Nutritional Treatment for Acquired Immunodeficiency Virus‐Associated Wasting Using β‐Hydroxy β‐Methylbutyrate, Glutamine, and Arginine: A Randomized, Double‐Blind, Placebo‐Controlled Study

Clark, Robert H.; Feleke, Getachew; Din, M.M. Gamal El; Yasmin, Tabassum; Singh, Gurdev; Khan, Faroque A.; Rathmacher, John A.

doi:10.1177/0148607100024003133

Cited by 211 publications

(149 citation statements)

References 41 publications

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“…12,33,50 HMB, in combination with arginine and glutamine, reversed muscle wasting associated with cancer cachexia 29 and HIV-wasting syndrome. 6 HMB also reduced creatine kinase activity following various types of exercise. 12,32,33 Other than CrM, none of these compounds have been tested in the mdx mouse or patients with DMD.…”

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confidence: 84%

Nutritional therapy improves function and complements corticosteroid intervention in mdx mice

et al. 2005

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Corticosteroid therapy for Duchenne muscular dystrophy is effective but associated with long-term side effects. To determine the potential therapeutic benefit from four nutritional compounds (creatine monohydrate, conjugated linoleic acid, ␣-lipoic acid, and ␤-hydroxy-␤-methylbutyrate) alone, in combination, and with corticosteroids (prednisolone), we evaluated the effects on several variables in exercising mdx mice. Outcome measures included grip strength, rotarod performance, serum creatine kinase levels, muscle metabolites, internalized myonuclei, and retroperitoneal fat pad weight. In isolation, each nutritional treatment showed some benefit, with the combination therapy showing the most consistent benefits. Prednisolone and the combination therapy together provided the most consistent evidence of efficacy; increased peak grip strength (P Ͻ 0.05), decreased grip strength fatigue (P Ͻ 0.05), decreased number of internalized myonuclei (P Ͻ 0.01), and smaller retroperitoneal fat pad stores (P Ͻ 0.001). This study provided evidence for therapeutic benefit from a four-compound combination therapy alone, and in conjunction with corticosteroids in the mdx model of DMD.

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confidence: 84%

Nutritional therapy improves function and complements corticosteroid intervention in mdx mice

et al. 2005

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“…In addition, the administration of a mixture containing HMB, arginine and glutamine in advanced stage (IV) cancer patients has shown efficacy in increasing both body mass and fat-free mass with respect to controls (19), but these data were not confirmed in a recent study in stage III-IV cancer patients (20). Positive results were observed in AIDS (21,22), but not in rheumatoid arthritis patients (23). Finally, HMB alone was shown to improve nitrogen balance in trauma patients (24), and to exert anti-inflammatory actions and to improve respiratory function in critically ill COPD patients (25).…”

Section: Introductionmentioning

confidence: 95%

β-hydroxy-β-methylbutyrate (HMB) attenuates muscle and body weight loss in experimental cancer cachexia

Muscaritoli¹

2011

Int J Oncol

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Abstract. ß-hydroxy-ß-methylbutyrate (HMB), a leucine metabolite, improves muscle mass and function. This study aimed at evaluating the effects of HMB administration in an experimental in vivo model of cancer cachexia (CC). Wistar rats were randomized to receive standard or 4% HMBenriched chow. Rats from both groups were randomized to receive an i.p. inoculum of AH-130 cells (TB). All rats were weighed and sacrificed at day 24. Liver, heart and muscles were dissected and weighed. The protein levels of p-p70S6k, p-eIf2·, p-mTOR and p-4-EB-P1 were evaluated by Western blotting on gastrocnemius muscle (GSN). As expected, the growth of the AH-130 ascites hepatoma induced significant carcass weight and GSN muscle loss. HMB treatment significantly increased GSN and heart weight in controls (p=0.002 and p<0.001, respectively). In HMB-treated TB, body weight was not lost but significantly (p=0.003) increased, and GSN loss was significantly (p=0.04) attenuated with respect to TB. Phosphorylated eIF2· markedly decreased in TB-rats vs. C. Feeding the HMB-enriched diet resulted in decreased p-eIF2· levels in control animals, while no changes could be observed in the TB group. Phosphorylated p70S6K and phosphorylated mTOR were markedly increased by HMB treatment in controls and further increased in TB. Phosphorylated 4-EB-P1 was markedly increased in TB but substantially unaffected by HMB treatment. Administration of HMB attenuates body weight and muscle loss in experimental CC. Increased phosphorylation of key anabolic molecules suggests that these actions are mediated by improved protein anabolism in muscle.

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“…However, V1 does not contain any meaningful amount of protein that could explain the weight gain. Treatment with beta-hydroxy beta-methylbutyrate, glutamine, and arginine supplements for 8 weeks resulted in 370.5 kg of weight gain, while those on placebo gained 0.3770.84 kg (Clark et al, 2000). In a 3-month study, the glutamine-antioxidant supplement increased body mass by 2.2 kg, whereas the control group gained 0.3 kg (Shabert et al, 1999).…”

Section: Discussionmentioning

confidence: 98%

“…FDA-approved stimulants, megestrol acetate (megace) and d-9-tetrahydrocannabinol (dronabinol), are unfortunately associated with increase in body fat rather than lean body mass (Gorter et al, 1992;Farrar, 1999). Another frequently used approach is to provide various nutritional supplements, that is, amino acids (Shabert et al, 1999;Clark et al, 2000) and lipids or fatty acids (Singer et al, 1997;de Luis Roman et al, 2001). Some of these nutritional regimens did yield positive results albeit with variable success rate.…”

Section: Introductionmentioning

confidence: 99%

Increased body weight and improved quality of life in AIDS patients following V-1 Immunitor administration

Jirathitikal¹,

Metadilogkul

Bourinbaiar³

2003

Eur J Clin Nutr

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Objectives: Development of affordable and safe therapy to reverse the loss of body mass is of critical importance since AIDSrelated wasting is associated with increased mortality. Method: We have demonstrated earlier that oral therapeutic HIV vaccine, V-1 Immunitor (V1), tested in a small group of AIDS patients in Thailand not only increases T-cell counts and decreases the viral load but also results in weight gain and prolonged survival. To further expand this observation, we retrospectively analyzed 650 HIV-positive patients who were followed for an average of 23 weeks.Results: The treatment with V1 resulted in a sustained and statistically significant increase in body mass across the whole population (mean7s.e.; 1.570.4 kg; P ¼ 6.5EÀ015). Among them, 384 (59%) patients gained an average of 4.270.2 kg; 107 (17%) had unchanged weight; and 159 (24%) had lost 3.870.3 kg. Thus, the prevailing majority of patients (76%) were able to gain or maintain weight. Treatment was well tolerated; in a survey of health status in a comparable but separate group of 382 patients, about 85% reported subjective improvement after V1 treatment, 6% reported no difference, and 9% of the patients reported minor adverse reactions, which did not last more than 1 week. Subjective improvement coincides with the reduction or clearance of oral thrush or mucocutaneous candidiasis in 87.5% of the patients. Conclusions:In an open label setting, V1 increases body weight, subjective assessment of quality of life, and is safe and effective for HIV patients with weight loss. These data provide the impetus of using V-1 Immunitor as an affordable and easy-toadminister means of treating AIDS-associated wasting and opportunistic infections.

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Nutritional Treatment for Acquired Immunodeficiency Virus‐Associated Wasting Using β‐Hydroxy β‐Methylbutyrate, Glutamine, and Arginine: A Randomized, Double‐Blind, Placebo‐Controlled Study

Abstract: The data indicate that the HMB/Arg/Gln mixture can markedly alter the course of lean tissue loss in patients with AIDS-associated wasting.

Cited by 211 publications

References 41 publications

Nutritional therapy improves function and complements corticosteroid intervention in mdx mice

Nutritional therapy improves function and complements corticosteroid intervention in mdx mice

β-hydroxy-β-methylbutyrate (HMB) attenuates muscle and body weight loss in experimental cancer cachexia

Increased body weight and improved quality of life in AIDS patients following V-1 Immunitor administration

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