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Health Concerns

Obesity and Weight Loss

Life Extension Suggestions

Nine Pillars of Successful Weight Loss

Rebalancing energy intake and expenditure to lose weight, by reducing caloric intake and increasing physical activity, is requisite for any weight loss regimen. However, alterations in metabolism, including age-related hormonal changes, can complicate successful weight loss by necessitating dramatic reductions in caloric intake that are difficult to sustain (Apostolopoulou 2012; Begg 2012; Aoki 2007; Björntorp 2001). Therefore, it is important to consider a multimodal approach to weight loss, in which low-calorie diet and exercise are augmented by steps to restore optimal levels of steroid and thyroid hormones, promote insulin sensitivity, and modulate macronutrient absorption. By this approach, one might not only increase their chance of successful weight and body fat loss, but also potentially reduce many of the other risks associated with obesity such as cardiovascular disease and cancer.

Eat for a Long and Healthy Life

Caloric restriction. Caloric restriction is the dramatic reduction of dietary calories to a level short of malnutrition (Lane 1998). Restriction of energy intake slows down the body’s growth processes, and causes it to instead focus on protective repair mechanisms; the overall effect is an improvement in several measures of wellbeing. Even in lean, healthy individuals, moderate caloric restriction (22-30% decreases in caloric intake from normal levels) improves heart function, reduces markers of inflammation (eg, C-reactive protein and tumor necrosis factor alpha [TNF-a]), reduces risk factors for cardiovascular disease (eg, LDL-C, triglycerides, and blood pressure), and reduces diabetes risk factors (eg, fasting blood glucose and insulin levels) (Walford 2002; Fontana 2004, 2006; Meyer 2006). The multicenter CALERIE trial on the effects of calorie-restricted diets in otherwise healthy, overweight volunteers has shown that moderate caloric restriction can reduce several cardiovascular risk factors (LDL-C, triglycerides, blood pressure, and C-reactive protein), in addition to promoting weight loss (Lefevre 2009).

It is important to remember that as more calories are eliminated from the diet, dietary levels of essential nutrients drop and may need to be replaced; in studies of 4 popular diet plans that limited calories to 1100-1700 per day (including the NIH and American Heart Association-recommended “DASH diet”), all were found to be on average only 43.5% sufficient in Recommended Daily Intakes (RDIs) for 27 essential micronutrients values, and deficient in 15 of them (Calton 2010). Eating for a long and healthy life likely involves calorie restriction and nutrient supplementation. Refer to the Life Extension protocol on Caloric Restriction for additional information on energy-restricted diets and a comprehensive list of nutrients that may simulate caloric restriction.

Increase Physical Activity

Increased physical activity promotes weight loss by addressing both sides of the energy balance equation. It increases energy expenditure leading to reduced body weight and fat mass, and exercise reduces appetite at least in the short term by delaying gastric emptying, or possibly increasing the body’s sensitivity to hormones that control appetite such as cholecystokinin (King 2012). It may also protect against the insulin resistance associated with obesity (Maarbjerg 2011). Several intervention studies in both young (Hebden 2012) and older adults have shown small-to-moderate decreases in body weight, fat mass, and/or waist circumference with regular, moderate exercise (30-45 minutes of moderate exercise, 3-5 times per week), especially when combined with reduced calorie diets. Exercise may also offset some of the lean muscle loss associated with weight loss in older individuals; loss of lean body mass is associated with decreased independence among this group (Stehr 2012).

Restore Resting Energy Expenditure

Black coffee consumption. Black coffee consumption has been associated with reductions in body weight; it adds fluid to the diet without adding additional calories, and contains compounds (eg, chlorogenic acid and caffeine) that may promote weight reduction (Dennis 2009; Onakpoya 2011). In a large population study of almost 60 000 healthy men and women over a 12-year period, coffee consumption was associated with less weight gain in women (Lopez-Garcia 2006). While some of this may have been attributable to caffeine content, the same study also revealed modest associations between greater decaffeinated coffee consumption and less weight gain, suggesting other components of coffee may also protect against weight gain. Intervention studies have reported similarly positive results. In one study, 33 healthy volunteers saw slight reductions of body weight and body fat following 4 weeks of consumption of 750 mL brewed coffee per day that contained roasted coffee constituents (Bakuradze 2011). In a second study, 15 overweight and obese volunteers consumed 11 grams per day of instant coffee enriched with 1000 mg chlorogenic acid (approximately 5 cups coffee per day) for 12 weeks and saw reductions in body weight of almost 12 pounds, compared to a loss of 3.7 pounds among volunteers who drank regular instant coffee (Thom 2007).

Green tea polyphenols. Green tea has exhibited anti-inflammatory activity in dozens of laboratory and animal studies (Singh 2010), as well as cholesterol-lowering effects in human trials (averaging about 9 mg/dL of LDL cholesterol decrease across 4 studies) (Hooper 2008). The effect of green tea on body composition has been the subject of at least 21 unique trials. Two analyses of these trials suggest a modest effect of green tea on body weight (Johnson 2012; Hursel 2009; Phung 2010). In an analysis of 11 randomized, controlled trials of green tea consumption for 12–13 weeks duration, green tea decreased body weight by about 3 pounds compared to control in Asian participants (Hursel 2009). A second analysis of 15 randomized trials demonstrated that consumption of green tea catechins with caffeine produced a greater decrease in BMI and body weight compared to control (Phung 2010).

Fucoxanthin. Fucoxanthin is a carotenoid from brown seaweed that has been shown to reduce white fat levels in animal models, by increasing energy expenditure through the activation of the thermogenic factor mitochondrial uncoupling protein 1 (UCP1) (Maeda 2005, D'Orazio 2012). In a 16 week trial of 151 obese, pre-menopausal women with and without non-alcoholic fatty liver disease (NAFLD), consumption of a combination of 2.4 mg fucoxanthin and 300 mg pomegranate seed oil, along with a reduced calorie diet (1800 calories/day), resulted in a significant reduction of body weight compared to placebo (an average of 12.1 pounds lost in NAFLD patients and 10.8 pounds lost in non-NAFLD patients) (Abidov 2010). Serum triglycerides and C-reactive protein levels also dropped in both groups taking fucoxanthin/pomegranate seed oil compared to control.

Fish oil. Fish oil, a rich source of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can only be synthesized to a limited extent by humans but are nonetheless essential for several metabolic processes. Omega-3 fatty acids have been well studied for the prevention of cardiovascular disease and their ability to lower inflammation and reduce hypertension; these processes are all associated with the progression of obesity and metabolic syndrome (Marik 2009; Geleijnse 2002). Some evidence suggests EPA and DHA may promote thermogenesis (Li 2008). Omega-3 fatty acids from fish oil may have protective effects against weight gain independent of their blood-pressure-lowering and anti-inflammatory roles. When combined with regular aerobic exercise, 6 grams per day of fish oil for 12 weeks demonstrated significantly lowered triglycerides, increased HDL cholesterol, improved endothelium-dependent arterial vasodilation, and improved arterial compliance in a study of 75 overweight volunteers (Hill 2007). Additionally, both fish oil and exercise independently reduced body fat, albeit modestly. Incorporating lean or oily fish, or fish oil into energy-restricted diets (1600 calories per day) resulted in about 2.2 pounds more loss of weight over 4 weeks than diets without fish in a group of 138 overweight and obese men (Thorsdottir 2007).

Capsaicin/ Cayenne. Capsaicin is a major “spicy” constituent of chili peppers (eg, cayenne). Regular intake of chili peppers delays oxidation of serum lipids, which contributes to reducing the risk of cardiovascular disease (Ahuja 2006). Because of the sensation of heat and increased energy expenditure when they are eaten, chili peppers are thought of as potential interventions for obesity management (Luo 2011). Capsaicin has been studied as a potential thermogenic compound in 10 long- and short-term studies, mostly in Asian populations where it is more commonly consumed. Results of capsaicin studies are mixed; it appears to significantly increase energy expenditure (up to 30% in some studies) and decrease appetite and energy intake, but these results are more robust in Asian participants than Caucasians (Hursel 2010).

Another compound that may increase resting energy expenditure is 3-acetyl-7-oxo-dehydroepiandrosterone (7-Keto® DHEA). For more information, see the discussion on restoring youthful hormone balance later in this protocol.

Restore Healthy Adipocyte (Fat Cell) Signaling

Irvingia gabonensis. Irvingia gabonensis is a mango-like West African fruit; extracts of its seeds have been shown to reduce fat stores, and promote healthy blood lipid and fasting blood glucose levels (Egras 2011). Irvingia gabonensis extracts are thought to work by inhibiting adipogenesis (ie, the development of fat cells) by down-regulating a protein involved in activating fat cell growth and proliferation. Three randomized controlled trials have investigated Irvingia extracts in healthy volunteers; all have demonstrated its ability to significantly decrease body fat stores, weight, and waist circumference (Ngondi 2005, 2009; Oben 2008). When compared to placebo, healthy overweight and/or obese volunteers taking 150 mg of Irvingia gabonensis seed extract before meals for 10 weeks exhibited a significantly greater decrease in body fat percentage (6.3% versus 1.9%), body weight (28.2 pounds versus 1.5 pounds), and waist circumference (-6.37 inches versus -2.09 inches), as well as significant drops in total- and LDL-cholesterol, C-reactive protein, and fasting blood glucose (Ngondi 2009). These kinds of results are seldom duplicated outside the clinical study setting, however.

Sphaeranthus indicus and Mangosteen (Garcinia mangostana). Mangosteen has long been used as a diabetic treatment in Southeast Asia; modern investigations suggest antioxidant and anti-inflammatory activities, especially in white adipose tissue (Devalaraja 2011). Sphaeranthus indicus (S. indicus) has been widely used in Ayurvedic medicine for a variety of ailments, and has been studied for its anti-inflammatory, blood sugar-lowering, and lipid-lowering activities in animal and cell culture models (Galani 2010). In a trial of 60 obese volunteers, 30 were randomized to receive 800 mg per day of the S. indicus and mangosteen combination for 8 weeks, while maintaining a restricted 2000 calorie per day diet and exercising (walking) for 30 minutes, 5 times a week. After 8 weeks, the group receiving the dual plant extract exhibited significant reductions in body weight (11 pounds versus 3.3 pounds for placebo), BMI (2.05 versus 0.5 for placebo), waist circumference (4.05 inches versus 2.02 for placebo), as well statistically significant reductions in total cholesterol, serum triglycerides, and serum glucose (Lau 2011).

Restore Brain Serotonin/ Suppress Hunger Signals

Tryptophan. Tryptophan is an essential amino acid and a precursor to serotonin, a neurotransmitter involved in gastrointestinal function as well as mood and feeding behavior. Increases in brain levels of serotonin signal satiety, while decreases signal the desire to eat (Lam 2010). Multiple studies have shown that calorie-restricted diets, while successful at reducing weight, also reduce circulating tryptophan levels by 14-23%. This may lead to reduced serotonin synthesis, increased hunger, and a reduction in the probability of maintaining weight loss (Wolfe 1997). In a study of 10 healthy, young, normal-weight men, 2- and 3-gram doses of tryptophan reduced energy intake compared to placebo when taken before a buffet-style meal (Hrboticky 1985). In 10 obese subjects, 1, 2, or 3 grams of tryptophan taken one hour before a plated meal reduced calorie consumption in a dose-dependent manner (Cavaliere 1997).

Saffron. Extracts of saffron stigma (Crocus sativus) have been studied for a variety of applications, including pain relief, anti-inflammation, and memory enhancement. In animal models, high doses of saffron have been shown to possess an antidepressent-like activity, which may explain its potential for reducing the desire to eat. In a study of 60 healthy, mildly overweight women on an unrestricted diet, 176.5 mg of saffron stigma extract per day for 8 weeks produced an average weight loss of about 2 pounds. Much of this weight reduction is attributed to a reduction in snacking frequency; at the study’s end, individuals on the saffron supplement reported having 5.5 snacks per week (compared to 8.9 snacks per week in the placebo group),  a reduction in snacking frequency of 55% from pre-trial levels (Gout 2010).

Pine nut oil. Pine nut oil, which contains a constituent called pinolenic acid, has been shown to reduce food intake. When doses of pine nut oil ranging from 2 to 6 grams were given to overweight female subjects prior to a buffet-style meal, food consumption was reduced up to 9% compared to placebo. The researchers suggested that this reduction of food intake was attributable to pine nut oil’s satiating effects, which may be mediated via modulation of cholecystokinin (CCK) and other appetite-suppressing compounds (Hughes 2008).

Control Rate of Carbohydrate Absorption

Seaweed extracts. Extracts from kelp (Ascophyllum nodosum) and bladderwrack (Fucus vesiculosus) have been demonstrated to inhibit the activity of the digestive enzymes alpha-amylase (α-amylase) and alpha-glucosidase (α-glucosidase) (Paradis 2011); inhibition of these enzymes interferes with the digestion of dietary starches, and may reduce or slow the absorption of high glycemic carbohydrates (Preuss 2009). A proprietary composition of demineralized polyphenols from brown seaweed was examined in 23 volunteers for its ability to reduce post-meal blood glucose and insulin secretion following consumption of a carbohydrate-containing meal. When taken just prior to the consumption of a meal containing 50 grams of carbohydrates (from bread), 500 mg of the seaweed extract was associated with a 12.1% reduction in insulin excretion and a 7.9% increase in insulin sensitivity when compared to placebo (Paradis 2011).

White kidney bean extract (Phaseolus vulgaris). White kidney bean contains an inhibitor of α-amylase (ie, a pancreatic digestive enzyme required for the conversion of starches to simpler sugars in animals) (Barrett 2011). By inhibiting α-amylase, absorption of starch from the diet is attenuated; individuals can still include a reasonable carbohydrate proportion in their diet but lessen or slow the absorption of high glycemic carbohydrates (Preuss 2009). Ten clinical trials have investigated the carbohydrate-blocking activity of Phaseolus vulgaris extracts. In 3 randomized, controlled studies, overweight and obese volunteers taking Phaseolus extracts (at doses ranging from 445 mg for 4 weeks to 3000 mg for 8–12 weeks) exhibited reduced body weights compared to controls (ranging from 1.9 to 6.9 pounds lost). A fourth study showed a loss in body weight only among participants who consumed the greatest amount of carbohydrates. Additional trials demonstrated significant weight loss over time, as well as reductions in plasma triglycerides and post-meal blood glucose (Barrett 2011).

L-arabinose. Sucrose (common sugar) is composed of 2 simple sugar molecules, glucose and fructose. It is poorly absorbed in the intestine in this form. In order to be utilized, it must first be broken down by the digestive enzyme sucrase. Blocking the enzymatic action of sucrase therefore reduces uptake of sucrose.

Researchers have identified a potent sucrase inhibitor called L-arabinose. L-arabinose, an indigestible plant compound, cannot be absorbed into the blood. Instead, it remains in the digestive tract and is eventually excreted (Seri 1996; Osaki 2001). By blocking metabolism of sucrose, L-arabinose inhibits the spike in blood sugar and fat synthesis that would otherwise follow a sugar-rich meal (Osaki 2001). In animal models, L-arabinose virtually eliminated the rise in blood sugar following administration of sucrose, with blood glucose levels rising only 2% higher than in control animals that did not receive sucrose. L-arabinose did not exert any effect on serum glucose levels in control animals that did not receive sucrose (Preuss 2007a).

L-arabinose has been shown to be safe in both short- and long-term studies, and may contribute to lowered levels of glycosylated hemoglobin (hemoglobin A1C), a measure of chronic exposure to sugar in the blood. A study concluded that combining L-arabinose and white kidney bean extract not only smoothed out postprandial glucose spikes and reduced insulin levels, it lowered systolic blood pressure as well (Preuss 2007b).

Glucomannan. Glucomannan is a soluble fiber derived from Amorphophallus konjac. It is thought to prolong gastric emptying time, which has several anti-obesity outcomes. It may increase satiety, reduce body weight, reduce the post-meal rise in plasma glucose, suppress liver cholesterol synthesis, and increase the elimination of cholesterol-containing bile acids (Doi 1995). An analysis of 14 randomized, controlled studies of glucomannan usage by 531 hyperlipidemic, diabetic, or obese adults and children demonstrated its ability to affect modest reductions in body weight (an average reduction of 1.8 pounds across all studies), when supplied at dosages between 3 and 15 grams per day (Sood 2008). Additionally, glucomannan demonstrated significant average reductions in total cholesterol (-19.28 mg/dL), LDL cholesterol (-15.99 mg/dL), triglycerides (-11.08 mg/dL), and fasting blood glucose (-7.44 mg/dL). Propolmannan is the name of a well-studied glucomannan soluble fiber.

Propolmannan and the Role of Bile Acids in Dietary Fat Absorption

Bile acids are excreted from the liver into the small intestine where they facilitate the absorption of dietary fats into the bloodstream. Dietary fat absorption is dependent on bile acids and the lipase enzyme. An intact soluble fiber binds to bile acids in the small intestine, thus helping to impede absorption of dietary fats (while simultaneously reducing serum LDL and total cholesterol).

Specially processed, propolmannan is a plant-derived polysaccharide fiber. Propolmannan is patented in 33 countries as a purified fiber that does not break down in the digestive tract.

Published research reveals propolmannan’s ability to not only increase the amount of bile acids in feces, but also reduce the rate of carbohydrate absorption and the subsequent glucose/insulin spike in the blood. When propolmannan is taken before meals, consistent and significant reductions in blood triglyceride, LDL, and total cholesterol are observed (Doi 1990).

Restore Youthful Hormone Balance

Hormone replacement therapy, using natural compounds like dehydroepiandrosterone (DHEA) and Armour® thyroid, may help aging individuals overcome some of the barriers that insufficient or imbalanced hormone levels pose against successful weight loss. Comprehensive blood testing to assess hormone levels should be undertaken before beginning a hormone restoration regimen under the care of an experienced physician. The Male Weight Loss Panel or Female Weight Loss Panel are designed specifically to assess blood parameters that may influence weight loss. More information is available in the chapters on Male and Female hormone restoration, as well as the Thyroid Regulation chapter.

DHEA and 7-Keto® DHEA. Low levels of sex hormones are associated with obesity (Apostolopoulou 2012), as well as systemic increases in inflammatory markers (Singh 2011). Dehydroepiandrosterone (DHEA) is an adrenal steroid hormone, a precursor to the sex steroids testosterone and estrogen. DHEA is abundant in youth, but steadily declines with advancing age and may be partially responsible for age-related decreases in sex steroids (Heffner 2011). DHEA supplementation (50 mg per day for 2 years) in elderly volunteers significantly lowered visceral fat mass and improved glucose tolerance, as well as decreased levels of inflammatory cytokines in a small study (Weiss 2011). High-dose DHEA induced thermogenesis, decreased body fat without decreasing food intake, and decreased glucose levels in animal models; 7-Keto® DHEA (3-acetyl-7-oxo-dehydroepiandrosterone) was shown to be 4-fold more thermogenic than DHEA (Ihler 2003). It may work by increasing the shuttling of energy substrates into the mitochondria for conversion into heat/energy, and may act upon the same enzyme systems as the thyroid hormone T3 (Bobyleva 1997; Ihler 2003). In human studies, overweight volunteers taking 100 mg of 7-Keto® DHEA twice daily lost significantly more weight and body fat than did the placebo group (6.3 pounds versus 2.2 pounds, respectively, and reductions in body fat of 1.8% versus 0.57%) (Kalman 2000). This weight reduction may be related to 7-Keto® DHEA’s effect on increasing resting energy expenditure (REE). In overweight subjects maintained on a calorie-restricted diet, 7 days of treatment with 7-Keto® DHEA increased REE by 1.4% (equivalent to an extra 115 calories burned per day), whereas subjects taking placebo saw their REE decrease by 3.9% (Zenk 2007). Studies in healthy volunteers demonstrated that 7-Keto® DHEA does not activate the androgen receptor and is not converted to other androgens or estrogens in the body (Davidson 2000).

Restore Insulin Sensitivity

Restoring the function of insulin at the cellular level is paramount to combatting diseases related to chronically elevated glucose levels. Several medical strategies can help accomplish this. Metformin is a blood-sugar-regulating drug used to treat diabetes (Barbero-Becerra 2012); doses ranging from 250 – 850 mg 3 times daily with meals may help facilitate weight loss and promote insulin sensitivity. A physician should be consulted before a metformin regimen is initiated. Restoring youthful levels of testosterone may help men improve their insulin sensitivity as well (De Maddalena 2012). In addition, a number of natural strategies may help improve insulin sensitivity.

Chromium. Chromium is an essential trace mineral and cofactor to insulin. Chromium enhances insulin activity and has been the subject of a number of studies assessing its effects on carbohydrate, protein, and lipid metabolism. 

Magnesium. Magnesium is an essential trace mineral with several potential protective activities against obesity-associated diseases. Population studies suggest a relationship between low magnesium and increased risk of metabolic syndrome and diabetes (Champagne 2008), and a controlled trial has demonstrated its ability to decrease fasting insulin concentrations by 2.2 μIU/mL in otherwise healthy overweight volunteers (Chacko 2011). Additionally, magnesium may enhance satiety (Liu 2006).

Inhibit the Lipase Enzyme

The lipase enzyme is responsible for facilitating the absorption of dietary fats. Taking steps to reduce the activity of the lipase enzyme may reduce the total amount of dietary fat absorbed. The pharmaceutical drug orlistat (Alli®, Xenical®), a lipase inhibitor, is sometimes prescribed by physicians as part of a weight management plan. In addition, the following natural intervention may help control fat absorption.

Green tea. Green tea is rich in powerful antioxidants called catechins. Studies have shown that green tea extracts are able to inhibit the activity of the lipase enzyme and reduce absorption of fats from the intestine (Juhel 2000; Koo 2007). In an animal model of obesity induced by a high-fat diet, supplementation with the green tea catechin epigallocatechin gallate (EGCG) attenuated insulin resistance and reduced cholesterol levels. Moreover, 16-weeks of treatment with EGCG mitigated increases in body weight, body fat, and visceral fat compared to no treatment. The researchers postulated that these anti-obesity effects may have been conferred in part by a reduction in fat absorption, which was obviated by increased fecal lipid content in animals that received the extract (Bose 2008). Another experiment showed that EGCG reduced the incorporation of lipids into fat cells, suggesting that green tea not only combats fat absorption from the gut, but also acts at the cellular level to combat fat storage (Lee 2009). A similarly designed trial in animals showed that 17 weeks of supplementation with EGCG offset some of the metabolic effects of a high-fat, Western-style diet including body weight gain and symptoms of metabolic syndrome; it also reduced markers of inflammation. Again, these results were partly attributed to reduced fat absorption (Chen 2011). In a human trial among moderately obese subjects, 3 months of supplementation with a green tea extract standardized to catechins reduced body weight by 4.6% and waist circumference by 4.4%; these study investigators also cited the ability of green tea constituents to reduce the activity of the lipase enzyme as a mechanism behind the observed metabolic benefits (Chantre 2002).