Fructose: Something that might actually be bad?
I was initially writing this article as a ‘HFCS clarification’ article, but it became so absurd that I had to defend something where it’s main assailants are just people who tout naturalistic fallacy, a hatred for corn, and a single study done by Princeton behavioral psychologists which has never been replicated (kinda bad study too, contradictory results in and of itself and even more so when compared to the rest of the literature).
Then in researching fructose itself, I became intrigued. It is an intestinal angel and a hepatic devil. Dose seems to be a huge concern, and there seems to be a lot of power in manipulating one’s fructose intake. It may be able to drastically increase physical performance and results, it might kill your liver. Despite all this, it is easily accessibly in society and people consume it daily in all the wrong scenarios.
A compound is rarely inherently good or bad, just the manner and dose it is ingested. However, society makes fructose just seem like pure evil by the manner in which many people consume it. Out of all the individuals reasons why people think society has magically gotten fatter, fructose is one of the only ones which can actually be at fault (to a degree).
This article is just a basic outline of how fructose acts in the body, viewing it from a health perspective (mostly bad) and from an exercise perspective (mostly good), then trying to balance the equation at the end.
Warning: Sciency; might want to open Wikitionary
Most of the implications from fructose on health are derived from one initial variation from glucose. Fructose and Glucose are both phosphorylated by different enzymes, and these enzymes differ in potency, speed, and regulation.
Both glucose and fructose are phosphorylated (addition of a phosphorus) in the liver, turning them into glucose-1-phosphate and fructose-1-phosphate respectively. The conversion of glucose to G1P is highly regulated by the enzyme hexokinase and is fairly unremarkable. The conversion of fructose to F1P via fructokinase, however, is unregulated and may be undergone very rapidly.
Fructose being converted into F1P requires a phosphate, and the phosphate being given to fructose is coming from ATP. It seems that after a fructose load is ingested the liver’s ATP levels can decrease dramatically concomitantly with a drastic rise in F1P levels, leading to a favorable environment for fat synthesis (from excess F1P) and other metabolic abnormalities. This is mainly due to ATP donating phosphate at a rate which exceeds the ability of ATP to replenish itself (due to the unregulated F1P conversation rate). The high levels of AMP/ADP in the liver act as signaling compounds which cause a variety of downstream effects. Namely:
(For clarification, once ATP is ‘used’ it turns into AMP; then awaits double phosphorylation to turn back into ATP, ADP is AMP + a single phosphate)
The increased levels of F1P, if not metabolized quickly enough, can also be degraded into Acetyl-CoA and Glycerol-3-phosphate, and then into triacylglycerides (fats), fructose can also act on genetic transcription that mediates this process. These will then be either stored in the liver (which leads to non-alcoholic fatty liver disease in excess and over time) or transported to other places in the body such as adipose tissue, of which they will require vLDL to be synthesized for transport. Long term ingestion can create enzymatic adaptation which makes the body better at this conversion process.
Uric acid is produced vicariously through the decreased ATP (or more so the increased AMP). Some of the AMP is degraded to a metabolite called Inosine Monophospate (IMP), which then turns to Uric acid and is sent out into systemic circulation.
Via uric acid production, fructose seems to be able to increase blood pressure. This effect occurs in everybody regardless of health status, as a 60g bolus has been shown to do this in young and otherwise healthy adults. 200g a day for 2 weeks raises all markers of metabolic syndrome, and seems to be able to do this despite a caloric deficit. (I say ‘seems’ as uric acid seems highly correlated with the increases in blood pressure, but has not yet been found to be causative; increases in uric acid via consumption of fructose will be accompanied by increases in blood pressure though, suggested another related variable that causes both).
Fruit does not seem to share this same relation, possibly since Vitamin C is inversely correlated with uric acid levels (and possibly that other lurking variable). The fiber and cellulose content may also slow the rate of uptake into the liver from the gut, which would reduce the significance of the drop in hepatic ATP levels.
In sum, fructose (via skipping the phosphofructokinase regulatory step) seems to cause a lot of shit in the liver from reduced ATP levels and being itself overproduced, which cause a signaling and substrate environment conducive to fat and cholesterol overproduction and causes an increase in blood pressure via degradation of AMP. All these effects seem to be dose dependent, and multiplied by time (based on enzymatic adaptation).
Doesn’t look good at the moment.
The above sounds all fancy bad-bad, but it’s not the end of the world; fructose does have benefits (like everything does if used correctly).
The benefits that fructose may confer during exercise are (much info from this review article here):
- It increases total carbohydrate oxidation in the body, possibly by having two sugar transports active in the gut (GLUT5 and GLUT2 for fructose, versus GLUT4 for glucose) instead of just one transport.
- Outside of that, it increases glucose uptake from the gut to the liver by creating a more conducive environment to absorption
- It can spare glucose to systemic circulation by itself being used in the liver; which would increase the amount of substrate for use by the muscles
In regards to carbohydrate oxidation, the more carbohydrate that is oxidized during exercise should lead directly to an increase in performance (from increased glycolysis rates). It seems that combining fructose and glucose in one solution results in significantly higher total oxidation rates when compared to an isocaloric glucose only solution. Other studies found similar results with differing fructose:glucose ratios.
Possible reasoning for this, as outlined in said article (and the next), is an apparent ‘limit cap’ on rates of glucose oxidation. Approximately 1g/min (60g glucose over an hour) seems to be the upper limit of glucose oxidation, possibly due to the glucose transport in the gut (SGLT-1) being maxed out at this rate (assuming no adaptation over time, which will happen but is hard to make empirical at the moment).
Building on this, it makes sense that adding fructose to a shake will increase total carbohydrate expenditure, as it does not use SGLT-1, but uses it’s own GLUT5 transport. Two maxed out pathways are better than one.
Dose for exercise
Given that the lack of literature on Glu + Fru during exercise is minimal, these suggestions are just taken from one of the previous studies with my thoughts added to them.
Firstly, I will be assuming that all of the ingested follow a Cheat Mode / Anaconda Protocol timing style with a carbohydrate ‘drip’ throughout a resistance training workout.
Given the supposed saturation of SGLT-1 at 1g/min, I see no reason to go over this. Glucose can only exert metabolic effects if it is in the blood, and consuming extra means sugary poop. So take the time you expect to exercise in minutes and use that as the upper limit for glucose intake (attempt to hit this upper limit if trying to build muscle or increase performance, less so if you want to spare some buffer room for a post-workout feast).
Fructose uptake in the gut seems to be maxed out at 0.38g/min. For simplicity you can just third the time you are working out (working out for an hour? 60min/3 = 20g fructose).
Adding those together, a basic and simple dose for an hour of exercise to bring you as close to the uptake max as possible would be 40g of a glucose-only product combined with 40g of sucrose (50/50 blend of glucose/fructose), which then adds up to 60g glucose and 20g fructose. Table sugar is fine if dissolved.
Despite fructose having a tendency to cause GI upset in high doses, 20g/hour does not seem to be a concern as one of the above studies noted no differences in GI symptoms as noted via questionnaire with 72g over 2 hours, well above the dose established here.
Tl;Dr. 40g of Glucose and 40g Sucrose, no need for more in a one hour time period
Bridging the Gap: What is the best for Health and Performance?
The best for health and performance would, theoretically, be a method in which we get the benefits of fructose and total carbohydrate oxidation during exercise but minimize overall consumption to avoid the other effects. Alternatively, if fructose is consumed we can make the environment of consumption as similar to fruit intake as possible rather than an environment similar to candy intake.
For exercise. 20g seems to be the max one can absorb in an hour (given no adaptations in gut transporters, which may be rife in our overfed society). This seems like a good starting point as many studies noting statistically significant changes in blood pressure and de novo lipogenesis were dosed at around 50g or above.
For consuming fructose outside of workouts, it may be advisable to treat fruit sources and non-fruit sources as different entities. Fruit has a low fructose load and is already protected by an environment of relatively slow intestinal uptake (via fiber content, cellulose) and with some antioxidants which may protect against the ATP drop or F1P overproduction.
For non-fruit fructose sources, the choices are either to avoid them entirely or to attempt to mimic the intestinal environment of fruit. Mimicking the intestinal environment would mean consuming antioxidants and fiber alongside the fructose source, either with a vegetable surplus or via supplementation. As this applies to Cheat Mode, it would mean that you can make any treats after a workout less likely to be adverse by consuming some fiber (psyllium husk, Metamucil) in a protein shake (which also slows down intestinal absorption of nutrients), or by sneaking in a buttload of vegetables. Fiber has a ton of other benefits (mostly the soluble) as I talked about before, so adding it in at this time could benefit you in more ways than just one.