Is there such as thing as a ‘metabolic advantage’?

Last Friday my blog focused on a study which found that fat intake (total fat, as well as levels of, saturated, unsaturated and polyunsaturated fat) appeared to have no impact on change in body weight over a period of several years. Partly in an attempt to explain how this can be so, I outlined the biochemical basis of the accumulation of fat in the fat. Several biochemical truths point to an excess of carbohydrate as a major driver of obesity. This throws up the possibility that a diet high in fat but low in carbohydrate might affect weight in a way that is independent of calories.

The idea that a particular diet might have weight loss benefits that cannot be predicted utterly by the calories contained in that diet is often referred to as ‘metabolic advantage’. I’ve found it to be a vexed topic, with commentators on it belonging to one of two camps. On the one hand we have those that believe ‘a calorie is a calorie’, and that the form that calories come in have not bearing on their impact on weight. On the other hand, we have those who maintain that the form calories come in can influence body weight in a way that is independent of the number of those calories, or who are least open to the idea that his can be true. Just to be clear, I am in the latter camp.

One of the commenters (Nigeoopoo) regarding my post last Friday asked, quite reasonably, what comes of fat calories eaten, say, in the absence of carbohydrate. My suggestion was that they might be metabolised into energy. Here’s my thinking on this:

As I described in my post, carbohydrate appears to play a key role in the ‘fixing’ of fat in the fat cells as something known as triglyceride (formed primarily from fatty acids). It follows that lower levels of carbohydrate in the diet will result in a shift in the conversion of triglyceride into fatty acids. The importance of this is that triglyceride cannot be burned as a fuel in the cells, but fatty acids can. Low-carb diets also can stimulate the production of ketones, at least some of which will be manufacturered from fat. So, in theory at least, cutting back on carbs ‘frees up’ fat to allow it to be metabolised (converted into energy).

Nigeepoo pointed out, quite correctly I think, that fat does not have much impact on what is known as the thermogenic effect of food. This, in short, is the rise in metabolic rate that occurs when food (fuel) is consumed.

The thing is, though, could the liberation of fatty acids (increasing fuel supply) stimulate calorie burning in other ways?

It’s well known that if when blood sugar levels drop, so do energy levels. Restoring blood sugar levels to normal generally causes energy levels to normalise too. In other words, altering fuel levels in the bloodstream can affect the amount of energy people feel they have. Interestingly, there is evidence that when calorie intake is restricted, individuals move less [1,2]. Could it be that making fuel (including fatty acids) more readily available in the body will enhance metabolism through increased activity? In theory at least, this is one way in which adjusting the make-up of the diet might have a ‘metabolic advantage’.

From what I can see, the search for conclusive proof that metabolic advantage exists in humans has been somewhat elusive. For example, studies in which quite carefully monitored individuals have been fed different diets of the same calorie content have failed to elicit a metabolic advantage. These studies are problematic, in that it is virtually impossible to control what human beings eat, even when installed, on a hospital ward. Also, such studies are expensive and labour intensive, and therefore tend to be of short duration. They may simply not go on long enough for any genuine metabolic advantage to be realised.

One way found these issues is to study animals. The diets of mice, for instance, can be utterly controlled and very accurately measured. Plus, researchers can conduct studies for as long as the mice remain alive.

One interesting animal study that appears to provide some evidence for metabolic advantage was published in the American Journal of Physiology, Endocrinology and Metabolism in 2007 [3]. In this study, mice were red one of four diets:

1. Regular mouse food (chow)

2. Regular mouse food but calories restricted by 1/3 compared to diet 1.

3. A high-fat, high-sugar diet containing the same number of calories as diet 1.

4. A high fat, low-carb (ketogenic) diet containing the same number of calories as diet 1.

The mice had their body weights monitored for 9 weeks.

Here are the results of this experiment.

The mice eating the regular chow and the high-fat, high-sugar diet gained weight.

The mice eating the calorie-restricted diet lost weight.

The mice eating the high-fat, low-carb (ketogenic) diet lost weight. This, despite the fact that they ate the same number of calories as mice on regular chow and high-fat, high-sugar diets who gained weight.

The weight loss seen in these mice was about the same as that seen in the mice who had been given 1/3 less calories to eat.

Seems to me that this is proof, in mice anyway, that the macronutrient make-up of the diet (irrespective of calories) can influence the impact it has on body weight.

The researchers went further in this study by taking mice that had been made ‘obese’ in the first phase of the study, and putting some of them of the high-fat, low-carb (ketogenic) diet. Others were left of the high-fat, high-sugar diet. Mice put on the high-fat, low-carb diet lost their excess weight over a period of 5 weeks. The other mice, not surprisingly, did not.

Again, both groups of mice consumed the same number of calories. So, here again, we have evidence of ‘metabolic advantage’.

One interesting aspect of this study is that it monitored gene expression, which can provide information in terms of what is going on in the body of these mice that could explain how a high-fat, low-carb diet has metabolic advantage.

Evidence was found of increased metabolism of fat, as well as reduction in biochemical pathways that cause the manufacture of fat.

Of course, the high-fat, low-carb diet would be expected to do this, because it should, by rights, lead to a reduction in insulin levels (insulin generally stimulates the manufacture of fat, while reducing it’s breakdown).

Analysis revealed that insulin levels declined dramatically on the high-fat, low-carb diet, and ended up at only 10 per cent of the level seen in the mice eating the calorie-restricted diet.

But what of the theory that a high-fat, low-carb diet might increase energy production? This study actually measured energy production by assessing heat production from the mice. The results showed that the high-fat, low-carb diet led to a significant enhancement in total energy production. This appeared to explain where the ‘missing’ calories went.

While this study was done in mice, it nonetheless provides at least some evidence for the contentious phenomenon known as metabolic advantage.

There is, as it happens, some evidence in humans too. In one review, researchers looked at the impact of diets of different composition on several body measurements including weight loss, fat loss and body fat percentage [4]. 87 individual trials were included in the review. Lower-carb (generally higher-protein) diets, compared to higher-carb ones, were found to bring about enhanced results in all the parameters assessed.

Specifically, in trials lasting 12 weeks or more, lower carb diets led to:

  • an additional 6.5 kg in weight loss
  • an additional 5.6 kg in fat loss
  • an additional 3.5 per cent reduction body fat

But look, even if like Nigeepoo you just don’t believe that the metabolic advantage exists, there is another reason for favouring lower-carb diets. In one of this comments, Nigeepoo alludes to the fact that such diets tend to sate the appetite more effectively than higher-carb ones. And he’s right. Generally speaking, when individuals migrate from a higher- to lower-car diet they end up eating less. Sometimes a lot less. Without undue hunger.

Whether the metabolic advantage is a real thing and clinically relevant or not is probably not as important as the fact the lower-carb diets generally are much more effective at sating the appetite than low-fat ones. And, even more important than this is the fact that, generally speaking, low-carb diets trump low-low fat ones in terms of weight loss and other important markers of health including blood fat and blood sugar levels.

References:

1. Redman LM, et al. Metabolic and behavioral compensations in response to caloric restriction: implications for the maintenance of weight loss. PLoS One. 2009;4(2):e4377

2. Weyer C, et al. Energy metabolism after 2 y of energy restriction: the biosphere 2 experiment. Am Clin Nutr. 2000;72(4):946-53

3. Kennedy AR, et al. A high-fat, ketogenic induces a unique metabolic state in mice. Am J Physiol Endocrinol Metab 2007;292:E1724-E1739

4. Krieger JW, et al. Effects of variation in protein and carbohydrate intake on body mass and composition during energy restriction: a meta-regression. Am J Clin Nutr. 2006;83(2):260-74

26 Responses to Is there such as thing as a ‘metabolic advantage’?

  1. Thras 19 October 2009 at 10:01 pm #

    After years of people saying “where are all the low-carbers” in the National Weight Control Registry, the first post-Atkins craze cohort appeared in 2007. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17925473&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

    The interesting thing is that it gives strong support to the metabolic advantage hypothesis. The low-carbers report that they eat about 500 calories a day more and exercise 1000 calories a week less (than calorie restricted individuals) for the same weight maintenance. The 4500 calories a week difference (more than a pound of fat-energy) is hard to explain without metabolic advantage.

  2. Nigeepoo 19 October 2009 at 10:21 pm #

    Of mice and (wo)men.

    Mice:- “The results showed that the high-fat, low-carb diet led to a significant enhancement in total energy production. This appeared to explain where the ‘missing’ calories went.”
    Men:- ~3% of dietary fat Calories are lost due to increased total energy production. This isn’t significant.

    The great thing about low-carb diets for humans is that it feels like there’s a metabolic advantage in that you can lose weight/bodyfat and feel like you’re eating more than on a low-fat diet. That’s good enough for me.

    What concerns me about the “A Calorie isn’t a Calorie” camp is that it encourages an “eat all you want and still lose weight” attitude. This leads to long-term disappointment after the initial “whoosh” of glycogen & water weight loss.

    It is also advantageous to occasionally up carb intake to break a stall, as hormones like tri-iodothyronine & leptin can drop if carb intake is permanently very low. Please see
    http://diabetesupdate.blogspot.com/2009/09/why-weight-loss-stops-on-long-term-low.html

    Cheers, Nige.

  3. Dr John Briffa 20 October 2009 at 12:27 am #

    Nigeepoo

    “~3% of dietary fat Calories are lost due to increased total energy production. This isn’t significant.”

    In your comment after the previous post you referred to this 3 per cent figure in reference to the thermogenic effect of fat. However, the point I’ve made above is that fat might enhance energy production through other mechanisms.

    “What concerns me about the “A Calorie isn’t a Calorie” camp is that it encourages an “eat all you want and still lose weight” attitude. This leads to long-term disappointment after the initial “whoosh” of glycogen & water weight loss.”

    Perhaps in your experience, but not necessarily for everyone. I’ve seen plenty of people go low-carb and lose their excess weight in the long term while still eating as much as they want.

  4. Jake 20 October 2009 at 12:57 am #

    “Could it be that making fuel (including fatty acids) more readily available in the body will enhance metabolism through increased activity?”

    It is certainly true in my case. Since being on a low carb diet, I have more energy. So I exercise more. Not because I think it is good for me but because I have to do something with that energy.

  5. Dr John Briffa 20 October 2009 at 1:03 am #

    Jake

    Thanks for sharing your experience.

    Very rarely, in my experience, does someone on a carb-controlled diet not experience enhanced energy, and a natural tendency to move more as a result.

  6. GoEd 20 October 2009 at 2:12 am #

    Here is a double blind randomised studie (free full text) that seems to indicate that some types of food gives a metabolic advantage.

    In this case they compared Medium Chain Triglycerids (which you can find a fair bit of in coconut oil) to Olive oil. It turned out that on same caloriec intake, the people with added MCTs lost statistically significantly more weight than the people with added olive oil.

    http://www.ajcn.org/cgi/reprint/87/3/621

  7. Bryce 20 October 2009 at 2:38 am #

    I’m one of those that has lost over 3 stone, kept it off, and done so by eating meat/fat indiscriminantly while eliminating sugar, reducing fruit to 1-2 servings/day, and reducing starch (potato/rice) to 2 servings/week.

    I used to be a die-hard low carb believer, and thought that all carbs were the devil, and that you’d never store fat without them. Not so.

    You can store fat as fat. The issue is not where the calories are stored, the issue is if the stored calories are released. Chronically elevated insulin levels inhibit the release of fat from adiposites. If you eat a whole lot of fat, you’ll store plenty of it as fat, but the release of fatty acids into the blood for use as energy will go on, relatively uninterrupted by insulin.

    Again, it’s not that carbs are stored as fat (though they certainly can be) that’s the problem. It’s that carbohydrate, in a person with metabolic syndrome, prevents fat from being released.

  8. Stephan 20 October 2009 at 6:57 am #

    Hi Dr. Briffa,

    Check this study out. Not only does it show that butter and coconut oil won’t cause fatty liver in rats like corn oil does, it also demonstrates the metabolic advantage in a major way.

    “Rats fed coconut (86% of saturated fatty acid) or butter (51% of saturated fatty acid) had an increased caloric intake (+143% and +30%). At the end of the study period, total lipid ingestion in term of percentage of energy intake was higher in both coconut (45%) and butter (42%) groups than in the standard (7%) diet group. No change in body mass was observed as compared with standard rats at the end of the experiment.”

    Coconut fed rats did have a significant increase in fat mass, but it didn’t even come close to accounting for a 143% increase in calorie intake over 14 weeks. They burned more energy spontaneously, due to more brown fat and more uncoupling proteins.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1805500/

  9. Nigeepoo 20 October 2009 at 9:24 am #

    Thras said:
    “…The low-carbers report that they eat about 500 calories a day more and exercise 1000 calories a week less (than calorie restricted individuals) for the same weight maintenance. The 4500 calories a week difference (more than a pound of fat-energy) is hard to explain without metabolic advantage.”

    The problem with studies where food intake isn’t rigorously controlled by the researchers is:-
    a) People are hopeless at estimating portion sizes, even if they use scales. See
    http://www.youtube.com/watch?v=JVjWPclrWVY
    b) Food labels aren’t particularly accurate. See
    http://www.muscletalk.co.uk/article-food-composition-analysis.aspx
    c) People who feel like they’re eating plenty will tend to overestimate their food intake compared to people who feel like they’re deprived.

    When push comes to shove, a Calorie is a Calorie only where weight is concerned. Where anything else is concerned e.g. body composition, health, wellbeing etc, the source of those Calories does make a difference.

    P.S. In post No. 2, I should have written “This can lead” instead of “This leads”, as everyone is different.

    P.P.S. I can confirm that Coconut oil raises metabolic rate thus increasing Calories out in the energy balance equation. I have secondary hypothyroidism (zero TSH) and taking Coconut oil in 2002 raised FT4 from 9.8pmol/L to ~15pmol/L.

  10. Dr John Briffa 20 October 2009 at 10:26 am #

    Nigeepoo

    “When push comes to shove, a Calorie is a Calorie only where weight is concerned. Where anything else is concerned e.g. body composition, health, wellbeing etc, the source of those Calories does make a difference.?”

    I don’t necessarily agree with the first statement, but the second point is very important – generally there’s too much emphasis on weight loss, I think, and not enough on changes in body composition.

    “taking Coconut oil in 2002 raised FT4 from 9.8pmol/L to ~15pmol/L”

    Did you lose any weight?

  11. simona 20 October 2009 at 2:13 pm #

    Nigepoo,

    I’m interested in the effects of low T3 on the body as my recent blood tests point to a deficiency in this regard. I read Jenny’s article on weight loss stalling and wasn’t convinced. I lost 33 kg in 14 months with a low carb diet and I’m still losing albeit much slower obviously, without counting calories. Regarding Lyle McDonald’s book, I read the paragraph referred to (google books) and he concludes by saying that low T3 in the euthyroid syndrome does not influence the metabolic rate. He talks about a threshold of 50 grams of carbs a day to avoid the decrease in T3. I’m going to check the references starting on page 49 when I have time.

    Could dr. Briffa comment on this?

  12. Nigeepoo 20 October 2009 at 3:54 pm #

    Dr John Briffa said:
    I don’t necessarily agree with the first statement, but the second point is very important – generally there’s too much emphasis on weight loss, I think, and not enough on changes in body composition.

    “taking Coconut oil in 2002 raised FT4 from 9.8pmol/L to ~15pmol/L”
    Did you lose any weight?”

    John,
    We’ll have to agree to disagree on the first statement.

    Shortly after getting the result of ~15pmol/L, my endocrinologist put me on levothyroxine as the response of my pituitary to a TRH test was “pathetic”. So yes, I started to slowly lose weight, but I can’t say for certain what caused it.

    “simona said:
    I’m interested in the effects of low T3 on the body as my recent blood tests point to a deficiency in this regard….Regarding Lyle McDonald’s book, I read the paragraph referred to (google books) and he concludes by saying that low T3 in the euthyroid syndrome does not influence the metabolic rate.”

    simona,
    Is your low T3 caused by hypothyroidism or by diet? There’s one way to find out.

    Cheers, Nige.

  13. simona 21 October 2009 at 7:25 pm #

    Nige,

    I don’t know. It’s hard to say as it wasn’t measured previously. According to the doctors I saw I’m not hypothyroid, my TSH is not even elevated and my T4 is within range. I’m not cutting calories, I’m not on a ketogenic diet either, and I don’t know of other causes, besides maybe stress or mineral deficiency. Hypothyroidism and euthyroid syndrome are two different things.

  14. Nigeepoo 21 October 2009 at 8:49 pm #

    Hi simona,

    Something’s affecting your conversion of T4 to T3. Stress is a possibility. Have you had cortisol tested? As you’re not on a ketogenic diet, Lyle’s comments don’t apply so the lack of T3 could be reducing your metabolic rate.

    If your FT3 is below the Reference Range, I would say that you *are* technically hypothyroid. However, I’m not a doctor. Awaiting Dr Briffa’s input.

    Cheers, Nige.

  15. David 22 October 2009 at 9:53 pm #

    John,

    Is the increased fat in the mouse study ‘natural’ (animal products – fat/butter (sat/mufa)), or ‘manufactured’ (vegtable oils (pufa))?

    Dave

  16. Dr John Briffa 22 October 2009 at 10:54 pm #

    David

    Fats used in the ketogenic diet and the percentage of the weight of the diet contributed by them were:

    lard – 47.5 per cent
    butter – 19.95 per cent
    vegetable oil – 11.4 per cent

  17. Gabriella 23 October 2009 at 8:02 pm #

    Hi Simona -
    Has your doctor prescribed a blood test to ascertain you do not have an autoimmune disorder called Hashimoto’s Thyroiditis? I had normal thyroid tests, however, I also had the usual symptons associated with low thyroid. I did some research on line and found an article on Hashimoto’s. I then asked my endocrinoglist to order a blood test to measure antibodies. Sure enough, they were very, very high. I am now on Synthroid + free T3 and all symptoms are gone. I also have a new endocrinologist.
    Cheers from sunny California, Gabriella

  18. Nancy Bruning 23 October 2009 at 8:05 pm #

    in all this debate about low-carb, I’d like to know the definition of low-carb. Is it low-glycemic carb –which has plenty of carbs, but of the slow release variety and hence without the insulin spike?

  19. Russelwannabe 25 October 2009 at 2:06 am #

    Hi there Simona,

    Please be aware that the common usage of TSH as an inflection on metabolic status of tissues is fallacious and there is no evidence supporting its use. (see fraser paper BMJ)

    A recent nature review concludes that serum levels of thyroid hormones cannot be used to infer tissue levels.

    Applying the commonly used tests for assessing thyroid hormone sufficiency are subsequently inadequate in addition to being scientifically indefensible. In your instance you may have levels within ‘ranges’ but still suffer from inadequate thyroid hormone regulation.

    Furthermore the available evidence suggests inhibition of T4 to T3 by cortisol only lasts for a number of weeks.

    As its late i havent been able to locate the two papers touched upon earlier.

  20. simona 31 October 2009 at 12:19 am #

    Thank you all for replying

    The consultant pathologist mentioned the antibodies, I suppose it’s going to be there once I see the results. My GP sent me to him because I had sky high LDL levels that doubled in a year of low-carbing. (maybe just coincidence, maybe not) They (the junior doctor taking my case history, the pathologist and the other doctor there, maybe an endocrinologist) are trying to say that it’s the diet and the weight loss that lowered my T3, and all that sat fat that raised my LDL. I don’t agree. I gave them the whole list of symptoms associated with hypothyroidism but they don’t want to know (hairloss, dry skin, feeling of cold, acne, menstrual problems, tiredness, depression) Two days ago, I received an appointment card to see a dietician. I didn’t even requested it, why would I, so they can tell me to eat vegetable oil, no eggs and no butter?
    I said I would like to have an NMR done and all the hormones including cortisol. He said they don’t do lipid subfractionation. We’ll see how it goes, but I’m not very hopeful.

  21. Nigeepoo 1 November 2009 at 1:28 pm #

    Hi again simona.

    Is your GP not going to do *anything* about your low FT3? No Cytomel? I think that you should argue the case for treatment.

    Regarding LDL, you’re stuck between a rock and a hard place because you can’t get lipid subfractions tested, so you don’t know how much type A vs type B LDL you have. You could try switching from sat to mono fats to see if it reduces your LDL, just to get the medics off your back.

    In the meantime, to improve your mood, you could try supplementing with 5,000iu/day Vitamin D3 and shed-loads of oily fish. I’ve just blogged about it. Vitamin D3 also helps with autoimmune problems.

    Cheers, Nige.

  22. Nigeepoo 8 January 2010 at 3:49 pm #

    Update: See I have a theory.

  23. Nigeepoo 16 January 2010 at 6:39 pm #

    See also Enzymes

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