Good Science: Doubly-labeled water

I was reading an interview with Rudolph L. Leibel and doubly-labeled water was mentioned. This sort of stuff fascinates me. Using doubly-labeled water, a mass spectrometer, loads of measurements and some mathematics, it's possible to work out how many kcals someone is burning. This method costs an arm & a leg. So, how does doubly-labeled water work?

Chemistry 101:

Water has the formula H2O. H stands for Hydrogen and O stands for Oxygen.

Elements have isotopes. Hydrogen has two isotopes, Deuterium and Tritium. Deuterium oxide, or D2O is known as heavy water and one use for heavy water is the manufacture of atomic bombs, if you recall the film "The heroes of Telemark". Deuterium is non-radioactive, as is heavy water. Tritium is radioactive.

Oxygen has three stable non-radioactive isotopes one of which is O-18. This can be used to make labeled water H2O-18. Mix D2O with a bit of H2O-18 and you have doubly-labeled water. Now what? To quote Leibel:-

"The interesting thing is that when you give somebody water like this, the deuterium comes out of the body which is determined by water turnover in the individual. The O-18 is in equilibrium with carbon dioxide, so the O-18 comes out by two mechanisms: first with normal water by transpiration, perspiration and urine, but also in the breath.

The difference between those two decay curves (the O-18 comes out faster), which we obtain by getting urine from these patients every day for 10 days-that gap is proportional to carbon dioxide production in that individual. By doing this, we can figure out how much carbon dioxide this person made over a period of 10 days. Knowing that, and knowing what the so-called diet quotient is - in other words, what the ratio of carbohydrates to fat in their diet is - you can back-calculate the amount of oxygen used to produce that amount of carbon dioxide.

So by some simple algebra using the rate of carbon dioxide excretion, you can actually calculate how much oxygen their body used in the process of oxidative metabolism. That is a very critical number because it tells you how much energy they burned. Oxygen consumption can be immediately converted into calories.

So we measure caloric expenditure both by figuring out how many calories it takes to make their body weight absolutely stable, and checking that number by also using this double-doped water excretion technique using mass spectroscopy. It's quite expensive: the isotopes to do such a study cost about $500, not including the spectroscopy."

See A comparative study of different means of assessing long-term energy expenditure in humans.

Ain't science wonderful?

The key to happiness

AC-CENT-TCHU-ATE THE POSITIVE (Mister In-Between)

(Johnny Mercer/Harold Arlen, sung by Bing Crosby)

You've got to accentuate the positive
Eliminate the negative
Latch on to the affirmative
Don't mess with Mister In-Between

You've got to spread joy up to the maximum
Bring gloom down to the minimum
Have faith or pandemonium
Liable to walk upon the scene

(To illustrate his last remark
Jonah in the whale, Noah in the ark
What did they do
Just when everything looked so dark)

Man, they said we better
Accentuate the positive
Eliminate the negative
Latch on to the affirmative
Don't mess with Mister In-Between
No, do not mess with Mister In-Between
Do you hear me, hmm?

(Oh, listen to me children and-a you will hear
About the elininatin' of the negative
And the accent on the positive)
And gather 'round me children if you're willin'
And sit tight while I start reviewin'
The attitude of doin' right

(You've gotta accentuate the positive
Eliminate the negative
Latch on to the affirmative
Don't mess with Mister In-Between)

You've got to spread joy (up to the maximum)
Bring gloom (down) down to the minimum
Otherwise (otherwise) pandemonium
Liable to walk upon the scene

To illustrate (well illustrate) my last remark (you got the floor)
Jonah in the whale, Noah in the ark
What did they say (what did they say)
Say when everything looked so dark

Man, they said we better
Accentuate the positive
Eliminate the negative
Latch on to the affirmative
Don't mess with Mister In-Between
No! Don't mess with Mister In-Between

When good science goes bad

I was rummaging through PubMed (as you do) and it occurred to me that there's a problem.

1) The conclusions in the abstracts don't always tie-up with the data in the full studies.
2) There is no mention of who funded the studies.
3) There is no mention of any conflict of interest for the authors.

Some abstracts link to a free full study and some don't. This makes it difficult to know which studies have been "fixed" to achieve a desired outcome by tweaking the methodology. For example, here are some studies involving Hunter SJ, in chronological order:-

Elderly women in northern New England exhibit seasonal changes in bone mineral density and calciotropic hormones which is about seasonal variations in Vitamin D status affecting bone density and was co-authored by Michael Holick.

Demonstration of Glycated Insulin in Human Diabetic Plasma and Decreased Biological Activity Assessed by Euglycemic-Hyperinsulinemic Clamp Technique in Humans which is about how high blood glucose glycates insulin before it's even secreted, resulting in it working less well in muscle cells.

Reduced prevalence of limited joint mobility in type 1 diabetes in a U.K. clinic population over a 20-year period which pretty much does what it says on the tin.

Then, Hunter starts working for The Sugar Bureau and begins co-authoring studies like this:-

Effect of eucaloric high- and low-sucrose diets with identical macronutrient profile on insulin resistance and vascular risk: a randomized controlled trial, scrutinised in Who pays the piper

Low-fat versus low-carbohydrate weight reduction diets: effects on weight loss, insulin resistance, and cardiovascular risk: a randomized control trial, scrutinised in Who pays the piper part 2

and

Session 4: CVD, diabetes and cancer Diet, insulin resistance and diabetes: the right (pro)portions, which concludes "based on the results of diabetes prevention trials focusing on lifestyle measures, evidence favours low-fat diets as the preferred approach for weight loss and diabetes prevention."

Evidence favours low-fat diets for weight loss and diabetes prevention, huh? See Low-carb diet pitted against low-fat PLUS medication (low-carb still wins) and Diabetes Update

So, getting paid by an organisation which promotes the consumption of sugar makes good science go bad.

Ghrelin, the other "in"

Having just written about Leptin, it's Ghrelin's turn now. When your stomach is empty, serum ghrelin level is high and when your stomach is full, serum ghrelin level is low. Interestingly, high serum ghrelin has a beneficial effect on the hippocampus (responsible for learning stuff) so do your studying when you're hungry!

As a full stomach reduces serum ghrelin and thus reduces appetite, anything that keeps the stomach full for longer reduces appetite for longer. This is where enterogastrones come in. The most useful one in terms of appetite control is cholecystokinin, the secretion of which is stimulated by proteins & fats. This is one reason why diets high in proteins & fats keep you full for longer. Another useful filler is fibre/fiber, of course. As shown on the BBC programme "The Truth about Food", blending a meal with water or some other low-calorie liquid like soup also slows stomach emptying.

Finally, sleep deprivation raises ghrelin so I must try harder to spend less time on my computer and get some shut-eye.

Don't fight it, if you like it.

I was listening to "Scream" by Timbaland in the car today and the first part of the title made me think of dieting. Sometimes our bodies fight our every effort to change our weight. This is a particular problem for people who are trying to lose weight. They feel cold, hungry & listless and they really want to EAT SOMETHING, damn it! It's because they are trying to change their set point weight. For information about set point weight, see Good Science: Dr. Leibel Explains Metabolic Slowdown with Weight Loss.

The problem with getting fat is that adipocytes (fat cells) can only hypertrophy (become larger in size) so much. When they reach a certain size, they secrete something (I don't know how this works so don't ask) that stimulates preadipocytes to become adipocytes. A larger number of something is called hyperplasia. Once adipocyte hyperplasia has occurred, we are stuck with them for life depending on what part of the body they've formed in. Visceral fat (the harmful fat around your internal organs) cannot be removed by liposuction. Only sub-cutaneous fat can. Losing weight & bodyfat results in adipocytes becoming smaller. However, the more of them there are, the smaller they have to become to achieve a given fat mass.

Adipocytes secrete leptin, the amount secreted reducing with reducing size. Leptin works by inhibiting the activity of neurons that contain neuropeptide Y (NPY) and agouti-related peptide (AgRP). Reducing serum leptin level acts on the hypothalamus, increasing our appetites and reducing our energy expenditures. When adipocytes become smaller than normal, leptin secretion reduces considerably and even though there are more of them, net serum leptin decreases and the end result is feeling cold, hungry & listless.

There's another problem that can occur with leptin. In the above example, there's a lack of leptin and the body doesn't work properly. This is analogous to type 1 diabetes. In some people, the hypothalamus becomes insensitive to leptin. Leptin resistance is analogous to type 2 diabetes in that the stuff's present at the correct level but it doesn't have the desired effect and the body doesn't work properly. The end result is also feeling cold, hungry & listless.

It's supposedly possible to restore the sensitivity of the hypothalamus to leptin, but that's for another blog post. So a fat person could say "I'm not fat, I'm hypothalamically-challenged!"

Ban Butter, Part 4,400?

By the time I've finished typing this, there will probably be over 4,400 blogs containing the phrase "Ban Butter". I'm not going to call Shyam Kolvekar rude names. He's a heart surgeon so he's probably very good at cutting people's chests open, removing clogged coronary arteries and grafting in veins removed from legs or whatever it is they do. I don't really wanna know!

He obviously doesn't read our blogs, or he wouldn't have said what he did. If he didn't get any money from Unilever for saying it, that's rather foolish. If I'm going to risk being called every rude name under the sun, I want it to be worth my while.

Anyway, in case you missed it, here's Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease.

See also Fats and Fatty Acids in Human Nutrition and specifically Dietary Fat and Coronary Heart Disease: Summary of Evidence from Prospective Cohort and Randomised Controlled Trials.

I personally use Anchor Spreadable (kept in the 'fridge) or Anchor/Kerrygold (kept out of the 'fridge) as they're from grass-fed cows.

Finally, for a little light relief, see Butter vs Margarine.

Update: From Hartke Is Online!

Good Calories, Bad Calories by Gary Taubes

I haven't yet fully read the book mentioned in the title, but I've read the Cliff Notes. I have the following comments, based on these notes:-

1) I agree with 99% of what Taubes has written. Do I really need to buy Good Calories, Bad Calories?
2) I disagree with the following:-

a) Fattening Diets
▪ it's impossible to fatten people on high-fat, high-protein diets: they just can't eat enough
▪ in one experiment, the volunteers would sit staring at "plates of pork chops a mile high" and refuse to eat enough to get an excess thousand cal/day

b) The Carbohydrate Hypothesis, II: Insulin
▪ so: carbs = glucose = glycerol phosphate = trigs = fattening

a) There's an obvious problem with trying to fatten someone using "plates of pork chops a mile high" and that is BOREDOM. Even I, who loves meat, would baulk at eating pork chops washed down with more pork chops plus a side helping of even more pork chops. However, if I had a plateful of fatty roast beef, pork, lamb & duck with all of the crackling/skin plus lashings of juices, I wouldn't have any difficulty in getting thousands of excess kcals/day. Om, nom, nom!

b) See I have a theory and Enzymes.

P.S. Today's featured article on Wikipedia is....The ketogenic diet!