15 ingredients for innovative post-COVID supplement formulations

Consumers are clamoring for nutraceuticals to help with their immunity and general wellness. Boost your formulations with these evidence-based vitamins, minerals and specialty chemicals.

Todd Runestad, Content Director, NaturalProductsInsider.com

April 19, 2021

8 Min Read
Council for Responsible Nutrition (CRN) Consumer Survey on Dietary Supplements reveals the highest overall dietary supplement

In April 2020—one year ago, and when COVID-19 was first sending shock waves throughout the world, market consultant giant Accenture issued a report saying that even then, one of the top four consumer health and wellness trends was nutraceuticals.

“The global pandemic,” concluded the report, “has created a huge surge in demand for everything wellness as consumers look to boost immune systems and improve overall physical and mental health.”

It noted ingredients from melatonin to collagen, essential oils to ginger and CBD.

Other research studies show surprising benefit with plain ol’ letter vitamins and select minerals. Basic nutrition stuff.

So it turns out that, as ever, the core natural products shopper—and the overall marketplace from health food store retailers to supplement manufacturers, entrepreneurial food and beverage startups seeking to bring more health to more people to multinationals looking to acquire the innovators—was right.

Healthier food, better lifestyle practices and pursuits, improved nutrition—and convenience and taste if you please—are the way forward.

A slew of nutrition research studies has been published in the last year, specifically investigating baseline nutritional status and therapeutic dosage levels, and the results are really not too surprising to natural products insiders.

Related:Patented botanical formulation kills COVID

It also points the way to ingredients to integrate into immunity as well as general health formulations to pinpoint consumers’ desires to use nutraceuticals in their quest for health and wellness in the age of coronaviruses.

Vitamin D? It might just be able to prevent, cure and treat COVID-19—what is now called SARS-CoV-2—despite the warning boxes on every supplement label per DSHEA saying supplements cannot “prevent, cure of treat” any disease. It is fairly unassailable at this point that vitamin D intake leads to improved outcomes, and higher baseline blood levels of vitamin D leads to better outcomes. In one study, 82.2% of hospitalized COVID patients had a vitamin D deficiency (defined at blood levels under 20 ng/ml).

One study showed those with deficiency levels (<20 ng/ml), compared with those of nicely high levels of >55 ng/ml were twice as likely to test positive for SARS-CoV-2—prevention!

Compared to those with levels north of 30 ng/ml, those under that threshold had a 2- to 3-fold higher risk of dying, and double the chances of having a poor COVID outcome. And for those with acutely deficient levels below 12 ng/ml, they had nearly 15 times a higher risk of dying and 6 times more likely to have a poor COVID outcome.

Related:Congress lauds vitamin D for COVID-19

People with levels above 40 ng/ml (the official cutoff of a deficiency is 20 ng/ml) almost never get SARS-CoV-2.

“We definitely see a connection here,” said Susan Hewlings, director of scientific affairs at ingredient supplier Nutrasource. “We have multiple mechanisms by which vitamin D can improve outcomes in COVID.”

A total of 220 scientists and doctors issued an open letter to all governments, public health officials, doctors and healthcare workers calling for immediate widespread increased vitamin D intakes. Specifically, they find that 6,200 IU/day is needed so that 97.5% of people to reach the 30 ng/ml threshold. At bare minimum, the authors recommend adults take 4,000 IU/day, which is widely regarded as safe. They recommend a loading dose of 10,000 IU/day for two to three weeks.

They note that the scores of studies show

  • Higher vitamin D blood levels are associated with lower rates of SARS-CoV-2 infection.

  • Higher D levels are associated with lower risk of a severe case—hospitalizations, ICU or death.

  • Vitamin D’s influence on COVID-19 is very likely causal, not just correlation.

“The preponderance of evidence indicates that increased vitamin D would help reduce infections, hospitalizations, ICU admissions and deaths,” said the authors. “There is no need to wait for further clinical trials to increase use of something so safe, especially when remedying high rates of deficiency/insufficiency should already be a priority.”  

“Nutritional research on nutrients is headlined by vitamin D3 and for good reason,” said Michael Murray, N.D., co-author of the Encyclopedia of Natural Medicine, known as the bible for nutritional research. “Those with science behind them become big sellers.”

Murray pointed to clinical trial in process with vitamin D, vitamin C, zinc, herbal medicines, probiotics, melatonin, selenium and quercetin—sales of the flavonoid quercetin have doubled in the last year.

Quercetin, according to a study, was ranked as the fifth best compound out of 18 candidates assessed to interfere with SARS-CoV-2 replication.

Researchers recommended that evidence supports quercetin being used with vitamin C because of overlapping antiviral and immunomodulatory properties, plus the capacity of vitamin C to recycle quercetin, increasing its efficacy.

The recommended dose is 1,000 mg/day.

And that’s not all.

Magnesium and vitamin K2 optimize vitamin D. One study found that people needed to take 146% more vitamin D to reach 40 ng/ml than those who also took 400 mg/day magnesium.

“Magnesium is needed to activate vitamin D,” said James DiNicolantonio, Pharm.D., author of three health books and director of scientific affairs at ingredient supplier AIDP. “Magnesium is the unsung hero that needs to activate the vitamin D.”

Vitamin K2 also boosts D. The same study also found that 244% more vitamin D was needed to achieve 40 ng/dl compared to those who supplemented with magnesium along with vitamin K2.

Another study, in Denmark, found a correlation between serum vitamin K2 status and the severity of SARS-CoV-2 illness. “Our study shows that low vitamin K status predicts mortality in patients with COVID-19,” said the authors.

Among all menaquinones, menaquinone 7, or K2 MK-7, has the best bioavailability and longest half-life. “Because of their structural differences, vitamins K1 and K2 do not have the same biological activities,” said Dr. Trygve Bergeland, VP Science at Kappa Bioscience AS, which supported new research into K2 and SARS-CoV-2. “With K2, the role of vitamin K extends beyond blood clotting, as it also regulates other important metabolic processes, such as calcification and inflammation. K1 is easily found in a balanced diet, which is not the case for K2. Deficiency might be more common than we think.”

“There is a need for further experimental evidence to link vitamin K deficiency with the pathology of COVID-19 and determine whether vitamin K2 supplementation has a place in treatment protocols. The potential role of vitamin K2 supplementation to prevent development of severe COVID-19 in subjects who have not yet contracted COVID-19, but are at risk for the infection, is also very relevant to assess,” Janssen concludes.

Zinc is another mineral of note. It has had 17 studies on nearly 7,000 patients with COVID. Its efficacy against SARS-CoV-2 is about between vitamin D and vitamin C.

In all the studies, zinc had a 39% improvement. But so-called “early” studies have better results—giving interventions early on in a patients’ diagnosis, versus other studies that give interventions as they are admitted to hospitals, or even late-stage studies where they are given interventions when things are looking pretty bleak.

In one provocative early study, researchers tested interventions early on—at four days after onset of COVID-19 symptoms. Researchers here combined zinc with the antibiotic azithromycin and the controversial hydroxychloroquine. It did find that the combination, compared to no treatment, led to about 80% decreased hospitalization and death among more than 500 patients.

“The optimal dose is 18 mg of ionic zinc,” said DiNicolantonio. “When you’re sick, more than 75 mg/day—Cold-EEZE, two lozenges every two hours. Use copper with zinc because zinc can cause a copper deficiency—1 mg copper.”

Vitamin C also deserves a place on the podium of vitamins worthy of inclusion in any post-COVID formulation. The catch is that the research showing potential is all using ultra-high-dose intravenous vitamin C. Administering I.V. vitamin C obviously gets the ascorbic acid straight into the bloodstream, with bioavailability being close to 100%. (Bioavailability is defined as the degree to which the nutrient becomes available to the target tissue after it has been administered.)

However, supplementing with oral vitamin C, as with supplements, leads to decidedly lower absorption levels. According to the Institutes of Health, vitamin C absorption is 70-90% when taken between doses of 30-180mg/day. But when doses go above 1,000 mg/day, absorption falls to less than 50%.

Do bioflavonoids help with vitamin C absorption? According to the Linus Pauling Institute at Oregon State University, one study showed a 35% increase of vitamin C bioavailability with bioflavonoids, but three other studies showed no difference.

Liposomal vitamin C has been shown to increase bioavailability by nearly 50% more than regular oral vitamin C but up to 5 times less than I.V. vitamin C.

Confirming the reports from small independent studies and 3 clinical trials, the Shanghai government has announced a recommendation to use high dose intravenous treatment of vitamin C to treat COVID-19. The dosage recommendation will vary with the severity of illness ranging from 50-200 milligrams per kilogram body weight (roughly 3.5-14g for an average-weight adult), administered via IV. Atsuo Yanagisawa, M.D., Ph.D. who is president of the Japanese College of Intravenous Therapy, states that this specific method of administration is very important because vitamin C’s effects are at least 10 times more powerful when taken by IV rather than orally, and that “Intravenous vitamin C is a safe, effective, and broad-spectrum antiviral.”

Want more? Here’s a list of short- and long-term health-promoting ingredients for immunity.

About the Author(s)

Todd Runestad

Content Director, NaturalProductsInsider.com, Natural Products Insider

Todd Runestad has been writing on nutrition science news since 1997. He is content director for NaturalProductsInsider.com and Natural Products Insider digital magazines. Other incarnations: supplements editor for NewHope.com, Delicious Living!, and Natural Foods Merchandiser. Former editor-in-chief of Functional Ingredients magazine and still covers raw material innovations and ingredient science.

Connect with me here on LinkedIn.


Todd writes about nutrition science news such as this story on mitochondrial nutrients, innovative ingredients such as this story about 12 trendy new ingredient launches from SupplySide West 2023, and is a judge for the NEXTY awards honoring innovation, integrity and inspiration in natural products including his specialty — dietary supplements. He extensively covered the rise and rise and rise and fall of cannabis hemp CBD. He helps produce in-person events at SupplySide West and SupplySide East trade shows and conferences, including the wildly popular Ingredient Idol game show, as well as Natural Products Expo West and Natural Products Expo East and the NBJ Summit. He was a board member for the Hemp Industries Association.

Education / Past Lives

In previous lives Todd was on the other side of nature from natural products — natural history — as managing editor at the Denver Museum of Nature & Science. He's sojourned to Burning Man and Mount Everest. He graduated many moons ago from the State University of New York College at Oneonta.


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