Lipodystrophy, or fat redistribution syndrome, is a disorder of the adipose (fatty) tissues that causes changes in the body shape due to loss and/or accumulation of body fat. Metabolic changes may also occur, causing increased resistance to insulin and abnormally high levels of cholesterol and triglycerides.
HIV-associated lipodystrophy is a syndrome that occurs in individuals who have HIV and are receiving antiretroviral therapy (particularly protease inhibitors). On average, HIV-associated lipodystrophy develops 18 months after initiation of therapy.
HIV-associated lipodystrophy is a progressive disease. The severity of the condition is directly proportional to the patient's age, duration of disease and length of protease inhibitor therapy.
Current studies show that this syndrome occurs in 2-60% of patients who are HIV positive. A recent five-year retrospective cohort study found that 13% of patients who were HIV-positive and treated with protease inhibitors developed lipodystrophy. An incidence rate of 4% has been reported in HIV-positive patients who are not receiving antiretroviral therapy.
Women are almost twice as likely to develop lipodystrophy than men. The increased risk is associated with an increased body mass index (BMI). Women are more likely to report fat accumulation in the abdomen and breasts, while men are more likely to experience fat depletion from the face and extremities.
HIV-associated lipodystrophy progressively worsens as treatment with protease inhibitors continues. However, discontinuing protease inhibitor therapy may lead to regression of the disease. Both lipohypertrophy and lipoatrophy have been treated with human growth hormone, naltrexone, anabolic steroids and a combination of dehydroepiandrosterone (DHEA) and cyclooxygenase inhibitors.
Most researchers believe that protease inhibitors are implicated in HIV-associated lipodystrophy, but the precise mechanisms that cause the condition remain unknown. Lipodystrophy does not appear to vary with the use of different protease inhibitors. An increased risk of lipodystrophy is reported with the addition of nucleoside reverse transcriptase inhibitors (like stavudine) to protease inhibitor therapy compared to monotherapy with protease inhibitors (Agenerase©, Aptivus©, Crixivan©, Invirase©, Kaletra©, Lexiva©, Norvir©, Prezista©, Reyataz© and Viracept©). Two main theories exist, based on in vitro studies.
Some researchers suggest that protease inhibitors cause a decreased production of retinoic acid and triglyceride uptake. Protease inhibitors have a high affinity for HIV-1 protease, an HIV enzyme similar to two endogenous proteins involved in lipid metabolism -
cytoplasmic retinoic acid-binding protein type 1 and lipoprotein receptor-related protein. Inhibition of cytoplasmic retinoic acid-binding protein type 1 impairs the production of retinoic acid, which results in a decreased fat storage and causes adipocytes apoptosis (fat cell death), with subsequent release of lipids into the circulation. This ultimately causes lipohypertrophy (fat build up). When the lipoprotein receptor-related protein is inhibited, it causes hyperlipidemia (high cholesterol) secondary to the failure of hepatic and endothelial removal of chylomicrons (fat particles present in lymph) and fatty acids from the circulation. This ultimately causes lipoatrophy (loss of fat).
The second theory suggests that antiretroviral therapy prevents the development of adipocytes (fat cells). Antiretrovirals, such as saquinavir, ritonavir and nelfinavir, directly inhibit the development of adipocytes from stem cells and increase the metabolic destruction of fat in existing adipocytes.
HIV-associated lipodystrophy is a progressive disease. The severity of symptoms is directly proportional to the patient's age, duration of disease and length of protease inhibitor therapy. Common symptoms are limited to the skin, and the condition may be disfiguring.
Lipohypertrophy, or fat build up ("fat pad'") may develop. Common symptoms include dorsocervical fat buildup (buffalo hump on the upper back or neck), increased circumference of the neck by 5-10cm, breast hypertrophy (increase in size), and fat accumulation on the body trunk (also called a crix belly or protease paunch).
Lipoatrophy (loss of fat under the skin, especially in the limbs and cheeks) may develop. Common symptoms include loss of fat from the cheeks, arms, shoulders, thigh and buttocks (peripheral wasting). The superficial veins (close to the skin surface) at these locations become highly visible.
Dyslipidemia (disorders in the lipoprotein metabolism) may occur in patients who have lipodystrophy. In general, patients who develop dyslipidemia have an increased risk of developing heart disease. However, studies show that unless HIV-infected patients with dyslipidemia have other risk factors making them predisposed to heart disease (like obesity or high blood pressure) their chances of heart attack are no greater than HIV-negative people.
Lipoatrophy is associated with hyperlipidemia (high cholesterol), insulin resistance (the body does not respond properly to insulin), hyperinsulinemia (high levels of insulin in the blood) and hyperglycemia (high blood sugar, which may lead to diabetes).
General: If a patient expresses clinical signs of lipodystrophy, metabolic tests may be conducted to confirm a diagnosis. Imaging studies may also be performed to obtain detailed information about the patient's fat distribution.
Cholesterol: A blood test may be conducted to determine the patient's cholesterol levels. Typically, a patient who has lipodystrophy will have a fasting cholesterol level that is greater than or equal to 5.5mmol/L, a fasting triglyceride level that is greater than or equal to 2mmol/L and increased apolipoprotein c-III and apolipoprotein E levels.
Hyperglycemia and/or hyperinsulinemia: Blood tests may be performed to determine if the patient has high levels of sugar in the blood. Patients with lipodystrophy typically have a C-peptide level that is greater than 2.5mmol/L, decreased fasting glucose (6.1-7.0mmol/L) level or diabetes mellitus with fasting blood glucose level that is greater than 7.0mmol/L. Patients may have increased levels of serum plasminogen activator inhibitor type 1, tissue-type plasminogen activator and soluble type 2 tumor necrosis factor-alpha receptor. Patients may have decreased levels of serum insulin-like growth factor binding protein type 1. Patients may have increased cortisol levels.
Imaging studies: A magnetic resonance imaging (MRI) or computerized tomography (CT) scan may detect the accumulation of visceral fat in the abdomen compared to subcutaneous fat. The organs in the abdomen are normal, and no ascites (fluid in the abdomen) is present. A dual-energy X-ray absorptiometry may detect lumbar (lower back) spine bone density reduction that is associated with increased visceral fat accumulation.
General: In some cases, lipodystrophy may regress once protease inhibitor treatment is discontinued. Both lipohypertrophy and lipoatrophy have been treated with human growth hormone, naltrexone, anabolic steroids and a combination of dehydroepiandrosterone (DHEA) and cyclooxygenase inhibitors.
Human growth hormones: Human growth hormones (Serostim©, Genotropin©, Norditropin© or Nutropin AQ©) have been used to treat both lipohypertrophy and lipoatrophy.
Hormones: Hormones like oxymetholone (Anadrol©), stanozolol (Winstrol©), testosterone (Delatest©, Depo-Testosterone©, Androderm©, Andro-LA©), nandrolone (Deca-Durabolin©) and DHEA have been used to induce varied metabolic effects.
Growth factors: Growth factors, such as Insulin-like growth factor-1, may increase lean body mass and decrease total fat mass in patients who have HIV-associated lipodystrophy.
Antilipemic (lipid-lowering) agents: Antilipemic (lipid-lowering) agents like fenofibrate (Tricor©) and gemfibrozil (Lopid©) have been used to reduce LDL serum levels. They have been shown to significantly reduce total cholesterol levels.
HMG-CoA reductase inhibitors: HMG-CoA reductase inhibitors like atorvastatin (Lipitor©) have been used to lower LDL cholesterol by reducing the production of mevalonic acid from HMG-CoA and stimulating LDL catabolism.
Anti-diabetic agents: Anti-diabetic agents like glucophage (Metformin©) have been used in combination with diet to lower blood glucose.
Surgery: Lipohypertrophy may be treated with liposuction (areas of fat are removed with a suction-pump device that is inserted through a small incision) or lipectomy (surgical removal of fat tissue). However, results are variable and recurrence is common.
Lipoatrophy may also be treated with surgery, including lipotransfer (surgically removing fat from one area of the body and transferring it somewhere else) or implants filled with hyaluronic acid, silicone or other substances to replace lost adipose tissue.
Ephedra: Ephedra contains the chemical ephedrine, which appears to cause weight loss when used in combination with caffeine, based on the available scientific evidence. The results of research on ephedrine alone without caffeine are unclear. The amounts of ephedrine in commercially available products have varied greatly.
Thousands of toxicity reports exist on ephedra, including over 100 deaths. Avoid in patients who have a history of high blood pressure, abnormal heart rate, heart attack, stroke, seizure, eating disorders, anxiety, prostate disease, mental illness, kidney disease, stomach ulcers, heart disease, eye disease, depression, diabetes, thyroid disease or sleep problems. Avoid if pregnant or breastfeeding because ephedra may cause harm to the mother and fetus.
5-HTP: 5-HTP inhibits eating behavior in animals by altering serotonin in the brain. Studies in humans also suggest that 5-HTP may suppress appetite, reduce caloric intake and promote weight loss in obese individuals. Large, well-designed studies comparing 5-HTP with prescription appetite-suppressant drugs are needed to make a firm recommendation.
Avoid if allergic to 5-HTP. Use cautiously with history of mental disorders. Avoid if pregnant or breastfeeding due to insufficient scientific evidence of safety.
Atkins diet: The Atkins diet has been shown to reduce weight in patients. However, one study found that the drastic weight loss, which occurs at the start of the Atkins diet, does not continue after about six months.
Avoid with severe kidney disease and renal disorders. Avoid if using growth hormones. Use cautiously with mood disorders, such as depression, schizophrenia or bipolar disorder, as well as individuals using medications for these purposes. Use cautiously in athletes due to potential for muscle cramps, negative feelings towards exercise, fatigue and hypoglycemia (low blood sugar). Use cautiously with osteoporosis, gout (foot inflammation), diabetes, menstrual disorders, gastrointestinal disorders, celiac disease, skin conditions, epilepsy and cardiovascular disease. Use cautiously in malnourished individuals, vegetarians or individuals with absorption concerns. Use cautiously if taking diuretics, medications that alter cholesterol, medications that alter blood sugar, medications for seizures, steroids or nonsteroidal anti-inflammatory drugs (NSAIDS). Use cautiously in anemic individuals, individuals with thyroid concerns and in individuals with previous history of stroke or heart attack. Avoid if pregnant or breastfeeding.
Psychotherapy: Several studies indicate that people who are overweight or obese may benefit from behavioral and cognitive-behavioral psychotherapy in combination with diet and exercise when attempting to lose weight.
Psychotherapy may not always fix mental or emotional conditions. Psychiatric drugs are sometimes needed. In some cases symptoms may worsen if the proper medication is not taken. Not all therapists are qualified to work with all problems. Use cautiously with serious mental illnesses or some medical conditions because some forms of psychotherapy may stir up strong emotional feelings and expressions.
Acupuncture: Evidence is inconsistent as to whether acupuncture might contribute to weight loss. Some studies show modest benefit, but others show none. Currently, there is insufficient evidence to recommend either for or against acupuncture in weight loss.
Ayurveda: Evidence is inconclusive as to whether the traditional herb Guggulu (Medohar) may contribute to weight loss in obese patients. More studies are needed to examine this treatment.
Betaine anhydrous: Although some animal studies have suggested a potential mechanism for beneficial effect on weight and adipose reduction, there is limited evidence in humans that betaine supplementation reduces body weight. More high-quality studies should be conducted in this area.
Bitter orange: One systematic review identified one randomized controlled trial that assessed a bitter orange preparation for weight loss. However, this study did not look at Citrus aurantium alone, and the sample size was not adequate. Nonetheless, weight loss appeared to be enhanced by the Citrus aurantium-containing product. Studies are needed to test the Citrus aurantium component without combining it with other ingredients postulated to have anti-obesity effects. Larger and longer studies are also needed to address both safety and efficacy.
Calcium: Diets with higher calcium density (high levels of calcium per total calories) have been associated with a reduced incidence of being overweight or obese in several studies. While more research is needed to understand the relationships between calcium intake and body fat, these findings emphasize the importance of maintaining an adequate calcium intake while attempting to diet or lose weight.
Damiana: "YGD," an herbal preparation containing yerbe mate (leaves of Ilex paraguayenis), guarana (seeds of Paullinia cupana) and damiana (leaves of Turnera diffusa var. aphrodisiaca), has been used for weight loss. More studies using damiana alone are needed before a recommendation can be made.
Evening primrose oil: Initial human study suggests that evening primrose oil may have no effects on weight loss.
Garcinia: Three clinical trials looked at the effect of hydroxycitric acid (HCA), the active ingredient in Garcinia cambogia, on weight loss. One of the three trials showed no significant difference in weight loss between the treatment group and placebo group, while one trial showed that a natural extract of HCA (HCA-SX) can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess body weights and BMI, while promoting healthy blood lipid levels. The third showed a significantly greater weight loss in the active-group. Further research is needed before a recommendation can be made.
Green tea: There are several small human studies addressing the use of green tea extract (GTE) capsules for weight loss or weight maintenance in overweight or average weight individuals. Study results are mixed. Better research is needed before a recommendation can be made in this area.
Guggul: There is insufficient evidence to support the use of guggul or guggul derivatives for the management of obesity.
Hypnotherapy: Research suggests that hypnosis may be valuable as an adjunct to cognitive behavioral therapy for weight loss. However, it is not clear if hypnotherapy used alone is beneficial in this area.
L-carnitine: In one double-blind clinical trial, L-carnitine had no effect on weight loss in obese patients. Further studies are needed before recommendations can be made.
Licorice: Preliminary data shows that licorice may reduce body fat mass. Further research is needed to confirm these results.
Macrobiotic diet: There is evidence that a macrobiotic diet may lead to reduced body size and obesity, and increased leanness in preschool children compared to children on a normal diet. Studies are needed to determine whether or not these changes contribute to good health in children.
Moxibustion: Evidence does not support use of moxibustion to aid in weight loss at this time, although it may contribute to increased psychological well-being and improved eating attitudes in obese patients. More studies are needed to determine whether or not moxibustion may play a role in weight loss.
Psyllium: The reviewed evidence seems to show that psyllium may improve blood sugar and lipid levels, which can relate to obesity in some children. However, further studies are needed to clarify its effects and the mechanisms involved. Body weight reduction has not been proven to be associated with psyllium use in adults.
Rhubarb: One three-stage study looked at the effects of rhubarb on simple obesity. Although the study indicated a positive effect compared to two other obesity treatments and a control group, more high quality studies are needed to confirm rhubarb's role in weight gain and loss.
Seaweed, kelp and bladderwrack: Bladderwrack and other seaweed products are often marketed for weight-loss. However, safety and effectiveness have not been studied in humans.
Soy: Due to limited human study, there is not enough evidence to recommend for or against the use of soy for weight reduction. Further research is needed before a recommendation can be made.
Spirulina: Spirulina is a popular therapy for weight loss, and it is sometimes marketed as a "vitamin-enriched" appetite suppressant. However, little scientific information is available on the effect of spirulina on weight loss in humans.
Taurine: Taurine has been shown to decrease the body weight of obese mice. More recent studies suggest that taurine has beneficial effects on serum lipids. One clinical trial suggested that taurine resulted in weight loss in overweight young adults. This study had limitations in reporting. Therefore, more well-designed and reported clinical trials are required before recommendations can be made.
Vitamin A: Daily vitamin A with calcium has been suggested for weight loss, and in one study an average loss of two pounds was reported after two years of supplementation in young women.
Yoga: Preliminary research does not provide clear answers. Yoga in addition to healthy eating habits may reduce weight. Better studies are necessary to form conclusions about the potential benefits of yoga alone.
Acupressure, shiatsu: Preliminary evidence suggests that acupressure may not be effective for weight loss.
Beta-glucan: Researchers suggest different types of fiber may have an effect on satiety and energy intake. This nonrandomized pilot study evaluated the influence of fermentable fiber with nonfermentable fiber. The aim of the study was to determine if fermentable fiber decreases hunger and energy intake and promote weight loss to a greater extent than nonfermentable fiber. However, the results of this study do not support a role for short-term use of fermentable fiber and nonfermentable fiber supplements in promoting weight loss.
Antiretroviral therapy, especially treatment with protease inhibitors, is responsible for lipodystrophy in HIV-patients. While antiretroviral therapy is a necessary treatment for HIV, patients may reduce their risk by taking antiretrovirals other than protease inhibitors. However, patients should follow the advice and treatment regimens that their qualified healthcare providers offer.
This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
- Academic Dermatology & Skin Cancer Institute. HIV lipodystrophy. www.adsci.com.
- HIV Medicine 2006. Lipodystrophy Syndrome. www.hivmedicine.com.
- Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com. Copyright © 2007.
- Tufts University. Lipodystrophy. www.tufts.edu.
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