Optimize your Body Fat Biochemistry! Part I
by Dr. Lonnie Lowery

The sports nutrition and weight control industries have always been fraught with scams. Recently, the proliferation of gurus, especially among professional athletes, is epidemic. Everyone has a gimmick! From convincing you that you have multiple food allergies (highly unlikely) to touting a single biochemical approach in their "system," I see real problems.

Equivocal science that is still at the "hypothesis stage" (a logical but unproven guess) is not appropriate for treatment of clients—at least not without disclosure that the system is indeed a debatable best guess. And tunnel vision that there’s only one valid reason we’re all fat is equally dangerous (or at least fruitless). The guru who buys into his/ her own "system" loses objectivity and that moves his emphasis from client to self.

This is bogus. This is wrong.

If you want to optimize fat loss or get better performance, applied knowledge is power. Don’t be spoon fed by a guru. Knowing the various biochemical pathways that MAY be principally at fault for your specific situation helps tremendously.

Let’s learn…

Insulin vs. Catecholamines: Duh! If there’s one thing that the low-carb craze has brought into the spotlight, it’s the fact that spiking insulin concentrations sky-high throughout the day (as Westerners have done for the past 20 years) will eventually make us FAT.

The longstanding low-fat, high-carb diet that has been so well promulgated is finally receiving critique in the scientific literature.(25) Still, blaming or tinkering with just one pathway can come back to bite you in the butt. Single-minded attention on combating insulin, for example via sympathetic catecholamines, has led many people to over-rely on substances that mimic or induce secretion of these hormones.

They do indeed oppose insulin and vice versa, and chronic and constant caffeine consumption, ephedra (or its adrenergic alternatives), and other stimulants are commonplace.(17,22) I’ve speculated before that excessive stimulation of adrenaline and nor-adrenaline (the sympathetic catecholamines) by means of common stimulants can ironically lead to more central body fat over time. Why? Because these stimulatory approaches can increase cortisol and related effects,(13, 14, 16) hamper glucose tolerance,(22) and decrease leptin production.(4)

Activation of the hypothalamic-pituitary-adrenal axis (HPA) is in fact associated with central obesity, hypertension and insulin resistance.(27) Don’t overdo it!

Optimize this System: It’s true that modulating insulin action is the most potent approach to addressing body fat for most of us, but changing the amount and timing of carbohydrate intake is smarter (and more sensible) than cranking up insulin-fighting adrenaline with a pill or drink. Changing your carb choices just doesn’t take the same kind of toll in the long run.

Lowering carb intake while maintaining at least some whole grains, legumes and whole fruits and vegetables can be coupled with more muscular activity to accomplish insulin management better than just blocking it with stimulants. Keep stimulant approaches acute and temporary while focusing on those carb types. In this manner, fat loss can be induced without exacerbating stress hormones or relative glucose intolerance. In fact, the opposite becomes true: fat loss plus improved glucose tolerance!

But don’t forget that as athletes we need some carbs, comprising about 55% of total kcal (12) during growth phases, to prevent fatigue, reduce catabolism, lower inflammatory cytokines during exercise and maintain full-looking muscles. If this makes you fat-gain paranoid, try spreading non-workout carbs over many meals throughout the first 2/3 of your day.

When compared to the typical "three squares", nibbling can drop overall insulin concentrations 28%.(11)

HBP: The hexosamine biosynthetic pathway (HBP) has some Medline surfers in an uproar too. There’s certainly good evidence that this pathway is linked to maintenance of glucose tolerance and body fat mass (6, 24) but again, a biochemical pathway doesn’t operate in a vacuum. There are other systems and pathways at work simultaneously in the body and they can up- and down-regulate to compensate for others. The HMP is a good example of this.

You see, the end-products of this pathway, like glucosamine, apparently induce insulin resistance (24) and quite possibly fat gain. Yet recent research show that Type II diabetics (who already have sorry glucose tolerance as it is) don’t get any worse by ingesting glucosamine tablets for their arthritis.(20) So far, the overall effect of the pathway just doesn’t seem to be noticeable on a whole-organism level. So, despite good biochemical evidence that the HMP bodes poorly for body composition, it seems—at least for now—that glucosamine will not make you wickedly glucose intolerant or fat.

Optimize this Pathway: As part of a comprehensive approach to body fat control, however, the HMP may contribute something, perhaps to a greater degree in certain individuals. Hence, it’s worthy of consideration, even if it’s not the end-all-be-all of body fat regulation, just as the insulin-catecholamine interaction isn’t.

But the HMP may play a role in some persons’ fatness. If all else fails and you’re double-dosing glucosamine for sore joints while experiencing unusually high (for you) fasting or post-prandial blood glucose concentrations, you may want to switch joint supplements (there are several), lower your carb intake 10-20% and give yourself two months to self-evaluate the results.

Leptin: Most of you are aware by now that fat cells are themselves endocrine in nature, secreting substances that affect overall physiology.(8) Leptin immediately comes to mind. It traverses the bloodstream and, if you’re not genetically mis-programmed with faulty leptin receptors on your hypothalamus, it influences your behavior. As body fat mass enlarges, so does the amount of leptin in your blood. That excess triggers increased physical activity and reduced feeding.

Subsequently, after a while, your fat mass returns to normal. The opposite happens when you force-down body fat (or even avoid carbs), say by way of an aggressive dieting phase: less circulating leptin and resulting sluggishness with greater feeding behaviors ("munchies") and weight gain.

Genetically, there are those lucky ones among us that can maintain leptin concentrations in the blood as they diet (within reason). This gives them an easier time, as they get less fatigued and hungry all the time. But what about those whose leptin levels drop like a badly-missed squat attempt? Research tells us that raising leptin levels in the blood also stimulates thyroid output, (19) so we really don’t want it to crash for multiple reasons, like less munchies, higher concentrations of metabolism-boosting thyroid, and greater tendency toward maintained physical activity… oh yeah.

Stimulants like ephedra come to mind as one way to fight the hunger of decreased leptin (their anorectic effects are known to account for about half of their fat loss effects) but we’re back to bodily homeostasis as a confounder. We’ve already mentioned that stimulants reduce friendly leptin levels,(4) which over time tends to counteract their initial effects. Criminy! Is there no easy way out?

Optimize this System: Addressing this bodily system is subtle and indirect, basically taking the form of self-monitoring your behaviors. If you’re 10% or more under your usual body weight, feel sluggish, tired and constantly have the munchies, depressed leptin may be contributing. Likewise, if you have an established family history of obesity and are heavy yourself, you may be struggling with hypothalamic or other fat-regulatory genetic mutations.

And the low-carb craze doesn’t help here. Excessive elimination of insulin-stimulating carbs from your diet can lower helpful leptin.(9) This is yet another reason why I continue to harp on never giving up those morning carbs—even if you’re on an otherwise low-carb diet.

Preparation before entering a target-date-specific diet phase is helpful. I recommend buying a pedometer to help establish baseline activity level during one-two weeks of typical activity. Write it down daily, and then see if that number of daily steps drops noticeably as the diet progresses. Draw a line graph with days 1-14 on the x-axis (horizontal bottom line) and number of steps on the y-axis (vertical line) if it helps.

If number of steps drops dramatically, then leptin and thyroid are likely taking a major hit, particularly for those who ditch carbs aggressively. (So for most of you, go eat some oats for breakfast!)

Since stimulants mess with this bodily system, they should be used sparingly. Instead, discipline and sometimes even forced physical activity outside the gym may be necessary until goals are met. Of course, undertaking any activity pattern that can’t be maintained indefinitely won’t be a long-term solution. Also, make sure that nothing "off-diet" is convenient in your house! Otherwise, just a week or two into a diet, you’re setting yourself up to fail. Remember, the munchie monster is much closer than usual once you’re a few weeks into a diet or even just 10 percent lighter than usual.

That’s enough to metabolize for now. Tune in next time for a few more fat-regulating pathways and systems, along with insights into how you might influence the ones that most pertain to you!

References and Further Reading (Parts I and II):

1. Ahren, B., et alo. Acylation stimulating protein stimulates insulin secretion. Int J Obes Relat Metab Disord. 2003 Sep;27(9):1037-43.

2. Booth, A., et al. Endogenous testosterone and competition: the effect of "fasting". Steroids. 1993 Aug;58(8):348-50.

3. Cianflone, K., et al. Critical review of acylation-stimulating protein physiology in humans and rodents. Biochim Biophys Acta. 2003 Jan 31;1609(2):127-43.

4. Considine, R. Regulation of leptin production. Rev Endocr Metab Disord. 2001 Oct;2(4):357-63.

5. Dorgan JF., et al. Effects of dietary fat and fiber on plasma and urine androgens and estrogens in men: a controlled feeding study. Am J Clin Nutr 1996 Dec;64(6):850-5.

6. Gabrieli, I., et al. Hyperglycemia induces PAI-1 gene expression in adipose tissue by activation of the hexosamine biosynthetic pathway. Atherosclerosis. 2002 Jan;160(1):115-22.

7. Groschl, M., et al. Endocrine responses to the oral ingestion of a physiological dose of essential amino acids in humans. J Endocrinol. 2003 Nov;179(2):237-44.

8. Guerre-Millo, M. Adipose tissue hormones. J Endocrinol Invest. 2002; 25(10): 855-861.

9. Havel, P. Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation-stimulating protein, and adiponectin. Curr Opin Lipidol 2002; 13(1): 51-59.

10. Hundal, R., et al. Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes. J Clin Invest. 2002 May;109(10):1321-6.

11. Jenkins, D., et al. Nibbling versus gorging: metabolic advantages of increased meal frequency. N Engl J Med 1989 Oct 5;321(14):929-34.

12. Lambert CP, et al. Macronutrient Considerations for the Sport of Bodybuilding. Sports Med. 2004;34(5):317-327.

13. Laurent, D., et al. Effects of caffeine on muscle glycogen utilization and the neuroendocrine axis during exercise. J Clin Endocrinol Metab. 2000 Jun;85(6):2170-5.

14. Lovallo, W., et al. Stress-like adrenocorticotropin responses to caffeine in young healthy men. Pharmacol Biochem Behav. 1996 Nov;55(3):365-9.

15. Matthan, N., et al. Hydrogenated fat consumption affects acylation-stimulating protein levels and cholesterol esterification rates in moderately hypercholesterolemic women. J Lipid Res 2001; 42(11): 1841-1848.

16. McCarty, M. Modulation of adipocyte lipoprotein lipase expression as a strategy for preventing or treating visceral obesity. Med Hypotheses. 2001 Aug;57(2):192-200.

17. Muller, M., et al. Thermic effect of epinephrine: a role for endogenous insulin. Metabolism 1992 Jun;41(6):582-587.

18. Ozata, M., et al. Improved glycemic control increases fasting plasma acylation-stimulating protein and decreases leptin concentrations in Type II diabetic subjects. J Clin Endocrinol Metab 2001; 86(8): 3659-3664.

19. Rosenbaum, M., et al. Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones. J Clin Endocrinol Metab 2002 May;87(5):2391-4.

20. Scroggie, D., et al. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial. Arch Intern Med. 2003 Jul 14;163(13):1587-90..

21. Sonko BJ., et al. Dose-response relationship between fat ingestion and oxidation: quantitative estimation using whole-body calorimetry and 13C isotope ratio mass spectrometry. Eur J Clin Nutr. 2001 Jan;55(1):10-8.

22. Thong, F. and Graham, T. Caffeine-induced impairment of glucose tolerance is abolished by beta-adrenergic receptor blockade in humans.
J Appl Physiol. 2002 Jun;92(6):2347-52.

23. Turcotte LP. Role of fats in exercise. Types and quality. Clin Sports Med 1999 Jul;18(3):485-98.

24. Virkamaki, A., et al. Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance in multiple insulin sensitive tissues. Endocrinology. 1997 Jun;138(6):2501-7.

25. Weinberg, S. The diet-heart hypothesis: a critique. J Am Coll Cardiol. 2004 Mar 3;43(5):731-3.

26. Yasruel, Z. et al. Effect of acylation stimulating protein on the triacylglycerol synthetic pathway of human adipose tissue. Lipids 1991; 26(7): 495-499.

27. Yudkin, J., et al. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 2000 Feb;148(2):209-14.

28. Zderic TW, Davidson CJ, Schenk S, Byerley LO, Coyle EF. High-fat diet elevates resting intramuscular triglyceride concentration and whole body lipolysis during exercise. Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E217-25. Epub 2003 Oct 14.

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