What is guggulsterones?

Guggulsterones, also known as Guggul or guggulipid, is an ethyl acetate extract of the gum resin of the guggul tree Commiphora mukul, a small bushy tree found in India, Bangladesh, and Pakistan. This yellowish gum resin has been used for more than 2000 years in Ayurvedic medicine to treat a variety of ailments, and many active constituents have been identified. It has been studied in the treatment of many conditions, including hyperlipidemia, obesity, and arthritis.

Although the majority of studies on guggulipid have been on its cholesterol lowering ability, it has also been identified as a weight loss agent. It activates lipolytic enzymes (1) and increases T3 levels, presumably due to increased conversion of T4 to T3 in the liver, although it may also stimulate the thyroid directly (2).

Quite a few studies have been done on both humans and animals accessing guggul's ability to stimulate fat loss. Animal studies have shown a positive effect (2, 3), and human studies have either shown a benefit or have been equivocal (3). Unfortunately, many of these studies were inadequately controlled. A study that controlled for BMI, concurrent drug use, diet, and exercise found that people who took guggul lost 1.92 kg after 15 days compared with .32 kg in the control group (3).

How does guggulsterones work?

As stated, orally administered guggulipid increases T3 (tryiidothyronine) levels in animal models. T3 is the conversion product of T4, which is produced by the thyroid gland. Thyroid hormone levels are intricately involved in metabolic homeostasis. Increased thyroid levels cause more fat to be burned and decreased levels increase the likelihood of fat being stored.

When one normally goes on a diet, the body responds by decreasing T3 levels and thus decreasing metabolic rate. But if T3 levels are increased, diets are much more effective at causing fat loss (4). It has not been established how guggulipid increases T3 levels, but the prevailing theory is that it is by decreasing lipid peroxidation (2).

• Cholesterol reduction - It is well established that orally administered guggulipid decreases LDL cholesterol and triglyceride (TG) levels while either having no effect on or slightly increasing HDL cholesterol levels (5, 8). Depending on dosage, it generally reduces LDL and TG levels between 10 to 25 percent (6, 7). Guggul functions in this respect by decreasing hepatic cholesterol biosynthesis (1). Two constituents of guggul, guggulsterones E and Z, have been identified as primarily responsible for its hypolipidemic properties, although these are definitely not the only active constituents in guggulipid (8, 9).
• Anti-inflammatory - Guggulipid is a potent anti-inflammatory agent, as evidenced by many studies done on individuals with arthritis (8, 9, 10). The compound primarily responsible for the anti-inflammatory properties of guggul is myrrhanol A, which is found in the acidic fraction of the extract (1, 8).
• Reduction in acne - There are many anecdotal reports of guggul causing a reduction of acne. There has been only one clinical study done, in which guggul was shown to be as effective as tetracycline (an antibiotic commonly used to treat acne) (8).
• Reduced oxidative stress - Guggulipid may significantly decrease lipid peroxidation (2). One controlled study showed a 33% decrease in lipid peroxides after 24 weeks of 50 mg of guggulipid per day (6).

The studies do not report serious side effects, although some users experienced gastrointestinal discomfort which did not necessitate discontinuation. High doses have been used without the incidence of ill effects. Guggul may compete with some cholesterol reducing medications, so if you are on such medications you should consult a doctor before taking guggul. Likewise, you should consult a doctor if you have a thyroid disorder.

The primary side effect that the athlete should be worried about is the possibility of muscle catabolism. Increased thyroid levels may also increase mitochondrial uncoupling of muscle tissue and decrease insulin secretion and nitric oxide production. Although fat loss will still be the primary effect, a portion of the weight lost may be from muscle. Fortunately, you can avoid or at least highly limit the amount of catabolism caused by increased thyroid levels by increasing your testosterone levels, because testosterone blocks the pathway through which thyroid-induced protein uncoupling occurs (11).

Simply stated, guggulsterones can really increase the metabolism to the point that your body is burning up everything in sight - from fat to some muscle as well. The best "remedy" for this is to make sure you do NOT cut calories too drastically and keep your protein in take higher then usual.

As guggul has various constituents, isolating the desirable ones may increase its effectiveness while reducing unwanted side effects. On the other hand, in the case of many of the constituents of guggul, the activity has not been adequately studied - especially for fat loss purposes - so it may be unwise to leave these out.

• Guggulipid standardized for total guggulsterones - The majority of studies - and all of the studies done on thyroid activity - have been done using guggulipid, usually an extract standardized to 10% guggulsterones (which is the exact amount found in Rx Fat Burner™). As it contains all of the constituents, this extract should stimulate the thyroid and have anti-inflammatory and hypolipidemic activity. The extract can be further divided into neutral, acidic, and basic portions. The acidic portion possesses the anti-inflammatory activity, while the neutral portion is hypolipidemic. The hypolipidemic portion has been studied in detail, and the E and Z guggulsterone isomers have very strong activity while some of the other isomers have weak activity.
• Guggulipid standardized for E- and Z-guggulsterones - Most standard guggul extracts contain .5-2% E- and Z-guggulsterones. Since these are the primary hypolipidemic agents, it is probable that they are also primarily responsible for some of guggul's other effects. Hence, increasing the total amount of E- and Z-guggulsterones may make the formulation much more potent. Products containing higher quantities of E- and Z-guggulsterones may be ideal, but two studies have shown that most products that claim to have higher quantities of E- and Z-guggulsterones than conventional extracts actually do not (12, 13). So, if you are buying a guggul extract that claims to have higher quantities of the E and Z isomers, chances are it isn't much more potent than other extracts despite label claims.
• Synthetic E- and Z-guggulsterones - This is a relatively new and promising development. These are just as effective as the E- and Z-guggulsterones derived from guggulipid, but they are much more concentrated. The only downside is that some of the other guggulsterones may have important activity as well. If your goal is cholesterol reduction or weight loss though, synthetic guggulsterones will probably be more effective than a standard guggul extract.
  
  Note: Rx Fat Burner Contains all three - E, Z and Lipid forms.

References

1. Kimura I, Yoshikawa M, Kobayashi S, Sugihara Y, Suzuki M, Oominami H, Murakami T, Matsuda H, Doiphode VV. New triterpenes, myrrhanol A and myrrhanone A, from guggul-gum resins, and their potent anti-inflammatory effect on adjuvant-induced air-pouch granuloma of mice. Bioorg Med Chem Lett 2001 Apr 23;11(8):985-9
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11327606&dopt=Abstract

2. Panda S, Kar A. Gugulu (Commiphora mukul) induces triiodothyronine production: possible involvement of lipid peroxidation. Life Sci 1999;65(12):PL137-41
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10503949&dopt=Abstract

3. Bhatt AD, Dalal DG, Shah SJ, Joshi BA, Gajjar MN, Vaidya RA, Vaidya AB, Antarkar DS. Conceptual and methodologic challenges of assessing the short-term efficacy of Guggulu in obesity: data emergent from a naturalistic clinical trial. J Postgrad Med 1995 Jan-Mar;41(1):5-7
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10740691&dopt=Abstract

4. Koppeschaar HP, Meinders AE, Schwarz F. The effect of a low-calorie diet alone and in combination with triiodothyronine therapy on weight loss and hypophyseal thyroid function in obesity. Int J Obes 1983;7(2):123-31 [abstract]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6408016&dopt=Abstract

5. Beg M, Singhal KC, Afzaal S. A study of effect of guggulsterone on hyperlipidemia of secondary glomerulopathy. Indian J Physiol Pharmacol 1996 Jul;40(3):237-40 [abstract]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8950139&dopt=Abstract

6. Singh RB, Niaz MA, Ghosh S. Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia. Cardiovasc Drugs Ther 1994 Aug;8(4):659-64 [abstract]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7848901&dopt=Abstract

7. Nityanand S, Srivastava JS, Asthana OP. Clinical trials with gugulipid. A new hypolipidaemic agent. J Assoc Physicians India 1989 May;37(5):323-8 [abstract]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2693440&dopt=Abstract

8. Urizar NL, Moore DD. Gugulipid: A Natural Cholesterol-Lowering Agent. Annu Rev Nutr 2003 Feb 26; [epub ahead of print]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12626688&dopt=Abstract

9. Meselhy MR. Inhibition of LPS-induced NO production by the oleogum resin of Commiphora wightii and its constituents. Phytochemistry 2003 Jan;62(2):213-8
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12482459&dopt=Abstract

10. Kimmatkar N, Thawani V, Hingorani L, Khiyani R. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial. Phytomedicine 2003 Jan;10(1):3-7 [abstract]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12622457&dopt=Abstract

11. Ferrando AA, Sheffield-Moore M, Paddon-Jones D, Wolfe RR, Urban RJ. Differential anabolic effects of testosterone and amino acid feeding in older men. J Clin Endocrinol Metab 2003
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12519877&dopt=Abstract

12. Mesrob B, Nesbitt C, Misra R, Pandey RC. High-performance liquid chromatographic method for fingerprinting and quantitative determination of E- and Z-guggulsterones in Commiphora mukul resin and its products. J Chromatogr B Biomed Sci Appl 1998 Dec 11;720(1-2):189-96 [abstract]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9892081&dopt=Abstract

13. Nagarajan M, Waszkuc TW, Sun J. Simultaneous determination of E- and Z-guggulsterones in dietary supplements containing Commiphora mukul extract (guggulipid) by liquid chromatography. J AOAC Int 2001 Jan-Feb;84(1):24-8 [abstract]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11234828&dopt=Abstract