Obesity: The Pandemic Where You Can't Afford to Capsize the Boat

But if we are to delve into the details of obesity, there are two dichotomous factors, which are at play. As I mentioned, too much sugar is a cornerstone of our nation’s various health problems. The fructose transporter GLUT5 plays a specific role in this problem, since we are taking in far too much fructose in our collective diet.^{60 61 62 63 64} By contrast, if we were to eat more vegetables and other healthful foods, we would see better results via the Nrf2 pathway.^{65 66 67 68 69 70} Most of us are aware that free radicals are categorized as ‘bad’ and antioxidants as ‘good’.⁷¹ But the details behind these scientific terms remain elusive, for most of the population.

Evolution of the consumption of high-fructose corn syrup (HFCS) and sucrose in the United States between 1970 and present. HFCS has increased rapidly to replace 50% of the sucrose consumption. Over this period, not only total sugar consumption but also total calorie intake and total fat intake have increased significantly. (USDA)]

Fructose metabolism in liver cells. Fructose metabolism (grey arrows) differs from glucose (black arrows) due to 1) a nearly complete hepatic extraction and 2) different enzyme and reactions for its initial metabolic steps. Fructose taken up by the liver can be oxidized to CO2 and then converted into lactate and glucose; glucose and lactate are subsequently either released into the circulation for extrahepatic metabolism or converted into hepatic glycogen or fat. The massive uptake and phosphorylation of fructose in the liver can lead to a large degradation of ATP to AMP and uric acid.⁶⁰

Summary of the potential mechanisms for fructose-induced insulin resistance.⁶⁰

The research on fructose has been steamrolling the scientific community since the viral popularity of pediatric endocrinologist Robert Lustig’s lecture, a few years ago.^{72 73 74 75} Not surprisingly, the food and beverage industry is trying like mad to stop any bad publicity from arising from the scientific community, around their sugary cash cow.⁷⁶ But the actual, unbiased data has been very damning.^{77 78 79 80} Take the following chart, which shows that fructose in beverages, which do not list it on the label, often contain quantities of fructose that surpass the amount of the substance in beverages which do list it on the label.

In an evolutionary sense, this level of fructose consumption is out of control and unprecedented.^{81 82 83} We’ve known for thousands of years, humans consumed about 20g of fructose each day.^{84 85} Their intake came from fruit and honey,⁸⁶ vastly different than more concentrated sources of fructose, like soda. For one thing – there is no fiber in soda, which might slow down hepatic absorption of fructose. Oh, and for those curious, we are now consuming about 80g of fructose per day, on average.^{87 88}

But why is fructose so harmful, and how does the GLUT5 transporter factor into this issue? GLUT5 was successfully cloned around 20 years ago and was initially described as a glucose transporter, until it became clear that it was specifically related to fructose.⁸⁹ The brain and kidneys have both shown levels of GLUT5 mRNA and/or protein.⁹⁰ This (indirectly) means that by eating too much fructose, your brain processes might be impaired.^{91 92 93} Since we now know that high levels of HA1c correlate with dementia, this shouldn’t be shocking news.⁹⁴

Your small intestine has the greatest amount of GLUT5, and it also controls the availability of fructose to other areas.⁹⁵ Interestingly, intestinal GLUT5 mRNA levels and fructose transport rates are very low until fructose is introduced, or after a few weeks of development (this appears to be genomic).^{96 97 98 99} The problems start to arise when too much fructose is introduced (via processed foods, usually) too early, creating a baseline of consumption, which seems to need to be satisfied.^{100 101 102 103} Though the science is still out, this ‘created need’ may force children to overeat, and as a result, become overweight and/or obese.

The GLUT5 transporter has been linked to hypertension, and also to diabetes.^{104 105} Since the United States spends over $240 billion on diabetes annually, scientific research into the area of GLUT5 should be pushed to the forefront, with the hope being that by better understanding the transport and processing of fructose, we can help improve the rates of disease - if not prevent them entirely.¹⁰⁶

For example, diabetes profoundly affects GLUT5 expression in the small intestine.¹⁰⁷ By down-regulating GLUT5 protein levels in those with high blood sugar, we may have a mechanism to help diabetics. Of course, there are many potential areas of research, which could be interesting for the GLUT5 transporter. But for the brevity of this article, I will stop here. I invite those further interested to research the GLUT5 transporter, via easily using a search engine to locate articles on PubMed relating to the topic.

One of the many issues with fructose is that it helps to cause non-enzymatic glycation – in layman’s terms; fructose helps to age your liver.¹⁰⁸ This shouldn’t be surprising. Remember – increased dietary intake of sugar was linked to dementia – premature aging/degradation of brain tissue usually due to excessive buildup of the beta amyloid protein.¹⁰⁹

By contrast, activation of the Nrf2 pathway may help to stop aging – not just in your liver, but also throughout the body.¹¹⁰ The Nrf2 pathway helps in regulating over 500 cytoprotective genes, which give your cells multiple layers of protection.^{111 112} Interestingly, research has found that dietary flavonoids help to activate this pathway, and thus, your diet can truly determine whether you age quickly or slowly.¹¹³ It really is this simple. Sort of.

You see, in science, one must resist the urge to oversimplify, and in this case we must remember to not forget all the other stressors to our cells. This means sleep quantity and quality, exercise, stress from work, genetics, epigenetics, pollution – it is truly a never ending list. However, we very much have control over what we put in our mouths.

The Nrf2 pathway has been recently found to react to apigenin and luteolin (dietary phytochemical flavones) in a favorable way.¹¹⁴ The antioxidant pathway is activated upon ingestion of apigenin and luteolin, and the flavones may be responsible for vital anti-inflammatory effects.

In fact, activation of the Nrf2 pathway is being studied fairly extensively, in regards to cancer prevention and treatment.¹¹⁵ Since dietary activation is very cheap (especially when compared to pharmaceutical drugs) this research could pave the way for widespread effective change in our world’s health. Mandatory spinach and kale consumption might be a potential guideline - if one was to hypothesize about potential ways this research could be implemented on a widespread basis.

So, if your diet is making you fat, old and sick, you now have some great motivation to affect change. What can be more powerful than that? By loading up on neuro-protective vegetables and healthy fats, as well as quality proteins (which contain essential amino acids) you will be helping to fight back against cellular aging, obesity and illness.

And good news – The Paleo Diet – by its very nature – eliminates all the bad choices for you, and emphasizes all the best foods. The work has already been done. It couldn’t get any easier. You have a path towards obesity, dementia and medication. You also have a path towards health, wellness and vitality. The choice is yours – so choose wisely.

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