro oleandrin, derived from the Nerium oleander plant and shown previously to have inhibitory activity against several viruses …

When administered both before and after virus infection, nanogram doses of oleandrin significantly inhibited replication by up to 3,000-fold, indicating the potential to prevent disease and virus spread in persons recently exposed to SARS-CoV-2, as well as to prevent severe disease in persons at high risk.

These results indicate that oleandrin should be tested in animal models and in humans exposed to infection to determine its medical usefulness in controlling the pandemic.”

Do Not Attempt to Use Oleander as a Home Remedy

It’s important to note that this was an in vitro test, meaning these results were observed in a cell culture. It has not been tested on animals or humans. The reason this is a crucial distinction is because the oleander plant is well-known for its extreme toxicity.

The fact that it killed the virus in a cell culture does not suggest it would be an effective remedy for the simple fact that its high toxicity just might kill the patient along with the virus. So, please, DO NOT attempt to use this plant as a home remedy against COVID-19.

Oleander grows well in subtropical climates such as Florida, and is toxic to pets. I strongly advise against growing oleander in your yard if you have pets or small children (and if you do, make sure they’re supervised around the plant), or harvesting the plant as a potential remedy. The results could be lethal.

This is definitely an instance in which we must allow scientists to methodically work through the scientific process to determine if, in fact, there’s a way to turn oleandrin into a useful drug.

American Botanical Council Issues Advisory

Among those who have issued urgent advisories against the use of oleander is the American Botanical Council (ABC), also known as the Herbal Medicine Institute — an independent, nonprofit research and education organization.³

When it comes to plants, herbs and botanicals, they are a premiere expert resource. In an August 18, 2020, advisory, the ABC warns consumers against producing oleander-based home-remedies due to the plant’s extreme toxicity:⁴

“ABC warns consumer not to ingest any parts of the plant, or capsules, tablets, teas, or extract preparations made from leaves or other parts of the oleander plant because it contains chemicals that can cause serious effects to the human heart, including death …

Oleander is a large white- or pink-flowering bush or small tree that is grown as an ornamental plant in many parts of the United States and elsewhere, including north Africa, the Mediterranean, and southwestern Asia.

All parts of the plant contain a poisonous substance called oleandrin, known technically as a cardiac glycoside, and other similarly toxic constituents. The structure of oleandrin and its activity are similar to digoxin, a glycoside from the equally toxic foxglove plant … Digoxin is a pharmaceutical drug used in conventional cardiology for heart failure and irregular heartbeat.

ABC does not know of any extracts or dietary supplement products sold in the U.S. that contain oleander. Oleander plant parts and its extracts are not sufficiently safe to be sold in dietary supplements …

According to ABC Founder and Executive Director Mark Blumenthal, ‘To be clear, ABC applauds appropriate scientific research into medicinal plants and fungi as sources of new medicines. We also acknowledge the very promising medical research conducted by Phoenix Biotechnologies and their oleandrin formulations.

However, ABC emphasizes the distinction between a scientifically studied, chemically-defined experimental new drug compound from a widely known poisonous plant and a simple home-made pill, tea, or extract made from the plant’s various parts.

With respect to oleander, all parts of the plant are highly toxic, dangerous, and life-threatening when ingested. Consumers should not, ever, try to make a home-made remedy from or self-treat with oleander.’”

Extreme Toxicity of Oleander

To get an idea of just how toxic oleander can be, consider this 2006 case report⁵ of two individuals who came down with several adverse symptoms, including nausea, vomiting, diarrhea and abnormal cardiac sinus rhythm, after eating a stew made with snails that had consumed the plant.

Their symptoms were diagnosed as being the result of toxic exposure to oleandrin and oleandrigenin, the presence of which were found in the snails. Other medical case reports have noted that:

• Oleandrin causes arrhythmia by interfering with the sodium-potassium pump of your heart. Ingestion of any part of the oleander plant is also associated with gastrointestinal effects, such as nausea, vomiting and diarrhea.

Both cardiac and gastrointestinal effects appear approximately four hours after ingestion. Even the smoke of the plant, when burned, is toxic. As noted by the authors, “Practicing physicians should understand the potential lethal properties of oleander and its availability throughout the world.”⁶

• According to a 1982 case report, 4 grams of oleander leaves provided a fatal dose of toxic glycosides.⁷

• A 2019 paper reported a fatal case of self-poisoning through the voluntary ingestion of oleander leaves. Toxic blood levels of oleandrin was estimated at 1 ng/mL to 2 ng/mL. Levels above 9.8 ng/mL are thought to be fatal.⁸

The authors of that 2019 paper point out that while oleander poisoning is typically accidental, knowledge about the plant’s toxicity could be used as a method for suicide (or homicide, for that matter).

Considering the fact that rates of depression, anxiety and suicide are currently higher than ever,^9,¹⁰ putting this information out there is a bit of a double-edged sword. If you are depressed, I urge you to seek professional help.

If you are feeling desperate or have any thoughts of suicide, call the U.S. National Suicide Prevention Lifeline, a toll-free number 1-800-273-TALK (8255), or call 911, or simply go to your nearest Hospital Emergency Department.

If you, your child or pet has ingested any part of the oleander plant, call 911, your local poison center, or the national toll-free Poison Help hotline at 1-800-222-1222. Do not make the patient throw up unless told to do so by poison control or a qualified health care provider.¹¹

Oleandrin Is a Cardiac Toxin

In an August 18, 2020, article published by The Conversation,¹² medical ethnobotanist Cassandra Quave also warns against self-medicating with oleander, noting that while more than 28,000 plant species are recognized for their medicinal value, not all plants are safe.

The oleander plant in particular has been responsible for poisonings all around the world.¹³ Again, all parts of the plant, including the smoke when burned, are poisonous. “If eaten, it causes cardiac arrhythmias, or irregular heart rates, and can be lethal to both humans and animals,” Quave warns.

Other potential side effects¹⁴ include dizziness, blurred vision or other vision disturbances, low blood pressure, drowsiness or fainting and headache. In nonlethal instances, symptoms can last up to three days, and frequently require hospitalization due to their severity. Quave adds:¹⁵

“Oleandrin is … known by scientists as a cardiac glycoside, a class of organic compounds with a common feature: They exhibit powerful effects on heart tissue, often with deadly consequences.

A pre-print article … reports how, in a test tube, oleandrin reduces production of the virus responsible for COVID-19. But this does not take into account the well-known cardiac toxicity of the chemical when consumed by an animal or human.

Particularly worrisome is the idea that consumers may misinterpret any publicity surrounding oleander and try to self-medicate with this highly poisonous plant. I’m also concerned the dietary supplements industry may try to take advantage of the public’s fear of COVID-19 by developing supplements containing oleandrin.

There are many other examples of natural plant extracts that are harmful. But oleander is particularly dangerous, because ingesting any part of the plant can lead to serious illness and possibly death.”

So, in closing, as reviewed in “Essential Nutrition to Protect Yourself From Coronavirus” and many other articles, there are several nutritional supplements that have significant scientific backing for their use against respiratory infections, including COVID-19. Oleander is not a safe medicinal plant, and I strongly advise against any attempt to use any part of the plant to self-medicate against any condition whatsoever.

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