Milk Fat Globule Membranes Power Up Strength Gains by Improving the Wiring of Subjects' Muscles | Plus: Its Proven Health, EPO & Immune-Boosting Effects Won't Hurt Either

At the moment it is by no means clear which type of athlete / gymrat would benefit from milk fat globule membrane supplementation and which wouldn't. It's after all well possible that the effects Soga et al. observed in rookies wouldn't occur in adv. trainees or professional athletes.
After the study on nucleotide supplements the Satako Soga's latest paper on the dietary supplementation with milk fat globule membrane is #2 on the list of studies with promising new ergogenics in less than a month. In view of the fact that the last year has been devoid of any true innovations, this is a welcome diversion from writing about whey (or other protein powders), creatine, beta alanine and baking soda, as well as the occasional study on HMB for me.

In spite of the fact that this is a follow up on previous rodent studies from the same researchers, I must warn you not to to expect too much of MFGMs, yet. More data and studies with more realistic resistance training + supplementation protocols from independent labs are warranted before MFGMs may eventually appear next to the previously mentioned top dogs on a list of "SuppVersity Recommended Supplements".
You can learn more about bicarbonate and pH-buffers at the SuppVersity

Instant Boost W/ Baking Soda

Build Bigger Legs W/ Bicarbonate

HIIT it Hard W/ NaCHO3

Creatine + BA = Perfect Match

Bicarb Buffers Creatine

Beta Alanine Fails to HIIT Back
But hey, let's keep the skepticism for the bottom line and take a look at what the scientists from the Kao Corporation did with their fourteen Japanese subjects. The men, who were aged 31–48 years and did not participate in regular strength training before the study, took 1 g of the  structural membranes of milk which are usually covering the triglyceride globules that are dispersed as emulsified bodies in milk or 1g of an identically looking whole milk powder as a placebo in tablet form for 4-weeks (composition see Table 1).
Table 1: Composition of MFGM and whole milk powder (Soga. 2015)
"On the exercise training enforcement days [i.e. the days on which the subjects were required to train], the subjects were instructed to take the tablet within 1 h before training. On the other days, the subjects were instructed to consume the tablet at the time of their choice during their daily routines.
The MFGM was prepared from buttermilk by filtering and centrifugation. The MFGM and whole milk powder compositions were analyzed at Japan Food Research Laboratories (Tokyo, Japan)" (Soga. 2015).
The exercise routine the subjects from both groups had to follow consisted of two workouts per week. The workouts had to be performed on nonconsecutive days for 4 weeks using StrengthErgo 240 stationary cycling exercise machines (Mitsubishi Electric Corporation, Tokyo, Japan). On these machines, the subjects completed 3 sets of 15 % maximal voluntary contraction (MVC) cycle exercises for 60 s and 7 sets of 20 % MVC cycle exercises for 40 s at 50 rpm.
Preliminary rodent studies show that sign. increases in swimming time to exhaustion occur with as little as the equivalent of 1g/day of MFMG (Haramizu. 2014a) - The dose-dependency of the effects suggest that it may be worth taking more than 1g/day for humans, too.
What's the optimal dosage? It is way too early to answer this question with confidence, but the dosage in Soga's study was selected based on the results of previous rodent studies, where the equivalent of the 1 g the subjects consumed in the study at hand turned out to be the minimal effective dosage. In view of the fact that you will find the same amount of MFGM in just 600 ml of full fat milk, I am yet inclined to believe that it may be worth checking if dose-escalations would not yield even better and still side-effect free increases in strength gains and/or increases in endurance performance and fatty acid oxidation as they were observed in previous rodent studies (Haramizu. 2014a). Furthermore, preliminary data from a 4-week safety evaluation by Hari et al. (2015) shows that even 6.5 g/day are without side-effects in healthy humans.
Physical function tests and surface electromyography (EMG) were conducted at baseline and at the end of the study period. In addition, some hemotological parameters were tested of which - surprise - the data in Figure 1 tells you that MFGMs have a small, but statistically significant "EPO-effect" and are thus capable of raising both the red blood cell and hemoglobin content - an effect that has been observed in rodents too (Haramizu. 2014b) and may be ascribed to the incorporation of MFGM phospholipids into red blood cells which would in turn be less vulnerable to exercise-related or other stressors. Whatever the reason for these changes may be, they are certainly in line with the previously mentioned (see red box) increase in fatty acid oxidation during endurance exercise that may be facilitated by an RBC and hemoglogin related increase in oxygen transport.
Figure 1: The significant increase in red blood cell and hemoglogin content could explain the previously observed increases in endurance performance and fatty acid oxidation in Haramizu et al. (2014a). The buffered decrease in white blood cell may not be statistically significant, but may still indicate beneficial effects on the immune system (Soga. 2015).
Both the increase in RBC and hemoglobin, as well as the buffering of the albeit non-significant decline in white blood cells in the placebo group, which may be a response to the exercise-induced stress and evidence of an immune-boosting effect of MFGM supplementation during any potentially exercise induced immune suppression, do yet need further investigation before they can be explained mechanistically.

No further research is needed, though, to state that all other blood markers. These included AST + ALT (liver health), glucose and triglycerides + cholesterol, neither of which was affected by the supplement. The latter cannot be said of the increase in leg extension strength before and after the intervention and the EMG activity which showed highly significant inter-group differences.
Do I even have to supplement? I mean, I can just drink 600ml of full fat milk, right? I don't doubt that you can do just that. The problem is that the milk you can drink will probably be pasturized - a process of which Cano-Ruiz et al. (1997) have shown that it will induce significant and potentially functionally relevant differences in the composition of the milk fat globule membrane. Whether the supplement that was used at the study at hand was made during the production of buttermilk before or after pasteurization is not clear. If we assume it was made after pasteurization, though, you could in fact hope for similar results from pasteurized whole milk. Otherwise, the milk would have to be raw (even if it is, though it cannot be guaranteed that the same amount of MFGMs from milk will have identical effects).
In fact, the differences in Figure 2 are pronounced enough to ask the question: Were they induced by the supplementation alone or did the pathetic training regimen have an effect here, as well? As I am going to point out in the bottom line one paragraph below, we will need studies with more realistic training programs to answer this question in a way that's relevant for trainees like you and me. In the mean time, however, there is no debating "that the daily intake of 1 g MFGM combined with regular, twice weekly exercise improved skeletal muscle strength (leg extension) in middle-aged adults, despite a lack of change in muscle mass" (Soga. 2015).
Figure 2: The MFGM supplementation lead to significant increases in leg extension strength, of which the increase in EMG activity (likewise sign.) suggests that they were mediated by neuronal changes (Soga. 2015).
The same goes for the increase in RMS of surface EMG, which indicates that the dietary provision of MFGM increased the average (RMS = root mean square) motor unit activity during muscle contraction and may thus mechanistically explain why the subjects got stronger even though they didn't make substantial gains in muscle mass: The supplement helped them to "make the most" of the muscle they had. This hypothesis is in line with results from rodent studies which
"[...] revealed that dietary MFGM combined with regular exercise improved muscle strength in adult mice primarily by stimulating the pathway involving “nervous system development” in the skeletal muscle (Haramizu. 2014b). This pathway includes functional annotations such as formation of synapses, growth of neurites, or development of NMJ. Dietary MFGM combined with exercise increased skeletal muscle expression of docking protein-7 (Dok-7) and muscle-specific receptor tyrosine kinase in mice, both of which play a critical role in NMJ [neuromuscular junction] formation. Defects in NMJ function causes muscle weakness in neuromuscular disorders, and Dok-7 gene therapy improves NMJ formation and rescues the motor activity" (Soga. 2015).
And still, even at the risk that I may sound like a broken record, I have to repeat that without future research it is impossible to tell (a) whether the assumptions we've made about the increase in red blood cell count are accurate and, maybe even more importantly, (b) who, i.e. which type of athlete, will benefit most from using MFGM supplements.
MFGMs can do much more! It's not like this was the first study on MFGMs. It's just the first study on exercise performance in humans. In rodents performance incre- ments (see red box), as well as increases in RBC and EMG have long been established. In older women MFGMs have been shown to improve or fully reverse frailty (Kim. 2015). As hinted at in the conclusion, the addition of MFGMs to infant formulas will also narrow the gap in cognitive development and lipid composition (+future VCD risk) between breastfed and formula-fed infants (Timby. 2014a,b).

Other purported benefits include anti-cancer effects (Lemonnier. 2003) stress protection, the potential to reduce the risk of Alzheimer's (Spitsberg. 2005) and increase gastrointestinal intergrity (Snow. 2010), and beneficial effects on blood lipids (Noh. 2004) and cardio-vascular health where some researchers expect beneficial, while others fear detrimental effects (Riccio. 2004; Spitsberg. 2005; Singh. 2006). Since most of these effects have been observed in vitro or in rodent studies, it is yet by no means clear which of them would occur in response to MFGM supplementation.
Bottom line: As I already pointed out in the introduction, it is way too early to celebrate MFGMs as "the next big thing" or the supplemental reincarnation of the "a gallon of milk per day" protocol which would have provided its followers a highly significant 6g+ dose of MFGM on a daily basis.

The reason(s) we need further research are simple. Firstly, we need independent validation of the results that were generated by scientists who work for a company that produces milk fat globule membranes. Secondly, studies in trained individuals in whom the purportedly mechanistically involved improvements in the neuronal wiring of the muscle may be significantly less pronounced, as well as studies involving more realistic resistance training and endurance training protocols to confirm the beneficial effects that were observed in this study and the rodent study by Haramizu et al. which found significant increases in maximal endurence (see red box) are required to be able to tell for whom MFGM supplements will be beneficial. And third- and lastly, experiments with different dosing protocols (timing and amount) are necessary to determine the optimal dosing schemes - preferably for different types of exercises.

With that being said, MFGMs are still one of the more promising newcomers, lately. Their effects are after all not restricted to performance enhancing in the narrow(er) sense, but extend into the realms of general health and fitness (see box on the right hand side of this bottom line). In conjunction with their potential use as additives to baby formula, where they have already been shown to improve risk markers of future cardiometabolic disease and the babies' cognitive development to an extent that marginalizes the benefits of breast-feeding in these areas, make them one of the hottest candidates on my personal "still insufficient evidence, but promising"-list of supplement to keep an eye on | Comment on Facebook!
References:
  • Cano-Ruiz, M. E., and R. L. Richter. "Effect of homogenization pressure on the milk fat globule membrane proteins." Journal of Dairy Science 80.11 (1997): 2732-2739.
  • Haramizu, Satoshi, et al. "Dietary milk fat globule membrane improves endurance capacity in mice." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 307.8 (2014): R1009-R1017.
  • Haramizu, Satoshi, et al. "Habitual exercise plus dietary supplementation with milk fat globule membrane improves muscle function deficits via neuromuscular development in senescence-accelerated mice." SpringerPlus 3 (2014): 339.
  • Kim, Hunkyung, et al. "Effects of Exercise and Milk Fat Globule Membrane (MFGM) Supplementation on Body Composition, Physical Function, and Hematological Parameters in Community-Dwelling Frail Japanese Women: A Randomized Double Blind, Placebo-Controlled, Follow-Up Trial." PloS one 6.10.2 (2015): e0116256.
  • Lemonnier, Lori A., et al. "Sphingomyelin in the suppression of colon tumors: prevention versus intervention." Archives of Biochemistry and Biophysics 419.2 (2003): 129-138.
  • Riccio, Paolo. "The proteins of the milk fat globule membrane in the balance." Trends in food science & technology 15.9 (2004): 458-461.
  • Singh, Harjinder. "The milk fat globule membrane—A biophysical system for food applications." Current Opinion in Colloid & Interface Science 11.2 (2006): 154-163.
  • Snow, D. R., et al. "Membrane-rich milk fat diet provides protection against gastrointestinal leakiness in mice treated with lipopolysaccharide." Journal of dairy science 94.5 (2011): 2201-2212.
  • Soga, Satoko, Noriyasu Ota, and Akira Shimotoyodome. "Dietary milk fat globule membrane supplementation combined with regular exercise improves skeletal muscle strength in healthy adults: a randomized double-blind, placebo-controlled, crossover trial." Nutrition Journal 14.1 (2015): 85.
  • Spitsberg, V. L. "Invited review: Bovine milk fat globule membrane as a potential nutraceutical." Journal of dairy science 88.7 (2005): 2289-2294.
  • Timby, Niklas, et al. "Neurodevelopment, nutrition, and growth until 12 mo of age in infants fed a low-energy, low-protein formula supplemented with bovine milk fat globule membranes: a randomized controlled trial." The American journal of clinical nutrition 99.4 (2014a): 860-868.
  • Timby, Niklas, et al. "Cardiovascular risk markers until 12 mo of age in infants fed a formula supplemented with bovine milk fat globule membranes." Pediatric research 76.4 (2014b): 394-400.
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