BCAAs – Second Experiment

I did a second experiment with BCAAs today. The last one was at a Crossfit competition (CrossFit Competition – Festivus Games). There was so much going on that day that I didn’t get a chance to compare the BCAA effects. I was also using Ketone Supplements that day so I could not isolate any effects.

This morning, before my MAF walk, I decided to try the second serving of BCAAs. They were given to me by athlete Van Wilder. I took them with Creatine in water before leaving the house around 5:30 AM. The product is Optimum Nutrition Essential AmiN.O. Energy. Here’s a picture of the product.

Here is the nutrition label.

These have as much caffeine as a cup of coffee but they are taken in much more quickly than coffee. I definitely noticed a buzz from the caffeine. I also had some strange data from my heart rate monitors. I also had some soreness/pain in my left knee so I took it a bit easier as documented here(Measuring Heart Rate).

I can’t say whether there was an effect beyond the caffeine effect.

In the meanwhile I ordered another product as recommended by Ben Greenfield (Everything You Need To Know About How To Use Amino Acids For Muscle Gain, Appetite Control, Injury Repair, Ketosis And More.) Ben provides some compelling arguments for why BCAAs (Kion Aminos) may be a good choice for fasted workouts with ketogenic athletes.  There are quite a few studies referenced on Ben’s page.

The Other Side

On the other side, Menno Hensellmen has some arguments against BCAAs and refers to this study for his position (Robert R. Wolfe. Branched-chain amino acids and muscle protein synthesis in humans: myth or reality?
Journal of the International Society of Sports Nutrition 2017 14:30).

An extensive search of the literature has revealed no studies in human subjects in which the response of muscle protein synthesis to orally-ingested BCAAs alone was quantified, and only two studies in which the effect of intravenously infused BCAAs alone was assessed. Both of these intravenous infusion studies found that BCAAs decreased muscle protein synthesis as well as protein breakdown, meaning a decrease in muscle protein turnover. The catabolic state in which the rate of muscle protein breakdown exceeded the rate of muscle protein synthesis persisted during BCAA infusion. We conclude that the claim that consumption of dietary BCAAs stimulates muscle protein synthesis or produces an anabolic response in human subjects is unwarranted.

I will report on the BCAAs.


Quality of Protein Matters for Muscle Protein Synthesis

A 2012 rat study that shows not all protein is of equal quality when it comes to Muscle Protein Synthesis (Norton LE1, Wilson GJ, Layman DK, Moulton CJ, Garlick PJ. Leucine content of dietary proteins is a determinant of postprandial skeletal muscle protein synthesis in adult rats. Nutr Metab (Lond). 2012 Jul 20;9(1):67. doi: 10.1186/1743-7075-9-67. ).

…only whey and egg groups increased post-prandial plasma Leu and stimulated MPS above food-deprived controls. Likewise, greater phosphorylation of p70 S6 kinase 1 (S6K1) and 4E binding protein-1 (4E-BP1) occurred in whey and egg groups versus wheat and soy groups. Experiment 2 demonstrated that supplementing wheat with Leu to equalize the Leu content of the meal also equalized the rates of MPS.

Protein Before Bed

Here’s an interesting study which indicates that Protein taken before bed stimulates Muscle Protein Synthesis (Tim Snijders, Peter T Res, Joey SJ Smeets, Stephan van Vliet, Janneau van Kranenburg, Kamiel Maase, Arie K Kies, Lex B Verdijk, Luc JC van Loon; Protein Ingestion before Sleep Increases Muscle Mass and Strength Gains during Prolonged Resistance-Type Exercise Training in Healthy Young Men, The Journal of Nutrition, Volume 145, Issue 6, 1 June 2015, Pages 1178–1184).

Methods: Forty-four young men (22 ± 1 y) were randomly assigned to a progressive, 12-wk resistance exercise training program. One group consumed a protein supplement containing 27.5 g of protein, 15 g of carbohydrate, and 0.1 g of fat every night before sleep. The other group received a noncaloric placebo. Muscle hypertrophy was assessed on a whole-body (dual-energy X-ray absorptiometry), limb (computed tomography scan), and muscle fiber (muscle biopsy specimen) level before and after exercise training. Strength was assessed regularly by 1-repetition maximum strength testing.

Results: Muscle strength increased after resistance exercise training to a significantly greater extent in the protein-supplemented (PRO) group than in the placebo-supplemented (PLA) group (+164 ± 11 kg and +130 ± 9 kg, respectively; P < 0.001). In addition, quadriceps muscle cross-sectional area increased in both groups over time (P < 0.001), with a greater increase in the PRO group than in the PLA group (+8.4 ± 1.1 cm2 vs. +4.8 ± 0.8 cm2, respectively; P < 0.05).

Both type I and type II muscle fiber size increased after exercise training (P < 0.001), with a greater increase in type II muscle fiber size in the PRO group (+2319 ± 368 μm2) than in the PLA group (+1017 ± 353 μm2P < 0.05).

Muscle Protein Synthesis Meal Spacing Maximum

I asked Dr Donald Layman the following question:

My question is about the three hour PMS window. The maximum happens at 90 minutes and the return to baseline is at 180 minutes. Does that mean that the cycle can be repeated every three hours? Is there a study showing the minimum interval between PMS cycles?

He responded!

Great Q! No clear study on 2nd meal timing. IMO 3 hr is too soon Our data shows initiation factors still fully active at 180 min, so meal effect should be limited at 3 hr Initiation factors do not reset until ~5 hr However, van Loon shows night meal effect @ 2.5hr post dinner

IMO, to max meal effect, I target meals at 4 to 5 hr apart, with 3 to 4 meals per day, and 1st and 3rd meals at ~45 g to max mPS response.

I am changing my eating pattern in response to this information. I am leaving Intermittent Fasting window and I am going to eat breakfast starting today (I ate breakfast).

7 AM, 12 Noon, 7 PM (after workout or earlier if it is an “off” day).


Fat Plus Protein Doesn’t Affect Muscle Protein Synthesis

Another related study shows that adding fat to protein doesn’t slow or stop Muscle Protein Synthesis (Gorissen SHM1, Burd NA1, Kramer IF1, van Kranenburg J, Gijsen AP, Rooyackers O, van Loon LJC. Co-ingesting milk fat with micellar casein does not affect postprandial protein handling in healthy older men. Clin Nutr. 2017 Apr;36(2):429-437.).

Co-ingesting milk fat with micellar casein does not impair protein-derived phenylalanine appearance in the circulation and does not modulate postprandial myofibrillar protein synthesis rates.


Spreading Out Protein is Better for Muscle Protein Synthesis

Spreading our your protein intake is better for Muscle Protein Synthesis than taking fewer larger protein meals (Areta JL1, Burke LM, Ross ML, Camera DM, West DW, Broad EM, Jeacocke NA, Moore DR, Stellingwerff T, Phillips SM, Hawley JA, Coffey VG. Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis. J Physiol. 2013 May 1;591(9):2319-31. doi: 10.1113/jphysiol.2012.244897. Epub 2013 Mar 4.)

20 g of whey protein consumed every 3 h was superior to either PULSE or BOLUS feeding patterns for stimulating MPS throughout the day.

This study provides novel information on the effect of modulating the distribution of protein intake on anabolic responses in skeletal muscle and has the potential to maximize outcomes of resistance training for attaining peak muscle mass.

Providing 20 g of protein every 3 hours stimulates MPS more than providing the same amount of protein in less regular doses (40 g every 6 hours), or more regular doses (10 g every 1.5 hour).

A related study shows the importance of spreading out protein over a day rather than eating most of your protein at a single meal, say dinner (Mamerow MM, Mettler JA, English KL, Casperson SL, Arentson-Lantz E, Sheffield-Moore M, Layman DK, Paddon-Jones D. Dietary protein distribution positively influences 24-h muscle protein synthesis in healthy adults. J Nutr. 2014 Jun;144(6):876-80.).

The consumption of a moderate amount of protein at each meal stimulated 24-h muscle protein synthesis more effectively than skewing protein intake toward the evening meal.

Blood Sugars Go Up After Protein

In many (maybe even most) people blood sugar levels often goes up by a small amount following consumption of protein. I did an experiment which showed this in myself (Blood Sugar Responses Compared). This effect is temporary and the levels often go lower after a few hours than before the protein was eaten.

This increase of blood sugar is actually a good thing. It indicates that your body is spending a lot of energy on Muscle Protein Synthesis. Muscle Protein Synthesis has a 3 hour window after eating protein (MPS peaks at 90 minutes and returns to baseline in 3 hours) (Protein Guru). This is similar to the effect from exercise where your blood sugar will go up immediately after intense exercise – even when you are fasted. Your body is mobilizing energy in the form of glucose from the liver (Protein Gurus – Part 2).

Contrary to a lot of misinformation out there this is not Gluconeogenesis (GNG) from the Protein. It is GNG that comes from the fat in your liver and bloodstream (Xinhua Chen, Nayyar Iqbal, and Guenther Boden. The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjects. J Clin Invest. 1999 Feb 1; 103(3): 365–372.).

This is basically the same as exercise where your blood sugar goes up with intensive exercise but if you look at the glucose levels over time they are lower averaged out over the entire day from higher protein consumption. This has been demonstrated through CGM.

GNG from your liver comes from the glycogen already in your liver which came from the fat in your bloodstream and liver. And believe me, we all need lower fat in our livers. That’s the main cause of T2D (in my opinion and that of many others).

If you are low carb your body has to produce glucose to make up for what you are not getting in your diet. Your body can produce glucose from any of the three – Carbs, Protein, and Fat. The body is really bad at doing it from Protein but if you only ate Protein and you ate an excessive amount the body would be forced to use Protein to make the needed glucose.
What is not commonly appreciated is that the liver only produces the glucose that it thinks that it needs. It’s not producing based on what you eat (outside of carbs). When you eat protein your body needs more energy to perform MPS so it sends up the glucose a small amount. Glucose for muscle building is a good thing.
Carbs, on the other hand, send up blood glucose by a large amount and are not a good thing when it builds up.

Protein Wisdom

This post is to distill my previous thoughts and posts on Protein.

Overfeeding Protein does not lead to weight gain (Too Much Protein?).

Leucine is an important component of Protein which is key to Muscle Protein Synthesis. It takes 3 grams of Leucine to achieve Muscle Protein Synthesis. It takes around 30g of protein to get 3g of Leucine. That’s around 4 ozs of lean chicken for instance (Protein Guru).

Protein should be eaten first (before vegetables, etc). Protein should be spread out by at least three hours between meals. (Protein Gurus).

That is the basis for my own strategy.

Another Protein Guru (Dr Van Loon)

Dr Van Loon is interviewed here (Optimizing Protein Intake with Luc van Loon, PhD). Here are the referenced studies:

  1. Post-Prandial Protein Handling: You Are What You Just Ate
  2. Protein ingestion before sleep improves postexercise overnight recovery
  3. Pre-sleep protein ingestion does not compromise the muscle protein synthetic response to protein ingested the following morning
  4. Strategies to maintain skeletal muscle mass in the injured athlete: nutritional considerations and exercise mimetics
  5. Skeletal muscle disuse atrophy is not attenuated by dietary protein supplementation in healthy older men
  6. Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates – A Substudy
  7. Habituation to low or high protein intake does not modulate basal or postprandial muscle protein synthesis rates: a randomized trial
  8. Ingestion of Wheat Protein Increases In Vivo Muscle Protein Synthesis Rates in Healthy Older Men in a Randomized Trial
  9. What is the Optimal Amount of Protein to Support Post-Exercise Skeletal Muscle Reconditioning in the Older Adult?
  10. Dietary protein for athletes: from requirements to optimum adaptation

Notes from the interview

  • How much protein?
    • 4-5 meals a day
    • 20-25g of protein per meal
    • Maybe more for elderly (45g?)
    • Maybe more for sedentary
  • Very little evidence for damage from too much protein
  • What happens to the 20g of protein?
    • 10g is retained in the gut
    • 10g of the 20 is released into the circulation
      • 2.2g of the circulated protein are being incorporated into muscle
        • By about 6 hours after the meal
  • Supplementing protein to older patients via tube into stomach increased MPS during sleep
    • Eat casein before bedtime can get additional muscle mass and strength
    • This doesn’t harm the next morning’s response to protein
  • Adding carbs or protein doesn’t affect muscle protein synthesis
  • Carbs help for regaining glycogen stores but they are not needed for MPS
  • Consuming Protein in the 12-hours after exercise increases MPS
  • During exercise MPS increases due to increased blood flow to the muscles when protein is available


Protein Gurus – Part 2

Another great article on Muscle Protein Synthesis (Researchers Point to the Optimal Protein Dose, Timing & Distribution to Maximize Muscle). They have the following takeaways from the scholars:

  1. Muscle protein synthesis is an anabolic response that occurs in response to protein feeding and resistance training. On the protein front, it specifically relates to leucine intake. To maximize the MPS response, ~2.5g of leucine is required. This is known as the “leucine threshold”.

  2. To maximize the muscle protein synthesis response over the course of a day, it seems that 3–4 evenly spaced meals that surpass the leucine threshold is a prudent strategy.

  3. A meal containing 0.4 grams of protein per kilogram of bodyweight (g/kg BW) from a high-quality protein source will allow an individual to hit the leucine threshold. For most people this is somewhere between 20–40g.

  4. The best sources of protein for this purpose are animal proteins (particularly whey protein) due to their high branched-chain amino acid composition. Plant-based protein sources will mean a higher protein intake is needed to hit the required level of leucine.

  5. When MPS is “spiked” in response to a protein feeding, it will drop back to baseline within 2–3 hours. This drop will occur regardless of whether protein or amino acids continue to be fed and leucine remains high. This is potentially due to high demand of ATP required by cells for MPS (i.e. MPS is an energy-expensive process and the cell will stop MPS to conserve energy).

  6. MPS is only a proxy measure for muscle hypertrophy, not an exact correlate. Net muscle protein balance (MPS vs. muscle protein breakdown) matters more. And further, there are many other factors than influence actual hypertrophy outside of MPS and MPB.

  7. Of all the macronutrients, it seems that timing and distribution (versus simply total daily intake) is most important when it comes to protein. However, there are pragmatic examples of scenarios where we may not theoretically maximize MPS, yet still preserve and/or build plenty of muscle mass. For example, daily intermittent fasting.

The whole article is worth reading.