Nutritional role of the leucine metabolite β-hydroxy β-methylbutyrate (HMB)

Nissen, Steven; Abumrad, Naji N.

doi:10.1016/s0955-2863(97)00048-x

Cited by 246 publications

(238 citation statements)

References 64 publications

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“…In agreement with human studies showing that HMB supplementation attenuates the exerciseinduced rise in creatine kinase, 12,21,31,32,33 the mdx mice (HMB and COMB ϩ PRED) showed a strong trend toward lower creatine kinase levels. It has been proposed that this ability to reduce creatine kinase levels results from a decrease in muscle proteolysis or by supplying increased amounts of cholesterol precursor (HMG-CoA) in muscle, thereby providing substrate for stabilizing and synthesizing the myocyte plasma membrane.…”

Section: Discussionsupporting

confidence: 87%

“…The HMB and COMB ϩ PRED interventions tended to have lower creatine kinase levels than PLTR. Using a one-tailed analysis (with the a priori hypothesis that HMB would reduce CK 12,21,31,32,33 ), the values were significant (P Ͻ 0.05; Fig. 4A).…”

Section: Resultsmentioning

confidence: 96%

“…It has been proposed that this ability to reduce creatine kinase levels results from a decrease in muscle proteolysis or by supplying increased amounts of cholesterol precursor (HMG-CoA) in muscle, thereby providing substrate for stabilizing and synthesizing the myocyte plasma membrane. 31 If this finding is replicated in boys with DMD, there may well be long-term benefits, assuming the lower serum creatine kinase is indicative of less muscle damage or secondary inflammation.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 87%

Section: Resultsmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Nutritional therapy improves function and complements corticosteroid intervention in mdx mice

et al. 2005

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“…HMB has been shown to enhance protein synthesis (9) and decrease muscle damage and protein breakdown (5,29,30) . It therefore seems advantageous to achieve higher plasma HMB levels and higher retention rates during exercise than those previously reported (5,20,31) . It is clear from our studies that the combination of significantly higher peak plasma concentrations and AUC, coupled with no differences in urinary excretion over the measurement period, indicates greater retention of HMB.…”

Section: Discussionmentioning

confidence: 77%

Free acid gel form of β-hydroxy-β-methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt

et al. 2010

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The leucine metabolite, b-hydroxy-b-methylbutyrate (HMB), is a nutritional supplement that increases lean muscle and strength with exercise and in disease states. HMB is presently available as the Ca salt (CaHMB). The present study was designed to examine whether HMB in free acid gel form will improve HMB availability to tissues. Two studies were conducted and in each study four males and four females were given three treatments in a randomised, cross-over design. Treatments were CaHMB (gelatin capsule, 1 g), equivalent HMB free acid gel swallowed (FASW) and free acid gel held sublingual for 15 s then swallowed (FASL). Plasma HMB was measured for 3 h following treatment in study 1 and 24 h with urine collection in study 2. In both the studies, the times to peak plasma HMB were 128 (SEM 11), 38 (SEM 4) and 38 (SEM 1) min (P,0·0001) for CaHMB, FASW and FASL, respectively. The peak concentrations were 131 (SEM 6), 249 (SEM 14) and 239 (SEM 14) mmol/l (P, 0·0001) for CaHMB, FASW and FASL, respectively. The areas under the curve were almost double for FASW and FASL (P,0·0001). Daily urinary HMB excretion was not significantly increased resulting in more HMB retained (P,0·003) with FASW and FASL. Half-lives were 3·17 (SEM 0·22), 2·50 (SEM 0·13) and 2·51 (SEM 0·14) h for CaHMB, FASW and FASL, respectively (P, 0·004). Free acid gel resulted in quicker and greater plasma concentrations (þ 185 %) and improved clearance (þ25 %) of HMB from plasma. In conclusion, HMB free acid gel could improve HMB availability and efficacy to tissues in health and disease. b-Hydroxy-b-methylbutyrate (HMB) is a five-carbon organic acid, produced in vivo from leucine (1) . Leucine has been shown to be a regulator of protein metabolism (2) and previous studies in human subjects have shown that dietary supplementation with 3 g of calcium HMB (CaHMB)/d attenuates the loss of muscle mass and function in various conditions such as resistance exercise training, cancer and AIDS (3 -7) . The mechanisms for these improvements are not yet clear. However, recent in vitro studies have shown that HMB stimulates protein synthesis through mammalian target of rapamycin phosphorylation, which is central to controlling translation initiation (8,9) . This effect on protein synthesis appears to be shared with the anabolic effects of amino acids (particularly leucine) and insulin (10,11) . In addition, HMB attenuates the induction of the ubiquitin -proteosome proteolytic pathway caused by proteolysis-inducing factor, lipopolysaccharide and angiotensin II, resulting in a decrease in muscle protein breakdown (12 -14) .Human studies have shown a positive effect of resistance exercise on muscle protein synthesis as early as 1 -2 h postexercise and lasting up to 48 h (15,16) . Studies have also shown that the timing of nutrient availability is critical for maximal post-exercise stimulation of protein synthesis as well as blunting of protein breakdown (17) . The most optimal time for delivery of nutrient appears to be within 2 h post-exercise. Dreyer et al. ...

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“…Among these specific compounds, there is also the bioactive metabolite of leucine -β-hydroxy-β-methylbutyrate (HMB). Approximately 5% of leucine metabolism leads to endogenous synthesis of HMB, which serves as a key carbon source for de novo cholesterol synthesis in tissues, which is necessary to maintain maximal cell function (21). Earlier studies have shown that dietary supplementation with HMB results in enhanced wound collagen deposition in rats.…”

Section: Introductionmentioning

confidence: 99%

Effect of HMB and 2-Ox administered during pregnancy on bone properties in primiparous and multiparous minks (Neivison vison)

Tomaszewska

Dobrowolski

Kostro

et al. 2015

Bulletin of the Veterinary Institute in Pulawy

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The aim of the study was to determine the mechanical and geometric properties as well as bone tissue density of long bones in primiparous and multiparous dams of minks supplemented with β-hydroxy β-methylbutyrate (HMB) and/or 2-oxoketoglutarate (2-Ox) during gestation. Powdered 2-Ox was given at the daily dosage of 0.4 g/kg b.w. separately or simultaneously with HMB, which was administered at the daily dosage of 0.02 g/kg b.w. The study demonstrates for the first time that administration of 2-Ox and/or HMB to dams markedly influences bone tissue density and the mechanical and geometrical properties of mother`s bones in minks. Moreover, it was demonstrated that the supplementation was more effective in the thoracic limb, which was comprehensively used in contrast to the pelvic limb. The mechanical parameters and bone tissue density significantly increased in the humerus in multiparous minks. Only such diet may provide satisfactory production results in the animals. Nutritional deficiencies occurring during pregnancies may trigger body`s own reserves to cover the bone mass increase in developing foetuses and support milk production. This can prevent regeneration of dams' organisms, which negatively affects their reproductive performance. 2-Ox or HMB may be regarded as a protective metabolite when administered orally to minks, counteracting the negative influences of pregnancy and lactation periods on bones condition. Both simultaneous treatment with 2-Ox and HMB and their separate administration were equally effective.

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Nutritional role of the leucine metabolite β-hydroxy β-methylbutyrate (HMB)

Cited by 246 publications

References 64 publications

Nutritional therapy improves function and complements corticosteroid intervention in mdx mice

Nutritional therapy improves function and complements corticosteroid intervention in mdx mice

Free acid gel form of β-hydroxy-β-methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt

Effect of HMB and 2-Ox administered during pregnancy on bone properties in primiparous and multiparous minks (Neivison vison)

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