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NUTRITIONAL THERAPY FOR THE TREATMENT AND
PREVENTION OF AIDS: SCIENTIFIC BASES
Lecture presented to the Ministers of Health of Angola, Botswana,
Democratic Republic of Congo, Lesotho, Malawi, Mauritius,
Mozambique, Namibia, Seychelles, South Africa, Swaziland, Tanzania,
Zambia, and Zimbabwe (Southern African Development Community SADC), Johannesburg, South Africa, January 20-21, 2003
By Roberto Giraldo1
CONTENTS
1. Nutritional immunology.
2. Nutritional deficiencies and HIV/AIDS.
3. Nutritional deficiencies and the progression of HIV-positive individuals to AIDS.
4. Nutritional deficiencies and the “transmission” of HIV/AIDS.
5. Reactivity on tests for HIV in sub-Saharan Africa not explained by sexual or
vertical transmission.
6. Oxidative stress and HIV/AIDS.
7. Nutritional and antioxidant deficiencies in the pathogenesis of AIDS.
8. Nutritional and antioxidant therapy for the prevention and treatment of AIDS.
9. Conclusions.
10. References.
1. NUTRITIONAL IMMUNOLOGY.
The effects of malnutrition on lymphoid organs were first described during the
middle of the 19th century (1). Lymphoid tissues are particularly vulnerable to the
damaging effects of malnutrition, and lymphoid atrophy is a prominent feature in
nutritional deprivation (2-5). Cell division is a very singular characteristic of the
functioning of immunocompetent cells. All types of immune cells and their products,
such as interleukins, interferons, and complement, are known to depend on
metabolic pathways that employ various nutrients as critical co-factors for their
actions and activities (5,6). Most of the host defense mechanisms are altered in
protein caloric malnutrition (PCM), as well as during deficiencies of trace elements
and vitamins (2,4,7,8).
Patients with PCM have impaired delayed cutaneous hypersensitivity, poor
lymphocyte proliferation response to mitogens, lower synthesis of lymphocyte DNA,
reduced number of rosetting T lymphocytes, impaired maturation of lymphocytes
1
Physician, specialist in internal medicine, infectious and tropical diseases. New
York. E-mail: [email protected] Website: www.robertogiraldo.com
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seen through an increased deoxynucleotidyl transferasa activity, decreased serum
thymic factor, fewer CD4+ cells, decreased CD4+/CD8+ ratio, impaired production
of interferon gamma and interleukin 2, altered complement activity (especially
reduction of C3, C5, factor B and total hemolytic activity), poor secondary antibody
response to certain antigens, reduced antibody affinity, impaired secretory
immunoglobulin A response, decreased antibody affinity, and phagocyte
dysfunction (2-7).
Human malnutrition is usually a composite syndrome of multiple nutrient
deficiencies. However, isolated micronutrient deficiencies do happen. Vitamin A
deficiency results in reduction in the weight of the thymus, decreased lymphocyte
proliferation, impaired natural killer cell and macrophage activities, and increased
bacterial adherence to epithelial cells (8-11). Vitamin B6 deficiency produces failure
of several components of both cell-mediated and humoral immune responses (2,4,7).
Vitamin C deficiency impairs phagocytosis and cell-mediated immune reactions
(12). Vitamin E deficiency also alters immune responsiveness (2,4,7). Zinc deficiency
generates lymphoid atrophy, reduces lymphocyte responses and skin delayed
hypersensitivity (2,4,7). Copper and selenium deficiencies impair T and B
lymphocyte functions (2,4,7). Dietary deficiencies of selected amino acids such as
glutamine and arginine also alter immunity (2,4,7).
Beta-carotene is a provitamin A carotenoid that may enhance T-cell and B-cell
immune function, possibly through conversion to vitamin A or by acting as an
antioxidant (13,14). Daily supplementation of beta-carotene among elderly
volunteers has led to an increase of T-lymphocytes and cells with interleukin-2
receptors (13). Furthermore, supplementation with beta-carotene or vitamin A is
associated with enhanced cellular immunity in both humans and animals (13,15-17).
In addition, vitamin A enhances humoral immunity, demonstrated by antibody
response to tetanus (18) and measles (19) antigens.
Supplementation with vitamin E in healthy elderly people significantly improved
lymphocyte proliferation, IL-2 production, DTH, and response to T-cell-dependent
vaccines, and reduced the incidence of infections (20,21).
Vitamin C is an antioxidant that plays a role in immune responses and the
formation of connective tissues. Proliferation of T and B lymphocytes increased
following supplementation with vitamin C (22), and increased levels of vitamin C
have been associated with lower rate of infections (23).
Several B-complex vitamins have roles in immune functions. Vitamin B6 deficiency
in healthy elderly individuals significantly reduced the total number of lymphocytes,
lymphocyte proliferation, and IL-2 production in response to mitogens; these
defects were corrected following B6 repletion (24). Riboflavin deficiency has been
shown to impair the ability to generate antibodies (25). Clinical studies show that
individuals with low serum vitamin B12 had impaired neutrophil function, while
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animal studies indicate that vitamin B12 supplements are associated with enhanced
humoral and cellular immune responses (25).
Selenium is necessary for the proper functioning of the enzyme glutathione
peroxidase, which acts as an antioxidant (26). Selenium deficiency is associated with
impaired phagocytosis, decresed CD4 T-lymphocytes, and the occurrence of
opportunistic infections (26). Selenium supplementation as parenteral nutrition
improved immune response in patients with chronic gut failure (27).
Zinc plays an important role in the growth, development, and function of natural
killer cells, macrophages, neutrophils, and T and B lymphocytes (28). Zinc
supplementation has resulted in significant reductions in the severity of diarrhea,
malaria, and acute respiratory infections among children (29).
Intrauterine malnutrition causes prolonged, even permanent, depression of
immunity in offspring (30,31).
Considerable data implicate excess lipid intake in the impairment of immune
responses (32). The potential for free radical damage is dependent in large part on
the level of potentially oxidizable fatty acids, mainly polyunsaturated fatty acids
(PUFAs) in the diet (32). High levels of dietary PUFAs have been shown to be
immunodepressive. Dietary fats may undergo free radical-mediated oxidation prior
to ingestion, as can occur when foods are fried (32). Animals fed oxidized lipids
show marked atrophy of the thymus and T lymphocyte dysfunctions (32).
At the molecular level, the damage to immunocompetent cells by several nutritional
deficiencies (PCM, Vitamin A, Vitamin C, Vitamin E, zinc, copper, zelenium
deficiencies) is caused by increased free radicals through oxidative stress (811,32,33).
2. NUTRITIONAL DEFICIENCIES AND HIV/AIDS.
Since the beginning of the AIDS epidemic, researchers have provided scientific
evidence that supports the possibility that AIDS can be effectively prevented,
treated, and overcome by guaranteeing an optimal nutritional status to the
individual or the patient (34,35). However, it seems that propaganda spread by
pharmaceutical companies to commercialize antiretroviral medications has
prevented these ideas from being widely accepted, despite the toxicity of these
medications.
Early in the AIDS era, well recognized researchers in the field of nutrition and
immunology, such as Dr. Ranjit Kumar Chandra, noticed that: “There is an
uncanny similarity between the immunological findings in nutritional deficiencies
and those seen in acquired immunodeficiency syndrome, AIDS” (34).
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“There is a similarity between the immune deficiency, multiple infections, and
severe weigh loss seen in AIDS patients, and the association of protein caloric
malnutrition (PCM) with reduced resistance to infection observed in malnourished
children, particularly in the Third World.” “It is also possible that nutritional
deficiency may play a significant role in the clinical course of the immunodeficient
state.” “These similarities between AIDS and PCM suggest that nutrition may
contribute to the immunodeficient state. The immunodeficiency in children with
PCM can be reversed by nutritional rehabilitation, which suggests that restoration
of nutritional state may be a useful adjunct to therapy for AIDS patients” (36).
As described above, the immunological alterations found in PCM are practically
identical to those of AIDS; impaired delayed cutaneous hypersensitivity, lymphocyte
proliferation response to mitogens, complement activity and secondary response to
antigens. There is also a reduced number of rosetting T lymphocytes, increased
deoxynucleotidyl transferase activity, decreased serum thymic factor, fewer helper
T cells, impaired production of interferon gamma and interleukins 1 and 2, reduced
antibody affinity, impaired secretory immunoglobulin A (IgA) antibody response
and phagocyte dysfunction. The proportion of helper/inducer T lymphocytes
recognized by the presence of CD4 positive antigen on the cell surface is markedly
decreased. The ratio CD4/CD8 is significantly decreased. Lymphoid atrophy is a
prominent feature of nutritional deprivation. Serum antibody responses are
generally intact in PCM. Most complement components are decreased, especially
C3, C5, factor B and total hemolytic activity (37-43).
“Nutritional problems have been a part of the clinical aspects of AIDS from its
earliest recognition as a new disease” (37,41). “In fact, in many AIDS patients, death
seams to be determined more by the individual’s nutritional status than by any
particular opportunistic infection. This is, when wasting of lean body mass
approaches 55% of normal for age, sex, and height, death is imminent regardless of
the forces resulting is such profound malnutrition” (37,41). Furthermore, the
severity of the clinical manifestations of AIDS is proportional to the degree of the
nutritional deficiencies (44-47).
“Macronutients are related to wasting and energy balance in HIV-infected patients,
while micronutrients play different roles in immune function” (48).
In addition to supporting optimal function of the immune system, nutrition is
especially critical in children, as it provides the best opportunity for normal growth
and development (49,50).
“All persons with HIV infection should be screened for nutritional problems and
concerns at the time of their first contact with a health care professional, and
routine monitoring should be performed on an ongoing basis” (49).
Scientific evidence strongly suggests that nutritional and antioxidant deficiencies are
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a requisite prior to both reacting positively on the tests for HIV (ELISA, Western
blot, Viral Load) (51-54) and for progressing to AIDS (55,56).
3 NUTRITIONAL DEFICIENCIES AND THE PROGRESSION OF HIVPOSITIVE INDIVIDUALS TO AIDS.
An optimal nutritional status as well as adequate vitamin levels are known to be by
themselves enough to prevent the development of AIDS in people who react
positively on the tests for HIV (57-64).
For example, regarding vitamins in HIV disease progression and vertical
transmission, researchers from the Harvard School of Public Health state: “The
higher rates of HIV progression and vertical transmission in developing countries
coincide with similarly higher rates of malnutrition and vitamin deficiencies,
indicating that HIV infection, may be modified by nutritional status.” “Numerous
observational studies report inverse association between vitamin status, measured
bio-chemically or as levels of dietary intake, and the risk of disease progression or
vertical transmission.” “Adequate vitamin status may also reduce vertical
transmission through the intra-partum and breastfeeding routes by reducing HIV
viral load in lower genital secretions and breast milk,” and “Vitamin supplements
may be one of the few potential treatments that are inexpensive enough to be made
available to HIV-infected persons in developing countries” (65).
Macronutrient (carbohydrates, proteins, fat, and fiber) deficiencies have been
associated with low CD4 cell counts in HIV-positive individuals. HIV-positive
individuals with low mean weight and low arm and muscle circumference (48,66)
and HIV-positive children with growth impairment were shown to have low CD4
cell counts (48,67).
Wasting, particularly loss of lean body mass, is associated with early mortality
(68,69) and susceptibility to opportunistic infections (48,69). In a case control study
nested within a follow up study, HIV-positive IV drug users with wasting (more
than 10% loss of weight from baseline to last visit before death; mean follow-up, 2.4
years) had an approximately 8 fold higher risk of mortality compared with controls,
after adjusting for CD4 cell counts (48,55).
Higher mortality has been associated with low serum albumin (48,70). Low lean
body mass index and high plasma levels of C-reactive proteins were also significant
predictors of mortality among HIV-positive individuals followed for 42 months
(48,71). Serum albumin and hemoglobin levels are also predictors of prognosis in
HIV-positive children (48,72). Micronutrient deficiencies in HIV-positive
individuals are associated with faster progression to AIDS (73).
A growing number of scientific trials implicate low serum vitamin A levels as a risk
factor for HIV-positive individuals to progress into the clinical manifestations of
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AIDS (74-86).
“The risk of death among HIV-infected subjects with adequate serum vitamin A
levels was 78% less, when compared with Vitamin A-deficient subjects” (65,78).
“In a study carried out among HIV-positive homosexual men, development of
Vitamin A deficiency over an 18-month period was associated with a decline in CD4
cell count, widely used as a marker of HIV immune impairment. Normalization of
vitamin A was associated with higher CD4 cell counts” (55,65).
“Lower serum levels of vitamin A were associated with a faster rate of progression
among men who participated in the Multicenter AIDS Cohort Study (MACS)”
(60,65).
In a nested case-control study, HIV-positive individuals with vitamin A deficiency
had a fourfold higher risk of death than controls after adjusting for CD4 cell counts
(48,55).
In a longitudinal study among HIV-positive IV drug users in Baltimore, low serum
retinal levels were associated with a fourfold increase in risk for mortality after
adjusting for CD4 cells counts (48,54).
In Rwanda higher likelihood of survival was noted among HIV-positive women with
higher serum retinol levels (48,87).
On the other hand: “Among well nourished HIV seropositive men who participated
in the San Francisco Men’s Health Study, high energy-adjusted vitamin A intake at
baseline was associated with higher CD4 cell count at baseline, as well as with lower
risk of developing AIDS during the 6 year period follow up” (62,65).
Development of vitamin A or B12 deficiency was significantly associated with a
decline in CD4 cell count in a longitudinal study in HIV-positive gay men (48,88). In
the same study, normalization of vitamin A, vitamin B12, and zinc was significantly
associated with higher CD4 cell count, a finding that was not affected by the use of
AZT.
In a randomized trial, daily supplementation with 180 mg of beta-carotene for 4
weeks was associated with a small increase in total white blood cell count, an
increase in CD4 cell count, and a beneficial change in CD4/CD8 ratio compared
with study participants receiving a placebo. These parameters decreased when
participants in the beta-carotene arm were switched to the placebo arm (48,89).
Daily supplementation with selenium or beta-carotene for 1 year led to significant
increase in glutathion peroxidase activity at 3 and 6 months among HIV-positive
men and women in France (48,90).
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In Thailand, HIV-positive pregnant women in the first trimester with CD4 counts
less than 200 cells/cubic mm had mean serum vitamin A beta-carotene levels 37%
lower than those in HIV-negative individuals (48,91).
In a longitudinal study in Miami, HIV-positive women with CD4 counts less than
200/cubic mm were more likely to have lower levels of plasma selenium and vitamin
A an E than men with similar CD4 cell counts (48,92).
In a placebo-controlled trial in South Africa among children born to HIV-positive
women, Vitamin A supplements resulted in approximately 50% reduction in
diarrheal morbidity and progression to AIDS among HIV-positive children (65,77).
Increased number of natural killer cells in HIV-infected children has also been
observed following vitamin A supplementation in South Africa (48,93).
In addition to vitamin A, a growing number of studies show that “HIV-positive”
individuals are at higher risk of deficiency of vitamins B1, B2, B6, B12, C, D, and E
(65,94-101). Furthermore, deficiencies of B-complex vitamins, vitamin C, vitamin E
and vitamin D increment the risk of progression of “HIV-positive” individuals to
AIDS (65,94-101). For example, Vitamin B6 deficiency in “HIV-positive” individuals
has been associated with reduced natural killer cell cytotoxicity and impaired
mitogen-induced lymphocyte proliferation (102).
In a randomized, placebo-controlled, double-blind study in Canada, a significant
reduction in viral load was achieved after 3 months of supplementation with large
daily doses of vitamins C and E (48,103).
In the MACS study (104) and in a study in San Francisco (105), high levels of
vitamin C, thiamin, or niacin intake were associated with a reduced risk of
progression to AIDS (48).
Also in the MACS study, high dietary intake of vitamins B1, B2, B6, and niacin
were associated with increased survival time of up to 1.3 years (48,106).
Increase intake of iron, vitamin E, and riboflavin significantly reduced the hazard
for AIDS (48,105).
Lower vitamin E levels increased the risk of progression to AIDS (48,107). In the
same study population, low serum vitamin B12 levels were associated with a twofold
increase in the risk for progression (48,108).
Plasma zinc and magnesium levels were shown to be significant predictors of CD4
cell count among HIV-positive individuals in the United States (48,109).
In San Francisco, higher dietary intake of zinc, thiamine, niacin, and riboflavin
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were positively related to CD4 cell counts (48,105).
In a case-control study nested in the MACS study, patients who progressed to AIDS
had significantly lower levels of serum zinc compared with nonprogressors and
HIV-negative participants (48,110).
Selenium deficiency in HIV-positive individuals has been observed to increase risk
of death among adults (48,111,112).
4. NUTRITIONAL
HIV/AIDS.
DEFICIENCIES
AND
THE
“TRANSMISSION”
OF
Several studies show that vitamin A deficiency is more prevalent among HIVpositive persons compared with HIV-negative individuals (45,56,58,76,83).
Low levels of vitamin A and carotenoid were found to be a risk factor for reacting
positively on HIV tests in Pune, India (113), for seroconversion among Kenyan men
with genital ulcers (114), and for seroconversion among Rwandan women (115).
There have been several trials concerning the role of vitamin A and carotenoid
deficiencies in mother to child transmission of HIV/AIDS (MTCT) during
pregnancy, delivery, and breastfeeding (116-133):
In Tanzania for example: “Multivitamin supplementation is a low-cost way of
substantially decreasing adverse pregnancy outcomes and increasing T-cell counts
in HIV-1 infected women” (116,117).
“A growing body of data suggests that low serum levels of vitamin A among HIVinfected pregnant women is associated with higher risk of vertical transmission of
HIV” (65).
“Mean vitamin A concentration in 74 mothers who transmitted HIV to their infants
was lower than that in 264 mothers who did not transmit HIV to their infants”
(121).
“In Malawi, higher serum retinol of HIV-infected pregnant women was associated
with a reduced risk of vertical transmission” (65,121).
“In Rwanda, low levels of serum vitamin A among HIV-infected women were
associated with increased risk of infant death or perinatal HIV-transmission (134).
“Women who had increasing serum retinol levels over time, however, were at a
lower risk, whereas women who had declining serum retinol were at a higher risk of
transmitting the virus” (65,133).
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“Vitamin A supplementation to a population of HIV-infected pregnant women,
many of whom had low vitamin A levels, was associated with a decreased number of
preterm births and with reduced mother-to-child transmission of HIV in preterm
babies, but was not associated with a reduction in HIV transmission overall.
Vitamin A decreased HIV transmission in the preterm babies by 47%” (124).
“Detection of vaginal HIV-1 DNA was associated with abnormal vaginal discharge,
lower absolute CD4 cell count, and severe vitamin A deficiency” (125).
“Women with CD4 cell depletion, especially those with vitamin A deficiency, may be
at increased risk of transmitting HIV-1 to their infants through breast milk” (132).
“Increased risk of maternal-infant transmission was associated with severe vitamin
A deficiency among non-breastfeeding women” in the United States (120).
“In Kenya, low plasma vitamin levels were associated with higher risk of viral
shedding in breast milk among HIV-infected women during pregnancy. These
results suggest that maternal vitamin A status before and after delivery is an
important factor for breast milk transmission of HIV” (48,135).
“Low serum levels of vitamin A and subclinical mastitis in women in Malawi (136)
and South Africa (137) have been associated with high viral load in breast milk and
an increased risk of HIV transmission through breast milk” (48).
Scientific studies support, therefore, the contention that the use of vitamins by
themselves, especially vitamin A, could be enough to avoid what is known as
transmission of HIV from person to person, and from mother to child during
pregnancy, delivery, and breastfeeding (65,113-133). If this is the case, as many
clinical trials and scientific papers contend, supplementation with antioxidant
vitamins such as vitamin A and carotenoids constitute an effective, inexpensive and
non-toxic practice for African countries.
5. REACTIVITY ON TESTS FOR HIV IN SUB-SAHARAN AFRICA NOT
EXPLAINED BY SEXUAL OR VERTICAL TRANSMISSION.
Recently, researchers from Emory University in Atlanta and from Albert Einstein
College of Medicine in New York City, after a comprehensive review concluded:
“An expanding body of evidence challenges the conventional hypothesis that sexual
transmission is responsible for more than 90% of adult HIV infections in Africa.
Differences in epidemic trajectories across Africa do not correspond to differences
in sexual behavior. Studies among African couples find low rates of heterosexual
transmission, as in developed countries. Many studies report HIV infections in
African adults with no sexual exposure to HIV and in children with HIV-negative
mothers. Unexplained high rates of HIV incidence have been observed in African
women during antenatal and postpartum periods” (138).
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Researchers state: “By the end of the 1980s, a consensus emerged among AIDS
experts dealing with Africa that over 90% of adult HIV infections in sub-Saharan
Africa were acquired through heterosexual contact and less than 2% through
unsafe injections [139-142]. Unfortunately, this consensus was achieved without
research to address confound between sexual and medical exposures” (138).
The very similar frequency of AIDS in both genders in Africa has been blamed by
HIV/AIDS researchers and institutions on sexual promiscuity. However, in one
model “Anderson and colleagues assumed a mean rate of annual partner change of
3.5 [143]. In contrast, surveys in 12 African countries show unweighted averages of
74% of men and 91% of women aged 15-49 years with no non-regular sex partners
in the past year, and only 3.7% of men and 0.7% of women with more than four
non-regular partners [144]” (138).
Empiric data show that promiscuity is, rather, a matter in developed countries: “A
survey in Denmark found that 19% of adults aged 18-59 years reported more than
one sex partner in the past year [145]; a survey in France found 17% of men and
7.9% of women aged 18-44 years reported more than one sex partner in the past
year [146]; and a survey in the UK found that 17% of men and 8.4% of women aged
16-44 years reported more than one sex partner in the past year [147]” (138).
Despite this, the frequency of AIDS in developed countries is about 11 men to 1
woman.
“A Zambian study that sequenced viruses to determine epidemiological linkage
reported at least 13% of sequences in newly infected persons were not related to
their partner’s HIV[148]” (138).
“A study in Zimbabwe in the 1990s found 2.1% HIV prevalence among 933 women
with no sexual experience [149]. In a 1988 study of discordant couples in Rwanda,
15 of 25 HIV-positive women with HIV-negative partners reported only one lifetime
sex partner [150]. In a 1990 study of teenagers in Uganda, 6.9% of women with no
sex partners in the last five years were HIV-positive vs 23% for those with one or
more partners; for men, 1% with no partners in the last five years were HIVpositive vs 2.5% of those reporting partners [151]. Among young adults 15-24 years
old in Tanzania, a 1995 study found HIV prevalence of 5.6% among men and 3.6%
among women who did not report any lifetime sexual activity vs 4.8% and 12% for
men and women reporting one or more sexual partners [152]. In a 1999 study in
South Africa, 6.8% of women and 1.2% of men 14-24 years old reported never
having sex were HIV positive; however, a validation study found some underreporting of sexual activity [153]. In a case-control study in Uganda, in two of seven
cases with only one lifetime sexual partner, the partner was HIV-negative, three
were HIV-positive, and two others not tested [154]” (138).
About a fifth of HIV-positive children in Africa have HIV-negative mothers: “A
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study in Kinshasha in 1985 found 39% (16 of 44) of HIV-positive inpatient and
outpatient children 1-24 months old to have HIV-negative mothers; only five of 16
had been transfused [155]. A study in Rwanda in 1984-86 found 20% (15 of 76) of
children 1-48 months old with AIDS or AIDS related complex had HIV-negative
mothers; only 15 children had been transfused [156]. In a later report from
Rwanda, 7.3% (54 of 704) of mothers of children with AIDS were HIV-negative;
transfusions were identified as a risk factor for 22 of the 54 children [157]. Of 26
children less than 15 years old admitted to Uganda Cancer institute with Kaposi’s
sarcoma during 1989-94 for which the mother was tested for HIV, 19% (5 of 26) had
HIV-negative mothers [158]. A study in Burkina Faso in 1989-90 found 23% (11 0f
48) of HIV-positive children to have HIV-negative mothers [159]. In a 1994 report
from Cote d’Ivoire, De Cock and colleagues report that 21% (3 of 14) of children
with HIV-1 had mothers without HIV-1, and one of two with HIV-2 had a mother
without HIV-2 [160]” (138).
“HIV incidence during antenatal and/or post-partum periods exceeded what could
be expected solely from sexual transmission” (138,161-171). “In one of the seven
studies of antenatal and post-partum women [171], 30 of 634 women had HIV
positive partners; three of these 30 women seroconverted in a year” (138,171). “HIV
prevalence in African men is generally lower than in women, and many infected
men are partnered with infected women. In eight studies of African couples with
HIV in one or both partners [150,172-178], the average percent of women with HIV
was more than double the percent without HIV who had HIV-positive partners”
(138). The high prevalence of HIV reactivity in women during antenatal or postpartum periods “suggests that something more than simply heterosexual
transmission is involved” (138). “Whatever happens during one or two pregnancies
and post-partum periods – whether iatrogenic or sexual or something else – may
largely account for observed high levels of HIV among low risk women in at least
some African communities” (138).
“The recognition that significant proportions of HIV in African adults and children
cannot be explained on the basis of current knowledge about sexual and vertical
transmission” allowed the researchers from Emory University and Albert Einstein
College of Medicine to postulate a hypothesis of “iatrogenic transmission” through
medical instruments such as syringes and injections (138).
At this point it is important to remember that there are several publications
seriously criticizing the accuracy of tests currently used to diagnose HIV infection
(179-184).
Long ago, HIV researchers were aware of the lack of specificity of the HIV antibody
tests, especially in countries in Africa where “reactivity may be affected when
subjects have dad recurrent malaria and other parasitic diseases [perhaps because
of autoantibodies involving antigens in the lymphocyte cell line used to grow the
virus] [185] or previous pregnancies [perhaps because of antibodies to DR4 or other
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HLA types] [186-188]” (189). The US researcher insisted that: “Since the reliability
of ELISA test for the measurement of HTLV-III/LAV antibody in Africa sera has
been questioned, the extent of this problem remains uncertain” (189). Speaking
about the seroepidemiology in Central African countries, a British immunologist
states: “It now appears that some of the results obtained were false positives” (190).
Mann also knew that tests for HIV often wrongly identify antibodies to HIV in
blood samples (191). “False positives can also occur, if, for example, the frozen
blood has thawed and then been refrozen. To make the situation even more
complex, many Africans probably have relatively high levels of antibodies, proteins
that signal the body’s attempt to fight disease, in their blood, as a result of having
other infections, such as malaria. These numerous antibodies tend to bond to one
another and cause blood samples to become sticky, which may lead to false positive
results” (191).
“Results in serological surveys for antibodies against HIV in Africa were initially
distorted by a high false-positive rate” (192).
It is amazing to note that public health officials also know that “serologic studies of
HIV in Africa have been inconsistent because of problems in interpretation of the
results from ELISA and Western blot tests of banked specimens, particularly from
malaria endemic areas, and the validity of these data has been questioned” (193).
Currently, pharmaceutical companies that make and commercialize the kits for HIV
tests acknowledge the inaccuracy of these tests. Accordingly, the inserts that come
with the kits typically state the following: “Elisa testing alone cannot be used to
diagnose AIDS, even if the recommended investigation of reactive specimens
suggests a high probability that the antibody to HIV-1 is present” (194). The insert
for one of the kits for administering the Western blot warns: “Do not use this kit as
the sole basis of diagnosis of HIV-1 infection” (195). The insert that comes with a
popular kit to run viral load warns: “The amplicor HIV-1 monitor test, version 1.5,
is not intended to be used as a screening test for blood or blood products for HIV or
as a diagnostic test to confirm the presence of HIV infection” (196). Abbott goes
even farther when it warns: “At present there is no recognized standard for
establishing the presence or absence of antibodies to HIV-1 and HIV-2 in human
blood” (194).
There are abundant scientific publications explaining that there are more than 70
different documented conditions that can cause the antibody tests to react positive
without an HIV infection (179-184). Some of the conditions that cause false positives
on HIV tests are: past or present infection with a variety of bacteria, parasites,
viruses, and fungi including tuberculosis, malaria, leishmaniasis, influenza, common
cold, leprosy and history of sexually transmitted diseases; the presence of
polyspecific antibodies, hypergammaglobulinemias, the presence of autoantibodies
against a variety of cells and tissues, vaccination, and the administration of gamma
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globulins or immunoglobulins; the presence of autoimmune diseases like
erythematous lupus, sclerodermia, dermatomyositis and rheumatoid arthriris; the
existence of pregnancy and multiparity; a history of rectal insemination; addiction
to recreational drugs; several kidney diseases, renal failure and hemodialysis; a
history of organ transplantation; presence of a variety of tumors and cancer
chemotherapy; many liver diseases including alcoholic liver disease; hemophilia,
blood transfusions and administration of coagulation factor; even the simple
condition of aging, to mention just a few of the conditions (182-184). Interestingly,
most of these conditions are common to the African scenario.
The above considerations permit the proposition that reacting positively on tests for
HIV is caused by multiple, repeated, and chronic exposure to chemical, physical,
biological, mental, and nutritional stressor agents (184). One of the first
consequences of poverty is malnutrition, making individuals susceptible to
infectious and parasitic diseases, which in turn stimulate the production of
polyspecific antibodies, many of which are being detected by HIV tests.
Many are attempting to explain that the current morbidity and mortality of African
communities are a consequence of HIV infections. However, it is possible that
reacting positively on the so-called tests for HIV in Africa is a result of chronic
exposure to poverty and its consequences, such as malnutrition, infections, and
parasites (184).
6. OXIDATIVE STRESS AND HIV/AIDS.
Moreover, since the beginning of the AIDS epidemic, free radicals and specifically
oxidizing agents have been implicated in the pathogenesis of the new syndrome
(197,198). There have been international meetings concerning the role of oxygen free
radicals in HIV/AIDS (199,200).
There is today a growing number of scientific publications indicating that oxidizing
stress is an absolute requisite for both testing positive on the tests for HIV (201-207)
and for developing the clinical manifestations of AIDS (208-230).
Free radical reactions of special significance to immunological phenomena are, for
example, the many oxidizing agents that can abstract a hydrogen atom from thiol
groups to form thiol radicals (231-233). Thiol groups are important for enzyme
activities, receptor functions, disulphite links in immunoglobulins, and T cell
activation and proliferation. The super oxide anion radical can react with nitric
oxide, resulting in loss of endothelium-derived relaxing factor activity, which is
important in the inflammation/disinflammation process. Methionine oxidation can
cause protein damage with subsequent changes in immunogenicity. Proteolysis can
be increased by free radical damage. The per oxidation of lipids by reactive free
radicals produce many biological modulators such as, for example, the 4-hydroxyalkelans, which produces strong chemotactic activity for phagocytes, alters the
14
adenyl cyclasa system, increases capillary permeability, and alters lymphocyte
activation. Lipid hydroperoxides, also from per oxidation of lipids, alter lymphocyte
activation. Conditions favoring lipid per oxidation may result in chemo taxis of
leukocytes, protein modification, immune complex injury, and cell death (231-233).
Free radicals are produced throughout the regular immune system network. Despite
the beneficial effects of the inflammation responses, they can also aggravate existing
tissue damage by releasing free radicals. When uncontrolled, initiated by an
abnormal stimulus, or occurring for prolonged periods of time, inflammation may
become a disease process (231-233). It is critical for optimal immune responses that
there be a balance between free radical generation and antioxidant protection.
During phagocytosis by polymorphonuclear leukocytes, for example, super oxide
anion radicals are released. These oxygen free radicals can oxidize thiol groups to
thiol radicals, and can stimulate lipid per oxidation with the formation of H 2O2,
which is highly significant in the mechanisms of cell injury. Oxygen free radicals
produced during phagocytosis of immune complexes are associated with injury to
immune complexes (231-233).
It has often been proposed that free radicals and specifically oxidizing species play
important roles in the pathogenesis of AIDS (189-200,234-236).
The above are the scientific fundamentals for the use of antioxidants such as vitamin
A and carotenoids, vitamin C, vitamin E, selenium, n-acetyl cisteine, l-gluthamin,
zinc, cooper, manganese, alphalipoic acid, coenzyme Q10, and flavonoids or vitamin
P, as supplementation for the prevention and treatment of AIDS (48,188-236).
7. NUTRITIONAL AND ANTIOXIDANT
PATHOGENESIS OF HIV/AIDS.
DEFICIENCIES
AND
THE
African countries have a high incidence of malnutrition, vitamin deficiencies, and
anemia, as well as bacterial, viral, fungal, and parasitic infections and infestations.
For any infectious or parasitic disease to start, it is always a requisite that the host
suffer immunodeficiency (237). At the same time, infectious and parasitic diseases
themselves cause additional immune suppression and more malnutrition (238,239).
This immune suppression is secondary to the accumulation of free radicals,
especially oxidizing species, that occurs during and after infectious and parasitic
diseases (232,240).
Therefore, in African countries there is a persistent circular occurrence; poverty,
malnutrition, immune suppression, infectious and parasitic diseases, more immune
suppression, and more malnutrition (241,242).
On the other hand, there is growing scientific data showing that many chronic
diseases of adulthood have their origin at “in utero programming” (243-246). This
15
includes illnesses such as coronary heart disease and stroke, hypertension, type II
diabetes and other endocrine alterations (243-248), as well as several immunological
disturbances (249-259). Therefore, it appears that whatever happens during
embryonic and fetal times will be remembered by cells, tissues, organs, and systems
throughout a lifetime.
“Research in Gambia associated season of birth with infectious disease mortality
after the age of 15 years, suggesting an association between prenatal undernutrition,
immune function, and adult vulnerability to infectious disease” (255,259). Prenatal
undernutrition has been found to impair antibody responses to vaccination with
Salmonella thyfi that last at least up to adolescent times (253). The findings of these
researchers “suggest a role for fetal and early infant experience in programming the
immune system” which may accompany the individual during its entire life
(252,253).
It is scientifically known that prenatal undernutrition alters several aspects of cellmediated immunity, causes involution of lymphoid tissues such as the thymus, and
suppression of antibody responses to vaccination. These deficits persist for weeks or,
in some cases, even years (249-259).
In addition, “murine models have documented impairments in immunity after
maternal undernutrition that last through adulthood and into the next generation,
despite ad libitum feeding of both F1 and F2 generations” (260). Also in mice,
deprivation of zinc during pregnancy causes immunodeficiency that can last at least
for three generations (261).
It is therefore very probable that in Africa the consequences of poverty and
malnutrition are being transmitted from generation to generation with a cumulative
effect and that AIDS in Africa may be the topmost consequence of these cumulative
effects of poverty.
In this light, the crucial role of maternal undernutrition in the pathogenesis of
pediatric AIDS has to be seriously considered to be the case in developing countries
(262,263). This reasoning also indicates that malnutrition constitutes the main risk
factor for AIDS in adults in developing countries (262,263). Scientifically speaking,
there is no rational for indicting sexual promiscuity as the cause of AIDS in Africa,
while underestimating the role of poverty, malnutrition, infections and parasites.
8. NUTRITIONAL AND ANTIOXIDANT THERAPY FOR THE PREVENTION
AND TREATMENT OF AIDS.
“It is not surprising, therefore, that dietary therapy for AIDS has been proposed,
debated, and more importantly surreptitiously or overtly used from the early days
of the epidemic” (41).
16
Twenty years later, researchers insist: “Because nutrient deficiencies may play an
important role in the pathogenesis of HIV disease, medical nutrition therapy and
counseling are critical aspects of treatment” (49). Nutritional (264-286) and
antioxidant (287-305) therapy is then a must in preventing and treating AIDS.
“Supplementation of several amino acids has been suggested as a method for
reducing weight loss among HIV-infected individuals. A combination of three amino
acids known as HMB/Gln/Arg-beta-hydroxy-beta-methylbityrate (HMB), a
metabolite of leucine, L-glutamine (Gln), and L-arginine (Arg), given for 8 weeks to
patients with HIV-associated wasting, resulted in significant weight gain for patients
in the treatment arm compared with those receiving placebo [306]” (48).
Clinical trials have identified in detail the vitamin and mineral needs of HIVpositive persons and those with AIDS. These studies suggest the need for increasing
the intake of the micronutrients vitamin A and carotenoids, vitamin C, vitamin E,
selenium, n-acetyl cisteine, l-gluthamin, zinc, cooper, manganese, alphalipoic acid,
coenzyme Q10, flavonoids or vitamin P, and B-complex vitamins as supplementation
for the prevention and treatment of AIDS (34-56,197-236,264-305).
When providing Vitamin A as a supplement its potential teratogenic property (307)
should be kept in mind. In this regard, the World Health Organization recommends
that pregnant women should not take more than 10,000 IU of Vitamin A per day
(65).
If we really want to prevent and treat AIDS in Africa, it is an absolute requisite to
provide at least the minimum food needs to HIV-positive individuals, to AIDS
patients, as well as to all African communities.
A diet providing adequate sources of macronutrients, vitamins, minerals, and
antioxidants would have lots of fruits especially papaya, mango, kiwi, pineapple,
avocado, bananas, and dry fruits, as well as vegetables, legumes and alga. Use few
animal products. Prefer white fatty fish, sheep and goat meat. Prefer sea salt. Use
60-80% fresh, whole, raw organic food. Use garlic, onions, asparagus, beets,
cabbage, broccoli, cauliflower, Brussels sprouts, carrots, yeast, whet, and pollen, as
well as sprouts, legumes, and cereals. Prefer cold press oils (below 40 degrees
Celcius), since this process preserves essential and polyunsaturated fatty acids
needed in anti-inflammatory and regenerative processes. Carcamo, sunflower, and
olive oils, in this order, are good sources of vitamin F or linoleic acid. Lino oil is a
good source of alpha linoleic acid. Eat whole cereals in any manner (rice, barley,
wheat, oat). Decrease sugar and candies. Prefer raw organic vegetables and legumes.
Drink lots of liquids; water (at least 1.5 litters per day), juices with fresh fruits and
vegetables, especially carrots, vegetable broths, and green juices as a source of
chlorophyll (for example, blend with water lettuce, spinach, celery, mint, parsley,
coriander, and similar foods, and consume without draining). Also, it is very
convenient to use bifidogenic foods, for example yogurt and kumis, better made with
17
sheep or goat milk, as well as tofu and miso. Coconut oil is a good source of louric
and caprilic acids which are anti candida (271,276,280-286,308).
Some immune stimulant and/or antioxidant herbs (289,293,294,308-311) are; Aloe
(Aloe vera), astragalus (Astragalus membranaceus), Siberian ginseng
(Eleutherococcus senticosus), Fo-ti (Polygonum multiforum), turmeric (Curuma
longa), echinacea (Echinacea angustifolia y E. purpurea), garlic (Allium sativum),
licorice or liquorice (Glycyrrhiza glabra), golden seal (Hydrastis Canadensis), cat’s
claw (Uncaria tomentosa), ginkgo (Ginkgo biloba), grape fruit seeds (Vitis vinifera),
zarzaparrilla or smilax (Smilax officinalis y S. aspera), African potato (Hyposis
hemerocallidea/rooperi), and sutherlandia/cancerbush/kankerbos (Sutherlandia
frutensces). Sedative and relaxing herbs include; peace flower (Passiflora incarnata),
valerian (Valeriana officinalis), chamomile (Matricaria chamomilla), mint (Menta
sativa), lavender (Lavanda officinalis), and Siberian ginseng (Eleuterococus
senticosus).
There are numerous scientific papers and books that review the issue of nutritional
and antioxidant therapy for the prevention and treatment of AIDS (264-315).
9. CONCLUSIONS
A) Nutritional and antioxidant deficiencies have been documented in all patients
with AIDS as well as in persons who react positively on “tests for HIV.”
B) Scientific data indicate that nutritional and antioxidant deficiencies are a
requisite prior to reacting positively on “tests for HIV.”
C) Nutritional and antioxidant deficiencies are also a requisite of “HIV-positive”
individuals prior to the development of the clinical manifestations of AIDS.
D) Reactivity on “tests for HIV” in sub-Saharan Africa cannot be explained by
sexual or vertical transmission. It is very probable that reacting positively on the socalled tests for HIV in Africa is a result of chronic exposure to poverty and its
consequences, such as malnutrition, infections, and parasites.
E) Nutritional and antioxidant deficiencies play a major role in the pathogenesis of
AIDS.
F) Nutritional and Antioxidant supplements are being used successfully in
preventing and treating AIDS. An optimal nutritional and antioxidant status can
guarantee success in preventing and treating AIDS.
G) Some of the nutritional and antioxidant supplements that have been used in the
treatment and prevention of AIDS are; combinations of amino acids, vitamin A and
carotenoids, vitamin C, vitamin E, selenium, n-acetyl cisteine, l-gluthamin, zinc,
18
cooper, manganese, alphalipoic acid, coenzyme Q10, B-complex vitamins, and
flavonoids or vitamin P.
H) To prevent and treat AIDS in Africa, it is an absolute requisite to provide at least
the minimum food needs to HIV-positive individuals, to AIDS patients, and to all
African communities. Moreover, diets rich in fresh and organic fruits, vegetables,
and cereals, as well as diets rich in bifidogenic foods (yogurt, kumis) are known to
be immune stimulants.
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