Obesity

Chromium Enhances Insulin's Actions

Chromium is an essential trace element required for normal carbohydrate metabolism. Chromium increases insulin binding, the number of insulin binding receptors, and insulin sensitivity (Anderson 1997; Vincent 2000).

Human studies show that chromium picolinate decreases insulin levels and improves glucose disposal in obese and type 2 diabetics ( Anderson et al 1997; Bahadori et al 1999; Ghosh et al 2002). Chromium picolinate was evaluated for treatment of insulin resistance syndrome in obese rats. Oral chromium picolinate improved carbohydrate and lipid metabolism and enhanced skeletal muscle glucose transport in the obese rats (Cefalu et al 2002). In infant rats, elevated doses of chromium picolinate increased muscle mass by stimulating protein anabolism (muscle building) (Bernao et al 2004). In growing pigs, plasma glucose concentrations in chromium-supplemented pigs were lower before feeding, suggesting increased insulin sensitivity (Van de Ligt et al 2002).

Chromium polynicotinate (600 mcg daily for two months) given to modestly dieting and exercising African-American women caused a significant loss of fat and sparing of muscle compared with placebo (Crawford et al 1999). A formula including chromium polynicotinate reduced appetite, inhibited fat synthesis, and decreased body weight in 60 moderately obese subjects in an eight-week randomized, double-blind, placebo-controlled trial (Preuss et al 2004). Another double blind, four-week trial with a formula including chromium increased the rate of body fat loss and helped to maintain muscle mass (Hoeger et al 1998).

Always take antioxidants when taking chromium to protect against any oxidative reactions that might occur in response to chromium (Hendler et al 2001).

Magnesium Is as Important as Chromium

Although chromium has received considerable media attention, scientific literature shows that magnesium has a more important role in regulating carbohydrate metabolism. Magnesium is involved in a number of reactions required for cells to uptake and metabolize glucose. Magnesium deficiency causes insulin resistance and elevated blood sugar levels (Paolisso et al 1990; Nadler et al 1993; Nadler et al 1995; Lefebvre et al 1994).

Approximately 68 percent of Americans are magnesium deficient. When magnesium-deficient individuals undertake a diet, they often become severely magnesium deficient, which aggravates insulin resistance and contributes to failure of the diet.

Drug Therapy for Obesity

Sibutramine. Sibutramine helps control feelings of hunger and appetite by regulating neurotransmitters involved in energy intake and expenditure. Sibutramine increases signal transmission between nerves in the central nervous system (CNS).

Sibutramine has demonstrated energy-producing (thermogenetic) effects in animal studies (Connoley et al 1999). Obese Zucker rats treated with 10 mg/kg of sibutramine were found to consume smaller amounts of carbohydrates and fats (LeBlanc et al 2003), resulting in both increased energy expenditure and decreased body weight (Casado et al 2003). Most interestingly, sibutramine targets a type of fat known as “brown” fat. “Brown” fat activation is thought to allow more calories to be burned than stored (Giordano et al 2002).

In a 24-week clinical study consisting of 1047 patients treated with varying doses of sibutramine or a placebo, sibutramine demonstrated dose-responsive weight loss ( Weintraub et al 1991; Bray et al 1996; Hanotin et al 1998; Bray et al 1999). Even intermittent sibutramine treatment was found to reduce body weight (Wirth et al 2001).

A 2004 study of obese patients with type 2 diabetes found treatment with sibutramine was associated with significant reductions in body fat mass and weight. Significant improvements in plasma glucose control, plasma lipids, and markers of insulin resistance were also observed (Tankova et al 2004).

Another study of obese patients treated for 12 months with a combination of sibutramine and a low-calorie diet demonstrated significant improvements in glucose tolerance, insulin sensitivity, and some lipid levels (Sabuncu et al 2004). Further, sibutramine, when combined with metformin, was also shown to be a useful adjunctive treatment for obese individuals with type 2 diabetes mellitus (McNulty et al 2003).

Sibutramine is generally well tolerated. However, safety concerns have arisen regarding possible increased heart rate (5–6 beats per minute increase) and blood pressure (1–2 mm Hg increase) (de Simone et al 2005; Gaciong et al 2005; Faria et al 2005; Jordan et al 2005). Individual response to sibutramine may vary; therefore, blood pressure and heart rate should be monitored carefully.

Sibutramine should not be taken with other centrally acting antidepressants such as tricyclic antidepressants, selective serotonin reuptake inhibitors, ergotamine derivatives, opiates, herbs such as St. John's wort, supplement precursors to serotonin (e.g., L-tryptophan), and certain other medications because of the very rare but potential risk of serotonin syndrome (Trakas et al 2000; Giese et al 2001).

Orlistat. Orlistat is an inhibitor of intestinal lipase, an enzyme involved in the breakdown of dietary fat. At a therapeutic dose of 120 mg three times daily with main meals, orlistat inhibits the absorption of approximately 30 percent of the dietary fat ingested. Based on a weight-reduction diet of about 2200 calories a day, this would amount to a 200-calorie reduction in total caloric intake.

Animal studies have demonstrated orlistat'sability to inhibit absorption of fat regardless of the type of fat (e.g., saturated fat, polyunsaturated fat) (Porsgaard et al 2003), as well as the absorption of triglycerides (Isler et al 1995). Experiments in mice suggest that orlistat treatment also reduce interest in consuming dietary fat (Ackroff et al 1996). Further, in rats, the use of orlistat has demonstrated decreased atherosclerosis in the aorta (Ueshima et al 2004).

Clinical studies with orlistat have produced positive results. In double-blind, placebo-controlled, parallel-group randomized studies, a total of 171 subjects received oral daily doses that ranged from 30 to 1200 mg orlistat or a placebo three times a day for 9 to 10 days, resulting in a steep dose-response up to approximately 400 mg/day (Zhi et al 1994). Further, early dose-ranging trials showed that an additional weight loss of 1.75 kg with 360 mg a day of orlistat (120 mg three times daily) was observed in a 12-week period (Drent et al 1995).

A 2004 double-blind study showed that orlistat combined with a reduced-calorie diet produced weight loss and improvements in risk factors in overweight and obese patients with poorly controlled type 2 diabetes, hypertension, or hypercholesterolemia. (Guy-Grand et al 2004). A prospective, multicenter, open-label, randomized, controlled study showed that orlistat modified several cardiovascular risk factors in patients with both metabolic syndrome and type 2 diabetes (Didangelos et al 2004).

The Xenical in the Prevention of Diabetes in Obese Subjects trial (a four-year study involving more than 3000 patients randomized to either orlistat 120 mg three times daily or placebo) showed that orlistat treatment resulted in a greater reduction in the incidence of type 2 diabetes over four years and produced greater weight loss in a clinically representative obese population (Torgerson et al 2004).

Orlistat is generally well tolerated, although side effects can include flatulence and frequent loose stools but not frank diarrhea or intestinal malabsorption (Harp 1999). Consistent with orlistat's mechanism of action, malabsorption of fat-soluble vitamins is a potential risk (Cahill et al 1999).

A Prescription Drug That Causes Weight Loss... and Extends Life Span

Metformin is a prescription drug used to treat type 2 diabetes. Published research shows that it also helps nondiabetics lose weight (Paolisso et al 1998) . Metformin reduces the release of glucose (sugar) stored in the liver as glycogen. This prevents blood glucose levels from rising too high, so the body does not need to produce as much insulin (Davidson et al 1997; Maggs 1997; Pugh 1997) . Metformin also prevents some of the detrimental effects associated with normal aging (Kiho et al 2005). Phenformin, a similar drug, extended the life span of mice in a Russian study (Anisimov et al 2003).

In women, a common cause of obesity is polycystic ovary syndrome, which is characterized by high blood levels of insulin. Metformin helps women with polycystic ovary syndrome lose weight (Velazquez et al 1997; Holte et al 1998; Mauras et al 1998; Morin-Papunen et al 1998; Nestler et al 1998a,b).

Metformin can be used with relative safety to lose weight (Mogul et al 2003). Consider consulting your physician about taking metformin. A typical dose is 500 mg three times a day, a few minutes before meals. Metformin is not recommended for individuals who have kidney disease, heart failure, or any medical condition that could make blood acidic (Bralow et al 2004). Consult your physician about the appropriateness of combining metformin with any of your medications. Nausea or diarrhea may occur when using metformin.

Green Tea Enhances Metabolic Rate

Green tea and green tea extract have shown an ability to increase metabolic rate.

• A study in mice found that the primary polyphenol found in green tea (epigallocatechin gallate, or EGCG) decreased diet-induced obesity by decreasing energy absorption and increasing fat burning (Klaus et al 2005).
• Another study in mice evaluated the effects of caffeine, polyphenols, and L-theanine, the three major components of green tea. Additive benefits were found from green tea polyphenols, caffeine, and theanine on fat accumulation (Zheng et al 2004). Furthermore, another study showed that feeding 4 percent green tea powder to mice resulted in weight loss as well as lower concentrations of total cholesterol in the liver, triglycerides in serum and liver, and fatty acids in serum (Sayama et al 2000).
• A well-known study examined whether or not green tea extract, rich in caffeine and polyphenols, could increase 24-hour energy expenditure and fat oxidation in humans. On separate occasions, subjects were randomly assigned to one of three treatments: green tea extract and caffeine (90 mg EGCG and 50 mg caffeine), caffeine (50 mg), and placebo, which were ingested at breakfast, lunch, and dinner. The results showed that treatment with the green tea extract (which included caffeine) resulted in a significant increase in metabolic rate, as evidenced by a significant increase in 24-hour energy expenditure (Dulloo et al 1999).
• An open-label trial demonstrated that after three months, green tea extract decreased body weight by 4.6 percent and waist circumference by 4.48 percent (Chantre et al 2002).

Green tea is available in both caffeinated and decaffeinated forms. For more safety information about green tea, please see “Safety Caveats” at the end of this chapter.

Conjugated Linoleic Acid Increases Metabolic Rate and Reduces Abdominal Obesity

Conjugated linoleic acid (CLA) is found in ruminant meats such as beef and lamb and in dairy products such as milk and cheese. Many studies support the anticancer, antiobesity, antidiabetic, and antiatherogenic properties of CLA (Lee et al 1994; Park et al 1997, 1999; West et al 1998; Yamasaki et al 2003).

Human clinical trials have shown reductions in body fat from CLA supplementation.

• Supplementation with 1.8 g daily of CLA for 12 weeks reduced body fat in healthy, exercising humans of normal body weight (Thom et al 2001).
• Men with abdominal obesity who consumed 4.2 g daily of CLA for 4 weeks decreased their abdominal diameter (Riserus et al 2001).
• Supplementation with 3.4 or 6.8 g of CLA daily for two weeks decreased body fat mass in overweight and obese people, and the trans-10, cis-12 CLA isomer inhibited the activities of the fat-storage enzyme lipoprotein lipase (Pariza et al 2001).
• The cis-9, trans-11 isomer, a specific isomer of CLA, increases metabolic rate and energy production (thermogenesis) (Ryder et al 2001; Brown et al 2003).

Evidence from a short-term study (12 weeks) has suggested that treatment with CLA may worsen insulin resistance (Riserus et al 2002). However, a long-term study (one year) in overweight and obese men and women has shown that CLA is effective for weight loss with no adverse effects on insulin sensitivity (Gaullier et al 2004). A 36-week toxicity study in animals given CLA at doses far exceeding those given to humans also showed CLA to be without toxicity (Scimeca 1998).