The Fat Switch

by Richard J. Johnson

the onset of menarche is dependent on fat stores; and once initiated, as little as a 10 to 15 percent decrease in weight can cause menstruation to stop.13,44-45 According to Frisch and McArthur, an 18-year-old girl needs about 35 pounds of fat to maintain normal menstruation.46 This is the reason anorexia nervosa is associated with irregular or absent menstruation. It also explains why female marathon runners and ballerinas frequently have irregular menses.47

Some authors believe that the reason men are the hunters in most hunter-gatherer societies is to allow the women to maintain their fat stores so the pregnancies can be successful.

This is not simply the case for humans. Pets such as dogs and cats can also become obese, likely related to the same process of being provided excessive amounts of food coupled with a reduction in exercise. Evidence such as this suggests there is a strong role for cultural and behavioral mechanisms in driving obesity. Furthermore, environmental, genetic, and congenital factors are also likely to modify these behaviors.

an elevated uric acid is also common in individuals with obesity and insulin resistance, and this was known since the original study by Kylin in 1923.23 An elevated serum uric acid is so universal in these people that many authorities suggested an elevated serum uric acid should be considered a criteria for this syndrome. Even more striking, even if you are skinny and completely healthy, if you have an increased serum uric acid you have a remarkable risk for developing obesity, high blood pressure, fatty liver, and metabolic syndrome.24-28 In other words, an elevated uric acid is not only common in obesity, but it also precedes and predicts its development. Could uric acid activate the metabolic switch to make one fat?

Uric acid was long considered important only as a cause of gout and kidney stones. Recent studies are challenging this concept, and suggest it may have a role in the stimulation of fat stores and insulin resistance.

Life in the RNA World would also need tactics to survive when under attack. If an early RNA life form was injured, resulting in loss of some of its structure, what would be a better danger signal to the organism than one of its own degradation products? The major degradation product of nucleic acids is uric acid. As we shall see, recent studies suggest uric acid functions as a major alarm signal of the organism, telling it that the nucleic acids that drive all cell functions are under attack. Like ATP, uric acid likely represents a carryover from the RNA world and may have a survival role that is used by all living organisms.

To conclude, uric acid should be viewed as a “mayday” signal by the animal under conditions of starvation or stress.74 Uric acid functions by acting on the mitochondria energy factories where it causes oxidative stress and disrupts energy metabolism. The result is an increase in fat accumulation, insulin resistance, a rise in blood pressure, the stimulation of inflammation and activation of the immune system. These findings are similar to what animals undergo when they activate the switch to maximize fat storage. These findings may also remind you of the metabolic syndrome that affects over one fourth of the American population today. So this raises important questions. If uric acid is involved in fat accumulation, is there evidence that uric acid levels cycle in animals in which obesity is tightly regulated? Could uric acid be involved in the metabolic switch that animals use to become fat or lean?

leptin is the hormone released from fat cells that tells the brain to quit eating. Unfortunately, studies by Peter Havel’s group has shown that drinks rich in fructose do not stimulate the release of leptin as effectively as glucose based drinks, and this can translate into a lesser sensation of satiety and the intake of more food.104 In addition to not stimulating leptin release in response to food, our group also found that rats fed fructose become leptin resistant.105 This means that even if leptin is released, it will not effectively tell the brain to quit eating, and as a result one will eat more calories than one needs.

Fructose is distinct from other foods in that it activates the fat switch that preferentially shunts the food we eat into fat. By activating the switch, obesity results from both an increase in food intake and a decrease in physical activity. The law of thermodynamics holds. However, unlike classical thinking, obesity occurring in response to fructose is not due to the animal choosing to eat too much or deciding to exercise too little. Rather, the switch is signaling the animal to eat too much and to exercise too little.

the ability to grow vegetables and to domesticate animals improved the chances to avoid periods of famine, and represented a major advance in civilization. However, one problem was that this forced humans to eat new types of food. One of these was starch, which is the principal carbohydrate stored in many plants. Starch consists of many polymers of glucose and requires an enzyme (amylase) to degrade it so that it can be absorbed. Recently it was discovered that many humans living in farming populations carry a more active form of amylase compared to populations that subsist by hunting and gathering.136 The higher activity of this enzyme is due to the duplication of the amylase gene and results in more rapid and efficient digestion of starch. This change is specific for humans and is not seen in chimpanzees and other apes that have continued to live the same way as they did millions of years ago. Unlike the mutations associated with uricase and vitamin C, however, not all humans share the same genetic changes, but rather the alterations in amylase represent a recent change which is still taking over the population.

The earliest sources of fructose were from fruit and honey. Later, sugarcane was introduced in India and spread throughout the world. In these early days only the rich could afford sugar, and only the rich developed obesity, diabetes, and gout.

Mead was another drink that was developed by fermenting honey with yeast. Mead was developed nearly 8000 years ago, possibly in Crete. Over time it became most popular in northern Europe where grapes were less available for producing wine. Indeed, mead was a popular drink among the Vikings and was considered the drink of the Norse gods. While the fermentation of honey would have likely eliminated much of the fructose, the mead was often supplemented with additional honey or fruit.

Obesity, diabetes and angina were first described in India and it was in India where sugar was introduced.

The increased intake of sugar, and of sugared-alcohol drinks, is likely why so many kings became obese (the “Adipose Rex” syndrome). William the Conqueror, for example, became so fat during his later years that he was accused of looking like a pregnant woman by King Philip of France. He became so angry at this accusation that he stormed the city of Mantes near Paris in 1087, where he set the city on fire.

Increased production made sugar affordable to the common man. Once this happened, obesity and diabetes transitioned from being a disease of the wealthy to being a disease of humankind.

According to some linguists, the phrase “honeymoon” originated during this time and referred to the highly desired dowry of honey or honey drinks (such as mead) that the newlyweds would receive and which was to last until the next full moon.

Up until 1500, obesity (which was then called corpulency) had been rare among the common people. However, beginning in the early 1600s we see reports of obesity and its complications, with the vast majority of reports being from England and the Netherlands, the two countries where sugar intake increased first.

England hoarded sugar and paid the price—for it was England where the epidemic of obesity, diabetes and heart disease began.

According to import and export data, the per capita intake of sugar increased from 4 pounds per year in 1700, to 18 pounds in 1800, and to 90 pounds in 1900.32

Sugar, by raising uric acid levels, is a known cause of gout,

Today fluoride has been added to the drinking water of over 200 million people in the United States, and since the early 1950s, fluoride has been commonly added to toothpaste. The benefits of this approach remain debated, for fluoride can also be associated with toxicity, leading to discoloration of teeth and possibly other side effects.97 Cleave and others such as Phillipe Hujoel from the University of Washington have noted a yet another negative consequence, for it has masked the tell-tale sign that sugar intake is increasing.92,95 In so doing, fluoride use may have effectively removed this “alarm signal” that tells us we are eating too much sugar.

we have identified a scientific mechanism by which fructose causes metabolic syndrome. Specifically, we found that fructose increases uric acid in the cell that then alters the mitochondria to preferentially shunt the energy from food into fat. The mitochondrial oxidative stress also has a role in causing insulin resistance and hypertension.113 Fructose also causes leptin resistance, and blocks ATP production.114

What about Fruits and Fruit Juices? Animals use fruits to increase their fat stores by waiting until the fruit is very ripe or by gorging on as many fruit as possible. One reason for waiting until fruit is ripe is that it increases the amount of fructose and decreases the vitamin C levels.130 However, the fruits we typically eat are not mushy ripe fruits but rather are more tart and contain less fructose and have high contents of vitamin C, antioxidants, potassium and fiber. As a consequence, high intake of fruits in humans is associated with a reduced frequency of diabetes.131

These studies suggest that the benefits of vitamin C and other substances in fruits likely outweigh the negative effects of fructose. However, it should be emphasized that the ingestion of large amounts of fruits, especially for those fruits low in vitamin C, is not recommended. Dried fruits, for example, contain high concentrations of fructose and have lost their vitamin C content. Fruit juices and punches are also problematic, for the rapid intake of juice could lead to significant elevations in the concentration of fructose in the liver, which is key for activating the metabolic switch. Drinking fruit juices is associated with an increased risk for obesity and diabetes, especially in children.131,133-134 This has led to recommendations by the American Pediatric Association to restrict fruit juices in children.135

Natural fruits contain antioxidants that block fructose effects. In contrast, fruit juices contain more fructose and can overcome any benefits fruits may have.

Both fructose and uric acid can be shown to activate the fat switch in cells by acting on the energy factories, or mitochondria, in the cell. There is evidence that both fructose and uric acid are used by animals to increase their fat stores and become insulin resistant. Furthermore, there is increasing evidence that they may have a role in human obesity and diabetes, although more studies are needed.

While sugar (fructose) is likely the major driver of the obesity epidemic, heavy beer drinking is another cause. Other foods that can raise uric acid are also likely involved, although to a lesser extent. This includes the umami foods.

Beer, like sugar, is very potent at raising uric acid levels, but this occurs over hours instead of minutes. As you will recall, we have found that uric acid directly causes oxidative stress to the mitochondria and leads to fat accumulation in cells. This suggests that beer should be similar to sugar in its ability to increase fat stores.

Beer is much more effective than other alcohol-containing drinks in its ability to raise uric acid levels.7 This is why gout is more commonly observed in people who drink beer as opposed to wine.

should not be surprising, then, that studies have suggested that people who are eating foods high in glutamate content are at increased risk for obesity. For example, one study followed 10,095 healthy Chinese adults for an average of 5.5 years and found that those individuals that ingested high amounts of MSG had a higher risk for developing obesity.17 MSG has also been found to induce obesity in mice, particularly if given early in life.18 In addition to obesity, it can cause insulin resistance, hypertriglyceridemia, and an increase in abdominal girth.19 Cats given MSG also develop increased body fat and insulin resistance.20

High fat diets provide a fuel for weight gain if the fat switch is turned on. However, if the fat switch is turned off, such as by a low carbohydrate diet, then diets high in fat and protein may result in weight loss.

By the time we reach our thirties and forties, the average person is gaining 1 or 2 pounds per year.1 Studies have shown that this equates to eating only a few extra calories per day (less than the calories in a single apple) more than we need to maintain our normal weight.1-2

Exercise daily. An exercise program that includes short (3-5 minute) high intensity exercise, as well as aerobics and weight lifting, is beneficial. Exercise burns fat and prevents weight gain. It has also been shown to help maintain weight loss in animals.5 Exercise may be of benefit by helping keep the fat switch from being turned on, as chronic exercise has been shown to lower uric acid levels and to improve mitochondrial function, and even to stimulate the regeneration of mitochondria, which is called mitochondria biogenesis.

Get adequate sleep. Sleeping at least 8 hours a day has many health benefits. Getting to bed early and having the room dark is important. During sleep the biological systems associated with stress are turned off, including a decrease in the sympathetic nervous system and a fall in uric acid levels. At the same time beneficial hormones, such as the anti-oxidant, melatonin, are released from the brain. This allows the body to relax, resulting in a dilation of the blood vessels and a fall in blood pressure.

While natural fruits contain fructose, most have only 6 to 8 grams per fruit, and hence are much less than in an average dessert or soft drink. More importantly, natural fruits are rich in vitamin C, antioxidants, flavonols, and other substances that combat the metabolic effects of fructose.

Cherries may be particularly healthy as they contain substances that lower uric acid.8

dried fruits are less safe, as the drying process tends to concentrate the fructose while at the same time remove many of the antioxidants.

fruit juices remain dangerous due to the rapid ingestion with its effect to rapidly raise fructose concentrations in the liver.

despite the widespread belief that honey is healthy, I recommend treating honey like sucrose, and to use it sparingly in foods or to limit it to special occasions.

Starches and High Glycemic Foods. Lean animals do not develop obesity when fed starch, which suggests that foods such as rice, potatoes and pasta might be safe for those individuals who are not overweight.

At this time we do not know how much starch is being converted to fructose in humans, and it likely varies among individuals.

my recommendations for those who are at normal weight are to avoid drinks containing high amounts (>10 grams) of glucose-containing liquids, such as your typical soft drink, and to avoid large portions of high glycemic foods such as white rice, bread, and potatoes.

If weight does not remain stable with the simple measures of reducing added sugars containing fructose and avoidance of eating excessive amounts of high glycemic index containing carbohydrates, then it remains possible that more significant restrictions of high glycemic foods may be necessary (see next Chapter).

most of these substitute sugars have had limited testing for toxicity, and there is ample concern that toxicity may exist. For example, when aspartame is metabolized in the body, there is the generation of methanol (wood alcohol) and formaldehyde, substances that can be extremely toxic to the body.

Sucralose is an organochlorine and was originally made with the thought it would be an effective insecticide like the related organochlorine compound, DDT.

Another sugar substitute is sorbitol, which is commonly used in syrups. Unfortunately, sorbitol is rapidly absorbed in humans13 where it is metabolized to fructose by the polyol pathway, so it is no safer than sugar. Xylitol is another sugar alcohol that is safer than sorbitol as only a small fraction of xylitol is metabolized by fructokinase.14 This likely accounts for why xylitol is better at preventing caries than sorbitol.15 Nevertheless, xylitol reduces vitamin C levels in the liver16 and can raise serum triglycerides and uric acid in humans when given intravenously.17 Hence, xylitol is also not an ideal sugar substitute.

Avoiding sugar substitutes is wise. If you desire something sweet, have a natural fruit.

Reducing Umami Foods. Most umami foods are rich in purines and may be able to stimulate the production of fat by increasing uric acid levels. As such, reducing intake of umami foods may also be of benefit in re...

The primary culprit in western society is beer, which often contains high amounts of RNA due to the presence of yeast. For those who love beer, it is best to graduall...

reduce foods to which monosodium glutamate have been added