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A study of AIDS/ HIV Patients, Representative of Immuno-Compromised Individuals, to
Understand the Role of Various Macro and Micro Nutrients in the Body’s Immune Function
FND451: Advanced Nutrition
Research Paper, Group #4
Aaron Carrington
LaTricia Jones
Sarah Rattigan
Melinda Rudisill
Introduction
Proper nutrition plays a vital role in health. It provides the immune system with a variety
of nutrients required for optimum performance. When under attack, suboptimal nutrition further
weakens the immune system and leaves the body vulnerable. This idea is illustrated in the natural
progression of several disorders and disease states, and is especially evident in individuals
infected with HIV. This paper examines the role of nutrition in the treatment of HIV/AIDS
patients as a method of observing the importance of various macro and micro nutrients in
immunity.
The Immune system and Various Nutrient Roles
Deficiency is detrimental to the immune system and several factors contribute to the
problem. When the immune system is challenged, specific immunity is stimulated.
Consequently, there is a significant increase in the body’s demand for a ready source of energy.
Energy generation is mediated by various electron carriers and cofactors largely derived from
micronutrients. Additionally, the immune response triggers anabolic activity and is inhibited
when deficient in building blocks necessary for the synthesis of critical mediators. Cellular
proliferation is another integral part of the immune response. Therefore, an ample supply of
nucleotides for DNA and RNA synthesis must be present, in addition to other components
necessary for protein and phospholipid generation. Examples include micronutrients like zinc,
iron and magnesium, which are involved in nucleotide and nucleic acid synthesis. Vitamins A
and D regulate gene expression in immune cells and influence their maturation, differentiation
and responsiveness. Vitamins C and E play important roles as antioxidants by neutralizing free
radicals formed during the oxidative burst that occurs as part of the immune response. Adequate
intake is important because several of these nutrients cannot be manufactured by the body and
must be provided by the diet. (Calder 2013).
Malnutrition and its Effects on immunity
In malnutrition, the immune system response is weakened by insufficient intake of
energy and macronutrients. An example of the effect of protein-energy malnutrition on the
immune system includes injury to the intestinal barrier function which may allow transmission of
harmful bacteria. The atrophy of lymphoid organs may be an immune affected result of proteinenergy malnutrition. Additionally, protein-energy malnutrition (PEM) has been observed to
result in a decrease in the production of CD4+ T cells in the body (Duggal 2012). A lower ratio
of CD4+:CD8+ cells further diminishes natural killer cell activity (Calder 2013). Despite lower
fat-free and total fat masses in HIV patients, adequate nutritional status can help maintain lean
body mass, reduce the severity of symptoms, and generally improve quality of life (Mahan
2012).
Resting Energy Expenditure is increased by 10% in asymptomatic HIV patients, and 2050% in patients experiencing symptoms of infection, which further complicates achieving
adequate intakes (Mahan 2012). Thus, protein-energy malnutrition is observed to contribute to
decreased ability of the body to fight off infections, as observed in HIV patients. Malnutrition
has been observed to directly impair absorption, storage, and utilization of nutrients.
Malnutrition synergizes with micronutrient deficiencies increasing vulnerability to infectious
diseases (Ivers 2009). In fact, it has been observed that the occurrence of opportunistic
infections is increased with even just a 5% weight loss in HIV patients (Heller 1997). Causes of
weight loss and wasting are believed to be inadequate nutrient intake, malabsorption, and
increased metabolic rates in response to infection (Mahan 2012). Because malnutrition causes
immune system dysfunction, it can thus be considered one of the most common causes of
immunodeficiencies throughout the world (Duggal 2012). Malnutrition follows a negative
feedback loop, where compromised immunity results in frequent diarrhea and further weight loss
(Ivers 2009). Therefore, it is known that adequate nutrient and caloric intake are critical to
maintaining a properly functioning immune system.
Nutrient Deficiencies and their Effects on Immunity
The role of nutrition in immunity can be examined by studying patients that are
immunocompromised. HIV/ AIDS patients were chosen because they have been observed in
many nutritional studies. As a result, several nutritional deficiencies that may contribute to
decreased immunity status have been identified. Another advantage of clinical trials with
HIV/AIDS patients is that patients can be supplemented and/or adjusted, and the effect on the
immune system can readily be seen by any change in immunity status. Common nutrient
diagnoses in HIV patients are reflective of any immunocompromised patient, and addressing
these diagnoses is critical for slowing the progression of the disease and maintaining the immune
system apart from the potential benefits of extra supplementation (Mahan 2012).
Deficiencies of various micronutrients can lead to disease progression via suppression of
the immune system (Mahan 2012). During the body’s response to infection, levels of Vitamin A,
B12, zinc, and selenium are low. Low levels of these nutrients are associated with increased
disease progression (Mahan 2012). Duggal et al (2012) observed that immuno-depleted HIV
patients have several reoccurring nutrient deficiencies. Noteworthy were the deficiencies in
essential amino acids, which resulted in decreased protein synthesis. As a result, cytokine
production was decreased as well. Cytokines are key components of immune response.
Deficiencies in Omega-3 fatty acids are problematic as well, as they are precursors for
eicosanoids, signaling molecules involved in immune response (Duggal 2012).
Vitamin A deficiency was observed to result in depressed cellular immunity, and
deficiencies of zinc directly correlated with decreased lymphocyte cell functionality (Duggal
2012). This was corroborated by Calder et al (2013), who reported that vitamin A deficiency
impairs barrier function, alters immune responses, increases susceptibility to infections, and
depresses natural killer cell activity. Another micronutrient, vitamin D, was noted to act as a
hormone involved in immuno-regulation and lymphocyte differentiation (Duggal 2012). Vitamin
D was also reported to encourage phagocytoses and reduce susceptibility to infection (Calder
2013). Vitamin B-12 is essential for cellular replication, and deficiencies were shown to interfere
with leukocyte replication and antibody formation (Duggal 2012). Zinc plays an important role
in immunity by its involvement in the synthesis of DNA, cellular growth and differentiation, and
antioxidant defense. Zinc deficiencies impair phagocytosis, reduce the number and function of Tcells, decrease natural killer cell activity, reduce cell-mediated immune responses, and increase
susceptibility to infection (Calder 2013). Selenium was observed to act as an antioxidant,
contributing to antibody response and cytotoxicity of natural killer cells (Duggal 2012). A
deficiency in selenium has been linked to diminishing natural killer cell activity and increased
bacterial disease (Calder 2013). By studying these deficiencies in HIV patients, it can be seen
that consumption of essential amino acids, omega 3 fatty acids, vitamins A, D, B-12, zinc, and
selenium are necessary to maintain a functioning immune system.
These observations were corroborated by Neves et al (2006), who noted that deficiencies
of Vitamins A, B-12, zinc, and selenium were all shown to correlate with increased HIV related
mortality and decreased CD4+ counts over time. This further indicates the importance of
Vitamins A, B-12, zinc, and selenium in maintaining immune function.
Supplementation and its Effects on Immunity
As deficiencies are seen to contribute to increased disease progression and decreased
immune function, the effects of supplementation should be studied for their usefulness in
correcting these deficiencies and resulting complications. Shabert et al (1999) reports that
supplementation with L-glutamine, antioxidants, omega 3 fatty acids, vitamin A, and vitamin D
may improve the compromised immune system of an HIV/AIDS patient. Due to an HIV/AIDS
patient’s increased risk of body wasting, less L-glutamine, which is primarily synthesized in
skeletal muscle, may be produced. The immune system requires L-glutamine as the primary fuel
for enterocytes and colonocytes and its stores of immune tissue. Unfortunately, the body will
exhaust itself in producing enough L-glutamine for the immune system to properly function
(Shabert 1999). This process is especially dangerous for HIV/AIDS patients because it increases
their rate of body wasting. Shabert et al (1999) reports that when patients were given a
supplement containing the amino acid L-gluatmine and the antioxidants vitamin C, E, and
selenium, they experienced improved weight gain and restored body cell mass. However, it is
important to note that this study of L-glutamine was published 16 years ago, and further
investigation may be needed.
HIV patients have been observed with increased incidences of hypertriglyceridemia and
increased levels of pro-inflammatory cytokines. Metkus et al (2013) observed that omega 3 fatty
acids have beneficial effects on high triglyceride levels and HIV related inflammation. This
includes the reduction of inflammatory eicosanoids production from arachnidonic acid, the
increased metabolism of omega 3 fatty acids to anti-inflammatory lipid modulators, and a
decreased activation of nuclear factor kappa B by inflammatory stimuli. This study reported a
modest decrease in the serum triglyceride count and the inflammatory markers IL-6 and TNF-α
with omega 3 supplementation. It did note however, that omega 3 therapy may not be
appropriate to treat hyperglycedemia in every AIDS patient. The authors admitted the study was
limited by factors such as small sample size and lack of gender diversity (Metkus 2013).
Although Vitamin A plays a vital role in immunity, the mechanics of its involvement is
not widely understood. Supplementation has been shown to correct deficiency in HIV patients,
but it is unclear how much this contributes to restoring immune function. A meta analysis of the
effect of vitamin A in HIV patients found no conclusive evidence that supplements improved
CD4 count or delayed HIV progression. However, it found evidence of reducing symptoms
common in immune compromised patients, such as anemia, pneumonia, and diarrhea. (Annan
2011).
Vitamin D deficiency is common in HIV/AIDS patients as well. Supplementation with
Vitamin D presents potential difficulties for the immunocompromised. While it activates the
innate immune system, it also dampens the adaptive immune system. The innate immune system
is the body’s first line of defense and is nonspecific. Conversely, the adaptive immune system is
comprised of highly specialized cells and processes that defend against specific pathogens. The
adaptive immune system creates a “memory” of the specific pathogen, which leads to an
enhanced response during later encounters (Mora 2008). Although the importance of Vitamin D
in immune function is understood, the future of supplementation use remains unclear.
Adequate zinc intake is essential for immune system function, nevertheless, it is
estimated that zinc deficiency occurs in over 50% of HIV infected adults (Baum 2010). This
scenario presents a favorable opportunity for nutritional intervention as well. Several studies
have investigated the effects of zinc supplementation on disease progression and immune system
function in HIV infected individuals. Noteworthy, was a prospective randomized clinical trial of
HIV adults with low zinc levels. Results reported that supplementation at nutritional doses
(supplementation was approximately 133% AI) can delay immunologic failure and reduce
diarrhea over time (Baum 2010). Advantages of this trial were that it was a long term and that
supplementation dose was determined by subject’s gender. Other studies have demonstrated that
short term zinc supplementation to deficient subjects can be effective in treating diarrhea in
children, as well as decreasing the incidence of opportunistic infections in adults (Sazawal 1995)
(Mocchegiani 1995). These studies support other research that points to zinc supplementation as
a successful strategy only when the patient is deficient, and only when doses are sized as to
correct the deficiency. Zinc over supplementation has resulted in increased disease progression.
In a U.S. cohort study, a high intake of bio-available zinc was correlated to an increased
progression to AIDS and death (Maggie 2012). This is likely because zinc is a component of
structural and catalytic proteins of the HIV virus (Maggie 2012).
Selenium is another micronutrient whose low concentrations correlate with low CD4
counts, greater disease progression, and higher mortality (Hoffman 2008). Selenium plays a role
in immunity by its incorporation into selenoproteins that neutralize reactive oxygen species and
regulate redox reactions (Hoffman 2008). Especially important is selenium’s role in immune
cells like neutrophils, macrophages, NK cells, and T lymphocytes (Ferencik 2003).
Supplementation with selenium has slowed disease progression and improved CD4 cell counts in
patients with HIV (Hoffman 2008). This is supported by many research studies mostly
performed on adults (Maggie 2012). Selenium levels appear to decline in the later stages of
AIDS, when the immune function is at its worst, and selenium supplementation represents a cost
effective means to delay disease progression (Huang 2012). HAART (highly active antiretroviral
therapy) has improved immune function in HIV positive individuals and minimized the
contributions of the HIV virus to diminished selenium status (Huang 2012). It appears as if more
research is needed to determine if selenium supplementation beyond adequate intake is clinically
useful.
Vitamin B12 levels are often low in patients with HIV/ AIDS, even those that are
asymptomatic (Rule 1994). Assessment of vitamin B12 status in the early stages of infection can
be a predictor of disease course (Rule 1994). Supplementation with vitamin B12 can help
prevent the consequences of deficiency, but does not appear to have a significant role in boosting
immune function or delaying the progress of the virus (Remacha 1999). The benefits of
supplementation with B12 are limited to HIV infected individuals with deficiency and are related
to the benefits of adequate nourishment on the immune system in general.
Multivitamin supplements can delay the progression of HIV to AIDS and optimize
immune system function by improving nutrition status. In clinical trials multivitamin
supplements have been shown to delay the progression of asymptomatic HIV infection to AIDS,
as well as delay the initiation of ART therapy (Fawzi 2004). This is useful because vitamin
supplements are a low cost treatment alternative. It appears as though vitamin A in supplements
may reduce their benefit, and that the greatest benefit comes from antioxidant vitamins (Fawzi
2004). Vitamin A supplementation has generated controversy in research as many long-term
studies have implicated it as potentially harmful, facilitating disease progression and mother to
child transmission of the HIV virus. This is in contrast to earlier short term and in vitro studies
that pointed to potential benefits (Fawzi 2004). Vitamin support is most effective when its
purpose is to address deficiencies supported by biochemical evidence (Suttajit 2007). Issues
regarding toxicity, high urine losses of nutrients, and newer nutritional concerns for AIDS
patients such as cardiovascular disease and diabetes, present an opportunity for the ideal vitamin
doses in treatment of HIV infected patients to be investigated and redefined (Suttajit 2007).
In general, it is recommended that immune-deficient patients consume high-energy, highprotein, nutrient-dense diets (Heller 1997). It is recommended that the immunocompromised
patient meet with an RD to assess their particular nutrient needs and nutrition barriers. In regards
to prolonging the life of an AIDS patient specifically, it is recommended that the patient meet
with an RD at least twice a year (Mahan 2012). This enables the RD to take initial assessments,
plan nutrition interventions as necessary, and perform monitoring and evaluations at
predetermined time points (American Dietetic Association 2010).
Conclusion
Nutrition has a direct affect on the immune system. For the immunocompromised
HIV/AIDS patient, studies have shown the critical role adequate nutrition plays in maintaining
immune function. Malnutrition is a primary health concern for those with HIV/AIDS and other
immune-deficient persons, as it can perpetuate immune system decline. Research has
demonstrated how deficiencies of vitamins and minerals halts or attenuates immune response and
increases the incidence of opportunistic infections. Consequently it is of primary importance to
address nutrient deficiencies. While supplementation has been shown to slow disease
progression, over supplementation may promote it. This should be taken into consideration when
developing interventions. The new age of ART therapy in HIV treatment offers new factors to
consider such has the effects of supplementation on comorbid conditions and medications. The
influence of nutrition over immunity is apparent and creates an opportunity for the RD and other
health professionals to optimize the body’s innate defense system.
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