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E 400 (Jarrow) Each bottle, 250 softgels. Each softgel, 400 IU of vitamin E (d-alpha tocopherol) along with selenium from yeast at 100 mcg and mixed tocopherols: d-alpha, 11 mg; d-beta, 1 mg; d-gamma, 50mg and d-delta, 18 mg. These other tocopherols comprise less than 2% of the formula. Other ingredients include gelatin, olive oil, glycerin, water, beeswax, lecithin, carob, anatto extract and titanium dioxide. Suggested use is one cap per day with a meal.

REMEMBER: Do not take extra vitamin E if using the protease inhibitor drug, amprenavir (Agenerase).

This is a fat-soluble vitamin that works best with the mineral selenium. It is a powerful antioxidant and helps to maintain the integrity of the membranes that surround cells. In addition, it has indirect activity against HIV. Vitamin E belongs to a class of antivirals which, in the laboratory, inhibit a section of the virus called the Long Terminal Repeat (LTR) which is basically the viral “on/off switch.” Evidence shows it helps with Hepatitis C too.

Research has shown that, like the other antioxidants, vitamin E is synergistic (works together in a more powerful manner) with other antioxidants. In particular it is recycled (returned to a state of being able to control free radicals) inside of the cell by glutathione. Glutathione, in turn, is reactivated by vitamin C. This is why it is important to take a balanced combination of antioxidant substances for the greatest effect.

A brief overview of viral growth and development:
As many of you may know, HIV, after infecting a cell, inserts its genetic machinery into the genes of the human cell in order to replicate. HIV is a retrovirus and uses RNA pieces which must be converted into DNA in order to grow. HIV uses an enzyme (enzymes, among other things, accelerate the rate reactions occur) called reverse transcriptase (RT) in order to convert its viral RNA into DNA. RT is a very error-prone enzyme, with a high mutation rate. While this often results in producing uninfective HIV, it also is flexible and helps to produce HIV’s that are resistant to the effects of various drugs, developing drug resistance.

AZT, ddI, ddC, d4T, 3TC and the non-nucleoside reverse transcriptase inhibitors, all inhibit RT, the first step in HIV’s replication cycle after the virus attaches to the cell and injects its RNA and other enzymes into the cell. The HIV-DNA is “integrated” into the cell’s DNA with the help of the enzyme, integrase. However, once the virus has used RT, the nucleoside analogs and non-nucleoside analog reverse transcriptase inhibitors (nevirapine, delavirdine, etc.) no longer control HIV replication. These cells are already infected and are known as chronically infected cells. Understanding the replication cycle of HIV is important to understand different targets in that cycle for which a therapy might have an impact.

Unfortunately, perhaps in part because of the high error rate when RT makes HIV-DNA, mutations occur in the translation of retroviral RNA into DNA. As these mutations increase in number, the structure of the viral products changes and the drugs designed to bind to the viral surfaces no longer fit properly and become ineffective. Scientists call this “viral resistance” to the particular drug. (Others suggest that viral variants are “already there” and simply take over when their drug resistant brethren are wiped out by antiviral therapy. Arguing against this notion is the observation that people seem to be initially infected with only one specific strain of HIV.)

The long terminal repeat (LTR) is the part of the HIV-DNA which controls the rate and degree of viral production. Either end of the HIV genome consists of repeating sequences of nucleotides (the LTR). In the middle are all the genes that will express other HIV proteins (like envelope proteins) when the cell is activated. But the end piece is vital for turning on the production of these proteins and controlling how much of them are produced. There are also drugs available which do not effect RT but other viral products. The best known are the protease inhibitors. Altogether, HIV makes some 15 proteins.

In order to replicate, HIV also must use parts of the human cell (referred to as “cellular” as opposed to viral parts). The good thing about these cellular components of viral growth is that they are human proteins and molecules rather than RT and are, therefore, much less likely to mutate. When cells become “activated,” their DNA is turned on to produce various types of proteins. In this process, a variety of other protein factors are brought into play to help this activation, including proteins known as transcription factors.

An important one for human cell production is called nuclear factor kappa B (NF-kB) HIV replication needs this NF-kB transcription factor (among others) in order to replicate. The NF-kB binds to the LTR which thus serves as an “on/off switch.”

NF-kB is used in many different human cells, particularly immune cells, in the activation process. NF-kB is activated by critical immune messengers called cytokines which the body uses as a signaling system between immune cells.

Many of these immune messengers have been found to be excessively produced during HIV infection and several of them, notably tumor necrosis factor (TNF), actually direct the body to produce more free radicals and are therefore called inflammatory cytokines (see antioxidant section for a review of free radicals and inflammation). TNF has been shown to upregulate NF-kB activity and thus produce more HIV.

In other words, HIV is an infection which causes inflammation in the immune system and other organs. This inflammation results in the production of free radicals. These free radicals in turn play a role in activating immune cells to produce cytokines like TNF. The TNF then activates NF-kB which in turn creates more HIV. Thus, HIV is actually forcing immune cells to produce the very inflammatory products and cytokines which increase viral growth. Free radicals also increase the production of other tissue-damaging free radicals.

Some of the cytokines may also be involved in directing uninfected cells to commit suicide. Thus a vicious, self-sustaining cycle is created called oxidative imbalance, where we have few antioxidant stores and many free radicals and increasingly damaged tissues in the lymph nodes, intestines, spleen, and elsewhere.

Antioxidants, which diminish free radicals, have in a number of laboratory studies, been shown to inhibit HIV growth by inhibiting NF-kB along the LTR. Laboratory studies of viral inhibition have been completed for vitamin E derivatives, vitamin C, glutathione (which also slows viral incorporation into acutely infected cells), NAC, alpha lipoic acid (thioctic), as well as the bioflavonoid quercetin, amongst others.

These compounds, by either stopping viral activation or slowing it down, in chronically infected cells in which RT inhibitors are ineffective, represent, at the very least, an additional mechanism for slowing disease progression.

Like other diseases, HIV will probably only be controlled with a combination of different approaches working against different areas of the virus in different virus/cell populations. It is also important to remember that this is not just a battle to fight the virus but also to improve immune function and help to repair damaged tissues. Antioxidant use represents only one part of a multifactorial combination strategy to either halt or slow down disease progression.

Back to Vitamin E:
Vitamin E is particularly important if using AZT to reduce bone marrow toxicity. Laboratory research at Tulane University revealed that vitamin E may potentiate the effectiveness of AZT and reduce AZT’s toxicity. This only makes sense if these compounds are working on different pools of virus within the body. Do not take extra vitamin E if using the protease inhibitor drug, amprenavir (Agenerase).