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Effects of (-)-hydroxycitrate on Net Fat Synthesis as De Novo Lipogenesis

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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 3×500 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 first book The Ketogenic Diet, 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.

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