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      VITAMIN A, BETA-CAROTENE & CANCER

Abstract:  Vitamin A used in amounts of about 5,000 IU appears usually to reduce the risk of most causes of cancer by about 34%.  This result is derived from a total of 46 comparisons from 34 studies.  A listing of results of this research follows.  A similar risk benefit was found for seven types of cancer, and this benefit may apply to all cancer. Beta Carotene is taken in the analysis as 3 IU equivalent for 1 IU of Vitamin A.   But Vitamin A in amounts of above about 5,000 IU appears to be harmful, users should not take more that this amount or of its equivalent of 15,000 IU of Beta-carotene.  Most research was for diet amounts, and typical diets include 2,500 IU of Vitamin A. Thus diet supplements of Vitamin A may have marginal benefit for those who have good dietary habits. and will produce minimal or no benefit for diet amounts much above 4,000 IU. 

See other papers of antioxidants and CV disease for Vitamin E;  Vitamin A;  Vitamin C; and Selenium ;papers of antioxidants and cancer for Vitamin E;  Vitamin C; and Selenium. and Antioxidants, Death from All Causes and Antioxidants, a Global Analysis.

As described more completely for Vitamin A and Coronary Heart disease, Vitamin A designates a family of vitamins that are fat soluble. Most tables of vitamin values in foods are expressed in IU units of Vitamin A.  But most research is based on values of Beta-carotene, and most users take Vitamin A supplements as Beta-carotene. The body converts Beta-carotene to Vitamin A.  But it is claimed by some experts that the body converts Beta-carotene to Vitamin A only in amounts needed.  Typical conversion ratios from IU of Beta-carotene to IU equivalents in Vitamin A vary widely, and typically from from 1 to 2 to up to 1 to 6.  Life Ahead assumes a conversion value of 3 Beta-carotene to 1 Vitamin A for both the research results in Table A following and for user values in the program.  But it should be kept mind that Life Ahead values Beta Carotene IU's from supplements as of only 1/3rd the value of IU's of Vitamin A cited in usual tables food nutrient values. Values of Beta-carotene are sometimes expressed in mg, and 1 mg of Beta-carotene equals about 1600 IU of Beta-carotene.

The observation study research results found for Vitamin A and Beta-Carotene are summarized in Table B appended.  Differences in amounts of vitamin used are expressed in IU's of Vitamin A.  30 of 34 observation study measurements or about 90% of risk measurements showed a benefit.  An average risk measured for those taking Vitamin A from all 34 observation studies is 0.66. or a reduction in risk of 34%.  Three studies of risk for measurements of Vitamin A in blood averaged only 0.42 for a 58% reduction in risk.   These results were consistent for types of cancer as breast cancer 0.66 from 8 comparisons, 0.75 from 7 ovarian and cervical studies; and 0.66 for 9 comparisons of lung cancer.  See Table A for a summary of these results. An average risk value could be about 0.66 for a difference of about 4000 IU of Vitamin A. 

A concern is noted for the results from the large Physicians study.  This group that probably used a more healthful diet than usual probably were using reasonably adequate Vitamin A in diets, and this may be why the substantial supplement addition did not contribute. Life Ahead now would compute little advantage for taking Vitamin A supplements for those having much above 3000 IU in their diets.  Because nearly any antioxidant cause of cancer will be duration dependent a typical duration of use in the research to date probably was about 10  years.  This is an insufficient time for full potential benefit from an antioxidant to develop.

The results of the clinical studies show no beneft of vitamin A on risk of cancer  In fact, an average risk from 18 different measurememts of risk on various cancer causes showed negative benefit of 1.12.   A number of these clinical results on presumab ly healthy people were obtained on smokers in Finland in a single large study.  Antioxidants do not benefit smokers.   The short duration of the clinical studies could have been factor, and the Physicians in RA2 as before probably were getting enough Vitamin A in their diets.  As for the results of Vitamin A on heart disease, a possible reason for this lack of measured benefit is that use of the very high amounts of Vitamin A used in these studies that averaged 3 times the maximum levels used in the observation studies became counter-productive.  Observation study BC1 of Hunter comfirmed directly the much higher risks for use of very large amounts of vitamin A.  The amounts of Vitamin A used in these clinical studies of an average 12,000 equivalent IU for vitamin A are far above the 4-5,000 maximum for the RDA, and above the 5,000 IU level that can provide other health negatives such as bone loss. 

Data confirming this hypothesis comes from information in Hunter's large study BC1. Adding supplements of Vitamin A for those participants that had very low Vitamin A from food provided a benefit.  But supplements added to those having higher amounts of Vitamin A in in food provided no further benefit.  A maximum value of Beta-carotene benefit appears obtained at about 15,000 IU, or the equivalent of 5,000 IU of preformed Vitamin A as used herein. Risks for a total of Vitamin A beyond 10,000 IU actually reversed to higher values in this table of results.  This same maximum amount of Vitamin A also appeared indicated useful for heart disease.  The research to date shows that use of the very large amounts of Beta-carotene employed in the clinical studies probably not only was of no value but produced reverse or negative health benefit.

Life Ahead now values Vitamin A for both heart disease and cancer only for amounts up a total of 5,000 IU equivalent of preformed Vitamin A (or 15,000 IU of Beta-carotene) in a total of food plus supplements.  It thus provides a value for a Beta-carotene or Vitamin A supplement only when amounts in food are deficient vs. the present RDA values.  Again, Life Ahead values Vitamin A as one of 4 antioxidants, and will give no credit to any further amount of any of these antioxidants when a total limiting value of all antioxidants is attained.  As a general guide, vitamin supplements of Vitamin A or Beta-carotene may not produce much benefit in reducing risk of cancer because diet can supply much of the amount needed for best benefit.

Life Ahead values vitamin A and cancer as dependent on years of exposure as is done for other antioxidants. Study BC1 confirms the time related effect of vitamin A on cancer.  A formula derived for exposure and years of use with maximum value for Vitamin A of 5,000 IU is:

  Risk ratio of Vitamin A and cancer, with yrs of exposure to vitamin or its supplements and amt as amount of Vitamin A in IU

    risk ratio = exp( - 0.00038 * yrs * amt ^ ^0.5 )           

  For use of beta carotene, at 3 units per unit of vitamin A  and maximum 15,000 IU this becomes         

   risk ratio - exp ( - 0.00022 * yrs * amt ^^0.5 )

                                                                                          Table B

EFFECT of VITAMIN A and BETA-CAROTENE on CANCER