Friday, February 15, 2013

The Half-Life of Human Fat Tissue is 600 Days?



In the 1940s, some of the toxic effects of fish oil (such as testicular degeneration, softening of the brain, muscle damage, and spontaneous cancer) were found to result from an induced vitamin E deficiency. Unfortunately, there isn't much reason to think that just supplementing vitamin E will provide general protection against the unsaturated fats. The half-life of fats in human adipose tissue is about 600 days, meaning that significant amounts of previously consumed oils will still be present up to four years after they have been removed from the diet.  - Dr. Ray Peat


If there was ever an adage passed around by Dr. Peat’s followers that’s left my head spinning, it’s this one.  Several people have so far asked me to comment on it so here we go.

Bear in mind that triglycerides are continuously being broken down into their component fatty acids and glycerol by the enzyme hormone-sensitive lipase (HSL), which is inhibited by insulin and activated by noradrenalin.  Some degree of lipolysis and reesterification is happening all the time.  This is called the triglyceride-fatty acid cycle.2

Dr. Peat says that the half-life of fat in the adipose tissue is 600 days.  The half-life is the time it takes for the concentration of a substance to decrease by half.  So after 1 half-life, the concentration would have fallen to one-half of the original concentration; after 2 half-lives, the concentration would have fallen to one-quarter of the original concentration; after 3 half-lives, the concentration would have fallen to one-eighth of the original concentration; and so forth.

The half-life quoted by Dr. Peat was not explained in the study referenced by him, and so I followed the breadcrumbs to a paper by Hirsch and colleagues, which was luckily available (Hirsch, Farquhar, Ahrens, Peterson, & Stoffel, 1960).

Briefly, subjects consumed a diet that was supplemented with massive amounts of corn oil daily (40 percent of total calories) for about 40 months.  Periodic samples of their subcutaneous adipose tissue were biopsied and analyzed by gas-liquid chromatography.3

The natural logarithm was taken of the percentage of linoleate—the main fat in corn oil—in the adipose tissue at the beginning of the study over the percentage of linoleate at the end of the study, giving the product of the rate constant and the time for this change in percentage of linoleate to occur.  Then, given the duration of the experiment (1,120 days), the sum of the rate constants was determined of (1) the mixing of ingested fats with the body's total fat pool, K1, and (2) DNL and the removal of fatty acids via oxidation, K2, per first order kinetics.  And finally, with this calculated rate constant, a half-life was conceived of 350 to 750 days (t1/2 = 0.693 ÷ [K1+K2]).

If we were to accept this, we’d also have to accept a big assumption: That the adipose tissue can be reduced to one big compartment wherein fatty acids—a representative sample of the dietary fats assimilated over the years—mix freely.

It turns out this compromise limits the utility of the calculation, and more definitive isotopic studies have shown that the turnover occurs much faster—on the order of weeks to months—than what the calculation predicted (a quick crosscheck in a few physiology textbooks confirmed this).

The original data are also unreliable to begin with because only samples from a limited, unrepresentative lot were analyzed; so, the samples weren’t representative of the other storage sites in the body that have different rates of lipolysis and reesterification, as well as varying sensitivities to the lipolytic hormones.  The subjects consumed kilograms of linoleate, yet their fat tissue showed no change in the percentage of linoleate for months.  DNL rates were unchanged.  It doesn’t add up.

The fat tissue is highly dynamic, and fatty acids can be mobilized, oxidized, and stored at incredible rates per needs.  The speed with which we can “burn” through fat stores is illustrated by an experiment where subjects were put through an intensive calorie-restricted, boot-camp style workout program for 8 weeks (Friedl et al., 1994).  At the study’s end the subjects’ body fat percentages fell, on average, from 14.3 percent to 5.8 percent—the lowest it can possibly go!  So, on average, about 6.5 kilograms of body fat was lost over the course of the study by the subjects, whose average starting weight was about 76 kg.  To put it another way, on average, 116 grams of body fat was lost per day. (A far cry from Dr. Peat’s estimate of 4 years.5)

Generally, ingested fats show up in adipose tissue depots and in the bloodstream (in lipoproteins or as FFA) and the ultimate storage site is determined by the places where blood flows the greatest.  Women, for instance, store a greater proportion of ingested fats in the subcutaneous adipose tissue depots than men because of these regional blood flow differences (Jensen, Sarr, Dumesic, Southorn, & Levine, 2003).

In principle, on activation by the lipolytic hormones, short, polyunsaturated fats (e.g., linoleate) would be mobilized in preference to longer, saturated fats because they are more accessible to the water-soluble enzyme, HSL, which catalyzes the release of fatty acids from glycerol. (To add another layer of complexity, depending on the circumstances, adipose tissue depots contribute differentially to the blood FFA pool [Mittendorfer, Liem, Patterson, Miles, & Klein, 2003]).  Nonetheless, in reality, on average, plenty of saturated  (e.g., stearate and palmitate) and monounsaturated fats (e.g., oleate and palmitoleate) are released in addition to polyunsaturated fats, so when fats are mobilized a mixture is available for use as fuel by tissues elsewhere (Staiger et al., 2004).

This flies in the face of what Dr. Peat thinks; that is, that the adipose tissue preferentially releases polyunsaturated fatty acids and retains saturated fatty acids for itself to oxidize for energy.  Actually, white adipose tissue doesn’t oxidize much fat at all.

The half-life of blood FFA is about 3 minutes, and given 5 liters of blood in the circulatory system, we can say that about 0.7 grams of FFA are cleared from the blood every 30 minutes.  So, over the course of a day, blood FFA, which is mostly derived from the upper body subcutaneous fat, would turnover 60 times (1,800 minutes ÷ 30 minutes), and thus, in sum, about 40 grams of FFA would turnover each day under normal, weight-static, low-stress conditions (60 x 0.7).  I think this can serve as a reasonable starting estimate of the rate at which fat stores turnover, setting aside a few assumptions for now. (I've seen other estimates of 100 to 120 grams per day.)

In summary, the speed with which we burn through fat stores is determined predominantly by the body’s demand for fatty acids, and its ability to oxidize them for energy.  A case in point is endurance training, an activity where fatty acids in the adipose tissue, blood, and muscles are mobilized and burned at an incredibly fast rate, to where body fat can be reduced to the lowest level possible in just a matter of time.  Also, for the most part, equal amounts of fatty acids—unsaturated & saturated—are released into the bloodstream when fats are mobilized, providing a mixture of fatty acids for tissues elsewhere.  And finally, ingested fats are distributed throughout the body and, following the flow of blood, are stored & show up in various adipose tissue depots pronto. (Why in the corn oil study the percentage of linoleate in the subjects' adipose tissue remained unchanged for months, despite the massive quantities of corn oil employed, I don’t know, but we can speculate.)

So how much time does it actually take to fully renew our fat tissue?  I can’t say for sure because there are too many variables involved in the complex machine that is the human body.  But for most people, it should take significantly less than 4 years—assuming a perfect zero order decay process, as Dr. Peat has done—from the time when oil was ingested.


References

Frayn, K. N., Williams, C. M., & Arner, P. (1996). Are increased plasma non-esterified fatty acid concentrations a risk marker for coronary heart disease and other chronic diseases? Clinical science (London, England : 1979), 90(4), 243–53. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8777830
Friedl, K. E., Moore, R. J., Martinez-Lopez, L. E., Vogel, J. A., Askew, E. W., Marchitelli, L. J., Hoyt, R. W., et al. (1994). Lower limit of body fat in healthy active men. Journal of applied physiology (Bethesda, Md. : 1985), 77(2), 933–40. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8002550
Hirsch, J., Farquhar, J. W., Ahrens, E. H., Peterson, M. L., & Stoffel, W. (1960). Studies of adipose tissue in man. A microtechnic for sampling and analysis. The American journal of clinical nutrition, 8, 499–511. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/13714574
Jensen, M. D. (2002). Adipose tissue and fatty acid metabolism in humans. Journal of the Royal Society of Medicine, 95 Suppl 4, 3–7. Retrieved from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1308942&tool=pmcentrez&rendertype=abstract
Jensen, M. D., Sarr, M. G., Dumesic, D. A., Southorn, P. A., & Levine, J. A. (2003). Regional uptake of meal fatty acids in humans. American journal of physiology. Endocrinology and metabolism, 285(6), E1282–8. doi:10.1152/ajpendo.00220.2003
Mittendorfer, B., Liem, O., Patterson, B. W., Miles, J. M., & Klein, S. (2003). What does the measurement of whole-body fatty acid rate of appearance in plasma by using a fatty acid tracer really mean? Diabetes, 52(7), 1641–8. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12829627
Staiger, H., Staiger, K., Stefan, N., Wahl, H. G., Machicao, F., Kellerer, M., & Häring, H.-U. (2004). Palmitate-induced interleukin-6 expression in human coronary artery endothelial cells. Diabetes, 53(12), 3209–16. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15561952



1Oils in Context,” thanks to Danny Roddy for helping me find this article.
2 noradrenalin is secreted by the nerve endings of the SNS, which extensively permeates the fat tissue.  In response to any sort of stimulation, by way of the β3 and β2 adrenergic receptors in the adipose tissue & muscles, respectively, noradrenalin exerts a potent lipolytic effect.  The activation of the SNS also increases blood flow to the fat tissue so that the newly mobilized fats can be carried elsewhere to the tissues that need them.
3 gas-liquid chromatography is an analytical technique used to separate compounds (e.g., fatty acids), without decomposing them, from a mixture, to determine the identity (in conjunction with mass spectroscopy) and the proportion of each compound in the mixture.
4 or, based on a rate of 0.12 percent fat loss per day, per Dr. Peat's 4-year estimate would amount to 1.5 grams/d: (1) 2 percent x 7 kg .0084 kg (or 84 g) body fat lost in 8 weeks, or 56 days, and thus (2) 84 g ÷ 56 days = 1.5 g/day.
5 using linoleic acid (molar mass of 280.4455) and average blood FFA levels over the course of 24 hours of 480 micromoles/L (Frayn, Williams, & Arner, 1996).