Integrative Medicine

COVID-19 Functional Treatment and Prophylaxis

By Kim Crawford, M.D. Last updated: March 6, 2021
COVID-19 Functional Treatment and Prophylaxis

COVID-19 Functional Treatment

As I write this article, it’s early March, 2021. My original, complete and very long article was published on April 13, 2020. It’s a masterpiece of information if I say so myself, has become the gold standard for U.S. functional treatment and can be found here. Currently we are racing to beat a couple of viral variants, with two governors opening up their states too early; long before even 10% of their population is vaccinated. I desperately hope that everyone stays the course, and we take advantage of the amazing scientific developments that have produced not one, not two, but three vaccines, approved for emergency use by our FDA. Meanwhile, as the virus continues to circulate, I’m being called on by my patients, friends and neighbors for help. We will always want strong immune systems as I suspect more epidemics are coming our way. Integrative medicine will be needed more than ever. Sadly, from now until the end of the summer and perhaps beyond, there will remain a high need for COVID-19 functional treatment.

  • Review of lifestyle for best immune health
  • Supplements which support immune health
  • Anti-viral supplements
  • Anti-viral peptide
  • Ozone
  • Proposed regimen for prophylaxis and treatment

Basic Lifestyle Strategies for Immune Health

Diet: You want to eat a diet that doesn’t support inflammation. You want to eliminate foods which are known to trigger inflammation or cause leaky gut. Keeping it as simple as possible, I’ll tell you to watch your intake of starchy carbs, processed foods, sugars and lectins. The most gut-damaging lectins are gluten, grains, high-lectin beans (such as kidney beans versus lentils) and low-fat dairy. If you can get it, A2 dairy contains a less gut-busting type of casein and is derived from Jersey or Guernsey cows. High fat A2 dairy is pretty safe. Immune-boosting foods include garlic, horseradish and wasabi. We used to recommend hot peppers in that list, but now we know (bummer!) that they are high in lectins. Garlic is actually an anti-viral.  It’s important to eat to support the health of your microbiome. Microbiome health equals better immune health, so let’s discuss that next.

Microbiome Health
The human microbiome is made up of 10–100 trillion symbiotic microbial cells with unique genes, mostly from bacteria (and some yeast) in the gut. Our “bad” or unhealthy gut bacteria (“gut bugs”), of which we have up to ten times more than human cells, thrive on the things that create inflammation in our body. We discussed that above, but let me emphasize this again, as it is so crucially important: refined carbs, unhealthy fats, processed foods and lectins (to name the biggest offenders.) We need to consume good prebiotic food as our GI tract’s “fertilizer” for probiotics. First, let’s discuss what makes for good probiotics.

Probiotics: High quality yoghurt, kefir (preferably home-made) and fermented foods provides a fair amount, but I generally supplement everyone. The literature supports the use of sporulating probiotics as more immune-supporting and able to lead to a more diverse microbiome.

Prebiotics: Prebiotic fiber is made up of non-digestible carbohydrate compounds found in fibrous foods that support the growth of healthy gut bacteria. Foods, spices, and supplements high in polyphenols will promote gut diversity. Red onions, artichokes, berries, hazelnuts, dark chocolate, and cloves are good sources of polyphenols. White and  (better yet), red onions as well as garlic, chicory, asparagus, unripe banana and Jerusalem artichoke are great “gut foods.” A major way that they assist gut health is by producing healthy gut byproducts such as butyrate.

To further increase butyrate production, you can intermittently eat a nutritional ketosis diet. However, easier for most: simply cook with either MCT oil or ghee or to increase  butyrate production by your “gut bugs.” And by the way, try to eat lots of mushrooms which play a role in supporting your GI tract lining and boosting your immune system. More about mushroom extract to follow. In our home, we stir up the following as a veggie-topper: MCT oil-add a clove of crushed garlic, sliced red onions, sliced leeks and some baby bello mushrooms. Now, let’s cover a topic that most of you don’t realize affects many aspects of your health, including your gut and therefore your immune health.

Stress Management

Stress depresses the immune system. Notice that you get more colds when you are under stress? There’s a very good explanation. It occurs via several mechanisms of action. First; sustained high cortisol levels cause gut hyper-permeability=leaky gut- which then causes systemic inflammation as GI waste contents literally leak into the bloodstream. Cortisol also interferes with T-cell (a type of white cell) function, making your body more susceptible to certain pathogens like viruses. Easy things to help you are manage your stress include regular “COVID-safe” outdoor exercise, deep breathing, and activating the parasympathetic nervous system by singing and even gargling. Some people like liposomal GABA supplements. I prescribe the intra-nasal peptide, selank for some patients. And of course, it’s important to get adequate, restful sleep.

A Word on Sleep

We are a nation of insomniacs. We watch T.V. or use our phones in bed. We eat too late. We don’t even try to get 8 hours of sleep per night. During times like these, we should make more of an effort, so that we make sure our immune system repair systems get put through all their paces; while we sleep. There are many things we can do as Functional doctors, to help our patients sleep-from simple things such as long-acting or sub-lingual melatonin preparation or peptides such as DSIP (delta sleep inducing peptide). But first, we start by advising everyone to practice “good sleep hygiene” which includes no T.V. or computers in the bedroom, having a pre-sleep ritual, and sleeping enough hours to awaken refreshed each morning. Now let’s discuss what supplements you can take to boost your immune system.

Supplements to support the immune system

Vitamin D

Vitamin D is well-known for its role in calcium balance and bone growth, but is also well-studied for its anti-inflammatory properties. Vitamin D is also noted to be anti-cancer, anti-autoimmune disease and anti-heart disease. What you might not know is that vitamin D is needed for a properly functioning immune system.

Within the immune system, vitamin D inhibits negative immune pathways and promotes positive ones. It also positively impacts the composition of the microbiome and the gut barrier. As one small example, a study in Japan showed that children taking 1,200 units of vitamin D per day during the winter time reduced their risk of getting influenza-A-infection by approximately 40 percent. By mid-summer of 2020, several clinical studies show that low vitamin D levels are a risk factor for coronavirus infection. What level is adequate? About 75 ng/ml. I live in sunny Florida and so do 1/3 of my patients- even all of us need supplementation, as “getting enough sun” will never give you adequate vitamin D3 levels.

Multivitamin supplements

You want to make sure you are either “juicing veggies” which is easy if you have a garden but difficult for most of us, or using powdered, organic fruit and vegetable supplements. Another option is to be sure you’re taking good oral vitamin supplements, high in antioxidants- especially vitamin A variants called carotenoids. Vitamin C is necessary but you need more of it than you get in a multi-vitamin. We’ll discuss vitamin C in the “anti-virals” section.

Reishi mushroom extract

All types of mushrooms contain natural polysaccharides (beta-glucans) in their cell walls. Beta-glucans ramp up the immune system via several mechanisms, such as activating what is called the “complement” component of the immune system, enhancing macrophages (a protective white blood cell that kills certain foreign invaders) and boosting natural killer (NK) cell function. There is an especially “active” species of mushrooms called ganoderma lucidum or reishi mushrooms. They are not considered tasty enough to eat outright, but they are used to formulate potent immune enhancing supplements.

Reishi mushroom extract is quite anti-inflammatory and immune stimulating. Reishi extract has a demonstrably positive effect on natural killer cell activity. It stimulates macrophage activity, increases T cell activity and is markedly superior to other mushroom extract in terms of it’s total immune-enhancing properties.

Melatonin

Melatonin is a powerful  anti-oxidant and an anti-inflammatory- not just something you take to help you sleep. Something that surprises just about everyone-it’s a potent immune booster, too! It blocks what are called inflammasomes, which are part of our innate immune system. Once the coronavirus enters our cells, we can measure a rise in inflammasomes in the blood. These inflammasomes facilitate the release of all inflammatory cytokines which cause or at least mediate the cellular damage caused by the virus itself. We know that blocking or at least lowering the level of inflammasomes would (theoretically) be a good thing. There is ample evidence of the benefits in animal studies.

In one study (referenced below)- in an animal model of acute lung injury, melatonin markedly reduced lung damage by inhibiting the inflammasome response. In rodent models of acute respiratory distress syndrome similar to the ARDS (acute respiratory distress syndrome)  caused by coronaviruses, melatonin significantly slowed down the progression of lung damage.

When melatonin is given to mice with severe heart infection issues, it transforms the life-threatening condition into a milder one and improves the chances of survival of the mice. Finally, a study, done in 2020 demonstrates melatonin’s benefit in sepsis (severe, life-threatening infection).

As a last comment in favor of melatonin supplementation; numerous studies in humans demonstrate that it improves sleep depth and duration. When stress and sleeplessness is a national problem, given the low to no side effect profile of melatonin, it seems prudent to recommend this supplement as safe, effective and probably immune boosting.

DHEA

The intermediary hormone, DHEA is well known to positively impact adrenal function and therefore cortisol levels. It has demonstrable anti-inflammatory properties and is most likely immune-supporting and even enhancing via several complex hormonal pathways. Now let’s discuss supplements and peptides which exhibit anti-viral properties. Yes, I did mention that garlic was anti-viral, so indeed garlic supplements are also a bit anti-viral; just not enough to make it into my COVID protocol.

Specifically Anti-viral supplements and peptides

Vitamin C

For a quarter of a century, it has been known that critically ill patients, including those with sepsis and multiple organ failure, have very low vitamin C status. It has also been demonstrated that these critically ill patients have higher requirements for vitamin C, with gram doses required to normalize their blood levels, 20–30 times more than is required for the general population.

The Chinese doctors in Wuhan initially used data on intravenous vitamin C,  the anti-malarial drug hydroxychloroquine and  the antibiotic-zithromax. The Chinese doctors also gave patients oral doses of the supplements zinc and melatonin. What got the most initial attention (at least in the U.S.) was the data on the SARS virus; suggesting that hydroxychloroquine was “the” answer. Now, we have come full circle, fully excluding anti-malarials and antibiotics (and just recently ivermectin-the anti-parasitic) as treatment options.

Numerous studies in the U.S., using  doses of IV vitamin C have been approved to treat SARS-CoV-2.  Initially, a randomized clinical trial, published in JAMA in the fall of 2019 was conducted in 167 patients with sepsis-related ARDS indicated that administration of approximately 15 grams per day of IV vitamin C for 4 days may decrease mortality in these patients. It appeared to decrease the time spent on ventilators.  Many more very encouraging studies with IV vitamin C- especially in combination with other drugs or supplements are still underway. Some reports reveal an average of as low as 48 hours on a ventilator versus the national average of 10-21 days. Liposomal preparations of products can be used to substitute for IV infusions- so in light of all of the positive data on IV vitamin C, it seems prudent to extrapolate that data to liposomal vitamin C.

Zinc

Zinc is an anti-viral mineral which helps our bodies slow the replication of invading viruses. Zinc has been shown to have anti-viral activity against many viruses, including some coronaviruses- although it is not yet tested fully or specifically on the novel coronavirus. However in the summer of 2020, RNA-dependent RNA polymerase-the enzyme needed for the reproduction of RNA viruses such as SARS-CoV-2 has been found to be blocked by zinc.

Zinc has been shown to help shorten the duration of the common cold (typically a rhinovirus but sometimes a coronavirus) if it is taken early on, in a sufficient dose.  When taking long term zinc supplementation, check to make sure you have enough dietary or supplemental copper “on board.” Similarly, if you are taking the peptide GHK-Cu, you must take zinc supplementation.

It is well know that zinc deficiency causes  a decreased sense of smell. Whether or not this has anything to do with the symptomatic loss of sense of smell as a symptom of infection is unknown. We do, however know that zinc supplementation does not appear to work to restore the sense of smell.

Quercetin

Zinc is transported into cells by the ionophore-quercetin, found naturally in large amounts in capers and lesser amounts in red onions. A randomized controlled trial involving over 1,000 people indicated that supplementation with 1,000 milligrams of quercetin per day for 12 weeks was associated with a reduction in the rate and severity of upper respiratory tract infections in individuals over 40. A 2020 study using IV vitamin C and quercetin in COVID patients concluded that quercetin displays a broad range of antiviral properties which can interfere at multiple steps of pathogen virulence -virus entry, virus replication and protein assembly.

Nitric Oxide

Nitric oxide (NO) is well known to be bactericidal; able to act directly as an anti-microbial  that can disrupt  bacterial structural proteins, fats, and nucleic acids.  Certain families of immune cells have been reported to produce NO which has contributed to the resolution of both bacterial and influenza infections. The non-proven clinical inference is that higher NO levels contribute to a more rapid clearing of both bacterial and viral host invaders. Given it’s low side-effect profile and the need for adequate nitric oxide levels for good health and maintenance of our vasculature anyway, we have many reasons not to shy away from this supplement.

Anti-viral Rx peptide: Alpha-thymosin-1 

The mechanism of action of alpha-thymosin-1 (chemically “tweaked” and approved as the hepatitis treatment drug zadaxin) is not completely understood but is thought to be related to its ability to augment T-cell function. It has been shown to increase natural killer cell (NK cell) activity, T “helper cell” activity, cytotoxic T cell activity and to increase antibody responses to T-cell dependent (e.g.: viruses) antigens.

The drug is approved for primary treatment for patients with acute infections, such as seen in severe sepsis, and for chronic infections including chronic hepatitis B (CHB), chronic hepatitis C (CHC), and HIV, as an adjunct treatment for certain cancers, and as an enhancement to both hepatitis B and influenza vaccines in immune-depressed individuals.

Alpha-thymosin-1 has undergone around 80 clinical studies, with demonstrable activity against a number of viruses, with minimal to no side effects- even in the elderly and infirm. It is currently (and notably) used as a vaccine adjuvant for HINI; resulting in higher antibody (and immunity) post-vaccination in (mostly) immuno-compromised patients. aT1 has also shown been used in the successful treatment of  patients infected with the highly pathogenic avian influenza H5N1 strain.

Severe Acute Respiratory Syndrome (SARS) was identified in Asia in 2003 and then rapidly spread to many countries in Europe, South America and North America before it was contained. After a near pandemic of the virus between November 2003 and July 2003, about 8000 cases were reported with 77 deaths worldwide .

At that time, an animal model demonstrated efficacy of Alpha-thymosin 1 (aT1) against the virus. Many persons were given aT1 prophylactically during that outbreak, due to the animal studies, as well as several  published reports in China suggesting that aT1 treatment likely contributed to controlling spread of the disease. In 2020, data  regarding ACE receptor inhibition and antioxidant capacity of aT1 suggested possible mechanisms of action.

It is used widely by Functional Medicine M.D.’s  based on the experience we have with the SARS coronavirus, as well as with other respiratory coronaviruses regarding both prophylaxis and treatment. Due to the nature of drug patents, there has been little appetite to study aT1; with the two studies done demonstrating reduced mortality rates post-infection.

IV and Rectal Insufflation Ozone

Ozone whole blood irradiation is a powerful tool against viruses (and everything else including Chronic Lyme Disease). This has been studied extensive and is currently used as a major treatment modality in Europe; both by MAH (major auto hemotherapy) or rectal insufflation. I kid you not.

Timing and dosing

The COVID-19 disease progression occurs in two distinct stages as follows. First- a reminder to take your temperature and your pulse oximeter reading twice daily and keep a record of your symptoms. Note that when your pulse oximeter drops below 95%, that this warrants a call to your physician.

  • The first stage of this disease is approximately the first week when your immune system is gearing up. This is when “immune boosters” as well as immune support and anti-virals are sensible choices. Take your multi-vitamin, vitamin D, melatonin, quercetin, NO supplement,  zinc, the reishi and the anti-virals. During this stage you might not even have a fever- but you’ll probably have fatigue, muscle aches, maybe an early cough and possibly a headache or some diarrhea. If you have chest pressure or  shortness of breath, seek medical assistance please.

High antioxidant MVI with fish oil: Many good brands come as a multi-capsule packet so just take 3 packets (instead of 2) daily. I like Lifepak Nano by Pharmanex. Please note that one aspirin per day is a prudent addition for some people, despite the anti-clotting activity of fish oils alone.

Melatonin: Studies have demonstrated that the maximal efficacy is 10-20 mg per night. Long-acting will give you better sleep benefits. Designs for Health has a good LA supplement, and if you need to get your stress levels down, they have a good liposomal GABA, too.

Zinc: If you haven’t been taking any zinc, assume you’re a little deficient; take 50-60 mg per day.

Quercetin: 500 mg per day and 1000 mg per day for “outings.”

Vitamin D: You want a level of 75 ng/dL which takes most Americans 2-3 weeks of 6000-8000 IU/day. If you are just starting out with vitamin D, you are presumed deficient, so 8000-10,000 IU per day is appropriate for the first week.

DHEA: Men with a history of prostate cancer and women with PCOS or a history of breast cancer must take the keto form of this hormone; if at all, since the keto form has not been studied for immune enhancement. Otherwise, men should take a daily dose of 50 mg; women-25 mg.

Reishi: Find a good brand; and follow the labeling directions. I use reishimax by Pharmanex.

NO: A popular brand gives you the accurate, typical twice daily dose. (Neo40).

Vitamin C: Liposomal preparations can generally be taken in dosing of 3 grams per dose without GI distress and I suggest you try that dose (1 TBSP: DFH or Quicksilver brands), four times daily to give you the dosing being used in some U.S. clinical studies.

Alpha-thymosin-1: There is no “accepted” dosing for COVID-19 treatment: and since there is such a large window of “no side effects” compared to upper level dosing, many functional practitioners are giving the maximal dose of 1.5-2.5 mg  2x/day for active cases. This is the dose I have used in the active cases I’ve treated, with everyone thus far (over 100 patients as of 3/2021) recovering at home. Note that all patients have been on this “full protocol” other than ozone therapy. Patients with known good NO food consumption (e.g. arugula and beets) did not necessarily take NO supplements. Due to the large % of variants in Florida, I’m prescribing on the higher end of the aT1 dosing. I am also currently having patients who already have home ozone set-ups incorporate this once daily.

  • The second stage of COVID comes around week two which is often an exaggerated inflammatory response, or “cytokine storm.” This is when you want to continue “support” and anti-virals, but do back off on immune boosters such as the reishi, probiotics, colostrum (if you’re taking it-it wasn’t mentioned but some people are taking this for immune support), and DHEA. If you are not taking an aspirin daily, now is the time (with your doctor’s blessing) to add it.

COVID-10 Prophylaxis and exposure with no symptoms: For everyday immune support, I recommend a good MVI with fish oil, vitamin D, zinc, reishi, DHEA, melatonin, and, for those with high blood pressure or other NO deficiency symptoms- a NO supplement. For “outings” where you maintain social distancing and wear a mask, it also seems prudent for both you and household members to take some vitamin C and a prophylactic (450 MCG) dose of the alpha-thymosin-1.

Final thoughts on Long-Haul COVID

Although there is no definitive proof, it appears that people who suffer from brain fog, cognitive impairment, mood issues, muscle aches, fatigue for weeks and even months after recovering from acute COVID, have some sort of variant of CFIDS. They appear to have mitochondrial failure and reduced neurogenesis; and (luckily!) seem to respond to peptides and integratives that repair these pathways. Research with exosomes is also quite promising.

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