It's True: Fructose Makes You Fat - In Fact, It Even Makes You Make Fat! Study Shows, HFCS Beverages Kickstart Endogenous Palmitic Acid Production, Sugary Ones Don't

In the fashion business, "light or not light" (light=diet as in "Diet Coke" US vs Coke Light Germany) is not really a question to ask.

Actually I have given up writing about fructose. It appears as if everyone was so bamboozled by the obvious bullsh*t you can read all over the Internet that it's useless to tell them that you are not going to get obese from eating one, two or even ten apples a day! In view of the fact that today's SuppVersity article is about the negative effects of fructose, I am yet quite confident that more than the few enlightened SuppVersity regulars will read it.

I mean, who would not want to know whether moderate amounts of various sugars (including fructose, sucrose, and glucose) in sugar-sweetened beverages (SSBs) will have differential effects on fatty acid synthesis and degradation in healthy young men?

Now that I'd probably even have Dr. Lustig attention, let's first take a look at what exactly Michel Hochuli and his colleagues from the University Hospital Zurich did to answer this question.

The study we are dealing with is a randomized controlled crossover trial with a total of four different dietary interventions. During each of these, subjects were supplied with SSBs containing various sugars in different concentrations in random order during 3 weeks:

• 40 g fructose per day [medium fructose (MF)]
• 80 g fructose per day [high fructose (HF)]
• 80 g glucose per day [high glucose (HG)]
• 80 g sucrose per day [high sucrose (HS)]

In the second part of the study, in addition, hyperinsulinemic euglycemic clamps were performed with nine participants after each intervention to assess glucose metabolism and the dynamics of acylcarnitines. What adds to the significance of the data is the fact that the subjects were 34 healthy, normal-weight men - no rats, or type II diabetics and thus a study population of which you can expect that the things that happen to them, after the ingestion of the differently sweetened SSBs could happen to you, as well.

Figure 1: Relative levels of palmitate to linoleic acid ratio (left) and palmitoylcarnitine (right) after the ingestion of the four test-SSBs; values expressed rel. to baseline (Hochuli. 2014)

Apropos "things that can happen, when you consume too much SSBs", as you can see in Figure 1 the things that did happen were (a) a significant increase in fatty acid synthesis as it can be seen from the relative abundance of palmitate (16:0) and the molar fatty acid ratio of palmitate to linoleic acid (16:0 to 18:2; Figure 1, left) in the high fructose (HF) and medium fructose groups (MF).

These changes went hand in hand with increases in fasting palmitoylcarnitine (=palmitic acid that's "carried" by carnitine to the mitochondria for oxidation) that signifies impaired or at least insufficient fatty acid oxidation  and, last but not least, a decreased inhibition of lipolysis by insulin in the clamp condition.

Now, this is what happens next...

In a lab setting and after the consumption of an isolated test beverage this obviously isn't much of a problem, but if you think of a real-life SSB-consumption scenario, you will have to agree that people tend to use their fructose sweetened beverage to wash down a greasy piece of pizza ... and, believe it or not, this is where the whole fructose problem begins.
It's the combination of sugar (➲ insulin), fructose (➲ palmitic acid production + blockade of the inhibitory effect of insulin on the former) and fat from your delicious piece of pro-obesogenic Americanized and super-sized Italian cuisine (➲ influx of free fatty acids via the portal vein) that will elevate their blood lipids to a degree which impairs their glucose metabolism (Roden. 1996). This, in turn will keep the insulin up, the palmitic acid production running (remember, fructose reduced the ability of insulin to blunt this process) and the free fatty acids (in this case palmitic acid) accumulating.

Now even that wouldn't be a problem. People could, after all, burn the fat off by fasting. Unfortunately, the combination of insulin resistance and impaired fatty acid oxidation leaves them starving in abundance. What nutrients are their cells supposed to use? Glucose? Doesn't work, because of the insulin resistance. Fats? Can't be oxidized because of the elevated insulin levels. The consequence? Well, if we are talking about the average overweight inhabitant of the Western obesity belt, he will find himself sneaking through the kitchen, opening the fridge and annihilating a family packet of ice-cream only 30 minutes after his 1,500kcal+ "all American" version of the Italian way of making use of leftovers... eventually al this takes us - you won't believe it - back to the simple but undeniable truth that eating processed foods promotes overeating and overeating promotes obesity, hyperlipidemia and diabetes. My gosh! Who would have thought that?
References: 

• Hochuli, et al. "Sugar-Sweetened Beverages With Moderate Amounts of Fructose, but Not Sucrose, Induce Fatty Acid Synthesis in Healthy Young Men: A Randomized Crossover Study."  J Clin Endocrinol Metab (2014). Early Release.
• Priore, Paola, et al. "Extra virgin olive oil phenols down-regulate lipid synthesis in primary-cultured rat- hepatocytes." The Journal of Nutritional Biochemistry (2014). Accepted Manuscript.
• Roden, Michael, et al. "Mechanism of free fatty acid-induced insulin resistance in humans." Journal of Clinical Investigation 97.12 (1996): 2859.