PharmD alum advocates for responsible regulation of vitamins

The patient was a healthy man with no significant medical history. Like many others, though, he was concerned about contracting COVID-19. So in the summer of 2020, he began taking a supplement of vitamin B6 to “strengthen” his immune system.

In May 2021, the man’s health took a turn for the worse. Doctors struggled to explain his mysterious symptoms, such as numbness in his hands.

Months later, a blood test revealed an unusually high level of the active form of vitamin B6. The man stopped taking the supplement and most of his symptoms subsided within a few months.

In the fall of 2021, UCSF School of Pharmacy alum Ana Najafi, PharmD ’21, learned of this patient’s experiences and began to dig into the literature. As a strategic pharmaceutical development associate for Emery Pharma, Najafi was tasked with following up on his case, which he had submitted to the company via an online inquiry form.

Najafi and her colleagues soon amassed a sizable body of case reports, scientific studies, and regulatory data on vitamin B6. The evidence was clear: high doses of vitamin B6 could be dangerous yet were widely available across the U.S. without a prescription or even a warning label.

In September 2021, Emery Pharma, a contract research organization, filed a citizen petition with the FDA, making the case for more stringent regulation of vitamin B6. Citizen petitions are the formal process for individuals or organizations to make requests of the FDA to change its policies.

The petition received expected pushback from industry groups, but Najafi hopes that Emery Pharma’s efforts will improve awareness and regulation around vitamins and supplements, advancing drug safety on a larger scale.

“Now that we’ve posted the petition, we’re getting a serious influx of even more patients letting us know that they’ve been affected by this,” she said. “They’re so touched that we’re talking about this issue and trying to make change happen.”

Najafi spoke to Emily Vivian Huang about the vitamin B6 citizen petition, its implications for the vitamins and supplements industry, and her thoughts on her budding career and its potential impact on patients.

Huang: Tell me more about your current job in the pharmaceutical industry.

Najafi: Since graduating with my PharmD a few months ago, I’ve been working at Emery Pharma, a contract research organization in the East Bay.

Emery Pharma is contracted by other companies in the life sciences industry to help solve scientific challenges. For example, companies that are in preclinical drug development will approach us for help designing custom studies that will bring their product from the bench to the shelf. Sometimes, that’s PK-PD [pharmacokinetic-pharmacodynamic] studies, sometimes it’s cytotoxicity. But that’s one arm of what they do.

The other arm is very investigational, research-type work. For example, Emery Pharma’s claim to fame is that they discovered a cancerous impurity in Zantac [a heartburn medication]. Another partner company approached them saying that they were noticing these high levels of NDMA, a known carcinogen, in Zantac. Emery Pharma figured out that if Zantac wasn’t stored in a controlled temperature environment, it would progressively form more and more of this carcinogen.

So Emery Pharma filed a citizen petition with the FDA and it resulted in a nationwide recall of Zantac. I got exposure to this kind of innovative, entrepreneurial contract research-type work during an initial role here in 2016, before I earned my PharmD. Then I went to pharmacy school at UCSF, graduated, and long story short, I’m back here.

Huang: Recently, Emery Pharma filed a citizen petition with the FDA to revise the labeling and prescription regulations on high vitamin B6 doses. What prompted this petition to happen?

Najafi: During the COVID pandemic, a few different vitamins were improperly touted as a means to decrease COVID severity. People were taking vitamin C supplements, vitamin D, vitamin B—specifically, vitamin B6.

In June, we were approached by a patient in his mid-60s. He had no past medical history, and he’d started taking supplements during the pandemic, one of which was 100 mg of vitamin B-6 daily [50 times the maximum Recommended Dietary Allowance]. After a month, he started to experience heat sensitivity, burning and tingling of the hands and feet, severe numbness in his hands, extreme thirst, frequent urination, and flushing. We learned that originally, doctors thought it was potentially diabetic neuropathy. Then MS [multiple sclerosis] was thrown around, then they thought it was maybe a pinched nerve.

Ultimately, they wrote it off as idiopathic neuropathy, which—being a health care provider, you’re like, “Hmm. Sudden onset idiopathic neuropathy. That’s interesting.”

After another few weeks, he noticed his symptoms weren’t going away. He begged for blood tests and they found that his vitamin B6 level was three times the normal. After hearing his story, we decided to look further into the case. The more we looked into it, and came across more and more case studies of patients with similar stories, the scarier it got.

We ended up filing a citizen petition with the FDA. We presented the evidence of the benefits, the risks, the adverse events, the pharmacokinetic profile, and asked them to revise the regulations related to vitamin B6.

As you know, the FDA doesn’t monitor vitamins and supplements before they hit the market, but they do have the authority to take them off the market if they’re found to be unsafe. We made the case that this is unsafe. It was a very interesting process to go through because with prescription drugs, when a new drug reaches the market, there has to be significant data to support its benefits as well as its risks. And I think if this were a prescription drug, you would see black box warnings and medication guides and a very detailed and defined side effect profile.

But because it’s a vitamin, it’s essentially unregulated by the FDA. We petitioned them to assess the evidence that we presented to them, and to implement proper labeling along the lines of, “this medication can be dangerous when used in large amounts for a long time, so stop taking it if you experience tingling, burning, and numbness, and see your health care practitioner as soon as possible.”

We’re petitioning for a label, and we’re petitioning to reclassify doses that are greater than 10 mg as available by prescription only. Such is the case with high doses of vitamin D as well. So, there is precedence for this.

Huang: In the past, Emery Pharma also submitted a citizen petition to the FDA regarding unsafe levels of carcinogens in ranitidine (Zantac), which was successfully recalled. How does the vitamin B6 citizen petition compare to the Zantac recall of 2020?

Najafi: I think that this one is much tougher, because with the Zantac citizen petition that we filed, there are significant standards and regulations in place, since Zantac is a prescription drug.

There’s a limit to certain impurities that drugs available commercially are allowed to have—no more than one part per million. We noticed that the levels were way beyond acceptable, giving us a clear argument for pulling the drug from the shelves, especially because we were dealing with a known carcinogen, NDMA.

In the case of vitamin B6, it’s completely different. There aren’t clear, black-and-white guidelines for vitamins and supplements. It’s much more difficult to make the case and compel somebody to act on something when there aren’t already standards in place. We have to make the case that this vitamin or supplement in specific doses causes toxicity without question, and that this toxicity is enough for them to act on it.

Huang: As a result of all this, what broader changes in the vitamins and supplements industry would you like to see?

Najafi: Number one, I want to see significant efforts in education. I read an article in Pharmacy Times the other day that showed that more than half of the people surveyed believed that vitamins and supplements available over the counter have been declared safe and effective by the FDA. I think it’s a real shame and danger that it’s not a widespread, known fact that dietary supplements and vitamins are unregulated.

This is a real opportunity for pharmacists to step in and to take that patient medication history, figure out what vitamins and supplements they’re taking, counsel on whether they need to be on that vitamin or supplement, and really monitor patients for adverse effects.

I would like to see vitamin B6 doses greater than 10 mg no longer be available over the counter. Similar to vitamin D—where you can get 1000, 2000, 3000 IUs over the counter, but doses that are 25,000 or 50,000 IU are prescription only because those have the potential for harm. It’s crucial to allow a safety margin for doses that patients are allowed to be taking over the counter, and [more strictly regulate] doses for which toxicity starts to occur.

Overall, awareness and education are important, and I think it should be a cultural shift for both pharmacists and providers to be looking for these kinds of things, especially because patients don’t tend to be forthcoming about the vitamins and supplements that they’re taking.

Huang: How did UCSF prepare you to work where you are in the industry today?

Najafi: At UCSF we don’t just list off drugs and the side effects. We really dive deep into mechanisms, and so when I was researching this Vitamin B6 issue, I was looking at the pharmacokinetics, the chemical structure, the clearance, and the half-life. I think that these are really specialized niches for pharmacists because nobody else has that kind of training. Overall, I think UCSF does a really good job of providing a holistic education—a comprehensive, scientific background on every drug that we talk about.

Huang: What do you enjoy the most about working in pharmaceutical industry?

Najafi: I think health care can be about caring for and working one-on-one with an individual, or working on a much broader reach with many more people. With the pharmaceutical industry, you’re working on a product to treat an illness, to get it past preclinical drug development, and then onto the shelves to help multiple patients.

I’m also really inspired by innovation. We get to work with companies that are doing many different things in many different areas. One day I’ll be working on a dermatology product for atopic dermatitis, and the next it’ll be a new Alzheimer’s disease therapy, and the next day, it’s monitoring estrogen levels in patients who are wearing a specific device.

Huang: Finally, what are some pieces of advice that you can share for current pharmacy students interested in pursuing careers in industry?

Najafi: I'd suggest first getting involved in a smaller pharmaceutical company. It allows a lot more opportunities to work with different groups of people and gain exposure to marketing, commercialization, and pharmacoeconomics research.

It’s also always important to try to look at the big picture when you’re in school and when you’re getting that didactic coursework. Try to look at the real-world implications, try to see what kind of broader applications there might be with what you’re learning, and how you can use that to advocate for others.

More

• Does Vitamin B6 Need a Warning Label? (WebMD)
• Emery Pharma's FDA citizen petition (Emery Pharma; PDF)