Is Sugar Toxic? Does fructose contribute to obesity and diabetes?

Feed animals enough pure fructose or enough sugar, and their livers convert the fructose into fat — the saturated fatty acid, palmitate, to be precise, that supposedly gives us heart disease when we eat it, by raising LDL cholesterol. The fat accumulates in the liver, and insulin resistance and metabolic syndrome follow.

Michael Pagliassotti, a Colorado State University biochemist who did many of the relevant animal studies in the late 1990s, says these changes can happen in as little as a week if the animals are fed sugar or fructose in huge amounts — 60 or 70 percent of the calories in their diets. They can take several months if the animals are fed something closer to what humans (in America) actually consume — around 20 percent of the calories in their diet. Stop feeding them the sugar, in either case, and the fatty liver promptly goes away, and with it the insulin resistance.

When Tappy fed his human subjects the equivalent of the fructose in 8 to 10 cans of Coke or Pepsi a day — a “pretty high dose,” he says —– their livers would start to become insulin-resistant, and their triglycerides would go up in just a few days. 

Thompson believes that many pre-cancerous cells would never acquire the mutations that turn them into malignant tumors if they weren’t being driven by insulin to take up more and more blood sugar and metabolize it.

To me this suggests that fructose at least plays SOME role in metabolic syndrome

Sucrose and HFCS-55 (high fructose corn syrup) have approximately the same relative sweetness.

Sweetness comparison for selected nutritive sweeteners

Sugars

Sweetness intensity (crystalline)

Relative sweetness (10% syrup)

Absolute sweetness (syrups)

Fructose 180 117 —

Sucrose 100 100 100

HFCS-55 — 99 97

Glucose 74–82 65 —

You’ll note that this contrasts with how fructose crystals are much sweeter.

Fructose and Sucrose content of vegetables

click through for the table

How fructose and HFCS increase uric acid and give you high blood pressure

So this article below introduces the idea of fructose and its effects on Uric acid. It also mentions some things I’ve talked about before about how fructose doesn’t provoke an insulin response. 

Fructose elevates uric acid, which decreases nitric oxide, raises angiotensin, and causes your smooth muscle cells to contract, thereby raising your blood pressure and potentially damaging your kidneys. Increased uric acid also leads to chronic, low-level inflammation, which has far-reaching consequences for your health. For example, chronically inflamed blood vessels lead to heart attacks and strokes; also, a good deal of evidence exists that some cancers are caused by chronic inflammation. 

Fructose does not appropriately stimulate insulin, which in turn does not suppress ghrelin (the “hunger hormone”) and doesn’t stimulate leptin (the “satiety hormone”), which together result in your eating more and developing insulin resistance.

glucose actually accelerates fructose absorption, making the potential health risks from HFCS even more profound.

There are more than 3,500 articles to date showing a strong relationship between uric acid and obesity, heart disease, hypertension, stroke, kidney disease, and other conditions. In fact, a number of studies have confirmed that people with elevated serum uric acid are at risk for high blood pressure, even if they otherwise appear to be perfectly healthy.

Uric acid levels among Americans have risen significantly since the early half of the 20th Century. In the 1920s, average uric acid levels were about 3.5 ml/dl. By 1980, average uric acid levels had climbed into the range of 6.0 to 6.5 ml/dl and are probably much higher now.

How Does Your Body Produce Uric Acid?

It’s a byproduct of cellular breakdown. As cells die off, DNA and RNA degrade into chemicals called purines. Purines are further broken down into uric acid.

Fructose increases uric acid through a complex process that causes cells to burn up their ATP rapidly, leading to “cell shock” and increased cell death. After eating excessive amounts of fructose, cells become starved of energy and enter a state of shock, just as if they have lost their blood supply. Massive cellular die-off leads to increased uric acid levels.

According to Dr. Johnson1, sugar activates its own pathways in your body—those metabolic pathways become “upregulated.” In other words, the more sugar you eat, the more effective your body is in absorbing it; and the more you absorb, the more damage you’ll do.

You become “sensitized” to sugar as time goes by, and more sensitive to its toxic effects as well.

The flip side is, when people are given even a brief sugar holiday, sugar sensitization rapidly decreases and those metabolic pathways become “downregulated.” Research tells us that even two weeks without consuming sugar will cause your body to be less reactive to it.

This video adds a bit. Here are my very rough notes, which may be imperfect.

Fructose is 7 times more likely to brown, and form AGE -advanced glycation end products than glucose

Fructose does not suppress ghrelin (because it does not cause an insulin spike).

If you eat glucose it gets used all over your body. 80% of glucose gets used in the body. 20% gets used in the liver and most gets converted to glycogen. Your liver can store unlimited amounts of glycogen without toxicity.

Some portion of the glucose will get converted into fat/VLDL.  (maybe 0.5% depending)

When you drink alcohol.

80% of ethanol calories hit the liver.

Ethanol generates reactive oxygen species which damage proteins in the liver.

You get a lot of VLDL /fat from ethanol.

100% of fructose gets metabolized by the liver.

Uric acid gets created as a waste product as fructose is metabolized.

Uric acid contributes to gout.

Uric acid blocks the synthesis of Nitric Oxide. Nitric Oxide lowers blood pressure. So the result is that your blood pressure rises.

Another fructose by-product is xylose-5-phosphate, which stimulates pp2a which then activates lipogenesis (new fat making).

With glucose almost none of it ends up as fat. With fructose 30% ends up as fat.

In 6 days of med students drinking lots of fructose, triglyceride levels doubled.

One of the byproducts of fructose metabolism limits the effectiveness of insulin in the liver. via JNC1 IRS1

The higher insulin levels go, the less well the brain recognizes leptin. So the brain gets confused - thinks it’s starving despite high fat stores.

Fiber is the antidote for high sugar levels. Fiber reduces the rate of intestinal carbohydrate absorption. Downside: “In life you’ve got 2 choices - fat or fart.”

Fiber increases the speed of transit of intesinal contents to the ileum which raises PYY and produces a satiety signal.

Inhibits absorption of some free fatty acids in the colon which are metabolized by colonic bacteria to short chain fatty acids which suppress insulin levels.

As pubmed says

Gout is a kind of arthritis that occurs when uric acid builds up in the joints.

Here is a good powerpoint presentation on what happens to fructose in liver cells.

Fructose + ATP => Fructose1P + ADP

ADP=>IMP=>IMP=>Uric acid

As wikipedia explains, fructose is absorbed more rapidly if glucose is present, leading to a more rapid increase in triglyceride levels and the by products of fructose metabolism:

 Studies show the greatest absorption rate occurs when glucose and fructose are administered in equal quantities.[24] When fructose is ingested as part of the disaccharide sucrose, absorption capacity is much higher because fructose exists in a 1:1 ratio with glucose. It appears that the GLUT5 transfer rate may be saturated at low levels, and absorption is increased through joint absorption with glucose. One proposed mechanism for this phenomenon is a glucose-dependent cotransport of fructose. 

This is yet another reason to limit fructose consumption. Please see this post of mine on fructose if you haven’t already.

What sugars are in coconut water?

Research by Kuberski6 identified the sugars contained in coconut water, detecting glucose, sucrose and fructose in the proportion of approximately 50, 35 and 15%, respectively, but their study did not relate whether these proportions remained constant during different months. The current study found that the proportions of these sugars varied depending on the stage of maturation of the coconuts: glucose, from 34 to 45%; sucrose, from 53 to 18% and; fructose, from 12 to 36%.

via paleohacks

Too much fructose leads to weight gain & diabetes. Don't gorge on fruit.

fructose is “isocaloric but not isometabolic.” This means you can have the identical amount of calories from fructose or glucose, fructose and protein, or fructose and fat, but the metabolic effect will be entirely different.

fructose consumption leads to decreased signaling to the central nervous system from two hormones, leptin and insulin, both of which play key roles in hunger and satiety, as well as weight control.

Here’s a linked paper which gives a bit more science

Because fructose does not stimulate insulin secretion from pancreatic ß cells, the consumption of foods and beverages containing fructose produces smaller postprandial insulin excursions than does consumption of glucose-containing carbohydrate. Because leptin production is regulated by insulin responses to meals, fructose consumption also reduces circulating leptin concentrations. The combined effects of lowered circulating leptin and insulin in individuals who consume diets that are high in dietary fructose could therefore increase the likelihood of weight gain and its associated metabolic sequelae. In addition, fructose, compared with glucose, is preferentially metabolized to lipid in the liver. Fructose consumption induces insulin resistance, impaired glucose tolerance, hyperinsulinemia, hypertriacylglycerolemia, and hypertension in animal models.

high-carbohydrate meals stimulate leptin production in humans relative to high-fat meals

Diets high in fructose induce insulin resistance in rodents (87–89) and in dogs (90). For example, Thorburn et al (91) fed rats a diet containing 35% of energy as fructose for 4 wk and found reduced insulin sensitivity associated with impaired hepatic insulin action and whole-body glucose disposal. 

There are numerous studies in which dietary fructose has been shown to induce hyperlipidemia in rodents (104, 107–109). Herman et al (107) reported that rats fed a high-fructose diet had sustained elevations in serum triacylglycerol. Circulating triacylglycerol concentrations rose and remained elevated during the entire time fructose was fed (100 d) and fell promptly when a standard chow diet was instituted. The same investigators also concluded that there was a greater capacity of human liver to metabolize fructose to lipid compared with glucose because high-sucrose diets led to elevated serum triacylglycerol concentrations in humans, whereas the same amount of glucose resulted in lower concentrations of serum triacylglycerol 

Similar to insulin resistance and hyperlipidemia, many published experiments have shown that high-fructose diets induce hypertension in animals, including rodents (125–128) and dogs (90).

To put it in simpler terms…when you eat fructose alone, your blood sugar levels remain elevated. Not only that, but your liver tends to convert the fructose into fat, so the amount of in your blood gets elevated.  Not only that, but you don’t get the same feeling of fullness, so you just tend to eat more. If your there is too much fat in your bloodstream, you eventually get diabetes.

Here is an article that talks about that

a defect in insulin-stimulated glucose transport in skeletal muscle is the primary metabolic abnormality in insulin-resistant type 2 diabetics. Fatty acids appear to cause this defect in glucose transport by inhibiting insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1 associated phosphatidylinositol 3-kinase activity.

Here is a table, listing the amount of fructose present in various foods

Fruit Serving Size Grams of Fructose

Limes 1 medium 0

Lemons 1 medium 0.6

Cranberries 1 cup 0.7

Passion fruit 1 medium 0.9

Prune 1 medium 1.2

Apricot 1 medium 1.3

Guava 2 medium 2.2

Date (Deglet Noor style) 1 medium 2.6

Cantaloupe 1/8 of med. melon 2.8

Raspberries 1 cup 3.0

Clementine 1 medium 3.4

Kiwifruit 1 medium 3.4

Blackberries 1 cup 3.5

Star fruit 1 medium 3.6

Cherries, sweet 10 3.8

Strawberries 1 cup 3.8

Cherries, sour 1 cup 4.0

Pineapple 1 slice

(3.5” x .75”) 4.0

Grapefruit, pink or red 1/2 medium 4.3

Boysenberries 1 cup 4.6

Tangerine/mandarin orange 1 medium 4.8

Nectarine 1 medium 5.4

Peach 1 medium 5.9

Orange (navel) 1 medium 6.1

Papaya 1/2 medium 6.3

Honeydew 1/8 of med. melon 6.7

Banana 1 medium 7.1

Blueberries 1 cup 7.4

Date (Medjool) 1 medium 7.7

Apple (composite) 1 medium 9.5

Persimmon 1 medium 10.6

Watermelon 1/16 med. melon 11.3

Pear 1 medium 11.8

Raisins 1/4 cup 12.3

Grapes, seedless (green or red) 1 cup 12.4

Mango 1/2 medium 16.2

Apricots, dried 1 cup 16.4

Figs, dried 1 cup 23.0

It’s worth noting that this table is somewhat skewed. 1/16 of a water melon is 286 grams, where as a medium orange is less than half that. Who’s to say you won’t eat 1/32 of a watermelon etc.

This site, listing fructose amounts per 100g is also useful.

Agave / Agave nectar - Has a high fructose-to-glucose ratio

Aparagus  - Contains significant amounts of fructans

Apples - 6g fructose per 100g

Artichoke  - Contains significant amounts of fructans

Banana - 4.85g fructose per 100g

Blackberries - 2.4g fructose per 100g

Blueberries - 5.0g fructose per 100g

Cherries - 5.3g fructose per 100g

Currants - 3.5g fructose per 100g

Grapes - 8g fructose per 100g

Honeydew Melon - 2.9g fructose per 100g

Inulin  - Source of fructans; sometimes added to foods such as yoghurt

Kiwi fruit - 4.3g fructose per 100g

Lemon Lime soda/softdrink - 5.8g fructose per 100g

Mango - 5.5g fructose per 100g

Onion  - Contains significant amounts of fructans

Orange juice - 2.7g fructose per 100g

Oranges - 2.2g fructose per 100g

Pears - 6.2g fructose per 100g

Pineapple - 7.2g fructose per 100g

Plum - 3.0g fructose per 100g

Raisins - 30g fructose per 100g

Raspberries - 2.3g fructose per 100g

Strawberries - 2.4g fructose per 100g

Tangerines - 2.4g fructose per 100g

Watermelon - 3.35g fructose per 100g

Note that agave syrup is blamed because of its high fructose to glucose ratio, which is ironic because it’s claimed as a healthy alternative, and arguably healthier choices could be found.

Fructans is mentioned above

A fructan is a polymer of fructose molecules. They occur in foods such as agave, artichokes, asparagus, green beans, leeks, onions (including spring onions), yacon, jícama, and wheat.

Some people have trouble digesting fructose, and for those with intestinal difficulties, it is recommended that they avoid fructans.

Here’s some more about fructose malabsorption syndrome

Even in healthy persons, however, only about 25-50g of fructose per sitting can be properly absorbed. Persons with fructose malabsorption may absorb less than 25g per sitting.

This is yet another reason not to have too much fructose at once.

The article also has this table, which is interesting

Food Fructose (grams / 100 grams) Glucose (grams / 100 grams)

Sucrose (for reference) 50 50

Apples 5.9 2.4

Pears 6.2 2.8

Fruit juice e.g. Apples, Pears 5 to 7 2 to 3

Watermelon 3.4 1.6

Raisins 29.8 27.8

Honey 40.9 35.7

High fructose corn syrup 42 to 55 45 to 58

It’s not that the ratio is particularly worse in high fructose corn syrup - it’s that the quantity of sugar consumed is typically much larger than that that would be consumed when eating fruit.

If you eat small enough portions, less sugar enters your system and therefore less insulin is needed to control a blood sugar rise, and therefore less damage is done.

Let’s look at how many calories are actually burned from eating and sitting around.

A person who weighs 150 lbs. burns about 64 calories per hour while sleeping; someone who weighs 200 lbs. burns approximately 86 calories per hour while sleeping, according to Fit Watch.

Eating burns about 140 calories per hour; watching TV or reading burns around 75; and doing homework, or anything that requires heavy concentration or brain activity, burns around 110.

Let’s be generous and assume 100 calories per hour are burned. That’s 25 grams of carbohydrate. So if you were taking small nibbles or a few pieces of fruit here and there, that’s about 1.5 pieces oranges per hour, about 200 grams of orange. The calculations are similar for standard serving sizes of other fruits. Assuming there is some glucose in the fruit, for which there will be an insulin response, the amount you can eat rises somewhat.

How to make sense of the data on fructose? As I see it, each food has a functional purpose. Protein sources like steak are effective at building muscles. On the other hand if early man came upon an orchard full of fruit in the early summer, he might well gorge and it might be an evolutionary advantage for him to get fatter to take advantage of all the fruit in front of him. Now, as fruit is available in huge quantities everywhere, the possibility of getting fat from gorging on fruit is real. 

What’s the upshot? If you want to lose weight and attain better health, pay attention to the amount of fructose you consume.

If you want to improve your insulin response, consider combining fruit with protein, as protein causes insulin levels to rise, without affecting your blood sugar.

Pure protein — protein sources that do not contain any carbohydrates — do not affect your blood glucose levels

Insulin does many things at once. It causes amino acids to be taken in to cells and causes blood sugar to be lowered via a number of different mechanisms.

So, as I see it the takeaways are:

1) Avoid sugary drinks and any drinks with high fructose corn syrups (includes most sodas).

2) If you are eating a fruit that contains fructose, don’t eat too much, so as not to raise the blood sugar too high, as insulin won’t help enough. Don’t gorge on fruit. 

3) Consider eating fruit with a meal in which you have some protein.

4) Be careful with respect to the total amount of fructose you consume in any given day. The less fructose you consume the better it is for your blood sugar & the more it prevents obesity, but fruit is good for other reasons, so try to find the compromise that’s right for you.

Why is high fructose corn syrup worse for me than cane sugar?

HFCS has been shown in certain studies to cause more harm than cane sugar.  ”Rats with access to high-fructose corn syrup gained significantly more weight than those with access to table sugar, even when their overall caloric intake was the same. “ [1]

“In addition to causing significant weight gain in lab animals, long-term consumption of high-fructose corn syrup also led to abnormal increases in body fat, especially in the abdomen, and a rise in circulating blood fats called triglycerides. ” [1]

I found this convincing, because it compares the effect of sucrose and HFCS specifically; it doesn’t just study the effect of HFCS in isolation: 

“The first study showed that male rats given water sweetened with high-fructose corn syrup in addition to a standard diet of rat chow gained much more weight than male rats that received water sweetened with table sugar, or sucrose, in conjunction with the standard diet. The concentration of sugar in the sucrose solution was the same as is found in some commercial soft drinks, while the high-fructose corn syrup solution was half as concentrated as most sodas.” [1] [2]


At the same time, there is a lot of literature that claims that HFCS isn’t necessarily more harmful than cane sugar. 

“There is, however, no direct evidence for more serious metabolic consequences of high fructose corn syrup versus sucrose consumption.” [3]

“The progressive replacement of sucrose by HFCS is however unlikely to be directly involved in the epidemy of metabolic disease, because HFCS appears to have basically the same metabolic effects as sucrose. ” 
[4] 

More studies will have to be conducted to conclusively state if HFCS is indeed worse than sucrose. Neither are good for you, of course, in excessive amounts. I suppose that meanwhile, to be on the safe side, you should reduce the intake of both. 

http://www.princeton.edu/main/news/archive/S26/91/22K07/

http://www.sciencedirect.com/science/article/pii/S0091305710000614

http://physrev.physiology.org/content/90/1/23.short

http://www.sciencedirect.com/science/article/pii/S0899900710000730