Philosophical Society of Washington

Minutes of the 2041st Meeting

Speaker: Orville A. Levander, U.S. Department of Agriculture
Topic: “Dietary Oxidative Stress: Boon or Bane in Infection”

The President Mr. Ohlmacher called the 2041st meeting to order at 8:16 p.m. on March 3, 1995. The Recording Secretary read the minutes of the 2040th meeting and they were approved with a correction. The President then read a portion of the minutes of the 433rd meeting March 2, 1895.

The President introduced Mr. Orville A. Levander of the U.S. Department of Agriculture to discuss “Dietary Oxidative Stress: Boon or Bane in Infection”.

Mr. Levander began by observing that some infectious diseases seem to be making a comeback as apparently new pathogenic forms appear that are more resistant to commonly used drugs or possess greater virulence. Books describing this phenomenon such as Richard Preston's non-fiction “The Hot Zone” have raised public awareness of biosafety issues. New research indicates that there may be a relationship between these new forms of infectious disease and the trace mineral selenium in the diet. Mr. Levander's research has revealed some salubrious effects of selenium.

While selenium is more toxic than arsenic on a molar basis, there is also an absolute dietary requirement for it. Selenium is an integral component of at least 5 proteins and special genetic machinery exists to incorporate it. Its various mineral forms have a highly irregular distribution in soil. Some inland areas may have almost none, while some lowland alluvial areas may have sufficiently high concentrations to make plants growing there toxic. White muscle disease in sheep and cattle is caused by selenium deficiency. The so-called “alkali disease” with symptoms of characteristic hoof malformation is caused by selenium toxicity.

The U.S. recommended daily allowance for selenium is 50 micrograms per day, though it must be understood that it is difficult to determine a safe range of intake. Keshan disease is a selenium deficiency disease with a high incidence in that district of China and also in Szechwan. It is caused by an average daily intake of 7.7 micrograms per day for men 6.6 micrograms per day for women. The incidence of Keshan disease fell after 1970 when dietary supplements were introduced. However, other cofactor diseases such as influenza have also been implicated in the incidence of certain symptoms of this disease. One of the disease symptoms is cardiomyopathy in which incidental coxsackievirus infection had been implicated.

How is it that infection by a relatively benign virus in a host suffering from a trace mineral deficiency leads to a severe disease condition found only in the most virulent form of the virus and not otherwise associated with the deficiency alone? Does a non-virulent strain of the virus in a selenium deficient host convert to a virulent strain? Selenium deficient female mice do not recover as rapidly from the infection as non-deficient mice. Furthermore, after passage through deficient hosts the virus seems to retain its more virulent character even in non-deficient mice [1,2].

Two other experiments show similar effects. One experiment is based on the observation that older mice are more resistant to infection by the CVB3/20 coxsackievirus than younger mice. This effect is reversed with selenium deficiency. Older mice that are also selenium deficient are as susceptible to the virus as young mice. In this case also, the virus passing through a deficient host apparently causes a non-virulent virus to become virulent. In a second experiment, the mitogen response test of T-cell production and growth is depressed in patients taking fish oil with or without vitamin E.

These tests employ lard, special fish oil with vitamin E removed, selenium and vitamin E. The vitamin E prevents the deleterious formation of aliphatic hyperperoxides from the high concentrations of unsaturated fatty acids in the fish oil. Fish oil administered without vitamin E depletes the body's store of vitamin E and potentiates the heart damage observed with the virus infection. (Normal fish oil contains a small but sufficient amount of vitamin E to prevent these problems.)

Mr. Levander speculates that these effects seen with the coxsackievirus, a picornavirus or “small RNA virus”, may also hold true for other RNA viruses such as polio, influenza and HIV. It has been observed that during an epidemic as much as 1-2% of the viral genome may change in one year. One infected person may harbor viruses with more than 100 different point mutations. There may be regulatory or reproductive proteins used by these virus that contain selenium, so that with a selenium deficiency there are increased virus mutations.

[1] M.A. Beck, P.C. Kolbeck, Q. Shi, L.H. Rohr, V.C. Morris, and O.A. Levander, “Increased Virulence of a Human Enterovirus (Coxsackievirus B3) in Selenium-Deficient Mice”, J. Infectious Diseases 170, 351-357, 1994.
[2] M.A. Beck, P.C. Kolbeck, L.H. Rohr, Q. Shi, V.C. Morris, and O.A. Levander, “Vitamine E Deficiency Intensifies the Myocardial Injury of Coxsackievirus B3 Infection of Mice”, J. Nutr. 124, 345-358, 1994.

The President thanked the speaker on behalf of the Society. The President presented the name of one new member. The President then announced the speaker for the next meeting, recapitulated the parking statement, and adjourned the 2041st meeting at 9:33 p.m.


Respectfully submitted,
John S. Garavelli
Recording Secretary

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