Compelling evidence has also been accumulating for the following:
Omega-3 Fatty Acids
Omega-3 fatty acids are essential oils—they are not made in the body and must be consumed from external sources. Their anti-inflammatory and immune-modulating capabilities make them a valuable component of general health (Wall 2010); additionally, they appear to have therapeutic value for people with HIV who suffer from high triglyceride levels. A number of published medical reports have described changes in lipid metabolism, increased levels of serum triglycerides, and low levels of HDL cholesterol in people with HIV; moreover, combination antiretroviral treatment is reported to be a risk factor (Grinspoon 2005; DAD Study Group 2007; Hellerstein 1993; d'Arminio 2004). A combination of dieting and omega-3 supplements (6 g per day) was found to cause a major drop in serum triglycerides and levels of arachidonic acid (Woods 2009). A small systematic review found that varying doses of omega-3 fatty acids caused significant reductions in triglyceride concentrations in people with HIV who were taking antiretroviral therapy (Oliveira 2011). A study involving 48 HIV-infected patients (47 males, 1 female) with HAART-associated hypertriglyceridemia found that a 12-week course of omega-3 fatty acids (4 g per day) led to significant reductions in triglyceride levels compared with placebo (Peters 2011). Wohl and associates found that omega-3 fatty acids (in the form of fish oil supplements), plus dietary and exercise counseling, lowered fasting triglyceride levels in HIV-infected patients with hypertriglyceridemia taking antiretroviral medication; however, the difference was not significant compared with participants who received counseling without the fish oil supplements (Wohl 2005). In other studies of HIV-infected patients with elevated triglyceride levels who were using antiretroviral therapy, omega-3 supplementation was associated with significant decreases in triglycerides (Carter 2006; Gerber 2008; De Truchis 2007).
Whey protein contains all essential and nonessential amino acids, which are important for maintaining an adequate immune system response. Whey is also an important supplement to help boost the body’s synthesis of glutathione, and various therapeutic benefits, including its immune-enhancing properties, make it of great interest to people with HIV (Marshall 2004). In a study involving 41 HIV-infected patients, those who received 40 g of whey protein each day benefitted from a CD4 count increase of 31 cells/µL, versus the control group, which showed a decline of 5 cells/µL over the same 12-week period (Sattler 2008). Whey protein has been found to improve immune function, elevate cellular glutathione levels, and maintain muscle mass (Marshall 2004; Micke 2002). Although large randomized controlled trials will impart greater insights into the potential benefits of whey protein in patients with HIV, the results so far are encouraging (Hummelen 2010).
Lactoferrin is derived from whey protein. It has been found to inhibit viruses by binding to viral receptor sites, thus preventing the virus from infecting healthy cells (van der Strate 2001). In vitro studies show that lactoferrin is an effective inhibitor of HIV entry (Swart 1996, 1998; Berkhout 2002). It may also effectively inhibit initial HIV infection by blocking uptake into epithelial cells and transfer from dendritic cells to CD4+ cells (Carthagena 2011)
One study that compared 22 asymptomatic and 45 symptomatic patients with HIV to 30 healthy control subjects found that plasma lactoferrin levels were decreased in patients infected with HIV (Defer 1995). In a six-month trial involving 22 HIV-1-infected children, oral lactoferrin caused a small decrease in viral load and an increase in CD4+ cell numbers; lactoferrin plus antiretroviral therapy was more effective than lactoferrin alone (Zuccotti 2006).
Coenzyme Q10 (CoQ10)
CoQ10 is present in all cells of the human body and is essential for proper cell function. Low levels of CoQ10 have been detected in people with HIV, and one study found that the level of CoQ10 deficiency corresponds with the stage of HIV infection (Folkers 1988). CoQ10 supplementation increases a number of immune parameters, including T-cell counts (Folkers 1991; Yamashita 1997), an important consideration in HIV. A known antioxidant, it has also been found to contribute to the improvement of antioxidant defenses in HIV-infected men when administered as part of a regimen consisting of various antioxidants (Batterham 2001). In a case study involving a 52-year-old man with HIV, the patient suffered from drug-related skeletal myopathy caused by zidovudine. Daily supplementation of CoQ10 led to recovery, allowing the patient to continue his HIV drug treatment (Rosenfeldt 2005). Cherry and associates tested a water-soluble formulation of CoQ10 on cultured rat cells and found that it was effective in preventing neurotoxicity caused by d4T (stavudine; the HIV medication most commonly associated with neuropathy) (Cherry 2010). Although studies on the effects of CoQ10 in HIV are limited, findings so far highlight this as a promising area for further study.
Selenium is required for proper immune system function (Look 1997) and facilitates a multitude of antioxidant activities in the body (Hoffmann 2008; Tinggi 2008). It also decreases the effect of inflammatory cytokines, which may reduce the risk of developing neurological damage, Kaposi's sarcoma (a common HIV-associated cancer), and wasting syndrome (Baum 2000). In people with HIV, selenium deficiency has corresponded with disease progression to AIDS or death (Campa 1999; Baum 2000; Look 1997). Shor-Posner and colleagues found that, among HIV-infected drug users, low selenium was a significant risk factor for developing mycobacterial disease (Shor-Posner 2002). The HIV-inhibiting effects of selenium have also been observed in human cell cultures (Hori 1997; Kalantari 2008). In human studies, selenium supplementation has been found to reduce the incidence of diarrhea and decrease the number of patient hospitalizations (Kupka 2009; Burbano 2002).
Zinc and Magnesium
On average, patients with HIV/AIDS who have low zinc levels have a higher viral load and lower T-cell counts (Ferencik 2003; Rousseau 2000). A U.S. study of 231 HIV-infected adults found that taking zinc supplements every day for 18 months reduced the rate of diarrhea by more than 50% compared with placebo and lowered the risk of immunological failure by 400% (CD4 T cell counts of <200 cells/µL). However, it did not affect viral load, nor did it have an impact on mortality (Baum 2010; Mehta 2010). In a literature review of six human studies involving 1,009 participants, the use of zinc supplements appeared to decrease opportunistic infection among adults and children with HIV. Only the adults were found to have higher CD4 counts; no adverse events were reported for adults or children from using zinc supplementation (Zeng 2011).
Some antiretroviral drugs appear to chelate magnesium post-interaction with integrase. Therefore, supplemental magnesium may ensure that magnesium levels are not depleted (Liao 2010).
The human gut contains naturally growing bacteria that possess an array of beneficial functions; these include their ability to provide essential nutrients to the body, break down foods that are otherwise indigestible, via fermentation reactions, for example, and prevent the growth of harmful pathogens (Hooper 2001; Ley 2006). However, the gut is largely compromised in patients with HIV. Acute HIV infection is marked by the dramatic depletion of CD4+ cells from the gastrointestinal (GI) tract. The GI tract is believed to be a particularly attractive target for HIV replication because the CD4 cells it contains are primarily CD4+ memory cells, which are are preferential targets for HIV replication. (CD4+ "memory" cells are named as such because they "remember" antigens they previously encountered; this allows them to mount a more rapid response in subsequent encounters.) Moreover, the CD4+ cells in the GI tract express substantial amounts of CCR5—a receptor commonly used by HIV to enter and infect cells (Mehandru 2005; Johnson 2008). As HIV depletes the gut of immune cells, intestinal epithelial permeability generally increases, and the human host becomes increasingly vulnerable to microbial invasion and disease progression (Brenchley 2008).
Probiotics are living microorganisms that, when provided in sufficient quantities, impart health benefits. Certain strains of probiotics are associated with reduced inflammation (Furrie 2005; O'Mahony 2005; Braat 2004) and permeability (Isolauri 1993; Madsen 2001; Ukena 2007), both of which are of notable interest for patients with HIV. In several studies involving people with HIV/AIDS, consuming probiotics was associated with improvements in CD4 cell counts (Trois 2008; Anukam 2008; Irvine 2010). More recently, Hummelen and colleagues found that adding probiotics to micronutrient-fortified yogurt did not boost CD4 cell count after one month, versus the same preparation without the added probiotics; although the added probiotics were well tolerated, and no adverse events were reported (Hummelen 2011). Larger clinical studies with longer follow-up periods are needed to fully assess the impact of probiotic supplementation on people with HIV, but results so far are promising.
Reishi (Ganoderma lucidum, or lingzhi) is a mushroom native to Asia that has been a highly valued part of traditional herbal medicine for centuries (Sanodiya 2009). It has been used to treat a wide range of health problems and promote long life, but is most commonly used as an immune-enhancing supplement (Sanodiya 2009; Batra 2013). Several studies have demonstrated reishi’s immune-potentiating ability (Jin 2012). A preliminary study included five female monkeys with simian acquired immunodeficiency syndrome, caused by inoculation with a virus that is closely related to HIV, called simian immunodeficiency virus. Three of the monkeys received reishi extract and two received no treatment for one year. Treated monkeys had a higher survival rate (2/3 vs. 0/2) and the surviving monkeys experienced a decrease in viral load and less damage in lymphatic and other tissues (Lu 2011).
Reishi’s active constituents include triterpene compounds and polysaccharides; these constituents are central to reishi’s anti-viral and anticancer effects, as well as reishi’s ability to stimulate immune cells (Boh 2013; Gill 2016; Kladar 2015). Triterpenes and related compounds from reishi have been found to have specific anti-HIV-1 activity (el-Mekkawy 1998; Min 1998; Akbar 2011). Reishi also contains proteins, fibers, phenolic compounds, minerals, vitamins, and other potentially beneficial constituents (Batra 2013; Sanodiya 2009). Extracts from reishi have been found in laboratory and animal studies to modulate both innate and adaptive immunity, stimulating macrophages, T cells (both CD4+ and CD8+ T lymphocytes, as well as others), B cells, dendritic cells, and natural killer cells, and altering the balance of other chemicals, called cytokines, that regulate immune cell activities (Lin 2005; Guggenheim 2014). Both its antiviral and general immune-enhancing properties make reishi extract a good choice for individuals with HIV infection.