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Thursday, February 6, 2014

Straight Talk on Fats, Metabolism, and Body Temperature


It’s popular to talk about certain foods that stimulate thermogenesis, or heat production, as a means to aid in weight loss – the most fashionable of which is probably coconut oil.   While that’s all good and desirable, the heat generated upon eating makes a relatively small contribution when compared to all the heat generated by all the reactions in the body, including the process of keeping the gut in a state of continuous readiness to digest and assimilate the next meal. 

All metabolic processes in the body generate heat.  In other words, metabolism is unavoidably heat-generating.  The minimum amount of heat generation is set by the resting metabolic rate,[*] which is, in turn, set by the thyroid hormone, among other ancillary factors.  The heat generated from eating – directly related to the energy costs of digesting, absorbing, and converting the myriad of components of food into their appropriate storage forms – adds to the heat generated by the resting metabolic rate.  As far as diet-related heat generation is concerned, of all the macronutrients, protein has the greatest effect.  Carbohydrate has a lesser effect than protein, and fat has a negligible effect.  

Eating can also activate uncoupling proteins, whose function is to process nutrients for heat rather than energy in the mitochondria.  Although the extent to which this adds to heat generation is probably minor, the intensity with which these uncoupling proteins generate heat is governed and fine-tuned by hormones, in particular thyroid hormone and noradrenalin.1 Uncoupling helps to decrease oxidative stress, while maintaining a high rate of ATP generation – an example of a substrate cycle in which a substance (in this case a proton gradient across the inner mitochondrial membrane) is generated and subsequently dissipated, in a reverse reaction using different enzymes, wasting energy in the process.2  

Although fat has a negligible effect in terms of increasing heat generation after eating, it does play an important role in regulating body temperature, as one of the myriad of reactions mentioned above not involved with eating.  This reaction, in which fat is used to generate heat, is another example of a substrate cycle.  In essence, triacylglycerol, composed of 3 fatty acids and 1 glycerol, is broken down (lipolysis) and the fatty acids subsequently released are taken back up by the releasing fat cell and esterified into triacylglycerol therein.[†]  This process, lipolysis and esterification, constitutes one substrate cycle, and the heat generated from the reactions in said cycle plays an even greater role in regulating body temperature than the physical role of fat as an insulator!  Like the uncoupling proteins, this substrate cycle is regulated by thyroid hormone and noradrenaline.

At least on the order of days, weeks, or even months, the addition of a particular food into a person’s diet in the absence of other changes will probably not have a significant effect in terms of changing a person’s body fat and weight.  A case in point is MCT oil, which has been promoted hard for its ability to aid in weight loss.  The results of clinical studies in which MCT oil was put up against a different oil and weight changes were tracked over time have been overwhelmingly unimpressive to say the least.  Yet, a value to which it is not legitimately entitled continues to be placed on MCT oil by the likes of Dave Asprey and the atrocity that is the Bulletproof Diet.

However, the effects of changing the composition of the fats in a person’s diet are not as ineffectual as I may have indicated above.  Interesting are the experiments in which behavioral changes are observed upon changing the fatty acid composition of the diet of an animal kept in captivity.  Lizards, for instance, will become more active at night and prefer to spend more time in colder places so their bodies become colder by increasing the PUFA in their diets; on the other hand, reducing the PUFA in their diets will elicit the opposite behavior.  For what it’s worth, perhaps nothing to you, I’ve always had a low tolerance to heat – the slightest increase in temperature would make me break out in a sweat, and make my nose stuffy and ears bright red.  But since reducing the fat and increasing the sugar in my diet (effectively reducing the PUFA in my body), my tolerance to heat has improved and I layer up more than I used to as the ambient temperature goes down.
                                                                                           
Of course, there is a ceiling on the degree to which the metabolic rate can be increased, being limited by the risk of overheating from running things so quickly, among other things.  But the main factor that limits a person’s metabolic rate is the availability of oxygen. 

Oxygen decreases the reliance on non-oxidative metabolism, and, merely by the law of mass action, leads to more energy generation and less fat storage.  I suppose exercise, by strengthening the heart and respiratory system – and therefore blood circulation and lung ventilation – would help to increase the efficiency of the delivery of oxygen to tissues.  However, exercise need not be heavy and exhaustive to be effective, only regular and consistent.  Isotonic movements, in which tension is applied and work is accomplished, is probably less stressful than isometric movements, in which no work is performed but much heat is generated.[‡]  The great force and resistance involved in isometric movements tends to compress blood vessels to where blood perfusion becomes greatly reduced so as to create a significant degree of tissue hypoxia, resulting in a greater reliance on non-oxidative metabolism and higher levels of lactate.  Bulging muscles may look good (I guess?) but they appear to come at a price.

But other stressors can decrease the availability of oxygen to tissues, in part by increasing the use of fat for fuel.  More glucose is used non-oxidatively as a result, which, in turn, depletes glycogen and increases lactate and acidity.  As it happens, this stress-induced oxygen depletion is usually offset because the increase in acidity and lactate increases the efficiency with which oxygen moves from the blood to tissues by way of the Bohr effect and the increase in 2,3-diphosphoglycerate (2,3-DPG) within red blood cells.  The ratio of pyruvate to lactate is one of the best indicators as to the extent of oxidative versus non-oxidative metabolism.

A healthy and robust metabolism implies low levels of the stress hormones.   Limiting the stress hormones limits the use of fat for fuel and the production of lactate and ensures the efficient turnover of ATP.  As it happens, ATP, bearing a high density of negative charge, binds and keeps noradrenalin, positively charged under physiological conditions, inside storage ‘bubbles’ inside cells, regulating their release.[§] (The fact that both ATP and noradrenalin are involved in pain transmission further serves to explain their co-localization inside cells.) The carbon dioxide and heat generated as by products of metabolism both increase the delivery of oxygen to tissues, like lactate does, and, stated above, more oxygen means more energy generation and less fat storage.  The oxidative metabolism of glucose generates the most heat, carbon dioxide, and ATP.

The capacity to use the increased oxygen is limited by the availability of all the B vitamins, including thiamin, riboflavin, niacin, pantothenic acid, and others.  A regular and adequate supply of these vitamins improves the reserve and capacity of the Krebs cycle and respiratory chain.  The active thyroid hormone, T3, stimulates all the reactions involved in the oxidative metabolism of glucose, increasing the requirement for all the B vitamins.  The ingestion of simple carbohydrate also increases the requirement for the B vitamins, in particular thiamin.3

If the body temperature cannot be kept up naturally, the next best option is to keep warm artificially as to keep all the chemical processes in the body operating as fast as they would at higher temperatures.  Trapped air is particularly important to conserve heat in cold ambient temperatures.  Therefore insulation, which for us means clothing, is an important factor determining the amount of heat lost from the body.  The thickness, in particular, as well as the looseness and color of the clothing determines how effective it is as an insulator. 

Questions I get a lot relate to digestion and the simplest thing to do with problems concerned with digestion is to increase the body temperature as high as to what’s tolerable.  Not only is digestion, and therefore the extraction of nutrients, slower at lower temperatures, but parasites and bacteria also have a greater chance of breaking through the gut lining to cause serious infections at those temperatures.  To make matters worse, the activity of the immune system decreases as the temperature decreases, so the likelihood of mounting an effective immune response to the pathogens that do get into the body decreases, too.[**]  Within narrow limits, the temperature at which the body ‘sets’ is determined by the composition of the fats in a person’s diet: the most protective fats are the ones that are the most saturated.

The percentage of PUFA in tissues limits the rate of energy expenditure.  One reason for this is that at higher temperatures, the spontaneous oxidation of PUFA – therefore the production toxins – increases as the temperature increases.  Since reading about hibernation as it relates to PUFA in HLAF, I’ve been thinking more and more about this idea.  Lo and behold, squirrels, professional hibernators, must carefully eat just the right amount and kinds of nuts and seeds in order to store enough PUFA in their tissues for a successful hibernation through the winter, but not so much as to disrupt hibernation from the excessive production of toxic PUFA oxidation products.

Although obesity in humans is associated with a shorter lifespan, in wild animals there is no such association, unless they are domesticated and deliberately fattened by humans.  Obviously a multifactorial and complex matter, the saturation index and therefore the fat composition of the diet, is one factor that may explain these associations.4

log (maximum lifespan years)
Combined with the observation that a higher (resting) energy expenditure is generally associated with a longer lifespan5,6 we are beginning to move even further away from the idea that fat is merely an inert sink in to which surplus nutrients are converted and stored until they are needed elsewhere in the body. 


The formation of fat from carbohydrate is an extremely inefficient process – only by eating carbohydrate in incredible amounts over long periods of time will a person begin to create and accumulate fat made from carbohydrate.7 The conversion of carbohydrate to fat is simply a highly energy-consuming process and the activity of the fat synthesizing enzymes is not nearly as active as they are in other animals, like birds and rodents.  So the most efficient way to change the fat composition of the body is by adjusting the fat composition of the diet.  Butter, cocoa butter, tallow, and suet are among some of the most saturated and stable fats currently known.  Good quality chocolate is unusually high in the commonest saturated fats in mammals: palmitate and stearate.  Shifting the diet to include more of these fats and less of more unsaturated fats is sufficient to bring about the positive changes discussed up to now.

Regarding lab tests to assess the state of a person’s metabolism, unless the person is experienced interpreting those tests, tests aren’t as important or informative as signs and symptoms are.

For instance, and because I received this question recently, blood levels of histamine are useless because, as it happens, histamine is concentrated locally.  So regardless of normal, or even low, levels of histamine in the blood, a person could still be exposed to high amounts of histamine (and would benefit from an anti-histaminic agent – my personal favorites being meclizine and diphenhydramine.)

Furthermore, having normal blood glucose levels, as deemed by the “establishment,” does not as a matter of course imply that there is a normal use of glucose by cells.  So despite normal blood glucose levels, it would be impossible to rule out the existence of a deficit in energy production resulting from the inadequate oxidative metabolism of glucose.  By the same token, high blood glucose levels do not necessarily spell gloom and doom; in fact, it could mean quite the opposite.  If cells are burning glucose intensely, for instance, certain hormones are released that in turn stimulate the liver to make more glucose in order to keep up with the increased demands for glucose.  A case in point is exercise, during which glucose levels increase at the same time muscles are vigorously burning glucose.

In cases such as these, a doctor may have no choice but to declare a clean bill of health when the patient feels anything but.  Or, even worse, they may result in treatments that are 180 degrees off the mark.  I’ve read too many cases like the one in which a person was declared to have diabetes and was treated with drugs that, in one way or another, decrease blood glucose levels despite the fact that the person’s symptoms did not line up with that diagnosis all along. 

I say all this to say that blood tests are not foolproof in that when interpreting them, it should be remembered that biological markers are dynamic in nature, and one test result merely represent a snapshot in time.  In many cases, a proper diagnosis isn’t possible in the absence of multiple tests under different conditions, such as when the patient is sick versus well.  Given the complexity of diseases and the variability among people, arriving at an accurate diagnosis is an art as much as it is a science, guided by intuition as much as by years of experience and practice.  Sometimes, the response to an empirical treatment is used to make a diagnosis.

Of all the signs and symptoms, monitoring the axillary body temperature every morning will yield the biggest bang for your buck.  The temperature to aim for is about 98° F.  The body temperature, in conjunction with improvements in other non-specific signs and symptoms (e.g. fatigue, apathy, drowsiness, mental depression) and general well-being should be used to guide treatment decisions.  Exercise, including isotonic contractions, improves cardiopulmonary fitness, and therefore the delivery of oxygen, and increases musculature and bone density – both of which increase the resting metabolic rate and the capacity for heat regulation.  Small meals consisting of sugar and protein throughout the day helps to keep the blood sugar up and the stress hormones down.  Since the conversion of carbohydrate to fat is so inefficient, adding small amounts of fat in the diet – in particular good quality chocolate, butter, tallow, and suet – is protective.


REFERENCES

1.       Hern├índez, A. & Obreg├│n, M. J. Triiodothyronine amplifies the adrenergic stimulation of uncoupling protein expression in rat brown adipocytes. Am. J. Physiol. Endocrinol. Metab. 278, E769–77 (2000).
2.       Brand, M. D. Uncoupling to survive? The role of mitochondrial inefficiency in ageing. Exp. Gerontol. 35, 811–20 (2000).
3.       Lonsdale, D. A review of the biochemistry, metabolism and clinical benefits of thiamin(e) and its derivatives. Evid. Based. Complement. Alternat. Med. 3, 49–59 (2006).
4.       Pamplona, R. et al. Mitochondrial membrane peroxidizability index is inversely related to maximum life span in mammals. J. Lipid Res. 39, 1989–94 (1998).
5.       Speakman, J. R. et al. Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer. Aging Cell 3, 87–95 (2004).
6.       Speakman, J. R., Selman, C., McLaren, J. S. & Harper, E. J. Living fast, dying when? The link between aging and energetics. J. Nutr. 132, 1583S–97S (2002).
7.       Acheson, K. J. et al. Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man. Am. J. Clin. Nutr. 48, 240–7 (1988).







[*] The metabolism required to maintain life.
[†] Because glycerol is not taken back up into fat cells as efficiently as glucose is, for every round of this substrate cycle, glucose is taken up from the blood and converted to glycerol in fat cells.
[‡] Imagine straining at stool while on the toilet as an example of an isometric movement.
[§] Noradrenalin bears a positive charge under physiological conditions because the acidity (pKa) of its amine groups is less than the acidity inside cells.  So, more noradrenalin’s amine groups are protonated, and therefore positively charged, under physiological conditions, allowing them to form salt linkages with negatively charged ATP molecules.
[**] Fats also alter the immune system directly.  For instance, omega-3 fatty acids suppress the immune system, decreasing the resistance to infections and wound healing; on the other hand, saturated fats do not suppress the immune system in the same way.

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