Research Review

Kovacs EM and MS Westerterp-Plantenga Effects of (-)-hydroxycitrate on net fat synthesis as de novo lipogenesis. Physiol Behav. (2006) May 23; [Epub ahead of print]

(-)-Hydroxycitrate (HCA) might promote weight maintenance by limiting the capacity for de novo lipogenesis (DNL). It was investigated whether HCA may reduce DNL in humans during a persistent excess of energy intake as carbohydrate. In a double-blind, placebo-controlled, randomized and cross-over design, 10 sedentary lean male subjects (mean+/-S.D., age: 24+/-5 years, BMI: 21.8+/-2.1 kg/m(2)) performed a glycogen depletion exercise test followed by a 3-day high-fat diet (F/CHO/P, 60/25/15% energy; 100% of energy expenditure (EE)) and a 7-day high-CHO diet (F/CHO/P, <5/>85/10% energy; 130-175% of EE; overfeeding). During overfeeding, they ingested 3x500 mg/day HCA or placebo (PLA). Each intervention ended with a 60-h stay in the respiration chamber (days 9 and 10). Body weight increased during overfeeding (mean+/-S.E., HCA: 2.9+/-0.2 kg, PLA: 2.8+/-0.2 kg). Respiratory quotient (RQ) was >1.00 in all subjects indicating that DNL was present. On day 9, 24-h EE was lower with HCA compared to PLA (P<0.05). On day 10, resting metabolic rate and RQ during night were lower (P<0.01 and P<0.05, respectively). Non-protein RQ, fat balance and net fat synthesis as DNL tended to be lower (P<0.1) with HCA compared to PLA indicating lower DNL; activity-induced EE was higher with HCA (P<0.05) indicating the urge to eliminate the excess of energy ingested. We conclude that an experimental condition resulting in DNL in humans was created and that treatment with HCA during overfeeding with carbohydrates may reduce DNL.

My comments: I choose this week's study for two reasons as it addresses two separate issues, that of de novo lipogenesis (DNL, the synthesis of fat from carbohydrates) as well as the supplement hydroxycitric acid (HCA) which has been touted as a 'fat-burner' (for use on a fat loss diet) for quite some time.

DNL has been the subject of much debate for years and many readers have probably seen it claimed that 'carbs in excess of needs simply get converted to fat and stored'. This is true if you're looking at rats, mice and hamsters. One study (Acheson et. al., 1982) in humans gave the subjects 500 grams of carbohydrates (2000 calories) all at once; conversion of carbs to fat was insignificant. The majority of research in humans has not found DNL to contribute significantly to fat gain except under a few very extreme conditions. They are

1. An artificially low-fat diet: less than 10% of total calories which well-meaning but otherwise misguided athletes and bodybuilders sometimes try to achieve

2. Chronic massive carbohydrate overfeeding: one study (Acheson et. al., 1988) gave 700-900 grams of carbohydrates for 3 straight days following glycogen depletion. In the first 24 hours, as glycogen was refilled, there was no net DNL. Over the next 2 days, as carb intake remained massive and sustained, DNL increased and a significant amount of fat was synthesized. This is part of why diets like Bodyopus and my Ultimate Diet 2.0 taper carbohydrates down as the carb-load continues.

This study created a situation similar to both, for the first 3 days, the subjects followed a low-carbohydrate diet with glycogen depletion (sound familiar). Then they were overfed for the next 7 days on 85% carbohydrates(5% fat and 10% protein) with caloric intake at 130-170% over maintenance. Massive carbohydrate overfeeding accompanied by a very low fat intake, and DNL increased significantly as indicated by a respiratory quotient (RQ) greater than 1.0.

Along with this, the researchers gave the subjects HCA to see if it blunted DNL during the overfeeding, which it did. Back in my original Ketogenic Diet book, I mentioned that HCA might have some use during CKD style carb-loads for this very reason: empirically, some people found that HCA would limit bloating and puffiness during their carb-load.

But what relevance does this study have to normal conditions? Essentially none. Unless you're deliberately overfeeding carbs for many days in a row (along with an extremely low-fat intake), DNL generally contributes minimally, if at all to fat gain (for review, see Hellerstein, 1999). As well, HCA only has an impact in humans during massive carbohydrate overfeeding, although one study (Westerterp-Plantenga, 2002) suggested it might help reduce food intake. Its use as a fat-burner on a diet (by definiton you can't be overfeeding carbs, except during refeeds or CKD style carb-loads) was misguided anyhow, since that's not how it works.

Summing up: except under the most extreme of dietary conditions, DNL contributes almost insignificantly to fat gain in humans. Which isn't to say that carbs don't contribute to fat gain, it's simply generally not through direct conversion to fat. And while HCA might have some use during those types of extreme dietary conditions, in general it's fairly useless as a supplement; especially as any kind of fat burner on a diet.

Feature Article:

Where is the Bodyfat Part 1

Intro: the following article is actually a chapter from an unfinished book project tentatively called The Bodyrecomposition Handbook. It deals with the location of bodyfat in the human body. In part 1, I'll talk about essential and brown adipose tissue; visceral, subcutaneous and stubborn bodyfat are covered in 2 weeks.

Where is it

When people talk about bodyfat, they are usually referring to the fat that is visible to the naked eye but this isn't really complete or correct. They are simply fixating on what they want to get rid of to make themselves look better naked.

The human body has at least 4 different depots of stored fat, although we'll actually distinguish a fifth that isn't used in the research. Let's look at each of the major places that bodyfat is found in this chapter, and then get into more details about some of them in the next few chapters.

The first type of fat: Essential bodyfat

Essential bodyfat refers to the fat found around your organs (where it serves an important cushioning role), in your nervous system (nerves are surrounded by sheaths of fat), and especially in your brain. On that note, low fat diets can impair neural development in developing babies because of the high fat content found there. Without enough dietary fat, baby brains don't develop well. As well, deficiencies of certain type of fatty acids in the brain seem to be related to both depression and psychosis. Whether this is a function of diet, or of bad development as a child is unknown.

For the most part, we don't really need to worry that much about essential fat. As the name implies, essential bodyfat is exactly that: essential. You can't lose it and, even if you could, you wouldn't want to because you'd be dead.

In men, essential fat typically makes up about 3% of total bodyfat. Meaning that anytime you hear someone claiming a bodyfat percentage below 3%, you should be fairly suspicious. Either they're lying or, more likely, the methodology they used to measure bodyfat was inaccurate.

In females, essential fat is higher, and usually estimated at 9-12% or so. That difference in essential fat (3 vs. 9-12%) is a big part of the difference in total bodyfat levels in men and women. That is, a man at 10% bodyfat is roughly equivalent to a female at 16-19% bodyfat; they are both 7% above their essential bodyfat levels. Again, you'll hear of women (mainly bodybuilders) reporting values below 9%, which has more to do with the problems in the equations than anything else.

For the most part, with the exception of the chapters on measuring body composition, we won't really talk about essential bodyfat. Even if you're obsessive about getting rid of all of your bodyfat, you don't want to lose essential fat and probably couldn't do it in the first place. It's there for a reason, enough said.

The second type of fat: Brown adipose tissue (BAT)

I mentioned BAT in the last chapter and want to discuss it briefly again here, mainly just to get it out of the way. In comparison to normal white adipose tissue (WAT), BAT is very different. Whereas the main role of WAT is energy storage, the main role of BAT is energy utilization, primarily to provide heat. As mentioned last chapter, WAT is primarily stored triglyceride with a small amount of enzymes. What I didn't mention last chapter is that WAT also has very few mitochondria (the powerhouse of the cell) which makes energy by burning free fatty acids.

In contrast, BAT has very little lipid but quite a bit of mitochondria, which is why it's so good at energy (and heat) production. On top of that, BAT appears geared to burn fat almost exclusively. And when it does so, the energy produces is lost as heat, it's not used to fuel any other chemical reactions.

The discovery of BAT, and it's functions, opened up an entirely new area of obesity research, as researchers thought that BAT activation might help to burn off excess calories and limit or help cure obesity. It was also thought that defects in BAT activity might be a contributing factor to obesity. You may have heard some hubub over something called a beta-3 adrenoreceptor or the development of beta-3 agonists for the treatment of obesity. If not, I'll get to it in a couple of chapters. I bring it up here because most of the beta-3 receptors are found on BAT tissue, not on WAT.

BAT is also a major site of something called uncoupling proteins (UCPs) which we will talk about later. UCPs uncouple energy production from energy use which is just a complicated way of saying that they waste energy. However, while BAT is one of the main sites of UCPs, they are also found in both muscle and adipose tissue and can be manipulated to a very slight degree with nutrition. So we'll discuss them later in the context of metabolic rate.

Great, right? A form of fat that is geared towards burning WAT and that contains UCP's which waste even more energy. As always, there's a catch.

Animals have a considerable amount of BAT, which is activated whenever the animal needs to generate heat to stay alive. BAT is also found in newborn babies and serves the same role, heat production because babies are very bad at heat regulation in the first few days of life.

However, in adults, there is typically very little BAT. At some point soon after birth, it appears that most of the BAT goes away because it is no longer needed. For many years, it was felt that there was no BAT in adult humans, but that's not entirely true. Even normal adult humans have a tiny amount, underneath the shoulder blades and around the kidneys for example. We just don't have very much. I should mention that autopsies of humans exposed to chronic cold (I'm a lumberjack and I'm ok) have shown increased amounts of BAT. So under extreme circumstances, it looks like humans still have the capacity to produce BAT.

Obviously, the capacity for BAT in humans is there. Gene studies of normal WAT show that the genes to make it into BAT are there, they simply aren't activated. Researchers aren't exactly sure why. It may be because we lost our fur and started wearing clothes so long ago and no longer need BAT to help us keep warm. Or it may be related to something else entirely.

If it were possible to get normal WAT to turn into BAT somehow (maybe some weird drug), it could probably be very useful for fat loss and obesity treatment. Basically the body would waste fat energy as heat (anyone familiar with the drug DNP knows what this is about).

But in general, adult humans have very little BAT. No BAT means no B-3 receptors. Very few in any event. Actually, that's not entirely true, humans have some B-3 receptors in other tissues but they don't appear to be very important in the overall scheme. Which is why the B-3 agonist drugs (compounds that activate the B-3 receptors to increase energy expenditure and cause fat loss) which worked great in animals didn't do very much in humans.

It's conceivable that a dieter could expose themselves to chronic cold and get some increase in BAT levels, but I doubt anyone would be willing to put themselves through that kind of misery in the long-term unless they had to. It's also been hypothesized that chronic exposure to the catecholamine hormones (which mimics cold exposure) might cause BAT levels in humans to increase, but it's never been proven. Chronic use of ephedrine or clenbuterol might theoretically work, but nobody's studied in it humans yet. And since you have to sleep eventually, keeping catecholamine levels increased around the clock isn't possible anyhow.

So, until researchers come up with a neat way to get adult humans to produce more BAT, short of being cold and miserable all the time, we can pretty much ignore it and its functions. Simply put: there isn't enough BAT in adult humans to really have an impact on energy balance or fat utilization. It'd be great if there was, because we could force the body to burn off fat for heat but for right now worrying about BAT and energy balance just isn't that meaningful.

Questions and Answers

Q: I think I am ready to take the plunge and order the Rapid Fatloss Handbook. It will take a week to ship, what do I begin to do now in order to ramp up to the diet? In terms of eating? At the gym?

A: Nothing really. If someone has been dieting, I'd suggest that they take at least 1-2 weeks at maintenance calories (and at least 100-150 grams of carbs) prior to starting the diet so that they aren't going into it with an already impaired metabolic rate from dieting. Ensuring that you are eating sufficient lean protein and vegetables will make the shift to the rapid fat loss diet a little easier. Beyond that, nothing really has to be done in preparation.

Q: I have the hardest time losing weight/fat and I'm hoping you can help. I have used a number of standard maintenance calorie estimation equations but I find that reducing my calories below that point doesn't really cause much fat loss. My morning temperature is about 97 degrees if that has anything to do with it. I"ve heard a lot about 'starvation mode' and how it can cause fat loss to plateau, what do you think about that?

A: A low body temp relative to normal indicates that metabolism is suppressed. Every degree below a norm of 97.8-98.2 is about a 10% reduction from so called 'normal' metabolism. This is related to changes in thyroid, nervous system, insulin and leptin levels. So your true maintenance is probably a good 10% below any estimation equations you may be using. which is why the equations aren't accurate for you and why you're not getting the predicted fat loss.

Basically, to lose fat effectively, you may simply need a larger deficit which means either cutting calories more or doing more activity.

Or see about getting the hormonal issues fixed. In order of ease/offensiveness to most people:

1. Taking 1-2 weeks at maintenance eating (and at least 100-150 g carbs/day and normal caloric intake) can help. This helps to upregulate leptin, thyroid and nervous system activity. This is the full diet break described in both the Rapid Fat Loss handbook and my Guide to Flexible Dieting.

2. The ephedrine/caffeine stack would be the next step as that serves to fix the nervous system impairment.

3. Getting some thyroid blood work done (and taking thyroid medication if necessary) would be the more involved step but woman moreso than men tend to have low thyroid as a matter of course.

In terms of the starvation mode thing, there is NO doubt that a lowering of metabolic rate occurs with dieting (part of this is due to the loss of bodymass, part of this is adaptive and due to hormones), I'm not disagreeing with that at all. All it means is that fat loss becomes harder/slows down; I disagree with the stance that it is ever sufficient to slow it completely, it can simply make fat loss so slow as to be effectively zero (and certainly smaller than either the variance in our ability to measure changes/the changes in scale weight that occur a sa matter of course).

That is, say you were at a point where you were only losing .5 lbs fat/week. As you well know, a female can swing a good 5-7 lbs water weight throughout the month. Even a 2 lb fat loss/month can be overwhelmed by normal monthly variance. And calipers, with their 3-5% variance wouldn't pick up that small a fat loss. Fat loss may very well be occurring but it's so slow as to be negligible/unmeasurable by our available methods.

Q: I'd like to read your conclusions of your researches (even anecdotal info. would be interesting) concerning the use of 25 to 50grams of a protein drink, and what ever else with it, during the night at sleeping time, partaking when getting up to pee, say. 8 to 10 hours with nothing can't be good.

A: A bunch of years back, there was actually some research looking at the issue of eating across the entire 24 hours versus having a 'break'. Unfortunately, the data was fairly mixed and it was mainly in hospitalized individuals so it's questionable how relevant this is to healthy individuals. As I recall, 2 studies suggested that the gut needed a 'break' from eating (to heal or rebuild without having to deal with nutrient absorption/digestion) and the other 2 did not.

Before continuing, I would like to say that I think interrupting the normal sleep cycle deliberately to eat is a mistake. I think the importance of sleep outweighs any potential benefit of getting in some nutrients (clearly people have gotten big and strong without waking up in the middle of the night to eat). But if you normally get up to use the bathroom anyhow, it would be trivial to slug down a premixed protein drink or something in the interim.

The liquid will probably wake you up again in a few hours to pee at which time you can drink some more, by the time you wake up again, it'll be morning and time for breakfast.

It makes some logical sense to provide nutrients to the body during fasting. What appears to happen is that protein 'stored' in the body during the normal eating phase is mobilized during the sleeping phase (to ensure that the body has amino acids for other purposes). This is referred to as diurnal cycling in the research literature.

Would eating a large slowly digesting protein shake at bedtime (for example, some casein or milk protein isolate, or even whole food) perhaps with some carbs, fiber and fat help with recovery or growth? It seems reasonable unless there is some disadvantage (from a gut/intestinal standpoint) to doing so.

At this point, I'm not sure I have any firm conclusion. The research is mixed and people have clearly made progress without doing it, making me question the necessity of such a strategy. Would they have made more progress eating through the night? I simply don't know.