Intermittent Fasting in Trained Women Adds Same Amount of Muscle, Strips Extra Body Fat (4-6%) | No Effect of HMB

HMB did matter, but not significantly; and fasted training was not involved in the extra-fat loss and improvement in body composition.
While it has long been discussed if serious gainz are even possible on time-restricted feeding regimen, such as classic 'intermittent fasting', SuppVersity readers have known for years that "New 'Lean Gains' Study Confirms: IF Gets Athletes Lean & Improves Insulin Sensitivity W/Out Impairing Their Gains" (➡article discussing Moro 2016) - that's in men, though, and that, in turn, is one of several factors that make the latest study by Tinsley et al. (2019) worth looking at.

In their latest study, the Texas Tech University researchers combined two research questions into one study: (a) Does time-restricted feeding affect the adaptive response to resistance training women? (b) Can this effect be augmented and/or modulated by supplementing the leucine-metabolite HMB during the fasting phases (and once in the PM)?
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You're wondering why on earth someone would still do research on HMB? Well, the study was supported by MTI Biotech Inc. who sell HMB and there's nothing reprehensible about financial support from the supplement industry... as long as it does not lead to irreproducible (and, for many, hardly credible) results as it may have been the case of the notorious free-form HMB study by Wilson et al. The reason we should still keep the role of the sponsor of which the scientists write that neither this nor the other supporter, Dyamatize, "play[ed] a role in the overall design or execution of the study, the analysis, and interpretation of the data, or the presentation of the results found in this article" is that sponsorship can lead to an often unconscious reporting bias and/or a certain emphasis on pro-supplement conclusions in the discussion of the results.

But we will get to potential issues with the presentation and interpretation of the results later. Let's first take a look at the study design as it is described in the abstract:
"This study employed a randomized, placebo-controlled, reduced factorial design and was double-blind with respect to supplementation in TRF groups. Resistance-trained females were randomly assigned to a control diet (CD), TRF, or TRF plus 3 g/d HMB (TRFHMB).
Figure 1: Study timeline and assessments. RT, resistance training (Tinsley 2019).
TRF groups consumed all calories between 1200 h and 2000 h, whereas the CD group ate regularly from breakfast until the end of the day. All groups completed 8 wk of supervised RT and consumed supplemental whey protein. Body composition, muscular performance, dietary intake, physical activity, and physiological variables were assessed. Data were analyzed prior to unblinding using mixed models and both intention-to-treat (ITT) and per protocol (PP) frameworks" (Tinsley 2019).
A closer look at what exactly the 18 and 30 y-old women with significant training experience (≥1 y of RT at a frequency of 2 to 4 sessions per week w/ weekly training of major upper- and lower-body muscle groups), who were recruited via posters, e-mail announcements, and word of mouth, did in this prospectively registered (clinicaltrials.gov) experiment.
Starting to Have Breakfast is Worst New Year's Resolution ... Unless You Want to Gain Weight more
Habituation effects were addressed: From my article about the habituation effect of breakfast eating on the metabolic effects of breakfast skipping and the ill effects of changing this habit, you will remember that it can be an issue if you put subjects who are used/not used to eating first thing in the morning on a time-restricted feeding regimen. Against that background it's of particular importance that Tinsley et al. (2019) stratified participant based on not just on BF% at screening (15–21% or >21%) but also based on their habitual breakfast consumption (≥5 d/wk compared with <5 d/wk), before they then randomly assigned the women to one of the three study groups using sequences produced from a random sequence generator.

Also noteworthy: The way fasting and training were timed precludes interference effects of fasted training... I mean, not that we could assume that this would explain the extra fat loss, anyway.
Here's the gist as far as diet, supplementation, and, obviously, the ladies' training regimen are concerned:
  • ⏲ the feeding window of the TRF and TRFHMB participants was set to 1200 h - 2000 h each day, while and CD participants were instructed to consume breakfast as soon as possible after waking and to continue to eat at self-selected intervals throughout the remainder of the day;
  • ๐Ÿ• the only dietary advice the subjects received was to hit their protein intake goals of by consuming whey protein supplement (regular concentrate, nothing fancy ๐Ÿ’ฒ "Elite 100% Whey", Dymatize Enterprises, LLC) on both training and non-training days in order to achieve a protein intake ≥1.4 g/kg/d; 
  • ๐Ÿฃ the target energy intake was prescribed by multiplying resting energy expenditure (REE), assessed via indirect calorimetry, by an activity factor of 1.5 and then subtracting 250 kcal; in that, "[t]he goal of the small caloric reduction was to promote fat loss while still providing adequate nutritional support for muscular hypertrophy"; effectively, the women thus ate more, though that pre-intervention 250, 162, and 90kcal/day for CD, TRF, and TRFHMB, respectively;
  • ๐Ÿฑ the macronutrients averaged out at 28/40/32 for proteins, carbs, and fats - with no inter-group differences and a de-facto protein intake of 1.6g/kg per day in all three groups
  • ๐Ÿ’Š on top of the whey all subjects consumed, they received either placebo (calcium lactate) or calcium 3x1g HMB supplements; both were identical in appearance and taste, and were matched for calcium (102 mg), phosphorus (26 mg), and potassium (49 mg) content;
  • Table 1: Overview of the ladies' workout regimen. Workouts were supervised and took place in the PM (12-18h, with fasting subjects consuming their first meal early if they came in between 12-13h); 25g whey were consumed right after every workout (Tinsley 2019).
    ๐Ÿ’Šx⏲ participants were instructed to ingest 2 capsules on 3 occasions each day: upon waking, midmorning while still fasting, and prior to bed, for a total dose of 3 g/d;
  • ๐Ÿ’Š the women "were discouraged from consuming any additional sports supplements beyond those provided by study investigators, with the exception of common multivitamin/mineral supplements" (Tinsley 2019).
  • ๐Ÿ’ช the ladies trained for 8-weeks under supervision and on three non-consecutive days each week (i.e., Mondays, Wednesdays, and Fridays), and 2 different upper- and lower-body sessions were alternated (Table 1); the women trained to momentary failure
  • ๐Ÿฝ the training times were not set in stone, but nobody was allowed to train fasted; hence participants who came in early in the training window from 12-18h, had to break their fast early
In short: The researchers mimicked what a dedicated but not necessarily crazy gymrat could, in fact, be doing for 8 weeks or even longer to improve her physique. Speaking of which, as the scientists report as early as in the abstract, all subjects saw...
Figure 2: Body composition data (per protocol analysis | in the intention to treat analysis, which includes all subjects regardless of adherence, the fat loss advantage was visible but not sign.)
  • comparable fat-free mass (FFM) accretion ๐Ÿ’ช (+2% to 3% relative to baseline) and skeletal muscle hypertrophy ๐Ÿคน‍♀️ occurred in all groups, but ...
  • statistically different effects on fat mass ๐ŸคŸ (CD: +2%; TRF: −2% to −4%; TRFHMB: −4% to −7%) were observed in the per-protocol analysis (meaning, when only those who actually adhered to their protocol were included - for all subjects, including those who didn't fast appropriately the effect was no longer significant).
Finally, it's worth mentioning that "[m]uscular performance improved without differences between groups"; and that "[n]o changes in physiological variables occurred in any group, and minimal side effects were reported" (Tinsley 2019).
This study and the latest meta-analysis show: athletes & experienced gymrats don't benefit from HMB supplements.
Did you notice something? Yes, HMB is even mentioned... at least not until the scientists conclude the abstract to their study by somewhat cumbersomely referring to the fact that
"[s]upplemental HMB during fasting periods of TRF did not definitively improve outcomes" (that's my emphasis in a quote from Tinsley 2019).
To me, this seems to be even a tad bit too unbiased; because, as non-significant as the difference may be, the increased fat loss with HMB the scientists observed (cf. Fig.1 FM dark vs. light grey bars) is a recurring theme in HMB research... one of which the previously discussed HMB ↔ body comp. meta-analysis shows that it is yet by no means observed in every study (see Figure 2 | here).

Hence, the take-home is: breakfast skipping works for both sexes and the combination of a small caloric deficit with plenty of high-quality protein will improve your body composition.

So simply stating that "non-significant benefits" have been observed, in the conclusion to the abstract would be perfectly ok, IMHO. The strange "not definitively", on the other hand, could also imply that there some women would indeed benefit and will rather confuse than enlighten the reader without full-text access, whose take away message should be: in the short run and at moderate deficits of only -250kcal/d, time-restricted feeding in the form of breakfast skipping helps women lose extra body fat without measurable effects on lean mass acquisition (let alone loss) when protein intakes are high and high EAA proteins (whey) are provided | Comment!
References:
  • Moro, Tatiana, et al. "Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males." Journal of Translational Medicine 14.1 (2016): 290.
  • Tinsley, Grant M., et al. "Time-restricted feeding plus resistance training in active females: a randomized trial." The American Journal of Clinical Nutrition (2019).
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