HMB

HMB (short for β-Hydroxy β-Methylbutyrate) is a metabolite of the amino acid leucine that, along with KIC (α keto-isocaproate) and isovaleryl-CoA, mediate the effects of leucine. Approximately 5% of dietary leucine is oxidized into HMB, and HMB appears to be the main metabolite of leucine that more effectively prevents the breakdown of muscle protein.

When compared to leucine, HMB appears to be significantly more potent on a gram per gram basis at attenuating the rate of muscle protein breakdown but is less effective than leucine at inducing muscle protein synthesis. Due to this, HMB is marketed as an anti-catabolic agent (purposed to reduce the rate of muscle breakdown) rather than an anabolic agent (purposed to increase muscle mass).

Human trials don't normally tend to be structured to properly assess the effects of HMB, as most of the studies are a standard diet paired with an exercise regimen investigating the role of HMB in promoting muscle protein synthesis (of which it is similar to leucine in the sense that there are positive results, but quite unreliably so); the limited evidence that assesses HMB during periods of muscle loss are either underpowered or not in athletes.

HMB, currently, appears to be a pretty interesting supplement for the purpose of reducing muscle wasting during periods where muscle atrophy is accelerated (cachexia, AIDS, bedrest) and should theoretically work in athletes on a calorie restricted diet but is not fully established for this role yet (which is a notable issue, since glutamine has a large dichotomy between clinical and healthy populations).

Supplementation of HMB tends to be in the dosage range of 1-3g daily for the purpose of reducing muscle mass losses over time (anti-catabolic). As HMB is said to be 20-fold more potent than leucine for this purpose, it is seen as equivalent to 20-60g of leucine supplementation.

For the purpose of muscle protein synthesis, HMB and leucine are fairly equivalent if not the latter (leucine) being more potent on a gram basis. HMB is not advised for inducing muscle protein synthesis since leucine is likely more effective as well as cheaper.

Supplementation of HMB prior to an exercise session would require the usage of an HMB free acid rather than a calcium salt, and the above dosage range still holds. For this specific purpose, HMB is to be taken 30-45 minutes before a workout.

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects hmb has on your body, and how strong these effects are.

Grade	Level of Evidence [show legend]
	Robust research conducted with repeated double-blind clinical trials
	Multiple studies where at least two are double-blind and placebo controlled
	Single double-blind study or multiple cohort studies
	Uncontrolled or observational studies only

Level of Evidence ? The amount of high quality evidence. The more evidence, the more we can trust the results.	Outcome	Magnitude of effect ? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.	Consistency of research results ? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.	Notes
	Power Output	-	Moderate See all 12 studies	Limited evidence supports the increase in power output, which may be due to chance; more often than not, there is no significant influence
	Muscle Damage	Notable	High See all 3 studies	Decrease creatine kinase exists following acute supplementation (15-30 minutes before a workout) of HMB free acid to about a third of control, and is effective in trained individuals
	Fat Mass	Minor	Low See all 7 studies	There may be a decrease in fat mass associated with HMB supplementation when combined with resistance training, but this reduction is not a large magnitude and usually does not occur; quite unreliable
	Cortisol	-	Very High See all 3 studies	No significant influence on cortisol levels following acute ingestion
	Food Intake	-	High See all 4 studies	Although there are sporadic alterations seen in food intake in studies using HMB supplementation, they are not reliable and the exact change observed changes. It is likely that there is no significant effect per se and this is due to the study population
	Lean Mass	-	High See all 8 studies	No significant influences on lean body mass associated with HMB supplementation
	Testosterone	-	Very High See all 3 studies	No significant influence of acute usage on testosterone levels
	Training Volume	-	Very High See all 3 studies	No significant influence on training volume when used acutely
	Total Cholesterol	Minor	- See 2 studies	One underpowered study noted an increase in total cholesterol while another suggested no significant effect. The exact effect of HMB on total cholesterol is not currently known and required replication
	Anaerobic Running Capacity	-	- See study	No significant improvement in sprint capacity in trained persons supplementing HMB
	Bone Mineral Density	-	Very High See 2 studies	Studies that assess bone mineral density via DEXA, albeit short in duration and in athletes rather than populations at risk for osteoporosis, fail to find significant alterations in bone mineral density.
	C-Reactive Protein	-	- See study	No significant influence on C-reactive protein
	Fatigue	-	Very High See 2 studies	No significant reduction in exercise-induced fatigue associated with HMB supplementation in athletes
	Growth Hormone	-	- See study	Serum growth hormone is not significantly altered with HMB supplementation in athletes
	HDL-C	-	Very High See 2 studies	No significant influence on HDL cholesterol levels
	IGF-1	-	- See study	No significant alterations in circulating IGF-1 concentrations
	Interleukin 6	-	- See study	No significant alterations in circulating IL-6 concentrations
	LDL-C	-	Very High See 2 studies	No significant influence on LDL cholesterol levels
	Liver Enzymes	-	Very High See 2 studies	No significant alterations in serum liver enzymes are noted with HMB supplementation
	Muscle Soreness	-	Very High See 2 studies	No significant influence on perceived muscle soreness following exercise with HMB supplementation
	Range of Motion	-	- See study	No significant influence on range of motion (impaired in both groups due to soreness post workout)
	Blood Glucose	Minor	- See study	A lone study that is underpowered suggest a decrease in blood glucose (measured by chance during a blood panel); not enough robust evidence supports a reduction in blood glucose but it cannot be ruled out
	Urea	Minor	- See study	A slight increase in urea has been noted, requires replication
	Triglycerides	-	- See study	No significant influence on triglycerides
	VO₂ Max	-	- See study	No significant influence on VO2 max in trained athletes

Studies Excluded from Consideration

• Confounded with Arginine and Lysine, and one with Vitamin D^[1][2][3]

• Confounded with other amino acids^[4]

• Does the feeding window matter for muscle mass?

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