HOW SWEET IT IS! TO FRUIT OR NOT TO FRUIT IN DIABETES
Ryan Bradley, ND, MPH September, 2012
"Eat more fruits and vegetables" is perhaps the most common dietary advice we hear from doctors, nutritionists, and books on healthy eating. Especially during the summer months it’s easy to find fresh fruits, and because of its sweetness, it is easier to eat than vegetables for many people. Fruit is an important source of vitamin, minerals and antioxidants, including very potent "flavonoid" compounds (e.g., resveratrol in grapes, quercetin in citrus, ellagic acid in pomegranates, and fisetin in strawberries)- however, many fruits are also very high in simple sugars. How do these issues balance out especially for people with diabetes? In this month’s complementary corner, we’re going to clarify this issue to the best of our abilities, given the state of the science. We’ll discuss the differences between the naturally-occurring sugars in fruit and refined sugars, the effects of fructose and fruit on blood sugar, and explore some of the exciting research on specific fruit compounds which may help mitigate the effects of high blood sugar on the body!
Not All Sugars Are Created Equal
Before describing fruit’s effects on blood sugar, we should first explain the different types of sugar in the body. From a chemical perspective, "sugar" simply refers to a carbohydrate a complex of carbon, hydrogen and oxygen and there are hundreds of different types of naturally-occurring sugars. The simplest sugars are called "monosaccharides" and are relatively small. This group includes such well-known personalities as fructose (the main sugar in fruits) and glucose (the main sugar in our bodies- which is why when you or your doctor checks your "blood sugar", it is the glucose in your blood that is measured). Fructose is present in the diet in several forms as a simple sugar in fruits and honey, bound to glucose as part of sucrose (i.e., white table sugar), and in the refined sweetener "high fructose corn syrup" (which has a 55:45 fructose:glucose ratio, compared to the 50:50 split of white table sugar).
Sweet Effects on the Body?
Biochemists have done a great job at looking at the specific chemical pathways taken by sugars in the body, but most doctors and nutritional scientists have had a harder time understanding the differences in how the whole body deals with different sugars- and the different effects these sugars have on the body. Glucose and fructose are both absorbed directly from the intestines, but the body uses them very differently after this point. While glucose is immediately available for use by the body, fructose undergoes metabolic processing in the liver, where it may be converted to glucose, stored as glycogen (a storage form of carbohydrates), or converted into fats called triglycerides (which can build up causing "fatty liver").
Because fructose does not cause an immediate rise in blood sugar (as glucose does), it has been recommended as a replacement sweetener for people with diabetes. Unfortunately, recent trials have questioned whether fructose is safe replacement for glucose. Teff et al. found fructose-sweetened beverages, when compared to glucose-sweetened drinks, led to a decrease in the appetite suppressing hormone leptin and an increase in the appetite-stimulating hormone grehlin.1 This finding leads to the concern whether too much fructose might lead to a stimulated appetite and the overconsumption of calories. Adding additional concern, Stanhope et al. have found fructose-sweetened beverages (compared to glucose-sweetened beverages) may decrease insulin sensitivity, increase triglycerides, and increase fat deposits in the abdomen, i.e, "belly fat".2,3 Notably, these studies designed the fructose- and glucose-sweetened drinks to be 25% of daily calories, which seems like a large percentage of daily calories, until you consider that many Americans do consume excess calories from sugar-sweetened beverages with as many as 50% of Americans drinking sodas every day. Because of these and other studies, many doctors and nutritionists are now cautioning against excess fructose consumption by minimizing fructose-sweetened drinks, sodas and foods (Quick tip: Look for and avoid "high-fructose corn syrup" and "crystalline fructose" when you find it on food labels!).
But do these findings apply to fruit? Keep reading.
Fruits vs. Fructose
The studies from Teff and Stanhope's groups involved fructose-sweetened beverages, not on the effects of eating whole fruit in a naturally-occurring form. Fortunately, other researchers have begun looking at the short- and long-term effects of eating whole fruit.
From a long-term, population-based perspective, fruit consumption may protect against the development of diabetes. In a British study of 5,996 people not known to have diabetes, those reporting eating fruit five or more times per week had a slightly lower hemoglobin A1c (5.33% vs. 5.43%).4 While just a small difference, it was nonetheless statistically significant, and suggests overall fruit consumption may have some protective effect against the development of type 2 diabetes, although it could be that fruit consumption was otherwise linked to other healthy behaviors and fruit has no direct effect. A meta-analysis of similar epidemiologic studies sought to examine the relationship between fruit consumption and the development of type 2 diabetes. These researchers found a non-significant trend toward reduced rates of diabetes among those with the highest fruit consumption, though the researchers noted a high degree of variability in the study making it difficult to draw firm conclusions.5 (The protective effects of green, leafy vegetables were much clearer in this analysis, so don’t forget to eat more kale.)
In the shorter-term, trials have examined the effects of naturally-occurring fructose in the body. Researchers in Ontario, Canada, completed a six-month study of 152 individuals with type 2 diabetes who were randomized to either a high-fiber or a low-glycemic index (GI) diet (both diets also conformed to standard guidelines around reduced fat and cholesterol).6 The low GI diet encouraged consumption of fruits of GI of less than 70 (e.g., citrus, apples, pears, and berries). Higher GI fruits (e.g., bananas, raisins, grapes, melons, and tropical fruits) were recommended as part of the high-fiber diet. At the end, the results suggested several benefits in the low-GI fruit group including: a reduction in blood sugar (about a -0.5% change in HbA1c), an increase in healthy HDL cholesterol (7.3% improvement), and a reduction in blood pressure (4% improvement).
A different study in Mexico evaluated the effects of a low-fructose diet (<20 grams/day) vs. a moderate natural fructose diet (50-70g/day) in 131 non-diabetic obese patients examined. 7 After six-weeks, both groups had improvements in several important parameters, including weight, blood pressure, cholesterol, and blood sugar, with the only significant difference between groups being greater weight loss in the moderate-fructose group (4.2kg vs. 2.8kg in the low-fructose group).
Although this finding may relate to differences in fructose, other variables like differences in take of fiber and flavonoids may also contribute. So, other than fructose, what does fruit offer for our health?
Sweeter Than it Tastes: Vitamins, Minerals and Flavonoids
Fruit contains much more than fructose, of course. In addition to water and fiber, a typical apple contains about 14% of the recommended daily value of vitamin C, as well as small amounts of B1, B2, B6, E, and K. Additionally, it contains an array of minerals potassium, magnesium, and calcium-to name a few. ALL fruits have a mixture of these vitamins and minerals, and we could write a thesis on how vitamins and minerals support blood sugar control. Whole fruits, however, have something not present in most multivitamins: flavonoids.
The term "flavonoids" refers to a diverse group of compounds produced by plants for a variety of functions, including providing the bright pigments of fruits and vegetables. Most recent research shows that flavonoids may have tremendous benefit in the humans or animals, including antioxidant, anti-inflammatory, or anticancer activity. Researchers are now exploring how specific flavonoids may have benefit in animal models in diabetes.
Quercetin, a flavonoid present in apples, onions, grapes, leafy greens, and tomatoes, is one of the most widely consumed flavonoids in the human diet. It is typically poorly absorbed, however, and much of it remains inside the digestive tract until excreted. Glucose and fructose on the other hand are usually absorbed from the intestine quickly by a number of sugar transport enzymes the most dominant of which is called "GLUT2". An in vitro (test-tube) study found high levels of quercetin and related compounds may block fructose and glucose absorption by GLUT2.8 Blocking intestinal absorption of glucose and fructose may be one mechanism of how a whole fruit could be less damaging in diabetes than a fructose-sweetened drink!
Other flavonoids are better absorbed, and may also have benefits for diabetes. Fisetin, present in strawberries and onion, has been explored for these purposes. Rat used as models of diabetes were found to have significant improvements in blood sugar, insulin, and HbA1c after 30 days of fisetin treatment, comparable to the effects of the drug gliclazide.9 This study further found fisetin improved the activity of several key enzymes involved in carbohydrate metabolism.
In addition to direct glucose-lowering activity, fisetin may also protect against complications of diabetes. Many of the complications of diabetes are a result of protein glycation the process by which excess blood sugars become attached to proteins and enzymes throughout the body (imagine "glazing" the machinery of your body in crystallized sugar!).One of the sugars most implicated in protein glycation is methylglyoxal (MG), a 3-carbon sugar byproduct of glucose metabolism. MG is removed from the body by the enzyme glyoxalase-1, which requires the antioxidant glutathione as a necessary co-factor. Fisetin has been found to increase levels of glutathione, upregulate glyoxalase-1, and reduce levels of MG and subsequent protein glycation.10 In simpler words: fisetin may help lower blood sugar, and may help block the effects of high blood sugar. Although very promising, these studies are preliminary and only in rats and mice; no definitive clinical research has been performed on fisetin in people.
Summary Recommendations
As naturopathic doctors our bias will always lean toward recommending a natural food based by diet, rich in fruits and vegetables. Upon applying current knowledge and integrating nutrition and endocrinology, it seems logical (and frankly common sense) that drinking a lot of refined fructose-sweetened drinks will cause serious metabolic problems- and this position is now supported by more and more clinical and observational research. We would also expect whole fruit containing hundreds of compounds in addition to fructose would be a healthy option for adults, even those with diabetes. However, as with every component of a healthy diet, moderation remains critical to balance, and all dietary choices must be kept relative to one another. For example, eating a handful of cherries is a lot better than eating an entire bag of cherries, and eating an entire bag of cherries may still be better for you than eating an entire bag of cookies!
Hopefully more clinical research will be performed soon to answer these basic, and common questions: If I have diabetes, am I a better off eating or not eating fruit? And if I eat fruit, how much can I eat safely? Until then, our recommendation is to enjoy 2-3 servings of fresh, whole, ideally organic, fruit per day (rather than juices, purees and processed fruit products). When possible, choose fruits with a lower glycemic index: berries, citrus, apples, and pears.
In health,
Ryan Bradley ND, MPH and Bill Walter, ND
REFERENCES:
1. Teff KL, Elliott SS, Tschop M, et al. Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J Clin Endocrinol Metab. Jun 2004;89(6):2963-2972.
2. Stanhope KL, Schwarz JM, Keim NL, et al. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest. May 2009;119(5):1322-1334.
3. Stanhope KL, Bremer AA, Medici V, et al. Consumption of fructose and high fructose corn syrup increase postprandial triglycerides, LDL-cholesterol, and apolipoprotein-B in young men and women. J Clin Endocrinol Metab. Oct 2011;96(10):E1596-1605.
4. Sargeant LA, Khaw KT, Bingham S, et al. Fruit and vegetable intake and population glycosylated haemoglobin levels: the EPIC-Norfolk Study. Eur J Clin Nutr. May 2001;55(5):342-348.
5. Carter P, Gray LJ, Troughton J, Khunti K, Davies MJ. Fruit and vegetable intake and incidence of type 2 diabetes mellitus: systematic review and meta-analysis. BMJ. 2010;341:c4229.
6. Jenkins DJ, Srichaikul K, Kendall CW, et al. The relation of low glycaemic index fruit consumption to glycaemic control and risk factors for coronary heart disease in type 2 diabetes. Diabetologia. Feb 2011;54(2):271-279.
7. Madero M, Arriaga JC, Jalal D, et al. The effect of two energy-restricted diets, a low-fructose diet versus a moderate natural fructose diet, on weight loss and metabolic syndrome parameters: a randomized controlled trial. Metabolism. Nov 2011;60(11):1551-1559.
8. Kwon O, Eck P, Chen S, et al. Inhibition of the intestinal glucose transporter GLUT2 by flavonoids. FASEB J. Feb 2007;21(2):366-377.
9. Prasath GS, Subramanian SP. Modulatory effects of fisetin, a bioflavonoid, on hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in hepatic and renal tissues in streptozotocin-induced diabetic rats. Eur J Pharmacol. Oct 15 2011;668(3):492-496.
10. Maher P, Dargusch R, Ehren JL, Okada S, Sharma K, Schubert D. Fisetin lowers methylglyoxal dependent protein glycation and limits the complications of diabetes. PLoS One. 2011;6(6):e21226.