Things I've Changed My Mind On | Episode 5

The mark of any good scientist is their willingness to change their mind based on evidence. No matter how strongly we feel about a topic, we must always consider new data, and if the data is strong enough over time, we change our minds. In this episode, Dr. Norton goes down a list of the things he felt most strongly about and later changed his mind on as new data emerged.

What Have I Changed my Mind On?

BCAA

Mechanistic data demonstrated that the BCAA, specifically leucine stimulates muscle protein synthesis (MPS). 1

My thesis specifically studies leucine and MPS and why leucine content of protein sources was a great indicator of protein quality as it relates to stimulating MPS. 2 3 4 5 6

I was sponsored by a supplement company (Scivation) from 2004-2014 that sold a BCAA supplement called Xtend that I believed in and personally used and recommended during that time period.

I co-founded a supplement company called Carbon Supplements along with Bodybuilding.com in 2015 and one of our products contained BCAA

That company ended in 2017-2018 and around that time quite a bit more research had come out on BCAA supplementation in humans
- BCAA increased MPS in humans but did not appear to increase muscle mass. 7 8 9 10
- Research has demonstrated that compared to intact protein supplementation, matched for BCAA content, that supplemental BCAAs are inferior for anabolism compared to consuming intact protein sources with the same BCAA content. 11
- While BCAA do not increase LBM there is some evidence they may help maintain LBM during a period of caloric restriction better than placebo. 12
When I started my newest supplement company, Outwork Nutrition, in 2020, I decided to leave a product containing BCAA out of the product line because I felt that enough data had been collected demonstrating that BCAA supplementation wasn’t worth it and I could no longer justify it’s inclusion in my products despite my pre-existing bias

Fasted Cardio

When I did my first bodybuilding show in 2001 I performed fasted cardio and advocated for fasted cardio on the bodybuilding.com forums. I also did fasted cardio for my prep in 2002.
- The idea was that fasted exercise would force the body to rely on stored fat for fuel rather than burn fuels in the bloodstream consumed through the diet. The research did indicate that fasted exercise did in fact increase fat oxidation more than fed cardio, but fat oxidation is NOT the same thing as fat loss 13
Then I had a discussion with a smart friend on one of the message boards I posted on and he had a very good argument as to why fasted cardio was likely not superior to fed cardio and possibly inferior.
I dug into the research and found that there was really no data to support fasted cardio being superior to fed cardio when studies measured the actual loss of body fat. 14 15
I then began to tell people not to do cardio fasted as it could be catabolic and cause muscle loss especially since it might elevate cortisol levels compared to fed cardio. 16
However, when 24 hour energy intake and macros are equated between groups there appears to be no difference on body composition. 17
Now I think both approaches are fine and one isn’t superior to the other, so I recommend people do what is easiest for them

High vs. Low Intensity Cardio

Like fasted cardio, I originally recommended low intensity cardio because it burned a greater percentage of calories from fat compared to high intensity cardio which burned more glucose. 18

However when it comes to fat loss, it appears there is no difference between high or low intensity cardio when total work is equated between groups. 19 20

My recommendations now are that people simply perform the version of cardio they enjoy most and are consistent with. HIIT is probably more taxing but provides a time advantage. Low intensity is more time but less taxing and allows you to multi-task if you want. Just figure out the tradeoffs for you.

Meal Frequency

When I first got into bodybuilding I recommended eating every 2-3 hours to keep a steady drip of amino acids for maximum anabolism and metabolic rate since more frequent meals ‘stoke the metabolic furnace’

Research did not support the effect of meal frequency on fat loss when calories were equated between diets. 21 22 23

Research from my PhD indicated that consuming meals more frequently past a certain point did not further increase the amplitude nor duration of MPS and I reduced my meal frequency from 7-8 meals per day to 3-5. 24

I also recommended against intermittent fasting based on my own research demonstrating that it’s unlikely you can make up for low protein at one time of the day by having a massive amount of protein at another time of day since MPS caps out after a certain amount of protein.25
While more extreme forms of fasting may cause unfavorable changes in lean mass, traditional 16:8 fasting does not appear to result in loss of lean mass compared to continuous feeding so long as people resistance train and consume enough total protein over at least 3 meals in that time and train during their feeding window. 26 27 28

LDL cholesterol and saturated fat

My PhD lab was more skewed towards semi-low carb & one of the prevailing thoughts at the time was that LDL cholesterol in isolation did not matter compared to the HDL:LDL ratio and the type of LDL (small oxidized vs large fluffy). Additionally some shorter RCTs did not show a benefit to lowering saturated fat on CVD and mortality. 29

It wasn’t until a few years ago when I began speaking to lipid specialists who understood the mechanism behind LDL causing damage to the endothelium as well as reading the Mendelian randomization (MR) studies that I began to change my view on LDL and saturated fat. 30

LDL carries one lipoprotein B (LPB) per particle. Native LDL (not just small oxidized) can penetrate the endothelium & once inside the endothelium the LPB is enzymatically modified & retained within the intima. This traps the LDL & all the cholesterol & lipid it carries inside. 31

The MR studies assessed lifetime exposure to LDL & risk of cardiovascular disease (CVD) and found an absolutely LINEAR effect of LDL exposure on the risk of CVD. 32
Saturated fat increases LDL production & is associated with increased CVD incidence and mortality. 33 34 35

Figure. Log-Linear Effect of Each Unit Long-Term Exposure to Lower LDL-C on Risk of CHD

Sugar, Fructose, and High Fructose Corn Syrup (HFCS)

When I came to graduate school I believed that sugar, in particular, fructose and high fructose corn syrup were fattening/obesogenic beyond the calories they contained. That they had a unique fattening effect beyond the energy they contained.
- Justifications for this were the following:
  - Sugar (sucrose) contains 50% fructose, and HFCS contains 55-60% fructose and fructose has been demonstrated to increase de novo lipogenesis in the liver. 36
  - Sugar & HFCS/fructose consumption were associated with obesity. 37 38
  - Sugar, HFCS, & Fructose consumption decrease fat oxidation. 39 40 41
  - Fructose in particular was worse than glucose also because it did not stimulate leptin production and can’t be stored as muscle glycogen. 42 43
  - Studies in rodents demonstrated high fructose consumption ‘turned on’ fat storage genes compared to other carbs. 44
After overhearing a random conversation at a grad school mixer, I began to rethink my beliefs
- I began looking for studies to ‘prove’ my beliefs & I found the opposite
- Research demonstrated that when calories were equated sucrose, fructose, & even HFCS were NOT uniquely fattening. 45 46 47
- There was also little evidence that sugars in general are uniquely deleterious for health compared to other carbs or fats when calories are equated between diets other than perhaps a small increase in LDL 48

Artificial sweeteners

When I did my first bodybuilding show I was told that diet soda with artificial sweeteners (AS) aka non-nutritive sweeteners (NNS) were the same as normal soda
- Claim was that they still stimulate insulin so there is still fat gain
- They also ‘cause cancer’
- More recently people have claimed they ruin your gut microbiome
As I looked into the data however, it simply did not support the claims
Only in cohort and cross sectional studies supported an association between NNS and fat gain. 49
In human RCTs where NNS has been substituted in place of sugar sweetened beverages (SSBs) people consistently LOSE body weight. 50
Interestingly, substituting NNS in place of SSB caused more body weight loss than compared to water being substituted for SSB. 51
Though it’s popular to claim NNS cause cancer, it’s not supported by strong data. They are all weak associations that are not consistent in the literature and well over half the studies show no association between NNS and cancer and none of them show strong associations. 52
Effects on the gut microbiome are also inconsistent. Even studies demonstrating changes in the gut microbiome do not show these changes to be negative. It appears sucralose and saccharin can induce changes in the microbiome but it is not clear whether or not these changes are bad, good, or neutral for health. 53 54 55

References

Intro
Change Your Mind Based on Evidence
Alan Aragon vs Gary Taubes
Branched Chain Amino Acids
Fasted Cardio
High vs Low Intensity Cardio
Outwork Nutrition
Meal Frequency
Intermittent Fasting
LDL Cholesterol & Saturated Fat
REPS Research Review
Sucrose, Fructose, & HFCS
Artificial Sweeteners
Conclusion