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Weight Loss

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).

Guarana seed extract. Guarana fruit (Paullinia cupana) seed extract has traditionally been used as a stimulant by people of the Amazon region, where guarana is a native plant. Guarana seeds contain as much as 6% caffeine (Schimpl 2013). Caffeine, which is sometimes referred to as guaranine when extracted from guarana, can stimulate fat burning and increase metabolic rate (Rodrigues 2012; Hursel 2013; Senchina 2014). Guarana contains other classes of compounds with bioactive properties, including saponins and polyphenols (Rodrigues 2012; Duenas 2015; Ding 2015).

A study in 637 individuals over the age of 60 years living in the Amazon region of Brazil found those who reported ingesting guarana habitually had lower rates of obesity, metabolic syndrome, and high blood pressure compared with those who reported never ingesting guarana. In addition, guarana consumers had lower levels of markers of oxidized protein (Krewer Cda 2011). In a placebo-controlled study in 47 healthy overweight individuals, a product containing guarana and two other herbs, yerba mate (Ilex paraguariensis) and damiana (Turnera diffusa), resulted in over 15-fold greater weight loss over 45 days as well as reduced time to feeling full (Andersen 2001).

Guarana extract may contain up to four times the concentration of caffeine as coffee, and caffeine overdose from guarana has been reported. Guarana should be consumed judiciously especially in those with heart conditions including hypertension, atrial fibrillation, and other arrhythmias; or other conditions such as anxiety or hyperthyroidism that may predispose to sensitivity to caffeine and stimulants (Moustakas 2015; Ciszowski 2014; Fabrizio 2016).

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).

Saccharomyces cerevisae. Saccharomyces cerevisae (S. cerevisae) is a common yeast used in making bread and alcoholic beverages. Yeast hydrolysate is made using enzymes to digest S. cerevisae. This process yields peptides—short chains of amino acids—that have been found to reduce appetite and decrease abdominal fat accumulation (Yasueda 2013; Park 2013; Nature Education 2016).

A placebo-controlled trial examined the effect of one gram per day of S. cerevisae yeast hydrolysate in obese adults. After six weeks, the S. cerevisae hydrolysate group reduced caloric intake to a significantly greater degree than those receiving placebo. After 10 weeks, the placebo group gained an average of over 1.8 pounds, while the yeast hydrolysate group lost over 5.7 pounds. They also lost significantly more abdominal fat than the placebo group (Jung 2014). A four-week placebo-controlled trial in 20 obese young women found supplementation with yeast hydrolysate resulted in over two pounds more weight loss compared with placebo (Jung, Kim 2011).

A study in which subjects underwent brain mapping and completed mood questionnaires found depression and anxiety scores were improved after two weeks of taking yeast hydrolysate (Lee 2009). Given the evidence for a close association between mood disorders and obesity (Mansur 2015), yeast hydrolysate’s positive impact on weight management may result in part from this neuropsychological effect. Findings from animal research suggest its effects on body weight and body fat may also be related to inhibition of ghrelin, a hormone that stimulates hunger and fat accumulation (Hong 2015; CST 2013) and modulation of other appetite-regulating compounds (Jung 2009; Jung 2008). Several animal studies have found yeast hydrolysate administration resulted in improvements in glucose and lipid metabolism (Jung 2016; Jung, Lee, Jung 2011; Jung 2012; Kim 2004; Park 2013), providing evidence for yet another possible beneficial mechanism underlying the weight loss and anti-obesity effects of S. cervisiae yeast hydrolysate.

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).

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. 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).

Gynostemma pentaphyllum. Gynostemma pentaphyllum (G. pentaphyllum) is an Asian medicinal plant that has been shown to activate a critical enzyme called adenosine monophosphate-activated protein kinase (AMPK) (Li 2012; Park 2014). This enzyme, which affects glucose metabolism and fat storage, has been called a “metabolic master switch” because it controls numerous aspects of energy metabolism (Winder 1999 Park 2014). A sign of the ability of AMPK activation to favorably influence weight comes from studies of the diabetes drug metformin, an AMPK activator. Benefits of metformin include weight loss, reduced belly fat, and improved blood glucose and fat levels (Matsui 2010; Yanovski 2011; Fowler 2007).

Some benefits of caloric restriction and vigorous exercise appear to result from activation of AMPK during energy deficit (O’Neill 2011; Lee 2013). Studies suggest AMPK activation protects against obesity (Yang 2010). For instance, AMPK activation has been shown to reduce weight gain in animals (Nguyen 2010; Han 2016).

In a preclinical study, obese mice supplemented with G. pentaphyllum showed impressive declines in markers associated with obesity and its related diseases (Gauhar 2012). A study of obese people with elevated waist-to-hip ratio showed that daily supplementation with G. pentaphyllum extract for 12 weeks significantly reduced body weight, total abdominal fat area, body fat mass, percent body fat, and body mass index compared with a placebo group of similarly obese patients (Park 2014).

Hesperidin. Hesperidin and related flavonoids are found in a variety of plants, but especially in citrus fruits, particularly their peels (Umeno 2016; Devi 2015). Digestion of hesperidin produces a compound called hesperetin along with other metabolites. These compounds are powerful free radical scavengers and have demonstrated anti-inflammatory, insulin-sensitizing, and lipid-lowering activity (Li 2017; Roohbakhsh 2014). Findings from animal and in vitro research suggest hesperidin’s positive effects on blood glucose and lipid levels may be related in part to activation of the AMP-activated protein kinase (AMPK) pathway (Jia 2015; Rizza 2011; Zhang 2012). Accumulating evidence suggest hesperidin may help prevent and treat a number of chronic diseases associated with aging (Li 2017).

Hesperidin may protect against diabetes and its complications, partly through activation of the AMPK signaling pathway. Coincidentally, metformin, a leading diabetes medication, also activates the AMPK pathway. In a six-week randomized controlled trial on 24 diabetic participants, supplementation with 500 mg of hesperidin per day improved glycemic control, increased total antioxidant capacity, and reduced oxidative stress and DNA injury (Homayouni 2017). Using urinary hesperetin as a marker of dietary hesperidin, another group of researchers found those with the highest level of hesperidin intake had 32% lower risk of developing diabetes over 4.6 years compared to those with the lowest intake level (Sun 2015).

In a randomized controlled trial, 24 adults with metabolic syndrome were treated with 500 mg of hesperidin per day or placebo for three weeks. After a washout period, the trial was repeated with hesperidin and placebo assignments reversed. Hesperidin treatment improved endothelial function, suggesting this may be one important mechanism behind its benefit to the cardiovascular system. Hesperidin supplementation also produced a 17% treatment effect (improvement) in levels of the inflammatory marker high-sensitivity C-reactive protein (hs-CRP), as well as significant decreases in levels of total cholesterol, apolipoprotein B (apoB), and markers of vascular inflammation, relative to placebo (Rizza 2011). In another randomized controlled trial in overweight adults with evidence of pre-existing vascular dysfunction, 450 mg per day of a hesperidin supplement for six weeks resulted in lower blood pressure and a decrease in markers of vascular inflammation (Salden 2016). Another controlled clinical trial included 75 heart attack patients who were randomly assigned to receive 600 mg hesperidin per day or placebo for four weeks. Those taking hesperidin had significant improvements in levels of high-density lipoprotein (HDL) cholesterol and markers of vascular inflammation and fatty acid and glucose metabolism (Haidari 2015).

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).


Disclaimer and Safety Information

This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the treatments discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.

The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. The publisher has not performed independent verification of the data contained herein, and expressly disclaim responsibility for any error in literature.