Delayed Onset Muscle Soreness

Muscle soreness after exercise is very common and has been heavily researched, although little has been proven to help.  The vast majority of interventions have no benefit.  The most important thing is getting in condition ahead of time by doing the desired exercise at a lower level before doing it at a higher level.  Keeping yourself reasonably well hydrated is good, but don't overdo it like a minority of marathon runners do, since this can cause hyponatremia or too little sodium.  Contrary to folklore, stretching exercises are of no benefit and salt tablets are a bad idea.  

Other interventions are less well proven.  Consuming protein immediately after exercise has helped in a couple studies, not just for the soreness, but also for muscle recovery.  However, don't eat mammal meat, i.e., beef and pork, since it has many bad health effects.  One good study found a protease supplement helped.  L-carnitine or acetyl-L-carnitine may help some people.  While there is no research on delayed onset muscle soreness with vitamin D (2000 units/day) or magnesium (250 mg twice a day), other research has found them helpful for muscle strength.  Taurine probably helps, since it reduced DNA damage and increased performance.  I can't help but think that a healthy diet as described in my Recommendations for Healthy Living would help.  Hydroxy-methylbutyrate looks good for untrained or older adults, although at $50 per month it is quite expensive.

A whirlpool afterward for 24 minutes might help, but cooler might be better than hotter.  Warm is OK.  Massage might help some with soreness, but not with muscle recovery.  

Things that don't help include vitamins C and E.  Avoid ibuprofen, acetaminophen, or other anti-inflammatories.  Acupunture, low level electrical current, pulsed ultrasound, homeopathy, infrared irradiation, laser therapy, cryotherapy, ice massage, astaxanthin, deep heat, phosphatidylserine, magnets, fish oil, and chondroitin have all failed. 

Don't exercise to the extreme.  Ultramarathon, marathon, and long-distance bicyclers sometimes do damage their hearts due to their extreme amount of exercising.  However, vigorous exercise is better than less intense, at least for those who have first gotten themselves into condition.

Protein After Exercise Helps: Postexercise protein supplementation improves health and muscle soreness during basic military training in Marine recruits. Elevated postexercise amino acid availability has been demonstrated to enhance muscle protein synthesis acutely. In a study of 387 marines during the 54-day basic training were either placebo (0 g carbohydrate, 0 g protein, 0 g fat), control (8, 0, 3), or protein supplement (8, 10, 3). The protein-supplemented group had an average of 33% fewer total medical visits, 28% fewer visits due to bacterial/viral infections, 37% fewer visits due to muscle/joint problems, and 83% fewer visits due to heat exhaustion. Muscle soreness immediately postexercise was reduced by protein supplementation on both days 34 and 54. Flakoll PJ, et al. Iowa State University. . J Appl Physiol 2004 Mar;96(3):951-6.  Muscle soreness was less after an 8% carbohydrate and 2% protein drink than after a 10% carbohydrate drink. Int J Sports Nutr 2005 Dec;15(6):610-24.  

Massage Helps Some: Sport massage did not reduce girth or pain in the lower leg after eccentric exercise within 72 hours.  J Athl Train 2005 Jul;40(3):181-5.  Massage treatment had significant effects on plasma creatine kinase activity, with a significantly lower peak value at 4 days postexercise (P < .05), and upper arm circumference, with a significantly smaller increase than the control at 3 and 4 days postexercise (P < .05). However, no significant effects of massage on recovery of muscle strength and ROM were evident. Massage was effective in alleviating DOMS by approximately 30% and reducing swelling, but it had no effects on muscle function. J Athl Train 2005 Jul;40(3):174-80.  A review concluded that muscle soreness associated with DOMS is reduced with massage, although whether force recovers more quickly is still unclear. J Sports Med Phys Fit 2005 Sep;45(3):370-80.

Protease Helped Muscle Soreness and Healing: Protease supplementation has been shown to lessen soft tissue injury resulting from intense exercise. In a DB PC study of 10 matched pairs of male participants running at a 10% downgrade for 30 min at 80% of their predicted maximal heart rate, those taking two protease tablets (325 mg pancreatic enzymes, 75 mg trypsin, 50 mg papain, 50 mg bromelain, 10 mg amylase, 10 mg lipase, 10 mg lysozyme, 2 mg chymotrypsin) four times a day beginning 1 day before exercise and lasting a total of 4 days had superior recovery of contractile function and diminished effects of delayed-onset muscle soreness. Protease supplementation may also facilitate muscle healing and allow for faster restoration of contractile function after intense exercise. J Sport Sci 2004 Apr;22(4):365-72.  However, bromelain by itself did not help. Clin J Sports Med 2002 Nov;12(6):373-8.

Avoid Dehydration Before Exercise: A dehydrated individual who performs eccentric exercise may exacerbate skeletal muscle damage, leading to structural, contractile, and enzymatic protein denaturation, in addition to the myofiber and connective damage resulting from the eccentric muscle tension. Significantly dehydrated participants who rested and returned to a normothermic condition did not experience increased characteristics of delayed onset muscle soreness (DOMS).  Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process. Br J Nutr 2006 May;95(5):976-81. 

Whirlpool Might Help a Little: Cold whirlpool (24 min) and contrast therapy were found to return subjects to baseline values of resting elbow flexion and perceived soreness significantly more than warm whirlpool or no treatment (P < .01). Additionally, warm whirlpool was found to be more effective than no treatment in the return of resting elbow flexion (P < .01). J Athl Train 1998 Jul;33(3):222-228.  

Taurine Helped Exercise Performance: DNA migration increased 24 hr after exercise (p<0.01). Significant increases were also found in VO(2)max, exercise time to exhaustion and maximal workload with taurine (p<0.05). Taurine reduced exercise induced DNA damage. Role of taurine supplementation to prevent exercise-induced oxidative stress in healthy young men. Zhang M, Izumi I, et al, Toyama University, Japan. Amino Acids. 2004 Mar;26(2):203-7  

Taurine Helps Rat Exercise Tolerance: In a 2-week rat study of the effect of varying doses of taurine on a transient exercise performance, best results, a 25-50% increase in exercise to exhaustion, were obtained between 100 and 500 mg/kg/day. Miyazaki T, et al, Mito, Japan. Amino Acids. 2004 Oct 22. A couple other studies had similar findings.

Amino-Acid Supplements Mixed Picture: Branch-chained amino acid supplementation before exercise attenuates the breakdown of muscle proteins during exercise in humans and that leucine strongly promotes protein synthesis in skeletal muscle in humans and rats, suggesting that a BCAA supplement may attenuate muscle damage induced by exercise and promote recovery from the damage. J Nutr 2006 Feb;136(2):529S-532S.  Supplementation with 3 g/d beta-hydroxy-beta-methylbutyrate (HMB) and 0.3 g/d alpha-ketoisocaproic acid (KIC) for 14 days beforehand reduced signs and symptoms of exercise-induced muscle damage. Int J Sports Nutr 2005 Aug;15(4):413-24. However, short-term supplementation with 40mg/kg bodyweight/day of HMB had no beneficial effect on a range of symptoms associated with eccentric muscle damage. Int J Sports Nutr 2001 Dec;11(4):442-50.  5 days of creatine supplementation did not reduce indirect markers of muscle damage or enhance recovery from high-force eccentric exercise. J Strength Cond Res 2001 May;15(2):178-84. Other studies find the same results for creatine.

Light concentric exercise has a temporarily analgesic effect on delayed-onset muscle soreness, but no effect on recovery from eccentric exercise.  Appl Physiol Nutr Metab 2006 Apr;31(2):126-134.  Microcurrent electrical neuromuscluar stimulation treatment, within the parameters used for this experiment, was not effective in reducing the pain or loss of ROM associated with delayed-onset muscle soreness.  J Athl Train 1999 Oct;34(4):334-337.  Pulsed ultrasound as used in this study did not significantly diminish the effects of delayed-onset muscle soreness on soreness perception, swelling, relaxed-elbow extension angle, and strength. J Athl Train 1998 Oct;33(4):341-346.  

Others study show that ibuprofen and that ketoprofen are of no value for delayed muscle soreness, whether taken before or after the event.

Individuals performing novel exercise, particularly with a significant eccentric component, should use caution when training in a hot, humid environment and implement frequent rest and rehydration breaks.  A single bout of eccentric exercise confers a long-lasting protective effect against subsequent bouts of the same exercise.

There was no pain reduction by infrared light-emitting diode irradiation in a pilot study on experimentally induced delayed-onset muscle soreness in humans. Lasers Med Sci 2006;21(1):11-8.  Rofecoxib and tramadol do not attenuate delayed-onset muscle soreness or ischaemic pain in human volunteers. Can J Physiol Pharm 2005 Dec;83(12):1137-45.  Neither drug had any influence on whole body protein breakdown, as measured by rate of phenylalanine appearance, on serum creatine kinase, or on rating of perceived muscle soreness compared with PLA. Both ibuprofen and acetaminophen suppress the protein synthesis response in skeletal muscle after eccentric resistance exercise. Am J Physiol Endocrinol 2002 Mar;282(3):E551-6.  Chondroitin sulfate supplementation was not found to be effective in the prevention of DOMS, nor did it influence biochemical indices of inflammation and muscle damage following heavy eccentric loading of the arm flexors. J Sports Med Phys Fitness 2005 Dec;45(4):553-60.  Ice massage is ineffective in reducing the indirect markers associated with exercise-induced muscle damage and enhancing recovery of muscle function in male exercisers unaccustomed to eccentric biased exercise.  Scand J Med Sci Sports 2005 Dec;15(6):416-22.  

Astaxanthin supplementation does not attenuate muscle injury following eccentric exercise in resistance-trained men. Int J Sports Nutr 2005 Aug;15(4):401-12.  Light immobilization had no effect on enhancing recovery of muscle function and delayed-onset muscle soreness after eccentric-exercise-induced muscle damage. J Athl Train 2005 Jul;40(3):197-202.  Acupuncture had little effect upon the cardinal signs and symptoms of DOMS. J Clin Physiol 2000 Nov;20(6):449-56.  Lack of effect of combined low intensity laser therapy/phototherapy (CLILT) on delayed onset muscle soreness in humans. Lasers Surg Med 1999;24(3):223-30.  Homeopathic Arnica 30x is ineffective for muscle soreness after long-distance running: a randomized, double-blind, placebo-controlled trial. Clin J Pain 1998 Sep;14(3):227-31. The use of cryotherapy immediately following damaging eccentric exercise may not provide the same therapeutic benefits commonly attributed to cryotherapy following traumatic muscle injury. Int J Sports Med 1997 Nov;18(8):588-93.

Supplementation with phosphatidylserine was not effective in attenuating the cortisol response, perceived soreness, and markers of muscle damage and lipid peroxidation following exhaustive running. Med Sci Sports Exer 2005 Aug;37(8):1300-6.  Static magnetic fields neither prevent nor diminish symptoms and signs of delayed onset muscle soreness. Arch Phys Med Rehab 2005 Mar;86(3):565-70.  Deep heat did not help as a preventative mechanism on delayed onset muscle soreness. J Strength Cond Res 2004 Feb;18(1):155-61.  Vitamin E supplementation was not effective at attenuating putative markers of membrane damage, oxidative stress, and performance decrements after repeated bouts of whole-body concentric/eccentric resistance exercise. J Strength Cond Res 2003 Nov;17(4):801-9. Multiple studies also show no benefit from vitamin C.  Neither fish oil (1.8 g/d) nor soy isoflavones (120 mg/d) helped reduce DOMS. Med Sci Sports Exer 2002 Oct;34(10):1605-13.

Stretching Doesn't Help: Overall, the evidence suggests that increasing range of motion beyond function through stretching is not beneficial and can actually cause injury and decrease performance. Minn Med 2003 May;86(5):58-61.  A review of the best research to date found that stretching before or after exercising does not confer protection from muscle soreness. Stretching before exercising does not seem to confer a practically useful reduction in the risk of injury, but the generality of this finding needs testing. Insufficient research has been done with which to determine the effects of stretching on sporting performance. Brit Med J 2002 Aug 31;325(7362):468.

Muscles Helped by Magnesium Supplements: Several DB studies show improved muscle function in strength, decreased creatine kinase and lactate and oxygen uptake on exercise in athletes or normals. Usually 360 mg/d or 8 mg/kg. Over 500 mg may cause diarrhea and magnesium may interfere with zinc and iron. Am J Clin Nutr 8/00 72:587S. Zinc over 50 mg/d may interfere with copper and decrease HDL at 50-100mg/d. Chromium supplement no value in several studies.

Muscles: Magnesium Supplement Helped in Weight Training: In a 7 week study of just 26 adults, researchers found that those randomized to magnesium supplement enough to increase intake to 8 mg/kg had a significantly greater increase in strength during weight lifting training. W. Wash Univ., J Am Coll Nutr 1992 Jun;11(3):326

Muscles: Magnesium Supplement No Benefit in Marathon Trial: 20 runners randomized for four weeks before marathon to 365 mg of magnesium found no benefit to performance or muscle damage prevention or recovery. Cape Town, Int J Sport Nutr 1992 Jun;2(2):154

Muscles: Mg No Help in Alcoholic Liver Disease: In a 6-week DB PC study of 59 patients with alcoholic liver disease, there was no difference between placebo and Mg for muscle mass or strength, both of which increased. Spironolactone treatment was associated with a 33% increase in the content of Na,K-pumps (p<0.001). Magnesium supplementation and muscle function in patients with alcoholic liver disease: a randomized, placebo-controlled trial. Aagaard NK, et al. Aarhus University Hospital, Denmark. . Scand J Gastroenterol. 2005 Aug;40(8):972-9.

Muscle Soreness: Only Training and L-Carnitine Help; Massage Might: PubMed articles 12/2/01 found no benefit from ultrasound, hyperbaric oxygen, NSAIDs, aspirin, acupuncture, or stretching. Training does help. In shape runners have immediate soreness, but not delayed soreness. No help came from phototherapy, laser, cryotherapy, homeopathy, transcutaneous electrical nerve stimulation, upper body ergometry, or alcohol. Post-exercised massage may help, but the seven studies which have been done are of poor quality and don't have uniform results. Another reviewer conclude there was no benefit from post-exercise massage. Br J Sports Med 1998 Sep;32(3):212-4. Trained individuals had only 40% of the CK creatine kinase elevation (a muscle enzyme and thus marker of muscle breakdown) of untrained despite greater soreness. Int J Sports Med 1997 Aug;18(6):431-7. Three g/day of L-carnitine for 3 weeks may have helped untrained with reduced CK and reduced soreness. : Int J Sports Med 1996 Jul;17(5):320-4. Vit C helped in one small study (Pain 1992 Sep;50(3):317-21) but not another. A Romanian study claims there are 6 DB studies with over 100 athletes and l-carnitine showing benefits acutely and chronically. Physiologie 1989 Apr-Jun;26(2):111-29. L-carnitine $10 for 60 500mg tabs.

Muscle Soreness: Electrical Stimulation No Benefit: The use of microcurrent electrical neuromuscular stimulation on pain and loss of range of motion associated with delayed-onset muscle soreness resulted in no significant difference in the measurement of subjective pain scores or elbow extension when the MENS group was compared with the sham group. Effect of Microcurrent Stimulation on Delayed-Onset Muscle Soreness: A Double-Blind Comparison. Allen JD, et al. Purdue University, Lafayette, IN. J Athl Train 1999 Oct;34(4):334-337.

Muscle Soreness: Flexible Magnets Are Not Effective in Decreasing Pain Perception and Recovery Time After Muscle Microinjury. Borsa PA, et al. Oregon State University. J Athl Train 1998 Apr;33(2):150-155.

Branched Chain Amino Acids Help: BCAA catabolism in skeletal muscle is regulated by the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, located at the second step in the BCAA catabolic pathway. The activity of the BCKDH complex is regulated by a phosphorylation/dephosphorylation cycle. Almost all of BCKDH complex in skeletal muscle under normal and resting conditions is in an inactive/phosphorylated state, which may contribute to muscle protein synthesis and muscle growth. Exercise activates the muscle BCKDH complex, resulting in enhanced BCAA catabolism. Therefore, exercise may increase the BCAA requirement. It has been reported that BCAA supplementation before exercise attenuates the breakdown of muscle proteins during exercise in humans and that leucine strongly promotes protein synthesis in skeletal muscle in humans and rats, suggesting that a BCAA supplement may attenuate muscle damage induced by exercise and promote recovery from the damage. The authors examined the effects of BCAA supplementation on delayed-onset muscle soreness (DOMS) and muscle fatigue induced by squat exercise in humans. The results obtained showed that BCAA supplementation prior to squat exercise decreased DOMS and muscle fatigue occurring for a few days after exercise. These findings suggest that BCAAs may be useful for muscle recovery following exercise. Nutraceutical effects of branched-chain amino acids on skeletal muscle. Shimomura Y, et al. Nagoya Institute of Technology, Japan. . J Nutr 2006 Feb;136(2):529S-532S. Ed: Price is $20 per pound.

Beta-hydroxy-beta-methylbutyrate, abbreviated HMB, is found naturally in living matter as a metabolite of the essential amino acid L-leucine. It is naturally synthesized in our bodies (0.2 to 0.4 g of HMB/day). HMB may have anticatabolic, as well as immunomodulatory, properties. It is popular among athletes engaged in strenuous physical activity. Branched-chain amino acids L-leucine, L-isoleucine and L-valine are known to be beneficial to catabolic patients (sepsis, trauma, burns, etc.) by improving hepatic protein synthesis and nitrogen economy. These amino acids make up about one-third of muscle protein. Of these, L-leucine has the highest oxidation rate. L-leucine has been shown to stimulate protein synthesis in muscle, and decreases in leucine levels in skeletal muscle occur after exhaustive exercise. It has been speculated that the L-leucine metabolite HMB may be responsible for the inhibitory effect of L-leucine on protein breakdown.

Hydroxy Methylbutyrate Increased Muscle Stregthen: Thirty-nine men and 36 women, ages 20-40 were randomized to placebo HMB 3.0 gd). All subjects trained three times per week for 4 wk. In the HMB group, plasma creatine phosphokinase levels tended to be suppressed compared to the placebo group following the 4 wk of resistance training (HMB:174.4  to 173.5; P:155.0 to 195.2). There were no significant differences in strength gains based on prior training status or gender with HMB supplementation. The HMB group had a greater increase in upper body strength than the placebo group (HMB:7.5 kg; P:5.2 kg; P = 0.008). The HMB groups increased fat-free weight by 1.4 kg and decreased percent fat by 1.1% while the placebo groups increased fat-free weight by 0.9 kg and decreased percent fat by 0.5% (fat-free weight P = 0.08, percent fat P = 0.08, HMB compared to placebo). Nutritional supplementation of the leucine metabolite beta-hydroxy-beta-methylbutyrate (hmb) during resistance training. Panton LB, et al. East Tennessee State University. . Nutrition 2000 Sep;16(9):734-9. Ed: This amount costs $50 per month. HMB seems of very minor value for young people and definitely a waste of money.  It may have greater value in the elderly and in wasting diseases.

Hydroxy Methylbutyrate Safe; Helped Cholesterol, Blood Pressure: The leucine metabolite, beta-hydroxy-beta-methylbutyrate (HMB) enhances the effects of exercise on muscle size and strength. Summarizing safety data collected in nine studies in which humans were fed 3 g HMB/d from 3 to 8 wk in duration, included both males and females, young and old, exercising or nonexercising, HMB did not adversely affect any surrogate marker of tissue health and function. HMB significantly improved one indicator of negative mood (Unactivated Unpleasant Affect category, P < 0.05). No untoward effects of HMB were indicated. HMB supplementation resulted in a net decrease in total cholesterol (5.8%, P < 0.03), a decrease in LDL cholesterol (7.3%, P < 0.01) and a decrease in systolic blood pressure (4.4 mm Hg, P < 0.05). These effects of HMB on surrogate markers of cardiovascular health could result in a decrease in the risk of heart attack and stroke. beta-hydroxy-beta-methylbutyrate (HMB) supplementation in humans is safe and may decrease cardiovascular risk factors. Nissan S, et al. Iowa State University. J Nutr 2000 Aug;130(8):1937-45.

Hydroxy Methylbutyrate Helped COPD ICU: In a 7-day DB PC trial of 34 COPD patients on ventilators in intensive care, beta-hydroxy-beta-methylbutyrate (HMB) 3 g/d lowered white blood cell count, C-reactive protein, and creatinine significantly, while cholesterol and total protein were significantly higher. Body weight remained unchanged in both groups. 56% of the HMB group and 25% of the control group had improved pulmonary function. Anti-inflammatory and anticatabolic effects of short-term beta-hydroxy-beta-methylbutyrate supplementation on chronic obstructive pulmonary disease patients in intensive care unit. Hsieh LC, et al. Kaohsiung, Taiwan. Asian Pac J Clin Nutr 2006;15(4):544-50.

Hydroxy Methylbutyrate Mixed Results for Fit Athletes; Mostly No Benefit: In a 9-week DB PC study of 34 resistance trained men, 3g/d of beta-hydroxy-beta-methylbutyrate found leg extension strength increased significantly more in the HMB-supplemented (HMB 14.7%; Placebo 4.8%, P=0.041). beta-Hydroxy-beta-Methylbutyrate (HMB) supplementation of resistance trained men. Thomson JS, et al. Massey University, Auckland, New Zealand. Asia Pac J Clin Nutr 2004;13(Suppl):S59. However, in a 6-week DB PC of rugby players, Aerobic and anaerobic ability was unaffected by oral supplementation with HMB or a combination of HMB and creatine monohydrate. J Sports Med Phys Fit 2003 Mar;43(1):64-8. The same was found after four weeks for football players. J Strength Cond Res 2003 Feb;17(1):34-9. And after 10 days in another football study.  Strength Cond Res 2004 Nov;18(4):747-52.

Hydroxy Methylbutyrate Helped AIDS Cachexia, Cancer Wasting and Elderly Women: Also, HMB, arginine, and glutamine can be safely used to treat muscle wasting associated with AIDS and cancer. JPEN 2004 Mar-Apr;28(2):65-75. Supplementation of beta-hydroxy-beta-methylbutyrate, arginine, and lysine for 12 wk positively altered measurements of functionality, strength, fat-free mass, and protein synthesis, suggesting that the strategy of targeted nutrition has the ability to affect muscle health in elderly women. Nutr 2004 May;20(5):445-51.

Hydroxy Methylbutyrate Increased Muscle and Decreased Fat in 70 Year Old Men: In an 8-week DB PC study of 31 adults age 70 in a 5 d/wk exercise program, HMB (3 g/d) tended to increase fat-free mass gain (HMB, 0.8 kg; placebo, -0.2 kg; P = 0.08)(2.2 pound difference). It also increased the percentage of body fat loss (skin fold: HMB, -0.66%; placebo, -0.03%; P = 0.05). CT scans also indicated a greater decrease in the percentage of body fat with HMB supplementation (P < 0.05). Body composition in 70-year-old adults responds to dietary beta-hydroxy-beta-methylbutyrate similarly to that of young adults. Vukovich MD, et al. South Dakota State University. . J Nut 2001 Jul;131(7):2049-52.

Hydroxy Methylbutyrate Alone Juven, an enteral supplement which is a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine (ARG), and glutamine (GLN) has been shown to restore muscle in cachetic acquired immunodeficiency syndrome (AIDS). In a 28-day DB PC study of 100 adult trauma patients with severe injury receiving standard tube feeds and one of three iso-nitrogenous supplements; HMB, HMB/ARG/ GLN, or placebo, the change in nitrogen balance from the first 7 days to the last 7 days was -4.3 for the HMB and -5.6 g/d HMB/ARG/GLN groups compared with -8.9 g/d for the PLAC group. HMB alone may improve nitrogen balance in critically injured adult patients and that this effect is not a result of lowered muscle protein turnover as originally hypothesized. Beta-hydroxy-beta-methylbutyrate supplementation in critically ill trauma patients. Kuhls DA, et al. University of Nevada. . J Trauma Jan;62(1):125-31.

Hydroxy Methylbutyrate Reduced Muscle Damage in Untrained: In a DB PC study of six non-resistance trained male subjects performed an exercise protocol designed to induce muscle damage on two separate occasions, performed on the dominant or non-dominant arm in a counter-balanced crossover design, HMB/KIC (3 g HMB and 0.3 g alpha-ketoisocaproic acid, daily) attenuated the creatine kinase response, the percentage decrement in one repetition maximum, and the percentage increase in limb girth (P < 0.05). In addition, delayed onset muscle soreness was reduced at 24 h post-exercise (P < 0.05). Supplementation with beta-hydroxy-beta-methylbutyrate (HMB) and alpha-ketoisocaproic acid (KIC) reduces signs and symptoms of exercise-induced muscle damage in man. van Someren KA, et al. Kingston University, United Kingdom. Int J Sport Nutr Exerc Metab 2005 Aug;15(4):413-24.

Hydroxy Methylbutyrate/Glutamine/Arginine No Better Than Non-Essential Amino Acids for Rheumatoid Arthritis: Rheumatoid arthritis (RA) is complicated by cytokine-driven alterations in protein and energy metabolism and consequent muscle wasting (cachexia). In a DB PC study of 40 RA patients, beta-hydroxy-beta-methylbutyrate, glutamine and arginine (HMB/GLN/ARG) vs. a nitrogen (7.19 g/day) and calorie (180 kcal/day) balanced mixture of non-essential amino acids alanine, glutamic acid, glycine, and serine (placebo) for 12 weeks found that HMB/GLN/ARG was not superior to placebo in the treatment of rheumatoid cachexia (groupxtime interactions P>0.05 for all outcomes). Both amino acid mixtures significantly increased fat-free mass (727 g, P<0.01), total body protein (719 g, P=0.02), arms (112 g, P<0.01) and legs (283 g, P<0.01) lean mass, and some measures of physical function. Patients in the HMB/GLN/ARG group reported fewer gastrointestinal complaints compared to placebo. Dietary treatment of rheumatoid cachexia with beta-hydroxy-beta-methylbutyrate, glutamine and arginine: a randomised controlled trial. Marcora S, et al. University of Wales-Bangor, UK. . Clin Nutr 2005 Jun;24(3):442-54.

Hydroxy Methylbutyrate/Glutamine/Arginine May Help Wound Healing: In a 7-14-day DB PC study of 35 healthy, nonsmoking human volunteers 70 years or older using subcutaneous implantated polytetrafluoroethylene tubes into the deltoid region as a measure of collagen repair, 14 g arginine, 3 g HMB, and 14 g glutamine (total nitrogen 3.59 g) daily found a significant increase in collagen deposition without an effect on total protein accumulation and no side-effects. This may provide a safe nutritional means for increasing wound repair in patients. Effect of a specialized amino acid mixture on human collagen deposition. Williams JZ, et al. Johns Hopkins. Ann Surg 2002 Sep;236(3):369-74.

ß-Hydroxy-ß-methylbutyrate (HMB) is a metabolite of leucine formed by transamination to -ketoisocaproate in muscle followed by oxidation of the -ketoisocaproate in the cytosol of the liver, and possibly other tissues. Beta-hydroxy-beta-methylbutyrate (HMB) prevents muscle protein degradation in cancer-induced weight loss through attenuation of the ubiquitin-proteasome proteolytic pathway. HMB plasma levels peak within 60 to 120 min depending on the amount of HMB consumed and whether glucose is consumed with HMB. The plasma half-life is approximately 2.5 hr. Plasma HMB reaches baseline levels at approximately 9 hr following ingestion. However, 70 to 85% of the ingested oral HMB is retained in the body for further metabolism. HMB production in the body may be a first-order reaction controlled by enzyme and KIC concentrations. It has been calculated that, under normal conditions, ~5% of leucine oxidation proceeds via this pathway. If humans are assumed to have enzyme actions similar to those seen in pigs, a 70-kg human would produce from 0.2 to 0.4 g HMB/day depending on the level of dietary leucine. At leucine intakes of 20-50 g/day (which are used therapeutically), the concentrations of leucine and KIC in the liver increase and could result in HMB production reaching gram quantities per day.