Unfortunately, 70% of the United States is now overweight.1 And nearly half of that 70% is obese – a truly scary prospect for the future of our nation’s health.2 But despite this alarming obesity epidemic (technically it is a pandemic, because the entire world is suffering from this problem) there has never been more debate about what exactly is causing the issue.3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 While this article will cover specific transcription factors and antioxidant pathways, the big bullet points for preventing obesity are simple.26 27 28 29 30 31 32 33 34 35
For starters, we are eating too many calories.36 37 38 39 Secondly, we are eating too much sugar and not enough nutrients.40 41 42 43 44 45 46 47 48 49 50 Third, we are not getting enough exercise.51 52 53 And lastly, we are stressed like never before, and sleeping less than ever.54 55 56 57 58 59 In a way, the rest of the debate is just minutia, because until we fix these four problems, we are not going to be able to stop this boat from capsizing.
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.
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 – a 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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