Inflammation! It's in the news these days as our understanding of biology and the disease process deepens. Is inflammation an inevitable and unchangeable consequence of aging with HIV, or are there things we can and should do about it?
Our bodies have a remarkable capacity to respond to assaults from our environments. Infections, excessive sun, injuries and toxins can all challenge our health and well-being. These responses operate everywhere, from the surface of our skin to the marrow of our bones -- but challenges can reduce their capacity to respond adequately or safely.
If we keep living long enough, we start to face the simple realities of aging and deteriorating. Some people start out with weaknesses that may result in conditions like asthma or arthritis. And now that inflammation has been implicated in a range of disorders that become more prevalent as we age -- such as heart disease, cancers and dementia (e.g., Alzheimer's disease) -- there may be a wider array of therapeutic implications than previously considered.
HIV represents an insidious assault, and inflammation figures big in the mix. For years, many scientists have recognized that the infection results in a kind of accelerated senescence, or rapid rate of aging, that manifests from the cellular level to the way our organs function. The first line of defense against any pathogen (or infectious agent like HIV or syphilis, etc.), is what is known as the innate immune response. (Noted researcher Jay Levy recently included the innate immune response as one of six key areas of HIV research he believes should get more attention.) The innate immune response is characterized by a variety of white blood cells known as neutrophils, natural killer cells, basophils, eosinophils and others. If this doesn't deal with the problem, a specific immune response arises, represented by T cells (CD4+ and CD8+ lymphocytes) and B cells. The B cells excrete antibodies that bind to the pathogen or to an infected cell, targeting them for destruction by macrophages or cell-killing (cytotoxic) CD8+ cells.
This immune response is undertaken via intense communication between the cells. How does one cell talk to another? One important way is the release from cells of proteins known as cytokines. Some of these are associated with inflammation, particularly tumor necrosis factor alpha (TNF) and interleukin-6 (IL-6) as well as other markers like d-dimer, C-reactive protein, hyaluronic acid, intestinal fatty-acid binding protein, soluble CD14 and lipopolysaccharide. These are elevated in untreated HIV disease and, even with treatment, often remain chronically elevated.
The problem here is that the inflammatory cytokines and activities can have a number of deleterious effects on the body's tissues, whether the lining of the gut, the arteries that carry blood from the heart or the neurons of our brains and peripheral nerves. These organs are all affected by HIV -- and the damage goes on even among people on antiretroviral therapy whose virus is below detectable. In addition, antiretroviral therapies can add some degree of toxic burden because the way they work can cause damage to healthy cells and tissues.
So what can be done about all this? How can we augment the effects of antiretroviral therapy to thwart the damage of the residual HIV, offset those toxicities and live a healthier, happier life?
Probably the first and best is staying active and exercising! While this actually can in itself cause inflammation (sore muscles, anyone?), the strength conferred to lean tissue provides a buffer against the damage. And of course, exercise can be vital to manage weight and the extra inflammation and stress caused by obesity.
Obviously, nutrition is also a key part -- you have to have the fuel for the body to be able to respond more appropriately and have the tools it needs in the form of essential vitamins and minerals (micronutrients) to function properly. Eating well is important for all people -- and makes extra good sense in this context.
Avoiding the bad foods that contribute to inflammation is critical. These include processed foods and meats, too much sugar (especially bad sugars like high fructose corn syrup), alcohol and pretty much all soft drinks. But if you must have a soft drink, natural ginger ale made from real ginger is a good option.
There are lots of good foods to eat. For example:
- Pick your fats, proteins and carbs wisely. Healthy fats include fish oils (wild is better), flax oil and nuts like almonds, Brazil nuts and others.
- Green leafy vegetables like spinach, kale and others are filled with chlorophyll, carotenoids and other important nutrients.
- Quercetin, a potent anti-inflammatory is found naturally in apples, onion and garlic.
- Turmeric contains curcumin, which has demonstrated a range of values in reducing inflammation and improving gut function.
- Eating a good amount of yogurt and other delicious fermented foods like sauerkraut, along with enough fiber, can help provide the gut with healthful bacteria needed for digestion of foods, and absorption and even synthesis of micronutrients.
Do Supplements Have a Role?
Given that HIV's damage is focused on the gut, there is little wonder that the blood level of most micronutrients declines. Among adults not on treatment, a recent study suggested that a very simple and inexpensive multivitamin could slow disease progression a whopping 40%! This isn't a replacement for antiretroviral therapy, obviously, but it may give millions the time they need to get access to first- or second-line drugs. Some 25 million people in the world are clinically eligible for antiretroviral therapy (CD4<500) but do not yet have access.
This dramatic clinical effect may be explained in part by the biology of these essential agents in our diet. When there is an excess amount of inflammation, these nutrients are critical for dampening those excesses by helping metabolism function properly.
Probiotics, as I note in a recent article, can add a great deal to help improve gut function.
N-acetylcysteine (NAC) and alpha lipoic acid have been mainstays of my own treatment for hepatitis C in order to help reduce the damage caused by the inflammatory response to that virus. These are critical antioxidants that help to regenerate the body's natural antioxidant defense system, the simple and elegant glutathione molecule. This is one of the important pathways to chronic, unchecked inflammation that can be addressed. NAC may also help reduce levels of IL-6 and CRP.
Other inflammatory responses like prostaglandin E2 generation may be offset by omega-3 fatty acids, which probably are best gotten from food. However, supplements may make up for a deficient diet and may provide other benefits. Vitamin D3 is also important in this regard and you should check your blood levels.
We still need good clinical trials to assess these kinds of options, not only to see how markers of inflammation and translocation might be reduced, but whether this has a meaningful and important clinical benefit in people with HIV.
George M. Carter is administrator for the New York Buyers' Club (NYBC) and founder/director of the Foundation for Integrative AIDS Research (FIAR). He has been undertaking systematic reviews and meta-analyses of various questions around integrative medicine and HIV with a team at the Mount Sinai School of Medicine.