Tag Archives: Insulin Resistance


Potassium Rich Vegetables


The question of how much salt we should eat has become one of the biggest debates in the Paleo communityand it’s a debate that shouldn’t even exist. Some in the community have started to argue that not only is the standard U.S. recommendation to eat less than 2,300mg of sodium per day wrong, but that we should be eating double to triple that amount 

They also argue that as long as it’s sea salt and not table salt, it’s healthy. The problem with that notion is that most of the negative health effects of too much salthigh blood pressure, cardiovascular disease, insulin resistance, and autoimmune diseasehave to do with the same culprit: simple sodium chloride. And sodium chloride is the same whether it comes in the form of coarse pink colored crystals or refined white table salt.  

Ultimately, most of the arguments supporting more salt in our diet are based on unproven theories and research that has been shown to have serious methodological flaws 

A few years ago, we addressed this question of a high-salt diet and the many negative effects it can have on our healthSince this is such an important question, with such a significant impact on our health, that it’s worth revisiting now. So, in this series, we dive further into the question of how much salt humans should consumeMore importantly, in this series we address the other side of the equationpotassium.  

Perhaps one of the most important, and overlooked, aspects of a healthy diet is the sodium:potassium ratio. Our hunter-gatherer ancestors typically ate a ratio between 1:5 and 1:10. The western diet is closer to 1:1 or even 2:1 sodium to potassium. The Paleo Diet® mimics this ancestral ratio. In our series, Mark J. Smith, Ph.D., explains this ratio and why being closer to our hunter-gatherer ancestors is so important. Dr. Marc Bubbs takes it a step further, addressing several recent studies which show that increasing potassium in our diet can mitigate much of thnegative impact of high sodium intake 

In our third article, Trevor Connor, M.S., addresses one of the arguments made to support a high salt dietthe belief that a low-sodium diet causes insulin resistance. Despite that popular claim, most current research shows the exact opposite. 

Finally, if you are convinced that a sodium:potassium ratio closer to our ancestors is important for your health, then you may be wondering how to get more potassium in your diet. It’s simple: eat more fruits and vegetables. In this series we include a potassium-power house of a salad recipe to get you started.

The Sodium/Potassium ratio and Its Importance in Human Health

By Mark J. Smith, PhD

Salt vs Potassium Foods


When Dr. Loren Cordain first introduced the concept of Paleolithic nutrition, the scientific research illustrated the importance of three critical nutrient ratios: omega-6 to omega-3 fatty acids, calcium to magnesium, and sodium to potassium (Na+/K+). The evidence suggested these three ratios were quite different in a Paleolithic diet when compared to a typical Western diet. Furthermore, the ratios found in a Paleolithic diet were far more beneficial to human health. Smith explains perhaps the most important of these three ratios.


The Effects of Salt Substitute on Community-Wide Blood Pressure and Hypertension

By Dr. Marc Bubbs ND, MSc, CISSN, CSCS


High blood pressure, or hypertension as it’s referred to in medical circles, is the primary or contributing cause to over 400,000 deaths in the U.S. annually and a high-salt diet is a major contributing factor to hypertension. The problem is that in many parts of the country, getting Americans to reduce the salt in their diet is extraordinarily difficult. In this article, Bubbs addresses several recent studies showing that there is an alternative—an increase in the amount of potassium we eat.


Does a Low-Salt Diet Cause Insulin Resistance?

By Trevor Connor, M.S. 

Low-Salt Diet Cause Insulin Resistance


One of the arguments used by members of the Paleo community who support a high-salt diet is that a low-sodium diet causes insulin resistance, which can lead to diabetes. Connor addresses this argument and why the limited research backing it has serious methodological flaws. Once the well conducted studies are identified, the science tells a very different story: a highsalt diet causes insulin resistance. And potassium in the diet can reduce the impact.


Recipe: Blueberry and Roasted Beet Kale Salad 

By Lorrie CordainPaleo Recipe Blueberry and Roasted Beet Kale Salad horizontal

What’s the easiest way to improve the sodium:potassium ratio in your diet? Reduce processed foods high in salt and eat a lot more vegetables and fruit. This recipe, straight out of the Real Paleo Diet Cookbook, is packed with a whole lot of both. Plus, it’s quick and easy to prepare. 


Low-Salt Diet Cause Insulin Resistance


[Part Three in Our Series on the Importance of Sodium and Potassium In Our Diet]

Of all the recent developments in the Paleo nutrition world, perhaps the biggest, and most misguided, is the belief that a healthy diet includes copious quantities of salt. Some voices within the Paleosphere not only suggest that the current U.S. dietary recommendation (RDA) to consume less than 2,300 milligrams (mg) of sodium per day is wrong, but in fact, we should be eating as much as three times that recommendation.

In his blog, one popular writer stated, “I feel the data supports an intake between 3,000 and 7,000 milligrams of sodium [per day].” That data is a combination of theories claiming our Paleolithic ancestors consumed high quantities of salt and a few recent studies indicating that a low-salt diet may contribute to cardiovascular disease (CVD) and insulin resistance.

None of that data holds up under scientific scrutiny.

Recently, Dr. Loren Cordain performed an in-depth analysis of the sodium content of all natural foods and showed that it would have been very difficult, if not impossible, for our hunter-gatherer ancestors to have consumed even the RDA of 2,300mg/day, let alone the 7,000mg recommended by some Paleo bloggers. The ethnographic data indicates that consumption was closer to 1,000mg/day in hunter-gatherer societies[1]

 Despite the large body of research suggesting there were low salt levels in historical dietssome still look for ways to claim our Paleolithic ancestors ate in excess of 3,000 mg/day. Two popular theories have developed out of reverse engineering approach to the science, to back into a place where the science confirms what we want to believe. One suggests that hunter-gatherers got that sodium from animal blood. The other is that they followed wild animals to salt licks. While both sound reasonable at firstthey deserve a closer look to see if they hold up under scientific weight.

 An analysis of wild moose blood (a decent analogue to wild animal blood) found that 100 milliliters (ml) of blood contained 63mg of sodium. So, to get 1,000mg of sodium, you would have to drink 1.59 liters. Or, to put it in daily terms, to consume the modern RDA of sodium, you’d have to drink a gallon of blood every dayNow imagine how much blood would be required for every person in a village to get 7,000mg per day. It’s enough to make a vampire jealous.

 Likewise, while the salt lick theory seems reasonable, remember that the Paleolithic era lasted over one million years. Imagine what it would take for every humanoid ancestor to get 3,000 to 7,000mg of sodium per day from salt licks for a million years. This raises the question: Just how many salt licks were there on Earth? More importantly, if they were that pervasive, why isn’t there a single mention of them in any studies of ancient villages or cultures?

 Occam’s Razor states that the simplest answer is usually the correct oneAnd, in this case, the simple answer is clear: The large body of research shows that hunter-gatherer societies consumed around 1,000mg of sodium per day.


The New Argument: A Diet Low in Salt is Bad for Us

Other voices in the Paleosphere recommend a high-salt diet based on their claim that a lowsalt diet is bad for our health. This argument was given credence by a series of studies in the early 2010s that showed a J-shaped curve relationship between salt and mortality. This J-shaped relationship indicated that people who consumed large amounts of salt had higher rates of mortality, but so did people who consumed low quantities of salt[2-7]

We wrote a thorough analysis of these studies a few years agoand our points are well summarized in a 2013 meta-analysis led by Graham McGregor and colleagues. The team concluded “these two papers have many methodological flaws, such as measurement error in assessing daily salt intake, confounding factors not controlled for, and reverse causality (that is, the low salt intake is the result rather than the cause of participants’ illness.) [8]

While the J-shaped curve theory of salt consumption hasn’t been holding up in recent research, many proponents of high-salt diets are now arguing that a low-salt diet leads to insulin resistance. Several recent studies, in both rats and humans, have shown that when salt is heavily reduced in the diet, it leads to a reduction in body water which then stimulates the renin-angiotensin-aldosterone system (RAAS). That’s a mouthful, but what’s important is that an activated RAAS inhibits insulin and leads to insulin resistance. [9-14]

Interestingly, howeverone of those studies, published in 2014, lookeat RAAS specifically and concluded that it was “probably not a mediator of increased insulin resistance on a low-salt diet.” [9]


The Actual Data: A Low-Salt Diet May Improve Insulin Sensitivity… 

Two meta-analyses written by Niels Graudal and colleagues summarized the existing research on a low-salt diet and insulin resistance and concluded there was a relationship which gave credence to the theory. [15, 16] However, McGregor and colleagues also addressed these conclusions in their 2013 paper[8]

The meta-analysis, however, was flawed from a public health perspective, as they included a large number of short term trials with a large change in salt intakefor example, from 20g/day to less than 1g/day for only four to five daysand such metabolic studies are irrelevant to the current public health recommendations for a modest reduction in salt intake for a long period of time.

A 2016 meta-analysis published in Clinical Nutrition Research addressed the concerns of extreme sodium reduction and short study lengths.[11] The authors divided 25 studies on low-sodium diets and insulin resistance into short-term vs. long-term studies and extreme salt restriction vs. moderate reductions. 

The results are shown in Table 2, copied from the meta-analysis, below:

Low-sodium diets and insulin resistance

Taken from: Oh, H., et al., Low Salt Diet and Insulin Resistance. Clin Nutr Res, 2016. 5(1): p. 1-6.

It is important to note that for the purposes of the analysis, the authors defined “moderate reduction” as 390 to 780mg of sodium per dayin line with the low end of what has been seen in hunter-gatherers diets. Studies with extreme salt-restriction limited consumption to less than 390mg/daybelow the recommended minimum intake. Even the 2014 study looking at RAAS activation on a low-salt diet admitted in their methodology: “10 mmol/day sodium is at the extreme lower end of the physiological range of sodium intake and not practical for long term use.”

In Table 2, studies that concluded a lowsalt diet contributes to insulin resistance were all in the short term column and almost all were in the extreme sodium restriction columnAs the authors point out, the human body will react to any extreme change in the short run. Short-term insulin resistance might simply be a temporary result of a sympathetic stress response and not something that would continue in the long term. 

To further make this point, all the studies that used moderate sodium restriction or were carried out over a long term had either no impact on insulin resistance or, in three cases, improved insulin resistance.


A High-Salt Diet May Make Insulin Sensitivity Worse 

A 2018 study in the journal PNAS addressed the question of salt and insulin resistanceHowever, this study was exploring ways in which a high-saltnot a low-saltdiet might cause insulin sensitivity. The study stated that “in contrast to short-term studies, long-term intake of a high-salt diet is associated with increased frequencies of obesity, insulin resistance, nonalcoholic fatty liver disease, and metabolic syndrome.” [17] 

Without diving deep into the mechanism, the authors of the study found that feeding mice a one percent salt solution for 30 weeks increased their natural production of fructose. Fructose is associated with insulin resistance, diabetes, and obesity. 

Another 2018 study written by Zhaofei Wan et. al. looked at how a high-salt diet may contribute to insulin resistance in humans. They found that feeding subjects 18g of salt per day activated NLRP3 inflammasome, which in turn promoted a form of inflammation associated with insulin resistance. [18] 

To be fair, this study was also a oneweek study and the effects may also be a short-term reaction to increased salt consumption. But, even if it is just short term, another interesting discovery of the study was that taking 4.5g/day of potassium along with the added salt seemed to undue many of the inflammatory effects of the high-salt diet. 


In Short: The Data Continues to Show That a Healthy Diet is Low in Salt and High in Potassium

Sodium is an essential nutrient; we need it to survive. But wmust be careful not to translate that into a “more is better” approach by pointing to the health benefits of consuming adequate levels of sodium and extrapolating from there. In the case of sodium, more is not better, and a very convincing body of science shows that 7,000mg/day contributes to a slew of health problemsincluding insulin resistance. 

The 2018 study by Wan et. al. focused, for the first eight pages, entirely on inflammatory markers, reactive oxygen species, and the effects of salt on THP-1 monocytes. In short, iyou’re looking for a nerdy read from a bunch of scientists holed up in a lab, this is not one to miss. 

So, it was interesting to see them take a very Paleo turn in the discussion section of their articleThey state: “increasing evidence suggests that compared with prehistoric or primitive humans, modern people with more sodium and less potassium intake are more vulnerable to suffering from CVD.” 

Their final recommendation stated that “potassium is abundant in fresh fruits and vegetables. Therefore, a greater fresh fruit and vegetable consumption and reasonable salt restriction could protect against the occurrence of insulin resistance and CVD.” This squarely coincides with The Paleo Diet. We hope this recommendation begins to persuade more people to reconsider their sodium intake.


Read More in Our Series on Sodium and Potassium in the Diet:


  1. Denton, D., Salt intake and high blood pressure in man. Primitive peoples, unacculturated societies: with comparisons, in The Hunger for Salt, An Anthropological, Physiological and Medical Analysis. 1984, Springer-Verlag: New York. p. 556-584.
  2. O’Donnell, M., et al., Urinary sodium and potassium excretion, mortality, and cardiovascular events. N Engl J Med, 2014. 371(7): p. 612-23.
  3. O’Donnell, M.J., et al., Urinary sodium and potassium excretion and risk of cardiovascular events. JAMA, 2011. 306(20): p. 2229-38.
  4. Pfister, R., et al., Estimated urinary sodium excretion and risk of heart failure in men and women in the EPIC-Norfolk study. Eur J Heart Fail, 2014. 16(4): p. 394-402.
  5. He, F.J., et al., Does reducing salt intake increase cardiovascular mortality? Kidney Int, 2011. 80(7): p. 696-8.
  6. He, F.J. and G.A. MacGregor, Cardiovascular disease: salt and cardiovascular risk. Nat Rev Nephrol, 2012. 8(3): p. 134-6.
  7. Stolarz-Skrzypek, K., et al., Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion. JAMA, 2011. 305(17): p. 1777-85.
  8. He, F.J., J. Li, and G.A. Macgregor, Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials. BMJ, 2013. 346: p. f1325.
  9. Garg, R., B. Sun, and J. Williams, Effect of low salt diet on insulin resistance in salt-sensitive versus salt-resistant hypertension. Hypertension, 2014. 64(6): p. 1384-7.
  10. Prada, P.O., et al., Low salt intake modulates insulin signaling, JNK activity and IRS-1ser307 phosphorylation in rat tissues. J Endocrinol, 2005. 185(3): p. 429-37.
  11. Oh, H., et al., Low Salt Diet and Insulin Resistance. Clin Nutr Res, 2016. 5(1): p. 1-6.
  12. Townsend, R.R., S. Kapoor, and C.B. McFadden, Salt intake and insulin sensitivity in healthy human volunteers. Clin Sci (Lond), 2007. 113(3): p. 141-8.
  13. Fliser, D., et al., The effect of dietary salt on insulin sensitivity. Eur J Clin Invest, 1995. 25(1): p. 39-43.
  14. Iwaoka, T., et al., The effect of low and high NaCl diets on oral glucose tolerance. Klin Wochenschr, 1988. 66(16): p. 724-8.
  15. Graudal, N.A., T. Hubeck-Graudal, and G. Jurgens, Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride. Cochrane Database Syst Rev, 2011(11): p. CD004022.
  16. Graudal, N.A., T. Hubeck-Graudal, and G. Jurgens, Effects of low-sodium diet vs. high-sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride (Cochrane Review). Am J Hypertens, 2012. 25(1): p. 1-15.
  17. Lanaspa, M.A., et al., High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism. Proc Natl Acad Sci U S A, 2018. 115(12): p. 3138-3143.
  18. Wan, Z., et al., Involvement of NLRP3 inflammasome in the impacts of sodium and potassium on insulin resistance in normotensive Asians. Br J Nutr, 2018. 119(2): p. 228-237.

Leptin Resistance | The Paleo Diet

What’s all the buzz about leptin? With over half the American population trying desperately to lose weight,1 it’s no wonder we’ve become fascinated with a hormone that prompts us to think obesity or starvation.

Robert H. Lustig, MD, professor of pediatrics at UCSF and a member of the Endocrine Society’s Obesity Task Force explains “Leptin is a protein that’s made in the fat cells, circulates in the bloodstream, and goes to the brain; it’s the way your fat cells tell your brain that your energy thermostat is set right…and you have enough energy stored in your fat cells to engage in normal, relatively expensive metabolic processes.” Dr. Lustig goes on to discuss that levels are likely genetically set for each person. When an unbalance occurs exceeding your leptin threshold, the brain responds to the energy sufficiency, allowing you to “burn energy at a normal rate, eat food at a normal amount, engage in exercise at a normal rate, and you can engage in expensive processes, like puberty and pregnancy.”2

When the body doesn’t respond to the signal, it cannot stimulate your metabolism or suppress your appetite, inducing leptin resistance. This can make losing weight difficult if not impossible. With insulin resistance, pre-diabetes, and ultimately a diagnosis of Type II Diabetes on the rise, so too are the number of individuals diagnosed with leptin resistance.

The Standard American Diet (SAD), leading a predominantly sedentary lifestyle, too much stress, and not enough sleep all contribute to leptin resistance.3 Assessing whether leptin resistance is contributing to shedding stubborn pounds once and for all, shouldn’t start with the notion of a magic bullet, but an overhaul of lifestyle.

Sure, it’s easy to find leptin supplements online that promise the oomph you need to kickstart your new weight loss regime. But are they effective? Not according to research.

Because leptin is a digestible protein that doesn’t enter the bloodstream, the body just breaks it up. Further, leptin supplements sold online don’t actually contain leptin, but rather ingredients that are purported to help improve leptin functioning or feelings of fullness.4

So what’s the answer? As always, we need to go back to basics and look at the problem, rather than the symptom.

Leptin and insulin communicate and work in conjunction with other hormones to control our energy balance and as insulin levels rise, so do leptin levels. If we start by following a balanced, Paleo eating plan, which prevents blood sugar spike to begin with, we regulate our blood sugar and leptin release, reducing our chances of developing leptin and insulin resistance.

The takeaway: stop doing your body a disservice. Ask yourself:

  1. Am I eating right?
  2. Are my macronutrients balanced?
  3. Is my food timing in check?
  4. Am I exercising regularly?

If you answered ‘No’ to any of these questions, you may be hindering your weight loss and setting yourself up for additional adverse effects, like increasing your risk for cardiovascular disease (CVD) and other metabolic diseases.

“With obesity, leptin cannot tell our brain to stop eating, but it can still tell our brain to increase the activity of the cardiovascular system,” said Dr. Eric Belin de Chantemele, physiologist in the Department of Physiology at the Medical College of Georgia at Georgia Regents University. 5

Researchers have also shown that fat-derived leptin directly activates aldosterone synthase expression in the adrenal glands, resulting in production of more of the steroid hormone aldosterone. Increased aldosterone directly effects blood pressure by regulating salt-water balance in the body, contributes to widespread inflammation, blood vessel stiffness and scarring, enlargement and stiffness of the heart, and impaired insulin sensitivity. High levels of aldosterone are an obesity hallmark and a leading cause of metabolic and cardiovascular problems6

Avoid widespread inflammation. Stop insulin resistance in its tracks. Keep blood sugar low. These three key health tenants fit the bill and are easily achieved by following a Paleo diet. Add a little patience into the mix and avoid the urge for ‘get results fast!’ and Viola! We give our bodies the time to calm inflammation, shed the extra weight, and reset its hormonal cascade.

Take action now, before you need medical intervention!


1. “Americans’ Desire to Shed Pounds Outweighs Effort.” Gallup.com. N.p., n.d. Web. 19 Oct. 2015

2. “Leptin Hormone & Supplements: Do They Work for Obesity & Weight Loss?” WebMD. WebMD, n.d. Web. 19 Oct. 2015

3. Galland, M.D. Leo. “Leptin: How to Make This Fat-Burning Hormone Work for You.” The Huffington Post. TheHuffingtonPost.com, n.d. Web. 19 Oct. 2015

4. “The Facts on Leptin: FAQ.” WebMD. WebMD, n.d. Web. 19 Oct. 2015

5. “Satiety Hormone Leptin Plays a Direct Role in Cardiovascular Disease in Obesity.” ScienceDaily. ScienceDaily, n.d. Web. 19 Oct. 2015

6. Anne-Cécile Huby, Galina Antonova, Jake Groenendyk, Celso E. Gomez-Sanchez, Wendy B. Bollag, Jessica A. Filosa, Eric J. Belin de Chantemèle. The Adipocyte-Derived Hormone Leptin is a Direct Regulator of Aldosterone Secretion, Which Promotes Endothelial Dysfunction and Cardiac Fibrosis. Circulation, 2015; CIRCULATIONAHA.115.018226 DOI: 10.1161/CIRCULATIONAHA.115.018226

polycystic ovary syndrome (PCOS) | The Paleo Diet


If you haven’t heard, a research team at the University of California – San Francisco — Lynda Frassetto, MD, Umesh Masharani, MD, Heather Huddleston, MD, Michael Cohn, PhD, and Ashley Mason, PhD — is getting ready to conduct a study of dietary treatments polycystic ovary syndrome (PCOS). They will test a Paleolithic Diet and an American Diabetes Asssociation diet to see if either or both improves insulin resistance and menstrual cycle regularity for women with PCOS.

They cannot do it alone, however. As many of you can imagine, it is difficult for researchers to land funding from the National Institutes of Health (NIH) to do nutrition-related research in the context of disease treatment or management. This study will give them the early data they need to start large, truly definitive studies of the links between diet (including a Paleo Diet) and insulin resistance.

Please check out their crowdfunding website to learn more about the study, the researchers, and make tax-deductible donations to help this research happen. And, if you are going to AHS, one of the backer rewards is having lunch with the researchers – a pretty rare opportunity!

Click Here to Support the Study


Loren Cordain, Ph.D., Professor Emeritus

The Toxins Lurking in Our Food

When most people think about a Paleo Diet, they think a healthy diet, rich in whole foods, sans dairy and grains. But one important and sometimes overlooked aspect is the low toxin burden. Avoiding processed foods, artificial ingredients, and excessive pesticides and herbicides is at the very least prudent.

When asked how to “bulk up” on the Paleo Diet, two basic, yet critical concepts in nutrition come to mind.

First, there are many toxins, dietary, environmental, and otherwise, that are readily stored in our body. This was demonstrated in epic fashion, by accident, during Biosphere 2.

Biosphere 1 is Earth. Biosphere 2 was an enormous, man-made, Earth-like structure that was completely closed off from the outside world.


Deidos, Wikipedia Creative Commons

It was constructed to see, among other things, if a small group of people could be completely self-sufficient. On some levels, due in part to poor planning, it failed – food and oxygen needed to be added from the outside. However, eight volunteers still lived inside and collected data for two years.6, 7

The participants subsisted primarily on agriculture, but weren’t able to provide enough food to sustain themselves. They could only raise approximately 1,800 of the estimated 2,500 calories necessary to maintain weight. As such, all of them lost weight.

Toxins Lurking in Our Food - Graph 1

But that’s not the point of this article.

Their food was organic, herbicide, pesticide-free, and very nutrient-dense – all aspects in line with the principles of a Paleo Diet, and far different from their usual diet.

The thing that stuck with me since I visited the site over a decade ago is this:

PCBs are synthetic organic chemicals, classified as Persistent Organic Pollutants. DDE is a breakdown product of the insecticide DDT. Both are toxins.8 However, their exposure to these toxins should have been extremely low. So why did they suddenly appear in their blood?

These toxins, like many others found in processed and/or inorganic foods, plastics, etc., can be stored in the body. As the participants lost weight, the toxins were released from storage and eventually excreted.4

Toxins Lurking in Our Food - Graph 2

The second concept is what these toxins can potentially do to your health and quality of life. A large body of research implicates food additives and environmental toxins as causal agents in the obesity epidemic.2 Not in the sense that they cause massive rapid weight gain overnight, but rather they cause the pancreas to secrete just a little more insulin than necessary, predisposing it to insulin resistance and the accumulation of body fat.2

Food additives, emulsifiers, preservatives, and even some artificial sweeteners have been shown to possess this ability.5

If you’re trying to gain weight, avoid toxins (dietary or otherwise): 1) to ensure a high ratio of muscle to fat mass; and 2) because some of those toxins may be stored. On the flipside, if you’re trying to lose weight, avoid toxins (dietary or otherwise) to prevent insulin hypersecretion which could decrease the rate of fat loss and slow down your progress.

William Lagakos, Ph.D.

William Lagakos, Ph.D.Dr. William Lagakos received a Ph.D. in Nutritional Biochemistry and Physiology from Rutgers University where his research focused on dietary fat assimilation and integrated energy metabolism. His postdoctoral research at the University of California, San Diego, centered on obesity, inflammation, and insulin resistance. Dr. William Lagakos has authored numerous manuscripts which have been published in peer-reviewed journals, as well as a non-fiction book titled The Poor, Misunderstood Calorie which explores the concept of calories and simultaneously explains how hormones and the neuroendocrine response to foods regulate nutrient partitioning. He is presently a nutritional sciences researcher, consultant, and blogger.


1. Corkey BE. Banting lecture 2011: hyperinsulinemia: cause or consequence? Diabetes. Jan 2012;61(1):4-13.

2. Corkey BE. Diabetes: have we got it all wrong? Insulin hypersecretion and food additives: cause of obesity and diabetes? Diabetes Care. Dec 2012;35(12):2432-2437.

3. Dedios, John. Bio2_Sunset_001. Digital image. Wikipedia Creative Commons. Wikipedia, 30 Sept. 2011.

4. Imbeault P, Chevrier J, Dewailly E, Ayotte P, Despres JP, Tremblay A, Mauriege P. Increase in plasma pollutant levels in response to weight loss in humans is related to in vitro subcutaneous adipocyte basal lipolysis. Int J Obes Relat Metab Disord. Nov 2001;25(11):1585-1591.

5. Saadeh M, Ferrante TC, Kane A, Shirihai O, Corkey BE, Deeney JT. Reactive oxygen species stimulate insulin secretion in rat pancreatic islets: studies using mono-oleoyl-glycerol. PLoS One. 2012;7(1):e30200.

6. Walford RL, Mock D, MacCallum T, Laseter JL. Physiologic changes in humans subjected to severe, selective calorie restriction for two years in biosphere 2: health, aging, and toxicological perspectives. Toxicol Sci. Dec 1999;52(2 Suppl):61-65.

7. Walford RL, Mock D, Verdery R, MacCallum T. Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. J Gerontol A Biol Sci Med Sci. Jun 2002;57(6):B211-224.

8. Wang SL, Tsai PC, Yang CY, Guo YL. Increased risk of diabetes and polychlorinated biphenyls and dioxins: a 24-year follow-up study of the Yucheng cohort. Diabetes Care. Aug 2008;31(8):1574-1579.

9. Weyer, Christian, Roy L. Walford, Inge T. Harper, Mike Milner, Taber MacCallum, P. A. Tataranni, and Eric Ravussin. “Energy Metabolism after 2 Y of Energy Restriction: The Biosphere 2 Experiment.” American Journal of Clinical Nutrition 53rd ser. 72.946 (2000): 1-8. Print.

The Paleo Diet And Gout | The Paleo Diet

I have a question regarding the paleo diet and gout – what is the effect of the Paleo Diet on seniors with respect to gout? I’ve heard that protein in one’s diet can have an adverse effect.

Dr. Cordain’s Response:

Gout is considered as part of a metabolic syndrome and insulin resistance is at the root of gout. Along these lines, gout was rare among pre-agricultural populations (Hunter-gatherers). Serum uric acid levels depend on the amount entering the blood and the amount leaving the blood.

The amount of uric acid entering the blood depends on the amount of it produced by the liver (1/3 from the diet and 2/3 from the body turn-over of cells) and the amount of uric acid leaving the blood depends on the kidneys’ excretion capacity. The metabolic syndrome and insulin resistance induce kidney underexcretion of uric acid. On the other hand, when the kidney is
faced with high protein purine-containing foods, serum uric acid levels decrease because the kidney increases uric acid excretion (this is an evolutionary trade-off).

So, the real problem is increased liver production of uric acid and kidney uric acid underexcretion. High glycemic load foods (as found in the typical western diet and not in The Paleo Diet) and subsequent hyperinsulinemia halt the kidneys’ capacity to excrete uric acid. Regarding liver production of uric acid: fructose, and particularly High Fructose Corn Syrup (HFCS), decreases inorganic phosphate in the liver and this increases the production
of uric acid from purines.

The Paleo Diet helps to fight gout as is based on low glycemic load foods, high protein and no HCFS foods.


Loren Cordain, Ph.D., Professor Emeritus

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