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) Excess 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 a load of CH2s, so lets 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...

Metabolic flexibility - do you have it?

I'm not quite sure what the picture below means (I need to do a spot of reading!).

Metabolic flexibility "bowl" and "Adaptability envelope"

While replying to Kade Storm this morning, it suddenly occurred to me that the Eskimos have an unusual ability. RER (a.k.a. RQ) normally varies from 0.7 (100% fat-burning) to 1.0 (100% carb-burning aerobically) to >1.0 (100% carb-burning, some anaerobically). Eskimos manage to get an RER of 0.600 *Mind blown.*

One theory that comes to mind is BAT. As Eskimos live in a very cold environment, it's possible that this has resulted in them having a large amount of BAT. BAT is very metabolically-active and turns ATP into heat via UCPs.

Nowadays, first-world people don't live in a cold environment (unless they're old and/or poor), so we don't have much BAT after infancy. Naturally-skinny people may be that way due to having more BAT. They seem to be able to eat whatever and as much as they want without getting fat. I would like to scratch their eyes out!

It's all in a day's work (as measured in Joules)

The title is from the "Physics Man" sketch on The Now Show. Work is another word for energy and there are two different units for it.

The calorie (cal) is the amount of energy required to heat 1g of water by 1°C. This is a tiny amount of energy. The dietary Calorie (Cal) = 1,000cal = 1kcal.

The Joule (J) is the SI unit of energy. 1J = 1kg*m^2/s^2.
1Joule/sec = 1Watt (W).

1kcal = 4.186kJ.

At rest, an average human body uses ~1kcal/min = ~4,186J/min = ~69.8J/sec = ~69.8W.

The brain uses ~5g of glucose/hour = 18.75kcal/hour (1g of carb = 3.75kcals, usually rounded-up to 4) = 78487.5J/hour = ~21.8W.

The heart uses ~10W. The liver, kidneys, gut and lungs run continuously so they use energy all of the time.

Skeletal muscle uses a variable amount of energy using a variable proportion of fuels, depending on what you're doing with it. A chap called Steve sent me a spreadsheet of results in 2004 when he underwent a metabolic test on a stationary bike while breathing through a respiratory gas analyser, which calculated kcals burned and fuel usage by measuring Respiratory Exchange Ratio (RER).

At~1kcal/min (resting), he burned ~95% from fat (~0.11g/min), ~5% from carbs (~0.01g/min).
At 2kcal/min (12% max), he burned 100% from fat (0.22g/min), 0% from carbs (0.00g/min).
At 3kcal/min (18% max), he burned 100% from fat (0.33g/min), 0% from carbs (0.00g/min).
At 4kcal/min (24% max), he burned 99% from fat (0.44g/min), 1% from carbs (0.01g/min).
At 5kcal/min (29% max), he burned 48% from fat (0.27g/min), 52% from carbs (0.69g/min).
At 6kcal/min (35% max), he burned 62% from fat (0.41g/min), 38% from carbs (0.61g/min).
At 7kcal/min (41% max), he burned 58% from fat (0.45g/min), 42% from carbs (0.78g/min).
At 8kcal/min (47% max), he burned 46% from fat (0.41g/min), 54% from carbs (1.15g/min).
At 9kcal/min (53% max), he burned 42% from fat (0.53g/min), 58% from carbs (1.39g/min).
At 10kcal/min (59% max), he burned 44% from fat (0.49g/min), 56% from carbs (1.49g/min).
At 11kcal/min (65% max), he burned 38% from fat (0.46g/min), 62% from carbs (1.82g/min).
At 12kcal/min (71% max), he burned 41% from fat (0.55g/min), 59% from carbs (1.89g/min).
At 13kcal/min (76% max), he burned 37% from fat (0.53g/min), 63% from carbs (2.18g/min).
At 14kcal/min (82% max), he burned 30% from fat (0.47g/min), 70% from carbs (2.61g/min).
At 15kcal/min (88% max), he burned 14% from fat (0.23g/min), 86% from carbs (3.44g/min).
At 16kcal/min (94% max), he burned 0% from fat (0.00g/min), 100% from carbs (4.27g/min).
At 17kcal/min (100% max), he burned 0% from fat (0.00g/min), 100% from carbs (4.53g/min).

Over a wide range of intensities, the number of grams of fat Steve burned/min was fairly constant.

Note that 17kcals/min = 1186.6W, or 1.19kW. This level can be maintained for only a few seconds, as carbs are burned both aerobically and anaerobically, which exhausts PhosphoCreatine stores in muscles and also causes an accumulation of lactate in muscles. See Why do muscles hurt after exercise?

Muscle mass is very metabolically-active compared to fat mass, as one pound of fat mass burns only about 2kcal a day. See also Dissecting the Energy Needs of the Body – Research Review

Here's another Physics Man.