In 1996, when I was 19, I landed my first research job as a summer student intern doing lung cancer epidemiology. In 1997, I got another internship doing research on micronutrients in a nutrition lab. At the time, I was a strong believer in the power of nutrition, vitamins, and all things natural to change the world. As it turned out, this was a very interesting time for research at the intersection of nutrition and lung cancer.

The 1970s, 1980s, and early 1990s had seen a series of very promising studies on the potential for beta-carotene (the provitamin our body converts to vitamin A) to prevent cancer–particularly lung cancer, the leading cause of cancer death.1 Notably, the research included:

  1. Molecular and cellular studies showing beta-carotene to be a powerful anti-oxidant with potent anti-inflammatory and anti-cancer properties.
  2. Animal studies showing the potential of beta-carotene to prevent cancer.
  3. Large observational studies of people showing that high levels of beta-carotene and high intake of beta-carotene in diet were correlated with lower cancer risk.

At the time, there were also news headlines along the lines of “studies show beta-carotene prevents cancer,” books pushing beta-carotene’s benefits, and plenty of supplements to boost your intake of beta-carotene. 

Question: So, why aren’t we all supplementing our diets with extra beta-carotene?

Answer: Despite all of the evidence and hype presented above, beta-carotene does not prevent lung cancer.

While the rest of the world may have been ready to take beta-carotene, several scientists saw the need to pursue large (thousands of people) double-blinded placebo-controlled randomized controlled trials to determine whether or not beta-carotene actually prevented cancer in people at high risk for lung cancer. I can still remember talking about these studies with my mentors. The results were truly shocking. 

The first two studies found beta-carotene supplementation significantly increased the risk of lung cancer among smokers.2, 3 Subsequent studies either confirmed these results or at best found to effect on cancer.4  

How could we have gotten things so wrong? What lessons can we learn here?

Key takeaways from this example:

  1. Unless we know that something is safe and effective in humans as a result of adequately-designed clinical trials, we don’t know that it is safe and effective. We will talk in later blogs about what makes a clinical trial adequate. Whenever possible, it should be large, randomized, blinded (meaning neither the researchers nor participants know what they are getting until the end of the trial), and with a placebo or other control group.
  2. Basic science (molecular, cellular and animal studies) and observational (correlational) studies should NOT be assumed to predict how a treatment will work in people. We will also go into these points in more depth in later blogs, but in a nutshell: a) People are not simply large mice or collections of cells. Basic science results need to be confirmed; and b) Correlation does not prove causation. In this example, it is possible that other factors (e.g. people who eat a lot of vegetables are also richer and see their doctors more) could explain the link between beta-carotene and cancer.
  3. Don’t get lost in hype. I italicized several words in this blog—anti-inflammatory, anti-oxidant, anti-cancer, prevents cancer—that should look familiar as they continue to show up in a lot of news stories, books and supplement packages. 
  4. Natural is not always safe. This is a point you can expect I’ll make in the future. Even before these studies were done, it was known that too much vitamin A (several times what you would get in your diet or a typical multi-vitamin) is toxic and could cause serious health effects including rash, abdominal pain, and even coma. Ironically, one of the most common cause of vitamin A toxicity is people taking megadoses of supplements for their health.

As a postscript: In doing research for this blog, I was surprised that there were still books by pseudo-experts pushing the benefits of beta-carotene. A quote from one of these books suggests that it protects “against HIV/AIDS, measles, malaria, cancer, diarrhea, blindness, and other life-threatening illness,” and that people were still selling and taking high doses of beta-carotene (mostly as a “natural tanning” supplement) and thus putting themselves at risk for vitamin A toxicity.

References:

1. Peto R, Doll R, Buckley JD, Sporn MB. Can dietary beta-carotene materially reduce human cancer rates? Nature 1981;290:201-208.

2. Alpha-Tocopherol BCCPSG. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994;330:1029-1035.

3. Omenn GS, Goodman GE, Thornquist MD, et al. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst 1996;88:1550-1559.

4. Goralczyk R. Beta-carotene and lung cancer in smokers: review of hypotheses and status of research. Nutr Cancer 2009;61:767-774.