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New Research on Thermogenesis

New Research on Thermogenesis

 

by Ward Dean M.D.

Obesity is an undesirable side effect caused by variations in normal human metabolism. Inadequate neurotransmission, thermogenesis, or acylation can account for 90 percent of all cases of obesity. Of the remainder, five percent are attributable to genetic traits, and five percent to gluttony.1Whatever its cause, obesity increases risks for degenerative diseases and mortality. Obesity can be managed with exercise and lifestyle modifications to reduce body fat stores and health risks. In far too many cases, mainstream medicine often utilizes pharmaceutical drugs such as dexfenfluramine, sibutramine and orlistat to alter food intake. While these drugs can be effective, they are not without serious side effects and require careful monitoring by a physician.2 Ongoing research is shedding light on some of the mechanisms underlying the cause of obesity. In light of these new findings, alternative therapies with thermogenic compounds, such as ephedra and caffeine, can be viewed as safe and effective adjuncts to weight management protocols.

 

Age-Related Thermogenesis

Age-related declines in the energy homeostat manifest as increased fatigue and reduced energy.3 Increases in obesity, diabetes, atherosclerosis, hypertension, depression and fatigue are just a few of the physiological and psychological problems that accompany decreased energy production with advanced age. Humans are dependent upon thermogenesis as the primary mechanism for heat production and thermoregulation. Metabolic heat, generated from the beta-oxidation of fatty acids mobilized from triglyceride stores, is mediated by interscapular brown adipose tissue (BAT). This metabolic generation of heat is induced by the actions of norepinephrine as well as the body’s response to cold. Animal studies have shown that thermogenesis drops significantly with advanced age. In one study researchers measured both cold- and norepinephrineinduced BAT nonshivering thermogenesis in male Fischer 344 rats. Of particular interest was the finding that the age-related decline in thermogenesis, while pronounced in male rats, was not so great in females.4 The researchers speculate that the observed decline in thermogenesis is due to a drop in the beta-oxidation of lipids by brown adipose tissue. The fact that the older animals have less functional BAT than do their younger counterparts disposes them to increased accumulation of body fat and may explain why men experience sudden weight gains after age 40.

 

Inducing Thermogenesis

Numerous studies have shown that ephedra is an effective agent for stimulating thermogenesis in humans. Ephedra an herb also known as ma huang, contains the alkaloid ephedrine which is commonly used in over-the-counter products designed to relieve nasal congestion, bronchitis and asthma. Ephedrine effectively induces thermogenesis by increasing cellular utilization of energy in the cells of adipose tissue and skeletal muscles,5 resulting in the elimination of excess energy (calories). In an in vitro study ephedra was found to stimulate cellular respiration of BAT cells to eight times above basal values.6 In another study researchers found that dieting women given ephedrine lost twice as much fat (9.9 pounds more) and three-quarters less muscle (6.2 pounds less) compared to those given a placebo, even though total weight loss was similar (22.2 pounds vs 18.5 pounds).7

 

Ephedra and Caffeine

Researchers have found ingesting caffeine with ephedra enhances the thermogenic effects of ephedra significantly. In one study researchers found that the combination of ephedra and caffeine is 20 to 29% more effective than dexfenfluramine (Redux). Participants in this study lost 20% more weight with ephedra and caffeine than with dexfenfluramine (18.3 pounds vs 15.2 pounds). Of particular interest is that when the subgroup of patients who were the most overweight (40% or more overweight) was analyzed, it was found that those who took ephedra and caffeine lost 29% more weight than those who took dexfenfluramine (19.8 pounds vs 15.4 pounds).8 In 1993 the International Journal of Obesity published the proceedings of a conference held in Geneva, Switzerland, covering the use of ephedrine, xanthines (such as caffeine), and other thermogenic agents for the management of obesity. Among the many benefits of ephedra and other thermogenic ingredients for weight management included in the review:

1. Ephedrine, caffeine, and aspirin are shown to be effective for inducing thermogenesis. They also seem to prevent the decline in metabolism that usually accompanies dieting.

2. Ephedrine has both thermogenic and appetite-suppressing properties.

3. While the stimulating effects of ephedrine disappear quickly due to the development of tolerance, the thermogenic properties are maintained and even enhanced by continued usage.

4. The use of other thermogenic ingredients, like aspirin and xanthines (caffeine), can enhance the thermogenic effects of ephedrine-based products.

 

Phytoceuticals for Weight Loss

A number of other phytoceuticals have been shown to either stimulate thermogenesis or to inhibit fat gains, benefiting weight control and contributing to improved health profiles.

 

Forskolin (Coleus forskohlii)

Forskolin is an Ayurvedic Indian herb that has been shown to stimulate fat breakdown and inhibit fat synthesis. Forskolin activates the enzyme adenylcyclase, which increases the level of cyclic AMP in cells.9 Once formed, cyclic AMP multiplies the thermogenic actions of noradrenaline and increases the production and release of thyroid gland hormones.10 This increases metabolic rate and fat burning. Forskolin compensates for the decreased response of fat cells to fat breakdown signals from noradrenaline and genetically determined fat cell siterelated differences in the adenylate cyclase system and adrenoceptor status. This causes fat accumulations in the buttocks, legs and other regions where fat stores are difficult to lose.11 Other important benefits from taking Forskolin include the lowering of elevated blood pressure and improving the functioning of the heart. Forskolin has been used for the treatment of congestive heart failure, angina, eczema, asthma and allergies. 12 Forskolin is well-suited for individuals who have problems controlling weight, particularly in hard-to-lose body sites. Potassium Salicylate

 

Potassium Salicylate

is a natural source of salicylic acid, which acts like aspirin in the body to stimulate increased thermogenesis and fat burning.13 Salicylic acid increases the thermogenic actions of ephedrine and caffeine by inhibiting feedback control mechanisms that block higher levels of thermogenesis. The combination of a salicylate compound, ephedrine and caffeine has produced close to five pounds a week of weight loss without dieting.14 In one study researchers found that people taking salicylate in conjunction with ephedrine and caffeine lost three times as much weight as those taking a placebo (4.8 pounds vs 1.5 pounds).15 In animal studies, the increase in energy expenditure found during treatment with ephedrine alone was doubled, and the obese group lost greater than 75% of body fat.16

 

Yohimbine

Yohimbine (the principle alkaloid in the African herb corynanthe yohimbe) antagonizes alpha-2 receptors on fat cells. These receptors inhibit lipolysis (fat breakdown) and promote fat gain.18 Located predominantly in the hard-to-lose fat regions like the hips, thighs and buttocks, alpha-2 receptors outnumber the fat-burning beta-3 receptors by four-to-one. Alpha-2 receptor activity and site number determines to a great degree the amount of fat gained in any part of the body, as well as the ease or difficulty in losing it.19-20

 

Gugulipid Extract

Gugulipid, an extract from the Guggul plant of India, stimulates the thyroid gland and causes weight loss. In one three-month study of overweight people, a gugulipidbased formula caused 12.1 to 12.7 more pounds of weight loss than a placebo (17- 18 pounds vs 5.3 pounds).21 Another benefit of gugulipid is the lowering of elevated triglyceride and cholesterol levels.

 

Conclusion

Obesity increases risks for degenerative diseases and mortality. Unlike drugs that carry serious side effects, thermogenic compounds and plant phytoceuticals have been shown to safely and effectively support weight control by:

• Stimulating lipolysis (fat breakdown) and inhibiting fat synthesis

• Amplifying noradrenaline’s lipolytic actions from activating beta 3- adrenoreceptor on fat cells

• Increasing the thermogenic properties of ephedrine to normalize body composition of the obese to that of the lean

• Increasing adenylcyclase and cyclic AMP that causes fat cells to release triglycerides and shrink in size

• Blocking alpha-2 receptors on fat cells that inhibit fat breakdown and promote fat gain

 

References

1. Thurmon TF, How can genetics help in the management of obesity? J La State Med Soc, 2000 Jan;152(1)’ 21-30.

2. Finer N, Present and future pharmacological approaches, Br Med Bull 1997;53(2):409-32.

3. Dean, W, The Neuroendocrine Theory of Aging Part III, Energy Homeostat Dysfunction. Vitamin Research News 1999 July; 13(7).

4. McDonald RB, Horwitz BA. Brown adipose tissue thermogenesis during aging and senescence. J Bioenerg Biomembr. 1999 Oct;31(5):507-16.

5. Dullo AG, Miller DS. Aspirin as a promoter of ephedrineinduced thermogenesis: potential use in the treatment of obesity. Am J Clin Nutr 45:564-9, 1987.

6. Bukowiecki L, Jahjah L, Follea N. Ephedrine, a potential slimming drug, directly stimulates thermogenesis in brown adipocytes via beta-adrenoreceptors. Int. J Obes 1982;6(4):343-50.

7. Astrup A, Buemann B, Christensen NJ, et al. The effect of ephedrine/caffeine mixture on energy expenditure and body composition in obese women. Metabolism: Clinical and Experimental. 41(7): 686-688, 1992.

8. Astrup A, Breum L, Toubro S, et al. The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet. A double blind trial. Int. J Obes 16(4): 269-77, 1992.

9. Ho R; Shi QH Forskolin as a novel lipolytic agent. Biochem Biophys Res Commun, 107(1):157-64 1982 Jul.

10. Hellstrom L et al. Adipocyte lipolysis in normal weight subjects with obesity among first-degree relatives. Diabetologia, 39(8):921-8 1996 Aug.

11. Hellstrom L; et al. Alterations in adipocyte adenylate cyclase activity in morbidly obese and formerly morbidly obese humans. Surgery, 21(8):228-34; discussion 234-5 1990 Aug.

12. Burns TW; et al. Alpha-2 adrenergic activation inhibits forskolin-stimulated adenylate cyclase activity and lipolysis in human adipocytes. Life Sci, 31(8):815-21 1982 Aug.

13. Dulloo AG; Miller DS Aspirin as a promoter of ephedrineinduced thermogenesis: potential use in the treatment of obesity. Am J Clin Nutr, 45(3):564-9 1987 Mar.

14. Daly PA , Krieger DO et al: Ephedrine, caffeine and aspirin: safety and efficacy for treatment of human obesity. Int J. Obesity, 17 suppl, 1:S73-S78, 1993.

15. Atkinson RL; et al. Combined drug treatment of obesity. Obes Res, 3 Suppl 4(-AU-):497S-500S 1995 Nov

16. Atkinson RL; et al. Ephedrine, caffeine and aspirin: “overthe- counter drugs that interact to stimulate thermogenesis in the obese. Nutrition, 3 Suppl 4(1):7-9 1989 Jan-Feb.

17. Berlan M; Galitzky J; Riviere D; Foureau M; Tran MA; Flores R; Louvet JP; Houin G; Lafontan M Plasma catecholamine levels and lipid mobilization induced by yohimbine in obese and non-obese women. Int J Obes, 15(5):305-15 1991.

18. Zahorska-Markiewicz B; Kucio C; Piskorska D Adrenergic control of lipolysis and metabolic responses in obesity. Horm Metab Res, 15(5):693-7 1986 Oct.

19. Berlan M; Carpene C; Lafontan M; Dang-Tran L. Alpha-2 adrenergic antilipolytic effect in dog fat cells: incidence of obesity and adipose tissue localization. Horm Metab Res, 15(5):257-60 1982 May.

20. Hellstrom L; Rossner S; Hagstrom-Toft E; Reynisdottir S. Lipolytic catecholamine resistance linked to alpha 2- adrenoceptor sensitivity—a metabolic Predictor of weight loss in obese subjects. Int J Obes Relat Metab Disord, 21(4):314-20 1997 Apr.

21. Paranjape P, Patki P and Pawardhan B: Ayuvedic treatment of obesity: a randomised double-blind, placebo-controlled clinical trial. J of Ethnopharmacology 29(1):1-11, 1990.

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