Eat the Rainbow: When More of a Good Thing Is Not Better

When Good Chemistry Becomes a Bad Assumption

Last week we explored the remarkable chemistry of whole foods, how the food matrix, preparation and even the microorganisms in our gut influence what our bodies ultimately receive. But that raises an interesting question. If we identify a phytochemical in colourful fruits or vegetables that helps protect our cells, why not extract it, concentrate it and put it into a pill? Surely ten times as much of something protective should provide ten times the protection. Well, that sounds reasonable enough, but biology has a rather interesting way of challenging what seems obvious. We have a multi-billion dollar industry very good at identifying individual bioactive compounds, isolating them and packaging them into supplements. What we have not always been as good at is understanding what happens when we deliver those compounds at concentrations far beyond what we would normally obtain from food. That is not as much an industry concern. The fact is that biological effects depend on dose, chemical environment and how our bodies absorb and metabolize them. More of a protective compound does not necessarily mean more protection. And in several cases, we have learned this the hard way.

The Experiment That Surprised Researchers

Beta-carotene is one of the carotenoids responsible for the orange and yellow colours in foods such as carrots, sweet potatoes and squash. Researchers had observed that people eating plenty of carotenoid-rich fruits and vegetables tended to have lower rates of certain cancers, particularly lung cancer. Beta-carotene appeared to be one of the promising protective compounds, so researchers decided to test whether giving people concentrated beta-carotene supplements would provide even greater protection. Two major randomized clinical trials involving more than 47,000 participants produced a rather disturbing surprise. In a Finnish study involving nearly 30,000 male smokers, those receiving 20 mg of beta-carotene daily experienced 18% more lung cancers than those not receiving it. A second study involving more than 18,000 smokers and asbestos-exposed individuals found 28% more lung cancers among those taking a combination of beta-carotene and vitamin A. Rather than preventing cancer, the concentrated supplements increased the risk in these high-risk populations. The findings were significant enough that the second trial was stopped early. Subsequent studies investigated what might explain these results. Laboratory and animal research demonstrated that at high concentrations, particularly in the oxidative environment created by cigarette smoke, beta-carotene undergoes chemical changes that interfere with normal cellular signalling and growth regulation. In other words, the chemistry of a compound associated with protective foods changed under conditions of concentrated supplementation and oxidative stress. The clinical trials established the increased risk; the experimental research provided possible explanations for why it occurred.

The lesson is not that carrots or other colourful vegetables are harmful. It is that isolating and concentrating a phytochemical from a healthy food will not guarantee the same protective effects as eating that food.

The Body Doesn't Work on a More-Is-Better Principle

Vitamin C offers another example of why concentration matters. At normal physiological levels, vitamin C acts as an antioxidant, helping protect our cells from oxidative damage. At sufficiently high concentrations and under particular chemical conditions, however, it also acts as a pro-oxidant, generating reactive molecules that damage cells. Sustained oxidative stress contributes to cellular damage and biological aging. Although ordinary oral vitamin C supplementation has not been shown to accelerate aging, the chemistry illustrates why increasing the concentration of a beneficial substance does not automatically increase its protective effects. Our bodies also regulate what they absorb and retain. At ordinary dietary intakes, approximately 70–90% of vitamin C is absorbed, but at oral doses above 1,000 mg, absorption falls below 50%, with much of the excess eliminated through urine. Other bioactive compounds have their own absorption limits, metabolic pathways and biological effects. Some are beneficial at particular concentrations but behave differently at much higher doses. And for many isolated phytochemicals, we simply do not have enough long-term human evidence to know what repeated high-dose supplementation does. This brings us back to the food matrix we discussed last week. In whole foods, phytochemicals arrive alongside fibre, vitamins, minerals and numerous other bioactive compounds, generally at concentrations very different from those found in supplements. Their interactions are naturally balanced to influence absorption, metabolism and biological activity. Removing one compound, concentrating it and swallowing it in a capsule is not the same biological experience as eating the whole food.

A Pill Has a Job. So Does Food.

There is an important distinction here. Supplements have a legitimate and sometimes essential role in healthcare. Vitamin D, for example, is important for people who require supplementation because of inadequate intake, limited sunlight exposure or particular medical circumstances. If your doctor has recommended or prescribed vitamin D, take it as directed. The same applies to iron for iron deficiency, folic acid around pregnancy and other supplements used to address identified nutritional needs. But taking a supplement to correct a deficiency is quite different from taking concentrated vitamins and phytochemicals in the hope that more will make us healthier. We spend considerable amounts of money on supplements, often treating them as a convenient way to check off our nutritional responsibilities. Yet swallowing a handful of isolated compounds does not recreate the complex chemistry of a colourful, varied diet, nor does it guarantee the health benefits associated with eating those foods. And that is where we return to the rainbow. We are not trying to collect the largest possible dose of a few protective chemicals. We are trying to build a way of eating that consistently delivers a diversity of phytochemicals and other nutrients, in the company of the many compounds naturally present in whole foods. Red tomatoes, orange carrots, leafy greens, purple berries, beans, herbs and spices all contribute something different. No single food does everything, and no single supplement replaces that diversity.

The real investment in health is not checking off a nutritional box with another pill. It is developing a food culture, your unique food culture, that delivers the remarkable variety of protective compounds found in whole foods, that is introducing yourself to 15 minutes that allow for you to also be eating the rainbow, day after day.

Principle References:

  1. Alpha-Tocopherol, Beta carotene cancer prevention study group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N. Engl. J. Med. 330(15), 1029–1035 (1994). https://doi.org/10.1056/NEJM199404143301501
  2. G.S. Omenn, G.E. Goodman, M.D. Thornquist, J. Balmes, M.R. Cullen, A. Glass et al., Effects of a combination of beta carotene and vitamin a on lung cancer and cardiovascular disease. N. Engl. J. Med. 334, 1150–1155 (1996). https://doi.org/10.1056/nejm199605023341802
  3. Liu C, Wang XD, Bronson RT, Smith DE, Krinsky NI, Russell RM. Effects of physiological versus pharmacological beta-carotene supplementation on cell proliferation and histopathological changes in the lungs of cigarette smoke-exposed ferrets. Carcinogenesis. 2000 Dec;21(12):2245-53. doi: 10.1093/carcin/21.12.2245. PMID: 11133814.
  4. Neuhouser ML, Patterson RE, Thornquist MD, Omenn GS, King IB, Goodman GE. Fruits and vegetables are associated with lower lung cancer risk only in the placebo arm of the beta-carotene and retinol efficacy trial (CARET). Cancer Epidemiol Biomarkers Prev. 2003 Apr;12(4):350-8. PMID: 12692110.
  5. Du J, Cullen JJ, Buettner GR. Ascorbic acid: chemistry, biology and the treatment of cancer. Biochim Biophys Acta. 2012 Dec;1826(2):443-57. doi: 10.1016/j.bbcan.2012.06.003. Epub 2012 Jun 20. PMID: 22728050; PMCID: PMC3608474.
  6. NIH Office of Dietary Supplements. Evidence on absorption, dose and elimination.
    Vitamin C - Health Professional Fact Sheet
  7. US Preventive Services Task Force (2022). Recommends against beta-carotene supplementation for cancer or cardiovascular disease prevention.
    Recommendation: Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer

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