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VITAMIN A and BETA-CAROTENE and CARDIOVASCULAR DISEASE                            

Abstract: Research to date shows that Vitamin A in amounts up to about 5000 IU units used over periods of 7 or more years is an antioxidant that can reduce risk of heart disease about 30% for a added amount of about 3,000 IU per day.   Beta-carotene, the most popular source of Vitamin A in supplements is converted to Vitamin A by the body in variable amounts.  Life Ahead now assumes 3 IU of Beta carotene provides 1 IU of Vitamin A.  Because a typical US diet includes about 2,500 IU of Vitamin A,  use of a supplement of Vitamin A of about 3,000 IU or a supplement of Beta-carotene of 10,000 IU per day might be prudent.  But many diets included more than this 2,500 IU of Vitamin A, and the addition of a further Vitamin A supplement to these diets will produce little benefit.  Very high amounts of Beta Carotene in supplements appear to be harmful to CV disease. This is shown following.

Life Ahead credits modest benefits for Vitamin A from a total of food and supplements for amounts only up to 5,000 IU per day, and credits no benefits of the Vitamin for those that smoke cigarettes.  Higher amounts of Vitamin A than this are not useful and can be harmful.  Life Ahead also values Vitamin A as one of 4 antioxidants that in total have a limiting value.  Vitamin A has a lesser effect on heart disease than does the other antioxidant vitamins, modest supplement amounts might be helpful, but high amounts can be harmful.

Vitamin A designates a family of vitamins that are fat soluble. Retinol a most active agent of this family.  Caratenoids are Vitamins that are converted to Vitamin A by body chemistry.  Beta carotene is a carotenoid that is converted to Vitamin A efficiently and probably is the dietary factor and supplement most commonly taken by individuals. Values of agents related to Vitamin A can be quite confusing.   One basis is the retinol equivalent called the RE.  Most tables of Vitamin values in foods are expressed in IU units of Vitamin A.  One RE is 5 IU of vitamin A. But most research results are related to Beta-carotene values, and most users take Vitamin A as Beta-carotene. And values of Beta-carotene differ substantially from those of Vitamin A per se.  The conversion ratios from IU of Beta-carotene to IU equivalents in Vitamin A differ from various sources from 2 to 1 to up to 6 to 1. Further confusing is that values of Beta-carotene are sometimes expressed in mg. rather than IU.  1 mg of Beta-carotene equals about 1600 IU.  It has been stated that the body converts Beta-carotene to Vitamin A only in amounts needed. Life Ahead assumes as approximation a conversion value of 3 to 1 for Beta-carotene to Vitamin A for both research and user values. 

Table B following lists the results of studies found published in the health literature. 19 of the 20 comparisons in this observation study group showed a benefit for use of moderate amounts of Vitamin A equivalents averaging about 3,000 IU per day. 9 study comparisons in 7 studies valued the risk ratios of Vitamin A equivalents in blood. All studies of these studies showed a substantial benefit, with an average risk ratio of 0.58.   There were 12 other observation study values that averaged a 0.68 risk ratio. A meta analysis of 15 studies found a value of 0.78.  This 3000 per day of Vitamin A is the equivalent of about 9,000 IU of beta carotene.  There is much supporting information on the benefits of fruits and vegetables that derive much of their measured benefits  from included amounts of beta carotene and vitamin A. Considered overall, the research results today support a highly likely benefit for Vitamin A up to about 5,000 IU per day.

No useful data were found verifying the importance of Vitamin A duration.  But as an antioxidant it probably derives from the same biochemical processes as other antioxidants as Vitamin E that have verified effects of duration of us. This Life Ahead adopts a risk basis based on duration of use. The basis used is an estimate of 20 years for development of blood values and 10 years exposure prior to start of prospective studies. This conservative approach requires long time use of the vitamin for useful benefit.

The RDA or nutrition desired values for Vitamin A now are 5,000 IU for men and 4,000 IU for women.  These RDA values of Vitamin A are near unique because unlike RDA values of other antioxidants they do reflect a likely limit for the useful value of this nutrient.  Research has indicated that amount of vitamin A above 5,000 IU per day contribute to osteoporosis and weakening of bone health.   Thus this value should be a limiting value for healthful amounts of the nutrient, and this limit is observed in the Life Ahead program.

A major problem in the health valuation of Beta-carotene has been results from clinical studies that found not only no benefit but even a  likelihood of harm from excessive amounts of the Vitamin. These results are listed as Studies C1 through C4 in the Table B.  An evident problem in each of these studies was that they used enormous amounts of Beta-carotene, as several times more than the typical amounts used in either the observation studies or is considered via the RDA.  Studies C3 and C4 were for smokers, and smoking can erase the benefit of antioxidants.  Studies C1, C3 and C4 were done for much too short a duration to measure the effect of Vitamin A as an antioxidant.  But on balance they suggest that the excessive amounts of Vitamin A used may have been the key factor responsible for their failure to find benefit.  This is indicated from the lack of benefit found from Study C that studied the effect of duration for periods up to 11 years. Study C3 found the large amount of Vitamin A used was harmful with near statistical significance.  On balance it is felt that the results from these studies of very large amounts of Vitamin A are not pertinent to the value of Vitamin A in food plus moderate value supplements in the range of 5,000 IU equivalent or lower.  Life Ahead now credits no benefits from amounts above 5,000 IU of Vitamin A and 15,000 IU of beta carotene. Clinical studies really measure only a further advantage for adding supplement to a base population amount of a nutrient that already may or may n ot be obtaining sufficient overall antioxidant.  Such clinical studies have potential of measuring  much lower values for risk than do observation studies, and involve problems in measurement.

An approximate estimate of the risk ratio for Vitamin A and cardiovascular diseases is: where amt is IU of Vitamin A and yrs is years of exposure basis is:

           Risk Ratio =  exp ( -0.00030 * yrs * amt ^ ^0.5 )

For use with Beta Carotene at a 3/1 ratio to Vitamin A the formula is

          Risk Ratio = exp( -0.00017 * yrs * amt ^ ^0.5 )

Life Ahead does not value Vitamin A or Beta-carotene directly.  Rather it includes its contribution in combination with antioxidants with Vitamin C, E, and Selenium.  Vitamin A is valued at a lower contribution to antioxidant value than is Vitamin E.  A total dietary value of only up to 5,000 IU of Vitamin A is accepted in this total, and supplements of it are not credited with any value for those smoking cigarettes.  This is about the same amount that is suggested by the RDA.  See the Antioxidant Model.  Because most people will not obtain the desired 5,000 IU equivalent from their dietary foods, a Beta-carotene supplement of about 10,000 IU or a bit less will be a usually desirable for health-interested persons. Note these values and those of other supplements also are adjusted further for body weight and gender in Life Ahead's suggested targets.

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.

Life Ahead "Good" diet #2 includes 3600 IU, the "Poor" diet #3 includes 2200 IU of Vitamin A.  From this and results of various research studies it seems likely that rather few people today obtain enough Vitamin A from foods to meet the RDA values. Fruits and some vegetables, with carrots as of note are good sources of Vitamin A.  But the vitamin also is included in cereals and a very broad range of foods.

                                                                                            Table B

EFFECT of BETA-CAROTENE and VITAMIN A on HEART or CARDIOVASCULAR DISEASE