Are vitamin and mineral deficiencies a major cancer risk?

Key Points

  • Acute deficiencies of vitamins and minerals are rare in developed countries, but suboptimal nutrient intake — less than the recommended daily allowance (RDA) — is a widespread problem. Research indicates that considerable metabolic damage can still occur when nutrient intake levels fall below the RDA — even though they might not cause acute disease.

  • Evidence indicates that deficiencies of iron and zinc, and the vitamins folate, B12, B6 and C, can cause DNA damage and lead to cancer.

  • New animal bioassays of nutritional deficiencies are needed, particularly for studying cancer.

  • Reduced folate intake has been associated with cancer. Folate, B6 and B12 deficiencies cause the incorporation of deoxyuracil into DNA, leading to DNA breakage, and could promote tumorigenesis.

  • The relationship of vitamin and mineral deficiencies and cancer is extremely complex. An integrated analysis of the findings from epidemiological, animal-model, metabolic and intervention studies, as well as from genetic polymorphism research, is required.

  • Approaches to eliminating micronutrient deficiencies include improving diet, fortifying foods and providing multivitamin and mineral supplements. Prevention strategies such as these could have a significant impact on cancer and public health, with minimal risk being involved.

Abstract

Diet is estimated to contribute to about one-third of preventable cancers — about the same amount as smoking. Inadequate intake of essential vitamins and minerals might explain the epidemiological findings that people who eat only small amounts of fruits and vegetables have an increased risk of developing cancer. Recent experimental evidence indicates that vitamin and mineral deficiencies can lead to DNA damage. Optimizing vitamin and mineral intake by encouraging dietary change, multivitamin and mineral supplements, and fortifying foods might therefore prevent cancer and other chronic diseases.

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Figure 1: Incorporation of uracil in DNA.

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Acknowledgements

This work was supported by grants from the National Foundation for Cancer Research, the US Department of Energy, the Wheeler Fund for the Biological Sciences at the University of California Berkeley, the Ellison Medical Foundation and the National Institute of Environmental Health Sciences Center. We thank L. Gold and J. Nides for their many useful comments.

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Correspondence to Bruce N. Ames.

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DATABASES

Cancer.gov

adult acute lymphoblastic leukaemia

brain cancer

breast cancer

cervical cancer

childhood acute lymphoblastic leukaemia

colorectal cancer

hepatic carcinoma

lung cancer

lymphoma

oesophageal cancer

oral cancer

pancreatic cancer

prostate cancer

stomach cancer

GenBank

HPV

LocusLink

catalase

haem oxygenase II

MTHFR

TP53

FURTHER INFORMATION

The International Bibliographic Information on Dietary Supplements (IBIDS):

Linus Pauling Institute Micronutrient Information Center

National Institute of Health Office of Dietary Supplements

Scientific evaluation of US dietary reference intakes

Glossary

DEFICIENCY

Dietary intake of a vitamin or mineral at a level that is less than 50% of the recommended daily allowance — as distinguished from acute deficiency. For example, acute vitamin C deficiency causes scurvy.

RECOMMENDED DAILY ALLOWANCE

(RDA). The dietary-intake level that is sufficient to meet the daily nutrient requirements of nearly all healthy individuals in a defined group.

CASE–CONTROL STUDY

An epidemiological study design in which individuals are selected based on the presence (case) or absence (control) of disease. Well-designed case–control studies require that the two groups are derived from the same population.

PROSPECTIVE COHORT STUDY

An epidemiological study design in which individuals with known characteristics (such as occupational exposure, smoking and exercise) are enrolled and followed over time for specific outcomes. The rate of cancer (or other disease) in the exposed population is compared to that in the unexposed population.

META-ANALYSIS

A retrospective analysis of the results from different studies, making certain assumptions, to reach a conclusion that is based on the pooled data.

CONFOUNDING FACTOR

These occur because behaviour-related variables of interest tend to cluster. An exposure (for example, vegetable consumption) might be of interest in protecting against a particular cancer. However, if smokers eat fewer vegetables than non-smokers, we might falsely attribute a risk reduction to vegetables that is really owing to the fact that a higher proportion of vegetable-eaters are non-smokers. Confounding factors can be controlled for by separating the smokers and the non-smokers and asking whether the vegetable–cancer association is seen in both groups, or by more sophisticated, but conceptually similar, statistical techniques.

INTERVENTION STUDY

Often called a clinical trial or experimental study, an epidemiological analysis of a hypothesized cause–effect relationship that is performed by modifying a supposed causal factor, such as lack of vitamin C consumption, in a population.

RECALL BIAS

Occurs in individuals that describe events (such as exposures, diseases and pregnancy outcome) of the past in a non-comparable manner. It is primarily a problem in case–control studies when that presence of the disease in one group might result in differential recall (for example, of alcohol consumption or dietary behaviour) between the cases and controls.

COMET ASSAY

A technique that uses electrophoresis of immobilized single cells to measure DNA strand breaks.

PACK YEARS

The number of years of tobacco use, multiplied by the number of packs per day. For example, 1 pack year is 20 cigarettes per day for 1 year, 40 cigarettes per day equals 2 pack years.

HAEMOCHROMATOSIS

A genetic disorder and the most common form of iron overload disease, which is characterized by iron deposition in the liver and other tissues as a result of a small increase in intestinal iron absorption over many years. It most often affects white northern Europeans: 1 in 8–12 is a carrier of the abnormal gene, and men are five times more likely to be diagnosed with haemochromotosis than women.

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Ames, B., Wakimoto, P. Are vitamin and mineral deficiencies a major cancer risk?. Nat Rev Cancer 2, 694–704 (2002). https://doi.org/10.1038/nrc886

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