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Nutrition and AIDS: An interview with Dr. Marianna Baum
Part II: Selenium levels make the difference
(New HIV subtype posses significant new risk for heterosexuals)
Richard A. Passwater, Ph.D.
Last month, Dr. Marianna Baum and I discussed the relationships between HIV infection, nutritional status and immune function in HIV-positive persons and AIDS patients.
This month, we will discuss a grave new danger from new forms of the HIV virus that causes AIDS. These new forms of HIV are readily transmitted heterosexually and progress to AIDS more rapidly. The present drugs, which are not especially effective anyway, may not be as effective against the newer strains. Dr. Baum’s research indicates that the trace mineral selenium is the most important nutrients against HIV.
Dr. Baum’s research group is currently preparing several reports on selenium and AIDS and malnutrition and AIDS. She is a Professor and Chief of the Nutrition Division of the Department of Epidemiology and Public Health of the University of Miami School of Medicine. She holds the Foggarty International training grant relating to AIDS for Latin America and the Caribbean. Her current research team includes 12 researchers from various countries. Her group is presenting reports on the HIV situation in their own countries as well as basic AIDS research.
Passwater: You delivered an important report at the International Symposium on Human Viral Diseases in Nonnweiler, Germany on April 21. What was your Atake home@ message?
Baum: I reported on the selenium status in HIV-infected individuals and its effect on disease progression and mortality. We have looked at selenium status in three cohorts. A cohort is a group of people who have something in common when they are first assembled and who are then observed for a period of time to see what happens to them. We studied not only adults -- in cohorts of HIV-infected homosexual men and HIV-infected drug abusers -- but also HIV-infected children. We found that children actually had the highest prevalence of selenium deficiency. People don’t often think of children as having AIDS, but there are over a million children worldwide suffering with AIDS. In all three cohorts, there was an association with some immune function markers and the deficiency of selenium.
Passwater: Then it seems that selenium status may be central to the development of AIDS. Do HIV-infected persons lose their selenium stores as the disease progresses with time? Is oxidative stress consuming the body’s antioxidant stores or is the HIV virus using up the selenium? Just what is going on with selenium status?
Baum: What our data that we have published show is that as the disease progresses the prevalence of selenium deficiency increases. It is not possible to tell at this time whether it is the disease progression that causes the selenium deficiency or whether a selenium deficiency causes the disease progression. This is because the studies that we have completed so far have been observational studies and both changes are occurring at the same time.
As you know, we now have clinical intervention studies underway using selenium supplements. There were some studies reported in which the patients were given selenium supplements. In those studies, the patients receiving selenium supplements had fewer hospitalizations and a better quality of life, but there was no report on the effect of selenium supplementation on immune status markers or
Of course, we will be looking to see if selenium affects the host or the virus or both. We find the research of Dr. Will Taylor, that you reported in your November 1994 interview very interesting.
Passwater: Great! Let’s review Dr. Taylor’s observations briefly. He has found evidence for new genes in HIV that contain codons that can specify selenocysteine. He suggests that selenium may be a Aswitch@ that can act as a braking mechanism that limits the replication of the virus. If there is adequate selenium present, then the brake is on HIV replication. But, if there is a deficiency of selenium, then the virus replicates and invades other cells looking for more selenium.
Baum: Yes, according to Dr. Taylor’s theory, for which he now has some in vitro evidence, the virus may make several selenium-containing proteins. HIV could use these to monitor host antioxidant status, and to respond to oxidative stress in various ways. If selenium is deficient, then the virus multiplies more freely than if selenium is present in normal amounts. So, according to this theory, the individuals who have low levels of selenium, theoretically, should have a high HIV viral load. We have just been funded by the National Institutes of Health to look into this.
We will be measuring the viral loads of all our HIV-infected persons and then comparing their viral loads to their blood selenium levels. Our hypothesis, based on Dr. Taylor’s research, is that the viral load is going to be significantly higher in selenium-deficient individuals. The data should be obtained by the end of this summer.
Passwater: Fortunately, we are able to directly monitor HIV particles as viral load now instead of having to use less precise indirect measurements of immune system parameters such as CD4 or other surrogate molecules. Since your April report and since your selenium supplementation studies started, a French group (Delmas-Beauvieux et al., Am. J. Clin. Nutr. July 1996) has published that selenium supplements significantly increase glutathione levels in HIV-infected persons. This research group from the University of Bordeaux has also recently published in letter form that serum selenium levels predict the outcome in HIV-infected persons.
Baum: Yes, they obtained good results using 100 micrograms of selenium as selenomethionine. We are using 200 micrograms of selenium as selenomethionine and will soon be publishing our results on blood selenium levels as a predictor of mortality.
Passwater: If an HIV-infected individual becomes selenium deficient would you expect that to worsen the secondary effects such as cardiomyopathy (damage to the heart) of AIDS?
Baum: Yes. We are just completing a study with HIV-infected children that was designed to investigate this question. The reason we looked at selenium was that a few years ago, about 1991 I believe, there was a report that showed that selenium deficiency occurs in Keshan disease, which appears to involve a viral infection as a cofactor, and Coxsackie virus infection and it causes cardiomyopathy. We selected children who had cardiac problems and measured their blood levels of selenium. One third of them had very low levels of selenium and we are in the process of analyzing the data right now.
Passwater: In Part I, we mainly discussed your research with malnutrition in general, and the B-complex vitamins in specific, in regards to AIDS. In Part II, we have been discussing the importance of selenium. Are most of your current studies looking at selenium alone, all antioxidants or total nutrition and AIDS?
Baum: Our approach has been to measure the nutritional status of all of the micronutrients. Then we determine what is the prevalence of the deficiencies in the various cohorts. Interestingly, the deficiency patterns are different in the different cohorts. In homosexual men, we see deficiency of vitamin B-12, B-6, and zinc. In HIV-positive drug users, we see mainly deficiencies of antioxidants. In spite of them consuming three-to-four times the RDA. For example, with vitamin A, 60 percent of them have vitamin A deficiency. Truly an interesting phenomenon. I think that the drug abusers may have a higher requirement for antioxidants than non-users of illicit drugs.
Passwater: Interesting indeed. Do you have an explanation?
Baum: We know that it is not the use of the drugs themselves affecting immunity. As an example, cocaine use has never been shown to significantly affect immunity.
Passwater: A few have speculated that drug use and/or poor nutritional habits among male homosexuals might be risk co-factors in HIV-infection.
Baum: My experience has been that the homosexual men under our study and treatment have been superbly nourished compared to the general population. They had excellent diets and on top of this, about 85 percent take dietary supplements.
Passwater: At the International Symposium on Human Viral Diseases in Nonnweiler, Germany in April, you were one of only 16 invited presenters. Other speakers included past guests of this column, Drs. Luc Montagnier, Gerhard Schrauzer and Will Taylor, as well as future interviewee, Dr. Orville Levander. What other reports were given there that may be of interest to our readers?
Baum: Well, Drs. Orville Levander and Melinda Beck reported on their continuing research and how selenium deficiencies in a person can facilitate the conversion of rather harmless viruses to mutate into viruses that are especially harmful even to healthy persons. This may be why influenza epidemics such as the Hong-Kong flu or swine flu originate in the selenium-deficient regions of Asia, and deadly viruses such as HIV and Ebola originate in the selenium-deficient regions of Africa.
Passwater: I have known Dr. Levander since 1970 when we were both researching selenium in nearby laboratories in Maryland. He will be discussing this research and its implications in this column in the very near future. Any other important reports?
Baum: Our readers may also be interested in the report by Dr. Esteban Domingo of the University of Madrid in Spain. Dr. Domingo studies viruses and their mutation rate. His premise was that the healthier the person is, the more the viruses mutate. He characterized viruses and their mutation rates as Aclouds@ somewhat in the manner that we depict electrons orbitals as clouds of probability. The viruses don’t exist in a host as one specific form, but since they are continuously mutating, they are present in various forms simultaneously. The greater the varieties of forms present, the larger the Acloud@ representing these forms. According to Dr. Domingo, the healthier the person is, the more mutated the virus is. A healthy person with a strong immune defense forces the virus to keep mutating probably as an attempt to find a weak link in the immune response. The fewer defenses a person has, the smaller the Acloud@ of viruses formed.
Passwater: The rapidity of viral mutations keeps everyone guessing what influenza strains will appear which makes it difficult to produce an appropriate Aflu shot.@ HIV mutates so rapidly that so far it has been impractical to design a vaccine against it. HIV is an especially fast Amoving target@ for our immune systems to hit. That’s also why no drug has been able to subdue it for more than a two or three months. Dr. Domingo’s description and observations are interesting. They remind me of Dr. Robin Weiss’ comments that most lentiviruses are notoriously variable in genome sequence, and that within a single infected host, millions of genetic subtypes exist. Weiss called these swarms of related but non-identical genomes Aviral quasispecies. The term Apopulation polymorphism@ has also been used.
Dr. Domingo’s point is well taken though. HIV subtypes are becoming a great concern. Virologists, serologists, immunologists, and geneticists are adding a lot of important understanding to what is going on, but their discipline-specific nomenclature is making it difficult for scientists in other disciplines to follow. We are wading through HIV groups AM@ and AO,@ plus HIV subtypes AA@ through AF.@
As I understand it, our immune systems drive the HIV to escape by changing the ENV area of the viral genome which encodes the C2 to the V5 regions in glycoprotein gp120. It seems that two systems are in use -- that of the geneticists and that of the serologists. The world of serology uses antibodies to recognize antigens. They can only infer what genes are present in the virus. Geneticists identify the genes of the virus. They know what the virus is capable of expressing, but they are uncertain whether or not it is expressed. A genotype is the set of genes a virus or other organism has for a particular characteristic. A phenotype is the expressed characteristic. Does a change in phenotype mean a change has occurred in the genotype? Maybe, but not necessarily. Thus, when we speak of HIV mutation, I have several thoughts. Is the genetic variation important to pathogenesis? Do HIV mutants differ in virulence or transmission route?
Let’s review the point of HIV subtypes for our readers and ignore the serologists classification of serotype groups AM@ which is common and AO@ which is rare. When we talk about HIV subtypes, we are not talking about the differences between HIV-1 and HIV-2. HIV-1 is the strain that we are most familiar within the U. S., Western Europe, Central America and Haiti. HIV-2 is found in West Africa and sporadically in Europe and parts of South America. Although HIV-1 and HIV-2 have no great resemblance to each other as they differ considerably in genomic structure and antigenicity, both types cause similar clinical syndromes.
Baum: HIV-2 doesn’t cause as much disease and if people have HIV-2 first it is protective, that is, they are less likely to get HIV-1. What we are researching are subtypes of HIV-1. Subtypes AA@ through AF@ of HIV have now been identified. Various countries have different subtypes of HIV-1. The sequence of the viral envelop is different. Yes, as Dr. Domingo pointed out, single nucleotide or amino acid replacements can lead to important phenotypic changes (increased virulence, escape from neutralization by antibodies or from cytotoxic cell responses, etc.). The quasispecies genetic organization of RNA viruses is relevant to viral pathogenesis as well as to viral adaptability and long-term evolution.
In the U. S., Latin America and Caribbean, the HIV subtype so far has been confined to subtype AB.@ In Africa the subtype is AC.@ Initially Thailand also had subtype AB,@ but now, subtypes AD@ and AE@ are prevalent in Thailand. Not only are these subtypes transmitted heterosexually more easily, but they are more aggressive strains and causes a faster disease progression. They now have two new AIDS epidemics, and they are worse than the HIV-1 subtype AB@ epidemic.
Passwater: Wow! That is worrisome. If in the U. S. the AIDS epidemic has been confined principally to drug abusers and male homosexuals, and we have been able to slow the epidemic with education and other effective preventive programs, what will happen when a new HIV subtype that evades our defenses by having a different transmission route is brought here or the subtype AB@ naturally mutates? What will happen in the U.S. if a subtype that is readily transmitted heterosexually and does its damage more quickly gets a foothold?
Baum: This is precisely what we are working on and this is why the National Institutes of Health (NIH) is funding our research in Honduras. We are doing a study of the various HIV subtypes in Honduras. As we have discussed, in the United States, we have subtype AB@ of HIV which is transmitted primarily homosexually or blood-to blood. The epidemic in Central America seems to be different. It is an heterosexual epidemic. Preliminary studies by the Centers for Disease Control and the World Health Organization showed that they are a different kind of HIV that has mutated. We, together with Harvard, were funded by NIH to further investigate the subtype of HIV in Honduras. We have already found that at least 20 percent of the samples that we have analyzed are of a subtype of HIV that is much more easily transmitted heterosexually than the subtype that we have here.
In addition to looking at the subtypes of HIV, we are drawing blood samples from these individuals and examining their nutritional status with particular attention to their selenium levels. We hope to be able to follow the progress of their disease. They are of particular scientific interest because people in developing countries tend to have greater nutritional deficiencies which may speed the disease progress. In addition, they don’t have access to medication, correcting nutritional status may be the main way that we can slow down the disease progression.
Passwater: Is this a question of Awhen@ rather than Aif?@
Baum: At least one of the subtypes is here already! It is in the U. S. It has already been published that servicemen who served in Africa and the Far East have been infected with at least one of the subtypes. It just has not yet been documented by the CDC.
Passwater: Dr. Baum, you are not giving us much good news. Fortunately your research on selenium provides us with positive information and great hope. Your research also reminds me of Dr. Levander’s comment that we are our brother’s keeper. If we don’t help our fellow man, then viral mutants will be created that we can’t handle and these viral mutants may wipe us all out, even the very healthy and well-nourished.
Baum: Exactly. It also means that people just can’t go out and have indiscriminant sex without proper protection.
Passwater: Well, let’s leave that problem and go back to the International Virus Symposium. I agree that Dr. Domingo’s report is certainly significant to the AIDS and other virus problems. What other reports were of particular interest?
Baum: Dr. Jian-Cun Hou of Beijing, China reported that selenium supplements reduced the mortality from epidemic hemorrhagic fever from 100 percent to only 37 percent within nine days.
Passwater: This certainly was an informative conference. Could there be any other report of major interest?
Baum: Several. Dr. Shu-Yu Yu also of Beijing, China reported that selenium supplementation reduced liver cancer incidence by 35 percent in a population of 130,000 in Qidong county.
Dr. Will Taylor of the University of Georgia reported on his continuing research that you discussed in November 1994. He has now found that there is a glutathione peroxidase gene in Coxsackie viruses, which, as in the cases of ebola and HIV, may help explain why selenium is protective against these viruses.
Dr. Luc Montagnier of the Pasteur Institute reported on the role of oxidative stress in HIV infection and AIDS, and Dr. Gerhard Schrauzer of the Biological Trace Element Research Institute in San Diego, continued to present evidence to support his premise using animal models, that selenium deficiency may be a cofactor in human breast cancer.
Passwater: Our long-term readers may be familiar with the latter researchers as they have discussed their research with us in previous columns. It is exciting to see that their research is now leading other scientists into productive research with great potential benefit. Thank you Dr. Baum for chatting with us about your research and bringing us up-to-date on the research of our colleagues.
© 1996 Whole Foods Magazine and Richard A. Passwater, Ph.D.
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