Reversing Altered Metabolic Functions to Enhance Long-Term Weight Control

By Jim English

According to the Centers for Disease Control (CDC) an estimated 65 percent of all American adults are currently either obese or clinically overweight, and health experts are now predicting that obesity will soon surpass smoking as the single largest contributing factor to early death and loss of quality of life. (1)

A report in the New England Journal of Medicine places much of the blame for the continuing obesity epidemic on the lack of “effective population-level interventions to reduce obesity.” In other words, current weight control options are simply not working. (2)

The severity of the problem was highlighted in a recent report commissioned by the British drug manufacturer, GlaxoSmithKline. Researchers working for the company randomly contacted 12,599 households across the United States to interview people about their efforts to lose weight. The 3,500 adults who completed the full survey reported making an average of 1.5 serious attempts to lose weight in the year prior to their interviews, and a stunning 15 total attempts at weight control over the course of their adult lifetimes. (3 These numbers are especially revealing in light of the fact that 75 percent of the respondents were overweight or clinically obese at the time of their interviews, based on self-reported Body Mass Index (BMI) measurements.

…The 3,500 adults who completed the full survey reported making an average of 1.5 serious attempts to lose weight in the year prior to their interviews, and a stunning 15 total attempts at weight control over the course of their adult lifetimes.

Findings such as these are causing leading obesity experts to return to the most basic and obvious question of all: Why is it so difficult to lose weight and to keep those extra pounds from coming back?

Losing Weight is Difficult

In the February 2011 issue of Scientific American, science writer David Freedman observed that, “It doesn’t seem as though it should be so hard. The basic formula for weight loss is simple and widely known: consume fewer calories than you expend. And yet if it really were easy, obesity would not be the nation’s number one lifestyle-related health concern.” (4)

“…if it were really that easy, obesity would not be the nation’s number one lifestyle-related health concern.”

“Almost everybody who tries to diet seems to fail in the long run,” adds Freedman. This observation is supported by a major review of 31 diet studies that was published in the April 2007 issue of American Psychologist. In their paper, researchers from UCLA discovered that as many as two-thirds of all dieters end up weighing more than they did before their diet within two years. (5)

“You can initially lose 5 to 10 percent of your weight on any number of diets, but then the weight comes back,” said Traci Mann, UCLA associate professor of psychology and lead author of the study. “We found that the majority of people regained all the weight, plus more. Sustained weight loss was found only in a small minority of participants, while complete weight regain was found in the majority. Diets do not lead to sustained weight loss or health benefits for the majority of people.”

According to Janet Tomiyama, co-author of the study, “Several studies indicate that dieting is actually a consistent predictor of future weight gain. We asked what evidence is there that dieting works in the long term, and found that the evidence shows the opposite” In fact, one of the studies under review found that both men and women who participated in formal weight-loss programs gained significantly more weight over a two-year period than those who had not participated in a weight-loss program.

“We concluded most of them would have been better off not going on the diet at all.”

What happens to people on diets in the long run, Mann asked. “We concluded most of them would have been better off not going on the diet at all. Their weight would be pretty much the same, and their bodies would not suffer the wear and tear from losing weight and gaining it all back.” Making matters worse, losing and gaining weight has now been linked to cardiovascular disease, stroke, diabetes and altered immune function. (6)

How Weight Loss Alters Metabolism

To address the obesity problem the National Institutes of Health has poured nearly $800 million a year into research seeking to unravel the metabolic, genetic and neurological foundations of weight control. According to Freedman, this research has “provided important insights into the ways proteins interact in our body to extract and distribute energy from food and produce and store fat.”

One of the major outcomes of this research is a new understanding of how normal metabolic functions are significantly altered by the very act of dieting. Specifically, following a period of significant weight loss, metabolic alterations result in a decline in energy production as the body gears up to amplify fat production and increase fat storage to begin packing pounds back on again. These chronic metabolic alterations have been shown to reduce energy production (resulting in fatigue) while increasing appetite (to stimulate intake of excess calories) and shunting of consumed calories into production of increased fat stores to reverse weight losses.

The Role of Lipoprotein Lipase (LPL) in Fat Production

Researchers have discovered that the very process of losing weight triggers a change in the levels and distribution of an enzyme, lipoprotein lipase (LPL), that controls how fats are metabolized and stored. Referred to as the “metabolic gatekeeper,” LPL plays a critical role in determining whether circulating triglycerides are metabolized by muscles cells for energy production, or converted into fat for storage in adipocytes (fat cells).

Historically, LPL activity played a critical role in the early development of the species. LPL activity is inversely regulated in fat cells and muscle tissues in response to eating cycles. Eating a meal results in increased LPL activity in fat cells and decreased activity in muscle cells, allowing the body to maximize energy storage (as fat) when food is available. Between meals, or when food is not available, LPL activity decreases in fat cells while it is increased in muscle cells to maximize energy output during periods of food-seeking behavior.

For our physically active hunter-gather ancestors, subsisting on a diet high in protein and low in fat, LPL provided a critical genetic advantage that improved the odds for survival.

By regulating how fats are metabolized, transported and stored, LPL allowed early humans to utilize fat storage as an energy reserve when food was abundant, to be drawn down during times when food was scarce. For our physically active hunter-gather ancestors, subsisting on a diet high in protein and low in fat, this ability to use LPL to store and release fats as needed provided a critical genetic advantage that increased the odds for survival during times of famine

Obviously, early humans with this adaptation were better suited to survival, and thereby passed this metabolic regulatory mechanism on to modern humans. Unfortunately, for modern humans who live a largely sedentary lifestyle with unlimited access to an abundant food supply rich in fats and refined carbohydrates, this retained genetic trait has fueled an explosive epidemic of obesity and obesity-related diseases (Pandora’s Seed in sidebar).

In his book, “Pandora’s Seed: The Unforeseen Cost of Civilization”, author and anthropological geneticist Spencer Wells observes that, “Our current health crisis began 10,000 years ago, when humans slowly moved away from hunting and gathering to take up farming as a more reliable source of food. As a result, the leading health threat facing adults – death from physical trauma – was replaced by a new threat from infection as animals were domesticated and people moved into crowded cities that hastened the spread of infectious diseases.” According to Wells, humans are now facing new set of health threats that are also tied to agriculture. Wheat, rice and corn supply more than half the calories consumed by people worldwide, and high-carbohydrate, processed foods have generated the modern epidemics of obesity, Type 2 diabetes and heart disease. Combined with our modern sedentary lifestyle, the modern diet represents “a profound shift in the causes of disease,” writes Wells. “More and more, we are causing our own deaths.”

Altered LPL Ratio and Obesity

In a lean, healthy body, LPL is evenly distributed in equal amounts between muscle cells and fat tissues. Research carried out over the past two decades has shown that eating a diet high in refined carbohydrates can significantly alter this ratio, resulting in higher LPL activity in fat cells. This, in turn, results in a significant increase in the conversion of consumed calories into fat reserves. Conversely, this altered ratio also dramatically reduces LPL activity in muscle cells, resulting in reduced energy production, increased insulin resistance and further weight gains.

In what is one of the most perverse twists in genetic programming, when an obese individual is able to successfully lose weight, instead of reverting to the previous, pre-obese LPL/ratio as might be expected, LPL levels in fat cells actually rise dramatically (Fig. 1). This effect has also been observed in athletes. As little as two weeks of physical rest (detraining) results in a ten-fold increase in the adipose/muscle LPL ratio, leading to a significant increase in the creation of new fat stores.

This “rebound” effect is yet another inherited metabolic adaptation, triggered when the body mistakenly interprets a reduction in caloric intake and subsequent weight loss as evidence of another life-threatening famine. The body’s answer to this perceived threat is to further limit energy expenditures and speed up the conversion of any available calories into additional fat stores to increase the odds of survival.

This chronic alteration in LPL ratios explains why, in addition to rapidly regaining all of their hard-lost weight, most people actually gain more weight than they originally lost when they attempt to return to a normal, healthy diet. The post-weight-loss alteration in LPL activity actively works to suppress energy production and enhance appetite and stimulate intake of additional calories, allowing the body to resume the conversion of dietary lipids into fat stores for long-term survival

Normalizing Metabolic Alterations to Support Weight Loss

A new appreciation for the adaptive genetic and metabolic mechanisms behind the obesity epidemic has generated a number of promising new leads for researchers. Topping the list of promising weight-control options are several natural herbal compounds that have traditionally been used to support and maintain healthy weight. Of particular interest are several recent studies revealing how two traditional compounds, Cordyceps Sinensis and Crataegus Fructi, support weight control by normalizing a host of chronic metabolic, chemical and behavioral components involved in unwanted weight gains, especially after excess weight has been lost.

Cordyceps Sinensis

Cordyceps sinensis is an extremely exotic – and expensive – medicinal fungus found only at very high altitudes in the Himalayan Plateaus. The difficulty and cost of harvesting Cordyceps in such extreme conditions has historically made it one of the most highly valued of all traditional medicinal crops. Even today, naturally harvested Tibetan Cordyceps costs $1,500 per pound for the lowest grade, to more than $8,000 per pound for the best quality product. Despite such high costs, the adaptogenic and medicinal benefits of Cordyceps have made it one of the most highly prized staples of Tibetan, Chinese and traditional herbal medicines, commonly reserved for the elderly as a rejuvenating agent to fight fatigue and prevent aging.

The development of modern “submerged culture” processes has led to the commercial cultivation of Cordyceps on an industrial scale, and all scientific research published in the last twenty years is based on hot water extracts cultivated in this manner. In this relatively short period of time researchers have discovered a number unique mechanisms to support the healing claims historically attributed to Cordyceps.

Reversing Insulin Resistance

Early research revealed that administration of Cordyceps to mice led to significant improvements in serum lipids, including reduced serum total cholesterol (TC), increased high-density lipoprotein (HDL), and decreases in both LDL (low density lipoprotein) and VLDL (very low-density lipoprotein) levels. (7) Additional animal studies have shown that Cordyceps also protects against the formation and accumulation of cholesterol deposits in the aorta by inhibiting oxidation of low-density lipoprotein by free radicals. (8)

Cordyceps has also been shown to aid in reversing insulin resistance. Insulin resistance severely impairs the body’s ability to absorb glucose, resulting in dangerously high blood levels of glucose and insulin. As insulin drives the excess glucose out of the blood for storage as fat, the body is deprived of necessary fuel for energy, resulting in increased fatigue and unhealthy weight gains.

In 2002 researchers discovered that Cordyceps extracts help to reduce insulin resistance and restore insulin sensitivity in both healthy and diabetic animals. After only 17 days of treatment with Cordyceps researchers noted significant improvements in fasting blood glucose levels, fasting plasma insulin levels, glucose insulin index and oral glucose tolerance in treated animals. (9)

In another study researchers observed that animals treated with Cordyceps for 10 days showed significant improvements in whole-body glucose disposal, accompanied by a reduction in insulin secretion after eating meals high in carbohydrates. (10)

In 2006 researchers found that Cordyceps significantly normalized blood glucose responses when given to diabetic rats during an oral glucose tolerance test. (11) That same year researchers at the Institute of Chinese Medical Sciences in Macau found that Cordyceps extract produced a significant drop in blood glucose levels when given to diabetic mice. Serum insulin levels were also normalized, indicating that Cordyceps was stimulating pancreatic release of insulin while reducing insulin resistance. (12)

In a related study published in 2006, scientists at the Department of Bioscience Technology in Taiwan revealed that the fermented mycelia and broth of Cordyceps exerted anti-hyperglycemic activities while causing significant reductions in blood serum glucose concentrations in diabetic rats, further supporting its potential role as a functional food for metabolic disorders and for people at risk of becoming obese and developing diabetes. (13)

Crataegus (Fructus Crataegi)

Crataegus (Fructus Crataegi) is a traditional botanical widely used to promote liver health and blood circulation. Previous studies had revealed that Crataegus is a rich source of potent flavonoids – antioxidant plant compounds that confer protective health benefits. The flavonoids contained in Crataegus have been shown to prevent oxidation of low-density lipoproteins (LDLs) that are implicated in the formation of arterial plaques and cardiovascular disease. Crataegus has also been shown to act as a powerful antioxidant, targeting dangerous free radicals (superoxide, hydroxyl, and peroxyl radicals), that damage heart tissues.

This last cardiotonic benefit was amply illustrated in a study published in the Feb. 2010 issue of the journal, Phytomedicine. Researchers at Ohio State University deprived animal hearts of blood for 30 minutes, mimicking the effects of a severe heart attack. Then, as circulation was gradually restored (reperfusion), the researchers infused the hearts with Crataegus extract. The result was that in addition to promoting significant recovery of cardiac contractile function, the Crataegus extract significantly reduced the size and amount of tissue damage (infarct size) while suppressing the damaging enzymatic cascade that typically wreaks havoc on cellular proteins and heart tissues immediately after a heart attack. (14)

Inhibiting Creation of Fat

In addition to its powerful cardiotonic benefits, research is revealing how Crataegus can aid in preventing uncontrolled weight gains and obesity by reversing metabolic alterations that drive increased creation and storage of fat.

In one study, researchers fed hamsters a high-fat diet to elevate their blood lipids and induce obesity. The overweight hamsters were then treated with Crataegus extract for a period of seven days. At the end of the treatment period the researchers noted that the Crataegus-treated animals had significantly lower appetites and reduced intake of food. In addition to resulting in a significant loss of total body weight, the size and weight of white fat cells were markedly reduced in the treated hamsters. Additionally, the lipid profiles of the Crataegus-treated animals were significantly improved, resulting in decreased total cholesterol (TC), reduced triglycerides (TG), lowered LDL (bad cholesterol) levels, and elevated HDL (good cholesterol) levels. (15)

In addition to its powerful cardiotonic benefits, breaking research is revealing how Crataegus can aid in preventing uncontrolled weight gains and obesity by reversing metabolic alterations that drive increased creation and storage of fat.

In a related study, Crataegus was shown to exert impressive metabolic and anti-obesity benefits by acting on a family of receptors called Peroxisome Proliferator-Activated Receptors (PPARs). PPARs play a vital role in lipid and glucose metabolism by controlling how glucose is converted into fat and stored in fat cells in obese individuals. Specifically, Crataegus was shown to work by activating a set of receptors called PPAR-alpha to increase the burning of fatty acids in muscle cells while preventing the storage of fatty acids in new adipocytes (fat cells).

Reversing LPL Alterations

In 2006 researchers set out to investigate whether Crataegus flavonoids can affect lipid metabolism by regulating LPL expression. To confirm the effect, the researchers treated mice with either Crataegus flavonoids or pioglitazone (an antidiabetic drug used to treat Type 2 diabetes) and measured LPL levels in serum, adipose tissue, and muscle tissues. Serum LPL levels were not affected by treatment with either Crataegus flavonoids or pioglitazone, but the researchers noted that the Crataegus-treated animals showed significant increases in LPL activity in muscle tissues, and a significant decrease in LPL levels in fat tissues. The researchers speculated that Crataegus flavonoids aid in regulating LPL expression via the Peroxisome Proliferator-Activated Receptors (PPAR) pathway. (16)

Summary

As scientists continue to unravel the underlying biological mechanisms of natural compounds, research on traditional herbs is revealing a host of unique properties that may prove useful to those seeking to manage long-term weight goals, especially after losing unwanted pounds. By reversing the chronic metabolic, chemical and behavioral alterations observed in post-obese individuals, these compounds may prove useful in controlling obesity and promoting long-term maintenance of optimal weight.

References

1. Centers For Disease Control – http://www.cdc.gov/chronicdisease/resources/publications/AAG/obesity.html.

2. Olshansky SJ, Passaro DJ, Hershow RC, Layden J, Carnes BA, et.al., A potential decline in life expectancy in the United States in the 21st century. N Engl J Med. 2005 Mar 17;352(11):1138-45.

3. Janine L. Pillitteri, Saul Shiffman, Jeffrey M. Rohay, Andrea M. Harkins, Steven L. Burton and Thomas A. Wadden. Use of Dietary Supplements for Weight Loss in the United States: Results of a National Survey. Obesity (2008) 16 4, 790–796. doi:10.1038/oby.2007.136.

4. Freedman, D.H. How to fix the obesity crisis. Scientific American, Feb 2011.

5. Koh JH, Kim JM, Chang UJ, Suh HJ. Hypocholesterolemic effect of hot-water extract from mycelia of Cordyceps sinensis. Biol Pharm Bull. 2003 Jan;26(1):84-7.

6. Yamaguchi Y, Kagota S, Nakamura K, Shinozuka K, Kunitomo M. Inhibitory effects of water extracts from fruiting bodies of cultured Cordyceps sinensis on raised serum lipid peroxide levels and aortic cholesterol deposition in atherosclerotic mice. Phytother Res. 2000 Dec;14(8):650-2.

7. Zhao CS, Yin WT, Wang JY, Zhang Y, Yu H, Cooper R, Smidt C, Zhu JS. CordyMax Cs-4 improves glucose metabolism and increases insulin sensitivity in normal rats. J Altern Complement Med. 2002 Jun;8(3):309-14.

8. Balon TW, Jasman AP, Zhu JS. A fermentation product of Cordyceps sinensis increases whole-body insulin sensitivity in rats. J Altern Complement Med. 2002 Jun;8(3):315-23.

9. Lo HC, Tu ST, Lin KC, Lin SC. The anti-hyperglycemic activity of the fruiting body of Cordyceps in diabetic rats induced by nicotinamide and streptozotocin. Life Sci. 2004 Apr 23;74(23):2897-908.

10. Li SP, Zhang GH, Zeng Q, Huang ZG, Wang YT, Dong TT, Tsim KW. Hypoglycemic activity of polysaccharide, with antioxidation, isolated from cultured Cordyceps mycelia. Phytomedicine. 2006 Jun;13(6):428-33. Epub 2005 Sep 19.

11. Lo HC, Hsu TH, Tu ST, Lin KC. Anti-hyperglycemic activity of natural and fermented Cordyceps sinensis in rats with diabetes induced by nicotinamide and streptozotocin. Am J Chin Med. 2006;34(5):819-32.

12. Swaminathan JK, Khan M, Mohan IK, Selvendiran K, Niranjali Devaraj S, Rivera BK, Kuppusamy P. Cardioprotective properties of Crataegus oxycantha extract against ischemia-reperfusion injury. Phytomedicine. 2010 Aug;17(10):744-52. Epub 2010 Feb 18.

13. Kuo DH, Yeh CH, Shieh PC, Cheng KC, Chen FA, Cheng JT. Effect of shanzha, a Chinese herbal product, on obesity and dyslipidemia in hamsters receiving high-fat diet. J Ethnopharmacol. 2009 Jul 30;124(3):544-50. Epub 2009 May 18.

14. Fan C, Yan J, Qian Y, Wo X, Gao L. Regulation of lipoprotein lipase expression by effect of hawthorn flavonoids on peroxisome proliferator response element pathway. J Pharmacol Sci. 2006 Jan;100(1):51-8. Epub 2006 Jan 11.