Fructose A Bodybuilders Worst EnemyBy Steve Jones Editor-In-Chief
The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome.
Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that “a calorie is just a calorie” and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease.
How does this relate to those looking to build lean muscle and also keep body fat levels at bay? Well, anything that damages your body’s insulin metabolism, causes stress at a mitochondrial level and stimulates fat accumulation is certainly not conducive to achieving bodybuilding goals yet alone living a long and healthy disease free lifestyle!
Fructose-Induced Weight Gain and Metabolic Syndrome
Experimental studies from the 1950s showed the peculiar ability of fructose to induce insulin resistance in laboratory rats. Today, fructose intake has been shown to induce all features of metabolic syndrome in rats, as well as oxidative stress, endothelial dysfunction, fatty liver, microalbuminuria and kidney disease (rev. in. Similar findings can be shown when animals are fed sucrose or high-fructose corn syrup (HFCS), both which contain fructose.[2,3] In contrast, administration of glucose or starch results in fewer features of metabolic syndrome when provided equivalent intake.[4,5]
This is an interesting fact as many fitness folk recommend fructose in the nutrition programs over more simple sugars like pure glucose or starches. In fact many supplement companies still use pure fructose as a natural sweetener despite all of the bad effects on metabolism. Science has proven that fructose is more damaging to the body than straight glucose but let’s not fluff around, we will let science do the talking.
The Obesity Factor
Obesity is now killing more people than both cigarettes and alcohol combined! Fructose may increase the risk for obesity by altering satiety, resulting in increased food intake. The intake of fructose is not effective in stimulating insulin and leptin secretion in humans, and hence may not induce a satiety response. Other mechanisms may also be operative. For example, a high intake of fructose induces leptin resistance in rats. Fructose also encourages food intake due to stimulation of dopamine in the mesolimbic system and effects on the hypothalamus.[8,9] Food intake is also stimulated by hepatic ATP depletion, which
occurs in animals and humans administered fructose. Fructose may also affect metabolic rate. A recent study in humans documented a reduction in resting energy
expenditure in overweight and obese subjects fed fructose but not glucose.
So in simple laymen’s terms fructose does not have an appetite suppressing effect. Induces leptin resistance therefore encouraging increased food intake! Hardly a great equation for those looking to lose weight both short and long term. And to top off all that bad news, fructose reduces your metabolic rate. Yes, you burn less fat throughout the day!
A Role for Uric Acid in Fructose-induced Fat Accumulation
The observation that fructose-fed rats develop fatty liver and metabolic syndrome without requiring increased energy intake suggests that the metabolism of fructose may be
different from that of other carbohydrates. Fructose is distinct from glucose only in its initial metabolism. The first enzyme to metabolize fructose is fructokinase (also known as ketohexokinase [KHK]).
The metabolism of fructose to fructose-1-phosphate by KHK occurs primarily in the liver, is rapid and without any negative feedback, and results in a fall in intracellular phosphate and ATP levels.[14–16] This has been shown to occur in the liver in humans with relatively small doses of oral fructose (60 g fructose alone or 39 g fructose with 39 g glucose).
The decrease in intracellular phosphate stimulates AMP deaminase (AMPD), which catalyzes the degradation of AMP to inosine monophosphate and eventually uric acid. The increase in intracellular uric acid is followed by an acute rise in uric acid in the circulation likely due to its release from the liver. Fructose also stimulates uric acid synthesis from amino acid precursors, such as glycine.
In addition to inhibiting AMPK, uric acid may stimulate hepatic lipogenesis. The mechanism appears to be mediated by uric acid–dependent intracellular and mitochondrial oxidative stress. Although uric acid is a potent antioxidant in the extracellular environment, when uric acid enters cells via specific organic anion transporters, it induces an oxidative burst that has been shown in vascular smooth muscle cells, endothelial cells, adipocytes, islet cells, renal tubular cells, and hepatocytes.[29–31] Uric acid–induced oxidative stress appears to be mediated by the stimulation of NADPH oxidase, which translocates to mitochondria.[28,29,32] Uric acid can also generate triuretcarbonyl and aminocarbonyl radicals as well as alkylating species upon reaction with peroxynitrite and can also directly inactivate nitric oxide (NO) to 6-aminouracil.[33,34]
The induction of oxidative stress in the mitochondria causes a reduction in aconitase-2 activity in the Krebs cycle, resulting in citrate accumulation that is transported into the cytoplasm where it activates ATP citrate lyase, acetyl CoA carboxylase, and fatty acid synthase, leading to fat synthesis. Uric acid also causes a reduction in enoyl CoA hydratase-1, a rate-limiting enzyme in ?-fatty acid oxidation. The consequence is fat accumulation in the hepatocyte.[19,35]
Recently, we identified another mechanism by which uric acid may increase the risk for hepatic fat accumulation and metabolic syndrome. Fructose (or sucrose) ingestion is known to increase hepatic KHK levels. The increased expression of KHK is driven in part by the production of uric acid from fructose A rise in intracellular uric acid activates the nuclear transcription factor, carbohydrate responsive element–binding protein. When KHK expression is increased in HepG2 cells by uric acid exposure, the triglyceride accumulation in response to fructose is enhanced.
This is relevant to subjects with nonalcoholic fatty liver disease (NAFLD). Subjects with NAFLD ingest more fructose-containing soft drinks than age, sex, and BMI-matched control subjects and have increased KHK expression in their liver. Subjects with NAFLD who have the highest fructose intake also show the greatest ATP depletion in response to a fructose load, and those subjects with the highest uric acid levels show a greater nadir in the ATP depletion. These data are consistent with an induction of KHK in the liver with subsequent increased sensitivity to the effects of fructose via a uric acid–dependent mechanism.
Fructose-Induced Hyperuricemia, Insulin Resistance, and Diabetes
The observation that uric acid can induce mitochondrial oxidative stress and fatty liver may explain how fructose induces insulin resistance. Mitochondrial oxidative stress has a role in driving insulin resistance. In turn, the development of fatty liver is also linked with insulin resistance.
To read the full article “Fructose- A Bodybuilders Worst Enemy” purchase Volume 7 Issue 1 of Natural Bodz magazine Click here