MEDIBOLICS™

 

Wasting Syndrome
Treatment Advocacy Issues

Complementary Treatments for Lipodystrophy

With Suggestions to Improve Insulin Sensitivity

by Michael Mooney

(The original version of this article titled Protease Inhibitors and Potbellies was published in
Medibolics Volume 2, Number 2, Nov. 1997. I update parts of it as I learn more. The protein nutrition section of this version was updated June 19, 1999. Minor changes were made in the section on growth hormone on August 4, 1999. A recommendation regarding the Atkins diet was added August 20, 1999. Changes in the dietary fat section were added January 14, 2000.)

 

While the protease inhibitor (PI) cocktails can bring viral loads down to undetectable levels and have given many people with AIDS (PWAs) a new lease on life, protease inhibitors are not always benign drugs. As we approach year three of the triple-combo era, numerous problems have appeared among people who are on protease inhibitors. One of the most common of these side effects (and perhaps the least understood) is the protease belly or "Crix belly" phenomenon. Crix belly, so named because it was mostly observed among people being treated with Crixivan, is a condition most notably marked by the appearance of a large protruding potbelly. (At the same time this is happening some people report that they feel like they are losing muscle mass and fat, too, especially in the arms and legs.) Another sometimes concurrent but rare condition is the so-called "buffalo hump," which is a fat pad that grows on the back of the neck that resembles what is seen in Cushing's syndrome. Women are also experiencing an increase in breast size as the breasts seem to gain fat (called lipoma), and many people are losing fat in their cheeks while one or all of these other things are happening to them. "Lipodystrophy" is the medical term that has been given to this syndrome, but it can also simply be called "bodyfat redistribution."

It now appears that lipodystrophy is not a side effect entirely specific to Crixivan, but may be seen with the usage of any of the available protease inhibitors, and has even been seen to a lesser degree in HIV patients before protease inhibitors were available. However, the various cocktails of powerful drugs being used today to combat the HIV virus seem to increase the severity of this syndrome over the simpler drug combos of a few years ago. And in some cases, the addition of the appetite stimulant Megace to the protease inhibitors seems to increase the potential for bodyfat redistribution.

There are several reasons why this might happen. Crix-belly in many respects resembles the potbelly seen in disease states like Cushing's syndrome, alcoholic hepatitis, and heart disease. In these diseases the potbelly is associated with the development of insulin resistance1-3 and is primarily composed of enlarged fat deposits surrounding the visceral organs, like the stomach, and kidneys, under the abdominal muscle wall.4

The potential for liver burden or toxicity induced by many of the common AIDS medications has been documented and the protease inhibitors are no exception to this rule. Elevated triglycerides, liver enzymes, and blood glucose and even diabetes have all been observed in patients on protease inhibitor therapy. All of these conditions are symptoms of diminished insulin sensitivity, so it is probable that the protease inhibitors' effects on liver metabolism are inducing a state of insulin resistance in patients on protease inhibitor therapy.

Complications of insulin resistance include hyperglycemia (high blood sugar), diabetes, and cardiovascular disease, and the FDA has recently documented over 80 cases of diabetes that appear to be associated with protease inhibitor therapy. Indeed, from early 1998, numerous studies have documented an association between the use of protease inhibitors and measurements that indicate insulin resistance is present including data by Kathleen Mulligan, Ph.D. of San Francisco General Hospital, confirming that protease inhibitors can cause the blood chemistry changes that are typical of insulin resistance;61 Dr. Ravi Walli of Ludwig-Maximilians Universitat Munchen in Germany reporting that peripheral insulin resistance is common in patients on protease inhibitors;62 and Dr. Andrew Carr of St. Vincent's Hospital of Sydney, Australia, detailing his hypothesis of the cytoplasmic (cellular) retinoic acid-binding protein type I (CRABP-1) biochemistry involved in the liver dysfunction that may promote insulin resistance.63

Additionally, some people who are using protease inhibitors are being found to have accelerated cardiovascular disease, which is also a common outcome of progressive insulin resistance.

A look at Harrison's Principles of Internal Medicine shows us that lipodystrophy can be associated with insulin resistance, and so we see that the components in this puzzle, lipodystrophy, elevated triglycerides, elevated blood glucose, elevated insulin levels, diabetes, cardiovascular disease and insulin resistance are all appearing.

While this article does not offer a "cure" for bodyfat redistribution as protease belly, buffalo hump, loss of facial fat, or lipoma, it offers tools that are documented to improve insulin sensitivity that may help people gain some control over some aspects of this problem until medical science gains enough of an understanding to solve it.

Does Crixivan Lower Testosterone?

Several doctors I have spoken to have told me that they have seen that Crixivan can lower testosterone production, and low testosterone production is known to correlate with increased insulin resistance in men.5

In contrast, women exhibit insulin resistance when testosterone is elevated.6 However, low testosterone does correlate with increased visceral fat in studies with HIV-negative women.7 One study showed that about 50 percent of HIV-positive premenopausal women have low testosterone levels, which was associated with low body cell mass, and a tendency towards having fat mass that is above normal.38

It may be that normalizing a testosterone deficiency while being careful about keeping testosterone blood measurements no higher than mid-normal would be beneficial to HIV-positive women to improve nutrient partitioning away from fat tissue while lean tissue increases. This is an area that needs more investigation, as not enough has been done to study testosterone and wasting in HIV-positive women.

We also know that the antiretrovirals can cause muscle myopathy,8 so it can be several things (including low testosterone production) that might add up to a loss of lean body mass, and an increase in visceral fat.

While this remains to be proven, one of the things that was presented by Dr. Gorbach from Tufts University when he reviewed their Nutrition for Life Cohort (600 HIV+ men during 254 days on protease inhibitor combos) at the Bethesda National Institutes of Health conference, was that although people tend to put weight back on with protease inhibitors, his data assert that they regain mostly fat, not lean tissue. Note: fat weight is not correlative with survival, but lean tissue is.9 The loss of lean tissue and reciprocal gaining of fat so that total body weight stays the same, is typical of early stage wasting.10 11 This increase in fat mass again suggests an impairment in glucose disposal and insulin sensitivity.

For those who have the potbelly, I would be concerned about any apparent muscle wasting and have the blood testosterone levels checked, including both free and total testosterone. If total testosterone is low, or in some cases, even mid-normal for men, because of the tendency for HIV-positive men to have decreased free testosterone levels, which correlates with a progressive decrease in CD4 T cells,39 a doctor should consider beginning testosterone replacement therapy. We should also note that free testosterone measurements have been shown to be more correlative with lean body mass than total testosterone in wasting HIV-positive men12 and women.13

Women and Testosterone

Studies show that HIV-positive women who are losing lean body mass may also need testosterone,13 but the appropriate dosage of testosterone enanthate injections for women is usually much lower than the dosage for men, between 2.5 and 20 mg per week. This is something for a doctor to determine by taking blood tests, usually two to three days after the fourth weekly injection for a representative average level. Some HIV-positive women are using testosterone creams that are compounded by a pharmacy like Women's International Pharmacy (1-800-279-5708). However, testosterone enanthate injections deliver a longer-lasting blood level of testosterone than the creams, which have a relatively short life span in the body. If a cream is used, it is best to apply it two times per day, while the injections are best given once per week, as studies show that testosterone enanthate maintains useful blood levels for under 10 days.14

I note that I have had several women tell me that while they experience little benefit from a testosterone cream, testosterone injections give them immediate improvements in muscle tone, libido, energy, and feelings of well-being. Others do well on the creams. The typical dose of testosterone in creams for women is in the range of 2 to 5 mg two times per day. Call Women's International Pharmacy for their information packet on hormone creams.

It is also important to note that the women are much more sensitive to side effects from testosterone, so the physician should monitor a female patient closely for any virilizing side effects, which include oily skin, acne, peach fuzz, hair loss, and clitoral enlargement and immediately lower the dose or cease the therapy if these kinds of symptoms start to occur.

"Normal" Testosterone Levels May Not Be Enough (Men Only)

I should also note that finding the correct testosterone dose for each individual is not always easy, as data from studies by researchers like Dr. Judith Rabkin suggest that being HIV-positive can mean that the "normal" range for testosterone measurements does not necessarily apply to men. In her study with HIV-positive hypogonadal men, Dr. Rabkin found that the dose of testosterone enanthate needed to be above 200 mg every two weeks to improve quality of life. The dosage she found to be effective was 400 mg every two weeks (which I suggest is best given as 200 mg per week for more consistent blood levels, less peak/trough effect, and reduced potential for side effects). At 400 mg given every two weeks the men's blood testosterone levels averaged about 1100 ng/dL one week after the fourth injection (on a scale where the "normal" range is 300 to 990 ng/dL). In private correspondence Dr. Rabkin said that she is not sure whether 300 mg every two weeks would yield a satisfactory result or whether the men would respond satisfactorily if their average levels only reached 800 ng/dL. She said that some men did receive benefit at about 700 ng/dL though.15 Remember, the bottom of the "normal" scale was 300, so the "normal" scale didn't seem to apply well to these HIV-positive men. Sometimes "normal" is just a fairy tale.

Free Testosterone

I assert that men's apparent need for testosterone at higher than the standard replacement dose of 100 mg per week (for HIV-negative hypogonadal men) may be the result of hormonal resistance to testosterone. Hormonal resistance appears to happen with several hormones in HIV pathology. However, published studies suggest that the need for higher testosterone doses is most likely caused by elevated sex-hormone binding globulins and lowered free testosterone, which is common in HIV.39 42 When this is the case, total testosterone measurements do not adequately reflect the person's state of health.

Supplementing testosterone to bring free testosterone levels in the body into an optimal range can be beneficial to hypogonadal men in general, by improving the partitioning of nutrients more towards lean tissue and less toward fat tissue, especially visceral fat.16 Significant data also suggests that appropriate testosterone supplementation can improve blood lipid chemistry in ways that reduce the potential for cardiovascular disease in men who are deficient.50

Buffalo Hump

We have reports that application of the Testoderm TTS or Androderm testosterone patches directly on the buffalo hump appears to shrink it. If this works, testosterone creams, made by compounding pharmacies like Women's International Pharmacy (1-800-279-5708), might work better as the dose of testosterone can be much greater in a cream than in a patch. While a study of adipocyte (fat cell) chemistry does provide a rationale as to why application through the skin might work, application of a cream would not be likely to work to reduce the belly because of the greater distance from the skin through the stomach muscles to the fat cells inside.

Anabolic Steroids Improve Insulin Sensitivity & Glucose Disposal

One study showed that the injectable anabolic steroid nandrolone decanoate (Deca Durabolin) improved glucose disposal and lowered insulin levels when administered at 300 mg per week, while it did not have any effect at 100 mg.40 While this injectable beta esterified anabolic steroid may have a beneficial effect on insulin sensitivity another study found that it appears to enhance noninsulin-mediated glucose disposal.80 This study and other studies state that oral 17-alpha alkylated anabolic steroids, such as oxymetholone (Anadrol-50), oxandrolone (Oxandrin) and stanozolol (Winstrol) promote insulin resistance because of their effect on liver metabolism.44 58 This raises questions about using oral steroids when lipodystrophy is present.

The Paradoxical Effects of Oral Steroids

However, oral steroids decrease triglycerides (fats) because of their effect of increasing post-heparin hepatic triglyceride lipase, which breaks down triglycerides.57 59 For this reason oral steroids should help to decrease visceral fat, although they promote insulin resistance, and I have had reports of each of the oral steroids stanozolol, oxymetholone and oxandrolone reducing or eliminating the protease belly in HIV-positive males. Indeed, data from a retrospective study of 700 patients recently released by Dr. Douglas Dieterich gave inferential indication that the use of oral anabolic steroids, like Oxandrin (and injectable steroids like testosterone and nandrolone) may be highly effective in decreasing the potential for lipodystrophy-associated body habitus changes to occur.60 (Other oral steroids like Winstrol and Anadrol also have this potential benefit.) More study needs to be done to confirm this trend, though.

Human Growth Hormone (Serostim)

While human growth hormone does not appear to have an anabolic effect on the part of lean body mass that is muscle for many HIV(+) people (see the new data by Kotler) (see also Serostim Growth Hormone: How Much Muscle Does It Really Build?) and its relative weakness as an agent to increase total lean body mass is detailed in the article Cost Comparison of Anabolic Agents, growth hormone does appear to have a role in reducing lipodystrophy because of its metabolic effects, including an increase in lipid oxidation (fat burning), as was asserted by a poster presentation from Dr. Gabe Torres of New York, that was presented at the XII International Conference on AIDS in Geneva.56

It should be noted that Dr. Torres said that while five patients had partial or total reduction of fat redistribution on 5 and 6 mg doses of growth hormone, which I assert are overdoses for most people, four of the subjects (80%) suffered from either elevated glucose, elevated pancreatic enzymes, or carpal tunnel syndrome, so growth hormone at these doses increased the potential for serious health problems. Elevated blood glucose can lead to diabetes and the problems that result including cardiovascular problems, eye damage, and neuropathy; elevated pancreatic enzymes can lead to pancreatitis; and carpal tunnel syndrome is quite painful and may require surgery.

I suggest that if growth hormone is implemented, it should be considered that Serono's full vial dose is an overdose for many HIV(+) people and this may be why 5 and 6 mg dose caused these side effects. It is advisable to adjust the dose down for each individual in an attempt to gain the possible benefit without promoting the problems. At this time I have reports of a reduction of protease belly and other types of lipodystrophy with doses as low as 1 mg per day and up to 3 mg per day with no side effects. I assert that lower daily doses are safer than higher doses administered every few days, and at a correct dose growth hormone may be an important part of the tools that address the underlying metabolic problem. While growth hormone will have a less powerful effect at a lower dose, at the proper individual dose there will still be a significant effect on fat cell metabolism with significantly less potential for problems.

Exercise

Exercise, too, improves insulin sensitivity,17 so people with insulin resistance should consider some kind of regular exercise, especially weight-training, which builds lean body mass. Aerobic exercise does not build significant lean body mass. Aerobics can be useful in an effort to reduce lipodystrophy but if a person is losing lean body mass it should be avoided, at least until the person has regained any lost weight or stabilized. Aerobics will use energy that the body would normally use for rebuilding lean body mass, while accelerating the loss of lean body mass. If you are weight stable and not in danger of losing weight, to optimally burn fat and reduce lipodystrophy, I suggest doing aerobics three times per week on alternate days to weight training days, first thing in the morning on an empty stomach for best effect.

Nutritional Considerations

Carbohydrates
I would also suggest altering your diet so that it is balanced somewhat like what might be called an "evolutionary-type hunter-gatherer diet." This mean getting more protein and a moderate amount of the healthy types of fats, while eating fewer high-calorie, starchy complex carbohydrates or high-glycemic, sugary, simple carbohydrates.

Currently, many progressive nutritionists are recommending that people with insulin resistance consider reducing their total calorie intake and intake of high-calorie complex carbohydrates that can release into the blood stream quickly,18 including wheat breads and most processed wheat products. These kinds of carbohydrates actually are quite calorie dense and can upset insulin metabolism as much as sweets.19 20 They are even more problematic when included in high fat foods. (Think pizza and ice cream.) Also on the list of carbohydrates to avoid is the sugar called fructose, which is known to promote insulin resistance, and raise cholesterol.51 Look for it on ingredient panels as fructose or high-fructose corn syrup. I also underline that some people will experience a reduction in insulin resistance just by reducing the total calories in their diet, as many people simply eat too many calories. However, if you are having a hard time maintaining weight because of wasting or infection, getting plenty of healthy calories is essential for keeping and building lean body mass, so be careful about reducing your intake of food.

At the same time, I recommend an increase in the intake of complex carbohydrates sources that contain less total calories but lots of fluid and nutrients, like vegetables. Compared to grains, vegetables are more nutrient dense, and less calorie dense. While some vegetables like potatoes and carrots have high glycemic indexes, they supply good amounts of nutrients per calorie, and they do not contain a great amount of calories for their volume like grains or sweets do, so their effect on insulin production, insulin resistance and bodyfat accumulation is not as great. (Carrots contain only 195 calories per pound, boiled potatoes contain 450 calories per pound, while breads contain about 1200 to 1500 calories per pound, and sugar and sweets contain about 1700 calories per pound.)

Other good carbohydrate sources are beans, yams and green peas, and whole fruits like oranges, grapes, apples, pears, and cherries. In other words try to eat natural food carbohydrate sources that are "one step away from nature".

If you do want to include grains in your diet, barley, cream of rye, oatmeal and brown rice have relatively lower glycemic indexes than most wheat products, but be careful to moderate the total amount of these high calorie starch sources. If you include them in your diet, I suggest eating servings that are about one third as much you'd really like to eat. (Again, try to moderate your total carbohydrate calories if your goal is to reduce insulin resistance.)

While a high-carbohydrate diet has been recommended by some nutritionists for conditions of insulin resistance (diabetes), a study by Chen of Stanford University, showed that a lower-fat, higher-carbohydrate diet led to higher day-long blood glucose, insulin, and triglycerides, as well as post-prandial (after a meal) accumulation of triglycerides, and increased VLDLs (very low density lipoproteins),55 which can increase the risk of cardiovascular disease. The idea that lower carbohydrates diets are superior is supported in an article in Nutrition Reviews by dietitian Nancy Sheard, who said,"Recent studies indicate that a diet high in monounsaturated fat and low in carbohydrate can produce a more desirable plasma glucose, lipid, and insulin profile."77 A study published in the Journal of the American Medical Association further supported this approach when it showed significantly elevated triglycerides and LDL cholesterol levels with a high carbohydrate diet, while a high-monounsaturated fat diet let to a lower-risk lipid profile.78

Fats
While it is also best to reduce any excessive intake of fats, I generally don't advocate a very low-fat diet, which might compromise immune function, but a reduction in excess saturated fats, found in animal fat products like butter and lard, and excess omega-6, an essential fatty acid that is found in common vegetable oils, like corn, safflower, and sunflower oils that appear in so many of the most popular foods.

While we need a small daily intake of omega-6 fat, and data suggests that we probably need a small amount of saturated fat to be healthy, most Americans get far too much of these two types of fats, and excess saturated fats and omega-6 fats can promote insulin resistance.52 68-70

At the same time I recommend purposely getting some regular intake of fresh food sources of the essential fatty acid called omega-3, which can reduce insulin resistance,52 and reduce the potential for atherosclerosis and heart attacks.65 66 Americans typically get about 1/4 as much omega-3 as we need to be healthy.

Omega-3 fats are found abundantly in cold water fish like salmon, sardines, tuna, rainbow trout, anchovies, and herring, and in lesser amounts in flax seed oil, some nuts and seeds and beans, like walnuts, pumpkin seeds and soy beans, and in much smaller quantities in dark green leafy vegetables.

Consider also including some daily consumption of monounsaturated fats from sources like olive oil and avocados. These too can help to normalize blood fats and reduce the risk of cardiovascular disease.

Data also suggests that high amounts of saturated fat in the diet promotes more bodyfat accumulation compared to polyunsaturated fats,85 86 so if you want to be lean, eat clean.

Finally, avoid eating any food that contain artificial fats or processed fats, like hydrogenated or partially hydrogenated oils. Partially hydrogenated oils are found in foods like margarine, french fries, potato chips, shortening, many baked goods, and mayonaise. Harvard researchers have found a very strong link between these types of unhealthy fats and cardiovascular disease.79

It is important to state that people should experiment with the amount of fat that they take in. Some people have reported that they have had the most success in reducing the pot belly or any type of bodyfat accumulation by reducing their fat intake substantially, so that their total fat intake is only about 10% of total calories. If you eat a low fat diet it becomes all the more important to be very selective about the sources of the fats you eat, as your immune system and overall health depend on getting a certain amount of the essential fatty acids on a daily basis.

If a low fat works for you, consider using an essential fatty acid supplement, and I recommend Udo's Choice Ultimate Oil Blend, which is available in natural food stores. Udo's Choice has a specific balance of omega-3 and omega-6 fats, favoring omega-3, so that you are getting a consistent source of these two essential fatty acids.

Protein
HIV has protein malnutrition as a common theme; a lack of optimal protein intake contributes to the loss of lean body mass and makes it hard to maintain it. To reduce the potential for loss of lean body mass, or to increase lean body mass, I suggest that your dietary protein intake totals at least 0.8 grams of protein per pound of body weight per day. If you lift weights, studies by world-renowned protein scientist Dr. Peter Lemon show that you probably need at least 0.8 grams of protein per pound of body weight per day for optimal increases in lean body mass.71 72 If you are not allergic to dairy protein, consider eating cottage cheese or using it occasionally for between meal protein snacks, as cottage cheese is a "best" protein for building muscle; one reason is that it contains a substantial amount of the amino acid L-glutamine, which is discussed below.

Protein Reality Checks
Also consider supplementing your food protein with a protein powder drink two or three times per day, as it can be hard to eat enough protein to build your body with the burden that HIV creates, while it is much easier to drink it. Protein types that are contained in common protein powders include animal source proteins like whey, caseine, and egg, and vegetable proteins like soy, rice, and pea. Note that the dairy protein called caseine (seen on protein powder labels as caseinate and found in great quantity in cottage cheese) may be somewhat more effective for improving muscle growth than other proteins, like whey.73 Whey protein appears in products like Next Nutrition Designer Whey Protein. I underline that the marketing and advertising that most companies, including Next Nutrition, employ to sell their proteins, that says that one type of whey protein is superior to another type is for the most part just hype; none of the various types of whey proteins (ultra-filtered whey, ion-exchanged whey, etc.) are probably any better or worse than any other whey proteins for effect on muscle growth. And to reiterate, all whey proteins are probably slightly inferior on a dose-for-dose basis to caseine proteins for building muscle. However, it appears that if you have enough protein intake any differences in effect on muscle growth between various proteins may be insignificant; the important thing is to get plenty of protein intake, wherever it comes from.

To be clear, medical-grade whey proteins like Immunocal and Optimune can contain significant amounts of specific protein fractions, such as glutamyl-cysteine and immunoglobulins, that support various aspects of healthy immune function, but this is independent of any potential to support muscle growth. Additionally, lab tests show that Immunocal and Optimune contain these specific protein fractions in amounts that are superior to what are contained in any of the proteins sold on the bodybuilding market.

Consider also that proteins of animal origin are superior to vegetable proteins for building muscle; it is hard to increase lean body mass on a strict vegetarian diet because of the amino acid imbalances in vegetable proteins.

The Zone Diet
Although I do not agree with some of his more dogmatic concepts, my recommendations for "evolutionary, hunter-gatherer diet" nutrition have some similarities to the "zone" diet outlined in the book Mastering the Zone, by Dr. Barry Sears. While there are many aspects of the zone diet that can be criticized scientifically, I have had numerous reports that the use of the zone diet has helped people with lipodystrophy reduce blood glucose, insulin, cholesterol, triglycerides, the pot belly, and lipodystrophy symptoms in general.

The Atkins Diet
The Atkins diet is a very, very low carbohydrate, high protein, higher fat diet, that can decrease bodyfat significantly in normally healthy people. I have been hearing reports of people with lipodystrophy who have adherred to the rather strict Atkins regimen and brought their protruding belly and their blood glucose, insulin, cholesterol and triglyeride levels down to normal, so I recommend experimenting with the Atkins diet, being sure to favor omega-3 fats while reducing omega-6 fats and saturated fats - if you are capable of the discipline required. This diet may reduce lipodystrophy symptoms better than the diet I described above, but it is much harder to be consistent with the Atkins diet. It is also very hard to get enough nutrients from it for optimal health - taking dietary supplements is a must. If you do try it, please give me feedback on your results by emailing me at mmooney@icnt.net.

Dietary Supplements

Supplements that have been shown to improve insulin sensitivity include:

1. Chromium,21and I recommend 200 to 400 micrograms (mcg) of chromium three times per day in the polynicotinate or picolinate form, as one recent (non-HIV) study with diabetics showed that 1,000 mcg. of chromium per day increased insulin sensitivity by about 40 percent without toxicity.22

2. The herb silymarin (milk thistle) as a "standardized extract" in a dose of 200 mg three times per day has been shown to be effective in improving liver function and improving insulin sensitivity.41 There has been talk that silymarin can alter liver function in a way that might affect the metabolism of protease inhibitors, so it is possible that people who are taking protease inhibitors should not take silymarin. There is no conclusive data on this yet.

3. But the best supplement for improving insulin sensitivity and glucose disposal may be the antioxidant called alpha lipoic acid (ALA), at 100 to 300 mg three times per day.23 ALA improves insulin dependent and non-insulin dependent glucose uptake, and it has been shown to effectively help lower blood sugar comparable to insulin itself.24 I believe this is one very important reason ALA is a must for anyone taking HIV medications, especially the protease inhibitors. HIV-nutrition expert Lark Lands, Ph.D., also asserts that ALA is a must for people with HIV because of its effect on improving glutathione production and recycling.25 I underline the fact that studies last year at Stanford University showed that glutathione levels directly correlate with increased survival for people with HIV.26

4. Also worth considering is the dietary supplement called EPA (fish oil), which has been shown to reduce insulin resistance,52 and lower triglycerides somewhat in a study with HIV-positive men.28

5. And taking a very high potency complete multivitamin, multimineral, antioxidant supplement that includes chromium, vitamins A, D, E, and calcium and magnesium will help improve insulin sensitivity.29-33 67 I recommend taking a supplement that contains doses that are much higher than the RDAs, though, as numerous studies have shown that higher nutrient levels are required for overall health and immune function in HIV disease.53 54

6. High dose biotin supplementation is frequently prescribed by nutritionally-oriented medical doctors to improve glucose metabolism in diabetes.74 75 High dose biotin is also known to improve diabetic neuropathy.76 The dose of biotin that is commonly used is 1,000 mcg three times per day.

7. As noted by Canadian protein chemist Chester Myers, Ph.D., N-acetyl cysteine (NAC) can be a valuable addition to the supplements that address lipodystrophy, because of its effect on improving glutathione, which is necessary for glucose tolerance factor metabolism. I suggest 500 to 1,000 mg of NAC three times per day.

8. Also carnitine, as the prescription version called Carnitor, would be beneficial in higher doses, about 500 to 1,000 mg three times per day. Carnitine helps to lowers triglycerides,27 which are generally elevated when lipodystrophy is present. Note that the acetyl-L-carnitine form of carnitine may be more effective than plain carnitine, but it is more expensive.

Cardiovascular Disease

As I mentioned in the beginning of this article, we are also beginning to see cardiovascular disease in people on protease inhibitors. When cardiovascular disease is a consideration, we want to make sure that specific preventive nutrients are included. While there are many that can be included for this purpose, to keep it simple I suggest the following: Vitamin E at 400 to 800 IU three times per day to reduce the potential for oxidation of blood fats that can contribute to atherosclerosis;46 vitamin C at 1,000 to 2,000 mg three times per day to assist Vitamin E in reducing blood fat oxidation;47 folic acid at 800 mcg three times per day to reduce the potential for elevated homocysteine, which appears to be another major contributory factor to cardiovascular disease.43 48 It should also be noted that vitamins B6 at 50 mg three times per day and B12 at 200 to 500 mcg three times per day help to reduce homocysteine. Of course, everyone who is HIV positive should already be taking high doses of supplemental B vitamins, as studies by Dr. Marianna Baum, of the University of Miami, showed that HIV-positive people frequently require 6 to 25 times the RDA of these essential nutrients to stay healthy.53 54

Glutamine

For any loss of muscle, Judy Shabert, M.D., M.P.H., R.D., asserts that supplementing with high doses of the amino acid L-glutamine, will help reduce the catabolic process of breaking down muscle tissue,34 and a recent study of wasting HIV patients by Prang showed that this might be true. (See Dr. Shabert's article in the August 1997 issue of POZ magazine, and see the Prang study by going to L-Glutamine Promotes Gain In Weight and Body Cell Mass.) For frank wasting, HIV-positive people are using between 12 and 36 grams per day of L-glutamine. (One tablespoon is 12 grams.) I have friends who have halted their random diarrhea and improved their lean body mass using these kinds of L-glutamine doses, and in Prang's study wasting and diarrhea and were checked by using 30 to 40 grams of glutamine per day. Glutamine has also been shown to have a powerful effect on improving glutathione production,35 and glutamine improves insulin sensitivity.83 84

If you are losing weight I suggest that you supplement your diet with a tablespoon of L-glutamine added to each serving of supplemental protein two or three times per day between meals. If your weight is stable, L-glutamine may be supplemented at lower doses, such as one or more teaspoons per day.

Important note: most dietary supplements only stay in the blood for a few hours, so it is wise to take them several times per day.)

Metformin

Realize that while taking dietary supplements, especially alpha lipoic acid, may help, it is wise to investigate the use of the drugs that are prescribed to improve glucose disposal or insulin sensitivity. Ask your doctor about these drugs, which include Metformin.37 New data presented by Saint-Marc at the 6th Retrovirus Conference, in February, 1999, indicates that Metformin may decrease visceral fat more effectively than Serostim growth hormone while decreasing blood glucose, insulin and lipid levels.60 Serostim can increase blood glucose, insulin and insulin resistance.81 82 This means that Metformin might be found to be superior to Serostim growth hormone because it not only addresses fat redistribution, but reduces some of the underlying metabolic problems that growth hormone can promote. An important consideration is that while Serostim is priced at $6,000 per month, which makes it inaccessible for a majority of people who have lipodystrophy, Metformin is available with a doctor's prescription at any pharmacy; if a person has to pay for it themselves, it only costs about $35 per month.

However, cautions about the use of Metformin are warranted. Dr. Michael Dube, of the University of Southern California at Los Angeles says, "Lactic acidosis, which can be fatal, is a rare side effect of metformin that is more likely to occur when there is some impairment of kidney function. Lactic acidosis is also a rare side effect of use of nucleoside analogs. There is no way to know at this time if using the two together might result in more frequent or more severe lactic acidosis problems. In my opinion, metformin and NRTI's should therefore only be used together with great caution. Also, keep in mind that metformin can lower vitamin B12 levels."

Reconstructive Surgery

I also have numerous reports of people who are quite satisfied after reconstructive surgery for lipodystrophy. I should also note that I know people who have gotten rid of their potbelly simply by switching from Crixivan to another protease inhibitor. However, while Crixivan may be a promoter of lipodystrophy, it appears that any of the other protease inhibitors can also promote it.

My special thanks go to Jim Brockman, who is the first researcher in AIDS medicine to hypothesize that insulin resistance was involved in bodyfat redistribution. His guidance sparked my investigation into this important area.

References:

1. Karnieli, E, et al. Insulin resistance in Cushing's syndrome. Horm Metab Res (1985) 17(10):518-521.

2. Oehler, G, et al. Hyperinsulinaemia and impaired glucose tolerance in chronic inflammatory liver disease (author's disease). Z Gastroenterol (1981) 19(1):26-32.

3. Laakso, M, Insulin resistance and coronary heart disease. Curr Opin Lipidol (1996) 7(4):217-226

4. Bj÷rntorp, P. The regulation of adipose tissue distribution in humans. Int J Obes Relat Metab Disord (1996) 20(4):291-302.

5. Haffner, SM. Decreased testosterone and dehydroepiandrosterone sulfate concentrations are associated with increased insulin and glucose concentrations in nondiabetic men. Metabol (1994) 43(5):599-603.

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