Metabolic Inflexibility: What it really means.

Here's a picture from Metabolic Flexibility and Insulin Resistance.

The Metabolically-Inflexible (MI) & Insulin Resistance

Here's another picture.

Fig 2. ● = Metabolically-Flexible (MF). ○ = Metabolically-Inflexible (MI).

Salient points:
1) Excessively high serum FFA a.k.a. NEFA is bad.
2) Respiratory Quotient (RQ) a.k.a. Respiratory Exchange Ratio (RER) changes due to dietary changes are more sluggish in the MI than in the MF.
3) Under Insulin Clamp conditions, RQ/RER is lower in the MI than in the MF, due to impairment of glucose oxidation and non-oxidative glucose disposal.

I have posted this because of Danny Roddy's post Is Supplemental Magnesium A Surrogate For Thyroid Hormone? , which leads onto A Bioenergetic View of High-Fat Diets.

In the first article, Danny Roddy writes:-
"Additionally, taking magnesium while actively engaging in a diet or lifestyle that reduces the respiratory quotient (e.g., high-fat diet, light deficiency, excessive exercise) seems pretty silly. For example, as a rule, diabetics have a reduced respiratory quotient (Simonson DC, et al. 1988), tend to have higher levels of free fatty acids or NEFA (Kahn SE, 2006), and are often deficient in magnesium (De Valk HW, 1999)."

The second sentence (diabetics have a reduced respiratory quotient...and are often deficient in magnesium) seems to contradict the first sentence (...taking magnesium while actively engaging in a diet or lifestyle that reduces the respiratory quotient seems pretty silly).

Simonson DC, et al. 1988 is Oxidative and non-oxidative glucose metabolism in non-obese type 2 (non-insulin-dependent) diabetic patients.
"In conclusion, during the postabsorptive state and under conditions of euglycaemic hyperinsulinaemia, impairment of glucose oxidation and non-oxidative glucose disposal both contribute to the insulin resistance observed in normal weight Type 2 diabetic patients. Since lipid oxidation was normal in this group of diabetic patients, excessive non-esterified fatty acid oxidation cannot explain the defects in glucose disposal."

Impaired glucose oxidation with normal lipid oxidation lowers RQ/RER. Therefore, lower RQ/RER must be bad, right? Wrong. From the above study:-
"...euglycaemic insulin clamp studies were performed..."
Remember Salient point 3)? Simonson DC, et al. 1988 is an insulin clamp study, the results of which don't apply to free-living people (who aren't insulin clamped).

See also Determinants of the variability in respiratory exchange ratio at rest and during exercise in trained athletes. RER/RQ increases & decreases with increases & decreases in exercise intensity. This is Metabolic Flexibility (MF). Sorry, Danny.

Respiratory Exchange Ratio (RER) explained.

Science!

What the heck is this?

RER has been mentioned a few times on this blog. By measuring the rate of CO2 exhaled and the rate of O2 inhaled, it's possible to work out how many kcals/min the body is generating from food at any instant and from what fuel mixture.

An RER of 0.700 means that 100% of energy is being generated from fat.
An RER of 1.000 means that 100% of energy is being generated from carbohydrate aerobically.
An RER of >1.000 means that 100% of energy is being generated from carbohydrate, some aerobically and some anaerobically.

How does this work? Fats are an ester of fatty acids + glycerol. Acid + Alcohol = Ester + Water.

Saturated fatty acids (the easiest type to calculate) have the generic formula CH3(CH2)nCOOH, where n can be from 0 to 16. Here are some saturated fatty acids and their n values:- Acetic (0), Propionic (1), Butyric (2), Lauric (10), Myristic (12), Palmitic (14) and Stearic (16). The total number of carbon atoms in each fatty acid is n+2. Stearic acid is mostly CH2s, so I'll approximate fat to n(CH2).

n(CH2) + 3/2n(O2) = n(CO2) + n(H2O) + Heat. The ratio of CO2 to O2 is 2/3, so RER = 0.666.

As fats contain things other than CH2 (e.g. glycerol CH2OHCHOHCH2OH), this raises RER to 0.700. Burning protein gives an RER = 0.800.

Carbohydrates have the generic formula n(CH2O), where n = 6 for glucose.

n(CH2O) + n(O2) = n(CO2) + n(H2O) + Heat. The ratio of CO2 to O2 is 1.000, so RER = 1.000.

So how on earth can Eskimos have an RER = 0.600? I have a theory. When hydrogen is oxidised, water only is produced. There is no CO2, so RER = 0.000. Therefore, if some hydrogen was being burned (by gut bacteria, say), this could result in RER falling below 0.700. Maybe...

Everyone is Different, Part 2.

Cont'd from We are not all the same.

A long, long time ago...


I learned that Everyone is Different, thanks to a study by Julia H. Goedecke, Alan St Clair Gibson, Liesl Grobler, Malcolm Collins, Timothy D. Noakes and Estelle V. Lambert.

Well, stone the flamin' crows! Timothy D. Noakes' name just popped up in Alan Aragon's article 2013 NSCA Personal Trainers Conference: Looking Back at my Debate with Dr. Jeff Volek. Dr. Noakes has had problems with his blood glucose level and has adopted a very-low-carb/ketogenic diet.

What also caught my eye in Alan Aragon's article was (Note: TTE = Time To Exhaustion):-
"However, the authors’ conclusion is misleading since 2 of the 5 subjects experienced substantial drops in endurance capacity (48 and 51-minute declines in TTE, to be exact). One of the subjects had a freakishly high 84-minute increase in TTE, while the other increases were 3 and 30 minutes."

I expect that the subjects with 84 and 30 minute increases in TTE would be praising ketogenic diets, whereas the subjects with 48 and 51 minute declines in TTE would be cursing them and the subject with 3 minutes increase would be "Meh". Vive la difference!

Also note that sprint capability...remained constrained during the period of carbohydrate restriction. As mentioned in It's all in a day's work (as measured in Joules), exercise above a certain intensity (~85%VO2max) burns significant amounts of carbs, no matter how fat-adapted someone is.

Cont'd on Everyone is Different, Part 3.

On burning, storing and recomposing.

Burning

I couldn't resist!


On my adventures around the interwebs, I've noticed the following:- "Humans aren't Calorimeters. Therefore calories are irrelevant to humans." While I agree with the first sentence, I don't agree with the second one.

Calorimeters burn (oxidise) foods at high temperatures with a flame using oxygen, which produces carbon dioxide, water (depending on what's being burned) & heat energy.

Humans burn (oxidise) foods at 37ºC with enzymes , charge transporters etc using oxygen, which produces carbon dioxide, water (depending on what's being burned), mechanical energy & heat energy.

As both oxygen & carbon dioxide are gases, these can be measured by a respiratory gas analyser, to establish the rate of burning and what's being burned at any instant. See It's all in a day's work (as measured in Joules). When resting, burning occurs at a rate of ~1kcal/minute and, as it's measured while fasted, ~0.11g/min of fat is burned, & ~0.01g/min of carbohydrate is burned. Also note that a lot of mechanical energy can be produced, which can increase the rate of burning by a factor of seventeen.

In conclusion, humans burn (oxidise) foods, though not with a flame, and they can produce mechanical energy in addition to heat energy. The rate of burning and what's being burned at any instant can be measured.

Storing

When we eat food, it's digested and absorbed. As a digested meal is absorbed, it appears in the blood as glucose, triglycerides & amino acids. These then disappear from the blood due to burning and storage.

Fig. 1 Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism

Fig. 1 above shows the effects of a 100g Oral Glucose load (▪▫) or a 40g Oral Fat load (●○) on blood glucose level over a period of 360 minutes. Note that subjects are resting during the 360 minutes. As the 100g Oral Glucose load produces a large insulin response (See Fig. 2 below ▪▫), fat-burning is temporarily reduced.

Fig. 2 Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism

Therefore, ~1kcal/minute resting burning rate is derived ~100% from carbohydrate. Therefore, carbohydrate-burning rate is ~0.25g/min. At this rate, it would take ~400 minutes to burn 100g of glucose. If less than 100% of energy is derived from carbohydrate, it would take longer. However, it actually takes ~180 minutes for blood glucose level to fall from maximum to minimum. Therefore, some glucose from the Oral Glucose load is stored (mostly as glycogen in muscles and liver).

Fig. 3B Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism

Fig. 3B above shows the effects of a 40g Oral Fat load (●○) on blood triglyceride (fat) level over a period of 360 minutes. Note that subjects are resting during the 360 minutes. As the 40g Oral Fat load produces no significant insulin response (See Fig. 2 above ●○), fat-burning is unaffected.

Therefore, fat-burning rate is ~0.11g/min. At this rate, it would take ~364 minutes to burn 40g of fat. If less than 100% of energy is derived from fat, it would take longer. Everyone is Different. shows the variation in % of energy from fat at rest. However, it actually takes 180 to 240 minutes for blood triglyceride (fat) level to fall from maximum to minimum. Therefore, some fat from the Oral Fat load is stored (as fat in adipocytes), even though there is no significant insulin response.


Therefore there are times when stuff is stored (anabolism) and there are times when stuff is withdrawn from stores (catabolism). If more stuff is stored than is withdrawn over a period of time, weight goes up, and vice-versa.

Recomposing

After doing intense exercise e.g. sprinting, resistance training with weights etc, muscles become very sensitive to insulin. Therefore, if intense exercise is done just before stuff is stored, amino acids & glucose are preferentially stored in muscles rather than adipocytes. This increases muscle mass relative to fat mass.

If non-intense exercise is done at times when stuff is withdrawn from stores, this maximises the amount of fat withdrawn from adipocytes and minimises the amount of amino acids withdrawn from muscles. This decreases fat mass relative to muscle mass.

It's therefore possible to increase muscle mass at certain times and decrease fat mass at other times, while keeping overall mass relatively constant i.e. it's possible to gain muscle and lose body-fat without being in an overall caloric deficit.


See The Energy Balance Equation, for more information.