Making Weight: Thermogenesis

Some natural ingredients help the body boost output of calories via thermogenesis. Thermogenesis (production of heat in the body) increases the resting metabolic rate (RMR) and lipolysis, the rate at which fat is released from body stores and broken down, to help burn calories. Thermogenic ingredients affect the sympathetic nervous system, which is involved in the regulation of lipolysis. The sympathetic nervous system can also affect white adipose tissue and thus help regulate body fat.

Caffeine has long been used as a weight management ingredient, and science confirms its efficacy. A 2006 prospective study from Harvard that included 18,417 men and 39,740 women with no chronic diseases reported a lower mean weight gain in participants who increased their caffeine consumption than in those who decreased their consumption from 1986 to 1998.¹ An increase in coffee and tea consumption was also associated with less weight gain. In men, the association between caffeine intake and weight was stronger in younger participants; in women, the association was stronger in those who had a body mass index (BMI) greater than or equal to 25, who were less physically active, or who were current smokers.

The Harvard researchers attributed the weight management connection to the caffeine in coffee and tea, but other research has noted teas of all types contain significant amounts of catechins that have been shown to have biological activity. Epigallocatechin gallate (EGCG), for instance, is the most studied tea component. According to researchers at the Maastricht University, The Netherlands, catechins can inhibit an enzyme involved in the breakdown of a neurotransmitter called norepinephine that can stimulate the activity of the sympathetic nervous system that, in turn, influences metabolism to promote the breakdown of body fat.²

Pharmachem Laboratories is so confident green tea has weight-management properties beyond caffeine that its green tea extract Teavigo® is caffeine free and relies on the potential of EGCG; the ingredient is processed so it has a minimum of 90-percent EGCG.

Whatever the reason, green tea extract aids weight management, research has shown that it does just that. Researchers from Velleja Research, developers of GreenSelect Phytosome, a green tea extract from Indena, reported a product that contained it has a high safety profile and appears to be a safe and effective tool for weight loss."³ They studied coated tablets of Monoselect Camellia in 50 obese men and women on a low-calorie diet, and compared their weight loss to those who were on the same diet, but did not take the supplement. After 90 days of treatment, significant weight loss and decreased BMI were observed in the group taking Monoselect Camellia (14-kg loss in the green tea group compared to a 5-kg loss in the diet-only group).

Green tea combined with other ingredients has also shown to be beneficial to weight management. A mixture of EGCG from standardized green tea extract and N-oleoyl-phosphatidyl-ethanolamine (NOPE) derived from soy phospholipids (as PhosphoLean® NOPE + EGCG from Chemi Nutra, offering 85 mg NOPE and 50 mg EGCG/d) along with a calorie-restricted diet boosted weight loss more than placebo (3.28 kg lost with treatment and 2.67 kg lost with placebo).⁴ NOPE-EGCG treatment also increased feelings of fullness, decreased depressive symptoms and reduced severity of binge eating. NOPE affects receptors that signal to the body that its full. That added to the thermogenic principles of green tea may combine to help weight loss.

Hormones play a big role in regulating appetite and increasing thermogenesis, and supplementing with hormone precursors have shown to assist in weight regulation. 7-Keto® (3-acetyl-7-oxo-dehydroepiandrosterone), a natural metabolite of dehydroepiandrosterone, is naturally produced in humans, but declines with age, so supplementing may help a person reach levels that allow the body to burn fat like they did when they were younger.

A formula containing 7-Keto, L-tyrosine, asparagus root extract, choline bitartrate, inositol, copper gluconate, manganese and potassium iodide (as 7-Keto Naturalean from Nutra Bridge) combined with a reduced-calorie diet and an exercise program resulted in a significant weight loss compared with diet and exercise alone in a 2002 study.⁵ And a 2007 study found administration of 7-Keto, calcium citrate, green tea extract, ascorbic acid, chromium nicotinate and cholecalciferol (as HUM5007), and 7-Keto alone increased the RMR of overweight subjects maintained on a calorie-restricted diet.⁶ The researchers concluded, HUM5007 and 7-Keto increased RMR above basal levels and may benefit obese individuals with impaired energy expenditure."

Nutra Bridge's 7-Keto has been the subject of two new dietary ingredient (NDI) notifications, which are submitted to FDA to show safety. And indeed, studies have shown 7-Keto is safe and well tolerated in normal healthy men at doses up to 200 mg/d for four weeks.⁷

Capsaicin, the primary pungent principle in red hot peppers, can increase metabolism by influencing the activity of calcium channel proteins in the cell membrane. In 1999, Canadian researchers said ingestion of red pepper decreased appetite and subsequent protein and fat intakes in Japanese females, and energy intake in Caucasian males.⁸ They said this effect might be related to an increase in sympathetic nervous system activity. In Japanese women, adding red pepper to a carbohydrate-filled breakfast significantly decreased the desire to eat and hunger before lunch, and decreased protein and fat intakes at lunch. In Caucasian men, adding red pepper to an appetizer significantly reduced the calorie and carbohydrate intakes during the rest of the lunch and in a snack served several hours later.

Another botanical, bitter orange (Citrus aurantium), stimulates thermogenesis and suppresses appetite because its dominant amine, p-synephrine, a stable isomer of synephrine, stimulates beta-3 receptors. These receptors increase lipolysis, but do not affect blood pressure. P-synephrine has structural similarities to ephedrine and nor-epinephrine, which has caused confusion about the safety of bitter orange, but research has shown it exhibits different pharmacokinetic and receptor binding properties.⁹ Ephedrine contains m-synephrine, which affects alpha, beta-1 and beta-2 receptors, increasing blood pressure and heart rate. However, p-synephrine makes minimal contact with alpha-1, and -2, and beta-1 and -2 receptors, which are responsible for causing negative cardiovascular and central nervous systems side effects.

In 2011, Sidney J. Stohs, Ph.D., dean emeritus of the Creighton University School of Pharmacy and Health Professions, Omaha, NE, and other researchers from Montana State University, Bozeman, reported ingesting a product containing bitter orange extract, caffeine and green tea extract did not lead to increased cardiovascular stress in mildly overweight individuals.¹⁰ It did, however, increase fat oxidation. And in 2010, HerbalGram, a publication from the American Botanical Council (ABC), published a review by Stohs and Harry G. Preuss, M.D., professor of medicine and pathology at Georgetown University Medical Center, Washington, that determined bitter orange and bitter orange extract are safe for use as ingredients in foods and dietary supplements.¹¹

In July 2011, Stohs released a paper that reported the naturally occurring p-synephrine in a branded bitter orange extract (as Advantra Z from Nutratech) exhibited approximately twice the physiological activity compared to an equal weight of synthetic p-synephrine, showing natural is the better way to go for weight management.¹² Stohs said bitter orange extracts derived from the immature bitter orange fruit not only contain natural p-synephrine, but also flavonoids and other protoalkaloids. These compounds provide additional health benefits that are not present in synthetic p-synephrine.

Fucoxanthin, a major carotenoid found in edible seaweed such as Undaria pinnatifida and Hijikia fusiformis, has also shown to boost fat burning in humans. A 2005 study found it increased the expression of mitochondrial uncoupling protein 1 (UCP1), which is usually expressed only in brown adipose tissue (BAT) and is a key molecule for metabolic thermogenesis. The researchers showed feeding lipids from Undaria pinnatifida reduced abdominal white adipose tissue (WAT) weights in rats and mice.¹³ A 2011 review from China noted numerous studies have shown fucoxanthin has considerable potential in human health including affecting metabolism and satiety, and possessing antioxidant, anti-inflammatory, anticancer, antiobese, antidiabetic, antiangiogenic and antimalarial activities.¹⁴ Although the review noted some studies showed the bioavailability of fucoxanthin to be low in humans, many studies have suggested combining it with an edible oil or lipid could increase the absorption rate.

As thermogenesis stimulates fatty acid oxidation, fat is broken down in the form of long-chain fatty acids and metabolized through a process called beta-oxidation. As fatty acids enter the mitochondria to be processed, they are transported via L-carnitine, which is biosynthesized from the amino acids lysine and methionine. A 2011 study found increasing L-carnitine via supplementation increased fat burning during exercise. ¹⁵ Supplementation with Carnipure L-carnitine (from Lonza) along with a low-fat diet and fiber-fortified cookies reduced body fat by 1.5 pounds/week and cholesterol, while maintaining or increasing RMR and without depleting lean body mass, according to a 1992 study.

Dehydrated cactus leaves (Opuntia ficus indica) also has fat-dissolving properties. In vitro tests on NeOpuntia® (a Opuntia ficus indica ingredient from Nexira) showed it decreased fatty acid bioavailability by more than 28 percent, and an unpublished pilot clinical study also suggests that 1.6 g of NeOpuntia per meal increased fat excretion on an average of 2 percent compared to placebo.

In February 2012, Dr. Mehmet Oz praised raspberry ketones in a segment on his show called, "Raspberry Ketone: Miracle Fat-Burner in a Bottle." He said raspberry ketone supplements can burn fat all over the body, are safe, are healthy and have no side effects. He explained the compound regulates the hormone adiponectin, which "tricks your body into thinking it's skinny," i.e., boosts metabolism. He recommended supplementation, as he said to get the effective dose of 100 mg/d of raspberry ketones, one would need to eat 90 pounds of raspberries.

Science also suggests they're beneficial to weight loss. In October 2010, a study from the Korean FDA said raspberry ketones prevented high-fat-diet-induced elevation in body weight and increased fat burning in male mice.¹⁶ That study also noted an in-vitro immunoassay showed 10 mcg of raspberry ketone increased fatty acid oxidation and suppressed lipid accumulation. And a 2005 study from Japan, also performed on rats, concluded raspberry ketones prevented and reduced obesity and fatty liver by increasing fat metabolism, or more specifically, by increasing the hormone norepinephrinem, which induces fat burning.¹⁷

References Listed on the next page.

References:

1.       Lopez-Garcia E et al. Changes in caffeine intake and long-term weight change in men and women." Am J Clin Nutr. 2006 Mar;83(3):674-80.

2.       Hursel R, Westerterp-Plantenga MS. Thermogenic ingredients and body weight regulation." Int J Obes (Lond). 2010 Apr;34(4):659-69.

3.       Di Pierro F et al.  Greenselect Phytosome as an adjunct to a low-calorie diet for treatment of obesity: a clinical trial." Altern Med Rev. 2009 Jun;14(2):154-60.

4.       Rondanelli M et al.  Administration of a dietary supplement ( N-oleyl-phosphatidylethanolamine and epigallocatechin-3-gallate formula) enhances compliance with diet in healthy overweight subjects: a randomized controlled trial." Br J Nutr. 2009 Feb;101(3):457-64.

5.       Zenk, J.L. et al. The effect of 7-Keto Naturalean on weight loss: A randomized, double-blind, placebo-controlled trial." Current Therapeutic Res. 2002 April; 63(4)263-272

6.       Zenk JL, Frestedt JL, Kuskowski MA.  HUM5007, a novel combination of thermogenic compounds, and 3-acetyl-7-oxo-dehydroepiandrosterone: each increases the resting metabolic rate of overweight adults." J Nutr Biochem. 2007 Sep;18(9):629-34.

7.       Davidson M et al. Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers." Clin Invest Med. 2000 Oct;23(5):300-10.

8.       Yoshioka M et al. Effects of red pepper on appetite and energy intake." Br J Nutr. 1999 Aug;82(2):115-23.

9.       Stohs SJ, Preuss HG, Shara M. A review of the receptor-binding properties of p-synephrine as related to its pharmacological effects." Oxid Med Cell Longev. 2011;2011:42973.

10.   Seifert JG et al. Effect of acute administration of an herbal preparation on blood pressure and heart rate in humans." Int J Med Sci. 2011 Mar 2;8(3):192-7.

11.   Stohs, SJ, Preuss, HG The Safety of Bitter Orange (Citrus aurantium) and p-Synephrine" HerbalGram. 2010; 89 34-39

12.   Benjamin T Wall et al. " Chronic oral ingestion of l-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans" J Physiol. 2011 February 15; 589(Pt 4): 963973. DOI:  10.1113/jphysiol.2010.201343

13.   Maeda H et al. Fucoxanthin from edible seaweed, Undaria pinnatifida, shows antiobesity effect through UCP1 expression in white adipose tissues." Biochem Biophys Res Commun. 2005 Jul 1;332(2):392-7.

14.   Juan Peng et al. Fucoxanthin, a Marine Carotenoid Present in Brown Seaweeds and Diatoms: Metabolism and Bioactivities Relevant to Human Health" Mar. Drugs 2011, 9, 1806-1828; DOI:10.3390/md9101806

15.   In Kaats GR et al. " The short-term therapeutic efficacy of treating obesity with a plan of improved nutrition and moderate caloric restriction." Curr Ther Res.1992;51(2):261-274

16.   Park KS. Raspberry ketone increases both lipolysis and fatty acid oxidation in 3T3-L1 adipocytes." Planta Med. 2010 Oct;76(15):1654-8

17.   Morimoto C et al Anti-obese action of raspberry ketone." Life Sci. 2005 May 27;77(2):194-204.