| ||A diet high in fructose can increase uric acid levels, but allopurinol may help lower the resulting high blood pressure, researchers say.|
Men who took the drug to mitigate the effects of a high-fructose diet did not experience the increase in blood pressure observed among men on the same diet who did not take the drug, Richard Johnson, MD, of the University of Colorado, and colleagues said at the American Heart Association's High Blood Pressure Research Conference in Chicago.
"These results support the idea that fructose, such as present in table sugar and high-fructose corn syrup, could have a role in the epidemic of obesity and metabolic syndrome," Johnson said. "Further, they suggest that [the two sweeteners] could have a role in high blood pressure, and that this might be mediated by uric acid."
Eating a lot of fructose -- typically from sugary drinks sweetened with high-fructose corn syrup -- has previously been associated with increased levels of uric acid.
"It has been known for a long time that fructose can raise uric acid levels, and in the last few years epidemiological studies have also confirmed that those with the highest fructose intake have higher uric acid levels," Johnson said.
"Reducing sugar intake was an old treatment for gout as well, and was even espoused by Sir William Osler," the renowned physician widely credited with advancing modern medicine.
Robert Lustig, MD, of the University of California San Francisco, was a co-author on a paper in the Journal of Pediatrics published last summer (2008) that found evidence of this link in adolescents. The more sugary beverages the teens consumed, the greater their serum uric acid levels and, hence, their systolic blood pressure.
"The fact that this paper addresses this mechanism in humans rather than just rats is extremely important," Lustig said.
But he cautioned that uric acid is likely not the only cause of the metabolic syndrome.
"I absolutely think that uric acid is the main driver of hypertension" with regard to fructose consumption, Lustig said. "But it may not be the driver of the visceral adiposity, the dyslipidemia," and other components of the metabolic syndrome.
Still, Johnson and colleagues wanted to know whether allopurinol, which is primarily used to treat gout, could combat the blood-pressure-increasing effects of a high-fructose diet.
So they evaluated 74 adult men who were put on a diet that included 200 grams of fructose a day, on top of their regular diet (typically, people in the U.S. consume about 50 to 70 grams of fructose per day).
Half of the men were randomized to allopurinol.
After two weeks, those who weren't on the drug had a 6 mm Hg-increase in systolic blood pressure and a 3 mm Hg-increase in diastolic pressure (P<0.004 and P<0.007, respectively).
On the other hand, those on allopurinol had no increase in diastolic pressure and a nonsignificant 1 mm Hg-increase in systolic pressure, Johnson said.
The drug also lowered serum uric acid levels compared with controls (P<0.0001).
In addition, markers of the metabolic syndrome increased among men eating lots of fructose but not taking allopurinol. Incidence of the disease jumped from 19% at baseline to 44% after two weeks, Johnson said.
For this group, mean fasting triglycerides increased by about 55 mg/dL while HDL cholesterol fell by about 2.5 mg/dL (P<0.002 and P<0.001, respectively).
Fasting insulin and HOMA scores (which quantify insulin resistance and beta-cell function) increased, but plasma glucose didn't change, the researchers said.
For those on allopurinol, Johnson said there was a lowering of LDL cholesterol compared with controls. But there was no reduction in HOMA scores or triglyceride levels.
"I think there's more to it than just uric acid," Lustig said. "Uric acid is responsible for hypertension, but dyslipidemia is due to other effects in the liver on lipid pathways. There are other ways fructose induces these problems."
Fructose is one of the sweetest naturally occurring sugars and is frequently found in fruits, some vegetables, honey, and some other plants. What makes it different from other sugars is how the body treats it.
Lustig noted that fructose can only be metabolized by the liver, unlike glucose, which can be used by all organs of the body.
In the liver, fructose is phosphorylated, which depletes phosphate levels in the liver and increases uric acid production, he added.
"The liver is under greater substrate pressure with fructose than with glucose, which means you'll gen[erate] more uric acid for the same number of calories," Lustig said.
Once in the bloodstream, uric acid inhibits endothelial nitric oxide synthase (eNOS), thus reducing the production of the nitric oxide essential for keeping the vessels flexible. In turn, that leads to high blood pressure, Lustig said.
Either way, Johnson added, the take-home message is that "we should probably reduce our intake of added sugars, and that the benefits may be greater than simple weight loss."
| ||If you take a sugar holiday for even a couple of weeks, you will find that sugar cravings will diminish. Fructose consumption in large amounts results in craving for more. Cravings decrease when fructose intake is low.|
Research from the University of California at San Francisco indicates that fructose can trick our brains into craving more food, even when we�re full. It works by impeding the body�s ability to use leptin, the �satiation hormone� that tells us when we�ve had enough to eat.
IBS (Irritable Bowel Syndrome)
| ||Thirty to sixty percent (30-60%) of patients with irritable bowel syndrome have fructose intolerance and can be cured by avoiding foods made with fructose.|
Elevated Insulin Levels
| ||Please see the link between Metabolic Syndrome and Fructose Avoidance.|
Metabolic Syndrome (Syndrome X)
| ||Metabolic syndrome, characterized by truncal obesity, hypertriglyceridemia, elevated BP, and insulin resistance, is recognized increasingly as a major risk factor for kidney disease and also is a common feature of patients who are on dialysis. One feature that is common to patients with metabolic syndrome is an elevated uric acid. |
Although often considered to be secondary to hyperinsulinemia, recent evidence supports a primary role for uric acid in mediating this syndrome. Specifically, fructose, which rapidly can cause metabolic syndrome in rats, also raises uric acid, and lowering uric acid in fructose-fed rats prevents features of the metabolic syndrome. Uric acid also can accelerate renal disease in experimental animals and epidemiologically is associated with progressive renal disease in humans. It is proposed that fructose- and purine-rich foods that have in common the raising of uric acid may have a role in the epidemic of metabolic syndrome and renal disease that is occurring throughout the world. [J Am Soc Nephrol 17: 165-168, 2006]
Problem Caused By Being Overweight
| ||Research from the University of California at San Francisco indicates that fructose can trick our brains into craving more food, even when we�re full. It works by impeding the body�s ability to use leptin, the �satiation hormone� that tells us when we�ve had enough to eat. |
"Our data indicate that chronic fructose consumption induces leptin resistance prior to body weight, adiposity, serum leptin, insulin, or glucose increases, and this fructose-induced leptin resistance accelerates high-fat induced obesity." [Am J Physiol Regul Integr Comp Physiol. 2008 Nov;295(5):R1370-5. Epub 2008 Aug 13]
In plain English this means: Regular use of a lot of fructose produces leptin resistance. Leptim resistance results in weight gain.
Gout / Hyperuricemia
| ||In the United States, levels of gout have doubled over the last few decades, which coincided with a substantial increase in the consumption of soft drinks and fructose (a simple sugar and the only carbohydrate known to increase uric acid levels). The authors point out that sugary soft drinks are the largest single food source of calories in the US diet, and that the per capita intake of commercial high fructose corn syrup in the United States is now up to a whopping 29 kilograms (over 60 pounds) per year!|
It is also known exactly how fructose spikes uric acid levels acutely. Fructose, like alcohol, increases blood levels of uric acid within minutes by using the high energy phosphate ATP in the liver for its own metabolism. This process converts ATP to AMP, which is a chemical forerunner to uric acid.
Conventional dietary recommendations for gout have focused on the restriction of purines (found in high levels in meat and meat products, especially liver and kidney) and alcohol but with no restriction of sugar sweetened soft drinks.
So researchers in the US and Canada examined the relation between intake of sugar sweetened soft drinks and fructose and the risk of gout.
They followed over 46,000 men aged 40 years and over with no history of gout. The men completed regular questionnaires on their intake of more than 130 foods and beverages, including sugar sweetened soft drinks and diet soft drinks, over a period of 12 years. Different types of fruits and fruit juices (high in natural fructose) were also assessed.
At the start of the study, and every two years thereafter, information on weight, regular use of medications and medical conditions were also recorded. Gout was diagnosed according to American College of Rheumatology criteria.
During 12 years of follow-up, the researchers documented 755 newly diagnosed cases of gout.
The risk of gout increased with increasing intake of sugar sweetened soft drinks. The risk was significantly increased with an intake level of 5-6 servings per week and the risk was 85% higher among men who consumed two or more servings of sugar-sweetened soft drinks per day compared to those who consumed less than one serving per month.
These associations were independent of other risk factors for gout such as body mass index, age, diuretic use, high blood pressure, alcohol intake, and dietary factors.
Diet soft drinks were not associated with the risk of gout.
Fruit juice and fructose-rich fruits (apples and oranges) were also associated with a higher risk of gout. However, the authors stress that this finding needs to be balanced against the benefit of fruit and vegetable intake to prevent other chronic disorders like high blood pressure, coronary heart disease, stroke and certain types of cancer.
In conclusion, the findings provide prospective evidence that consumption of fructose sweetened soft drinks and fructose is strongly associated with an increased risk of gout, say the authors. Furthermore, fructose rich fruits and fruit juices may also increase the risk. In contrast, diet soft drinks were not associated with the risk of gout.
Kidney Weakness / Disease
| ||The metabolic syndrome has recently been recognized as a risk factor for kidney disease, but the mechanisms mediating this risk remain unclear. High fructose consumption by animals produces a model of the metabolic syndrome with hypertension, hyperlipidemia, and insulin resistance. The present study was conducted to test the hypothesis that consumption of a high-fructose diet could accelerate the progression of chronic kidney disease. Consumption of a high-fructose diet greatly accelerates progression of chronic kidney disease in the rat remnant kidney model. [Am J Physiol Renal Physiol 293: F1256-F1261, 2007. First published August 1, 2007]|
This study is consistant with others showing that kidney damage is induced from high fructose intake. A diet high in fructose can result in high blood pressure and continuing kidney damage.
Increased Risk of Hypertension
| ||Increased fructose consumption results in kidney damage and hypertension, as well as other health problems.|
Analyzing data from over 4500 participants in the National Health and Nutrition Examination Survey (NHANES), Jalal and her colleagues found that consuming as little as 74 grams of fructose � about 2 � 12-ounce cans of non-diet soda � was associated with a blood pressure of at least 135/85. According to guidelines established in 1997, a blood pressure reading of 130/85 signifies hypertension in diabetic persons; 140/90 signifies hypertension in the remainder of the population.
Furthermore, as fructose consumption increased, so did systolic blood pressures among NHANES participants. In quantifying the risk for hypertension imposed by ingesting fructose, Jalal and her associates noted that daily consumption of 74 grams or more was associated with a 28% higher risk for a blood pressure of 135/85 or higher, a 36% higher risk for a blood pressure of 140/90 or higher, and an 87% higher risk for a blood pressure of 160/100 or higher. In other words, the higher a person�s blood pressure was, the more likely they were to be consuming more than 74 grams of fructose daily.
Notably, NHANES participants reported no previous histories of hypertension. Therefore, regular consumption of fructose can drive one�s blood pressure upward, even if it is usually normal. [Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure: The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure [JNC VI]. Arch Int Med 157:2413-2446]