Negative vitamin C studies often flawed

Many vitamin studies that report negative findings have design flaws, according to new research from the Linus Pauling Institute at Oregon State University (Nutrients. 2013 Dec 16;5(12):5161-92. DOI: 10.3390/nu5125161).

While  Oregon State University's press release said most large, clinical trials of all vitamin supplements are flawed, Alexander Michels, research associate, and  Balz Frei, professor and director of the Linus Pauling Institute, specifically looked at vitamin C (ascorbic acid) and found flawed approaches to study design, often due to misunderstanding its "redox chemistry and biology."

They said the primary issues they saw with human cell studies revolve around a culture media that is highly oxygenated, leading to damage of the vitamin C before it can realize its full effect on the cells.

In animal studies, the research is limited because most animals, including mice, make their own vitamin C, so it is not a true "vitamin" to them. Michels and Frei acknowledged some mice have been genetically altered so that they don't make vitamin C, but they argured this model still doesn't mimic how vitamin C affects humans. Because these animals don't need to obtain vitamin C from their diets, it's expected that their uptake of this nutrient would be poor.

Even though randomized controlled trials (RCTs) are considered the gold standard for drugand supplementstudies, the researchers also questioned the veracity of vitamin C RCT results. "RCT study designs have serious limitations and pitfalls, and require careful scrutiny to avoid misinterpretation of results and erroneous conclusions," they wrote.

Michels and Frei argued the drive to establish correlations or show a treatment effect in RCTs often overlooks cofounders that could affect results. They said many vitamin C supplementation studies look at the vitamin as part of combination with other antioxidant vitamins, such as vitamin E and beta-carotene, which would cloud results from vitamin C alone. Plus, Michels and Frei said vitamin C status is often not measured at the start of the study or after supplementation, so it's unclear how much the subjects absorbed into their tissues.

Lastly, Michels and Frei argued that most of the RCTs conducted in humans use healthy, usually medical professional, populations, who are not likely to have a reduced vitamin C level.  They said study subjects should have low plasma vitamin C levels at baseline to increase the likelihood of changes after vitamin C supplementation.

"Understanding the study population, limitations of study design and the nuances of the ascorbic acid chemistry is necessary to avoid many of these pitfalls and artifacts," Michels and Frei wrote.

While not in the actual study, the press release quoted Frei as saying studies that try to study nutrients like prescription drugs leads to conclusions with little scientific meaning.

I started this blog by saying it was good news, but that's not really true. It's bitter sweet news. Sure, it's good that studies that show vitamin C's ineffectiveness may not due to the supplementation, but studies conducted on vitamins with good designs would be the real good news.

With the changing nature of food and plant materialswhich is what these nutrients areand with studies humans that live in the real world, creating a well-designed RCT has proven to be a uphill climb.

This is an accent that will continue in 2014 and beyond. But I am happy some researchers are willing to start the hike.