Nutritional Support for HIV
The Effects of Vitamin Supplements on Patients with HIV
Given the deteriorating effects of HIV/AIDS progression on the immune system and nutrient status, it is not surprising that nutritional supplements have been shown to be extremely beneficial in patients with HIV. Taking vitamin supplements lowered the risk of HIV disease progression in several studies (Kawai 2010; Fawzi 2004; Mehta 2010b; Tang 1993; Abrams 1993). The use of vitamin supplements has also been associated with improved pregnancy outcomes in HIV-infected pregnant women (Fawzi 1998; Kawai 2010), increased appetite in HIV-infected children (Mda 2010a), and better health and survival of children with HIV (Semba 2005; Fawzi 1999; Coutsoudis 1995).
In addition, nutritional supplements have been found to improve comorbidities associated with HIV. In HIV-infected patients being treated for tuberculosis (TB), for example, the consumption of micronutrients (vitamins A, B complex, C, and E, plus selenium) corresponded with a lower risk of TB recurrence and a significantly lower incidence of peripheral neuropathy (a side effect of TB treatment); this treatment also raised CD4+ and CD3+ counts (Villamor 2008). In a recent study of children with HIV, a daily supplement of vitamins A, B complex, C, D, E, and folic acid, plus zinc, iron, and copper (at levels based on recommended daily allowances) corresponded with faster recovery from diarrheal episodes and pneumonia (Mda 2010b).
The Power of Antioxidants
Antioxidants are widely known for their health benefits and may be particularly important for people with HIV. In 1985, Life Extension was among the first organizations to propose that patients with HIV/AIDS would benefit from taking high doses of antioxidants. Since then, many scientific studies have examined a wide range of nutrients and supplements for use in HIV/AIDS.
Under normal circumstances, metabolic processes in the body generate free radicals. At low/moderate concentrations, these reactive oxygen species are not harmful, but instead have a variety of beneficial functions (Valko 2007). At high concentrations, however, they become extremely destructive (Valko 2007). Normally, the human body keeps these levels in check by neutralizing free radicals with its own natural antioxidant defense system. However, some conditions can boost the production of free radicals and create oxidative stress—a condition in which the body's antioxidant defenses are unable to neutralize the overwhelming quantity of free radicals being produced. This can lead to cellular damage and the development of disease (Valko 2007).
HIV is associated with substantial oxidative stress (Oguntibeju 2010; Srinivas 2008; Wanchu 2009; Aquaro 2008; Kashou 2011; Bautista 2001; Deresz 2010; Ogunro 2005), and reactive oxygen species participate in the progression of HIV to AIDS (Kashou 2011). As HIV progresses, antioxidant levels decline (Pasupathi 2009; Bilbis 2010). Compounding this problem further is the fact that various HIV treatments have been shown to increase oxidative stress (Deresz 2010; Wang 2007; Masiá 2007; Ngondi 2006). Combined, these factors create an unhealthy environment that could be further exacerbated by the inadequate intake or poor absorption of nutrients that are commonly associated with HIV (Tang 2005; Drain 2007). Antioxidant micronutrient deficiencies are common among people with HIV (Allard 1998). Reduced serum levels of vitamins E (a powerful antioxidant) have been associated with a higher risk of developing AIDS (Tang 1997).
Antioxidant supplements have been found to counteract some of the damaging effects associated with HIV. Taking supplements of vitamin E (800 IU per day) and vitamin C (1000 mg per day) for 3 months lowered oxidative stress among patients with HIV and produced a trend toward a decrease in viral load (Allard 1998). High serum levels of vitamin E have been linked with a slower progression of HIV (Tang 1997). In large study in Tanzania involving 1,075 pregnant women with HIV, taking a daily multivitamin combination consisting of vitamins C (500 mg), E (30 mg), and various B vitamins and folic acid improved CD4, CD3, and CD8 cell counts and lowered the risk of fetal death, low birth weight, preterm birth, and small size for gestational age (Fawzi 1998).
Other antioxidants have also shown beneficial effects in people with HIV. A study involving 331 AIDS patients found that when patients received supplements including various carotenoids (natural pigments with antioxidant properties), as well as multivitamins and minerals, mortality rates were lower, and CD4 T cell counts were higher, compared with patients who received the same supplementation without the carotenoids (Austin 2006). In HIV-infected patients following a stable HAART regimen, the use of broad-spectrum, high-dose micronutrient supplementation with antioxidants corresponded with a 24% increase in CD4 cell count (Kaiser 2006). Other important antioxidants that have been highlighted in the HIV literature include:
Glutathione is thought to be an extremely important antioxidant for HIV-infected patients, because it appears to interfere with HIV’s entry into its target cells (Markovic 2004). Glutathione deficiency—a common finding in HIV (Morris 2012)—is associated with compromised T-cell function and decreased survival (Herzenberg 1997). Some nutrients that offer a host of health benefits also assist in the production of glutathione. One of these is N-Acetylcysteine.
N-acetylcysteine (NAC) is of particular interest for people with HIV/AIDS, because it reinstates glutathione levels and has been found to maintain glutathione concentrations (Fawzi 2004; McComsey 2003), improve T-cell counts, and reduce viral load in patients with advanced AIDS (McComsey 2003; Standish 2001; Tantcheva 2003). In many studies, the use of NAC oral supplements has correlated with better quality of life and patient well-being (Atkuri 2007). A study involving 81 HIV-infected patients showed that 8 weeks of oral NAC supplementation correlated with significant improvements in whole blood glutathione concentrations, as well as increased T-cell glutathione levels (De Rosa 2000). NAC is known for exerting antioxidant effects against the activity of glycoprotein 120 (gp120) (Visalli 2007), an HIV protein that induces oxidative stress during the infection of macrophages (a type of white blood cell) (Visalli 2007).
Green tea leaves contain compounds called catechins, which have powerful antioxidant properties. The most abundant catechin in green tea, epigallocatechin gallate (EGCG), has also been found to suppress HIV (Li 2011). Kawai and colleagues found that EGCG can bind to T-cells and block the virus from attaching to them (Kawai 2003). When HIV comes into contact with a helper T cell in the human body, glycoprotein 120 (gp120) on its surface binds to a CD4 receptor on the surface of the T cell, ultimately leading to infection (Nance 2009). In several studies, EGCG blocked the attachment of gp120 to CD4 cells with varying degrees of inhibition (Williamson 2006; Kawai 2003). EGCG also appears to lower the risk of HIV transmission—normally, fibrils in human sperm collect HIV viruses and deliver them to target cells. EGCG inhibits this activity and degrades the fibrils, thereby lowering transmission risk (Hauber 2009). EGCG has also been found to inhibit a variety of HIV subtypes at physiologic concentrations without damaging human cells (Nance 2009). When coupled with other nutrients (vitamin C or lysine), green tea extract inhibited the production of HIV in chronically infected T cells; in latently infected cells, combining the green tea extract with vitamin C and amino acids resulted in significantly greater suppressive action than when any of the three were applied individually (Jariwalla 2010).
This powerful antioxidant plays a central role in the defense against free radicals (Shay 2009). It also recycles other important antioxidants, including glutathione (Shay 2009), and decreases intracellular signaling that promotes inﬂammation (Zhang 2007). Taking a 300 mg supplement of alpha-lipoic acid three times per day for six months significantly elevated blood glutathione levels in a group of HIV-infected men and women aged 44-47 years (Jariwalla 2008). In the lab, alpha-lipoic acid has been shown to inhibit HIV replication (Baur 1991). Its ability to scavenge reactive oxygen species has been found to block nuclear factor-kappa B, a transcriptional activator that is instrumental in the regulation of HIV gene expression (Suzuki 1992). In a study by Merin and associates, applying alpha-lipoic acid to cells infected with HIV completely stopped “initiation of HIV-1 induction by [tumor necrosis factor-alpha] (Merin 1996)."
Also an antioxidant, acetyl-L-carnitine (ALC) boosts immune function and helps the body convert fat into energy. A number of studies have reported positive effects of ALC supplementation in people with HIV, especially its positive impact on the side effects of certain antiretroviral drugs. People with HIV who use the NRTIs zalcitabine, didanosine, or savudine often experience peripheral neuropathy (peripheral nerve damage) and myopathy (muscle tissue disease) (Youle 2007a). These outcomes have been observed in other NRTIs as well and can discourage patients from adhering to their medication regimens (Youle 2007a). However, ALC may help to mitigate these effects.
ALC is known to be involved with peripheral nerve regeneration (Hart 2004). In a small study by Osio and associates (n=20), taking 2,000 mg of oral ALC each day for a month led to significant reductions in pain intensity scores among HIV-infected patients taking antiretroviral therapy (Osio 2006). A larger study involving 90 HIV-positive patients with antiretroviral toxic neuropathy found that taking 500 mg of ALC intramuscularly twice per day for 14 days resulted in statistically significant improvements in weekly mean pain ratings versus placebo. When these patients subsequently took 1,000 mg of oral ALC twice per day for six weeks, symptomatic improvements were observed (Youle 2007b). A cohort study involving 21 HIV patients with NRTI-related neuropathy who were reviewed after receiving acetyl-L-carnitine for a mean of 4.3 years, 13 of the 16 patients who completed the study reported "very much or moderate" symptomatic improvement, and 9 were pain-free (Herzmann 2005). Hart and associates observed that when HIV-infected patients with antiretroviral toxic neuropathy took ALC treatment, 76% of patients experienced reductions in neuropathic pain (Hart 2004). In a small study involving 21 participants, receiving 3,000 mg of ALC daily for 24 weeks corresponded with improvements in subjective pain ratings (Valcour 2009). A very small review and meta-analysis of 14 studies that described various analgesics did not find a significant benefit of taking 1 gram of ALC daily in treating HIV-associated sensory neuropathy; the authors pointed out that this review was limited by the small number of eligible studies, as well as the differences in study designs and size, which made comparisons across studies difficult (Phillips 2010).
Certain vitamins have amassed a notable amount of clinical evidence to highlight their potential supplemental value in people with HIV:
Vitamin D has a multitude of important functions within the human body, including its roles in supporting proper immune function, regulating bone metabolism, and maintaining calcium and phosphorus homeostasis (Bikle 2009; Holick 2006). In people with HIV, vitamin D deficiency is common, as is lower-than-normal bone mineral density (Rodríguez 2009; Conrado 2011; Adeyemi 2011; Dao 2011; Kim 2011; Fox 2011; Giusti 2011; Gutiérrez 2011; Guillemi 2010). Additionally, people with HIV appear to be at an increased risk of osteopenia and osteoporosis (Gutiérrez 2011; Rodríguez 2009; Post 2011). In a recent review of the medical literature, McComsey and colleagues concluded that HIV infection should be regarded as a risk factor for bone disease (McComsey 2010).
Deficient levels of vitamin D in HIV-infected individuals may be due to the virus itself (Gutiérrez 2011; Conrado 2011) as well as to the effects of antiretroviral treatment (Lake 2011; Gutiérrez 2011; Conrado 2011; Fox 2011; Conesa-Botella 2010; Mueller 2010; Rodríguez 2009; Van Den Bout-Van Den Beukel 2008). Tenofovir, for example, is a widely used NRTI that is associated with low bone mineral density (Stellbrink 2010; Carr 2010; Grund 2009; Gallant 2004), as well as increased levels of parathyroid hormone (PTH) (Childs 2010). (Increased PTH levels are associated with decreased bone mineral density (Childs 2010).) Non-nucleoside reverse transcriptase inhibitors (NNRTI) have also been implicated in vitamin D deficiency; one in particular—efavirenz—has been linked to low concentrations of 25-hydroxyvitamin D (the form of vitamin D that is measured to determine vitamin D status in the human body) (Welz 2010; Fox 2011; Dao 2011).
As people with HIV continue to live longer, bone loss prevention becomes an even more prominent consideration in this aging population (Post 2011). Some studies have shown a correlation between vitamin D status and CD4 counts (Villamor 2006; Adeyemi 2011; Welz 2010; Stein 2011; Ross 2011), while others did not find this relationship (Dao 2011; Arpadi 2009). Interestingly, some studies that detected vitamin D deficiencies in HIV patients found that uninfected individuals also had low levels of vitamin D (Dao 2011; Adeyemi 2011). In the United States, vitamin D deficiency is highly prevalent in the general population, regardless of HIV status (Dao 2011).
Beta-carotene is a plant pigment found in colorful fruits and vegetables and is converted into vitamin A in the body. It plays important roles in human growth, vision, and its support of the immune system. In people with HIV who were given 100,000 international units (IU) of vitamin A from beta-carotene daily for 4 weeks, white blood cell counts rose 66%, and T-helper cells rose slightly. Six weeks after cessation of the beta-carotene treatment, the immune-cell measurements returned to pretreatment levels (Fryburg 1995). In a Uganda study involving 181 children with HIV, vitamin A supplementation was associated with significantly lower mortality rates, as well as improvements in chronic diarrhea and persistent cough (Semba 2005). In another study, 687 children in Tanzania with pneumonia received 400,000 IU of vitamin A at baseline, as well as 4 months after discharge, and, then 8 months after discharge. None of the children showed any signs of vitamin A deficiency when they started treatment. Vitamin A supplementation was associated with a 49% drop in mortality and a 92% decrease in diarrhea-related deaths. Plus, AIDS-related deaths plummeted 68% (Fawzi 1999). In a population in South Africa that is not generally vitamin A deficient, children with HIV-infected mothers received 50,000 IU of vitamin A at ages 1 month and 3 months, 100,000 IU at 6 months and 9 months, and then 200,000 IU at 12 months and 15 months; this resulted in a significant reduction in morbidity from diarrheal disease (Coutsoudis 1995). In a U.S. study involving HIV-infected children, the use of vitamin A supplementation prior to influenza vaccination muted the increase of HIV viral load post-immunization (Hanekom 2000).
Kennedy-Oji and associates observed improved weight retention among South African HIV-infected women with vitamin A supplementation (Kennedy-Oji 2001). Conversely, vitamin A deficiency in HIV-positive women has been associated with increased mother-to-child transmission of the infection (Semba 1994). However, the potential value of vitamin A supplements in pregnant women with HIV remains questionable, particularly as some studies have indicated that vitamin A supplementation may increase the HIV load in breast milk (Villamor 2010) and may potentially elevate the risk of HIV transmission from mother to child (Wiysonge 2011). A recent review of studies encompassing 6,517 women with HIV in South Africa, Zimbabwe, Malawi, and Tanzania found that vitamin A supplement use among HIV-infected pregnant women correlated with improved birth weights; although the review found no evidence that vitamin A supplements increase the risk of mother-to-child transmission of HIV, the authors pointed out the moderate quality of scientific evidence in these studies.
B vitamins are responsible for an array of important functions within the body, including proper functioning of the brain and immune system (Kaplan 2007; Rall 1993). A number of reports have documented the beneficial effects of B vitamin supplementation in people with HIV. In a study involving 281 HIV-infected patients, taking vitamin B6 (more than 2 times the RDA), vitamin B1 (more than 5 times the RDA), or vitamin B2 (more than 5 times the RDA) was independently associated with improved survival (Tang 1996). In 108 HIV-infected men tracked over an 18-month period, low B12 levels at the beginning of the study were significant predictors of faster disease progression (as determined by CD4 cell count); although the development of B12 deficiency corresponded with a drop in CD4 cell count, the normalization of vitamin B12 levels corresponded with higher CD4 cell counts (Baum 1995).