Micronutrient Synergy in the Control of HIV Infection and AIDS

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Micronutrient Synergy in
the Control of HIV Infection and AIDS
Raxit J. Jariwalla, Aleksandra Niedzwiecki and Matthias Rath
Dr. Rath Research Institute, Santa Clara, CA
USA
1. Introduction
Acquired immune deficiency syndrome (AIDS) has become a global health pandemic and
the most common cause of death among young adults aged 20-24 years (Patton et al., 2009).
According to the UN/AIDS Global Report published in November 2010 (UNAIDS 2010),
about 1.8 million persons died from AIDS-related causes in the year 2009 alone. At the end
of that year, the epidemic had left behind totally 16.6 million orphans, defined as those
under 18 who had lost one or both parents to AIDS. Since the beginning of the epidemic,
nearly 30 million people have died from AIDS-related causes.
At the end of 2009, an estimated 30.8 million adults and 2.8 million children were living
with HIV, the human immunodeficiency virus linked to AIDS; with women accounting for
just over one-half of all adults living with HIV worldwide. During the same year, about 2.6
million persons became newly infected with HIV, including 370,000 children. Of all people
living with HIV, about 68% reside in Sub-Saharan Africa (UNAIDS 2010).
Despite these gruesome statistics, there is no cure in sight. Current treatment is based on the
use of antiretroviral (ARV) drugs targeted against HIV at various steps in viral replication
(Sleaseman and Goodenow 2003). Although ARV drugs can reduce viral load in the
bloodstream, they neither cure HIV infection nor restore the immune system to combat
AIDS (Roederer 1998, Pakker et al., 1998). Virus is known to persist indefinitely in reservoirs
of latently-infected cells and emergence of drug-resistant strains is common. Furthermore,
the effectiveness of ARVs in having any clinical benefits at all depends upon a number of
factors, particularly the CD4 count and the nutritional status of patients at the point at
which ARV treatment is commenced (Hong et al., 2001, Paton et al., 2006). Additionally,
drugs are higly toxic and are often associated with adverse side effects to various organs of
the body, including the bone marrow and liver, (Fischl et al., 1987, Richman et al., 1987,
Costello et al., 1988, Abrescia et al., 2008), cellular mitochondria (Carr et al., 2001), and with
lipodystrophy and dyslipidemia (Carr et al., 1998).
Consequently, there is need for safe and effective, nontoxic therapy that can not only restore
the immune system and keep virus multiplication/spread in check but also block AIDS
progression without harming cells of the host. This review will focus on the relationship of
nutrition to infection and immunity and evidence from experimental and clinical studies on
the potential value of micronutrients and their combinations in controlling HIV infection
and reducing symptoms associated with AIDS.

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2. Nutritional deficiencies in HIV and AIDS
The relationship between nutrition, infection and immunity is well established since the
early 1940’s (Scrimshaw 2003, Webb and Villamor 2007). It is for instance well recognized
that nutritional deficiency can lower immunity and predispose individuals to microbial
infection. Conversely, nutritional supplementation can improve immune function and
prevent/confer resistance to infection.
As the latent period between HIV infection and AIDS manifestation has been estimated at 8-
10 years (Morgan et al 2002), nutritional cofactors, besides HIV, have been implicated in
AIDS development (Beach et al., 1992, Baum et al., 1995, Jariwalla et al., 2008a, 2009).
Furthermore, nutrient supplementation in asymptomatic HIV-infected individuals was
shown to delay the onset of AIDS (Abrams et al., 1993, Tang et al., 1993), supporting
involvement of nutritional status as a contributory factor in AIDS development.
It is universally known since the emergence of the AIDS epidemic in the early 1980’s that
nutritional deficiencies are prevalent in persons with HIV infection and AIDS (Gray 1984,
Beach et al., 1992, Jariwalla 1995; see also Table 1). These deficits include: (i) specific
micronutrient abnormalities such as reduced blood levels of the common ACE vitamins,
minerals, trace elements including selenium, amino acids such as cysteine, and the tri-peptide
glutathione, which displays a global systemic deficiency; (ii) macronutrient abnormalities such
as protein calorie malnutrition, which has been linked to a wasting disease, characteristic of
AIDS. Malnutrition has also been linked to the spread of AIDS and TB in developing countries
and with reduced survival (Paton et al., 2006, Turchenko et al., 2008)

MICRONUTRIENT ABNORMALITIES
Vitamins
Vitamin A
Vitamin B12
Vitamin B6
Vitamin C

Vitamin E





MACRONUTRIENT DEFECITS
Protein Calorie Malnutrition
Abnormal Lipids (Dyslipidemia)
Trace Elements
Selenium
Zinc

Amino Acids
Cysteine
Peptides
Glutathione
Table 1. Commonly occurring nutritional deficiencies in HIV infection and AIDS
3. Impact of nutritional deficiencies
Micronutrient deficiencies in particular vitamin and mineral deficiencies can promote and
strengthen microbial growth by weakening the immune system of the host, making it prone
to acquiring new infections (Scrimshaw 2003, Webb and Villamor 2007; see Fig 1).

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Fig. 1. Impact of micronutrient deficiencies on infectious diseases
4. Essential role of micronutrients in cell physiology and immunity
Micronutrients are essential for sustaining all cellular functions including metabolic
reactions in the cytosol and biochemical functions within cellular organelles (Fig 2).
Vitamins and minerals are needed in smaller amounts than proteins, fats and sugars but
without them, cells cannot convert food into biological energy and build different body
structures.


Fig. 2. Micronutrients are essential for sustaining all cellular functions
Micronutrients are also critical for optimum functioning of the immune system including
cell-mediated immunity, antibody production (humoral immunity) and optimum thymus
function (Fig. 3).
The pathological basis of AIDS is a dysfunctional immune system clinically indicated by
abnormally low levels of white blood cells. Micronutrients are essential for blood formation,

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including white blood cells. Of particular importance are: vitamin B-3, vitamin B-5, vitamin
B-6, vitamin B-12, vitamin C, folic acid and iron. Any textbook of biology or biochemistry
documents these scientific facts. Moreover, no less than nine Nobel Prizes in Medicine have
been awarded to date on the discovery of the health benefits of vitamins, relevant to their
role in cellular physiology and impact on the immune system (Nobel Prize Committee
website, Nobelprize.org).


Fig. 3. Nutrients are critical for optimum immune defense of a host
5. Role of micronutrients in suppression of virus infection
Additionally, experimental studies have shown that specific micronutrients can suppress
virus infection at various steps in the viral life cycle that include blocking (a) virus entry, (b)
virus multiplication, (c) virus activation in latently infected cells and (d) virus spread (Fig 4).
Prevent viral entry into cells (Vitamin C, EGCG)
Stop viral multiplication (Vitamin C, N-Acetylcysteine)
Prevent activation of “silent” viruses (Vitamin C)
Limit spread of infections (Lysine, Vitamin C)
In the case of HIV, micronutrients have been shown to block virus expression at all stages of
virus-host interactions, which include acute infection, chronic expression and activation
from latently infected cells (Fig 5). The specific micronutrients demonstrated to affect
different phases of virus infection are listed in Table 2. Most of them are reducing agents

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with antioxidant properties. They include: vitamins C and E, amino acid thiols such as
cysteine or its derivative N-acetyl cysteine (NAC), disulfides such as alpha-lipoic acid,
tripeptides such as glutathione and its derivative glutathione monoester, polyphenols such
as epigallo-catecheine gallate (EGCG from green tea) and the trace element selenium.
Among them, ascorbic acid (vitamin C or ascorbate) is the most versatile, capable of
blocking HIV replication in all phases of HIV infection namely, acute, chronic and latent
infection (Harakeh et al., 1990; Harakeh and Jariwalla, 1991, 1995). Cysteine and glutathione
monoester inhibit chronic HIV expression (Mihm et al., 1991; Kalebic et al., 1991) whereas
NAC and selenium are effective in inhibiting HIV activation in latently-infected cells
(Roederer et al., 1990, Harakeh and Jariwalla 1991; Sappey et al., 1994). It has been reported
that alpha-lipoic acid can block acute infection (Bauer et al., 1991) and flavonoids including
the polyphenol EGCG inhibit HIV at an early stage, blocking interaction of the virus with


Fig. 4. Nutrients can directly suppress viral infections